Phytoplasmas are insect-vectored bacteria that cause disease in a wide range of

plant species. The increasing availability of molecular DNA analyses, expertise and
additional methods in recent years has led to a proliferation of discoveries of
phytoplasma-plant host associations and in the numbers of taxonomic groupings for
phytoplasmas. The widespread use of common names based on the diseases with which
they are associated, as well as separate phenetic and taxonomic systems for
classifying phytoplasmas based on variation at the 16S rRNA-encoding gene,
complicates interpretation of the literature. We explore this issue and related
trends through a focus on Australian pathosystems, providing the first
comprehensive compilation of information for this continent, covering the
phytoplasmas, host plants, vectors and diseases. Of the 33 16Sr groups reported
internationally, only groups I, II, III, X, XI and XII have been recorded in
Australia and this highlights the need for ongoing biosecurity measures to prevent
the introduction of additional pathogen groups. Many of the phytoplasmas reported
in Australia have not been sufficiently well studied to assign them to 16Sr groups
so it is likely that unrecognized groups and sub-groups are present. Wide host
plant ranges are apparent among well studied phytoplasmas, with multiple crop and
non-crop species infected by some. Disease management is further complicated by the
fact that putative vectors have been identified for few phytoplasmas, especially in
Australia. Despite rapid progress in recent years using molecular approaches,
phytoplasmas remain the least well studied group of plant pathogens, making them a
"crouching tiger" disease threat.
Background: (-)-alpha-Bisabolol, also known as levomenol, is an unsaturated
sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic
products due to its anti-inflammatory and skin-soothing properties. (-)-alpha-
Bisabolol is currently manufactured mainly by steam-distillation of the essential
oils extracted from the Brazilian candeia tree that is under threat because its
natural habitat is constantly shrinking. Therefore, microbial production of (-)-
alpha-bisabolol plays a key role in the development of its sustainable production
from renewable feedstock. Results: Here, we created an Escherichia coli strain
producing (-)-alpha-bisabolol at high titer and developed an in situ extraction
method of (-)-alpha-bisabolol, using natural vegetable oils. We expressed a
recently identified (-)-alpha-bisabolol synthase isolated from German chamomile
(Matricaria recutita) (titer: 3 mg/L), converted the acetyl-CoA to mevalonate,
using the biosynthetic mevalonate pathway (12.8 mg/L), and overexpressed farnesyl
diphosphate synthase to efficiently supply the (-)-alpha-bisabolol precursor
farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway
and farnesyl diphosphate synthase enabled a dramatic increase in (-)-alpha-
bisabolol production in the shake flask culture (80 mg/L) and 5 L bioreactor
culture (342 mg/L) of engineered E. coli harboring (-)-alpha-bisabolol synthase.
Fed-batch fermentation using a 50 L fermenter was conducted after optimizing
culture conditions, resulting in efficient (-)-alpha-bisabolol production with a
titer of 9.1 g/L. Moreover, a green, downstream extraction process using vegetable
oils was developed for in situ extraction of (-)-alpha-bisabolol during
fermentation and showed high yield recovery (>98%). Conclusions: The engineered E.
coli strains and economically viable extraction process developed in this study
will serve as promising platforms for further development of microbial production
of (-)-alpha-bisabolol at large scale.
A universal feature of the replication of positive-strand RNA viruses is the
association with intracellular membranes. Carnation Italian ringspot virus (CIRV)
replication in plants occurs in vesicles derived from the mitochondrial outer
membrane. The product encoded by CIRV ORF1, p36, is required for targeting the
virus replication complex to the outer mitochondrial membrane both in plant and
yeast cells. Here the yeast Saccharomyces cerevisiae was used as a model host to
study the effect of CIRV p36 on cell survival and death. It was shown that p36 does
not promote cell death, but decreases cell growth rate. In addition, p36 changed
the nature of acetic acid-induced cell death in yeast by increasing the number of
cells dying by necrosis with concomitant decrease of the number of cells dying by
programmed cell death, as judged by measurements of phosphatidylserine
externalization. The tight association of p36 to membranes was not affected by
acetic acid treatment, thus confirming the peculiar and independent interaction of
CIRV p36 with mitochondria in yeast. This work proved yeast as an invaluable model
organism to study both the mitochondrial determinants of the type of cell death in
response to stress and the molecular pathogenesis of (+)RNA viruses. (C) 2016
Elsevier Ireland Ltd. All rights reserved.
1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative
agents associated with the development of cholangiocarcinoma in employees working
in printing plant in Osaka, Japan. However, few reports have demonstrated an
association between these agents and cholangiocarcinoma in rodent carcinogenicity
studies. Moreover, the combined effects of these compounds have not been fully
elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2-DCP
and DCM, alone or combined, in the livers of gpt delta rats. Six-week-old male F344
gpt delta rats were treated with 1,2-DCP, DCM or 1,2-DCP+DCM by oral administration
for 4weeks at the dose (200mgkg(-1) body weight 1,2-DCP and 500mgkg(-1) body weight
DCM) used in the carcinogenesis study performed by the National Toxicology Program.
In vivo mutagenicity was analyzed by gpt mutation/Spi(-) assays in the livers of
rats. In addition, gene and protein expression of CYP2E1 and GSTT1, the major
enzymes responsible for the genotoxic effects of 1,2-DCP and DCM, were analyzed by
quantitative polymerase chain reaction and western blotting. Gpt and Spi(-)
mutation frequencies were not increased by 1,2-DCP and/or DCM in any group.
Additionally, there were no significant changes in the gene and protein expression
of CYP2E1 and GSTT1 in any group. These results indicated that 1,2-DCP, DCM and
1,2-DCP+DCM had no significant impact on mutagenicity in the livers of gpt delta
rats under our experimental conditions. Copyright (c) 2016 John Wiley & Sons, Ltd.
This paper presents the simulation results of a linear, fully integrated, two-stage
digitally programmable 130 nm CMOS power amplifier (PA) operating at 2.4 GHz. Its
power stage is composed of a set of amplifying cells which can be enabled or
disabled independently by a digital control circuit. All seven operational modes
are univocal in terms of 1 dB output compression point (OCP1dB), saturated output
power (P-SAT) and power gain at 2.4 GHz. The lowest power mode achieves an 8.1 dBm
P-SAT, a 13.5 dB power gain and consumes 171 mW DC power (P-DC) at an OCP1dB of 6
dBm, whereas the highest power mode reaches an 18.9 dBm P-SAT and a 21.1 dB power
gain and consumes 415 mW P-DC at an OCP1dB of 18.2 dBm.
The glycogen branching enzyme (EC 2.4.1.18), which catalyses the formation of
alpha-1,6-glycosidic branch points in glycogen structure, is often used to enhance
the nutritional value and quality of food and beverages. In order to be applicable
in industries, enzymes that are stable and active at high temperature are much
desired. Using genome mining, the nucleotide sequence of the branching enzyme gene
(glgB) was extracted from the Geobacillus mahadia Geo-05 genome sequence provided
by the Malaysia Genome Institute. The size of the gene is 2013 bp, and the
theoretical molecular weight of the protein is 78.43 kDa. The gene sequence was
then used to predict the thermostability, function and the three dimensional
structure of the enzyme. The gene was cloned and overexpressed in E. coli to verify
the predicted result experimentally. The purified enzyme was used to study the
effect of temperature and pH on enzyme activity and stability, and the inhibitory
effect by metal ion on enzyme activity. This thermostable glycogen branching enzyme
was found to be most active at 55 degrees C, and the half-life at 60 degrees C and
70 degrees C was 24 h and 5 h, respectively. From this research, a thermostable
glycogen branching enzyme was successfully isolated from Geobacillus mahadia Geo-05
by genome mining together with molecular biology technique.
The microbial populations in the activated sludge of two Polish wastewater
treatment plants (WWTPs) were identified and quantified using Illumina sequencing
of 16S ribosomal RNA amplicons over a 2-year period. Their dynamics over time were
compared to Danish WWTPs (data collected in previous studies by Center for
Microbial Communities, Aalborg University). The bacterial communities in Polish and
Danish WWTPs were similar to each other, but the microbial diversity in Polish
WWTPs was lower. The dominant genera in Polish WWTPs were more abundant than in
Danish WWTPs; 30 of them constituted more than half the of activated sludge
community. Polish WWTPs showed a higher abundance of bacteria involved in nitrogen
and chemical oxygen demand removal (Proteobacteria and Bacteroidetes), while
polyphosphate-acculumating bacteria were the dominant bacterial group in Danish
plants. The microbial community structures in the examined Polish WWTPs were
relatively similar to each other and showed strong seasonal variations which are
not normally observed in Danish WWTPs.
Background: Broad-range 16S rRNA PCR can be used for the detection and
identification of bacteria from clinical specimens in patients for whom there is a
high suspicion of infection and cultures are negative. The aims of this study were
(1) to compare 16S rRNA PCR results with microbiolog ical culture results, (2) to
assess the utility of 16S rRNA PCR with regard to antimicrobial therapy, and (3) to
compare the yield of 16S rRNA PCR for different types of clinical specimen and to
perform a cost analysis of the test. Methods: A retrospective study was performed
on different clinical specimens which had 16S performed over 3 years (2012-2015).
Standard microbiological cultures were performed on appropriate media, as per the
laboratory protocol. Patient clinical and microbiological data were obtained from
the electronic medical records and laboratory information system, respectively. 16S
rRNA PCR was performed in a reference laboratory using a validated method for
amplification and sequencing. The outcomes assessed were the performance of 16S
rRNA PCR, change of antimicrobials (rationalization, cessation, or addition), and
duration of therapy. Concordance of 16S rRNA PCR with bacterial cultures was also
determined for tissue specimens. Results: Thirty-two patients were included in the
study, for whom an equal number of specimens (n = 32) were sent for 16S rRNA PCR.
16S rRNA PCR could identify an organism in 10 of 32 cases (31.2%), of which seven
were culture-positive and three were culture-negative. The sensitivity was 58%
(confidence interval (CI) 28.59-83.5%) and specificity was 85% (CI 61.13-96%), with
a positive predictive value of 70% (CI 35.3-91.9%) and negative predictive value of
77.2% (CI 54.17-91.3%). Antimicrobial therapy was rationalized after 16S rRNA PCR
results in five patients (15.6%) and was ceased in four based on negative results
(12.5%). Overall the 16S rRNA PCR result had an impact on antimicrobial therapy in
28% of patients (9/32). The highest concordance of 16S rRNA PCR with bacterial
culture was found for heart valve tissue (80%), followed by joint fluid/tissue
(50%). Conclusions: Despite the low diagnostic yield, results of 16S rRNA PCR can
still have a significant impact on patient management due to rationalization or
cessation of the antimicrobial therapy. The yield of 16S rRNA PCR was highest for
heart valves. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of
International Society for Infectious Diseases.
Brinjal little leaf (BLL) is a widespread disease of phytoplasma etiology in India
that induces severe economic losses. Surveys were conducted in eight brinjalgrowing
states of India during July 2014 to September 2015 and eighteen BLL samples showing
little leaf, phyllody and witches' broom symptoms were collected for phytoplasma
identification. Presence of phytoplasmas was confirmed in all the eighteen BLL
samples using polymerase chain reaction with phytoplasma-specific primer pairs
(P1/P6, R16F2n/R16R2). Pair wise sequence comparison and phylogenetic relationship
of 16S rRNA gene sequences of BLL phytoplasma strains confirmed that sixteen out of
eighteen BLL strains belonged to clover proliferation phytoplasma (16SrVI) group
and two BLL strains (GKP-A and GKP-B) from Gorakhpur, Uttar Pradesh, were
classified under 16SrII group. Further virtual RFLP analysis of 16S rDNA sequences
allowed finer classification of BLL strains into 16SrII-D and 16SrVI-D subgroups.
BLL phytoplasma strains belonging to 16SrVI-D subgroup were found as the most
widespread phytoplasma strains associated with BLL disease in India. 16SrVI-D
subgroup phytoplasma association with two symptomatic weed species viz. Cannabis
sativa subsp. sativa at Noida, Uttar Pradesh and Portulaca oleracea at IARI fields,
New Delhi was also confirmed by nested PCR assays with similar set of phytoplasma-
specific primers, pairwise 16S rDNA sequence comparison, phylogeny and virtual RFLP
analysis. Out of five identified leafhopper species from BLL-infected fields at
Noida, Uttar Pradesh and Delhi, only Hishimonas phycitis was identified as carrier
and natural vector of 16SrVI-D subgroup of phytoplasmas by nested PCR assays,
sequence comparison, phylogeny, virtual RFLP analysis and transmission assays.
Surveys for the Cote d'Ivoire lethal yellowing (CILY) phytoplasma were conducted in
eight severely CILY-affected villages of Grand-Lahou in 2015. Leaves,
inflorescences and trunk borings were collected from coconut palms showing CILY
symptoms and from symptomless trees. Total DNA was extracted from these samples and
tested by nested polymerase chain reaction/RFLP and sequence analysis of the 16S
rRNA, ribosomal protein (rp) and the translocation protein (secA) genes. The CILY
phytoplasma was detected in 82.9% of the symptom-bearing palms collected from all
the surveyed villages and from all the plant parts. Trunk borings were recommended
as the most suitable plant tissue type for sampling. Results indicate that the CILY
phytoplasma may have a westward spread to other coconut-growing areas of Grand-
Lahou. CILY phytoplasma strains infecting coconut palms in the western region of
Grand-Lahou exhibited unique single nucleotide polymorphisms on the rp sequence
compared to the strains from the eastern region. Moreover, single nucleotide
polymorphisms on the SecA sequence distinguished the CILY phytoplasma from the Cape
St. Paul Wilt Disease phytoplasma in Ghana, and the Lethal Yellowing phytoplasma in
Mozambique.
Advances in sequencing technologies continue to provide unprecedented opportunities
to characterize microbial communities. For example, the Pacific Biosciences Single
Molecule Real-Time (SMRT) platform has emerged as a unique approach harnessing DNA
polymerase activity to sequence template molecules, enabling long reads at low
costs. With the aim to simultaneously classify and enumerate in situ microbial
populations, we developed a quantitative SMRT (qSMRT) approach that involves the
addition of exogenous standards to quantify ribosomal amplicons derived from
environmental samples. The V7-9 regions of 18S SSU rDNA were targeted and
quantified from protistan community samples collected in the Ross Sea during the
Austral summer of 2011. We used three standards of different length and optimized
conditions to obtain accurate quantitative retrieval across the range of expected
amplicon sizes, a necessary criterion for analyzing taxonomically diverse 18S rDNA
molecules from natural environments. The ability to concurrently identify and
quantify microorganisms in their natural environment makes qSMRT a powerful, rapid
and cost-effective approach for defining ecosystem diversity and function. (C) 2017
Elsevier B.V. All rights reserved.
1A6/DRIM is a nucleolar protein with a nucleolar targeting sequence in its 3'-
terminus. Bioinformatic analysis indicated that human 1A6/ DRIM shares 23% identity
and 43% similarity with yeast Utp20, which has been reported as a component of U3
snoRNA protein complex and has been implicated in 18S rRNA processing. In the
present study, we found, by utilizing RT-PCR with RNA extracted from anti-1A6/DRIM
inummoprecipitates and Northern blotting, that 1A6/DRIM is associated with U3
snoRNA. Pulse-chase labeling assays showed that silencing of 1A6/DRIM expression in
HeLa cells resulted in a delayed 18S rRNA processing. Furthermore,
immunoprecipitations revealed that 1A6/DRIM was also associated with fibrillarin,
another U3 RNP component in HeLa cells. These results indicate that 1A6/DRIM is
involved in 18S rRNA processing and is the bona fide mammalian Utp20. (c) 2007
Elsevier B.V. All rights reserved.
Aims: 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic condition associated
with an increased risk of developing schizophrenia. Previous studies have shown
that negative symptoms represent the most specific clinical characteristic of
psychosis in 22q11.2DS and are strongly associated with outcome. However, the
psychological mechanisms associated with these symptoms in this population are
poorly understood. In accordance with recent conceptualizations in the field of
schizophrenia, the present study aims at investigating whether negative symptoms
are associated with the presence of negative performance beliefs and cognitive
deficits. Methods: Thirty-five participants with 22q11.2DS and 24 typically
developing individuals aged between 11 and 24 years were included in the study.
Self-reported schizotypal symptoms (cognitive-perceptual, paranoid, negative and
disorganization symptoms) and dysfunctional beliefs (negative performance beliefs
and need for approval) were assessed. Measures of processing speed, verbal memory,
working memory, executive functioning and face recognition-were also extracted from
a broad cognitive evaluation protocol. Results: Adolescents with 22q11.2DS reported
significantly higher score on the negative dimension of the Schizotypal Personality
Questionnaire than controls, even when controlling for the influence of
anxiety/depression and intellectual functioning. Negative and paranoid symptoms
were associated with the severity of negative performance beliefs and lower face
recognition abilities. Mediation analyses revealed that negative performance
beliefs significantly mediated the association between face recognition and
negative/paranoid symptoms. Conclusions: These findings suggest that negative
performance beliefs and basic social cognitive mechanisms are associated with
negative and paranoid symptoms in individuals with 22q11.2DS. Implications for
intervention are discussed in this article.
Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic
disorder that is associated with a 25-fold increase in schizophrenia. Both
individuals with 22q11.2DS and those with schizophrenia present with social
cognitive deficits, which are putatively subserved by a network of brain regions
that are involved in the processing of social cognitive information. This study
used two-tensor tractography to examine the white matter tracts believed to
underlie the social brain network in a group of 57 young adults with 22q11.2DS
compared to 30 unaffected controls. Results: Results indicated that relative to
controls, participants with 22q11.2DS showed significant differences in several DTI
metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-
frontal tract, and inferior longitudinal fasciculus. In addition, participants with
22q11.2DS showed significant differences in scores on measures of social cognition,
including the Social Responsiveness Scale and Trait Emotional Intelligence
Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an
association between DTI metrics and positive and negative symptoms of psychosis, as
well as differentiation between individuals with 22q11.2DS and overt psychosis,
relative to those with positive prodromal symptoms or no psychosis. Conclusions:
Findings suggest that white matter disruption, specifically disrupted axonal
coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for
social cognitive difficulties and psychosis in individuals with 22q11.2DS.
Through the comprehensive analysis of the genomic DNA sequence of human chromosome
22, we identified a novel gene of 702 kb encoding a big protein of 2481 amino acid
residues, and named it as TPRBK (TPR containing big gene cloned at Keio). A novel
protein TPRBK possesses 25 units of the TPR motif, which has been known to
associate with a diverse range of biological functions. Orthologous genes of human
TPRBK were found widely in animal species, from insecta to mammal, but not found in
plants, fungi and nematoda. Northern blotting and RT-PCR analyses revealed that
TPRBK gene is expressed ubiquitously in the human and mouse fetal tissues and
various cell lines of human, monkey and mouse. lmmunofluorescent staining of the
synchronized monkey COS-7 cells with several relevant antibodies indicated that
TPRBK changes its subcellular localization during the cell cycle: at interphase
TPRBK locates on the centrosomes, during mitosis it translocates from spindle poles
to mitotic spindles then to spindle midzone, and through a period of cytokinesis it
stays on the midbody. Co-immunoprecipitation assay and immunofluorescent staining
with adequate antibodies revealed that TPRBK binds to Aurora B. and those proteins
together translocate throughout mitosis and cytokinesis. Treatments of cells with
two drugs (Blebbistatin and Y-27632), that are known to inhibit the contractility
of actin-myosin, disturbed the proper intracellular localization of TPRBK.
Moreover, the knockdown of TPRBK expression by small interfering RNA (siRNA)
suppressed the bundling of spindle midzone microtubules and disrupted the midbody
formation, arresting the cells at G(2) + M phase. These observations indicated that
a novel big protein TPRBK is essential for the formation and integrity of the
midbody, hence we postulated that TPRBK plays a critical role in the progress of
mitosis and cytokinesis during mammalian cell cycle. (C) 2012 Elsevier B.V. All
rights reserved.
Graphene and other two-dimensional materials have received considerable attention
regarding their potential applications in nano-electronics. Here, we report top-
gate nonvolatile memory field-effect transistors (FETs) with different layers of
MoSe2 nanosheets channel gated by ferroelectric film. The conventional gate
dielectric of FETs was replaced by a ferroelectric thin film that provides a
ferroelectric polarization electric field, and therefore defined as an Fe-FET where
the poly (vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) was used as the gate
dielectric. Among the devices with MoSe2 channels of different thicknesses, the
device with a single layer of MoSe2 exhibited a large hysteresis of electronic
transport with an over 10(5) write/erase ratio, and displayed excellent retention
and endurance performance. The possible mechanism of the device's good properties
was qualitatively analyzed using band theory. Additionally, a comprehensive study
comparing the memory properties of MoSe2 channels of different thicknesses is
presented. Increasing the numbers of MoSe2 layers was found to cause a reduced
memory window. However, MoSe2 thickness of 5 nm yielded a write/erase ratio of more
than 10(3). The results indicate that, based on a Fe-FET structure, the combination
of two-dimensional semiconductors and organic ferroelectric gate dielectrics shows
good promise for future applications in nonvolatile ferroelectric memory.
Relationships between the abundance of potential geosmin- and 2-methylisoborneol-
producing (2-MIB) cyanobacteria and bacteria, and concentrations of the two taste
and odour compounds (T&Os) were examined in a 7 day incubation of natural water
from the surface and bottom of three reservoirs in southeast Queensland, Australia.
Only a single known T&O-producing cyanobacterium (Geitlerinema spp.) was detected
by microscopy at low density, and only in one reservoir. Densities of potential
T&O-producing Streptomyces (determined by quantitative polymerase chain reaction
(qPCR) assay) were highest in the bottom water and varied from 0.7 x 10(3) to 775 x
10(3) cells L-1. Geosmin ranged from 6 to 59 ng L-1 (with the highest
concentrations in the bottom water), while 2-MIB varied from 6 to 47 ng L-1 (with
the highest concentration in surface water). Concentrations of both compounds
declined during the incubation under both light and dark conditions. Presence of
the geosmin synthase gene, geoA, in cyanobacteria and Streptomyces was examined by
different PCR approaches. Cloning of PCR products from amplification of geoA showed
a high similarity to geoA in cyanobacteria, but not to streptomycetes. Our results
demonstrate that more research on the ecology and molecular biology of T&O
producers is required to better understand the dynamics of T&Os and to monitor
emerging T&O episodes.
We have carried out animal toxicity tests of chemicals for a chemical safety
program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here,
we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental
and reproductive toxicity test. The test chemical was administered daily by gavage
to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were
treated for 42 d beginning 14 d before mating. Females were treated from 14 d
before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased
respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both
sexes), but resolved within 30 min of administration, suggesting central nervous
system depression. No notable changes were observed in body weight, food
consumption, functional battery tests, or blood test. Increased liver weight with
centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d
(both sexes). There were no biochemical or histopathological changes related to
hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation,
and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d.
Immunohistochemical staining indicated alpha(2u)-globulin nephropathy, a male rat-
specific toxicity. Although kidney weight was also increased in females dosed at
500 mg/kg/d, it was not considered to be an adverse effect because there were no
histopathological changes. Pup weights on postnatal day 0 were decreased at 500
mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-
adverse-effect-level for repeated-dose and reproductive/developmental toxicity for
1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.
The mu-opioid receptor (MOR) plays a mandatory role in the action of most opioid
drugs, such as morphine, fentanyl, and heroin. it has been revealed that a
deficiency in the MOR gene (Oprm 1) or a difference in the 3' noncoding region of
the gene markedly affects the sensitivity of mice to opioids. As the 3' noncoding
region of the human OPRM1 gene had not yet been characterized, in the present study
we conducted 3'-rapid amplification of cDNA ends (3'RACE)-PCR and identified the 3'
end of the human MOR-1 mRNA, the most abundant transcript among OPRM1 gene
transcripts. The poly(A) signal was located at 13612-13617 nucleotides downstream
from the stop codon in the OPRM1 gene. Reverse transcription PCR analyses showed
that the region from the stop codon to the poly(A) signal was transcribed. In the
3' UTR, we identified 33 AU-rich regions and more than 300 putative transcription
factor-binding sites. Furthermore, we compared the 3' noncoding regions of the
human and mouse OPRM1/Oprm1] genes and found apparent homology. In Northern
blotting with mouse brain mRNAs, a same-size band was detected by a probe for the
MOR-1 coding region and by a probe for a mouse genome region corresponding to the
human MOR-1 3'UTR. Since 3'UTRs affect gene expression, the present
characterization of the 3' noncoding region in the human OPRM1 gene should lead to
a better understanding of the mechanisms underlying OPRM1 gene regulation and
individual differences in sensitivity to opioids. Published by Elsevier B.V.
An integrated electronic-photonic phase-locked loop (PLL) modulates the frequency
of a tunable laser for use in frequency-modulated continuous-wave (FMCW) lidar 3D
imaging. The proposed lidar can perform 180k range measurements per second. The rms
depth precision is 8 mu m at distances of +/- 5 cm from the range baseline. The
range window is 1.4 m, with a precision of 4.2 mm at the edges of the window.
Optical circuitry, including input light couplers, waveguides, and photodiodes, is
realized on a 3 mm x 3 mm silicon-photonic chip. The 0.18-mu m CMOS ASIC of the
same area comprises the frontend transimpedance amplifier, analog electro-optical
PLL, and digital control circuitry consuming 1.7 mA from a 1.8 V supply and 14.1 mA
from a 5-V supply. The latter includes 12.5-mA bias current for the distributed
Bragg reflector section of the tunable laser. The two chips are integrated using
through-silicon-vias implemented in the silicon-photonic chip.
3D printing has shown promise for neural regeneration by providing customized nerve
scaffolds to structurally support and bridge the defect gap as well as deliver
cells or various bioactive substances. Low-level light therapy (LLLT) exhibits
positive effects on rehabiliation of degenerative nerves and neural disorders. With
this in mind, we postulate that 3D printed neural scaffold coupling with LLLT will
generate a new strategy to repair neural degeneration. To achieve this goal, we
applied red laser light to stimualte neural stem cells on 3D printed scaffolds and
investigated the subsequent cell response with respect to cell proliferation and
differentiation. Here we show that cell prolifeartion rate and intracellular
reactive oxgen species synthesis were significantly increased after 15 s laser
stimulation follwed by 1 d culture. Over culturing time of 14 d in vitro, the laser
stimulation promoted neuronal differentiation of neural stem cells, while the glial
differentiation was suppressed based on results of both immunocytochemistry studies
and real-time quantitative reverse transcription polymerase chain reaction testing.
These findings suggest that integration of 3D printing and LLLT might provide a
powerful methodology for neural tissue engineering.
With the advances of stem cell research, development of intelligent biomaterials
and three-dimensional biofabrication strategies, highly mimicked tissue or organs
can be engineered. Among all the biofabrication approaches, bioprinting based on
inkjet printing technology has the promises to deliver and create biomimicked
tissue with high throughput, digital control, and the capacity of single cell
manipulation. Therefore, this enabling technology has great potential in
regenerative medicine and translational applications. The most current advances in
organ and tissue bioprinting based on the thermal inkjet printing technology are
described in this review, including vasculature, muscle, cartilage, and bone. In
addition, the benign side effect of bioprinting to the printed mammalian cells can
be utilized for gene or drug delivery, which can be achieved conveniently during
precise cell placement for tissue construction. With layer-by-layer assembly,
three-dimensional tissues with complex structures can be printed using converted
medical images. Therefore, bioprinting based on thermal inkjet is so far the most
optimal solution to engineer vascular system to the thick and complex tissues.
Collectively, bioprinting has great potential and broad applications in tissue
engineering and regenerative medicine. The future advances of bioprinting include
the integration of different printing mechanisms to engineer biphasic or triphasic
tissues with optimized scaffolds and further understanding of stem cell biology.
3-mercaptopyruvate sulfurtransferase (3-MST) was a novel hydrogen sulfide (H2S)-
synthesizing enzyme that may be involved in cyanide degradation and in thiosulfate
biosynthesis. Over recent years, considerable attention has been focused on the
biochemistry and molecular biology of H2S-synthesizing enzyme. In contrast, there
have been few concerted attempts to investigate the changes in the expression of
the H2S-synthesizing enzymes with disease states. To investigate the changes of 3-
MST after traumatic brain injury (TBI) and its possible role, mice TBI model was
established by controlled cortical impact system, and the expression and cellular
localization of 3-MST after TBI was investigated in the present study. Western blot
analysis revealed that 3-MST was present in normal mice brain cortex. It gradually
increased, reached a peak on the first day after TBI, and then reached a valley on
the third day. Importantly, 3-MST was colocalized with neuron. In addition, Western
blot detection showed that the first day post injury was also the autophagic peak
indicated by the elevated expression of LC3. Importantly, immunohistochemistry
analysis revealed that injury-induced expression of 3-MST was partly colabeled by
LC3. However, there was no colocalization of 3-MST with propidium iodide (cell
death marker) and LC3 positive cells were partly colocalized with propidium iodide.
These data suggested that 3-MST was mainly located in living neurons and may be
implicated in the autophagy of neuron and involved in the pathophysiology of brain
after TBI.
Oxidative stress is closely involved in neurodegenerative diseases. The present
study aimed to examine the effect of anti-oxidant DHM (dihydromyricetin) on 3NP (3-
nitropropionic acid) -induced behavioral deficits of experimental rats and striatal
histopathological injury by using behavioral, imaging, biochemistry, histochemistry
and molecular biology technologies. The experimental results showed that both motor
dysfunctions and learning and memory impairments induced by 3NP were significantly
reduced after DHM treatment. 3NP-induced striatal metabolic abnormality was also
remarkably improved by DHM treatment, showed as the increased glucose metabolism in
PET/CT scan, decreased MDA (malondialdehyde) and increased SOD (superoxide
dismutase) activity in enzyme histochemical staining. In addition, the cell
apoptosis was evidently detected in the striatum of the 3NP group, while in the 3NP
+ DHM group, the number of apoptotic cells was remarkably reduced. 3NP treatment
obviously induced down-regulation of Bcl-2, and up-regulations of Bax and Cleaved
Caspase-3, while these changes were significantly reversed by DHM treatment. The
present results suggested that DHM showed its protective effect by anti-oxidant and
anti-apoptosis mechanisms.
The 45 degrees beam splitting mirror plays a vital role on image quality in the
Holographic system, in order to study the influence of environment temperature
variation on the 45 degrees beam splitting mirror in the Holographic system, finite
element analysis method is used to simulate the anti-three through seven mirror
deformation at 27 degrees C, 28 degrees C and 29 degrees C temperature in theory. A
new real-time monitoring and displaying photoelectric system for ambient
temperature and beam splitting mirror distortion detection is designed to provide
real-time temperature change and deformation detection, which is made up of laser
speckle interferometer, chip temperature sensor, two-operational amplifier, MCU and
LED indicator. And the out-plane displacement value measured in the experiment
under the condition of temperature correspondingly are 406nm, 420nm and 427 nm.
Finally, the relation equation of temperature and mirror deformation is established
by the method of exponential equation fitting, which will provide preliminary
theoretical and experimental reference for further research.
A thermotolerant bacterium Paenibacillus thiaminolyticus with an ability to produce
extracellular -mannanase was isolated from a soil sample. Bacterium produced 45U/mL
-mannanase at 50 degrees C. The culture conditions for high-level production of -
mannanase were optimized. Optimized MS medium [wheat bran 2% (w/v), ammonium
sulfate 0.3% (w/v), yeast extract, and peptone (0.025% each) pH 6.5] was inoculated
with 2% of 16H old culture. The culture was incubated at 50 degrees C for 48H
resulting in 24-folds higher -mannanase production (1,100 +/- 50U/mL). Optimum pH
and temperature for enzyme activity of the crude enzyme was 6.0 and 60 degrees C,
respectively. The enzyme demonstrated 65% relative enzyme activity at 37 degrees C.
The hydrolytic activity of the crude enzymatic preparation was assessed on various
agro residues. Thin-layer chromatographic analysis showed that the enzyme activity
to saccharify heteromannans resulted in production of a mixture of manno-
oligosaccharides (MOS) and enzyme exhibited classic endo-activity. To evaluate the
possible prebiotic potential of the MOS thus obtained, initial screening for their
ability to support the growth of probiotics was carried out by the pure culture
method. Bifidobacterium and Lactobacillus sp. responded positively to the addition
of enzymatically derived oligosaccharides and their numbers increased
significantly. (C) 2015 International Union of Biochemistry and Molecular Biology,
Inc.
Serotonin N-hydroxycinnamoyltransferase (SHT) is a key enzyme in the synthesis of
feruloylserotonin (FS) and 4-coumaroylserotonin (CS). These serotonin derivatives
show strong antioxidant activity, making them valuable for both nutritional and
pharmacological use in humans. Ectopic expression of SHT under the control of the
endosperm specific-glutelin and prolamin promoters from rice was produced via
Agrobacterium-mediated transformation. SHT expression was confirmed by Southern
blot analysis, followed by Northern blotting and SHT enzyme activity analyses using
total RNA and protein, respectively, extracted from transgenic seeds. The glutelin
A3 (GluA3) promoter produced low SHT mRNA expression in rice seeds, whereas the
prolamin promoter expressed high levels of SHT mRNA. In spite of the ectopic
expression of SHT in rice seeds, both transgenic genotypes accumulated levels of
serotonin derivatives similar to those found in wild-type rice. Furthermore, our
data suggest that serotonin, rather than phenylpropanid-CoAs, is the rate-limiting
substrate in the biosynthesis of serotonin derivatives in SHT-overexpressing
transgenic rice seeds.
A compact, low-noise and inexpensive preamplifier circuit has been designed and
fabricated to optimally readout a common cathode (1 x 16) channel 4H-SiC Schottky
photodiode array for use in ultraviolet experiments. The readout uses an
operational amplifier with 10 pF capacitor in the feedback loop in parallel with a
low leakage switch for each of the channels. This circuit configuration allows for
reiterative sample, integrate and reset. A sampling technique is given to remove
Johnson noise, enabling a femtoampere level readout noise performance. Commercial-
off-the-shelf acquisition electronics are used to digitize the preamplifier analog
signals. The data logging acquisition electronics has a different integration
circuit, which allows the bandwidth and gain to be independently adjusted. Using
this readout, photoresponse measurements across the array between spectral
wavelengths 200 nm and 370 nm are made to establish the array pixels external
quantum efficiency, current responsivity and noise equivalent power. Published by
Elsevier B.V.
Silicon RF power amplifiers (PAs) are in various RF front end modules (FEMs) today
for handset and WLAN applications. Even though III-V semiconductor-based RF PAs can
still offer superior frequency and breakdown performance with higher POUT and
power-added-efficiency (PAE) and faster time-to-market, silicon-based RF PAs do
have the advantages in offering higher monolithic integration with added
functionalities (e.g., on-chip digital control and selection on power level,
modulation, frequency band, matching, predistortion, etc.), which can translate to
lower cost and smaller sizes attractive for broadband multi-mode multi-band handset
transmitters. Therefore, some key techniques for designing high-efficiency
4G/5G/WLAN broadband wireless silicon PAs will be discussed.
Although gain of chromosome 5p is one of the most frequent DNA copy-number
imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its
selection remain poorly understood. In a previous cross-sectional clinical study,
we showed that the microRNA processor Drosha (located on chromosome 5p)
demonstrates frequent copy-number gain and overexpression in cervical SCC,
associated with altered microRNA profiles. Here, we have conducted gene
depletion/overexpression experiments to demonstrate the functional significance of
up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA interference
(RNAi) produced significant, specific reductions in cell motility/invasiveness in
vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue.
Unsupervised hierarchical clustering following global profiling of 319 microRNAs in
18 cervical SCC cell line specimens generated two groups according to Drosha
expression levels. Altering Drosha levels in individual SCC lines changed the group
into which the cells clustered, with gene depletion effects being rescued by the
RNAi-resistant mutation. Forty-five microRNAs showed significant differential
expression between the groups, including four of 14 that were differentially
expressed in association with Drosha levels in clinical samples. miR-31 up-
regulation in Drosha-overexpressing samples/cell lines was the highest-ranked
change (by adjusted p value) in both analyses, an observation validated by northern
blotting. These functional data support the role of Drosha as an oncogene in
cervical SCC, by affecting expression of cancer-associated microRNAs that have the
potential to regulate numerous protein-coding genes. Copyright (C) 2011
Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons,
Ltd.
Aim: An RNA-seq analysis recently identified a 236-nucleotide transcript upstream
from malS in Salmonella enterica serovar Typhi. Here, we investigated its molecular
characteristics and function. Materials & methods: RACE and northern blotting were
used to determine the molecular characteristics of the sequence, and mutagenesis,
microarray, immunoblotting and an invasion assay were used to investigate the
functions of the transcript. Results: The transcript was identified as the malS 5'-
untranslated region (UTR), which could influence the expression of the flagellar
and SPI-1 genes and the invasion of HeLa cells by S. Typhi. Deletion of bax
increased the expression of the invasion genes and the invasive capacity of S.
Typhi, whereas the expression of the malS 5'-UTR reduced the expression of bax.
Conclusion: The malS 5'-UTR reduces the expression of bax and increases the
invasive capacity of S. Typhi.
This paper presents the design of a compact 60-GHz phase shifter that provides a 5-
bit digital phase control and 360 degrees phase range for beam-forming systems. The
phase shifter is designed using the proposed cross-coupled bridged T-type topology
and switched-varactor reflective-type topology. The topologies are analyzed using a
small-signal equivalent circuit model. Furthermore, the design equations are
derived and investigated. To validate the theoretical analysis, 60-GHz 5-bit 360
degrees phase shifters are designed in a commercial 65-nm CMOS technology. The
fabricated 360 degrees phase shifter features good performance of 32 phase states
from 57 to 64 GHz with an rms phase error of 4.4 degrees, a total insertion loss of
14.3 +/- 2 dB, an rms gain error of 0.5 dB, P-1 dB of better than 9.5 dBm, and the
power consumption of almost zero. To the best of our knowledge, the designed 360
degrees phase shifter with the size of 0.094 mm(2) is the smallest 5-bit passive
phase shifter at frequencies around 60 GHz.
By differential high-throughput RNA sequencing (dRNA-seq) we have identified
"product RNAs" (pRNAs) as short as 8-12 nucleotides that are synthesized by
Bacillus subtilis RNA polymerase (RNAP) in vivo using the regulatory 6S-1 RNA as
template. The dRNA-seq data were confirmed by in vitro transcription experiments
and northern blotting. In our libraries, we were unable to detect statistically
meaningful numbers of reads potentially representing pRNAs derived from 6S-2 RNA.
However, pRNAs could be synthesized in vitro from 6S-2 RNA as template by the B.
subtilis sigma(A) RNAP. 6S-1 pRNA levels are low during exponential, increase in
stationary and burst during outgrowth from stationary phase, demonstrating that
pRNA synthesis is a conserved regulatory mechanism, but a more dynamic and fine-
tuning process than previously thought. Most pRNAs have a length of 8-15 nt, very
few up to 24 nt. The average length of pRNAs tended to increase from stationary to
outgrowth conditions. Synthesis of pRNA is initiated at C40 of 6S-1 RNA and U41 of
6S-2 RNA, yielding pRNAs with a 5'-terminal G or A residue, respectively. A B.
subtilis 6S-1 RNA mutant strain encoding a pRNA with a 5'-terminal A residue showed
the same relative distribution of similar to 14-nt pRNAs between the different
growth states, but generally displayed lower pRNA levels than the reference strain
encoding wild-type 6S-1 RNA. A similar to two-fold lower affinity of the C40U
mutant 6S-1 RNA towards sigma(A) RNAP may have contributed to this reduction in
pRNA levels. We infer that 6S-1 pRNA synthesis, although evolutionarily optimized
for initiation with a + 1G residue, is not primarily regulated at the transcription
initiation level via growth phase-dependent variations in the cellular GTP pool.
The "central dogma" of molecular biology describes how information contained in DNA
is transformed into RNA and finally into proteins. In order for proteins to
maintain their functionality in both the parent cell and subsequent generations, it
is essential that the information encoded in DNA and RNA remains unaltered. DNA and
RNA are constantly exposed to damaging agents, which can modify nucleic acids and
change the information they encode. While much is known about how cells respond to
damaged DNA, the importance of protecting RNA has only become appreciated over the
past decade. Modification of the nucleobase through oxidation and alkylation has
long been known to affect its base-pairing properties during DNA replication.
Similarly, recent studies have begun to highlight some of the unwanted consequences
of chemical damage on mRNA decoding during translation. Oxidation and alkylation of
mRNA appear to have drastic effects on the speed and fidelity of protein synthesis.
As some mRNAs can persist for days in certain tissues, it is not surprising that it
has recently emerged that mRNA-surveillance and RNA-repair pathways have evolved to
clear or correct damaged mRNA.
A cDNA clone of Eucommia ulmoides Oliv. encoding auxin binding protein 1 (ABP1),
one of the putative receptors of auxin, was isolated, and the seasonal expression
of ABP1 in relation to IAA and ABA annual variation was investigated by different
technical approaches including RT-PCR, real-time PCR, northern blotting, western
blotting, and immunolocalization. In the cambial region, ABP1 expression at both
the protein and the mRNA level was found to be high, low, and remarkably scarce in
the active, quiescent, and resting stages, respectively, during cambium
periodicity. The signal abundance of ABP1 follows the opposite pattern to ABA
accumulation and correlates with auxin responsiveness of the cambial tissues,
suggesting a role for ABP1 in mediating auxin-dependent regulation of cambial
activation in the activity-dormancy cycle. This paper attempts to explain why IAA
would 'boost' the reactivation of a quiescent cambium, and not that of a resting
cambium. Results also show that ABP1 expression is improved by IAA, while inhibited
by ABA.
The monkey is an important experimental model in the pharmacological evaluation of
new drugs. We isolated monkey multidrug resistance-associated protein 2 (MRP2) cDNA
to examine expression profiles among various tissues and measured ATPase activity
to assess substrate specificity. The amino acid sequence encoded by monkey MRP2
cDNA was very similar (96% identity) to the reported human MRP2 cDNA (GenBank
accession no. NM_000392). The tissue distribution of MRP2 in monkeys was partially
different from that in humans. We found relatively high expression of MRP2 in the
monkey kidney and small intestine using Northern blotting. Substrate specificity
was compared between human and monkey MRP2. The affinity of 17 beta-estradiol 17-
(beta-D-glucuronide), methotrexate, vinblastine, and probenecid to monkey MRP2 was
higher than that to human MRP2. Functional and expression differences between human
and monkey MRP2 should be incorporated into the evaluation of candidate drugs. (C)
2008 Elsevier B.V. All rights reserved.
Introduction: Most disseminated cancers remain fatal despite the availability of a
variety of conventional and novel treatments including surgery, chemotherapy,
radiotherapy, immunotherapy, and biologically targeted therapy. A major factor
responsible for the failure of chemotherapy in the treatment of cancer is the
development of multidrug resistance (MDR). The overexpression of various ABC
transporters in cancer cells can efficiently remove the anticancer drug from the
cell, thus causing the drug to lose its effect.Areas covered: In this review, we
summarised the ongoing research related to the mechanism, function, and regulation
of ABC transporters. We integrated our current knowledge at different levels from
molecular biology to clinical trials. We also discussed potential therapeutic
strategies of targeting ABC transporters to reverse MDR in cancer cells.Expert
opinion: Involvement of various ABC transporters to cancer MDR lays the foundation
for developing tailored therapies that can overcome MDR. An ideal MDR reversal
agent should have broad-spectrum ABC-transporter inhibitory activity, be potent,
have good pharmacokinetics, have no trans-stimulation effects, and have low or no
toxicity. Alternatively, nanotechnology-based drug delivery systems containing both
the cytotoxic drug and reversing agent may represent a useful approach to reversing
MDR with minimal off-target toxicity.
PurposeDespite being the third most common ABCA4 variant observed in patients with
Stargardt disease, the functional effect of the intronic ABCA4 variant c.5461-10T>C
is unknown. The purpose of this study was to investigate the molecular effect of
this variant. MethodsFibroblast samples from patients carrying the ABCA4 variant
c.5461-10T>C were analysed by isolating total RNA, followed by real-time polymerase
chain reaction (RT-PCR) using specific primers spanning the variant. For detection
of ABCA4 protein, fibroblast samples were lysed and analysed by SDS-PAGE followed
by immunoblotting using a monoclonal ABCA4 antibody. ResultsThe ABCA4 variant
c.5461-10T>C causes a splicing defect resulting in the reduction of full-length
mRNA in fibroblasts from patients and the presence of alternatively spliced mRNAs
where exon 39-40 is skipped. A reduced level of full-length ABCA4 protein is
observed compared to controls not carrying the variant. ConclusionsThis study
describes the functional effect and the molecular mechanism of the pathogenic ABCA4
variant c.5461-10T>C. The variant is functionally important as it leads to splicing
defects and a reduced level of ABCA4 protein.
Objective/Background: Matrix metalloproteinases (MMPs) have already been identified
as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the
current data remain inconclusive. In this study, the expression of MMPs at mRNA and
protein levels were investigated in relation to the degradation of collagen I and
collagen III. Methods: Tissue samples were obtained from 40 patients with AAA
undergoing open aortic repair, and from five healthy controls during kidney
transplantation. Expression of MMPs 1, 2, 3, 7, 8, 9, and 12, and tissue inhibitor
of metalloproteinase (TIMP)1, and TIMP2 were measured at the mRNA level using
quantitative reverse transcription polymerase chain reaction. At the protein level,
MMPs, collagen I, and collagen III, and their degradation products carboxy-terminal
collagen cross-links (CTX)-I and CTX-III, were quantified via enzyme linked
immunosorbent assay. In addition, immunohistochemistry and gelatine zymography were
performed. Results: In AAA, significantly enhanced mRNA expression was observed for
MMPs 3, 9, and 12 compared with controls (p <= .001). MMPs 3, 9, and 12 correlated
significantly with macrophages (p = .007, p = .018, and p = .015, respectively),
and synthetic smooth muscle cells with MMPs 1, 2, and 9 (p = .020, p = .018, and p
= .027, respectively). At the protein level, MMPs 8, 9, and 12 were significantly
elevated in AAA (p = .006, p = .0004, and p < .001, respectively). No significant
correlation between mRNA and protein was observed for any MMP. AAA contained
significantly reduced intact collagen I (twofold; p = .002), whereas collagen III
was increased (4.6 fold; p < .001). Regarding degraded collagen I and III relative
to intact collagens, observations were inverse (1.4 fold increase for CTX-1 [p
< .001]; fivefold decrease for CTX-III [p = .004]). MMPs 8, 9, and 12 correlated
with collagen I (p = .019, p < .001, and p = 0.003, respectively), collagen III (p
= .015, p < .001, and p < .001, respectively), and degraded collagen I (p = .012, p
= .049, and p = .001, respectively). Conclusion: No significant relationship was
found between mRNA and protein and MMP levels. MMPs 9 and 12 were overexpressed in
AAA at the mRNA and protein level, and MMP-8 at the protein level. MMP-2 was
detected in synthetic SMCs. Collagen I and III showed inverse behaviour in AAA. In
particular, MMPs 8, 9, and;12 appear to be associated with collagen I, collagen
III, and their degradation products. (C) 2017 European Society for Vascular
Surgery. Published by Elsevier Ltd. All rights reserved.
Purpose of review One of the most important challenges in the intestinal ( ITx) and
multivisceral transplant ( MVTx) is to achieve a successful abdominal wall closure.
Recent findings A tension-free primary closure should be our aim. In most of the
cases, we need to perform a component separation technique, alone or combined, to
the use of a synthetic mesh. If those options are not feasible, the abdominal wall
composite vascularized allograft transplant ( AW-CVA) utilizing direct orthotopic
vascularization can be considered. The nonvascularized abdominal rectus fascia has
also become an alternative method used worldwide, proving to be simple and well
tolerated procedure. Furthermore, the use of the AW has been recently proposed as a
new tool for a sentinel monitoring of the intestinal or pancreas allograft. Summary
There are different validated options for abdominal wall closure following
intestinal transplantation. The long-term benefits of transplanting the abdominal
wall, full or partial thickness and vascularized or nonvascularised, were shown.
New developments might help to expand their applications in different areas such as
reconstructive surgery and immunology.
The Arabidopsis thaliana late embryogenesis abundant gene AtEm6 is required for
normal seed development and for buffering the rate of dehydration during the latter
stages of seed maturation. However, its function in salt stress tolerance is not
fully understood. In this investigation, cell suspension cultures of three plant
species rice (Oryza sativa L.), cotton (Gossypium hirsutum L.), and white pine
(Pinus strobes L.) were transformed using Agrobacterium tumefaciens strain LBA4404
harboring pBI-AtEm6. Integration of the AtEm6 gene into the genome of rice, cotton,
and white pine has been confirmed by polymerase chain reaction, Southern blotting,
and northern blotting analyses. Three transgenic cell lines from each of O. sativa,
G. hirsutum, and P. strobus were used to analyze salt stress tolerance conferred by
the overexpression of the AtEm6 gene. Our results demonstrated that expression of
the AtEm6 gene enhanced salt tolerance in transgenic cell lines. A decrease in
lipid peroxidation and an increment in antioxidant enzymes ascorbate peroxidase,
glutathione reductase and superoxide dismutase activities were observed in the
transgenic cell lines, compared to the non- transgenic control. In rice, AtEM6
increased expression of Ca2+-dependent protein kinase genes OsCPK6, OsCPK9,
OsCPK10, OsCPK19, OsCPK25, and OsCPK26 under treatment of salt. These results
suggested that overexpression of the AtEM6 gene in transgenic cell lines improved
salt stress tolerance by regulating expression of Ca2+-dependent protein kinase
genes. Overexpression of the AtEM6 gene could be an alternative choice for
engineering plant abiotic stress tolerance.
A novel gene, named NgAOX1a, was isolated from Nicotiana glutinosa by RT-PCR
(reverse transcription-PCR). The full-length cDNA of NgAOX1a was 1448 bp, including
a 1062-bp ORF (open reading frame), a 124 bp 5' UTR (untranslated region) and a 262
bp 3' UTR. The ORF encodes a 353-amino-acid protein which contains two conserved
cysteine residues, four iron-binding motifs, five alpha-helix regions and six
conserved histidine residues. The phylogenetic tree showed that NgAOX1a belongs to
the AQX1 (alternative oxidase 1)-type group. Alignment analysis showed that NgAOX1a
shares a high similarity with other known AOXs. Four exons and three introns were
detected in the genomic DNA sequence, and Southern-blotting analysis suggested that
NgAOX1a is a single-copy gene. A series of putative cis-acting elements were
examined in the 5'-flanking region of NgAOX1a. Northern-blotting analysis showed
that the transcript levels of NgAOX1a can be markedly accumulated when tobacco
seedlings are treated with various abiotic stimuli, such as exogenous signalling
molecules for plant defence response, salicylic acid and H2O2, and the exogenous
TCA (tricarboxylic acid) cycle metabolite citrate. However, it could be suppressed
by abiotic stress, such as CoCl2, an inhibitor of ethylene, which indicates that
the expression of NgAOX1a may be regulated by ethylene. In addition, NgAOX1a can
also be strongly induced by three viral pathogens, tobacco mosaic virus, potato
virus X and potato virus Y. These results indicate that NgAOX1a may be involved in
multi-signal transduction pathways and may play an important role in defence
response.
To identify genes expression in Chenopodium album exposed to NaCl stress and screen
ESTs related to salt stress, a subtractive suppression hybridization (SSH) library
of C. album under salt stress was constructed in the present study. Random EST
sequencing produced 825 high-quality ESTs with GenBank ID GE746311-GE747007, which
had 301 bp of average size and were clustered into 88 contigs and 550 singletons.
They were classified into 12 categories according to their function annotations.
635 ESTs (76.97%) showed similarities to gene sequences in the non-redundancy
database, while 190 ESTs (23.03%) showed low or no similarities. The
transcriptional profiles of 56 ESTs randomly selected from 347 unknown or novel
ESTs of SSH library under varying NaCl concentration and at different time points
were analyzed. The results indicated that a high proportion of tested ESTs were
activated by salt stress. Four in 56 ESTs responded to NaCl were also enhanced in
expression level when exposed to ABA and PEG stresses. The above four ESTs were
validated by northern blotting which was consistent with the results of RT-PCR. The
results suggested that genes corresponded to these ESTs might be involved in stress
response or regulation. The complete sequences and detailed function of these ESTs
need to be further studied.
Phosphorylation of protein kinases has profound effects on their activity and
interaction with other proteins. Tyrosine phosphorylation was reported to be
involved in various physiological processes in plants; however, no typical receptor
tyrosine kinase has been isolated from plants thus far. Dual-specificity kinases
are potentially responsible for the phosphorylation of both tyrosine and
serine/threonine of target proteins. A cDNA clone encoding a putative dual-
specificity protein kinase was isolated by screening the cDNA GAL4 activation
domain (AD) fusion library of soybean (Glycine max L.), and its entire length was
obtained using 5'-rapid amplification of cDNA ends. The predicted polypeptide of
330 amino acid residues, designated as GmSTY1, contains all 11 conserved
subdomains, which share common characteristics with both the serine/ threonine and
tyrosine protein kinases reported thus far. In addition, three potential N-linked
glycosylation sites (NXS/T), as well as phosphorylation motifs (SXXXS/T), were
observed, suggesting that GmSTY1 may be post-translationally modified. Furthermore,
a potential N-myristoylation motif (MGARCSK) was found, suggesting that the GmSTY1
protein could associate with membranes in vivo. Southern blotting analysis revealed
a single-copy of GmSTY1 in the genome. Northern blotting analysis showed that this
gene was upregulated by drought and salt treatment in a time-dependent manner;
however, exogenous abscisic acid (ABA) could not significantly affect the mRNA
accumulation of GmSTY1. Interestingly, the transcript of this gene was remarkably
downregulated by cold treatment during the early stages of the response, but
upregulated later. These results indicate that the protein kinase was possibly
regulated by abiotic stresses in an ABA-independent pathway.
Mitogen-activated protein kinase (MAPK) cascades are signalling modules that
transduce extracellular signalling to a range of cellular responses. Plant MAPK
cascades have been implicated in development and stress response. In this study, we
isolated a novel group C MAPKK gene, ZmMKK4, from maize. Northern blotting analysis
revealed that the ZmMKK4 transcript expression was up-regulated by cold, high salt
and exogenous H(2)O(2), but down-regulated by exogenous abscisic acid (ABA). Over-
expression of ZmMKK4 in Arabidopsis conferred tolerance to cold and salt stresses
by increased germination rate, lateral root numbers, plant survival rate,
chlorophyll, proline and soluble sugar contents, and antioxidant enzyme [peroxidase
(POD), catalase (CAT)] activities compared with control plants. Furthermore, ZmMKK4
enhanced a 37 kDa kinase activity after cold and salt stresses. RT-PCR analysis
revealed that the transcript levels of stress-responsive transcription factors and
functional genes were higher in ZmMKK4-over-expressing plants than in control
plants. In addition, ZmMKK4 protein is localized in the nucleus. Taken together,
these results indicate that ZmMKK4 is a positive regulator of salt and cold
tolerance in plants.
Citrullus colocynthis (L.) Schrad. is commonly known as colocynth. The fruit pulp
of colocynth has medicinal properties while the seeds have nutritive qualities. C.
colosynthis is resistant to high temperatures and grows in the desert regions of
North Africa, the Middle East and Western Asia. C. colocynthis likely carries genes
of interest that could be explored for inducing abiotic stress resistance in
transgenic plants. Although the tissue culture and molecular biology of this
species have been explored, the latter has been primarily used to resolve taxonomic
relationships with other members of the Citrullus genus and curcubits. Genetic
mining of the plant is scarce while genetic transformation protocols are also rare.
The aim of the present review is to present a brief overview of the
biotechnological perspectives of C. colocynthis.
Purpose of review This review provides an update and summary of recent
neuropsychological findings in epilepsy focusing on three major clinical topics
among the many developments in the field. We will critically outline the current
state with regard to cognition in new-onset epilepsies, social cognition in
epilepsy, and the long-term outcome of epilepsy surgery and the cognitive outcomes
of superselective surgical procedures. Recent findings Current studies indicate
that neuropsychological impairments are prevalent already at the onset of epilepsy
and even before, social cognition (i.e., emotion recognition and theory of mind) is
impaired in different epilepsy populations, the long-term outcome of epilepsy
surgery is mostly characterized by a stable or even improved cognitive status, and
superselective epilepsy surgeries are associated with a promising
neuropsychological outcome. Summary The high prevalence of cognitive deficits
around epilepsy onset challenges the assumption that epilepsy is the major cause of
cognitive problems and calls for early neuropsychological diagnostics. Social
cognition seems to be a relevant domain that is not yet routinely considered in
epilepsy. The cognitive long-term outcome of epilepsy surgery is mostly positive.
Stereotactic thermocoagulation and gamma knife surgery appear to be cognitively
safe procedures.
microRNAs (miRNAs) play a crucial role in tissue development and the pathology of
many diseases, however, the effects and roles of miRNAs in the development of semen
abnormalities in infertile males have not yet been investigated. In this study, we
analyzed and compared the miRNA expression profiles of abnormal semen from 86
infertile males with normal semen from 86 healthy males using an miRNA microarray.
In total, 52 miRNAs were differentially expressed between the abnormal semen of
infertile males and the normal semen of healthy males. The differential expression
of selected miRNAs was validated by real time qRT-PCR and northern blotting: miR-
574-5p, miR-297, miR-122, miR-1275, miR-373, miR-185 and miR-193b were upregulated
(fold change >1.5, p<0.001) and miR-100, miR-512-3p, miR-16, miR-19b, miR-23b and
miR-26a were downregulated (fold change <0.667, p<0.001) in the semen of infertile
males with semen abnormalities. In conclusion, this study provides new insights
into specific miRNAs that arc associated with semen abnormalities in infertile
males.
Background: Respiratory morbidity in Australian Indigenous children is higher than
their non-Indigenous counterparts, irrespective of urban or remote residence. There
are limited studies addressing acute respiratory illness (ARI) in urban Indigenous
children, particularly those that address the upper airway microbiome and its
relationship to disease. We aimed to describe the prevalence of upper airway
viruses and bacteria in symptomatic and asymptomatic urban-based Australian
Indigenous children aged less than 5 years. Methods: A cross-sectional analysis of
data collected at baseline in an ongoing prospective cohort study of urban
Aboriginal and Torres Strait Islander children registered with a primary health
care service in the northern suburbs of Brisbane, Australia. Clinical, demographic
and epidemiological data and bilateral anterior nasal swabs were collected on
enrolment. Polymerase chain reaction was performed on nasal swabs to detect 17
respiratory viruses and 7 bacteria. The primary outcome was the prevalence of these
microbes at enrolment. Logistic regression was performed to investigate differences
in microbe prevalence between children with and without acute respiratory illness
with cough as a symptom (ARIwC) at time of specimen collection. Results: Between
February 2013 and October 2015, 164 children were enrolled. The median age at
enrolment was 18. 0 months (IQR 7.2-34.3), 49.4% were boys and 56 children (34.2%)
had ARIwC. Overall, 133/164 (81%) nasal swabs were positive for at least one
organism; 131 (79.9%) for any bacteria, 59 (36.2%) for any virus and 57 (34.8%) for
both viruses and bacteria. Co-detection of viruses and bacteria was more common in
females than males (61.4% vs 38.6%, p = 0.044). No microbes, alone or in
combination, were significantly associated with the presence of ARIwC. Conclusions:
The prevalence of upper airways microbes in asymptomatic children is similar to
non-Indigenous children with ARIwC from the same region. Determining the aetiology
of ARIwC in this community is complicated by the high prevalence of multiple
respiratory pathogens in the upper airways.
We identified a Nodulin-related protein 1 (NRP1) encoded by At2g03440, which was
previously reported to be RPS2 interacting protein in yeast-two-hybrid assay.
Northern blotting showed that AtNRP1 expression was suppressed by heat stress (42A
degrees C) and induced by low temperature (4A degrees C) treatment. Strong GUS
staining was observed in the sites of meristematic tissues of pAtNRP1:: GUS
transgenic plants, such as shoot apex and root tips, young leaf veins, stamens and
stigmas of flowers, and abscission layers of young siliques. To study AtNRP1
biological functions, we have characterized both loss-of-function T-DNA insertion
and transgenic overexpression plants for AtNRP1 in Arabidopsis. The T-DNA insertion
mutants displayed no obvious difference as compared to wild-type Arabidopsis under
heat stress, but the significant enhanced susceptibility to heat stress was
revealed in two independent AtNRP1-overexpressing transgenic lines. Further study
found that the decreased thermtolerance in AtNRP1-overexpressing lines accompanied
significantly decreased accumulation of ABA after heat treatment, which was
probably due to AtNRP1 playing a role in negative-feedback regulation of the ABA
synthesis pathway. These results support the viewpoint that the application of ABA
inhibits nodulation and nodulin-related gene expression and threaten adverse
ambient temperature can impact the nodulin-related gene expression.
Although a great deal of progress has been made toward understanding the role of
abscisic acid (ABA) in fruit ripening, many components in the ABA signalling
pathway remain to be elucidated. Here, a strawberry gene homologous to the
Arabidopsis gene ABI1, named FaABI1, was isolated and characterized. The 1641bp
cDNA includes an intact open reading frame that encodes a deduced protein of 546
amino acids, in which putative conserved domains were determined by homology
analysis. Transcriptional analysis showed that the levels of FaABI1 mRNA expression
declined rapidly during strawberry fruit development as evidenced by real-time PCR,
semi-quantitative reverse transcriptionPCR, and northern blotting analyses,
suggesting that the Ser/Thr protein phosphatase PP2C1 encoded by FaABI1 may be
involved in fruit ripening as a negative regulator. The results of Tobacco rattle
virus-induced gene silencing and PBI121 vector-mediated overexpression suggested
that the down- and up-regulation of FaABI1 mRNA expression levels in degreening
strawberry fruit could promote and inhibit ripening, respectively. Furthermore,
alteration of FaABI1 expression could differentially regulate the transcripts of a
set of both ABA-responsive and ripening-related genes, including ABI3, ABI4, ABI5,
SnRK2, ABRE1, CHS, PG1, PL, CHI, F3H, DFR, ANS, and UFGT. Taken together, the data
provide new evidence for an important role for ABA in regulating strawberry fruit
ripening in the processes of which the type 2C protein phosphatase ABI1 serves as a
negative regulator. Finally, a possible core mechanism underlying ABA perception
and signalling transduction in strawberry fruit ripening is discussed.
In this paper, the concept of multi-objective optimization is introduced in the
automation of the placement task in analog integrated circuits layout design. To
bridge the difficulties found on state-of-the-art works on fulfilling proximity
constraints, here, cells are organized into proximity groups which implement the
desired set of symmetry and proximity requirements. Then, an innovative archived-
based multi-objective simulated annealing algorithm, operating over an absolute
representation, is proposed to optimize the placement of each proximity group. In
contrast to traditional single-objective placement approaches, the resulting Pareto
fronts of placements, representing the tradeoffs between the optimization
objectives of each group, are combined, bottom-up, through the design hierarchy,
until a final front is obtained. This way, the problem's complexity is reduced, and
split over multiple executions of the optimization kernel with less design
variables, and also, analog designer becomes aware of the design tradeoffs. The
proposed multi-objective and hierarchical methodology was implemented, and,
experimental results prove that previous efforts on single-objective absolute
representations are no match for the obtained floorplans. Furthermore, the obtained
Pareto fronts contain the solutions found with the most recent published
topological representations for the well-known Microelectronics Center of North
Carolina benchmark sets, and, allowed an improvement of placement area up to 23% on
a previously optimized folded cascode operational amplifier for the United
Microelectronics Corporation 0.13 gm fabrication process. (C) 2015 Elsevier Ltd.
All rights reserved.
This study examined whether child abuse history in teen mothers impacts offspring
externalizing problems indirectly, through its influence on attachment and maternal
hostility. In a longitudinal sample of 112 teen mother-child dyads, mothers
reported on their own abuse experiences, attachment and maternal hostility were
assessed via direct observations, and externalizing problems were measured using
maternal reports. Compared with mothers with no abuse history, mothers with a
history of sexual and physical abuse were more likely to have an insecurely
attached infant, which predicted higher externalizing problems in preschool, which
in turn predicted subsequent increases in externalizing problems in Grade 3.
Furthermore, relative to the no abuse history group, mothers with a history of
sexual and physical abuse showed more hostility toward their child at preschool,
which in turn predicted elevated externalizing problems in Grade 3. Mothers'
history of either sexual or physical abuse alone did not have significant indirect
effects on externalizing problems. Fostering secure attachment and reducing risk
for maternal hostility might be important intervention goals for prevention
programs involving at-risk mothers with abuse histories. (C) 2016 Elsevier Ltd. All
rights reserved.
Background This study assessed the knowledge of personal safety skills among
children with developmental disabilities and their parents' perceptions of
children's knowledge. Method This exploratory study examined the mental health
records of 37 children with developmental disabilities referred for an abuse risk
reduction group in a community mental health setting. Qualitative analysis of
children's responses to questions about personal safety skills (knowledge related
to physical development and personal safety, an appropriate and inappropriate touch
and safety skills to respond to an inappropriate touch) indicated participants'
varied and inconsistent levels of knowledge. Results Consistent with the
literature, the results indicate risk factors for sexual abuse among children with
developmental disabilities, including children's difficulty distinguishing between
an appropriate and inappropriate touch and the lack of knowledge regarding
appropriate venues for disclosing an inappropriate touch. Among parents, a lack of
certainty regarding their children's knowledge and the ability to keep themselves
safe was identified. Conclusion Results support the need for education about
personal safety for children with developmental disabilities and their families.
Introduction: Posttraumatic stress symptoms (PTS) are associated with increased
risk of obstetric complications among pregnant survivors of trauma, abuse and
interpersonal violence, but little is known about how PTS affects women's actual
experiences of obstetric care. This study investigated the rate at which abuse
history was detected by obstetricians, whether abuse survivors experienced more
invasive exams than is typically indicated for routine obstetric care, and whether
psychological distress was associated with abuse survivors' sense of self-efficacy
when communicating their obstetric care needs.Methods: Forty-one pregnant abuse
survivors completed questionnaires about abuse history, current psychological
distress and self-efficacy for communicating obstetric care needs and preferences.
Electronic medical records (EMRs) were reviewed to examine frequency of invasive
prenatal obstetric procedures (e.g. removal of clothing for external genital
examination, pelvic exams and procedures) and to examine the detection rate of
abuse histories during the initial obstetric visit.Results: The majority of
participants (83%) reported at least one past incident of violent physical or
sexual assault. Obstetricians detected abuse histories in less than one quarter of
cases. Nearly half of participants (46%) received invasive exams for non-routine
reasons. PTS and depression symptoms were associated with lower self-efficacy in
communicating obstetric care preferences.Discussion: Women most at risk for
experiencing distress during their obstetric visits and/or undergoing potentially
distressing procedures may also be the least likely to communicate their distress
to obstetricians. Results are discussed with implications for improving screening
for abuse screening and distress symptoms as well as need for trauma-sensitive
obstetric practices.
This paper tests the hypothesis that the association between childhood maltreatment
and adult personality dysfunction is at least partially attributable to insecure
attachment, that is that attachment style mediates the relationship between
childhood maltreatment and adult personality dysfunction. Associations between
childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), anxious
and avoidant attachment in romantic relationships, as measured by the Experiences
in Close Relationships-Revised (ECR-R), and five personality domains, as measured
by the Severity Indices of Personality Problems (SIPP-118), were examined in a
sample of 72 psychiatric inpatients. The SIPP-118 domains included relational
capacities, identity integration, self-control, responsibility, and social
concordance. The direct effect of childhood trauma on all SIPP-118 domains was not
significant after controlling for the indirect effect of attachment. In regression
modeling, a significant indirect effect of childhood trauma via adult attachment
style was found for SIPP-118 relational capacities, identity integration, self-
control, and social concordance. Specifically, anxious attachment was a significant
mediator of the effect of childhood trauma on self-control, identity integration,
and relational domains. These results suggest that childhood trauma impacts a broad
range of personality domains and does so in large part through the pathway of
anxious romantic attachment style.
Background: Alterations in gray matter development represent a potential pathway
through which childhood abuse is associated with psychopathology. Several prior
studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex
regions in abused compared with nonabused adolescents, although most prior research
is based on adults and volume-based measures. This study tests the hypothesis that
child abuse, independent of parental education, predicts reduced cortical thickness
in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in
subcortical regions during adolescence. Methods: Structural MRI scans were obtained
from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused
adolescents (ages 13-20). Abuse was operationalized using dichotomous and
continuous measures. We examined associations between abuse and brain structure in
several a priori-defined regions, controlling for parental education, age, sex,
race, and total brain volume for subcortical GMV. Significance was evaluated at p <
.05 with a false discovery rate correction. Results: Child abuse exposure and
severity were associated with reduced thickness in ventromedial prefrontal cortex
(PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral
parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right
middle, and right superior temporal gyri. Neither abuse measure predicted cortical
surface area or subcortical GMV. Bilateral PHG thickness was inversely related to
externalizing symptoms. Conclusions: Child abuse, an experience characterized by a
high degree of threat, is associated with reduced cortical thickness in
ventromedial and ventrolateral PFC and medial and lateral temporal cortex in
adolescence. Reduced PHG thickness may be a mediator linking abuse with
externalizing psychopathology, although prospective research is needed to evaluate
this possibility.
The significant co-occurrence between men's violence against female partners and
child abuse and neglect is well documented. It is less clear how child safety
should be managed in family violence research with their mothers. This issue is
salient to isafe, a New Zealand-based Internet intervention study testing
improvement in safety decisions and mental health outcomes for women experiencing
intimate partner violence. This article discusses the legislative, professional,
and ethical considerations that contribute to the development of the child safety
protocols and discusses the development of the isafe protocol. Hypothetical
scenarios of the application of the isafe protocol are used to illuminate the
issues and provide a basis for future discussion.
Child sexual abuse (CSA) is a global public health problem with major consequences
for the individual child and society. An earlier Swedish study showed that the
school nurses did not initially talk about nor mention CSA as one form of child
abuse. For the child to receive adequate support, the disclosure is a precondition
and is dependent on an available person prepared to listen. The aim of the study
was to explore the ability of the school nurses to detect and support sexually
abused children. It is a secondary analysis of focus group interviews with school
nurses. Thematic analysis was performed. Results showed that the school nurses
avoided addressing CSA due to arousal of strong emotions, ambivalence, and a
complicated disclosure process. In order to detect CSA and support abused children,
attentiveness of sexual abuse as a possible cause of physical and mental illhealth
is crucial.
The current study examined the mediating effects of the teacher and peer
relationships between parental abuse/neglect and a child's emotional/behavioral
problems. A total of 2070 student surveys from the panel of the Korean Child Youth
Panel Study (KCYPS) were analyzed by path analysis. The key findings of this study
are outlined below. Firstly, parental physical and emotional abuse and neglect had
significant effects on children's problems. The direct effect of parental abuse on
emotional/behavioral problems was higher than the direct effect of parental neglect
on emotional/behavioral problems. Secondly, the teacher relationship partially
mediated the effects of the parental abuse/neglect on emotional/behavioral
problems. Thirdly, the peer relationship also partially mediated the effects of
parental abuse/neglect on children's emotional/behavioral problems. The indirect
effect of parental neglect via teacher relationships and peer relationships was
stronger than the indirect effect of parental abuse. This study is significant in
that it identified that parental abuse/neglect was mediated by the teacher and peer
relationship, thereby suggesting an implication for effective intervention with
children who have suffered abuse and neglect. In terms of the teacher and peer
relationship, understanding the influence of parental abuse and neglect on
children's problems was discussed, and the limitations and recommendations for
future study were suggested. (C) 2016 Elsevier Ltd. All rights reserved.
Abuse-related trauma remains a global health issue. However, there is paucity in
nationwide reports. We aim to estimate the incidence of abuse-related trauma
forward medical care and identify its characteristics and clinical course in
Taiwan. Patients with trauma between 2005 and 2007 that occurred 3 months before or
after a diagnosis of abuse were identified from a randomly sampled nationwide
longitudinal health insurance database of 1 million beneficiaries. The patients'
demographic data, injury pattern, and medical resource utilization were measured,
stratified by age and sex, and compared using chi-square test. Risk factors of next
trauma event were identified using Cox regression analysis. Ninety-three patients
(65 females) were identified (mean age, 20.6 +/- 16.3 years), including 61.3% under
18 years of age. For the first trauma event, 68 patients (73.1%) visited the
emergency room, 63 (67.7%) received intervention, and 14 (15.1%) needed hospital
care. Seven (7.5%), all less than 11 years old, had intracranial hemorrhage and
required intensive care. Thirty-three (35.5%) left with complications or sequelae,
or required rehabilitation, but all survived. Of the 34 victims of sexual abuse, 32
were aged less than 18 years. Men received more mood stabilizers or antipsychotics
(50.0% vs 10.7%, P = 0.030) and reeducative psychotherapy (25.0% vs 0, P = 0.044).
Risk factors for a next trauma event were injury involving the extremities (hazard
ratio [HR]: 5.27 [2.45-11.33]) and use of antibiotics (HR: 4.21 [1.45-12.24]) on
the first trauma event. Abuse-related trauma has heterogeneous presentations among
subgroups. Clinicians should be alert in providing timely diagnosis and
individualized intervention.
Purpose of review This review addresses some of the more salient articles in the
field of child maltreatment published in 2015, with a goal of helping the general
practitioner understand the evolution of research in the field of child abuse
pediatrics (a board-certified specialty since 2009). Recent findings Researchers
continue to refine the database for child abuse pediatrics. Several articles focus
on the inconsistencies in approach to the evaluation of possible physical child
abuse between hospitals and practitioners. Multiple researchers aim to develop a
protocol that standardizes the response to findings of a sentinel injury, such as a
rib fracture, abdominal trauma, or unexplained bruising in a nonambulatory infant.
Professionals are also working to improve our understanding about the impact of
trauma on children and how best to ameliorate its effects. Summary With solid,
evidence-based literature published on various topics in the field of child abuse
pediatrics, experts work to refine and unify the clinician's approach to the
evaluation of possible physical abuse.
When Abusive Head Trauma (AHT) is suspected in a child, a dilated eye examination
by an ophthalmologist is an essential part of the medical workup, as the presence
and pattern of retinal hemorrhages can have a high positive predictive rate for
abusive head injury. This article proposes to review the clinical presentation,
pathophysiology, natural history, sequelae, and differential diagnosis of retinal
hemorrhages and other ocular lesions associated with AHT.
The frequency and severity of physical abuse influences children's outcomes, yet
little theory-based research has explored what predicts its course. This study
examined the potential role of social information processing (SIP) factors in the
course of abuse. Mothers with histories of perpetrating physical abuse (N = 62)
completed measures of SIP, and the frequency and severity of mother-perpetrated
physical abuse were collected from Child Protection Services records. Poorer
problem-solving capacities were significantly related to greater frequency of
physical abuse. Hostile attributions toward children were positively associated
with abuse severity. Controlling for demographics and co-occurrence of neglect, SIP
factors together accounted for a significant proportion of variance in the
frequency of physical abuse, but not severity. With the exception of unrealistic
expectations, preliminary evidence supported a link between maternal SIP and the
course of abuse perpetration. Future research directions and implications for
intervention are discussed.
Shaken baby syndrome is a term often used by the physicians and public to describe
abusive trauma inflicted on infants and young children. Advances in the
understanding of the mechanisms and the associated clinical spectrum of injury has
lead us to modify our terminology and address it as "abusive trauma" (AT).
Pediatric abusive head trauma is defined as an injury to the skull or intracranial
contents of an infant or a young child (<5 y age) due to inflicted blunt impact
and/or violent shaking. This chapter focuses on the imaging aspects of childhood
abusive trauma along with a brief description of the mechanismand pathophysiology
of abusive injury. The diagnosis of AT is not always obvious, and abusive injuries
in many infants may remain unrecognized. Pediatricians should be cognizant of AT
since pediatricians play a crucial role in the diagnosis, management and prevention
of AT.
This article reviews the evolution of the diagnosis and treatment of Hodgkin
lymphoma (HL) since its discovery in 1832. The morphological, phenotypic and
molecular characteristics of both nodular lymphocyte-predominant HL and classical
HL are revised in the light of recent molecular information and possible impact on
the identification of risk groups as well as the use of targeted therapies. The
seminal contribution of Gianni Bonadonna to developing new treatment strategies for
both advanced and early-stage HL is highlighted.
An analytic design guide to design a three-stage cascade CMOS operational amplifier
compensated by AC boosting frequency compensation (ACBC) method is presented in
this paper. The procedure allows electrical parameters such as gain bandwidth (GBW)
product or phase margin to be related to the value of circuit elements such as
aspect ratio or biasing currents of transistors. The presented design guide is
suited for pencil-and-paper design and yields accurate performance without
unnecessary circuit constraint introduction. Simulation results using TSMC 0.18 mu
m CMOS process verifies accuracy and robustness of proposed procedure. Various load
capacitors and circuit conditions are simulated and, based on obtained results, the
presented design guide is comprehensive and efficient since it leads us from
frequency response parameters to aspect ratio of MOSFETs.
Programmable AC power sources have been widely used to implement and support a wide
range of Test Procedure Specifications (TPS's). Traditionally, these power sources
use analog control circuits to provide key control and protection functions like
load regulation, current limit and frequency conversion. While this is a proven
design, it suffers from a number of drawbacks. With the advent of recent advances
in DSP technologies, a full digital implementation of an AC power source design
supporting high switching frequencies is now feasible. This paper discussed some of
the advantages derived from an all-digital implementation of a programmable poser
source and the benefits this provides for ATE system use.
This paper describes a new calibration system developed at INMETRO to guarantee
traceability of low-frequency alternating current (ac) voltage calibrations (<1
kHz) to a programmable Josephson ac waveform synthesizer. The automated full-
synchronous system allows the synchronization of a commercial calibrator or signal
synthesizer with a programmable Josephson voltage synthesizer system to be made by
employing digital sampling and signal processing techniques, aided by adaptive
digital control. It allows accurate determination of the spectral content of ac
signals with minimum human intervention. System operation, measurement techniques,
and data analysis are detailed.
The voltage source converters (VSC) are the key power interfaces between the
individual ac grids and dc grids in the hybrid power system. When the ac grid is
unbalanced, the grid currents are distorted and the harmonic is induced. Meanwhile,
the oscillations in the active and reactive power are also increased, which may
damage these interfaces. In order to ensure the safety of the converters and the
grid facility, a flexible control strategy is proposed for the ac/dc hybrid grid in
this paper. At first, the current harmonic for the VSC is theoretically analyzed
under unbalanced conditions. Furthermore, the methods to separate the positive- and
negative-sequence components of the ac grid voltages are summed up and analyzed.
Based on the theoretical analysis, different protected control methods are
compared. A new control method, which can flexibly control oscillations of the
active and reactive power by introducing a parameter k, has been proposed. The
estimation of maximum current in each phase is discussed; meanwhile, the
relationship between the voltage ripple on dc link and the parameter k is given.
Finally, the validity and advantages of the proposed method are verified by the
simulating and experimental results.
Based on single-phase ac-ac converter with controllable phase and amplitude
(ACCPA), a three-phase ACCPA without third harmonic trap was proposed for power
transmission control in grid by adopting a symmetrical relationship of three phase.
The three-phase ACCPA is comprised of two parts, which are used to adjust the phase
and amplitude of three-phase output voltage, respectively, and continuously. Its
front part is made up of three buck-type ac converters, and the back part is a
three-phase boost-type ac converter. The operation principle of three-phase ACCPA,
the adjustable ranges of the phase and amplitude of the front part, and the
calculation formulas of control parameters under ideal conditions were studied and
deduced in detail. Furthermore, the control accuracy of the phase angle was
discussed for the three-phase ACCPA with digital control, and then, the method to
select close-loop control parameters was obtained. The control strategy of three-
phase ACCPA was presented and a prototype was fabricated. The experimental
waveforms and testing results verified the correctness of the theoretical analysis
and the feasibility of the control strategy.
This article deals with the simulation of the power converter with voltage-source
inverter and sine-filter. The repetitive control system was designed. The existing
power converter has a control system which makes Fourier transform of the output
voltage to inject these harmonics with opposite phase. The new proposed system
based on repetitive controller which is much simpler and with smaller CPU load. The
higher harmonics elimination works perfect and the power converter produces output
voltage with less than 5% THD under linear or non-linear load. This paper describes
the improved control system structure and its implementation in MATLAB Simulink
environment. The advantages of the repetitive algorithm facing Fourier transform
harmonic compensation are shown. The performance of the new control method is shown
in simulation results. The algorithm is carried out in C language using MATLAB S-
Function block so it is suitable for implementation in the real-time control
systems.
Various species of amoebas belonging to the genus Acanthamoeba are widely
distributed in many parts of the world. Some strains of these protozoans may exist
as parasites and pose risks to human health as causative agents of serious human
diseases. Currently in China there IS a lack of information about the distribution
of Acanthamoeba strains in the environment. Accordingly, 261 environmental water
samples taken from rivers, sewage, and pharmaceutical factory drains were collected
in Qinghai Province, China. The material was filtered and then analysed with both
LAMP and PCR assays. Of the samples examined, Acanthamoeba DNA was found in 32
(14.68%) samples with the use of LAMP; in 13 of these samples, DNA from this amoeba
was also detected using PCR. Sequencing of selected positive samples confirmed that
the PCR products were fragments of the Acanthamoeba 18S rRNA gene and that isolates
represent the T4 genotype, known as the Most common strain related to AK cases. The
results indicate that surface water, as well as water taken from sewage And
pharmaceutical drains, may be a source of acanthamoebic strains potentially
pathogenic for humans in China. It has been also demonstrated that LAMP assays is
more sensitive than PCR and can be regarded as useful tool for screening the
environment for Acanthamoeba spp. (C) 2017 Elsevier B.V. All rights reserved.
Particle accelerators consist of an enormous number of components and many of them
operate with pulse voltage or current. Such accelerator components require precise
voltage or current to keep the beams very stable. For this reason, many pulse power
supplies used for accelerators have own subsystems to improve their performances.
One example is a power supply for the scanning magnets of a pencil beam proton
therapy. They use not only high-voltage inverters for the high-speed ramping but
also low-voltage inverters for the precise current control. However, the use of
intelligent digital controllers possibly simplifies such precise power supplies. We
propose a method for precise current control using a digital control system. Our
previous work has successfully controlled the pulse current of power supplies for
synchrotron main magnets. In the next step, we have modified our previous method
for faster power supplies such as ones for scanning magnets. In addition, we
developed a control board using a high-performance FPGA so that our method can be
implemented in the board. In this paper, we describe the details of our proposed
method, and the experiments using a small-scale power supply and the developed
control board.
This paper presents the design of a compact, wearable, rechargeable acceleration
recorder to support long-term monitoring of ambulatory patients with motor
disorders, and of software to display and analyze its output. The device consists
of a microcontroller, operational amplifier, accelerometer, SD card, indicator LED,
rechargeable battery, and associated minor components. It can operate for over a
day without charging and can continuously collect data for three weeks without
downloading to an outside system, as currently configured. With slight
modifications, this period could be extended to several months. The accompanying
software provides flexible visualization of the acceleration data over long
periods, basic file operations and compression for easier archiving, annotation of
segments of interest, and functions for calculation of various parameters and
detection of immobility and vibration frequencies. Applications in analysis of gait
and other movements are discussed.
A high performance interface circuit of sigma-delta accelerometer with low harmonic
distortion used many kinds of circuit processing techniques is presented in this
work. Multi-bit, dynamic element matching, correlated-double-sampling and
electrostatic force feedback linearization circuit are used simultaneously in order
to achieve the design indicators. Because of the usage of multi-bit, the design to
operational amplifier (OPA) becomes easier, and only a single-stage folded-cascode
amplifier is used in the modulator, the OSR is only 64. It highly reduced the
difficulty of circuit. The test results indicate that the chip area is only about
10mm(2) and the power dissipation is 10mW with a sampling frequency of 60 kHz. The
dynamic range (DR) of the system can be lower than -130 dB, the SNR and SNDR reach
to -120 dB and -110 dB respectively with a resolution about 17 bits when referred
to 3g full scale DC acceleration under CMOS 0.5 mu m process. The dc nonlinearity
of it is 0.2%. This paper realizes an approach which can both simplify the design
of the interface circuit and improve the performance of it.
In this article we address the increasingly important yet understudied phenomenon
of nonnative accentedness on decision making. In three experimental studies, we
investigated whether messages about a company delivered in nonstandard-American-
accented speech influenced choice. In Study 1, we found that individuals were more
likely to choose a company or a product when a message was read in a standard
American English accent than when the message was delivered with a Mandarin Chinese
or a French accent. In Study 2, we found that expectations regarding company
messages are violated when speakers have accents and that, in turn, expectation
violations mediated the relationship between accent and choice. In Study 3, we
replicated the findings of the effect of accent on choice using Indian and British
accents. We also hypothesized and found support for a conditional indirect effects
model such that implicit pro-American bias moderated the indirect relationship
between accent and choice as mediated by expectation violations. Theoretical and
practical implications of this topic of study are discussed.
Acceptance is a key construct in both rational emotive behavior therapy (REBT) and
acceptance and commitment therapy (ACT). The objectives of this study were to
assess and compare the properties of ACT acceptance with those of REBT acceptance
in predicting emotions. A sample of 112 subjects, comprising different educational
and occupational status, completed three measures of acceptance (REBT and ACT), two
of mindfulness, as well as completing depression and anxiety scales. Both ACT
acceptance as process and REBT acceptance could predict significant ACT acceptance
as outcome. Mindfulness as a trait also predicted the level of ACT outcome
acceptance as well as the level of REBT acceptance, but mindfulness as process
predicted only ACT outcome acceptance. The results show that REBT acceptance, ACT
acceptance and mindfulness can explain anxiety and depression in different ways.
The results show that the difference between ACT acceptance and REBT acceptance
primary concern the process of acceptance, most likely due to the underlying
cognitive processing. The outcome acceptance and emotional level are similar in the
two conditions. Future research should employ multiple cognitive measurements.
Immigrant and refugee women from diverse ethnic backgrounds encounter multiple
barriers in accessing mental healthcare in various settings. A systematic review on
the prevalence of mental health disorders among culturally and linguistically
diverse (CALD) women in Australia documented the following barriers: logistical,
language and communication, dissonance between participants and care providers and
preference for alternative interventions. This article proposes recommendations for
policies to better address the mental health needs of immigrant and refugee women.
Key policy recommendations include: support for gender specific research,
implementation and evaluation of transcultural policies, cultural responsiveness in
service delivery, review of immigration and refugee claims policies and social
integration of immigrants.
OBJECTIVE: Cervical imaging practices are poorly understood in young children with
traumatic brain injury (TBI). We therefore sought to identify child-level and
hospital-level factors associated with performance of cervical imaging of children
with TBI from falls and abusive head trauma (AHT) and to describe across-hospital
variation in cervical imaging performance. We hypothesized that imaging decisions
would be influenced by hospital volume of young injured children. METHODS: We
performed a retrospective study of children younger than 2 years of age with TBI
from 2009 to 2013 in the Premier Perspective Database. After adjustment for
observed patient characteristics, we evaluated variation in advanced cervical
imaging (computed tomography or magnetic resonance imaging) in children with AHT
and TBI from falls. RESULTS: Of 2347 children with TBI, 18.7% were from abuse and
57.1% were from falls. Fifteen percent of children with TBI underwent advanced
cervical imaging. Moderate or severe head injuries were associated with increased
odds of cervical imaging in AHT (odds ratio 7.10; 95% confidence interval 2.75,
18.35) and falls (odds ratio 2.25; 95% confidence interval 1.19, 4.27). There was
no association between annual hospital volume of injured children and cervical
imaging performance. The adjusted probability of imaging across hospitals ranged
from 4.3% to 84.3% in AHT and 3.1 to 39.0% in TBI from falls (P < .001).
CONCLUSIONS: These results highlight variation across hospitals in adjusted
probability of cervical imaging in AHT (nearly 20-fold) and TBI from falls (over
10-fold) not explained by observed patient characteristics. This variation suggests
opportunities for further research to inform imaging practices.
ObjectiveThe aim of this study was to explore the preferred acculturation
strategies adopted by Indian subcontinental adolescents living in Australia. The
study also examined the demographic, ethnocultural, and psychological factors that
could influence subcontinental migrant groups' attitudes towards acculturation and
their acculturation strategies. MethodA cross-sectional design was used in which
the dependent variables were the four acculturation strategies. Multivariate data
analysis was conducted. Pearson's correlation, analysis of variance, and step-wise
multiple regression analyses were performed to establish the relationships among
the study variables. ResultsIntegration was the most preferred strategy and
marginalisation was the least preferred strategy for all ethnic groups.
Acculturation preferences are predicted partly by the adolescents' ethnicity, their
ethnic identity, friendship choices, acculturative stress, sense of mastery (self-
concept) and gender. The findings provide significant information on the
acculturation practices of Indian subcontinental adolescents, including their
ethnic identity search and commitment, their psychological well-being and their
integration strategies. ConclusionsEducational institutions could benefit from
increased awareness of the needs of these culturally diverse groups, especially if
this information is incorporated into teacher training materials. The inclusion of
intercultural relations courses in the academic curriculum would promote harmonious
relations between culturally diverse ethnic groups.
In order to improve the dynamic responses of multimode controlled primary-side
regulation flyback converter, a novel digital control method is proposed in this
paper. A new DAC sampling method, which can capture the output voltage during
dynamic transition, is introduced. Based on it, a dynamic module which can monitor
the variation of the output voltage to improve the dynamic performance is proposed.
In a 5-V/1-A primary-side regulation flyback converter, the maximum undershoot
voltage and overshoot voltage of the proposed control scheme in this study are
0.472 and 0.192 V, respectively. They are much lower compared to 1.296 and 0.584 V
in the traditional control scheme. The maximum undershoot and overshoot recovery
times are reduced from 10.86 to 1.29 ms and 126.3 to 53.68 ms, respectively. The
proposed control scheme was then verified by a FPGA controlled prototype.
This study proposes high-performance voltage controller design that employs a
capacitor current control model for single-phase stand-alone inverters. The single-
phase stand-alone inverter is analyzed via modeling, which is then used to design
the controller. A design methodology is proposed to maximize the bandwidth of the
feedback controller. Subsequently, to compensate for the problems caused by the
bandwidth limitations of the controller, an error transfer function that includes
the feedback controller is derived, and the stability of the repetitive control
scheme is evaluated using the error transfer function. The digital repetitive
controller is then implemented. The simulation and experimental results show that
the performance of the proposed controller is high in a 1.5 kW single-phase stand-
alone inverter prototype.
This work presents a novel mixed-signal control scheme for a boost power factor
correction (PFC) rectifier. The digital controller modulates the inductor peak
current to produce a low-distortion ac line current in discontinuous conduction
mode (DCM) and continuous conduction mode (CCM), without the need for average
current sensing. A lookup table (LUT) optimizes efficiency at low input currents,
by allowing operation at 125-500-kHz DCM based on calculated thresholds. At high
input currents, the converter operates at 1-MHz CCM for reduced inductor footprint.
An analog off-time generator with a digital frequency locked loop facilitates CCM
operation, eliminating the need for slope compensation in the current loop and
reduces frequency variations. The LUT is programmed with an adaptive output voltage
of 250/450 V for low/highmains line voltage (85-265Vrms) to optimize efficiency
over a broad range of conditions. The 150-W PFC prototype operates up to 1 MHz with
a peak efficiency of 95% and a total harmonic distortion of 5%.
The theoretical and experimental analysis of a modified version of the SEPIC dc-dc
converter used as preregulator operating in discontinuous conduction mode (DCM) is
presented in this paper. The proposed converter presents a low input current ripple
operating in DCM, and the switch voltage is lower than the output voltage. The
switch voltage reduction increases the converter reliability and a low drain-to-
source on-resistance (RDSon) MOSFET can be used depending on the converter
specification. Moreover, a digital control technique is applied to the proposed
converter in order to reduce the third-harmonic input current distortion resultant
of the operation in DCM. Finally, a 100-W prototype was developed operating with
efficiency equal to 95.6%.
In high-performance magnetic resonance imaging systems, the gradient driver is
required to supply the gradient coil with a large current (>600 A) and a high
voltage (>2000 V) to achieve a strong gradient field and a fast slew rate. In
addition, extremely high fidelity for reproducing the current command from the
central system is very critical to imaging quality. This paper presents the
solutions for the different elements of the driver: 1) high-bandwidth (BW) power
inverter; 2) ripple cancelation filter; 3) multioutput power supply (PS); and 4)
digital control. A high-BW power inverter requires a stacked-bridges structure to
achieve a high output ripple frequency with the existing commercial power
semiconductor modules. The high voltage and the high frequency for large power
modules can be obtained easier and with lower loss using the new silicon carbide
devices. The control needs a digital implementation and a very fast processor.
Digital control provides compensation and feedforward to improve the response. A
capability improvement is obtained by reducing the switching frequency when large
currents with a very low-frequency variation are needed. The control can handle it
very well, but the filter has to be designed to eliminate more than one ripple
frequency. Finally, many PS solutions have been used for multiple isolated outputs,
but digital control compensation permits the use of much simpler unregulated PS and
keeps the performance. A 2 MVA, 900 A/1200 V, platform has been built and fully
tested. The experimental results proved the validity of the proposed structure and
the modulation technique.
Drug release belongs to the most challenging aspects of nanoparticles addressing
molecular biology and medicine. Besides targeted delivery, obvious challenges are
related to high drug load and continuous slow drug release. Based on our recently
developed concept of inorganic-organic hybrid nanoparticles (IOH-NP), we here
present [ZrO](2+)[AAP](2-) IOH-NPs containing the analgetic phosphate prodrug
acetaminophen phosphate for drug release. [ZrO](2+)[AAP](2-) combines an uncomplex
synthesis in water with a high prodrug load of 68 wt.%.[ZrO](2+)[AAP](2-)
nanoparticles exhibit a diameter of 37(11) nm and can be readily obtained as
colloidally highly stable suspension in water. The chemical composition is studied
in detail based on infrared spectroscopy, energy-dispersive X-ray analysis,
thermogravimetry and elemental analysis. Moreover, the release of acetaminophen
from [ZrO](2+)[AAP](2-) is studied by means of model experiments indicating the
carbon content of the nanoparticles and, in alternative, the fluorescence of
labeled nanoparticles. Both data show a continuous release of 80 wt.% of the
analgetic acetaminophen on a time scale up to 48 h. (C) 2016 Elsevier Inc. All
rights reserved.
We have reported that orally administrated acetate contributed to suppression of
lipogenesis in the liver and to reduction of lipid accumulation in the adipose
tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The aim of this study was
to investigate the effect of acetate on skeletal muscle and adipose tissues.
Treatment with acetate showed a higher rate of oxygen consumption and a smaller
size of lipid droplets in white adipose and brown adipose tissues. An analysis by
Northern blotting revealed that the transcripts of myoglobin and Glut4 genes in the
abdominal muscle of the OLETF rats were increased by acetate treatment, while the
transcripts of lipolytic genes increased in the white adipose and brown adipose
tissues. It is possible that acetate has effects on lipid metabolism in the
skeletal muscles and the adipose tissues, and has functions that work against
obesity and obesity-linked type 2 diabetes.
Acetate has been found to have an inhibitory effect on the activity of
carbohydrate-responsive element-binding protein (ChREBP) in cultured hepatocytes,
this being a transcription factor that regulates several genes required for the
conversion of glucose to fatty acids in the liver. The aim of this study was to
investigate whether an oral administration of acetate would contribute to reducing
lypogenic genes and protecting against obesity. We orally injected 5.2mg/kg BW of
acetate to obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF)
rats. The treatment with acetate showed a marked reduction in lipid accumulation in
the adipose tissue, protection against accumulation of fat in the liver, and
improved glucose tolerance. An analysis by Northern blotting revealed that the
transcripts of several lipogenic genes in the liver of OLETF rats were decreased by
the acetate treatment. On the basis of those results, it was indicated that acetate
was a potential compound to improve obesity and obesity-linked type 2 diabetes.
Research was carried out for the appraisal of toxic and anti-enzymetic action of
acetone extracts of Datura inoxia and Azadirachta indica against Tribolium
castaneum, Trogoderma granarium and Sitophilus granarius in the grain research
training and storage management cell of department of entomology and in protein
molecular biology laboratory (PMBL) department of biochemistry (UAF) during the
year 2014. Various dilution levels viz., 5.0, 10.0, 15.0 and 20.0% of both plants
extracts were assessed against test insects. Toxic effect of plant extracts in T.
castaneum, T. granarium and S. granarius was observed after an exposure period of
2, 4, 6, 8 and 10 days while inhibition of different enzymes acetylcholinesterase
(AChE), a-carboxylesterase (alpha-CE), beta-carboxylesterase (beta-CE), acid
phosphatases (ACP) and alkaline phosphatases (ALP) were calculated
spectrophotometrically in the survivors of toxicity assay. The results evidenced
that both plant extracts had lethal effects against three stored grain insect
species. Comparison of means of mortality in T. castaneum, T. granarium and S.
granarius proved that A. indica extract was more effective, causing maximum 38.41,
24.35 and 28.56% mortality, respectively. D. inoxia resulted in 15.12, 13.52 and
14.07% maximum mortality in T. castaneum, T. granarium and S. granarius,
respectively. The results also revealed significant inhibition of AChE, alpha-CE,
beta-CE, ACP and ALP upon exposure to various concentrations of tested plants.
Plant extract of A. indica proved more efficient for the inhibition of all test
enzymes in three stored grain insect pests. The results suggest the ability of
using these plants extracts for wheat flour and grains protection as a safe
alternative to insecticides.
Bacterial community analyses of samples from a pilot plant for the treatment of
acid mine drainage (AMD) from the lignite-mining district in Lusatia (East Germany)
had previously demonstrated the dominance of two groups of acidophilic iron
oxidizers: the novel candidate genus "Ferrovum" and a group comprising Gallionella-
like strains. Since pure culture had proven difficult, previous studies have used
genome analyses of co-cultures consisting of "Ferrovum" and a strain of the
heterotrophic acidophile Acidiphilium in order to obtain insight into the life
style of these novel bacteria. Here we report on attempts to undertake a similar
study on Gallionella-like acidophiles from AMD. Isolates belonging to the family
Gallionellaceae are still restricted to the microaerophilic and neutrophilic iron
oxidizers Sideroxydans and Gallionella. Availability of genomic or metagenomic
sequence data of acidophilic strains of these genera should, therefore, be relevant
for defining adaptive strategies in pH homeostasis. This is particularly the case
since complete genome sequences of the neutrophilic strains G. capsiferriformans
ES-2 and S. lithotrophicus ES-1 permit the direct comparison of the metabolic
capacity of neutrophilic and acidophilic members of the same genus and, thus, the
detection of biochemical features that are specific to acidophilic strains to
support life under acidic conditions. Isolation attempts undertaken in this study
resulted in the microaerophilic enrichment culture ADE-12-1 which, based on 16S
rRNA gene sequence analysis, consisted of at least three to four distinct
Gallionellaceae strains that appear to be closely related to the neutrophilic iron
oxidizer S. lithotrophicus ES-1. Key hypotheses inferred from the metabolic
reconstruction of the metagenomic sequence data of these acidophilic Sideroxydans
strains include the putative role of urea hydrolysis, formate oxidation and
cyanophycin decarboxylation in pH homeostasis.
In this study, laccase from Trametes versicolor was immobilized in poly(acrylamide-
crotonic acid)/sodium alginate [P(AAm-CrA)/alginate], poly(acrylamide-crotonic
acid)/K-carrageenan [(P(AAm-CrA)/K-car)], poly(acrylamide-citraconic acid)/sodium
alginate (P(AAm-CA)/alginate), and poly(acrylamide-citraconic acid)/K-carrageenan
(P(AAm-CA)/K-car) semi-interpenetrating network by entrapment method. Optimum pH
and temperatures values were determined between 5.0-6.0 and 40-50 degrees C for
free laccase (FL) and immobilized laccases, respectively. After 42 days of storage
at 4 degrees C, FL and immobilized laccases retained their original activities in
the range of 55%-73%. Percent decolorization of Acid Orange 52 by free enyzme and
enyzmes immobilized in hydrogels was found between 63% and 39%. Percent
decolorization of Acid Orange 52 in the presence of mediator by free enyzme was
found 73% and enyzmes immobilized in hydrogels were found as 73%. (C) 2015
International Union of Biochemistry and Molecular Biology, Inc.
c-Myc overexpression has been implicated in several malignancies including gastric
cancer. Here, we report that acidified bile acids enhance tumor progression and
telomerase activity in gastric cancer via c-Myc activation both in vivo and in
vitro. c-Myc mRNA and protein levels were assessed in ten primary and five local
recurrent gastric cancer samples by quantitative real-time polymerase chain
reaction and western blotting analysis. The gastric cancer cell line MGC803 was
exposed to bile salts (100mol/L glycochenodeoxycholic acid and deoxycholic acid) in
anacidmedium (pH 5.5) for 10min daily for 60weeks to develop an MGC803-resistant
cell line. Control MGC803 cells were grown without acids or bile salts for 60weeks
as a control. Cell morphology, proliferation, colony formation and apoptosis of
MGC803-resistant cells were analyzed after 60weeks. To determine the involvement of
c-Myc in tumor progression and telomere aging in MGC803-resistant cells, we
generated xenografts in nude mice and measured xenograft volume and in vivo
telomerase activity. The c-Myc and hTERT protein and mRNA levels were significantly
higher in local recurrent gastric cancer samples than in primary gastric cancer
samples. MGC803-resistant cells showed a marked phenotypic change under normal
growth conditions with more clusters and acini, and exhibited increased cell
viability and colony formation and decreased apoptosis in vitro. These phenotypic
changes were found to be dependent on c-Myc activation using the c-Myc inhibitor
10058-F4. MGC803-resistant cells also showed a c-Myc-dependent increase in
xenograft growth and telomerase activity in vivo. In conclusion, these observations
support the hypothesis that acidified bile acids enhance tumor progression and
telomerase activity in gastric cancer and that these effects are dependent on c-Myc
activity. These findings suggest that acidified bile acids play an important role
in the malignant progression of local recurrent gastric cancer.
Thermoelectric (TE) materials are important for the sustainable development because
they enable the direct harvesting of low-quality heat into electricity. Among them,
conducting polymers have attracted great attention arising from their advantages,
such as flexibility, nontoxicity, easy availability, and intrinsically low thermal
conductivity. In this work, a novel and facile method is reported to significantly
enhance the TE property of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
(PEDOT:PSS) films through sequential post-treatments with common acids and bases.
Compared with the as-prepared PEDOT:PSS, both the Seebeck coefficients and
electrical conductivities can be remarkably enhanced after the treatments. The
oxidation level, which significantly impacts the TE property of the PEDOT:PSS
films, can also be well tuned by controlling the experimental conditions during the
base treatment. The optimal PEDOT:PSS films can have a Seebeck coefficient of 39.2
mu V K-1 and a conductivity of 2170 S cm(-1) at room temperature, and the
corresponding power factor is 334 mu W (m(-1) K-2). The enhancement in the TE
properties is attributed to the synergetic effect of high charge mobility by the
acid treatment and the optimal oxidation level tuned by the base treatment.
Background: Carbapenem-resistant Acinetobacter baumannii has emerged as an
important cause of infection in burn patients. This study aimed to characterize the
antimicrobial susceptibility pattern, determine the prevalence of oxacillinase and
metallo-beta-lactamase (MBL) genes, and type the A. baumannii isolates obtained
from burn patients. Methods: During a 1-year period, a total of 40 nonduplicated
isolates of A. baumannii were obtained from burn patients who were hospitalized in
the Taleghani Burn Hospital in Ahvaz, in the southwest of Iran. Testing for
antimicrobial susceptibility was carried out by disk diffusion and E-test. To
screen MBL production, a double disk synergy and MBL E-test were performed. The
presence of bla(OXA-23-like), bla(OXA-24-like), bla(OXA-51-like) and bla(OXA-58-
like), bla(VIM), bla(IMP) and bla(SPM), and bla(NDM) was sought by polymerase chain
reaction (PCR). Repetitive extragenic palindromic sequence-based PCR was carried
out for determination of isolates clonality. Results: Overall, 92.5% of isolates
were carbapenem-resistant. Polymyxin B, colistin, and ampicillin-sulbactam were the
most effective agents in vitro, with a susceptibility rate of 100%, 97.5%, and
72.5%, respectively. According to the double disk synergy and E-test, 55.6% and
97.3% of isolates were MBL producers, respectively. Furthermore, 70% of isolates
harbored bla(OXA-23-like) and 20% were positive for bla(OXA-24-like). However, no
encoding genes were detected for bla(VIM), bla(IMP) and bla(SPM), bla(NDM), and
bla(OXA-58-like). Repetitive extragenic palindromic sequence-based PCR revealed
that carbapenem-resistant isolates belonged to four clones, including A, B, C, and
D; the predominant clones were B and C. Conclusion: The rate of carbapenem
resistance was high, and it appeared that bla(OXA-23-like) and bla(OXA-24-like)
contributed to the carbapenem resistance of A. baumannii isolates. This result
suggests that the two predominant clones of A. baumannii were spread among burn
patients. In order to prevent future dissemination of resistant isolates among burn
patients, an effective infection control plan is necessary. Copyright (C) 2017.
Published by Elsevier Taiwan LLC.
The aim of the present study was to investigate the resistance of Acinetobacter
baumannii, which was induced by cefepime (FEP), cefoperazone-sulbactam (SCF),
tazobactam (TZP), levofloxacin (LEV), amikacin (AK), imipenem (IPM), and
ciprofloxacin (CIP), in vitro. Multi-step drug resistance selection of 16 A.
baumannii strains was performed using seven antibacterial agents (FEP, TZP, CIP,
AK, IPM, SCF, and LEV). The minimum inhibitory concentration (MIC) was determined
using the agar dilution method. Random amplified polymorphic DNA polymerase chain
reaction was performed to analyze the genotypes and the carrying rates of aac(3)-I,
aac(6)-I, ant(3)-I, aph(3)-Via, OXA-23, OXA-24, AmpC, TEM-1, metallo--lactamase
gene (IMP), armA, rmtA, rmtB, parC, gyrA and adeB. Expression of adeB was
determined using semi-quantitative reverse transcription-polymerase chain reaction
(Semi-qRT-PCR). Among the 16 strains, 15 strains with drug resistance (93.8%) were
obtained following in vitro induction. Notable increases (8- to 128-fold) were
noted in the MIC and different genotypes were showed in RAPD of the strains before
and after performing the drug resistant test. PCR data revealed significant
differences (P<0.05) between the carrying rates of resistant genes before and after
drug induction, with the exception of rmtA, OXA-24, TEM-1, and IMP. Significant
increases were demonstrated in the comparative adeB grayscale in strains that
underwent drug induction when compared with the sensitive strains (55.69 +/- 43.11%
vs. 10.08 +/- 26.35%; P=0.001). Findings of the present study suggest that the
active efflux pump, adeB, has an important role in multidrug resistance of the A.
baumannii induced by antibacterial agents in vitro.
We characterized 72 isolates with reduced susceptibility to carbapenems (50
Acinetobacter spp., 13 Proteus mirabilis, five Escherichia coli, one Morganella
morganii, one Enterobacter cloacae, one Providencia rettgeri, and one Pseudomonas
aeruginosa) from a hospital in Sofia, Bulgaria. Different -lactamase genes were
identified by polymerase chain reaction and sequencing. Bacterial strain typing was
performed by enzymatic macrorestriction and pulsed-field gel electrophoresis (PFGE)
typing as well as multilocus sequence typing for selected isolates. The majority of
Acinetobacter baumannii (46/50) and one Acinetobacter pittii isolate harbored
carbapenemase genes bla(OXA-23) or bla(OXA-72); two A. baumannii contained both
genes. PFGE typing of all A. baumannii showed the presence of nine different clones
belonging to eight sequence types ST350, ST208, ST436, ST437, ST449, ST231, ST502,
and ST579. Molecular characterization of the remaining isolates confirmed the
presence of one NDM-1-producing E. coli-ST101 clone (five isolates) and one P.
mirabilis clone (13 isolates) with VIM-1 and CMY-99. Furthermore, NDM-1 was
identified in P. rettgeri and M. morganii and VIM-2 in the P. aeruginosa isolate.
The permanent introduction of OXA-23/72 carbapenemase-producing A. baumannii clones
into the hospital and the repeated occurrence of one VIM-1-producing P. mirabilis
and one NDM-1-producing E. coli-ST101 clone over a period of more than 1 year is of
concern and requires intensified investigations.
Background Acotiamide is widely used to improve symptoms in patients with
functional dyspepsia (FD) in multiple large-scale clinical studies, but there are
few reports about the drug's mechanism of action. The aim of this study was to
assess the effects of acotiamide on gastric accommodation and gastric emptying,
gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a
placebo-controlled study. Methods We conducted a randomized, double-blind placebo-
controlled study. Fifty Japanese FD patients were randomly assigned to either
placebo (n = 25) or acotiamide 100 mg x 3/day for 2 weeks (n = 25). At baseline and
at 2 weeks of treatment, we evaluated the patients' gastric motility using
scintigraphy to determine the accommodation and emptying values, gastrointestinal
symptom rating scale (GSRS), HR-QOL (SF-8), and anxiety and depression scale
(HADS). Results Four patients failed to complete the medication regimen and were
omitted from analysis; data from 24 placebo patients and 22 acotiamide patients
were analyzed. Acotiamide significantly increased gastric accommodation compared to
the placebo (p = 0.04 vs. p = 0.08; respectively). Acotiamide significantly
accelerated gastric emptying (50 % half-emptying time) (p = 0.02 vs. p = 0.59).
Acotiamide significantly improved the total GSRS scores compared to placebo (p =
0.0007 vs. p = 0.14). HR-QOL did not differ significantly between the two groups,
but acotiamide significantly improved the HADS anxiety score compared to placebo (p
= 0.04 vs. p = 0.20). Conclusions Our placebo-controlled study demonstrated that
acotiamide significantly increased both gastric accommodation and gastric emptying
in Japanese FD patients. Acotiamide also improved the patients' dyspeptic symptoms
and anxiety score.
The objective of this study was to determine global gene expression in relation to
Vestibular schwannomas (VS) growth rate and to identify signal transduction
pathways and functional molecular networks associated with growth. Repeated
magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate.
Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS.
Double stranded cDNA was synthesized from the mRNA and used as template for in
vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was
hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software.
Differential gene expression was defined as a 1.5-fold difference between fast and
slow growing tumors (>< 0.5 ccm/year), employing a p-value < 0.01. Deregulated
transcripts were matched against established gene ontology. Ingenuity Pathway
Analysis was used for identification of signal transduction pathways and functional
molecular networks associated with tumor growth. In total 109 genes were
deregulated in relation to tumor growth rate. Genes associated with apoptosis,
growth and cell proliferation were deregulated. Gene ontology included regulation
of the cell cycle, cell differentiation and proliferation, among other functions.
Fourteen pathways were associated with tumor growth. Five functional molecular
networks were generated. This first study on global gene expression in relation to
vestibular schwannoma growth rate identified several genes, signal transduction
pathways and functional networks associated with tumor progression. Specific genes
involved in apoptosis, cell growth and proliferation were deregulated in fast
growing tumors. Fourteen pathways were associated with tumor growth. Generated
functional networks underlined the importance of the PI3K family, among others.
This work presents a method to determine mechanical transfer functions from forces,
acting on the stator teeth of an electrical machine, to surface velocities at sound
radiating surfaces. The method allows an efficient analysis of drive trains in
their target application and real environment. The determined transfer functions
are used in a transient acoustic model for the simulation of electrical drive
trains. The proposed model takes care of the nonlinear power electronics, the
digital control and sensors, as well as of tolerance afflicted geometries of
electrical machines and real and in tolerance deviating material properties. The
model is validated by means of vibration measurements. The benefits of a closed
simulation in time domain are declared. Exemplary applications of the proposed
model are discussed and the potential of the acoustic evaluation during the design
process of an electrical machine is illustrated.
Conversion of mechanical forces, vibrations and sound which have energy in the
range of milli- to tens of watts (also referred to as "small kinetic energies" in
this paper) into electricity has received global attention owing to the potential
in powering electronic devices. However, most of the small kinetic energy
generators can only generate electric power below 1 mu W/cm(3). As a result, an
energy storage device is required to accumulate the energy generated until it
reaches a sufficient level. Herein, we report the exceptionally-high
acoustoelectric conversion ability of randomly-orientated electrospun
poly(vinylidenefluoride-co-trifluoroethylene) nanofiber nonwoven webs. The
optimized device under sound is able to generate peak voltage and current of 14.5 V
and 28.5 mu A with a volume power density output of 306.5 mu W/cm(3) (5.9 mW/cm(3)
based on nanofiber web thickness). Without accumulation in any energy storage unit,
the electricity generated by the nanofiber device is sufficient to light up tens of
commercial LEDs, run electrochemical reactions and protect metals from corrosion.
Such a novel acoustoelectric generator may offer an effective solution to recycling
noise pollution into usable electricity.
Intergeneric hybridization is an important strategy to introgress alien genes into
common wheat for its improvement. But presence of cross ability barrier mechanism
regulated by Kr1 gene played a major destructive role for hybridization than other
reported genes. In order to know the underlying molecular mechanism and to dissect
out this barrier, a new annealing system, ACP (anneling control primer) system was
used in chromosome 5B (containing Kr1 gene) specific Recombinant Inbred Line (RIL)
population. Two differentially expressed fragments for Kr1 gene was identified,
cloned and sequenced. Further the expression was confirmed by northern blotting
analysis. Sequence analysis of the resulted clones revealed classes of putative
genes, including stress responsive and signal transduction.
Objective: To unravel the interplay between HIV-1 and its host cell, the effect of
HIV-1 infection on cellular gene expression was investigated. Methods: HIV-1(SF33)-
infected and uninfected H9 T cells were screened by differential display and RNase
protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)-infected P4-CCR5
HeLa cells, which were also examined after PDS5A siRNA knockdown in regard to HIV-1
replication by quantitative RT-PCR, p24 ELISA and LTR-driven beta-galactosidase
expression. The PDS5A knockdown effect on cellular gene expressions was studied by
microarray analysis. PDS5A tissue expression was determined by Northern blotting.
Results: Regulator of cohesion maintenance, homolog A (PDS5A) was found to be down-
regulated by HIV-1. When PDS5A was suppressed by siRNA, HIV-1 replication was
unaffected. PDS5A was found to be highly expressed in skeletal muscle tissue, and
to lesser degrees in pancreas, heart, placenta, lung, kidney, liver and brain.
Microarray analysis of PDS5A knockdown revealed 91 differential gene products over-
representing cell cycle, transport and protein stability regulation, including 4
genes (PP2A, RANTES, PCAF, TCF7L2) previously reported to interact with HIV-1.
Conclusion: The data show a downregulation of proliferation-associated host gene
PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not
viral replication. Copyright (C) 2011 S. Karger AG, Basel
Powder coatings have been receiving attention because they are environmentally
friendly. They do not contain solvents in their composition, and their components
have decorative and corrosion-protection functions, among many others. However, the
presence of polymers in their composition increases the risk of combustion in
adverse situations. In this context, this study aims to develop and characterize
acrylic-based powder paints with the addition of 2 wt % and 4 wt % montmorillonite
clays (MMT) as Cloisite 30B (MMT-30B) and Cloisite 15A (MTT-15A), employed as flame
retardants. The characterization of the coatings was carried out by
thermogravimetric analysis (TGA), X-ray diffraction, and scanning electron
microscopy. After application of the coatings on carbon steel substrates,
flammability tests were performed. The coatings with 2 wt % MMT-30B showed overall
better results, especially in the flammability tests. Flames spread less on these
coatings than on the other systems. However, when the surface and bottom
temperatures were analyzed by the cone calorimeter test, the samples prepared with
4 wt % MMT-15A were considered safer to be applied in fire scenarios. (c) 2017
Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45031.
Purpose/Background: The aim of this study was to evaluate the effects of quetiapine
XR and lithium on actigraphy-measured circadian parameters in patients with bipolar
II depression. Methods/Procedures: This was an 8-week, open-label, prospective,
randomized comparative study. The assessments included the 17-item Hamilton
Depression Rating Scale score and actigraphic measures concerning the previous 7
days, collected at each visit (weeks 0 [baseline], 1, 2, 4, 6, and 8); the
actigraphic data were analyzed with a cosinor analysis. Findings/Results:
Medication, time, and the interaction between medication and time were
significantly associated with acrophase for the entire group (Ps = 0.003, 0.020,
and 0.042, respectively). More specifically, acrophase was significantly delayed at
weeks 1 and 6 (Ps = 0.004 and 0.039, respectively) in the quetiapine XR group. The
F statistics significantly increased over time for the entire group (P < 0.001),
and there was a significant increase in F statistics on weeks 4 and 6 in the
quetiapine XR group (Ps = 0.016 and 0.020, respectively) and on weeks 4 and 8 in
the lithium group (Ps = 0.001 and 0.016, respectively). In addition, scores on the
17-item Hamilton Depression Rating Scale were significantly associated with the F
statistics during 8 weeks for the entire group (P = 0.008).
Implications/Conclusions: Both quetiapine XR and lithium affected several circadian
parameters, including peak activity time and robustness of circadian rhythm, but
exerted different effects on acrophase in patients with bipolar II depression. In
particular, clinical depressive symptoms were associated with robustness of
circadian rhythm during the course of the 8-week treatment.
Actinobacteria are Gram-positive bacteria commonly found in soil, freshwater and
marine ecosystems. In this investigation, bias in codon usages of ninety
actinobacterial genomes was analyzed by estimating different indices of codon bias
such as Nc (effective number of codons), SCUO (synonymous codon usage order), RSCU
(relative synonymous codon usage), as well as sequence patterns of codon contexts.
The results revealed several characteristic features of codon usage in
Actinobacteria, as follows: 1) C- or G-ending codons are used frequently in
comparison with A- and U ending codons; 2) there is a direct relationship of GC
content with use of specific amino acids such as alanine, proline and glycine; 3)
there is an inverse relationship between GC content and Nc estimates, 4) there is
low SCUO value (<0.5) for most genes; and 5) GCC-GCC, GCC-GGC, GCC-GAG and CUC-GAC
are the frequent context sequences among codons. This study highlights the fact
that: 1) in Actinobacteria, extreme GC content and codon bias are driven by
mutation rather than natural selection; (2) traits like aerobicity are associated
with effective natural selection and therefore low GC content and low codon bias,
demonstrating the role of both mutational bias and translational selection in
shaping the habitat and phenotype of actinobacterial species. (C) 2016 Institut
Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Mirror neurons (MNs) are a fascinating class of cells originally discovered in the
ventral premotor cortex (PMv) and, subsequently, in the inferior parietal lobule
(IPL) of the macaque, which become active during both the execution and observation
of actions. In this review, I will first highlight the mounting evidence indicating
that mirroring others' actions engages a broad system of reciprocally connected
cortical areas, which extends well beyond the classical IPL-PMv circuit and might
even include subcortical regions such as the basal ganglia. Then, I will present
the most recent findings supporting the idea that the observation of one's own
actions, which might play a role in the ontogenetic origin and tuning of MNs,
retains a particular relevance within the adult MN system. Finally, I will propose
that both cortical and subcortical mechanisms do exist to decouple MN activity from
the motor output, in order to render it exploitable for high-order perceptual,
cognitive, and even social functions. The findings reviewed here provide an
original framework for envisaging the main challenges and experimental directions
of future neurophysiological and neuroanatomical studies of the monkey MN system.
In this paper a new framework is introduced to develop a coupled active and
reactive market in distribution networks. Distributed energy resources (DERs) such
as synchronous machine-based distributed generations and wind turbines offer their
active and reactive powers to the proposed market. For the considered DERs,
multicomponent reactive power bidding structures are introduced based on their
capability curves. Also, the hourly speed variations of wind turbines are
considered in the proposed model. A distribution company buys active and reactive
powers from a wholesale market and sells them via this market. The demand side is
active, and responsive loads or aggregators can participate in the market using a
demand bidding/buyback program. The objective function of the proposed market is to
minimize the active and reactive power costs of DERs and distribution companies,
the penalty cost of CO2 emission, and the cost of running a demand bidding/buyback
program. The effectiveness of the proposed method is examined on a 22-bus 20-kV
radial distribution test system.
A highly reconfigurable merged analog baseband (MABB) with not only tunable
bandwidth (BW), gain, and order but also reconfigurable power, noise, and linearity
is proposed for multistandard integrated wireless receivers in this brief. The MABB
could arrange the total gain to different stages for noise and linearity tradeoffs
by introducing the merged biquad topology. To save power, the operational amplifier
(Opamp) for the proposed MABB can reduce the GBW, as long as it meets the GBW
requirement for different BW, gain, and order. A flexible power-efficient high-GBW
Opamp with an adaptive common-mode bias circuit is also proposed for the eighth-
order active-RC MABB. The proposed MABB covers a cutoff frequency range from 200
kHz to 20 MHz, whereas the gain could be tuned between 0 and 72 dB. The proposed
highly reconfigurable MABB is suitable for multistandard integrated wireless
receivers.
With the development of integrated circuits, the fully integrated continuous time
filter has been focused widely. A Nth-order universal filter based on Current
Feedback Operational Amplifier (CFOA) is proposed. Compared with available
circuits, the proposed circuit using less components (2n CFOAs, n capacitors, and
3n resistors) can realize the universal filter functions without changing circuit
configuration, and the operating frequency of proposed filter circuit is at least
10 MHz. All of capacitors in proposed circuit are grounded, this is another benefit
from integration point of view. PSPICE simulations have been carried out using 0.18
mu m CMOS technology, and sensitivity analysis of proposed Nth-order low-pass
filter circuit is completed. (C) 2015 Elsevier GmbH. All rights reserved.
This paper presents different state feedback approaches of finite control set model
predictive control (FCS-MPC) applied to a grid-connected voltage-source converter
(VSC) with an LCL filter. Besides converter-side current feedback, two
multivariable control approaches and line-side current control are introduced and
compared based on theoretical and experimental evaluation. As the LCL filter
introduces an additional resonance frequency to the system, the use of different
active damping (AD) methods in combination with FCS-MPC is discussed. Furthermore,
practical control implementation issues are discussed. The presented methods reveal
the great potential, high dynamic performance, and flexibility of FCS-MPC, enabling
multivariable control as well as both reduced switching losses and low harmonic
current distortion at the same time. Eventually, the feasibility of the theoretical
control concepts is shown in a laboratory environment.
Capacitor current feedback active damping is extensively used in grid-connected
converters with an LCL filter. However, systems tends to become unstable when the
digital control delay is taken into account, especially in low switching
frequencies. This paper discusses this issue by deriving a discrete model with a
digital control delay and by presenting the stable region of an active damping loop
from high to low switching frequencies. In order to overcome the disadvantage of
capacitor current feedback active damping, this paper proposes a modified approach
using grid current and converter current for feedback. This can expand the stable
region and provide sufficient active damping whether in high or low switching
frequencies. By applying the modified approach, the active damping loop can be
simplified from fourth-order into second-order, and the design of the grid current
loop can be simplified. The modified approach can work well when the grid impedance
varies. Both the active damping performance and the dynamic performance of the
current loop are verified by simulations and experimental results.
The high-power grid-connected inverters with LCL filters have been widely used.
Current control plays a key role in the grid-connected inverter control system. To
cope with the inherent resonance of the LCL filter, active damping (AD) methods are
usually employed. However, the AD performance is impaired by control delays which
are introduced in the digital control implementation process. Besides, the lag
phase due to control delays limits the system bandwidth and stability margin. The
effects of control delays are more noteworthy in the high-power grid-connected
inverter due to its low switching frequency. This paper investigates the current
control strategy based on multisampling for the high-power grid-connected inverter
with the LCL filter. First, the multisampled AD scheme is studied, which can reduce
control delays effectively and improve AD performance. Besides, the multisampled
control without additional damping whether passive or active is researched. Through
the inverter-side current feedback, the system can realize single-current-loop
control based on multisampling. Thus, the control system is simplified and it can
be stable, and achieve better dynamic performance. Finally, experimental results
show that the proposed control schemes are effective.
Resonant poles of LCL filters may challenge the entire system stability especially
in digital-controlled pulse width modulation (PWM) inverters. In order to tackle
the resonance issues, many active damping solutions have been reported. For
instance, a notch filter can be employed to damp the resonance, where the notch
frequency should be aligned exactly to the resonant frequency of the LCL filter.
However, parameter variations of the LCL filter as well as the time delay appearing
in digital control systems will induce resonance drifting, and thus break this
alignment, possibly deteriorating the original damping. In this paper, the
effectiveness of the notch filter-based active damping is first explored,
considering the drifts of the resonant frequency. It is revealed that when the
resonant frequency drifts away from its nominal value, the phase lead or lag
introduced by the notch filter may make itself fail to damp the resonance.
Specifically, the phase lag can make the current control stable despite of the
resonant frequency drifting, when the grid current is fed back. In contrast, in the
case of an inverter current feedback control, the influence of the phase lead or
lag on the active damping is dependent on the actual resonant frequency.
Accordingly, in this paper, the notch frequency is designed away from the nominal
resonant frequency to tolerate the resonance drifting, being the proposed robust
active damping. Simulations and experiments performed on a 2.2-kW three-phase grid-
connected PWM inverter verify the effectiveness of the proposed design for robust
active damping using digital notch filters.
Control of the LCL-type three-phase grid-connected converter is difficult due to
high resonance peak of the LCL filter. Active damping is the state-of-the-art
solution to this problem, but the damping performance will be affected by the
inherent time delay of digital control, especially for high-power low switching
frequency applications. Based on a discrete-time stability analysis of an LCL-type
converter with capacitor-current-feedback active damping, a simple and effective
time delay compensation method, which is based on area equalization concept, is
proposed. The method can reduce the negative impact of the computation delay
significantly. It has the potential to serve as a general solution to time delay
compensation of a digitally controlled PWM converter. The validity of the proposed
method is proved by experimental results.
The wind power generation techniques are continuing to develop and increasing
numbers of doubly fed induction generator (DFIG)-based wind power systems are
connecting to the on-shore and off-shore grids, local standalone weak networks, and
microgrid applications. The impedances of the weak networks are too large to be
neglected and require careful attention. Due to the impedance interaction between
the weak network and the DFIG system, both subsynchronous resonance (SSR) and high-
frequency resonance (HFR) may occur when the DFIG system is connected to the series
or parallel compensated weak network. This paper will discuss the SSR and the HFR
phenomena based on the impedance modeling of the DFIG system and the weak networks,
and the cause of these two resonances will be explained in details. The following
factors will be discussed in this paper: 1) transformer configuration; 2) different
power scale of DFIG system with different parameters; 3) L or LCL filter adopted in
the grid side converter (GSC); 4) rotor speed; 5) current closed-loop controller
parameters; and 6) digital control delay. On the basis of the analysis, active
damping strategies for HFR using virtual impedance concept will be proposed.
Energy storage systems (ESSs) are generally planned based on the active power.
While, reactive power is another important aspect of the ESSs that has not been
adequately addressed and discussed. Moreover, ESSs are often managed individually,
but coordinated planning on the ESSs and distributed generators (DGs) may result in
more suitable outcomes. In order to address these issues, a coordinated ESS and DG
planning is presented in this paper. In the proposed planning, the place and
capacity of the ESSs and DGs are determined at the same time. The active and
reactive powers are included in the planning for both the ESSs and DGs. In other
words, the optimal active and reactive capacities are denoted for both the ESSs and
DGs on the network. The proposed coordinated ESS and DG planning is carried out on
a radial distribution network under deregulated electricity market. Objective
function of the proposed planning is to maximize the profit of distribution company
(DISCO) subject to the secure operation of the network. The planning is expressed
as a nonlinear, mixed integer optimization problem and solved by advanced PSO as a
strong Meta-heuristic optimization technique. Simulation results demonstrate the
great impacts of the proposed planning on the network. The results demonstrate the
priority of the proposed coordinated DG and ESS planning compared to the individual
ESS planning. Additionally, it is verified that considering reactive power of the
DGs and ESSs changes the results of the planning and provides more realistic and
reasonable outputs. The proposed planning significantly increases DISCO profit
while guarantees the safe operation of the network through satisfying several
security constraints.
In this paper we present an analysis of the voltage amplifier needed for double
differential (DD) sEMG measurements and a novel, very simple circuit for
implementing DD active electrodes. The three-input amplifier that standalone DD
active electrodes require is inherently different from a differential amplifier,
and general knowledge about its design is scarce in the literature. First, the
figures of merit of the amplifier are defined through a decomposition of its input
signal into three orthogonal modes. This analysis reveals a mode containing EMG
crosstalk components that the DD electrode should reject. Then, the effect of
finite input impedance is analyzed. Because there are three terminals, minimum
bounds for interference rejection ratios due to electrode and input impedance
unbalances with two degrees of freedom are obtained. Finally, a novel circuit
design is presented, including only a quadruple operational amplifier and a few
passive components. This design is nearly as simple as the branched electrode and
much simpler than the three instrumentation amplifier design, while providing
robust EMG crosstalk rejection and better input impedance using unity gain buffers
for each electrode input. The interference rejection limits of this input stage are
analyzed. An easily replicable implementation of the proposed circuit is described,
together with a parameter design guideline to adjust it to specific needs. The
electrode is compared with the established alternatives, and sample sEMG signals
are obtained, acquired on different body locations with dry contacts, successfully
rejecting interference sources.
The performance of some Fourier transform based fundamental current detection
algorithms is evaluated and compared in this paper. Some difficult conditions are
imposed by a load which draws a highly distorted current with a slight fluctuation,
i. e. with non-equal semi-periods. The implemented algorithms are Recursive
Discrete Fourier Transform (RDFT), Discrete Fourier Transform (DFT) implemented
through a Finite Impulse Response (FIR) filter and respectively the Fast Fourier
Transform (FFT) with Butterfly operation and radix-2 decimation in time (DIT). A
digital signal processor (DSP) based solution is used for real-time implementation,
namely a dSPACE 1103 controller development board. MATLAB/Simulink software is used
for the design of the algorithms because it provides specialized tools and blocks.
For the performance comparison one used criteria like total harmonic distortion
(THD) and settling time of detected fundamental current and also the run time for
the DSP. This study may be useful as a guide for engineers in selecting the
suitable Fourier transform based control algorithm for active power filters or
other grid-synchronized equipments which are operating in difficult load
conditions.
A high-efficiency, high-power-density buffer architecture is proposed for power
pulsation decoupling in power conversion between dc and single-phase ac. We present
an active decoupling solution that yields improved efficiency and reduced circuit
complexity compared to existing solutions. In the proposed architecture, the main
energy storage capacitor is connected in series with an active buffer converter
across the dc bus. The series-stacked capacitor blocks the majority of the dc bus
voltage to reduce the voltage stress on the buffer converter, such that fast, low-
voltage transistors can be employed for the buffer converter. Moreover, the series
capacitor provides the majority of the power pulsation decoupling through a wide
voltage swing, and the buffer converter only needs to process a small fraction of
the total power of the entire architecture, allowing a very small active circuit
volume and very high system efficiency. The circuit operation and design
constraints are analyzed in detail. In the proposed buffer architecture, the series
stacking of a nearly lossless capacitor and a lossy converter presents a challenge
of capacitor voltage balancing and power loss compensation. We propose a control
scheme exploiting the small ripple in the bus voltage and dc input current to
compensate for the power loss in the buffer converter while maintaining the voltage
balance. Light-load techniques are also introduced to ensure that the buffer
architecture meets strict ripple requirements while providing sufficient loss
compensation. A 2-kW hardware prototype based on low-voltage GaN switches has been
built to demonstrate the performance of the proposed solution. A power density of
25W/cm(3) (410 W/in(3)) by rectangular box volume and an efficiency above 98.9%
across a wide load range has been experimentally verified.
A power divider/combiner circuit, which simultaneously achieves wide bandwidth,
flat gain characteristics, and bidirectional operation, is proposed for
multichannel broadband system applications. The proposed circuit utilizes cascode-
based bidirectional amplifier cores, which steer the operation modes between a
divider and a combiner depending on the control input, and a two-stage distributed-
amplifier topology with artificial transmission lines. Implemented in a 130-nm
silicon-germanium BiCMOS technology platform, the proposed divider/combiner
provides the advantage of seamless integration with digital control blocks. The
power divider/combiner exhibits the flat in-band gain of 9 dB and the operational
bandwidth of 2-22 GHz, which covers S-, C-, X-, and Ku-bands. In addition, it shows
the amplitude imbalance of 0.8 dB, the phase imbalance of 3.5 degrees, the port-to-
port isolation of 22 dB, the output 1-dB compression point of 3 dBm, and good
impedance matching under 100-mW dc power consumption.
Equivalently implementing a generalized memristor by using common components and
then making a nonlinear circuit with a reliable property, are conducive to
experimentally exhibit the nonlinear phenomena of the memristive chaotic circuit
and show practical applications in generating chaotic signals. Firstly, based on a
memristive diode bridge circuit, a new first-order actively generalized memristor
emulator is constructed with no grounded restriction and ease to realize. The
mathematical model of the emulator is established and its fingerprints are analyzed
by the pinched hysteresis loops with different sinusoidal voltage stimuli. The
results verified by experimental measurements indicate that the emulator uses only
one operational amplifier and nine elementary electronic circuit elements and is an
active voltage-controlled generalized memristor. Secondly, by parallelly connecting
the proposed emulator to a capacitor and then linearly coupling with an RC bridge
oscillator, a memristor based chaotic circuit without any inductance element is
constructed. The dynamical model of the inductorless memristive chaotic circuit is
established and the phase portraits of the chaotic attractor with typical circuit
parameters are obtained numerically. The dissipativity, equilibrium points, and
stabilities are derived, which indicate that in the phase space of the inductorless
memristive chaotic circuit there exists a dissipative area where are distributed
two unstable nonzero saddle-foci and a non-dissipative area containing an unstable
origin saddle point. Furthermore, by utilizing the bifurcation diagram, Lyapunov
exponent spectra, and phase portraits, the dynamical behaviors of the inductorless
memristive chaotic circuit are investigated. Results show that with the evolution
of the parameter value of the coupling resistor, the complex nonlinear phenomena of
the coexisting bifurcation modes and coexisting attractors under two different
initial conditions of the state variables can be found in the inductorless
memristive chaotic circuit. Finally, a prototype circuit with the same circuit
parameters for numerical simulations is developed, from which it can be seen that
the prototype circuit has a simple circuit structure and is inexpensive and easy to
practically fabricate with common components. Results of both the experimental
measurements and the numerical simulations are consistent, verifying the validity
of the theoretical analyses.
Transformation of research in all biological fields necessitates the design,
analysis and, interpretation of large data sets. Preparing students with the
requisite skills in experimental design, statistical analysis, and interpretation,
and mathematical reasoning will require both curricular reform and faculty who are
willing and able to integrate mathematical and statistical concepts into their life
science courses. A new Faculty Learning Community (FLC) was constituted each year
for four years to assist in the transformation of the life sciences curriculum and
faculty at a large, Midwestern research university. Participants were interviewed
after participation and surveyed before and after participation to assess the
impact of the FLC on their attitudes toward teaching, perceived pedagogical skills,
and planned teaching practice. Overall, the FLC had a meaningful positive impact on
participants' attitudes toward teaching, knowledge about teaching, and perceived
pedagogical skills. Interestingly, confidence for viewing the classroom as a site
for research about teaching declined. Implications for the creation and development
of FLCs for science faculty are discussed. (C) 2016 by The International Union of
Biochemistry and Molecular Biology
An active matrix organic light emitting diode (AMOLED) display driver IC, enabling
real-time thin-film transistor (TFT) nonuniformity compensation, is presented with
a hybrid driving method to satisfy fast driving speed, high TFT current accuracy,
and a high aperture ratio. The proposed hybrid column-driver IC drives a mobile UHD
(3840 x 2160) AMOLED panel, with one horizontal time of 7.7 mu s at a scan
frequency of 60 Hz, simultaneously senses the TFT current for back-end TFT
variation compensation. Due to external compensation, a simple 3T1C pixel circuit
is employed in each pixel. Accurate current sensing and high panel noise immunity
is guaranteed by a proposed current-sensing circuit. By reusing the hybrid column-
driver circuitries, the driver embodies an 8 bit current-mode ADC to measure OLED
V-I transfer characteristic for OLED luminance-degradation compensation.
Measurement results show that the hybrid driving method reduces the maximum current
error between two emulated TFTs with a 60 mV threshold voltage difference under 1
gray-level error of 0.94 gray level (37 nA) in 8 bit gray scales from 12.82 gray
level (501 nA). The circuit-reused current-mode ADC achieves 0.56 LSB DNL and 0.75
LSB INL.
\There are many factors that affect the performance of active power filter, which
is a key factor for command current tracking control. Aiming at the deficiency of
traditional PR controller, this paper puts forward an improved PR controller-vector
resonant controller. The controller has the advantages of stronger anti-
interference ability and greater gain at the resonance point, and it can improve
the accuracy of harmonic compensation in the current compensation control. In this
paper, the digital controller in the digital control system has been given a
detailed design. Finally, the experimental results show that the control strategy
can further reduce the harmonic content and improve the compensation accuracy.
This paper presents a power electronic converter used to redistribute the power
among the phases in unbalanced power systems, which is supposed to be designed
based on the involved degree of unbalance. A bidirectional converter is chosen for
this purpose, whose modeling is presented in the dq0 system. This solution can be
considered as part of a unified control system, where conventional active power
filters may be solely responsible for compensating harmonics and/or the tuning of
passive filters becomes easier, with consequent reduction in involved costs in a
decentralized approach. The adopted control strategy is implemented in digital
signal processor TMS320F2812, while experimental results obtained from an
experimental prototype rated at 17.86 kVA are properly discussed considering that
the converter is placed at the secondary side of a transformer supplying three
distinct single-phase loads. It is effectively shown that the converter is able to
balance the currents in the transformer phases, thus leading to the suppression of
the neutral current.
This paper reports a source follower-based active RC filter topology for RF front-
ends in wideband systems. In the proposed active RC filter, the noise figure and
bandwidth are improved through adopting the proposed sub-1 Omega Z(out) source
follower, which replaces the conventional operational amplifier-based unity gain
buffer and through simply changing its location in the filter. Applying the
proposed scheme to the conventional Sallen-Key filter also improves the stopband
rejection performance. Furthermore, the proposed filter topology ultimately
suppresses the DC offset voltage and flicker noise of the unity gain buffer, which
is the only active circuit in the filter. The proposed biquad filter is implemented
in 0.18 mu m CMOS and the measurements exhibit >26 dBm IIP3, +12 dBm input P-1dB,
and <15 dB noise figure over 50-450 MHz of a 6 bit tunable frequency range. The
proposed biquad filter consumes 14 mA from a 1.8 V supply and the chip occupies
1000x500 mu m(2).
Recently, we have reported on a compact microcontroller-based unit developed to
accurately synchronize excimer laser pulses (Mingesz et al. 2012 Fluct. Noise Lett.
11, 1240007 (doi:10.1142/S021947751240007X)). We have shown that dithering based on
random jitter noise plus pseudorandom numbers can be used in the digital control
system to radically reduce the long-term drift of the laser pulse from the trigger
and to improve the accuracy of the synchronization. In this update paper, we
present our new experimental results obtained by the use of the delay-controller
unit to tune the timing of a KrF excimer laser as an addition to our previous
numerical simulation results. The hardware was interfaced to the laser using
optical signal paths in order to reduce sensitivity to electromagnetic interference
and the control algorithm tested by simulations was applied in the experiments. We
have found that the system is able to reduce the delay uncertainty very close to
the theoretical limit and performs well in real applications. The simple, compact
and flexible system is universal enough to also be used in various
multidisciplinary applications.
The current-mode first-order allpass filter (APP) using only the active elements
has been studied in the present paper. The proposed circuit comprises two
operational transconductance amplifiers (OTAs) and one operational amplifier (OA)
which is suitable to future development into an integrated circuit. The pole
frequency and phase response can be electronically adjusted with changing the dc
bias currents of OTAs. The APF has high output impedance, which is easy to cascade
in high-order filter or drive load without using a buffering device. The current-
mode quadrature oscillator is included to show the usability of the proposed
filter. The results of PSPICE simulation are accordant with the theoretical
analysis.
An 8th-order Cheybshev-II ladder active-RC BPF was fabricated in a 40 nm CMOS low-
leakage digital process. A new technique to design for zero capacitance spread
(ZCS) is reported to enable the application of integrator frequency compensation
(IFC). Combined with wideband op-amps employing a current-reusing, split-path feed-
forward compensation (FFC) technique, significant power savings is achieved in a
standard 40 nm CMOS process. The BPF measures a center frequency (CF) of 85-225 MHz
and four programmable bandwidth-to-center frequency (BW/CF) ratios of 5%-40%. Both
the CF and BW/CF ratio are digitally programmable. It also measures a maximum in-
band IIP3 of 31 dBm at 0 dB gain and a maximum in-band frequency-response deviation
of 0.2 dB while consuming 33 mA from a 1.5 V supply.
Aims: Activin E is a newly identified member of the transforming growth factor-beta
superfamily. To assess the role of activin E in glucose/energy metabolism, we
investigated the transcriptional regulation of activin E in the liver. Main
methods: Northern blotting, Western blotting, quantitative real-time polymerase
chain reaction (PCR), reporter assays and chromatin immunoprecipitation assays were
used in this study. Key findings: Insulin up-regulated activin E expression at the
mRNA and protein level in HepG2 cells. Reporter assays revealed that the putative,
functional, promoter sequence of human activin E gene was responsible for the
effect of insulin. Mutational analysis of the promoter revealed that
CCAAT/enhancer-binding proteins (C/EBPs) play a key role in regulating activin E
expression and in the stimulatory effect of insulin on activin E transcription.
Chromatin immunoprecipitation assays revealed that the C/EBPs can bind to the
activin E promoter in HepG2 cells. The expression of activin E mRNA was up-
regulated in the liver of diet-induced obese mice. Significance: These observations
suggest that activin E plays a pathophysiological role in glucose metabolism. (C)
2009 Elsevier Inc. All rights reserved.
Background and purpose: Few studies have examined why some patients with dementia
stop attending medical consultations. We conducted a retrospective study to
investigate factors associated with discontinuous clinic attendance. Methods:
Participants were 988 patients with dementia from university hospital (UH) clinics
and affiliated local hospital (LH) clinics. We compared continuous and
discontinuous attenders on cognitive and affective functions and activities of
daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176;
discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). Results:
The total annual rate of discontinuation was 8.0%, and the mean period of
attendance before discontinuation was 2.2 2.4 years (UH, 2.8 +/- 3.0; LH, 1.5 +/-
1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia
Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and
psychological symptoms of dementia (BPSD) score, and ADL were significantly worse
in the discontinuous group than the continuous group for both UH and LH patients (P
< 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and
Abe's BPSD score (UH). The most common reason for discontinuation was returning to
the family doctor (39.1% for UH), and cessation of hospital attendance at their own
discretion (35.3% for LH). Conclusions: We identified the main reasons for
discontinuation of attendance as returning to the family doctor and cessation of
hospital attendance at their own discretion. The best predictors of discontinuation
were ADL decline and worsening BPSD. There were significant differences in
discontinuation between UH and LH patients with dementia.
This paper presents the A-Diakoptics methodology (Diakoptics based on actors) for
the high performance simulation of microgrids. Microgrids are clusters of loads and
microsources that operate within a single controllable system, which provides
electricity and heat to its local area even if they get separated from the
distribution system. Several commercial solutions are addressing this topic using
numerous methods; however, to keep the computing time required to solve the system
when the size of the system grows represents a major challenge. In this paper, this
challenge is addressed by separating the distribution grid in independent
subnetworks. Then, for the computational implementation, each subnetwork is
assigned to an independent solver using the actor model. As a result, the solution
algorithm is composed of multiple parallel and concurrent solvers. These exchange
information using high-speed communication interfaces for reducing the
computational burden without losing accuracy. A-Diakoptics is an advanced algorithm
that combines existing methods for simulating large distribution systems; these
methods are upgraded to make them suitable for parallel processing and to cover the
basic needs for the simulation of smart grid applications.
This paper presents a digital control technique to achieve valley switching in a
bidirectional flyback converter used to drive a dielectric electroactive polymer-
based capacitive incremental actuator. This paper also provides the design of a low
input voltage (24 V) and variable high output voltage (0-2.5 kV) bidirectional dc-
dc flyback converter for driving a capacitive incremental actuator. The incremental
actuator consists of three electrically isolated-mechanically connected capacitive
actuators. It requires three high-voltage (HV) (2-2.5 kV) bidirectional dc-dc
converters to accomplish the incremental motion by charging and discharging the
capacitive actuators. The bidirectional flyback converter employs a digital
controller to improve the efficiency and charge/discharge speed using the valley
switching technique during both charge and discharge processes, without the need to
sense signals on the output HV side. Experimental results verifying the
bidirectional operation of a HV flyback converter are presented using a 3-kV
polypropylene-film capacitor as the load. The energy-loss distributions of the
converter are presented when 4- and 4.5-kV HV MOSFETs are used on HV side. The
flyback prototype with a 4 kV MOSFET demonstrated 89% charge energy efficiency to
charge the capacitive load from 0 V to 2.5 kV, and 84% discharge energy efficiency
to discharge it from 2.5 kV to 0 V.
The mother's immune system has to adapt to pregnancy accepting the semi-allograft
fetus and preventing harmful effects to the developing child. Aberrations in feto-
maternal immune adaptation may result in disease of the mother, such as liver
injury. Five pregnancy-associated liver disorders have been described so far,
however, little is known concerning immune alterations promoting the respective
disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver
enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and
intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune
liver injury of the mother can be affected by pregnancy. This review intends to
summarize current knowledge linking feto-maternal immunology and liver inflammation
with a special emphasis on novel potential biomarkers.
Background: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid
myelitis (AFM) is essential to understand how the virus causes neurological damage
and to characterize EV-D68 strains associated with AFM. Case presentation: A
previously healthy 4-year-old boy presented with sudden weakness and limited
mobility in his left arm. Two days earlier, he had an upper respiratory illness
with mild fever. At admission, his physical examination showed that the child was
febrile (38.5 degrees C) and alert but had a stiff neck and weakness in his left
arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination
showed a mild increase in white blood cell count (80/mm(3), 41% neutrophils) and a
slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular
biology tests for detecting viral infection in CSF were negative. The patient was
then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24
h, the muscle weakness extended to all four limbs, which exhibited greatly reduced
mobility. Due to his worsening clinical prognosis, the child was transferred to our
Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid
paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative,
except for a focal signal alteration in the dorsal portion of the medulla
oblongata, also involving the pontine tegmentum, whereas spine MRI showed an
extensive signal alteration of the cervical and dorsal spinal cord reported as
myelitis. Signal alteration was mainly localized in the central grey matter, most
likely in the anterior horns. Molecular biology tests performed on nasopharyngeal
aspirate and on bronchoalveolar lavage fluid were negative for bacteria but
positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and
intravenous immunoglobulins were administered. After 4 weeks of treatment, the
signs and symptoms of AFM were significantly reduced, although some weakness and
tingling remained in the patient's four limbs. MRI acquired after 3 weeks showed
that the previously reported alterations were no longer present. Conclusion: This
case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are
circulating in Europe. EV-D68 disease surveillance is required to better understand
EV-D68 pathology and to compare various strains that cause AFM.
Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic
haematopoietic stem cell transplantation, with a significant proportion of patients
failing to respond to first-line systemic corticosteroids. Reliable biomarkers
predicting disease severity and response to treatment are warranted to improve its
management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acutephase
protein produced locally at the site of inflammation, could represent a novel acute
GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma
levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in
115 pediatric patients on day of transplantation, likely due to conditioning, and
at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was
also found increased in skin and colon biopsies from patients with active disease.
Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome
since they resulted significantly higher in both severe and therapyunresponsive
patients. Multiple injections of rhPTX3 in the murine model of GvHD did not
influence the disease course. Taken together, our results indicate that PTX3
constitutes a biomarker of GvHD severity and therapy response useful to tailor
treatment intensity according to early risk-stratification of GvHD patients.
Objective and design Cisplatin-based chemotherapy has been widely used in the
perioperative period of cancer surgery, which exacerbates the risk of renal injury.
In this study, we examined whether dexmedetomidine (DEX), a commonly used
anesthetic adjuvant, shows a protective effect against cisplatin-induced acute
kidney injury. Materials Acute kidney injury in mice was induced by cisplatin.
Treatments Mice were administered with DEX 25 mu g/kg or atipamezole 250 mu g/kg
(once a day, for 3 days) after cisplatin treatment. Methods The renal function and
tubular damage score were evaluated at 72 h following cisplatin administration.
Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80(+)
macrophages, CD3(+) T cells, and NF-kappa B were examined by immunohistochemistry
staining or Western blot. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1
beta, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured
using real-time polymerase chain reaction. Results DEX treatment preserved renal
function and reduced tubular damage score of mice after cisplatin administration.
Mice treated with DEX exhibited less apoptotic tubular cells in response to
cisplatin insult, which was associated with decreased Bax and reduced activation of
p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into
the kidneys following cisplatin treatment, which was involved in the inhibition of
NF-kappa B activation and decreased expression of TNF-alpha, IL-1 beta, IL-6, and
MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may
be related to alpha(2) adrenoceptor-dependent pathway. Conclusion We demonstrate
that DEX protects the kidney against cisplatin-induced AKI by the regulation of
apoptosis and inflammatory response.
Background: Cell necrosis, oxidative damage, and fibrogenesis are involved in
cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1)
levels are diminished. This study evaluates whether the exogenous administration of
low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride
(CCl4)-induced liver damage compared to healthy controls (Wt Igf(+/+)).
Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in
mice with a partial deficit of this hormone (Hz Igf1(+/-)). Methods: Three groups
of 25 +/- 5-week-old healthy male mice (Wt Igf(+/+)) were included in the protocol:
untreated controls (Wt). Controls that received CCl4 (Wt + CCl4) and Wt + CCl4 were
treated subcutaneously with IGF-1 (2 mu g/100 g body weight/day) for 10 days (Wt +
CCl4 + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1(+/-)) groups were
studied: untreated Hz, Hz + CCl4, and Hz + CCl4 + IGF-1. Microarray and real-time
quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases
levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end
of the treatment in all groups. All data represent mean +/- SEM. Results: An
altered gene coding expression pattern for proteins of the extracellular matrix,
fibrosis, and cellular protection were found, as compared to healthy controls, in
which IGF-1 therapy normalized in the series including healthy mice. Liver
histology showed that Wt + CCl4 + IGF1 mice had less oxidative damage, fibrosis,
lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl4.
Moreover, there was a correlation between MDA levels and the histological damage
score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings
were identified, denoting a much more vulnerable hepatic parenchyma. Conclusions:
IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-
regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient
mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver
damage, could be a feasible therapeutic option.
Adenoviruses cause a variety of diseases that range from mild to fatal in
vulnerable patients. Its evolution occurs as a process of selection pressure; for
example, genetic recombination generates intermediate strains that can be more
infectious or pathogenic than parental strains. This study sought to determine the
diversity of circulating adenoviruses in Paraguayan children less than 5 years of
age hospitalized with acute lower respiratory infection, by using molecular biology
and bioinformatics tools, though amplification of penton, hexon and fiber genes in
26 samples of nasopharyngeal aspirates. It was demonstrated the circulation of
three species: B (4/26), C (21/26), and D (1/26), as well as recombination events
corresponding to the HAdV-D isolate, with at least three different genotypes (D49,
D9 y D15). The HAdV-D are associated with gastrointestinal or ocular diseases, and
less commonly with respiratory infections. Recently, however, it has been reported
changes in behavior of these viruses due to recombination, allowing them to expand
their host cell repertoire. These data extend the knowledge about the genetic
diversity of HAdV in Paraguay and strongly support the importance of genomic
analysis using bioinformatics tools in epidemiological surveillance of emerging
recombinant strains of HAdV.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. While
survival rates for ALL have improved, central nervous system (CNS) relapse remains
a significant cause of treatment failure and treatment-related morbidity.
Accordingly, there is a need to identify more efficacious and less toxic CNS-
directed leukemia therapies. Extensive research has demonstrated a critical role of
the bone marrow (BM) microenvironment in leukemia development, maintenance, and
chemoresistance. Moreover, therapies to disrupt mechanisms of BM microenvironment-
mediated leukemia survival and chemoresistance represent new, promising approaches
to cancer therapy. However, in direct contrast to the extensive knowledge of the BM
microenvironment, the unique attributes of the CNS microenvironment that serve to
make it a leukemia reservoir are not yet elucidated. Recent work has begun to
define both the mechanisms by which leukemia cells migrate into the CNS and how
components of the CNS influence leukemia biology to enhance survival,
chemoresistance, and ultimately relapse. In addition to providing new insight into
CNS relapse and leukemia biology, this area of investigation will potentially
identify targetable mechanisms of leukemia chemoresistance and self-renewal unique
to the CNS environment that will enhance both the durability and quality of the
cure for ALL patients.
RNA-sequencing of the patient's bone marrow detected fusion transcripts in which
the coding sequence of the FAM53B gene (from 10q26) was fused to a genomic sequence
(from 19q13) that mapped upstream of the SLC7A10 locus. Reverse transcription-
polymerase chain reaction together with Sanger sequencing verified the presence of
this fusion transcript. The FAM53B fusion transcript is not expected to produce any
chimeric protein. However, it may code for a truncated FAM53B protein consisting of
the first 302 amino acids of FAM53B together with amino acids from the 19q13
sequence. Functionally, the truncated FAM53B would be similar to the protein
encoded by the FAM53B sequence with accession no. BC031654.1 (FAM53B protein
accession no. AAH31654.1). Furthermore, the truncated protein contains the entire
conserved domain of the FAM53 protein family. The chromosome aberration t(10;19)
(q26;q13) detected in this study was previously reported in a single case of ALL,
in which it was also the sole karyotypic change. Both patients entered complete
hematological and cytogenetic remission following treatment.
Purpose ETV6/RUNX1(+) acute lymphoblastic leukemia (ALL), which is the most common
genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we
analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with
the aim of identifying significant prognostic variables. Materials and Methods
Sixty-three patients were diagnosed with ETV6/RUNX1(+) ALL from 2005 to 2011.
Prognostic variables studied included minimal residual disease (MRD) as detected by
ETI/6/RUNX1(+) fusion, and the presence of additional cytogenetic abnormalities.
Results The 5-year event-free survival was 84.1 +/- 4.6%, with 10 patients
relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative
incidence of relapse of 15.9 4.6%. Multivariate analysis revealed that the presence
MRD, as detected by real-time quantitative-polymerase chain reaction or
fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission
induction, and the presence of additional structural abnormalities of 12p
(translocations or inversions) negatively affected outcome. Despite treatment such
as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients
died from disease progression for overall survival of 82.5 +/- 6.9%. Conclusion
ETV6/RUNX1(+) ALL may be heterogeneous in terms of prognosis, and variables such as
MRD at end of remission induction or additional structural abnormalities of 12p
could define a subset of patients who are likely to have poor outcome.
IntroductionThe translocation t(12;21)(p13;q22) resulting in the fusion gene ETV6-
RUNX1, is the most frequent gene fusion in childhood B lymphoblastic leukemia. In
the Nordic Society of Paediatric Haematology and Oncology ALL-2008 treatment
protocol, treatment stratification in B-lineage ALL is based on results of minimal
residual disease (MRD) analysis with fluorescence-activated cell sorting (FACS). In
this study, we determined whether RT-qPCR of the ETV6-RUNX1 fusion transcript can
be a reliable alternative for MRD analysis. MethodsSeventy-eight bone marrow
samples from 29 children at diagnosis and day 15, 29, and 78 during treatment were
analyzed for MRD with FACS and with quantitative reverse transcription polymerase
chain reaction (RT-qPCR). Fusion transcript MRD was defined as the ETV6-RUNX1/GUSB
ratio at the follow-up time point (day 15/29/78) divided with the ETV6-RUNX1/GUSB
ratio at diagnosis (%). ResultsMRD analysis with FACS and with RT-qPCR of ETV6-
RUNX1 fusion transcript showed strong correlation. All cases showed concordant
results at the treatment stratifying time points day 29 and day 78, when comparing
the two methods with a cutoff set to 0.1%. ConclusionRT-qPCR is a valuable addition
and could also be an alternative to FACS in cases where FACS is not achievable for
MRD analysis.
Glucocorticoids (GCs) induce apoptosis in lymphoid lineage cells and are therefore
used in the therapy of acute lymphoblastic leukemia (ALL) and related malignancies.
MicroRNAs (miRNAs) and the related mirtrons are similar to 22 nucleotide RNAs
derived from polymerase-II transcripts and implicated in the control of essential
biological functions, including apoptosis. Whether GCs regulate miRNA-encoding
transcription units is unknown. We investigated miRNA/mirtron expression and GC
regulation in 8 leukemia/lymphoma in vitro models and 13 ALL children undergoing
systemic GC monotherapy using a combination of expression profiling techniques,
real time reverse transcription (RT)-PCR and northern blotting to detect mature
miRNAs and/or their precursors. We found that mature miRNA regulations can be
inferred from expression data of their host genes. Although a simple miRNA-
initiated canonical pathway to GC-induced apoptosis or cell cycle arrest did not
emerge, we identified several miRNAs/mirtrons that were regulated by GC in patients
and cell lines, including the myeloid-specific miR-223 and the apoptosis and cell
cycle arrest-inducing miR15 similar to 16 clusters. In an in vitro model,
overexpression of miR15b similar to 16 mimics increased and silencing by miR15b
similar to 16 inhibitors decreased GC sensitivity. Thus, the observed complex
changes in miRNA/mirtron expression during GC treatment might contribute to the
anti-leukemic GC effects in a cell context-dependent manner.
Treatment of acute myelogenous leukemia (AML) over the past four decades remains
mostly unchanged and the prognosis for the majority of patients remains poor. Most
of the significant advances that have been observed are in defining cytogenetic
abnormalities, as well as the genetic and epigenetic profiles of AML patients.
While new cytogenetic and genetic aberrations such as the FLT3-ITD and NPM1
mutations are able to guide prognosis for the majority of patients with AML,
outcomes are still dismal and relapse rates remain high. It is thought that relapse
in AML is in part driven by minimal residual disease (MRD) that remains in the
patient following treatment. Thus, there is a need for sensitive and objective
methodology for MRD detection. Methodologies such as multiparameter flow cytometry
(MFC), quantitative real-time polymerase chain reaction (RQ-PCR), digital PCR
(dPCR), or next-generation sequencing (NGS) are being employed to evaluate their
utility in MRD assessment. In this review, we will provide an overview of AML and
the clinical utility of MRD measurement. We will discuss optimal timing to MRD
measurement, the different approaches that are available, and efforts in the
standardization across laboratories.
The mammalian target of rapamycin (mTOR) has recently been implicated in leukaemic
cell growth, tumour-associated angiogenesis and expression of vascular endothelial
growth factor (VEGF). We examined whether mTOR plays a role as regulator of growth
and VEGF-expression in acute myeloid leukaemia (AML). Three mTOR-targeting drugs,
rapamycin, everolimus (RAD001) and CCI-779, were applied. The effects of these
drugs on growth, survival, apoptosis and VEGF expression in primary AML cells and
various AML cell lines were examined. Growth of AML cells and AML-derived cell
lines was assessed by (3)H-thymidine incorporation, survival was examined by light-
and electron microscopy, by Tunel assay and by AnnexinV-staining, and the
expression of VEGF by Northern blotting, RT-PCR and ELISA. Rapamycin was found to
counteract growth in the AML cell lines U937 and KG1a as well as in primary AML
cells in 14/18 patients examined. The effects of rapamycin and its derivatives were
dose-dependent (IC(50): 10 pM-100 nM). It was also found that exposure to mTOR-
targeting drugs resulted in apoptosis and in decreased expression of VEGF in
leukaemic cells. mTOR-targeting drugs exert antileukaemic effects on AML cells in
vitro through multiple actions, including direct inhibition of proliferation,
induction of apoptosis and suppression of VEGF. Based on this study and other
studies, mTOR can be regarded as a potential drug target in AML.
Background/Purpose: Mutations in the tet oncogene family member 2 gene (TET2) are
frequently found in adult patients with acute myeloid leukemia (AML). Reports of
TET2 mutations in children are limited. We assessed the prevalence of TET2
mutations in Taiwanese children with AML and analyzed their prognosis. Methods:
Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled at
the National Taiwan University Hospital. The analysis for TET2 mutations was
performed using direct sequencing. Clinical characteristics and overall survival
(OS) were compared between patients with and without TET2 alterations. Results:
Intronic and missense mutations were identified. No nonsense or frameshift
mutations were observed. Two putative disease-causing missense mutations (S609C and
A1865G) were identified in one patient. We estimated the prevalence of TET2
mutations in the current patient population to be 1.4%. The most common
polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L (6%).
Patients with polymorphism I1762V had an increased 10-year survival rate compared
with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square test; OS
was not different when examined using the Kaplan-Meier method (p = 0.104).
Conclusion: The prevalence of TET2 mutations in children with AML compared with
adults with AML was lower and less complex. Patient prognosis associated with TET2
mutations in children requires further investigation. Copyright (C) 2015, Formosan
Medical Association. Published by Elsevier Taiwan LLC.
Several studies have reported previously that acute myeloid leukemia (AML) may
express WT1 detected by RT-PCR and/or Northern blotting. The diagnostic utility of
WT1 expression in AML using immunohistochemistry has not been reported previously.
Paraffin-embedded tissue sections from 55 AML, 12 acute lymphoblastic leukemia
(ALL), and 10 normal bone marrow specimens were immunostained for WT1 (anti-N
terminus antibody). 22/55 AML cases (40%) demonstrated nuclear immunopositivity for
WT1, including 20/47 bone marrow trephines and 2/4 granulocytic sarcomas. All the
ALL and normal bone marrow specimens were negative. A significant proportion of AML
expresses nuclear immunostaining for WT1, a finding that has only been described
previously in Wilms' tumor and desmoplastic small round cell tumor. This finding is
important for the correct interpretation of immunohistochemical findings in the
diagnosis of "small round cell'' tumors of childhood, especially in cases of
extramedullary deposits of AML, in which traditional myeloid markers may be
negative.
The karyotype is critical for the evaluation of acute myeloid leukemia (AML) at
diagnosis. Cytogenetic abnormalities detected in AML are one of the most powerful
independent prognostic factors. It impacts on the choice of treatment in clinical
trials. All chromosomes can be targeted, common chromosomal abnormalities are
recurrent and may be associated with a cytological well-defined type. In 40% of the
cases, the karyotype is normal and must be associated with molecular biology
studies that can refine the prognosis. The usefulness of the karyotype is more
limited during the follow-up of the patient due to its limited sensitivity, but it
is still useful in the clinical management of relapse. Since 2001, the WHO (World
Health Organization) classification of hematological malignancies integrates
cytogenetic data in the classification of AML. Karyotype is therefore mandatory in
the diagnosis of AML.
Purpose: To correlate visual acuity outcomes and clinical features with
quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN).
Methods: Retrospective, consecutive case series. Results: In total, 14 eyes of 13
patients were diagnosed with ARN, based on the American Uveitis Society criteria,
and were followed for a mean of 324.5 days (median 250.5 days, SD +/- 214 days).
Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of
14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%)
and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 x
10(6)/mL (median 2.10 x 10(6)/mL, range: 0-5.60 x 10(7)/mL). Eyes with quantitative
PCR DNA copy number of 5.0 x 10(6)/mL (n = 6 eyes) had worse baseline visual acuity
(logMAR 1.48 +/- 0.71 vs 0.94 +/- 0.76, p = 0.196) and final visual acuity (logMAR
2.10 +/- 0.60 vs 0.82 +/- 0.81, p = 0.007) compared with patients with a DNA copy
number <5.0 x 10(6)/mL (n = 8 eyes). Patients with a DNA copy number of 5.0 x
10(6)/mL were more likely to have at least 5 clock hours of retinitis on
funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p =
0.08). Conclusions: Quantitative DNA copy number of 5.0 x 10(6)/mL is associated
with more extensive retinitis, worse visual acuity, and development of retinal
detachment in patients with acute retinal necrosis.
This review summarizes present evidence for the role of YKL-40 in the diagnosis,
prognosis and cause of cardiovascular and alcoholic liver disease. The question of
whether YKL-40 is merely a marker or a causal factor in the development of
cardiovascular and liver disease is addressed, with emphasis on the Mendelian
randomization design. The Mendelian randomization approach uses genetic variants
associated with lifelong high plasma YKL-40 levels that are largely unconfounded
and not prone to reverse causation. Thus, the approach mimics a controlled double-
blind randomized trial, but it uses genetic variants rather than a drug and
placebo, and like a blinded trial, it allows inference about causality. Moreover,
the review also covers background on the molecular biology and functions of YKL-40,
YKL-40 levels in healthy individuals and reference range, and the role of YKL-40 as
a biomarker of cardiovascular and alcoholic liver disease. YKL-40 is a plasma
protein named after its three N-terminal amino acids, Y (tyrosine), K (lysine) and
L (leucine), and its molecular weight of 40kDa. It is produced by local
inflammatory cells in inflamed tissues, such as lipid-laden macrophages inside the
vessel wall and perhaps also hepatic stellate cells. Observational studies show
that plasma YKL-40 levels are elevated in patients with cardiovascular and liver
disease and are associated with disease severity and prognosis. Furthermore,
elevated plasma YKL-40 levels in apparently healthy individuals are associated with
a 2-fold increased risk of future ischemic stroke and venous thromboembolism, but
not with myocardial infarction, suggesting that YKL-40 could play a role in the
formation of embolisms rather than atherosclerosis per se. Further, elevated YKL-40
levels combined with excessive alcohol consumption are associated with 10-years
risk of alcoholic liver cirrhosis of up to 7%, suggesting that YKL-40 can be used
as a strong noninvasive marker of predicting alcoholic liver cirrhosis.
Importantly, in Mendelian randomization studies, genetically elevated plasma YKL-40
levels were not associated with risk of cardiovascular and alcoholic liver disease,
thus suggesting that plasma YKL-40 does not play a causal role in the development
of these diseases. Despite this, plasma YKL-40 levels may play a role in disease
progression after diagnosis, and inhibition of YKL-40 activity might be a novel
therapy in some cardiovascular and liver diseases.
Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I
encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients
(Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised
patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative
HIV antigen/antibody testing), female patient, without previous illness who
developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral
magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense
lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid
(CSF) analysis yielded lymphocytic pleocytosis and elevated protein level.
Polymerase chain reaction testing for HSV type I showed a positive result in repeat
lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir
treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to
1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression
on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir
resistance testing showed mutation of thymidine kinase gene at position A156V
prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved
dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in
case of clinical worsening of patient's condition. To our knowledge, this is the
first report of acyclovir resistance in HSV type I encephalitis of an
immunocompetent and previously healthy patient in Austria.
Introduction: The recent approval of adalimumab (trade name Humira, Abbvie inc.) by
the FDA for the treatment of noninfectious intermediate, posterior and panuveitis
marks the first on label' non-corticosteroid drug available to ophthalmologists.
Immunomodulatory (IMT) and biologic agents have long been shown to be effective in
inducing remission of chronic uveitis but have remained as orphan drugs due to lack
of financial incentive and perceived need. Areas covered: Here we provide detail
into the background and use of adalimumab for uveitic patients. Topics include
pharmacology, therapeutic indications and usage, dosage, drug safety, physician
monitoring, side effects and adverse events. Expert opinion: We see the approval of
adalimumab for uveitis as an important milestone improving upon the accepted
standards of care for patients with this severe, sight threatening disease. We
implore medical professionals to consider the use of IMT and biologic treatments
for patients with recurrent non-infectious uveitis, referring to ocular immunology
and uveitis specialists when necessary.
Aims: Trophoblast fusion in the placenta is prerequisite to successful pregnancy
and the pathological conditions related to it. The presence of syncytin-1, is not
sufficient to explain the complete event and ADAM12 is a major co-player candidate.
Via differential splicing, the ADAM12 gene produces a short and a long form, being
the ADAM12-S and the ADAM12-L respectively. Methods and results: We investigated
the localisation of both variants in the human placenta using whole mount in situ
hybridisation, immunohistochemistry and Northern blotting in 1st (n = 8) and 3rd (n
= 8) trimester placentae and in the case of NB in several cell lines. In Northern
blotting, 1st and 3rd trimester placentae were positive for the ADAM12-S and Bewo,
293HEK, JAR, leucocytes, macrophages, 1st and 3rd trimester placentae were positive
for ADAM12-L. In whole mount in situ hybridisation, the 1st and 3rd trimester
placental syncytium was positive for both variants. In immunohistochemistry,
ADAM12-L localised in the cytotrophoblast of both 1st and 3rd trimester placentae,
while ADAM12-S localised in the complete syncytium, often including the
cytotrophoblast. Conclusion: The different localisation of ADAM12-S and ADAM12-L
indicates a possible different role making ADAM12-L a candidate for the fusion
event, while the syncytial localisation of the ADAM12-S makes it a candidate for
cell-cell and cell-matrix interactions between the placental syncytium and the
maternal interface. (C) 2011 Elsevier GmbH. All rights reserved.
This paper proposes an adaptive controller with an improved high-frequency
injection method for sensorless synchronous reluctance drive systems. A
mathematical model is presented to show that the use of a high-frequency injection
method that takes into account the effects of unequal mutual-inductances and the
influence of speed reduces the rotor position estimation error. The adaptive speed
control algorithm offers improved transient performance in comparison to typical
proportional-integral (PI) controllers that are employed in sensorless drive
systems. To demonstrate the viability, the proposed adaptive controller and the
modified high-frequency injection method are implemented using a TMS-320F-28335A
digital signal processor to control a 500 W prototype synchronous reluctance motor
drive. Experimental results are presented to show that the transient, load
disturbance, and tracking responses of the proposed drive system are superior in
comparison to a drive that uses a PI controller. Both experimental and theoretical
analyses clearly indicate that the proposed high-frequency injection method with an
adaptive speed-loop controller offers improved performance in adjustable speed
synchronous reluctance drive systems.
In this paper, a current sensorless adaptive secondary-side control is proposed for
the series resonant converter (SRC), making it a good candidate for MHz 48 voltage
regulators. By means of varying ac equivalent resistance, the output voltage
regulation is achieved by controlling the duty cycle of the synchronous MOSFET. By
taking advantage of the secondary-side control, SRCs can operate under zero-voltage
switching at any input voltage and load conditions. A current sensorless adaptive
digital control is proposed to control the current-type synchronous MOSFETs, which
automatically compensates the delay caused by the current-sensor circuit and the
gate driver, and also eliminates the current sensor in the power path. A hybrid
control strategy is introduced to overcome the efficiency degradation caused by the
secondary-side control.
A recursive smoothing filter employing a bank of fading-memory polynomial sub-
filters is presented. Variance estimates are used to mix the outputs of the sub-
filters, imparting variable gain and phase characteristics that permit it to
automatically adapt to signal parameter changes. The proposed adaptive technique
does not involve the estimation of plant parameters; therefore, it may be used in
both open-loop and closed-loop configurations. In open-loop estimation problems,
variable gain/bandwidth allows it to reduce the impact of random errors caused by
sensor noise and the impact of bias errors caused by model mismatch during `
maneuvers'. In feedback control problems, variable phase/delay allows it to act as
a lag filter for an improved steady-state response (i.e. greater noise attenuation)
and act as a lead filter, or a proportionalderivative controller, for an improved
transient response (i.e. increased closed-loop damping) for input discontinuities.
Copyright (C) 2015 John Wiley & Sons, Ltd.
In this paper, a novel mixed iterative adaptive dynamic programming (ADP) algorithm
is developed to solve the optimal battery energy management and control problem in
smart residential microgrid systems. Based on the data of the load and electricity
rate, two iterations are constructed, which are P-iteration and V-iteration,
respectively. The V-iteration is implemented based on value iteration, which aims
to obtain the iterative control law sequence in each period. The P-iteration is
implemented based on policy iteration, which updates the iterative value function
according to the iterative control law sequence. Properties of the developed mixed
iterative ADP algorithm are analyzed. It is shown that the iterative value function
is monotonically nonincreasing and converges to the solution of the Bellman
equation. In each iteration, it is proven that the performance index function is
finite under the iterative control law sequence. Finally, numerical results and
comparisons are given to illustrate the performance of the developed algorithm.
This paper proposes a dimmable energy-efficient light-emitting diode (LED) driver
for applications in interior lighting. High efficiency is achieved by an adaptive
voltage regulation, which minimizes power losses in the linear current regulator. A
digital control mechanism employing a resistive digital-to-analog converter for
feeding the analog feedback input of a dc-dc converter is introduced. It is shown
that the digital control methodology gives maximum design flexibility and enhances
control over regulation speed and stability. In an experimental setup, the proposed
concept is verified and evaluated. Operating at an input voltage of 24 V, the LED
driver provides a relatively wide output voltage range of 3.5-38 V. Output current
is regulated to 700 mA with a steady-state precision of more than 98.8%, whereas
pulsewidth modulation dimming with a frequency of 1 kHz and shortest on-time of 4
mu s is employed. A peak efficiency of the complete system of 93.9% is achieved.
Environmental governance systems are under greater pressure to adapt and to cope
with increased social and ecological uncertainty from stressors like climate
change. We review principles of social cognition and decision making that shape and
constrain how environmental governance systems adapt. We focus primarily on the
interplay between key decision makers in society and legal systems. We argue that
adaptive governance must overcome three cooperative dilemmas to facilitate
adaptation: (1) encouraging collaborative problem solving, (2) garnering social
acceptance and commitment, and (3) cultivating a culture of trust and tolerance for
change and uncertainty. However, to do so governance systems must cope with biases
in people's decision making that cloud their judgment and create conflict. These
systems must also satisfy people's fundamental needs for self-determination,
fairness, and security, ensuring that changes to environmental governance are
perceived as legitimate, trustworthy, and acceptable. We discuss the implications
of these principles for common governance solutions (e.g., public participation,
enforcement) and conclude with methodological recommendations. We outline how
scholars can investigate the social cognitive principles involved in cases of
adaptive governance.
Adjuvants are substances added to vaccines to improve their immunogenicity. Used
for more than 80years, aluminum, the first adjuvant in human vaccines, proved
insufficient to develop vaccines that could protect against new challenging
pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants
(Adjuvant Systems) have opened the door to the delivery of improved and new
vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept
started through serendipity. The access to new developments in technology,
microbiology and immunology have been instrumental for the dicephering of what they
do and how they do it. This knowledge opens the door to more rational vaccine
design with implications for developing new and better vaccines.
In recent years, immunotherapy has gained renewed interest as an alternative
therapeutic approach for solid tumors. Its premise is based on harnessing the power
of the host immune system to destroy tumor cells. Development of immune-mediated
therapies, such as vaccines, adoptive transfer of autologous immune cells, and
stimulation of host immunity by targeting tumor-evasive mechanisms have advanced
cancer immunotherapy. In addition, studies on innate immunity and mechanisms of
immune evasion have enhanced our understanding on the immunology of liver cancer.
Preclinical and clinical studies with immune-mediated therapies have shown
potential benefits in patients with liver cancer. In this review, we summarize
current knowledge and recent developments in tumor immunology by focusing on two
main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
(TIMPs) are thought to be predominant proteases and protease inhibitors involved in
the pathogenesis of inflammatory bowel diseases (IBD) through their ability to
remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by
their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked
with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD.
Moreover, recurrent phases of tissue destruction and subsequent tissue repair can
cause serious complications in IBD patients such as fistulas and fibrosis. The aims
of this review are (i) to summarize current literature on genetic association,
mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients
and various animal models, including those with transgenic and knockout mice; (ii)
to compare biochemical and molecular biological data in humans with those obtained
in animal model studies and (iii) to critically evaluate and translate how this
knowledge may be used in practical terms to understand better the pathophysiology
and mechanisms operating in IBD and to apply this for improvement of clinical
outcomes at diagnostic, prognostic and therapeutic levels.
CRISPR-Cas are self-/nonself-discriminating systems found in prokaryotic cells.
They represent a remarkable example of molecular memory that is hereditarily
transmitted. Their discovery can be considered as one of the first fruits of the
systematic exploration of prokaryotic genomes. Although this genomic feature was
serendipitously discovered in molecular biology studies, it was the availability of
multiple complete genomes that shed light about their role as a genetic immune
system. Here we tell the story of how this discovery originated and was slowly and
painstakingly advanced to the point of understating the biological role of what
initially was just an odd genomic feature.
In this chapter has been proposed a robust sensorless cascade control scheme for a
Permanent Magnet Synchronous Motor (PMSM) drive. A Discrete Time Variable Structure
Control (DTVSC) is considered and the rotor position and speed are obtained through
an Adaptive Extended Kalman Filter (AEKF). The performance of the filter is
improved by an on line adjustment of the input and measurement noise covariances
obtained by a suitably defined estimation algorithm. The proposed solution is
experimentally tested on a commercial PMSM drive equipped with a control system
based on a floating point Digital Signal Processor (DSP).
This paper presents a power system harmonic elimination using the mixed adaptive
linear neural network and variable step-size leaky least mean square (ADALINE-
VSSLLMS) control algorithm based active power filter (APF). The weight vector of
ADALINE along with the variable step-size parameter and leakage coefficient of the
VSSLLMS algorithm are automatically adjusted to eliminate harmonics from the
distorted load current. For all iteration, the VSSLLMS algorithm selects a new rate
of convergence for searching and runs the computations. The adopted shunt-hybrid
APF (SHAPF) consists of an APF and a series of 7th tuned passive filter connected
to each phase. The performance of the proposed ADALINE-VSSLLMS control algorithm
employed for SHAPF is analyzed through a simulation in a MATLAB/Simulink
environment. Experimental results of a real-time prototype validate the efficacy of
the proposed control algorithm.
The proposed frequency-locked loop (FLL) utilizes the flat frequency response
characteristics of the moving window filter (MWF) in closed-loop and adaptive
sampling pulse adjustment for capacitance measurement. An operational amplifier
(op-amp) based relaxation oscillator generates a square wave whose fundamental sine
wave is extracted by MWF. Then, the fundamental sine wave is tracked by the FLL to
estimate its frequency which is inversely proportional to the unknown capacitance.
The FLL employs another MWF to track the center frequency and its variation due to
capacitance. The MWF offers an almost flat frequency response around the center
frequency in closed-loop. However, the small magnitude and phase errors observed in
the flat frequency response had been corrected by adjusting the sampling pulses
adaptively. Experimental investigation demonstrates the capabilities of the scheme
for wider and accurate capacitance measurement.
The proof of principle of an acquisition system of +/-50ppm repeatability, 10 V
range, real-time delay less than 1.2 its is presented. The system will be
integrated into the digital control loop of a high -voltage modulator under design
at ETH Zurich and University of Laval for the new particle accelerator under study
at CERN, the Compact LInear Collider (CLIC). Initial specifications are presented
and translated into system requirements. Main design choices are discussed and
Pspice simulation results are reported to prove that the proposed system meets the
demanding requirements.
In comparison with conventional operational amplifier, ring amplifier can achieve
better power efficiency for switched capacitor circuits. However, the cascade-
inverter architecture of ring amplifier may suffer from undesirable oscillation
which has a great impact on transient stability. This paper presents a latched-
based ring amplifier which is capable of decreasing the probability of oscillation.
Besides, two auto-zero schemes are employed in different pipelined stages to reduce
the common-mode voltage offset and to increase the stability. The prototype ADC was
fabricated in a 90-nm CMOS technology. The measured SNDR and SFDR are 52.06 dB and
63.15 dB, respectively, for a Nyquist frequency input sampled at 35 MS/s, and the
ADC consumes 3.65 mW.
Background/Aims: The organization of actin cytoskeleton in podocyte foot processes
plays a critical role in the maintenance of the glomerular filtration barrier. The
cAMP pathway is an important regulator of the actin network assembly in cells.
However, the role of the cAMP pathway in podocytes is not well understood. Type 1
adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue,
is a member of the family of enzymes that catalyses the formation of cAMP. In this
study, we characterized the expression and role of Adcy1 in the kidney. Methods:
Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ
hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1
knockout mice (Adcy1-/-). Results and Conclusion: Adcy1 is expressed in the kidney
specifically by podocytes. In the kidney, Adcy1 does not have a critical role in
normal physiological functioning as kidney histology and function are normal in
Adcy1-/-mice. However, albumin overload resulted in severe albuminuria in Adcy1-/-
mice, whereas wild-type control mice showed only mild albumin leakage to urine. In
conclusion, we have identified Adcy1 as a novel podocyte signaling protein that
seems to have a role in compensatory physiological processes in the glomerulus.
Copyright (C) 2010 S. Karger AG, Basel
The endogenous oxytocin system plays a vital role in facilitating parturition,
lactation and social interaction in humans and other mammals. It also impacts on a
number of important endocrine, immune and neurotransmitter systems. A well-
regulated oxytocin system has been proposed to increase resilience, and therefore
reduce the likelihood of an individual developing mental illness or substance
dependence. This review discusses the adverse external influences that can modulate
oxytocin receptor and protein levels and impact on substance use and mental health.
The paper highlights the impact of adversity such as poor maternal care, parental
substance use and child abuse or neglect. We review clinical and preclinical data
on the impact of adversity on the basis of the time of exposure from infancy and
early childhood, to adolescence, adulthood to older age. Previous research suggests
that dysregulation of the endogenous oxytocin system may be implicated in
determining susceptibility to stress, anxiety, addiction and mental health
conditions. The impact of external influence seems to be strongest in specific time
periods where the system shows experience-based development or natural fluctuations
in oxytocin levels. Interventions that target the oxytocin system during or soon
after exposure to adversity may prove protective. Copyright (C) 2016 Wolters Kluwer
Health, Inc. All rights reserved.
Background and aims Deficits in social cognitive abilities including emotion
recognition and theory of mind (ToM) can play a significant role in interpersonal
difficulties observed in alcohol use disorder (AUD). This meta-analysis aims to
estimate mean effect sizes of deficits in social cognition inAUD and examines the
effects of demographic and clinical confounding factors on the variability of
effect sizes across studies. Methods A literature review was conducted on research
reports published from January 1990 to January 2016. Twenty-five studies
investigating ToM and facial emotion recognition performances of 756 individuals
with AUD and 681 healthy controls were selected after applying inclusion and
exclusion criteria. Weighted effect sizes (d) were calculated for ToM, decoding and
reasoning aspects of ToM, total facial emotion recognition and recognition of each
of six basic emotions. Results Facial emotion recognition was significantly
impaired [d=0.65,95% confidence interval (CI)=0.42-0.89], particularly for disgust
and anger. AUDwas also associated with deficits in ToM (d=0.58, 95% CI=0.36-0.81).
These deficits were evident in tasks measuring both decoding (d=0.46, 95% CI=0.19-
0.73) and reasoning (d=0.72, 95% CI=0.37-1.06) aspects of ToM. The longer duration
of alcohol misuse and more depressive symptoms were associated with more severe
deficits in recognition of facial emotions. Conclusions Alcohol use disorder
appears to be associated with significant impairment in facial emotion recognition
and theory of mind.
Aims To investigate whether: (1) childmaltreatment is associated with life-time
cannabis use, early-onset cannabis use, daily cannabis use and DSM-IV cannabis
abuse in young adulthood; and (2) behaviour problems, tobacco use and alcohol use
at age 14 are associated with cannabis use. Design Birth cohort using linked
government agency child protection data to define exposure to child maltreatment.
Setting The Mater-University of Queensland Study of Pregnancy in Brisbane,
Australia. Participants Of the original cohort of 7223 mother and child pairs,
obtained from consecutive presentations for prenatal care at a hospital serving a
cross-section of the community, 3778 (52.3%) of the young people participated at
age 21 years. Measurements Exposure to child maltreatment was established by
substantiated government agency reports. Cannabis outcomes were by self-report
questionnaire and Composite International Diagnostic Interview (CIDI)-Auto at age
21. Associations were adjusted for a range of potential confounders. Additional
adjustment was carried out for variables measured at age 14-youth behaviour
problems [Achenbach Child Behavior Checklist (CBCL)], tobacco use and alcohol use.
Findings After adjustment, substantiated child maltreatment was associated with any
life-time cannabis use [odds ratio (OR) = 1.60, 95% confidence interval (CI) =
1.08-2.39], cannabis use prior to age 17 (OR = 2.47, 95 % CI = 1.67-3.65), daily
cannabis use (OR = 2.68, 95% CI = 1.49-4.81) and DSM-IV cannabis abuse/dependence
(OR = 1.72, 95% CI = 1.07-2.77). Externalizing behaviour and tobacco and alcohol
use at age 14 were associated significantly with almost all cannabis outcomes (P <
0.05), with internalizing behaviour associated inversely (P < 0.05). Conclusions
Children in Australia who are documented as having been maltreated are more likely
to go on to use cannabis before the age of 17, use cannabis as an adult, use
cannabis daily and meet DSM-IV criteria for cannabis dependence. Externalizing
behaviour in adolescence appears partly to mediate the association with adult
cannabis use.
The purpose of this project was to examine the emotional health and wellbeing of
Canadian caregivers of persons with significant mental health or addictions
problems. We assessed the emotional health of caregivers by care-receiver condition
type (i.e. mental health or addictions vs. physical or other health problems),
levels of caregiver stress and methods particularly for reducing stress among
caregivers of persons with mental health or addictions disorders. Weighted cross-
sectional data from the 2012 General Social Survey (Caregiving and Care Receiving)
were modelled using weighted descriptive and logistic regression analyses to
examine levels of stress and the emotional health and well-being of caregivers by
care-receiver condition type. Caregivers of persons with mental health or
addictions problems were more likely to report that caregiving was very stressful
and that they felt depressed, tired, worried or anxious, overwhelmed; lonely or
isolated; short-tempered or irritable; and resentful because of their caregiving
responsibilities. The results of this study suggest that mental health and
addictions caregivers may experience disparate stressors and require varying
services and supports relative to caregivers of persons with physical or other
health conditions.
Defined as sexually explicit material that elicits erotic thoughts, feelings, and
behaviours, internet pornography is a prevalent form of media that may facilitate
problematic use and craving for engagement. Research suggests that superordinate
cognitions and information processing, such as desire thinking and metacognition,
are central to the activation and escalation of craving in addictive behaviours.
The current study aimed to contribute to the literature by testing the proposed
metacognitive model of desire thinking and craving in a sample of problematic
pornography users, while revising the model by incorporating negative affect. From
a theoretical perspective, environmental cues trigger positive metacognitions about
desire thinking that directly influence desire thinking, resulting in the
escalation of craving, negative metacognitions, and negative affect. Participants
were recruited via an online survey and screened for problematic internet
pornography use. Path analyses were used to investigate relationships among the
aforementioned constructs in a final sample of 191 participants. Consistent with
previous research, results of this study validated the existence of metacognitive
processes in the activation of desire thinking and escalation of craving, while
indicating that desire thinking has the potential to influence negative affect.
Additionally, results supported the role of significant indirect relationships
between constructs within the revised model of metacognition, desire thinking, and
psychopathology. Collectively, the findings demonstrate the clinical value of a
metacognitive conceptualisation of problematic pornography use. Exploring the
metacognitive mechanisms that underpin problematic internet pornography use may
give rise to the development of new treatment and relapse prevention strategies.
(C) 2017 Elsevier Ltd. All rights reserved.
In many low-to-mid power applications, critical mode boost power factor corrector
converters are widely used because of its low switching loss and simple control.
However, near the zero crossing of the input line voltage, an input current
distortion and a low power factor are caused by delayed switching period and
negative input currents. Generally, an additional on-time method according to the
input voltage is used to compensate the input current distortion. However, a
detailed quantitative analysis for the exact additional on time has not been
studied till now. In this paper, the explicit form of the optimized additional on
time has been obtained using a quantitative analysis and the advantage of the
digital control. From a state trajectory and "net input charge" analysis, it is
shown that the optimized on time should be related to not only the input voltage,
but also the output power. Also, in order to improve the efficiency in a high input
and light load condition, circulating currents are reduced in the inevitable dead
angle with a gate turning-off technique. By using digital control, the optimized
additional on time and the gate turn-off technique have been implemented with the
90-230 V-rms input and 380 V/200 W output prototype.
For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the
optimal surgical approach and extent of lymph nodes dissection remain
controversial. Immunohistochemistry (IHC) has been reported to be available for
identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a
prospective case series of patients who underwent R0 resection and lower
mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical
University Union Hospital for Siewert type II AEJ. The outcomes were analyzed
retrospectively. A total of 1325 lymph nodes were collected from 49 patients,
grouped into 3 groups: lower mediastinal, paracardial, and abdominal. The former 2
groups were examined by monoclonal antibodies against Ber-Ep4 and CD44v6. The
incidence of LNMM in mediastinal group was 37% (18/49) for Ber-Ep4 and 33% (16/49)
for CD44v6. While in routine histological diagnosis, the number of patients with
the positive lymph nodes was 7 (14%). When combining IHC with histopathology (HE)
staining, the incidence of positive mediastinal lymph nodes was increased to 24%,
with a total number of 37 lymph nodes from 28 patients (57%). Micrometastases
indicated by Ber-Ep4 and CD44v6 were associated with the depth of tumor invasion
(P=0.020 and 0.037, respectively), histopathological nodal status (P=0.024 and
0.01, respectively), and Lauren classification (P=0.038 and, respectively).
Expression of CD44v6 and Ber-Ep4 was positively correlated (r=0.643, P<0.001). The
3- and 5-year survival rates for all patients were 66% and 50%, respectively. The
patients with LNMM had a lower 3-year survival rate of 51%, compared to 80% from no
LNMM group; 5-year survival rate was also lower in LNMM group, which is 29% versus
68% (P=0.006) in the no LNMM group. Patients with positive Ber-Ep4 cells had a
lower survival, but not statistically significant (P=0.058). CD44v6-positive group
had a significantly reduced survival (P<0.001). In patients group with negative
lower mediastinal lymph nodes, patients without LNMM obtained a significant
survival benefit (P=0.021). Our study demonstrated that routine test for LNMM is
necessary for patients with negative lymph nodes. As a positive prognostic factor,
thorough lower mediastinal lymphadenectomy in an invasive approach should be
considered when necessary. Ber-Ep4 and CD44v6 were shown to be great markers for
detecting LNMM.
Aims: Human papillomavirus (HPV) is known as causative for squamous cell carcinoma
(SCC) of the oropharynx, but is also found not infrequently in carcinomas of the
sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour
HPV33 and have a significant morphological overlap with adenoid cystic carcinoma
(ACC), a rare and aggressive carcinoma originating in the minor salivary glands.
Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been
reported. To clarify the occurrence of these tumours we screened a large material
for the presence of HPV-related ACC-like carcinoma. The identified tumours were
characterized immunohistochemically and with fluorescence in-situ hybridization,
and clinicopathological information for all cases is presented. Methods and
results: Forty-seven candidate cases were screened for presence of HPV. Six cases
were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas
of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB,
MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was
largely negative in contrast to what was found in ACC. One patient experienced a
local recurrence 11 years after initial treatment and the remaining five patients
were alive without evidence of disease. Conclusion: We report six new cases of HPV-
related ACC-like carcinoma and found that, although in a small material, the
prognosis for these patients seems more favourable than for ACC. For the
distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB
immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are
valuable.
The aim of the present study was to investigate the role of chemokine (C-X-C motif)
ligand 12 (CXCL12) and its receptor, chemokine (C-X-C motif) receptor 4 (CXCR4) in
the pathogenesis of adenomyosis (AD). Immunohistochemistry and reverse
transcription-quantitative polymerase chain reaction analysis were used to measure
the protein and mRNA expression of CXCL12 and CXCR4 in eutopic endometrial and
ectopic foci tissue samples. Samples from a total of 36 patients with AD (study
group) were compared with endometrial tissue samples from 33 patients who underwent
uterine fibroids surgery (control group) during the same period. All data are
presented as the mean +/- standard deviation and were analyzed with SPSS software
(version 16.0). Analysis of variance was used for between group analysis and
pairwise comparison was performed using Fisher's least significant difference post
hoc test. The results of the present study revealed that CXCL12 and CXCR4 protein
expression was significantly increased in ectopic foci tissue compared with eutopic
endometrial tissue samples from patients with AD. CXCL12 and CXCR4 protein
expression in ectopic foci and eutopic endometrial tissue samples were
significantly increased compared with the control group (P< 0.05 for between group
comparisons). No significant differences were identified in CXCL12 and CXCR4
protein expression between the proliferative and secretory phases within each
group. Furthermore, CXCL12 and CXCR4 mRNA expression was significantly increased in
ectopic foci tissue and eutopic endometrial tissue compared with the control group
(P< 0.05 for between group comparisons). CXCL12 mRNA expression was markedly
increased in ectopic foci tissue compared with eutopic endometrial tissue of
patients with AD. The expression of CXCR4 mRNA was significantly increased in
eutopic endometrial tissue compared with ectopic foci tissue and the control group
(P< 0.05 for between group comparisons). No significant differences were identified
in CXCL12 and CXCR4 mRNA expression between proliferative and secretory phase
within each group. In conclusion, CXCL12 and CXCR4 may induce the ectopia, and
promote the spread and localized growth of endometrial cells in the development of
AD.
Objective: We investigated the expression and potential roles of interleukin (IL)-
2, IL-4, IL-6, IL-10, IL-17A, IL-37, Interferon (IFN)-gamma, and Tumor Necrosis
Factor (TNF) in patients with adenomyosis. Materials and methods: This prospective
study examined 16 women with histologically proven adenomyosis and 52 women without
adenomyosis, all of whom were undergoing a hysterectomy for non-endometrial
pathology at the Department of Gynaecology, the First Hospital of Jilin University,
Changchun, China, from December 2011 to September 2012. Serum samples were
collected from the patients, and the concentrations of serum IL-2, IL-4, IL-6, IL-
10, IL-17A, IL-37, IFN-gamma, and TNF were measured by Enzyme-Linked Immunosorbent
Assay (ELISA). We then calculated specificity and sensitivity of cytokines, taking
Cancer Antigen (CA) 125 as a reference, distinguishing cases from controls by
receiver operating characteristic (ROC) curve. The correlation between individual
cytokines and CA 125 was also analysed. Results: IL-37 was detectable in 69.2% and
the other cytokines in 30.8% of sera samples from the 52 controls. All the eight
cytokines were detectable in the sera samples from 16 patients with adenomyosis.
Significantly higher levels of serum IL-37 and IL-10 and significantly lower levels
of serum IL-17A and TNF were detected in adenomyosis patients when compared with
controls (p< 0.05). Conclusions: Serum levels of IL-10, IL-17A, IL-37, and TNF
varied significantly between cases and controls, and could be involved in the
pathogenesis of adenomyosis.
Objectives: Inflammatory response and cytokine activation are markedly stimulated
in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-
inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine,
released by all cell types, binds to a class of G protein-coupled receptors to
induce various skeletal muscle effects. The aim of this work was to investigate
whether activation of adenosine receptors, particularly adenosine A2B receptors,
could stimulate IL-6 gene expression in rat L6 skeletal muscle cells. Materials and
Methods: The rat L6 skeletal muscle cells were cultured in 25 cm2 flasks. These
differentiated cells were treated and then quantitative reverse transcription-
polymerase chain reaction (Probe-based) was used to analyze IL-6 gene expression
level among different treatment conditions. Results: Adenosine-5'-N-ethyluronamide
(NECA), a stable adenosine analogue, concentration-and time-dependently stimulates
IL-6 gene expression in skeletal muscle cells. The effect of NECA is inhibited by a
selective adenosine A2B receptor antagonist, PSB 603. By using cyclic adenosine
monophosphate (cAMP)-arising reagent forskolin, cAMP is found to be involved in the
up-regulation of IL-6 induction. Conclusion: Here, a novel relationship between
adenosine and IL-6 up-regulation has been demonstrated for the first time; IL-6 up-
regulation induced by NECA is mediated by adenosine A2B receptor activation in
skeletal muscle and is dependent on mainly a cAMP pathway. Adenosine A2B receptors
are, thus, potentially important pharmacological targets in treating inflammation
and related diseases in skeletal muscle tissues.
Adenosine triphosphate- binding cassette proteins constitute a large family of
active transporters through extracellular and intracellular membranes. Increased
drug efflux based on adenosine triphosphate- binding cassette protein activity is
related to the development of cancer cell chemoresistance. Several articles have
focused on adenosine triphosphate- binding cassette gene expression profiles
( signatures), based on the expression of all 49 human adenosine triphosphate-
binding cassette genes, in individual tumor types and reported connections to
established clinicopathological features. The aim of this study was to test our
theory about the existence of adenosine triphosphate- binding cassette gene
expression profiles common to multiple types of tumors, which may modify tumor
progression and provide clinically relevant information. Such general adenosine
triphosphate- binding cassette profiles could constitute a new attribute of
carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients-
breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation
and quantitative real- time polymerase chain reaction were followed. Gene
expression data from individual tumor types as well as a merged tumor dataset were
analyzed by bioinformatics tools. Several general adenosine triphosphate- binding
cassette profiles, with differences in gene functions, were established and shown
to have significant relations to clinicopathological features such as tumor size,
histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed
among the most upregulated or downregulated ones. In conclusion, the results
supported our theory about general adenosine triphosphate- binding cassette gene
expression profiles and their importance for cancer on clinical as well as research
levels. The presence of ABCC7 ( official symbol CFTR) among the genes with key
roles in the profiles supports the emerging evidence about its crucial role in
various cancers.
Background:To perform a molecular epidemiological analysis of viral conjunctivitis
among excess conjunctivitis cases recorded at the University Hospital of Patras,
Greece, for the period March to June 2012. Methods: A structured questionnaire
containing demographic and clinical data was developed in order to collect
retrospective data on the cases. Eye swab specimens were collected and molecular
detection of adenoviruses was performed by nested PCR. Positive results were
confirmed by sequencing. To determine the relatedness between the isolated
sequences, a phylogenetic analysis was conducted. Results: The epidemiological
analysis (including retrospective data) included 231 conjunctivitis cases (47.1%
male, and 52.8% female). Based on clinical features 205 of the cases were diagnosed
of viral origin (46.3% male and 53.7% female), 4 of bacterial origin (50% male and
50% female) while 22 were undefined conjunctivitis. The outbreak excess cases
(included 156 cases) affected all age groups regardless gender predilection. For
the positive samples indicated that 29 samples (72.5%) were AdV17, and 5 (12.5%) as
AdV54. Conclusions: Molecular analysis could define the cause of viral
conjunctivitis, while epidemiological data contributed to the assessment of the
risk factors and underlined possible preventive measures. This study is one of the
very few on viral conjunctivitis in Greece. This outbreak underscores the need for
a national surveillance system for acute infectious conjunctivitis outbreaks. The
epidemiological as well as molecular investigation on HAdV ocular infections is
rather absent in Greece, which has no surveillance system for viral conjunctivitis.
The dopamine receptor-D4 and the dopamine transporter have been investigated for
their role in attention deficit hyperactivity disorder (ADHD) in children. Reports
of their genetic association with ADHD have shown mixed results. The aim of the
study was to evaluate the association of variable number tandem repeats (VNTRs) of
the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with
44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was
conducted at a tertiary care centre in Mumbai. Variable number tandem repeats of
DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by PCR-AGE. Several allele
repeats of the genes were observed in the screened subjects. Statistical
significance was observed for the 10R/10R genotype of the DAT1 3'UTR VNTR between
cases and controls.
Objective-Endothelial activation is implicated in atherogenesis and diabetes. The
role of peroxisome proliferator-activated receptor-delta (PPAR-delta) in
endothelial activation remains poorly understood. In this study, we investigated
the anti-inflammatory effect of PPAR-delta and the mechanism involved. Methods and
Results-In human umbilical vein endothelial cells (HUVECs), the synthetic PPAR-
delta ligands GW0742 and GW501516 significantly inhibited tumor necrosis factor
(TNF)-alpha-induced expression of vascular cell adhesion molecule-1 and E-selectin
(assayed by real-time RT-PCR and Northern blotting), as well as the ensuing
endothelial-leukocyte adhesion. Activation of PPAR-delta upregulated the expression
of antioxidant genes superoxide dismutase 1, catalase, and thioredoxin and
decreased reactive oxygen species production in ECs. Chromatin immunoprecipitation
assays showed that GW0742 switched the association of BCL-6, a transcription
repressor, from PPAR-delta to the vascular cell adhesion molecule ( VCAM)-1
promoter. Small interfering RNA reduced endogenous PPAR-delta expression but
potentiated the suppressive effect of GW0742 on EC activation, which suggests that
the nonliganded PPAR-delta may have an opposite effect. Conclusions-We have
demonstrated that ligand activation of PPAR-delta in ECs has a potent
antiinflammatory effect, probably via a binary mechanism involving the induction of
antioxidative genes and the release of nuclear corepressors. PPAR-delta agonists
may have a potential for treating inflammatory diseases such as atherosclerosis and
diabetes.
Aims/hypothesis The aim of this study was to investigate changes in insulin
sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from
long-term nitric oxide (NO)-deficient rats. Methods Male Sprague-Dawley rats
received N-omega-nitro-Larginine methyl ester (L-NAME 0.5 mg/ml) in their drinking
water for 4 weeks, while control rats received plain drinking water. During the
experimental period, changes in plasma glucose, insulin and C-peptide levels were
measured. After administration of L-NAME for 4 weeks, insulin sensitivity was
evaluated in vivo and in vitro. An insulin binding assay was also performed to
determine the number and binding affinity of insulin receptors in adipocytes.
Adipocyte Retn mRNA levels were examined using northern blotting. Results
Successful induction of NO deficiency was demonstrated by an increase in systemic
blood pressure. No difference in plasma glucose levels was found between the two
groups. Compared with the control rats, plasma insulin and C-peptide levels were
significantly decreased in the NO-deficient rats, and insulin sensitivity was
significantly increased. Insulin-stimulated glucose uptake and insulin binding
capacity, but not binding affinity, were significantly increased in adipocytes
isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not
plasma resistin levels, were significantly decreased in NO-deficient rats, and the
Retn mRNA levels were negatively correlated with insulin sensitivity.
Conclusions/interpretation Insulin sensitivity was increased in NO-deficient rats
and this was associated with insulin binding capacity and downregulated Retn
expression. These findings suggest that NO plays a regulatory role in metabolism.
Dysregulation of NO production may result in the development of metabolic
disorders.
Leptin is an adipocytokine that regulates body weight, and maintains energy
homeostasis by promoting reduced food intake and increasing energy expenditure.
Leptin expression and secretion is regulated by various factors including hormones
and fatty acids. Butyrate is a short-chain fatty acid that acts as source of energy
in humans. We determined whether this fatty acid can play a role in leptin
expression in fully differentiated human adipocytes. Mature differentiated
adipocytes were incubated with or without increasing concentrations of butyrate.
RNA was extracted and leptin mRNA expression was examined by Northern blot
analysis. Moreover, the cells were incubated with regulators that may affect
signals which may alter leptin expression and analyzed with Northern blotting.
Butyrate stimulated leptin expression, and stimulated mitogen activated protein
kinase (MAPK) and phospho-CREB signaling in a time-dependent manner. Prior
treatment of the cells with signal transduction inhibitors as pertusis toxin, G(i)
protein antagonist, PD98059 (a MAPK inhibitor), and wortmannin (a PI3K inhibitor)
abolished leptin mRNA expression. These results suggest that butyrate can regulate
leptin expression in humans at the transcriptional level. This is accomplished by:
1) G(i) protein-coupled receptors specific for short-chain fatty acids, and 2) MAPK
and phosphatidylinositol-3-kinase (P13K) signaling pathways.
Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is
subject to hormonal or metabolic control. In the present study, we have
characterized an adipose tissue transcription factor that is influenced by
fasting/refeeding regimens and insulin. Northern blotting showed that refeeding
increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an
increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-
element-binding protein)-1c in adipose tissue were also increased by refeeding. In
streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels
of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and
electrophoretic mobility-shift assay studies indicated that the putative sterol
response element is located in the region between bases - 109 and - 100 of the
human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to
differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4,
suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin
immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the
putative sterol-response element in the GLUT4. Furthermore, treating
streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In
addition, we have identified an Sp1 binding site adjacent to the functional sterol-
response element in the GLUT4 promoter. The Sp1 site appears to play an additive
role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that
upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in
adipose tissue.
Background: Autologous fat grafting is a prevalent technique used for softtissue
augmentation; however, the poor survival rate of the grafted tissue remains a
drawback of this method. Although adipose-derived stem cells (ASCs) are an
attractive candidate for enhancing graft retention, the poor posttransplantation
viability of these cells limits their application. Here we investigated whether
overexpression of the antiapoptotic protein heat-shock protein 70 (Hsp70) could
enhance ASCs' therapeutic potential for fat transplant survival. Methods:
Recombinant adenoviral vectors were used to overexpress Hsp70 in ASCs isolated from
a healthy woman. The Hsp70 expression was assessed by quantitative real- time
polymerase chain reaction and Western blot analyses. The adipose tissue granules
aspirated from anotherwomanweremixed with ASCs expressing green fluorescent protein
(GFP)-tagged Hsp70 (group A) or GFP alone (group B), untreated ASCs (group C), and
phosphate-buffered saline (group D). Fat mixtures were then injected subcutaneously
into the backs of nude mice, and graft survival was compared after 3 months.
Results: Adipose-derived stem cells transduced with recombinant adenoviral vectors
exhibited significantly increased Hsp70 expression in vitro. Meanwhile, weight
retention analyses demonstrated that fat grafts using the group A cell population
exhibited significantly higher survival rates than the other treatment groups in
vivo. Moreover, histological analyses revealed that fat grafts containing GFP-
Hsp70-expressing ASCs yielded significantly lower levels of tissue fibrosis and fat
cysts/vacuoles, higher capillary densities, and increased numbers of viable
adipocytes than the control groups. Conclusions: Our data indicate that Hsp70
overexpression enhances the efficacy of ASC therapy by improving the survival and
quality of the transplanted fat tissues.
Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT)
in the context of obesity, mediates obesity-induced metabolic dysfunction and
insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH)
induce body weight reductions and insulin resistance of different magnitudes,
suggesting different hypoxia inducible factor (HIF)-1 alpha-related activity.
Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH,
or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated
(pAKT)/AKT), HIF-1 alpha transcription using chromatin immunoprecipitation (ChIP)-
sequencing, angiogenesis using immunohistochemistry, and gene expression of
different fat cell markers and HIF-1 alpha gene targets using quantitative
polymerase chain reaction or microarrays. Body and vWAT weights were reduced in
hypoxia (SH >IH >RA; P>>SH = RA; P < 0.001). IH induces preferential whitening of
vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1
alpha activity that is unsustained over time and is accompanied by concurrent
vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous
changes in HIF-1 alpha transcriptional activity and brown/beige/white fat balance
in IH and SH should enable exploration of mechanisms by which altered sympathetic
outflow, such as that which occurs in apneic patients, results in whitening, rather
than the anticipated browning of adipose tissues that occurs in SH.
Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located
in the perivascular niche. Based on their surface markers, these have been assigned
to two main categories: CD31(-)/CD45(-)/CD34(+)/CD146(-) cells (adventitial
stromal/stem cells [ASCs]) and CD31(-)/CD45(-)/CD34(-)/CD146(+) cells (pericytes
[PCs]). These populations display heterogeneity of unknown significance. We
hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of
primitivity, could help to better define ASC and PC subclasses. To this end, the
stromal vascular fraction from a human lipoaspirate was simultaneously stained with
fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH
substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual
ASCs (n=67) and PCs (n=73) selected from the extremities of the ALDH-staining
spectrum were transcriptionally profiled by Fluidigm single-cell quantitative
polymerase chain reaction for a predefined set (n=429) of marker genes. To these
single-cell data, we applied differential expression and principal component and
clustering analysis, as well as an original gene coexpression network
reconstruction algorithm. Despite the stochasticity at the single-cell level,
covariation of gene expression analysis yielded multiple network connectivity
parameters suggesting that these perivascular progenitor cell subclasses possess
the following order of maturity: (a) ALDH(br)ASC (most primitive); (b)
ALDH(dim)ASC; (c) ALDH(br)PC; (d) ALDH(dim)PC (least primitive). This order was
independently supported by specific combinations of class-specific expressed genes
and further confirmed by the analysis of associated signaling pathways. In
conclusion, single-cell transcriptional analysis of four populations isolated from
fat by surface markers and enzyme activity suggests a developmental hierarchy among
perivascular mesenchymal stem cells supported by markers and coexpression networks.
Stem Cells2017;35:1273-1289
Extensive research has been performed to determine the effect of freezing protocol
and cryopreservation agents on the viability of adipose tissue-derived stromal/stem
cells (ASCs) as well as other cells. Unfortunately, the conclusion one may draw
after decades of research utilizing fundamentally similar cryopreservation
techniques is that a barrier exists, which precludes full recovery. We hypothesize
that agents capable of inducing a subset of heat shock proteins (HSPs) and
chaperones will reduce the intrinsic barriers to the post-thaw recovery of ASCs.
ASCs were exposed to 43 degrees C for 1 h to upregulate HSPs, and the temporal HSP
expression profile postheat shock was determined by performing quantitative
polymerase chain reaction (PCR) and western blotting assays. The expression levels
of HSP70 and HSP32 were found to be maximum at 3 h after the heat shock, whereas
HSP90 and HSP27 remain unchanged. The heat shocked ASCs cryopreserved during
maximal HSPs expression exhibited increased post-thaw viability than the nonheat
shocked samples. Histochemical staining and quantitative reverse transcription-PCR
indicated that the ASC differentiation potential was retained. Thus, suggesting
that the upregulation of HSPs before a freezing insult is beneficial to ASCs and a
potential alternative to the use of harmful cryoprotective agents.
The long-term effect of feeding the catecholamine analog ractopamine (RAC;
ractopamine hydrochloride, Elanco Animal Health, Indianapolis, IN) on the
expression of genes involved in energy and lipid metabolism in subcutaneous adipose
tissue was studied. Large White pigs (84 kg) were fed corn- and soybean meal-based
diets supplemented with 0, 20, or 60 mg/kg of RAC for 14, 28, or 42 d. Expression
(mRNA abundance) in adipose tissue of sterol regulatory binding protein-1 (SREBP-
1), PPAR alpha, PPAR gamma 2, fatty acid synthase (FAS), glucose transporter 4
(GLUT4), and stearoyl-CoA desaturase was determined by Northern blotting. Feed
intakes did not differ, and RAC (20 and 60 mg/kg) improved BW gain at d 14, 28, and
42 (P < 0.05) and increased loin eye area (measured on d 42 only; P < 0.05).
Expression of SREBP-1 and PPAR gamma 2 declined (P < 0.05) with RAC by d 28 and 42,
whereas expression of PPAR alpha was increased (P < 0.05) on d 14, 28, and 42.
After 14 d, expression of FAS and GLUT4 was decreased (P < 0.05) with 60 mg/kg of
RAC, whereas both RAC concentrations attenuated FAS expression on d 28 and 42.
Overall, adipose tissue stearoyl-CoA desaturase expression was not affected by RAC
but showed somewhat less expression (P < 0.15) on d 28 at 60 mg/kg of RAC. Although
prolonged, chronic RAC feeding most likely downregulates adipose tissue membrane
beta-adrenergic receptors, mRNA abundances of anabolic lipid metabolism
transcription factors, glucose transporters, and enzymes (SREBP-1, PPAR gamma 2,
FAS, GLUT4) were still attenuated up to d 42. Conversely, a transcription factor
related to oxidative metabolism expression (PPAR alpha) was enhanced. We conclude
that even after 42 d, RAC still decreased expression of lipogenic genes in adipose
tissue by yet undefined cyclic adenosine monophosphate-directed mechanisms, but in
contemporary lean pigs, this effect is likely of limited practical significance.
Conveyor systems allow quick and efficient transportation for a wide variety of
materials, which make them very popular in the material handling and packaging
industries. Many kinds of conveying systems are available and used according to the
various needs of different industries. Adjustable speed drives are used for the
operation of the conveyors used in a number of industries. We can use adjustable
electric drives in a number of industrial applications. A typical adjustable speed
drive consists of an induction motor and a power electronic converter. In most
cases, motor speed is commanded so that the control system requires an actual speed
signal for closing the speed loop. In industrial applications, speed sensors, as
well as sensorless solutions, are used. Due to the possibility of current speed
sensor noises and for maintenance and economic aspects, the trend is to substitute
speed sensors by computational solutions. Comprehensive reviews of the sensorless
drives show that there are still some persistent problems associated with the
sensorless control, that needs new solutions. In ASDs, the advanced control
approach of IM is the FOC method, used in modern industrial drives. The current
stator controller is the integral part of various FOC systems. In the classical FOC
solution, PI or hysteresis controllers are generally used. However, PCCs are
reported to have better properties. System sensitivity to inaccuracy and changes of
motor equivalent circuit parameters are another problem in electrical drives.
Almost all of the FOC systems are very sensitive to such inaccuracies; therefore,
some parameters should be estimated online, and a robust structure of the control
is required. The real-time implementation of the system is an important task even
for electric drives or power converters.
Four groupA streptococcal glycolipopeptide vaccine candidates with different
lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of
the compounds was evaluated by macrophage and dendritic cell uptake studies and by
in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates
showed significant induction of the IgG response.
Despite the immense public health successes of immunization over the past century,
effective vaccines are still lacking for globally important pathogens such as human
immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in
immunology and biotechnology over the past few decades have facilitated a shift
from empirical to rational vaccine design, opening possibilities for improved
vaccines. Some of the most important advancements include (i) the purification of
subunit antigens with high safety profiles, (ii) the identification of innate
pattern recognition receptors (PRRs) and cognate agonists responsible for inducing
immune responses, and (iii) developments in nano- and microparticle fabrication and
characterization techniques. Advances in particle engineering now allow highly
tunable physicochemical properties of particle-based vaccines, including
composition, size, shape, surface characteristics, and degradability. Enhanced
collaborative efforts between researchers in immunology and materials science are
expected to rise to next-generation vaccines. This process will be significantly
aided by a greater understanding of the immunological principles guiding vaccine
antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted
adjuvants and particle physicochemical properties, this review aims to provide an
overview of the current literature to guide and focus rational particle-based
vaccine design efforts.
Critical issues about scientific reproducibility have been raised about biomedical
research, including the reliability of data and analyses within a given study. The
case example in this article examined a reproducibility issue pertaining to the use
of administrative data systems for evaluation of child maltreatment (CM)
prevention, making use of a prevention study conducted over a decade ago that
provided a unique opportunity. The place-randomization study, which randomized
counties to condition, found that community-wide implementation of a parenting and
family support intervention produced positive impact on county-wide rates for
substantiated CM cases and out-of-home placements, documented through a state
information system. The key consideration is whether and to what extent the
administrative record data re-examined retroactively a decade later for the
original study's time period would yield comparable results to those based on data
acquired at the time of the study. The results indicated that despite small changes
over time, the same data patterns and statistical effects were reproducible for the
two archival outcome variables. For substantiated CM, the reproduced analyses
reflected higher effect sizes and a clear pattern of reduction as a function of
intervention. For out-of-home placements, effect sizes were quite comparable to the
original ones, reflecting preventive impact. Overall, this case study illustrated
the verifiability of data reproducibility in the context of a population outcome
evaluation, which underscores the importance of reliable population-prevalence
measurement as an essential part of a comprehensive public health strategy aimed at
the prevention of CM. (C) 2016 Elsevier Ltd. All rights reserved.
Aims: Ancient DNA (aDNA) extracted from historical bones is damaged and fragmented
into short segments, present in low quantity, and usually copurified with microbial
DNA. A wide range of DNA quantification methods are available. The aim of this
study was to compare the five most common DNA quantification methods for aDNA.
Materials and Methods: Quantification methods were tested on DNA extracted from
skeletal material originating from an early medieval burial site. The tested
methods included ultraviolet (UV) absorbance, real-time quantitative polymerase
chain reaction (qPCR) based on SYBR (R) green detection, real-time qPCR based on a
forensic kit, quantification via fluorescent dyes bonded to DNA, and fragmentary
analysis. Differences between groups were tested using a paired t-test. Results:
Methods that measure total DNA present in the sample (NanoDrop (TM) UV
spectrophotometer and Qubit (R) fluorometer) showed the highest concentrations.
Methods based on real-time qPCR underestimated the quantity of aDNA. The most
accurate method of aDNA quantification was fragmentary analysis, which also allows
DNA quantification of the desired length and is not affected by PCR inhibitors.
Conclusions: Methods based on the quantification of the total amount of DNA in
samples are unsuitable for ancient samples as they overestimate the amount of DNA
presumably due to the presence of microbial DNA. Real-time qPCR methods give
undervalued results due to DNA damage and the presence of PCR inhibitors. DNA
quantification methods based on fragment analysis show not only the quantity of DNA
but also fragment length.
Considerable evidence suggests that adolescent exposure to delta-9-
tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the
risk of developing schizophrenia-related symptoms in early adulthood. In the
present study, we used a combination of behavioral and molecular analyses with in
vivo neuronal electrophysiology to compare the long-termeffects of adolescent
versus adulthood THC exposure in rats. We report that adolescent, but not adult,
THC exposure induces long-term neuropsychiatric-like phenotypes similar to those
observed in clinical populations. Thus, adolescent THC exposure induced behavioral
abnormalities resembling positive and negative schizophrenia-related endophenotypes
and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA)
pathway. Furthermore, we observed profound alterations in several prefrontal
cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our
findings demonstrate a profound dissociation in relative risk profiles for
adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and
molecular markers resembling neuropsychiatric pathology.
Several studies have confirmed that maltreatment and abuse in childhood are related
to conduct problems. Less is known about such relationships with concurrent
adversities in adolescence and, also, when compared with other severe adversities
and possible multiple additive effects. The study encompassed a community
population of 4881 adolescents 15-16 years of age 50.1 % boys and 49.9 % girls.
Youth with and without conduct problem scores within the deviant range on the
Strength and Difficulties Questionnaire (SDQ) was compared on 12 concurrent
adversities. Based on self-reports, 4.4 % of the adolescents had conduct problem
scores within the deviant range and more girls (5.1 %) than boys (3.7 %). In the
deviant conduct problem group, 65.1 % had experienced two or more concurrent
adversities compared with 26.3 % of youths in the non-deviant group (OR 5.23, 95 %
CI 3.91-7.01). Likewise, the deviant conduct problem group was from 1.71 to 8.43
times more at the risk of experiencing the different adversities. Parental mental
health problems and experiences of violence were multivariately strongest
associated with conduct problem scores within the deviant range on the SDQ. A
strong multiple additive relationship with adversities was found. Two-thirds of
youth with SDQ conduct problem scores within the deviant range reported two or more
concurrent adversities. Clinicians should seek information about kinds and amount
of possible traumatic adversities in youth with conduct problems and offer evidence
based treatment.
Objective: To investigate the association between the perception of expressed
emotion and psychopathology of school-going adolescents in a non-clinical sample.
Methods: The cross-sectional field study was conducted in Kocaeli, Turkey, and
comprised high-school students during the 2014-15 school years. Data was collected
using the Information Collection Form, Strengths and Difficulties Questionnaire and
Shortened Level of Expressed Emotion Scale. SPSS 21 was used for data analysis.
Results: Of the 487 subjects, 295(60.57%) were girls and 192(39.43%) were boys. The
overall median age was 16 (inter-quartile range: 15-17 years). There were
significant positive relationships between the scales in terms of emotional
problems (p<0.001), behavioural problems (p<0.001), Attention-deficit/hyperactivity
disorder (p<0.001), and peer relationship problems (p<0.001). There was also a
negative significant relationship between pro-social behaviours and expressed
emotion (p<0.001). Conclusion: The concept of perceived expressed emotion in non-
clinical adolescents is useful in alarming clinicians and preventing mental
disorders.
This study proposes and tests a new model that seeks to explain associations
between religion, spirituality and health outcomes among adolescents. Specifically,
we test for mediating effects of perceived spirituality on religion-health
relations. Using data from the 4-H Study of Positive Youth Development, we find
that perceived spirituality mediates religion-health relations, but that varies
based on youths' conceptualisation of spirituality. With findings confirming that
perceived spirituality potentially promote youths' psychosocial health, we offer
some future research directions and implications regarding relations between
youths' spirituality, religion and health behaviours.
Purpose The aim of this study is to find out the overall prevalence rates for the
major forms of abuse among adolescents in the Kingdom of Saudi Arabia and the
differences in prevalence by age, gender and living arrangement. Methods The cross-
sectional study was conducted in secondary high schools in five of the 13 main
regions of Kingdom of Saudi Arabia during 2012. Through a multistage stratified
sampling technique, a sample (n = 16 939) of adolescents (15-19 years) were
identified and invited to participate. The ISPCAN Child Abuse Screening Tool-Child
was used for data collection. The previous year's occurrence of violence exposure,
psychological, physical and sexual abuse, and neglect were assessed. Results Nearly
90% of the adolescents were between 16 and 18 years of age, and over 80% were cared
for by both of their biological parents. Annual prevalence of various forms of
abuse in the year before the 2012 assessment ranged between 0.10 and 0.65, with the
lowest rate for sexual abuse and the highest for psychological abuse.
Significantly, greater rates of all forms of abuse/exposure were found when
participants lived with their mother or father only (versus with both), and even
greater rates for all when they lived with their biological parent and a step-
parent. Rates for violence exposure, psychological abuse and neglect were
significantly greater for girls, and rate of sexual abuse was greater for boys.
Conclusions More attention should be given to the effect of adolescent maltreatment
particularly among girls. In addition, sexual abuse prevention programme should be
targeted among boys.
Background Studies of children with food allergy typically only include the mother
and have not investigated the relationship between the amount of allergen needed to
elicit a clinical reaction (threshold) and health-related quality of life (HRQL).
Our aims were (i) to compare self-reported and parent-reported HRQL in different
age groups, (ii) to evaluate the impact of severity of allergic reaction and
threshold on HRQL, and (iii) to investigate factors associated with patient-
reported and parent-reported HRQL. Methods Age-appropriate Food Allergy Quality of
Life Questionnaires (FAQLQ) were completed by 73 children, 49 adolescents and 29
adults with peanut, hazelnut or egg allergy. Parents (197 mothers, 120 fathers)
assessed their child's HRQL using the FAQLQ-Parent form. Clinical data and
threshold values were obtained from a hospital database. Significant factors for
HRQL were investigated using univariate and multivariate regression. Results Female
patients reported greater impact of food allergy on HRQL than males did. Egg and
hazelnut thresholds did not affect HRQL, but lower peanut threshold was associated
with worse HRQL. Both parents scored their child's HRQL better than the child's own
assessment, but whereas mother-reported HRQL was significantly affected by
limitations in the child's social life, father-reported HRQL was affected by
limitations in the family's social life. Severity of allergic reaction did not
contribute significantly to HRQL. Conclusion The risk of accidental allergen
ingestion and limitations in social life are associated with worse HRQL. Fathers
provide a unique perspective and should have a greater opportunity to contribute to
food allergy research.
Pre-ejection period (PEP) reactivity to reward has been posited as a specific index
of behavioral approach and incentive motivation, suggesting it might be uniquely
associated with the affective and motivational deficits of anhedonia. This study
evaluated PEP reactivity to a reward task as a predictor of depressive symptoms
among adolescents, examining global depressive symptoms as well as specific
anhedonic and nonanhedonic symptoms clusters. Participants included 76 adolescents,
ages 11-15 years (52% female). This study found marginal support for an association
between PEP reactivity to reward and concurrent anhedonia symptoms, but no
association with nonanhedonic or the global scale. Findings are discussed in terms
of potential associations between peripheral psychophysiological measures and
dopaminergic functioning and also the utility of this measure for future research
on anhedonia.
Several studies have recently demonstrated that the volumes of specific brain
regions are reduced in children and adolescents with post-traumatic stress disorder
(PTSD) compared with those of healthy controls. Our study investigated the
potential association between early traumatic experiences and altered brain regions
and functions. We conducted a systematic review of the scientific literature
regarding functional magnetic resonance imaging and a meta-analysis of structural
magnetic resonance imaging studies that investigated cerebral region volumes in
pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the
PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data
regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial
volumes that fit the inclusion criteria were extracted and combined in a meta-
analysis that assessed differences between groups. The meta-analysis found reduced
total corpus callosum areas and reduced total cerebral and intracranial volumes in
the patients with PTSD. The total hippocampus (left and right hippocampus) and gray
matter volumes of the amygdala and frontal lobe were also reduced, but these
differences were not significant. The functional studies revealed differences in
brain region activation in response to stimuli in the post-traumatic stress
symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD
exhibited structural and functional brain abnormalities and that some of the
abnormalities occurred in different brain regions than those observed in adults.
Childhood maltreatment is strongly associated with depression, which is
characterized by reduced reactivity to reward. Identifying factors that mitigate
risk for depression in maltreated children is important for understanding
etiological links between maltreatment and depression as well as improving early
intervention and prevention. We examine whether high reward reactivity at
behavioral and neurobiological levels is a marker of resilience to depressive
symptomology in adolescence following childhood maltreatment. A sample of 59
adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44)
completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal
changes to positive relative to neutral images were extracted in basal ganglia
regions of interest. Participants also completed a behavioral reward-processing
task outside the scanner. Depression symptoms were assessed at the time of the MRI
and again 2 years later. Greater reward reactivity across behavioral and
neurobiological measures moderated the association of maltreatment with baseline
depression. Specifically, faster reaction time (RT) to cues paired with monetary
reward relative to those unpaired with reward and greater BOLD signal in the left
pallidum was associated with lower depression symptoms in maltreated youth.
Longitudinally, greater BOLD signal in the left putamen moderated change in
depression scores over time, such that higher levels of reward response were
associated with lower increases in depression over time among maltreated youths.
Reactivity to monetary reward and positive social images, at both behavioral and
neurobiological levels, is a potential marker of resilience to depression among
adolescents exposed to maltreatment. These findings add to a growing body of work
highlighting individual differences in reactivity to reward as a core
neurodevelopmental mechanism in the etiology of depression.
While exposure to adverse family experiences (AFEs), subset of adverse childhood
experiences (ACEs), has been associated with childhood obesity, less is known about
the impact of exposures to each type of AFE. Using 2011-2012 National Survey of
Children's Health data, we evaluated associations between exposure to individual
AFEs and overweight/obesity status in children 10 years or older, adjusting for
socio-demographic factors. Caregivers reported their child's height, weight, and
exposure to nine AFEs; body mass index (BMI) was classified by Center for Disease
Control and Prevention's (CDC) guidelines. At Mayo Clinic, we calculated
frequencies and weighted estimates of socio-demographic factors and AFEs.
Unadjusted and adjusted weighted multinomial logistic regression models were
employed to assess the independent associations of each AFE and the different AFE
composite scores with BMI category. Exposure to two or more AFEs was independently
associated with increased odds of overweight (odds ratio [OR], 1.33; 95% confidence
interval [CI], 1.13, 1.56) and obese (OR, 1.45; 95% CI, 1.21, 1.73) status after
adjustment for age, household income, parents' education-level, race and sex. Death
of parent (OR, 1.59; 95% CI, 1.18, 2.15) and hardship due to family income (OR,
1.26; 95% CI, 1.06, 1.50) were independently associated with obesity status with
adjustment for other AFEs and socio-demographic factors. Our results suggest that,
in addition to cumulative exposure to AFEs, exposure to certain childhood
experiences are more strongly associated with childhood obesity than others. Death
of parent and hardship due to family income are individual AFEs, which are strongly
predictive of obesity. (C) 2016 Elsevier Inc. All rights reserved.
BackgroundIncreasing evidence supports that mentalization deficits may have a role
in the genesis of young age depression; however, few studies examined this issue in
clinical populations. MethodsOutpatients aged 14-21, suffering from various
psychiatric disorders, were assessed using the Mentalization Questionnaire (MZQ),
the Beck Depression Inventory (BDI), and the Childhood Trauma Questionnaire (CTQ),
using data from age-matched healthy students for comparison. The relationship
between CTQ, MZQ, and BDI scores was examined at the cross-sectional level,
including mediation analyses, and longitudinally, in a subsample who underwent a
psychotherapy intervention. ResultsOf 83 subjects, 33 (39.8%) had mentalization
levels that were 1 standard deviation below those of comparison subjects. In the
whole sample, the levels of mentalization were inversely associated with BDI
(r=-.68, p<.001) and CTQ scores (r=-.30, p=.006). Moreover, MZQ scores mediated a
large part of the effect of childhood trauma on depression (total effect: 10.6, 95%
CI: 5.3, 15.9; direct effect: 6.5, 95% CI: 2.1, 10.8; indirect effect: 4.1, 95% CI:
1.5, 7.4). This effect was almost entirely explained by the Affect Regulation
subscale. In patients re-evaluated after four sessions (n=37), the decrease in BDI
scores correlated with the increase in MZQ scores (r=.40, p=.02). ConclusionsIn a
juvenile clinical sample, deficits of mentalization abilities were associated with
the severity of depression and explained part of the depressogenic effects of
childhood trauma.
Social network sites (SNSs) are relatively new phenomena, and the relationship
between SNSs and psychopathology remains unclear. The purpose of this study was to
evaluate the type of SNSs depressed adolescents use and the incidence of depressive
disclosure on SNSs among them. The study was designed to be cross-sectional. The
sample consisted of 53 adolescents diagnosed with depressive disorder, as confirmed
by K-SADS-PL, and 55 non-depressed adolescents. The Children's Depression
Inventory, Social Anxiety Scale and Social Network Use Questionnaire were
administered. The primary finding was that the amount of time spent on the Internet
and on SNSs was significantly higher among depressed adolescents than non-depressed
adolescents. Additionally, depressed adolescents reported significantly higher
disclosure of anhedonia, worthlessness, guilt, loss of concentration, irritability
and thoughts of suicide on SNSs. The intensity of the depression sharing was
significantly higher in the depressed group. Depressed young people use social
networks to express their symptoms. Adolescents' disclosure on social networks may
be able to guide relatives, friends and mental health professionals.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) and anxiety are
frequently comorbid disorders associated with different types of abnormal
performance on neuropsychological tests. Although some studies have shown that
comorbid anxiety alters ADHD test performance, results inconsistently show both
improvements and worsening of different abilities, with failures to replicate
across different anxiety disorders. Alternatively, trait anxiety may reflect a more
stable influence on ADHD test performance than various diagnosable anxiety
disorders. Method: To better understand the possible enhancing or deleterious
effects of anxiety on ADHD cognitive impairments, this study examined the effect of
individual differences in trait anxiety measured by the Multidimensional Anxiety
Scale for Children (MASC) on a battery of computerized, rapid-performance tests
measuring attention and impulsivity-related performance in 98 Diagnostic and
Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) Combined-Subtype
ADHD adolescents and 123 healthy controls. It was hypothesized that trait anxiety
would attenuate response inhibition and attention deficits in ADHD. Results: ADHD-
diagnosed adolescents with higher trait anxiety performed better on indices of
sustained attention, reaction time, and motor variability, and had altered overall
test-performance strategy, while response inhibition was affected in both ADHD and
non-ADHD. Conclusions: This study provides the first evidence that pathological
levels of anxiety are not needed to see differences in ADHD neuropsychological test
performance. Instead, mildly elevated trait anxiety confers a protective influence
by reducing the degree of impairment seen in ADHD. These findings suggest that
better performing ADHD adolescents might have optimized levels of cortical arousal,
and raise new questions about how best to identify the neurobiological substrates
responsible for the beneficial effects.
BackgroundNeglect is often overlooked in adolescence, due in part to assumptions
about autonomy and misinterpretation of behaviors being part of normal adolescent
development. Emotional maltreatment (abuse or neglect) has a damaging effect
throughout the lifespan, but is rarely recognized amongst adolescents. Our review
aims to identify features that adolescents experiencing neglect and/ or emotional
maltreatment report. MethodA rapid review methodology searched 8 databases (1990-
2014), supplemented by hand searching journals, and references, identifying 2,568
abstracts. Two independent reviews were undertaken of 279 articles, by trained
reviewers, using standardised critical appraisal. Eligible studies: primary studies
of children aged 13-17 years, with substantiated neglect and/ or emotional
maltreatment, containing self-reported features. Results19 publications from 13
studies were included, demonstrating associations between both neglect and
emotional maltreatment with internalising features (9 studies) including
depression, post traumatic symptomatology and anxiety; emotional maltreatment was
associated with suicidal ideation, while neglect was not (1 study); neglect was
associated with alcohol related problems (3 studies), substance misuse (2 studies),
delinquency for boys (1 study), teenage pregnancy (1 study), and general
victimization for girls (1 study), while emotionally maltreated girls reported more
externalising symptoms (1 study). Dating violence victimization was associated with
neglect and emotional maltreatment (2 studies), while emotional abuse of boys, but
not neglect, was associated with dating violence perpetration (1 study), and
neither neglect nor emotional maltreatment had an association with low self-esteem
(2 studies). Neither neglect nor emotional maltreatment had an effect on school
performance (1 study), but neglected boys showed greater school engagement than
neglected girls (1 study). ConclusionsIf asked, neglected or emotionally maltreated
adolescents describe significant difficulties with their mental health, social
relationships, and alcohol or substance misuse. Practitioners working with youths
who exhibit these features should recognize the detrimental impact of maltreatment
at this developmental stage, and identify whether maltreatment is a contributory
factor that should be addressed.
Background: Rumination predicts depression in adults and adolescents. The
development of rumination has been linked to parenting practices, but only limited
research has investigated this and research has tended to rely on self-report
parenting measures. Aims: To investigate the relationship between female adolescent
rumination and maternal modelling, criticism and positivity using an observational
measure of parental behaviour. Method: A cross-sectional design was used. Daughters
aged 16-18 years and their mothers (n = 154 dyads) completed questionnaire measures
of rumination and affect. Mothers of girls with rumination scores in the upper and
lower quartile (both n = 26) also completed the Five Minute Speech Sample, which
was used to measure maternal criticism and positivity. Results: Mothers of low
rumination girls made significantly more positive comments about their daughters
than the mothers of high ruminators. Mothers made very few critical comments. Self-
reported rumination was not correlated in mothers and daughters, suggesting a lack
of support for the potential role of modelling. Conclusion: Overall, low maternal
positivity was associated with rumination in female adolescents. There was no
evidence that maternal rumination or criticism were associated with adolescent
rumination. The results suggest a number of implications for future research,
including the need for prospective longitudinal studies using observational
parenting measures.
An Internet-based relapse prevention supplement to adolescent substance abuse
treatment programming is a promising modality to reinforce treatment gains and
enhance recovery; however, an evidence base is lacking. To assess the efficacy of
the online Navigating my Journey (NmJ) program. 129 adolescent-aged participants
(ages 13-23) receiving substance abuse treatment participated in a randomized
parallel group study comparing two conditions: experimental (NmJ) versus attention
control (viewed wellness articles from the Nemours Foundation at their discretion).
Participants in the experimental condition were asked to complete 12 core lessons
over 3 months. Lesson content was developed to teach evidence-based relapse
prevention skills. Data were collected at four time points: baseline, 1-month
follow up, 3-month follow up, and 6-month follow up. We used a linear mixed
modeling approach to test for differences between conditions on each outcome.
Participants in the experimental condition reported a significantly greater
increase in motivation to reduce or not misuse drugs from baseline to 3-month
follow up and from baseline to 6-month follow up, compared to the control
participants. Participants in the experimental condition also reported a greater
decrease in drug use score from baseline to 3-month follow up, compared to the
control participants. An analysis of age as a potential moderator suggested that
the intervention may be more effective for older adolescents. Greater use of the
program was associated with greater self-efficacy and lower self-reported substance
use over time. Relapse prevention treatment with adolescents may be facilitated by
theory-based online interventions. NCT02125539.
Carotenoids are plant secondary metabolites that comprise two main groups:
carotenes and xanthophylls. The latter group includes zeaxanthin which is
synthesized by beta-carotene hydroxylase catalyzing the hydroxylation of the beta-
rings of beta-carotene molecules. To develop tools to alter carotenoid biosynthesis
in plants, we isolated a cDNA clone encoding a candidate beta-carotene hydroxylase,
CrtH1, from the flower petals of Adonis aestivalis. CrtH1 protein has homology to
beta-carotene hydroxylases from other organisms, and possesses the four histidine
motifs conserved in this family of enzymes. Sequence analysis predicted the
presence of a putative plastid transit peptide at the amino terminus and four
transmembrane helical regions. Southern-blot analysis showed CrtH1 to be encoded by
a multicopy gene family with at least three members in A. aestivalis. Analysis of
CrtH1 transcript abundance by Northern blotting indicates it is highly expressed in
flower petals, roots and stems, with relatively low expression in leaves and
developing seeds. CrtH1 was able to catalyze the formation of zeaxanthin and its
intermediate precursor beta-cryptoxanthin from beta-carotene in functional assays
conducted in E. coli. Expression of CrtH1 in Arabidopsis thaliana wild type and a
mutant deficient for endogenous beta-carotene hydroxylases enhanced the
biosynthesis of violaxanthin in the seeds.
The cDNA AmphiARF , encoding a novel member of ARF family was for the first time
identified from the gut cDNA library of amphioxus Branchiostoma becheri
tsingtauense . The deduced amino acid sequence includes the motifs involved in GTP
binding (DVGG, NKQD and SAK) and hydrolysis (GXDXXGK), and a glycine at position 2
for N-terminal myristoylation, which are all characteristic of ARFs. However, it
has a 46 amino acid C-terminal extension (positions 183-227), which was not found
in any ARF family previously described including ARF-like proteins. This suggests
that AmphiARF is a new member of ARF family, which was also supported by the
phylogenetic analysis. It is highly likely that the extended C-terminal of AmphiARF
is a novel addition occurring after cephalochordate/vertebrate split. Northern
blotting analysis revealed that AmphiARF transcript was present in all tissues
examined, consistent with the involvement of ARFs in the fundamental role like
vesicular trafficking of proteins.
In whole cell patch-clamp recordings, we characterized the L-type Ca2+ currents in
bovine adrenal zona fasciculata (AZF) cells and explored their role, along with the
role of T-type channels, in ACTH- and angiotensin II (ANG II)-stimulated cortisol
secretion. Two distinct dihydropyridine-sensitive L-type currents were identified,
both of which were activated at relatively hyperpolarized potentials. One activated
with rapid kinetics and, in conjunction with Northern blotting and PCR, was
determined to be Ca(v)1.3. The other, expressed in approximately one-half of AZF
cells, activated with extremely slow voltage-dependent kinetics and combined
properties not previously reported for an L-type Ca2+ channel. The T-type Ca2+
channel antagonist 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-
fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2) inhibited Ca(v)3.2 current in these
cells, as well as ACTH- and ANG II-stimulated cortisol secretion, at concentrations
that did not affect L-type currents. In contrast, nifedipine specifically inhibited
L-type currents and cortisol secretion, but less effectively than TTA-P2.
Diphenylbutylpiperidine Ca2+ antagonists, including pimozide, penfluridol, and
fluspirilene, and the dihydropyridine niguldipine blocked Ca(v)3.2 and L-type
currents and inhibited ACTH-stimulated cortisol secretion with similar potency.
This study shows that bovine AZF cells express three Ca2+ channels, the voltage-
dependent gating and kinetics of which could orchestrate complex mechanisms linking
peptide hormone receptors to cortisol secretion through action potentials or
sustained depolarization. The function of the novel, slowly activating L-type
channel is of particular interest in this respect. Regardless, the well-correlated
selective inhibition of T- and L-type currents and ACTH- and ANG II-stimulated
cortisol secretion by TTA-P2 and nifedipine establish the critical importance of
these channels in AZF cell physiology.
Background Although it has been well established that atrial natriuretic peptide
gene-disrupted (ANPS(-/-)) mice are a useful model of salt-sensitive hypertension,
surprisingly little is known about the control of their intrarenal renin-
angiotensin system (RAS) and pressure-natriuresis mechanism, key components in
blood pressure, fluid and electrolyte regulation. The aim of this study was to
determine whether ANP disruption results in changes in the renal and adrenal local
RAS and the acute pressure natriuresis mechanism. Methods Renal and adrenal renin,
angiotensin type 1 (AT(1))((A and B)) and angiotensin type 2 (AT(2)) receptor
messenger RNA expression levels were determined by northern blotting or real time
reverse transcriptase polymerase chain reaction. Plasma aldosterone and renal and
adrenal angiotensin II peptide levels were determined by radioimmunoassay. To
examine the acute pressure natriuresis response, changes in renal interstitial
hydrostatic pressure (RIHP) were assessed after manipulations of renal arterial
pressure (RAP) in anaesthetized mice. Results Renal and adrenal renin mRNA and
angiotensin II levels were lower in ANPS(-/-) and (+/-) mice compared with (+/+)
mice. ANP(-/-) mice also had greater renal AT(1A) and adrenal AT2 mRNA levels
compared with the other genotypes. RAP and RIHP were significantly higher in (-/-)
mice compared with (+/+) mice. Furthermore, there was a blunted slope of the RAP-
RIHP relationship after increases in RAP in ANP(-/-) mice. Conclusion These data
indicate that ANP disruption results in a blunting of the dynamic properties of the
acute pressure-natriuresis mechanism at increased levels of RAP, as well as a
reduced expression of renal and adrenal local RAS.
Background: Anaphylaxis is a life-threatening emergency of which reliable
epidemiological data are lacking. This study aimed to analyze how quickly patients
presenting with anaphylaxis were treated in emergency and whether treatment
followed the European Academy of Allergy and Clinical Immunology (EAACI)
guidelines. Methods: Patient data were collected between April 2009 and April 2013.
Emergency doctors completed a questionnaire for adult patients presenting at the
emergency department (ED) of the St. Pierre hospital in Brussels with anaphylaxis.
Inclusion criteria were based on the Sampson criteria of anaphylaxis. Data were
analyzed using a Microsoft Excel database. Results: About 0.04% (100/230878) of all
emergency visits in adults presented with anaphylaxis. 64% of patients received
their first medical help later than 30 min after symptom onset. 67% of patients
received adrenaline, 85% oral antihistamines, and 89% received IV
glucocorticosteroids. 46/100 patients were discharged directly from the ED, of
which 87% received further medical prescriptions for self-administration: 67%
corticosteroids, 83% antihistamines, and 9% intramuscular adrenaline. 74% were
instructed to consult an allergologist for adequate diagnosis. 54/100 patients were
hospitalized. Conclusion: The majority of patients were treated according to the
EAACI guidelines for management of anaphylaxis, but only a minority received the
recommended adrenaline auto-injector for self-administration at discharge. Because
the majority of patients received medical help later than 30 min after symptom
onset, adrenaline auto-injector prescription is a necessity. The low rate of
doctors prescribing adrenaline auto-injectors in the ED setting underlines the need
to train doctors of various backgrounds in prevention and treatment of anaphylaxis
and the close collaboration with allergologists.
BACKGROUND: Allergy immunotherapy can result in systemic allergic reactions and
even life-threatening anaphylaxis requiring epinephrine administration. OBJECTIVE:
The objective of this study was to describe epinephrine use in the clinical trial
development programs of 3 rapidly dissolving sublingual immunotherapy tablets
(SLITtablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Horsholm, Denmark/Torii
Pharmaceutical Co., Ltd., Tokyo, Japan). METHODS: Data on epinephrine use were
collected from 13 timothy grass SLIT-tablet trials (MK-7243; <= 2800 bioequivalent
allergen units/75,000 SQ-T dose, n =2497; placebo, n = 2139), 5 short ragweed SLIT-
tablet trials (MK-3641; <= 12 Amb a 1-U, n =1725; placebo, n =770), and 11 house
dust mite (HDM) SLIT-tablet trials (MK-8237; <= 12 SQ-HDM; n=3930; placebo, n
=2246). RESULTS: In grass SLIT-tablet trials, epinephrine was used 13 times (grass
SLIT-tablet, n =10; placebo, n =3). Eight administrations were for grass SLIT-
tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for
local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was
used 9 times in 8 subjects (ragweed SLIT-tablet, n =7; placebo, n =1 =2
administrations for protracted anaphylaxis]). Four administrations were for ragweed
SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth
and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was
administered 13 times (HDM SLIT-tablet, n =8; placebo, n =5). Four administrations
were for HDM SLITtablet- related AEs: 1 for systemic allergic reaction and 3 for
local events. Of the 16 epinephrine administrations for events related to SLIT-
tablet treatment, 11 occurred within the first week of treatment (7 administrations
on day 1) and 5 were subject self-administered. CONCLUSIONS: Epinephrine
administrations in response to SLIT-tablet-related reactions in clinical trials are
uncommon, typically occur within the first week of treatment, and are rarely self-
administered. All SLIT-tablet-related events treated with epinephrine were
nonserious. (C) 2016 American Academy of Allergy, Asthma & Immunology
3 beta-Hydroxysteroid dehydrogenase type II deficiency (3 beta HSD2) congenital
adrenal hyperplasia is a rare cause of ambiguous genitalia, resulting in abnormal
virilisation in both 46XY and 46XX. We describe a case of 46XY ambiguous genitalia
that was misdiagnosed as androgen insensitivity syndrome. The correct diagnosis was
made after adrenarche. Genotyping demonstrated compound heterozygosity in two
alleles, the previously described c.244G >A (p.Ala82Thr), and a novel 931C >.T(p.
Gln311*) variant. We suggest that adrenarche unmasked the condition by driving
cortisol production to rates that caused the mutant 3bHSD2 enzyme to become rate
limiting for cortisol production. This case illustrates how markedly different the
effects of this condition may be on androgen production compared with
glucocorticoid and mineralocorticoid production. It also demonstrates how current
guidelines based on urinary steroids and cortisol sufficiency may not arrive at the
correct diagnosis, and underlines the importance of gene testing in the work-up of
disorders of sexual differentiation.
Background: Attachment anxiety and avoidance have been found to be associated with
worry. A substantial body of research suggests that intolerance of uncertainty
(IOU) is a phenomenon which predicts level of worry, yet the relationship between
attachment, IOU and worry remains to be investigated. Methods: The present study
recruited 281 participants from the community within Australia to complete an
online survey incorporating the Intolerance of Uncertainty Scale, the Experiences
in Close Relationships Scale-Revised, and the Penn State Worry Questionnaire.
Results: The analyses revealed attachment anxiety and attachment avoidance were
positively correlated with IOU, and that attachment anxiety, attachment avoidance
and IOU were positively correlated with worry. Furthermore, IOU was found to
mediate the relationship between attachment anxiety and worry, even when attachment
avoidance was entered as a covariate. By contrast, for the relationship between
attachment avoidance and worry, intolerance of uncertainty only mediated the
association if attachment anxiety was ignored. Conclusions: The results of the
study suggest that IOU may play a key role in the relationship between adult
attachment difficulties and the experience of worry. These findings may have
significant implications for the conceptualisation and psychological treatment of
attachment related difficulties. (C) 2017 Elsevier Ltd. All rights reserved.
Context: Psychosocial factors can impact lung transplant outcomes. However, it is
currently unknown whether abuse survivorship influences lung transplant survival.
Objective: To characterize the abuse history of adult lung transplant patients and
determine whether such history is associated with mortality. Patients and Other
Participants: Adult lung transplant recipients evaluated from 2000 to 2004. Main
Outcome Measures: The main outcome was post-lung transplantation survival. The
secondary outcomes included demographic, transplantation, or psychological
assessment differences between those with a history of abuse survivorship and those
without. Results: Thirty-three lung transplant recipients (35.5% male, median age:
55 years) were included. A history of abuse survivorship was common (24.2%) and was
associated with decreased survival following lung transplantation (P = .003). There
was no difference in sex, marital status, or smoking history between abuse
survivors and those who denied being the victim of abuse. Abuse survivors had a
higher Personality Assessment Screener total score, a measure of maladaptive
personality traits (P = .02). Conclusion: Abuse survivorship is common in lung
transplant patients and associated with increased posttransplant mortality and
increased maladaptive personality traits. This preliminary evidence suggests that
lung transplant patients should be screened for abuse history and provided with
appropriate treatment of survivorship issues to potentially improve their health
outcomes from transplantation.
Background: Symptom clusters have not previously been explored among individuals
with atrial fibrillation of any type. Objective: The purpose of this study is to
determine the number of symptom clusters present among adults with chronic atrial
fibrillation and to explore sociodemographic and clinical factors potentially
associated with cluster membership. Methods: This was a cross-sectional secondary
data analysis of 335 Australian community-dwelling adults with chronic (recurrent
paroxysmal, persistent, or permanent) atrial fibrillation. We used self-reported
symptoms and agglomerative hierarchical cluster analysis to determine the number
and content of symptom clusters present. Results: There were slightly more male
(52%) than female participants, with a mean (SD) age of 72 (11.25) years. Three
symptom clusters were evident, including a vagal cluster (nausea and diaphoresis),
a tired cluster (fatigue/lethargy, weakness, syncope/dizziness, and
dyspnea/breathlessness), and a heart cluster (chest pain/discomfort and
palpitations/fluttering). We compared patient characteristics among those with all
the symptoms in the cluster, those with some of the symptoms in the cluster, and
those with none of the symptoms in the cluster. The only statistically significant
differences were in age, gender, and the use of antiarrhythmic medications for the
heart cluster. Women were more likely to have the heart symptom cluster than men
were. Individuals with all of the symptoms in the heart cluster were younger (69.6
vs 73.7 years; P = .029) than those with none of the symptoms in the heart cluster
and were more likely to be on antiarrhythmic medications. Conclusion: Three unique
atrial fibrillation symptom clusters were identified in this study population.
This review discusses the unmet needs of patients with attention
deficit/hyperactivity disorder (ADHD) who are transitioning into adulthood.
Although awareness and recognition of ADHD in children, adolescents, and adults
have improved in recent years, there is often an interruption in management of the
disorder when adolescent patients transition to adult health care services. This
review has the following objectives: (1) to identify key issues patients with ADHD
(with or without an early diagnosis) face during transition into adulthood; (2) to
review the current clinical practice and country-specific approaches to the
management of the transition into adulthood for patients with ADHD; (3) to discuss
challenges facing clinicians and their patients when drug treatment for ADHD is
initiated; (4) to review current ADHD guidelines on transition management in Hong
Kong, Singapore, South Korea, Turkey, and Africa; and (5) to examine economic
consequences associated with ADHD. The review suggests that the transition period
to adult ADHD may be an underresearched and underserved area. The transition period
plays an important role regarding how ADHD symptoms may be perceived and acted upon
by adult psychiatrists. Further studies are needed to explore the characteristics
of the transition period. If only a fraction of adolescents go on to have mental
disorders during adulthood, especially ADHD, it is crucial to identify their
characteristics to target appropriate interventions at the beginning of the course
of illness. There continues to be low recognition of adult ADHD and a severe lack
of medical services equipped to diagnose and care for patients with ADHD
transitioning from child to adult services.
Recent studies have examined non-suicidal self-injury in community and clinical
samples, but there is no published research on non-suicidal self-injury in
individuals with autism spectrum disorder. This lack of research is surprising,
since individuals with autism spectrum disorder have high rates of risk factors for
non-suicidal self-injury, including depression and poor emotion regulation skills.
Using an online survey, we examined non-suicidal self-injury methods, frequency,
severity, functions, and initial motivations in adults with autism spectrum
disorder (n=42). We also compared their non-suicidal self-injury characteristics to
those of a gender-matched group of adults without autism spectrum disorder (n=42).
Of the participants with autism spectrum disorder, 50% reported a history of non-
suicidal self-injury. This proportion is higher than non-suicidal self-injury rates
previously reported for college students, adult community samples, and adolescents
with autism spectrum disorder, which suggests that adults with autism spectrum
disorder have increased risk for engaging in non-suicidal self-injury. Women with
autism spectrum disorder were significantly more likely to endorse non-suicidal
self-injury, relative to men with autism spectrum disorder. A history of non-
suicidal self-injury was not related to current depression or emotion dysregulation
for the participants with autism spectrum disorder. Non-suicidal self-injury
characteristics among the adults with autism spectrum disorder were similar to non-
suicidal self-injury in adults without autism spectrum disorder. These preliminary
findings highlight the need for increased awareness and further research about non-
suicidal self-injury within autism spectrum disorder.
Field programmable gate arrays (FPGAs) have established themselves as one of the
preferred digital implementation platforms in a plethora of current industrial
applications, and extensions and improvements are still continuously being included
in the devices. This paper reviews recent advancements in FPGA technology,
emphasizing the novel features that may significantly contribute to the development
of more efficient digital systems for industrial applications. Special attention is
paid to the design paradigm shift caused by the availability of increasingly
powerful embedded (and soft) processors, which transformed FPGAs from hardware
accelerators to very powerful system-on-chip (SoC) platforms. New analog resources,
floating-point operators, and hard memory controllers are also described, because
of the great advantages they provide to designers. Software tools are being
strongly influenced by the design paradigm shift, which requires fromthem a much
better support for software developers. Focusing mainly on this issue, recent
advancements in software resources [intellectual property (IP) cores and design
tools] are also reviewed. The impact of new FPGA features in industrial
applications is analyzed in detail in three main areas, namely digital real-time
simulation, advanced control techniques, and electronic instrumentation, with focus
on mechatronics, robotics, and power systems design. The way digital systems are
being currently designed in these areas is comprehensively reviewed, and a critical
analysis of how they could significantly benefit from new FPGA features is
presented.
Research documents how exposure to adversity in childhood leads to negative health
outcomes across the lifespan. Less is known about protective factors - aspects of
the individual, family, and community that promote good health despite exposure to
adversity. Guided by the Resilience Portfolio Model, this study examined protective
factors associated with physical health in a sample of adolescents and adults
exposed to high levels of adversity including child abuse. A rural community sample
of 2565 individuals with average age of 30 participated in surveys via computer
assisted software. Participants completed self-report measures of physical health,
adversity, and a range of protective factors drawn from research on resilience.
Participants reporting a greater burden of childhood victimization and current
financial strain (but not other adverse life events) had poorer physical health,
but those with strengths in emotion regulation, meaning making, community support,
social support, and practicing forgiveness reported better health. As hypothesized,
strengths across resilience portfolio domains (regulatory, meaning making, and
interpersonal) had independent, positive associations with health related quality
of life after accounting for participants' exposure to adversity. Prevention and
intervention efforts for child maltreatment should focus on bolstering a portfolio
of strengths. The foundation of the work needs to begin with families early in the
lifespan. (C) 2017 Elsevier Ltd. All rights reserved.
Background: Given growing numbers of older adults with mental and substance use
disorders (MSUDs), this study examined the association between ten types of adverse
childhood experiences (ACEs) and lifetime MSUDs among those aged 50+. Methods: Data
(N=14,738 for the 50+ age group) came from the 2012 to 2013 National Epidemiologic
Survey on Alcohol and Related Conditions. Using multivariable binary logistic
regression analyses, we examined relationships between ten ACEs and six lifetime
MSUDs (major depressive disorder (MDD) and anxiety, post-traumatic stress, alcohol
use, drug use, and nicotine use disorders). Gender differences were examined using
tests of interaction effects and gender-separate logistic regression models.
Results: Of the sample, 53.2% of women and 50.0% of men reported at least one ACE.
For both genders, parental/other adult's substance abuse was the most prevalent
(22.6%), followed by physical abuse, and emotional neglect. Child abuse and neglect
and parental/other adult's mental illness and substance abuse had small but
consistently significant associations with MSUDs (e.g., odds ratio = 1.28, 95% CI=
1.12-1.46 for parental/other adult's substance misuse and MDD). Although the
relationship between total number of ACEs andMSUDs was cumulative for both men and
women, the associations of physical abuse, sexual abuse, emotional neglect, and
parental separation/divorce with MSUDs were stronger among men. Conclusions: This
study underscores the significant yet modest association between ACEs and lifetime
MSUDs in late life. More research is needed to investigate why ACEs seem to have
greater effects on older men and to discern the sources of gender differences in
ACEs' effects.
Background: Adverse childhood experiences (ACEs) have been associated with an
increased risk of a variety of diseases, including cancer. However, research has
largely ignored how ACEs impact cancer screening, a potential intermediate outcome.
As such, the present study examined the association between ACEs and ever and
recent use of Papanicolaou (Pap) test, among women aged 21 and older. Materials and
Methods: Analyses used the 2009 Tennessee Behavioral Risk Factor Surveillance
System (n = 1527) to model odds of ever and recently (within the last 3 years)
engaging in Pap tests screening from nine different adversities. Bivariate and
multivariate logistic regression models were run to accomplish this. Results: In
bivariate and multivariate models, living in a household in which adults treated
each other violently increased odds of ever receiving a Pap test. In bivariate
models, physical and sexual abuse was associated with decreased odds of receiving a
recent Pap test. After accounting for confounders, only the latter association
remained significant. Conclusions: Results highlight a potential mechanism by which
early childhood experiences can impact the development of cervical cancer.
Providers of care should consider modifications to their screening practices,
including screening for child abuse, to better serve all women.
Substantial research shows that early adversity, including child abuse and neglect,
is associated with diminished health across the life course and across generations.
Less well understood is the relationship between early adversity and adult
socioeconomic status, including education, employment, and income. Collectively,
these outcomes provide an indication of overall life opportunity. We analyzed data
from 10 states and the District of Columbia that used the adverse childhood
experiences (ACE) module in the 2010 Behavioral Risk Factor Surveillance System to
examine the association between ACEs and adult education, employment, and income.
Compared to participants with no ACEs, those with higher ACE scores were more
likely to report high school non-completion, unemployment, and living in a
household below the federal poverty level. This evidence suggests that preventing
early adversity may impact health and life opportunities that reverberate across
generations. Current efforts to prevent early adversity might be more successful if
they broaden public and professional understanding (i.e., the narrative) of the
links between early adversity and poverty. We discuss our findings within the
context of structural policies and processes that may further contribute to the
intergenerational continuity of child abuse and neglect and poverty. (C) 2016 The
Authors. Published by Elsevier Ltd.
Adverse childhood experiences (ACEs) have been linked to increased use of tobacco
products later in life. However, studies to date have ignored smokeless tobacco
products. To address this, data from the 2011 Behavioral Risk Factor Surveillance
System, which interviewed adults 18 years and over (N = 102,716) were analyzed.
Logistic regression models were fit to estimate odds ratios of ever smoking,
current smoking and current smokeless tobacco use in relation to ACEs. Results
showed that less than 4 % of respondents currently used smokeless tobacco products,
while 44.95 and 18.57 % reported ever and current smoking, respectively. Physical
abuse (OR 1.40; 95 % CI 1.14, 1.72), emotional abuse (OR 1.41; 95 % CI 1.19, 1.67),
sexual abuse (OR 0.70; 95 % CI 0.51, 0.95), living with a drug user (OR 1.50; 95 %
CI 1.17, 1.93), living with someone who was jailed (OR 1.50; 95 % CI 1.11, 2.02)
and having parents who were separated or divorced (OR 1.31; 95 % CI 1.09, 1.57)
were associated with smokeless tobacco use in unadjusted models. After accounting
for confounders, physical abuse (OR 1.43; 95 % CI 1.16, 1.78), emotional abuse (OR
1.32; 95 % CI 1.10, 1.57), living with a problem drinker (OR 1.30; 95 % CI 1.08,
1.58), living with a drug user (OR 1.31; 95 % CI 1.00, 1.72) and living with adults
who treated each other violently (OR 1.30; 95 % CI 1.05, 1.62) were associated with
smokeless tobacco use. Living with someone who was mentally ill (OR 0.70; 95 % CI
0.53, 0.92) was associated with smokeless tobacco use after accounting for
confounders and all ACEs. Results indicated that some childhood adversities are
associated with use of smokeless tobacco products. Special attention is needed to
prevent tobacco use of different types among those experiencing ACEs.
Objective: To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium
valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register
(www.ukaed.info). Methods: Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV
(n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted.
All patients had anonymously provided information on seizure type and frequency and
completed the Liverpool Adverse Event Profile (LAEP). Results: The number of
seizure-free patients in the last 4 weeks was overall CBZ/VPA
/LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was
CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was
CBZ/VPA/LTG/LEV=59%/71%/67%/57%. Mean LAEP scores were
CBZ/VPA/LTG/LEV/CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly
higher in patients reporting depression and in patients with active epilepsy than
in patients without depression and remission. Central nervous system (CNS) adverse
effects including memory problems, difficulty concentrating, depression,
unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were
significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of
anger was significantly more frequent in LEV, and depression was significantly more
frequent in CBZ compared to the other drugs. Conclusion: In this Internet-based
register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were
similar. Self-reported CNS adverse effects were significantly more frequent than in
controls. In addition, anger was associated with LEV and depression with CBZ.
Confounding factors were depression and uncontrolled epilepsy.
Background: Aeluropus lagopoides is a salt and drought tolerant grass from Poaceae
family, distributed widely in arid regions. There is almost no information about
the genetics or genome of this close relative of wheat that stands harsh conditions
of deserts. Objectives: The main aim of this research was to isolation and
characterization of salt and drought inducible genes from A. lagopoides by
Differential Display Amplified fragment length polymorphism (DD-AFLP) method.
Material and Methods: In this research A. lagopoides was grown under salt or
drought conditions and after modifying the DD-AFLP method several fragments were
isolated and after nomination their induction was studied by reverse northern
blotting. Results: DD-AFLP led to the improvement of a non-radioactive method for
which many parameters were optimized. Having screened approximately 1600
transcript-derived fragments, 1.4 percent of them showed varied expression levels
in response to high salt or drought treatments. The relative abundance of twenty
one selected differentially expressed fragments was inspected by reverse northern
blotting that affirmed the potential of this applied method. Sequence comparisons
revealed that some of the isolated genes are involved in osmotic adjustment,
regulation of transcription, cation transportation and stress responses. These data
clearly show that the modified DD-AFLP method was a successful and reliable
approach for the isolation of differentially expressed genes.
We had previously reported that Vibrio hollisae produces aerobactin in response to
iron starvation. In the present study, we identified in V hollisae ATCC33564 the
aerobactin system cluster which consists of eight genes, hatCDB, iucABCD and iutA.
The hatCDB genes encode proteins homologous to components of bacterial ATP binding
cassette transport systems for ferric aerobactin. The iucABCD and iutA orthologs
code for aerobactin biosynthesis enzymes and the ferric aerobactin receptor,
respectively. In accordance with their iron-regulated expression, putative Fur box
sequences were found within the respective promoter regions of hatC, iucA and iutA.
The monocistronic iutA transcript was detected by northern blotting. Moreover,
phenotypic comparison between the wild-type strain and its targeted gene
disruptants supported the biological functions that were expected for the
respective operons and genes on the basis of the homology search. The arrangement
of the aerobactin gene clusters thus far found in Vibrio and enterobacterial
species was compared and discussed from an evolutionary point of view. (c) 2006
Elsevier SAS. All rights reserved.
Active Electronically Scanned Array (AESA) technology will enable next generation
radars achieve better jamming resistance capability and low probability of
intercept by spreading their emissions over a wide frequency range. These radars
systems consist of a large number of transmit/receive modules (TRMs) which are
electronically scanned in a tight time-synchronized manner. This requires digital
control to move closer to the radio front end on the antennas. Other emerging
technologies, such as cognitive radars and MIMO radars, will continue to drive the
need for complex timing, synchronization, and high mix RF and digital measurement
requirements. To meet these challenges, radar engineers will need a platform based
approach which delivers capabilities such as multi-channel phase aligned
measurements over wide bandwidths and high-throughput streaming. This paper
discusses the fundamentals of AESA radars and trends in radar systems. It analyzes
the impact of these trends on test system architecture and explains how the
advances in PXI modular instrumentation can meet these challenging requirements.
Obesity continues to be a major global problem. Various cancers are related to
obesity and proper understanding of their aetiology, especially their molecular
tumour biology is important for early diagnosis and better treatment. Genes play an
important role in the development of obesity. Few genes such as leptin, leptin
receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and
melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity.
MicroRNAs control gene expression via mRNA degradation and protein translation
inhibition and influence cell differentiation, cell growth and cell death.
Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2,
extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of
the breast, uterus, renal, thyroid and liver are also related to obesity. Any
disturbance in the production of sex hormones and insulin, leads to distortion in
the balance between cell proliferation, differentiation and apoptosis. The possible
mechanism linking obesity to cancer involves alteration in the level of adipokines
and sex hormones. These mediators act as biomarkers for cancer progression and act
as targets for cancer therapy and prevention. Interestingly, many anti-cancerous
drugs are also beneficial in treating obesity and vice versa. We also reviewed the
possible link in the mechanism of few drugs which act both on cancer and obesity.
The present review may be important for molecular biologists, oncologists and
clinicians treating cancers and also pave the way for better therapeutic options.
ObjectiveThe aim of our study was to investigate, in bipolar patients, whether
affect lability was associated with suicidal ideation incidence during 2-year
follow-up, and which subtype of affect lability was associated with suicidal
ideation. MethodA total of 319 euthymic or mildly depressed bipolar outpatients
recruited in the French FondaMental Advanced Centres of Expertise for Bipolar
Disorder were divided into two subgroups according to the occurrence of suicidal
ideation during a 2-year follow-up. Affect lability was assessed by the French
version of the Affect Lability Scale. ResultsBipolar patients with high affect
lability were more likely to report suicidal ideation during follow-up, even after
adjustment for age, study level, rapid cycling, current depression level, anxiety
disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The
risk of suicidal ideation increased with the level of affect lability. More
specifically, the propensity to switch from neutral to elation affect, from anxious
to depressive affect (or inversely), and from neutral to anger affect predicted
suicidal ideation. ConclusionReducing affective lability could become a new
therapeutic target of suicidal prevention in bipolar disorder.
Objective: To examine the association between gestational age (GA) at birth across
the normal GA spectrum (37-41 weeks) and the temperament and health of 3-month old
infants.Methods: The sample comprised 242 low-risk mothers and infants without
chronic illnesses or severe pregnancy complications. Infant temperament was defined
by three constructs: Negative Affectivity (NA), Extraversion, and Regulation,
assessed by parents' reports on the Infant Behavior Questionnaire. Infants' health
was defined as the number of nonroutine doctors' visits attended by the infants
since their release from the hospital after birth. Analyses employed a continuous
measure of GA to assess outcomes across GAs and a categorical measure (37, 38, 39-
41 weeks GA) to examine contrasts.Results: Extraversion was positively related to
GA primarily due to the lower scores of infants born at 37 weeks compared to
infants born at 39-41 weeks GA. NA showed a similar effect. The odds of infants
born at 37 weeks attending a nonroutine medical visit were 2.8 times that of
infants born full-term.Discussion: Infants born at 37 weeks GA express less affect
and use more nonroutine medical services than do infants born at 39-41 weeks GA.
The findings underscore the importance of considering the risks of pregnancy
prolongation with the developmental risk associated with early-term delivery.
Background: The ability to recognize emotional expression is essential for social
interactions, adapting to the environment, and quality of life. Emotion recognition
is impaired in people with Alzheimer's disease (AD), thus rehabilitation of these
skills has the potential to elicit significant benefits. Objective: This study
sought to establish whether emotion recognition capacity could be rehabilitated in
people with AD. Methods: Thirty-six participants with AD were assigned to one of
three conditions: an experimental group (EG) that received 20 sessions of
rehabilitation of emotion recognition and 20 sessions of cognitive stimulation
therapy (CST), a control group (CG) that received 40 sessions of CST, and a
treatment as usual group (TAU). Results: A positive treatment effect favoring the
EG was found; participants were better able to correctly identify emotions (p =
0.021), made fewer errors of commission (p = 0.002), had greater precision of
processing (p = 0.021), and faster processing speed (p = 0.001). Specifically, the
EG were better able to identify sadness (p = 0.016), disgust (p = 0.005), and the
neutral expression (p = 0.014), with quicker processing speed for disgust (p =
0.002). These gains were maintained at one month follow-up with the exception of
processing speed for surprise, which improved. Conclusion: Capacity to recognize
facial expressions of emotions can be improved through specific rehabilitation in
people with AD, and gains are still present at a one month follow up. These
findings have implications for the design of rehabilitation techniques for people
with AD that may lead to improved quality of life and social interactions for this
population.
In response to Palermo (2016, Australian Psychologist, in press) comments, some
aspects of the target paper are further elaborated here. In particular, given
Palermo's timely emphasis on the potential social and cultural implications of
research demonstrating the beneficial consequences of negative affect, the
historical background, and practical implications of the experimental evidence are
elaborated. Furthermore, the reviewer also comments on the applicability of
alternative theoretical conceptualizations to the data reported here, and this
issue also receives further attention. Overall, it is concluded that there is now
strong and convergent evidence for the often beneficial consequences of mild
negative affect, and these findings deserve serious consideration in practical
applications of psychology, and in our conceptions of what represents a healthy and
balanced emotional life. Embracing and accepting periods of negative affectivity
should be recognised as a normal and healthy part of the human condition, and the
cultural bias towards positive affect should be tempered by an appreciation of the
adaptive benefits of dysphoria.
The subtle relationship between feeling and thinking, affect and cognition has
fascinated philosophers and writers since time immemorial, yet, empirical research
on this topic was relatively neglected by psychologists until recently. There have
been many claims emphasising the beneficial cognitive and behavioural consequences
of positive affect. Many recent works suggest that negative affect may also
facilitate optimal performance in many situations, consistent with evolutionary
theories suggesting the adaptive signalling function of various affective states.
This paper reviews traditional and current psychological theories linking affect to
social thinking and behaviour. A variety of empirical studies from our laboratory
will also be presented, demonstrating that in many situations, negative affect
promotes optimal performance in cognitive and social tasks, including tasks such as
memory, social judgements, motivation, and strategic interpersonal behaviours.
These results will be interpreted in terms of a dual-process theory that predicts
that negative affect promotes a more accommodative, vigilant, and externally
focused thinking strategy. The relevance of these findings for recent affect-
cognition theories will be discussed, and the practical implications of negative
affect promoting improved social thinking and performance in a number of applied
fields will be considered.
Background: One in twenty-five people suffer from a mood disorder. Current
treatments are sub-optimal with poor patient response and uncertain modes-of-
action. There is thus a need to better understand underlying mechanisms that
determine mood, and how these go wrong in affective disorders. Systems biology
approaches have yielded important biological discoveries for other complex diseases
such as cancer, and their potential in affective disorders will be reviewed. Scope
of review: This review will provide a general background to affective disorders,
plus an outline of experimental and computational systems biology. The current
application of these approaches in understanding affective disorders will be
considered, and future recommendations made. Major conclusions: Experimental
systems biology has been applied to the study of affective disorders, especially at
the genome and transcriptomic levels. However, data generation has been slowed by a
lack of human tissue or suitable animal models. At present, computational systems
biology has only be applied to understanding affective disorders on a few
occasions. These studies provide sufficient novel biological insight to motivate
further use of computational biology in this field. General significance: In common
with many complex diseases much time and money has been spent on the generation of
large-scale experimental datasets. The next step is to use the emerging
computational approaches, predominantly developed in the field of oncology, to
leverage the most biological insight from these datasets. This will lead to the
critical breakthroughs required for more effective diagnosis, stratification and
treatment of affective disorders. (C) 2016 Elsevier B.V. All rights reserved.
Individuals can apply different processing strategies to deal with situations they
encounter. One central question in social-cognition research refers to the factors
that determine reliance on different processing strategies. Parting from a
functional perspective, which holds that processing strategies need to be adjusted
to the requirements of the situation, we argue that individuals' mood carries
information about the benign versus problematic nature of the situation and thus
that mood can regulate cognitive processing. Focusing on mental abstraction, we
propose that positive mood contributes to a processing style characterized by
reliance on prior knowledge in the form of general knowledge structures, whereas
negative mood elicits a processing style characterized by attention to details and
consideration of new situation-specific information.
Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV-1
infection are extraordinarily mutated. One goal of HIV-1 vaccine development is to
induce antibodies that are similar to the most potent and broad BNAbs isolated from
infected subjects. The most effective BNAbs have very high mutation frequencies,
indicative of the long periods of continual activation necessary to acquire the
BNAb phenotype through affinity maturation. Understanding the mutational patterns
that define the maturation pathways in BNAb development is critical to vaccine
design efforts to recapitulate through vaccination the successful routes to
neutralization breadth and potency that have occurred in natural infection.
Studying the mutational changes that occur during affinity maturation, however,
requires accurate partitioning of sequence data into B-cell clones and
identification of the starting point of a B-cell clonal lineage, the initial V(D)J
rearrangement. Here, we describe the statistical framework we have used to perform
these tasks. Through the recent advancement of these and similar computational
methods, many HIV-1 ancestral antibodies have been inferred, synthesized and their
structures determined. This has allowed, for the first time, the investigation of
the structural mechanisms underlying the affinity maturation process in HIV-1
antibody development. Here, we review what has been learned from this atomic-level
structural characterization of affinity maturation in HIV-1 antibodies and the
implications for vaccine design.
Alterations in mitochondrial respiration contribute to the development and
progression of cancer via abnormal biogenesis, including generation of reactive
oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of
the cytochrome bc1 complex serving respiration in mitochondria. In the present
study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its
association with clinical outcomes of patients. UQCRH expression in HCC was
determined via semiquantitative and quantitative real-time reverse transcriptase
polymerase chain reaction of 96 surgically resected HCC tissues positive for
hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC
tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in
HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-
Meier analysis revealed significantly shorter overall (P=0.005) and recurrence-free
survival (P=0.027) in patients with tumors overexpressing UQCRH. The prognostic
impact of UQCRH was significant in subgroups of patients divided according to the -
fetoprotein (AFP) level. The patient subgroup with higher AFP levels (20ng/mL)
exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and
recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without
UQCRH overexpression. In contrast, no marked survival differences were observed
between subgroups with lower AFP levels (<20ng/mL). Multivariate analysis defined
UQCRH as an independent poor prognostic factor. Conclusively, our results indicate
that UQCRH overexpression is correlated with poor outcomes of HCC patients.
Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH
overexpression could be a useful indicator for clinical treatment.
Recent forecasts suggest that African countries must triple their current
electricity generation by 2030. Our multicriteria assessment of wind and solar
potential for large regions of Africa shows how economically competitive and low-
environmental-impact renewable resources can significantly contribute to meeting
this demand. We created the Multicriteria Analysis for Planning Renewable Energy
(MapRE) framework to map and characterize solar and wind energy zones in 21
countries in the Southern African Power Pool (SAPP) and the Eastern Africa Power
Pool (EAPP) and find that potential is several times greater than demand in many
countries. Significant fractions of demand can be quickly served with "no-regrets"
options-or zones that are low-cost, low-environmental impact, and highly
accessible. Because no-regrets options are spatially heterogeneous, international
interconnections are necessary to help achieve low-carbon development for the
region as a whole, and interconnections that support the best renewable options may
differ from those planned for hydropower expansion. Additionally, interconnections
and selecting wind sites to match demand reduce the need for SAPP-wide conventional
generation capacity by 9.5% in a high-wind scenario, resulting in a 6-20% cost
savings, depending on the avoided conventional technology. Strategic selection of
low-impact and accessible zones is more cost effective with interconnections
compared with solutions without interconnections. Overall results are robust to
multiple load growth scenarios. Together, results show that multicriteria site
selection and deliberate planning of interconnections may significantly increase
the economic and environmental competitiveness of renewable alternatives relative
to conventional generation.
X-linked agammaglobulinemia (XLA) has been associated with a broad range of
infections, but enteroviral disease represents one of the most damaging infections.
The risk of enteroviral infection in XLA is lower now than in the setting of
intramuscular immunoglobulin or in patients without immunoglobulin replacement, but
the rate of infection has not declined significantly in the era of intravenous
immunoglobulin replacement. Enteroviruses can cause inflammation of nearly every
organ, but in XLA, infections often manifest as dermatomyositis or chronic
meningoencephalitis. Difficulty and delay in recognizing symptoms and lack of
specific therapy contribute to the poor outcomes. Furthermore, cerebrospinal fluid
detection of enteroviruses is not very sensitive. Reluctance to perform brain
biopsies can lead to significant delays. The other feature compromising outcomes is
the lack of specific therapy. High-dose peripheral and intraventricular
immunoglobulin have been used, but failure is still common. New antienteroviral
drugs are in development and show promise for immunodeficient patients with life-
threatening infections with enterovirus. (C) 2016 American Academy of Allergy,
Asthma & Immunology.
This paper presents a 1V -70dB THD audio Automatic Gain Control (AGC) circuits. The
proposed AGC is based on feedback topologies and the gain is digital controlled. A
pi-type resistors network is used in the Programmable Gain Amplifier (PGA) as the
passive feedback device to realize gain linearity in decibels and increase the gain
accuracy. The hysteresis comparator eliminate the chattering effects when the
output signal of Peak Detector changes rapidly around the threshold. The design is
implemented in 0.18 mu m CMOS and occupies an active area of 0.41mm2. The power
consumption of AGC is about 0.17mW at 1V supply voltage. The gain of PGA in the AGC
loop ranges from 0dB to 40dB in 2dB step with gain error not more than 0.2dB. The
integrated noise in the audio range (20 Hz similar to 20 kHz) is 2.28 mu VRMS when
the gain is set at 40dB. The total harmonic distortion (THD) is below -70dB over
the audio frequencies at 0.4-Vpp differential output.
Background: Age might affect the change in care needs in patients with
hepatocellular carcinoma after treatment during their transition process from
hospital to home. However, there have been no studies that focus on this.
Objective: The aim of this study is to examine changes in unmet supportive care
needs in young (G65 years old) and elderly (Q65 years old) groups of patients with
hepatocellular carcinoma from before discharge to 2 months after discharge.
Methods: A longitudinal prospective study design was used with recruited
participants at a teaching hospital in Taiwan. Data were collected 3 times: within
3 days before discharge and at 1 and 2 months after discharge. A set of
questionnaires was used to assess participants' levels of supportive care needs,
symptom distress, anxiety, and depression. Results: A total of 104 patients
completed the data collection process. Supportive care needs decreased monthly
after discharge, with health system and information being the domain with the
highest level of unmet needs in the 2 groups. The young group had a higher level of
overall unmet needs before discharge, but they had a lower level of overall needs
compared with the elderly group after 2 months of discharge. Conclusions: Age could
be a significant potential factor to affect change in unmet needs during
transition. Implications for Practice: Comprehensive assessment in care needs
especially in the health system and information and physical and daily living
domains before discharge is recommended to design personalized education programs
before discharge.
The proportion of workers in their 50s, 60s, and 70s is larger than ever before.
Current work-force trends indicate global increases in retirement ages and that
many individuals are working until later ages than in decades past, and older
people are applying for jobs and at later ages. Research to date on age
discrimination in selection has focused primarily on disparate treatment or
intentional discrimination. However, based on accumulated knowledge about age-
related changes in cognitive and physical abilities as well as changes in
personality and work motivation across the life course, we suggest that more
attention be paid to the possibility of age-based subgroup differences on selection
procedures, manifested as adverse impact and differential prediction. We provide
recommendations to guide future human resource management research and practice.
(C) 2016 Elsevier Inc. All rights reserved.
Objective: Patients over 60 years of age have higher mortality and morbidity after
major liver resections. Nitric oxide (NO) derived from the catalytic activity of
Nos2 plays a beneficial role in liver regeneration (LR) after partial hepatectomy
(PH). In this experiment, we evaluated the effect of Nos2 knockout (KO) on LR in
aged mice after PH. Materials and Methods: In this experimental study, 52 two-year-
old Nos2 KO and 46 the same age wild-type (WT) C57BL/6J mice were subjected to 2/3
PH. Liver tissues were collected at 11 time points after PH. Mice survival ratio
and liver coefficient (liver-weight/ body-weight) was calculated. Transcript and
protein levels were estimated by reverse transcriptase-quantitative polymerase
chain reaction (RT-qPCR) and Western blot, respectively. Results: The aged Nos2 KO
mice had lower survival ratio (P=0.039) and liver coefficient (P=0.002) at the
termination phase. Nos2 transcript level was obviously increased after PH in WT
mice and undetected in the Nos2 KO mice. During LR, the expression at the
transcript level of Cyclin D1, Cyclin A2 and Cyclin B1 and protein expression level
of proliferation marker Ki67 and proliferation-associated transcription factors
JNK1, NF-kB and STAT3 were decreased or delayed. The expression of pro-apoptotic
proteins, CAS-PASE3, CASPASE9 and BAX, was increased in the Nos2 KO mice.
Conclusion: Decreased survival ratio and impaired LR in aged Nos2 KO mice is
probably due to decreased liver cell proliferation and increased liver cell
apoptosis.
The health benefits of playing football and the importance of exercise and social
contact for healthy ageing are well established, but few older adults in the UK
take enough exercise. Football is popular, flexible in format and draws players
into engrossing, effortful and social exercise, but the physical demands of play at
full speed may make it unsustainable for some older adults. Restricted to walking
pace, will play still be engaging? Will health benefits be retained? Will physical
demands remain manageable? This pilot study aims to investigate: (1) the experience
of older adults playing walking football every week, is it sustainable and
rewarding, (2) the intensity and locomotor pattern of walking football, (3) the
scale and nature of walking football health benefits and (4) possible cognitive
benefits of playing walking football through measures of processing speed,
selective and divided attention and updating and inhibition components of executive
function. 'Walking football' and 'waiting list' groups were compared before and
after 12 weeks of one-hour per week football. Walking football was found to be
engaging, sustainable for older adults and moderately intensive; however, selective
health and cognitive benefits were not found from this brief intervention.
The question of specific properties of life compared to nonliving things
accompanied biology throughout its history. At times this question generated major
controversies with largely diverging opinions. Basically, mechanistic thinkers, who
tried to understand organismic functions in terms of nonliving machines, were
opposed by those who tried to describe specific properties or even special forces
being active within living entities. As this question included the human body,
these controversies always have been of special relevance to our self-image and
also touched practical issues of medicine. During the second half of the twentieth
century, it seemed to be resolved that organisms are explainable basically as
physicochemical machines. Especially from the perspective of molecular biology, it
seemed to be clear that organisms need to be explained solely by the chemical
functions of their component parts, although some resistance to this view never
ceased. This research program has been working quite successfully, so that science
today knows a lot about the physiological and chemical processes within organisms.
However, again new doubts arise questioning whether the mere continuation of this
analytical approach will finally generate a fundamental understanding of living
entities. At the beginning of the twenty-first century the quest for a new
synthesis actually comes from analytical empiricists themselves. The hypothesis of
the present paper is that empirical research has been developed far enough today,
that it reveals by itself the materials and the prerequisites to understand more of
the specific properties of life. Without recourse to mysterious forces, it is
possible to generate answers to this age-old question, just using recent,
empirically generated knowledge. This view does not contradict the results of
reductionistic research, but rather grants them meaning within the context of
organismic systems and also may increase their practical usefulness. Although
several of these properties have been discussed before, different authors usually
concentrated on a single one or some of them. The paper describes ten specific
properties of living entities as they can be deduced from contemporary science. The
aim is to demonstrate that the results of empirical research show both the
necessity as well as the possibility of the development of a new conception of life
to build a coherent understanding of organismic functions.
Important energy reductions can be achieved in the building sector by providing
occupants with feedback about their energy-consumption levels. Recent studies link
the success of energy-feedback methods to the level of occupant engagement with
people in their social circles and the resulting peer pressure to conform to
certain social norms. Despite promising results, the literature remains limited in
scope to individual rather than groups of buildings. This has limited the design of
feedback initiatives leveraging social connections that exist, or that can be
induced, within and between buildings. The current paper addresses the identified
gap by proposing a multilayer agent-based model that serves as a test bed to
simulate and optimize feedback methods applied on any building stock
(e.g.,community and city). Monte Carlo and sensitivity analyses show that
connecting occupants of different buildings, while increasing their engagement with
the feedback mechanism, can lead to energy reductions exceeding 10%. The findings
confirm the role of social networks in energy-conservation diffusion, setting the
stage for large-scale and socially engaging energy-conservation initiatives. (C)
2017 American Society of Civil Engineers.
Extensively employed in reproductive science, the term fetal-maternal interface
describes how maternal and fetal tissues interact in the womb to produce the
transient placenta, purporting a theory of pregnancy where mother', fetus', and
placenta' are already-separate entities. However, considerable scientific evidence
supports a different theory, which is also elaborated in feminist and new
materialist literatures. Informed by interviews with placenta scientists as well as
secondary sources on placental immunology and the developmental origins of health
and disease, I explore evidence not of interfacing during pregnancy, but of intra-
action, or the mutual emergence of entities in simultaneous practices of
differentiation and connection. I argue that attending to evidence that can be
figured as intra-action enables us to recognize, account for, and attend to diffuse
responsibilities for fetal-maternal outcomes that extend beyond mothers to the
biosocial milieus of pregnancy. In reimaging the intra-action of placentas, a new
understanding of what constitutes a healthy pregnancy' becomes possible.
Background: The collection of subgingival plaque samples with paper points is time-
consuming and accident-sensitive. However, the collection of saliva is simple and
contains pathogens of all intraoral surfaces. The aim of this study is to
investigate whether a sampling strategy with mouthrinse (mouthrinse sample [MSP];
test) leads to results comparable with standard sampling method (multiple site test
from the deepest pocket of each quadrant [MT4]; control). Methods: In 50 patients
with periodontitis, subgingival plaque was sampled from the deepest pocket of each
quadrant by using paper points and by gaining saliva with saline mouthrinse.
Analysis was performed using a commercially available polymerase chain reaction
test for 11 periodontal pathogens. Results: Detection frequency of Aggregatibacter
actinomycetemcomitans (MT4/MSP: 42%/36%), Porphyromonas gingivalis (78%/66%),
Tannerella forsythia (98%/84%), Treponema denticola (94%/74%), Parvimonas micra
(86%/62%), Campylobacter rectus (90%/76%), Eubacterium nodatum (64%/30%),
Prevotella intermedia (58%/54%), and Eikenella corrodens (90%/82%) was higher with
MT4 than MSP. For Fusobacterium nucleatum (100%/100%), there was no difference
between test and control. Only detection frequency of Capnocytophaga species
(68%/74%) was higher with MSP than MT4. Differences were significant for P.
gingivalis, T. forsythia, T. denticola, P. micra, C. rectus, and E. nodatum.
Conclusions: There is no significant difference between MT4 and MSP for detection
frequency of key pathogen A. actinomycetemcomitans. Key pathogens P. gingivalis, T.
forsythia, T. denticola, P. micra, C. rectus, and E. nodatum show statistically
higher detection frequencies with MT4.
This paper proposes a probabilistic optimization method that produces optimal
bidding curves to be submitted by an aggregator to the day-ahead electricity market
and the intraday market, considering the flexible demand of his customers (based in
time dependent resources such as batteries and shiftable demand) and taking into
account the possible imbalance costs as well as the uncertainty of forecasts
(market prices, demand, and renewable energy sources (RES) generation). The
optimization strategy aims to minimize the total cost of the traded energy over a
whole day, taking into account the intertemporal constraints. The proposed
formulation leads to the solution of different linear optimization problems,
following the natural temporal sequence of electricity spot markets. Intertemporal
constraints regarding time dependent resources are fulfilled through a scheduling
process performed after the day-ahead market clearing. Each of the different
problems is of moderate dimension and requires short computation times. The
benefits of the proposed strategy are assessed comparing the payments done by an
aggregator over a sample period of one year following different deterministic and
probabilistic strategies. Results show that probabilistic strategy reports better
benefits for aggregators participating in power markets.
This paper examines the association between the Great Recession and four measures
of the risk for maternal child abuse and neglect: (1) maternal physical aggression;
(2) maternal psychological aggression; (3) physical neglect by mothers; and (4)
supervisory/exposure neglect by mothers. It draws on rich longitudinal data from
the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study
of families in 20 U.S. cities (N = 3177; 50% African American, 25% Hispanic; 22%
non-Hispanic white; 3% other). The study collected information for the 9 year
follow-up survey before, during, and after the Great Recession (2007-2010).
Interview dates were linked to two macroeconomic measures of the Great Recession:
the national Consumer Sentiment Index and the local unemployment rate. Also
included are a wide range of socio-demographic controls, as well as city fixed
effects and controls for prior parenting. Results indicate that the Great Recession
was associated with increased risk of child abuse but decreased risk of child
neglect. Households with social fathers present may have been particularly
adversely affected. Results also indicate that economic uncertainty during the
Great Recession, as measured by the Consumer Sentiment Index and the unemployment
rate, had direct effects on the risk of abuse or neglect, which were not mediated
by individual-level measures of economic hardship or poor mental health. (C) 2016
Elsevier Ltd. All rights reserved.
A growing body of research suggests that bipolar spectrum disorders (BSDs) are
associated with high aggression. However, little research has prospectively
examined how aggression may affect time to onset of hypomanic/manic versus major
depressive episodes. In a longitudinal study, we tested the hypothesis that
aggression would prospectively predict a shorter time to the onset of
hypomanic/manic episodes and a longer time to the onset of major depressive
episodes, based on the behavioral approach system theory of BSDs. Young adults
(N=120) diagnosed with cyclothymia, bipolar II disorder, or bipolar disorder not
otherwise specified were followed every 4 months for an average of 3.55 years.
Participants completed measures of depressive and manic symptoms, family history of
mood disorder, impulsivity, and aggression at baseline and were followed
prospectively with semistructured diagnostic interview assessments of
hypomanic/manic and major depressive episodes and treatment seeking for mood
problems. Cox proportional hazard regression analyses indicated that overall,
physical, and verbal aggression predicted a longer time to major depressive episode
onset, even after controlling for baseline depressive and manic symptoms, family
history of mood disorder, treatment seeking for mood problems, and impulsivity.
Aggression, however, did not significantly predict time to onset of hypomanic/manic
episodes, controlling for the same covariates. The findings suggest that approach-
related behaviors may be utilized to delay the onset of major depressive episodes
among people with BSDs.
Fipronil is an important member of the phenylpyrazole group of insecticides and is
widely used for various crops and vegetables to control insects, thereby exposing
birds, animals, and humans to fipronil. Currently, there is limited information on
the effects of fipronil exposure in Japanese quail. Therefore, our aim was to
assess the reproductive toxicological effects of fipronil in the Japanese quail in
a 15-day gavage study and then its recovery over a period of 60 days. Fipronil-
administration led to significant losses in both feed intake and body weight.
Whereas, the gonadosomatic index was not affected, and histological changes
observed in the testes were reversible, particularly by day 45 and day 60 of
recovery. Cloacal gland atrophy, reduced foam quantity and a reduction in
fertility, sexual and aggressive behaviors, and serum testosterone with elevated
estradiol (E2) hormone levels were also observed. All these changes gradually
reversed during various recovery periods. Further, alterations in hepatic
vitellogenin (Vtg) and estrogen receptor alpha (ER alpha) gene expression, assessed
by quantitative polymerase chain reaction, were also observed. Specifically, ER
alpha 1 was induced after fipronil administration, while the Vtg transcript was
elevated during both exposure and recovery periods. Our results showed that
fipronil exposure has a profound negative influence on reproductive traits in the
male Japanese quail and exhibits an estrogenic activity that can raise the
incidence of infertility in males. Nevertheless, most of the changes could be
reversed after a recovery period of 30-45 days. (C) 2016 Elsevier Ltd. All rights
reserved.
Although previous studies in inmates, forensic and psychiatric samples suggest the
relation between childhood trauma and suicide behavior as well as between childhood
trauma and violent delinquency, the understanding of possible underlying mechanisms
is still fragmentary. In a naturalistic study design, we tested if suicidal
attempts and violent crimes are differently associated with adverse childhood
experiences and levels of appetitive aggression in male forensic psychiatry
inpatients. Adverse childhood experiences and appetitive aggression styles were
collected by means of self-report measures, suicide attempts were taken from the
medical history and violent crimes were appraised by official court records. The
data were analyzed by the means of generalized linear models. Results revealed that
appetitive aggression and adverse childhood experiences were significant predictors
of suicide attempts, whereas violent crimes were associated solely with appetitive
aggression. Suicide attempts and violent delinquency in forensic patients seem to
be both positively associated with high levels of appetitive aggression, whereas
their etiological pathways might differ with regard to adverse childhood
experiences. Considering these interrelations to a greater extent might improve
both diagnostics and treatment of forensic patients. (C) 2016 Elsevier Ireland Ltd.
All rights reserved.
Sphingomyelin phosphodiesterase 3 (Smpd3), which encodes neutral sphingomyelinase 2
(nSMase2), is a key molecule for skeletal development as well as for the
cytodifferentiation of odontoblasts and alveolar bone. However, the effects of
nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still
unclear. In this study, the authors analyzed the effects of Smpd3 on the
cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3
increases the mRNA expression of calcification-related genes, such as alkaline
phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related
transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of
nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and
osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation.
Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3
in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated
subjects, the authors identified a single nucleotide polymorphism (SNP),
rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people.
Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity
or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2,
suggesting that this SNP inhibits Smpd3 such that it has no effect on the
cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial
role in maintaining the homeostasis of PDL tissue.
Background: Dendritic cells (DCs) form a key link between innate and adaptive
immune responses. The aim of this study is to analyze presence and distribution of
immature (im) and mature (m) DCs in gingival tissue samples obtained from patients
diagnosed with aggressive periodontitis (AgP), chronic periodontitis (CP), and
clinically healthy periodontium (control group). Methods: Gingival tissue samples
obtained from patients with: 1) AgP (aged= 35 years); and 3) control group (aged
>18 years) (n = 10 per group) were collected. Two-way analysis of variance and
posterior Fisher least significant difference test were used to observe differences
between the means of cells positively marked for imDC (S100, CD1a, and CD207) and
mDC (CD208) immunomarkers. Results: imDCs were more numerous in AgP than CP and
control groups, being statistically significant only for S100+ cells. Conversely,
mDCs were visualized in higher numbers in CP than AgP and control groups (both P
<0.05). Considering frequency of immunostained cells, the number of S100+ cells was
greater than CD207+ and CD1a+ cells, followed by a lesser number of CD208+ cells,
in all groups. Conclusions: Considering that the ability of DCs to regulate
immunity is dependent on DC maturation, results suggest that predominance of imDCs
appears to be involved in AgP pathogenesis, probably due to lack of ability to
induce immune cell activation. Further studies are necessary to elucidate the role
of DC maturation in regulating immune responses in periodontal disease.
Fragile x syndrome (FXS) is the most common form of inherited mental retardation
disease. This is caused due to expansion of CGG triplet in 5'-untranslated region
of fragile x mental retardation 1 (FMR-1) gene. In most of the cases, abnormally
large size of the CGG repeat (>200) undergoes hypermethylation, which in turn
silences the FMR-1 gene causing thereby complete lack of its protein product called
fragile x mental retardation protein (FMRP). Lack of FMRP due to gene silencing or
production of faulty protein due to point mutation in KH2 domain of FMRP alters the
translational process in neurons and leads to expression of mental retardation
phenotype on the patients. The FMRP is expressed ubiquitously in all tissues;
however, it is predominantly expressed in neurons and testis. It possesses
heterogeneity and is found in many isoforms due to alternative splicing of the FMR-
1 transcript. Based on our data from the Western-, slot-, Northern blotting and
immunohistochemical studies, we report here the down regulation of Fmr-1 gene and
FMRP in mice brain in age-dependent manner. The present finding is important in
respect to FMRP-dependent various brain functions i.e., learning, memory, cognition
etc. that decrease with advancing age.
Background: Early life stress (ELS) and addiction are related to age-related
diseases and telomere shortening. However, the role of telomere length (TL) in
crack cocaine addiction remains unknown. The purpose of this study was to
investigate the TL in a sample of crack cocaine dependent-women who reported an ELS
history and in a community-based sample of elderly women as a reference group for
senescence. Methods: This study included treatment seeking crack cocaine dependents
women (n = 127) and elderly women without a psychiatric diagnosis (ELD, n = 49).
The crack cocaine sample was divided in two groups according to their Childhood
Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and
neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S
ratio obtained from peripheral blood DNA using quantitative PCR assay. esults:
CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group,
despite their younger age. Among crack cocaine sample, CRACK-ELS group had
significantly shorter telomeres than the CRACK group. Correlation analysis within
crack cocaine group indicated that TL was negatively correlated with emotional
abuse scores. Conclusions: These results support previous findings associating
telomere shortening with both ELS and drug addiction. This study suggests new
evidence of a distinct biological phenotype for drug-dependent women with ELS. The
results support the biological senescence hypothesis underpinning ELS experience.
(C) 2016 Elsevier Inc. All rights reserved.
Significance: With the growing population of baby boomers, there is a great need to
determine the effects of advanced age on the function of the immune system. Recent
Advances: It is universally accepted that advanced age is associated with a chronic
low-grade inflammatory state that is referred to as inflamm-aging, which alters the
function of both immune and nonimmune cells. Mononuclear phagocytes play a central
role in both the initiation and resolution of inflammation in multiple organ
systems and exhibit marked changes in phenotype and function in response to
environmental cues, including the low levels of pro-inflammatory mediators seen in
the aged. Critical Issues: Although we know a great deal about the function of
immune cells in young adults and there is a growing body of literature focusing on
aging of the adaptive immune system, much less is known about the impact of age on
innate immunity and the critical role of the mononuclear phagocytes in this
process. Future Directions: In this article, there is a focus on the tissue-
specific monocyte and macrophage subsets and how they are altered in the aged
milieu, with the hope that this compilation of observations will spark an expansion
of research in the field.
Rationale: Leukocyte telomere length (LTL) is a biological marker of aging, and
shorter LTL is associated with adverse cardiovascular outcomes. Reduced
regenerative capacity has been proposed as a mechanism. Bone marrow-derived
circulating progenitor cells are involved in tissue repair and regeneration.
Objective: Main objective of this study was to examine the relationship between LTL
and progenitor cells and their impact on adverse cardiovascular outcomes. Methods
and Results: We measured LTL by quantitative polymerase chain reaction in 566
outpatients (age: 63 +/- 9 years; 76% men) with coronary artery disease.
Circulating progenitor cells were enumerated by flow cytometry. After adjustment
for age, sex, race, body mass index, smoking status, and previous myocardial
infarction, a shorter LTL was associated with a lower CD34+ cell count: for each
10% shorter LTL, CD34+ levels were 5.2% lower (P< 0.001). After adjustment for the
aforementioned factors, both short LTL (< Q1) and low CD34+ levels (< Q1) predicted
adverse cardiovascular outcomes (death, myocardial infarction, coronary
revascularization, or cerebrovascular events) independently of each other, with a
hazard ratio of 1.8 and 95% confidence interval of 1.1 to 2.0, and a hazard ratio
of 2.1 and 95% confidence interval of 1.3 to 3.0, respectively, comparing Q1 to Q2-
4. Patients who had both short LTL (< Q1) and low CD34+ cell count (< Q1) had the
greatest risk of adverse outcomes (hazard ratio = 3.5; 95% confidence interval,
1.7-7.1). Conclusions: Although shorter LTL is associated with decreased
regenerative capacity, both LTL and circulating progenitor cell levels are
independent and additive predictors of adverse cardiovascular outcomes in coronary
artery disease patients. Our results suggest that both biological aging and reduced
regenerative capacity contribute to cardiovascular events, independent of
conventional risk factors.
One of the most significant reliability issues in switching-mode power supplies is
electrolytic capacitor degradation caused by aging. This paper proposes an output
voltage transient analysis method to detect capacitor wear-out at the output stage
of a step-down dc-dc converter. Changes in the converter output voltage dynamics
are evaluated by analyzing the output voltage step response with respect to a
decrease in the capacitance. The sensitivity of the method is assessed with respect
to parameter variations using an equivalent main circuit model. The feasibility of
the presented method is verified by experimental tests using a converter prototype.
The results show that the presented method is practical and adequate for detecting
capacitor degradation in various operating conditions.
The detection of degradations and resulting failures in electronic
components/systems is of paramount importance for complex industrial applications
including nuclear power reactors, aerospace, automotive, and space applications.
There is an increasing acceptance of the importance of detection of failures and
degradations in electronic components and of the prospect of system-level health
monitoring to make a key contribution to detecting and predicting any impending
failures. This paper describes a parametric system identification-based health-
monitoring method for detecting aging degradations of passive components in switch-
mode power converters (SMPCs). A nonparametric system response is identified by
perturbing the system with an optimized multitone sinusoidal signal of the order of
mVs. The parametric system model is estimated from nonparametric system response
using recursive weighted least-square (WLS) algorithm. Finally, the power-stage
component values, including their parasitics, are extracted from numerator and
denominator coefficients based on the assumed Laplace system model. These extracted
component values provide direct diagnostic information of any degradation or
anomalies in the components and the system. A proof of concept is initially
verified on a simple point-of-load (POL) converter but the same methodology can be
applied to other topologies of SMPC.
Background-Circulating levels of chemerin are significantly higher in hypertensive
patients and positively correlate with blood pressure. Chemerin activates
chemokine-like receptor 1 (CMKLR1 or ChemR23) and is proposed to activate the
"orphan" G protein-coupled receptor 1 (GPR1), which has been linked with
hypertension. Our aim was to localize chemerin. CMKLR1, and GPR1 in the human
vasculature and determine whether 1 or both of these receptors mediate
vasoconstriction. Methods and Results-Using immunohistochemistry and molecular
biology in conduit arteries and veins and resistance vessels, we localized chemerin
to endothelium, smooth muscle, and adventitia and found that CMKLR1 and GPR1 were
widely expressed in smooth muscle. C9 (chemerin149-157) contracted human saphenous
vein (pD(2)=7.30 +/- 0.31) and resistance arteries (pD(2)=7.05 +/- 0.54) and
increased blood pressure in rats by 9.1 +/- 1.0 mm Hg at 200 nmol. Crucially, these
in vitro and in vivo vascular actions were blocked by CCX832, which we confirmed to
be highly selective for CMKLR1 over GPR1. C9 inhibited cAMP accumulation in human
aortic smooth muscle cells and preconstricted rat aorta, consistent with the
observed vasoconstrictor action. Downstream signaling was explored further and,
compared to chemerin. C9 showed a bias factor=approximate to 5000 for the Gi
protein pathway, suggesting that CMKLR1 exhibits biased agonism. Conclusions-Our
data suggest that chemerin acts at CMKLR1, but not GPR1, to increase blood
pressure. Chemerin has an established detrimental role in metabolic syndrome, and
these direct vascular actions may contribute to hypertension, an additional risk
factor for cardiovascular disease. This study provides proof of principle for the
therapeutic potential of selective CMKLR1 antagonists.
Biofilm formation usually increases antimicrobial resistance capacity of
Staphylococcus aureus, which poses considerable challenges to successful
eradication of staphylococcal infections. Very little is known about the biofilm-
forming capacity and antibiotic resistance pattern of dominant S. aureus clonal
lineages in China. In this study, the disk diffusion method and the microtiter
plate assay were, respectively, performed to determine the antibiotic resistance
and biofilm-forming capacity of 84 different S. aureus isolates belonging to 10
dominant clonal lineages in China. It was shown that isolates of different clonal
lineages had obvious variations in biofilm-forming capacity. Resistance to
individual antibacterial agents was most frequently observed to erythromycin
(72.6%) and azithromycin (72.6%). Then, all tested isolates were further screened
for the presence of 16 resistance genes by polymerase chain reaction (PCR), and no
significant correlation was found between clonal lineage and the distribution of
resistance genes. Overall, our results indicate that biofilm producers of S. aureus
have a greater likelihood to carry more antibiotic resistance genes than non-
biofilm producers (p<.01), further implying that biofilm may promote the
dissemination of antibiotic resistance determinants. Practical
applicationsStaphylococcus aureus is the leading cause of nosocomial infections and
often associated with food poisoning worldwide. Biofilm formation of S. aureus
influences the efficacy of antimicrobial therapy and promotes the persistence of
infections; however, the knowledge about biofilm formation capacity of isolates
belonging to different clonal lineages is little. Therefore, this study on biofilm
formation capacity and antibiotic resistance pattern of dominant S. aureus clonal
lineages could help to fix this information gap.
Gene editing technologies are a group of recent innovations in plant breeding using
molecular biology, which have in common the capability of introducing a site-
directed mutation or deletion in the genome. The first cases of crops improved with
these technologies are approaching the market; this has raised an international
debate regarding if they should be regulated as genetically modified crops or just
as another form of mutagenesis under conventional breeding. This dilemma for
policymakers not only entails issues pertaining safety information and
legal/regulatory definitions. It also demands borrowing tools developed in the
field of social studies of science and technology, as an additional basis for sound
decision making.
BACKGROUNDWeeds can be a greater constraint to crop production than animal pests
and pathogens. Pre-emergence herbicides are crucial in many cropping systems to
control weeds that have evolved resistance to selective post-emergence herbicides.
In this study we assessed the potential to evolve resistance to the pre-emergence
herbicides prosulfocarb + S-metolachlor or pyroxasulfone in 50 individual field
Lolium rigidum populations collected in a random survey in Western Australia prior
to commercialisation of these pre-emergence herbicides. RESULTSThis study shows for
the first time that in randomly collected L. rigidum field populations the
selection with either prosulfocarb + S-metolachlor or pyroxasulfone can result in
concomitant evolution of resistance to both prosulfocarb + S-metolachlor and
pyroxasulfone after three generations. CONCLUSIONSIn the major weed L. rigidum,
traits conferring resistance to new herbicides can be present before herbicide
commercialisation. Proactive and multidisciplinary research (evolutionary ecology,
modelling and molecular biology) is required to detect and analyse resistant
populations before they can appear in the field. Several studies show that evolved
cross-resistance in weeds is complex and often unpredictable. Thus, long-term
management of cross-resistant weeds must be achieved through heterogeneity of
selection by effective chemical, cultural and physical weed control strategies that
can delay herbicide resistance evolution. (c) 2016 Society of Chemical Industry
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress
signaling. However, its molecular mechanism remains to be elucidated. In this
investigation, cell suspension cultures of two different plant species rice (Oryza
sativa L.) and white pine (Pinus strobes L.) were transformed using Agrobacterium
tumefaciens strain LBA4404 harboring pBI-AtZIP60. Integration of the AtbZIP60 gene
into the genome of rice and white pine has been confirmed by polymerase chain
reaction (PCR), southern blotting, and northern blotting analyses. Six transgenic
cell lines from O. sativa and three transgenic cell lines from P. strobus were used
to analyze the salt, drought, and cold tolerance conferred by the overexpression of
the AtbZIP60 gene. Our results demonstrated that expression of the AtbZIP60 gene
enhanced salt, drought, and cold tolerance in rice and white pine transgenic cell
lines. In rice, transcription factor AtbZIP60 increased expression of Ca2+-
dependent protein kinase genes OsCPK6, OsCPK9, OsCPK10, OsCPK19, OsCPK25, and
OsCPK26 under treatment of salt, drought, and cold. These results demonstrated that
overexpression of the AtbZIP60 gene in transgenic cell lines improved salt,
drought, and cold stress tolerances by regulating expression of Ca2+-dependent
protein kinase genes. Overexpression of the AtbZIP60 gene could be an alternative
choice for engineering plant abiotic stress tolerance.
An efficient transformation system for Chinese cabbage cotyledon explants was
developed using Agrobacterium tumefaciens strains LBA4404 harbouring the plasmid
pMOG411 and the plasmid pBin Omega SCK respectively. Various factors affecting the
transformation efficiency and subsequent regeneration were identified. The age of
seedlings, growth conditions and status of Agrobacterium suspension, preculture of
explants, cocultivation time, ratio between Agrobacterium and explants,
acetosyringone and concentration of kanamycin had a significant influence on
transformation frequency and plant regeneration. The presences of the antibacterial
peptide gene and the cowpea trypsin inhibitor gene in those selected shoots in
kanamycin medium were confirmed by PCR, Southern blotting and Northern blotting,
The frequency of regeneration from cotyledons was analyzed in eight parental lines
of Chinese cabbage and five lines were suitable for obtaining transformed plants,
among which Qingmaye C and Qingmaye D were more responsive than other lines.
'Mexican' lime (Citrus aurantifolia Swingle) was transformed with constructs that
contained chimeric promoter-gus gene fusions of phloem-specific rolC promoter of
Agrobacterium rhizogenes, Arabidopsis thaliana sucrose-H+ symporter (AtSUC2) gene
promoter of Arabidopsis thaliana, rice tungro bacilliform virus (RTBV) promoter and
sucrose synthase l (RSs1) gene promoter of Oryza sativa (rice). Histochemical beta-
glucuronidase (GUS) analysis revealed vascular-specific expression of the GUS
protein in citrus. The RTBV promoter was the most efficient promoter in this study
while the RSs1 promoter could drive low levels of gus gene expression in citrus.
These results were further validated by reverse transcription real-time polymerase
chain reaction and northern blotting. Southern blot analysis confirmed stable
transgene integration, which ranged from a single insertion to four copies per
genome. The use of phloem-specific promoters in citrus will allow targeted
transgene expression of antibacterial constructs designed to battle huanglongbing
disease (HLB or citrus greening disease), associated with a phloem-limited Gram-
negative bacterium.
To improve the transformation efficiency of wheat (Triticum aestivum L.) mediated
by Agrobacterium tumefaciens, we explored the possibility of employing the basal
portion of wheat seedling (shoot apical meristem) as the explants. Three genotypes
of wheat were transformed by A. tumefaciens carrying beta-1, 3-glucanase gene.
After vernalization, the seeds to be transformed were germinated. When these
seedlings grew up to 2 similar to 5 cm, their coleoptile and half of the cotyledon
were cut out, and the basal portions were infected by A. tumefaciens. A total 27 T-
0 transgenic plants were obtained, and the average transformation efficiency was as
high as 9.82%. Evident segregation occurred in some of the T-1 plants, as was
indicated by PCR and Southern blotting analysis. Investigation of the T-2 plants
revealed that some transformed plants had higher resistance to powdery mildew than
the controls. Northern blotting revealed that beta-1, 3-glucanase gene was normally
expressed in the T-2 plants, which showed an increased resistance to powdery
mildew. The results above indicate that the exogenous gene has been successfully
integrated into the genome of wheat, transmitted and expressed in the transgenic
progeny. From all the results above, it can be concluded that Agrobacterium
inoculum to the basal portion of wheat seedling is a highly efficient and
dependable transformation method. It can be developed into a practicable method for
transfer of target gene into wheat.
Constantly elevated temperatures cause an array of physio-biochemical changes in
tomato (Lycopersicum esculentum Mill.) which make the fruit ripen quickly and up to
50 % yield loss. The development of tomato cultivars, using genetic engineering
approaches which delay ripening, offers a new way to keep tomatoes healthy under
heat stress. Over-expression of small heat shock protein gene, viscosity 1 (vis 1)
plays a role in increasing juice viscosity, early ripening and tissue soften which
emphasizes the importance of this gene in premature ripening. The aim of this work
was therefore to develop a useful system for silencing the vis1 gene using small
interfering RNA strategy. Agrobacterium strain GV3101 harbouring the binary vector
pICBV19 containing the gus and bar genes was used to adapt the transformation
process in this study. The primers were designed to amplified the first exon of the
vis 1 gene and the amplified fragment was used for cloning into the pFGC5941 at
XhoI/NcoI site at sense orientation then additional fragment was subsequently
cloned at BamHI/XbaI to form sense/antisense cloned fragment interrupted by the
CHSA-intron Agrobacterium strain LBA4404 with the binary vector pFGC5941 which
harbors vis1 gene under the control of the 35S promoter containing bar gene under
the control of a mannopine synthase 2'(Mas2') as selectable marker, was used to
reduce the expression of vis1 gene in fruit. Polymerase chain reaction (PCR), RT-
PCR and northern blotting analysis were applied to detect putative transgenic
plants. Significantly, silencing of vis 1 gene was potently occur and new
transgenic tomato cultivars were produced with enhanced ripening qualities for
recommendation for growing under heat stress.
To induce virus resistance in tobacco and rice we constructed hairpin RNA
expression system harbouring inverted repeat fragments of coat protein cDNA of
Potato virus Y (PVY) or Rice stripe virus (RSV). These structures were driven by
three promoters [cauliflower mosaic virus 35S (CaMV 35S), polyubiqutin gene of
maize (Ubi), and Pharbitis nil leucine zipper gene (PNZIP)] which have different
tissue-specific activity. PVY resistance ratios were 65.18, 24.33 and 83.54 % in
transgenic tobacco plants harboring p35S-PVY, pUbi-PVY and pPNZIP-PVY. RSV
resistance was 16.21, 28.61 and 29.33 % in transgenic rice plants harboring p35S-
RSV, pUbi-RSV and pPNZIP-RSV. Northern blotting and GUS assay demonstrated that
virus resistance levels were related to promoter activity. Therefore, choice of the
more effective and tissue-specific promoter to reinforce transcription of hpRNAs
will favour the cultivation of highly virusresistant transgenic plants.
Potato is one of the main targets for genetic improvement by gene transfer. The aim
of the present study was to establish a robust protocol for the genetic
transformation of three dihaploid and four economically important cultivars of
potato using Agrobacterium tumefaciens carrying the in vivo screenable reporter
gene for green fluorescent protein (gfp) and the marker gene for neomycin
phosphotransferase (nptII). Stem and leaf explants were used for transformation by
Agrobacterium tumefaciens strain LBA4404 carrying the binary vector pHB2892.
Kanamycin selection, visual screening of GFP by epifluorescent microscopy, PCR
amplification of nptII and gfp genes, as well as RT-PCR and Southern blotting of
gfp and Northern blotting of nptII, were used for transgenic plant selection,
identification and analysis. Genetic transformation was optimized for the best
performing genotypes with a mean number of shoots expressing gfp per explant of 13
and 2 (dihaploid line 178/10 and cv. 'Baltica', respectively). The nptII marker and
gfp reporter genes permitted selection and excellent visual screening of transgenic
tissues and plants. They also revealed the effects of antibiotic selection on
organogenesis and transformation frequency, and the identification of escapes and
chimeras in all potato genotypes. Silencing of the gfp transgene that may represent
site-specific inactivation during cell differentiation, occurred in some transgenic
shoots of tetraploid cultivars and in specific chimeric clones of the dihaploid
line 178/10. The regeneration of escapes could be attributed to either the
protection of non-transformed cells by neighbouring transgenic cells, or the
persistence of Agrobacterium cells in plant tissues after co-cultivation.
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress
signaling, pathogen defense, and flower development. However, molecular mechanism
involved in plant salt tolerance via overexpression of transcription factor
AtbZIP60 is elusive. In this investigation, cell suspension cultures of four
different plant species cotton (Gossypium hirsutum L.), Virginia pine (Pinus
virginiana L.), white pine (Pinus strobus L.), and Arabidopsis (Arabidopsis
thaliana) were transformed via Agrobacterium tumefaciens LBA4404 harboring pBI-
AtZIP60. Integration of AtbZIP60 into the genome of G. hirsutum, P. virginiana, P.
strobes, and A. thaliana has been confirmed by polymerase chain reaction, Southern
blotting, and northern blotting analyses. Six transgenic cell lines from each of
four species were used to analyze the salt tolerance conferred by the
overexpression of AtbZIP60. Our results demonstrated that expression of AtbZIP60
enhanced salt tolerance of transgenic cells in all transgenic lines, and that
improved salt tolerance was associated with increased activities of both H+-ATPase
and acid phosphatase and decreased lipid peroxidation (thiobarbituric acid reactive
substances) in transgenic cell lines from cotton (Gh1, Gh2, Gh3, Gh4, Gh5, and
Gh6), Virginia pine (Pv1, Pv2, Pv3, Pv4, Pv5, and Pv6), white pine (Ps1, Ps2, Ps3,
Ps4, Ps5, and Ps6), and Arabidopsis (At1, At2, At3, At4, At5, and At6). This
investigation demonstrated that the expression of AtbZIP60 gene in transgenic cell
lines reduced salt-induced oxidative damage by increasing the activities of both
H+-ATPase and acid phosphatase, and that the overexpression of AtbZIP60 gene could
be valuable for engineering plant salt tolerance.
The Arabidopsis thaliana bZIP60 (AtbZIP60) transcription factor regulates stress
signaling. However, its involvement in plant salt tolerance is not fully
understood. In this investigation, cell suspension cultures of three different
plant species: tobacco (Nicotiana tabacum), rice (Oryza sativa L.), and slash pine
(Pinus elliottii Engelm.) were transformed via Agrobacterium tumefaciens LBA4404
harboring pBI-AtbZIP60deltaC. Integration of AtbZIP60deltaC into the genome of
tobacco, rice, or slash pine has been confirmed by polymerase chain reaction,
Southern blotting, and Northern blotting analyses. Six transgenic cell lines from
each of three species were used to analyze the salt tolerance conferred by the
overexpression of AtbZIP60deltaC. Our results demonstrated that expression of
AtbZIP60deltaC enhanced salt tolerance of transgenic cells in all transgenic lines
and that improved salt tolerance was associated with increased activities of both
ascorbate peroxidase and superoxide dismutase, and decreased lipid peroxidation
(thiobarbituric acid reactive substances). This investigation has demonstrated that
the expression of AtbZIP60deltaC gene in transgenic cell lines attenuated salt-
induced oxidative damage by increasing the activities of antioxidant enzymes and
the overexpression of AtbZIP60deltaC gene could be an alternative choice for
engineering plant salt tolerance.
The aim of the present study was to produce marker-free transgenic potato resistant
to PVY by using a construct generating self-complementary hairpin RNAs. The method
has two steps: 1) establishing a robust protocol for the genetic transformation of
economically important cultivars of potato by using gfp and nptII genes; 2)
applying the protocol for the transfer of marker-free hairpin construct and
analysis of transgenic plants by PCR. In the first step internodes were transformed
by Agrobacterium tumefaciens LBA4404 with pH82892 construct. Kanamycin, visual
screening of GFP, PCR of nptII and gfp as well as RT-PCR and Southern blotting of
gfp and Northern blotting of nptII were used for transgenic plant selection. Good
regeneration and transformation efficiency were obtained for the cvs. Baltica and
Desiree while the cvs. Agave and Delikat showed lower figures. In the second step
A. tumefaciens with construct: 35SCaMV enhancer and promoter, two repeated inverted
PVY-CP sequences separated by an intron and pAnos terminator was used Regenerated
plants without selection, were analysed by PCR using primers in the: 35S promoter,
promoter and hairpin region, or in both repeated PVY-CP sequences. A large number
of transgenic plants were identified for the most responsive cv. Baltica (17 out of
33) and Desiree (23 out of 66), but only I for the cv. Agave (out of 3) and none
for the cv. Delikat. This simple two-step strategy might be applied to generate
marker-free transgenic plants in other cvs. or plant species.
The disciplinary structure of research on complex problems related to human
activities is supported by the fundaments of the social, life, and hard sciences.
In this work, we looked at the development of scientific research in the field of
biofuels, as a sustainable source of energy, searching for references regarding its
scientific roots and social relevance. Scientific communications on biofuels
published between 1998 and 2007 were analyzed using a combination of bibliometric
methods and text mining techniques. This field of research was characterized as
interdisciplinary, with marked social relevance. Our bibliometric analysis shows
that, in this research subject, 132 different, interacting fields of knowledge
overlap, with dominance of Chemistry, Engineering and Agricultural Sciences.
Through the use of text mining techniques, this field was configured into three
groups of Disciplinary Dimensions. The first and most influential group includes
the Agricultural Sciences, Social Sciences, and Environmental Sciences. The second
group, which gives the field its technological basis, includes Chemistry,
Engineering, and Microbiology. The third group includes disciplines with emerging
involvement in the field of biofuels: Biology and Biochemistry, Animal and Plant
Sciences, Molecular Biology and Genetics, Economics, Material Sciences,
Nanosciences and Nanotechnology, Geosciences, Physics, Humanities,
Multidisciplinary Sciences, Mathematics, and Computer Sciences. This study suggests
that the first group of Disciplinary Dimensions conforms to the elements that
socially validate the progress of research in the field of biofuels. This study
also proposes a metric that can be used to measure the interdisciplinarity and the
social framing of any other research field.
The transport sector is one of the main sources of greenhouse gases, adding in
Spain near a quarter of the total national emissions, the majority in road
transport. Therefore, road contribution to climate change should be mitigated to
achieve the proposed goals in the fight against climate change. Policies and
strategies suggest several preventive mitigation options, but have paid little
attention to compensatory mitigation. We have conducted a theoretical case study in
a Spanish province, Segovia, estimating the carbon dioxide emissions in the road
network between 2015 and 2050, and analysing different compensation possibilities
through conservation agriculture, agroforestry, afforestation and hedgerow
plantation. We have calculated carbon sequestration in the reference period and
costs per tonne for each option, estimating the budget range of offsetting road
carbon emission, and funding possibilities, especially through fuel taxes. The
paper demonstrates that offsetting carbon emissions produced by roads in this area
is technically possible and highly desirable, unifying carbon sequestration,
biodiversity improvement and rural development. The main challenge is funding,
which depends largely on the political will and the awareness of the citizens. (C)
2017 Elsevier B.V. All rights reserved.
African horse sickness (AHS) is a fatal disease of equids relevant to the global
equine industry. Detection of AHS virus (AHSV) during outbreaks has become more
rapid and efficient with the advent of group specific reverse transcriptase
quantitative polymerase chain reaction (GS RT-qPCR) assays to detect AHSV nucleic
acid. Use of GS RT-qPCR together with recently described type specific (TS RT-qPCR)
assays cannot only expedite diagnosis of AHS but also facilitate further evaluation
of the dynamics of AHSV infection in the equine host. A potential limitation to the
application of these assays is that they detect viral nucleic acid originating from
any AHS live attenuated vaccine (LAV), which is the vaccine type routinely
administered to horses in South Africa. The aim of this study was to contrast the
dynamics and duration of the RNAaemia to the serological responses of horses
following immunization with a commercial polyvalent AHSV-LAV using GS and TS RT-
qPCR assays and serum neutralisation tests. The results of the study showed
extended RNAemia in vaccinated horses, and that more horses tested positive on GS
RT-qPCR with lower Cq values after receiving the AHSV-LAV containing types 1, 3 and
4 prior to the vaccine containing types 2, 6, 7 and 8, rather than when the vaccine
combinations were reversed. Furthermore, lower Cq values were obtained when
vaccines were administered 4 weeks apart as compared with a longer interval or 12
weeks apart. These findings are of particular relevance in regions where AHSV-LAVs
are used as the use of these vaccines may complicate the accurate interpretation of
diagnostic testing results. (C) 2017 Elsevier Ltd. All rights reserved.
BACKGROUND The time of progression towards AIDS can vary greatly among seropositive
patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene,
a ligand-activated transcription factor, regulates the transcription immune pathway
genes and can therefore be targets of viral replication mechanisms influencing time
of progression to AIDS. OBJECTIVE To verify the association of single nucleotide
polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2
(PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood
samples were obtained from 96 HIV-1 positive individuals following informed
consent. DNA was isolated and genotyped through real time polymerase chain reaction
(PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic
features and behaviors were answered and time of progression to AIDS was estimated
based on medical chart analysis. FINDINGS Patients with the GG genotype for
rs7643645 were shown to be related with a more rapid disease progression when
compared to GA and AA genotypes. This result was maintained by the Multivariate Cox
Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and
CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of
the nuclear receptors in T-Lymphocytes, suggesting their possible role in the
immune response. In addition, nuclear receptors have been shown to inhibit the HIV
replication, although no such mechanism has been thoroughly elucidated to date.
This is the first time an association between NR1I2 polymorphism and time of
progression to AIDS is reported and supports an apparent relationship between the
gene in the immune response and identifies another genetic factor influencing AIDS
progression.
Background: The presence of gross deletions in the human immunodeficiency virus nef
gene (g Delta nef) is associated with long-term nonprogression of infected
patients. Here, we investigated how quickly genetic defects in the nef gene are
associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors.
Methods: This study was divided into three phases over a 20-yr period; baseline,
KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene
amplicons were obtained using reverse transcription polymerase chain reaction (PCR)
and nested PCR from 10 long-term slow progressors (n = 1,396), and nested PCR from
36 control patients (n = 198), and 28 ART patients (n = 157), and these were then
sequenced. The proportion of g Delta nef, premature stop codons, and not in-frame
insertion or deletion of a nucleotide was compared between three phases, control,
and ART patients. Results: The proportion of defective nef genes was significantly
higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG
plus ART phase (7.8%), and on-ART patients (6.6%; p < 0.01). Small in-frame
deletions or insertions were significantly more frequent among patients treated
with KRG alone compared with controls (p < 0.01). Significantly fewer instances of
genetic defects were detected in samples taken during the KRG plus ART phase (7.8%;
p < 0.01). The earliest defects detected were g Delta nef and small in-frame
deletions after 7 mo and 67 mo of KRG intake, respectively. Conclusion: KRG
treatment might induce genetic defects in the nef gene. This report provides new
insight into the importance of genetic defects in the pathogenesis of AIDS. (C)
2017 The Korean Society of Ginseng, Published by Elsevier Korea LLC.
Background: CSF PCR is the standard diagnostic technique used in resource-rich
settings to detect pathogens of the CNS infection. However, it is not currently
used for routine CSF testing in China. Knowledge of CNS opportunistic infections
among people living with HIV in China is limited. Methods: Intensive cerebrospiral
fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal
etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus
(CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus
(EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time
polymerase chain reaction (PCR). Results: Cryptococcal meningitis accounted for
63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for
Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive,
12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1
(1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high
GCS score tended to have a lower mortality rate, whereas patients with multiple
pathogens infection, seizures or intracranial hypertension showed higher odds of
death. Conclusion: CNS OIs are frequent and multiple pathogens often coexist in
CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The
utility of molecular diagnostics for pathogen identification combined with the
knowledge provided by the investigation may improve the diagnosis of AIDS related
OIs in resource-limited developing countries, but the cost-efficacy remains to be
further evaluated.
Three novel differential amplifier topologies using double gate a-IGZO TFTs on
flexible substrate are presented in this paper. The designs exploit positive
feedback and a load with self-biased top gate to achieve the highest static gain in
single stage a-IGZO amplifiers reported to date. After fabrication, the three
amplifiers exhibit respectively a static gain of 14 dB, 21.5 dB, and 30 dB, with a
bandwidth of 2 kHz, 400 Hz, and 150 Hz. Also, for each circuit the input referred
noise has been measured to be 420 mu V-rms, 195 mu V-rms, and 146 mu V-rms,
respectively. Based on these results, the a-IGZO amplifier providing the highest
gain is suitable as front-end for heart rate measurements and, with some further
optimization verified in simulation, can also be used for other bio-potential
applications, like electro hysterogram and electro cardiogram.
Typical variable air volume (VAV) terminals spend the majority of time at their
minimum airflow set points. These are often higher than the minimum ventilation
requirements defined by code, resulting in excess energy use and a risk of over-
cooling the spaces. We developed and tested a time-averaged ventilation (TAV)
control strategy in an institutional building on the UC Berkeley campus to address
this issue. Whenever a zone does not require cooling, TAV alternates the VAV damper
between partially open and fully closed so that the average airflow matches a
predefined ventilation setpoint. Compared to the existing, base case scenario using
single-max VAV logic, this strategy reduced the mean zone airflow fraction from
0.44 to 0.27 during the intervention period. The corresponding reductions in
average heating, cooling, and fan power were 41%, 23%, and 15% respectively. In
addition to being programmed directly in a native control system, TAV may be
applied via sMAP as a low-cost retrofit strategy in any building that has a BACnet
network and direct digital control (DDC) to each VAV terminal. (C) 2016 Elsevier
B.V. All rights reserved.
Numerous studies have reported an association between fine particulate matter
(PM2.5) and human health. Often these relationships are influenced by environmental
factor that varies spatially and/or temporally. To our knowledge, there are no
studies in Canada that have considered energy generation and fuel sales as PM2.5
effects modifiers. Determining exposure and disease-specific risk factors over
space and time is crucial for disease prevention and control. In this study, we
evaluated the association of PM2.5 with diabetes, asthma, and High Blood Pressure
(HBP) incidence in Canada. Then we explored the impact of the energy generation and
fuel sales on association changes. We fit an age-period-cohort as the study design,
and We applied an over-dispersed Poisson regression model to estimate the risk. We
conducted a sensitivity analysis to explore the impact of variation in clean energy
rates and fuel sales on outcomes changes. The study included 117 health regions in
Canada between 2007 and 2014. Our findings showed strong association of PM2.5 with
diabetes, asthma, and HBP incidence. A two-year increase of 10 mu g/m(3) in PM2.5
was associated with an increased risk of 534% (95% CI: 2.28%; 12.53%) in diabetes
incidence, 2.24% (95% CI: 0.93%; 538%) in asthma incidence, and 8.29% (95% CI:
3.44%; 19.98%) in HBP incidence. Our sensitivity analysis findings suggest higher
risks of diabetes, asthma and HBP incidence when there is low clean energy
generation. On the other hand, we found lower risk when we considered high rate of
clean energy generation. For example, considering only diabetes incidence, we found
that the risk in health regions with low rates of clean electricity is
approximately 700% higher than the risk in health regions with high rates of clean
electricity. Furthermore, our analysis suggested that the risk in regions with low
fuel sales is 66% lower than the risk is health regions with low rates of clean
electricity. Our study provides support for the creation of effective environmental
health public policies that take into account the risk factors present in Canadians
health regions. (C) 2017 Elsevier B.V. All rights reserved.
Effectively analyzing and then treating energy-related air pollution requires
examining every factor, from the pollution source to the end of treatment. This
paper applies index decomposition analysis and a whole process treatment
perspective to identify the factors facilitating air pollution reduction across
three stages: source prevention, process control, and end-of-pipe treatment.
Empirical research using data from China's Jiangsu Province and its 13 cities
reveals differences in local approaches to pollution prevention. At the provincial
level, end-of-pipe treatment remains the primary approach to control air pollution
emissions, indicating that the pattern of "pollute first, govern later" has not yet
been fundamentally reversed. At the city level, 13 cities can be divided into four
types, based on their approach to air pollution treatment: the leading type,
process-dependent type, end-dependent type, and lagging type. Of these, 7 cities
are using multiple control approaches, reflecting the comprehensive effect of whole
process treatment. The Jiangsu Province should consider further strengthening
effective whole process air pollution treatment models, by transitioning to
pollution control, adjusting industrial structure, promoting technological
progress, and consuming clean energy. (C) 2016 Elsevier Ltd. All rights reserved.
The paper presents the design and some results for an experimental platform aimed
to control the air pressure inside a small tank. The basic idea is to allow to the
control algorithm to select an appropriate characteristic of the controller driving
the air compressor, from an available set. In this first approach, the goal is to
make functional the hardware circuits and to design the software support inside an
Integrated Development Environment with a Very High Level Programming Language.
After some functional tests, future work is intended to implement artificial
intelligent based algorithms in order to exploit the multicharacteristics features
with a fuzzy decisions set for selecting an optimal control. The main parts of the
controller are an industrial pressure sensor, a PIC (TM) 16F877 microcontroller
from Microchip (TM) and the air pressure part consisting, mainly, from a car
compressor and a small tank. Additional elements make the operation safe. The
solution with the microcontroller is put in operation in parallel with another one,
using an industrial digital controller from Honeywell (TM). The platform is
intended both for research activities, dealing with all kind of control algorithms
implemented in software, associated with pneumatic systems, and for academic
purpose, joining in an unique structure sensors, microelectronics, interface
techniques, industrial controllers, motors, pneumatic elements and software.
BACKGROUNDFilling creams can provide an adequate substrate for spoilage yeasts
because some yeasts can tolerate the high osmotic stress in these products. To
discover the source of spoilage of a cream-filled baked product, end products, raw
materials, indoor air and work surfaces were subjected to microbiological and
molecular analyses. The efficacy of disinfectants against spoilage yeasts was also
assessed. RESULTSThe analyses on end products revealed the presence of the closest
relatives to Zygosaccharomyces bailii with counts ranging from 1.40 to
4.72logcfug(-1). No spoilage yeasts were found in the indoor air and work surfaces.
Polymerase chain reaction-denaturing gradient gel electrophoresis analysis, carried
out directly on filling creams collected from unopened cans, showed the presence of
bands ascribed to the closest relatives to Z.bailii sensu lato, although with
counts<1logcfug(-1). Susceptibility testing of yeast isolates to disinfectants
showed a significantly lower effect of 10% alkyl dimethyl benzyl ammonium chloride.
Different responses of isolates to the tested disinfectants were seen. CONCLUSIONTo
guarantee the quality of end products, reliable and sensitive methods must be used.
Moreover, hygiene and the application of good manufacturing practices represent the
most efficient way for the prevention and minimization of cross-contamination. (c)
2016 Society of Chemical Industry
The l(1)-optimal digital autopilot needed to control of the roll for an aircraft
under an arbitrary unmeasured disturbances is addressed in this paper. This
autopilot has to achieve a desired lateral motion control via minimizing the upper
bound on the absolute value of the difference between the given and true roll
angles. It is ensured by means of the two digital l(1)-optimal controllers of PI
type The main result consists in establishing the fact that this controller can be
robust in the presence of parametric and nonparametric uncertainties.
Autoimmune regulator (Aire) is essential in the perinatal period to prevent the
multiorgan autoimmunity. Here we show that Aire-regulated single positive thymocyte
trafficking in neonatal period is critical for thymic egress. Reduced thymic
emigration was found in Aire(-/-) mice during neonatal period, leading to enhanced
homeostatic expansion of peripheral T cells as early as 2 weeks of age. In neonatal
Aire(-/-) mice, thymic expression of CCR7 ligands were dramatically reduced,
resulting in decreased thymocyte motility and thymocyte emigration. This reduction
of thymic egress in Aire(-/-) mice was alleviated beyond 3 weeks of age by an early
upregulation of S1P(1) signaling. As the numbers and quality of thymic emigrants
are essential for the establishment and maintenance of peripheral tolerance, the
reduced thymic emigration during neonatal period may deteriorate autoimmunity
caused by the emigration of autoreactive T cells.
BACKGROUND: Characterizing associations between the upper and lower airways is
important for asthma management. OBJECTIVES: This study aimed to assess the
determinants of incomplete asthma control in patients with allergic rhinitis (AR)
and asthma. METHODS: Multiple factors including age, sex, atopy, smoking history,
medication use, Asthma Control Questionnaire (ACQ) score, FEV1, fraction of exhaled
nitric oxide (F-ENO), and rhinitis questionnaire score were examined. AR was
defined by rhinitis symptoms and the sensitization to inhaled allergens. ACQ was
used to dichotomize the subjects into the incompletely controlled group (ACQ score
>= 0.75) and the well-controlled group. The factors that contribute to incomplete
asthma control were assessed by a multivariate analysis. RESULTS: A total of 260
patients with AR and asthma were enrolled and 108 patients (42%) were classified as
incomplete asthma control. The incompletely controlled group was older (P<.05), and
had more airflow limitation, more airway inflammation, and more severe rhinitis
symptoms (all P<.001). In contrast, the well-controlled group was more likely to be
taking nasal corticosteroids (NCSs) (P<.01). In a multivariate model adjusted by
age, asthma treatment, airflow limitation, and FENO, persistence and severity of
rhinitis (odds ratio [OR], 2.57; 95% CI, 1.41-4.70, and OR, 2.00; 95% CI, 1.10-
3.65) and nonuse of NCSs (OR, 3.83; 95% CI, 1.50-9.81) were independently
associated with incomplete asthma control. CONCLUSIONS: The persistence and
severity of AR and the use of NCSs were associated with the level of asthma control
in patients with AR and asthma. Further studies are required to determine whether
appropriate treatment of rhinitis would improve asthma control. (C) 2016 American
Academy of Allergy, Asthma & Immunology
Background: Asthma is characterized by a heterogeneous inflammatory profile and can
be subdivided into T(h) 2-high and T(h) 2-low airway inflammation. Profiling of a
broader panel of airway cytokines in large unselected patient cohorts is lacking.
Methods: Patients (n = 205) were defined as being "cytokine-low/high" if sputum
mRNA expression of a particular cytokine was outside the respective 10th/90th
percentile range of the control group (n = 80). Unsupervised hierarchical
clustering was used to determine clusters based on sputum cytokine profiles.
Results: Half of patients (n = 108; 52.6%) had a classical T(h) 2-high ("IL-4-, IL-
5-and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis
revealed 5 clusters. Patients with an "IL-4-and/or IL-13-high"pattern surprisingly
did not cluster but were equally distributed among the 5 clusters. Patients with an
"IL-5-, IL-17A-/F-and IL-25-high"profile were restricted to cluster 1 (n = 24) with
increased sputum eosinophil as well as neutrophil counts and poor lung function
parameters at baseline and 2 years later. Four other clusters were identified: "IL-
5-high or IL-10-high"(n = 16), "IL-6-high"(n = 8), "IL-22-high"(n = 25). Cluster 5
(n = 132) consists of patients without "cytokine-high"pattern or patients with only
high IL-4 and/or IL-13. Conclusion: We identified 5 unique asthma molecular
phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2
cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori
type 2 versus non-type 2 molecular phenotypes.
Aluminium (Al) toxicity is a worldwide problem in agricultural practice. Based on
evidence that Al resistance may be an inducible process and that rice is one of the
most Al-resistant crops, the gene transcriptional responses to Al were investigated
in two contrasting rice cultivars (resistant XN1 versus sensitive XX2) using
differential display reverse transcription-PCR (DDRT-PCR) in combination with
northern blotting analysis. A total of 37 genes were identified as differentially
expressed, of which five have been previously known as Al regulated while the
others are novel genes. Among the up-regulated genes, four encode ion transporters,
two are involved in signal transduction, and five in the synthesis of cysteine and
metallothionein. These could be members that are potentially involved in Al
adaptation or resistance. On the other hand, the transcription of 17 genes was
strongly inhibited under Al stress. These genes are associated with cytoskeletal
dynamics and metabolism, and could be possible targets associated with Al toxicity.
All of these differentially expressed genes may represent candidates that function
in Al responses. The results suggest, at the transcriptional level, that
cytoskeletal disruption may be associated with Al toxicity, whereas ion transport
and sulphur metabolism could play major roles in Al adaptation or tolerance in
rice.
Properly designed alarm systems can benefit operators in conducting routine and
emergency tasks. With the digitization of main control rooms, the alarm interface
can be designed in various ways that are different from the traditional "alarm
tile" style. An innovative alarm bar interface is proposed in this paper. A
preliminary lab experiment was conducted to compare the traditional alarm tile and
the new alarm bar interfaces. Sixteen university students were recruited to
participate in the experiment, in which two emergency scenarios, Loss of Coolant
Accident and Steam Generator Tube Rupture, were tested. The experiment task
included two parts: alarm detection and identification. The subjective ratings
supported the innovative alarm bar design for better parameter trend perception.
The objective performance measures showed that the simpler design of the alarm tile
interface better aided the alarm detection performance, whereas the alarm bar
interface had almost the same alarm identification performance as the alarm tile
interface. Relevance to industry: An alarm system is critical for a complex
industrial system. The experimental results show that design evaluation is more
complex than it may seem. Although it has not been proved to be overwhelmingly
superior to the tile design, the alarm bar design shows promise for aiding
operators and needs to be further validated. (C) 2014 Elsevier B.V. All rights
reserved.
PurposeMore than 25% of US adults experience mental health or substance use
conditions annually, yet less than half receive treatment. This study explored how
rural participants with behavioral health conditions pursue and receive care, and
it examined how these factors differed across American Indian (AI) and geographic
subpopulations. MethodsWe undertook a qualitative follow-up study from a statewide
survey of unmet mental health and substance use needs in South Dakota. We conducted
semistructured phone interviews with a purposive sample of key informants with
varying perceptions of need for mental health and substance use treatment.
ResultsWe interviewed 33 participants with mental health (n = 18), substance use (n
= 9), and co-occurring disorders (n = 6). Twenty participants (61.0%) lived in
rural communities that did not overlap with AI tribal land. Twelve participants
(34.3%) were AI, 8 of whom lived on a reservation (24.2%). The discrepancy between
actual and perceived treatment need was related to how participants defined mental
health, alcohol, and drug use problems. Mental health disorders and excessive
alcohol consumption were seen as a normal part of life in rural and reservation
communities; seeking mental health care or maintaining sobriety was viewed as the
result of an individual's willpower and frequently related to a substantial life
event (eg, childbirth). Participants recommended treatment gaps be addressed
through multicomponent community-level interventions. DiscussionThis study
describes how rural populations view mental health, alcohol, and drug use.
Enhancing access to care, addressing discordant perceptions, and improving
community-based interventions may increase treatment uptake.
Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for
traumatic brain injury (TBI); however, it remains unclear whether outcomes differ
for those with and without a history of preinjury abuse. A meta-analysis was
performed to examine this issue. The PubMed, Embase, and PsycINFO databases were
searched for research that compared the neuroradiological, cognitive, or
psychological outcomes of adults with and without a documented history of alcohol
and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were
analyzed using a random-effects model: Hedges's g effect sizes measured the mean
difference in outcomes of individuals with/without a history of preinjury abuse,
and Bayes factors assessed the probability that the outcomes differed. Patients
with a history of alcohol and/or substance abuse had poorer neuroradiological
outcomes, including reduced hippocampal (g=-0.82) and gray matter volumes (g=-0.46
to -0.82), and enlarged cerebral ventricles (g=-0.73 to -0.80). There were limited
differences in cognitive outcomes: Executive functioning (g=-0.51) and memory (g=-
0.39 to -0.43) were moderately affected, but attention and reasoning were not. The
findings for fine motor ability, construction, perception, general cognition, and
language were inconclusive. Postinjury substance and alcohol use (g=-0.97 to -1.07)
and emotional functioning (g=-0.29 to -0.44) were worse in those with a history of
alcohol and/or substance abuse (psychological outcomes). This study highlighted the
type and extent of post-TBI differences between persons with and without a history
of alcohol or substance abuse, many of which may hamper recovery. However,
variation in the criteria for premorbid abuse, limited information regarding the
history of abuse, and an absence of preinjury baseline data prevented an assessment
of whether the differences predated the TBI, occurred as a result of ongoing
alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance
abuse and TBI.
Pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) enzymes are
responsible for the operation of ethanolic fermentation pathway that appears to
correlate to an extent with anoxia tolerance in plants. This study was undertaken
with the objective of (a) analysing the rice pdc gene family and (b) altering the
efficacy of the ethanolic fermentation process, through production of transgenic
rice plants over- and under-expressing pyruvate decarboxylase (employing Ospdc1
gene from rice) as well as over-expressing alcohol dehydrogenase (employing Ghadh2
gene from cotton) proteins. Correlations noted in this study between the pattern of
expression of the Pdc alpha-subunit and Ospdc2 transcript as well as between the
Pdc beta-subunit and Ospdc1 transcript suggest the possibility that alpha-subunit
is encoded by Ospdc2 and that beta-subunit is encoded by Ospdc1. The fact that
levels of Pdc beta-subunit were particularly high in pUH-sPdc1 (plasmid construct
designed for over-expression of Ospdc1) seedlings while levels of beta-subunit
levels were negligible or lower in pUH-asPdc1 (plasmid construct designed for
under-expression of Ospdc1) seedlings also support these observations. Transgenics
raised for over-expression of Pdc and Adh and under-expression of Pdc were
confirmed for the transgene presence and effects by PCR, Southern blotting,
Northern blotting, Western blotting and isozyme assays. Pdc and Adh over-expressing
rice transgenics at early seedling stage under unstressed control growth conditions
showed slight, consistent advantage in root vigour as compared to that of wild-type
seedlings. (C) 2007 Elsevier Masson SAS. All rights reserved.
Background: Prior research has repeatedly shown that alcohol dependence is
associated with a large range of impairments in psychological processes, which
could lead to interpersonal deficits. Specifically, it has been suggested that
these interpersonal difficulties are underpinned by reduced recognition and sharing
of others' emotional states. However, this pattern of deficits remains to be
clarified. This study thus aimed to investigate whether alcohol dependence is
associated with impaired abilities in decoding contextual complex emotions and with
altered sharing of others' emotions. Methods: Forty-one alcohol-dependent
individuals (ADI) and 37 matched healthy individuals completed the Multifaceted
Empathy Test, in which they were instructed to identify complex emotional states
expressed by individuals in contextual scenes and to state to what extent they
shared them. Results: Compared to healthy individuals, ADI were impaired in
identifying negative (Cohen's d=0.75) and positive (Cohen's d=0.46) emotional
states but, conversely, presented preserved abilities in sharing others' emotional
states. Conclusions: This study shows that alcohol dependence is characterized by
an impaired ability to decode complex emotional states (both positive and
negative), despite the presence of complementary contextual cues, but by preserved
emotion-sharing. Therefore, these results extend earlier data describing an
impaired ability to decode noncontextualized emotions toward contextualized and
ecologically valid emotional states. They also indicate that some essential
emotional competences such as emotion-sharing are preserved in alcohol dependence,
thereby offering potential therapeutic levers.
Some addicted patients have social cognition deficits that require therapists to
have special skills to ensure treatment success. Specific remediation techniques
that teach addicted patients to look at the relevant emotional cues when
interacting with people should be tested as adjunctive treatment.
Considerable evidence has identified biased cognitive processing of alcohol-related
stimuli as an important factor in the maintenance of alcohol-seeking and relapse
among individuals suffering from alcohol use-disorders (AUDs). In addition, a large
body of research has demonstrated that exposure to alcohol cues can elicit powerful
alcohol cravings. Little is known, however, about the possible relationship between
attentional bias and cue-induced cravings, and even less is known about these
processes in social drinkers without a personal history of AUDs. The goal of this
study was to examine the possibility that attentional biases toward alcohol-related
stimuli would predict elevated cue-induced alcohol craving in this population.
Young adult social drinkers (N = 30, Mean age = 22.8 +/- 1.9, 61% female) recruited
from an urban university population completed a visual dot probe task in which they
were presented with alcohol and neutral stimulus pictures that were immediately
followed by a visual probe replacing one of the pictures. Attentional bias was
measured by calculating reaction times to probes that replaced alcohol stimuli vs.
neutral stimuli. Participants then completed a classic alcohol cue-exposure task
and reported cravings immediately before and after alcohol and neutral cue-
exposures. Not surprisingly, exposure to alcohol cues elicited significant
cravings. Consistent with the study hypothesis, larger attentional biases toward
alcohol stimuli predicted higher levels of alcohol craving. Findings demonstrate
that heightened attention to alcohol stimuli can significantly impact motivation to
consume in healthy young adults, and suggest a possible pathway linking cognitive
processes early in the drinking trajectory to the later development of AUDs. (C)
2017 Elsevier Ltd. All rights reserved.
AimsTo examine the association between a life-time history of insomnia and
hypersomnia compared with no sleep disturbance and substance use patterns and
amounts before and after a substance use treatment episode. DesignSecondary
analysis of data from the Drug Abuse Treatment Outcome Studies conducted from 1991
to 1994. SettingData were collected at 96 substance use treatment programs in 11
United States cities, including short-term in-patient, long-term residential,
methadone maintenance and out-patient drug-free treatment modalities.
ParticipantsStudy samples included 7168 adults at treatment entry and 2965 at
12months post-treatment entry whose primary substance use at entry was alcohol
(14.7%), cocaine (62.7%) or heroin (22.6%). MeasurementsLife-time history of
insomnia and hypersomnia was assessed via self-report. Type and frequency of
substance use were assessed at treatment entry. Substance use was also assessed
12months following treatment completion. Associations were examined using linear
and logistic regression with age, sex, race, education level, depression history,
treatment modality and in-treatment substance use as covariates. FindingsLife-time
history of insomnia, hypersomnia, both or neither was reported by 26.3, 9.5, 28.0
and 36.2% of participants, respectively. Compared with no sleep disturbance, life-
time insomnia and hypersomnia were associated at treatment entry with unique
substance use patterns and a higher frequency of any substance use (P<0.001). All
types of sleep disturbance were associated with higher rates of cocaine use at 12-
month post-entry (odds ratios: 1.30-1.57). ConclusionsThere is evidence of an
adverse association between substance use and sleep disturbance including higher
frequency of all substance use before substance abuse treatment and higher rates of
cocaine use after a treatment episode.
Rationale Social cognition influences social interactions. Alcohol reportedly
facilitates social interactions. However, the acute effects of alcohol on social
cognition are relatively poorly studied. We investigated the effects of alcoholic
or non-alcoholic beer on emotion recognition, empathy, and sexual arousal using the
dynamic face emotion recognition task (FERT), Multifaceted Empathy Test (MET), and
Sexual Arousal Task (SAT) in a double-blind, random-order, cross-over study in 60
healthy social drinkers. We also assessed subjective effects using visual analog
scales (VASs), blood alcohol concentrations, and plasma oxytocin levels. Alcohol
increased VAS ratings of stimulated, happy, talkative, open, and want to be with
others. The subjective effects of alcohol were greater in participants with higher
trait inhibitedness. Alcohol facilitated the recognition of happy faces on the FERT
and enhanced emotional empathy for positive stimuli on the MET, particularly in
participants with low trait empathy. Pictures of explicit sexual content were rated
as less pleasant than neutral pictures after non-alcoholic beer but not after
alcoholic beer. Explicit sexual pictures were rated as more pleasant after
alcoholic beer compared with non-alcoholic beer, particularly in women. Alcohol did
not alter the levels of circulating oxytocin. Alcohol biased emotion recognition
toward better decoding of positive emotions and increased emotional concern for
positive stimuli. No support was found for a modulatory role of oxytocin. Alcohol
also facilitated the viewing of sexual images, consistent with disinhibition, but
it did not actually enhance sexual arousal. These effects of alcohol on social
cognition likely enhance sociability. www.clinicaltrials.gov/ct2/show/NCT02318823
RefTarget Address="http://www.clinicaltrials.gov/ct2/show/NCT02318823"
TargetType="URL"/>
Background and aimsHIV-infected people with substance use disorders are least
likely to benefit from advances in HIV treatment. Integration of extended-release
naltrexone (XR-NTX) into HIV clinics may increase engagement in the HIV care
continuum by decreasing substance use. We aimed to compare (1) XR-NTX treatment
initiation, (2) retention and (3) safety of XR-NTX versus treatment as usual (TAU)
for treating opioid use disorder (OUD) and/or alcohol use disorder (AUD) in HIV
clinics. DesignNon-blinded randomized trial of XR-NTX versus pharmacotherapy TAU.
SettingHIV primary care clinics in Vancouver, BC, Canada and Chicago, IL, USA.
ParticipantsFifty-one HIV-infected patients seeking treatment for OUD (n=16), AUD
(n=27) or both OUD and AUD (n=8). MeasurementsPrimary outcomes were XR-NTX
initiation (receipt of first injection within 4weeks of randomization) and
retention at 16weeks. Secondary outcomes generated point estimates for change in
substance use, HIV viral suppression [HIV RNA polymerase chain reaction (pcr)<200
copies/ml] and safety. FindingsTwo-thirds (68%) of participants assigned to XR-NTX
initiated treatment, and 88% of these were retained on XR-NTX at 16weeks. In
comparison, 96% of TAU participants initiated treatment, but only 50% were retained
on medication at 16weeks. Mean days of opioid use in past 30 days decreased from
17.3 to 4.1 for TAU and from 20.3 to 7.7 for XR-NTX. Mean heavy drinking days
decreased from 15.6 to 5.7 for TAU and 12.5 to 2.8 for XR-NTX. Among those with
OUD, HIV suppression improved from 67 to 80% for XR-NTX and 58 to 75% for TAU. XR-
NTX was well tolerated, with no precipitated withdrawals and one serious injection-
site reaction. ConclusionsExtended-release naltrexone (XR-NTX) is feasible and safe
for treatment of opioid use disorder and alcohol use disorder in HIV clinics.
Treatment initiation appears to be lower and retention greater for XR-NTX compared
with treatment as usual ( NCT01908062).
In this paper, a three-stage operational amplifier with low-power consumption for
ALD has been designed. Based on TSMC 0.55 mu m CMOS process, using HSPICE 2008
software for circuit simulation, the results showed that the proposed op-amp has
more than 100dB open loop gain, meanwhile the static power consumption is less than
900 mu w. The circuit's phase margin is 103degrees, CMRR is 51dB and power supply
rejection ratio is 57dB.
One-step aldol condensation of methyl acetate with formaldehyde (or trioxane) for
preparing methyl acrylate at 623 K-653 K has stimulated researchers' attention in
recent years. Herein, a new methodology for one-step synthesis of methyl acrylate
from methyl acetate and trioxane promoted by generated trifluoromethanesulfonate
ionic liquid, via aldol condensation, at mild temperature was developed. The
kinetic and thermodynamic studies on this new process were also firstly
investigated systematically. Experiments were conducted in a batch reactor under
the temperatures of 283 K-298 K and reaction times of 10 min - 100 min, wherein the
side reactions could be ignored. The proposed mechanism based kinetic model was
established and simulated with experimental data. The model showed good agreement
with experimental results within the range of acceptable deviation, thereby the pre
exponential factor and activation energy of each reaction step were obtained.
Moreover, the equilibrium constant and enthalpy change of each reversible reaction
were also calculated through Van't Hoff formula. (C) 2017 Elsevier B.V. All rights
reserved.
Background: Inflammation is a key feature of aldosterone-induced vascular damage
and dysfunction, but molecular mechanisms by which aldosterone triggers
inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that
recognizes endogenous danger signals triggering sterile inflammation. Methods: We
analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3
knockout (NLRP3(-/-)), caspase-1 knockout (Casp-1(-/-)), and interleukin-1 receptor
knockout (IL-1R(-/-)) mice treated with vehicle or aldosterone (600 mu gkg(-1)d(-1)
for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Results:
Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced
vascular dysfunction. Long-term infusion of aldosterone in mice resulted in
elevation of plasma interleukin-1 levels and vascular abnormalities. Mice lacking
the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from
aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-
dependent interleukin-1 secretion by bone marrow-derived macrophages by activating
nuclear factor-B signaling and reactive oxygen species generation. Moreover,
chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that
NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition,
aldosterone increased the expression of NLRP3, active caspase-1, and mature
interleukin-1 in human peripheral blood mononuclear cells. Hypertensive patients
with hyperaldosteronism or normal levels of aldosterone exhibited increased
activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on
the inflammasome may be mediated through high blood pressure. Conclusions:
Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-
1R, is critically involved in the deleterious vascular effects of aldosterone,
placing NLRP3 as a potential target for therapeutic interventions in conditions
with high aldosterone levels.
Aldosterone has been shown to stimulate renal TGF-beta(1) expression. However, the
mechanisms for aldosterone-induced TGF-beta(1) expression have not been clearly
determined in mesangial cells. We examined the role of extracellular-signal
regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and activator
protein-1 (AP-1) in the aldosterone-induced TGF-beta(1) expression in rat mesangial
cells. TGF-beta(1) protein in the conditioned medium released from rat mesangial
cells was measured by sandwich ELISA, TGF-beta(1) mRNA expression was analyzed by
Northern blotting, AP-1 DNA binding activity was measured by EMSA and the ERK1/2,
JNK activity was analyzed by western blotting. Aldosterone significantly stimulated
TGF-beta(1) protein production and TGF-beta(1) mRNA expression in mesangial cells
in a dose-dependent manner. Aldosterone significantly increased AP-1 DNA binding
activity in mesangial cells. Pre-treatment of cells with AP-1 inhibitor, curcumin,
blocked aldosterone-induced AP-1 DNA binding activity as well as aldosterone-
induced TGF-beta(1) production. Aldosterone increased phosphorylation of ERK1/2 and
JNK in mesangial cells. Pre-treatment of cells with ERK1/2 inhibitor, PD98059, or
JNK inhibitor, SP600125 significantly inhibited aldosterone-induced ERK1/2 and JNK
activity and subsequently TGF-beta(1) production, respectively. We conclude that
aldosterone-induced TGF-beta(1) expression in mesangial cells is regulated by the
ERK1/2, JNK and AP-1 intracellular signaling pathways.
The objective of this study was to measure the effect of selection for tolerance on
the severity of the Aleutian disease (AD) lesions in mink. Sensitivity and
specificity of antibody detection in the blood by counter-immunoelectrophoresis
(CIEP) relative to the presence of Aleutian mink disease virus (AMDV) in the spleen
by PCR in naturally infected farmed mink were also estimated. Carcasses of 680
sero-positive (CIEP-P) black mink from 28 farms in Nova Scotia, Canada, and from
132 sero-negative (CIEP-N) mink from 14 of these farms were collected at pelting
time. A total of 116 of the CIEP-P mink were from three farms where animals have
been selected for tolerating AD for almost 20 years. The severity of the AD lesions
was assessed by histopathological examination of kidneys, lungs, heart, brain and
liver on a scale of 0 to 4. Sensitivity and specificity of CIEP relative to PCR
were 0.97 and 0.85, respectively, and 16.5% of CIEP-N mink were PCR positive, which
could be one of the reasons for the failure of virus eradication by CIEP in Canada.
The CIEP-N and tolerant CIEP-P animals had 9.39 and 6.23 greater odds of showing
lower lesion severity, respectively, than the CIEP-P animals (P < 0.01). The CIEP-N
mink had a slightly higher chance (P = 0.07) of showing lower lesion severity (odds
ratio 1.51) compared with tolerant CIEPP mink. The results suggested that tolerant
mink had significantly reduced severity of AD lesions despite having anti-viral
antibodies and carrying the virus. (C) 2017 The Authors. Published by Elsevier Ltd.
The objective of this study was to assess the sensitivity of the Omni Klentaq-LA
DNA polymerase for detecting Aleutian mink disease virus (AMDV) in mink blood and
tissues by PCR without DNA extraction. The presence of AMDV DNA was directly tested
by Klentaq in the plasma, serum, whole blood, and spleen homogenates of 188 mink 4
and 16 months after inoculation with the virus. Samples from bone marrow, small
intestine, liver, lungs, kidneys, and lymph nodes of 20 of the same mink were also
tested by Klentaq. DNA was extracted from paired samples of plasma and the
aforesaid tissues by a commercial nucleic acid extraction kit (Dynabeads Silane)
and tested by PCR. Compared with the extracted DNA, Klentaq detected a
significantly greater number of samples in the whole blood, serum, plasma, spleen,
and small intestine. It was concluded that Klentaq is a preferred system for
directly detecting AMDV DNA in mink blood and tissues. The lower success rate of
extracted DNA compared with Klentaq could be the result of DNA losses during the
extraction process. This is an important factor in chronically infected mink, which
have a low AMDV copy number in the bloodstream. Direct AMDV detection also reduces
the cost of PCR amplification and lowers the risk of sample contamination.
Background: Childhood adversities and emotional dysregulation are connected with
chronic pain, alexithymia, and depression. Longitudinal studies exploring the
impact of their co-occurrence on the pain situation are rare.Aims: The influence of
alexithymia, depression, baseline pain situation, and treatment options on the
course of chronic pain in a clinical sample was studied.Methods: The baseline data
was collected from chronic pain patients (n=154) before their first pain clinic
visit, and the follow-up data after 1 year by self-report questionnaires. Study
variables consisted of pain intensity, pain disability, alexithymia (TAS-20),
depression (BDI-II), and treatment interventions. Statistical analyses were
performed to find out differences between baseline and follow-up, as well as
between alexithymic and non-alexithymic patients, and to estimate the effect of the
treatment provided.Results: At follow-up, the majority of the patients had pain
intensity and disability severe enough to disrupt with their daily living. None of
treatment interventions was related to better outcome. Alexithymic patients
reported more pain disability and depression at both baseline and at follow-up. The
effect of alexithymia on pain disability was mediated by depression. The use of
opioids was connected to alexithymia and depressiveness. Alexithymia and depression
made a substantial contribution to poorer outcome.Conclusions: Severe pain
intensity and disability with depression and alexithymia predicted difficulties in
achieving improvement. Depression and alexithymia probably impair compliance with
treatment and adherence to interventions. Their co-occurrence with a more severe
pain situation and with the use of opioids indicates psychological problems
underlying the pain experience.
Background and objectives: Alexithymia is a multidimensional personality construct
including the components difficulties identifying feelings (DIF), difficulties
describing feelings (DDF), and externally oriented thinking (EOT). Different
features of alexithymia are thought to reflect specific deficits in the cognitive
processing and regulation of emotions. The aim of the present study was to examine
for the first time patterns of deployment of attention as a function of alexithymia
components in healthy persons by using eye-tracking technology. It was assumed that
EOT is linked to avoidance of negative images. Methods: 99 healthy adults viewed
freely pictures consisting of anxiety-related, depression-related, positive, and
neutral images while gaze behavior was registered. Alexithymia was assessed by the
20 Item Toronto Alexithymia Scale. Measures of anxiety, depression, and (visual-
perceptual) intelligence were also administered. Results: A main effect of emotion
condition on dwell times was observed. Viewing time was lowest for neutral images,
longer for depression-related and happy images, and longest for anxiety-related
images. Gender and EOT had significant effects on dwell times. EOT correlated
negatively with dwell time on depression-related (but not anxiety-related) images.
There were no correlations of dwell times with depression, trait anxiety,
intelligence, DIF, or DDF. Limitations: Alexithymia was assessed exclusively by
self-report. Conclusions: Our results show that EOT but not DIF or DDF influences
attention deployment to simultaneously presented emotional pictures. EOT may reduce
attention allocation to dysphoric information. This attentional characteristic of
EOT individuals might have mood protecting effects but also detrimental impacts on
social relationships and coping competencies. (C) 2016 Elsevier Ltd. All rights
reserved.
In legume plants, uricase gene (Nodulin-35) plays a positive role in metabolism of
ureide and amide compounds in symbiotic nitrogen-fixing in the nodules. In this
study, a pot experiment was performed to examine the effects of ammonium
application on the transcription of MsU2 gene and distribution of major nitrogen
compounds in alfalfa Medicago sativa. Data showed that alfalfa plant has a
significant difference in contents of nitrogen compounds in xylem saps compared
with soybean plant, and belongs to typical amide type legume plants with little
ureide accumulation, and the accumulation of asparagines and ureide in the tissues
of alfalfa is mainly gathered in the nodules. Northern blotting showed that
excessive ammonium significantly inhibited the transcription of MsU2 gene in the
nodules and roots, and mRNA accumulation of MsU2 gene in the plants exposed to
excessive ammonium decreased gradually with culture time extension, indicating that
application of ammonium significantly inhibited the transcription of MsU2 gene in
the alfalfa plants. Although the application of excessive ammonium increased the
contents of amino acids in various tissues of alfalfa, the accumulation of
allantoin reflecting the strength of uricase activity is remarkably reduced in the
xylem saps, stems and nodules when alfalfa plants exposed to excessive ammonium,
suggesting that application of excessive ammonium generated a negative effect on
symbiosis fixing-nitrogen system due to inhibition of ammonium ion on uricase
activity in the nodules of alfalfa. This result seems to imply that application of
excessive ammonium in legume plants should not be proposed to avoid affecting the
ability of fixing nitrogen in the nodules of legume plants, and reasonable dose of
ammonium should be recommended to effectively utilize the fixed N from atmosphere
in legume plant production.
The imminent depletion of fossil fuels and the surging global demand for renewable
energy have led to the search for nonconventional energy sources. After a few
decades of trial and error, the world is now testing the sources of the third
generation of fossil fuels, which contain for most parts microalgae. With more than
80% oil content, being adaptable in growth parameters and highly versatile,
microalgae are highly promising sources of biofuels in the present time. The
present article makes a sweeping attempt to highlight the various methods employed
for cultivation of microalgae, techniques to harvest and extract biomass from huge
algal cultures, as well as their downstream production and processing procedures.
The advantages, limitations, and challenges faced by each of them have been
described to some extent. Major concerns pertaining to biofuels are supposed to be
their environmental sustainability and economic viability along with their cost
effectiveness. This would require a great deal of empirical data on existing
systems and a great deal of optimization to generate a more robust one. We have
concluded our article with a SWOT analysis of using algae for biodiesel production
in a tabulated form. (C) 2015 International Union of Biochemistry and Molecular
Biology, Inc.
The natural variation of environmental factors in freshwater basins determines
their biodiversity. Among them, calcium is a key physiological compound for
freshwater invertebrates. It is required for shell formation, muscle contraction,
it mediates gene expression and allows counteracting acidosis during stress
periods, among other functions. Although the distribution of different freshwater
species has been suggested to be linked with the environmental calcium
concentration, as yet no research studies have confirmed this. Identifying whether
environmental calcium concentrations might determine the invasion success of alien
species would be critical in developing and implementing effective management
strategies to control them. Here, a multidisciplinary approach integrating field
surveys, analytical chemistry techniques, molecular biology analyses and a lab-
scale experiment was taken to decipher whether the environmental calcium
Concentration might hamper the establishment of Corbicula fluminea in northwestern
Iberian rivers. A Principal Component Analysis on water chemistry variables from 13
water bodies identified environmental calcium concentration, among others, as one
key factor that best characterized the distribution area of C. fluminea. The
calcium content in animals' bodies from two representative rivers was dependent on
the environmental calcium concentration of freshwater basins; the lower the
concentration, the lower the body's content. The expression of stress- and calcium
homeostasis-related genes was higher in C fluminea from low calcium concentration
environments than in those from calcium-rich freshwater basins. Finally, under
experimental conditions, lower water calcium concentrations decreased C fluminea
growth rates. The present data suggest, for the first time, that environmental
calcium concentration may act as a determinant factor on the invasion success of C.
fluminea in freshwater environments. Our results provide new clues for the
identification of basins with increased risk of potential invasion by C fluminea
based on environmental calcium levels. (C) 2016 Elsevier B.V. All rights reserved.
Munchausen syndrome by proxy (MSBP), also known as fabricated or induced illness in
a child by a caretaker, is a form of abuse where a caregiver deliberately produces
or feigns illness in a person under his or her care, so that the proxy will receive
medical care that gratifies the caregiver. The affected children are often
hospitalized for long periods and endure repetitive, painful and expensive
diagnostic attempts. We present an analytically confirmed case of MSBP by
alimemazine. A 3-year-old boy was brought repetitively to a Pediatric Emergency
Department by his mother because he presented limb tremors, dysarthria,
obnubilation, and ataxia and generalized tonic-clonic seizures coinciding with
intermittent fever. Neither the rest of the physical examination nor the
complementary tests showed any significant alterations. MSBP was suspected and a
routine systematic toxicological analysis in urine and blood was requested.
Alimemazine was detected in all biological samples. The administration of this drug
was never mentioned by the mother and the subsequent interview with her
corroborated the suspicion of MSBP. Clinically, after separation from the mother,
the child's neurological symptoms gradually improved until the complete
disappearance of the cerebellar symptoms. Alimemazine was quantified in serum,
urine, gastric content and cerebrospinal fluid samples by gas chromatography-mass
spectrometry (maximum serum level was 0.42 mu g/ml). Hair quantification of
alimemazine was performed by ultra-performance liquid chromatography-tandem mass
spectrometry in different segments of hair. The results confirmed regular substance
use during the at least eight last months (8.8, 14.7, 19.7 and 4.6 ng/mg hair
starting from most proximal segment). This patient represents the first case
published with analytical data of alimemazine in blood, urine, gastric content,
cerebrospinal fluid and hair, which allowed us to prove an acute and repetitive
poisoning with alimemazine as evidence of MSBP. (C) 2016 Elsevier Ireland Ltd. All
rights reserved.
Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary
technique available in all laboratories of pathology. This method is generally used
for diagnostic purposes, but several studies have investigated the sensitivity and
specificity of different immunohistochemical anti-bodies as a surrogate test in the
determination of predictive biomarkers in non-small cell lung cancer (NSCLC),
particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic
Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical
examination of the works comparing the consistency of IHC expression and
conventional molecular techniques to identify genetic alterations with predictive
value in NSCLC is discussed. Summarizing, data on sensitivity and specificity of
antibodies against ALK and ROS1 are very consistent and time has come to trust in
IHC at least as a cost-effective screening tool to identify patients with
rearranged tumors in clinical practice. On the other hand, mutant-specific
antibodies against EGFR demonstrate a good specificity but a lowto- fair
sensitivity, raising some cautions on their employment as robust predictive
biomarkers. A brief comment on preliminary experiences with antibodies against
BRAF, RET, HER2 and c-MET is also included.
Allatostatins are important regulatory neuropeptides which are widely distributed
in invertebrates and execute their functions through either neural or Immoral
routes. However, the regulatory mechanism of the gene expression is unclear. In
this paper, we report a naturally occurring amisense transcript, named as asMacro-
AST A, of the crustacean FGLamide allatostatin gene (Macro-AST A) from the prawn,
Macrobrachium rosenbergii. The asMacro-ASTA contains an 843-bp sequence fully
complementary to the 3'end of the Macro-ASTA. To our knowledge, this is the first
report of a natural antisense transcript in crustacean and the first endogenous
antisense transcript of all identified allatostatin genes. Northern blotting
analysis demonstrated that the gene was expressed in the thoracic ganglia where the
sense gene was also expressed. Furthermore, we have detected a RNA-RNA duplex
between the sense-antisense complementary region by using RNasc protection analysis
and RT-PCR. These results suggest that the antisense gene may play a role in the
regulation of Macro-AST A gene expression. (c) 2006 Elsevier Inc. All rights
reserved.
Traditional digital controls mostly use digital-analog converters to convert input
and output voltages into digital coding to achieve control. This paper proposes the
use of two digital ramps with two different frequencies to replace a digital-analog
converter. This approach can produce seven bit resolution for the DPMW signal. In
addition, we use an all-digital DLL phase correction concept to further enhance the
resolution of the DPWM signal by an additional three bits, resulting in 10-bit DPWM
signal resolution. The proposed circuit uses 0.35 mu m CMOS processes, with a core
area of 0.987 mm(2), a system switching frequency of 500 KHz, an input voltage
range of 3.3-4.2 V, and an output voltage range of 5 V. Output voltage measurement
accuracy reaches 99%, while the system reaches efficiency of 91% with output loads
of up to 500 mA. (C) 2015 Elsevier Ltd. All rights reserved.
Background: Knockdown resistance (kdr), caused by alterations in the voltage-gated
sodium channel (Na-v), is one of the mechanisms responsible for pyrethroid (PY)
resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different
mutations were described in the IIIS6 Na-v segment in populations from Asia, North
America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous
mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6
Na-v segments. The Phe1534Cys kdr mutation in the IIIS6 Na-v segment is the most
prevalent in populations of Ae. aegypti worldwide, also found in Ae. albopictus
from Singapore. Herein, we investigated the DNA diversity corresponding to the IIS6
and IIIS6 Na-v segments in natural populations of Ae. albopictus from Brazil.
Methods: DNA from eight Brazilian Ae. albopictus natural populations were
individually extracted and pooled by states of origin, amplified, cloned and
sequenced for the corresponding IIS6 and IIIS6 Na-v segments. Additionally, samples
from each location were individually genotyped by an allelic specific PCR (AS-PCR)
approach to obtain the genotypic and allelic frequencies for the 1534 Na-v site.
Results: No non-synonymous substitutions were observed in the IIS6 sequences.
However, the Phe1534Cys kdr mutation was evidenced in the Ae. albopictus Na-v IIIS6
segment sequences from Parana (PR) and Rondonia (RO) states, but not from Mato
Grosso (MT) state. The 1534Cys(kdr) allele varied from 3% (Marilena/PR and Porto
Velho/RO) to 10% ( Foz do lguacu/ PR). To our knowledge, this paper reports the
first occurrence and provides distribution data of a possible kdr mutation in Ae.
albopictus in South America. Conclusion: The emergence of a likely kdr mutation in
Ae. albopitus natural populations is a signal of alert for vector control measures
since PY are the most popular insecticides adopted by residents. Additionally, once
the kdr allele is present, its frequency tends to increase faster under exposition
to those compounds. Although the Asian tiger mosquito is not incriminated as an
important vector of dengue, chikungunya and Zika viruses in South America, its
importance in this regard has been extensively discussed since Ae. albopictus is
rapidly spreading and can also migrate between sylvatic and urban environments.
Therefore, insecticide resistance monitoring initiatives should also be extended to
Ae. albopictus in Brazil in order to maintain chemical compounds as an efficient
vector control tool when needed.
Introduction: Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma
[PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a
diagnostic clue to these entities. Targeted therapies against BRAF-V600 protein
have shown promising results in GNT. The aim of this study was to assess the
utility of BRAF-V600E immunohistochemistry (IHC, clone VE1) in daily practice in a
series of 140 glial, and GNT compared to molecular biology (MB) techniques.
Methods: We performed BRAF-V600E IHC on all 140 cases. We used Sanger sequencing
and allele-specific quantitative PCR (ASQ-PCR) to detect BRAF-V600E mutation when
sufficient amount of materiel was available. Results: BRAF-V600E immunostaining was
detected in 29.5% of cases (41/140 cases; 61.5% GG/GC/AGG (32/52), 33% PXA, 6.6%
pilocytic astrocytomas). In 47 cases, MB could be performed: Sanger sequencing and
ASQ-PCR in 34 cases, ASQ-PCR only in 11 cases, and Sanger sequencing only in two
cases. In initial tumors, Sanger sequencing identified BRAF-V600E mutation in 19.5%
tumors (seven of 36 tested cases). ASQ-PCR showed mutation in 48.5% tumors (17/35
tested cases). In six cases (5 GG, one PXA), the results were discordant between
IHC and MB; the five GG cases were immunopositive for BRAF-V600E but wild type with
both MB techniques. In another 7 GG, the percentage of mutated (ganglion) cells was
low, and Sanger sequencing failed to detect the mutation, which was detected by IHC
and ASQ-PCR. Conclusions: In tumors with few mutated cells (e.g., GG), anti-BRAF-
V600E IHC appears more sensitive than Sanger sequencing. The latter, although
considered as the gold standard, is not to be used up-front to detect BRAF mutation
in GG. The combination of IHC and ASQ-PCR appears more efficient to appraise the
indication of targeted therapies in these glioneuronal tumors.
BACKGROUND: It is unclear whether allergen immunotherapy (AIT) can be safely
initiated during the pollen season (coseasonal initiation [CSI]) because of a
potential increased risk of systemic allergic reactions. OBJECTIVE: To
systematically review publications reporting the safety of subcutaneous
immunotherapy (SCIT) and sublingual immunotherapy (SLIT) CSI to validate or
invalidate the perception of increased safety risk. METHODS: PubMed, EMBASE, Ovid,
Literatura Latino Americana em Ciencias da Saude (LILACS), and Cochrane Library
databases were searched without limits for studies of any design reporting SCIT or
SLIT CSI for pollen allergen. Congress abstracts were included. RESULTS: Nineteen
eligible studies were identified: 8 SCIT (n = 947 subjects total; n[340 double-
blind placebo-controlled [DBPC]) and 11 SLIT (n = 2668 subjects total; n = 565
DBPC). Study characteristics and safety reporting were heterogeneous. No
epinephrine administrations were reported. Discontinuation frequencies were 6% or
less and 10% or less with SCIT and SLIT CSI, respectively. In SCIT studies,
systemic allergic reaction frequency was 0% to 7% with "up to peak season" or CSI,
0% to 6% with "after peak season" or out-of-season initiation, and 0% to 7% with
placebo. In SCIT studies, serious treatment-related adverse event (AE) frequency
with CSI ranged from 0% to 2%; few severe AEs were reported. In SLIT studies,
systemic allergic reaction frequency ranged from 0% to 4% with CSI, 0% with out-of-
season initiation, and 0% to 2% with placebo. Overall, 2 serious treatment-related
AEs with SLIT CSI were reported. Severe AE frequency in SLIT studies ranged from 0%
to 8% with CSI, 0% to 12% with out-of-season initiation, and 0% to 8% with placebo.
CONCLUSIONS: No increase in AEs of concern was observed with SCIT or SLIT CSI;
however, additional data with standardized regimens and doses are needed. (C) 2016
American Academy of Allergy, Asthma & Immunology
Allergic diseases often occur early in life and persist throughout life. This life-
course perspective should be considered in allergen immunotherapy. In particular it
is essential to understand whether this al treatment may be used in old age adults.
The current paper was developed by a working group of AIRWAYS integrated care
pathways for airways diseases, the model of chronic respiratory diseases of the
European Innovation Partnership on active and healthy ageing (DG CONNECT and DG
Sante). It considered (1) the political background, (2) the rationale for allergen
immunotherapy across the life cycle, (3) the unmet needs for the treatment, in
particular in preschool children and old age adults, (4) the strategic framework
and the practical approach to synergize current initiatives in allergen
immunotherapy, its mechanisms and the concept of active and healthy ageing.
BackgroundClinical efficacy of pollen allergen immunotherapy (AIT) has been broadly
documented in randomized controlled trials. The underlying clinical endpoints are
analysed in seasonal time periods predefined based on the background pollen
concentration. However, any validated or generally accepted definition from
academia or regulatory authorities for this relevant pollen exposure intensity or
period of time (season) is currently not available. Therefore, this Task Force
initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed
to propose definitions based on expert consensus. MethodsA Task Force of the
Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed
the literature on pollen exposure in the context of defining relevant time
intervals for evaluation of efficacy in AIT trials. Underlying principles in
measuring pollen exposure and associated methodological problems and limitations
were considered to achieve a consensus. ResultsThe Task Force achieved a
comprehensive position in defining pollen exposure times for different pollen
types. Definitions are presented for pollen season', high pollen season' (or peak
pollen period') and high pollen days'. ConclusionThis EAACI position paper provides
definitions of pollen exposures for different pollen types for use in AIT trials.
Their validity as standards remains to be tested in future studies.
There is no universally accepted grading system to classify the severity of
systemic allergic reactions (SARs), including anaphylaxis. Although a consensus
definition for anaphylaxis was established in 2005, the signs and symptoms required
to define a reaction as anaphylaxis are inconsistently applied in research and
clinical practice. As a result, it is difficult to compare and evaluate safety
outcomes in surveys, clinical practice and trials, and pharmacovigilance data. In
2010, the World Allergy Organization (WAO) proposed a uniform grading system to
classify allergen immunotherapy SARs. The basis of the grading system is the organ
system(s) involved and reaction severity. The final grade is determined by the
physician/health care professional after the event is over. Although the 2010 WAO
grading system was developed to classify allergen immunotherapy SARs, with
appropriate modifications, it can be used to classify SARs from any cause. The
purpose of this Rostrum is to present a proposed modification of the 2010 WAO SAR
grading system that will make it applicable to all SARs due to any cause. The
modified grading system allows for classification of less severe SARs, which may be
underreported or overreported in clinical trials and surveillance studies,
depending on the criteria specified for adverse event reporting. The universal use
of the proposed modified SAR grading system will allow for better safety
comparisons across different venues and treatment protocols. (C) 2016 American
Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:58-62)
Keratinocytes (KCs) play a key role in all phases of skin sensitization. We
recently identified interleukin-18 (IL-18) production as useful end point for
determination of contact sensitization potential of low molecular weight chemicals.
The aim of this study was to identify genes involved in skin sensitizer-induced
inflammasome activation and to establish their role in IL-18 production. For gene
expression analysis, cells were treated for 6 h with p-phenylenediamine (PPD) as
reference contact allergen; total RNA was extracted and examined with a
commercially available Inflammasome Polymerase Chain Reaction (PCR) array. Among
genes induced, NLRP12 (Nod-like receptor P12) was selected for further
investigation. NLRP12 promoter region contains Blimp-1 (B-lymphocyte-induced
maturation protein-1)/PRDM1 binding site, and from the literature, it is reported
that Blimp-1 reduces NLRP12 activity and expression in monocytes/macrophages. Their
expression and role in KCs are currently unknown. To confirm NLRP12 expression and
to investigate its relationship with Blimp-1, cells were exposed for different
times (3, 6 and 24 h) to the extreme sensitizer 2,4-dinitrochlorobenzene (DNCB) and
the strong sensitizer PPD. Allergens were able to induce both genes, however, with
different kinetic, with DNCB more rapidly upregulating Blimp-1 and inducing IL-18
production, compared to PPD. NLRP12 and Blimp-1 expression appeared to be inversely
correlated: Blimp-1 silencing resulted in increased NLRP12 expression and reduced
contact allergen-induced IL-18 production. Overall results indicate that contact
allergens of different potency differently modulate Blimp-1/NLRP12 expression, with
strong allergen more rapidly downregulating NLRP12, thus more rapidly inducing IL-
18 production. Data confirm that also in KCs, NLRP12 has an inhibitory effect on
inflammasome activation assessed by IL-18 maturation.
Background There is limited understanding of how maternal diet affects breastmilk
food allergen concentrations, and whether exposure to allergens through this route
influences the development of infant oral tolerance or sensitization. Objective To
investigate how maternal dietary egg ingestion during early lactation influences
egg protein (ovalbumin) levels detected in human breastmilk. Methods In a
randomized controlled trial, women were allocated to a dietary group for the first
six weeks of lactation: high-egg diet (>4 eggs per week), low-egg diet (one-three
eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6
weeks of lactation for the measurement of ovalbumin. The permeability of the
mammary epithelium was assessed by measuring the breastmilk sodium : potassium
ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and
prior to the introduction of egg in solids at 16 weeks. Results Average maternal
egg ingestion was associated with breastmilk ovalbumin concentration. Specifically,
for each additional egg ingested per week, there was an average 25% increase in
ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin
concentrations were significantly higher in the ` high-egg' group (>4 eggs per
week) compared with the ` egg-free' group (P = 0.04). However, one-third of women
had no breastmilk ovalbumin detected. No detectable associations were found between
mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant
plasma egg-specific IgG4 levels were also positively associated with maternal egg
ingestion, with an average 22% (95% CI: 3-45%) increase in infant egg-specific IgG4
levels per additional egg consumed per week (P = 0.02). Conclusions and Clinical
Relevance Increased maternal egg ingestion is associated with increased breastmilk
ovalbumin, and markers of immune tolerance in infants. These results highlight the
potential for maternal diet to benefit infant oral tolerance development during
lactation.
The ocular surface is constantly exposed to environmental irritants, allergens and
pathogens, against which it can mount a prompt immune response to preserve its
integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal
immune system must also discriminate between harmless and potentially dangerous
antigens, a seemingly complicated task. Despite its unique features, the ocular
surface is a mucosal lining, and as such, it shares some homeostatic and
pathophysiological mechanisms with other mucosal surfaces. The purpose of this
review is to explore the mucosal homeostatic immune function of the ocular surface
in both the healthy and diseased states, with a special focus on mucosal immunology
concepts. The information discussed in this review has been retrieved by PubMed
searches for literature published from January 1981 to October 2016.
Allergic rhinitis (AR) is a common illness in children and can impair their quality
of life. Furthermore, many children remain symptomatic despite maximizing systemic
antihistamine and topical therapies. It is at this clinical juncture that
immunotherapy may be considered. The efficacy and safety associated with both
subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as
treatment options for pediatric patients, with specific focus on current literature
as it relates to SLIT in children, including those with perennial allergic
rhinitis. Although there is more extensive experience with SLIT treatment in
Europe, grass and ragweed tablet forms of SLIT are approved in the US. Approaches
to the care of pediatric patients with allergic rhinitis are presented. (C) 2016
American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract
2017;5:46-51)
Background: Allergic rhinitis (AR) is the most common chronic disease among
children. To characterize the disease, a modified classification of severity (m-
ARIA) has recently been validated in AR children. When medical treatment fails,
surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our
objective was to assess the prevalence of NOD and their influence in medical
treatment response among children with persistent AR (PER). Methods: In a
prospective, real-life study, 130 paediatric PER patients (13.1 +/- 2.8years,
females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were
assessed for their response (R, responders; NR, non-responders) to medical
treatment (intranasal steroids and antihistamines or antileukotrienes) by direct
questioning and nasal symptom visual analogue scale, the presence of NOD (septal
deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal
symptoms, rhinitis severity (modified ARIA criterion) and asthma control
(International Consensus On Pediatric Asthma criterion). Results: After 2months of
treatment, the NR group presented a higher prevalence of obstructive septal
deformity and severe inferior turbinate enlargement when compared with the R group.
Higher septal deformity and turbinate enlargement scores were strongly associated
with treatment refractoriness. The prevalence of severe PER was also higher for the
NR group. Higher asthma control scores were associated with the probability of
treatment-induced improvement. Conclusions: In paediatric PER patients, medical
therapy refractoriness was associated with NOD, mainly septal deformity and
turbinate enlargement. In those patients, ENT examination will facilitate an early
NOD diagnosis in order to indicate potential corrective surgery.
Background Over the past decade, regulatory bodies and scientific societies
recommended, as primary efficacy outcome, a score that reflects both symptom
severity and use of rescue medication for clinical trials in allergy immunotherapy
(AIT). Objective We sought to compare the results obtained with two subject-
specific scores, the Combined Score (CS) and the Adjusted Symptom Score (AdSS), for
assessment of AIT in seasonal allergic rhinoconjunctivitis due to birch and grass
pollen allergens. Methods CS and AdSS were evaluated in subjects receiving a 300IR
dose of allergen extract daily, by sublingual route, in four clinical trials with
the 5-grass pollen tablet (NCT00367640, NCT00409409, NCT00955825 and NCT00418379)
and one with the birch pollen solution (NCT01731249). The CS is derived from the
Rhinoconjunctivitis Total Symptom Score (RTSS) and the Rescue Medication Score
(RMS) giving equal weight to symptoms and medication use. The AdSS is a symptom
score adjusting for rescue medication use. Efficacy end-points were analysed using
an analysis of covariance linear model. Results In all trials, despite the
different constructs of the two scores, Combined Score or Adjusted Symptom Score
were similarly reduced in the 300IR group compared to the placebo group. Treatment
effect was consistently demonstrated with both scores, CS and AdSS, used as either
daily scores or average of the daily scores over the pollen season. Minor
differences with the same statistical conclusions were observed between the
results, leading to the same interpretation. Conclusions and Clinical Relevance The
two scores, combined and adjusted scores, for evaluation of clinical efficacy of
AIT have led to similar results, with similar statistical conclusions and similar
interpretation.
Background: Limited accessibility to providers may delay appropriate control of
asthma exacerbations. The objective of our study is to estimate the contributors to
the hospital/emergency department (ED) visits among adults with asthma focusing on
the availability of healthcare providers. Methods: We conducted a pooled cross-
sectional analysis using the 2011-2013 Asthma Call-Back Survey linked with 2012-
2016 Area Health Resource Files. We employed multivariable logistic regression with
dichotomous outcomes of hospitalization and ED visits. Key covariates were the
availability of county-level healthcare provider variables per 100,000 persons such
as the number of lung disease specialists (including pulmonary care specialists,
and allergy and immunology specialists), the number of hospitals, the number of
safety-net facilities including rural health centers (RHCs) and federally qualified
health centers (FQHCs), and the number of primary care physicians (PCPs). Results:
Among 25,621 adults, proportions of hospital visits and ED visits were 3.3% and
13.2%, respectively. An additional RHC reduced by 3% the odds of having an ED visit
(odds ratio [OR] = 0.97, p=.004). Patients with cost barriers to seeing a PCP were
60% (OR = 1.60, p=.028) more likely to have a hospital visit than those without. In
addition, patients with cost barriers to seeing a specialist were 90% (OR = 1.90,
p=.007) and 111% (OR =2.11, p=.001) more likely to have a hospital visit and ED
visit, respectively, than those without. Conclusions: Hospital and ED visits among
adults with asthma are partially related to the availability of providers, and more
related to financial barriers. Therefore, financial support for the vulnerable
asthma population might be a target for policy makers interested in reducing
hospitalizations and ED visits.
Background: Porphyromonas gingivalis (Pg) capsule enables evasion from
phagocytosis, invasion of keratinocytes, and bacterial survival. In mixed
infection, the capsule also participates in coaggregation, which may lead to
characteristic virulence not present in the monoinfection. The aim of this study is
to evaluate the role of Pg capsule as a virulence factor in coaggregated mixed
infection with Fusobacterium nucleatum (Fn). Methods: Mixed infections containing
Fn and non-capsulated or capsulated strains of Pg were compared with the same
infection with lactose as coaggregation inhibitor. Murine experimental
periodontitis was used to assess disease severity. Primary polymorphonuclear
leukocytes and keratinocytes were used to examine phagocytosis and bacterial
invasion, respectively. Results: Mixed infection with capsulated Pg augmented
alveolar bone loss compared with that of mixed infection with non-capsulated Pg.
Addition of lactose led to attenuation of bone loss in the capsulated mixed
infection and to intensification of bone loss in the non-capsulated mixed
infection. In the latter mixed infection, Fn evaded phagocytosis, whereas in the
capsulated mixed infection Pg displayed a greater capacity for invasion of
keratinocytes. Conclusions: Pg capsule was found to serve as a unique virulence
factor in mixed infection with Fn. Capsule-dependent coaggregation led to augmented
invasion of Pg and may be responsible for the severity of disease after mixed
infection with Fn.
Background: Leukotoxin (Ltx) expressed by Aggregatibacter actinomycetemcomitans is
a powerful exotoxin, which can cause imbalance in host response. Immunoreactivity
to Ltx is a marker for presence of leukotoxic A. actinomycetemcomitans, a presence
that may modify the disease pattern of colonized individuals. The aim of the
present study is to examine presence of systemic immunoreactivity to A.
actionmycetemcomitans Ltx with respect to clinical and inflammatory findings in
individuals with or without periodontitis (N = 88). Methods: Periodontal status was
examined in patients with severe periodontitis (n = 49) and healthy controls (n =
39), and patients received periodontal treatment. Systemic biomarkers associated
with inflammation and infections as well as clinical parameters were analyzed at
baseline and 3 and 6 months after treatment. Results: Presence of immunoreactivity
against Ltx was associated with impaired remission of disease after periodontal
treatment. This immunoreactivity was also significantly associated with increased
systemic levels of A. actinomycetemcomitans-specific immunoglobulins and increasing
age. Conclusion: Presence and levels of systemic immunoreactivity against A.
actinomycetemcomitans Ltx are associated with decreased remission after otherwise
successful periodontal treatment.
Among athletes and coaches, there is a common perception that high training loads
and competitions, applied chronically, with inadequate nutritional control and/or
recovery periods, may reduce the immune resistance, increasing susceptibility to
infection episodes, mainly upper respiratory tract infection (URTI). In this sense,
this study is focused on reviewing the interactions between immunological
parameters with the overtraining syndrome, specifically in team sports, considering
its intermittent nature. Thus, a review of national and international journals
related to the topic was held. The correlations between exercise, immune system and
susceptibility to URTI have been evaluated mainly in individual and endurance
sports compared to the team sports. The modulations of leukocytes throughout the
season, against the totalization of training loads and competitions, when analyzed
specifically for neutrophils and monocytes, are possibly related to tissue repair
processes and incidence of URTI. Modulations related to lymphocytes seem to be more
directly related to the incidence of URTI. Moreover, an understanding of all the
proposed markers, including immunological markers, in association with the
performance indicators and control of training, appears to be a more promising
avenue for clinical diagnosis of the athlete's immune status and prevention of
overtraining syndrome than the search for a unique marker of overtraining.
Background Adrenaline auto-injectors (AAI) should be provided to individuals
considered to be at high risk of anaphylaxis. There is some evidence that the rate
of AAI prescription is increasing, but the true extent has not been previously
quantified. Aim To estimate the trends in annual GP-issued prescriptions for AAI
among UK children between 2000 and 2012. Design and setting Retrospective cohort
study using data from primary care practices that contributed to The Health
Improvement Network (THIN) database. Method Children and young people aged between
0-17 years of age with a prescription for AAIs were identified, and annual AAI
device prescription rates were estimated using Stata (version 12). Results A total
of 1.06 million UK children were identified, providing 5.1 million person years of
follow-up data. Overall, 23 837 children were deemed high risk by their GPs, and
were prescribed 98 737 AAI devices. This equates to 4.67 children (95% confidence
interval [CI] = 4.66 to 4.69), and 19.4 (95% CI = 19.2 to 19.5) devices per 1000
person years. Between 2000 and 2012, there has been a 355% increase in the number
of children prescribed devices, and a 506% increase in the total number of AAI
devices prescribed per 1000 person years in the UK. The number of devices issued
per high-risk child during this period has also increased by 33%. Conclusion The
number of children being prescribed AAI devices and the number of devices being
prescribed in UK primary care between 2000 and 2012 has significantly increased. A
discussion to promote rational prescribing of AAIs in the NHS is needed.
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in
the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for
the management of insect venom allergy. To inform this process, we sought to assess
the effectiveness, cost-effectiveness and safety of AIT in the management of insect
venom allergy. Methods: We undertook a systematic review, which involved searching
15 international biomedical databases for published and unpublished evidence.
Studies were independently screened and critically appraised using established
instruments. Data were descriptively summarized and, where possible, meta-analysed.
Results: Our searches identified a total of 16 950 potentially eligible studies; of
which, 17 satisfied our inclusion criteria. The available evidence was limited both
in volume and in quality, but suggested that venom immunotherapy (VIT) could
substantially reduce the risk of subsequent severe systemic sting reactions (OR =
0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-
specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse
effects were experienced in both the build-up and maintenance phases, but most were
mild with no fatalities being reported. The very limited evidence found on
modelling cost-effectiveness suggested that VIT was likely to be cost-effective in
those at high risk of repeated systemic sting reactions and/or impaired quality of
life. Conclusions: The limited available evidence suggested that VIT is effective
in reducing severe subsequent systemic sting reactions and in improving disease-
specific quality of life. VIT proved to be safe and no fatalities were recorded in
the studies included in this review. The cost-effectiveness of VIT needs to be
established.
During the last two decades, hyper-immunoglobulin (Ig) E syndromes have been
characterized clinically and molecularly in patients with genetically determined
primary immunodeficiencies. However, the detection of low IgE levels, defined here
as below detection limit in the routine clinical immunology laboratory, has
received little attention. We analysed the association of serum IgA, IgM and IgG
levels (including IgG subclasses) with low, normal or high serum IgE levels in
patients evaluated in a singlecentre out-patient immunodeficiency and allergy
clinic. The correlation of serum IgE levels with IgG subclasses depended on the
clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2
and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy,
IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with
low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low
IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical
clustering of non-IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1-4) validated
that non-IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of
low-IgE patients. These results suggesto guide the clinical management of patients
with low serum IgE levels.
Purpose of review Although chronic rhinosinusitis with nasal polyps, asthma, and
allergy share common inflammatory mechanisms, there is no evidence of cause-and-
effect relationship. In this review, we present new studies investigating the
complex immunology that links these diseases. Advances in new therapies as well as
evidence regarding indication and timing of surgery, especially of more complex
cases, are highlighted. Recent findings New studies have endotyped patients in an
effort to describe the exact inflammatory profile of each phenotype, whereas
described cytokines seem to play a significant role in amplification of T2
inflammation, directly or via innate lymphoid cells. New mAbs that block specific
cytokines of these pathways have been developed and seem to show reduced asthma
severity as well as improved sinonasal outcomes. Moreover, it has been shown that
operating early in the course of disease leads not only to bigger improvements in
SNOT-22 outcomes but also to reduced asthma incidence postoperatively in refractory
cases. Summary Applying data from current studies in clinical practice, we could
better manage refractory cases with asthma and polyps, both medically and
surgically. Treatment has to be patient-centered, and this demands a
multidisciplinary-team approach of the airway diseases.
BACKGROUND: The difference in clinical presentation, causality assessments, and
outcomes of patients with delayed antibiotic-associated cutaneous adverse drug
reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined.
OBJECTIVE: We examined the etiology of AA-cADR, with regard to the type of
antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-
cADR. METHODS: A retrospective observational inpatient cohort study of cADR was
performed from January 2004 to August 2014. Patients were divided into AA-cADR and
NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug
eruption, acute generalized erythematous pustulosis, drug reaction with
eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease,
Stevens-Johnson syndrome, and toxic epidermal necrolysis. RESULTS: Of the 84
patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median
length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs
1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR
compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days,
P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-
cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further
antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30
of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs
21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and
carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. CONCLUSIONS:
Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes,
and were associated with longer length of stay, higher age-adjusted Charlson
comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide
and sulfonamide antibiotic exposure predominated. (C) 2016 American Academy of
Allergy, Asthma & Immunology
A recreational scuba diver wore a second scuba regulator against his face during a
scuba dive, attached by an elastic rubber cord necklace. After surfacing, the
diver's left face became swollen. Through a process of elimination all other items
of scuba equipment were excluded as potential causes. A dive with the same
equipment minus the necklace confirmed the involvement of the necklace in the
pathogenesis of the hypersensitive reaction. In vitro ImmunoCap IgE assay was
positive to latex (1.30 kUa/L), subsequent patch testing for contact dermatitis
provoked a reaction for benzophenone-4, (a UV stabalizer) and Fourier Transform
Infra Red spectroscopy identified the elastic as ethylene propylene rubber,
containing additional unidentified compounds. Allergy to natural rubber latex
occurs in as many as 6% of Americans and Australians. Around three million American
residents are thought to scuba dive each year. Recreational divers are, therefore,
advised to check such necklaces, which are typically worn around the throat, for
frayed ends and exposed rubber filaments.
Allogenic lymphocyte immunotherapy (LIT) as a treatment for unexplained recurrent
spontaneous abortion (URSA) is still controversial due to the lack of enough
controls to evaluate its effectiveness. Eighteen randomized, placebo-controlled
trials with LIT for URSA were included in the meta-analysis. Live birth rates for
each group were extracted, and the overall odds ratio (OR) for LIT was calculated.
The success rate of treatment group was significantly higher (OR 3.74, 95% CI 3.07
similar to 4.57). LIT performed before and during pregnancy had dramatically
improved the live birth rate in women with URSA (OR 4.67, 95% CI 3.70 similar to
5.90). The overall OR was 5.25 (95% CI 4.16 similar to 6.64), which supports a low
dose of lymphocytes for treating URSA. Our results indicate that LIT provides a
significantly beneficial effect over placebo for URSA. LIT given before and during
pregnancy is superior to LIT given only before pregnancy, and the lower doses per
treatment (less than 100 x 10(6) lymphocytes or 100 mL peripheral blood) achieved a
better outcome.
Objectives. To perform a state of the art about immunological features in renal
transplantation, immunosuppressive drugs and their mechanisms of action and
immunologically high risk transplantations such as ABO and HLA-incompatible
transplantation. Material and methods. An exhaustive systematic review of the
scientific literature was performed in the Medline database and Embase using
different associations of the following keywords (MESH): "allogenic response;
allograft; immunosuppression; ABO incompatible transplantation; donor specific
antibodies; HLA incompatible; desensitization; kidney transplantation".
Publications obtained were selected based on methodology, language, date of
publication (last 10 years) and relevance. Prospective and retrospective studies,
in English or French, review articles; meta analysis and guidelines were selected
and analyzed. This search found 4717 articles. After reading titles and abstracts,
141 were included in the text, based on their relevance. Results. The considerable
step in comprehension and knowledge allogeneic response this last few years allowed
a better used of immunosuppression and the discover of news immunosuppressive
drugs. In the first part of this article, the allogeneic response will be
described. The different classes of immunosuppressive drugs will be presented and
the actual management of immunosuppression will be discussed. Eventually, the
modalities and results of immunologically high-risk transplantations such as ABO
and HLA incompatible transplantations will be reported. Conclusions. The knowledge
and the control of allogeneic response to allogeneic graft allowed the development
of renal transplantation. (C) 2016 Elsevier Masson SAS. All rights reserved.
Alloparenting, defined as care provided by individuals other than parents, is a
universal behavior among humans that has shaped our evolutionary history and
remains important in contemporary society. Dysfunctions in alloparenting can have
serious and sometimes fatal consequences for vulnerable infants and children. In
spite of the importance of alloparenting, they still have much to learn regarding
the underlying neurobiological systems governing its expression. Here, they review
how a lack of alloparental behavior among traditional laboratory species has led to
a blind spot in our understanding of this critical facet of human social behavior
and the relevant neurobiology. Based on what is known, they draw from model systems
ranging from voles to meerkats to primates to describe a conserved set of
neuroendocrine mechanisms supporting the expression of alloparental care. In this
review we describe the neurobiological and behavioral prerequisites, ontogeny, and
consequences of alloparental care. Lastly, they identified several outstanding
topics in the area of alloparental care that deserve further research efforts to
better advance human health and wellbeing. (c) 2016 Wiley Periodicals, Inc. Develop
Neurobiol 77: 214-232, 2017
Objective: Anxiety and mood disorders (AMD) are the most frequent mental disorders
in the human population. They have recently shown increasing prevalence, and
commonly disrupt personal and working lives. Objective: The aim of our study was to
analyze the spectrum of circulating steroids in order to discover differences that
could potentially be markers of affective depression or anxiety, and identify which
steroids could be a predictive component for these diseases. Methods: We studied
the steroid metabolome including 47 analytes in 20 men with depression (group D),
20 men with anxiety (group AN) and 30 healthy controls. OPLS and multivariate
regression models were used for statistical analysis. Results: Discrimination of
group D from controls by the OPLS method was absolute, as was group AN from
controls (sensitivity = 1.000 (0.839, 1.000), specificity = 1.000 (0.887, 1.000)).
Relatively good predictivity was also found for discrimination between group D from
AN (sensitivity = 0.850 (0.640, 0.948), specificity = 0.900 (0.699, 0.972)).
Conclusion: Selected circulating steroids, including those that are neuroactive and
neuroprotective, can be useful tools for discriminating between these affective
diseases in adult men. (C) 2016 Published by Elsevier Inc.
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy
compromises such as preterm birth, prenatal stress and intrauterine growth
restriction are associated with an increased risk of developing behavioural and
mood disorders, particularly during adolescence. These pathologies involve the
premature loss or alteration of trophic steroid hormones reaching the fetus leading
to impaired neurodevelopment. While the specific programming mechanisms are yet to
be fully elucidated, in adult life, dysfunctions of allopregnanolone action are
prevalent in individuals with depression, post-traumatic stress disorder and
anxiety disorders. The objective of this study was to assess if changes in
concentrations of the neurosteroid, allopregnanolone, may be a fetal programming
factor in priming the brain towards a negative behavioural phenotype during the
childhood to adolescent period using a guinea pig model. Pregnant guinea pigs
received either vehicle (45% (2-hydroxypropyI)-beta-cyclodextrin) or the 5 alpha-
reductase inhibitor, finasteride (25 mg/kg maternal weight) from gestational age 60
until spontaneous delivery (similar to 71 days gestation). Male and female
offspring from vehicle and finasteride treated dams were tested at postnatal day 20
(juvenile-equivalence) in an open field arena, and hippocampus and amygdala
subsequently assessed for neurological changes in markers of development and GABA
production pathways 24 h later. Females with reduced allopregnanolone exposure in
utero displayed increased neophobic-like responses to a change in their environment
compared to female controls. There were no differences in the neurodevelopmental
markers assessed; MAP2, NeuN, MBP, GFAP or GAD67 between intrauterine finasteride
or vehicle exposure, in either the hippocampus or amygdala whereas GAT1 staining
was decreased. This study indicates that an intrauterine reduction in the supply of
allopregnanolone programs vulnerability of female offspring to anxiety-like
disorders in juvenility without impacting long term allopregnanolone
concentrations. (C) 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
High-temperature requirement A (HtrA; DegP) from Escherichia coli, an important
element of the extracytoplasmic protein quality-control system, is a member of the
evolutionarily conserved family of serine proteases. The characteristic feature of
this protein is its allosteric mode of activation. The regulatory loops, L3, L2, L1
and LD, play a crucial role in the transmission of the allosteric signal. Yet, the
role of LD has not been fully elucidated. Therefore, we undertook a study to
explain the role of the individual LD residues in inducing and maintaining the
proteolytic activity of HtrA. We investigated the influence of amino acid
substitutions located within the LD loop on the kinetics of a model substrate
cleavage as well as on the dynamics of the oligomeric structure of HtrA. We found
that the mutations that were expected to disturb the loop's structure and/or
interactions with the remaining regulatory loops severely diminished the
proteolytic activity of HtrA. The opposite effect, that is, increased activity, was
observed for G174S substitution, which was predicted to strengthen the interactions
mediated by LD. HtrAG174S protein had an equilibrium shifted toward the active
enzyme and formed preferentially high-order oligomeric forms.
Modern microsurgical techniques have made possible a broad spectrum of novel means
for the reconstruction of complex bone and soft tissue defects. These techniques,
in combination with developments in transplant immunology, have led to successful
hand and facial allotransplantation and achievement of the highest rung in the
reconstructive ladder - truly replacing like with like. The utilization of
contemporary microsurgical technique in the context of vascularized composite
allotransplantation (VCA) (1) permits successful technical execution and
feasibility of VCA, (2) facilitates the study of immunologic tolerance in VCA
preclinical models, and (3) optimizes functional VCA outcomes.
In this paper, a new Voltage-Mode (VM) first-order All-Pass Filter (APF) topology
composed of only a grounded capacitor is proposed. The proposed APF uses a single,
minus-type, second-generation, current conveyor (CCII-), which can be constructed
by only five MOS transistors. It has low power consumption. The resonance frequency
of the proposed APF can be adjusted by changing only a resistor value. However, it
needs a single matching condition. As an application, a quadrature oscillator
example is given. A non-ideality analysis for the proposed APF is also given. A
number of time domain and frequency domain simulation results and an experimental
test result are included to confirm the theory. (C) 2015 Sharif University of
Technology. All rights reserved.
The transcription factor encoded by the gene Knotted1 is a nuclear homeodomain
protein, regulating meristematic cells at the shoot apical meristem. It has been
demonstrated that Knotted1 (KN1) expression specifies stem cell fate in
adventitious shoot induction in herbaceous plants. This gene may thus potentially
identify the initiation of meristem development in adventitious shoot induction in
difficult-to-regenerate plants such as Prunoideae. We isolated an almond (Prunus
dulcis Mill.) KN1-type gene using degenerate primers targeting the most conserved
regions of Knotted1 gene. The 5' and 3' ends of the isolated sequence were obtained
by rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR), and the
gene was named P. dulcis Knotted1-like (PdKn1). PdKn1 transcripts were detected by
reverse transcription (RT)-PCR mainly in shoot apical and axillary meristems. The
RT-PCR and RT-quantitative PCR PdKn1 expression in almond leaf explants was found
to anticipate the organization of adventitious shoot meristems. Apricot RNA
isolated from induced leaf explants cross-hybridized with the almond probe PdKn1 in
Northern blotting. We suggest that almond PdKn1 may be a useful marker to study the
adventitious regeneration system by revealing the potential organogenic conditions,
not only in almond but also in other Prunoideae.
Laminin (Lm) alpha 4 chain, a constituent of Lm-411 and Lm-421, is mainly localized
to mesenchyme-derived tissues, and is suggested to have a role in formation and
function of endothelium, transmigration of inflammatory cells through endothelium,
and invasion of certain tumors. In this study, we evaluated the distribution of
alpha 4 chain Lms in 33 conventional (clear cell) renal cell carcinomas (RCCs) (31
primary tumors, two metastases), two papillary RCCs, and two oncocytomas by
immunohistochemistry. In all tumors, immunoreactivity for Lm alpha 4 chain was
found in vasculature and stroma. Basement membranes were detected around tumor cell
islets in 34/37 tumors. They showed immunoreactivity for Lm alpha 4 chain in 28/34
cases. Northern blotting, inhibition of protein secretion with monensin, and
immunoprecipitation combined with Western blotting showed that Caki-2, ACHN, and
Caki-1 renal carcinoma cell lines produce alpha 4 chain Lms. In cell adhesion
assay, recombinant human Lm-411 did not promote adhesion of renal carcinoma cells
but inhibited adhesion to fibronectin (Fn). In cell migration assay, the cells
migrated more on Lm-411 than on Fn. The results suggest that alpha 4 chain Lms have
a de- adhesive function and could thus play a role in detachment, migration and
invasion of renal carcinoma cells in vivo.
The AMPA receptor subunit GluR2 is downregulated in neurons following a wide range
of neurological insults. Here we report that suppression of GluR2 gene promoter
activity is associated with kainate (KA)-induced downregulation of GluR2 subunit
levels in primary cultured cortical neurons. RT-PCR and Northern blotting showed a
significant decrease in GluR2 mRNA in cultured neurons after KA exposure.
Transfection of cultured neurons with an expression vector pGL3-GluR2(-298/+283),
where the reporter gene firefly luciferase was driven by the GluR2 promoter,
revealed that KA exposure suppressed the transcriptional activation of the GluR2
promoter. Furthermore, the expression of the RE1-silencing transcription factor
(REST) was increased in KA-exposed cortical neurons; enhanced binding of REST to
RE1-like silencer element in the proximal promoter of the GluR2 subunit gene was
evidenced by electrophoresis mobility shift assay. Chromatin immunoprecipitation
showed that suppressed activity of the GluR2 promoter in cultured neurons after KA
exposure was related to deacetylation of histone H4. These results indicate that
REST as a crucial factor binds to RE1-like silencer element in the GluR2 promoter,
suppressing transcription of the GluR2 subunit gene during KA exposure. Our data
suggest that transcriptional suppression of the G1uR2 subunit gene may contribute
at least in part to downregulation of GluR2 subunit protein in neurons during KA
exposure. Because our experiments showed a reduction of glutamate release in KA-
exposed cortical neurons, REST may play a latent role in delayed neuronal death or
in seizure-induced tolerance. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
alpha-Glucans are present in virtually all domains of life, and these glucose
chains linked by alpha-1,4- and alpha-1,6-linked branches form the most important
storage carbohydrates in cells. It is likely for this reason that alpha-glucans are
not generally considered as bioactive molecules as beta-glucans are. Nevertheless,
it is known that depending on their source, many alpha-glucans play important roles
as modulators of immune response. Recent efforts have attempted to elucidate the
mechanisms through which alpha-glucans exert their immunostimulant effects;
however, the main challenge is the accurate identification of the receptors of
immune cells involved in their recognition. Here, we review the adjuvant properties
reported for some polysaccharides and ultimately focus on alpha-glucans and how
their structural characteristics, such as molecular weight, solubility and
derivatization, influence their immunostimulatory properties. As a final point, we
discuss the potential and associated challenges of using these polysaccharides as
adjuvants, particularly in mucosal vaccination. (C) 2017 Elsevier Ltd. All rights
reserved.
Changes in the gastrointestinal microbial community are frequently associated with
chronic diseases such as Inflammatory Bowel Diseases. However, understanding the
relationship of any individual taxon within the community to host physiology is
made complex due to the diversity and individuality of the gut microbiota. Defined
microbial communities such as the Altered Schaedler Flora (ASF) help alleviate the
challenges of a diverse microbiota by allowing one to interrogate the relationship
between individual bacterial species and host responses. An important aspect of
studying these relationships with defined microbial communities is the ability to
measure the population abundance and dynamics of each member. Herein, we describe
the development of an improved ASF species-specific and sensitive real-time
quantitative polymerase chain reaction (qPCR) for use with SYBR Green chemistry to
accurately assess individual ASF member abundance. This approach targets
hypervariable regions V1 through V3 of the 16S rRNA gene of each ASF taxon to
enhance assay specificity. We demonstrate the reproducibility, sensitivity and
application of this new method by quantifying each ASF bacterium in two inbred
mouse lines. We also used it to assess changes in ASF member abundance before and
after acute antibiotic perturbation of the community as well as in mice fed two
different diets. Additionally, we describe a nested PCR assay for the detection of
lowly abundant ASF members. Altogether, this improved qPCR method will facilitate
gnotobiotic research involving the ASF community by allowing for reproducible
quantification of its members under various physiological conditions. (C) 2017
Elsevier B.V. All rights reserved.
Because of their prominent roles in regulation of gene expression, it is important
to understand how levels of Krupple-like transcription factors SP1 and SP3 change
in germ cells during spermatogenesis. Using immunological techniques, we found that
both factors decreased sharply during meiosis. SP3 declined during the leptotene-
to-pachytene transition, whereas SP1 fell somewhat later, as spermatocytes
progressed beyond the early pachytene stage. SP3 reappeared for a period in round
spermatids. For Sp1, the transition to the pachytene stage is accompanied by loss
of the normal, 8.2-kb mRNA and appearance of a prevalent, 8.8-kb variant, which has
not been well characterized. We have now shown that this pachytene-specific
transcript contains a long, unspliced sequence from the first intron and that this
sequence inhibits expression of a reporter, probably because of its many short
open-reading frames. A second testis-specific Sp1 transcript in spermatids of 2.4
kb also has been reported previously. Like the 8.8-kb variant, it is compromised
translationally. We have confirmed by Northern blotting that the 8.8-, 8.2-, and
2.4-kb variants account for the major testis Sp1 transcripts. Thus, the unexpected
decline of SP1 protein in the face of continuing Sp1 transcription is explained, in
large part, by poor translation of both novel testis transcripts. As part of this
work, we also identified five additional, minor SpI cap sites by 5' rapid
amplification of cDNA ends, including a trans-spliced RNA originating from the
Glcci1 gene.
Modern drives consist of alternating current electric motors, and the field-
oriented control (FOC) of such motors enables fast, precise, and robust regulation
of a drive's mechanical variables such as torque, speed, and position. The control
algorithm, implemented in a microprocessor, requires feedback from motor currents,
and the quality of this feedback is essential to a drive's control properties.
Motor phase currents are sampled and processed in order to extract their mean over
a digital control interval. Afterwards, the mean phase currents are transformed
into a rotating field-oriented reference frame to enable controlling the mechanical
variables. The field-oriented frame rotates continuously, but in practice the
transformation is carried out using a discrete angular position. This paper
investigates how the discretization impacts the computed field-oriented currents in
high speed drives, where the rotor displacement during a control interval is
substantial. A continuous-time model of field-oriented currents is indicated as a
reference to quantify errors. An original approach to normalize variables and to
solve the model analytically is proposed in order to investigate how the errors
related to rotor position discretization are influenced by drive operating
conditions. The analytical solution is validated by computer simulation. The
results show that the currently applied methodology of computing field-oriented
current components, due to an invalid assumption, introduces errors of a few
percent when a drive operates at high speed. These errors can be compensated using
the presented solution. (C) 2016 Elsevier Inc. All rights reserved.
This article draws upon recent geographical work on assemblage to reconsider how we
understand alternative food economies. In particular it brings attention to the
devices upon which these economies relyspecifically plastics. Since the mid-
twentieth century, plastics have developed close and complex relations with our
agrifood systems; they facilitate commodity valuation and product circulation
worldwide but are also recognised as problematic due to their environmental and
human health impacts. Despite this paradox and the attention plastics increasingly
receive, we know little of their relations with alternative food initiatives
(AFIs). How do plastics inhabit alternative food economies? What associations and
circulations become performed? What do these markets look like from a device-
oriented perspective? To address these questions, the paper draws on fieldwork
undertaken in Brisbane (Australia) with two AFIsa weekly organic market and an
online box program/wholesaler. Using visualisation and an assemblage approach
discloses the presences, flows, functions, and tensions of plastics in AFIs. In
this way, plastics are revealed but also act to reveal alternative food economies.
This analysis steps away from evaluations of AFIs' (in)effective challenge to
neoliberalisation to consider them as complex, processual, sometimes ambivalent
efforts that not only distribute good food' but engage in important ways with
things like plastics.
Background: We developed and validated a kinetic microplate hemolytic assay (HA) to
quantify classical and alternative complement activity in a single dilution of
human plasma or serum. Methods: The assay is based on monitoring hemolysis of
sensitized sheep (or uncoated rabbit) red blood cells by means of a 96-well
microplate reader. The activity of the calibrator was evaluated by reference to 200
healthy adults. The conversion of 50% hemolysis time into a percentage of activity
was obtained using a calibration curve plotted daily. Results: The linearity of the
assay as well as interference (by hemolysis, bilrubinemia and lipemia) was assessed
for classical pathway (CP). The within-day and the between-day precision was
satisfactory regarding the performance of commercially available liposome
immunoassay (LIA) and ELISA. Patients with hereditary or acquired complement
deficiencies were detected (activity was measured <30%). We also provided a
reference range obtained from 200 blood donors. The agreement of CP evaluated on
samples from 48 patients was 94% with LIA and 87.5% with ELISA. The sensitivity of
our assay was better than that of LIA, and the cost was lower than either LIA or
ELISA. In addition, this assay was less time consuming than previously reported
HAs. Conclusions: This assay allows the simultaneous measurement of 36 samples in
duplicate per run of a 96-well plate. The use of a daily calibration curve allows
standardization of the method and leads to good reproducibility. The same technique
was also adapted for the quantification of alternative pathway (AP) activity.
NO-mediated alternative pathway plays an important role in protecting wheat
seedlings against drought stress through dissipating excessive reducing equivalents
generated by photosynthesis. Alternative pathway (AP) has been proven to be
involved in responses to various stresses. However, the mechanisms of AP in defense
response to drought stress are still lacking. The aims of this work are to
investigate the role of AP in drought tolerance and how AP is induced under drought
stress using two wheat cultivars with different drought tolerance. Our results
showed that Longchun22 cultivar is more tolerant to drought than 98SN146 cultivar.
Seedlings exposed to drought led to a significant increase in AP, and it increased
more in Longchun22. Furthermore, chlorophyll fluorescence parameters (Fv/Fm, I
broken vertical bar PSII, qP) decreased significantly in drought-treated seedlings,
especially in 98SN146, indicating that photoinhibition occurred under drought
stress. Pretreatment with SHAM, the malate-oxaloacetate shuttle activity and
photosynthetic efficiency were further inhibited in drought-treated seedlings,
resulting in more serious oxidative damage as indicated by higher levels of
malondialdehyde and hydrogen peroxide. Moreover, NO modulated AP under drought
stress by increasing AOX1a expression and pyruvate content. Taken together, these
results indicate that NO-mediated AP is involved in optimizing photosynthesis under
drought stress by avoiding the over-reduction of photosynthetic electron transport
chain, thus reducing reactive oxygen species production and oxidative damage in
wheat leaves.
A hallmark of male germ cell gene expression is the generation by alternative
polyadenylation of cell-specific mRNAs, many of which utilize noncanonical
A(A/U)UAAA-independent polyadenylation signals. Cleavage factor I (CFlm), a
component of the pre-mRNA cleavage and polyadenylation protein complex, can direct
A(A/U)UAAA-independent polyadenylation site selection of somatic cell mRNAs. Here
we report that the CFlm subunits NUDT21/CPSF5 and CPSF6 are highly enriched in
mouse male germ cells relative to somatic cells. Both subunits are expressed from
spermatogenic cell mRNAs that are shorter than the corresponding somatic
transcripts. Complementary DNA sequencing and Northern blotting revealed that the
shorter Nudt21 and Cpsf6 mRNAs are generated by alternative polyadenylation in male
germ cells using proximal poly(A) signals. Both sets of transcripts contain CFlm
binding sites within their 3 '-untranslated regions, suggesting autoregulation of
CFlm subunit formation in male germ cells. CFIm subunit mRNA and protein levels
exhibit distinct developmental variation during spermatogenesis, indicating stage-
dependent translational and/or posttranslational regulation. CFIm binding sites
were identified near the 3 ' ends of numerous male germ cell transcripts utilizing
A(A/U)UAAA-independent sites. Together these findings suggest that CFIm complexes
participate in alternative polyadenylation directed by noncanonical poly(A) signals
during spermatogenesis.
To identify a novel regulatory factor involved in brain development or synaptic
plasticity, we applied the differential display PCR method to mRNA samples from
NMDA-stimulated and un-stimulated neocortical cultures. Among 64 cDNA clones
isolated, eight clones were novel genes and one of them encodes a novel zinc-finger
protein, HIT-4, which is 317 amino acid residues (36-38 kDa) in length and contains
seven C(2)H(2) zinc-finger motifs. Rat HIT-4 cDNA exhibits strong homology to human
ZNF597 (57% amino acid identity and 72% homology) and identity to rat ZNF597 at the
carboxyl region. Furthermore, genomic alignment of HIT-4 cDNA indicates that the
alternative use of distinct promoters and exons produces HIT-4 and ZNF597 mRNAs.
Northern blotting revealed that HIT-4 mRNA (similar to 6 kb) is expressed in
various tissues such as the lung, heart, and liver, but enriched in the brain,
while ZNF597 mRNA (similar to 1.5kb) is found only in the testis. To evaluate
biological roles of HIT-4/ZNF597, targeted mutagenesis of this gene was performed
in mice. Homozygous (-/-) mutation was embryonic lethal, ceasing embryonic
organization before cardiogenesis at embryonic day 7.5. Heterozygous (+/-) mice
were able to survive but showing cell degeneration and vacuolization of the
striatum, cingulate cortex, and their surrounding white matter. These results
reveal novel biological and pathological roles of HIT-4 in brain development and/or
maintenance.
Many basic cellular processes are shared across vast phylogenetic distances,
whereas sex-determining mechanisms are highly variable between phyla, although the
existence of two sexes is nearly universal in the animal kingdom. However, the
evolutionarily conserved DMRT1/dsx/mab3 with a common zinc finger-like DNA-binding
motif, DM domain, share both similar structure and function between phyla. Here we
report that six transcripts of the chicken DMRT1 were generated in gonads by
multiple alternative splicing. By cDNA cloning and genomic structure analysis, we
found that there were nine exons of DMRT1, which were involved in alternatively
splicing to generate the DMRT1 transcripts. Northern blotting and reverse
transcription (RT) PCR analysis revealed that the expression of chicken DMRT1 was
testis-specific in adults. Whole-mount in situ hybridizations and RT-PCR indicated
that DMRT1 b was specially expressed in embryo gonads and higher in male than
female gonads at stage 31. The female gonad had stronger DMRT1 c expression than
the male one, whereas DMRT1 f was detectable only in the male gonad at stage 31 of
the key time of sex gonadal differentiation. The differential expression of these
transcripts during gonadal differentiation provides new insight into roles of
alternative splicing of DMRT1 in governing sex differentiation of the chicken.
The pre-mRNA of the fragile X mental retardation 1 gene (FMR1) is subject to exon
skipping and alternative splice site selection, which can generate up to 12
isoforms. The expression and function of these variants in vivo has not yet been
fully explored. In the present study, we investigated the distribution of Fmr1 exon
12 and exon 15 isoforms. Exon 12 encodes an extension of KH2 domain, one of the RNA
binding domains in the FMR1 gene product (FMRP) and we show that exon 12 variant
proteins differentially interact with kissing complex RNA. Alternative splicing at
exon 15 produces FMRPs differing in RNA binding ability and each is distinguished
by unique post-translational modifications. Using semiquantitative RT-PCR and
Northern blotting, we found that particular Fmr1 exon 12 and exon 15 isoforms
change during neuronal differentiation. Interestingly, Fmr1 exon 12 variants
display tissue-specific and developmental differences, while exon 15-containing
transcripts vary less. Altogether, the spatio-temporal plasticity of FMR1 mRNA is
consistent with complex RNA processing that is mis-regulated in fragile X syndrome.
(C) 2009 Elsevier Inc. All rights reserved.
Abcc4 gene codes for a protein (ABCC4) involved in the transportation of different
classes of drugs outside the cells. Various important drugs transported by ABCC4
include antiviral and anticancer drugs as well as endogenous molecules such as bile
acids, cyclic nucleotides, folates, prostaglandins and steroids. Alternative
splicing generates multiple mRNAs that encode protein isoforms having diverse
functions. In this study, we have identified a novel transcript of mouse Abcc4 gene
using a combination of bioinformatics and molecular biology techniques. This
transcript was found to be different from the reported transcript in having a
different first exon that was found to be located on previously identified first
intron. Newly identified transcript was found to be expressed across different
tissues we studied and in different developmental stages. Expression level of novel
and reported transcripts was studied using quantitative real-time PCR. After
conceptually translating the novel transcript, various post-translational
modifications were studied. Translation efficiency and predicted half life of
encoded protein isoforms were analysed in silico. Molecular modelling was performed
to compare the structural differences in both isoforms. The diversity at N-termini
in these protein isoforms explains the diverse function of ABCC4 in mouse. (C) 2016
Elsevier B.V. All rights reserved.
Our aim of the project is to demonstrate all the protections and interlocks
available in the critical equipments of power station such as Boiler, Turbine, the
Alternator, and how these critical equipments are protected from abnormal
conditions and parameters. The failure of any one of these equipments will lead to
loss of power generation. The cost of these equipments is huge. Boiler has got
protection against abnormal drum level, abnormal live steam pressure, abnormal live
steam temperature, abnormal furnace pressure. Turbine has got protection against
abnormal condenser vacuum, abnormal lubricating oil pressure, abnormal axial
shiftand abnormal turbine speed. Similarly the generator has also got the following
protections 1.10.5kv earth fault, 220kv earth fault, differential protection,
incomplete phase condition, rotor earth fault, stator inter turn fault, over
current protection, stator overvoltage, rotor overvoltage. These protections are
classified as class a, class b and class c protections. Distributed digital
controls and numerical protections relays play vital role in providing protections
to critical equipments to demonstrate these protections in real sense in our
project kit. However an effort has been made to demonstrate the functioning of
these protections with the aid of a programmable logic controller. Also a few
suggestions to improve the existing system are also discussed.
Various types of long-term stable relationships that individuals uphold, including
cooperation and competition between group members, define social complexity in
vertebrates. Numerous life history, physiological and cognitive traits have been
shown to affect, or to be affected by, such social relationships. As such,
differences in developmental modes, i.e. the 'altricial-precocial' spectrum, may
play an important role in understanding the interspecific variation in occurrence
of social interactions, but to what extent this is the case is unclear because the
role of the developmental mode has not been studied directly in across-species
studies of sociality. In other words, although there are studies on the effects of
developmental mode on brain size, on the effects of brain size on cognition, and on
the effects of cognition on social complexity, there are no studies directly
investigating the link between developmental mode and social complexity. This is
surprising because developmental differences play a significant role in the
evolution of, for example, brain size, which is in turn considered an essential
building block with respect to social complexity. Here, we compiled an overview of
studies on various aspects of the complexity of social systems in altricial and
precocial mammals and birds. Although systematic studies are scarce and do not
allow for a quantitative comparison, we show that several forms of social
relationships and cognitive abilities occur in species along the entire
developmental spectrum. Based on the existing evidence it seems that differences in
developmental modes play a minor role in whether or not individuals or species are
able to meet the cognitive capabilities and requirements for maintaining complex
social relationships. Given the scarcity of comparative studies and potential
subtle differences, however, we suggest that future studies should consider
developmental differences to determine whether our finding is general or whether
some of the vast variation in social complexity across species can be explained by
developmental mode. This would allow a more detailed assessment of the relative
importance of developmental mode in the evolution of vertebrate social systems.
Hardness cations are ubiquitous and abundant in source water, while the effect of
hardness on the performance of coagulation for dissolved organic matter (DOM)
removal in water treatment remains unclear due to the limitation of methods that
can characterise the subtle interactions between DOM, coagulant and hardness
cations. This work quantified the competition between coagulant Al3+ and hardness
cations to bind onto DOM using absorbance spectroscopy acquired at different Al3+
concentrations in the absence and presence of Ca2+ or Mg2+. The results indicate
that, in the presence of either Mg2+ or Ca2+, an increasing depression of the
binding of Al3+-DOM could be observed in the differential spectra of DOM with the
increasing of Mg2+ or Ca2+ at a level of 10, 100 and 1000 mu M, with the
observation being more significant at higher pH from 6.5 to 8.5. The results of
zeta potentials of DOM indicate that the competition of hardness cations results in
the negative DOM being less efficiently neutralised by Al3+. This study
demonstrates that the removal of DOM by coagulation would significantly deteriorate
with the presence of hardness cations, which would compete with coagulant Al3+ to
neutralise the unsaturated sites in DOM. (C) 2017 Elsevier Ltd. All rights
reserved.
Background and ObjectivePeriodontal disease is a chronic infectious disease that
results in bone loss. Many epidemiological studies have reported the progression of
periodontal tissue destruction in patients with diabetes; however, the associated
mechanism remains unclear. In this study, we comprehensively investigated how
diabetes affects the periodontal tissue and alveolar bone loss using a ligature-
induced periodontitis model in streptozotocin-induced diabetic (STZ) mice. Material
and MethodsDiabetes was induced by intraperitoneal injection with streptozotocin in
6-wk-old C57/BL6J male mice. A silk ligature was tied around the maxillary left
second molar in 9-wk-old wild-type (WT) and STZ mice. Bone loss was evaluated at 3
and 7 d after ligation. mRNA expression levels in the gingiva between the two
groups were examined by DNA microarray and quantitative polymerase chain reaction
at 1, 3 and 7 d post-ligation. Tartrate-resistant acid phosphatase and alkaline
phosphatase staining of the periodontal tissue was performed for evaluation of
osteoclasts and osteoblasts in histological analysis. ResultsIn the gingiva,
hyperglycemia upregulated the osteoprotegerin (Opg) mRNA expression and
downregulated Osteocalcin mRNA expression. In the ligated gingiva, tumor necrosis
factor- (Tnf-) mRNA expression was upregulated at 1 d post-ligation in STZ mice but
not in WT mice. At 3 d post-ligation, alveolar bone loss was observed in STZ mice,
but not in WT mice. Significantly severe alveolar bone loss was observed in STZ
mice compared to WT mice at 7 d post-ligation. Bone metabolic analysis using DNA
microarray showed significant downregulation in the mRNA expression of glioma-
associated oncogene homologue 1 (Gli1) and collagen type VI alpha 1 (Col6a1) at the
gingiva of the ligated site in STZ mice compared to that in WT mice. Quantitative
polymerase chain reaction showed that Gli1 and Col6a1 mRNA expression levels were
significantly downregulated in the gingiva of the ligated site in STZ mice compared
to WT mice. Histological analysis showed lower alkaline phosphatase activity in STZ
mice. In addition, an increased number of tartrate-resistant acid phosphatase-
positive multinucleated cells were observed at the ligated sites in STZ mice.
ConclusionsThese results suggest that an imbalance of bone metabolism causes
osteoclastosis in insulin-deficient diabetes, and that alveolar bone loss could
occur at an early phase under this condition.
The lung alveolar epithelium consists of type I and type II pneumocytes. In vivo,
the type II cell is the progenitor cell from which the type I cell originates. When
freshly-isolated type II cells are cultured under conventional conditions they
rapidly lose their phenotypic properties and attain characteristics of type I
cells. Taking advantage of this transdifferentiation, we sought to identify genes
that are differentially expressed during culture of rat type II cells. Using
suppression subtractive hybridization (SSH), a vacuolar-type H+ stop-ATPase (V-
ATPase) C2 subunit gene (Atp6v1c2) was found to be enriched in freshly isolated rat
type II cells compared to those cultured for 4 days. Northern blotting and reverse-
transcription polymerase chain reaction (RT-PCR) confirmed the differential
expression of Atp6v1c2 during in vitro culture of isolated type II cells.
Expression of Atp6v1c2 was significantly reduced early during in vitro culture:
almost 90% reduction was observed after 24 h of incubation as determined by real-
time PCR. In situ hybridization showed that Atp6v1c2 is expressed in both
bronchiolar and alveolar lung epithelial cells, an expression pattern similar to
that of surfactant protein B (SP-B). Multi-tissue Northern blotting revealed a
unique tissue distribution with Atp6v1c2 expression limited to lung, kidney and
testis. The presence and expression of Atp6v1c2 gene transcript isoforms, resulting
from alternative splicing, were also investigated. Elucidation of differential
expression of Atp6v1c2 in type II cells and further studies of its regulation may
provide information useful in understanding the molecular mechanism underlying
phenotypic and functional changes during transdifferentiation of alveolar
epithelial cells.
Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus causing hemangiomas
and myeloid tumors in chickens. Interleukin-6 (IL-6) is a multifunctional pro-
inflammatory interleukin involved in many types of cancer. We previously
demonstrated that IL-6 expression was induced following ALV-J infection in
chickens. The aim of this study is to characterize the mechanism by which ALV-J
induces IL-6 expression, and the role of IL-6 in tumor development. Our results
demonstrate that ALV-J infection increases IL-6 expression in chicken splenocytes,
peripheral blood lymphocytes, and vascular endothelial cells. IL-6 production is
induced by the ALV-J envelope protein gp85 and capsid protein p27 via PI3K- and NF-
kappa B-mediated signaling. IL-6 in turn induced expression of vascular endothelial
growth factor (VEGF)-A and its receptor, VEGFR-2, in vascular endothelial cells and
embryonic vascular tissues. Suppression of IL-6 using siRNA inhibited the ALV-J
induced VEGF-A and VEGFR-2 expression in vascular endothelial cells, indicating
that the ALV-J-induced VEGF-A/VEGFR-2 expression is mediated by IL-6. As VEGF-A and
VEGFR-2 are important factors in oncogenesis, our findings suggest that ALV-J
hijacks IL-6 to promote tumorigenesis, and indicate that IL-6 could potentially
serve as a therapeutic target in ALV-J infections.
Insulin-degrading enzyme (IDE) is a zinc metalloprotease, known to degrade insulin
peptide and amyloid-beta (A beta); the key protein involved in Alzheimer's disease
(AD). Considering the important role played by IDE in disease progression of AD and
type 2 diabetes mellitus (T2DM), we endeavored to identify the Caenorhabditis
elegans (C. elegans) IDE orthologous genes and test them for their role in AD
related outcomes. We employed bioinformatics, reverse genetics and molecular
biology approaches towards identification and functional characterization of
putative IDE candidates in C. elegans. Using in-silico analysis we have identified
seven C elegans genes that possess HXXEH motif, an identifying marker of IDE. We
further carried out functional analysis of the identified genes in A beta
expressing C elegans strain CL4176 [myo-3/A beta 1-42 long 3'-UTR] via studying
effect on A beta induced toxicity, cholinergic neuroanatomy, content of
acetylcholine/acetylcholine-esterase, extent of reactive oxygen species and
expression of FOXO transcription factor DAF-16. Our findings reveal that amongst
the identified putative IDE orthologs, a functionally uncharacterized gene C28F5.4
had a profound effect on the tested endpoints. Knocking down C28F5.4 modulated the
AD associated conditions by decreasing A beta induced toxicity, severely
compromising cholinergic neuroanatomy, reducing expression of acetylcholine-
transporter, decreasing acetylcholine content, elevating ROS, with no effect on
DAF-16 stress-response protein. These studies provide crucial insight into the
structural/functional orthology of IDEs across human and nematode species and
further our understanding of the involvement of these proteins and insulin pathway
in AD. Further studies could aid in identifying novel drug-targets and in
understanding the common modulating factors between AD and T2DM. (C) 2016 Elsevier
B.V. All rights reserved.
Alzheimer's disease (AD) has been associated with magnesium ion (Mg2+) deficits and
interleukin-1 beta (IL-1 beta) elevations in the serum or brains of AD patients.
However, the mechanisms regulating IL-1 beta expression during Mg (2+)
dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1 beta
reduction using a recently developed compound, magnesium-L-threonate (MgT). Using
human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model
system, we delineated the signaling pathways by which MgT suppressed the expression
of IL-1 beta in glial cells. In detail, we found that MgT incubation stimulated the
activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and
peroxisome proliferator-activated receptor gamma (PPAR gamma) signaling pathways by
phosphorylation, which resulted in IL-1 beta suppression. Simultaneous inhibition
of the phosphorylation of ERK1/2 and PPAR gamma induced IL-1 beta upregulation in
MgT-stimulated glial cells. In accordance with our in vitro data, the
intracerebroventricular (i.c.v) injection of MgT into the ventricles of APP/PS1
transgenic mice and treatment of Ab precursor protein (APP)/PS1 brain slices
suppressed the mRNA and protein expression of IL-1 beta. These in vivo observations
were further supported by the oral administration of MgT for 5 months. Importantly,
Mg (2+) influx into the ventricles of the mice blocked the effects of IL-1 beta or
amyloid beta-protein oligomers in the cerebrospinal fluid. This reduced the
stimulation of IL-1 beta expression in the cerebral cortex of APP/PS1 transgenic
mice, which potentially contributed to the inhibition of neuroinflammation.
Cellular & Molecular Immunology (2017) published online 9 November 2015
The current study determined the ability of a p75(NTR) antagonistic cyclic peptide
to rescue cells from beta amyloid (A beta) (1-40)-induced death. p75(NTR)-,
p140(trkA)-NIH-3T3 cells or E17 foetal rat cortical neurones were incubated with I-
125-NGF or I-125-A beta (1-40) and increasing concentrations of the cyclic peptide
(CATDIKGAEC). Peptide ability to displace I-125-NGF or I-125-A beta (1-40) binding
was determined. Duplicate cultures were preincubated with CATDIKGAEC (250 nM) or
diluent and then stimulated with A beta (1-40). Peptide ability to displace A beta
(1-40) binding, interfere with A beta (1-40)-induced signalling and rescue cells
from A beta-mediated toxicity was determined by immunoprecipitation and
autoradiography, Northern blotting, JNK activation, MTT and trypan blue assays. The
peptide inhibited NGF and A beta (1-40) binding to p75(NTR), but not to p140(trkA).
A beta (1-40) induced c-jun transcription (57.3% +/- 0.07%) in diluent-treated
p75(NTR)-cells, but not in cells preincubated with the cyclic peptide. Also, at 250
nM, the peptide reduced A beta (1-40)-induced phsophorylation of JNK by 71.8% +/-
0.03% and protected neurones against A beta-induced toxicity as determined by:
trypan blue exclusion assay (53% +/- 11% trypan blue-positive cells in diluent
pretreated cultures vs. 28% +/- 5% in cyclic peptide-pretreated cultures); MTT
assay (0.09 +/- 0.03 units in diluent-pretreated cells vs. 0.12 +/- 0.004 units in
cyclic peptide-pretreated cells); and visualization of representative microscopic
fields. Our data suggest that a cyclic peptide homologous to amino acids 28-36 of
NGF known to mediate binding to p75(NTR) can interfere with A beta (1-40)
signalling and rescue neurones from A beta (1-40)-induced toxicity.
Although frontal presentations of Alzheimer's disease (fv-AD) have already been
described in the literature, we still know little about patients' social cognitive
abilities, especially their theory of mind (ToM). We report the case of FT, a 61-
year-old woman who was diagnosed with fv-AD. Two assessments of social cognition,
using a false-belief task, the Reading the Mind in the Eyes test, and a task
probing knowledge of social norms, were performed one year apart. FT exhibited
cognitive ToM and social knowledge deficits from the onset. Affective ToM was
initially preserved, but deteriorated as the disease progressed.
Alzheimer's disease (AD), since its characterization as a precise form of dementia
with its own pathological hallmarks, has captured scientists' attention because of
its complexity. The last 30 years have been filled with discoveries regarding the
elusive aetiology of this disease and, thanks to advances in molecular biology and
live imaging techniques, we now know that an important role is played by calcium
(Ca2+). Ca2+, as ubiquitous second messenger, regulates a vast variety of cellular
processes, from neuronal excitation and communication, to muscle fibre contraction
and hormone secretion, with its action spanning a temporal scale that goes from
microseconds to hours. It is therefore very challenging to conceive a single
hypothesis that can integrate the numerous findings on this issue with those coming
from the classical fields of AD research such as amyloid-beta (A beta) and tau
pathology. In this contribution, we will focus our attention on the Ca2+ hypothesis
of AD, dissecting it, as much as possible, in its subcellular localization, where
the Ca2+ signal meets its specificity. We will also follow the temporal evolution
of the Ca2+ hypothesis, providing some of the most updated discoveries. Whenever
possible, we will link the findings regarding Ca2+ dysfunction to the other players
involved in AD pathogenesis, hoping to provide a crossover body of evidence, useful
to amplify the knowledge that will lead towards the discovery of an effective
therapy. (C) 2016 Elsevier Ltd. All rights reserved.
AimsTo explore the common effects of the clusterin (CLU) rs11136000 variant on the
default mode network (DMN) in amnestic mild cognitive impairment (aMCI) subjects
and remitted geriatric depression (RGD) subjects. MethodsFifty-one aMCI subjects,
38 RGD subjects, and 64 cognitively normal elderly subjects underwent resting-state
fMRI scans and neuropsychological tests at both baseline and a 35-month follow-up.
Posterior cingulate cortex seed-based functional connectivity (FC) analysis was
used to obtain the DMN patterns. ResultsA CLU genexdiseasextime interaction for
aMCI subjects was mainly detected in the core cortical midline structures of the
DMN, and the interaction for RGD subjects was mainly detected in the limbic system.
However, they overlapped in two frontal regions, where consistent effects of the
CLU gene on FC alterations were found between aMCI and RGD groups. Furthermore, the
alterations of FC with frontal, parietal, and limbic regions compensated for
episodic memory impairments in CLU-CT/TT carriers, while no such compensation was
found in CLU-CC carriers. ConclusionThe CLU gene could consistently affect the DMN
FC with frontal regions among individuals at risk for Alzheimer's disease, and the
CLU-T allele was associated with more compensatory neural processes in DMN changes.
Young individuals better memorize initially seen faces with emotional rather than
neutral expressions. Healthy older participants and Alzheimer's disease (AD)
patients show better memory for faces with positive expressions. The socioemotional
selectivity theory postulates that this positivity effect in memory reflects a
general age-related preference for positive stimuli, subserving emotion regulation.
Another explanation might be that older participants use compensatory strategies,
often considering happy faces as previously seen. The question about the existence
of this effect in tasks not permitting such compensatory strategies is still open.
Thus, we compared the performance of healthy participants and AD patients for
positive, neutral, and negative faces in such tasks. Healthy older participants and
AD patients showed a positivity effect in memory, but there was no difference
between emotional and neutral faces in young participants. Our results suggest that
the positivity effect in memory is not entirely due to the sense of familiarity for
smiling faces.
Chronic neuroinflammation is thought to potentiate medial temporal lobe (MTL)
atrophy and memory decline in Alzheimer's disease (AD). It has become increasingly
important to find novel immunological biomarkers of neuroinflammation or other
processes that can track AD development and progression. Our study explored which
pro- or anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD
neuropathology over 24 months. Using Alzheimer's Disease Neuroimaging Initiative
data (N = 285), CSF inflammatory biomarkers from mass spectrometry and multiplex
panels were screened using step-wise regression, followed up with 50%/50% model
retests for validation. Neuronal Pentraxin 2 (NPTX2) and Chitinase-3-like-protein-1
(C3LP1), biomarkers of glutamatergic synaptic plasticity and microglial activation
respectively, were the only consistently significant biomarkers selected. Once
these biomarlcers were selected, linear mixed models were used to analyze their
baseline and longitudinal associations with bilateral MTL volume, memory decline,
global cognition, and established AD biomarkers including CSF amyloid and tau.
Higher baseline NPTX2 levels corresponded to less MTL atrophy [R-2 = 0.287, p <
0.001] and substantially less memory decline [R-2 = 0.560, p < 0.001] by month 24.
Conversely, higher C3LP1 modestly predicted more MTL atrophy [R-2 = 0.083, p <
0.001], yet did not significantly track memory decline over time. In conclusion,
NPTX2 is a novel pro -inflammatory cytokine that predicts AD-related outcomes
better than any immunological biomarker to date, substantially accounting for brain
atrophy and especially memory decline. C3LP1 as the microglial biomarker, by
contrast, performed modestly and did not predict longitudinal memory decline. This
research may advance the current understanding of AD etiopathogenesis, while
expanding early diagnostic techniques through the use of novel pro -inflammatory
biomarkers, such as NPTX2. Future studies should also see if NPTX2 causally affects
MTL morphometry and memory performance. (C) 2016 Elsevier Inc. All rights reserved.
Alzheimer's disease patients display neuropathological lesions, including the
accumulation of amyloid-beta (A beta) peptide and neurofibrillary tangles. Although
the mechanisms causing the neurodegenerative process are largely unknown,
increasing evidence highlights a critical role of immunity in the pathogenesis of
Alzheimer's disease. In the present study, we investigated the role of regulatory T
cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of
Tregs (CD4(+)CD25(+) T cells) and Teffs (CD4(+)CD25(-) T cells) in an adoptive
transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice
improved cognitive function and reduced deposition of A beta plaques. In contrast,
adoptive transfer of Teffs diminished behavioral function and cytokine production.
Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61).
Depletion of Tregs for four months resulted in a marked aggravation of the spatial
learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in
decreasing glucose metabolism, as assessed by positron emission tomography (PET)
with F-18-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. Importantly, the
deposition of A beta plaques and microglia/macrophage was increased in the
hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the
vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg
administration ameliorates disease progression and could be an effective
Alzheimer's disease treatment.
Introduction: Subjective cognitive decline (SCD) could indicate preclinical
Alzheimer's disease, but the existing literature is confounded by heterogeneous
approaches to studying SCD. We assessed the differential cognitive, affective, and
neuroimaging correlates of two aspects of SCD: reporting high cognitive
difficulties on a self-rated questionnaire versus consulting at a memory clinic.
Methods: We compared 28 patients from a memory clinic with isolated SCD, 35
community-recruited elders with similarly high levels of self-reported cognitive
difficulties, and 35 community-recruited controls with low self-reported cognitive
difficulties. Results: Increased anxiety and amyloid beta deposition were observed
in both groups with high self-reported difficulties, whereas subclinical depression
and (hippocampal) atrophy were specifically associated with medical help seeking.
Cognitive tests showed no group differences. Discussion: These results further
validate the concept of SCD in both community-and clinic-based groups. Yet,
recruitment methods influence associated biomarkers and affective symptomatology,
highlighting the heterogeneous nature of SCD depending on study characteristics.
(C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights
reserved.
this paper presents an amplitude modulation transmitter for 50 MHz application with
low power consumption. The transmitter consists of Gilbert cell mixer, cross
coupled with symmetric load voltage controlled oscillator, two stage operational
amplifier and a high pass filter implemented in TSMC CMOS 0.18 mu m process. A 200
mV RF input of 50 MHz and 500 mV LO output of 1.5 GHz are applied at both RF and LO
ports of the mixer with conversion gain of 14.25 dB results to a 300 mV IF output
of 1.2 GHz. The reference voltage V-dd = 1.8 V, the tuning range of oscillator is 0
to 2 GHz and the amplifier has a gain of 42.1 dB, phase margin of 56 degrees, unity
gain bandwidth of 1.43 GHz and slew rate of 291 V/mu s. The overall power
consumption is 74.3 mW and a chip size of 9.68 nm(2). The chip is connected to an
I/O pad with rectangular pad frame of size 0.46 mu m(2).
Using a field-programmable gate array (FPGA) development board, a digital signal
processor (DSP) builder, and the phase-to-amplitude conversion principle, a low-
cost system for measuring the amplitude-to-amplitude (AM/AM) and amplitude-to-phase
(AM/PM) distortion curves of radio frequency (RF) power amplifiers (PAs) is
presented. The state of the art based on the measurements and preliminary studies
of AM/AM and AM/PM distortion curves is discussed. A full digital control of the
test bed simulated/emulated in Matlab/Simulink is introduced to recalculate the
known AM/AM and AM/PM measurements stored as look-up table (LUT). Finally, the low-
cost system comprises the memory polynomial model (MPM) that involves the
nonlinearity order and memory effects of real PAs. (C) 2015 Elsevier B.V. All
rights reserved.
Considerable interest in the relationship between biodiversity and disease has
recently captured the attention of the research community, with important public
policy implications. In particular, malaria in the Amazon region is often cited as
an example of how forest conservation can improve public health outcomes. However,
despite a growing body of literature and an increased understanding of the
relationship between malaria and land use/land cover change (LULC) in Amazonia,
contradictions have emerged. While some studies report that deforestation increases
malaria risk, others claim the opposite. Assessing malaria risk requires
examination of dynamic processes among three main components: (i) the environment
(i.e. LULC and landscape transformations), (ii) vector biology (e.g. mosquito
species distributions, vector activity and life cycle, plasmodium infection rates),
and (iii) human populations (e.g. forest-related activity, host susceptibility,
movement patterns). In this paper, we conduct a systematic literature review on
malaria risk and deforestation in the Amazon focusing on these three components. We
explore key features that are likely to generate these contrasting results using
the reviewed articles and our own data from Brazil and Peru, and conclude with
suggestions for productive avenues in future research. This article is part of the
themed issue 'Conservation, biodiversity and infectious disease: scientific
evidence and policy implications'.
How can a firm develop, distribute, and use knowledge more effectively and
efficiently in ways that increase its ability to pursue an ambidextrous
orientation? Synthesizing insights from social cognition and upper-echelons
perspectives, we offer a new theoretical vantage point that brings the role of top
management teams' cognitive structure to the fore and, in particular, the enabling
influence of transactive memory systems. We argue that transactive memory provides
a top management team with a system for generating, distributing, and integrating
knowledge based on members' specific areas of expertise in ways that increase its
ability to both differentiate and integrate strategic agendas for ambidexterity.
From a multisource study of top management teams in a sample of technology-based
small-to-medium-sized firms, we find that while top management teams with well-
developed transactive memory systems are able to pursue an ambidextrous
orientation, the impact of transactive memory is also shaped by diverse
organizational experience and functional expertise within these teams. We discuss
the scope and significance of these findings for theory, future research, and
managerial practice.
Electrical arcs emit extremely high intensity light across a wide spectrum that can
damage the eye's delicate structures, such as the cornea or the retina. Developing
industry safety standards to mitigate light hazards is a critical component of arc
flash safety. Accurate measurement of light intensity is the first step in
understanding the level of eye protection needed. Traditionally, light measurement
devices are an assembly of light-detecting resistors made from cadmium sulfide
(CdS) or silicon (Si) cells. However, their response times are inadequate for
capturing the peak light intensity or the dynamic changes during the initial arc
flash. In addition, the brightness of an arc flash is greater than the measurable
light levels from traditional light measurement devices. Furthermore, the light
sensitivity of traditional sensors does not match the Commission Internationale de
l'Eclairage luminosity function V (lambda) curve, which defines the human eye's
sensitivity to bright light as a function of wavelength under typical ambient light
conditions. This paper discusses a novel light measurement technique to overcome
the limitations of traditional approaches. This design is capable of measuring the
light intensity of the arc flash as perceived by the human eyes. These results can
be used to evaluate the potential of an arc flash to harm the eyes.
Background: Evidence for extreme ambient temperature effects on the risk of mental
disorders (MDs) is limited. In this study, we evaluated the short-term effects of
daily mean temperature on hospital admissions of MDs in Shanghai, China. Methods:
We obtained daily hospital admission data for MDs, daily meteorological and ambient
pollution data in Shanghai from January 2008 to December 2015. Adjusted for time
trend, air pollution, relative humidity and other confounders, a quasi-Poisson
generalized additive model (GAM) combined with a distributed lag non-linear model
(DLNM) was used to analyze the lag-exposure-response relationship between daily
mean temperature and hospital admissions for MDs. Results: Total daily hospital
admissions for MDs during the study period were 93,971. With a reference of median
temperature (18.3 degrees C), there was a significant positive association between
the temperature above threshold (24.6 degrees C) and MD hospital admission visits
at a lag of 0-1 days. The relative risks of extreme hot temperatures (33.1 degrees
C, 99% percentile) over the lag 0-1 days compared to median temperature were 1.266
(95% confidence intervals: 1.074-1.493). No effect of cold weather on the hospital
admissions for MDs was observed. Conclusions: This study suggests that extreme hot
temperature poses significant risks on MD; health counseling and cooling measures
should be considered for the susceptible population. (C) 2017 Elsevier B.V. All
rights reserved.
Beyond the universality of the symmetry concept, there are different emphases on
its application in different branches of science. Chemistry, being between particle
physics and astrophysics, represents a bridge in, and a utilitarian approach to,
the application of the symmetry concept, which has proved immensely fruitful in
twentieth-century science. Some pivotal discoveries, especially in structural
chemistry, molecular biology, and materials science, emerged by relaxing some of
the stipulations of the classical teachings about symmetry. This highly personal
presentation relies on ideas expressed by a number of notable individuals in recent
science, among them J. Desmond Bernal, Francis Crick, Ronald J. Gillespie,
Aleksandr I. Kitaigorodskii, Alan L. Mackay, George A. Olah, Linus Pauling, Roger
Penrose, Dan Shechtman, James D. Watson, Steven Weinberg, and Eugene P. Wigner.
Recently, most of sonokembang, Pterocarpus indicus trees are dying in Malang. In
2012, the death rate of trees reached ca. 11%. In addition, death of trees spread
to other regencies in East Java. Euplatypus parallelus is a specific species of
ambrosia beetles that were the causal agents to the dying and wilting of
sonokembang trees in Malang. Wilting is caused mainly by the pathogenic fungi
carried by ambrosia beetles. To confirm the microbial communities related to E.
parallelus that attack sonokembang, E. parallelus and some attacked trees were
collected in Malang city. Isolation and identification of these species were
conducted at the Laboratory of Mycology, Faculty of Agriculture, University of
Brawijaya and Laboratory of Molecular Biology, Islamic State University, Malang.
Results showed that there were nine microbes including five genera of fungi, two
genera of yeasts and one genus of bacterium were identified. The microbial
communities that were found namely Aspergillus spp., Penicilium spp., Trichoderma
spp., Fusarium spp., Acremonium spp., Gliocladium spp. (fungi), Streptomyces spp.
(bacteria), Saccharomyces spp., and Candida spp. (yeast).
The modifiable areal unit problem and the ecological fallacy are known problems
that occur when modelling multiscale spatial processes. We investigate how these
forms of spatial aggregation error can guide a regionalization over a spatial
domain of interest. By regionalization' we mean a specification of geographies that
define the spatial support for areal data. This topic has been studied vigorously
by geographers but has been given less attention by spatial statisticians. Thus, we
propose a criterion for spatial aggregation error, which we minimize to obtain an
optimal regionalization. To define the criterion we draw a connection between
spatial aggregation error and a new multiscale representation of the Karhunen-Loeve
expansion. This relationship between the criterion for spatial aggregation error
and the multiscale Karhunen-Loeve expansion leads to illuminating theoretical
developments including connections between spatial aggregation error, squared
prediction error, spatial variance and a novel extension of Obled-Creutin
eigenfunctions. The effectiveness of our approach is demonstrated through an
analysis of two data sets: one using the American Community Survey and one related
to environmental ocean winds.
ObjectiveWe examined the relationship between American Indian men's attitudes
toward pregnancy prevention, STI/HIV prevention, and sexual risk behavior.
Attention was given to: (1) attitudes and intentions to use condoms and sexual risk
behavior; (2) STI/HIV prevention characteristics and sexual risk behavior; (3)
attitudes toward abstinence and monogamy and sexual risk behavior; and (4)
decision-making in relationships and sexual risk behavior. Study DesignOur sample
included 120 heterosexual American Indian men aged 18 to 24 living on a
reservation. Data were collected during in-depth interviews. A community-based
participatory research framework was used to ensure the relevancy and acceptability
of the study given the sensitivity of the topic. Principal FindingsResults
demonstrated that attitudinal factors were associated with sexual risk behavior,
particularly inconsistent condom use. Attitudes associated with consistent condom
use suggested greater levels of positive dispositions toward prevention and
intention to use condoms. Consistent condom use was associated with more cautious
attitudes toward sex with multiple sex partners. Study results suggested that
American Indian men who reported sex with multiple partners exhibited a set of
attitudes and beliefs toward pregnancy prevention and STI/HIV prevention that
corresponded with a disposition resulting from their behaviors, in that engaging in
sexual risk behavior elevated their levels of risk perception. ConclusionsOur
findings suggest that heterosexual American Indian men living in rural environments
need sexual and reproductive health programs and clinical services that address
differing attitudes toward condom use within the context of multiple sex partners
and sexual risk behavior.
Nitrile-converting enzymes, including nitrilase and nitrile hydratase (NHase), have
received increasing attention from researchers of industrial biocatalysis because
of their critical role as a tool in organic synthesis of carboxylic acids and
amides from nitriles. To date, these bioconversion approaches are considered as one
of the most potential industrial processes using resting cells or purified enzymes
as catalysts for production of food additives, pharmaceutical, and agrochemical
precursors. This review focuses on the distribution and catalytic mechanism
research of nitrile-converting enzymes in recent years. Molecular biology aspects
to improve the biocatalytic performance of microbial nitrilase and NHase are
demonstrated. The process developments of microbial nitrilase and NHase for organic
synthesis are also discussed.
Aminoacylase 1 (ACY1) is important for regulating the proliferation of numerous
types of cancer. However, the expression and mechanisms underlying the function of
ACY1 in colorectal cancer remain unclear. In order to investigate the expression
and function of ACY1 in colorectal cancer, tumor tissue and blood samples were
collected for analysis from 132 patients diagnosed with colorectal cancer. Reverse
transcription-quantitative polymerase chain reaction analysis and western blotting
identified significantly increased expression of ACY1 mRNA in colorectal tumor
tissue (P<0.05 vs. adjacent normal tissue) and notably increased ACY1 protein
levels. This ACY1 mRNA expression was found to be positively correlated with tumor
stage. In addition, plasma ACY1 concentration was increased in patients with
colorectal cancer compared with healthy controls. Furthermore, in vitro knockdown
of ACY1 in human colorectal cancer HT-29 cells was shown to inhibit proliferation
and increase apoptosis. This effect was found to be associated with the activation
of ERK1 and TGF-beta 1 signaling. In conclusion, the results of the present study
suggest that ACY1 promotes tumor progression, and thus may be a potential target
for the diagnosis and treatment of colorectal cancer.
Bacillus thuringiensis insecticidal crystal proteins bind to cell-surface receptors
which represent a family of aminopeptidases [APN (aminopeptidase N)] present on the
brush border membrane of insect midgut cells of susceptible insects leading to pore
formation and death of the insect. We report here for the first time the presence
of a novel APN in the fat body of the moth Achaea janata. Northern blotting
detected at least one APN-specific transcript in the fat body, whereas two
transcripts of different sizes were detected in the midgut. We have cloned two
full-length APN cDNAs of 3015 bp and 2850 bp from fat body and midgut respectively,
which encode proteins of 1004 and 950 amino acids. These two APNs share only 33%
amino acid sequence identity, but both display the typical APN features, such as
the N-terminal signal peptide, several putative glycosylation sites, C-terminal
glycosylphosphatidylinositol anchor signal, the APN-specific zinc-binding/gluzincin
motif HEXXHX18E and gluzincin motif GAMENWG. The fat body APN manifested a
variation in its expression with respect to tissue and developmental stage. In
spite of the abundance of the APN transcript in the fat body, fairly low APN
activity was detected in this tissue. The fat-body-and midgut-specific APNs showed
differential interaction with various Cry1A toxins. Besides, the level of toxicity
of different Cry subtypes varied enormously with mode/site of delivery, such as
intrahaemocoelic injections and feeding bioassays. These data indicate that the fat
body might be a potential alternative Cry toxin target site in the moth.
The long-term cardiac effects of amiodarone resemble many aspects of
hypothyroidism. The anti-arrhythmic potential of amiodarone may therefore be the
result of a drug-induced, local hypothyroid-like condition. To investigate this
controversial issue, we compared gene expression profiles in the hearts of rats
treated with amiodarone with those of rats with hypothyroidism. Wistar male rats
were assigned to 3 groups (n = 6-8): Control, systemic hypothyroidism
(Hypothyroidism) and amiodarone treatment (Amiodarone, 150 mg/kg/day, p.o., 4
weeks). Electrocardiogram (ECG) recordings, gene profiling by DNA microarray and
Northern blotting were carried out. Amiodarone, like Hypothyroidism, caused
significant prolongation of RR and QT intervals in ECGs. Microarray analysis of
8435 genes in the left ventricular myocardium revealed a significant similarity in
expression profiles between Hypothyroidism and Amiodarone (R=0.63, p<0.00001). The
gene expression profiles of Hypothyroidism and Amiodarone showed closer correlation
when top 100 up-regulated and 100 down-regulated genes in Hypothyroidism, (total
200 genes)were analyzed (R=0.78,p<0.00001). Northern blots of left ventricular
myocardium, showed a parallel decrease in mRNAs for myosin heavy chain (MHC)-alpha
and a parallel increase for myosin heavy chain (MHC)-beta in Hypothyroidism and
Amiodarone. In the liver and pituitary, in contrast, Northern blots showed quite
different changes in the transcripts of the representative T3-responsive genes in
the Hypothyroidism and Amiodarone. In conclusion, long-term treatment with
amiodarone causes cardioselective hypothyroid-like alterations in gene expression
profiles. The potent anti-arrhythmic activity of amiodarone may be attributable, in
part at least, to this unique transcriptional remodeling. (C) 2007 Elsevier B.V.
All rights reserved.
RNA interference (RNAI) is a powerful tool for functional gene analysis, which has
been successfully used to down-regulate the levels of specific target genes. In
this study a microRNA 159a-based binary vector was constructed which can be used
for hpRNA expression. Hairpin (hp) RNA expression cassettes carrying the gene
sequences are typically constructed on binary plasmid and delivered into plant
cells by Agrobacteriurn-mediated genetic transformation. This system allows simple
insertion of 21- nt target gene sequences into microRNA backbone, to facilitate the
processing of microRNA hpRNA by the endogenous machinery of host, thereby producing
artificial microRNA carrying the sequence of target gene(s). The functionality of
new vector system was tested by silencing viral gene in transgenic plants. Strong
down regulation of viral gene was observed in virus infected tobacco plants
transformed with PAmiR(159) vector. The processing of amiRNA leading to viral-
specific siRNA was confirmed by northern blotting. This vector system provides an
important addition to the plant molecular biologists' toolbox, which will
significantly facilitate the use of RNAi technology for analyses of various gene
functions in plant cells.
Context: Amitriptyline, a tricyclic antidepressant is used for the management of
psychological disorders and various types of pain. In the previous work, it is
founded that amitriptyline inhibited the migration of polymorphonuclear (PMN) into
the site of inflammation. Aims: To evaluate the effect of amitriptyline on the
expression of some inflammatory mediators such as intercellular adhesion molecule
(ICAM-1), vascular cell adhesion molecule (VCAM-1), cyclooxygenase 2 (COX2) and
inducible nitric oxide synthase (iNOS). Methods: An in vitro model system of LPS-
stimulated human endothelial cells and U-937 macrophages and also in vivo model of
carrageenan-induced paw edema in rat were used. The expression of inflammatory
mediator genes was determined by qRT-Real-time PCR. In endothelial cells, soluble
forms of ICAM-1 and VCAM-1 were quantified by ELISA. Results: The expression of
ICAM-1, VCAM-1, COX2, iNOS, sICAM-1 and sVCAM-1 significantly decreased by
amitriptyline. The finding of this study also confirmed that intraperitoneal (i.p.)
injection of amitriptyline inhibited carrageenan-induced inflammation in rat paw
edema. Conclusions: The results of the present study provide further evidence for
the anti-inflammatory effect of amitriptyline. This effect appears to be mediated
by down-regulation of inflammatory genes.
A cDNA sequence OsMT3 was initially isolated from the subtractive cDNA library of
ammonium-fed rice (Oryza sativa L.) leaves, which was further confirmed by Northern
blot to be highly ammonium-up-regulated as compared to nitrate. Its full-length
cDNA was cloned by RT-PCR, and in silico analysis reveals that the cDNA includes an
open reading frame of 186 bp and encodes a rice metallothionein type 3 peptide.
Northern blotting analysis showed that OsMT3 gene predominantly expressed in rice
leaves, weakly in stems, and barely in buds and roots. The gene transcripts in
leaves were significantly induced by polyethylene glycol (PEG), low temperature,
NaCl and Cu2+, but not by Pb2+. Activities of three anti-oxidative enzymes
(superoxide dismutase, catalase and peroxidases) and two non-enzymic antioxidants
(reduced ascorbate and reduced glutathione) little differed in ammonium-and
nitrate-fed rice leaves, indicating that the induced OsMT3 expression was not
mediated by ammonium-elicited oxidative signals.
Background: The aim of this study was to investigate the application of mucous
membrane keratinocyte cultures on amniotic membrane and on poly(L-lactic acid)
(PLLA) Purasorb PL38 to cover tissue loss in the oral cavity. Developments in
molecular biology techniques and tissue engineering allow the culturing and
identification of cells that can be anchored in the wound to achieve integrity of
the tissue. Transplantation of tissues obtained from the patient's own cells is
superior to allogenous transplantation where there is a possibility of
transfection, rejection and the need for long-term immunosuppression. Methods: In 9
patients (15 procedures) keratinocytes cultured on amniotic membrane and PLLA were
transplanted to cover antro-oral fistulas and bone loss after osteoradionecrosis.
Results: In all 6 patients with outlasting antro-oral fistulas, the defects were
healed. In 3 patients with 5 cases of tissue loss after osteoradionecrosis, we
obtained healing of the wound in only 1 case. Histological examination of the
cultures indicated that cultured cells formed well-differentiated layers, very
similar to the keratinocytes of mucous membranes, although those seeded on amniotic
membrane formed a single layer of cells, while those seeded on the PLLA scaffold
were arranged on 2 or more layers: these differences were shown to be statistically
significant with a morphometric analysis. Conclusions: Autologous transplants of
epithelium cultured on amniotic membrane and PLLA constitute a new and effective
way of covering nonhealing tissue loss in the oral cavity in chosen cases, using
modern methods of tissue engineering.
In this paper, we presented a novel operational amplifier (op-amp) only with
solution-processed n-type amorphous indium-gallium-zinc oxide (a-IGZO) thin-film
transistors (TFTs). The a-IGZO TFTs and common-source amplifier were fabricated on
glass substrate through the solution process and confirmed to show stable
electrical characteristics suitable for display driving circuits. Based on the
experimental results, we designed an op-amp to have an overall gain of 30.5 dB, a
cut-off frequency of 1.47 kHz, and a unit gain frequency of 6.65 kHz when supply
voltage was +/- 15 V. Finally, by constituting the comparator, the proposed op-amp
is expected to be used in power control and driving systems for display
applications.
In this paper, we present an operational amplifier (op-amp) and a pulsewidth-
modulation (PWM) controller fabricated with amorphous indium-gallium-zinc oxide
thin-film transistors (a-InGaZnO TFTs), to build an adaptive dc-dc converter for
display driving systems. The fabricated a-InGaZnO TFT presents electrical
characteristics suitable for accomplishing an op-amp composed only with n-type TFTs
to have an overall gain of 24.5 dB, a cutoff frequency of 6 kHz, and a unit gain
frequency of 32 kHz operating at +/- 15 V. The fabricated op-amp is used to
construct a comparator and an error amplifier on the glass, which are combined to
realize a PWM controller. The resulting PWM controller can successfully control the
output voltage of an external dc-dc converter that follows the input voltage to the
error amplifier, and can operate at 100 Hz to control the duty ratio from 24.3% to
66.1% when the reference voltage varies from 2 to 6 V, respectively.
Background and ObjectiveBacteria in the dental biofilm surrounding marginal
gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm
consume nutrients from the gingival crevicular fluid. Furthermore, some gram-
negative bacteria in mature dental biofilms produce butyrate. Thus, gingival
epithelial cells in close proximity to mature dental biofilms are at risk of both
starvation and exposure to butyrate. In the present study, we determined the
combined effects of starvation and butyrate exposure on gingival epithelial cell
death and the underlying mechanisms. Material and MethodsThe Ca9-22 cell line was
used as an in vitro counterpart of gingival epithelial cells. Cell death was
measured as the amount of total DNA in the dead cells using SYTOX Green dye, which
penetrates through membranes of dead cells and emits fluorescence when it
intercalates into double-stranded DNA. AMP-activated protein kinase (AMPK)
activity, the amount of autophagy, and acetylation of histone H3 were determined
using western blot. Gene expression levels of microtubule-associated protein 1
light chain 3b (lc3b) were determined using quantitative reverse transcription-
polymerase chain reaction. ResultsButyrate-induced cell death occurred in a dose-
dependent manner whether cells were starved or fed. However, the induction of cell
death was two to four times higher when cells were placed under starvation
conditions compared to when they were fed. Moreover, both starvation and butyrate
exposure induced AMPK activity and autophagy. While AMPK inactivation resulted in
decreased autophagy and butyrate-induced cell death under conditions of starvation,
AMPK activation resulted in butyrate-induced cell death when cells were fed.
Combined with the results of our previous report, which demonstrated butyrate-
induced autophagy-dependent cell death, the results of this study suggest that the
combination of starvation and butyrate exposure activates AMPK inducing autophagy
and subsequent cell death. Notably, this combination markedly induced LC3B
production and the induction was attenuated by AMPK inhibition. LC3B knockdown, in
turn, significantly decreased butyrate-induced cell death. Therefore, AMPK-
dependent LC3B induction apparently plays an important role in butyrate-induced
cell death. There was a lack of correspondence between the levels of AMPK
activation and LC3B induction; this may reflect the histone deacetylase-inhibitory
capacity of butyrate on histone proteins. ConclusionTaken together, starvation and
butyrate exposure promote autophagy via AMPK signaling, while the histone
deacetylase-inhibitory effects of butyrate alter chromatin to transcriptionally
active state, resulting in strong LC3B induction and subsequent cell death. These
findings may help improve the understanding of the cellular processes underlying
periodontal disease initiation.
MicroRNAs (miRs) have emerged as important clinical biomarkers with both diagnostic
and prognostic value for relevant diseases, such as cancer. MiRs pose unique
challenges for detection and are currently detected by northern blotting, real-time
PCR, and microarray techniques. These expensive, complicated, and time-consuming
techniques are not feasible for on-site miR determination. In this study,
amperometric magnetobiosensors involving RNA-binding viral protein p19 as a
selective biorecognition element were developed for miR quantification. The p19-
based magnetosensors were able to detect 0.4 fmol of a synthetic target and
endogenous miR-21 (selected as a model for its role in a wide variety of cancers)
in only 2 h in total RNA extracted from cancer cells and human breast-tumor
specimens without PCR amplification and sample preprocessing. These results open up
formidable perspectives for the diagnosis and prognosis of human cancers and for
drug-discovery programs.
In this brief, a 1-V potentiostat circuit for a glucose sensor has been proposed.
Test results of this 1-V potentiostat demonstrate high linearity with respect to
glucose concentration, which is comparable with conventional potentiostat designs.
This high linearity is achieved with the help of a transconductance enhanced bulk-
driven operational amplifier. The overall current consumption of the circuit is
around 22 mu A. The potentiostat is tested as a glucose biosensor for glucose
concentration ranging from 0 to 30 mM. The design is realized in a 0.35-mu m bulk-
CMOS process, and the area for the core layout is 0.13 mm(2). The proposed low-
power potentiostat can be incorporated in an implantable glucose sensor system due
to its low-power operation and small footprint.
Here we report a homologue of the apolipoprotein D gene (AniphiApoD) in amphioxus,
Branchiostoma belcheri tsingtauense, the first such finding in a basal chordate
cephalochordate. The main features of the protein predicted from AmphiApoD are
characteristic of the apolipoprotein D. Phylogenetic analysis places AmphiApoD at
the base of the phylogenetic tree, suggesting that AmphiApoD is the archetype of
the vertebrate ApoD genes. Both whole mount in situ hybridization and Northern
blotting and RT-PCR as well as in situ hybridization histochemistry reveal that
AmphiApoD is expressed in tissues derived from mesoderm and endoderm including
notochord and hind-gut, which contrasts with the strong expression patterns of ApoD
genes in the ectodermal derivatives in mammals and birds. The expression profiles
of the ApoD gene may have been changed to be expressed in the endo-mesodermal
derivatives in amphioxus after the vertebrate and cephalochordate lineages
diverged; alternatively, the ApoD gene may first have been expressed in the endo-
mesoderm during embryogenesis in the last common ancestor of all chordates, and
subsequently came to be expressed in the ectodermal derivatives of vertebrates
including mammals and birds. (c) 2006 International Federation for Cell Biology.
Published by Elsevier Ltd. All rights reserved.
In vertebrates, many responses to stress as well as homeostatic maintenance of
basal metabolism are regulated by plasma glucocorticoid hormones (GCs). Despite
having crucial functions, levels of GCs are typically variable among individuals.
We examined the contribution of several physiological factors to individual
variation in plasma corticosterone (CORT) and the number of corticotropinreleasing
hormone (CRH) neurons in the magnocellular preoptic area of the brain in free-
living Allegheny Mountain dusky salamanders. We addressed three hypotheses: the
current-condition hypothesis, the facilitation hypothesis and the trade-off
hypothesis. Differential white blood cell count was identified as a strong
contributor to individual variation in baseline CORT, stress-induced CORT and the
number of CRH neurons. In contrast, we found no relationship between CORT (or CRH)
and body condition, energy stores or reproductive investment, providing no support
for the current-condition hypothesis or the tradeoff hypothesis involving
reproduction. Because of the difficulties of interpreting the functional
consequences of variation in differential white blood cell counts, we were unable
to distinguish between the facilitation hypothesis or the trade-off hypothesis
related to immune function. However, the strong association between differential
white blood cell count and hypothalamic-pituitary-adrenal/interrenal (HPA/I)
activation suggests that a more thorough examination of immune profiles is critical
to understanding variation in HPA/I activation.
Resource availability can significantly alter host-parasite dynamics. Abundant food
can provide more resources for hosts to resist infections, but also increase host
tolerance of infections by reducing competition between hosts and parasites for
food. Whether abundant food favors host resistance or tolerance (or both) might
depend on the type of resource that the parasite exploits (e.g., host tissue vs.
food), which can vary based on the stage of infection. In our study, we evaluated
how low and high resource diets affect Cuban tree frog (Osteopilus septentrionalis)
resistance and tolerance of a skin-penetrating, gut nematode Aplectana sp. at each
stage of the infection. Compared to a low resource diet, a high resource diet
enhanced frog resistance to worm penetration and tolerance while worms traveled to
the gut. In contrast, a low resource diet increased resistance to establishment of
the infection. After the infection established and worms could access food
resources in the gut, a high resource diet enhanced host tolerance of parasites. On
a high resource diet, parasitized frogs consumed significantly more food than non-
parasitized frogs; when food was then restricted, mass of non-parasitized frogs did
not change, whereas mass of parasitized frogs decreased significantly. Thus, a high
resource diet increased frog tolerance of established worms because frogs could
fully compensate for energy lost to the parasites. Our study shows that host-
parasite dynamics are influenced by the effect of resource availability on host
resistance and tolerance, which depends on when parasites have access to food and
the stage of infection.
A full length amphioxus cDNA, encoding a novel phosducin-like protein (Amphi-PhLP),
was identified for the first time from the gut cDNA library of Branchiostoma
belcheri. It is comprised of 1 550 bp and an open reading frame (ORF) of 241 amino
acids, with a predicted molecular mass of approximately 28 kDa. In situ
hybridization histochemistry revealed a tissue-specific expression pattern of
Amphi-PhLP with the high levels in the ovary, and at a lower level in the hind gut
and testis, hepatic caecum, gill, endostyle, and epipharyngeal groove, while it was
absent in the muscle, neural tube and notochord. In the Chinese Hamster Ovary (CHO)
cells transfected with the expression plasmid pEGFP-N1/Amphi-PhLP, the fusion
protein was targeted in the cytoplasm of CHO cells, suggesting that Amphi-PhLP is a
cytosolic protein. This work may provide a framework for further understanding of
the physiological function of Amphi-PhLP in B. belcheri.
Promethins have been shown to be present in the vertebrates examined so far, yet
little is known to date about them in invertebrates. Here we isolated a cDNA
encoding a promethin-like homolog from the gut cDNA library of the amphioxus
Branchiostoma belcheri, a cephalochordate occupying a nodal position transient from
invertebrates to vertebrates. It contained a 504 bp open reading frame
corresponding to a protein of 167 amino acids. Primary structural examination
showed that the deduced promethin-like homolog was a transmembrane protein with
three potential transmembrane helices, resembling the vertebrate promethins.
Phylogenetic analysis showed that B. belcheri promethin-like homolog was located at
the base of the vertebrate counterparts, suggesting that it represents the
archetype of vertebrate promethins. Both Northern blotting and in situ
hybridization histochemistry revealed a tissue-specific expression pattern of
promethin-like gene, like that of mammalian promethins. This is the first report on
invertebrate promethin-like homolog, paving the way for further insights into the
evolution and function of promethins.
An amphioxus cDNA, AmphiGM2AP, encoding GM2 activator protein was isolated from the
gut cDNA library of Branchiostoma belcheri. It is 907 by long, and its longest open
reading frame codes for a precursor protein consisting of 242 amino acid residues
with a signal peptide of 14 amino acids. The deduced amino acid sequence includes a
conserved domain typical of GM2APs between residues 53 and 224, a single N-linked
glycosylation site at position 65 and 8 conserved cysteines. Phylogenetic analysis
showed that amphiGM2AP forms a club together with invertebrate GM2APs, indicating
that AmphiGM2AP is evolutionarily closely related to invertebrate GM2APs rather
than vertebrate ones. Both Northern blotting and in situ hybridization
histochemistry analyses revealed a tissue-specific expression pattern of AmphiGM2AP
in adult amphioxus with the strongest expression in the digestive system, which is
in contrast to the widespread expression pattern of human, mouse and sheep GM2AP
genes. It is suggested that AmphiGM2AP is possibly involved in the take-in of
digested food components like lipid molecules.
A nifU- like gene exhibiting similarity to nifU of nitrogen fixation gene cluster
was identified for the first time from the gut cDNA library of amphioxus
Branchiostoma belcheri. Both RT- PCR and Northern blotting as well as in situ
hybridization histochemistry verified that the cDNA represents an amphioxus nifU-
like gene rather than a microbial contaminant. The nifUlike gene encodes a protein
of 164 amino acid residues including a highly- conserved U- type motif ( C-X-26 -C-
X-43 -C), and shares 66 - 86% identity to NifU- like proteins from a variety of
species including vertebrates, invertebrates and microbes. It is expressed in a
tissue- specific manner in the digestive system including epipharyngeal groove,
endostyle, hepatic caecum and hindgut and in the gill, ovary and testis. Taken
together, it is highly likely that NifU- like protein plays some tissue- dependent
and critical role in amphioxus.
A nifU-Iike gene exhibiting similarity to nifU of nitrogen fixation gene cluster
was identified for the first time from the gut cDNA library of amphioxus
Branchiostoma belcheri. Both RT-PCR and Northern blotting as well as in situ
hybridization histochemistry verified that the cDNA represents an amphioxus nifU-
Iike gene rather than a microbial contaminant. The nifU-like gene encodes a protein
of 164 amino acid residues including a highly conserved U-type motif (C-X-26-C-X-
43-C), and shares 66-86% identity to NifU-like proteins from a variety of species
including vertebrates, invertebrates and microbes. It is expressed in a tissue-
specific manner in the digestive system including epipharyngeal groove, endostyle,
hepatic caecum and hind-gut and in the gill, ovary and testis. Taken together, it
is highly likely that NifU-like protein plays some tissue-dependent and critical
role in amphioxus.
The cDNA AmphiP23,encoding an amphioxus p23, was identified from the gut cDNA
library of amphioxus Branchiostoma belcheri. It contains a 513 bp open reading
frame corresponding to a deduced protein of 170 amino acids. Phylogenetic analysis
shows that vertebrate and invertebrate p23/p23-like proteins are each grouped
together, with AmphiP23 falling at the base of vertebrate p23/p23-like clade,
suggesting that the divergence of vertebrate and invertebrate p23 genes probably
occurs prior to the split of invertebrate/vertebrate from a common ancestor around
550 million years ago. Northern blotting reveals a ubiquitous expression pattern of
AmphiP23 in all adult tissues examined, while whole mount in situ hybridization
demonstrates a tissue- and stage-specific expression pattern of AmphiP23 in
developing embryos and larvae. Presumably, the ubiquitous expression pattern of
AmphiP23 in adult amphioxus represents the ancestral type of p23 gene prior to its
split to human paralogs p23 and tsp23, while the tissue- and stage-specific
expression pattern during early embryonic development implicates a role of AmphiP23
in anterior/posterior patterning. (c) 2006 Elsevier Inc. All rights reserved.
We investigated the developmental expression pattern of AmphiCAM in cephalochordate
amphioxus (Branchiostoma belcheri tsingtauense) We cultured and sampled the animals
at different developmental stages (eggs and larvae), and used in-situ hybridization
and northern blotting to document the spatial and temporal changes in AmphiCaM
expression The alimentary tract dominates the development from the late neurula
stage to the adult stage AmphiCaM expression increased significantly in the
alimentary tract during the late neurula stage and remained elevated in the adults
Our results indicate that AmphiCaM is involved in the differentiation of the
alimentary tract in amphioxus, and furthermore, provide an insight into the change
in function of CaM genes during evolution
Trypsin has been documented in a variety of species including both vertebrates and
invertebrates, but little is known about it in amphioxus, a model organism for
insights into the origin and evolution of vertebrates. Here we identified a trypsin
gene in Branchiostoma japonicum. The cDNA was 978 bp long with an ORF encoding a
deduced protein of 272 amino acids. The deduced protein had an N-terminal signal
peptide of 15 amino acids, a 16 activation peptide with the typical cleavage site
Arg/Ile, a Tryp_SPc domain with the catalytic triad His(72)-Asp(118)-Ser(215) and
the S1 substrate binding residue Asp(209), which are all characteristic of
trypsinogens. The recombinant trypsin protein was able to hydrolyse the trypsin
prototypic substrate BAEE, which was inhibited by the trypsin-specific inhibitor
soybean trypsin inhibitor. Both northern blotting and tissue-section in situ
hybridization demonstrated that trypsin gene was expressed in a tissue-specific
manner, with most abundant levels in the hepatic caecum, mid-gut and ovary. And the
whole mount in situ hybridization showed that it began to express in the middle
third of the full-length primitive gut in 2-day larvae, where the hepatic caecum
will form later during development. Phylogenetic analysis indicated that both
amphioxus and ascidian trypsins are more closer to each other than to vertebrate
trypsins, suggesting a continuous evolutionary divergence of vertebrate trypsins
after split from protochordate/vertebrate common ancestor.
Amphiregulin and epiregulin belong to the epidermal growth factor (EGF) family, and
act as mitogenic stimulators via binding to EGF receptors (EGFRs). Amphiregulin and
epiregulin are thought to play a role in regenerative responses in the
gastrointestinal tract. In this study, we investigated secretion of amphiregulin
and epiregulin in human colonic subepithelial myofibroblasts (SEMFs). The mRNA
expression and protein secretion of amphiregulin and epiregulin were evaluated by
Northern blotting and Western blotting, respectively. The trophic effects of
amphiregulin and epiregulin on SEMFs were analyzed by MTT assays. Amphiregulin and
epiregulin mRNAs were not detected in unstimulated SEMFs. Among the various
cytokines and growth factors, interleukin-1 beta, tumor necrosis factor-alpha, and
EGF strongly induced amphiregulin and epiregulin mRNA expression. These responses
were markedly reduced by AG1478, a specific inhibitor of EGF receptor tyrosine
kinases. Amphiregulin and epiregulin secretion were also detected at the protein
level. MTT assays demonstrated that amphiregulin and epiregulin stimulate the
proliferation of SEMFs. We demonstrated expression of amphiregulin and epiregulin
in SEMFs. Amphiregulin and epiregulin may play an important role in the mechanism
underlying wound healing in damaged colonic mucosa.
Purpose: To report the outcomes of primary transconjunctival 23-gauge (23-G)
vitrectomy in the diagnosis and treatment of presumed endogenous fungal
endophthalmitis (EFE). Methods: Retrospective analysis of patients with EFE who
underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral
center. Results: Nineteen eyes of 15 patients with EFE were included in the study.
Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15
patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture,
polymerase chain reaction, and histopathologic examinations. All affected eyes were
treated with intravitreal amphotericin B 5 mu g/0.1 mL. Fourteen patients received
additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the
diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative
agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the
most common complication (42% of eyes). Conclusions: EFE can be easily confirmed
using primary 23-G vitrectomy.
Several frequency compensation schemes have been proposed to stabilize multistage
amplifiers with negative feedback. The performance of these amplifiers can be
analyzed by inspecting their inputoutput transfer function as representation of
their frequency response. With many circuit elements affecting the output response,
it is relatively difficult to obtain the real transfer function of multistage
amplifiers based on only the original small-signal expressions. Instead, certain
techniques such as Miller's theorem are used to approximate important parameters
such as DC gain and dominant pole. These methods are not generally helpful for
approximating the nondominant poles which have a critical role on the loop
stability of nano-scale amplifiers. With this issue in mind, this work proposes a
systematic methodology to achieve the pole expressions of multistage amplifiers
with frequency compensation. The key in the proposed technique is to model the
equivalent impedance of the compensation loop at the output. The effectiveness of
the proposed approach has been verified through comparison between the transfer
functions obtained from theory and those transfer functions found in the
literature. (C) 2016 Elsevier GmbH. All rights reserved.
Recently, there are revolutionary achievements in silicon-based conventional
terahertz (THz) and millimeter-wave (mm-wave) integrated circuits, particularly
with the advancement of CMOS technology. However, unlike Radio Frequency Integrated
Circuits (RFICs), innovative designs and lack of various circuit techniques still
remain unknown in THz gap. In this paper, a multi-band THz amplifier is presented
in 40 nm CMOS technology with adaptive band selection technique. The smart
amplifier is able to adjust the band of operation with respect to input signal
power and frequency. In addition, the circuit performance will be adjusted to
achieve maximum power gain. In order to achieve multi-band external neutralization,
self-healing technique is vastly utilized by means of tunable transmission lines
(TTLs). The proposed smart system contains tunable transmission lines, a 5-stage
amplifier core, two Successive Approximation Register-based analog-to-digital
converters (SAR ADCs), a digital control core and two on-chip power sensing blocks.
The fabricated amplifier achieves P-1 of 1 dBm, P-sat of 6.1 dBm and power gain of
14.8 dB +/- <1.5 dB from 197 to 288 GHz frequency range. The proposed amplifier
demonstrates the highest operation frequency among all published state-of-arts in
all CMOS technologies.
A signal- and transient-current boosting (STCB) circuit is proposed and applied to
a single-stage amplifier driving large capacitive loads. The proposed STCB circuit
provides gain-bandwidth product (GBW) extension, slew-rate (SR) improvement and
gain enhancement to the amplifier, with only slight alterations to the frequency
response and transient response of the single-stage amplifier driving large
capacitive loads. No on-chip capacitor or resistor is required. The STCB amplifier
is fabricated in a commercial 0.18-mu m CMOS technology. The active chip area is
0.00705 mm(2). The supply is 1.8 V, and the current consumption is 20.3 mu A. The
capacitive load (C-O) ranges from about 4.4 nF to 19 nF. The measured results with
a similar to 19-nF load show the small-signal figure-of-merit (FOMS = GBW .
C-O/power) and the large-signal large-figure-of-merit (FOML = SR . C-O/power) are
150345 MHz . pF/mW and 31213 V/mu s . pF/mW, respectively, which correspond to
improvements of 1.52 times and 1.36 times, respectively, to the prior art. The
achieved phase margin and gain margin are 80.8 degrees and 36.3 dB, respectively.
Reconfigurable analog/mixed signal (AMS) platforms in scaled CMOS technology nodes
are gaining importance due to the increased design cost, effort and shrinking time-
tomarket. Similar to field programmable gate arrays (FPGA) for digital designs, a
Programmable ANalog Device Array (PANDA) provides a flexible and versatile solution
with transistor-level granularity and reconfiguration capability for rapid
prototyping and validation of analog circuits. This paper presents design and
synthesis methodology of a PANDA design on 65 nm CMOS technology, consisting of a
24 x 25 cell array, reconfigurable interconnect, configuration memory and serial
programming interface. To implement AMS circuits on the PANDA platform, this paper
further proposes a CAD tool for technology mapping, placement, routing and
configuration bit-stream generation. Several representative building blocks of AMS
circuits, such as amplifiers, voltage and current references, filters, are
successfully implemented on the PANDA platform. Dynamic reconfiguration capability
of PANDA is demonstrated through input offset cancellation of an operational
amplifier using an FPGA in a closed loop. Initial measurement results of PANDA
implemented circuits demonstrate the potential of the methodology for rapid
prototyping and hardware validation of analog circuits.
Analog layout generation in the advanced CMOS design is challenging by its
increasing layout constraints and performance requirements. This situation becomes
more intricate by the growing parasitic variability and manufacturing reliability.
To facilitate the feasibility of template-based layout migration, this paper first
introduces a layout preservation, which extracts placement and routing behaviors
from an existing layout into a crossing graph via constrained Delaunay
triangulation. And later this crossing graph can be migrated into multiple layouts
with placement and routing reconnection. The proposed approach also provides a
refinement for wire to optimize the performance metrics. This approach is applied
to a variable-gain amplifier, a folded-cascode operational amplifier, and a low
dropout regulator. The experimental results demonstrate more possibility on layout
migration, such that averagely more than 75% routing of migrated layout is
generated by our approach. Additionally, it exhibits the productivity with
qualified performance on different designs.
This study included 168 and 85 mother-infant dyads from Asian and United States of
America cohorts to examine whether a genomic profile risk score for major
depressive disorder (GPRS(MDD)) moderates the association between antenatal
maternal depressive symptoms (or socio-economic status, SES) and fetal
neurodevelopment, and to identify candidate biological processes underlying such
association. Both cohorts showed a significant interaction between antenatal
maternal depressive symptoms and infant GPRS(MDD) on the right amygdala volume. The
Asian cohort also showed such interaction on the right hippocampal volume and
shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise,
a significant interaction between SES and infant GPRS(MDD) was on the right
amygdala and hippocampal volumes and shapes. After controlling for each other, the
interaction effect of antenatal maternal depressive symptoms and GPRS(MDD) was
mainly shown on the right amygdala, while the interaction effect of SES and
GPRS(MDD) was mainly shown on the right hippocampus. Bioinformatic analyses
suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and
glutamate receptor activity as common biological processes underlying the influence
of antenatal maternal depressive symptoms on fetal cortico-limbic development.
These findings suggest gene-environment interdependence in the fetal development of
brain regions implicated in cognitive-emotional function. Candidate biological
mechanisms involve a range of brain region-specific signaling pathways that
converge on common processes of synaptic development.
The amyloid-beta (A beta) peptide, the proteolytic fragment of A beta precursor
protein (APP), aggregates and forms neuritic plaques, a major hallmark of
Alzheimer's disease (AD). The limiting step in generating the A beta peptide from
APP is cleavage by the P-secretase enzyme, BACE1 Regulation of the BACE1 gene is
likely to play an important role in AD etiology and treatment. We therefore studied
the activity of a 4.1-kb F-flanking region (-3765/+364, +1 being the transcription
start site) of the BACE1 gene, both in 5'- and T-deletion series and through
Northern blotting. We show that the BACE1 promoter has regulatory activity
throughout the 4.1-kb length, both positive and negative, and that this activity
can be quantitatively modeled according to promoter sequence length, with the
specific model depending on the presence of negative regulatory elements as the 5'-
most portion of the sequence. We also examined a previously identified 141-bp
proximal fragment (+224/+364) of the BACE1 promoter and two constituent (91- and
50-bp) subfragments. We report that the 91-bp fragment (+224/+314) is the most
likely seat of neuronal expression of the BACE1 gene and that it is the portion of
the 141-bp fragment that accounts for observed DNA-protein interactions in brain
extracts. The 50-bp fragment (+315/+364), which showed significant reporter gene
activity from the empty vector, binds nuclear proteins in a cell type-specific
manner and contains the AP2 site as shown by the electrophoretic mobility shift
assay. Overall, the 141-bp fragment had no strong matches within GenBank, and the
91-bp fragment is predicted to have several potential stem-loop sites. Taken
together, BACE1 gene promoter activity is differentially regulated, and the 91-bp
fragment represents a novel promoter region for cell type-specific regulation. This
fragment might be a useful target to regulate BACE1 expression leading to A beta
production and to understand the neuropathogenesis of AD.
Objective: Emotion processing abilities might be reduced in amyotrophic lateral
sclerosis (ALS). Previous studies of emotion processing in ALS have inconsistent
results, and are limited by variations in task difficulty, modalities examined, and
participants' cognitive status. The current study used a battery of emotion
processing tasks at differing levels of difficulty and across different modalities
(facial affect and voice prosody) to assess the extent of emotion processing
deficits in nondemented ALS. Method: 33 ALS participants with intact basic
cognition and 22 healthy controls completed the abbreviated Comprehensive Affect
Testing System (CATS), which assesses simple and complex facial affect recognition,
affective prosody recognition, cross-modal face-prosody integration, and semantic
comprehension of affect. Participants also completed measures of executive
function, mood, and functional impairment. Results: ALS participants showed
impairments on complex facial affect recognition, affective prosody recognition,
and cross-modal integration. In contrast, simple facial affect recognition and
semantic comprehension of affect were intact. ALS participants did not have
significant mood symptoms, and neither mood nor functional impairment was related
to emotion processing. Performance on the cross-modal composite was related to
executive function, however, this relationship was not apparent for facial or
prosody recognition within a single modality. Conclusions: These results indicate
that people living with ALS without dementia often have subtle difficulties with
recognizing emotions in both faces and voices, even in the context of intact basic
cognition. Clinicians should be aware of the potential for these emotion processing
difficulties to be present in ALS and to affect interpersonal behavior and quality
of life.
Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of
the nervous system involving both upper and lower motor neurons. The patterns of
structural and metabolic brain alterations are still unclear. Several studies using
anatomical MRI yielded a number of discrepancies in their results, and a few PET
studies investigated the effect of ALS on cerebral glucose metabolism. The aim of
this study was threefold: to highlight the patterns of grey matter (GM) atrophy,
hypometabolism and hypermetabolism in patients with ALS, then to understand the
neurobehavioral significance of hypermetabolism and, finally, to investigate the
regional differences between the morphologic and functional changes in ALS
patients, using a specially designed voxel-based method. Thirty-seven patients with
ALS and 37 age-and sex-matched healthy individuals underwent both structural MRI
and (18)[F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for
partial volume effects. Structural and metabolic abnormalities were examined in ALS
patients compared with control subjects using two-sample t tests in statistical
parametric mapping (SPM). Then, we extracted the metabolic values of clusters
presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM
atrophy and hypometabolism patterns were directly compared with a one-paired t test
in SPM. Results: We found GM atrophy as well as hypometabolism in motor and extra
motor regions and hypermetabolism in medial temporal lobe and cerebellum. We
observed negative correlations between the metabolism of the right and left
parahippocampal gyri and episodic memory and between the metabolism of right
temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal
pole, left hippocampus and right thalamus, while hypometabolism predominated in a
single cluster in the left frontal superior medial cortex. Conclusions: Our
findings provide direct evidence of regional variations in the hierarchy and
relationships between GM atrophy and hypometabolism in ALS. Moreover, the (18)FDG-
PET investigation suggests that cerebral hypermetabolism is deleterious to
cognitive function in ALS.
This study aims to explore the potential impairment of Theory of Mind (ToM; i.e.,
the ability to represent cognitive and affective mental states to both self and
others) and the clinical, neuropsychological and Quality of Life (QoL) correlates
of these cognitive abnormalities in the early stages of amyotrophic lateral
sclerosis (ALS), a multisystem neurodegenerative disease recently recognized as a
part of the same clinical and pathological spectrum of frontotemporal lobar
degeneration. Twenty-two consecutive, cognitively intact ALS patients, and 15
healthy controls, underwent assessment of executive, verbal comprehension,
visuospatial, behavioral, and QoL measures, as well as of the ToM abilities by
Emotion Attribution Task (EAT), Advanced Test of ToM (ATT), and Eyes Task (ET). ALS
patients obtained significantly lower scores than controls on EAT and ET. No
significant difference was found between the two groups on ATT. As regard to type
of ALS onset, patients with bulbar onset performed worse than those with spinal
onset on ET. Correlation analysis revealed that EAT and ET were positively
correlated with education, memory prose, visuo-spatial performances, and "Mental
Health" scores among QoL items. Our results suggest that not only "cognitive" but
also "affective" subcomponents of ToM may be impaired in the early stages of ALS,
with significant linkage to disease onset and dysfunctions of less executively
demanding conditions, causing potential impact on patients' "Mental Health."
We consider an image motion stabilization system embedded into a space telescope
for a scanning optoelectronic observation of terrestrial targets. Developed model
of this system is presented taking into account physical hysteresis of piezoceramic
driver and a time delay at a forming of digital control. We have presented
elaborated algorithms for discrete filtering and digital control, obtained results
on analysis of the image motion velocity oscillations in the telescope focal plane,
and also methods for terrestrial and in-flight verification of the system.
The optimal biogas system design model (OBSDM) described in this paper is intended
to be used as a decision-making tool to increase awareness of the potential of
biogas technology for different applications in Sub-Saharan Africa (SSA). The
decision-making tool identifies the most suitable biodigester design based on user
defined inputs, including energy and fertiliser requirements; feedstock (type,
amount, and rate of supply); water supply; land use (area, soil type, ground water
level); climate (temperature and rainfall); construction materials available
locally; and the priorities (based on sustainability criteria) of the intended
biogas user. The output of the model provides a recommended design with estimates
of the expected costs, energy and fertiliser production, and links to contact
biodigester suppliers. In order to test the model, data from household surveys
conducted in rural regions of Kenya and Cameroon were used as inputs to the model.
An innovative fixed dome biodigester design, which uses stabilised soil blocks
instead of bricks, was identified as optimal for both Kenyan and Cameroonian rural
households. The expected performance of the optimal biogas system design from the
model output was consistent with survey data on existing biogas systems in the
region. (C) 2017 Elsevier Ltd. All rights reserved.
To create possibilities for a more sustainable wastewater management, a novel
system consisting of electrodeionization (EDI) and solid oxide fuel cells (SOFCs)
is proposed in this study. This system is integrated with anaerobic
digestion/landfills to capture energy from carbonaceous and nitrogenous pollutants.
Both EDI and SOFCs showed good performances. EDI removed 95% and 76% ammonium-
nitrogen (NH4+-N) from diluted (0.025 M) to concentrated (0.5 M) synthetic ammonium
wastewaters, respectively, accompanied by hydrogen production. SOFCs converted the
recovered fuels, biogas mixtures of methane and carbon dioxide, to electricity.
Under the optimal conditions of EDI (3.0 V applied voltage and 7.5 mm internal
electrode distance (IED), and SOFCs (750 degrees C operating temperature), the
system achieved 60% higher net energy output as compared to conventional systems.
The estimated energy benefit of this proposed system showed that the net energy
balance ratio is enhanced from 1.11 (existing system) to 1.75 (this study) for a
local Hong Kong active landfill facility with 10.0 g L-1 chemical oxygen demand
(COD) and 0.21 M NH4+-N. Additionally, an average of 80% inorganic ions (heavy
metals and nutrient elements) can be removed from the raw landfill leachate by EDI
cell. The results are successful demonstrations of the upgrades of anaerobic
processes for energy extraction from wastewater streams. (C) 2017 Elsevier Ltd. All
rights reserved.
There is a rapid growing interest in using biomass as an alternative source for
clean and sustainable energy production. In this work, a hybrid system was
developed to combine anaerobic digestion (AD) and gasification for energy recovery
from yard waste and woody biomass. The feasibility of the proposed hybrid system
was validated experimentally and numerically and the energy efficiency was
maximized by varying energy input in the drying process. The experiments were
performed in two stages. At the first stage, AD of yard waste was conducted by
mixing with anaerobic sludge. At the second stage, co-gasification was added as
post-treatment for the AD residue for syngas production. The co-gasification
experiments of AD residue and woody biomass were conducted at varying mixing ratios
and varying moisture contents of AD residue. Optimal energy efficiency was found to
be 70.8% at mixing ratio of 20 wt% AD residue with 30 wt% moisture content. Two
kinetic models were then adapted for prediction of biogas produced in AD process
and syngas produced in gasification process, respectively. Both experimental and
numerical results showed that full utilization of biomass could be realized to
produce energy through the combination of these two technologies. (C) 2017 Elsevier
Ltd. All rights reserved.
Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia,
but its efficacy in treating anal canal high-grade squamous intraepithelial lesions
(HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy
of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative
participants with HSIL occupying aehalf the anal canal circumference were treated
with hemi-circumferential anal canal RFA. Participants were assessed every 3 months
for 12 months with high-resolution anoscopy; recurrence in the treatment zone was
re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions
(range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent
HSIL within the treated hemi-circumference within 1 year. Four participants (19 %)
had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted
again at 12 months. No participants had more than two RFA treatments. KM curve-
predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI
52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year
HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %),
respectively (p = 0.008), suggesting a learning curve with the treating physician.
Multivariable analysis showed decreased recurrence in the last 14 participants (HR
0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 %
CI 1.01-2.01). No participants had device or procedure-related serious adverse
events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high
rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal
adverse events. Lesion persistence was probably related to incomplete initial
ablation.
Aims: Verrucous carcinoma (VC) is a variant of well-differentiated squamous cell
carcinoma and in the anal region is regarded as synonymous with giant condyloma
(Buschke-Lowenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical
behaviour of both lesions are controversial. Recent studies suggest that VC at
other sites is not associated with human papillomaviruses (HPV). We hypothesized
that anal VC is also not related to HPV, while BLT is a HPV-induced lesion. Methods
and results: Ten cases of VC and four cases of BLT were included. Several
techniques were used for HPV detection: in-situ hybridization for HPV6, 11, 16 and
18, six different polymerase chain reaction (PCR) protocols for detection of at
least 89 HPV types from alpha-, beta-, gamma- and mu-PV genera and in-situ
hybridization for high-risk HPV E6/E7 mRNA; p16 immunohistochemistry and
morphometric analysis were also performed. Alpha-, gamma- and mu-PVs were not found
in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression
was not present in any of the lesions. Among microscopic features, only the absence
of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from
BLT. Conclusions: Our results suggest that anal VC, similarly to VC at other sites,
is not associated with HPV infection, and must be distinguished from BLT, which is
associated with low-risk HPV. Only with well-set diagnostic criteria will it be
possible to ascertain clinical behaviour and optimal treatment for both lesions.
The objective of this work is to minimize testing cost of analog and RF circuits
for which complete specification tests are available. We use an integer linear
program (ILP) to eliminate as many tests as possible without exceeding the required
defect level. The method leverages correlation among specifications, thereby
avoiding the tests for specifications that are sufficiently covered by tests for
other specifications. First, Monte Carlo simulation determines probabilities for
each test covering all other specifications it was not originally intended for.
These probabilities and the given defect level then define an ILP model for
eliminating unnecessary tests. An hypothetical example illustration of ten
specifications demonstrates that depending on the defect level requirement up to
half of the tests may be eliminated. Monte Carlo simulation using spice for
probabilistic characterization of tests versus specifications followed by ILP
optimization for two commercially available integrated circuits, an operational
amplifier and a radio frequency power controller (RFPC), are presented as evidence
of effectiveness of the technique.
The Water Cherenkov Detector Array (WCDA) is one of the core detectors in the Large
High Altitude Air Shower Observatory (LHAASO), and it consists of 3600
photomultiplier tubes (PMTs). Both high resolution time and charge measurement are
required over a large dynamic range from 1 photoelectron (P.E.) to 4000 P.E. The
prototype of an analogue front-end Application Specific Integrated Circuit (ASIC)
fabricated using Global Foundry 0.35 mu m CMOS technology is designed to read out
the PMT signal in the WCDA. This ASIC employs leading edge discrimination and an
(RC)4 shaping structure. Combined with the following Time-to-Digital Converter
(TDC) and Analog-to-Digital Converter (ADC), both the arrival time and charge of
the PMT signal can be measured. Initial test results indicate that time resolution
is better than 350 ps and charge resolution is better than 10% at 1 P.E. and better
than 1% with large input signals (300 P.E. to 4000 P.E.). Besides, this ASIC has a
good channel-to-channel isolation of more than 84 dB and the temperature dependency
of charge measurement is less than 5% in the range 0-50 degrees C
A low pass (LP) and complex band pass (CBP) reconfigurable analog baseband circuit
for software-defined radio (SDR) receivers is presented. It achieves 1-15 MHz LP
bandwidth, 2-8 MHz CBP bandwidth and 0-36 dB gain range with 1 dB step. Nulling-
resistor Miller feed-forward (NRMFF) differential-mode compensation, passive left
half-plane (LHP) zero common-mode compensation and Quasi-Floating Gate (QFG)
technique are proposed to improve the high frequency performance and driving
capability of the embedded fully differential operational amplifier (Op-Amp). The
analog baseband circuit has been implemented in 65 nm CMOS. It achieves 15.2 dB
m/27.1 dB m IB/OB-IIP3, -2 dB m IP1dB and 71 dB m IIP2 while consuming 3.6-9.1 mW
from a 1.2 V power supply and 0.75 mm(2) chip area. (C) 2014 Elsevier Ltd. All
rights reserved.
This paper presents the results of study on utilization of Z-copy Voltage
Controlled Current Follower Differential Input Transconductance Amplifier (ZC-
VCCFDITA) active element in a single purpose filtering structure. This active
element has three voltage-controlled parameters (intrinsic resistance of current
input, voltage gain and transconductance of output section) and is very useful for
design of oscillators, signal generators and frequency filters with just one active
element. In this paper, the important parameters of possible behavioural model of
ZC-VCCFDITA are shown and a particular solution of the controllable band-pass
filter is presented. Theoretical, calculated, simulated and moreover also measured
results are mutually compared.
Automation of analog integrated circuit (IC) design process is very important
because of the optimization contradictions. In this study, benefits of multi-
objective evolutionary algorithms are presented on two stage operational amplifier
design using Harmony Search Algorithm (HSA) and Non-dominated Sorting Genetic
Algorithm (NSGA-II). HSA is a new kind of multi-objective evolutionary algorithm
which was inspired from the musicians those are looking for the best combination of
musical sounds of different instruments that produces most pleasing sound. NSGA-II
is an advanced version of genetic algorithm. It combines both current parents and
their child population to select new parents. These kinds of design automation
tools are required for analog circuit design because there are several
contradictions in the design. In this work, transistor sizes which effects all
constraints indirectly were automatically synthesized by HSA an NSGA-II.
Noise optimization is a challenging problem for nanoscale metal-oxide-silicon
field-effect transistor circuits. This brief presents a technique that uses
transconductance-to-drain current (g(m)/I-D)-dependent transistor-noise parameters
to explore the design space and to evaluate tradeoff decisions. An expression for
the corner frequency of the folded-cascode amplifier is derived. The design process
demonstrated in this brief using the folded-cascode amplifier is applicable to a
wide class of amplifier circuits.
This paper reviews the importance of device-circuit interactions (DCI) and its
consideration when designing thin film transistor circuits and systems. We examine
temperature-and process-induced variations and propose a way to evaluate the
maximum achievable intrinsic performance of the TFT. This is aimed at determining
when DCI becomes crucial for a specific application. Compensation methods are then
reviewed to show examples of how DCI is considered in the design of AMOLED
displays. Other designs such as analog front-end and image sensors are also
discussed, where alternate circuits should be designed to overcome the limitations
of the intrinsic device properties.
This paper presents analog building blocks that find potential applications in
display panels. A buffer (source-follower), subtractor, adder, and high-gain
amplifier, employing only n-type enhancement amorphous gallium-indium-zinc-oxide
thin-film transistors (a-GIZO TFTs), were designed, simulated, fabricated, and
characterized. Circuit simulations were carried out using a neural model developed
in-house from the measured characteristics of the transistors. The adder-subtractor
circuit presents a power consumption of 0.26 mW, and the amplifier presents a gain
of 34 dB and a power consumption of 0.576 mW, with a load of 10 M Omega//16 pF. To
the authors' knowledge, this is the highest gain reported so far for a single-stage
amplifier with a-GIZO TFT technology.
This paper presents a new environment for characterizing foundry CMOS device models
and analog basic blocks. This environment can also be used to design some analog
basic building blocks. It designs analog circuits by dividing them into a set of
basic building blocks connected together, where each block is optimized separately
considering other blocks' loading and/or boundary conditions. It can run over
different technologies using foundry models and simulation measurements without
approximations, hand calculations or simplified equations. The efficiency of the
complete flow is evaluated through designing a single-ended two-stage operational
amplifier over 180nm, 130nm, 90nm, 65nm and 40nm technologies.
Circuit parameters and configuration are very important when studying the
synergistic effects total dose/SET. We explore a method combining dynamic parameter
measurement and spectrum analysis which lead to a better understanding of this
complex phenomenon. In this paper symbolic circuit analysis is used to obtain the
relationship between input, output and noise injection due to photocurrent
generation in the form of a rational function using symbolic variables in the
complex frequency domain. This simulation technique was able to predict the impact
of (i) total dose level, (ii) circuit parameters, and (iii) the injected energy on
the ASET shapes. Basic mechanisms as field collapse and collection efficiency were
also predicted and assessed.
This paper presents an optimization-based design methodology for fully differential
amplifiers (FDAs) including the effects of real common-mode feedback (CMFB)
circuits as constraints in the design flow. The sizing procedure is performed
separately for the main amplifier and for the CMFB circuit, reducing the number of
free variables and exploring the design space in a more efficient way. Also, this
methodology can be employed to design single and two-stages FDAs whereas a second
pole compensation scheme is necessary. In order to validate the proposed
methodology, a two-stage fully differential amplifier with a no capacitor feed-
forward (NCFF) compensation technique was designed in 0.13 mu m CMOS technology
with a 1.2 V power supply. The presented results also include a pole-zero pair
mismatch analysis and proposes a solution in order to compensate the generated
pole-zero doublet that might affect the performance of the amplifier. We can show
that this approach reduces the overall static power consumption while satisfying
the design specifications.
Four parts of opamp OP1177ARZ manufactured by Analog Devices have been tested. The
chips have been compared visually and with specialized software. Forms of
ionization response in three checkpoints have been registered, and maps of response
amplitudes on the crystal surface have been constructed. It has been fixed, that
crystals samples are various in spite of identical crystals marking. So TID
behavior of various samples has been observed.
A systematic method is proposed to approach complete fault coverage for
catastrophic faults in analog circuits. In the proposed method, a fault propagation
graph is first created from the circuit netlist. Standard graph theory techniques
are then employed to identify a minimal set of observation points (MOP) such that,
by monitoring these points, complete fault coverage can be achieved, i.e., all
potential catastrophic faults of the circuit can be detected theoretically. The
developed method is valuable because of the increasingly critical quality
requirements for modern IC applications and the lack of existing methods that can
achieve sub-ppm test escapes in the state-of-the-art. A widely used benchmark
circuit, a CMOS operational amplifier, is utilized to demonstrate and validate the
method. Simulation results show that all catastrophic faults can be detected by
monitoring the identified MOP.
An analog front-end (AFE) for a multifunction environmental sensor is proposed. The
AFE is designed to be able to sense 1 mu V, 1 fC, and 1 pA level signals in a low-
frequency band around DC, and consists of an instrumentation amplifier (IA), a
charge amplifier (CA), and a continuous time delta-sigma (CT-Delta Sigma) ADC. To
reduce the low-frequency noise of operational amplifier (OPAMP) which is used for
signal path, this paper proposes a weak-inversion biasing technique. The designed
IA achieved 26 nVrms input-referred noise (IRN) in the band of 0.1-10 Hz with 0.22
mm(2) die area. The designed CA achieved 25 aCrms IRN in charge sensing mode and 19
fArms IRN in current sensing mode in the band of 0.01-1 Hz, respectively, and
occupies 0.12 mm(2) die area. The AFE has been fabricated in a 0.18 mu m CMOS
process with 4.5 mm(2) die area. The current consumption at 2.56 kHz output data
rate (ODR) is 2.5 mA, reducing to 2 mu A at 0.01 Hz ODR.
This paper presents an accurate design approach for two-stage CMOS operational
amplifiers developed based on the usual design procedure. It eliminates the errors
existed in design results by employing the accurate MOS model and carrying out the
design procedure iteratively. The specifications of the amplifier designed by this
approach match exactly with the user specified values. A design example in 0.18 mu
m CMOS technology is given to illustrate the effectiveness of the proposed design
approach.
Analog ICs are widely used in communication, sense and power systems of spacecraft.
They are produced with variety of technologies (CMOS, BiCMOS, functional options).
This paper provides TID degradation analysis for most common analog ICs -
operational amplifiers, voltage comparators and linear stabilizers. General trends
in radiation behavior and recommendations for analog IC's radiation testing are
presented.
The article presents functional schemes of two IPmodules included into a new (2016)
radiation-hardened structured arrays (SA) MH2XA010. The microcircuits of the main
modifications of op amps (OAs) with current negative feedback (CNF) can be realized
on the base of SA (due to the interconnection wiring of elements). The terminal
parameters of op amps are considered, the practical recommendations for choosing
the steady-state behaviors, the active and passive elements of SA, providing the
peak values of the slew rate and the upper frequency limit of op amp in a wide
range of changes of transfer ratios are given. The properties of a new subclass of
op amps based on SA MH2XA010 -circuits with the so called generalized current
negative feedback, combining the properties of classical op amps with voltage
feedback and op amps with CNF are examined.
The article suggests a new method of the errors evaluation from the several common-
mode signals in the differential difference operational amplifiers (DDAs), based on
the theory of autonomous multiport circuit. These errors of DDA in its main
connection circuits can be described by feeding a special current autonomous
parameter to the classical equivalent circuit of DDA. This parameter is connected
with the highimpedance node of DDA and depends on the level of the common-mode
components in the inputs of some input differential stages and also on the
parameters spread of the elements. The paper shows that in DDAs the common-mode
rejection ratio (CMRR) significantly worsens in comparison with classical op-amp.
The parametric and circuitry methods of CMRR increase in the DDAs based on the
inherent compensation of parasitic impedances are considered.
An architectural performance comparison of bandgap voltage reference variants,
designed in a 0.18 mu m CMOS process, is performed with respect to single event
transients. These are commonly induced in microelectronics in the space radiation
environment. Heavy ion tests (Silicon, Krypton, Xenon) are used to explore the
analog single-event transients and have revealed pulse quenching mechanisms in
analogue circuits. The different topologies are compared, in terms of cross-
section, pulse duration and pulse amplitude. The measured results, and the
explanations behind the findings, reveal important guidelines for designing analog
integrated circuits, which are intended for space applications. The paper includes
an analysis on how pulse quenching occurs within the indispensable current mirror,
which is used in every analog circuit.
The paper presents a high-voltage integrated-circuit driver capable of producing
analog voltages up to 300 V, using Dalsa's 0.8-mu m HV CMOS/DMOS process, suitable
for MEMS and medical systems. The IC driver includes a HV operational amplifier
(op-amp) with a class-B output stage, and HV analog switches with improved off-
isolation performance. In contrast to previous frequency compensation schemes,
where only one dominant pole occurs below the unity-gain bandwidth, the HV op-amp
employs a novel frequency compensation topology with three poles and two zeros
located within the unity-gain bandwidth, and is capable of driving large capacitive
loads from 100 pF to 10 nF. Theoretical analysis of off-isolation of the HV analog
switches is also reported and confirms the improvement in off-isolation
performance.
Functional errors in analog portion of mixed signal circuits become more severe and
improvements in verification methods are increasingly important. Current
verification methods fall into two categories, simulation-based verification and
formal verification (Barke et al. [1]), focusing on verifying analog circuit
function/performance, This paper proposes a novel approach verifying analog circuit
design using causal reasoning. Causal reasoning is the inductive reasoning process
to create a new design. The flow begins with mining the causal reasoning steps
(design plan) that produced the circuit, including starting ideas, design step
sequence, and their justifications (Jiao et al., 2015 [2]).. Then, topological
features corresponding to the starting ideas and design step sequence are verified
individually by replacing the related devices with ideal behavior model.
Performance is evaluated through Cadence Spectre simulation. Comparison with new
circuit performance reveals incorrect functional issues and/or performance
potentials for improvement. They are negative causes of certain starting ideas or
design steps, which might have been omitted during the design process. The paper
discusses three operational amplifier designs realized in 0.2-mu m CMOS technology
to illustrate the verification approach. (C) 2016 Elsevier B.V. All rights
reserved.
This paper presents a new family of Class-AB operational transconductance amplifier
(OTA) circuits based on single-stage topologies with non-linear current amplifiers.
The proposed variable-mirror amplifier (VMA) architecture is mainly characterized
by generating all Class-AB current in the output transistors only, by exhibiting
very low sensitivity to both technology and temperature deviations, and by avoiding
the need for any internal frequency-compensation mechanism. Hence, this family of
OTAs is well-suited for low-power switched-capacitor circuits and specifically
optimized for switched-OpAmp fast on-off operation and multi-decade load-
capacitance specifications. Analytical expressions valid in all regions of
operation are presented to minimize VMA settling time in discrete-time circuits.
Also, a complete OTA design example integrated in 0.18 mu m 1P6M MiM 1.8 V CMOS
technology is supplied with detailed simulation and experimental results. Compared
to resistor-free state-of-art Class-AB OpAmp and OTA literature, the proposed
architecture returns the highest measured figure-of-merit value.
This paper presents a digital testing strategy for characterizing an analog circuit
block. The operational amplifier (op amp) is evaluated due to its wide application
in electronic circuits and systems. In the proposed strategy, the op amp device
under test (DUT) is configured to respond to a testing pulse, and the associated
output is digitized by a digital buffer to reduce the high cost of generating a
high-frequency clock. The testing procedure is divided into two modes to estimate
the reference slew rate and then to evaluate the practical slew rate to moderate
the difficulty of designing a digital buffer that has a highly precise delay time.
The testing concept, accuracy, time, and hardware are also comprehensively
investigated to describe the proposed testing strategy. The digital compatibility,
the simplicity, and the testing capability of the high-performance op amp are the
main advantages of the proposed testing strategy. Easily available discrete devices
were experimentally employed to verify the functionality of the proposed testing
strategy. An integrated application to test the op amp DUT embedded in a second-
order Sallen-Key low-pass filter was simulated with the HSPICE tool to verify the
testing feasibility and the effectiveness of the proposed strategy.
We report a pulse width modulation (PWM) buck converter that is able to achieve a
power conversion efficiency (PCE) of >80% in light loads (80% efficiency for a wide
range of load conditions from 45 mu A to 4.1 mA, while generating 1 V output from
2.5-3.3 V supply. The converter occupies 0.375 mm(2) in 0.18 mu m CMOS processes
and requires two external components: 1.2 mu F capacitor and 6.8 mu H inductor.
ADC/DAC radiation failures are mainly due to radiation-induced degradation of
precision parameters of the transfer characteristic such as gain, zero offset,
full-scale voltage, integral and differential non-linearity, conversion error.
ADC/DAC radiation failure specifics is that even a slight deviation of electrical
parameter of internal elements (comparator threshold, internal reference voltage,
switch leakage, operational amplifier gain, etc.) often leads to significant
degradation of ADC/DAC accuracy. ADC/DAC radiation test procedure and facilities
are developed and test results are introduced.
The work proposes an improved technique to design a low power 8-bit asynchronous
successive approximation register (ASAR), an analog-to-digital converter (ADC). The
proposed ASAR ADC consists of a comparator, ASAR (digital control logic block), and
a capacitivedigital-to-analog convertor (C-DAC). The comparator is a preamplier-
based improved positive feedback latch circuit which has a built-in sample and hold
(S/H) functionality and saves an enormous amount of power. The implemented digital
control logic block performing the successive approximation (SA) algorithm is
totally unrestrained of the external clock pulse. The outputs from the comparator
are given to a XOR logic whose outputs serve as an internally generated clock
(ready signal) to trigger the digital control block. Hence, an external clock is
not required to initiate the digital control block making its operation
asynchronous. By implementing this, the ADC can circumvent the usage of an
oversampled clock and can operate on a single low-speed sample clock. This, in
turn, saves power and it cuts down the required resilience in sampling rates. The
proposed ADC has been designed and simulated using UMC-0.18 mu m CMOS technology
which dissipates 32.18 mu W power when operated on a single 1V power supply and
achieves complete 8-bit conversion in 1.09 mu s. The relative accuracy of capacitor
ratio, aperture jitter and FOM are 0.39%, 1.2 ns and 125 fJ/conversion-step,
respectively.
Due to technology scaling, the design of the conventional-type analog-to-digital
converter (ADC), which uses an operational amplifier as one of its building blocks,
becomes more difficult. In this brief, new techniques to design time-based ADC
(TADC), which uses a voltage-controlled oscillator (VCO), are proposed. The VCO is
followed by a time-to-digital converter, implemented in a Sigma Delta architecture.
A novel architecture, using a multibit, nonlinear internal quantizer and a feedback
digital-to-time converter, implemented by using phase interpolation, is employed to
compensate the nonlinear transfer curve of the VCO. Dynamic element matching and
calibration are used to improve the robustness of the TADC against mismatch. The
TADC uses an implicit sample and hold that relaxes the bounds on input frequency. A
TADC implemented in 0.13-mu m CMOS technology achieves a measured signal-to-noise +
distortion ratio of 60.2 dB and a dynamic range of 11 b for a bandwidth of 2 MHz.
This paper presents a 14.9-bit 3.57-MS/s algorithmic ADC that uses iterative gain
enhancement, a technique that uses multiple clock phases to increase the effective
op-amp gain in a switched-capacitor circuit. Using an op-amp that gives only 30-dB
loop gain in a feedback circuit without gain enhancement, application of the
iterative gain enhancement technique boosts the loop gain to 81 dB. The algorithmic
ADC uses a capacitor sharing and scaling technique, which saves power and reduces
errors. The ADC has an active area of 0.75 mm2 in 0.25-mu m CMOS and dissipates
16.2 mW. Iterative gain enhancement increases the SNDR from 44.6 dB to 78.5 dB and
the SFDR from 45.9 dB to 96.2 dB. Reducing the number of gain-enhancement
iterations for the LSBs increases the conversion rate from 3.57 MS/s to 4.65 MS/s
with only minor performance degradation.
A wide-bandwidth (BW) power-efficient continuoustime Sigma Delta modulator (CT
Sigma Delta M) is presented. The modulator introduces a third-order filter
implemented with a lossless integrator and a multiple-feedback single-amplifier
biquadratic filter with embedded loop stability compensation. An active summing
block is implemented by employing a common-gate current buffer followed by a
transimpedance amplifier. This combination relaxes the specification requirements
of the operational amplifier by making its required BW independent of the closed-
loop gain. The proposed technique achieves optimum BW with reduced power
consumption, making it functional for over gigahertz operation. Fabricated in a
standard 40-nm CMOS technology, and clocked at 3.2 GHz, the CT Sigma Delta M
achieves a signal-to-noiseand-distortion ratio of 65.5 dB over 75-MHz BWwhile
consuming 22.8 mW of power. The obtained Walden's figure of merits is 98 fJ/conv-
step.
A 400-800 MHz spectrum sensing system is designed and implemented using 0.18-mu m
CMOS technology for cognitive radios in the UHF TV band. Based on envelope
detection, the system employs a down converter, a digitally controlled oscillator,
a low-pass filer (LPF), a rectifier, a comparator, and a digital control unit to
realize spectrum sensing with 10-bit frequency representation. With variable-gain
function of the LPF, signal strength can be measured and presented with a 5-bit
signal strength index.
This study presents a self-testing platform with a foreground digital calibration
technique for successive approximation register (SAR) analog-to-digital converters
(ADCs). A high-accuracy digital-to-analog converter (DAC) with digital control is
used for the proposed self-testing platform to generate the sinusoidal test signal.
This signal is then implemented using an Arduino board, and the clock signal is
generated to test the ADCs. In addition, fast Fourier transform and recursive
discrete Fourier transform (RDFT) processors are adopted for dynamic performance
evaluation and calibration of the ADCs. The third harmonic distortion caused by the
non-linearity of the track-and-hold circuit, the mismatch of the DAC capacitor
array, and the direct current (DC) offset of the comparator can be calculated using
the processors to improve the ADC performance. The advantages of the proposed
platform include its low cost, high integration, and no need for an extra analogy
compensation circuit to deal with calibration. In this work a 12 bit SAR ADC and an
RDFT processor are used in the Taiwan Semiconductor Manufacturing Co., Ltd. (TSMC)
0.18 mu m standard complementary metal-oxide-semiconductor (CMOS) process with a
sampling rate of 18.75 kS/s to validate the proposed method. The measurement
results show that the signal-to-noise and distortion ratio is 55.07 dB before
calibration and 61.35 dB after calibration.
This paper describes a versatile composite amplifier in which a current feedback
amplifier (CFA) drives an operational amplifier (OPA). In the conventional OPA-CFA
composite amplifier, an OPA drives a CFA resulting in a composite structure that
combines the DC input stability of the OPA and the high speed capability of the
CFA. The proposed composite configuration combines different features of the CFA
and OPA, specifically the constant bandwidth property of the CFA and the high power
and high current output capacity of the OPA. The new circuit is easily implemented
in the standard inverting and non-inverting configurations using commercially
available devices, and the accuracy and constant bandwidth features were
experimentally verified. Local feedback around the associated CFA ensures that the
proposed composite amplifier possesses a higher level of bandwidth constancy than a
single CFA.
The paper presents the structure and the principle of operation of the improved'
Howland current pumps (or voltage-controlled current sources (VCCSs) for a grounded
load). In particular, under review is the VCCS employing power operational
amplifier (op amp) and the VCCS using low power op amp and an additional power
transistor, extending working dynamic range. On the basis of analysis of the
operational principle, the equations for transfer functions of both circuits and
formulas for the related dynamic electrical parameters are obtained. Moreover,
using these formulas, a design procedure is developed, and recommendations for
simulation modelling are given. The efficiency of the proposed procedure is
verified by simulation modelling and experimental testing of sample electronic
circuits of VCCSs. Copyright (c) 2013 John Wiley & Sons, Ltd.
Analogical reasoning is an important mechanism for social cognition in typically
developing children, and recent evidence suggests that some forms of analogical
reasoning may be preserved in autism spectrum disorder. An unanswered question is
whether children with autism spectrum disorder can apply analogical reasoning to
social information. In all, 92 children with autism spectrum disorder completed a
social content analogical reasoning task presented via photographs of real-world
social interactions. Autism spectrum disorder participants exhibited performance
that was well above chance and was not significantly worse than age- and
intelligence quotient-matched typically developing children. Investigating the
relationship of social content analogical reasoning performance to age in this
cross-sectional dataset indicated similar developmental trajectories in the autism
spectrum disorder and typically developing children groups. These findings provide
new support for intact analogical reasoning in autism spectrum disorder and have
theoretical implications for analogy as a metacognitive skill that may be at least
partially dissociable from general deficits in processing social content. As an
initial study of social analogical reasoning in children with autism spectrum
disorder, this study focused on a basic research question with limited ecological
validity. Evidence that children with autism spectrum disorder can apply analogical
reasoning ability to social content may have long-range applied implications for
exploring how this capacity might be channeled to improve social cognition in daily
life.
The paper aim draws together two ideas that have figured in different strands of
discussion in business ethics: the ideas of intuition and of reflection. They are
considered in company with the third, complementary, idea of analysis. It is argued
that the interplay amongst these is very important in business ethics. The
relationship amongst the three ideas can be understood by reference to parts of
modern cognitive psychology, including dual-process theory and the Social
Intuitionist Model. Intuition can be misleading when based on fast and frugal
heuristics, and reasoning needs social exchange if it is to support moral judgment
effectively, but in the complex institutional environment of business, reflection
and analysis can underpin social communication and feedback to develop sound
intuition. Reflection and analysis are both more deliberate, systematic judgment
processes than intuition, but are distinguished by the fact that reflection
embraces hypothetical thinking and imagination, while analysis is careful, step-by-
step reasoning. Examples of business ethics problems illustrate the need for both
of these processes, and also suggest how they themselves can be enhanced in the
same social exchange process that underpins the development of good intuition.
In this paper the results of layout design and circuit-topological computer
simulation of some elements of analytical microsytem-on-chip with the "silicon-on-
insulator" (SOI)-structures are presented. These elements were: an input cascade, a
basic element of operational amplifier and a ring oscillator based on standard bulk
CMOS technology and CMOS technology with the SOI-structures. Also the polysilicon-
on-insulator resistive elements were studied in the wide temperature range. Such
elements can be used as regular elements matrix for analog and digital signal
processing in the integrated circuits and initial processing of analytical
information microsystem-on-chip or as sensitive elements of the intellectual
sensors of microsystemon-chip.
During development of adenovirus-based vaccines, samples have to be analyzed in
order to either monitor the production process or control the quality and safety of
the product. An important quality attribute is the total concentration of intact
adenoviruses, which currently is determined by quantitative polymerase chain
reaction (qPCR) or anion exchange-HPLC. Capillary Electrophoresis (CE) was
evaluated as alternative to the current methods with the aim to have one single
method that allows reliable and fast quantification of adenovirus particles
throughout the full process. Intact adenoviruses samples from downstream processing
and upstream processing were analyzed directly by CE with UV-detection at 214 nm.
Only the samples with high amounts of DNA required a simple sample pretreatment by
benzonase. Adenovirus particles were separated from matrix components such as cell
debris, residual cell DNA, and/or proteins on a PVA-coated capillary using a BGE
consisting of 125 mM Tris, 338 mM tricine and 0.2% v/v polysorbate-20 at pH 7.7.
Full factorial design of experiments was used for method optimization as part of
the analytical quality by design (AQbD) method development approach. The method was
validated for the quantification of adenoviruses on five representative samples
from the manufacturing process in the range of 0.5 x10(11)-1.5 x10(11) adenovirus
particles per ml (similar to 80 to 250 pmo1/1). The CE method showed intermediate
precision of 7.8% RSD on concentration and an accuracy (spiked recovery) of 95-
110%. CE proved highly useful for process development support and is being
implemented for in-process control testing for adenovirus vaccine manufacturing.
The anaerobic ammonium oxidation (anammox) process has been recognized as a
promising sewage treatment approach. Considering the susceptibility, it is
meaningful to study the behaviors of anammox bacteria under the unfavorable
conditions. Here, we found that anammox bacteria more probably tended to
aggregation by the regulation of c-di-GMP against the unfavorable environmental
stresses (low temperature, aerobic condition and low pH). Further using multiple
protein sequence alignment, we systematically examined the functionality of
thirteen genes encoding putative c-di-GMP metabolic enzymes in anammox organism
Candidatus Jettenia caeni, revealing most of the predicted enzymes were predicted
to be active. Particularly, ectopic expression of jcaA, a gene encoding a protein
with both GGDEF domain and EAL domain, suggested that it encoded a functional
enzyme capable of both synthesizing and degrading c-di-GMP, which was clearly
confirmed by in vitro enzymatic assays and reverse transcription polymerase chain
reaction (RT-PCR). Furthermore, the catalytic mechanism was simulated by the means
of three-dimensional homology modeling and molecular docking. The identification of
cdi-GMP turnover and its role in granulation for anammox organism provides a new
perspective for regulation of its aggregation capability and further promotion of
anammox performance in the application of wastewater treatment process. (C) 2017
Elsevier Ltd. All rights reserved.
Henoch-Schonlein purpura (HSP) is a systemic vasculitis mediated by autologous
immune complex. Animal models of HSP are scarce. Here, we describe the
characteristics of HSP rabbit model in the acute and recovery phase. First, we
constructed the HSP rabbit models, and then assessed immunologic indicators of
models by enzyme-linked immunosorbent assay and immunoturbidimetry.
Histomorphological characteristics were analyzed by haematoxylin-eosin,
immunofluorescence and special staining. In the acute stage (24 h) after antigen
challenge, the model group rabbits featured skin ecchymosis and abnormal laboratory
examination results. Three weeks following the allergic reaction, purple spots
improved markedly, and edema and blood seeping decreased, but obvious inflammation
was present in the skin, kidneys, joints, gastrointestinal, lung and liver.
Serological results of CD4, CD/CD8, IL-2, IL-4, and TNF-alpha, IgA, IgG, TropI, Alb
and T were still abnormal. IgA and C3 expressed in skin and kidney and eosinophils
expressed in skin and lungs were increased. The rabbit model can mimic human HSP
lesions in symptoms, pathology, and immunology and may provide valuable insight
into the pathogenesis of HSP and serve as a tool for future therapeutic development
targeting HSP.
Anaphylaxis is an increasingly prevalent life-threatening allergic condition that
requires people with anaphylaxis and their caregivers to be trained in the
avoidance of allergen triggers and in the administration of adrenaline
autoinjectors. The prompt and correct administration of autoinjectors in the event
of an anaphylactic reaction is a significant challenge in the management of
anaphylaxis. Unfortunately, many people do not know how to use autoinjectors and
either fail to use them or fail to use them correctly. This is due in part to
deficiencies in training and also to the lack of a system encouraging continuous
practice with feedback. Assistive smartphone healthcare technologies have
demonstrated potential to support the management of chronic conditions such as
diabetes and cardiovascular disease, but there have been deficiencies in their
evaluation and there has been a lack of application to anaphylaxis. This paper
describes AllergiSense, a smartphone app and sensing system for anaphylaxis
management, and presents the results of a randomized, controlled, prepost
evaluation of AllergiSense injection training and feedback tools-with healthy
participants. Participants whose training was supplemented with AllergiSense
injection feedback achieved significantly better practiced injections with 90.5%
performing correct injections compared to only 28.6% in the paper-only control
group. In addition, the results provide insights into possible self-efficacy
failings in traditional training and the benefits of embedding self-efficacy theory
into the technology design process.
Background The mechanisms involved in the amplification of the mast cell response
during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the
critical involvement of neutrophils. These innate immune cells are highly abundant
in peripheral blood and can be rapidly activated to trigger both local and systemic
inflammation. Objective To investigate neutrophil activation in peripheral blood
during acute human anaphylaxis. Methods Patients presenting to the emergency
department with anaphylaxis underwent blood sampling upon enrolment and at up to
three subsequent time-points. Traditional anaphylaxis biomarkers, histamine and
mast cell tryptase, were measured by ELISA and ImmunoCAP, respectively. Plasma
myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L
concentrations by cytometric bead array, and both compared to healthy controls.
Results In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine
positive, and 47 (70%) were mast cell tryptase positive. At enrolment,
myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4,
10.5) fold higher in moderate and severe patients, respectively, compared with
healthy controls, and remained stable over the first 5 h following symptom onset.
At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower
in moderate and severe patients, respectively, than healthy controls, and was
stable over the first 5 h. There were no associations between myeloperoxidase or
soluble CD62L concentrations and either histamine or mast cell tryptase
concentrations. Conclusions and Clinical Relevance These results provide compelling
evidence for the involvement of neutrophils during acute human anaphylaxis,
suggesting they are activated early in the reaction, regardless of mast cell
activation. This important finding increases our understanding of the basic
mechanisms of anaphylaxis, a necessary precursor to improving treatment and
prevention.
BACKGROUND: Anaphylaxis diagnostic criteria were proposed at the Second Symposium
on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive
and 82% specific when retrospectively validated. OBJECTIVE: To prospectively
evaluate the diagnostic accuracy of the National Institute of Allergy and
Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for
diagnosis of anaphylaxis in the emergency department (ED). METHODS: We conducted a
prospective observational study of patients seen in our institution's ED from April
2010 to March 2013. Patients seeking care for an allergic reaction and possible
anaphylaxis were enrolled. Patients and providers completed questionnaires
regarding onset, trigger, and signs and symptoms. Records were reviewed
independently and blindly by 2 board-certified allergist-immunologists, and their
final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard.
Two-by-two tables were built, and test characteristics were calculated. RESULTS:
Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for
anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%),
of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement
between allergist-immunologists was substantial (k = 0.7). Test characteristics
(95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-
98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-
73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio,
3.26; and negative likelihood ratio, 0.07. CONCLUSIONS: Prospectively, the
NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower
specificity (71%) than on retrospective assessment. These criteria are likely to be
useful for the diagnosis of anaphylaxis in the ED. (C) 2016 American Academy of
Allergy, Asthma & Immunology
Background: High serum basal tryptase (sBT) levels have been identified as a risk
factor for both venom-and food-induced severe allergic reactions. The aim of this
study was to compare sBT levels in children with different severity of actual drug
hypersensitivity reactions (DHRs) with those of age-and sex-matched controls
without any history of DHRs. Method: Patients between 0 and 18 years of age with a
history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake
were included. Following ENDA (European Network for Drug Allergy) inquiries,
patients were evaluated with skin and/or provocation tests to define the actual
drug-hypersensitive patients. Serum BT levels were determined for both patients and
controls. Results: Of 345 children, 106 patients (30.7%) [(58.5% male), median age
(interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive.
Ninety-eight controls were also included. The sBT levels of drug-hypersensitive
patients with and without anaphylaxis and the control group were similar [2.6 (2.0-
3.6) lg/l vs. 2.8 (1.6-4.3) lg/l vs. 2.6 (1.8-3.6) lg/l, respectively, (p >0.05)].
The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) lg/l,
mild anaphylaxis 3.0 (1.9-4.9) lg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-
3.6) lg/l were also comparable (p >0.05). The onset of DHRs [those occurring in 1 h
(n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin
tests with the culprit drug, or the classification of the patients according to
different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did
not correlate with sBT levels. Conclusion: The sBT levels in children with actual
drug hypersensitivity would not be a risk factor for severe systemic reactions on
the contrary to children with allergic reactions to food or insect venom.
BACKGROUND: Anaphylaxis is a potentially life-threatening systemic allergic
reaction. Studies suggest that the incidence of anaphylaxis is increasing; however,
recent trends in emergency department (ED) visits for anaphylaxis in the United
States have not been studied. OBJECTIVE: To examine trends in the incidence and
rates of anaphylaxis-related ED visits from 2005 through 2014. METHODS: We
retrospectively analyzed data from a national administrative claims database
including commercially insured and Medicare Advantage patients. We identified all
ED visits for anaphylaxis and calculated rates as number of anaphylaxis-related ED
visits per 100,000 enrollees. Rates were compared over time and by age and trigger.
RESULTS: During the 10-year time period, 56,212 ED visits for anaphylaxis were
identified. The median (interquartile range) age was 36 (17-52 years) years, and
58% were female. Most cases (57%) were due to unspecified triggers, 27% were
associated with food, 12% were medication related, and 4% were due to insect venom.
The overall rate of anaphylaxis per 100,000 enrollees increased by 101%, from 14.2
in 2005 to 28.6 in 2014 (P<.001). Rates of ED visits for anaphylaxis increased in
all age groups, but the greatest increase was in children aged 5 to 17 years (196%
increase; P<.001). The rate of food-related anaphylaxis increased by 124% (P<.001),
and the rate of medication-related anaphylaxis increased by 212% (P<.001).
CONCLUSIONS: ED visits for anaphylaxis increased between 2005 and 2014. Increases
in ED visits were greatest among children. (C) 2016 American Academy of Allergy,
Asthma & Immunology
BACKGROUND: The prescribing pattern of epinephrine over time is an indicator of the
secular trend of anaphylaxis. However, it is not well known in a population level
in the United States. OBJECTIVE: To evaluate the trend of prescriptions for
epinephrine autoinjectors in Olmsted County, Minn, residents. METHODS: Outpatient
prescriptions for epinephrine were identified among residents of Olmsted County,
Minn, between January 1, 2004, and December 31, 2010. We used the first
prescription per patient per year, and the first prescription per patient during
the study period to calculate incidence rates. Incidence rates per 100,000 person-
years were calculated using patients prescribed epinephrine per year as the
numerator and age-and sex-specific counts of the population of Olmsted County as
the denominator. The relationships of age group, sex, and year of prescription with
incidence rates were assessed by fitting Poisson regression models using the SAS
procedure GENMOD. RESULTS: The overall incidence rate of epinephrine autoinjector
prescriptions during the study period was 757 per 100,000 person-years (95%
confidence interval: 740-774). The prescription rates per patient per year
increased over time, with an annual rate of increase of 8% (P < .001), but the
rates per patient remained stable (P = .077). For each year, incidence rates
overall were higher in women compared with men (P < .001). From ages 0 to 19,
incidence rates were higher in boys compared with girls. At age 20 and above,
incidence rates were higher in women compared with men. CONCLUSIONS: The overall
rate of epinephrine autoinjector prescriptions increased, but the rate of first-
time prescriptions was stable from 2005 to 2010. In childhood, boys were more
likely to receive a prescription than girls, but this reversed in later ages. (C)
2016 American Academy of Allergy, Asthma & Immunology
Background: Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen
of increased interest worldwide which has been detected in northern Africa.
Anaplasma platys is also present in this region and could possibly have a zoonotic
potential. However, only one recent article reports on the human esposure to A.
phagocytophilum in Morocco and no data are available on canine exposure to both
bacteria. Therefore, we conducted a cross-sectional epidemiological study aiming to
assess both canine and human exposure to Anaplasma spp. in Morocco. A total of 425
dogs (95 urban, 160 rural and 175 working dogs) and 11 dog owners were sampled from
four cities of Morocco. Canine blood samples were screened for Anaplasma spp.
antibodies by an enzyme-linked immunosorbent assay (ELISA) and for A.
phagocytophilum and A. platys DNA by a real-time polymerase chain reaction (RT-PCR)
targeting the msp2 gene. Human sera were tested for specific A. phagocytophilum
immunoglobulin G (IgG) using a commercial immunofluorescence assay (IFA) kit.
Results: Anaplasma spp. antibodies and A. platys DNA were detected in 21.9 and 7.5%
of the dogs, respectively. Anaplasma phagocytophilum DNA was not amplified.
Anaplasma platys DNA was significantly more frequently amplified for working dogs.
No statistically significant differences in the prevalence of Anaplasma spp.
antibodies or A. platys DNA detection were observed between sexes, age classes or
in relation to exposure to ticks. A total of 348 Rhipicephalus sanguineus (sensu
lato) ticks were removed from 35 urban and working dogs. The majority of dog owners
(7/10) were seroreactive to A. phagoyctophilum IgG (one sample was excluded because
of hemolysis). Conclusions: This study demonstrates the occurrence of Anaplasma
spp. exposure and A. platys infection in dogs, and A. phagocytophilum exposure in
humans in Morocco.
The lateral ponticle and epitransverse process are rare anatomical variations found
on the atlas vertebra of the cervical spine. When a lateral ponticle occurs, an
abnormal bony bridge extends from the superior articular facet to the transverse
process. This bony bridge bisects the transverse foramen wherein the vertebral
artery normally lies. In this case report, we describe a C1 specimen from an adult
male with a lateral ponticle on the right side and an epitransverse process on the
left side. Additionally, an articular facet-like structure was also found on the
lateral ponticle's surface. Relevant literature regarding the lateral ponticle
across age groups, sex, race, and species is also reviewed. We postulate that
genesis of the lateral ponticle of the atlas occurs in utero, specifically during
the lateral ossification of the ventral sclerotomes. To our knowledge, an articular
facet-like structure on such a ponticle has not been reported previously. Moreover,
simultaneous occurrence of a lateral ponticle and contralateral epitransverse
process has, to our knowledge, not been reported before.
The intervertebral disc (IVD) is a joint unique in structure and functions. Lying
between adjacent vertebrae, it provides both the primary support and the elasticity
required for the spine to move stably. Various aspects of the IVD have long been
studied by researchers seeking a better understanding of its dynamics, aging, and
subsequent disorders. In this article, we review the surgical anatomy, imaging
modalities, and molecular biology of the lumbar IVD. Clin. Anat. 30:251-266, 2017.
(c) 2017 Wiley Periodicals, Inc.
Granulomatosis with Polyangiitis (GPA) (formerly known as Wegener's granulomatosis)
is a vasculitis of unknown etiology affecting predominantly small- to medium-sized
vessels, usually involving the upper and lower respiratory tract and kidneys. Anti-
neutrophil cytoplasmic autoantibodies are probably the initial cause of the
inflammatory process that leads to the typical necrotizing lesions. In this issue
of the European Journal of Immunology, Szczeklik etal. [Eur. J. Immunol. 2017. 47:
724-733] report some interesting findings on the possible involvement of T-cell
subsets in the pathogenesis of the disease. This prospective study, performed on a
large cohort of patients, identifies Th17 lymphocytes as the possible pathogenic
subset of GPA, and Treg cells as the possible suppressors of the inflammatory
process. These two subsets in peripheral blood could be used as cellular biomarkers
of disease activity, and this would result particularly useful in the follow-up of
patients once the immunosuppressive treatment has been initiated.
Purpose of Review The ANCA-associated vasculitides are a group of small vessel
vasculitides characterized by autoantibodies recognizing the neutrophil cytoplasmic
antigens PR3 and MPO. We examine the current clinical and molecular immunology
understanding of ANCA-associated vasculitides and discuss the current needs in our
understanding of the pathogenic mechanisms of these rare diseases. Recent Findings
The majority of efforts to understand the pathogenesis of these diseases have
focused on dissecting neutrophil biology because the neutrophil is the primary
expressor of ANCA autoantigens. However, a number of important genetic, clinical,
and cellular biology observations suggest that attempts to understand the
pathogenesis of ANCA vasculitides should move away from emphasis on the role of the
neutrophil and instead re-focus on the potential role of other immune cell
mediators. Summary Whether or not neutrophils are the key determinant of ANCA-
associated vasculitis pathogenesis should be revisited in detail. A neutrophil-
centric view of the pathogenesis of these diseases cannot fully account for
important genetic, clinical, and cellular biology observations that implicate
important and under-appreciated roles for monocytes and T cells. Refocusing on
these findings will likely lead to new discovery of novel therapeutic targets and
the identification of clinically useful biomarkers for disease activity.
We studied date palm phytochelatin synthase type I (PdPCS1), which catalyzes the
cytosolic synthesis of phytochelatins (PCs), a heavy metal binding protein, in
plant cells. The gene encoding PdPCS1 (Pdpcs) consists of 8 exons and 7 introns and
encodes a protein of 528 amino acids. PCs gene history was studied using Notung
phylogeny. During evolution, gene loss from several lineages was predicted
including Proteobacteria, Bilateria and Brassicaceae. In addition, eleven gene
duplication events appeared toward interior nodes of the reconciled tree and four
gene duplication events appeared toward the external nodes. These latter sequences
belong to species with a second copy of PCs suggesting that this gene evolved
through subfunctionalization Pdpcs1 gene expression was measured in seedling
hypocotyls exposed to Cd, Cu and Cr using quantitative real-time polymerase chain
reaction (qPCR). A Pdpcsl overexpression was evidenced in P. dactylifera seedlings
exposed to metals suggesting that 1-the Pdpcsl gene is functional, 2-there is an
implication of the enzyme in metal detoxification mechanisms. Additionally, the
structure of PdPCS1 was predicted using its homologue from Nostoc (cyanobacterium,
NsPCS) as a template in Discovery studio and PyMol software. These analyses allowed
us to identify the phytochelatin synthase type I enzyme in date palm (PdPCS1) via
recognition of key consensus amino acids involved in the catalytic mechanism, and
to propose a hypothetical binding and catalytic site for an additional substrate
binding cavity.
Aim In the 19th/early 20th century, overfishing caused a drastic decline and
finally extinction of the local sturgeon populations in the eastern Atlantic. To
date, it is not known whether it was Acipenser sturio or the primarily North
American Acipenser oxyrinchus that occurred here. The aim of the study was to show
the historical pattern of sturgeon distribution and their diversity in this area
over the last 2500 years. This question is essential for international restoration
programmes. Location North-east Atlantic. Methods The study is based on 438
archaeological sturgeon remains from the estuaries of the rivers Rhine, Ems, Weser,
Elbe and Eider. All bones were analysed morphologically and in 38 cases genetically
by the amplification of two mitochondrial DNA fragments. Results The data from the
bones older than 1000 years show that only 1.4% derive from A. sturio. In the
south, this species was slightly more frequent. From the Elbe northwards, A.
oxyrinchus was for a long time by far the dominant sturgeon species. Main
conclusions The genetic identification of the oldest sturgeon bone shows A.
oxyrinchus occurred in the north-eastern Atlantic already 6000 years ago.
Consequently, the immigration of this species from North America to Europe occurred
even earlier, potentially during the last glacial. The north-south occurrence of
the two sturgeon species suggests that the distribution was the result of
interspecific competition under different and changing environmental conditions. As
previously published, genetic data from about 100- to 200-year-old museum specimens
show strong dominance of A. sturio in the North Sea area, obviously A. oxyrinchus
has been replaced in the time between 1000 and 200 years ago. Therefore, the
Holocene distribution of sturgeons in the northeast Atlantic had a complex pattern.
Determining the ecological bases of this distribution is important for the
justification and success of restoration programmes.
The importance of the performance of frequency regulation has already been
acknowledged by regulators and Independent System Operators (ISOs). A performance-
based frequency regulation market model considering both regulation capacity and
regulation mileage constraints is proposed in this paper. In the proposed market,
high-performance regulation resources have higher priorities to be selected in the
market. Market clearing prices are derived with Lagrange relaxation. The analysis
of the components of market clearing prices accurately indicates the correlation
between regulation capacity and regulation mileage. To accommodate the proposed
regulation market design, AGC allocation algorithm is adjusted based on the market
clearing results. The clearing procedure of the market model is demonstrated on an
illustrative case. The proposed market design is tested and verified with market
simulations and system dynamic simulations. Simulation results are discussed and
compared to show the effectiveness of the proposed market design. (C) 2016 Elsevier
Ltd. All rights reserved.
The increased penetration of renewable energy sources in existing power systems has
led to necessary developments in electricity market mechanisms. Most importantly,
renewable energy generation is increasingly made accountable for deviations between
scheduled and actual energy generation. However, there is no mechanism to enforce
accountability for the additional costs induced by power fluctuations. These costs
are socialized and eventually supported by electricity customers. We propose some
metrics for assessing the contribution of all market participants to power
regulation needs, as well as an attribution mechanism for fairly redistributing
related power regulation costs. We discuss the effect of various metrics used by
the attribution mechanisms, and we illustrate, in a game-theoretical framework,
their consequences on the strategic behavior of market participants. We also
illustrate, by using the case of Western Denmark, how these mechanisms may affect
revenues of the various market participants.
In ancillary service electricity markets, opportunity costs account for the profit
forgone by a generator due to the use of generating capacity for ancillary service
provision instead of energy sales. They are calculated for each generator providing
ancillary services and are included in the determination of market-clearing prices
by market operators throughout the U.S. Recent interest in the use of smart
heating, ventilating, and air-conditioning systems for ancillary service provision
prompts an investigation into their associated opportunity costs. This paper
proposes a definition for these costs and method of accounting for them through
time. This is done by recognizing the impacts intra-hour consumption modification
associated with ancillary service provision have on daily energy efficiency and
costs. A numeric example is presented to demonstrate the method. It is found that
marginal ancillary service opportunity costs vary over time and that properly
adjusting energy consumption at an hour of interest can reduce the total
opportunity cost of providing ancillary services.
Androgen insensitivity syndrome (AIS) is characterized by deficient or absent
virilization in 46,XY individuals despite normal or even elevated androgen levels.
AIS is usually caused by mutations in the androgen receptor (AR) gene. We aimed at
contrasting clinical, biochemical, and molecular genetic characteristics of three
patients (P1-P3) with clinically evident partial (PI) and complete (P2, P3) AIS
with and without AR gene mutations. AR expression was studied in cultured genital
skin fibroblasts (GSF) by Western immunoblotting, ligand binding analyses, Northern
blotting, semiquantitative reverse transcription-polymerase chain reaction (RT-
PCR), and RT-PCR spanning exons 1-8. AR gene DNA sequence was analyzed by single-
strand conformation analysis (SSCA), and DNA sequencing. GSF revealed reduced (P1)
or absent (P2, P3) ligand binding. Northern blots showed either slightly reduced
hybridization of the 10.5-kb AR transcript (P3) or no hybridization (P1, P2), as
confirmed by semiquantitative RT-PCR. RT-PCR spanning exons 1-8 detected single AR
mRNA bands in P1-P3 excluding splicing errors. Western analyses showed either low
(P1) or no (P2, P3) AR protein. While SSCA initially did not reveal any molecular
abnormality, sequencing showed a novel CAG (Gln) to TAG (stop) mutation at codon 59
(P3) and a previously described 2-bp deletion at codon 472, leading to a frameshift
and premature stop in codon 499 (P2). Intriguingly, P1 showed an unaltered DNA
sequence of the coding region of the AR gene including all intronexon boundaries.
In conclusion, patients with clinically evident complete AIS are likely to harbor
an AR gene mutation, demanding that the two polymorphic regions must always be
included in molecular analyses of the AR gene. Moreover, our data support the
concept that in a subset of AIS patients, particularly those with partial AIS,
molecular alterations outside the coding region of the AR gene must be presumed.
In this study, we attempted to explore the effect and possible mechanism of
Andrographolide on OVA-induced asthma. OVA challenge induced significant airway
inflammatory cell recruitment and lung histological alterations, which were
ameliorated by Andrographolide. The protein levels of cytokines in bron-choalveolar
fluid (BALF) and serum were reduced by Andrographolide administration as well as
the mRNA levels in lung tissue. Mechanically, Andrographolide markedly hampered the
activation of nuclear factor-kappa B (NF-kappa B) and NLRP3 inflammasome both in
vivo and vitro thus decreased levels of TNF-alpha and IL-1 beta. Finally, we
confirmed that ROS scavenging was responsible for Andrographolide's inactivation of
NF-kappa B and NLRP3 inflammasome signaling. Our study here revealed the effect and
possible mechanism of Andrographolide on asthma, which may represent a new
therapeutic approach for treating this disease.
Introduction: Therapeutic options for myelodysplastic syndromes (MDS) are limited
to hypomethylating agents (HMA) and lenalidomide. Rigosertib, a small molecule
which blocks RAS-mediated activation of proteins containing a common RAS binding
domain, appears to be a promising novel drug.Areas covered: Discovery, mechanism of
action of rigosertib, and results of clinical trials are described. More than 500
patients have been treated and the safety, pharmacokinetics, and efficacy of
rigosertib are summarized. These studies are placed in the context of the history
of therapeutic development in MDS and the promise of new, tailored treatments based
on emerging knowledge of the heterogeneity and molecular biology of the
disease.Expert opinion: In summary, the Phase III study failed to meet the primary
endpoint but clearly showed significant improvement in survival in a subset of very
high risk MDS patients who were primary HMA failures. A new Phase III trial
designed to validate these findings is now ongoing. Oral rigosertib, in a Phase II
trial, produced transfusion independence in similar to 35% patients with lower risk
MDS with or without recombinant erythropoietin. A methylation based signature
appears to distinguish between the two groups. Validation of these early
encouraging observations through future clinical trials is eagerly anticipated.
Background Most data on chronic spontaneous urticaria (CSU) originate from highly
selected patient populations treated at specialized centres. Little is known about
CSU patient characteristics and the burden of CSU in routine clinical practice.
AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation)
is an ongoing global study designed to assess chronic urticaria in the real-life
setting. Objective To describe the baseline characteristics of the first 1539
German AWARE patients with H1-antihistamine-refractory CSU. Methods This
prospective non-interventional study included patients (18-75 years) with a
diagnosis of H1-antihistamine-refractory CSU for >2 months. Baseline demographic
and disease characteristics, comorbidities, and pharmacological treatments were
recorded. Quality of life (QoL) was assessed using the dermatology life quality
index (DLQI), chronic urticaria QoL questionnaire (CU-Q(2)oL), and angioedema QoL
questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource
utilization and sick leave data were collected retrospectively. Results Between
March and December 2014, 1539 patients were assessed in 256 sites across Germany.
The percentage of females, mean age, and mean body mass index were 70%, 46.3 years,
and 27 kg/m(2), respectively. The mean urticaria control test score was 7.9, one in
two patients had angioedema, and the most frequent comorbidities were chronic
inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%),
asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at
least one pharmacological treatment including second-generation H1-antihistamines
(46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%).
The mean DLQI, total CU-Q(2)oL, and total AE-QoL scores were 8.3, 36.2, and 46.8,
respectively. CSU patients reported frequent use of healthcare resources, including
emergency services (29.7%), general practitioners (71.9%), and additional
allergists or dermatologists (50.7%). Conclusions and Clinical Relevance This study
reveals that German H1-antihistamine-refractory CSU patients have high rates of
uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have
impaired QoL, and rely heavily on healthcare resources.
AimsThymomas and thymic squamous cell carcinomas (TSQCCs) are rare thymic
epithelial tumours. Data on angiogenesis and vascular phenotype in these tumours
are limited, and no study has taken histological World Health Organization (WHO)
subtypes into account. The aim of this study was to compare vascularization,
pericytes coverage and expression of angiogenic growth factors in different WHO-
defined subtypes of thymoma Methods and resultsVascular density, diameter and
architecture and expression of -smooth muscle actin (SMA), platelet-derived growth
factor (PDGF) receptor- (PDGFR), vascular endothelial growth factor (VEGF) receptor
1 (VEGFR1) and VEGF receptor 2 (VEGFR2) were investigated in WHO type A, AB, B1, B2
and B3 thymomas and TSQCCs, by the use of immunostaining, quantitative morphometry,
and tumour vessel isolation by trypsin digestion. Expression levels of angiopoietin
1 (Ang-1), angiopoietin 2 (Ang-2), VEGF-A, PDGF-B and Hif-1 were examined by
quantitative reverse transcription polymerase chain reaction. A and AB thymomas
were characterized by a dense network of capillary-like vessels with tight pericyte
coverage, whereas B thymomas showed a loose vascular network with increasing
vascular diameters and increasing expression of SMA and PDGFR from B1 to B3
thymomas and TSQCCs. VEGFR1 and VEGFR2 were expressed in vessels of all analysed
tumour entities, and at higher levels in epithelial cells of A and B3 thymomas and
TSQCCs. mRNA of Ang-2, but not of Ang-1, was significantly up-regulated in all
thymoma subtypes, with the highest levels being found in A thymomas. In TSQCCs,
Ang-1 and VEGF were the predominantly up-regulated growth factors. Hif-1 was only
up-regulated in B3 thymomas and TSQCCs. ConclusionThymomas and TSQCCs differ
significantly in their vascular architecture and expression of key angiogenic
growth factors. The findings could help to improve the differential diagnosis of
difficult-to-classify thymic epithelial tumours, and indicate different mechanisms
of tumour angiogenesis and functional differences of tumour vessels of major
thymoma subtypes and TSQCCs.
Objective: To determine if the molecular profiles of endometriotic lesions contain
informative measures of inflammation and immune dysfunction that may contribute to
better understanding of the interplay between immune dysfunction and inflammation
and their contribution to endometriosis pathogenesis. Design: Immune and
inflammation transcriptomic analysis with the use of the Nanostring nCounter GX
Human Immunology V2 platform (579 human immune and inflammation-related genes and
15 housekeeping genes). Setting: Academic university and teaching hospital.
Intervention(s): None. Patient(s): Stage III-IV endometriosis patients with
infertility (n = 8) and fertile disease-free control women undergoing tubal
ligation (n = 8). Menstrual stage was matched to secretory phase in all
participants. Main Outcome Measure(s): Immune and inflammation transcriptomics
quantification from ectopic endometriotic lesions and matched eutopic endometrium
from patients. Endometria of fertile women served as control subjects. Result(s):
Our results displayed endometriotic lesions as molecularly distinct entities
compared with eutopic endometrium and endometrium of control samples; 396 out of
579 screened immune and inflammation-related genes were significantly different in
ectopic tissues compared with control endometrium. Most importantly, eutopic
endometrium of the patients displayed a unique molecular profile compared with the
control endometrium (91/579 genes were significantly different), particularly of
genes involved in regulation of cell apoptosis and decidualization. Conclusion(s):
We characterize differential expression of immune-inflammation genes in
endometriosis patients, and show molecular distinction of eutopic endometrium of
patients compared with control fertile women. (C) 2016 by American Society for
Reproductive Medicine.
Fish protein hydrolysate was prepared from muscle of small red scorpionfish
(Scorpaena notata) by treatment with a protease from the fungus Penicillium
digitatum. Protein hydrolysate was found to strongly inhibit the angiotensin I
converting enzyme and exhibited high antioxidative activity through 1,1-diphenyl-2-
picrylhydrazyl free radical scavenging assay. After ultrafiltration, peptides were
isolated by a two-step procedure: size exclusion chromatography on a Toyopearl HW-
40 followed by reversed-phase high-performance liquid chromatography with a high
purification yield of 2.5 mg of peptide per gram of initial protein. Two major
peptides were then identified by nanoscale liquid chromatography coupled to tandem
mass spectrometry (nano-LC-MS/MS), corresponding to the following sequences: Leu-
Val-Thr-Gly-Asp-Asp-Lys-Thr-Asn-Leu-Lys (1,204.665 Da) and Asp-Thr-Gly-Ser-Asp-Lys-
Lys-Gln-Leu (992.511 Da). These peptides, mainly composed of hydrophilic amino
acids, showed high antioxidative and angiotensin I converting enzyme inhibitory
activities. These data suggest that the two novel peptides isolated from the muscle
hydrolysate of small red scorpionfish can be a beneficial ingredient for functional
foods or pharmaceuticals against hypertension and oxidative stress. (C) 2016
International Union of Biochemistry and Molecular Biology, Inc.
Ca2+-activated Cl-channels play a crucial role in various physiological processes.
However, the role of TMEM16A in vascular endothelial dysfunction during
hypertension is unclear. In this study, we investigated the specific involvement of
TMEM16A in regulating endothelial function and blood pressure and the underlying
mechanism. Reverse transcription-polymerase chain reaction, Western blotting,
coimmunoprecipitation, confocal imaging, patch-clamp recordings, and TMEM16A
endothelial-specific transgenic and knockout mice were used. We found that TMEM16A
was expressed abundantly and functioned as a Ca2+-activated Cl-channel in
endothelial cells. Angiotensin II induced endothelial dysfunction with an increase
in TMEM16A expression. The knockout of endothelial-specific TMEM16A significantly
lowered the blood pressure and ameliorated endothelial dysfunction in angiotensin
II-induced hypertension, whereas the overexpression of endothelial-specific TMEM16A
resulted in the opposite effects. These results were related to the increased
reactive oxygen species production, Nox2-containing NADPH oxidase activation, and
Nox2 and p22phox protein expression that were facilitated by TMEM16A on angiotensin
II-induced hypertensive challenge. Moreover, TMEM16A directly bound with Nox2 and
reduced the degradation of Nox2 through the proteasome-dependent degradation
pathway. Therefore, TMEM16A is a positive regulator of endothelial reactive oxygen
species generation via Nox2-containing NADPH oxidase, which induces endothelial
dysfunction and hypertension. Modification of TMEM16A may be a novel therapeutic
strategy for endothelial dysfunction-associated diseases.
1. Angiotensin (Ang) II plays a major role in vascular remodelling. Matrix
metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the
tissue remodelling processes. The aim of the present study was to investigate
whether AngII modulates TIMP-2 expression in rat aortic smooth muscle cells in
vivo. 2. Angiotensin II (200 ng/kg per min, s.c.) or AngII + losartan (10 mg/kg per
day, s.c.) or normal saline was administered continuously by osmotic minipumps to
Sprague-Dawley rats for 1 week. In addition, the effect of endogenous AngII on
TIMP-2 expression was evaluated in renovascular hypertensive rats (two kidney, one
clip (2K1C) and one kidney, one clip (1K1C) models). Control rats (sham 2K1C and
sham 1K1C rats) underwent sham-clipping of the left renal artery. At the end of the
treatment, plasma renin activity was measured by radioimmunoassay, aortic TIMP-2
mRNA expression was evaluated by real-time polymerase chain reaction and/or
northern blotting and protein expression was evaluated by immunohistochemistry.
Systolic blood pressure (SBP) was measured twice a week by the tail-cuff method. 3.
Exogenous AngII administration produced the expected increase in SBP (P = 0.02)
compared with the control saline-treated group. The increase in SBP was abolished
in AngII + losartan-treated rats. Administration of AngII caused a significant
increase in TIMP-2 expression (P = 0.01) in rat aortic smooth muscle cells that was
abolished in AngII + losartan-treated rats. In renovascular hypertensive rats, SBP
was higher (P < 0.0001) in 2K1C and 1K1C rats compared with the corresponding sham-
operated rats. Plasma renin activity was higher (P < 0.01) in 2K1C rats compared
with the other groups. The expression of TIMP-2 was significantly (P < 0.05)
increased only in 2K1C rats. 4. Our in vivo data demonstrate that exogenous and
endogenous AngII increases TIMP-2 expression in rat aortic smooth muscle cells.
This effect is not dependent on the AngII-induced increase in blood pressure and is
mediated by angiotensin AT(1) receptors.
Angiotensin II is critical in pre-eclampsia pathogenesis. In addition, microRNA-155
regulates angiotensin II type I receptor expression. We have explored the function
of microRNA-155 in pre-eclamptic pregnant women. Human umbilical vein endothelial
cells were isolated and cultured from healthy puerperant women and pre-eclampsia
patients. The cells were transfected with a mature microRNA-155 plasmid. The effect
of microRNA-155 was assessed by Northern blotting, in situ hybridization,
quantitative real-time PCR, immunofluorescent staining and Western blotting. In
addition, activation of extracellular signal-regulated kinase 1/2 was assessed by
co-immunoprecipitation and Western blotting. Severely pre-eclamptic pregnant women
expressed less mature miR-155 compared to healthy pregnant women. In addition,
angiotensin H type 1 receptor expression decreased substantially in healthy cells
and miR-155-transfected cells compared to miR-155-mutant-transfected cells and
cells from pre-eclamptic patients. Mature miR-155 reduced angiotensin II-induced
extracellular signal-regulated kinase 1/2 activation. In conclusion, endogenous
mature miR-155 expression may be an important contributor to the pathogenesis of
severe pre-eclampsia.
Renin substrate, biological renin activity, and/or renin-secreting cells in kidneys
evolved at an early stage of vertebrate phylogeny. Angiotensin (Ang) I and II
molecules have been identified biochemically in representative species of all
vertebrate classes, although variation occurs in amino acids at positions 1, 5, and
9 of Ang I. Variations have also evolved in amino acid positions 3 and 4 in some
cartilaginous fish. Angiotensin receptors, AT(1) and AT(2) homologues, have been
identified molecularly or characterized pharmacologically in nonmammalian
vertebrates. Also, various forms of angiotensins that bypass the traditional renin-
angiotensin system (RAS) cascades or those from large peptide substrates,
particularly in tissues, are present. Nonetheless, the phylogenetically important
functions of RAS are to maintain blood pressure/blood volume homeostasis and ion-
fluid balance via the kidney and central mechanisms. Stimulation of cell growth and
vascularization, possibly via paracrine action of angiotensins, and the molecular
biology of RAS and its receptors have been intensive research foci. This review
provides an overview of: (1) the phylogenetic appearance, structure, and
biochemistry of the RAS cascade; (2) the properties of angiotensin receptors from
comparative viewpoints; and (3) the functions and regulation of the RAS in
nonmammalian vertebrates. Discussions focus on the most fundamental functions of
the RAS that have been conserved throughout phylogenetic advancement, as well as on
their physiological implications and significance. Examining the biological history
of RAS will help us analyze the complex RAS systems of mammals. Furthermore,
suitable models for answering specific questions are often found in more primitive
animals.
1. Several eel species have undergone extensive declines at both local and global
level. The aim of this study was to identify the reasons for the collapse of the
European eel (Anguilla anguilla) stock in an important area for biodiversity
conservation (Comacchio Lagoon, Italy), in order to support the development of eel
conservation plans. 2. The records of silver eel catches from Comacchio describe
the total migratory population and cover the period 1781- 2013. The data are
accompanied by information related to habitat loss and other local factors. The
role of local factors on the decline of the local stock was investigated, while
additional information from the literature was also used to discuss the effects of
global factors (including glass eel harvest for aquaculture, climateoceanographic
changes, habitat loss, pollution and parasitism) on the three eel species A.
anguilla, Anguilla japonica and Anguilla rostrata. 3. The records from Comacchio
provided significant information about the effects of local factors on the local
eel populations in the past. However, the current population collapse, which
started in the 1970s, could not be explained by local factors. 4. The literature on
global factors suggests that the three eel species are under combined threat from
various factors. The correlations between European aquaculture production data
compared with the Comacchio yields and published data from other European eel and
glass eel fisheries were found to be highly significant. Aquaculture, which depends
entirely on wild- caught glass eels, seems to play a key role in the decline of
natural stocks. 5. Conservative estimates using FAO data showed that the current
numbers of glass eels needed to support aquaculture production in Europe and Asia
exceeds 2 x 109 specimens. This requirement, largely supplied by A. anguilla glass
eels, can explain the decline of eel populations since the glass eel trade has been
expanded at an international level. Copyright # 2016 John Wiley & Sons, Ltd.
Even simple geometric shapes are seen as animate and goal-directed when they move
in certain ways. Previous research has revealed a great deal about the cues that
elicit such percepts, but much less about the consequences for other aspects of
perception and cognition. Here we explored whether simple shapes that are perceived
as animate and goal-directed are prioritized in memory. We investigated this by
asking whether subjects better remember the locations of displays that are seen as
animate vs. inanimate, controlling for lower-level factors. We exploited the
'Wolfpack effect': moving darts (or discs with 'eyes') that stay oriented toward a
particular target are seen to be actively pursuing that target, even when they
actually move randomly. (In contrast, shapes that stay oriented perpendicular to a
target are correctly perceived to be drifting randomly.) Subjects played a
'matching game' - clicking on pairs of panels to reveal animations with moving
shapes. Across four experiments, the locations of Wolfpack animations (compared to
control animations equated on lower-level visual factors) were better remembered,
in terms of more efficient matching. Thus perceiving animacy influences subsequent
visual memory, perhaps due to the adaptive significance of such stimuli. (C) 2017
Elsevier B.V. All rights reserved.
For more than a century researchers have used enculturated animals-those
extensively trained or reared by humans-to explore the effects of learning and
environment on the capacities for linguistic abilities outside of the human line.
Unfortunately, due to many controversies, the findings of these studies frequently
have been dismissed or outright ignored. However, experimental exploration of the
capacities of nonhumans is the only option to determine which, if any, language-
associated capacities are unique to humans. Researchers continue to publish
findings from language projects that move our understanding forward, including
descriptions of capacities, such as gestural comprehension, declarative
communication, and categorization, that are frequently considered to be specific
biological adaptations.
Social network analysis has become a prominent tool to study animal social life,
and there is an increasing need to develop new systems to collect social
information automatically, systematically, and reliably. Here we explore the use of
a freely accessible Automated Learning Device for Monkeys (ALDM) to collect such
social information on a group of 22 captive baboons (Papio papio). We compared the
social network obtained from the co-presence of the baboons in ten ALDM testing
booths to the social network obtained through standard behavioral observation
techniques. The results show that the co-presence network accurately reflects the
social organization of the group, and also indicate under which conditions the co-
presence network is most informative. In particular, the best correlation between
the two networks was obtained with a minimum of 40 days of computer records and for
individuals with at least 500 records per day. We also show through random
permutation tests that the observed correlations go beyond what would be observed
by simple synchronous activity, to reflect a preferential choice of closely located
testing booths. The use of automatized cognitive testing therefore presents a new
way of obtaining a large and regular amount of social information that is necessary
to develop social network analysis. It also opens the possibility of studying
dynamic changes in network structure with time and in relation to the cognitive
performance of individuals.
In the horse, breeding induces a transient endometrial inflammation. A subset of
mares are unable to resolve this inflammation, and they are considered susceptible
to persistent mating-induced endometritis PMIE Select seminal plasma proteins
cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to
affect the innate immune response to sperm in vitro. The objective of this study
was to determine whether the addition of CRISP-3 and lactoferrin at the time of
insemination had an effect on the mRNA expression of endometrial cytokines in
susceptible mares after breeding. Six mares classified as susceptible to PMIE were
inseminated during four consecutive oestrous cycles with treatments in randomized
order of: 1 mg/ ml CRISP-3, 150 mu g/ ml lactoferrin, seminal plasma (positive
control) or lactated Ringer's solution (LRS; negative control) to a total volume of
10 ml combined with 1 x 10(9) spermatozoa pooled from two stallions. Six hours
after treatment, an endometrial biopsy was obtained for qPCR analysis of selected
genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)- 1
beta, IL- 8, tumour necrosis factor (TNF)- alpha, interferon (INF)-gamma, anti-
inflammatory cytokines IL- 1RN and IL- 10, and inflammatory- modulating cytokine
IL- 6). Seminal plasma treatment increased the mRNA expression of IL- 1 beta (p
=.019) and IL- 8 (p =.0068), while suppressing the mRNA expression of TNF (p
=.0013). Lactoferrin also suppressed the mRNA expression of TNF (p =.0013). In
conclusion, exogenous lactoferrin may be considered as one modulator of the complex
series of events resulting in the poorly regulated pro-inflammatory response seen
in susceptible mares.
Existing research suggests that various forms of family violence such as domestic
violence and child abuse tend to coexist or cluster. Although the link between
animal cruelty and domestic violence is well publicized, little research has
examined various forms of animal abuse and possible links between corresponding
forms of interpersonal offenses. The present study examined a subsample obtained
from the FBI's Behavioral Analysis Unit. (BAU) III - Crimes Against Children, which
included the criminal histories of 150 adult males arrested for animal cruelty,
neglect or sexual abuse in the, U.S. between 2004 and 2009. The sample was
described in terms of demographic and criminal characteristics. Results indicated
that 41% of the offenders in the sample were arrested for interpersonal violence at
least once, 18% were arrested for a sex offense such as rape or child molestation,
and 28% were arrested for another interpersonal crime such as violating a
restraining order or harassment. Significant relationships were discovered between
Active animal cruelty (such as beating or stabbing) and both interpersonal violence
and substance abuse as well as between sexually abusing animals and sexual
offending against humans. These results point to the need for increased
collaboration between animal welfare agencies and the social service and legal
entities responsible for protecting domestic violence victims, children, elders,
and others at risk groups. (C) 2016 Published by Elsevier Ltd.
This review presents an overview of some of the pre-clinical and clinical issues
that have contributed to the failures of potential novel neuropsychiatric drugs,
which have prompted a re-examination of the role of animal models of
neuropsychiatric disorders. Advances both in basic neuroscience and technology have
driven the development of animal models of aspects of neuropsychiatric disorders.
Genetics and environmental factors have been the primary contributors to the
development of new animal models. Neuroimaging has contributed to the search for
biomarkers by which neuropsychiatric disorders may be identified and
differentiated, its progression monitored and that the effects of therapy assessed.
Parallel to these theoretical and practical advancements have been the changes in
the diagnosis and classification of neuropsychiatric disorders from DSM-4 to DSM-5,
and emergence of the NIH initiatives such as MATRICS; CNTRICS and RDoC. These
latter changes are shifting our concepts of neuropsychiatric disorders away from
phenomenology to their biology and thus aligning physiology with psychology. (C)
2017 Elsevier Ltd. All rights reserved.
We tested the two main evolutionary hypotheses for an association between immunity
and personality. The risk of-parasitism hypothesis predicts that more proactive
(bold, exploratory, risk-taking) individuals have more vigorous immune defenses
because of increased risk of parasite exposure. In contrast, the pace-of-life
hypothesis argues that proactive behavioral styles are associated with shorter
lifespans and reduced investment in immune function. Mechanistically, associations
between immunity and personality can arise because personality differences are
often associated with differences in condition and stress responsiveness, both of
which are intricately linked with immunity. Here we investigate the association
between personality (measured as proactive exploration of a novel environment) and
three indices of innate immune function (the non-specific first line of defense
against parasites) in wild superb fairy-wrens Malurus cyaneus. We also quantified
body condition, hemoparasites (none detected), chronic stress
(heterophil:lymphocyte ratio) and circulating corticosterone levels at the end of
the behavioral test (CORT, in a subset of birds). We found that fast explorers had
lower titers of natural antibodies. This result is consistent with the pace-of-life
hypothesis, and with the previously documented higher mortality of fast explorers
in this species. There was no interactive effect of exploration score and duration
in captivity on immune indices. This suggests that personality-related differences
in stress responsiveness did not underlie differences in immunity, even though
behavioral style did modulate the effect of captivity on CORT. Taken together these
results suggest reduced constitutive investment in innate immune function in more
proactive individuals. (C) 2016 Elsevier Inc. All rights reserved.
Mild therapeutic hypothermia is a candidate for the treatment of traumatic brain
injury (TBI). However, the role of mild hypothermia in neuronal sprouting after TBI
remains obscure. We used a fluid percussion injury (FPI) model to assess the effect
of mild hypothermia on pericontusion neuronal sprouting after TBI in rats. Male
Sprague-Dawley rats underwent FPI or sham surgery, followed by mild hypothermia
treatment (33 degrees C) or normothermia treatment (37 degrees C) for 3 h. All the
rats were euthanized at 7 days after FPI. Neuronal sprouting that was confirmed by
an increase in growth associated protein-43 (GAP-43) expression was evaluated using
immunofluorescence and Western blot assays. The expression levels of several
intrinsic and extrinsic sprouting-associated genes such as neurite outgrowth
inhibitor A (NogoA), phosphatase and tensin homolog (PTEN), and suppressor of
cytokine signaling 3 (SOCS3) were analyzed by quantitative real-time polymerase
chain reaction (RT-PCR). Our results revealed that mild hypothermia significantly
increased the expression level of GAP-43 and dramatically suppressed the expression
level of interleukin-6 (IL-6) and SOCS3 at 7 days after FPI in the ipsilateral
cortex compared with that of the normothermia TBI group. These data suggest that
post-traumatic mild hypothermia promotes pericontusion neuronal sprouting after
TBI. Moreover, the mechanism of hypothermia-induced neuronal sprouting might be
partially associated with decreased levels of SOCS3.
OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human
cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration, and
apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was
detected by fluorescent quantitative reverse transcriptase polymerase chain
reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939
and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3) and
1 negative control plasmid were constructed to infect QBC939 cells. The infection
efficiency, expression of ANXA5, apoptosis and cell cycle of QBC939 cell were
measured separately. RESULTS: The expression of ANXA5 in QBC939 cell was
significantly higher than RBE cell. Expressed ANXA5 protein in the QBC939-KD cell
(QBC939 cell treated by RNAi) was significantly lower than QBC939-BC (QBC939 cell)
and QBC939-NC cells (QBC939 cell treated by scramble plasmid). The ratio of G0/1
phase cells and apoptosis rate increased in QBC939-KD cell. The proliferation
activity and invasion ability decreased in QBC939-KD cell compared with QBC939-NC
and QBC939-BC cells. CONCLUSIONS: ANXA5 play important role in the migration and
apoptosis of CCA cells. Inhibiting the expression of ANXA5 significantly reduce the
proliferation, migration and invasion ability of QBC939 cells, and increase the
apoptosis of QBC939 cells.
The tumor suppressor p16INK4a has functions beyond cell-cycle control via cyclin-
dependent kinases. A coordinated remodeling of N- and O-glycosylation, and an
increase in the presentation of the endogenous lectin galectin-1 sensing these
changes on the surface of p16INK4a-expressing pancreatic carcinoma cells (Capan-1),
lead to potent pro-anoikis signals. We show that the p16INK4a-dependent impact on
growth-regulatory lectins is not limited to galectin-1, but also concerns galectin-
3. By monitoring its expression in relation to p16INK4a status, as well as running
anoikis assays with galectin-3 and cell transfectants with up- or downregulated
lectin expression, a negative correlation between anoikis and the presence of this
lectin was established. Nuclear run-off and northern blotting experiments revealed
an effect of the presence of p16INK4a on steady-state levels of galectin-3-specific
mRNA that differed from decreasing the transcriptional rate. On the cell surface,
galectin-3 interferes with galectin-1, which initiates signaling toward its pro-
anoikis activity via caspase-8 activation. The detected opposite effects of
p16INK4a at the levels of growth-regulatory galectins-1 and -3 shift the status
markedly towards the galectin-1-dependent pro-anoikis activity. A previously
undescribed orchestrated fine-tuning of this effector system by a tumor suppressor
is discovered.
BACKGROUND: Little is known about anorectal function and quality of life after
chemoradiation followed by local excision, which is an alternative to total
mesorectal excision for selected patients with early rectal cancer. OBJECTIVE: The
purpose of this study was to prospectively assess anorectal function and health-
related quality of life of patients with T2N0 rectal cancer who were treated with
an alternative approach. DESIGN: This was a prospective, phase II trial. SETTINGS:
The study was multicentric (American College of Surgeons Oncology Group trial
Z6041). INTERVENTIONS: Patients with stage cT2N0 rectal adenocarcinomas were
treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by
local excision. MAIN OUTCOME MEASURES: Anorectal function and quality of life were
assessed at enrollment and 1 year postoperatively with the Fecal Incontinence
Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment
of Cancer Therapy-Colorectal Questionnaire. Results were compared, and
multivariable analysis was performed to identify predictors of outcome. RESULTS:
Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year.
Compared with baseline, no significant differences were found on Fecal Incontinence
Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were
significantly worse in the lifestyle (p < 0.001), coping/behavior (p < 0.001), and
embarrassment (p = 0.002) domains. There were no differences in the Functional
Assessment of Cancer Therapy overall score, but the physical wellbeing subscale was
significantly worse and emotional well-being was improved after surgery. Treatment
with the original chemoradiation regimen predicted worse depression/self-perception
and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex
was predictive of worse scores in the Functional Assessment of Cancer Therapy
overall score and trial outcome index. LIMITATIONS: Small sample size, relatively
short follow-up, and absence of information before cancer diagnosis were study
limitations. CONCLUSIONS: Chemoradiation followed by local excision had minimal
impact on anorectal function 1 year after surgery. Overall quality of life remained
stable, with mixed effects on different subscales. This information should be used
to counsel patients about expected outcomes.
Numerous patients with anorectal malformations (ARMs) continue to experience fecal
incontinence and constipation following surgical procedures. One of the most
important factors that influences defecation is the striated muscle complex (SMC).
Wnt signaling regulates the expression of myogenic regulatory factors, which serve
an important role in muscle development. Therefore, the present study aimed to
investigate the expression pattern of Wnt3a protein (by immunohistochemistry and
western blot analysis) and mRNA [by reverse transcription-quantitative polymerase
chain reaction (RT-qPCR)] in the SMC of ARM model rats that were exposed to
ethylenethiourea. Immunostaining revealed that the expression of Wnt3a exhibits
space-and time-dependent changes in the developing SMC of ARM model rat embryos.
Immunohistochemistry demonstrated that on embryonic day 17 (E17), Wnt3a-positive
cells were observed in the SMC in normal embryos, and expression levels gradually
increased as the rat embryos developed. Similar changes in Wnt3a protein expression
were detected in ARM model rat embryos; however, the expression of Wnt3a was
significantly reduced compared with the normal rat embryos. Western blotting and
RT-qPCR also revealed lower expression levels of Wnt3a protein and mRNA,
respectively, in the SMC of ARMs model rat embryos compared with normal rat
embryos. These data revealed that the expression of Wnt3a in ARM embryos was
notably reduced, indicating a potential role for Wnt3a in the maldevelopment of the
SMC in patients with ARMs.
Purpose: A subgroup of individuals with anorexia nervosa (AN) displays social
difficulties; however, it is not clear if individuals with comorbid autism spectrum
disorders account for these difficulties. Methods: We compared social function
using the Autism Diagnostic Observation Schedule in 43 young females with first-
episode AN who did not have comorbid autism spectrum disorder, 28 individuals
recovered from adolescent-onset AN, and 41 healthy comparison individuals (age
range 14-22 years). We measured adaptive behavior with the Vineland-II parent
questionnaire, and aspects of social cognition with psychological tests, such as
the Reading-the-Mind-in-the-Eyes test, Profile of Nonverbal Sensitivity short
version, The Awareness of Social Inference Test, Animated Triangles, and the CANTAB
Affective Go/No-go task. Results: Participants with first-episode AN and those
recovered from AN displayed difficulties in social function, which were not
associated with body mass index or other state factors of the disorder in those
with first-episode AN. Mood problems and anxiety were not associated with these
difficulties. Parents rated participants with first-episode AN lower than recovered
and control participants on the Socialization Domain of Vineland-II. Finally, only
participants recovered from AN demonstrated deficits in specific domains of social
cognition: perceiving nonverbal bodily gesture and vocal prosody. Conclusions:
Young females with first-episode AN and those recovered from AN displayed
impairments in social function, which may represent more stable traits of the
disorder. Only participants recovered from AN demonstrated deficits in social
cognition. (C) 2016 Society for Adolescent Health and Medicine. All rights
reserved.
This study examines whether the perception of peripersonal action-space and
interpersonal social-space is modified in patients with restrictive-type anorexia
in two experimental conditions using videos. First, participants stopped the video
of an approaching stimulus when they felt the distance to be comfortable for
interacting with it (first-person perspective). Second, participants stopped the
video when an observed individual approaching a stimulus, or being approached by
it, was at a comfortable distance (third-person perspective). In the first-person
perspective, the results showed an estimation of peripersonal space that did not
differ from controls when an object was approaching and an increase in
interpersonal space compared with controls when a male or female individual was
approaching. In the third-person perspective, both individual-object and
individual-individual distances were larger in anorexic patients. These results
indicate a specific deficit in adjusting interpersonal distances in both the first-
person and third-person perspectives. Copyright (c) 2017 John Wiley & Sons, Ltd and
Eating Disorders Association.
We tested wild birds in Poland during 2008-15 for avian influenza virus (AIV). We
took 10,312 swabs and feces samples from 6,314 live birds representing 12 orders
and 84 bird species, mostly from orders Anseriformes and Charadriiformes, for
testing and characterization by various PCR methods. From PCR-positive samples, we
attempted to isolate and subtype the virus. The RNA of AIV was detected in 1.8%
(95% confidence interval [CI], 1.5-2.1%) of birds represented by 48 Mallards (Anas
platyrhynchos), 11 Mute Swans (Cygnus olor), 48 Common Teals (Anas crecca), three
Black-headed Gulls (Chroicocephalus ridibundus), one Common Coot (Fulica atra), one
Garganey (Spatula querquedula), and one unidentified bird species. Overall, the
prevalence of AIV detection in Mallards and Mute Swans (the most frequently sampled
species) was 2.0% (95% CI, 1.4-2.5%) and 0.5% (95% CI, 0.2-0.8%), respectively; the
difference was statistically significant (P = 0.000). Hemagglutinin subtypes from
H1 to H13 were identified, including H5 and H7 low pathogenic AIV subtypes.
Mallards and Common Teals harbored the greatest diversity of subtypes. We observed
seasonality of viral detection in Mallards, with higher AIV prevalence in late
summer and autumn than in winter and spring. In addition, two peaks in AIV
prevalence in summer (August) and autumn (November) were demonstrated for Mallards.
The prevalence of AIV in Mute Swans did not show any statistically significant
seasonal patterns.
Background: Glutamatergic system abnormalities are implicated in the
pathophysiology and treatment of both major depressive disorder and bipolar
depression (BDep). Subsequent to studies demonstrating the rapid and robust
antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist,
other glutamatergic modulators are now being studied in clinical trials of mood
disorders. A previous open-label study found that riluzole, administered in
combination with the mood stabilizer lithium, had antidepressant effects. Methods:
We conducted a randomized, double-blind, placebo-controlled trial of riluzole
monotherapy for the treatment of BDep. Nineteen subjects aged 18 to 70 years with
bipolar disorder currently experiencing a depressive episode were tapered off of
excluded medications and randomized to receive riluzole (50-200 mg/d) or placebo
for 8 weeks. Rating scale scores (Montgomery-angstrom sberg Depression Rating
Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and
Young Mania Rating Scale) were obtained weekly. Results: No significant differences
in depressive symptoms were observed between subjects treated with riluzole and
those receiving placebo (P = 0.12). Anxiety scores were significantly lower in the
placebo group (P = 0.046). An interim analysis was conducted that resulted in
stopping the study because of futility; no subjects had achieved treatment
response. Conclusions: Although we found no change in severity of depressive
symptoms in BDep patients receiving riluzole compared with placebo, this trial was
limited by the relatively high number of subject withdrawals and the small sample
size. Thus, while riluzole monotherapy did not demonstrate efficacy for BDep,
further studies examining riluzole as adjunctive therapy for this disorder may be
warranted.
A system of generating tunable orbital angular momentum (OAM) radio beams and a
method of measuring the OAM states are proposed and experimentally investigated.
The OAM beams, which are generated by a uniform circular array, can be dynamically
configured by controlling the digital signals in the baseband. A 2-D near-field
scanning platform is built to measure the OAM states of the system. The platform
can provide multiple feed ports for the transmitting array. Iteration is used to
calibrate the amplitude and phase of each feed port. The experimental results
demonstrate the feasibility of the proposed methods on generating and measuring
tunable OAM beams.
Cortical networks underpinning attentional control and mentalizing converge at the
right temporoparietal junction (rTPJ). It is debated whether the rTPJ is
fractionated in neighboring, but separate functional modules underpinning
attentional control and mentalizing, or whether one overarching cognitive mechanism
explains the rTPJ's role in both domains. Addressing this question, we combined
attentional control and mentalizing in a factorial design within one task. We added
a social context condition, in which another individual's mental states became
apparently task-relevant, to a spatial cueing paradigm. This allowed for assessing
cue validity-and context-dependent functional activity and effective connectivity
of the rTPJ within corresponding cortical networks. We found two discriminable rTPJ
subregions, an anterior and a posterior one. Yet, we did not observe a sharp
functional dissociation between these two, as both regions responded to attention
cueing and social context manipulation. The results suggest that the rTPJ is part
of both the ventral attention and the ToM network and that its function is defined
by context-dependent coupling with the respective network. We argue that the rTPJ
as a functional unit underpins an overarching cognitive mechanism in attentional
control and mentalizing and discuss how the present results help to further specify
this mechanism.
Purpose: To Compare tendon-to-bone healing in remnant-preserving and conventional
anterior cruciate ligament reconstruction. Methods: 72 New Zealand rabbits were
randomly assigned to conventional ACL reconstruction group (group A), remnant-
preserving and tensioning ACL reconstruction group (group B), and remnant-
preserving and graft through remnant sleeve ACL reconstruction group (group C),
with 24 rabbits (48 knees) in each group. The incidence and degree of bone tunnel
enlargement in each group were analyzed using CT 3D reconstruction. Graft tendon-
bone healing was monitored by HE and Masson staining, and osteoprotegerin (OPG) and
receptor activator of nuclear factor kappa B ligand (RANKL) mRNA expression in the
bone tissue surrounding the graft. Reverse transcriptase polymerase chain reaction
(RT-PCR) was used to evaluate the ratio of OPG/RANKL expression. Results:
Histological analysis showed that group C had the best graft tendon-bone healing,
followed by group B and group A at all time-points post-surgery. At weeks 3 and 6
post-surgery, OPG mRNA levels and OPG/RANKL values were higher in groups B and C
compared to group A (P < 0.05). RANKL mRNA levels of groups B and C were lower than
group A (P0.05). At 3 weeks post-surgery, the incidence and degree of bone tunnel
enlargement were greater in group A compared to groups B and C (P < 0.05).
Conclusion: Both remnant-preserving construction approaches promoted graft tendon-
bone healing, the underlying mechanism may be associated with the upregulation of
OPG mRNA and downregulation of RANKL mRNA in bone tunnel early post-operation.
Words activate cortical regions in accordance with their modality of presentation
(i.e., written vs. spoken), yet there is a long-standing debate about whether
patterns of activity in any specific brain region capture modality invariant
conceptual information. Deficits in patients with semantic dementia highlight the
anterior temporal lobe (ATL) as an amodal store of semantic knowledge but these
studies do not permit precise localisation of this function. The current
investigation used multiple imaging methods in healthy participants to examine
functional dissociations within ATL. Multi-voxel pattern analysis identified
spatially segregated regions: a response to input modality in anterior superior
temporal gyrus (aSTG) and a response to meaning in more ventral anterior temporal
lobe (vATL). This functional dissociation was supported by resting-state
connectivity that found greater coupling for aSTG with primary auditory cortex and
vATL with the default mode network. A meta-analytic decoding of these connectivity
patterns implicated aSTG in processes closely tied to auditory processing (such as
phonology and language) and vATL in meaning-based tasks (such as comprehension or
social cognition). Thus we provide converging evidence for the segregation of
meaning and input modality in the ATL.
Humans cannot help but attribute human emotions to non-human animals. Although such
attributions are often regarded as gratuitous anthropomorphisms and held apart from
the attributions humans make about each other's internal states, they may be the
product of a general mechanism for flexibly interpreting adaptive behavior. To
examine this, we used functional magnetic resonance imaging (fMRI) in humans to
compare the neural mechanisms associated with attributing emotions to humans and
non-human animal behavior. Although undergoing fMRI, participants first passively
observed the facial displays of human, non-human primate and domestic dogs, and
subsequently judged the acceptability of emotional (e.g. 'annoyed') and facial
descriptions (e.g. 'baring teeth') for the same images. For all targets, emotion
attributions selectively activated regions in prefrontal and anterior temporal
cortices associated with causal explanation in prior studies. These regions were
similarly activated by both human and non-human targets even during the passive
observation task; moreover, the degree of neural similarity was dependent on
participants' self-reported beliefs in the mental capacities of non-human animals.
These results encourage a non-anthropocentric view of emotion understanding, one
that treats the idea that animals have emotions as no more gratuitous than the idea
that humans other than ourselves do.
Introduction: C1q play an important role in clearance of immune complexes and
apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen
and development of anti-C1q antibody formation. Anti-C1q antibody is well studied
in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE
patients and their clinical manifestations is not clear. Aim: The aim of this study
was to investigate associations between anti-C1q antibody and clinical as well as
serological markers of SLE. Materials and Methods: Retrospective study of SLE
patients fulfilling either American College of Rheumatology (ACR) 1990 or Systemic
Lupus International Collaborating Clinics (SLICC) 2012 classification criteria were
recruited from inpatients and outpatients services of the Clinical immunology and
Rheumatology Department, Christian Medical College at Vellore, India between March
2013 and January 2015. Anti-C1q antibody was assayed by ELISA (Demeditec
Diagnostics GmbH, Germany). Logistic regression analysis was performed to find the
association of anti-C1q antibodies with serological and clinical parameters in SLE
including Lupus Nephritis (LN). Results: Sixty nine patients (54.76%) out of 126
SLE patients had LN. Anti-C1q levels were higher in patients with LN as compared to
those without (p<0.05). Anti-C1q antibody was also significantly associated with
positive C1q immunofluorescence staining in renal biopsy specimens (p<0.05).
Overall, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) {OR
1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and mucocutaneous manifestation {OR
4.72 (1.38-16.05)} were independently associated with anti-C1q levels in serum.
Conclusion: Renal SLEDAI, low C4 and mucocutaneous manifestations were
independently associated with raised anti C1q antibody in SLE patients.
The isoquinoline alkaloid berberine possesses many pharmacological activities
including antibacterial infection. Although the direct bactericidal effect of
berberine has been documented, its influence on the antibacterial functions of
macrophages is largely unknown. As inflammasome activation in macrophages is
important for the defense against bacterial infection, we aimed to investigate the
influence of berberine on inflammasome activation in murine macrophages. Our
results showed that berberine significantly increased ATP-induced inflammasome
activation as reflected by enhanced pyroptosis as well as increased release of
caspase-1p10 and mature interleukin-1 beta (IL-1 beta) in macrophages. Such effects
of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor
compound C or by knockdown of AMPKa expression, indicating the involvement of AMPK
signaling in this process. In line with increased IL-1 beta release, the ability of
macrophages to kill engulfed bacteria was also intensified by berberine. This was
corroborated by the in vivo finding that the peritoneal live bacterial load was
decreased by berberine treatment. Moreover, berberine administration significantly
improved survival of bacterial infected mice, concomitant with increased IL-1 beta
levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively,
these data suggested that berberine could enhance bacterial killing by augmenting
inflammasome activation in macrophages through AMPK signaling.
Gloverin is an antibacterial peptide which has been previously isolated in
Hyalophora gloveyi, and is known to exert an inhibition effect on the growth of
Gram-negative bacteria (GNB). When the expressed genes in the immunized Bombyx mori
were screened, gloverin like gene (BmGLP) was found and it was thought to respond
against the bacterial invasion. This study presents some data about the gene
organization and expression of this candidate for a novel antibacterial peptide in
Bombyx mori. The complete sequence, which was determined via RACE, revealed that
this BmGLP was identical to the recently reported clone BmGloverin2 mRNA. The
transcription of this gene was increased transiently, but to a high degree, around
7 similar to 11 hours after infection, as evidenced by the results of Northern
blotting hybridization analysis. Based on the tentative coding sequence, we
amplified the genomic sequence and determined that the gene harbored 3 introns.
Interestingly, we found retrotransposon relative sequences in introns 1 and 3. Both
Southern blotting analysis and sequencing data indicated that the BmGLP2 gene had
another relative- or pseudo- sequences in its genome. We also attempted the
generation of recombinant peptides in a prokaryotic cell system, but we obtained
only truncated peptides and were unable to determine the existence of. any
antibacterial activity with the cell extract under physiological conditions. In
further studies, the expression system and activity test conditions should be made
more representative of the actual insect organism. Finally, we have proposed the
possibility that some type of evolutionary link connects retrotransposons activity
in insect immunity gene variation.
The gene expression level for immune system genes was evaluated at different
lifecycle stages in the white shrimp (Litopenaeus vannamei). The gene-coding
pattern recognition protein, -glucan binding protein-high density lipoprotein
(BGBP), from haemocytes, the effector proteins peroxinectin and clotting protein
(CP), the antibacterial proteins Lysozyme, Penaeidin 3 and prophenoloxidase
(proPO), and the small heat-shock protein 10 were studied. The expression of BGBP
was detected from the Nauplii 3 substage and beyond (except for PL1). Peroxinectin
and CP were constitutively transcribed throughout the different substages.
Lysozyme, Penaeidin and proPO were also detected throughout the experimental stages
(except eggs and nauplii). Lysozyme was transcribed during most of the shrimp
substages, from Zoea 2 and beyond. Penaeidin 3 exhibited the lowest expression
level of the genes evaluated; however, its transcription was similar to those of
adults from post-larvae 11 and forward. proPO was higher transcribed during last
post-larval substages. Heat-shock protein-10 was detected in all shrimp substages
and exhibited higher expression at the PL substages compared to the first larval
substages. Evidence suggests that the shrimp immune system is partially activated
from the early larval substages, but is not completed until the shrimp have
undergone the metamorphic substages.
Despite several conventional potent antibacterial therapies, bacterial infections
pose a significant threat to human health because they are emerging as the leading
cause of death worldwide. Due to the development of antibiotic resistance in
bacteria, there is a pressing demand to discover novel approaches for developing
more effective therapies to treat multidrug-resistant bacterial strains and
biofilm-associated infections. Therefore, attention has been especially devoted to
a new and emerging branch of science "nanotechnology" to design non-conventional
antimicrobial chemotherapies. A range of nanomaterials and nano-sized carriers for
conventional antimicrobial agents have fully justified their potential to combat
bacterial diseases by reducing cell viability, by attenuating quorum sensing, and
by inhibiting/or eradicating biofilms. This communication summarizes emerging nano-
antimicrobial therapies in treating bacterial infections, particularly using
antibacterial, quorum quenching, and anti-biofilm nanomaterials as new approaches
to tackle the current challenges in combating infectious diseases.
Antibiotics are widely used in mariculture industry, and this study attempts to
determine the extent of water and sediment pollution by aritibiotic residues in 13
major mariculture sites in China. Through chemical and molecular biology analysis,
the results showed that the total concentrations of sulfonamides and tetracyclines
were in the range 62.0-373.8 ng L-1 and 0.2-259.1 ng L-1 respectively in water
samples, and in the range 0.19-1.59 ng g(-1) dry weight and 3.45-74.84 ng g(-1) dry
weight respectively, in sediments samples. The occurrence of antibiotic resistance
genes (ARGs) was detected in all sites. Compared with the tetracyclines resistance
genes, the absolute copy number and relative abundance of the sulfonamides
resistance genes were 4.3 times and 2.3 times higher in water and sediment from the
mariculture sites, With the dominant resistance genes being sul2. The abundance of
sul3 in the water phase was significantly correlated with the concentrations of
sulfamerazine, while the abundance of sul2 in the sediment phase was significantly
with sulfadiazine concentrations. The abundance of tetM in the sediment phase was
significantly correlated with the concentrations of oxytetracycline. The findings
demonstrate the persistence of antibiotic residues and ARGs in major mariculture
sites in Southeast China. (C) 2016 Elsevier B.V. All rights reserved.
The alga Cladophora glomerata can erupt in nuisance blooms throughout the lower
Great Lakes. Since bacterial abundance increases with the emergence and decay of
Cladophora, we investigated the prevalence of antibiotic resistance (ABR) in
Cladophora-associated bacterial communities up-gradient and down-gradient from a
large sewage treatment plant (STP) on Lake Ontario. Although STPs are well-known
sources of ABR, we also expected detectable ABR from up-gradient wetland
communities, since they receive surface run-off from urban and agricultural
sources. Statistically significant differences in aquatic bacterial abundance and
ABR were found between down-gradient beach samples and up-gradient coastal wetland
samples (ANOVA, Holm-Sidak test, p < 0.05). Decaying and free-floating Cladophora
sampled near the STP had the highest bacterial densities overall, including on
ampicillin-and vancomycin-treated plates. However, quantitative polymerase chain
reaction analysis of the ABR genes ampC, tetA, tetB, and vanA from environmental
communities showed a different pattern. Some of the highest ABR gene levels
occurred at the 2 coastal wetland sites (vanA). Overall, bacterial ABR profiles
from environmental samples were distinguishable between living and decaying
Cladophora, inferring that Cladophora may control bacterial ABR depending on its
life-cycle stage. Our results also show how spatially and temporally dynamic ABR is
in nearshore aquatic bacteria, which warrants further research.
The seasonal variation and removal efficiency of antibiotic resistance genes
(ARGs), including tetracycline resistance genes (tetG, tetM, and tetX) and
macrolide (ermB, ermF, ereA, and mefA), were investigated in two typical swine
wastewater treatment systems in both winter and summer. ARGs, class 1 integron
gene, and 16S rRNA gene were quantified using real-time polymerase chain reaction
assays. There was a 0.31-3.52 log variation in ARGs in raw swine wastewater, and
the abundance of ARGs in winter was higher than in summer. tetM, tetX, ermB, ermF,
and mefA were highly abundant. The abundance of ARGs was effectively reduced by
most individual treatment process and the removal efficiencies of ARGs were higher
in winter than in summer. However, when examining relative abundance, the fate of
ARGs was quite variable. Anaerobic digestion reduced the relative abundance of
tetX, ermB, ermF, and mefA, while lagoon treatment decreased tetM, ermB, ermF, and
mefA. Sequencing batch reactor (SBR) decreased tetM, ermB, and ermF, but biofilters
and wetlands did not display consistent removal efficiency on ARGs in two sampling
seasons. As far as the entire treatment system is concerned, ermB and mefA were
effectively reduced in both winter and summer in both total and relative abundance.
The relative abundances of tetG and ereA were significantly correlated with intI1
(p<0.01), and both tetG and ereA increased after wastewater treatment. This may
pose a great threat to public health.
The objectives of this study were to determine the kinetic parameters of purified
recombinant Bla(Mab) and Bla(Mmas) by spectrophotometry, analyze the genetic
environment of the bla(Mab) and bla(Mmas) genes in both species by polymerase chain
reaction and sequencing, furthermore, in silico models of both enzymes in complex
with imipenem were obtained by modeling tools. Our results showed that Bla(Mab) and
Bla(Mmas) have a similar hydrolysis behavior, displaying high catalytic
efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are
well inhibited by clavulanate. Bla(Mmas) hydrolyzes imipenem at higher efficiency
than cefotaxime and aztreonam. Bla(Mab) and Bla(Mmas) showed that their closest
structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase
activity toward imipenem observed at least for BlaMmas. They also seem to differ
from other class A -lactamases by the presence of a more flexible loop, which could
impact in the hydrolysis efficiency against some antibiotics. A -35 consensus
sequence (TCGACA) and embedded at the 3 end of MAB_2874, which may constitute the
bla(Mab) and bla(Mmas) promoter. Our results suggest that the resistance mechanisms
in fast-growing mycobacteria could be probably evolving toward the production of -
lactamases that have improved catalytic efficiencies against some of the drugs
commonly used for the treatment of mycobacterial infections, endangering the use of
important drugs like the carbapenems.
Natural tetracycline (TC) antibiotics were the first major class of therapeutics to
earn the distinction of 'broad-spectrum antibiotics' and they have been used since
the 1940s against a wide range of both Gram-positive and Gram-negative pathogens,
mycoplasmas, intracellular chlamydiae, rickettsiae and protozoan parasites. The
second generation of semisynthetic tetracyclines, such as minocycline and
doxycycline, with improved antimicrobial potency, were introduced during the 1960s.
Despite emerging resistance to TCs erupting during the 1980s, it was not until
2006, more than four decades later, that a third-generation TC, named tigecycline,
was launched. In addition, two TC analogues, omadacycline and eravacycline,
developed via (semi)synthetic and fully synthetic routes, respectively, are at
present under clinical evaluation. Interestingly, despite very productive early
work on the isolation of a Streptomyces aureofaciens mutant strain that produced 6-
demethyl-7-chlortetracycline, the key intermediate in the production of second- and
third-generation TCs, biosynthetic approaches in TC development have not been
productive for more than 50 years. Relatively slow and tedious molecular biology
approaches for the genetic manipulation of TC-producing actinobacteria, as well as
an insufficient understanding of the enzymatic mechanisms involved in TC
biosynthesis have significantly contributed to the low success of such biosynthetic
engineering efforts. However, new opportunities in TC drug development have arisen
thanks to a significant progress in the development of affordable and versatile
biosynthetic engineering and synthetic biology approaches,. and, importantly, to a
much deeper understanding of TC biosynthesis, mostly gained over the last two
decades.
abYsis is a web-based antibody research system that includes an integrated database
of antibody sequence and structure data. The system can be interrogated in numerous
ways from simple text and sequence searches to sophisticated queries that apply 3D
structural constraints. The publicly available version includes pre-analyzed
sequence data from the European Molecular Biology Laboratory European Nucleotide
Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank.
A researcher's own sequences can also be analyzed through the web interface. A
defining characteristic of abYsis is that the sequences are automatically numbered
with a series of popular schemes such as Kabat and Chothia and then annotated with
key information such as complementarity-determining regions and potential post-
translational modifications. A unique aspect of abYsis is a set of residue
frequency tables for each position in an antibody, allowing "unusual residues"
(those rarely seen at a particular position) to be highlighted and decisions to be
made on which mutations may be acceptable. This is especially useful when comparing
antibodies from different species. abYsis is useful for any researcher specializing
in antibody engineering, especially those developing antibodies as drugs. abYsis is
available at www.abysis.org. (C) 2016 Published by Elsevier Ltd.
The introduction of more sensitive techniques, such as LuminexA (R) for HLA
antibody screening of patients awaiting organ transplantation has resulted in a
better understanding of transplantation immunology and improvements in clinical
practice. The interpretation of the results obtained only by LuminexA (R) can lead
to inaccurate evaluation of a patient's antibody status and unjustified rejection
of a potential organ donor. The aim of this study was to demonstrate the benefits
of performing HLA antibody screening in the sera of patients on the waiting list
for organ transplantation by two different assays, complement dependent
cytotoxicity (CDC) and LuminexA (R). A retrospective analysis was performed on 563
pretransplant serum samples from 141 patients on the kidney transplantation waiting
list in Rijeka, tested from March 2012 until March 2015. All samples were tested in
parallel by the CDC assay and the LuminexA (R)-based assay. Out of the 563 samples
tested 302 (53.7%) tested negative for HLA antibodies and 88 (15.6%) positive by
both assays. From 173 (30.7%) samples with discordant results 149 (26.5%) were CDC
negative and LuminexA (R) positive, while 24 (4.3%) were CDC positive and LuminexA
(R) negative. Among the Luminex positive patients seven did not experience any
immunizing events. Evaluation of the HLA antibody status in patients on a waiting
list for organ transplantation should be based on the results of the both CDC and
LuminexA (R) (or other sensitive) assays in accordance to information about
patient's clinical status and exposure to immunizing events.
Effects in the liver of fatal intoxication with the binary toxin ricin are unclear.
We report a robust neutrophil influx into the liver of C57BL/6 mice after lethal
parenteral ricin challenge, occurring in peri-portal and centro-lobular hepatic
areas within 2 h, followed by the abrupt disappearance of hepatic
macrophages/Kupffer cells. Chemokine profiles determined by microarray,
ribonuclease protection assays, northern blotting, and enzyme-linked immunosorbent
assays showed rapid (2 h) upregulation and persistence of those for neutrophils
(CXCL1/KC, CXCL2/MIP-2) and monocytes (CCL2/MCP-1). Red blood cell pooling (8-12
h), loss of hepatocyte glycogen (8-48 h) associated with progressive hypoglycemia,
fibrin deposition (24-48 h), and death (72-96 h) followed. Monoclonal antibody to
ricin A chain, administered intravenously, blunted hypoglycemia, and abrogated
death. This outcome was observed when anti-ricin antibody was given before toxin
exposure as well as when administered approximately 10 h after toxin exposure.
Targeting antibody to specific amino-acid sequences on the ricin A chain (HAEL and
QXXWXXA) was critical to the therapeutic effect. Re-emergence of liver
macrophages/Kupffer cells and replenishment of glycogen in previously depleted
hepatocytes preceded full recovery of the host. These data identify critical events
for liver injury and healing in ricin intoxication, as well as a new means and
specific targets for post- exposure therapeutic intervention.
HIV-1 infection occurs primarily through mucosal transmission. Application of
biologically relevant mucosal models can advance understanding of the functional
properties of antibodies that mediate HIV protection, thereby guiding antibody-
based vaccine development. Here, we employed a human ex vivo vaginal HIV-1
infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to
probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-
neutralizing Abs (nnAbs) that were functionally modified by isotype switching. For
human vaginal explants, we developed a replication-competent, secreted NanoLuc
reporter virus system and showed that CD4 binding site bnAbs b12 IgG1 and CH31 IgG1
and IgA2 isoforms potently blocked HIV-1JR-CSF and HIV-1Bal26 infection. However,
IgG1 and IgA nnAbs, either alone or together, did not inhibit infection despite the
presence of FcR-expressing effector cells in the tissue. In macaques, the CH31 IgG1
and IgA2 isoforms infused before high-dose SHIV challenge were completely to
partially protective, respectively, while nnAbs (CH54 IgG1 and CH38 mIgA2) were
non-protective. Importantly, in both mucosal models IgG1 isotype bnAbs were more
protective than the IgA2 isotypes, attributable in part to greater neutralization
activity of the IgG1 variants. These findings underscore the importance of potent
bnAb induction as a primary goal of HIV-1 vaccine development. (C) 2016 The
Authors. Published by Elsevier B.V.
Immunoglobulin therapy is a key element in the management of most patients with
primary immunodeficiency disease. Allergist/immunologists should be familiar with
the appropriate evaluation of candidates for immunoglobulin, the characteristics of
immunoglobulin products, and how to use them to provide the best care to their
patients. Available immunoglobulin products appear to be equally efficacious, but
they are not interchangeable. Minimizing the risk of serious adverse events and
controlling minor side effects is important to ideal patient care. Immunoglobulin
may be administered intravenously or subcutaneously. Individualizing the choice of
immunoglobulin product, mode of administration, and site of care can optimize the
clinical outcome and minimize the burden of care. (C) 2016 American Academy of
Allergy, Asthma & Immunology.
Since the development of antibody-production techniques, a number of
immunoglobulins have been developed on a large scale using conventional methods.
Hybridoma technology opened a new horizon in the production of antibodies against
target antigens of infectious pathogens, malignant diseases including autoimmune
disorders, and numerous potent toxins. However, these clinical humanized or
chimeric murine antibodies have several limitations and complexities. Therefore, to
overcome these difficulties, recent advances in genetic engineering techniques and
phage display technique have allowed the production of highly specific recombinant
antibodies. These engineered antibodies have been constructed in the hunt for novel
therapeutic drugs equipped with enhanced immunoprotective abilities, such as
engaging immune effector functions, effective development of fusion proteins,
efficient tumor and tissue penetration, and high-affinity antibodies directed
against conserved targets. Advanced antibody engineering techniques have extensive
applications in the fields of immunology, biotechnology, diagnostics, and
therapeutic medicines. However, there is limited knowledge regarding dynamic
antibody development approaches. Therefore, this review extends beyond our
understanding of conventional polyclonal and monoclonal antibodies. Furthermore,
recent advances in antibody engineering techniques together with antibody
fragments, display technologies, immunomodulation, and broad applications of
antibodies are discussed to enhance innovative antibody production in pursuit of a
healthier future for humans.
Somatic mutations within the antibody variable domains are critical to the immense
capacity of the immune repertoire. Here, via a deep mutational scan, we dissect how
mutations at all positions of the variable domains of a high-affinity anti-VEGF
antibody G6.31 impact its antigen-binding function. The resulting mutational
landscape demonstrates that large portions of antibody variable domain positions
are open to mutation, and that beneficial mutations can be found throughout the
variable domains. We determine the role of one antigen-distal light chain position
83, demonstrating that mutation at this site optimizes both antigen affinity and
thermostability by modulating the interdomain conformational dynamics of the
antigen-binding fragment. Furthermore, by analyzing a large number of human
antibody sequences and structures, we demonstrate that somatic mutations occur
frequently at position 83, with corresponding domain conformations observed for
G6.31. Therefore, the modulation of interdomain dynamics represents an important
mechanism during antibody maturation in vivo.
Lung cancer has the highest mortality rate among cancer patients in the world, in
particular because most patients are only diagnosed at an advanced and noncurable
stage. Computed tomography (CT) screening on high-risk individuals has shown that
early detection could reduce the mortality rate. However, the still high false-
positive rate of CT screening may harm healthy individuals because of unnecessary
follow-up scans and invasive follow-up procedures. Alternatively, false-negative
and indeterminate results may harm patients due to the delayed diagnosis and
treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening,
could lower the false-positive and false-negative rate of CT screening at baseline
and thereby reduce the number of patients that need follow-up and diagnose patients
at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-
associated proteins to which the immune system might produce high-affinity
autoantibodies. This autoantibody response to tumor-associated antigens starts
during early stage lung cancer and may endure over years. Identification of tumor-
associated antigens or the corresponding autoantibodies in body fluids as potential
noninvasive biomarkers could thus be an effective approach for early detection and
monitoring of lung cancer. We provide an overview of differentially expressed
protein, antigen, and autoantibody biomarkers that combined with CT imaging might
be of clinical use for early detection of lung cancer.
Immune defenses are expected to be crucial for survival under the considerable
parasite pressures experienced by wild animals. However, our understanding of the
association between immunity and fitness in nature remains limited due to both the
complexity of the vertebrate immune system and the often-limited availability of
immune reagents in nonmodel organisms. Here, we use methods and reagents developed
by veterinary researchers for domestic ungulates on blood samples collected from a
wild Soay sheep population, to evaluate an unusually broad panel of immune
parameters. Our evaluation included different innate and acquired immune cell types
as well as nematode parasite-specific antibodies of different isotypes. We test how
these markers correlate with one another, how they vary with age-group and sex,
and, crucially, whether they predict over-winter survival either within or among
demographic groups. We found anticipated patterns of variation in markers with age,
associated with immune development, and once these age trends were accounted for,
correlations among our 11 immune markers were generally weak. We found that females
had higher proportions of naive T cells and gamma-delta T cells than males,
independent of age, while our other markers did not differ between sexes. Only one
of our 11 markers predicted overwinter survival: sheep with higher plasma levels of
anti-nematode IgG antibodies were significantly more likely to survive the
subsequent high mortality winter, independent of age, sex, or weight. This supports
a previous finding from this study system using a different set of samples and
shows that circulating antibody levels against ecologically relevant parasites in
natural systems represent an important parameter of immune function and may be
under strong natural selection. Our data provide rare insights into patterns of
variation among age-and sex groups in different T-cell subsets and antibody levels
in the wild, and suggest that certain types of immune response-notably those likely
to be repeatable within individuals and linked to resistance to ecologically
relevant parasites-may be most informative for research into the links between
immunity and fitness under natural conditions.
The scale and scope of the global epidemic, coupled to challenges with traditional
vaccine development approaches, point toward a need for novel methodologies for HIV
vaccine research. While the development of vaccines able to induce broadly
neutralizing antibodies remains the ultimate goal, to date, vaccines continue to
fail to induce these rare humoral immune responses. Conversely, growing evidence
across vaccine platforms in both non-human primates and humans points to a role for
polyclonal vaccine-induced antibody responses in protection from infection. These
candidate vaccines, despite employing disparate viral vectors and immunization
strategies, consistently identify a role for functional or non-traditional antibody
activities as correlates of immunity. However, the precise mechanism(s) of action
of these binding antibodies, their specific characteristics, and their ability to
be selectively induced and/or potentiated to result in complete protection merits
parallel investigation to neutralizing antibody-based vaccine design approaches.
Ultimately, while neutralizing and functional antibody-based vaccine strategies
need not be mutually exclusive, defining the specific characteristics of protective
functional antibodies may provide a target immune profile to potentially induce
more robust immunity against HIV. Specifically, one approach to guide the
development of functional antibody-based vaccine strategies, termed systems
serology, offers an unbiased and comprehensive approach to systematically survey
humoral immune responses, capturing the array of functions and humoral response
characteristics that may be induced following vaccination with high resolution.
Coupled to machine learning tools, large datasets that explore the antibody-ome
offer a means to step back from anticipated correlates and mechanisms of protection
and toward a more fundamental understanding of coordinated aspects of humoral
immune responses, to more globally differentiate among vaccine candidates, and most
critically, to identify the features of humoral immunity that distinguish
protective from non-protective responses. Overall, the systematic serological
approach described here aimed at broadly capturing the enormous biodiversity in
antibody profiles that may emerge following vaccination, complements the existing
cutting edge tools in the cellular immunology space that survey vaccine-induced
polyfunctional cellular activity by flow cytometry, transcriptional profiling,
epigenetic, and metabolomic analysis to offer a means to develop both a more
nuanced and a more complete understanding of correlates of protection to support
the design of functional vaccine strategies.
Acute myeloid leukemia (AML) is characterized by the proliferation of immature
myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired
drug resistance and relapse, new treatment strategies are needed. Here, we
demonstrate that IFN promotes AML blasts to act as effector cells within the
context of antibody therapy. Treatment with IFN drove AML blasts toward a more
differentiated state, wherein they showed increased expression of the M1-related
markers HLA-DR and CD86, as well as of FcRI, which mediates effector responses to
therapeutic antibodies. Importantly, IFN was able to up-regulate CD38, the target
of the therapeutic antibody daratumumab. Because the antigen (CD38) and effector
receptor (FcRI) were both simultaneously up-regulated on the AML blasts, we tested
whether IFN treatment of the AML cell lines THP-1 and MV4-11 could stimulate them
to target one another after the addition of daratumumab. Results showed that IFN
significantly increased daratumumab-mediated cytotoxicity, as measured both by Cr-
51 release and lactate dehydrogenase release assays. We also found that the
combination of IFN and activation of FcR led to the release of granzyme B by AML
cells. Finally, using a murine NSG model of subcutaneous AML, we found that
treatment with IFN plus daratumumab significantly attenuated tumor growth. Taken
together, these studies show a novel mechanism of daratumumab-mediated killing and
a possible new therapeutic strategy for AML.
Bacillus thuringiensis (Bt) is known as the most successful microbial insecticide
against different orders of insect pests in agriculture and medicine. Moreover, Bt
toxin genes also have been efficiently used to enhance resistance to insect pests
in genetically modified crops. In light of the scientific advantages of new
molecular biology technologies, recently, some other new potentials of Bt have been
explored. These new environmental features include the toxicity against nematodes,
mites, and ticks, antagonistic effects against plant and animal pathogenic bacteria
and fungi, plant growth-promoting activities (PGPR), bioremediation of different
heavy metals and other pollutants, biosynthesis of metal nanoparticles, production
of polyhydroxyalkanoate biopolymer, and anticancer activities (due to parasporins).
This review comprehensively describes recent advances in the Bt whole-genome
studies, the last updated known Bt toxins and their functions, and application of
cry genes in plant genetic engineering. Moreover, the review thoroughly describes
the new features of Bt which make it a suitable cell factory that might be used for
production of different novel valuable bioproducts.
The aim of this study was to investigate the effect of costimulation blockade with
cytotoxic T-lymphocyte-associated-antigen 4-immunoglobulin (CTLA4Ig) and anti-CD40L
monoclonal antibody (anti-CD40L mAb) on an experimental autoimmune myocarditis
(EAM) mouse model. Characteristics of myocardial tissue were observed by
hematoxylin and eosin (H&E) staining. The messenger RNA (mRNA) levels of CTLA4,
CD40L, IFN-gamma, and IL-4 were detected by real-time fluorescence quantitative
polymerase chain reaction (RT-qPCR). Serum concentrations of IFN-gamma and IL-4
were determined by ELISA. After immune intervention, the inflammatory score, mRNA
levels of CTLA4 and CD40L, and IFN-gamma level were decreased. Furthermore, these
parameters in the combinational intervention group (blockade by CTLA4Ig and anti-
CD40L mAb) were significantly decreased, compared to the single intervention group
(blockade by CTLA4Ig or anti-CD40L mAb). However, after costimulation, blockade
serum IL-4 levels were increased. Therefore, costimulation blockade by combination
CTLA4Ig and anti-CD40L mAb could more effectively inhibit the inflammatory response
of EAM than single use of CTLA4Ig or anti-CD40L mAb.
Objective: Arginine-specific cysteine proteases (Rgps) from Porphyromonas
gingivalis are important virulent factors of periodontal diseases. However, there
is no therapeutic drug that inhibits proinflammatory events induced by these
enzymes. In this study, we investigated proinflammatory activities of Rgps and
activated coagulation factor X (FXa) and examined the effect of DX-9065a, a new
selective inhibitor of FXa, on proinflammatory events induced by these proteinases.
Methods: Human gingival fibroblasts were stimulated with Rgps and FXa in the
presence or absence of DX-9065a, and then interleukin-6 (IL-6) and matrix
metalloproteinase-1 (MMP-1) release, their mRNA expression, and nuclear factor
kappa B (NF-kappa B) activation were assessed using an enzyme-linked immunosorbent
assay (ELISA), northern blotting, and a gel-mobility shift method, respectively.
Results: Rgps and FXa activated IL-6 and MMP-1 release in human gingival
fibroblasts through their amidolytic activities and in mitogen-activated protein
kinase (MAPK) and NF-kappa B dependent manners. DX-9065a inhibited FXa-mduced IL-6
mRNA expression and NF-kappa B activation. DX-9065a inhibited amidolytic activities
of FXa and Rgps in vitro and ex vivo. Conclusion: Rgps and FXa are potent
inflammatory mediators and DX-9065a may be a useful therapeutic drug for
periodontal disease.
In this study, drug target was identified using KEGG database and network analysis
through Cytoscape software. Designed series of novel benzimidazoles were taken
along with reference standard Flibanserin for insilico modeling. The novel 4-(1H-
benzo[d]imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a-j) analogs were
synthesized and evaluated for their antidepressant activity. Reaction of 4-(1H-
benzo[d]imidazol-2-yl)-4-oxobutanoic acid (1) with 4-(1H-benzo [d] imidazol-2-yl)-
4-oxobutanoyl chloride (2) furnished novel 4-(1H-benzo [d] imidazol-2-yl)-N-
(substituted phenyl)-4-oxobutanamide (3a-j). All the newly synthesized compounds
were characterized by IR, H-1-NMR, and mass spectral analysis. The antidepressant
activities of synthesized derivatives were compared with standard drug clomipramine
at a dose level of 20mg/kg. Among the derivatives tested, most of the compounds
were found to have potent activity against depression. The high level of activity
was shown by the compounds 3d, 3e, 3i, and it significantly reduced the duration of
immobility time at the dose level of 50mg/kg.
ObjectiveTo explore the prevalence and clinical profile of males and females who
develop antidepressant treatment-emergent mania (ATEM). MethodFrom an original
sample of 754 patients with BD, we identified ATEM+ cases (n = 75) and ATEM-
controls (n = 135) that met stringent criteria. We specifically examined the
combinations of clinical factors that best classified males and females as ATEM+
cases. ResultsSeventy-five individuals were classified as ATEM+; 87% of ATEM events
occurred during antidepressant monotherapy. Regression analyses demonstrated that
the presence of an alcohol and/or substance use disorder [Odds Ratio (OR) 6.37], a
history of one or more suicide attempts (OR 4.19) and higher number of depressive
episodes per year of illness (OR 1.71) correctly classified 73% of males. In
contrast, 84% of females were correctly classified on the basis of a positive
history of thyroid disorder (OR 3.23), a positive family history of BD I (OR 2.68)
and depressive onset polarity (OR 2.01). ConclusionUsing stringent definitions of
ATEM status to reduce the probability of inclusion of false-positive cases and
false-negative controls, we identified for the first time that the risk profiles
for the development of an ATEM differ significantly according to gender.
Approximately 40% of patients treated for depression do not respond to a trial of
an antidepressant. The aim of the proposed study was to evaluate the efficacy and
safety of switching to vilazodone in patients with major depressive disorder who
are unresponsive or only partially responsive to a trial of citalopram. Seventy-
nine adults with major depressive disorder were enrolled in an open-label study of
citalopram (20mg/day) for 6 weeks. Those still symptomatic after 6-weeks of
citalopram were randomly assigned to either a higher dose of citalopram (40mg/day)
or to vilazodone in a double-blind trial for 6 weeks. Of those who received
citalopram 20mg/day for 6 weeks, 20.3% were responders' (defined as 50% reduction
on the Montgomery-angstrom sberg Depression Rating Scale). Of the 42 who did not
respond, 23 were assigned to citalopram 40mg/day and 19 were randomized to 40mg/day
of vilazodone. Both groups showed decreases in all outcome measures, but there were
no significant differences between groups. Initial nonresponders to a low dose of
citalopram seem equally likely to respond to a higher dose of citalopram or to
vilazodone. Whether to increase an selective serotonin reuptake inhibitor or switch
to a different antidepressant may be best determined on the basis of their adverse
event profile.
Background: Major depressive disorder (MDD) is often resistant to treatment with
usual approaches. Patients with MDD have shown hypofunction of the frontotemporal
cortex in verbal fluency test (VFT)-related near-infrared spectroscopy (NIRS).
Methods: We examined whether the reactions to drug treatment in treatment-naive
patients with MDD could be predicted by NIRS outcomes at the initial investigation.
All subjects underwent psychological testing to determine levels of anxiety and
depression. VFT was used to examine the functioning of the frontotemporal lobes. We
administered selective serotonin reuptake inhibitors (SSRIs) for 12 weeks. Subjects
included 28 patients with MDD with response to SSRIs (Response group), 19 with no
response (Non-Response group), and 63 age-, sex-, and education years-matched
healthy controls (HC). Results: We found in the frontotemporal region that
hemodynamic responses were significantly smaller in patients with Response and Non-
Response groups than in HC before treatment. We also found in the medial frontal
region that hemodynamic responses were significantly larger in patients with
Response groups than in patients with Non-Response group before treatment. Patients
with MDD scored significantly higher anxiety and depressive states than those in HC
on several measures. The Response and Non-Response groups also had higher scores in
future denial, threat prediction, self-denial, past denial, and interpersonal
threat sections of Anxiety Cognition Scale (DACS). According to the stepwise
regression analysis, one variable was determined as independent predictors of
response: confusion (Post-POMS). Limitations: The number of patients and healthy
controls was relatively small, and we will increase the number of participants in
future studies. NIRS has reduced spatial resolution, which confuses the
identification of the measurement position when using NIRS alone. Conclusion:
Cognitive vulnerabilities are associated with predictors of SSRI treatment
response. Different hemodynamic activities in the frontotemporal cortex predict
response to SSRI treatment in MDD.
No study has investigated psychological dependence on antidepressants in patients
with panic disorder, which was addressed in this study. This study was carried out
in four psychiatric clinics in Tokyo, Japan. Individuals were eligible if they were
outpatients aged 18 years or older and fulfilled the diagnostic criteria for panic
disorder (ICD-10). Assessments included the Japanese Versions of the Severity of
Dependence Scale (SDS), the Self-Report Version of Panic Disorder Severity Scale
(PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report.
Eighty-four individuals were included; of these, 30 patients (35.7%) showed
psychological dependence on antidepressants (i.e. a total score of >= 5 in the
SDS). A multiple regression analysis showed that PDSS scores and illness duration
were correlated positively with SDS total scores. A binary regression model showed
that absence of remission (i.e. a total score of >= 5 in the PDSS) and longer
duration of illness increased the risk of dependence on antidepressants.
Approximately one-third of the patients with panic disorder, receiving
antidepressants, fulfilled the criteria for psychological dependence on these
drugs. The results underscore the need for close monitoring, especially for those
who present severe symptomatology or have a chronic course of the illness.
Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Objective: To assess systematically the effects of antidepressants and untreated
maternal depression on human placenta and the developing fetus.Methods: Pertinent
medical literature information was identified using MEDLINE/PubMed, SCOPUS and
EMBASE. Electronic searches, limited to human studies published in English,
provided 21 studies reporting primary data on placental and fetal effects of
antidepressant exposure or untreated gestational depression.Results: The impact of
antidepressants and non-medicated maternal depression on placental functioning and
fetal biochemical architecture seems to be demonstrated, although its clinical
significance remains unclear. More robust data seem to indicate that exposure to
either antidepressants or untreated maternal depression may induce epigenetic
changes and interfere with the physiological fetal behavior. Two cases of
iatrogenic fetal tachyarrhythmia have also been reported.Conclusions: Future
research should clarify the clinical relevance of the impact of antidepressant and
untreated maternal depression exposure on placental functioning. Moreover,
ultrasound studies investigating fetal responses to antidepressants or maternal
depressive symptoms are mandatory. This assessment should be performed during the
whole duration of gestational period, when different fetal behavioral patterns
become progressively detectable. Analyses of biochemical and epigenetic
modifications associated with maternal mood symptoms and antidepressant treatment
should also be implemented.
Antibodies against the toxin portion of recombinant immunotoxins (RIT) reduce their
efficacy and pose a potential safety risk. To overcome this problem we mutated the
very immunogenic immunotoxin SS1P to produce LMB-T20, a de-immunized RIT that has
the eight human T-cell epitopes in SS1P modified or removed. To determine the
effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-
competent BALB/c mice and found that these mice recognize two epitopes. One
corresponds to the human immunodominant T-cell epitope and the other to a human
subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized
with LMB-T20 did not have T-cell activation and did not develop anti-drug
antibodies (ADA), whereas mice immunized with SS1P, showed T-cell activation, and
developed ADA detected by both ELISA and drug neutralizing assays. The ability of
the mice treated with LMB-T20 to respond to other antigens was not compromised. We
conclude that elimination of T-cell epitopes is sufficient to prevent formation of
antibodies to an immunogenic foreign protein.Cellular & Molecular Immunology (2017)
published online 19 October 2015
Objectives - Whether and when to immunologically treat epilepsy patients with
suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically
challenging. Therefore, we evaluated the clinical outcome and eventual outcome
predictors of immunotherapy in a group of AB-negative patients with recent-onset
temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE,
subjective cognitive decline, and/or psychiatric symptoms. Methods - This
retrospective, observational, uncontrolled study monitored 28 TLE patients with
suggested AB-negative LE along with methylprednisolone immunotherapy. Results - All
patients had seizures, amygdala and/or - hippocampal enlargement, subjective
cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were
impaired in executive or memory functions, 39% (10/25) depressed, 81% were on
antiepileptic drugs when pulse therapy started. After a median follow-up of 18
months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27)
showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition
improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and
deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical
changes did not correlate to each other. Outcomes could not be predicted.
Conclusion - Immunological treatment of suggested AB-negative LE showed reasonable
seizure control, MRI and cognitive improvements. Treatment success was not
predictable from clinical features, nor definitely attributable to immunological
treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we
suggest that in presence of mild manifestations, and after initiating antiepileptic
drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be
documented before immunosuppressive treatment is initiated.
ERp57 is a member of a protein disulfide isomerase family and is a chaperone
responsible for the correct folding of newly synthesized glycoproteins in the
endoplasmic reticulum and in the assembly of the major histocompatibility complex
class I in the endogenous pathway of antigen presentation. This study reports the
identification of a full length ERp57 cDNA in rainbow trout that encodes a putative
477aa mature protein with an additional signal sequence of 16aa. The trout protein
shared 75% identity with the human homolog, but interestingly did not include
either a C terminal endoplasmic reticulum retention signal, Q/KEDL in humans, or a
nuclear localization signal which is highly conserved in mammals. Amino acid
sequence alignment revealed conservation of four classical domains in trout ERp57
and two conserved active CXXC redox motifs. Trout ERp57 protein was identified as a
single band around 57 kDa. Southern blotting analysis revealed that there two
copies of the ERp57 gene in the trout genome and northern blotting showed a wide
tissue distribution of gene expression in various tissues with the highest
expression in liver and egg. This study showed for the first time in teleost that
ERp57 transcript is upregulated in response to immune stimuli such as double
stranded RNA or phytohemagglutinin. Furthermore, upon treatment with ER stress
inducer A23187, trout ERp57 protein expression levels were increased both in
peripheral blood leukocytes and the RTS11 macrophage like cell line after 6 and 8 h
respectively. These findings suggest a possible conserved function for trout ERp57
in the ER and during the activation of the immune response. (C) 2012 Elsevier Ltd.
All rights reserved.
The MHC class I and II antigen processing and presentation pathways display
peptides to circulating CD8(+) cytotoxic and CD4(+) helper T cells respectively to
enable pathogens and transformed cells to be identified. Once detected, T cells
become activated and either directly kill the infected /transformed cells (CD8(+)
cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune
response (CD4(+) T cells). The immune surveillance of transformed/tumour cells
drives alteration of the antigen processing and presentation pathways to evade
detection and hence the immune response. Evasion of the immune response is a
significant event tumour development and considered one of the hallmarks of cancer.
To avoid immune recognition, tumours employ a multitude of strategies with most
resulting in a down-regulation of the MHC class I expression at the cell surface,
significantly impairing the ability of CD8(+) cytotoxic T lymphocytes to recognize
the tumour. Alteration of the expression of key players in antigen processing not
only affects MHC class I expression but also significantly alters the repertoire of
peptides being presented. These modified peptide repertoires may serve to further
reduce the presentation of tumour-specific/associated antigenic epitopes to aid
immune evasion and tumour progression. Here we review the modifications to the
antigen processing and presentation pathway in tumours and how it affects the anti-
tumour immune response, considering the role of tumour-infiltrating cell
populations and highlighting possible future therapeutic targets.
In the treatment of hemophilia A, the 20%-30% risk of developing of anti-factor
VIII (FVIII) antibodies, or inhibitors, is the dominant concern among healthcare
providers. Immune tolerance induction remains the only effective method of
eradicating inhibitors in approximately 75% of patients, but is accompanied by
significant emotional and economical burden. While certain risk factors, such as
the type of FVIII mutation, offer some insight, there remains no strategy to
confidently predict the development of an inhibitor. Moreover, even if such a
predictive tool existed, there is currently no proven protocol for tolerance
induction of a previously untreated patient. In recent years, the growing body of
knowledge concerning the fundamental immunology of inhibitors has shed light on
potential therapeutic interventions. In this review, we highlight these new
findings and their influences on translational medicine.
Mycobacterium tuberculosis produces dideoxymy-cobactin- 838 (DDM-838), a
lipopeptide that potently activates T cells upon binding to the MHC-like antigen-
presenting molecule CD1a. M. tuberculosis produces DDM-838 in only trace amounts
and a previous solid-phase synthesis provided sub-milligram quantities. We describe
a high-yielding solution-phase synthesis of DDM-838 that features a Mitsunobu
substitution that avoids yield-limiting epimerization at lysine during
esterification, and amidation conditions that prevent double-bond isomerization of
the Z-C20:1 acyl chain, and provides material with equivalent antigenicity to
natural DDM-838. Isomers of DDM-838 that varied in stereochemistry at the central
lysine and the C20:1 acyl chain were compared for their ability to be recognised by
CD1a-restricted T cell receptors (TCRs). These TCRs, derived from unrelated human
donors, exhibited a similar spectrum of reactivity towards the panel of DDM-838
isomers, highlighting the exquisite sensitivity of lipopeptide-reactive T cells for
the natural DDM stereochemistry.
The presence of anti-HLA antibodies in the serum of a patient result from an immune
response produced during an immunizing event as transfusion, pregnancy or graft.
These antibodies can be cytotoxic by activating the complement pathway via C1q and
may cause organ rejection during the transplant. Some male patients awaiting kidney
transplantation are seropositive for anti-HLA antibodies when they have no
immunizing antecedent event. These antibodies are qualified as natural antibodies.
Our work is to assess the cytotoxicity of natural anti-HLA antibodies in patients
followed at the immunology laboratory of the blood transfusion service and
hemovigilance (STSH) as part of the kidney transplant. Patients and methods. - We
evaluated the cytotoxicity of HLA antibodies detected in male Moroccan patients
without immunization history using C1q Screen One Lambda reagent for Luminex (TM)
Results. - Non-immunized men were positive for HLA antibodies screening in 25.4%.
These antibodies are not cytotoxic. Conclusion. - Our study showed a positivity
rate of natural HLA antibody low than the literature (25.4% against 63%). It
appears that these natural antibodies are not cytotoxic and their involvement in
renal transplant remains to be determined. (C) 2016 Association Societe de
nephrologie. Published by Elsevier Masson SAS. All rights reserved.
Glycyrrhiza uralensis has acquired significant importance due to its medicinal
properties and health function. In this study, the quality of G. uralensis
adventitious roots was evaluated in terms of genetic stability, active compounds,
and anti-inflammatory activity. Monomorphic banding pattern obtained from the
mother plant and tissue cultures of G. uralensis with randomly amplified
polymorphic DNA markers confirmed the genetic stability of adventitious roots.
Neoliquiritin (neoisoliquiritin), ononin, liquiritin, and glycyrrhizic acid were
identified from G. uralensis adventitious roots on the basis of high-performance
liquid chromatography-electrospray ionization-tandem mass spectrometry analysis.
This study also revealed that adventitious roots possessed a better anti-
inflammatory effect than native roots. To increase the contents of G. uralensis
active components, elicitors were used in the adventitious roots culture. The
combination of methyl jasmonate and phenylalanine synergistically stimulated the
accumulation of glycyrrhetinic acid (0.22 mg/g) and total flavonoid (5.43 mg/g)
compared with single treatment. In conclusion, G. uralensis adventitious roots can
be an exploitable system for the production of licorice. (C) 2016 International
Union of Biochemistry and Molecular Biology, Inc.
Background: One of the most significant contributors to morbidity and death in
patients with burns is infection, which accounts for 30%-75% of post-burn
fatalities. Because of concerns for the development of antibiotic resistance in
burn-related pathogens, the aims of this study were to identify antibiotic
resistance trends for the four most common burn-related pathogens over a six-year
period. Patients and Methods: The study used prospectively collected and de-
identified aggregate data for all burn patients admitted to the burn unit between
2009 and 2014. The database query included patient demographics along with all data
regarding cultures from any source (wound, sputum, urine, stool, blood), which
included isolated pathogens and antibiotic resistance profiles. Profiles were then
constructed using mean inhibitory concentration standards to determine whether each
pathogen was susceptible (S), intermediate (I), or resistant (R) to each
antibiotic. The aggregated data were then used to construct a heat map for the four
most common pathogens and their resistance profiles over the six-year study period.
Results: There were 368 patients with burns (248 with positive cultures, 120 with
negative cultures) in this study. The positive culture group was significantly
older (38 vs. 25y, p<0.001) and had longer hospitalizations (17 vs. 11 d, p<0.01)
compared with the negative group. Analysis of antibiotic resistance heat maps
constructed for the four most commonly isolated pathogens (methicillin-sensitive
Staphylococcus aureus, Enterococcus faecalis, methicillin-resistant S. aureus,
Pseudomonas aeruginosa) indicated a lack of notable resistance patterns for any of
the individual pathogens. Conclusions: Taken together, these results indicate that
there are no discernible patterns of antibiotic resistance across time (six years)
for the four most common burn-related pathogens. We conclude that antibiotic choice
in burn patients based on previous in-hospital trends may be a flawed strategy.
Emerging genomic technology to deliver point-of-care pathogen-specific antibiotic
sensitivities via polymerase chain reaction may be needed to more appropriately
guide antibiotic choice.
Antimicrobial peptides are central effector molecules in skin immunology. The
functions of antimicrobial peptides in skin diseases include the ability to act as
cytokines or growth factors, driving disorders such as psoriasis and rosacea, as
well as their action as natural antibiotics to control bacteria that influence
diseases such as atopic dermatitis and acne.
Purpose. The impact of an antimicrobial stewardship initiative on time to first
antibiotic dose and clinical outcomes in bacteremic patients was, evaluated.
Methods. A single-center, retrospective study was conducted for adult inpatients
who received antibiotics before and after implementation of a rapid administration
of antimicrobials by an infectious diseases specialist (RAIDS) protocol. Patients
admitted to an inpatient service from June to October 2011 (pre-RAIDS protocol) and
from December 2011 to February 2012 (post-RAIDS protocol) were eligible for
inclusion if (1) they were age 18 years or older, (2) their infection occurred two
or more days after hospital admission, and (3) they had a blood culture growing an
organism other than common skin contaminants (i.e., coagulase-negative
staphylococci, Bacillus species). The primary outcome was the time to the first
antibiotic dose (TFAD), defined as the time that elapsed from a positive blood
culture result to administration of the first empirical antimicrobial dose.
Results. A total of 111 bacteremic patients were included in the analysis.
Implementation of the RAIDS protocol led to significantly faster antibiotic order
entry, verification, and administration of empirical antibiotics in patients with
bacteremia. The median TFAD was approximately 8 hours faster in the post-RAIDS
group than in the pre-RAIDS group (9:09 hr:min versus 1:23 hr:min, p < 0.001).
Patients in the post-RAIDS group had a significant reduction in infection-related
mortality (p = 0.047), though all cause 30-day mortality was similar. Conclusion.
Early notification of an infectious diseases pharmacist about positive blood
cultures using the RAIDS protocol led to increased appropriateness of empirical
drug selection and a dramatic reduction in the administration of antibiotics and
was associated with decreased infection related mortality.
Background:Extrapulmonary tuberculosis (EPTB) constitutes about 15% to 20% of all
cases of tuberculosis (TB). The confirmation of EPTB has always been a challenge to
laboratory personnel. We aim to evaluate the diagnostic potential of immunostaining
with anti-MPT64 in various EPTB specimens.Materials and Methods:We studied a total
of 51 TB cases and 38 non-TB control specimens comprising of fine-needle aspirates
and formalin-fixed biopsies. These were investigated using a combination of the
Ziehl-Neelsen method, the Lowenstein-Jensen culture, immunostaining with anti-MPT64
and anti-BCG, and nested-polymerase chain reaction (PCR) for IS6110. Results of all
the tests were compared using nested-PCR as the gold standard.Results:Diagnostic
validation of immunostaining for anti-MPT64 was performed using nested-PCR as the
gold standard. The overall sensitivity, specificity, and positive and negative
predictive values for immunostaining with anti-MPT64 were 100%, 97%, 97%, and 100%,
respectively.Conclusions:Immunostaining using anti-MPT64 is a rapid and sensitive
method for establishing an early and specific diagnosis of Mycobacterium
tuberculosis infection. The technique is simple to be incorporated into routine
pathology laboratories.
Panax notoginseng, an important herbal medicine, has wide uses for its bioactive
compounds and health function. In this work, we compared the content of saponin in
cultivation and adventitious root. The total content of saponins in adventitious
root (8.48 mg.g(-1)) was found lower than in the native one (3-year-old) (34.34
mg.g(-1)). To enhance the content of bioactive compounds, we applied elicitors
jasmonic acid (JA) and methyl dihydrojasmonate (MDJ) to the adventitious root
culture. It was observed that the highest total content of saponins (71.94 mg.g(-
1)) was achieved after treatment with 5 mg.L-1 JA, which was 2.09-fold higher than
native roots and 8.45-fold higher than the control group. The findings from high-
performance liquid chromatography-electrospray ionization-tandem mass spectrometry
analysis showed that six new compounds were present after the treatment with the
elicitors. Furthermore, we found that JA and MDJ significantly upregulated the
expression of the geranyl diphosphate synthase, farnesyl diphosphate synthase,
squalene synthase, squalene epoxidase, dammarenediol synthase, and CYP716A47 and
CYP716A53v2 (CYP450 enzyme) genes; downregulated the expression of the cycloartenol
synthase gene; and increased superoxide dismutase and peroxidase activities. (C)
2016 International Union of Biochemistry and Molecular Biology, Inc.
Bioactive antioxidant peptides are more and more attracting the attention of food
manufacturers for their potential to transform food in functional food, able to
prevent a variety of chronic diseases associated with oxidative stress. In the
present study proteins extracted from different vegetable sources (KAMUT (R)
khorasan wheat, emmer, lupine and pea) were hydrolyzed with commercial enzymes and
Lactobacillus spp. strains. Hydrolysates were separated by size exclusion
chromatography and purified fractions were analyzed for their antioxidant activity.
Peptides from the fractions with the highest activity were identified by nanoLC-
ESI-QTOF-MS and thirteen peptides were selected for synthesis on the basis of their
sequence. Four peptides (VLPPQQQY, TVTSLDLPVLRW, VTSLDLPVLRW, FVPY) were found able
to scavenge superoxide anion and hydroxyl radicals, organic nitro-radicals (ABTS,
DPPH) and to inhibit lipid peroxidation. The impact of this work is targeted to add
hydrolysed vegetable proteins to reformulated functional food or to produce health-
promoting ingredients and nutraceuticals. (C) 2017 Elsevier Ltd. All rights
reserved.
BackgroundThere are few studies on the association between nutrient intake and
telomere length, which may reflect cumulative oxidative stress and indicate
biological ageing. In the present study, we evaluated longitudinal associations
between the consumption of micronutrients, including antioxidant nutrients and B
vitamins involved in one-carbon transfer pathways, and leukocyte telomere length
(LTL). MethodsThe study included 1958 middle-aged and older Korean men and women
(age range at baseline: 40-69 years) from a population-based cohort. We collected
dietary information at baseline using a semiquantitative food frequency
questionnaire (June 2001 to January 2003) and assessed the consumption of
micronutrients, including vitamins A, B-1, B-2, B-3, B-6, B-9 (folate), C and E, as
well as calcium, phosphorus, potassium, iron and zinc. We measured LTL using a
real-time polymerase chain reaction at the 10-year follow-up examination (February
2011 to November 2012). ResultsIn the multiple regression model adjusted for
potential confounders, LTL was positively associated with the consumption of
vitamin C (P < 0.05), folate (P = 0.05) and potassium (P = 0.05) in all
participants. In the age-stratified analysis, the association between the
consumption of vitamin C (P < 0.01), folate (P < 0.05) and potassium (P < 0.05)
with LTL was significant only among participants aged <50 years. ConclusionsOur
findings suggest that the earlier consumption of vitamin C, folate and potassium,
which are abundant in fruits and vegetables, can delay biological ageing in middle-
aged and older adults.
Rationale: Cigarette smoke extract inhibits chloride secretion in human bronchial
epithelial cells. Oxidants decrease gene expression, protein expression, and
function of the cystic fibrosis transmembrane conductance regulator (CFTR).
Objectives: Because cigarette smoke is a rich source of oxidants, we verified the
hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and
in vivo. Methods: The effects of cigarette smoke exposure on Calu-3 and T84 cell
CFTR expression and function were observed. Also studied were the nasal potential
differences (PDs) in 26 men (9 smokers, 17 nonsmokers) who had no detectable CFTR
gene mutations as determined during investigations for infertility. CFTR expression
and function were determined by Northern blotting, Western blotting, and cAMP-
dependent I-125 efflux assays. Extensive CFTR genotyping was performed in each
subject. Nasal PD measurements were made at baseline and during amiloride,
chloride-free buffer, and isoproterenol perfusions. Main Results: Cigarette smoke
decreased CFTR expression and function in Calu-3 and T84 cell lines. Furthermore,
the nasal PDs of cigarette smokers showed a pattern typical of CFTR deficiency with
a blunted response to chloride-free buffer and isoproterenol compared with
nonsmokers (-9.6 +/- 4.0 vs. -22.3 +/- 10.1 mV; p < 0.001). Conclusions: We
conclude that cigarette smoke decreases the expression of CFTR gene, protein, and
function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory
epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may
contribute to the physiopathology of cigarette-induced diseases such as chronic
bronchitis.
AIM: To investigate the molecular mechanism and functional consequences of heme
oxygenase-1 (HO-1) activation by lansoprazole in endothelial cells and macrophages.
METHODS: Expression of HO-1 mRNA was analyzed by Northern blotting. Western
blotting was used to determine the HO-1 and ferritin protein levels. NADPH-
dependent reactive oxygen species (ROS) formation was measured with lucigenin-
enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably
transfected with a 15-kb HO-1 gene that drives expression of the reporter gene
luciferase, was assessed using in vivo bioluminescence imaging. RESULTS:
Lansoprazole increased HO-1 mRNA levels in endothelial cells and HO-1 protein
levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in
both cell systems. Moreover, induction of the antioxidant proteins HO-1 and
ferritin by lansoprazole was followed by a decrease in NADPH-mediated ROS
formation. The radical scavenging properties of lansoprazole were diminished in the
presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene
expression by lansoprazole was not related to oxidative stress or to the activation
of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol
3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1
mRNA and promoter activity. CONCLUSION: Activation of HO-1 and ferritin may account
for the gastric protection of lansoprazole and is dependent on a pathway blocked by
LY294002. (C) 2009 The WIG Press and Baishideng. All rights reserved.
Plasma gelsolin (pGSN) is a multifunctional protein involved mainly in severing and
clearing of actin filaments. Its level correlates with inflammation and several
diseases making it a potential biomarker of diagnostic and prognostic values. The
pGSN level in groups of treated and untreated HIV-1-infected Indian patients is
investigated in this study. This study aims at investigating the levels of pGSN in
HIV-1-infected patients across different age, sex, severity of disease, and
treatment status. Blood samples of 213 patients were analyzed for CD4 counts by
flow cytometry and pGSN was quantified by enzyme-linked immunosorbent assay
(ELISA). The level of pGSN is significantly increased in HIV-1 infected patients
(227.2 +/- 54.3g/ml) compared to healthy volunteers (167.9 +/- 61.8g/ml). The level
correlates with CD4 cell counts as patients with lower CD4 counts showed higher
pGSN levels and vice versa. Gender does not affect pGSN level; however,
antiretroviral (ARV) treatment reduces pGSN toward normal. Within low CD4 cell
count group, the untreated patients have 52% higher pGSN than healthy volunteers,
whereas with treatment, the difference reduces to 24%. Similarly, high CD4 cell
count (>350 cells/mm(3)) group of patients showed 44% increase in pGSN in untreated
patients compared to 21% increase in treated patients. There is an upregulation of
pGSN in HIV-1 infection and it is inversely correlated with CD4 cell counts.
Treatment with ARV drugs decreases pGSN levels toward normal. The monitoring of
pGSN level in HIV-1-infected patients could be an important indicator of severity
of disease and recovery during treatment.
Antisynthetase syndrome (ASS) is recognized as a subgroup of idiopathic
inflammatory myopathies (IIMs). It is associated with autoantibodies directed
against aminoacyl-transfer ribonucleic acid (tRNA) synthetase enzymes. We report
the first case of anti-PL-7/anti-SSA 52kD ASS presenting as acute digital ischemia,
an association not described previously. Occlusive vasculopathy is a rare but
serious manifestation that can be seen at presentation in patients with ASS and may
herald the onset of severe interstitial lung disease (ILD). Comprehensive
evaluation should be performed to confirm the presence of subclinical myositis.
Extensive myositis-specific antibody testing is strongly recommended even if
initial screening autoimmune serologies are unrevealing.
The advertising as a form of business promotion has more and more widely in
different applications, and the lighting lamps is one of the key equipments in the
entire outdoor advertising facilities. In order to improve advertising
effectiveness and facilities security, especially for the outdoor advertising
lighting applications in some remote areas, occasionally occur the advertising
lamps stolen and damaged. A novel advertising lighting anti-thefts security system
based on digital control technologies is designed and implementation in this paper.
The designed system can achieve the real-time online status monitoring of
advertising lighting lamps, once the abnormal situation the system can be issued
on-site sound and light alarms and remote on-line notification, etc., which greatly
improving the anti-theft security performance of outdoor advertising lighting.
Graft-versus-host disease (GVHD) is a serious complication associated with
allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin
(ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its
efficacy remains unclear. We therefore identified nine randomized controlled trials
(RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group)
to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or
risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome.
Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004),
grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD
(RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI
0.180.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-
1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95%
CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG
marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00,
P = 0.05) without compromising overall survival or increased risk of infections.
Further studies are required to evaluate the optimal dosage and formulation of ATG
in different conditioning regimens of transplantation with varied sources of graft
and donor.
We previously described a Dermacentor varibialis (DV) cDNA that encodes a
ubiquitously expressed and tick saliva-secreted functional histamine release factor
(HRF) homolog. In this study gene specific primers based on DVHRF open reading
frame nucleotide sequence were utilized to amplify three orthologs, from the wood
tick, D. andersoni (DA), the black legged tick, the southern cattle tick, Boophilus
microplus (BM) and the lone star tick, Amblyomma americanum (AA). At nucleotide
level, sequence comparisons revealed 98 89 and 84% similarity to DVHRF for DAHRF,
AAHRF and BMHRF, respectively, while predicted polypeptide comparisons revealed 98,
96 and 91% similarity for DAHRF, AAHRF and BMHRF respectively. Phylogenetically,
the tick HRF clade, while distinct (100% bootstrap value), is closely related to
other arthropods, but distantly related to vertebrate and protozoan clades.
Consistent with sequence similarity analysis, a DVHRF-specific northern blotting
probe hybridized a similar to 900 base pair (bp) mRNA band on all RNA blots.
Likewise a mouse polyclonal antibody to E. coli-expressed recombinant (r) DVHRF,
cross-reacted baculovirus-expressed non-fusion rAAHRF, rDAHRF, and rBMHRF. As
revealed by northern blotting analysis of larvae and nymph RNA, DVHRF mRNA is
expressed in both immature and mature ticks indicating that its transcription is
not developmentally regulated. Unlike rHRF/TCTP proteins of other organisms, the
calcium-binding function may not be conserved for tick HRF homologs as revealed by
the (CaCl2)-Ca-45 + overlay assay. Apparent global expression of DVHRF and its
orthologs make this protein family an ideal target antigen for development of novel
tick control strategies targeting multiple tick species.
Purpose of review Aciclovir (ACV) is the first-line drug for the management of
herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term
administration of ACV for the treatment of severe infections in immunocompromised
patients can lead to the development of drug resistance. Furthermore, the emergence
of isolates resistant to ACV is increasingly recognized in immunocompetent
individuals with herpetic keratitis. This review describes the mechanisms involved
in drug resistance for HSV and VZV, the laboratory diagnosis and management of
patients with infections refractory to ACV therapy. Recent findings Genotypic
testing is more frequently performed for the diagnosis of infections caused by
drug-resistant HSV or VZV isolates. Molecular biology-based systems for the
generation of recombinant viruses have been developed to link unknown mutations
with their drug phenotypes. Fast and sensitive methods based on next-generation
sequencing will improve the detection of heterogeneous viral populations of drug-
resistant viruses and their temporal changes during antiviral therapy, which could
allow better patient management. Novel promising compounds acting on targets that
differ from the viral DNA polymerase are under clinical development. Summary
Antiviral drug resistance monitoring for HSV and VZV is required for a rational use
of antiviral therapy in high-risk populations.
Objective: Biomarkers are defined as anatomical, biochemical or physiological
traits that are specific to certain disorders or syndromes. The objective of this
paper is to summarise the current knowledge of biomarkers for anxiety disorders,
obsessive-compulsive disorder (OCD) and posttraumatic stress disorder
(PTSD).Methods: Findings in biomarker research were reviewed by a task force of
international experts in the field, consisting of members of the World Federation
of Societies for Biological Psychiatry Task Force on Biological Markers and of the
European College of Neuropsychopharmacology Anxiety Disorders Research
Network.Results: The present article (Part II) summarises findings on potential
biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine,
dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial
natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF
and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate
variability) and neurocognition. The accompanying paper (Part I) focuses on
neuroimaging and genetics.Conclusions: Although at present, none of the putative
biomarkers is sufficient and specific as a diagnostic tool, an abundance of high
quality research has accumulated that should improve our understanding of the
neurobiological causes of anxiety disorders, OCD and PTSD.
Children with autism spectrum disorder (ASD) experience internalizing and
externalizing problems at higher rates than typically developing children, which
could worsen social impairment. The present study compared impairment scores
(social responsiveness scale, 2nd edition; SRS-2 scores) in 57 children (3-17
years, 82.5% male) with ASD, either with or without heightened levels of anxiety or
ADHD symptoms, all per parent report. Children with heightened anxiety problems
showed higher scores on four SRS-2 subscales (Social Cognition, Social
Communication, Social Motivation, and Restricted Interests and Repetitive
Behavior). Children with heightened ADHD traits showed higher scores on two
subscales (Social Communication and Social Awareness). These findings suggest
similarities and differences in how social deficits in ASD may worsen with anxiety
or ADHD symptoms.
BackgroundHigh levels of maltreatment are found in children who are identified
because their parents visit the emergency department due to partner violence,
substance abuse or suicide attempt. However, it is unknown if these children
experience psychosocial problems. This study aims to assess their levels of post-
traumatic stress, anxiety, depression, behavioural problems and health-related
quality of life. MethodsA cross-sectional study was conducted in six hospitals. All
consecutive families of which a parent visited the emergency department due to
partner violence, substance abuse or suicide attempt between 1 July 2012 and 1
March 2014 with children aged 1.5-17years were approached for participation.
Parents and children aged 8years and older filled out questionnaires measuring
post-traumatic stress [13-item version of Children's Revised Impact of Event Scale
(CRIES-13)], anxiety, depression (Revised Child Anxiety and Depression Scale),
behavioural problems [Child Behavior Checklist (CBCL) and Youth Self-Report (YSR)]
and health-related quality of life (PedsQL). Scores of participants were compared
with reference data obtained in children in similar age ranges from representative
Dutch community samples (CRIES-13, Revised Child Anxiety and Depression Scale,
PedsQL and CBCL) and to a normed cutoff score (CRIES-13). ResultsOf 195 eligible
families, 89 (46%) participated in the study. Participating children did not score
different from community children, both on child-reported and parent-reported
instruments. Standardized mean differences of total sum scores were 0 (CRIES-13 and
CBCL 1.5-5), 0.1 (YSR), 0.2 (CBCL 6-18) and -0.3 (PedsQL) and not statistically
different from community children. Thirty-five percent of the participating
children scored above the cutoff score on the CRIES-13, indicating post-traumatic
stress disorder, but this difference was not statistically significant from
community children (mean difference 8%; 95% CI -4-22%). ConclusionsWe found no
differences in psychosocial problems between children whose parents visited the
emergency department due to partner violence, substance abuse or suicide attempt
and children from community samples. Because 35% of the children scored in the
range of post-traumatic stress disorder, we advise healthcare providers to pay
attention to post-traumatic stress symptoms
There is increasing interest in describing different variants and subtypes that
characterize the heterogeneity of behavior, problems with the aim of supporting
early detection and prevention, as well as facilitating research into etiological
differences. This work examines the course of co-occurrence of callous-unemotional
traits (CU), anxiety (ANX) and oppositionality (ODD-s) levels in a longitudinal
community sample. A sample of 622 3 year-old preschoolers, followed up until age 7,
was assessed annually with dimensional measures of callous-unemotional traits,
oppositional defiant disorder and anxiety and related psychological constructs
answered by parents, teachers and, performed by children. Growth-Mixture-Modeling
yielded six trajectories (null 58.9%, ANXincreasing 4.9%, CU + ANX + ODD 2.4%, CU +
ODD-decreasing 8.1%, ODD-increasing 16.4%, and ANX-decreasing 9.2%) that represent
the variants previously described with older subjects. The specifier ODD "with
limited prosocial emotion" (CU + ODD decreasing and increasing) showed deficits in
executive functioning, attention, aggressive behavior and social cognition in
comparison with null trajectory. The secondary variant showed a more severe
clinical picture and presented more difficulties in executive functioning, worse
environmental characteristics, and worse outcomes at age 7. It is possible to
identify the heterogeneity of disruptive behavior problems from preschool age. The
identification of homogeneous groups in this category of disorders may help to
design more suitable treatments with specific components for specific difficulties,
and to progress in the etiological research of each class. (C) 2017 Elsevier Ltd.
All rights reserved.
Background: Psychosocial distress is common among cancer patients. Significant
associations between coping and social support with distress and quality of life in
adult cancer patients have been identified before, but little is known about the
interrelationships between distress, medical coping, and social support in
adolescents and young adults (AYAs). Objective: The aims of this study are to
investigate the prevalence of psychological distress in Chinese AYAs with cancer
and examine the associations among distress, anxiety and depression, medical
coping, and social support in the same population. Methods: A total of 610 AYA
patients were recruited for this study; 551 patients completed the Chinese version
of the National Comprehensive Cancer Network Distress Thermometer (DT), the
Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and
the Social Support Rating Scale. Results: The prevalence of psychological distress
was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21-to
25-year-old patients; the DT scores were positively correlated with anxiety and
depression (PG. 01) but negatively correlated with medical coping and social
support (PG. 01). Conclusion: The prevalence of psychological distress in AYA
cancer patients was higher than that in the general cancer population. Medical
coping and social support can lower the prevalence of psychological distress in AYA
cancer patients. Implications for Practice: Findings suggest the need for evidence-
based intervention strategies to enhance medical coping and social support in AYA
cancer patients. Nurses are crucial to implementing psychological interventions in
AYA cancer patients.
This study identified predictors of anxiety and depression in patients with acute
coronary syndrome. Predictors included illness beliefs, fear/threat at the time of
the cardiac event, threat reappraisal over time and social support. A total of 97
participants completed questionnaires in hospital and 1- and 6-month follow-up.
Perceived threat and fear at the time of the cardiac event predicted affective
response at both time points, partly mediated by threat reappraisal.
Contemporaneous measures of illness beliefs contributed additional variance,
although not always in the predicted direction: high concern and control over the
illness were associated with emotional distress. Assessment of patients for risk of
negative emotional outcomes of acute coronary syndrome needs to consider their
beliefs about their illness and the degree of threat and fear experienced at the
time of the event. Interventions need to help people cope with negative emotional
states as well as challenging inappropriate illness beliefs.
The purpose of this study was to evaluate the effects of a home-based (HB) exercise
program on anxiety levels and metabolic functions in patients with anxiety
disorders in Taiwan. Purposive sampling was used to recruit 86 participants for
this randomized, experimental study. Participants were asked to complete a pretest
before the 3-month exercise program, a posttest at 1 week, and a follow-up test at
3 months after the exercise program. Study measures included four Self-Report
Scales and biophysical assessments to collect and assess personal data, lifestyle
behaviors, anxiety levels, and metabolic control functions. Of the 86 study
participants, 83 completed the posttest and the 3-month follow-up test, including
41 in the experimental group and 42 in the control group. Participants in the
experimental group showed significant improvements in body mass index, high-density
lipoprotein cholesterol levels, and the level of moderate exercise after the
program relative to the control group, as analyzed by generalized estimating
equations mixed-model repeated measures. State and trait anxiety levels were also
significantly improved from pretest to follow-up test in the experimental group.
Finally, the prevalence of metabolic syndrome declined for participants in the
experimental group. The HB exercise program produced positive effects on the
metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders.
Health providers should consider using similar HB exercise programs to help improve
the mental and physical health of patients with anxiety disorders in their
communities.
Research shows that anxiety may relate to any or all of the following: goal
conflict resolution; distraction, and the automatic detection of threat-related
stimuli. To investigate these relationships we used a modified Stroop task where
fearful and happy emotional target faces are overlaid with either emotionally
neutral, emotionally congruent or emotionally incongruent distracting words. A
trait anxiety related speed-accuracy trade-off seemed to primarily reduce accuracy
during incongruent trials with target fearful faces overlaid with the emotionally
conflicting word happy. We offer an explanation of this effect based upon theories
of how positive stimuli and threat-related stimuli differentially affect
information processing. Future studies should seek to verify how the anxiety
related speed-accuracy trade-off mechanism is activated, and elucidate how and when
positive stimuli affect anxiety more than threat-related stimuli do. (C) 2017
Elsevier Ltd. All rights reserved.
Context: Marine cyanobacteria offer a robust resource for natural products drug
discovery due to the secondary metabolites they produce.Objective: To identify
novel cyanobacterial compounds that exhibit CNS psychoactive effects.Materials and
methods: Cyanobacteria were collected from Las Perlas Archipelago, Panama and
subjected to dichloromethane/methanol extraction and fractionation by column
chromatography before being screened for affinity against a panel of CNS targets. A
50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was
subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20g per
animal, 2064H and 2064H3 were tested in mice using behavioral assays that included
the forced swim, open field and formalin tests.Results: 2064H was shown to bind to
the serotonin 2C (5-HT2C) receptor, a known target for depression and pain
treatment. 2064H showed 59.6% inhibition of binding of [H-3]-mesulergine with an
IC50 value of 179ng/mL and did not show inhibition of binding greater than 45% with
any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the
first minute of the tail suspension test. 2064H increased time, distance and number
of entries in the center region in the first half of the open field test. 2064H
increased overall nocifensive behaviors in the formalin test.Discussion and
conclusion: Overall, manipulating the 5-HT2C receptor with these receptor-specific
ligands derived from cyanobacteria altered pain, depression and anxiety-like
behaviors, illustrating the importance of this receptor in affective behaviors.
These results demonstrate the potential of cyanobacteria as a source for CNS active
compounds.
Symptoms of post-traumatic stress disorder are common in fibromyalgia patients.
This study compared post-traumatic stress disorder symptoms in fibromyalgia
patients and healthy controls and determined whether patient-control differences in
post-traumatic stress disorder symptoms mediated differences in mental health. In
all, 30 patients and 30 healthy controls completed questionnaires assessing
symptoms of post-traumatic stress disorder and mental health. Fibromyalgia patients
had greater symptoms of post-traumatic stress disorder and mental health than
controls. Patient-control differences in mental health symptoms were fully or
partially mediated by differences in post-traumatic stress disorder symptoms.
Healthcare providers should understand the role of trauma as management of trauma
symptoms may be one strategy for improving mental health.
Monitoring distress assessment in cancer patients during the treatment phase is a
component of good quality care practice. Yet, there is a dearth of prospective
studies examining distress. In an attempt to begin filling this gap and inform
clinical practice, we conducted a prospective, longitudinal study examining changes
in distress (anxiety, depression, and problems in living) by age and gender and the
roles of age and gender in predicting distress. Newly diagnosed Brazilian cancer
patients (N = 548) were assessed at three time points during chemotherapy. Age and
gender were identified on the first day of chemotherapy (T1); anxiety, depression,
and problems in living were self-reported at T1, the planned midway point (T2), and
the last day of chemotherapy (T3). At T1, 37 and 17% of patients reported
clinically significant levels of anxiety and depression, respectively. At T3, the
prevalence was reduced to 4.6% for anxiety and 5.1% for depression (p70 years (p
< .03). Female patients reported greater emotional, physical, and family problems
than their male counterparts (p < .04). For most patients, elevated levels of
distress noted in the beginning of treatment subsided by the time of treatment
completion. However, middle-aged and female patients continued to report heightened
distress. Evidence-based psychosocial intervention offered to at risk patients
during early phases of the treatment may provide distress relief and improve
outcomes over the illness trajectory while preventing psychosocial and physical
morbidity due to untreated chronic distress.
Individuals with high levels of worry are more likely than others to attend to
possible threats, although the extent of top-down attentional control processes on
this bias is unknown. We compared the performance of high (n = 26) and low worriers
(n = 26) on a probe discrimination task designed to assess attention to threat
cues, under cognitive load or no-load conditions. The expected difference between
groups was confirmed, with high worriers being more likely to attend to threat cues
than low worriers. Importantly however, there were no significant effects involving
condition (cognitive load vs. no-load), nor any significant association with self-
perceived attentional control ability. These results suggest that pathological
worriers are more likely to attend to threat than are individuals with low levels
of worry, regardless of task demands on limited cognitive control resources. This
finding is consistent with the dominance of habitual bottom-up influences over top-
down control processes in biased attention to threat.
Cognitive models of anxiety propose that heightened anxiety vulnerability is
characterized by a tendency to interpret ambiguous situations as threatening. The
presence of such an interpretive bias has been confirmed in younger adults, using
assessment measures that bypass the limitations of self-report and objectively
assess interpretive processing. A recent pioneering study published in 2015 has
sought to determine whether this anxiety-linked interpretive bias also is evident
in older adults. However, their evidence supporting this hypothesis comes only from
self-report measures and memory measures. The present study was designed to provide
a stronger test of the hypothesis by objectively assessing interpretive process in
high (n = 48) and low (n = 48) trait anxious older adults, using a text
comprehension approach that circumvents reliance on self-report or memory measures.
The findings were fully consistent with the hypothesis that older adults with
higher levels of trait anxiety, compared to those with lower levels of trait
anxiety, impose more threatening meanings on ambiguous information. These findings
provide the first evidence, from an assessment approach that overcomes the
limitations of self-report and memory measures, that elevated anxiety vulnerability
in older adults is characterized by a negative interpretive bias.
Extensive studies have reported cognitive abnormalities in neurodevelopmental
disorders, such as autism spectrum disorder (ASD). Another line of evidence
suggests that stress also affects cognitive functions. In this study, we
investigated whether there were associations between stress hormones and cognitive
functions in ASD and typically developing (TD) children. Cognitive functions in ASD
and TD children were evaluated with a battery of psychological tests for working
memory, behavioral flexibility, and social cognition for emotional assessments of
others. ASD children exhibited higher hair and salivary cortisol, which reflects
chronic and acute stress hormone levels of subjects, respectively, than TD
children. Autism-spectrum quotient (AQ) was positively correlated with hair
cortisol and the scores of Spence Children's Anxiety Scale in ASD children. In
addition, a negative correlation was present between spatial working memory
performance and hair cortisol in ASD, but not in TD, children. These results
suggest that chronic stress hormone elevation may have relationships with some
aspects of cognitive dysfunction in ASD subjects. (C) 2016 The Author(s). Published
by Elsevier Ltd on behalf of IBRO.
According to Attachment Theory (Bowlby, 1980), individual differences in adult
attachment styles are based on attachments formed during infancy with primary
caregivers. Adults who form secure attachments feel safe and secure in their
relationships. Those who form insecure attachments do not. According to Self-
Compassion Theory (Neff, 2003a, 2003b), and supported by research, self-compassion
(i.e., compassionate attitudes and behaviors towards oneself) is associated with a
variety, of positive psychological outcomes, while a lack of self-compassion is
associated with psychological distress (e.g., Barnard & Curry, 2011). Additionally,
the fear of self-compassion has been negatively associated with self-compassion
(Joeng,& Turner, 2015). In this current study, we extend the research on attachment
and self-compassion by examining how self-compassion and fear of self-compassion
mediate two types of insecure attachment styles, anxious attachment and avoidant
attachment, and two indicators of emotional distress, depression and anxiety, among
473 Korean college students. Structural equation modeling indicated that self-
compassion independently mediated, and fear of self-compassion and self-compassion
serially mediated, the paths from anxious and avoidant attachment to depression and
anxiety in expected directions. Results are interpreted from the perspective of
Korean culture, including the influence of Confucianism on the expression of self-
compassion. (C) 2017 Elsevier Ltd. All rights reserved.
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-
proteasome system, is highly expressed in several types of cancers; however, its
roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The
purpose of this study was to clarify the functional activities of UBE2S in OSCCs.
We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC
tissues by quantitative reverse transcriptase-polymerase chain reaction, Western
blotting, and immunohistochemistry (IHC). The correlations between UBE2S expression
and clinical classifications of OSCCs were analyzed using the IHC scoring system.
We also used UBE2S knockdown OSCC cells for functional assays (proliferation assay,
flow cytometry, and Western blotting). UBE2S was overexpressed in OSCCs in vitro
and in vivo and was correlated significantly (P < 0.05) with the primary tumoral
size. The cellular growth was decreased and the cell-cycle was arrested in the G2/M
phase in the UBE2S knockdown (shUBE2S) cells. The expression level of P21, a target
of the ubiquitin-proteasome system, was increased in the shUBE2S cells because of
lower anaphase activity that promotes complex subunit 3 (APC3), an E3 ubiquitin
ligase, compared with shMock cells. These findings might promote the understanding
of the relationship between UBE2S overexpression and oral cancer proliferation,
indicating that UBE2S would be a potential biomarker of and therapeutic target in
OSCCs. (C) 2017 Elsevier Inc. All rights reserved.
Objective: To detect the distribution and expression levels of the nucleotide-
binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in
Melanoma 2 (AIM2) inflammasomes in periapical lesions and to analyse the possible
microbial stimuli outside of teeth. Design: The distribution of NLRP3 and AIM2
inflammasomes in sixteen periapical lesions was investigated by
immunohistochemistry. Meanwhile, the relative gene expression levels of NLRP3 and
AIM2 in sixteen periapical lesions and three health periodontal tissue were
quantified by real-time polymerase chain reaction (PCR). Moreover, forty-seven
teeth without sinus tracts were obtained in the clinic and included in bacterial
analysis using PCR. Then, the mRNA levels of apoptosis-associated speck like
protein (ASC), caspase-1, interleukin-1 beta (IL-1 beta), NLRP3 and AIM2 in THP-1-
derived macrophages treated with lipopolysaccharides (LPS) of Porphyromonas were
also quantified by real-time PCR, and the IL-1 beta secretion level was
investigated using enzyme-linked immunosorbent assay (ELISA). Results: NLRP3 and
AIM2 were positively expressed in periapical lesions and were mainly distributed in
inflammatory cells. Most of the samples that demonstrated up-regulation of NLRP3
mRNA also demonstrated up-regulation of caspase-1 mRNA. Microbial analysis revealed
that Porphyromonas endodontalis was the most commonly detected species and was
detected in 27 of 47 cases (57.4%), followed by Fusobacterium nucleatum (20/47,
42.6%), Porphyromonas gingivalis (19/47, 40.4%), Tannerella forsythia (19/47,
40.4%), Actinomyces sp. (17/47, 36.17%), Treponema denticola (10/47,21.28%),
Actinomyces israelii (9/47,19.15%), Prevotella intermedia (6/47, 12.77%),
Enterococcus faecalis (1/47,2.13%) and Enterococcus faecium (0/47,0). Furthermore,
we found that LPS of P. gingivalis induced THP-1 cells to produce IL-1 beta and to
activate NLRP3 and AIM2 inflammasomes. Conclusions: Our results suggest that the
NLRP3 and AIM2 proteins play a part in the pathogenesis of periapical
periodontitis. Anaerobes, such as P. endodontalis, P. gingivalis, E nucleatum and
T. forsythia, were the main detected microbial stimuli that might activate
inflammasomes in periapical tissues. (C) 2017 Elsevier Ltd. All rights reserved.
Aims: Ligands for the vitamin D receptor (VDR) regulate apolipoprotein A-I (apo A-
I) gene expression in a tissue-specific manner. The vitamin D metabolite 24, 25-
dihydroxycholecalciferol (24, 25-(OH)(2)D(3)) has been shown to possess unique
biological effects. To determine if 24, 25-(OH)(2)D(3) modulates apo A-I gene
expression, HepG2 hepatocytes and Caco-2 intestinal cells were treated with 24, 25-
(OH)(2)D(3) or its precursor 25-OHD(3). Main methods: Apo A-I protein levels and
mRNA levels were measured by Western and Northern blotting, respectively. Changes
in apo A-I promoter activity were measured using the chlorampenicol
acetytransferase assay. Key findings: Treatment with 24, 25-(OH)(2)D(3), but not
25-OHD(3), inhibited apo A-I secretion in HepG2 and Caco-2 cells and apo A-I mRNA
levels and apo A-I promoter activity in HepG2 cells. To determine if 24, 25(OH)
(2)D(3) represses apo A-I gene expression through site A, the nuclear receptor
binding element that is essential for VDRs effects on apo A-I gene expression,
HepG2 cells were transfected with plasmids containing or lacking site A. While the
site A-containing plasmid was suppressed by 24, 25-(OH)(2)D(3), the plasmid lacking
site A was not. Likewise, treatment with 24, 25-(OH)(2)D(3) suppressed reporter
gene expression in cells transfected with a plasmid containing site A in front of a
heterologous promoter. Finally, antisense-mediated VDR depletion failed to reverse
the silencing effects of 24, 25-(OH)(2)D(3) on apo A-I expression. Significance:
These results suggest that the vitamin D metabolite 24, 25-(OH)(2)D(3) is an
endogenous regulator of apo A-I synthesis through a VDR-independent signaling
mechanism. (C) 2010 Elsevier Inc. All rights reserved.
Apolipoprotein E (apoE) is predominantly a lipid transport protein involved in
membrane repair and synaptic plasticity in brain. Its genotype is associated with
late-onset sporadic and familial Alzheimer's disease (AD). Its expression increases
when any injury takes place in the nervous system and in age-related disorders
including AD. However, it is not clearly understood how the level of apoE changes
in the normal aging brain. Therefore, we have analyzed the effect of age on apoE
protein and mRNA level in the cerebral cortex of young, adult, and old male AKR
strain mice. Western, northern, and RT-PCR results reveal that the level of apoE
protein and mRNA is higher in young as compared to adult and then remains unchanged
in old mouse cerebral cortex. This indicates that during normal aging, apoE level
is maintained in old similar to adult and suggests involvement of other factors in
maintaining apoE-mediated brain functions in old.
A critical process in apoptosis is the permeabilization of the mitochondrial outer
membrane (MOM). This process is known to be regulated by the multi-domain Bcl-2
family proteins. For example, the pro-apoptotic proteins Bax and Bak are
responsible for forming pores at MOM. The anti-apoptotic proteins (including Bcl-2,
Mcl-1 and Bcl-xL), on the other hand, can inhibit this pore-forming process.
Interestingly, although these two subgroups of proteins perform opposite apoptotic
functions, their structures are very similar. This raises two highly interesting
questions: (1) Why do these structurally similar proteins play opposite roles in
apoptosis? (2) What are the roles of different functional domains of a Bcl-2 family
protein in determining its apoptotic property? In this study, we generated a series
of deletion mutants and substitution chimera, and used a combination of molecular
biology, bio-informatics and living cell imaging techniques to answer these
questions. Our major findings are: (1) All of the Bcl-2 family proteins appear to
possess an intrinsic pro-apoptotic property. (2) The N-termini of these proteins
play an active role in suppressing their pro-apoptotic function. (3) The apoptotic
potency is positively correlated with membrane affinity of the alpha 5/6 helix
domains. (4) Charge distribution flanking the alpha 5/6 helices is also important
for the apoptotic potency. These findings explain why different members of Bcl-2
family proteins with similar domain composition can function oppositely in the
apoptotic process.
BACKGROUND CONTEXT: Degenerative disc disease (DDD) remains without an effective
therapy and presents a costly burden to society. PURPOSE: Based upon prior reports
concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells,
we performed a proof of principle study to determine whether NCCM could reduce
cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells. STUDY
DESIGN/ SETTING: This is an "in vitro" fundamental or basic science study. METHODS:
Nucleus pulpous cells derived from 15 patients undergoing spinal surgery were
treated with interleukin (IL)-1 beta and Fas ligand or etoposide in the presence of
NCCM. We determined proor antiapoptotic events using activated caspase assays and
determined genomic regulation of apoptosis using polymerase chain reaction arrays
validated usingWestern blotting methods. We interrogated cellular apoptotic
regulation using JC-1 dye and flow cytometry and performed enzyme-linked
immunosorbent assays to evaluate NP inflammatory cytokine secretion. RESULTS:
Notochordal cell-conditioned medium inhibits cytotoxic stress-induced caspase-9 and
-3/7 activities and maintains the mitochondrial membrane potential in human
NPcells, thereby suppressing the intrinsic apoptotic pathway. Gene expression
analysis revealed the X-linked inhibitor of apoptosis protein as a key player
responsible for evading etoposide-induced apoptosis in the presence ofNCCM, and we
verified these data using Western blotting. Enzyme-linked immunosorbent assay
results revealed distinct differences in IL-6 and IL-8 secretions by NP cells in
response to etoposide in the presence of NCCM. CONCLUSIONS: Here we demonstrate for
the first time that NCCM reduces cytotoxic stressinduced apoptosis in human NP
cells. Soluble factors present in NCCM could be harnessed for the development of
novel therapeutics for the treatment of DDD. (C) 2017 Elsevier Inc. All rights
reserved.
PCD (programmed cell death) is important mechanism for development, homeostasis and
disease. To analyze the gene expression pattern in brain cells undergoing PCD in
response to serum deprivation, we analyzed the cDNA microarray consisting of 2,300
genes and 7 housekeeping genes of cortical cells derived from mouse embryonic
brain. Cortical cells were induced apoptosis by serum deprivation.for 8 hours. We
identified 69 up-regulated genes and 21 down-regulated genes in apoptotic cells.
Based on the cDNA microarray data four genes were selected and analyzed by RT-PCR
and northern blotting. To characterize the role of UNC-51-like kinase (ULK2) gene
in PCD, we investigated cell death effect by ULK2. And we examined expression of
several genes that related with PCD. Especially GAPDH was increased by ULK2. Theses
findings indicated that ULK2 is involved in apoptosis through p53 pathway.
Background and Aim: The tumor-suppressing role of Ras-association domain family 1A
(RASSF1A) has been described in several systems. In this study, we tested its
tumor-suppressing ability and the potential molecular mechanisms in hepatocellular
carcinoma (HCC) from Qidong County. Methods: Reverse transcription polymerase chain
reaction and Northern blotting were employed to detect the expression of RASSF1A in
HCC. After establishing stable RASSF1A (wild type or mutant) expressing 'qi dong
gan ai yan jiu suo' ([Qidong Institute of Liver Cancer] QGY)-7703 cell lines, we
tested the effects of RASSF1A expression on cell growth by cell proliferation rate,
cell colony formation, and cell cycle progression. We also tested the effects of
RASSF1A expression on tumorigenesis in nude mice and on cellular sensitivity to
mitomycin treatment. Results: The RASSF1A transcript was not found in 75% (three of
four) of HCC cell lines and 67% (32/48) of HCC primary biopsies. The stepwise
regression analyses indicated that the loss of RASSF1A expression was more frequent
in patients who were hepatitis B virus surface antigen positive (HBsAg+) compared
to those who were HBsAg(-), both in tumor and corresponding non-cancerous tissues.
The wild-type (wt)-RASSF1A expression in the QGY-7703 cell line resulted in fewer
and smaller clones, decreased xenograft tumor volume and weight, and G(1)/S arrest
in vitro and in vivo. The wt-RASSF1A expression also decreased the cyclin D1
protein expression, which appeared to be at the level of post-transcriptional
control. In addition, the wt-RASSF1A expression increased cell growth inhibition
and the percentage of cells with sub-G(1) DNA content when the cells were treated
with mitomycin. Conclusion: RASSF1A is a tumor suppressor in HCC. The loss of
RASSF1A expression may be related to HBsAg+ in hepatocarcinogenesis. Its
inactivation may play an important role in the development of HCC.
Background: Neutrophil function is critical for initiation and progression of
infecto-inflammatory diseases. Key quorum-sensing plaque bacteria, such as
Fusobacterium nucleatum, act as bridging species between early and late colonizer
pathogens, such as Porphyromonas gingivalis, as the biofilm ages and periodontal
inflammation increases. This study is designed to determine impact of different F.
nucleatum strains on neutrophil function. Methods: Cells of human promyelocytic
leukemia cell line-60 were differentiated into neutrophil-like cells and cultured
with F. nucleatum strains of subspecies (ssp.) nucleatum ATCC 25586, ssp.
polymorphum ATCC 10953, and ssp. vincentii ATCC 49256. Neutrophil phagocytosis of
F. nucleatum strains and neutrophil apoptosis were analyzed by flow cytometry.
Superoxide generation was measured by cytochrome C reduction in the presence and
absence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) (1 mu M)
stimulation. Proinflammatory cytokine release was determined after 2, 6, and 24
hours of culture in the presence/absence of different F. nucleatum strains.
Expression of Toll-like receptor (TLR) 2, TLR4, and nuclear factor (NF)-kappa B
mRNA levels were analyzed using real-time quantitative polymerase chain reaction.
Each experiment was repeated at least three times in triplicate. Data were analyzed
using analysis of variance followed by post hoc Bonferroni correction. Results: All
strains of F. nucleatum significantly increased phagocytic capacity of neutrophils.
Neutrophil phagocytosis of F. nucleatum ssp. polymorphum was significantly greater
than that of F. nucleatum ssp. vincentii and ssp. nucleatum (P < 0.001). F.
nucleatum ssp. nucleatum and ssp. polymorphum significantly blocked fMLP-induced
superoxide generation (P < 0.001). Although F. nucleatum vincentii also reduced
superoxide generation (25%), the impact was not as strong as that of ssp. nucleatum
(83%) and ssp. polymorphum (100%). All F. nucleatum strains stimulated significant
increase in neutrophil apoptosis compared with control (P < 0.001) and
significantly increased expression of NF-B-k mRNA in neutrophils (P < 0.05). Levels
of interleukin-8 and tumor necrosis factor-alpha produced by neutrophils were
significantly increased in all F. nucleatum groups compared with control (P <
0.001). Conclusions: These findings suggest that different strains of F. nucleatum
impact neutrophil function in different ways. Two of three subspecies blocked
neutrophil superoxide generation in response to a secondary stimulus, preventing
oxidative killing by neutrophils. The direct role of bridging species in
pathogenesis of periodontitis may be greater than previously suspected in which
they create a favorable environment for pathogenic transition of the dental
ecosystem.
Background/Aims: High-glucose (HG)-induced mesangial apoptosis and fibrogenesis
possibly involves reactive oxygen species (ROS) formation and activated
mitochondrial stress. We investigated the therapeutic effect of the antioxidant N-
acetylcysteine (NAC) on cellular apoptosis and matrix accumulation in HG-treated
rat mesangial cells (RMCs). Methods: RMCs were cultured in media containing 5
(control) or 35 m M (HG) glucose. Cellular apoptosis was assayed by TdT-mediated
dUTP nick-end labeling staining. Collagen and transforming growth factor-1 gene
expression were measured by reverse transcriptase-polymerase chain reaction or
Northern blotting. Mitochondrial capacity and intracellular ROS generation was
assayed by fluorescence microscopy and flow cytometry, respectively. Cellular ATP
production and malondialdehyde (MDA) formation were determined by a luciferin-
luciferase reaction and high-performance liquid chromatography, respectively.
Cytochrome c release, caspase activation and poly(ADP) ribose polymerase cleavage
were assayed by Western blotting. Results: HG-treated RMCs displayed enhanced
cellular apoptosis (65%) and collagen gene expression (1.8-fold increase); these
reactions could be significantly suppressed by 1 m M NAC (p < 0.05). Intracellular
ROS generation, production of ATP and MDA, and caspase-3, -8 and -9 activities were
significantly increased in HG-treated RMCs, and were effectively attenuated by
addition of NAC. Conclusion: It is concluded that NAC prevents HG-induced mesangial
apoptosis and fibrogenesis pathways by the reduction of oxidative stress. Copyright
(c) 2008 S. Karger AG, Basel
Background: Many microRNAs (miRNAs) have recently been shown to demonstrate
critical roles in differentiation, proliferation and migration of vascular smooth
muscle cells (VSMCs). Methods and Results: In this study, a certain amount of miRNA
expression in VSMCs was evaluated by real-time polymerase chain reaction, and it
was found that microRNA-30e (miR-30e) was expressed more strongly than other common
vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of
function study was performed in vitro and in vivo. It was found that miR-30e in
VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e
inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore,
ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of
endogenous miR-30e by luciferase reporter assay, and it was confirmed that
overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic
switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and
migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of
miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of
IkBa, which is crucial for the NF.B signal pathway. Conclusions: The results of
this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect
via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More
specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs
partially through targeting Ube2i and downregulating the I kappa Ba/NF kappa B
signaling pathway.
Ascorbic acid plays an important role in the growth and immunity of the sea
cucumber, Apostichopus japonicus, a valuable commercial species in China, South
Korea, and Japan. In this study, we investigated the dietary ascorbic acid
requirements of two newly discovered color morphs of A. japonicus, white and
purple, and compared them with that of the common green morph. Six test diets were
formulated containing 0, 50, 100, 200, 400, and 800 mg ascorbic acid equivalent per
kg, as 1-ascorbyl-2-polyphosphate. The color morphs were fed the test diets for 60
days, and their growth, energy budget, and immunological performance recorded.
Dietary ascorbic acid levels had a significant effect on the growth of A. japonicus
(P= 200 mg/kg (P < 0.05). Superoxide dismutase (SOD) and catalase (CAT) activities,
and total anti-oxidative capacity (T-AOC) were generally higher at dietary ascorbic
acid levels of 100, 200, and 400 mg/kg compared with the other treatments. SOD and
CAT activities and T-AOC were significantly and positively correlated with SGR,
indicating that supplementary dietary ascorbic acid had a beneficial effect on
growth and immunity. SGR, energy intake, and the proportion of energy allocated to
growth decreased significantly in the white and purple morphs when ascorbic acid
levels reached 800 mg/kg (P < 0.05); as did those of the green morph, but not to a
significant level. Immune indicators decreased and MDA content increased slightly
at 800 mg/kg, indicating that high levels of dietary ascorbic acid do not benefit
growth or immunity. The SOD and CAT activities were higher in the purple morph than
the green and white morphs, indicatingits superior immune system capacity. Optimum
growth and immunity of A. japonicus were achieved at similar to 100 mg/kg of
ascorbic acid in the white morph and 200 mg/kg in the green and purple morphs.
Background: Appendiceal cancers are rare and consist of carcinoid, mucocele,
pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma
histologies. Current treatment involves surgical resection or debulking, but no
standard exists for adjuvant chemotherapy or treatment for metastatic disease.
Methods: Samples were identified from approximately 60,000 global tumors analyzed
at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples
with appendix primary tumor sites were identified (male/female ratio of 2: 3; mean
age =55). Sixty-two percent of samples were adenocarcinomas (used for analysis);
the rest consisted of 9% goblet cell, 15% mucinous; 6% pseudomyxoma, and less than
5% carcinoids and 2% neuroendocrine. Tests included sequencing [Sanger, next
generation sequencing (NGS)], protein expression/ immunohistochemistry (IHC), and
gene amplification [fluorescent in situ hybridization (FISH) or CISH]. Results:
Profiling across all appendiceal cancer histological subtypes for IHC revealed: 97%
BRCP, 81% MRP1, 81% COX-2, 71% MGMT, 56% TOPO1, 5% PTEN, 52% EGFR, 40% ERCC1, 38%
SPARC, 35% PDGFR, 35% TOPO2A, 25% RRM1, 21% TS, 16% cKIT, and 12% for TLE3. NGS
revealed mutations in the following genes: 50.4% KRAS, 21.9% P53, 17.6% GNAS, 16.5%
SMAD4, 10% APC, 7.5% ATM, 5.5% PIK3CA, 5.0% FBXW7, and 1.8% BRAF. Conclusions:
Appendiceal cancers show considerable heterogeneity with high levels of drug
resistance proteins (BCRP and MRP1), which highlight the difficulty in treating
these tumors and suggest an individualized approach to treatment. The incidence of
low TS (79%) could be used as a backbone of therapy (using inhibitors such as
5FU/capecitabine or newer agents). Therapeutic options includeTOPO1 inhibitors
(irinotecan/topotecan), EGFR inhibitors (erlotinib, cetuximab), PDGFR antagonists
(regorafenib, axitinib), MGMT (temozolomide). Clinical trials targeting pathways
involving KRAS, p53, GNAS, SMAD4, APC, ATM, PIK3CA, FBXW7, and BRAF may be also
considered. Overall, appendiceal cancers have similar patterns in their molecular
profile to pancreatic cancers (can we say this, any statistical analysis done?) and
have differential expression from colorectal cancers. These findings indicate the
need to evaluate patient samples for patterns in marker expression and alteration,
in order to better understand the molecular biology and formulate a personalized
therapy approach in these difficult to treat cancers (supported by a grant from
Caris Life Sciences).
Background and aims: Apple polyphenol contains abundant procyanidins, which have
been associated with an anti-atherosclerosis and cholesterol-lowering effect. The
aim of this study was to investigate whether apple procyanidins (APCs) feature
therapeutic efficacy in terms of regressing atherosclerosis and whether this
efficacy is due to mechanisms other than a cholesterol-lowering effect. Methods:
After eight weeks on an atherogenic diet, rabbits were given a normal diet for
another eight weeks to normalize the increased serum lipids level. The rabbits in
the baseline group were sacrificed at this stage. The control group was
subsequently fed a normal diet for eight weeks, while the APCs group was
administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and
aortic intimal-medial thickness (IMT) were serially examined, and the resected
aorta was examined histologically and through molecular biology. Results: Aortic
IMT on ultrasonography and the lipid accumulation area examined using Sudan IV
staining were significantly reduced in the APCs group as compared to the control
group. Serum lipid profiles were not different between the groups.
Immunohistochemistry showed significantly decreased staining of an oxidative stress
marker and significantly increased staining of ATP-binding cassette subfamily A
member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed
increased expression of ABCA1 mRNA and its protein in the APCs group. Conclusions:
This study revealed that APCs administration causes a regression of
atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent. (C) 2017
Elsevier B.V. All rights reserved.
Apples are a widely consumed fruit and have a high polyphenol content. The aim of
this study was to analyse the combined effects of osmotic dehydration (OD) and
ohmic heating (OH) with a pulsed vacuum (PV) on polyphenol retention during the
stored refrigeration of apple cubes. Treatments were performed using a 65 degrees
Brix sucrose solution at 30, 40 or 50 degrees C for 120 min, and then, samples were
stored for 28 days at 5 degrees C. OH provides an electric field of 13 V cm(-1),
and a pulsed vacuum was applied for 5 min at the beginning of the process. The
results indicated that a lower temperature process (30-40 degrees C) resulted in
the retention of more polyphenol compounds after treatment than a higher
temperature process (50 degrees C). Nevertheless, during refrigerated storage, we
observed that 50 degrees C preserved these compounds better due to polyphenol
oxidase inactivation. PVOD/OH treatment at 50 degrees C was determined to be the
best retention of polyphenols from the fresh apple for dehydrating apples.
We developed a 2.5x6.6 mm(2) 2-D array transducer with integrated transmit/receive
application-specific integrated circuit (ASIC) for real-time 3-D intracardiac
echocardiography (4-D ICE) applications. The ASIC and transducer design were
optimized so that the high-voltage transmit, low-voltage time-gain control and
preamp, subaperture beamformer, and digital control circuits for each transducer
element all fit within the 0.019-mm(2) area of the element. The transducer assembly
was deployed in a 10-Fr (3.3-mm diameter) catheter, integrated with a GE Vivid E9
ultrasound imaging system, and evaluated in three preclinical studies. The 2-D
image quality and imaging modes were comparable to commercial 2-D ICE catheters.
The 4-D field of view was at least 90 degrees x 60 degrees x 8 cm and could be
imaged at 30 vol/s, sufficient to visualize cardiac anatomy and other diagnostic
and therapy catheters. 4-D ICE should significantly reduce X-ray fluoroscopy use
and dose during electrophysiology ablation procedures. 4-D ICE may be able to
replace transesophageal echocardiography (TEE), and the associated risks and costs
of general anesthesia, for guidance of some structural heart procedures.
Animals domesticated for working closely with humans (e.g. dogs) have been shown to
be remarkable in adjusting their behaviour to human attentional stance. However,
there is little evidence for this form of information perception in species
domesticated for production rather than companionship. We tested domestic ungulates
(goats) for their ability to differentiate attentional states of humans. In the
first experiment, we investigated the effect of body and head orientation of one
human experimenter on approach behaviour by goats. Test subjects (N = 24)
significantly changed their behaviour when the experimenter turned its back to the
subjects, but did not take into account head orientation alone. In the second
experiment, goats (N = 24) could choose to approach one of two experimenters, while
only one was paying attention to them. Goats preferred to approach humans that
oriented their body and head towards the subject, whereas head orientation alone
had no effect on choice behaviour. In the third experiment, goats (N = 32) were
transferred to a separate test arena and were rewarded for approaching two
experimenters providing a food reward during training trials. In subsequent probe
test trials, goats had to choose between the two experimenters differing in their
attentional states. Like in Experiments 1 and 2, goats did not show a preference
for the attentive person when the inattentive person turned her head away from the
subject. In this last experiment, goats preferred to approach the attentive person
compared to a person who closed their eyes or covered the whole face with a blind.
However, goats showed no preference when one person covered only the eyes. Our
results show that animals bred for production rather than companionship show
differences in their approach and choice behaviour depending on human attentive
state. However, our results contrast with previous findings regarding the use of
the head orientation to attribute attention and show the importance of cross-
validating results.
Understanding verbal descriptions of everyday actions could involve the neural
representation of action direction (avoidance and approach) toward persons and
things. We recorded the electrophysiological activity of participants while they
were reading approach/avoidance action sentences that were directed toward a
target: a thing/a person (i.e., "Petra accepted/rejected Ramn in her group"/ "Petra
accepted/rejected the receipt of the bank"). We measured brain potentials time
locked to the target word. In the case of things, we found a N400-like component
with right frontal distribution modulated by approach/avoidance action. This
component was more negative in avoidance than in approach sentences. In the case of
persons, a later negative event-related potential (545-750 ms) with left frontal
distribution was sensitive to verb direction, showing more negative amplitude for
approach than avoidance actions. In addition, more negativity in approach-person
sentences was associated with fear avoidance trait, whereas less negativity in
avoidance-person sentences was associated with a greater approach trait. Our
results support that verbal descriptions of approach/avoidance actions are encoded
differently depending on whether the target is a thing or a person. Implications of
these results for a social, emotional and motivational understanding of action
language are discussed.
In this note, we propose symbolic models for networks of discrete-time nonlinear
control systems. If each subsystem composing the network admits an incremental
input-to-state stable Lyapunov function and if some small gain theorem-type
conditions are satisfied, a network of symbolicmodels, each one associated with
each subsystem composing the network, is proposed and shown to be approximately
bisimilar to the original network with any desired accuracy.
Background: Approximate string matching is the problem of finding all factors of a
given text that are at a distance at most k from a given pattern. Fixed-length
approximate string matching is the problem of finding all factors of a text of
length n that are at a distance at most k from any factor of length l of a pattern
of length m. There exist bit-vector techniques to solve the fixed-length
approximate string matching problem in time O(m [l/w]n) and space O(m [l/w] under
the edit and Hamming distance models, where w is the size of the computer word; as
such these techniques are independent of the distance threshold k or the alphabet
size. Fixed-length approximate string matching is a generalisation of approximate
string matching and, hence, has numerous direct applications in computational
molecular biology and elsewhere. Results: We present and make available libFLASM, a
free open-source C++ software library for solving fixed-length approximate string
matching under both the edit and the Hamming distance models. Moreover we describe
how fixed-length approximate string matching is applied to solve real problems by
incorporating libFLASM into established applications for multiple circular sequence
alignment as well as single and structured motif extraction. Specifically, we
describe how it can be used to improve the accuracy of multiple circular sequence
alignment in terms of the inferred likelihood-based phylogenies; and we also
describe how it is used to efficiently find motifs in molecular sequences
representing regulatory or functional regions. The comparison of the performance of
the library to other algorithms show how it is competitive, especially with
increasing distance thresholds. Conclusions: Fixed-length approximate string
matching is a generalisation of the classic approximate string matching problem. We
present libFLASM, a free open-source C++ software library for solving fixed-length
approximate string matching. The extensive experimental results presented here
suggest that other applications could benefit from using libFLASM, and thus further
maintenance and development of libFLASM is desirable.
A high-efficiency method is proposed to suppress magnetic core imbalance in phase-
shifted full-bridge (PSFB) converters. Compared with conventional solutions, such
as controlling peak current mode (PCM) or adding DC blocking capacitance, the
proposed method has several advantages, such as lower power loss and smaller size,
because the additional current sensor or blocking capacitor is removed. A time
domain model of the secondary side is built to analyze the relationship between
transformer core imbalance and cathode voltage of secondary side rectifiers. An
approximate control algorithm is designed to achieve asymmetric phase control,
which reduces the effects of imbalance. A 60 V/15 A prototype is built to verify
the proposed method. Experimental results show that the numerical difference of
primary side peak currents between two adjacent cycles is suppressed from 2 A to
approximately 0 A. Meanwhile, compared with the PCM solution, the efficiency of the
PSFB converter is slightly improved from 93% to 93.2%.
We investigated the changes in the expression profiles of the partially resistant
apricot (Prunus armeniaca L.) cultivar Goldrich following inoculation with Plum pox
virus (PPV) using cDNA-amplification fragment length polymorphism, (AFLP). Altered
expression patterns were detected and twenty-one differentially expressed cDNA had
homologies with genes in databases coding for proteins involved in metabolism,
signal transduction, defense, stress and intra/intercellular connections. Seven of
the modified expressed patterns were further investigated by semi-quantitative RT-
PCR or Northern blotting. The expression patterns of five of these genes were
confirmed in the partially resistant P armeniaca cv. 'Goldrich' and assessed in a
susceptible genotype. One of these cDNAs, coding for a putative class III
chitinase, appeared to be repressed in infected plants of the partially resistant
genotype and expressed in the susceptible one which could be related to the
partially resistant phenotype. On the contrary, the expression patterns of the
genes coding for a transketolase, a kinesin-like and an ankyrin-like protein, were
clearly linked to the susceptible interaction. These candidate genes could play a
role either in the compatible interaction leading to virus invasion or to the
quantitative resistance of apricot to PPV (c) 2006 Elsevier B.V. All rights
reserved.
Some fruits have a reduced harvesting period or a high degree of perishability,
which results in a very short shelf life. Therefore, in order to extend the shelf
life of foodstuffs, maintaining low the level at which microbial spoilage and
deterioration reactions can occur, fresh fruits have to be treated, obtaining semi-
finished products. Those products are commonly used as starting materials by some
food industries, like jams', gelatines' and marmalades' ones, due to the extension
of their productions throughout the whole year. Among the possible techniques, the
Southern Italy industry under study uses three different techniques to produce,
package and preserve semi-finished fruits: one based on individually quick
freezing, one on low-pressure superheated steam drying with far-infrared radiation,
and one on an ohmic aseptic treatment. In the last years, food industries have
focused their attention not only towards high quality products but also towards
environmental friendly productions. Therefore, the aim of this work is to use a
Life Cycle Assessment (LCA) approach to compare the environmental emissions of the
three different production and preservation techniques used by the industry under
study. The environmental impacts were evaluated using a detailed LCA analysis,
normalizing all the consumptions and emissions to the functional unit (one
apricots' kg on dry basis). Data were analysed using SimaPro 8.0.5 software,
whereas the Ecoinvent database and information collected from the chosen industrial
site were used for the life cycle inventory, according to the reference standard
for LCA (i.e., ISO 14040-14044). (C) 2017 Elsevier Ltd. All rights reserved.
In this article we investigate if the Swedish consumer prices for electricity are
adjusted equally fast regardless of whether the NordPool power market prices are
decreased or increased. Due to relatively moderate variations in the variables, we
have applied quantile regression, since it is mainly the large changes (above the
median) that essentially tend to have a considerable effect on the consumer prices.
Moreover, in order to adjust for stochastic- and deterministic trends,
autocorrelation, structural breaks as well as to measure APT effects in the short-
and in the medium-run, we apply a wavelet decomposition approach. Our results show
evidence that significantly positive asymmetric price transmission (APT) effects
exist in this market. More specifically, in the short-run (based on the wavelet
decomposition D1 for 1-2 months cycles), we find that that there is a higher
propensity to rapidly and systematically increase the consumer prices subsequently
to an increase in the NordPool market price, compared with the propensity to
decrease their customers prices subsequently to a corresponding drop in the
NordPool market prices. However, no significant APT effects were detected in the
medium- or in the long-run (i.e. the asymmetric price transmission effects are
observed only in the short-run). In summary, we could isolate significant APT
effects in the short-run (1-2 months decomposition cycles), and for large changes
in the dependent variable (percentiles = 0.9). Therefore, only large changes in the
NordPool prices lead to feedback effects in the form of asymmetric price
transmission effects. Our evidence supports the notion of firms' downward
stickiness of retail prices for maximizing profit, which are not expected to be
found on a fully efficient market. Although our finding shows that the price
inefficiency is short-lived, these large temporal inefficiencies are still costly
for the consumers. It should be noted that blunt traditional powerless methods do
not detect these APT effects, while our wavelet quantile methods are powerful and
make a significant contribution in the literature by providing new empirical
evidence.
DNA vaccines had been widely used in animal models against various viral
infections, while it was not so convincing for many infectious diseases especially
bacterial disease in aquaculture. Interleukin-8(IL-8) as one of the CXC chemokines,
its immunological role and adjuvant potential which had been proved in mammals were
rarely reported in fish species. In this study, recombination plasmid pcDNA3.1/IL-
8(pcIL-8) was conducted and the capacity of IL-8 as molecular adjuvant was explored
from several aspects by co-injecting with a DNA vaccine encoding a-enolase(pcENO)
against Streptococcus iniae infection in channel catfish. The results suggested
that co-injection of pcIL-8 with DNA vaccine increased the innate immunity and
specific antibody levels, as well as increased the immune-related genes involving
in pro-inflammatory response, humoral and cellular immunity. Moreover, pcIL-8
enhanced the immunoprotection of pcENO with the relative percent survival(RPS) of
60% to 80% against S. iniae infection at 4 week post vaccination(p.v.), with the
significantly higher RPS of 73.33% in pcENO+pcIL-8 group compared with that of
pcENO alone(53.33%) at challenge test of 8 weeks p.v. Taken together, these results
indicate pcIL-8 as a molecular adjuvant co-injected with DNA vaccine not only
improves the immunoprotection but also maintains long period of immunity for
channel catfish against S. iniae infection. Our study signifies that IL-8 holds
promise to serve as a potential adjuvant in DNA vaccines against bacterial
infections for long time.
Fish from aquaculture is becoming more important for human consumption. Sustainable
aquaculture procedures were developed as an alternative to overcome the negative
environmental impacts of conventional aquaculture procedures and wild fisheries.
The objective of this contribution is to determine what consumers expect from
sustainable aquaculture and whether they prefer sustainable aquaculture products. A
combination of qualitative research methods, with think aloud protocols and in-
depth interviews, as well as quantitative methods, using choice experiments and
face-to-face interviews, was applied. Data was collected in three different cities
of Germany. Results revealed that sustainable aquaculture was associated with
natural, traditional, local, and small scale production systems with high animal
welfare standards. Overall, participants paid a lot of attention to the declaration
of origin; in particular fish products from Germany and Denmark were preferred
along with local products. Frequently used sustainability claims for aquaculture
products were mostly criticized as being imprecise by the participants of the
qualitative study; even though two claims tested in the choice experiments had a
significant positive impact on the choice of purchase. Similarly, existing
aquaculture-specific labels for certified sustainable aquaculture had an impact on
the buying decision, but were not well recognized and even less trusted. Overall,
consumers had a positive attitude towards sustainable aquaculture. However,
communication measures and labelling schemes should be improved to increase
consumer acceptance and make a decisive impact on consumers' buying behavior. (C)
2017 Elsevier Ltd. All rights reserved.
This study evaluated the control of streptococcosis outbreaks in Brazil, isolated
from diseased sorubim and identified as Lactococcus garvieae by genetic sequencing.
This report determined the potential for lactococcosis control in sorubim
Pseudoplatystoma sp. with two vaccines: an aqueous-based, whole-cell inactivated
vaccine (bacterin) and an oil-adjuvanted bacterin. Their efficacy was evaluated at
30 days post-vaccination (d.p.v.) by challenge with L. garvieae, and the antibody
production response at 15, 30 and 60 d.p.v. and the non-specific immune response
were compared amongst treatments. High protection levels (P < 0.05) were achieved
with the oil-adjuvanted vaccine with a relative percentage survival value of 81.7%
at 30 d.p.v. Additionally, the oil-adjuvanted vaccine increased the immunogenicity
of the bacterin as indicated by greater agglutination antibody titres from 15 until
60 d.p.v. This is the first report of a positive effect of vaccine administration
on the specific immunity of sorubim, and the study showed that a specific antibody
plays an important role in sorubim defence against lactococcosis because the innate
immune responses were similar in all of the studied animals. These results
demonstrated that oil-adjuvanted vaccine can be an effective alternative for the
protection of sorubim from L. garvieae disease.
Peyronie's disease (PD) is a localized disorder of the connective tissue of the
tunica albuginea (TA) whose etiology has not been elucidated. Although several
studies have implicated genetic susceptibility and/or mechanical trauma as
triggering events for PD, the underlying molecular mechanisms remain largely
unknown. Aquaporin 1 (AQP1) is a water channel protein potentially implicated in
connective tissue resistance to mechanical stress, acting primarily by increasing
tension within the collagen network. Although it represents a potentially
attractive molecular target in PD, to date no studies had ever addressed whether
AQP1 is detectable and/or differentially expressed in the TA of these patients.
Herein the present study, through immunohistochemical and biochemical approaches,
we were able to detect AQP1 expression in the TA of control and PD affected
patients. We demonstrated that AQP1-like immunoreactivity and expression are
significantly increased in plaques of PD patients Vs controls, implying that AQP1
overexpression might be the consequence of a localized maladaptive response of the
connective tissue to repeated mechanical trauma. In summary, these data support the
idea that AQP1 might represent a potentially useful biomarker of mechanical injury
in the TA and a promising target for the treatment of PD.
The dogfish ortholog of aquaporin 4 (AQP4) was amplified from cDNA using degenerate
PCR followed by cloning and sequencing. The complete coding region was then
obtained using 5' and 3' RACE techniques. Alignment of the sequence with AQP4 amino
acid sequences from other species showed that dogfish AQP4 has high levels (up to
65.3%) of homology with higher vertebrate sequences but lower levels of homology to
Agnathan (38.2%) or teleost (57.5%) fish sequences. Northern blotting indicated
that the dogfish mRNA was approximately 3.2 kb and was highly expressed in the
rectal gland (a shark fluid secretory organ). Semi-quantitative PCR further
indicates that AQP4 is ubiquitous, being expressed in all tissues measured but at
low levels in certain tissues, where the level in liver >gill >intestine.
Manipulation of the external environmental salinity of groups of dogfish showed
that when fish were acclimated in stages to 120% seawater (SW) or 75% SW, there was
no change in AQP4 mRNA expression in either rectal gland, kidney, or
esophagus/cardiac stomach. Whereas quantitative PCR experiments using the RNA
samples from the same experiment, showed a significant 63.1% lower abundance of
gill AQP4 mRNA expression in 120% SW-acclimated dogfish. The function of dogfish
AQP4 was also determined by measuring the effect of the AQP4 expression in Xenopus
laevis oocytes. Dogfish AQP4 expressing-oocytes, exhibited significantly increased
osmotic water permeability (P-f) compared to controls, and this was invariant with
pH. Permeability was not significantly reduced by treatment of oocytes with mercury
chloride, as is also the case with AQP4 in other species. Similarly AQP4
expressing-oocytes did not exhibit enhanced urea or glycerol permeability, which is
also consistent with the water-selective property of AQP4 in other species.
Aquaporins (AQPs) are a family of small membrane proteins that transport water
molecules across the plasma membrane along the osmotic gradient. Mammals express 13
subtypes of AQPs, including the recently reported "subcellular AQPs", AQP11 and 12.
Each organ expresses specific subsets of AQP subtypes, and in the inner ear, AQPs
are essential for the establishment and maintenance of two distinct fluids,
endolymph and perilymph. To evaluate the contribution of AQPs during the
establishment of inner ear function, we used quantitative reverse transcription
polymerase chain reaction to quantify the expression levels of all known AQPs
during the entire development and maturation of the inner ear. Using systematic and
longitudinal quantification, we found that AQP11 was majorly and constantly
expressed in the inner ear, and that the expression levels of several AQPs follow
characteristic longitudinal patterns: increasing (Aqp0, 1, and 9), decreasing
(Aqp6, 8, and 12), and peak of expression on E18 (Aqp2, 5, and 7). In particular,
the expression level of Aqp9 increased by 70-fold during P3-P21. We also performed
in situ hybridization of Aqp11, and determined the unique localization of Aqp11 in
the outer hair cells. Immunohistochemistry of AQP9 revealed its localization in the
supporting cells inside the organ of Corti, and in the root cells. The emergence of
AQP9 expression in these cells was during P3-P21, which was coincident with the
marked increase of its expression level. Combining these quantification and
localization data, we discuss the possible contributions of these AQPs to inner ear
function.
Background: Tick-borne diseases greatly impact human and animal health worldwide,
and vaccines are an environmentally friendly alternative to acaricides for their
control. Recent results have suggested that aquaporin (AQP) water channels have a
key function during tick feeding and development, and constitute good candidate
antigens for the control of tick infestations. Methods: Here we describe the effect
of vaccination with the Ixodes ricinus AQP1 (IrAQP) and a tick AQP conserved region
(CoAQP) on I. ricinus tick larval mortality, feeding and molting. Results: We
demonstrated that vaccination with IrAQP and CoAQP had an efficacy of 32% and 80%,
respectively on the control of I. ricinus larvae by considering the cumulative
effect on reducing tick survival and molting. Conclusions: The effect of the AQP
vaccines on larval survival and molting is essential to reduce tick infestations,
and extended previous results on the effect of R. microplus AQP1 on the control of
cattle tick infestations. These results supports that AQP, and particularly CoAQP,
might be a candidate protective antigen for the control of different tick species.
(C) 2017 Elsevier Ltd. All rights reserved.
Our previous work supports a role for aquaporin-8 (AQP8) water channels in rat
hepatocyte bile formation mainly by facilitating the osmotically driven canalicular
secretion of water. In this study, we tested whether a condition with compromised
canalicular bile secretion, i.e., the estrogen-induced intrahepatic cholestasis,
displays defective hepatocyte AQP8 functional expression. After 17 alpha-
ethinylestradiol administration (5 mg center dot kg body wt(-1)center dot day(-1)
for 5 days) to rats, the bile flow was reduced by 58% (P < 0.05). By subcellular
fractionation and immunoblotting analysis, we found that 34 kDa AQP8 was
significantly decreased by similar to 70% in plasma (canalicular) and intracellular
(vesicular) liver membranes. However, 17 alpha-ethinylestradiol-induced cholestasis
did not significantly affect the protein level or the subcellular localization of
sinusoidal AQP9. Immunohistochemistry for liver AQPs confirmed these observations.
Osmotic water permeability (P-f) of canalicular membranes, measured by stopped-flow
spectrophotometry, was significantly reduced (73 +/- 1 vs. 57 +/- 2 mu m/s) in
cholestasis, consistent with defective canalicular AQP8 functional expression. By
Northern blotting, we found that AQP8 mRNA expression was increased by 115% in
cholestasis, suggesting a posttranscriptional mechanism of protein level reduction.
Accordingly, studies in primary cultured rat hepatocytes indicated that the
lysosomal protease inhibitor leupeptin prevented the estrogen-induced AQP8
downregulation. In conclusion, hepatocyte AQP8 protein expression is downregulated
in estrogen-induced intrahepatic cholestasis, presumably by lysosomal-mediated
degradation. Reduced canalicular membrane AQP8 expression is associated with
impaired osmotic membrane water permeability. Our data support the novel notion
that a defective expression of canalicular AQP8 contributes as a mechanism for bile
secretory dysfunction of cholestatic hepatocytes.
Four black fly species of the Simulium striatum species group have been recorded in
Thailand. These species are morphologically highly similar in all developmental
stages except for the number and arrangement of the pupal gill filaments. In this
study, we used multiple characters sources, including morphology, cytology,
molecular biology and ecology, to test the hypothesis of conspecificity for S.
quinquestriatum (Shiraki), S. nakhonense Takaoka & Suzuki and S. chiangmaiense
Takaoka & Suzuki. A molecular study based on the cytochrome c oxidase subunit I
(COI) was unable to separate these taxa. In contrast, the elongation complex
protein 1 (ECP1) sequences clearly differentiate S. quinquestriatum from S.
chiangmaiense and S. nakhonense. However, the latter two taxa could not be
differentiated based on molecular DNA sequences. Simulium chiangmaiense and S.
nakhonense are also similar in the larval habitat characteristics and have
undifferentiated polytene chromosome banding patterns. Morphological examination of
the number and arrangement of the pupal gill filaments found a number of
intermediate forms. Therefore, S. chiangmaiense and S. nakhonense are apparently
the same biological species that is polymorphic for the number and arrangement of
gill filaments. Thus, we synonymized S. chiangmaiense with S. nakhonense.
This study evaluated the ambient noise effect of onshore and offshore aquaculture
systems on oxidative status and on some immune parameters in gilthead sea bream
(Sparus aurata) juveniles. The experiment was performed for 40 days, projecting two
different playlists of acoustic stimuli: offshore aquaculture noise condition that
created the typical acoustic field in proximity of an offshore sea cage for fish
farming, using a random sequence of quite sea background and boat noises; and
onshore aquaculture noise condition that represented the acoustic field inside an
open concrete tank for fish farming. A third group without any acoustic projection
was used as a control. After 40 days from the beginning of acoustic noise, fish
exposed to the offshore aquaculture condition showed significantly higher levels of
total oxidant status, lysozyme activity, antiprotease activity and white blood
cells together with a lower albumin/globulin ratio in comparison to fish from the
control group; whereas fish exposed to the onshore condition showed analytical data
placed between the other groups, though never significantly different. These
results demonstrate that the offshore aquaculture noise, and in particular the sea
soundscape, adversely influences the oxidative status and the immune function of
gilthead sea bream determining a mild stress condition that could affect the sea
bream welfare.
The potential recovery of high-value products from brewery yeast waste confers
value to this industrial residue. Aqueous two-phase systems (ATPS) have
demonstrated to be an attractive alternative for the primary recovery of biological
products and are therefore suitable for the recovery of invertase from this
residue. Sixteen different polyethylene glycol (PEG)-potassium phosphate ATPS were
tested to evaluate the effects of PEG molecular weight (MW) and tie-line length
(TLL) upon the partition behavior of invertase. Concentrations of crude extract
from brewery yeast waste were then varied in the systems that presented the best
behaviors to intensify the potential recovery of the enzyme. Results show that the
use of a PEG MW 400 g mol(-1) system with a TLL of 45.0% (w/w) resulted in an
invertase bottom phase recovery with a purification factor of 29.5 and a recovery
yield of up to 66.2% after scaling the system to a total weight of 15.0 g. This
represents 15.1 mg of invertase per mL of processed bottom phase. With these
results, a single-stage ATPS process for the recovery of invertase is proposed. (C)
2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63,
Number 6, Pages 886-894, 2016
The function of AZI1 in systemic acquired resistance of Arabidopsis was confirmed
by investigation of the phenotypic features of wild-type Col-0, AZI1 T-DNA knockout
and AZI1 overexpressing plants after infection with virulent and avirulent
Pseudomonas syringae. Real-time quantitative PCR and Northern blotting analyses
showed that the transcript abundances of PR genes increased significantly in local
and systemic leaves of wild-type Col-0 and AZI1 overexpressing plants challenged
with avirulent P. syringae, whereas the mRNA accumulation of PR genes was obviously
attenuated in local and systemic leaves of AZI1 T-DNA knockout plants after
localized infiltration with avirulent Psm avrRpm1. The changes of metabolomic
profiles in distal leaves of three types of materials infected with avirulent P.
syringae were determined by H-1 NMR spectrometry and data mining showed that the
soluble carbonhydrates might function as signal substances in the systemic immunity
of Arabidopsis. At the same time, the expression of the sugar signaling genes in
local and distal leaves after infection of avirulent P. syringae was compared. As a
result, it was found that the transcript abundances of sugar signaling genes,
including SUS1, SUS2, SUS3, SUS6, SUT1, HXK1, HXK2, SNRK1.2, ERD6, TPS1, TOR,
SNRK1.1, SNRK1.3 and bZIP11, were obviously changed in distal leaves of different
materials with the modulated AZI1 activities, indicating sugar-related genes are
involved in regulation of the systemic immunity mediated by AZI1. These results
also illustrated that the immune system associated with sugar molecules probably
was an important part of the systemic acquired resistance in Arabidopsis. (C) 2016
Elsevier Masson SAS. All rights reserved.
The shape of the inflorescence in Arabidopsis thaliana ecotype Columbia is a raceme
with individual flowers developing acropetally. The ecotype Landsberg harboring the
erecta (er) mutation shows a corymb-like inflorescence, namely a compact
inflorescence with a flattened arrangement of flower buds at the tip. To gain
insight into inflorescence development, we previously isolated corymb-like
inflorescence mutants, named corymbosal (crm1), and found that the corymb-like
inflorescence in crm1-1 was due to reduced cell elongation of pedicels and stem
internodes. Double mutants of crm1 with er and crm2, and crm1-1 crm2-1 er-105
triple mutants show an additive phenotype. crm1-1 is caused by a mutation in BIG,
which is required for polar auxin transport. CRM1/BIG is expressed in inflorescence
meristems, floral meristems and vascular tissues. We analyzed a collection of 12
reduced lateral root formation (rlr) mutants, which are allelic to crm1-1, and
categorized the mutants into three classes, depending on the plant developmental
defects. Although all 12 alleles had new stop codons, the phenotype of heterozygous
crm1-1/doc1-1 and Northern blotting suggest that new crm1/big mutant alleles are
hypomorphic. Auxin-responsive DR5rev::GFP expression was decreased in crm1-1
vasculature of pedicels and stem internodes. PINFORMED1 (PIN1) and CRM1/BIG are
expressed in vasculature of pedicels and stem internodes. The severity of corymb-
like inflorescence in crm1/big mutants correlated with increased levels of PIN1.
Our results suggest that CRM1/BIG controls the elongation of the pedicels and stem
internodes through auxin action.
Quantitative real-time PCR (qRT-PCR) has become a routine and robust technique for
measuring the expression of genes of interest, validating microarray experiments
and monitoring biomarkers. However, concerns have been raised over the accuracy of
qRT-PCR in China as well as in the rest of the world. We have previously used qRT-
PCR to study the response of ANR1 and other root-expressed MADS-box genes to
fluctuations in the supply of nitrate, phosphate and sulphate under hydroponic
growth conditions. In this study, we have used both Northern blotting and qRT-PCR
analyses to confirm the nutritional regulation of MADS-box genes in Arabidopsis
thaliana and test whether both technologies produce the same results. The
information obtained indicated that the qRT-PCR results are consistent with those
obtained by Northern blotting hybridization for all the tested root-expressed MADS-
box genes, in response to different nitrate, phosphate and sulphate growth
conditions. Furthermore, our novel results showed that the expressions of AGL12,
AGL18, and AGL19 were all down regulated in response to S and P re-supply in both
qRT-PCR and Northern blotting analyses.
Arabidopsis thaliana is a long established model species for plant molecular
biology, genetics and genomics, and studies of A. thaliana gene function provide
the basis for formulating hypotheses and designing experiments involving other
plants, including economically important species. A comprehensive understanding of
the A. thaliana genome and a detailed and accurate understanding of the expression
of its associated genes is therefore of great importance for both fundamental
research and practical applications. Such goal is reliant on the development of new
genetic and genomic resources, involving new methods of data acquisition and
analysis. We present here the genome-wide analysis of A. thaliana gene expression
profiles across different organs and developmental stages using high-throughput
transcriptome sequencing. The expression of 25 706 protein-coding genes, as well as
their stability and their spatiotemporal specificity, was assessed in 79 organs and
developmental stages. A search for alternative splicing events identified 37 873
previously unreported splice junctions, approximately 30% of them occurred in
intergenic regions. These potentially represent novel spliced genes that are not
included in the TAIR10 database. These data are housed in an open-access web-based
database, TraVA (Transcriptome Variation Analysis, http://travadb.org/), which
allows visualization and analysis of gene expression profiles and differential gene
expression between organs and developmental stages.
The presented research hypothesis-driven laboratory exercise teaches advanced
undergraduate students state of the art methods and thinking in an integrated
molecular physiology context. Students understand the theoretical background of
iron acquisition in the model plant Arabidopsis thaliana. They design a flowchart
summarizing the key steps of the experimental approach. Students are made familiar
with current techniques such as qPCR. Following their experimental outline,
students grow Arabidopsis seedlings up to the age of six days under sufficient and
deficient iron supply. The Arabidopsis plants are of two different genotypes,
namely wild type and fit loss of function mutants. fit mutants lack the essential
transcription factor FIT, required for iron acquisition and plant growth. Students
monitor growth phenotypes and root iron reductase activity in a quantitative and
qualitative manner. Then, students determine gene expression regulation of FIT,
FRO2, and a reference gene by reverse transcription-quantitative PCR (RT-qPCR).
Finally, students interpet their results and build a model summarizing the
connections between morphological, physiological and molecular iron deficiency
responses. Learning outcomes and suggestions for integrating the course concept are
explained. (C) 2016 by The International Union of Biochemistry and Molecular
Biology.
Hypersensitive response (HR) is a form of programmed cell death (PCD) and the
primary immune response that prevents pathogen invasion in plants. Here, we show
that a microRNA miR164 and its target gene NAC4 (At5g07680), encoding a NAC
transcription factor, play essential roles in the regulation of HR PCD in
Arabidopsis thaliana. Cell death symptoms were noticeably enhanced in NAC4-
overexpressing (35S:NAC4) and mir164 mutant plants in response to avirulent
bacterial pathogens. NAC4 expression was induced by pathogen infection and
negatively regulated by miR164 expression. NAC4-binding DNA sequences were
determined by in vitro binding site selection using random oligonucleotide
sequences. Microarray, chromatin immunoprecipitation and quantitative real time
polymerase chain reaction (qRT-PCR) analyses, followed by cell death assays in
protoplasts, led to the identification of NAC4 target genes LURP1, WRKY40 and
WRKY54, which act as negative regulators of cell death. Our results suggest that
NAC4 promotes hypersensitive cell death by suppressing its target genes and this
immune process is fine-tuned by the negative action of miR164.
Hydrogen peroxide (H2O2) acts as a signaling molecule modulating the expression of
various genes in plants. However, the reference gene(s) used for gene expression
analysis of H2O2 signaling is still arbitrary. A reliable result obtained by
quantitative real-time RT-PCR (RT-qPCR) highly depends on accurate transcript
normalization using stably expressed reference genes, whereas the inaccurate
normalization could easily lead to the false conclusions. In this report, by using
geNorm and NormFinder algorithms, 12 candidate reference genes were evaluated and
compared in root and shoot tissues of Arabidopsis upon different doses of H2O2. The
results revealed that, in our experimental conditions, three novel reference genes
(TIP41-like, UKN, and UBC21) were identified and validated as suitable reference
genes for RT-qPCR normalization in both root and shoot tissues under oxidative
stress. This conclusion was further confirmed by publicly available microarray data
of methyl viologen and drought stress. In comparison with a single reference gene
(EF-1a), the expression pattern of ZAT12 modulated by H2O2, when using TIP41-like,
UKN, and UBC21 as multiple reference gene(s), was similar with the previous reports
by using northern blotting. Thus, we proposed that these three reference genes
might be good candidates for other researchers to include in their reference gene
validation in gene expression studies under H2O2-related oxidative stress.
Cotton (Gossypium L.) fiber is a unique experimental system for studying plant cell
elongation and cell wall biogenesis. Arabinogalactan proteins (AGPs) are
extracellular proteoglycans and play important roles in various aspects of plant
growth and development. In the present work, four AGP genes, GhAGP2, GhAGP3,
GhAGP4, and GhFLA1, were cloned from cotton fiber through 5' and 3' rapid
amplification of cDNA ends (RACE). All these genes code for classical AGPs
containing N-terminal signal sequence, a central domain rich in Ala, Ser, Thr,
Pro/Hyp, and C-terminal hydrophobic transmembrane domain. Additionally all the four
putative proteins contain two AGP-like domains, one fasciclin-like domain and a
putative C-terminal glycosylphosphatidylinositol lipid anchor signal sequence.
Northern blotting analysis with gene-specific probes indicates the transcripts of
GhAGP2 and GhFLA1 accumulate in Gossypium hirsutum fiber from 5 to 20 days post
anthesis, whereas GhAGP3 and GhAGP4 are abundantly expressed during the
developmental stage switching from elongation to the secondary cell wall synthesis.
Furthermore, quantitative reverse transcription polymerase chain reaction analysis
demonstrates that all these fasciclin-like AGP genes are specifically expressed not
only in G. hirsutum fibers but also in Gossypium barbadense fibers. The fasciclin-
like domains are typically found in adhesion proteins of animal cell, and the
specific expression patterns together with presence of fasciclin-like domains
suggest roles for fasciclin-like AGPs in cell-to-cell communication during cotton
fiber elongation and secondary cell wall development.
Eicosanoids derive from essential polyunsaturated fatty acids (PUFA) and play
crucial roles in immunity, development, and reproduction. However, potential links
between dietary PUFA supply and eicosanoid biosynthesis are poorly understood,
especially in invertebrates. Using Daphnia magna and its bacterial parasite
Pasteuria ramosa as model system, we studied the expression of genes coding for key
enzymes in eicosanoid biosynthesis and of genes related to oogenesis in response to
dietary arachidonic acid and eicosapentaenoic acid in parasite exposed and non-
exposed animals. Gene expression related to cyclooxygenase activity was especially
responsive to the dietary PUFA supply and parasite challenge, indicating a role for
prostanoid eicosanoids in immunity and reproduction. Vitellogenin gene expression
was induced upon parasite exposure in all food treatments, suggesting infection-
related interference with the host's reproductive system. Our findings highlight
the potential of dietary PUFA to modulate the expression of key enzymes involved in
eicosanoid biosynthesis and reproduction and thus underpin the idea that the
dietary PUFA supply can influence invertebrate immune functions and host-parasite
interactions. (C) 2016 Elsevier Inc. All rights reserved.
World experts of different disciplines, from molecular biology to macroecology,
recognize the value of cave ecosystems as ideal ecological and evolutionary
laboratories. Among other subterranean taxa, spiders stand out as intriguing model
organisms for their ecological role of top predators, their unique adaptations to
the hypogean medium and their sensitivity to anthropogenic disturbance. As the
description of the first eyeless spider (Stalita taenaria), an array of papers on
subterranean spider biology, ecology and evolution has been published, but a
comprehensive review on these topics is still lacking. We provide a general
overview of the spider families recorded in hypogean habitats worldwide, we review
the different adaptations of hypogean spiders to subterranean life, and we
summarize the information gathered so far about their origin, population structure,
ecology and conservation status. Finally, we point out the limits of the knowledge
we currently have regarding hypogean spiders, aiming to stimulate future research.
Arbuscular mycorrhiza (AM) formed between plant roots and fungi is one of the most
widespread symbiotic associations in nature. To understand the molecular mechanisms
of AM formation, we profiled 30 symbiosis-related genes expressed in Amorpha
fruticosa roots colonized by Glomus mosseae and in non-mycorrhizal roots at
different stages using differential-display RT-PCR (DDRT-PCR). The expressed genes
were confirmed by reverse Northern blotting. Eleven fragments were sequenced and
putatively identified by homologous alignment. Of the eleven AM-related genes, five
were obtained at the early-stage of plant-fungus interaction and six at the later
stage. Three expressed sequence tag (ESTs) sequences were found to originate from
the fungi and eight from the host plant by use of PCR evaluation of gDNA of both
plant and fungi. The target genes included an ATP-binding cassette sub-family
transporter gene, a transposon-insertion display band, and a photosynthesis-related
gene. The results provided information on the molecular mechanisms underlying the
development of mycorrhizal symbiosis between woody plants and AM fungi.
Arbuscular mycorrhizal fungi (AMF) occur in the majority of terrestrial, and some
aquatic, habitats worldwide. They are important for the functioning of individual
plants and of entire ecosystems. Here, we review trends in research on species-
(species recognition, phylogenetic relationships, autecology) and community-level
AMF diversity patterns and aim to identify ways of improving the complementarity of
these approaches. Research into many aspects of AMF diversity has flourished in
parallel with the increasing availability of molecular biology techniques. However,
despite their shared goal of understanding AMF biodiversity, species- and
community-level perspectives, and the morphological and molecular approaches that
underpin them, currently have limited capacity for information exchange. We
indicate critical research gaps in AMF species and community characterisation and
outline important research directions. We propose steps that could link research
using different methods and targeting different aspects of diversity, in order to
maximise our understanding of AMF. (C) 2016 Elsevier Ltd and British Mycological
Society. All rights reserved.
Archaea are widespread organisms colonizing almost every habitat on Earth. However,
the molecular biology of archaea still remains relatively uncharacterized. RNA
metabolism is a central cellular process, which has been extensively analyzed in
both bacteria and eukarya. In contrast, analysis of RNA metabolism dynamic in
archaea has been limited to date. To facilitate analysis of the RNA metabolism
dynamic at a system-wide scale in archaea, we have established non-radioactive
pulse labeling of RNA, using the nucleotide analog 4-thiouracil (4TU) in two
commonly used model archaea: the halophile Euryarchaeota Haloferax volcanii, and
the thermo-acidophile Crenarchaeota Sulfolobus acidocaldarius. In this work, we
show that 4TU pulse labeling can be efficiently performed in these two organisms in
a dose-and time-dependent manner. In addition, our results suggest that uracil
prototrophy had no critical impact on the overall 4TU incorporation in RNA
molecules. Accordingly, our work suggests that 4TU incorporation can be widely
performed in archaea, thereby expanding the molecular toolkit to analyze archaeal
gene expression network dynamic in unprecedented detail.
Relative to other historic documents, newspapers have received little attention
from researchers as a source of archaeological data. Now that many historic
newspapers have been digitized and placed online, this traditionally underutilized
resource has the potential to yield new information about archaeological sites,
especially those in heavily developed urban areas where sites are inaccessible or
have been destroyed. In this article, a methodology is proposed by which archived
newspapers might be searched for data about archaeological sites. A case study
using newspapers from Allen County, Indiana and its principal city, Fort Wayne,
demonstrates the utility of the methodology by producing evidence about many
previously unrecorded archaeological sites.
Some species of the Arcobacter genus are considered emerging foodborne and
waterborne en. However, the presence of Arcobacter spp. in vegetables very little
is known, because most studies have focused on foods of animal origin. On the other
hand, quinolones are considered as first-line drugs for the treatment of infection
by campylobacteria in human patients, but few data are currently available about
the resistance levels to these antibiotics among Arcobacter species. Therefore, the
aim of this study was to investigate the presence and diversity of arcobacters
isolated from fresh vegetables such as lettuces, spinaches, chards and cabbages.
Resistance to quinolones of the isolates was also investigated. One hundred fresh
vegetables samples purchased from seven local retail markets in Valencia (Spain)
during eight months were analysed. The study included 41 lettuces, 21 spinaches, 34
chards and 4 cabbages. Samples were analysed by culture and by molecular methods
before and after enrichment. By culture, 17 out of 100 analysed samples were
Arcobacter positive and twenty-five isolates were obtained from them. Direct
detection by PCR was low, with only 4% Arcobacter spp. positive samples. This
percentage increased considerably, up 20%, after 48 h enrichment. By polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP), 17 out of the
25 isolates were identified as A. butzleri and 8 as A. cryaerophilus. Only two A.
butzleri isolates showed resistance to levofloxacin and ciprofloxacin. The
sequencing of a fragment of the QRDR region of the gyrA gene from the quinolones-
resistant isolates revealed the presence of a mutation in position 254 of this gene
(C-T transition). This study is the first report about the presence of pathogenic
species of Arcobacter spp. in chards and cabbages and confirms that fresh
vegetables can act as transmission vehicle to humans. Moreover, the presence of A.
butzleri quinolone resistant in vegetables could pose a potential public health
risk. (C) 2017 Elsevier Ltd. All rights reserved.
This work aimed to determine the presence of Arcobacter spp. in shellfish and to
determine its susceptibility to quinolones. One hundred samples (41 mussels, 37
clams, and 22 cockles) were purchased from different local retail shops in
Valencia, Spain, from September 2013 to June 2015. All samples were analyzed
simultaneously by culture, after an enrichment step, and by polymerase chain
reaction (PCR), directly and after enrichment. The susceptibility to levofloxacin
and ciprofloxacin of the isolates was tested using the disk-diffusion test and E-
test strips method. To clarify the mechanism of quinolone resistance, a fragment of
the quinolone resistance-determining region of the gyrA gene was sequenced. Thirty-
seven samples were positive and 49 isolates were obtained by culture, and
Arcobacter spp. DNA was detected in 32% of the samples by PCR. However, after 48-h
enrichment, the number of positive samples increased, and 68 of the 100 samples
yielded the specific Arcobacter spp. PCR product. In addition, 49 isolates were
identified by PCR-restriction fragment length polymorphism. The most commonly found
species was Arcobacter butzleri (25 isolates, 51.03%) followed by Arcobacter
cryaerophilus (19 isolates, 38.77%) and Arcobacter defluvii (5 isolates, 10.20%).
Only three isolates of A. butzleri were resistant to both antibiotics. A mutation C
to T transition in the position 254 of the gyrA gene was present in the three
resistant isolates. This study confirms that pathogenic arcobacters are frequently
found in edible shellfish samples. Moreover, this is the first time that A.
butzleri and A. cryaerophilus have been isolated from cockles.
Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby
attenuate colitis in mice by down-regulating the activation of mechanistic target
of rapamycin complex 1 (mTORC1). The present study was performed to address its
underlying mechanism in view of estrogen receptor (ER). The specific antagonist
PHTPP or siRNA of ER beta largely diminished the inhibitory effect of arctigenin on
the mTORC1 activation in T cell lines and primary CD4(+) T cells under Th17-
polarization condition, suggesting that arctigenin functioned in an ER beta-
dependent manner. Moreover, arctigenin was recognized to be an agonist of ER beta,
which could bind to ER beta with a moderate affinity, promote dissociation of ER
beta/HSP90 complex and nuclear translocation and phosphorylation of ER beta, and
increase the transcription activity. Following activation of ER beta, arctigenin
inhibited the activity of mTORC1 by disruption of ER beta-raptor-mTOR complex
assembly. Deficiency of ER beta markedly abolished arctigenin-mediated inhibition
of Th17 cell differentiation. In colitis mice, the activation of ER beta,
inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by
PHTPP treatment. In conclusion, ER beta might be the target protein of arctigenin
responsible for inhibition of mTORC1 activation and resultant prevention of Th17
cell differentiation and colitis development.
A method that can be used to more easily perform human body communication, (HBC)
has been developed. In the proposed method, Arduino technology is used as a
wearable device. Baseband communication is used in this study. Baseband
communication uses an operational amplifier to amplify the signal generated by the
Arduino, device and uses a comparator to remove noise. This study experimented with
a biological tissue equivalent phantom. An application was developed to measure
temperature and confirm the transmission and reception of a string. We successfully
transmitted a string using HBC with a simple circuit. In addition, changes in
impedance and voltage in the electrode were measured. Our experimental results
confirm effective HBC in the 300 Hz band.
Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure
(CRF). Defective nitric oxide ( NO) generation due to decreased endothelial NO
synthase ( eNOS) activity is a crucial parameter characterizing ECD. L-arginine is
the sole precursor for NO biosynthesis. Among several transporters that mediate L-
arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific
arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major
determinant of eNOS activity in CRF. We studied glomerular and aortic arginine
uptake, CAT-1, and CAT-2 messenger ribonucleic acid ( mRNA) expression, and CAT-1
protein in: ( a) rats 6 weeks following 5/6 nephrectomy ( CRF), (b) sham-operated
animals, and ( c) rats with CRF treated orally with either atorvastatin or arginine
in drinking water (modalities which have been shown to enhance eNOS activity and
improve endothelial function). Both glomerular and aortic arginine transport were
significantly decreased in CRF. Treatment with either arginine or atorvastatin
abolished the decrease in arginine uptake in CRF rats. Using reverse transcriptase-
polymerase chain reaction and Northern blotting, we found a significant increase in
glomerular and aortic CAT-1 mRNA expression in CRF. Western blotting revealed that
CAT-1 protein was decreased in CRF, but remained intact following arginine and
atorvastatin administration. Renal and systemic arginine uptake is attenuated in
CRF, through modulation of CAT-1 protein. These findings provide a possible novel
mechanism to eNOS inactivation and endothelial dysfunction in uremia.
We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and
dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or
indirectly via maternal social cognition. Participants were 207 (105 European-
American and 102 African-American) mothers and their children (52% females).
Sensitive maternal behavior was rated and aggregated across a series of tasks when
infants were 6 months, 1 year and 2 years old. At 6 months, mothers were
interviewed about their empathy, attributions about infant behavior and beliefs
about crying to assess their parenting-related social cognition. Mothers with long
alleles for AVPR1a and DRD4 engaged in more mother-oriented social cognition (i.e.
negative attributions and beliefs about their infants' crying, beta = 0.13, P <
0.05 and beta = 0.16, P < 0.05, respectively), which in turn predicted less
sensitive maternal behavior (beta = -0.23, P < 0.01). Both indirect effects were
statistically significant independent of one another and covariates [95% confidence
interval (CI): -0.22, -0.03 and beta = -0.03 for AVPR; 95% CI: -0.20, -0.03 and
beta = -0.04 for DRD4]. There were no significant direct effects of AVPR1a or DRD4
on maternal sensitivity (beta = 0.02, P = .73 and beta = -0.10, P = .57,
respectively). The results did not vary for African-American and European-American
mothers (Delta chi(2) = 18.76, Delta df = 16, P = 0.28). Results support the view
that one mechanism by which maternal genes are associated with parental behavior is
via social cognition.
New Findings What is the central question of this study? Can the change in plasma
arginine vasopressin concentration (P-[AVP]) in response to osmotic stimulation (P-
Osm) serve as a biomarker for NMDA receptor signalling in schizophrenia and
depression and thereby distinguish between these mental illnesses? What is the main
finding and its importance? In response to hyperosmotic challenge, depressed
subjects showed increased P-[AVP] response compared with healthy control and
schizophrenic subjects. However, schizophrenic subjects were not different from
healthy control subjects in this small sample. The P-[AVP] response to P-Osm' is a
suitable biomarker to distinguish depressed versus schizophrenic patients when used
with psychiatric screening. This is the first objective physiological measure for
schizophrenia or depression. Altered NMDA receptor activity and glutamate
signalling might underlie the pathogenesis of both schizophrenia and depression in
subgroups of patients. In schizophrenia, pharmacological modelling, post-mortem and
imaging data suggest reduced NMDA signalling. In contrast, recent clinical trials
demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed
patients suggest increased NMDA receptor signalling. We conducted a proof-of-
concept study to assess whether there is any in vivo evidence for an inverse
association in depression and schizophrenia with respect to the NMDA receptor
function. For this purpose, we used a translational approach, based on findings
from animal studies that NMDA receptor is a key mediator of arginine vasopressin
(AVP) release into the bloodstream. Using hypertonic saline to increase plasma
osmolality (P-Osm) and thereby induce AVP release, as done in animal studies, we
found that in depressed patients the NMDA receptor-mediated AVP release induced by
hypertonic saline infusion was significantly increased [0.24 (0.15) pgml(-
1)mosmol(-1), P<0.05] compared with schizophrenia patients [0.07 (0.07) pgml(-
1)mosmol(-1)]. Slopes for healthy control subjects were 0.11 (0.09) pgml(-
1)mosmol(-1) which was less than the depressed group. These findings are consistent
with implicated NMDA receptor-related abnormalities in depression and schizophrenia
in subgroups of patients and provide the first in vivo evidence of this dichotomy.
Arginine (Arg) presents a potent growth hormone (GH) releasing activity. in vivo
and in vitro studies carried out in our laboratory have demonstrated that acute
treatment with Arg also increases GH gene expression. Taking into account the
recognizable diabetogenic role of GH and that Arg increases insulin release, this
study aimed at evaluating the effects of oral chronic administration of Arg on GH
gene expression, by Northern blotting analysis, and on the insulin sensitivity, by
means of the Insulin Tolerance Test (ITT), blood glucose decay rate (kitt) and
insulin plasma concentration. We demonstrated that rats that consumed Arg (similar
to 35 mg/day) in drinking water, during 4 weeks, presented an increase in GH mRNA
content (p < 0.01), a decreased peripheral response to insulin, as shown by the
reduced blood glucose decay rate (p < 0.05), and a higher insulin plasma
concentration (p < 0.01) than control group. Arg treatment did not modify the
animals' food and water intake, while it decreased the heart rate and the arterial
blood pressure compared to control group (P < 0.05). According to the results
presented herein we conclude that chronic oral administration of arginine increases
GH gene expression and induces insulin resistance. The arterial blood pressure
decrease has already been pointed out in the literature, and seems to occur in
response to the dilating effect of nitric oxide generated from Arg, as well as from
NO generation in central and peripheral neuronal populations that express NOS and
are involved in the autonomic regulation of the cardiac function. (c) 2006 Elsevier
Inc. All rights reserved.
Antimicrobial peptides are important components of the host innate immune responses
by exerting broad-spectrum microbicidal activity against pathogenic microbes. The
first mollusk big defensin (designated AiBD) cDNA was cloned from bay scallop
Argopecten irradians by expressed sequence tag (EST) and rapid amplification of
cDNA ends (RACE) techniques. The scallop AiBD consisted of 531 nucleotides with a
canonical polyadenylation signal sequence AATAAA and a poly(A) tail, encoding a
polypeptide of 122 amino acids. The high similarity of AiBD deduced amino acid
sequence with big defensin from Tachypleus tridentatus and Branchiostoma belcheri
tsingtaunese indicated that AiBD should be a member of big defensin family. The
expression of AiBD in various tissues was measured by using Northern blotting
analysis. mRNA transcripts of AiBD could be detected in haemocytes of unchallenged
scallops. The temporal expression of AiBD in haemolymph after Vibrio anguilarum
challenge was recorded by quantitative real time PCR. The relative expression level
of AiBD in haemolymph was up-regulated evenly in the first 8 h, followed by a
drastic increase, and increased 131.1-fold at 32 h post-injection. These results
indicated that AiBD could be induced by bacterial challenge, and it should
participate in the immune responses of A. irradians. Biological activity assay
revealed that recombinant AiBD could inhibit the growth of both Gram-positive and
Gram-negative bacteria, and also showed strong fungicidal activity towards the
expression host. Recombinant expression of AiBD made it possible to further
characterize its functions involved in immune responses, and also provided a
potential therapeutic agent for disease control in aquaculture. (c) 2006 Elsevier
Ltd. All rights reserved.
Background: Long-acting injectable antipsychotics are treatment options for acute
and long-term treatment of patients with schizophrenia. In a previously published
12-week randomized, double-blind, placebo-controlled clinical trial of patients
with schizophrenia experiencing an acute psychotic episode, aripiprazole once-
monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on
the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at
week 10. Methods: To examine the efficacy of AOM 400 across a broader
representation of schizophrenia symptoms, including agitation, a post hoc analysis
of this trial was carried out to assess the change in PANSS Marder factor domains
(positive symptoms, negative symptoms, disorganized thought, uncontrolled
hostility/excitement, and anxiety/depression) and the PANSS excited component
(equivalent to Marder factor domain uncontrolled hostility/excitement plus the
tension item) by comparing differences in change from baseline between AOM 400 and
placebo using a mixed model for repeated measures. Results: The differences between
treatment and placebo for all factors were statistically significant, with
improvements seen as early as week 1 or 2, and maintained through week 12. Thus,
AOM 400, supplemented with oral aripiprazole in the first 2 weeks, showed
significantly greater efficacy versus placebo in acutely ill patients with
schizophrenia in all 5 Marder illness domains, as well as in agitation as
conceptualized by the PANSS excited component score. Conclusions: These findings
indicate that AOM 400 is efficacious across the spectrum of schizophrenia symptoms
in acutely ill patients, with implications for both short-term and, by extension,
long-term patient outcomes.
This paper develops Bayesian inference of extreme value models with a flexible
time-dependent latent structure. The generalized extreme value distribution is
utilized to incorporate state variables that follow an autoregressive moving
average (ARMA) process with Gumbel-distributed innovations. The time-dependent
extreme value distribution is combined with heavy-tailed error terms. An efficient
Markov chain Monte Carlo algorithm is proposed using a state-space representation
with a finite mixture of normal distributions to approximate the Gumbel
distribution. The methodology is illustrated by simulated data and two different
sets of real data. Monthly minima of daily returns of stock price index, and
monthly maxima of hourly electricity demand are fit to the proposed model and used
for model comparison. Estimation results show the usefulness of the proposed model
and methodology, and provide evidence that the latent autoregressive process and
heavy-tailed errors play an important role to describe the monthly series of
minimum stock returns and maximum electricity demand.
Superconducting synchronous generators (SCSGs) are drawing more attention in large
direct-drive wind turbine applications. Despite low weight and compactness, the
short circuit torque of an SCSG may be too high for wind turbine constructions due
to a large magnetic air gap of an SCSG. This paper aims at assessing the effects of
armature winding segmentation on reducing the short circuit torque of 10-MW SCSGs.
A concept of armature winding segmentation with multiple power electronic
converters is presented. Four SCSG designs using different topologies are examined.
Results show that armature winding segmentation effectively reduce the short
circuit torque in all the four SCSG designs when one segment is shorted at the
terminal.
A detailed discussion on genesis, determinant and algorithmic method of the
harmonic distortion of Switched Capacitor integrator and Switched-Capacitor based
second order Sigma-Delta modulator is presented. In many instances, people make
harmonic distortion analysis of signal through expanding periodic signal into
Fourier series or making Fourier transformation for non-periodic signal
respectively. Actually, due to the complexity of transient response of Switched-
Capacitor integrator, the output expression of second-order Sigma-Delta modulator
loop filter is also not trivial, so we will be in great trouble if traditional
method is employed when its harmonics are analyzed and calculated in such a way. A
fact that is noteworthy is no matter how complicated the output response of the
second integrator of the modulator is, its harmonic expression has the same
functional form whether in the whole time domain or at the discrete time moments.
From this we turn the harmonic analysis of the continuous-time transient response
into another thing, namely computing the harmonic coefficients of the transient
response at discrete time moments. The least square method is adopted in process of
calculation. When developing the output expression of second-order Sigma-Delta
modulator, the following point is clarified, that the harmonic distortion is
dominated by the first Switched-Capacitor integrator, owing to the suppression
resulted from the closed feedback of harmonic distortion of the second stage is
much greater than the first stage. In addition, it is avoided that the harmonic
distortion is once again brought into the feedback signal in calculation, through
the way that first the additive harmonic error model is utilized to get the
transfer function, second replaced by gain model in the form of power series. And
by doing so, both the feasibility and simplicity of the analysis and mathematical
derivation are enhanced effectively.
Aim: This study aimed to evaluate the benefits of Arnica montana on post-operative
blood loss and seroma production in women undergoing unilateral total mastectomy by
administering Arnica Montana 1000 Korsakovian dilution (1000 K). Materials and
Methods: From 2012 to 2014, 53 women were randomly assigned to A. montana or
placebo and were followed up for 5 days. The main end point was the reduction in
blood and serum volumes collected in drainages. Secondary end points were duration
of drainage, a self-evaluation of pain, and the presence of bruising or hematomas.
Results: The per-protocol analysis revealed a lower mean volume of blood and serum
collected in drainages with A. montana (-94.40 ml; 95% confidence interval [CI]:
22.48-211.28; P = 0.11). A regression model including treatment, volume collected
in the drainage on the day of surgery, and patient weight showed a statistically
significant difference in favor of A. montana (-106.28 ml; 95% CI: 9.45-203.11; P =
0.03). Volumes collected on the day of surgery and the following days were
significantly lower with A. montana at days 2 (P = 0.033) and 3 (P = 0.0223).
Secondary end points have not revealed significant differences. Conclusions: A.
montana 1000 K could reduce post-operative blood and seroma collection in women
undergoing unilateral total mastectomy. Larger studies are needed with different
dilutions of A. montana to further validate these data.
Among recent high profile scientific debates was the proposal that life could exist
with arsenic in place of phosphorous in its nucleic acids and other biomolecules.
Soon after its initial publication, scientists across diverse disciplines began to
question this extraordinary claim. Using the original article, its claims, its
scientific support, and the ensuing counterarguments, a two-day, active learning
classroom exercise was developed focusing on the presentation, evaluation, and
discussion of scientific argumentation and discourse. In this culminating
assignment of a first semester biochemistry course, undergraduate students analyze
the scientific support from the original research articles and then present and
discuss multiple scientific rebuttals in a lively, civil classroom debate. Through
this assignment, students develop a sense of skepticism, especially for the
original arsenic-based life claims, and learn to clearly articulate their
counterarguments with scientific support and critical reasoning. With its direct
integration into first-semester biochemistry curriculum and the excitement
surrounding arsenic based life, this assignment provides a robust, simple, and
stimulating framework for introducing scientific discourse and active learning into
the undergraduate molecular science curriculum. (c) 2016 by The International Union
of Biochemistry and Molecular Biology, 45(1):40-45, 2017.
Artemisinin, a sesquiterpene lactone isolated from Artemisia annua L. (sweet
wormwood), is extensively used in the treatment of malaria. In order to better
understand the metabolism of terpenes in A. annua and the influence of terpene
synthases on artemisinin yield, the expression pattern of a monoterpene alcohol
dehydrogenase (ADH2) has been studied using transgenic plants expressing promoter-
beta-glucuronidase (GUS) fusion. ADH2 played a major role in monoterpenoid
biosynthesis including carveol, borneol, and artemisia ketone through in vitro
biochemical analysis. In this study, the ADH2 promoter was cloned by the genome
walking method. A number of putative cis-acting elements were predicted in promoter
region, suggesting that the ADH2 is driven by a complex regulation mechanism. ADH2
gene was highly expressed in old leaves, whereas the artemisinin biosynthetic genes
were mainly expressed in bud and young leaves. The expression of ADH2 gene
increased quickly during leaf development, revealed by qRT-PCR. GUS expression
analysis in different tissues of transgenic A. annua demonstrates that ADH2
expression is exclusively located to T-shaped trichome, not glandular secretory
trichome. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Volume 63, Number 6, Pages 834-840, 2016
Two newly established canine histiocytic sarcoma (HS) cell lines, designated as
PWC-HS01 and FCR-HS02, were obtained from brain and articular tumors, respectively.
These 2 HS cell lines had phagocytic ability and modal chromosome aberrations.
Although morphologic features of both HS cells were similar, immunocytochemical
examinations revealed that the PWC-HS01 cell line expressed both dendritic cell
(ie, S100, CD208, CD1, and CD4) and macrophage (ie, CD68, CD163, and CD204)
markers. In contrast, the FCR-HS02 cell line was immunonegative for CD204 and CD68
but consistently positive for the dendritic cell markers. Moreover, reverse
transcription polymerase chain reaction analyses confirmed histiocytic
differentiation of both HS cell lines. These results suggest that HS from the
central nervous system may have a tendency to be more undifferentiated compared
with cases from other organs. In addition, the 2 newly established HS cell lines
were also tumorigenic and metastatic in immunodeficient mice, supporting that these
cell lines can be used as new tumor models for investigating canine histiocytic
diseases.
shmiRs are pri-miRNA-based RNA interference triggers from which exogenous siRNAs
are expressed in cells to silence target genes. These reagents are very promising
tools in RNAi in vivo applications due to their good activity profile and lower
toxicity than observed for other vector-based reagents such as shRNAs. In this
study, using high-resolution northern blotting and small RNA sequencing, we
investigated the precision with which RNases Drosha and Dicer process shmiRs. The
fidelity of siRNA release from the commonly used pri-miRNA shuttles was found to
depend on both the siRNA insert and the pri-miR scaffold. Then, we searched for
specific factors that may affect the precision of siRNA release and found that both
the structural features of shmiR hairpins and the nucleotide sequence at Drosha and
Dicer processing sites contribute to cleavage site selection and cleavage
precision. An analysis of multiple shRNA intermediates generated from several
reagents revealed the complexity of shmiR processing by Drosha and demonstrated
that Dicer selects substrates for further processing. Aside from providing new
basic knowledge regarding the specificity of nucleases involved in miRNA
biogenesis, our results facilitate the rational design of more efficient genetic
reagents for RNAi technology. (C) 2016 Elsevier B.V. All rights reserved.
This paper presents the development of an artificial neural network (ANN)-based
improved inductive signal conditioning circuit for pressure transducer with bellow
as sensor. A bellow is an elastic-type mechanical pressure sensor. The deflection
of the bellow due to applied pressure must be translated into an efficient
electrical signal for continuous monitoring, wireless transmission, and digital
readout. A ferromagnetic wire attached to the bellow as a part of an inductive coil
arrangement, gets deflected due to applied pressure, thereby changing the self
inductance of the coil. An op-amp inductive signal conditioning circuit (OISCC) is
designed to produce voltage proportional to changes in self-inductance, but the
OISCC voltage versus applied pressure exhibits a considerable nonlinearity error
due to stray inductances and component drifts. The ANN modeling estimates and
compensates the nonlinearity of OISCC. An embedded unit is used for implementation
of ANN learning process. The pressure transducer with significant stability has
exhibited high linearity and sensitivity of +/- 0.35% and 10 mH/psig, respectively,
in the measuring range of 0-70 psig. The design and experimental aspects of the
technique are reported.
One of the major challenges of developing and growing of parabolic trough solar
thermal power plants (PTSTPPs) is enhancing the techno-economic performance. The
goal of this study is to develop a unique artificial neural network (ANN) model
that gives the best approach to predict the levelized cost of electricity (LCOE) of
two different PTSTPPs integrated with thermal energy storage and fuel backup
system; the first one is using thermic oil as primary heat transfer fluid in the
solar field, while the other one is based on molten salt. By this way, the optimum
designs of the two plants were determined in the LCOE analysis by using the
obtained weights and biases of the best ANN topology. The techno-economic
potentials of using Molten salt in comparison to thermic oil of the two optimized
plants were investigated considering both hourly and annual performances. The
results show that it is possible to get minimum values of LCOE of 8.3 and 7.0
cent$/kWh for oil and salt configurations, respectively. Moreover, because of the
difference in dispatch of thermal energy system and solar field aperture area of
the plants, the annual power generation and capacity factor of salt plant are much
higher than those of oil plant with a difference of around 26%. (C) 2016 Elsevier
Ltd. All rights reserved.
Background: The androgen receptor splice variant 7 (AR-V7) is associated with
resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due
to limitations of the methods available for AR-V7 analysis, the identification of a
reliable detection method may facilitate the use of this biomarker in clinical
practice. Objective: To confirm AR-V7 as a predictor of resistance to hormonal
therapy and develop a new approach to assess AR-V7 by highly sensitive digital
droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. Design,
setting, and participants: Plasma samples were collected from 36 CRPC patients
before they began second-line hormonal treatment. Exosomes were isolated and RNA
extracted for analysis of AR-V7 by ddPCR. Outcome measurements and statistical
analysis: The absolute target gene concentration as copies per milliliter
(copies/ml) was determined by ddPCR. Statistical analyses were performed with SPSS
software (IBM Corp., Armonk, NY, USA). Results and limitations: A total of 26
patients received abiraterone and 10 enzalutamide; 39% of patients were found to be
AR-V7 positive (AR-V7(+)). Median progression-free survival was significantly
longer in AR-V7 negative (AR-V7(-)) versus AR-V7(+) patients (20 vs 3 mo; p <
0.001). Overall survival was significantly shorter in AR-V7(+) participants at
baseline compared with AR-V7(-) participants (8 mo vs not reached; p < 0.001).
Conclusions: This study demonstrates that plasma-derived exosomal RNA is a reliable
source of AR-V7 that can be detected sensitively by ddPCR assay. We also showed
that resistance to hormonal therapy may be predicted by AR-V7, making it a
clinically relevant biomarker. Patient summary: We report a first study on a method
for androgen receptor splice variant 7 (AR-V7) detection in RNA extracted from
cancer cell vesicles released in blood. Results confirmed the role of AR-V7 as a
predictive biomarker of resistance to hormonal therapy. Our assay showed that
vesicles are a reliable source of AR-V7 RNA and that the method is fast, highly
sensitive, and affordable. (C) 2016 European Association of Urology. Published by
Elsevier B.V. All rights reserved.
The molecular mechanisms of the endogenous circadian clocks that allow most animals
to adapt to environmental cycles have recently been uncovered. The draft genome of
the ascidian, Ciona intestinalis, a model animal that is close to vertebrates, has
been described. However, the C. intestinalis genome lacks the canonical clock genes
such as Per, Bmal and Clock that are shared by vertebrates and insects. Here, we
found the circadian rhythms at the physiological and molecular levels. The oxygen
consumption rate was lower during the light phase and higher during the dark phase
during a day, and the rhythm highly damped and continued under constant darkness.
From the microarray analysis, the 396 spots (1.8% of the total; corresponding to
388 clones) were extracted as candidates for circadian expression. We confirmed the
circadian expression of several candidate genes by northern blotting. Furthermore,
three of four rhythmic expressed genes showed phase-shifts to prolonged light
period. However, most of known clock genes did not oscillate. These data suggest
that C. intestinalis have a unique molecular circadian clock and the daily
environmental change is not such a strong effect for sea squirt in its evolution
when compared to vertebrates and insects.
Ascorbate peroxidase (APX) is one of the key enzymes of the plant antioxidant
system playing, along with catalase, a central role in hydrogen peroxide
scavenging. An approach to further increase the knowledge about cytosolic APX gene
organization can be achieved by isolating and characterisating new cDNAs, thus
providing new insights about the physiological roles and regulation of these
enzymes. A partial cDNA clone (corresponding to the 3' untranslated region),
cytosolic ascorbate peroxidase-related, was isolated from potato sprouts by RT-PCR.
Database analysis retrieved several expressed sequence tags (ESTs) coding potato
cytosolic ascorbate peroxidase, that were used to infer the complete cDNA sequence.
The deduced amino acid sequence revealed high homologies with other plant cytosolic
ascorbate peroxidases, confirming the reliability of the virtual cDNA. Northern
blot analysis revealed the existence of a single band related to the isolated cDNA
and the southern blotting results allowed the elaboration of a possible gene
organization.
Type VII collagen is the major component of anchoring fibrils in the epidermal
basement membrane. Its expression has been analyzed by immunostaining or Northern
blotting, but rarely at the protein level. In this study, we have quantitatively
examined the effects of ascorbic acid and various cytokines/growth factors on the
protein synthesis and secretion of type VII collagen by human dermal fibroblasts in
culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay
with two kinds of specific monoclonal antibodies against the non-collagenous
domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII
collagen synthesis, and markedly increased the secretion of type VII collagen into
the medium when compared with the control culture. This effect was not influenced
by the presence of transforming growth factor-beta 1 (TGF-beta 1). The synthesis of
type VII collagen was elevated by TGF-beta 1, platelet-derived growth factor, tumor
necrosis factor-alpha, and interleukin-1 beta, but not by TGF-alpha. Thus, our data
indicate that the synthesis and secretion of type VII collagen in human dermal
fibroblasts are regulated by ascorbate and the enhancement of type VII collagen
gene expression by cytokines/growth factors is accompanied with elevated production
of type VII collagen at the protein level.
Safety and reliability are major issues for the ASDEX Upgrade (AUG) pulsed power
supply systems. To avoid long downtimes during an experimental campaign, fault-
prone components have to be identified and treated early. This becomes even more
important due to the AUG participation in the EUROfusion Medium Sized Tokamak (MST)
program. Operating equipment which is up to 40 years old adds additional
complications. This contribution describes one such example where a 35 year old
flywheel generator at AUG was identified as fault-prone and pre-emptively upgraded
with a new drive converter with integrated control. Most challenging was to adapt a
modern converter, originally designed for wind turbines, toward a drive system for
a flywheel-motor-generator system. To identify the layout of the controller and the
control parameters, accurate modeling and comprehensive simulations were performed.
This effort paid off during commissioning and measuring results verified the
calculated design values. Finally, the system shows good performance during AUG
plasma experiments. (C) 2015 Elsevier B.V. All rights reserved.
1. Host-parasitoid systems are characterized by a continuous development of new
defence strategies in hosts and counter-defence mechanisms in parasitoids. This co-
evolutionary arms race makes host-parasitoid systems excellent for understanding
trade-offs in host use caused by evolutionary changes in host immune responses and
parasitoid virulence. However, knowledge obtained from natural host-parasitoid
systems on such trade-offs is still limited. 2. In this study, the aim was to
examine trade-offs in parasitoid virulence in Asecodes parviclava (Hymenoptera:
Eulophidae) when attacking three closely related beetles: Galerucella pusilla,
Galerucella calmariensis and Galerucella tenella (Coleoptera: Chrysomelidae). A
second aim was to examine whether geographic variation in parasitoid infectivity or
host immune response could explain differences in parasitism rate between northern
and southern sites. 3. More specifically, we wanted to examine whether the capacity
to infect host larvae differed depending on the previous host species of the
parasitoids and if such differences were connected to differences in the induction
of host immune systems. This was achieved by combining controlled parasitism
experiments with cytological studies of infected larvae. 4. Our results reveal that
parasitism success in A. parviclava differs both depending on previous and current
host species, with a higher virulence when attacking larvae of the same species as
the previous host. Virulence was in general high for parasitoids from G. pusilla
and low for parasitoids from G. calmariensis. At the same time, G. pusilla larvae
had the strongest immune response and G. calmariensis the weakest. These
observations were linked to changes in the larval hemocyte composition, showing
changes in cell types important for the encapsulation process in individuals
infected by more or less virulent parasitoids. 5. These findings suggest ongoing
evolution in parasitoid virulence and host immune response, making the system a
strong candidate for further studies on host race formation and speciation.
The article presents design of operational amplifier circuit in Austria Micro
Systems, 350 nm SiGe BiCMOS technology, suitable for Chua's diodes construction. By
connecting an external passive components it became the basis of Chua's circuit
that can be used for example in communications and cryptography. The whole design
is implemented in nanometer IC design kit from Mentor Graphics. The development kit
allows to implement both pre-layout simulations but also close to the reality post-
layout simulations, based on accurate models of technology processes which are
available from the manufacturer of the integrated circuits in which they will be
integrated. The results obtained are presented in this article.
Recurrent pneumonia with cavitation leading to pneumatoceles, secondary fungal
infections, and hemoptysis are major causes of mortality and morbidity in patients
with hyper-IgE syndrome. Prevention and aggressive treatment of pneumonia in these
patients are essential to prevent further lung damage, but treatment may be delayed
because the classic signs/symptoms of infection such as fever, chills, or rigors
may be lacking. Early imaging to identify infection is essential for diagnosis and
treatment. The mainstay of therapy is continuous, full-dose daily trimethoprim-
sulfamethoxazole and commonly fungal coverage. Because hyper-IgE syndrome is a
progressive disease, patients' condition may worsen despite compliance with
prophylactic therapy. (C) 2016 American Academy of Allergy, Asthma & Immunology.
Fungal specific CD154(+) T-cells have been described as a biomarker in invasive
aspergillosis. The influence of sample storage on the detection of these cells was
assessed. Six-hour delay prior to PBMC isolation is associated with an 18% decrease
of cell viability and alterations of the cellular composition of the sample. This
results in 87% reduction of CD154(+) A. fumigatus specific cells due to reduced
assay sensitivity and increased background values in unstimulated samples. If
prompt cell measurement is not feasible, isolated PBMCs can be frozen (at -20
degrees C and -80 degrees C) and processed later with comparable assay reliability
(mean value fresh vs. thawing: 0.126, 0.133; Pearson-Coefficient: 0.962).
A mycelium-bound lipase from Aspergillus oryzae (AOL) exhibited excellent
enantioselectivity for kinetic resolution of (RS)-1-phenylethanol ((RS)-1-PE) in
organic solvent. The various reaction parameters affecting the conversion and
enantioselectivity were studied, including type of acyl donor, solvent, molar
ratio, temperature, enzyme amount, and substrate concentration. The optimum
reaction conditions were found to be transesterification with vinyl acetate at 30
degrees C in methyl tert-butyl ether with a vinyl acetate: (RS)-1-PE molar ratio of
1: 1 and an enzyme concentration of 60 g/L. At the optimum reaction conditions, the
conversion could reach above 46% with >99% enantiomeric excess of the product, (R)-
1-phenylethyl acetate, when the substrate concentration was below 1.4 M. The enzyme
displayed an excellent enantioselectivity with an E-value of >200 and a strong
tolerance for high substrate concentration of up to 1.8 M. Those results indicated
that AOL was a promising biocatalyst in the kinetic resolution of (RS)-1-PE. (C)
2016 International Union of Biochemistry and Molecular Biology, Inc.
Aims: The study was carried out to isolate and identify the spontaneously growing
populations of bacteria and fungi on the surface of biologically recovered
polyhydroxyalkanoate (PHA) copolymer, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
[P(3HB-co-3HHx)]. Methodology and results: Large-scale PHA biosynthesis was carried
out using 300 L fermenter and a biological methodology developed in our laboratory
was utilized for PHA recovery. Using standard microbiological and molecular biology
techniques the naturally growing microbial populations on the surface of
biologically recovered PHA were identified. Scanning electron microscopy (SEM)
analysis showed that the identified bacterial (Bacillus cereus and Burkholderia
cepacia) and fungal isolates (Aspergillus niger, Byssochlamys nivea, Penicillium
citrinum and Penicillium griseofulvum) were able to grow on and degrade the P(3HB-
co-3HHx) copolymer. Conclusion, significance and impact of study: This is the first
report on biologically recovered PHA pellet addressing the occurrence of
microorganisms that grew spontaneously on it during storage under laboratory
conditions. Fungi appeared to be dominant over bacteria in their ability to
colonize the biologically recovered PHA.
Background: Indoor air pollution caused by fungal contamination is suspected to
have a public health impact. Monitoring of the composition of the indoor airborne
fungal contaminants is therefore important. To avoid problems linked to culture-
dependent protocols, molecular methods are increasingly being proposed as an
alternative. Among these molecular methods, the polymerase chain reaction (PCR) and
the real-time PCR are the most frequently used tools for indoor fungal detection.
However, even if these tools have demonstrated their appropriate performance, some
of them are not able to discriminate between species which are genetically close. A
solution to this could be the use of a post-qPCR high resolution melting (HRM)
analysis, which would allow the discrimination of these species based on the highly
accurate determination of the difference in melting temperature of the obtained
amplicon. In this study, we provide a proof-of-concept for this approach, using a
dye adapted version of our previously developed qPCR SYBR (R) Green method to
detect Aspergillus versicolor in indoor air, an important airborne fungus in terms
of occurrence and cause of health problems. Despite the good performance observed
for that qPCR method, no discrimination could previously be made between A.
versicolor, Aspergillus creber and Aspergillus sydowii. Methods: In this study, we
developed and evaluated an HRM assay for the discrimination between A. versicolor,
Aspergillus creber and Aspergillus sydowii. Results: Using HRM analysis, the
discrimination of the 3 Aspergillus species could be made. No false positive, nor
false negatives were observed during the performance assessment including 20
strains of Aspergillus. The limit of detection was determined for each species
i.e., 0.5 pg of gDNA for A. creber and A. sydowii, and 0.1 pg of gDNA for A.
versicolor. The HRM analysis was also successfully tested on environmental samples.
Conclusion: We reported the development of HRM tools for the discrimination of A.
versicolor, A. creber and A. sydowii. However, this study could be considered as a
study case demonstrating that HRM based on existing qPCR assays, allows a more
accurate identification of indoor air contaminants. This contributes to an improved
insight in the diversity of indoor airborne fungi and hence, eventually in the
causal link with health problems.
BACKGROUND: The current study was conducted to expedite international standardized
reporting of bone marrow disease in children with neuroblastoma and to improve
equivalence of care. METHODS: A multidisciplinary International Neuroblastoma
Response Criteria Bone Marrow Working Group was convened by the US National Cancer
Institute in January 2012 with representation from Europe, North America, and
Australia. Practical transferable recommendations to standardize the reporting of
bone marrow disease were developed. RESULTS: To the authors' knowledge, the current
study is the first to comprehensively present consensus criteria for the
collection, analysis, and reporting of the percentage area of bone marrow
parenchyma occupied by tumor cells in trephinebiopsies. The quantitative analysis
of neuroblastoma content in bone marrow aspirates by immunocytology and reverse
transcriptase-quantitative polymerase chain reaction are revised. The inclusion of
paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse
transcriptase-quantitative polymerase chain reaction is recommended.
Recommendations for recording bone marrow response are provided. The authors
endorse the quantitative assessment of neuroblastoma cell content in bilateral core
needle biopsies-trephines and aspirates in all children with neuroblastoma, with
the exception of infants, in whom the evaluation of aspirates alone is advised. It
is interesting to note that 5% disease is accepted as an internationally achievable
level for disease assessment. CONCLUSIONS: The quantitative assessment of
neuroblastoma cells is recommended to provide data from which evidence-based
numerical criteria for the reporting of bone marrow response can be realized. This
is particularly important in the minimal disease setting and when neuroblastoma
detection in bone marrow is intermittent, where clinical impact has yet to be
validated. The wide adoption of these harmonized criteria will enhance the ability
to compare outcomes from different trials and facilitate collaborative trial
design. (C) 2016 American Cancer Society.
Numerous evidences indicate that aspirin usage causes a significant reduction in
colorectal cancer. However, the molecular mechanisms about aspirin preventing colon
cancer are largely unknown. Quantitative reverse transcription polymerase chain
reaction (qRT-PCR) is a most frequently used method to identify the target
molecules regulated by certain compound. However, this method needs stable internal
reference genes to analyze the expression change of the targets. In this study, the
transcriptional stabilities of several traditional reference genes were evaluated
in colon cancer cells treated with aspirin, and also, the suitable internal
reference genes were screened by using a microarray and were further identified by
using the geNorm and NormFinder softwares, and then were validated in more cell
lines and xenografts. We have showed that three traditional internal reference
genes, beta-actin, GAPDH and a-tubulin, are not suitable for studying gene
transcription in colon cancer cells treated with aspirin, and we have identified
and validated TMEM208 and PQLC2 as the ideal internal reference genes for detecting
the molecular targets of aspirin in colon cancer in vitro and in vivo. This study
reveals stable internal reference genes for studying the target genes of aspirin in
colon cancer, which will contribute to identify the molecular mechanism behind
aspirin preventing colon cancer.
The consideration of worker heterogeneity in assembly lines has received a fair
amount of attention in the literature in the past decade. Most of this exploration
uses as motivation the example of assembly lines in sheltered work centers for the
disabled. Only recently has the community started looking at the situation faced in
assembly lines in the general industrial park, when in the presence of worker
heterogeneity. This step raises a number of questions around the best way to
incorporate heterogeneous workers in the line, maximizing their integration while
maintaining productivity levels. In this paper we propose the use of Miltenburg's
regularity criterion and cycle time as metrics for integration of workers and
productivity, respectively. We then define, model and develop heuristics for a line
balancing problem with these two goals. Results obtained through an extensive set
of computational experiments indicate that a good planning can obtain trade-off
solutions that perform well in both objectives. (C) 2017 Elsevier Ltd. All rights
reserved.
A thorough understanding of the molecular biosciences requires the ability to
visualize and manipulate molecules in order to interpret results or to generate
hypotheses. While many instructors in biochemistry and molecular biology use visual
representations, few indicate that they explicitly teach visual literacy. One
reason is the need for a list of core content and competencies to guide a more
deliberate instruction in visual literacy. We offer here the second stage in the
development of one such resource for biomolecular three-dimensional visual
literacy. We present this work with the goal of building a community for online
resource development and use. In the first stage, overarching themes were
identified and submitted to the biosciences community for comment: atomic geometry;
alternate renderings; construction/annotation; het group recognition; molecular
dynamics; molecular interactions; monomer recognition; symmetry/asymmetry
recognition; structure-function relationships; structural model skepticism; and
topology and connectivity. Herein, the overarching themes have been expanded to
include a 12th theme (macromolecular assemblies), 27 learning goals, and more than
200 corresponding objectives, many of which cut across multiple overarching themes.
The learning goals and objectives offered here provide educators with a framework
on which to map the use of molecular visualization in their classrooms. In
addition, the framework may also be used by biochemistry and molecular biology
educators to identify gaps in coverage and drive the creation of new activities to
improve visual literacy. This work represents the first attempt, to our knowledge,
to catalog a comprehensive list of explicit learning goals and objectives in visual
literacy. (c) 2016 by The International Union of Biochemistry and Molecular
Biology, 45(1):69-75, 2017.
Parental sense of competence is one of the central dimensions targeted on
psychosocial interventions aimed at supporting at-risk families. Researchers and
practitioners need reliable instruments to assess the parental role adapted for
these families. Although the parental sense of competence (PSOC) scale has been
frequently used to assess this construct, there is still no adapted version for
Portuguese parents. In this study, the reliability, validity and factor structure
of the PSOC scale is examined with a clinical sample of 146 mothers from at-risk
families receiving psychosocial interventions for family preservation from Child
Protective Services. Results show that the Portuguese version of the PSOC measures
three distinct constructs with acceptable psychometric properties: efficacy,
dissatisfaction and controllability. As expected, the obtained factors were
significantly and positively related to parenting alliance and family cohesion, and
negatively associated with parenting stress. In sum, the proposed Portuguese
version shows reliability and validity evidences to measure three relevant
dimensions of parental self-evaluation, and it constitutes a cost- and time-
effective instrument suited for at-risk mothers.
New Zealand kauri (Agathis australis) (D.Don) Lindl. is a large and long-lived tree
species endemic to the species-rich forests of the north of the North Island.
Agathis australis are culturally and ecologically significant, but little is known
about their ecophysiology. In particular, environmental drivers of fluxes of carbon
and water for A. australis trees have not been quantified. We measured leaf gas
exchange to explore the effect of leaf age, tree size, foliar nitrogen
concentration, photosynthetically active radiation (PAR) and vapour pressure
deficit (D) on assimilation rates (A) and stomatal conductance (g(s)). We also
measured carbon isotope discrimination of leaves and applied an optimal stomatal
behaviour model. Both g(s) and A were highest for year one leaves (130mmolm(-2)s(-
1) and 5molm(-2)s(-1), respectively) then declined with leaf age to < 80mmolm(-
2)s(-1) and < 3molm(-2)s(-1), respectively, in 4-5-year-old leaves. Instantaneous
water use efficiency (A/g(s)) was highly variable, but there was no leaf age-
related pattern. Our diurnal results indicate that A. australis g(s) peaks early in
the day (before 0900 h at 250mmolm(-2)s(-1)) and A is comparatively low, remaining
below 9molm(-2)s(-1) throughout the day. Overall, water use efficiency is low based
on intrinsic water use efficiency and the stomatal model. Isotopic analysis
indicated moderate water use efficiency over the life of leaves compared to other
temperate conifers. This information is valuable for modelling carbon and water
fluxes of A. australis and for improving our understanding of the threat of summer
droughts to these forest giants.
BackgroundHLA-E products, class Ib human leukocyte antigens, act in the immunology
of human reproduction as modulators of the maternal immune system during pregnancy.
AimsTo evaluate HLA-E role in the establishment of a viable pregnancy. Materials &
MethodsHLA-E was genotyped by sequence-based typing (SBT) and analyzed for specific
polymorphisms, comparing couples who underwent assisted reproduction treatment
(ART) and fertile control couples. ResultsThere was a significant difference in
HLA-E allele and genotype distributions between ART couples and control couples.
The allele HLA-E*01:03 was observed in 63.2% of ART men and in 35.1% of fertile men
(P = 0.0032). ConclusionThese results suggest that HLA-E allelic variants may play
a role in the modulation of immune responses in the context of the inability of
natural conception and establishment of a viable pregnancy.
Referring to two recent publications, we here propose that clinical reproductive
immunology has for decades stagnated because reproductive medicine, including
assisted reproduction (AR), has failed to accept embryo implantation as an immune
system-driven process, dependent on establishment of maternal tolerance toward the
implanting fetal semi-allograft (and complete allograft in cases of oocyte
donation). Pregnancy represents a biologically unique period of temporary (to the
period of gestation restricted) tolerance, otherwise only known in association with
parasitic infections. Rather than investigating the immune pathways necessary to
induce this rather unique state of tolerance toward the rapidly growing parasitic
antigen load of the fetus, the field, instead, concentrated on irrelevant secondary
immune phenomena (i.e., "immunological noise"). It, therefore, does not surprise
that interesting recent research, offering new potential insights into maternal
tolerance during pregnancy, was mostly published outside of the field of
reproductive medicine. This research offers evidence for existence of inducible
maternal tolerance pathways with the ability of improving maternal fecundity and,
potentially, reducing such late pregnancy complications as premature labor and
preeclampsia/eclampsia due to premature abatement of maternal tolerance. Increasing
evidence also suggests that tolerance-inducing immune pathways are similar in
successful pregnancy, successful organ transplantation and, likely also in the
tolerance of "self" (i.e., prevention of autoimmunity). Identifying and isolating
these pathways, therefore, may greatly benefit all three of these clinical areas,
and research in reproductive immunology should be accordingly redirected.
Recent studies on the association between particular single nucleotide
polymorphisms of serine-threonine kinase with no lysine (K) 4 gene (WNK4) and
essential hypertension have yielded controversial results. Here, frequencies of
Ala589Ser polymorphism within exon 8 of the WNK4 gene were assessed among 259
unrelated ethnic Chinese patients with essential hypertension and 235 strictly
matched normotensive controls. All subjects were derived from a relatively isolated
population identified in the Kerqin desert region in Zhangwu county of Liaoning,
northeastern China, which features a dry climate and the people having a high
dietary salt intake, in addition to a significantly higher prevalence (similar to
35%) of essential hypertension. Genotypes were verified with polymerase chain
reaction-restriction fragment length polymorphism and confirmed by direct
sequencing. Expression pattern and regulatory mechanisms of the WNK4 gene were also
explored using Northern blotting and in vitro hormone stimulation assays. Strong
associations between the Ala589Ser polymorphism and both raised systolic and
diastolic blood pressures were identified. In addition to the kidneys, WNK4 gene
expression was also found in many other organs. Several cis-acting elements had
been discovered in the promoter region of the gene. As revealed by preliminary
experiment, various hormones can down-regulate the expression of WNK4, among which
glucocorticoid hormone seems to act in a dose-dependent manner. The WNK4 gene
probably plays an important role in the pathogenesis of essential hypertension. As
a missense mutation, the Ala589Ser polymorphism may bring changes to the enzyme's
function(s), resulting in increased susceptibility to the disease.
Asthenozoospermia is an important cause of male infertility. The mutations in sperm
mitochondrial DNA (mtDNA) result in either functionless or malfunctioning some
proteins, subsequently affecting sperm motility leading to asthenozoospermia. The
purpose of this study was to investigate sperm mtDNA 4,977-bp deletion in infertile
men with low sperm motility/immotile spermatozoa compared to healthy subjects with
high sperm motility. Semen samples of 256 asthenozoospermic infertiles and 200
controls from northern Iran were collected. After extraction of spermatozoa total
DNA, Gap-polymerase chain reaction (Gap-PCR) was performed. The deletion was
observed in 85.93% of patients with asthenozoospermia compared with 14% in controls
[OR=37.5397, 95% confidence interval=12.937-108.9276, p<.0001]. It is concluded
that there is a strong association between sperm mtDNA 4,977-bp deletion and
asthenozoospermia-induced infertility in the population examined. Large-scale mtDNA
deletions in spermatozoa may induce bioenergetic disorders. Nevertheless, to
validate our results broader research may be needed.
BACKGROUND: Current US guidelines recommend the Asthma Control Test (ACT) for
assessing disease control and selecting treatment. OBJECTIVE: The goal of this
study was to prospectively assess the ACT and its component questions for their
utility in predicting the risk of severe asthma exacerbations. METHODS: Individuals
were participants in the Study of Asthma Phenotypes and Pharmacogenomic
Interactions by Race-Ethnicity, and those included in the current analysis had the
following characteristics: age 18 years or more, physiciandiagnosed asthma, and
longitudinal care received at a large health system in southeastern Michigan. Study
participants underwent a baseline evaluation, which included answering the ACT. A
severe asthma exacerbation was defined as one requiring oral steroids, an emergency
department visit, or inpatient admission. Receiver-operator characteristic curves
were used to measure and compare the predictive utility of the ACT and its
component questions for severe asthma exacerbations. RESULTS: Of 1180 participants,
354 (30.0%) experienced a severe asthma exacerbation within 6 months of their
baseline evaluation. When compared with the individual questions that composed the
ACT, the composite score was significantly better at predicting severe
exacerbations with 1 exception; the composite ACT score and the question assessing
rescue medication use were not significantly different (P =.580). Pharmacy-based
records of metereddose inhaler short-acting beta-agonist use and asthma severity
were also not significantly different from the composite ACT score. CONCLUSIONS:
Our study demonstrates that although the ACT is modestly predictive for
exacerbations, the composite score may not be superior to assessing rescue
medication use alone for predicting the risk of severe asthma exacerbations. (C)
2016 American Academy of Allergy, Asthma & Immunology.
BACKGROUND: Severe uncontrolled asthma (SUA) is associated with increased asthma
exacerbations. Whether high blood eosinophil counts are related to this burden is
uncertain. OBJECTIVES: To determine the relationship of blood eosinophil counts to
asthma exacerbations, utilization, and cost in patients with SUA. METHODS: Patients
with persistent asthma (age >= 12 years) were identified administratively with SUA
in phase I by evidencing (1) 2 or more asthma exacerbations; (2) 6 or more medium-
or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or
with long-acting beta(2)-agonist; and (3) 3 or more dispensed non-ICS controllers.
Of the 541 patients with SUA invited to participate in the prospective phase II
follow-up study, 261 (48.2%) had blood tests (index date) to determine eosinophil
count and other atopic biomarkers. The relationship of blood eosinophil cutoff
points to asthma exacerbations and direct costs 1 year after the index date were
determined by multivariable regression. RESULTS: A blood eosinophil cutoff point of
greater than or equal to 400 cells/mm(3) compared with less than 400 cells/mm(3),
but not 150 cells/mm(3) or 300 cells/mm(3), was a risk factor in the outcome year
in adjusted analyses for 2 or more asthma exacerbations (risk ratio, 1.55; 95% CI,
1.02-2.35; P = .04) and any asthma emergency department visit or hospitalization
(risk ratio, 2.29; 95% CI, 1.16-4.55; P = .02), but not for rate of asthma
exacerbations or incremental total direct asthma costs per patient ($ 202; 95% CI,
-286 to 691). CONCLUSIONS: A high blood eosinophil count was an independent risk
factor for 2 or more asthma exacerbations or any asthma emergency department visit
or hospitalization, but not direct costs in patients with SUA, possibly constrained
by limited power. (C) 2016 American Academy of Allergy, Asthma & Immunology
BACKGROUND: Severe bronchiolitis (ie, bronchiolitis requiring hospital admission)
is thought to markedly increase asthma risk, with 30%-50% developing asthma by age
5 years. To date, studies of this association are small, and most are from outside
the United States. OBJECTIVE: The objective of this study was to investigate the
association between severe bronchiolitis and risk of asthma in a US birth cohort.
METHODS: We studied a cohort nested within the Massachusetts General Hospital
Obstetric Maternal Study (MOMS), a prospective cohort of pregnant women enrolled
during 1998-2006. Children of mothers enrolled in MOMS were included in the
analysis if they received care within our health system (n = 3653). Diagnoses and
medications were extracted from the children's electronic health records; we also
examined pregnancy and perinatal risk factors collected for the underlying
pregnancy study. RESULTS: The birth cohort was 52% male, 49% white, and 105 infants
(2.9%) had severe bronchiolitis. Overall, 421 children (11.5%) developed asthma by
age 5 years. Among the children with severe bronchiolitis, 27.6% developed asthma
by age 5 years. In multivariable logistic regression adjusting for 12 risk factors,
severe bronchiolitis remained a strong risk factor for developing asthma by age 5
years (odds ratio 2.57; 95% confidence interval 1.61-4.09). Conclusions: In a large
Boston birth cohort, the frequency of severe bronchiolitis and childhood asthma was
similar to published data. Among children with severe bronchiolitis, the risk of
developing asthma was lower than prior studies but still high (27.6%). This
difference may be due to different study designs, populations, and outcome
definitions studied. (C) 2016 American Academy of Allergy, Asthma & Immunology.
BACKGROUND: Mexican-born children living in the United States have a lower
prevalence of asthma than other US children. Although children of Mexican descent
near the Arizona (AZ)Sonora border are genetically similar, differences in
environmental exposures might result in differences in asthma prevalence across
this region. OBJECTIVE: The objective of this study was to determine if the
prevalence of asthma and wheeze in these children varies across the AZ-Sonora
border. METHODS: The International Study of Asthma and Allergy in Children written
and video questionnaires were administered to 1753 adolescents from 5 middle
schools: Tucson (school A), Nogales, AZ (schools B, C), and Nogales, Sonora, Mexico
(schools D, E). The prevalence of asthma and symptoms was compared, with analyses
in the AZ schools limited to selfidentified Mexican American students. RESULTS:
Compared with the Sonoran reference school E, the adjusted odds ratio (OR) for
asthma was significantly higher in US schools A (OR 4.89, 95% confidence interval
[CI] 2.72-8.80), B (OR 3.47, 95% CI 1.88-6.42), and C (OR 4.12, 95% CI 1.789.60).
The adjusted OR for wheeze in the past year was significantly higher in schools A
(OR 2.19, 95% CI 1.20-4.01) and B (OR 2.67, 95% CI 1.42-5.01) on the written
questionnaire and significantly higher in A (OR 2.13, 95% CI 1.22-3.75), B (OR
1.95, 95% CI 1.07-3.53), and Sonoran school D (OR 2.34, 95% CI 1.28-4.30) on the
video questionnaire compared with school E. CONCLUSIONS: Asthma and wheeze
prevalence differed significantly between schools and was higher in the United
States. Environmental factors that may account for these differences could provide
insight into mechanisms of protection from asthma. (C) 2016 American Academy of
Allergy, Asthma & Immunology
BACKGROUND: Adding a long-acting beta(2)-agonist (LABA) to inhaled corticosteroids
(ICS) using a fixed-dose combination (FDC) inhaler is the UK guideline
recommendation for children aged more than 4 years with uncontrolled asthma. The
evidence of benefit of adding an FDC inhaler over a separate LABA inhaler is
limited. OBJECTIVE: The objective of this study was to compare the effectiveness of
a LABA added as an FDC inhaler, and as a separate inhaler, in children with
uncontrolled asthma. METHODS: Two UK primary care databases were used to create a
matched cohort study with a 2-year follow-up period. We included children
prescribed their first step-up from ICS monotherapy. Two cohorts were formed for
children receiving an add-on LABA as an FDC inhaler, or a separate LABA inhaler.
Matching variables and confounders were identified by comparing characteristics
during a baseline year of follow-up. Outcomes were examined during the subsequent
year. The primary outcome was an adjusted odds ratio for overall asthma control
(defined as follows: no asthma-related hospital admission or emergency room visit,
prescription for oral corticosteroids or antibiotic with evidence of respiratory
consultation, and <= 2 puffs of short-acting bagonist daily). RESULTS: The final
study consisted of 1330 children in each cohort (mean age 9 years; 59% male). In
the separate ICSDLABA cohort, the odds of achieving overall asthma control were
lower (adjusted odds ratio, 0.77 [95% confidence interval, 0.66-0.91]; P =.001)
compared with the FDC cohort. CONCLUSION: The study demonstrates a small but
significant benefit in achieving asthma control from an add-on LABA as an FDC,
compared with a separate inhaler and this supports current guideline
recommendations. (C) 2016 American Academy of Allergy, Asthma & Immunology
Background We have reported that increased fraction of exhaled nitric oxide (FeNO),
a measure of TH2-driven airway inflammation, and blood eosinophil count, a marker
of systemic eosinophil inflammation, correlated with asthma attacks in a
population-based study. Objective To investigate the relation between
simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels
and asthma events among asthmatics. Methods Measurements of FeNO (elevated = 25
ppb) and S-ECP (elevated = 20 ng/mL) were performed in 339 adult asthmatics. Asthma
events (attacks and symptoms) were selfreported. Results Simultaneously normal S-
ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously
elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma
attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs.
25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P =
0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently
associated with asthma attacks in the preceding 3 months after adjusting for
potential confounders (OR (95% CI) 4.2 (2.0-8.8). Conclusions Simultaneously
elevated FeNO and S-ECP levels were related to a higher likelihood of asthma
attacks in the preceding 3 months. This indicates that there is a value in
measuring both FeNO and systemic eosinophilic inflammation in patients with asthma
to identify individuals at high risk of exacerbations. Clinical relevance FeNO and
S-ECP are markers for inflammation in asthma, but are dependent on different
inflammatory pathways and weakly correlated. Simultaneous measurements of both
offer better risk characterization of adult asthmatics.
BACKGROUND: Obesity and asthma are common health problems in the United States.
OBJECTIVE: The objective of this study was to evaluate the clinical and economic
burdens of obesity on hospitalized children with acute asthma exacerbation in 2012.
METHODS: Hospital discharge records of patients aged 2 to 18 years with a diagnosis
of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data
were compiled by the Agency for Healthcare Research and Quality. The discharge
records were weighted to estimate the number of hospitalizations because of asthma
exacerbations in the United States. To classify whether the patient was obese or
not, we used the International Classification of Diseases, Ninth Revision, Clinical
Modification code 278.0x. We compared the odds of using noninvasive or invasive
mechanical ventilation, mean total charges for inpatient service, and length of
hospital stay between obese and nonobese patients. RESULTS: A total of 74,338
patient discharges were extracted. Of these, 3,494 discharges were excluded because
of chronic medical conditions. Using discharge weight variables, we estimated a
total of 100,157 hospitalizations with asthma exacerbations among children aged
between 2 and 18 years in 2012. Obesity was significantly associated with higher
odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher
mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and
longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared
with nonobesity. CONCLUSIONS: These findings suggest that obesity is a significant
risk factor of severe asthma exacerbation that requires mechanical ventilation, and
obesity is an economically complicating factor. (C) 2016 American Academy of
Allergy, Asthma & Immunology
A large number of asthmatic patients, particularly females, present inadequate
disease control. Depressive symptoms are reportedly common in asthma and have been
related to poor disease control, but the mechanism of this association is still
unclear. Poor quality sleep, frequently observed in asthmatics, is also a
manifestation of depression and has been related to uncontrolled asthma. This study
aimed to investigate the relationship between depressive symptoms, sleep quality,
and asthma control. This was a cross-sectional study of 123 women with previous
diagnosis of asthma from a reference center in Fortaleza, Brazil. Depressive
symptoms were assessed by the Beck Depression Inventory (BDI); quality of sleep was
evaluated by the Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness by the
Epworth Sleepiness Scale (ESS), and asthma control by the Asthma Control Test
(ACT). Inadequate asthma control (ACT5) in 99 (80.49 %), and excessive daytime
sleepiness (ESS >= 10) in 34 (27.64 %). Depressive symptoms were associated with
both poor quality sleep (R = 0.326) and inadequate asthma control (R = -0.299).
Regression analysis showed that depressive symptoms and sleep quality were
independent predictors of the level of asthma control. Asthma control in women is
independently associated with depressive symptoms and quality of sleep, suggesting
that these patients might benefit from simple measures to promote healthy sleep
behavior and sleep hygiene and also that routine screening for depression can be
relevant, particularly, in poorly controlled cases.
The health and economic burden of asthma in the United States is substantial.
Asthma self-management education (AS-ME) and home-based interventions for asthma
can improve asthma control and prevent asthma exacerbations, and interest in health
care-public health collaboration regarding asthma is increasing. However,
outpatient AS-ME and home-based asthma intervention programs are not widely
available; economic sustainability is a common concern. Thus, we conducted a
narrative review of existing literature regarding economic outcomes of outpatient
AS-ME and home-based intervention programs for asthma in the United States. We
identified 9 outpatient AS-ME programs and 17 home-based intervention programs with
return on investment (ROI) data. Most programs were associated with a positive ROI;
a few programs observed positive ROIs only among selected populations (eg, higher
health care utilization). Interpretation of existing data is limited by
heterogeneous ROI calculations. Nevertheless, the literature suggests promise for
sustainable opportunities to expand access to outpatient AS-ME and home-based
asthma intervention programs in the United States. More definitive knowledge about
how to maximize program benefit and sustainability could be gained through more
controlled studies of specific populations and increased uniformity in economic
assessments. Published by Elsevier Inc. on behalf of the American Academy of
Allergy, Asthma & Immunology.
Asthma is a condition that has consistently demonstrated significant health outcome
inequalities for minority populations. One approach used for care of patients with
asthma is the incorporation of technology for behavioral modification, symptom
monitoring, education, and/or treatment decision making. Whether such technological
interventions can improve the care of black and inner-city patients is unknown. We
reviewed all randomized controlled trial technological interventions from 2000 to
2015 performed in minority populations. A total of 16 articles met inclusion and
exclusion criteria; all but 1 was performed in a childhood or adolescent age group.
The interventions used MPEG audio layer-3 players, text messaging, computer/Web-
based systems, video games, and interactive voice response. Many used tailored
content and/or a specific behavior theory. Although the interventions were based on
technology, most required additional special staffing. Subject user satisfaction
was positive, and improvements were noted in asthma knowledge, medication
adherence, asthma symptoms, and quality of life. Unfortunately, health care
utilization (emergency department visits and/or hospitalizations) was typically not
improved by the interventions. Although no single intervention modality was vastly
superior, the computer-based interventions appeared to have the most positive
results. In summary, technology-based interventions have a high level of user
satisfaction among minority and urban/low-income individuals with asthma, and can
improve asthma outcomes. Further large-scale studies are needed to assess whether
such interventions can decrease health disparities in asthma. (C) 2016 American
Academy of Allergy, Asthma & Immunology.
BACKGROUND: Home-based interventions to improve indoor air quality have
demonstrated benefits for asthma morbidity, yet little is known about the effect of
environmental interventions in the school setting. OBJECTIVE: We piloted the
feasibility and effectiveness of a classroom-based air cleaner intervention to
reduce particulate pollutants in classrooms of children with asthma. METHODS: In
this pilot randomized controlled trial, we assessed the effect of air cleaners on
indoor air particulate pollutant concentrations in 18 classrooms (9 control, 9
intervention) in 3 urban elementary schools. We enrolled 25 children with asthma
(13 control, 12 intervention) aged 6 to 10 years. Classroom air pollutant
measurements and spirometry were completed once before and twice after
randomization. Asthma symptoms were surveyed every 3 months. RESULTS: Baseline
classroom levels of fine particulate matter (particulate matter with diameter of
<2.5 mu m [PM2.5]) and black carbon (BC) were 6.3 and 0.41 mu g/m(3), respectively.
When comparing the intervention to the control group, classroom PM2.5 levels were
reduced by 49% and 42% and BC levels were reduced by 58% and 55% in the first and
second follow-up periods, respectively (P<.05 for all comparisons). When comparing
the children randomized to intervention and control classrooms, there was a modest
improvement in peak flow, but no significant changes in forced expiratory volume in
1 second (FEV1) and asthma symptoms. CONCLUSIONS: In this pilot study, a classroom-
based air cleaner intervention led to significant reductions in PM2.5 and BC.
Future large-scale studies should comprehensively evaluate the effect of school-
based environmental interventions on pediatric asthma morbidity. (C) 2016 American
Academy of Allergy, Asthma & Immunology
Compelling evidences point out a crucial role for extracellular nucleotides such as
adenosine triphosphate (ATP) during inflammatory conditions. Once released into the
extracellular space, ATP modulates migration, maturation and function of various
inflammatory cells via activating of purinergic receptors of the P2Y- and P2X-
family. P2RX4 is an ATP-guided ion channel expressed on structural cells such as
alveolar epithelial and smooth muscle cells as well as inflammatory cells including
macrophages, dendritic cells (DCs) and T cells. P2RX4 has been shown to interact
with P2RX7 and promote NLRP3 inflammasome activation. Although P2RX7 has already
been implicated in allergic asthma, the role of P2RX4 in airway inflammation has
not been elucidated yet. Therefore, we used a selective pharmacological antagonist
and genetic ablation to investigate the role of P2RX4 in an ovalbumin (OVA) driven
model of allergen-induced airway inflammation (AAI). Both, P2RX4 antagonist 5-BDBD
treatment and P2rx4 deficiency resulted in an alleviated broncho alveolar lavage
fluid eosinophilia, peribronchial inflammation, Th2 cytokine production and
bronchial hyperresponsiveness. Furthermore, P2rx4-deficient bone marrow derived DCs
(BMDCs) showed a reduced IL-1 beta production in response to ATP accompanied by a
decreased P2rx7 expression and attenuated Th2 priming capacity compared to wild
type (WT) BMDCs in vitro. Moreover, mice adoptively transferred with P2rx4-
deficient BMDCs exhibit a diminished AAI in vivo. In conclusion our data suggests
that P2RX4-signaling contributes to AAI pathogenesis by regulating DC mediated Th2
cell priming via modulating IL-1 beta secretion and selective P2RX4-antagonists
might be a new therapeutic option for allergic asthma.
To summarize the principal findings on risk and protective factors for childhood
asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18
years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A
total of 227 studies were searched from databases. Among those, 41 systematic
reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors,
and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality,
as determined by the Assess Systematic Reviews tool. After reviewing all evidence,
parental asthma, prenatal environmental tobacco smoke, and prematurity
(particularly very preterm birth) are well-established risk factors for childhood
asthma. Current findings do suggest mild-to-moderate causal effects of certain
modifiable behaviors or exposures during pregnancy (maternal weight gain or
obesity, maternal use of antibiotics or paracetamol, and maternal stress), the
perinatal period (birth by Caesarean delivery), or postnatal life (severe
respiratory syncytial virus infection, overweight or obesity, indoor exposure to
mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive
evidence must be confirmed in interventional studies or (if interventions are not
feasible) well-designed prospective studies. (C) 2016 American Academy of Allergy,
Asthma& Immunology.
Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse
biological roles including the antitumor activity. In this study, we evaluated the
chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell
Counting Kit-8 analysis was performed to determine cell viability. Real-time
polymerase chain reaction and western blot were used to measure the messenger RNA
and protein expression. Results showed that astragaloside IV treatment could
suppress the proliferation of non-small cell lung cancer cells. In addition,
combined treatment with astragaloside IV remarkably enhanced the chemosensitivity
to gefitinib in three non-small cell lung cancer cell lines including NCI-H1299,
HCC827, and A549. Furthermore, compared with gefitinib-treated cells, the messenger
RNA expression of SIRT6 was obviously increased in non-small cell lung cancer cells
treated with gefitinib combined with astragaloside IV. In addition, downregulation
of SIRT6 was accomplished using small interference RNA technology. As a result,
SIRT6 inhibition abolished the sensitization role of astragaloside IV in non-small
cell lung cancer cells. Taken together, these data demonstrated that astragaloside
IV sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that
astragaloside IV may serve as potential therapeutic approach for lung cancer.
A retrospective chart review was completed of patients self-identified as lesbian,
gay, or bisexual seen through a program for survivors of torture between June 9,
2009 and December 31, 2014 (n = 50). Almost all (98 %) experienced persecution due
to their sexual orientation and 84 % were survivors of torture. The circumstances
under which the disclosure of sexual orientation took place in the country of
origin were often traumatic. In several, efforts were made to change their sexual
orientation often through forced marriage. Those in same sex relationships had
relationships often marred by tragedy. Women were more likely to be forced to move
from place to place, experience rape/sexual assault and threats whereas men were
more likely to be persecuted by people on the street. All presented with symptoms
of depression and anxiety. Providers need to be attuned to the potential traumatic
histories of those fleeing persecution due to sexual orientation, and the medical,
social, psychological, and legal implications.
This paper explores the engagement in physical activity as a potential coping
strategy for asylum seekers living in the Australian community without the right to
work and with prolonged uncertainty, and benefits or barriers to undertaking such
activity. Semi-structured in-depth interviews were held with 29 asylum seekers who
had arrived to Australia by boat and were living in the community in the cities of
Perth, Sydney or Melbourne in July-October 2013 after their release from
immigration detention. The ratio of the numbers of men and women interviewed (23
men and 6 women) was comparable to the ratio of men and women who came by boat to
Australia seeking asylum in 2012-2013. Nine participants reported that they
participated in physical activity as a coping strategy. Seven other participants
were so worried about their future and their families that they did not have the
mental or physical energy to engage in physical activity. A further six wanted to
participate in physical activity but faced a number of barriers to doing so. The
seven remaining participants were either not asked about their physical activity
engagement because they focused their discussion on other challenges or did not
elaborate on why they were not engaging in physical activity. The findings suggest
that physical activity, coupled with other coping strategies, are important for
some asylum seekers in trying to manage the distress of being denied the right to
work and living with prolonged uncertainty. In addition, these findings highlight
the critical barrier that government policy plays in disabling engagement in
physical activity, which further compounds social exclusion. This includes the lack
of welfare support provided, which hinders people's financial ability to access
activities and support in the community.
Construction of a random ssDNA sublibrary is an important step of the aptamer
screening process. The available construction methods include asymmetric PCR,
biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR
amplification is a key step. The main drawback of PCR amplification is
overamplification increasing nonspecific hybridization among different products and
by-products, which may cause the loss of potential high-quality aptamers,
inefficient screening, and even screening failure. Cycle number optimization in PCR
amplification is the main way to avoid overamplification but does not fundamentally
eliminate the nonspecific hybridization, and the decreased cycle number may lead to
insufficient product amounts. Here, we developed a new method, "asymmetric emulsion
PCR," which could overcome the shortcomings of conventional PCR. In asymmetric
emulsion PCR, different templates were separated by emulsion particles, allowing
single-molecule PCR, in which each template was separately amplified, and the
nonspecific hybridization was avoided. Overamplification or formation of by-
products was not observed. The method is so simple that direct amplification of 40
or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric
emulsion PCR would improve the screening efficiency of systematic evolution of
ligands by exponential enrichment. (C) 2015 The Authors. Biotechnology and Applied
Biochemistry published by Wiley Periodicals, Inc. on behalf of the International
Union of Biochemistry and Molecular Biology, Inc.
This paper presents a technique for reducing the input current ripple on multiphase
power converters that provide multiple heterogeneous power supply rails, such as
those present in portable electronics and computers. Through asymmetric
interleaving of individual phases, the input current ripple can be reduced compared
to conventional interleaving. The technique is derived based on an analytic
description of the relevant current waveforms. Practical requirements of a digital
control implementation of the proposed technique are analyzed, and its possible
performance improvement is quantified through simulations and experimental results.
With the proposed technique, close to a 3x reduction in input current ripple,
compared to conventional methods, is demonstrated using an experimental prototype
comprising a microcontroller that controls a multiphase 180 nm CMOS power
management IC.
Optically pure t-butyl 6-cyano-(3R, 5R)-dihydroxyhexanoate ((R)-1b) is the key
precursor for atorvastatin calcium, the most widely used cholesterol-lowering drug.
In this work, a strain ZJB-09224 capable of asymmetrically reducing t-butyl 6-
cyano-(5R)-hydroxy-3-oxohexanoate (1a) to corresponding optically pure (R)-1b was
successfully isolated from soil sample, identified belonging to Rhodotorula
glutinis based on the morphology, physiological tests, and the 18S rDNA sequence
analysis. It was found that heat treatment of cell suspension at 45 degrees C for
25 Min significantly improved R. glutinis ZJB-09224 stereoselectivity. The
asymmetric bioreduction of 1a was most efficient at pH 7.5, 35 degrees C, 50 mM
(15.0 g L-1) substrate concentration, 40.0 g DCW L-1 cell loading size, 0.54 M
(60.0 g L-1) sodium lactate acting as co-substrate. Under these optimal conditions,
0.046 M (R)-1b was produced with de (diastereomeric excess) value of 99.2% after 40
H conversion. Moreover, R. glutinis ZJB-09224 has a broad substrate spectrum,
making it a potential tool for some valuable chiral alcohol pharmaceutical
intermediates synthesis. (C) 2015 International Union of Biochemistry and Molecular
Biology, Inc. Volume 63, Number 6, Pages 795-804, 2016
The traditional power control schemes for induction heating device mainly focus on
the pulse frequency modulation (PFM) and the pulse density modulation. But they
cannot solve the problems of power control, efficiency, and load-adaption well.
This paper presents and analyzes the asymmetrical frequency modulation (AFM)
control scheme used in the full-bridge series resonant inverter. With the proposed
AFM control technique, the output power is controlled by two variables: the
operation frequency and the division factor. Better efficiency performance can be
achieved in the medium and low output power range when compared with PFM. The
principles as well as the zero-voltage switching condition of the AFM are explained
and the power losses of switches are analyzed. A control algorithm that schedules
the three control modes of AFM is experimentally verified with a digital signal
processor based induction heating prototype. The load-adaption, noise and thermal
distribution problem of switches are also analyzed.
Antithymocyte globulin (ATG) is often included in the conditioning regimen to
prevent graft vs. host disease in allogeneic hematopoietic stem cell (HSC)
transplantation. However, because ATG contains antibodies targeting a wide range of
antigens on human cells, its potential off-target effects remain a concern. Here,
we explored this question in humanized mice that permit the analysis of human cell
depletion in tissues. We showed that ATG binds to almost all lineages of human
hematopoietic cells including HSCs, and accordingly it is capable of depleting
almost all human hematopoietic cells. Interestingly, the efficacy of ATG was highly
variable depending on the tissue of residence, with human cells in bone marrow
significantly less susceptible than those in the blood and spleen. Recovery of
multilineage human lymphohematopoietic reconstitution in humanized mice that
received ATG 3 weeks after HSC transplantation indicates that ATG had a minimal
effect on human HSCs that have settled in bone marrow niches. However, efficient
human HSC depletion and engraftment failure were seen in mice receiving ATG at the
time of transplantation. Our data indicate that the efficacy of ATG is tissue-
dependent, and suggest a potential risk of impairing donor hematopoietic
engraftment when ATG is used in preparative conditioning regimens.Cellular &
Molecular Immunology (2017) published online 26 October 2015
Background: Autophagy is a bulk degradation pathway for long-lived proteins,
protein aggregates, and damaged organelles. ULK1 protein kinase and Vps34 lipid
kinase are two key autophagy regulators that are critical for autophagosome
biogenesis. However, it isn't fully understood how ULK1 regulates Vps34, especially
in the context of disease. Polyglutamine expansion in huntingtin (Htt) causes
aberrant accumulation of the aggregated protein and disrupts various cellular
pathways including autophagy, a lysosomal degradation pathway, underlying the
pathogenesis of Huntington's disease (HD). Although autophagic clearance of Htt
aggregates is under investigation as therapeutic strategy for HD, the precise
mechanism of autophagy impairment remains poorly understood. Moreover, in-vivo
assays of autophagy have been particularly challenging due to lack of reliable and
robust molecular biomarkers. Method: We generated anti-phosphorylated ATG14
antibody to determine ATG14-mediated autophagy regulation; we employed Huntington's
disease (HD) genetic cell models and animal models as well as autophagy reporter
animal model to understand autophagy signaling and regulation in vivo. We applied
biochemical analysis and molecular biology approaches to dissect the alteration of
autophagy kinase activity and regulation. Results: Here, we demonstrate that ULK1
phosphorylates ATG14 at serine 29 in an mTOR-dependent manner. This phosphorylation
critically regulates ATG14-Vps34 lipid kinase activity to control autophagy level.
We also show that ATG14-associated Vps34 activity and ULK1-mediated phosphorylation
of ATG14 and Beclin 1 are compromised in the Q175 mouse model of Huntington's
disease. Finally, we show that ATG14 phosphorylation is decreased during general
proteotoxic stress caused by proteasomal inhibition. This reduction of the specific
phosphorylation of ATG14 and Beclin 1 is mediated, in part, by p62-induced
sequestration of ULK1 to an insoluble cellular fraction. We show that increased
ULK1 levels and phosphor-mimetic mutant ATG14 facilitate the clearance of polyQ
mutant in cells. Conclusion: Our study identifies a new regulatory mechanism for
ATG14-Vps34 kinase activity by ULK1, which can be used as valuable molecular
markers for in-vivo autophagic activity as well as potential therapeutic target for
the clearance of polyglutamine disease protein.
Remodeling of endothelial basement membrane is important in atherogenesis. Since
little is known about the actual relationship between type IV collagen and matrix
metalloprotease-2 (MMP-2) in endothelial cells (ECs) under shear stress by blood
flow, we performed quantitative analysis for type IV collagen and MMP-2 in ECs
under high shear stress. The mRNA of type IV collagen from ECs exposed to high
shear stress (10 and 30 dyn/cm(2)) had a higher expression compared to ECs exposed
to a static condition or low shear stress (3 dyn/cm(2)) (P < 0.01). (3)H-proline
uptake analysis and fluorography revealed a remarkable increase of type IV collagen
under high shear stress (P < 0.01). In contrast, zymography revealed that exposing
to high shear stress, however similar positivity was leveled in the intracellular
MMP-2 in the control and high shear stress-exposed ECs, reduced the secretion of
MMP-2 in ECs. The results of Northern blotting, gelatin zymography and monitoring
the intracellular trafficking of GFP-labeled MMP-2 revealed that MMP-2 secretion by
ECs was completely suppressed by high shear stress, but the intracellular mRNA
expression, protein synthesis, and transport of MMP-2 were not affected. In
conclusion, we suggest that high shear stress up-regulates type IV collagen
synthesis and down-regulates MMP-2 secretion in ECs, which plays an important role
in remodeling of the endothelial basement membrane and may suppress atherogenesis.
Purpose of review ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL
cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its
genetics, its molecular and cellular biology, and also its inhibition. Recent
findings ACLY is a critical enzyme linking glucose catabolism to lipogenesis by
providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol
biosynthesis. Human genetic variants have been associated with enhanced growth and
survival of several cancers, and with attenuated plasma triglyceride responses to
dietary fish oil. In mice, liver-specific Acly deficiency protects from hepatic
steatosis and dyslipidemia, whereas adipose tissue-specific Acly deletion has no
phenotype, supporting therapeutic inhibition of ACLY. A lipid-regulating compound,
bempedoic acid, was discovered to potently inhibit ACLY, and in animal models, it
prevents dyslipidemia and attenuates atherosclerosis. Phase 2 clinical trials
revealed that bempedoic acid effectively lowers LDL-C as monotherapy, combined with
ezetimibe, added to statin therapy and in statin-intolerant hypercholesterolemic
patients. Summary The efficacy of bempedoic acid as an LDL-C-lowering agent has
validated ACLY inhibition as a therapeutic strategy. Positive results of phase 3
patient studies, together with long-term cardiovascular disease outcome trials, are
required to establish ACLY as a major new target in cardiovascular medicine.
Rationale: Forkhead box P3(+) T regulatory cells (Tregs) are key players in
maintaining immune homeostasis. Evidence suggests that Tregs respond to
environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-
driven inflammation affects Treg homeostasis, but the mechanisms governing this
phenomenon are unclear. Objective: Here, we address whether atherosclerosis impacts
Treg plasticity and functionality in Apoe(-/-) mice, and what effect Treg
plasticity might have on the pathology of atherosclerosis. Methods and Results: We
demonstrate that atherosclerosis promotes Treg plasticity, resulting in the
reduction of CXCR3(+) Tregs and the accumulation of an intermediate Th1-like
interferon (IFN)-gamma(+) CCR5(+) Treg subset (Th1/Tregs) within the aorta.
Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than
from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice
are dysfunctional in suppression assays. Using an adoptive transfer system and
plasticity-prone Mir146a-/-Tregs, we demonstrate that elevated IFN
gamma(+)Mir146a(-/-)Th1/Tregs are unable to adequately reduce atherosclerosis,
arterial Th1, or macrophage content within Apoe(-/-) mice, in comparison to
Mir146a(+/+) Tregs. Finally, via single-cell RNA-sequencing and real-time-
polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional
phenotype characterized by coexpression of Treg and Th1 lineage genes and a
downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and
Il10. In addition, an ingenuity pathway analysis further implicates IFN gamma, IFN
alpha, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated
protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg
plasticity. Conclusions: Atherosclerosis drives Treg plasticity, resulting in the
accumulation of dysfunctional IFN gamma(+) Th1/Tregs that may permit further
arterial inflammation and atherogenesis.
Objectives: The aim of this study is to determine the relationship between
atherosclerosis and periodontopathogenic microorganisms in chronic periodontitis
patients following periodontal treatment. Materials and Methods: A total of 40
patients were included in the study. 20 of these patients diagnosed with
atherosclerosis and chronic periodontitis formed the test group. The remaining 20
patients were systemically healthy patients diagnosed with chronic periodontitis
and formed the control group. All patients had nonsurgical periodontal treatment.
The periodontopathogenic microorganism levels were determined at baseline and at 6
months in microbial dental plaque samples and WBC, LDL, HDL, PLT, fibrinogen,
creatinine and hs-CRP levels were determined by blood samples. Results:
Statistically significant reduction has been achieved in clinical periodontal
parameters following non-surgical periodontal treatment in test and control groups.
Following periodontal treatment, WBC, LDL, PLT, fibrinogen, creatinine and hs-CRP
levels significantly decreased and HDL levels significantly increased in both test
and control groups. Similarly, the periodontopathogenic microorganism levels
significantly decreased following periodontal treatment in the test and control
groups. A statistically significant positive correlation has been determined
between the periodontopathogenic microorganism levels and WBC, LDL, PLT,
fibrinogen, creatinine, and hs-CRP levels in the test group. Conclusions: The
association between hs-CRP, WBC, LDL, PLT, fibrinogen, creatinine, and the amount
of periodontopathogenic microorganisms indicates the possibility that periodontal
treatment could decrease the risk atherosclerosis. More studies must be conducted
in order for these results to be supported.
Objective-UVB irradiation is an established treatment for immunoinflammatory
cutaneous disorders and has been shown to suppress cutaneous and systemic
inflammatory diseases through modulation of the adaptive immune response. However,
it remains unknown whether UVB irradiation prevents an immunoinflammatory disease
of arteries such as atherosclerosis. Approach and Results-Here, we show that UVB
exposure inhibits the development and progression of atherosclerosis in
atherosclerosis-prone mice by expanding and enhancing the functional capacity of
CD4(+) forkhead box P3(+) regulatory T cells and regulating proatherogenic T-cell
responses. Experimental studies in Langerhans cell-depleted mice revealed that
epidermal Langerhans cells play a critical role in UVB-dependent induction of
CD4(+) forkhead box P3(+) regulatory T cells, suppression of proatherogenic T-cell
responses, and prevention of atherosclerotic plaque development. Conclusions-Our
findings suggest the skin immune system as a novel therapeutic target for
atherosclerosis and provide a novel strategy for the treatment and prevention of
atherosclerosis.
It is accepted that inflammation plays a critical role in the development of
atherosclerosis; the pathogenesis is not clear. B-cell-produced interleukin (IL) 10
is an immune regulatory cytokine that can inhibit immune inflammation. This study
tests a hypothesis that a psychological stress hormone, cortisol, suppresses IL-10
expression in peripheral B cells of patients with atherosclerosis. Peripheral blood
samples were collected from patients with coronary artery atherosclerosis. B cells
were isolated from the blood samples to be analyzed for the expression of IL-10 and
micro RNA (miR) 98 by real-time polymerase chain reaction. We observed that the
frequency of IL-10(+) B cell was less in patients with atherosclerosis than healthy
controls. The serum cortisol levels were higher in the patients than that in
healthy controls. Peripheral B-cell frequency was negatively correlated with the
serum cortisol levels. Exposure of B cells to cortisol increased the expression of
miR-98 in B cells. Cortisol also inhibited the expression of IL-10 in B cells, in
which miR-98 played a critical role. Treating B cells from atherosclerosis patients
with anti-miR-98 liposomes reversed the ability of expression of IL-10 in the
cells. The expression of IL-10 is suppressed in peripheral B cells, which can be up
regulated by anti-miR-98 liposomes.
Paroxysmal dyskinesias (PDs) are a group of hyperkinetic movement disorders
characterised by circumscribed episodes of disturbed movement, superimposed on a
background state in which such abnormality is absent. There is no loss of
consciousness. Episodes can last seconds, minutes or hours, and the beginning and
end of the movement disturbance are abrupt. Neurological examination is typically
normal between episodes. PDs are associated with a broad spectrum of clinical
presentations, encompassing various aetiologies. In humans, three main groups of
PDs are distinguished, based on precipitating events rather than phenomenology: (1)
paroxysmal kinesigenic dyskinesia (PKD); (2) paroxysmal nonkinesigenic dyskinesia
(PNKD); and (3) paroxysmal exertion-induced dyskinesia (PED). In recent years,
there has been an expansion of the spectrum of manifestations of PD due to the
identification of genes associated with PD in humans (PRRT1, MR-1, SLC2A1 and
KCNMAI) and dogs (BCAN and P1GN). The precise pathophysiological mechanism
underlying the clinical manifestations of these reported mutations remains to be
elucidated. Progress is also being made in the field of immunology, and links to
gluten hypersensitivity in Border terriers with so-called canine epileptoid
cramping syndrome (CECS) have been reported. This review aims to synthesise a
classification scheme for veterinary PDs by reviewing human systems and applying
them to veterinary examples. However, it is anticipated that genetic advancement
will greatly aid in future stratification and therapy for PDs in dogs. Therefore,
classification systems should be viewed as works in progress that should be
modified as necessary. Crown Copyright (C) 2017 Published by Elsevier Ltd. All
rights reserved.
Large-scale atmospheric removal of greenhouse gases (GHGs) including methane,
nitrous oxide and ozone depleting halocarbons could reduce global warming more
quickly than atmospheric removal of CO2. Photo catalysis of methane oxidizes it to
CO2, effectively reducing its global warming potential (GWP) by at least 90%.
Nitrous oxide can be reduced to nitrogen and oxygen by photocatalysis; meanwhile
halocarbons can be mineralized by red-ox photocatalytic reactions to acid halides
and CO2. Photocatalysis avoids the need for capture and sequestration of these
atmospheric components. Here review an unusual hybrid device combining
photocatalysis with carbon-free electricity with no-intermittency based on the
solar updraft chimney. Then we review experimental evidence regarding
photocatalytic transformations of non-CO2 GHGs. We propose to combine Ti02-
photocatalysis with solar chimney power plants (SCPPs) to cleanse the atmosphere of
non-CO2 GHGs. Worldwide installation of 50,000 SCPPs, each of capacity 200 MW,
would generate a cumulative 34 PWh of renewable electricity by 2050, taking into
account construction time. These SCPPs equipped with photocatalyst would process 1
atmospheric volume each 14 16 years, reducing or stopping the atmospheric growth
rate of the non-CO2 GHGs and progressively reducing their atmospheric
concentrations. Removal of methane, as compared to other GHGs, has enhanced
efficacy in reducing radiative forcing because it liberates more-OH radicals to
accelerate the cleaning of the troposphere. The overall reduction in non-CO2 GHG
concentration would help to limit global temperature rise. By physically linking
greenhouse gas removal to renewable electricity generation, the hybrid concept
would avoid the moral hazard associated with most other climate engineering
proposals. (C) 2017 The Authors. Published by Elsevier Ltd.
Exposure to cold physical plasma has been proposed to be of therapeutical value in
in oncology via the generation of a number of biologically relevant redox-active
molecules. Cancer cells can be recognized and eliminated by cells of the immune
system, and accordingly many tumors are populated with these cells, among them T
helper cells (TH cells). These lymphocyte population is crucial for effector immune
responses against tumor antigens, in response to immunogenic cell death in
malignant cells. However, a number of TH populations exists, each having distinct
phenotypical features. Using a cold atmospheric pressure argon plasma jet, its
redox activity was tested in different TH cell subpopulations to better understand
the immunological consequences of potential antitumor plasma treatments in vivo.
The Arabidopsis vacuolar Na+/H+ antiporter gene, AtNHX1, was introduced into
soybean by Agrobacterium-mediated transformation. Four independent kanamycin
resistant lines were obtained. The result of PCR, Southern blotting and Northern
blotting analyses demonstrated that the AtNHX1 gene was successfully inserted into
the soybean genome and stably expressed in these kanamycin resistant lines. The
stability of AtNHX1 expression and salt resistance were evaluated in the soybean
transformants for over 6 generations. Two independently derived transgenic lines
with high expression level of AtNHX1 were selected, and propagated to generation T-
5 in the absence of selection pressure. PCR and RT-PCR examinations revealed that
AtNHX1 was highly expressed in all investigated transgenic T-5 progenies.
Furthermore, all transgenic T-5 plants showed resistant to salt stress, same as
those of homozygous T-2 plants. Taken together, our results indicated that
constitutive expression of AtNHX1 enhanced salt tolerance in soybean for over 6
generations, suggesting a great potential use of AtNHX1 for improving salt
tolerance in plants by genetic engineering.
The advent of atomic force microscopy (AFM) has provided a powerful tool for
investigating the behaviors of single native biological molecules under
physiological conditions. AFM can not only image the conformational changes of
single biological molecules at work with sub-nanometer resolution, but also sense
the specific interactions of individual molecular pair with piconewton force
sensitivity. In the past decade, the performance of AFM has been greatly improved,
which makes it widely used in biology to address diverse biomedical issues.
Characterizing the behaviors of single molecules by AFM provides considerable novel
insights into the underlying mechanisms guiding life activities, contributing much
to cell and molecular biology. In this article, we review the recent developments
of AFM studies in single-molecule assay. The related techniques involved in AFM
single-molecule assay were firstly presented, and then the progress in several
aspects (including molecular imaging, molecular mechanics, molecular recognition,
and molecular activities on cell surface) was summarized. The challenges and future
directions were also discussed.
Atomic Layer Deposition (ALD) is an enabling technology which provides coating and
material features with significant advantages compared to other existing techniques
for depositing precise nanometer-thin two-dimensional (2D) nanostructures. It is a
cyclic process which relies on sequential self-terminating reactions between gas
phase precursor molecules and a solid surface. ALD is especially advantageous when
the film quality or thickness is critical, offering ultra-high aspect ratios. ALD
provides digital thickness control to the atomic level by depositing film one
atomic layer at a time, as well as pinhole-free films even over a very large and
complex areas. Digital control extends to sandwiches, hetero-structures, nano-
laminates, metal oxides, graded index layers and doping, and it is perfect for
conformal coating and challenging 2D electrodes for various functional devices. The
technique's capabilities are presented on the example of ALD-developed ultra-thin
2D tungsten oxide (W0(3)) over the large area of standard 4" Si substrates. The
discussed advantages of ALD enable and endorse the employment of this technique for
the development of hetero-nanostructure 2D semiconductors with unique properties.
(C) 2016 Elsevier B.V. All rights reserved.
Atopic dermatitis (AD) or eczema is the most common chronic inflammatory skin
disease. It is a multifactorial disease with local and systemic immune changes.
Current therapies focus on restoring the local skin barrier or inhibiting immune
responses. In this issue of the European Journal of Immunology, Sehra et al. [Eur.
J. Immunol. 2016. 46: 2609-2613] describe a mouse model with T-cell-specific
expression of constitutively active Stat6 in Flaky tail mice, which have mutations
in the Flg and Tmem79 genes. The authors describe that it is the combination of
changes in the skin barrier proteins filaggrin and Tmem79, together with Th2
cytokine signaling in the constitutively active Stat6 transgene, that drives the
immune-pathomechanism in AD. These results are consistent with human studies where
it is demonstrated that diminished filaggrin expression in skin is a predisposing
factor for AD, but is neither required nor sufficient for disease indicating that
additional factors are required for disease development. The current mouse model by
Sehra et al. could be instrumental in evaluation new therapeutic strategies for AD.
Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment
options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-
23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for
psoriasis patients. We sought to assess efficacy and safety of ustekinumab in
patients with moderate-to-severe AD. In this phase II, double-blind, placebo-
controlled study, 33 patients with moderate-to-severe AD were randomly assigned to
either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks,
and last dose at 32 weeks. Background therapy with mild topical steroids was
allowed to promote retention. Study endpoints included clinical (SCORAD50) and
biopsy-based measures of tissue structure and inflammation, using protein and gene
expression studies. The ustekinumab group achieved higher SCORAD50 responses at 12,
16 ( the primary endpoint) and 20 weeks compared to placebo, but the difference
between groups was not significant. The AD molecular profile/transcriptome showed
early robust gene modulation, with sustained further improvements until 32 weeks in
the initial ustekinumab group. Distinct and more robust modulation of Th1, Th17 and
Th22 but also Th2-related AD genes was seen after 4 weeks of ustekinumab treatment
(i.e. MMP12, IL-22, IL-13, IFN-gamma, elafin/PI3, CXCL1 and CCL17; P<. 05).
Epidermal responses (K16, terminal differentiation) showed faster (4 weeks) and
long-term regulation (32 weeks) from baseline in the ustekinumab group. No severe
adverse events were observed. Ustekinumab had clear clinical and molecular effects,
but clinical outcomes might have been obscured by a profound "placebo" effect, most
likely due to background topical glucocorticosteroids and possibly insufficient
dosing for AD.
Introduction: The goal of replantation after dental avulsion is to maintain the
tooth in its socket. Presence of vital periodontal ligament cells on the root
surface of the replanted tooth and the immunologic status of the patient are
factors that protect against root resorption. It is known that dental constituents
play an active role in root resorption by inducing specific and non-specific immune
responses; however, little information exists regarding the influence of the
acquired immune response on replantation. Therefore, the aim of this study was to
evaluate the 5-year outcome of replantation in non-atopic and atopic patients.
Methods: Clinical and radiographic examinations were performed in 62 replanted
teeth during a 5-year period. The evaluation of atopy was based on the patients'
personal and family histories and skin prick test results. The X-2 and the Z tests
were used to assess the association between atopy and the outcome of the replanted
teeth (P < .05). Results: There were significant differences between the 1-year and
5-year outcomes of the replanted teeth (P < .05) and atopic and non-atopic patients
who had their teeth extracted because of inflammatory or replacement root
resorption after 5 years (P < .05). Conclusions: Being atopic may offer the
advantage of loss of fewer teeth because of replacement resorption, whereas being
non-atopic may create an advantage of loss of fewer teeth because of inflammatory
root resorption during the first 5 years after trauma.
1. Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family,
transports certain lipophilic drugs, such as digoxin. To investigate the roles of
this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA
library, named ABCA8a. 2. The deduced mouse ABCA8a protein is 66% identical with
that of human ABCA8 and possesses features common to the ABC superfamily. It was
found that ABCA8a was mainly expressed in the liver and heart, similar to human
ABCA8. 3. We further evaluated the effect of acute digoxin (a substrate for ABCA8)
intoxication on the mRNA expression of ABCA8 using northern blotting with a 3' non-
coding region as a probe to avoid cross-hybridization with other ABCA genes. 4.
Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly
reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but not
in the heart and kidney. 5. Real-time quantitative polymerase chain reaction
analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5,
ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin
did not affect ABCA8a mRNA expression in the liver. 6. The results suggest that
ABCA8 may play a role in digoxin metabolism in the liver.
There is a large body of literature on attachment styles and personality traits.
The purpose of this study was to compare two commonly used instruments of
attachment that measure secure, fearful, dismissing, and preoccupied styles.
Furthermore, we sought to determine which personality factors and facets were
common on both of the attachment measures. Overall, 273 undergraduates completed a
demographic measure, two attachment scales (RQ and RSQ), and the NEO-PI-R to
measure personality. We found high concordance between the NEO-PI-R factors and
facets that predicted RSQ and RQ attachment. On both measures of attachment, a
secure style was associated with lower neuroticism and higher extraversion. Fearful
attachment was consistently predicted by being female, having higher neuroticism
(specifically depression) as well as lower extraversion and agreeableness
(specifically trust). Individuals scoring higher on preoccupied attachment had
higher neuroticism (specifically depression) and lower agreeableness. Finally,
individuals scoring higher on dismissing attachment had lower trust. These results
confirm Griffin and Bartholemew's(1994) conceptualization of attachment as falling
on the dimensions of anxiety and avoidance. Individuals with higher anxiety had
higher neuroticism and lower agreeableness and those with higher avoidance had
lower levels of trust. Crown Copyright (C) 2017 Published by Elsevier Ltd. All
rights reserved.
The relationship between adolescents' communication with their significant others
(mother, father, and best friend) and quality of life (KIDSCREEN) was investigated
in 2262 Scottish adolescent pet owners. The variable attachment to pets was also
tested and assessed as a mediator of this relationship. A positive relationship
between adolescents' communication with their significant other (mother, father,
and best friend) and quality of life decreased when controlling for attachment to
dogs. In cat owners, a positive relationship between communication with a best
friend and quality of life decreased when controlling for attachment to cats. In
cat and dog owners, attachment to these pets predicted higher levels of quality of
life. Higher attachment to dogs and cats was explained by good best friend (IV) and
attachment to pets (DV) and best friends. Mediation effects of attachment to dogs
and cats might be explained in terms of the caring activities associated with these
types of pets.
The authors examined the association between maternal childhood abuse and the
frequency of providing social support to mothers when the victim is an adult and
investigated the mediating effects of internal working models (self-esteem,
positive relations with others) and maladaptive coping. Using data from the
National Survey of Midlife Development in the United States II, they analyzed a
sample of 887 adult children using a structural equation modeling approach. The
results showed that maternal childhood abuse was associated with providing less
frequent emotional support to mothers, although the authors did not find
significant mediating effects of internal working models and maladaptive coping in
the association between child abuse and intergenerational support giving. The
findings suggest implications for theory, practice, and policy to address specific
concerns and possible challenges that adults with a history of childhood abuse may
experience in the relationship with their mothers.
Much is unknown about adult attachment style formation. We investigate whether
negative reinforcement schedules promote hallmark features of secure and anxious
attachment styles in a shock threat support-seeking paradigm. Participants
ostensibly asked for help from another participant seated in another room. Each
time a shock threat signal appeared they were to press a button to indicate their
need for help. The supporter could then stop the imminent shock. The reliability of
the supporters was varied such that some supporters were consistent (continuous
reinforcement) whereas others were inconsistent (variable ratio reinforcement).
Results indicated that inconsistently responsive others, reinforcing on a variable
ratio schedule, led to heightened approach-related attentional biases toward the
supporter, measured by event-related potentials, increased positive attachment
associations with the supporter, implicitly measured via a lexical decision task,
and more negative explicit evaluations of the supporter.
Reder and Duncan's well-known studies of the 1990s on fatal child abuse drew
attention to how parental scripts regarding their children could dangerously
distort relationships in ways that were sometimes fatal to children. This article
reports on a new system for assessing the meaning of the child to the parent',
called the Meaning of the Child Interview (MotC). Parents are interviewed using the
established Parent Development Interview, or equivalent, and the transcript of the
interview is then analysed according to parental sensitivity and likely risk to the
child. The MotC constructs were developed from those used in observed parent-child
interaction (specifically, the CARE-Index) and the form of discourse analysis used
in the Dynamic Maturational Model - Adult Attachment Interview, allowing a more
systemic and inter-subjective understanding of parenting representations than often
put forward. This article discusses the theoretical background to the MotC, gives a
brief review of similar measures and then introduces the coding system and patterns
of caregiving. The validity of the MotC is addressed elsewhere.
Objective: A social-cognitive perspective on posttraumatic stress disorder (PTSD)
has been proposed and posits that impaired social cognition, rooted in attachment
insecurity, plays a role in the development of PTSD. Support for the role of
impaired social cognition in PTSD has been found in adults, but the social-
cognitive perspective on PTSD has not been examined in adolescents. This study
sought to explore differences in social cognition and PTSD on the basis of
attachment security, and it examined social cognition as a mediator in the relation
between attachment security and PTSD and with regard to PTSD symptom change during
inpatient treatment. Method: We recruited 142 adolescents from an inpatient
psychiatric hospital, where adolescents and their parents completed assessments at
admission and discharge. Results: Adolescents with a secure attachment demonstrated
better social-cognitive skills than did those with an insecure attachment. Social
cognition mediated the relation between adolescents' maternal attachment
representations and PTSD at admission across 3 self-and parent-report measures.
Social cognition also mediated the relation between adolescents' maternal
attachment representations at admission and PTSD treatment outcome. Conclusion:
This study provides the 1st support for the application of Sharp, Fonagy, and
Allen's (2012) social-cognitive perspective of PTSD to adolescents by showing a
link between clinically significant symptoms of PTSD and attachment security
through social-cognitive impairment. Findings indicate that improvement in PTSD
during medium-stay inpatient treatment is partially driven by baseline attachment
security and social-cognitive abilities, highlighting the potential of social-
cognitive skills as important targets of clinical intervention among adolescents
with PTSD.
There is preliminary evidence that the immune system's cytokines may have impact on
ADHD in children. Nevertheless, studies exploring the possible role of pro-
inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess
differences in serum IL-6 and TNF-alpha between patients and controls and their
possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44
inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy
controls were included. Major psychiatric disorders and organic comorbidities were
excluded. Serum samples for IL-6 and TNF-alpha and salivary samples to assess
cortisol awakening response were collected on the same day. Analysis of variance
was applied to study differences in IL-6 and TNF-alpha between groups. Pearson
correlations were used to study associations between IL-6, TNF-alpha, and CAR.
There were no significant differences in serum IL-6 or TNF-alpha levels between
patients and controls or between combined and inattentive patients. Negative
associations between IL-6 (r=-0386, p=0.020), TNF-alpha Cr=-0.372, p=0.023) and
cortisol awakening response were found in the inattentive subtype, whereas no
association was seen in the combined subtype. A negative correlation between 1L-6
and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral
pro-inflammatory markers, IL-6 and TNF-alpha, do not appear to be primarily
involved in ADHD in adults, although the role of other inflammatory markers cannot
be ruled out. The differences regarding the association between IL-6 and TNF-alpha
and morning cortisol response suggest possible underlying neurobiological
differences between the inattentive or combined patients that merit further
studies. (C) 2017 Elsevier Ltd. All rights reserved.
Two experiments were conducted to investigate the effects of coaction on saccadic
and manual responses. Participants performed the experiments either in a solitary
condition or in a group of coactors who performed the same tasks at the same time.
In Experiment 1, participants completed a pro-and antisaccade task where they were
required to make saccades towards (prosaccades) or away (antisaccades) from a
peripheral visual stimulus. In Experiment 2, participants performed a visual
discrimination task that required both making a saccade towards a peripheral
stimulus and making a manual response in reaction to the stimulus's orientation.
The results showed that performance of stimulus-driven responses was independent of
the social context, while volitionally controlled responses were delayed by the
presence of coactors. These findings are in line with studies assessing the effect
of attentional load on saccadic control during dual-task paradigms. In particular,
antisaccades - but not prosaccades - were influenced by the type of social context.
Additionally, the number of coactors present in the group had a moderating effect
on both saccadic and manual responses. The results support an attentional view of
social influences.
Moving beyond the distinction between biological and social facts has proved
challenging due to several basic methodological and ontological differences among
scientific disciplines. The aim of this paper is to show how attention schema
theory (hereafter AST), developed by Michael Graziano, provides a useful addition
to existing integrative approaches that can be used to overcome impediments to
interdisciplinary crossfertilization, such that the influence of a range of
interconnected institutional, situational, biographical, psychological, neural and
genetic variables can be considered simultaneously in a parsimonious way. The paper
provides an overview of three basic methodological and ontological differences
dividing scientists researching human nature and society. It then draws on AST and
a selection of existing approaches in the interdisciplinary vein to demonstrate how
to move beyond the reductionist tendencies of each discipline. In the view of AST,
intrinsic brain processes and social and situational aspects are intricately
intertwined and continuously influence each other in shaping specific attentional
focuses. Social identities, biographical experiences, symbols, roles and subject
positions contribute to directing attention to certain kinds of stimuli, details,
or information, while at the same time, intrinsic predispositions make individuals
inclined to attend to different types of information. By accounting for the brain
basis of awareness as a subjective experience, AST can be used to clarify how
social identities influence attention, and thus, the linkages between individual
cognition and wider institutional structures. Finally, the paper considers the
relationships between the cognitive and the institutional levels of analysis, and
highlights the importance of the latter as a distinct level of analysis. In this
way, the paper charts the multidirectional and interactive causal relationship
between intrinsic brain processes, attention and conscious awareness, and how they
relate to wider institutional structures and joint attentional interactions at
higher levels of aggregation.
Despite a wealth of knowledge about the neural mechanisms behind emotional facial
expression processing, little is known about how they relate to individual
differences in social cognition abilities. We studied individual differences in the
event-related potentials (ERPs) elicited by dynamic facial expressions. First, we
assessed the latent structure of the ERPs, reflecting structural face processing in
the N170, and the allocation of processing resources and reflexive attention to
emotionally salient stimuli, in the early posterior negativity (EPN) and the late
positive complex (LPC). Then we estimated brain-behavior relationships between the
ERP factors and behavioral indicators of facial identity and emotion-processing
abilities. Structural models revealed that the participants who formed faster
structural representations of neutral faces (i.e., shorter N170 latencies)
performed better at face perception (r = -.51) and memory (r = -.42). The N170
amplitude was not related to individual differences in face cognition or emotion
processing. The latent EPN factor correlated with emotion perception (r = .47) and
memory (r = .32), and also with face perception abilities (r = .41). Interestingly,
the latent factor representing the difference in EPN amplitudes between the two
neutral control conditions (chewing and blinking movements) also correlated with
emotion perception (r = .51), highlighting the importance of tracking facial
changes in the perception of emotional facial expressions. The LPC factor for
negative expressions correlated with the memory for emotional facial expressions.
The links revealed between the latency and strength of activations of brain systems
and individual differences in processing socio-emotional information provide new
insights into the brain mechanisms involved in social communication.
In heterosexual individuals, attention is automatically captured by physically
attractive members of the opposite sex. Although helpful for selecting new mates,
attention to attractive relationship alternatives can threaten satisfaction with
and commitment to an existing romantic relationship. The current study tested the
hypothesis that although a mating prime would increase selective attention to
attractive opposite-sex targets (relative to less attractive targets) among single
participants, this effect would be reduced among people already committed to a
long-term romantic partner. Consistent with hypotheses, whereas single participants
responded to a mating prime with greater attentional adhesion to physically
attractive opposite-sex targets (relative to less attractive targets), participants
in a committed romantic relationship showed no such effect. These findings extend
previous research suggesting the presence of relationship maintenance mechanisms
that operate at early stages of social cognition.
Fearful faces both capture our attention and hold it. However, little is known
about the time-course for the capture and hold of spatial attention by fearful, and
other emotional, faces. In three dot-probe studies we examined this time-course.
Experiments 1 and 2 used fearful and neutral faces. In Experiment 1, dot-probe
targets occurred 133, 266, and 532 ms post-face onset and in Experiment 2, dot-
probe targets occurred 84, 168, 336, and 672 ms post-face onset. In Experiment 1,
for both 133 and 266 ms conditions, reaction times were fastest for congruent
trials and slowest for incongruent trials with reaction times for baseline trials
falling between the two. The same pattern was found for the 84 and 168 ms
conditions in Experiment 2. For the later time-points in both experiments there
were no significant differences between conditions. To examine whether this time-
course is unique to fearful faces, a third dot-probe experiment using time-points
identical to Experiment 2 was conducted with happy and neutral faces. The results
from Experiment 3 suggest that happy faces captured and held attention in the 168
and 336 ms conditions. Together, the results indicate that attention is captured
and held by fearful faces at times earlier than approximately 300 ms, while happy
faces also captured and held attention, but on a slightly different time-course
from 168 to 336 ms.
Explicit tests of social cognition have revealed pervasive deficits in
schizophrenia. Less is known of automatic social cognition in schizophrenia. We
used a spatial orienting task to investigate automatic shifts of attention cued by
another person's eye gaze in 29 patients and 28 controls. Central photographic
images of a face with eyes shifted left or right, or looking straight ahead,
preceded targets that appeared left or right of the cue. To examine automatic
effects, cue direction was non-predictive of target location. Cue-target intervals
were 100, 300, and 800 ms. In non-social control trials, arrows replaced eye-gaze
cues. Both groups showed automatic attentional orienting indexed by faster reaction
times (RTs) when arrows were congruent with target location across all cue-target
intervals. Similar congruency effects were seen for eye-shift cues at 300 and 800
ms intervals, but patients showed significantly larger congruency effects at 800
ms, which were driven by delayed responses to incongruent target locations. At
short 100-ms cue-target intervals, neither group showed faster RTs for congruent
than for incongruent eyeshift cues, but patients were significantly slower to
detect targets after direct-gaze cues. These findings conflict with previous
studies using schematic line drawings of eye-shifts that have found automatic
attentional orienting to be reduced in schizophrenia. Instead, our data indicate
that patients display abnormalities in responding to gaze direction at various
stages of gaze processing-reflected by a stronger preferential capture of attention
by another person's direct eye contact at initial stages of gaze processing and
difficulties disengaging from a gazed-at location once shared attention is
established.
Attentional lapses are usually defined as temporary and often brief shifts of
attention away from some primary task to unrelated internal information processing.
This study addressed the incidence of attention lapses and differences in
attentional functioning in 30 children with attention-deficit/hyperactivity
disorder (ADHD), 26 healthy children, and 29 children with spina bifida
myelomeningocele and hydrocephalus (SBH). Assessments were conducted using
computerized tonic and phasic attention tests, the Symbol Digit Modalities Test
(SDMT), and the Trail Making Test Form B (TMT-B). The group with SBH differed from
normal controls on cognitive measures of attention and executive functions. The
ADHD group obtained lower scores than the SBH group and healthy children. ANOVA
results showed that there was an effect of shunt revisions and shunt-related
infections on neuropsychological performance. Lapses of attention together with
reaction time may thus represent important factors for the understanding of
cognitive deficits in SBH.
Introduction: Previous studies have demonstrated that students with attention-
deficit/hyperactivity disorder (ADHD) struggle particularly with grasping the
implicit, inferential level of narratives that is crucial for story comprehension.
However, these studies used offline tasks (i.e., after story presentation), used
indirect measurements (e.g., identifying main ideas), and/or yielded inconclusive
results using think-aloud techniques. Moreover, most studies were conducted with
preschool or elementary school children with ADHD, using listening or televised
story comprehension. In this study, we were interested in examining the
spontaneous, immediate activation and/or suppression of forward-predictive
inferences, backward-explanatory inferences, and inference-evoking textual
information, as they occur online during reading comprehension by adolescents with
ADHD. Method: Participants with and without ADHD read short narrative texts, each
of which included a predictive sentence, a bridging sentence that referred back to
the predictive sentence via actualization of the predicted event, and two
intervening sentences positioned between the predictive and bridging sentences that
introduced a temporary transition from the main (predictive) episode. Activation
and suppression of inferential and/or textual information were assessed using
naming times of word probes that were implied by the preceding text, explicitly
mentioned in it, or neither when following control texts. In some cases, a true-
false inferential or textual question followed the probe. Results: Naming
facilitations were observed for the control but not for the ADHD group, in
responding to inference probes that followed the predictive and bridging sentences,
and to text probes that followed the predictive sentences. Participants with ADHD
were accurate, albeit slower, than controls in answering the true-false questions.
Conclusions: Adolescents with ADHD have difficulties in generating predictive and
explanatory inferences and in retaining relevant textual information in working
memory while reading, although they can answer questions after reading when texts
are relatively short. These findings are discussed with regard to development of
comprehension strategies for individuals with ADHD.
Introduction: Cannabis users are at higher risk for any mental disorder than the
general population. However, there remains a shortage of research that examines the
relationship between reluctance to seek mental health treatment and subsequent
frequent cannabis use. This study evaluates whether negative attitudes toward
mental health treatment (i.e. attitudinal barriers) predict a high frequency of
cannabis use and whether using cannabis to cope with mental health symptoms (i.e.,
coping motives) explains this relationship. Methods: Participants were students at
Washington State University (WSU) who received violations for illegal cannabis use
or possession. Data were collected from participants 60 days after a mandated two-
part course for cannabis harm reduction (n = 98). A cross-sectional path analysis
was performed to assess whether coping motives mediated the relationship between
attitudinal barriers to mental health treatment and frequency of cannabis use after
controlling for mental health symptoms. Results: Coping motives fully mediated the
relationship between negative attitudes toward treatment and frequency of use
(indirect effect: (beta = 0.087, bootstrap CI: 0.016-0.541). The direction of
results was confirmed by switching the mediator and criterion variable. The model
fit well with the data (x(2) (2) = 0.367, p = 0.83, RMSEA = 0.00, CFI = 1, SRMR =
0.008). Conclusions: Reluctance to seek mental health treatment may be related to
higher levels of cannabis use through coping motives. Addressing attitudes toward
mental health treatment may be an alternative way to decrease frequency of use or
possibly promote mental health treatment-seeking behaviors when needed. Further
studies are needed to confirm the implications of this finding. Published by
Elsevier Ltd.
This study aims to investigate the impacts of a digital learning module with guided
peer feedback on students' domain-specific knowledge gain and their attitudinal
change in the field of biotechnology and molecular life sciences. The extent to
which the use of this module is appreciated by students is studied as well. A pre-
test, post-test design was used with 203 students who were randomly assigned to
groups of three. They were asked to work on the digital module with the aim of
exploring various perspectives, and the pros and cons on the topic of Genetically
Modified Organisms (GMOs). The results suggest that the module can be used to
foster students' domain-specific knowledge gain and their attitudinal change.
Furthermore, the module was evaluated positively in terms of students' motivation
and satisfaction with the learning experiences. (c) 2016 by The International Union
of Biochemistry and Molecular Biology, 45(1):31-39, 2017.
High-valent Au(III) complexes have attracted much attention as catalysts in many
reactions. Nevertheless Au(III) catalysts suffer from instability of the oxidized
metal complexes during preparation and use. Herein, we demonstrated that Au(III)
catalysts can be stabilized against reduction to metallic Au by modifying
supported-ionic-liquid-phase-stabilized Au(III) catalyst with CuCl2. It was found
that the that reduced Au could be re -oxidized in situ to Au3+ species by CuCl2
during the reaction and further stabilized by the electron transfer from Cu to
these active species. When evaluated in the acetylene hydrochlorination reaction,
the Au-Cu-IL/AC catalyst displayed an excellent specific activity with the turnover
frequency (TOF) as high as 168.5 h(-1) and more than 99.8% selectivity fot the
product, vinyl chloride (VCM). Furthermore, the Au-Cu-IL/AC catalyst demonstrated a
stable catalytic performance with a negligible loss of C2H2 conversion after 500 h
under typical industrial reaction conditions for acetylene hydrochlorination.
Therefore, the findings of this work provide an efficient approach for designing
stable high-valent metals for long-term operation, and also pave the way for the
application of Au-Cu-IL/AC catalyst in industrial VCM production. (C) 2017 Elsevier
B.V. All rights reserved.
A low-quiescent high-performance class-AB headphone amplifier is presented. The
effect of the input-referred offset on the quiescent power of audio power amplifier
(APA) that drives very small resistive load is described and analyzed. A digitally
assisted offset calibration-based APA topology together with improved frequency
compensation is proposed. This permits the use of low quiescent power and small
compensation capacitance. Implemented in 65-nm CMOS technology, the amplifier
occupies an area of 0.15 mm(2) and consumes 0.4 mW at +/- 1 V supplies. At the load
of 16 Omega//200 pF, the gain-bandwidth product is 1.78 MHz using a total
compensation capacitance of 8.5 pF. Other performance metrics are measured with -
89-dB total harmonic distortion (THD+ N), 93.5-dB signal-to-noise ratio, 84-dB
power supply rejection ratio (PSRR+), and 105-dB PSRR-@ 217 Hz. It can deliver a
peak power of 35 mW (1.5 Vpp swing) to the above load, yielding the best figure-of-
merit (FOM) = (peak load power/quiescent power) and the best FOM2 = [peak load
power/quiescent power * (THD+ N)%] with respect to other reported representative
works.
It is traditionally challenging to implement higher-order PWM closed-loop Class-D
audio amplifiers using analog intensive techniques in deep-submicron, low voltage
process technologies. This is primarily attributed to reduced power supply,
degraded analog transistor characteristics, including short-channel effects,
increased flicker noise, random telegraph noise, transistor reliability concerns
and passive component performance. In this paper, we introduce a global closed-loop
mixed-signal architecture incorporating digital control and integrate a fourth-
order amplifier prototype in 55 nm CMOS. A systematic approach to analyze, design
and compensate the feedback loop in the digital domain is also presented. The
versatility of implementing the loop gain poles and zeros digitally attains high
gain throughout the audio band and attenuates residual high frequency ripples
around the loop, simultaneously accomplishing improvements in THD+ N and PSRR. The
overall architecture is inherently amenable to implementation in deep-submicron and
is therefore compatible with scaled CMOS. The measured prototype achieves a high
105 dBA SNR, 0.0031% THD+ N, 92 dB PSRR and 85% efficiency when supplying 1 W into
emulated 8 speaker load. This performance is competitive with conventional designs
using large feature size precision CMOS or specialized BCD technologies and reports
the highest output power (1.5 W) for deep-submicron designs.
In this study a novel auditory version of the Single Category Implicit Association
Test (SC-IAT-A) was developed to investigate (a) the valence of adults'
associations to infant cries and laughs, (b) moderation of implicit associations by
gender and empathy, and (c) the robustness of implicit associations controlling for
auditory sensitivity. Eighty adults (50% females) were administered two SC-IAT-As,
the Empathy Quotient, and the Weinstein Noise Sensitivity Scale. Adults showed
positive implicit associations to infant laugh and negative ones to infant cry;
only the implicit associations with the infant laugh were negatively related to
empathy scores, and no gender differences were observed. Finally, implicit
associations to infant cry were affected by noise sensitivity. The SC-IAT-A is
useful to evaluate the valence of implicit reactions to infant auditory cues and
could provide fresh insights into understanding processes that regulate the quality
of adult-infant relationships.
Introduction. Plum cultivars exhibit differences in their fruit quality; however,
very little is known about the changes in fruit growth and quality of plum
cultivars maturing in different seasons. This study was conducted to contribute to
a better understanding of the fruit growth and ripening behavior of Japanese plum
(Prunus silicina Lindl.) varieties according to their maturing season. Materials
and methods. Three Japanese plum cultivars were studied: early- ['Black Amber'
(BA)], mid-['Amber Jewel' (AJ)] and late-season ['Angelino' (AG)] maturing. The
increase in fruit weight and diameter was determined from days after full bloom
(DAFB) to harvest, whilst changes in fruit pulp, skin and seed dry weights, fruit
firmness, soluble solid contents (SSC), and titratable acidity (TA) were studied
during days after stone hardening (DASH). Ethylene production, respiration rate,
activities of 1-aminocyclopropane-1-carboxylic acid synthase (ACS) and 1-
aminocyclopropane-1-carboxylic acid oxidase (ACO) enzymes, fruit firmness, fruit
color, SSC, TA, ascorbic acid, total antioxidant and carotenoid contents were
determined at alternate days during fruit ripening. Results and discussion. All
plum cultivars exhibited three distinct phases of fruit growth and development in
the DAFB. The AG fruit exhibited the longest duration of phase-III, about 64 days
and 12 days more, as compared with BA and AJ fruits, respectively. Fruit skin dry
weight (%) was higher for AG fruit, whilst, AJ and BA fruits exhibited the highest
increase in seed and pulp dry weight (%) during DASH. The BA and AJ fruits showed
climacteric fruit ripening with a sharp rise in ACS and ACO enzymes; whereas AG
fruit showed suppressed climacteric ripening. During the fruit ripening period AG
fruit remained more firm with higher SSC, and SCC: TA ratio as compared with BA and
AJ fruits. The level of ascorbic acid (24.8 mg 100 g(-1)) was higher in AG fruit.
Whilst, total carotenoids (0.66 mg 100 g(-1)) and total antioxidants (215 mu mol
Trolox 100 g(-1)) were higher in AJ and BA fruit respectively. Conclusion. The
physico-chemical changes during fruit ripening vary with cultivar and are
associated with the level of endogenous ethylene production. Japanese plum
cultivars exhibit varying levels of SSC, SSC: TA ratio, levels of individual and
total antioxidants of their ripe fruits.
Although recent scholarship focuses on the increasing significance of processes of
standardization in contemporary social life, much less attention has been given to
how standardization impacts intimate life, and how intimate standards are made
meaningful in interaction. This article draws from participant observation in
online transgender groups to examine how the medical standardization of
transsexuality, known as the wrong-body' model, impacts the way users understand
and communicate their gendered self. I show how rather than simply adopting the
wrong-body model, participants use its language and logic in ironic and playful
ways that carve out spaces for ways of knowing the self that feel authentically
their own. This case shows how intimate standards become part of the language of
the self in ways that may be unexpected.
Across a broad range of design professions, there has been extensive research on
design practices and considerable progress in creating new computer-based systems
that support design work. Our research is focused on educational/instructional
design for students' learning. In this sub-field, progress has been more limited.
In particular, neither research nor systems development have paid much attention to
the fact that design is becoming a more collaborative endeavor. This paper reports
the latest research outcomes from R&D in the Educational Design Studio (EDS), a
facility developed iteratively over four years to support and understand
collaborative, real-time, co-present design work. The EDS serves to (i) enhance our
scientific understanding of design processes and design cognition and (ii) provide
insights into how designers' work can be improved through appropriate technological
support. In the study presented here, we introduced a complex, multi-user, digital
design tool into the existing ecology of tools and resources available in the EDS.
We analysed the activity of four pairs of 'teacher-designers' during a design task.
We identified different behaviors - in reconfiguring the task, the working methods
and toolset usage. Our data provide new insights about the affordances of different
digital and analogue design surfaces used in the Studio. (C) 2017 Elsevier Ltd. All
rights reserved.
The aim of this study was to identify specific cognitive abilities that predict
functional outcome in high-functioning adults with autism spectrum disorder (ASD),
and to clarify the contribution of those abilities and their relationships. In
total, 41 adults with ASD performed cognitive tasks in a broad range of neuro- and
social cognitive domains, and information concerning functional outcomes was
obtained. Regression analyses revealed that emotion perception and verbal
generativity predicted adaptive functioning directly, and the former mediated
between the other two. These findings provide the first evidence of a triadic
relationship among neuro- and social cognition and functional outcome in this
population. Our results suggest that psychosocial interventions targeting these
cognitive abilities could benefit social adaptation in adults with ASD.
Background Cognitive differences, including deficits in self-awareness, are common
in high-functioning individuals with autism spectrum disorder (ASD) and represent a
fruitful target for intervention. The current project presents the preliminary
research undertaken in the development of metacognitive training (MCT), an
intervention designed to increase knowledge about personal strengths and challenges
in adolescents with ASD.Method Two groups of 4 adolescents with ASD completed MCT,
as well as measures to assess satisfaction and adverse effects. Visual inspection
and thematic analysis were used to interpret the data.Results Overall, both
participants and their parents rated MCT favourably; the youth most enjoyed the
interactive activities, whereas parents appreciated the opportunity for socialising
and psychoeducation. There were no systematic changes on quantitative measures of
adverse effects (i.e. self-esteem or depression).Conclusion Although the results
suggest further investigation of MCT may be warranted, certain modifications to the
MCT protocol and research methodology are needed.
The present study aimed to examine the effects of a novel avatar interviewing aid
during memory interviews with children with autism spectrum disorder (ASD). Thirty
children were recruited for our study (Age: M = 7.60, SD = 0.68), half with ASD (13
boys; 2 girls) and the other half being neurotypical (13 boys; 2 girls). Children
participated in a target event and were subsequently interviewed a week later by
either an avatar interviewer or a human. The participants were also asked six
misleading questions aimed to examine their suggestibility. Bayesian analysis
showed some increase in memory performance for both groups of children interviewed
by the avatar interviewer, and this effect exacerbated for children with ASD. These
results showed encouraging implications for future applications.
The ability of individuals with Autism Spectrum Disorder (ASD) to process context
has long been debated: According to the Weak Central Coherence theory, ASD is
characterized by poor global processing, and consequentlypoor context processing.
In contrast, the Social Cognition theory argues individuals with ASD will present
difficulties only in social context processing. The complexity theory of autism
suggests context processing in ASD will depend on task complexity. The current
study examined this controversy through two priming tasks, one presenting human
stimuli (facial expressions) and the other presenting non-human stimuli (animal
faces). Both tasks presented visual targets, preceded by congruent, incongruent, or
neutral auditory primes. Local and global processing were examined by presenting
the visual targets in three spatial frequency conditions: High frequency, low
frequency, and broadband. Tasks were administered to 16 adolescents with high
functioning ASD and 16 matched typically developing adolescents. Reaction time and
accuracy were measured for each task in each condition. Results indicated that
individuals with ASD processed context for both human and non-human stimuli, except
in one condition, in which human stimuli had to be processed globally (i.e., target
presented in low frequency). The task demands presented in this condition, and the
performance deficit shown in the ASD group as a result, could be understood in
terms of cognitive overload. These findings provide support for the complexity
theory of autism and extend it. Our results also demonstrate how associative
priming could support intact context processing of human and non-human stimuli in
individuals with ASD. Autism Res2017, 10: 520-530. (c) 2016 International Society
for Autism Research, Wiley Periodicals, Inc.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with atypical
cortical maturation leading to a deficiency in social cognition and language.
Numerous studies have attempted to classify ASD using brain measurements such as
cortical thickness, surface area, or volume with promising results. However, the
underpowered sample sizes of these studies limit external validity and
generalizability at the population level. Large scale collaborations such as
Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) or the Autism Brain
Imaging Data Exchange (ABIDE) aim to bring together like-minded scientists to
further improve investigations into brain disorders. To the best of our knowledge,
this study represents the largest classification analysis for detection of ASD vs.
healthy age and sex matched controls using cortical thickness brain parcellations
and intracranial volume normalized surface area and subcortical volumes. We were
able to increase classification accuracy overall from 56% to 60% and for females
only by 6%. These novel findings using Evolving Partitions to Improve Connectomics
(EPIC) underscore the importance of large-scale data-driven approaches and
collaborations in the discovery of brain disorders.
Machine learning approaches have been widely used for the identification of
neuropathology from neuroimaging data. However, these approaches require large
samples and suffer from the challenges associated with multi-site, multi-protocol
data. We propose a novel approach to address these challenges, and demonstrate its
usefulness with the Autism Brain Imaging Data Exchange (ABIDE) database. We predict
symptom severity based on cortical thickness measurements from 156 individuals with
autism spectrum disorder (ASD) from four different sites. The proposed approach
consists of two main stages: a domain adaptation stage using partial least squares
regression to maximize the consistency of imaging data across sites; and a learning
stage combining support vector regression for regional prediction of severity with
elastic-net penalized linear regression for integrating regional predictions into a
whole-brain severity prediction. The proposed method performed markedly better than
simpler alternatives, better with multi-site than single-site data, and resulted in
a considerably higher cross-validated correlation score than has previously been
reported in the literature for multi-site data. This demonstration of the utility
of the proposed approach for detecting structural brain abnormalities in ASD from
the multi-site, multi-protocol ABIDE dataset indicates the potential of designing
machine learning methods to meet the challenges of agglomerative data.
Social deficits are a core symptom of autism spectrum disorder; however, the
perturbed neural mechanisms underpinning these deficits remain unclear. It has been
suggested that social prediction errors-coding discrepancies between the predicted
and actual outcome of another's decisions-might play a crucial role in processing
social information. While the gyral surface of the anterior cingulate cortex
signalled social prediction errors in typically developing individuals, this
crucial social signal was altered in individuals with autism spectrum disorder.
Importantly, the degree to which social prediction error signalling was aberrant
correlated with diagnostic measures of social deficits. Effective connectivity
analyses further revealed that, in typically developing individuals but not in
autism spectrum disorder, the magnitude of social prediction errors was driven by
input from the ventromedial prefrontal cortex. These data provide a novel insight
into the neural substrates underlying autism spectrum disorder social symptom
severity, and further research into the gyral surface of the anterior cingulate
cortex and ventromedial prefrontal cortex could provide more targeted therapies to
help ameliorate social deficits in autism spectrum disorder.
We tested social cognition abilities of adolescents with autism spectrum disorders
(ASD) and neurotypically developed peers (NTD). A multi-faceted test-battery
including facial emotion categorization (FEC), classical false belief tasks (FBT),
and complex social cognition (SC), yielded significantly lower accuracy rates for
FEC and complex SC tasks in ASD, but no significant differences in performance
concerning FBT. A significant correlation between age and performance in a FEC task
and in a complex task was found only in ASD. We propose that dynamic and/or
fragmented FEC tasks can elicit deficits in implicit processing of facial emotion
more efficiently. The difficulties of ASD in solving complex SC tasks can be
ascribed to deficits in the acquisition and application of social schemata.
Objective Children with autism have sitting and on-task behavior problems in class.
In this study, the effect of three alternative classroom-seating devices such as
regular classroom chairs, therapy balls, and air cushions were examined on
students' classroom behavior. Materials & Methods 15 students with autism
participated in this A1-B-A2-C multiple treatments study from Mashhad's Tabasom
School, Mashhad, Iran in 2014. Students' behaviors were video recorded in three
phases: sitting on their common chairs during phase A, air-sit cushioned in phase
B, and ball chairs in phase C. Sitting times and on-task behaviors were quantified
by momentary time sampling and compared during different phases for important
changes during 8 wk. Additionally, the Gilliam Autism Rating Scale-Second Edition
test was used to examine stereotyped movements, social and communication skills of
the students in the before and after research. Results Significant increases in in-
seat behaviors in 86.7% (thirteen out of 15) of the students and on-task behaviors
in 53.3% of the students (eight out of 15) when seated on therapy balls. Air
cushions had no significant effects on in-seat/on-task behaviors. The results also
showed significant decrease in stereotyped movement and increase in communication
and social skills of these students. The teachers also preferred the use of the
balls and/ or air-cushioned chairs for their students. Conclusion Therapy ball
chairs facilitated in-seat behavior and decreased autism related behavior of the
students with Autism Spectrum Disorder in class.
People with autism spectrum disorder (ASD) have difficulties in identifying another
person by face and voice. This might contribute considerably to the development of
social cognition and interaction difficulties. The characteristics of the voice
recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral
test battery to systematically investigate voice processing in high-functioning ASD
(n=16) and typically developed pair-wise matched controls (n=16). The ASD group had
particular difficulties with discriminating, learning, and recognizing unfamiliar
voices, while recognizing famous voices was relatively intact. Tests on acoustic
processing abilities showed that the ASD group had a specific deficit in vocal
pitch perception that was dissociable from otherwise intact acoustic processing
(i.e., musical pitch, musical, and vocal timbre perception). Our results allow a
characterization of the voice recognition deficit in ASD: The findings indicate
that in high-functioning ASD, the difficulty to recognize voices is particularly
pronounced for learning novel voices and the recognition of unfamiliar peoples'
voices. This pattern might be indicative of difficulties with integrating the
acoustic characteristics of the voice into a coherent percepta function that has
been previously associated with voice-selective regions in the posterior superior
temporal sulcus/gyrus of the human brain. Autism Res2017, 10: 155-168. (c) 2016
International Society for Autism Research, Wiley Periodicals, Inc.
Individuals with autism spectrum disorders (ASD) show significant impairments in
social skills and theory of mind (ToM). The aim of this study was to evaluate ToM
and social information processing abilities in 52 children with ASD compared to 55
typically developing (TD) children. A mediation analysis evaluated whether social
information processing abilities can be mediated by ToM competences. In our
results, children with autism showed a deficit in social skills and ToM components.
The innovative results of our study applying mediation analysis demonstrate that
ToM plays a key role in the development of social abilities, and the lack of ToM
competences in children with autism impairs their competent social behavior.
Background: Responding to joint attention (RJA) is reduced in young children with
ASD despite being vital to the early development of social communication. For this
reason, RJA is a frequent target in early intervention programs. Clinical
guidelines suggest that exaggerating facial expressions or gestural pointing may
improve RJA in children with autism by clarifying the meaning of the gaze or
gesture. In the current study, we investigate the effect of intensity of emotional
expression on RJA in preschoolers with ASD. Method: Twenty-five preschoolers with
ASD and 21 typically developing peers were administered a specifically designed
eye-tracking task in which an actor directs attention to a moving object by looking
at it with an expression that was either neutral, mildly surprised or intensely
surprised. In a supplementary condition, gestural pointing was accompanied by a
neutral gaze shift. Results: Commensurate with previous studies, children with ASD
oriented less to the face of the actor and were less responsive to RJA when
compared to their typically developing peers. However, children with autism
differed in their response to RJA according to the different task conditions. They
demonstrated more frequent responses to RJA when the actor's facial expression was
either intense or supported by gestural pointing. Conclusions: We report initial
evidence for the importance of clarifying content cues in order to help
preschoolers with autism adhere to receptive joint attention (RJA) opportunities.
Our findings inform knowledge about early treatment and attention to emotional
expressions in autism and improve our understanding of how early interventions may
work to increase RJA in young children with ASD. (C) 2016 Elsevier Ltd. All rights
reserved.
Aim: Oxytocin presents an exciting potential to target the core symptoms of autism
spectrum disorder (ASD) pharmacologically in an easily administered, cost-effective
form with possibly minimal adverse effects. But, there are still major gaps in this
area of research. This paper reviewed randomized controlled trials (RCTs) examining
the effects of oxytocin administration on social cognition and restricted,
repetitive behaviors in individuals with an ASD. Method: Electronic literature
searches were conducted from PsycINFO, PubMed, Web of Knowledge, and EMBASE for
RCTs published through June 2015. Results: 12 RCTs were included in this review. 7
out of the 11 studies that examined social cognition reported improvements.
Additionally, one out of the 4 studies on restricted, repetitive behaviors,
reported improvements following oxytocin administration. However, results from our
meta-analyses suggest that oxytocin has no significant effect on these 2 domains.
Conclusion: Previous evidence revealed mixed findings about the effects of oxytocin
on ASD. Given the limited number of RCTs, our summary of findings on the
effectiveness of oxytocin on ASD should still be considered tentative.
The purpose of this study was to examine the utility of the Systematic Observation
of Red Flags as an observational level-two screening measure to detect risk for
autism spectrum disorder in toddlers when used with a video-recorded administration
of the Communication and Symbolic Behavior Scales. Psychometric properties of the
Systematic Observation of Red Flags were examined in a sample of 247 toddlers of
16- to 24months old: 130 with autism spectrum disorder, 61 with developmental
delays, and 56 typically developing. Individual items were examined for performance
to create an algorithm with improved sensitivity and specificity, yielding a total
Composite score and Domain scores for Social Communication and Restricted
Repetitive Behaviors. Codes indicating clear symptom presence were collapsed to
yield a count of the number of Red Flags for the overall scale and each symptom
domain. Results indicated significant group differences with large effects for the
Composite, both Domain scores, and Red Flags score, and good discrimination (area
under the curve=0.84-0.87) between autism spectrum disorder and nonspectrum groups
for the Composite, Social Communication Domain, and Social Communication Red Flags
score. The Systematic Observation of Red Flags provides an observational screening
measure for 16- to 24-month-olds with good discrimination, sensitivity, and
specificity. A cutoff of 20 on the Composite is recommended to optimally detect
autism spectrum disorder risk.
It has been recognized that individuals with autism spectrum disorder (ASD) show
discrepancies between their abstract capacities to solve social cognition dilemmas
and their ability to spontaneously decipher live social interactions. In the last
15 years, different paradigms have been designed to investigate how individuals
with ASD grasp information when emerged in naturalistic or live social
interactions. The present paper reviews three categories of such paradigms that
focus on (1) verbal questionnaires and interviews while participants view a
naturalistic social scenario, (2) eye tracking methods while participants view
naturalistic settings, and (3) simulation of social interactions using virtual
reality or robotics. This paper discusses the advantages and limitations of each
paradigm and suggests a new concept for combining these paradigms.
Autism is characterised by difficulties in social functioning, notably in
interactions with other people. Yet, most studies addressing social difficulties
have used static images or, at best, videos of social stimuli, with no scope for
real interaction. Here, we study one crucial aspect of social interactionsgaze
behaviourin an interactive setting. First, typical individuals were shown videos of
an experimenter and, by means of a deception procedure, were either led to believe
that the experimenter was present via a live video-feed or was pre-recorded.
Participants' eye movements revealed that when passively viewing an experimenter
they believed to be live, they looked less at that person than when they believed
the experimenter video was pre-recorded. Interestingly, this reduction in viewing
behaviour in response to the believed live presence of the experimenter was absent
in individuals high in autistic traits, suggesting a relative insensitivity to
social presence alone. When participants were asked to actively engage in a real-
time interaction with the experimenter, however, high autistic trait individuals
looked significantly less at the experimenter relative to low autistic trait
individuals. The results reinforce findings of atypical gaze behaviour in
individuals high in autistic traits, but suggest that active engagement in a social
interaction may be important in eliciting reduced looking. We propose that
difficulties with the spatio-temporal dynamics associated with real social
interactions rather than underlying difficulties processing the social stimulus
itself may drive these effects. The results underline the importance of developing
ecologically valid methods to investigate social cognition. Autism Res2017, 10:
359-368. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc.
on behalf of International Society for Autism Research.
To assess the impact of their child's symptoms of Autism Spectrum Disorder upon
parents' anxiety and depression, 68 mothers of boys aged 10 to 15 years (M = 12.6
years, SD = 1.6 years) completed the ASD Behaviour Checklist, the GAD7 and the PHQ9
at a single setting. Results indicated that the boys' restricted and repetitive
behaviours had the strongest relationship with their mothers' anxiety and
depression, followed by communication difficulties, but the latter set of
behaviours did not significantly add to the variance predicted by restricted and
repetitive behaviours. Their sons' intense reactions to stressors was the most
powerful ASD-related contributor to the anxiety and depression experienced by these
mothers. Several suggestions for enhancing parental coping with this aspect of
their child's ASD behavioural symptomatology are discussed.
Background: Although children with autism spectrum disorder (ASD) are more likely
to be exposed to harsh parental discipline, research on this issue is scarce. In
particular, few studies have examined the risk factors for harsh parental
discipline in this population. We responded to this gap in the literature by
testing multiple individual and environmental factors as potential predictors of
parental psychological aggression and physical assault toward children with ASD.
Guided by a developmental-ecological perspective, we hypothesized that harsh
parental discipline would be shaped by the characteristics of the child (symptom
severity), the parent (parenting stress), the family (economic pressure), and the
broader context (discrimination in the community). Method: A total of 424 Hong Kong
parents of children with ASD completed standardized questionnaires. The hypotheses
were tested using bivariate correlation and multivariate regression analyses.
Results: At the bivariate level, child symptom severity, parenting stress, family
economic pressure, and experienced discrimination were positively associated with
parental psychological aggression. Moreover, child symptom severity and parenting
stress were positively associated with parental physical assault. At the
multivariate level, parenting stress was significantly related to psychological
aggression, while child symptom severity and parenting stress were significantly
related to physical assault. Mediation analyses further demonstrated that
psychological aggression partially mediated the effect of parenting stress on
physical assault. Conclusions: Theoretically, our findings contributed to our
understanding of the origin of harsh parenting practices toward children with ASD.
Practically, our findings provided insights about ways to identify high-risk
families and to develop effective child maltreatment intervention programs. (C)
2016 Elsevier Ltd. All rights reserved.
Electrophysiologic studies suggest that autism spectrum disorder is characterized
by aberrant anatomic and functional neural circuitry. During normal brain
development, pruning and synaptogenesis facilitate ongoing changes in both short-
and long-range neural wiring. In developmental disorders such as autism, this
process may be perturbed and lead to abnormal neural connectivity. Careful analysis
of electrophysiologic connectivity patterns using EEG coherence may provide a way
to probe the resulting differences in neurological function between people with and
without autism. There is general consensus that electroencephalogram coherence
patterns differ between individuals with and without autism spectrum disorders;
however, the exact nature of the differences and their clinical significance remain
unclear. Here we review recent literature comparing electroencephalogram coherence
patterns between patients with autism spectrum disorders or at high risk for autism
and their non-autistic or low-risk for autism peers.
Detecting where our partners direct their gaze is an important aspect of social
interaction. An atypical gaze processing has been reported in autism. However, it
remains controversial whether children and adults with autism spectrum disorder
interpret indirect gaze direction with typical accuracy. This study investigated
whether the detection of gaze direction toward an object is less accurate in autism
spectrum disorder. Individuals with autism spectrum disorder (n=33) and
intelligence quotients-matched and age-matched controls (n=38) were asked to watch
a series of synthetic faces looking at objects, and decide which of two objects was
looked at. The angle formed by the two possible targets and the face varied
following an adaptive procedure, in order to determine individual thresholds. We
found that gaze direction detection was less accurate in autism spectrum disorder
than in control participants. Our results suggest that the precision of gaze
following may be one of the altered processes underlying social interaction
difficulties in autism spectrum disorder.
Interoceptive awareness is linked to emotional and social cognition, which are
impaired in individuals with autism spectrum disorder (ASD). It is unknown how this
ability is associated with age in either typical or atypical development. We used a
standard test of interoceptive accuracy (IA) to investigate these questions in
children and adults with and without ASD. Perceived number of heartbeats over 4
time intervals was compared with actual heart rate to determine IA. Effects of
group, age, IQ, heart rate, and mental counting ability on accuracy were assessed
using multiple regression. Post hoc correlations were performed to clarify
significant interactions. Age was unrelated to IA in both groups when IQ >= 115.
When IQ < 115, this relationship was positive in typical development and negative
in ASD. These results suggest that cognitive ability moderates the effect of age on
IA differently in autism and typical development.
Background: Autism spectrum disorder (ASD) is sexually dimorphic in brain
structure, genetics, and behaviors. In studies of brain tissue, the age of the
population is clearly a factor in interpreting study outcome, yet sex is rarely
considered. To begin to address this issue, we extend our previously published
microarray analyses to examine expression of small noncoding RNAs (sncRNAs),
including microRNAs (miRNAs), in ASD and in the control temporal cortex in males
and females. Predicted miRNA targets were identified as well as the pathways they
overpopulate. Findings: After considering age, sexual dimorphism in ASD sncRNA
expression persists in the temporal cortex and in the patterning that distinguishes
regions. Among the sexually dimorphic miRNAs are miR-219 and miR-338, which promote
oligodendrocyte differentiation, miR-125, implicated in neuronal differentiation,
and miR-488, implicated in anxiety. Putative miRNA targets are significantly over-
represented in immune and nervous system pathways in both sexes, consistent with
previous mRNA studies. Even for common pathways, the specific target mRNAs are
often sexually dimorphic. For example, both male and female target genes
significantly populate the Axonal Guidance Signaling pathway, yet less than a third
of the targets are common to both sexes. Conclusions: Our findings of sexual
dimorphism in sncRNA levels underscore the importance of considering sex, in
addition to age, when interpreting molecular findings on ASD brain.
Autism Spectrum Disorder (ASD) has been associated with reduced orienting to social
stimuli such as eyes, but the results are inconsistent. It is not known whether
atypicalities in phasic alerting could play a role in putative altered social
orienting in ASD. Here, we show that in unisensory (visual) trials, children with
ASD are slower to orient to eyes (among distractors) than controls matched for age,
sex, and nonverbal IQ. However, in another condition where a brief spatially
nonpredictive sound was presented just before the visual targets, this group effect
was reversed. Our results indicate that orienting to social versus nonsocial
stimuli is differently modulated by phasic alerting mechanisms in young children
with ASD. Autism Res2017, 10: 246-250. (c) 2016 The Authors Autism Research
published by Wiley Periodicals, Inc. on behalf of International Society for Autism
Research.
Background: Early research has documented that young children show an increased
interest toward objects that are verbally labeled by an adult, compared to objects
that are presented without a label. It is unclear whether the same phenomenon
occurs in neurodevelopmental disorders affecting social development, such as autism
spectrum disorder (ASD) and Williams syndrome (WS). Methods: The present study used
a novel eye-tracking paradigm to determine whether hearing a verbal label increases
the salience of novel objects in 35 preschoolers with ASD, 18 preschoolers with WS,
and 20 typically developing peers. Results: We found that typically developing
children and those with WS, but not those with ASD, spent significantly more time
looking at objects that are verbally labeled by an adult, compared to objects that
are presented without a label. Conclusions: In children without ASD, information
accompanied by the speaker's verbal label is accorded a "special status," and it is
more likely to be attended to. In contrast, children with ASD do not appear to
attribute a special salience to labeled objects compared to non-labeled objects.
This result is consistent with the notion that reduced responsivity to pedagogical
cues hinders social learning in young children with ASD.
Background The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among
the highest in the world (44.8 cases/100,000 person-years). Recommendations of the
Immunology of Diabetes Society advise evaluating autoantibody positivity in first-
degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the
disease. The aim of this study was to determine the prevalence of beta-cell
autoimmunity in FDRs of T1DM patients in Sardinia. Methods A total of 188 Sardinian
families were recruited in collaboration between diabetes and pediatric units of
university and district hospitals in Sardinia. The recruitment involved 188
patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies
(Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human
leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43
Aabs-positive FDR. Results The prevalence of Aabs (any type of autoantibody, single
or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53)
were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55%
(4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of
HLA-DR and DQ loci showed that 89% of FDR carried moderate-to high-risk genotypes,
with only 5 FDR with low-risk genotypes. Conclusions The prevalence of T1DM
autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian
population, higher than in other populations from the United States and Europe, and
similar to that observed in Finland. Autoantibody positivity strongly associated
with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM
patients in Sardinia and warrants longitudinal follow-up to estimate the risk of
progression to T1DM in high-risk populations.
Objective: To evaluate the role of auto-antibodies in Chinese patients with primary
and secondary infertility in routine clinical practice. Methods: We reviewed the
medical records of infertile Chinese patients of either gender (>= 18 year old) who
were failed to conceive after 12 months of regular sexual intercourse without the
use of contraception, and visited at department of Gynaecology and Obstetrics,
Renmin Hospital of Wuhan University, China between January 2004 to December 2014,
and undergone auto-antibody estimation along with other routine antenatal screening
tests. Immunological assay was performed using dot immuno-gold filtration assay.
Positive case was compared among patients with primary and secondary infertility.
Results: Our chart review study showed that the positive case of Anti-Sperm
Antibody (ASAb) was significantly higher in female with primary than male (p<0.05).
In female patients with primary infertility, all other auto-antibodies (anti-
Endometrium Antibody (EMAb), Anti-Ovary Antibody (AOAb), Anti-Zona Pellucida
Antibody (AZP)) and Anti-Cardiolipin Antibody (ACA) were significantly higher
compared to patients with secondary infertility (p<0.05). Moreover, positive case
of all auto-antibodies was significantly higher among female with primary fertility
than secondary fertility and control groups. Conclusion: Our study results
suggested the involvement of auto-antibodies related to reproduction system in
development of primary infertility. Auto-antibodies related to reproduction were
significantly higher in patients with primary infertility, this implicated
involvement of auto-immunological factors in development of infertility.
Objective The objective of this study was to investigate fatigue and cognitive
impairments in systemic lupus erythematous (SLE) in relation to diffuse white
matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate
biomarkers of brain white matter microstructural integrity, was obtained in
patients with SLE and age-matched controls. Fatigue and cognitive function were
assessed and related to SLE activity, clinical data and plasma biomarkers of
inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean
age 48.814.3 years) were included. Mean diffusivity (MD) was significantly higher
in all white matter fibre tracts in SLE patients versus age-matched healthy
controls (p<0.0001). Fatigue in SLE was higher than a normal reference range
(p<0.0001) and associated with lower MD (ss=-0.61, p=0.02), depression (ss=0.17,
p=0.001), anxiety (ss=0.13, p=0.006) and higher body mass index (ss=0.10, p=0.004)
in adjusted analyses. Poorer cognitive function was associated with longer SLE
disease duration (p=0.003) and higher MD (p=0.03) and, in adjusted analysis, higher
levels of IL-6 (ss=-0.15, p=0.02) but not with MD. Meta-analysis (10 studies,
n=261, including the present study) confirmed that patients with SLE have higher MD
than controls. Conclusion Patients with SLE have more microstructural brain white
matter damage for age than the general population, but this does not explain
increased fatigue or lower cognition in SLE. The association between raised IL-6
and worse current cognitive function in SLE should be explored in larger datasets.
Objectives: Autoimmune pancreatitis (AIP) is a representative IgG4-related and
inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis
resulting from AIP, we focused on methylation abnormalities and KRAS mutations in
AIP. Methods: Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK,
and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for
quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP
specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing
carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP)
samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct
sequencing. Results: Hypermethylation events (>= 10%) were identified in NPTX2,
Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases,
respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the
TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct
sequencing results for KRAS showed no single-point mutations in AIP. Conclusions:
These are the first studies characterizing methylation abnormalities in AIP. AIP's
inflammatory condition may be related to carcinogenesis. Further study will
elucidate methylation abnormalities associated with carcinogenesis in AIP.
The process of curing a patient by removing his illness by extracting blood is a
very old one. Many years ago, phlebotomy was practiced to cure illness. Now, this
old process, placed on a rational basis with therapeutic apheresis (TA), is being
followed in clinical practice. Therapeutic plasma exchange (TPE) with hollow fiber
modules has been used in different severe diseases for more than 40 years. Based on
many years of experience with the extracorporeal circulation in end-stage renal
disease, the authors herein give an overview of TA in immunological diseases,
especially in hematologic, autoimmune and dermatologic diseases. Updated
information on immunology and molecular biology of different immunological diseases
is discussed in relation to the rationale for apheresis therapy and its place in
combination with other modern therapies. With the introduction of novel and
effective biologic agents, TA is indicated only in severe cases, such as in rapid
progression despite immunosuppressive therapy and/or biologic agents. In mild forms
of autoimmune disease, treatment with immunosuppressive therapies and/or biologic
agents seems to be sufficient. The prognosis of autoimmune diseases with varying
organ manifestations has improved in recent years, due in part to very aggressive
therapy schemes. For the immunological diseases that can be treated with TA, the
guidelines of the German Working Group of Clinical Nephrology and of the Apheresis
Applications Committee of the American Society for Apheresis are cited. TA has been
shown to effectively remove the autoantibodies from blood and lead to rapid
clinical improvement.
Immune checkpoint inhibitors (ICI) represent a new revolutionary weapon in the
armamentarium of anti-cancer therapies. The side effects of these new agents
represent a new challenge for oncologists; they are usually unpredictable and
sometimes life threatening, if not managed rapidly and adequately. The most
frequent side effects are the dermatologic, but they are usually low grade side
effects and consequently easily manageable. Rash, pruritus and vitiligo are the
most frequent dermatologic side effects. We aimed in this review to describe first
all the dermatologic side effects of ICI according to the subtype of ICI and
combination therapies in the clinical trials, then to report all the rare case
reports dermatologic side effects, and finally to present the management algorithm
of these side effects.
Blood transcriptional profiles could serve as biomarkers of clinical changes in
subjects at-risk for or diagnosed with diabetes. However, transcriptional variation
over time is poorly understood due to the impracticality of frequent longitudinal
phlebotomy in large patient cohorts. We have developed a novel transcriptome
assessment method that could be applied to fingerstick blood samples self-collected
by study volunteers. FifteenL of blood from a fingerstick yielded sufficient RNA to
analyse >176 transcripts by high-throughput quantitative polymerase chain reaction
(PCR). We enrolled 13 subjects with type 1 diabetes and 14 controls to perform
weekly collections at home for a period of 6 months. Subjects returned an average
of 24 of 26 total weekly samples, and transcript data were obtained successfully
for >99% of samples returned. A high degree of correlation between fingerstick data
and data from a standard 3 mL venipuncture sample was observed. Increases in
interferon-stimulated gene expression were associated with self-reported
respiratory infections, indicating that real-world transcriptional changes can be
detected using this assay. In summary, we show that longitudinal monitoring of gene
expression is feasible using ultra-low-volume blood samples self-collected by study
participants at home, and can be used to monitor changes in gene expression
frequently over extended periods.
The importance of T-cell receptor (TCR) repertoire diversity is highlighted in
murine models of immunodeficiency and in many human pathologies. However, the true
extent of TCR diversity and how this diversity varies in health and disease is
poorly understood. In a previous issue of the European Journal of Immunology,
Lossius et al. [Eur. J. Immunol. 2014. 44: 3439-3452] dissected the composition of
the TCR repertoire in the context of multiple sclerosis (MS) using high-throughput
sequencing of TCR-beta chains in cerebrospinal fluid samples and blood. The authors
demonstrated that the TCR repertoire of the CSF was largely distinct from the blood
and enriched in EBV-reactive CD8(+) T cells in MS patients. Studies of this kind
have long been hindered by technical limitations and remain scarce in the
literature. However, TCR sequencing methodologies are progressing apace and will
undoubtedly shed light on the genetic basis of T-cell responses and the ontogeny of
T-cell-mediated diseases, such as MS.
Objectives: Human cytomegalovirus (HCMV) infection induces production of CD13-
specific autoantibodies, which may promote inflammation and tissue damage. HCMV
infection has been suggested as a cause of biliary atresia (BA), but little is
known of its role in other forms of neonatal cholestasis. We studied serum levels
of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of
different causes, including BA, and in mothers of healthy, term infants without
cholestasis, as well as in healthy blood donors. Methods: Using fluorescence-
activated cell sorting, we measured CD13-specific autoantibody levels in serum from
the above-mentioned groups. In addition, the effect of serum from mothers of
infants with neonatal cholestasis was tested on the differentiation of monocytes
into macrophages. Results: CD13-specific autoantibodies were found in mothers of
infants with neonatal cholestasis, but not in mothers of infants without
cholestasis and healthy blood donors, and were associated with HCMV seropositivity.
Sera from mothers of infants with all forms of neonatal cholestasis inhibited
differentiation of monocytes into macrophages, but this was not dependent on CD13-
specific autoantibodies. Conclusions: The significantly higher frequency of CD13-
specific autoantibodies in mothers of infants with neonatal cholestasis of all
forms compared with mothers of healthy infants without cholestasis suggests an
association, but does not prove that they are pathogenic. The presence of CD13-
specific autoantibodies does not correlate with HCMV IgG serostatus, suggesting a
more complicated mechanism that possibly reflects active HCMV infection in these
individuals. Further studies are needed to elucidate whether these autoantibodies
contribute to the development of cholestasis or represent an epiphenomenon.
In physiological circumstances, various tolerogenic mechanisms support the
protection of self-structures during immune responses. However, quantitative and/or
qualitative changes in regulatory immune cells and mediators can evoke auto-
reactive immune responses, and upon susceptible genetic background, along with the
presence of other concomitant etiological factors, autoimmune disease may develop.
In transplant immunology, tolerogenic mechanisms are also critical, since the
balance between of alloantigen-reactive effector cells and the regulatory immune
cells will ultimately determine whether a graft is accepted or rejected. Better
understanding of the immunological tolerance and the potential modulations of
immune regulatory processes are crucial for developing effective therapies in
autoimmune diseases as well as in organ transplantation. In this review, we focus
on the novel insights regarding the impaired immune regulation and other relevant
factors contributing to the development of auto-reactive and graft-reactive immune
responses in autoimmune diseases and transplant rejection, respectively. We also
address some promising approaches for modification of immune-regulatory processes
and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which
may be beneficial in future therapeutic strategies. (C) 2017 Elsevier B.V. All
rights reserved.
Background: Systemic autoinflammatory diseases (SAIDs) represent a growing number
of monogenic, polygenic or multifactorial disorders that are often difficult to
diagnose. Case presentation: Here we report a patient who was initially erroneously
diagnosed and treated for SAID. Symptoms consisted of recurrent fever, erythematous
and/or blistering skin lesions, angioedema, susceptibility to bleeding, external
ear infections and reversible anisocoria in the absence of laboratory evidence of
systemic inflammation. After two and a half years of extensive diagnostic work-up
and multiple empirical therapies, a final diagnosis of Munchausen by proxy syndrome
(MBPS) was established. Conclusions: The diagnosis of SAID needs to be carefully
reassessed if measurable systemic inflammation is missing, and MBPS should be
included in the differential diagnosis.
The human microbiome consists of all microorganisms occupying the skin, mucous
membranes and intestinal tract of the human body. The contact of the mucosal immune
system with the human microbiome is a balanced interplay between defence mechanisms
of the immune system and symbiotic or pathogenic microbial factors, such as
microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as
rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome, the
immune system is deranged to a chronic inflammatory state and autoantibodies are an
important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome
can lead to local mucosal inflammation and increased intestinal permeability.
Proinflammatory lymphocytes and cytokines can spread to the systemic circulation
and increase the risk of inflammation at distant anatomical sites, such as the
joints or salivary glands. Increased intestinal permeability increases antigen
exposure and the risk of autoantibody production. If the human microbiome indeed
plays such a critical role in SADs, this finding holds a great promise for new
therapeutic strategies, such as diet interventions and probiotics and prebiotics.
This review provides a background on the human microbiome and mucosal immunity in
the gut and oral cavity and gives a summary of the current knowledge on the
microbiome-SADs connection.
The paper deals with a hardware solution for the study of low power active filter
with Bode plotting. By using a DAQ card and an experimental platform it shows how
LabVIEW graphical programming environment can be used for manual or automated
testing and analysis of the first order active filter with operational amplifier
(op-amp). The hardware platform can provide a template to build real op-amp
circuits to better understand (together with a previous one paper for developing
the software simulation and demonstrations) the op-amp filters principles. The main
contribution for this paper refers to a software / hardware solution for obtaining
a manual / automat Bode plotting. For plotting the frequency response curve of a
filters, it is often necessary to measure the output signal over a range of input
frequency. The hardware experiments allows a range of test voltages with variable
frequency to be input and the filters response measured, displayed and analyzed.
The frequency scan range, scan rate and number of test points can be selected from
front panel controls. Another contribution is a practical tool for the analysis of
the response filter to various input signals (sine / square / triangular wave) and
calculating the filter gain depending on the amplitude measured in units of peak,
peak to peak or roots mean square signal level.
In the present paper a novel automatic gain control pre-amplifier for hearing aid
device is proposed and analyzed. The proposed design utilizes feedback and feed
forward loop in order to control the gain of the device. Input and output
thresholds have been accommodated to provide dual control. The weak input signal is
amplified in three modes. High gain for low input and low gain for high input forms
the basis of amplification. The measured average power dissipation of the complete
pre-amplifier is 410 mu W with a dual power supply of +/- 0.7 V in 180 nm
technology node. Frequency of operation is up to 20 kHz.
Mixed-signal integrated circuit design and simulation highly rely on behavioral
models of circuit blocks. Such models are used for the validation of design
specification, optimization of system topology, and behavioral synthesis using a
description language, etc. However, automatic behavioral model generation is still
in its early stages; in most scenarios designers are responsible for creating
behavioral models manually, which is time-consuming and error prone. In this paper
an automatic behavioral model generation method for switched-capacitor (SC)
integrator is proposed. This technique is based on symbolic circuit modeling with
approximation, by which parametric behavioral integrator model can be generated.
Such parametric models can be used in circuit design subject to severe process
variational. It is demonstrated that the automatically generated integrator models
can accurately capture process variation effects on arbitrarily selected circuit
elements; furthermore, they can be applied to behavioral simulation of SC Sigma-
Delta modulators (SDMs) with acceptable accuracy and speedup. The generated models
are compared to a recently proposed manually generated behavioral integrator model
in several simulation settings.
Technology is rapidly changing the nature of service, customers' service frontline
experiences, and customers' relationships with service providers. Based on the
prediction that in the marketplace of 2025, technology (e. g., service-providing
humanoid robots) will be melded into numerous service experiences, this article
spotlights technology's ability to engage customers on a social level as a critical
advancement of technology infusions. Specifically, it introduces the novel concept
of automated social presence (ASP; i. e., the extent to which technology makes
customers feel the presence of another social entity) to the services literature.
The authors develop a typology that highlights different combinations of automated
and human social presence in organizational frontlines and indicates literature
gaps, thereby emphasizing avenues for future research. Moreover, the article
presents a conceptual framework that focuses on (a) how the relationship between
ASP and several key service and customer outcomes is mediated by social cognition
and perceptions of psychological ownership as well as (b) three customer-related
factors that moderate the relationship between ASP and social cognition and
psychological ownership (i. e., a customer's relationship orientation, tendency to
anthropomorphize, and technology readiness). Finally, propositions are presented
that can be a catalyst for future work to enhance the understanding of how
technology infusion, particularly service robots, influences customers' frontline
experiences in the future.
Numerous epidemiological studies have demonstrated a close and bidirectional
association between depression and cardiovascular disorders (CVD). This comorbidity
places a significant burden on individuals and the healthcare system. Not
surprisingly, in the last two decades preclinical research in the field of
depression and CVD has rapidly progressed. Multiple studies have demonstrated that
aspects of human depression/cardiovascular comorbidity can be modeled in rodents
exposed to chronic stress paradigms and that a depressive-like syndrome can be
induced in rodent models of CVD. This research has provided insights into neural,
autonomic, humoral, immune and circulatory mechanisms linking cooccurring mood and
CVD. Recent investigations have started to address gender and individual
differences in the vulnerability to both disorders and have begun to explore the
efficacy of novel pharmacological interventions for the treatment of these comorbid
conditions. This review discusses relatively wellestablished findings and the
latest discoveries from rodent models of depression and CVD, with the aim of
providing an up-to-date reference which may guide future studies of the
relationship between mood and cardiovascular disturbances. (C) 2016 Elsevier Ltd.
All rights reserved.
Spinal cord injury (SCI) is a devastating event for individuals, who frequently
develop motor and sensory impairment as well as autonomic dysfunction. Previous
studies reported that autonomic activity plays a major role in social cognition and
that difficulties in the ability to interpret social information are commonly
observed in a variety of mental disorders, which in turn correlate with a poor
autonomic nervous system (ANS) regulation. It is well established that subjects
with SCI have an alteration in ANS regulation mechanisms. We hypothesized that
subjects diagnosed with SCI, who are experiencing a period of adaptation and socio-
labor insertion suffer alterations in an emotion recognition task, a component of
social cognition, which correlate with poor ANS regulation. We evaluated ANS
function by measuring the heart rate variability (HRV) in 18 healthy subjects and
10 subjects with SCI. A 5-min baseline HRV was compared to a task period while
performing The reading the mind in the eyes test (RMET). We found that while both
groups have similar general performance in the test, healthy subjects responded
with greater certainty during the RMET. This level of certainty during the RMET was
positively correlated with baseline HRV measures in this group. Also, the group of
healthy subjects exhibited higher HRV at baseline than participants with SCI.
Finally, the changes in HRV between baseline and task condition were significantly
higher in healthy individuals than in SCI participants. Our results show that
patients with SCI have low levels of autonomic regulation mechanisms which may
promote social cognition problems during their reinsertion to daily life.
Filamentous plant pathogens deliver effector proteins to host cells to promote
infection. The Phytophthora infestans RXLR-type effector PexRD54 binds potato ATG8
via its ATG8 family-interacting motif (AIM) and perturbs host-selective autophagy.
However, the structural basis of this interaction remains unknown. Here, we define
the crystal structure of PexRD54, which includes a modular architecture, including
five tandem repeat domains, with the AIM sequence presented at the disordered C
terminus. To determine the interface between PexRD54 and ATG8, we solved the
crystal structure of potato ATG8CL in complex with a peptide comprising the
effector's AIM sequence, and we established a model of the full-length PexRD54-
ATG8CL complex using small angle x-ray scattering. Structure-informed deletion of
the PexRD54 tandem domains reveals retention of ATG8CL binding in vitro and in
planta. This study offers new insights into structure/function relationships of
oomycete RXLR effectors and how these proteins engage with host cell targets to
promote disease.
Edwin M. Southern is a professor emeritus at the University of Oxford. He is
perhaps best known for development of the Southern blot (Dr. Southern was at the
University of Edinburgh when he wrote his landmark paper). The Southern blot
provided a scientific breakthrough by allowing scientists to detect a particular
DNA sequence without first purifying it from the rest of the genome; the basic
method involves the transfer of the DNA to a membrane, followed by detection with a
specific probe. Although few people perform Southern blots as originally carried
out by Southern, due in part to the more recent technique of the polymerase chain
reaction, the basic concept continues to play an important role in molecular
biology.
A new task force on postmortem imaging was established at the annual meeting of the
European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The
postmortem task force is separate from the child abuse task force as it covers all
aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of
the task force is the guidance and standardization of non-radiographic postmortem
imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines
the starting point of the task force, with a mission statement, outline of current
experience, and short- and long-term goals.
A novel nonparametric system identification (SI) algorithm is described, focusing
on PID-based control loops for buck converters with effective series resistance
(ESR) in the output filter. Dithering amplification effects on the control path are
exploited during the steady-state converter operation. The noise injected is used
to stimulate the loop reaction and to identify the output filter configuration.
Oversampling-dithering features of third-order Delta Sigma modulators are used to
increase the DPWM resolution during the converter nominal operation and, moreover,
as the core key to compute the SI algorithm. A modified structure of a noise shaper
is used to handle the resolution of the SI algorithm over a range of the desired
frequencies during the nonparametric identification. The SI algorithm comprises two
steps: the first processing step extracts the resonant frequency, and the second
extracts the ESR zero from the power spectrum density computation of the control
feedback error. The SI method has been validated with different buck converter
configurations, and has successfully been integrated and measured into a digitally
controlled buck converters prototype for automotive safety application.
Lignocellulosic biomass gasification followed by the Fischer-Tropsch (Fe) synthesis
is becoming a promising pathway to produce synthetic biofuels, having the potential
of being coupled with combined-cycle strategies in order to coproduce electricity.
In this work, the thermodynamic performance of this type of bioenergy system is
evaluated through exergy analysis. A base-case process combining biomass
gasification, FT synthesis and a combined cycle is defined. Furthermore, two
alternative configurations modifying the base-case process are considered: (i)
autothermal reforming (ATR) of a fraction of the FT tail gas to increase the fuel
yield, and (ii) combustion of a fraction of the conditioned biosyngas to increase
electricity production. The biomass conversion plants are simulated using Aspen
Plus (R) to obtain the data required for the assessment. The indirect gasifier and
the gas combustor are identified as the main sources of irreversibility within the
three process configurations, with exergy destruction ratios of 21% and 5-7%,
respectively. The gasification subsystem is found to contribute over 50% to the
overall exergy destruction, showing 68% efficiency. The power generation subsystem
also shows a high contribution to the overall exergy destruction (19-28%) due to
high fuel consumption and the significant thermodynamic irreversibility of the
cycle. Depending on the plant configuration, overall exergetic efficiencies of 24-
27% are attained. The ATR case leads to a higher yield of biofuels, at the expense
of lower electricity production. This configuration enhances the exergetic
efficiency of the system and thus its thermodynamic performance, in contrast to the
alternative configuration for increased power generation. (C) 2017 Elsevier Ltd.
All rights reserved.
An auto-zero and chopper operational amplifier with a 4.5-60 V supply voltage range
is realized, using a 0.18 mu m CMOS process augmented by 5 V CMOS and 60 V DMOS
transistors. It achieves a maximum offset voltage drift of 0.02 mu V/degrees C, a
minimum CMRR of 145 dB, a noise PSD of 6.8 nV/root Hz, and a 3.1 MHz unity gain
bandwidth, while dissipating 840 mu A of current. Up-modulated chopper ripple is
suppressed by auto-zeroing. Furthermore, glitches from the charge injection of the
input switches are mitigated by employing six parallel input stages with 800 kHz
interleaved clocks. This moves the majority of the glitch energy up to 4.8 MHz,
while leaving little energy at 800 kHz. As a result, the requirements on an
external low-pass glitch filter is relaxed, and a wider usable signal bandwidth can
be obtained. Maximum input bias current due to charge injection mismatch is reduced
from 1.5 nA to 150 pA by post production trimming with an on-chip charge mismatch
compensation circuit.
Short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme involved in the
oxidation of fatty acids and the catabolic pathway of valine and, to a lesser
extent, isoleucine. Deficiency of this enzyme was recently shown to cause an early
childhood Leigh syndrome phenotype. The few reported patients were compound
heterozygotes for two missense or missense with truncating variants in ECHS1 that
encodes SCEH. We describe two siblings with severe refractory lactic acidosis and
death within the first 2 days of life. Following negative clinical whole-exome and
whole-genome sequencing, we resorted to autozygome/exome analysis on research basis
and identified a homozygous splice site mutation (c.88+5G>A) in the two cases.
Analysis of cDNA confirmed complete replacement of the normal transcript with an
aberrant transcript (r.88_89ins 88+1_88+11) predicting premature truncation of the
protein [p.(Ala31Glufs*23)]. Furthermore, quantitative reverse transcriptase
polymerase chain reaction (RTPCR) showed marked reduction in ECHS1, most likely
nonsense-mediated decay (NMD)-mediated. This is the first report of homozygosity
for a truncating mutation in ECHS1, which may explain the severe phenotype. Our
report highlights the need to consider SCEH deficiency in patients with lethal
neonatal lactic acidosis, and the potentially limited sensitivity of untargeted
genomic sequencing towards non-canonical splicing mutations, which may explain at
least some of the negative' cases on clinical exome/genome sequencing.
This review presents a broader approach to the implementation and study of runs of
homozygosity (ROH) in animal populations, focusing on identifying and
characterizing ROH and their practical implications. ROH are continuous homozygous
segments that are common in individuals and populations. The ability of these
homozygous segments to give insight into a population's genetic events makes them a
useful tool that can provide information about the demographic evolution of a
population over time. Furthermore, ROH provide useful information about the genetic
relatedness among individuals, helping to minimize the inbreeding rate and also
helping to expose deleterious variants in the genome. The frequency, size and
distribution of ROH in the genome are influenced by factors such as natural and
artificial selection, recombination, linkage disequilibrium, population structure,
mutation rate and inbreeding level. Calculating the inbreeding coefficient from
molecular information from ROH (F-ROH) is more accurate for estimating autozygosity
and for detecting bothpast and more recent inbreeding effects than are estimates
from pedigree data (F-PED). The better results of F-ROH suggest that F-ROH can be
used to infer information about the history and inbreeding levels of a population
in the absence of genealogical information. The selection of superior animals has
produced large phenotypic changes and has reshaped the ROH patterns in various
regions of the genome. Additionally, selection increases homozygosity around the
target locus, and deleterious variants are seen to occur more frequently in ROH
regions. Studies involving ROH are increasingly common and provide valuable
information about how the genome's architecture can disclose a population's genetic
background. By revealing the molecular changes in populations over time, genome-
wide information is crucial to understanding antecedent genome architecture and,
therefore, to maintaining diversity and fitness in endangered livestock breeds.
This paper introduces a new voltage regulator module (VRM) that merges a highly
efficient switched-inductor converter as the main unit with a load-side switched-
capacitor-based converter to assist during load transient events. The resulting
hybrid-VRM exhibits improved dynamic performance for both loading and unloading
transient events, while maintaining a compact design with reduced output
capacitance and lower components stress. The hybrid controller that has been
developed allows operation that is based on output voltage measurement alone,
further reducing the circuit complexity. A power processing efficiency analysis
that has been carried out shows efficiency improvement in favor of the hybrid-VRM
when compared to time-optimal control under varying load conditions. The operation
of the VRM is verified on a 20-W, 12V-to-1.5-V prototype with peak power conversion
efficiency of 93%, demonstrating near-ideal transient recovery.
In some high-performance applications, an LC filter must be added to the auxiliary
resonant snubber inverter (ARSI) to reduce the output current ripple. However,
resonance occurs due to the additional LC filter, which makes the traditional
closed-loop control not suitable to be used directly. Therefore, this paper
presents a double-loop digital control based on the active damping method of
capacitor current feedback to stabilize the system. Most of the studies on active
damping methods are focused on the grid in consideration of zero resistance.
However, the load resistance should not be neglected in the drive system.
Therefore, the load resistance and digital control delays are considered in this
paper. Moreover, an improved loading method is proposed to improve the duty ratio
range. In order to verify the effectiveness of the controller, a prototype was
developed. The simulation and experimental results demonstrate that soft-switching
can be realized for the entire load range. The maximum duty ratio is improved by
0.01 by using the proposed loading method. The resonance can be eliminated by using
the proposed control method.
We report the cloning of a glycoside hydrolase family (GHF) 9 gene of rice (Oryza
sativa L. cv. Sasanishiki), OsCel9A, corresponding to the auxin-induced 51 kDa
endo-1,4-beta-glucanase (EGase). This enzyme reveals a broad substrate specificity
with respect to sugar backbones (glucose and xylose) in beta-1,4-glycans of type II
cell wall. OsCel9A encodes a 640 amino acid polypeptide and is an ortholog of
TomCel8, a tomato EGase containing a carbohydrate-binding module (CBM) 2 sequence
at its C-terminus. The expression of four rice EGase genes including OsCel9A showed
different patterns of organ specificity and responses to auxin. OsCel9A was
preferentially expressed during the initiation of lateral roots or subcultured root
calli, but was hardly expressed during auxin-induced coleoptile elongation or in
seed calli, in contrast to OsCel9D, a KORRIGAN (KOR) homolog. In situ localization
of OsCel9A transcripts demonstrated that its expression was specifically up-
regulated in lateral root primordia (LRP). Northern blotting analysis showed the
presence of a single product of OsCel9A. In contrast, both mass spectrometric
analyses of peptide fragments from purified 51 kDa EGase proteins and immunogel
blot analysis of EGase proteins in root extracts using two antibodies against
internal peptide sequences of OsCel9A revealed that the entire CBM2 region was
post-translationally truncated from the 67 kDa nascent protein to generate 51 kDa
EGase isoforms. Analyses of auxin concentration and time course dependence of
accumulation of two EGase isoforms suggested that the translation and post-
translational CBM2 truncation of the OsCel9A gene may participate in lateral root
development.
This paper proposes a digital phase leading filter current compensation (PLFCC)
technique for a continuous conduction mode boost power factor correction to improve
PF in high line voltage and light load conditions. The proposed technique provides
a corrected average inductor current reference and utilizes an enhanced duty ratio
feed-forward technique which can cancel the adverse effect of the phase leading
currents caused by filter capacitors. Moreover, the proposed PLFCC technique also
provides the switching dead-zone in nature so the switching loss can be reduced.
Therefore, the proposed PLFCC can significantly improve power quality and can
achieve a high efficiency in high line voltage and light load conditions. The
principle and analysis of the proposed PLFCC are presented, and performance and
feasibility are verified by experimental results from the universal input (90-260
V-AC) and 750 W-400 V output laboratory prototype.
This paper presents a shunt active power filter (APF) with division-summation (D-
Sigma) digital control and based on a three-phase three-wire inverter
configuration. The APF shapes source current by introducing one degree of freedom
to compensate load harmonic currents. The adopted D-Sigma digital control approach
can accommodate filter-inductance variation, reducing core size significantly, and
it can derive control laws directly. An average power method is adopted in this
paper for determining the fundamental current at the source side, which can readily
be implemented without complex calculation, frame transformation, and extra filter.
In the design and implementation, the inductances corresponding to various inductor
currents were estimated at the startup and stored in the microcontroller for
scheduling loop gain cycle by cycle, which can ensure the system stability.
Measured results from a 5-kVA three-phase APF have confirmed the analysis and
discussion of the APF.
There has been a growing demand of using multi-function inverters for grid-
connected systems applied to nonconventional energy sources, such as solar, wind
and so on. In addition to power quality conditioning, the inverter can also be used
for bidirectional active power exchange with a three-phase four-wire grid.
Therefore, the inverter acts as a multi-function compensator. The functions of the
proposed inverter system include active power injection, rectification and active
power filtering (APF) (including phase power balancing). This paper presents design
and implementation of a three-leg split-capacitor shunt multi-function inverter
with division-summation (D-Sigma) digital control. The adopted D-Sigma digital
control can accommodate filter inductance variation, reducing core size
significantly, and its control laws can be derived directly to cancel the variation
effects of dc-bus voltage, switching period and filter inductance. An average power
method is adopted in this paper for determining fundamental currents at the source
side. In the design and implementation, the inductances corresponding to various
inductor currents were estimated at the startup and stored in the microcontroller
for scheduling loop gain cycle by cycle, which can insure system stability.
Measured results from a three-phase four-wire inverter have confirmed the analysis
and discussion.
The activity of lateral habenula (LHb) represents a substrate for the encoding of
negative-valenced events. The exposure to aversive stimuli in naive mice is
sufficient to trigger a reduction in GABA(B)-mediated signaling in the LHb. This is
ultimately instrumental for the hyperactivity of LHb neurons and for the
establishment of depressive-like phenotypes. However, the mechanisms responsible
for the induction of this aversion-driven plasticity are missing. Using ex-vivo
patch-clamp recordings in slices, here we show that exposing mice to a series of
inescapable footshocks (FsE) rapidly reduces baclofen-mediated GABA(B) currents in
the LHb. This plasticity of GABA(B) signaling requires the activation of the
dopamine and stress pathways. Indeed, the systemic administration of dopamine and
glucocorticoids receptor antagonists prevents the FsE-induced reduction of GABA(B)
currents in the LHb. To test whether the recruitment of these receptors occurs
within the LHb, we exposed slices from control mice to either dopamine or
corticosterone. Both manipulations failed to alter the amplitudes of baclofen-
mediated GABA(B) currents. Altogether, these data suggest that dopamine and stress
signaling are necessary for the induction of FsE-evoked GABA(B) plasticity in the
LHb. However, the activation of these specific receptors may occur in structures
different than the LHb, suggesting a circuit-based mechanism for this form of
plasticity. These findings provide mechanistic insights on aversion-driven
plasticity within the LHb.
Previous observational research suggests that stretching is contagious in
budgerigars (Melopsittacus undulatus). Here we report the first experimental
evidence of this response through a reanalysis of a previous experiment testing for
contagious yawning in this species. Using a repeated measures design, 16 birds were
tested as pairs alongside familiar and unfamiliar conspecifics with and without
visual barriers. Our results show that stretching behavior was temporally clustered
only when the birds could see one another, corroborating previous observational
findings supporting contagion. Additionally, for the first time, we show an ingroup
bias in this response. That is, while the overall frequency of stretching did not
significantly differ as a function of conspecific familiarity, contagious
stretching was only present when cage mates were paired together. These findings
are discussed in relation to recent research studying social cognition in this
species.
Background: We developed a new oligonucleotide microarray comprising 16 identical
subarrays for simultaneous rapid detection of avian viruses: avian influenza virus
(AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and
infectious bursal disease virus (IBDV) in single-and mixed-virus infections. The
objective of the study was to develop an oligonucleotide microarray for rapid
diagnosis of avian diseases that would be used in the course of mass analysis for
routine epidemiological surveillance owing to its ability to test one specimen for
several infections. Methods and results: The paper describes the technique for
rapid and simultaneous diagnosis of avian diseases such as avian influenza,
Newcastle disease, infectious bronchitis and infectious bursal disease with use of
oligonucleotide microarray, conditions for hybridization of fluorescent-labelled
viral cDNA on the microarray and its specificity tested with use of AIV, NDV, IBV,
IBDV strains as well as biomaterials from poultry. Sensitivity and specificity of
the developed microarray was evaluated with use of 122 specimens of biological
material: 44 cloacal swabs from sick birds and 78 tissue specimens from dead wild
and domestic birds, as well as with use of 15 AIV, NDV, IBV and IBDV strains,
different in their origin, epidemiological and biological characteristics (RIBSP
Microbial Collection). This microarray demonstrates high diagnostic sensitivity
(99.16% within 95% CI limits 97.36-100%) and specificity (100%). Specificity of the
developed technique was confirmed by direct sequencing of NP and M (AIV), VP2
(IBDV), S1 (IBV), NP (NDV) gene fragments. Conclusion: Diagnostic effectiveness of
the developed DNA microarray is 99.18% and therefore it can be used in mass survey
for specific detection of AIV, NDV, IBV and IBDV circulating in the region in the
course of epidemiological surveillance. Rather simple method for rapid diagnosis of
avian viral diseases that several times shortens duration of assay versus classical
diagnostic methods is proposed.
BackgroundIn Bangladesh, nomadic duck flocks are groups of domestic ducks reared
for egg production that are moved to access feeding sites beyond their owners'
village boundaries and are housed overnight in portable enclosures in scavenging
areas. The objectives of this study were to measure the prevalence of influenza A
virus RNA and H5-specific antibodies in nomadic ducks and to characterize nomadic
duck raising practices in northeastern Bangladesh. MethodsWe tested duck egg yolk
specimens by competitive ELISA to detect antibodies against avian influenza A (H5)
and environmental fecal samples by real-time reverse-transcription polymerase chain
reaction (rRT-PCR) to detect influenza A virus RNA and H5 subtype. ResultsThe
median age of the ducks was 24months (range: 8-36months) and the median flock size
was 300 ducks (range: 105-1100). Of 1860 egg yolk samples, 556 (30%, 95% confidence
interval (CI): 28-32) were positive for antibodies against H5 and 58 flocks (94%)
had at least one egg with H5-specific antibodies. Of 496 fecal samples, 121 (24%,
95% CI: 22-29) had detectable influenza A RNA. Thirty-three flocks (53%) had at
least one fecal sample positive for influenza A RNA. ConclusionsNomadic ducks in
Bangladesh are commonly infected with avian influenza A (H5) virus and may serve as
a bridging host for transmission of avian influenza A (H5) virus or other avian
influenza A viruses subtypes between wild waterfowl, backyard poultry, and humans
in Bangladesh.
Magellanic penguins (Spheniscus magellanicus) are native to Argentina, Chile and
the Falkland Islands. Magellanic penguins are highly susceptible to blood parasites
such as the mosquito-borne Plasmodium spp., which have been documented causing high
morbidity and mortality in zoos and rehabilitation centres. However, to date no
blood parasites have been detected in wild Magellanic penguins, and it is not clear
whether this is reflective of their true absence or is instead related to an
insufficiency in sampling effort or a failure of the diagnostic methods. We
examined blood smears of 284 Magellanic penguins from the Argentinean coast and
tested their blood samples with nested polymerase chain reaction tests targeting
Haemoproteus, Plasmodium, Leucocytozoon and Babesia. No blood parasites were
detected. Analysing the sampling effort of previous studies and the
climatogeography of the region, we found there is strong basis to conclude that
haemosporidians do not infect wild Magellanic penguins on the Argentinean coast.
However, at present it is not possible to determine whether such parasites occur on
the Chilean coast and at the Falkland Islands. Furthermore, it is troubling that
the northward distribution expansion of Magellanic penguins and the poleward
distribution shift of vectors may lead to novel opportunities for the transmission
of blood parasites.
Problem. - Neurobiology, adorned with the most recent discoveries of the molecular
biology, the genetics and the cognitive sciences, is present everywhere: In the
report of the man with his body, with his intellectual faculties, with his
perception of others and himself. Our social conducts, morality and our affects
would be governed by neuronal substrata. Are things so simple? Methodology. - To
try to answer this question, the author is going to use the opposition "to explain"
and "understand", in a long-standing and often passionate debate which concerns the
epistemology and the ontology, two modalities to be inflexible. Different thus of
methods: In the mind of Dilthey, we explain the nature (submitted to the principle
of the causality) but we understand the psychic life (which sends back to the
sphere of the sense). Results. - If the debate to explain and understand is further
and far from being simple, the author adduces to draw from it some conclusions by
questioning the speech of the promising of a reductionist neurobiology which
believe to explain everything including all our actions in the name of the
neurobiological reason: (1) if this is the case, we would be slaves of a history
which already has its fate: The neurobiological-shaped man is neurobiological, (2)
this speech is based on the mechanism of the tautology, that is it goes round in
circles, teaches us absolutely nothing, (3) if the same neurobiologist asserts the
opposite, why while reporting me what I say, I have no precise and localizable
perception of my consciousness? (4) if the consciousness has no appropriate place
or, to say it differently, if there is no intellectual topic appropriate to the
consciousness, then what takes place in me will remain forever untranslatable and
will be condemned to the silence. To go out of one, exist thus, I need the
immediate and permanent help of an other one (or of contradiction), (5) if this
process is purely an event of the brain then all our actions, all our gestures, in
brief all that it is allowed us to live has to take place as it takes place, (6)
finally to assert it brings us nothing more because the explanation always leaves
something aside: the phenomenon of the life in which he is imperceptible. The
example of the alcoholic is significant: if a change of the intellectual mechanisms
is responsible of his alcohol addiction, why the alcoholic, by wanting to drink
"how everybody", makes as if written history beforehand was of not much importance?
If the alcoholic began thinking of his own cerebral dysfunction while he lives, his
life would have no shape. Indeed, if he receives the message and knows the felling
about which it is a question. Indeed, if he receives the message and knows the
feeling about which it is a question, he cannot, by force of circumstance, feel
what his brain passes on to him: he does not witness what appears in its brain. On
the other and he witnesses the world in which he lives but also on his condition of
mortal. So, without objects to be cultivated, that is without the world of the
presence which is the one of the existence and not the understanding, the
neurobiological explanation of his alcohol addiction will concern a knowledge but
will ignore any life. It means that there is well a gap to live and theorize and
that the alcoholic is not reduced to a cerebral dysfunction: he is in the life of
relation, that is it is capable of taking up himself by using its real-life
experience. The psychopathology implications are going to show themselves here of a
very big importance: any reduction comes to truncate the understanding of the man
sick coach in reality we constantly have to deal with the "global and complete"
man, with the anthropology of the human fate. Conclusion. - If the science brings
us news discovered in this domain, it has to keep always in mind that the life
remains imperceptible and deeply moving. Without this existential event which
allows us "to live", the air will become unbreathable in our more and more
technical-scientific world: it would like being sentenced to asphyxiation. (C) 2016
Elsevier Masson SAS. All rights reserved.
In recent years, transportation electrification has emerged as a trend to support
energy efficiency and CO2 emissions reduction targets. The true success, however,
of this trend depends on the successful integration of electric transportation
modes into the infrastructure systems that support them. Left unmanaged, plug-in
electric vehicles may suffer from delays due to charging or cause destabilizing
charging loads on the electrical grid. Online electric vehicles have emerged to
remediate the need for stationary charging and its effects. While many works have
sought to mitigate these effects with advanced control functionality, such as
coordinated charging, vehicle-to-grid stabilization, and charging queue management,
few works have assessed these impacts as a holistic transportation-electricity
nexus. This paper develops a hybrid dynamic system model for transportation
electrification. It also includes next generation traffic simulation concepts of
multimodality and multiagency. Such a model can be used by electrified
transportation fleet operators to not just assess but also improve their operations
and control. The hybrid dynamic system model is composed of a marked Petri-net
model superimposed on the continuous time kinematic and electrical state evolution.
The model is demonstrated on an illustrative example of moderate size and
functional heterogeneity.
Aluminum-doped zinc oxide (AZO) has attained intensive attention as being a very
good transparent conducting oxide for photovoltaic applications. In this work, AZO
films have been deposited on glass substrate by radio frequency (RF) magnetron
sputtering. The influences of substrate temperatures on morphological, structural,
optical and electrical properties of AZO films were systematically investigated.
The results indicate that all AZO films have the hexagonal structure with c-axis
preferred orientation. Morphological and electrical measurements have revealed that
the substrate temperatures have strong influence on the microstructure, optical and
electrical properties of AZO films. The AZO film is highly transparent from
ultraviolet up to near infrared range with highest average transparency exceeding
83%. The minimum resistivity is as low as 6.1 x 10(-4) Omega cm. The carrier
concentration and mobility are as high as 3.357 x 10(20) cm(-3) and 30.48 cm(2)/Vs,
respectively. Finally, the performances of the AZO film are evaluated by its
practical application in Cu(ln(1-x)Ga(x))Se-2 (CIGS) photovoltaic device as a
transparent electrode. Benefited from its highly transparent and conductive
feature, the most efficient device reveals an efficiency of 7.8% with a short-
circuit current density of 28.99 mA/cm(2), an open-circuit voltage of 430 mV, and a
fill factor of 62.44 under standard conditions. (C) 2017 Elsevier B.V. All rights
reserved.
The present study examines the molecular mechanism underlying in vitro-induced
resistance to FLC (fluconazole), KTC (ketaonazole), MCZ (miconazole) and CHX
(cycloheximide) in AS (azole-susceptible) strains of Candicia albicans when exposed
to CaCDR1/CaCDR2 inducers like FPZ (fluphenazine) and steroids [PRG (progesterone)
and beta-EST (beta-oestradiol)]. By employing spot and checkerboard titre assays,
we provide evidence of an in vitro-induced antagonism between tested drugs and
inducers, which was accompanied with a concomitant increase in CaCDR1 and CaCDR2
transcript levels. Notably, unlike AS isolates, parental WT (wild-type) and Delta
cdr2 null strains, Delta cdrl as well as Delta cdr1/Delta cdr2 nulls, when
challenged with the inducers could not display antagonism. Our results validated by
Northern blotting, reporter gene transcription and TRO (transcription run on)
assays show that in vitro-induced antagonism between tested drugs and inducer in AS
isolates was mainly due to a transient and reversible transcriptional activation of
CaCDR1. Notwithstanding our earlier observation that consistent high transcript
levels of CaCDR1 in clinical AR (azole-resistant) isolates were maintained due to
the combination of its transcriptional activation and enhanced mRNA stability via
elongated poly(A) tails, this study shows that transient and reversible
transcriptional activation of CaCDR1 was the major determinant of induced
antagonism in AS isolates. The distinct strategies between sustained (in AR
isolates) and transiently induced resistance mechanisms (in AS isolates) adopted by
Candida should become useful in improving therapeutic approaches.
Testicular maturation arrest is characterized by interruption of germ cell
development and differentiation. Genetic factors play important role in the
causation of human disease, including male infertility. The objective was to study
copy number variations in testicular maturation arrest using single nucleotide
polymorphism (SNP) microarray technique. Conventional cytogenetics, targeted
fluorescence insitu hybridization (FISH) and sequence-tagged site (STS) polymerase
chain reaction (PCR) were used to confirm some of the SNP microarray findings. SNP
microarray on 68 cases of testicular maturation arrest detected copy number
variations (CNVs) mostly on sex chromosomes involving pseudoautosomal regions (PAR)
1, 2 and 3 as well as azoospermic factors (AZFs) besides three cases of chromosomal
abnormalities (two Klinefelter syndromes and one case of dicentric Y). The AZF
deletion was observed in 14 (20.6%) cases and the AZFc gain was observed in 6
(8.8%) cases. PAR 1 and 2 CNVs was observed in 5 (7.3%) cases. PAR 3 CNVs was
detected in 19 cases and 2 controls. The TSPY2 gene gain (within PAR 3 CNVs) was
observed in 16 cases and 1 control. CNV containing autosomal genes possibly
associated with male infertility in this study was SPATA31A2-A5 (9p12) in five
cases. In this study, SNP microarray identified possible underlying aetiology in
55.9% (38/68) cases besides identifying minimal critical region of AZFc deletion as
0.51mb (Y:24356128-24873665) involving TTY5, RBMY2FP, RBMY1F, RBMY1J, TTY6 and PRY
genes. SNP microarray seems superior, sensitive, specific as well as cost-effective
method and has potential to be the first tier investigations to explore underlying
genomic factors of testicular maturation arrest. The present study is an attempt to
find out probable genomic factors with idiopathic testicular maturation arrest.
Properly regulated immunity requires precise integration of activating and
inhibitory signals. As for other lymphocytes, B cells express an antigen-specific
activating receptor, the B-cell antigen receptor (BCR), and inhibitory receptors
(e.g. Fc gamma RIIb) that exercise checkpoint control on B-cell activation.
Moreover, following BCR engagement, CD19 recruits proteins that amplify BCR
signaling, while CD22 initiates a negative feedback loop by recruiting proteins
that inhibit BCR signaling. Initial BCR signaling is mediated by protein tyrosine
kinases and lipid kinases; inhibitory receptors directly antagonize the actions of
these enzymes by recruiting protein tyrosine phosphatases and lipid phosphatases
and positioning them close to actively signaling BCRs. Previously it was thought
that inhibitory receptors such as Fc gamma RIIb and CD22 were essential for
bringing these phosphatases near the BCR. In this issue of the European Journal of
Immunology, Manno et al. show that a tripartite inhibitory module consisting of the
adaptor proteins Dok-3 and Grb2 and the lipid phosphatase SHIP1 binds directly to
activated BCRs and limits the Ca2+ mobilization that is required for B lymphocyte
activation. This reveals that the BCR can be both an activating and inhibitory
receptor, one that activates signaling enzymes while initiating a negative feedback
loop that prevents excessive signaling.
Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease.
Antibodies are pivotal in providing protection against FMDV infection. Serological
protection against one FMDV serotype does not confer interserotype protection.
However, some historical data have shown that interserotype protection can be
induced following sequential FMDV challenge with multiple FMDV serotypes. In this
study, we have investigated the kinetics of the FMDV-specific antibody-secreting
cell (ASC) response following homologous and heterologous inactivated FMDV
vaccination regimes. We have demonstrated that the kinetics of the B cell response
are similar for all four FMDV serotypes tested following a homologous FMDV
vaccination regime. When a heterologous vaccination regime was used with the
sequential inoculation of three different inactivated FMDV serotypes (O, A, and
Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The
studies also revealed that the local lymphoid tissue had detectable FMDV-specific
ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of
short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to
inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of
intraserotype response following a sequential vaccination regime of four different
FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid
tissue, further evidence of a TI-2 response to FMDV.
Chronic inflammation in the tumor microenvironment and evasion of the antitumor
effector immune response are two of the emerging hallmarks required for oncogenesis
and cancer progression. The innate immune system not only plays a critical role in
perpetuating these tumor-promoting hallmarks but also in developing antitumor
adaptive immune responses. Thus, understanding the dual role of the innate system
in cancer immunology is required for the design of combined immunotherapy
strategies able to tackle established tumors. Here, we review recent advances in
the understanding of the role of cell populations and soluble components of the
innate immune system in cancer, with a focus on complement, the adapter molecule
Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells.
Around 65% of primary immunodeficiencies are antibody deficiencies. Functional
tests are useful tools to study B-cell functions in vitro. However, no accepted
guidelines for performing and evaluating functional tests have been issued yet.
Here, we report our experience on the study of B-cell functions in infancy and
throughout childhood. We show that T-independent stimulation with CpGmeasures
proliferation and differentiation potential of memory B cells. Switched memory B
cells respond better than IgM memory B cells. On the other hand, CD40L, a T-
dependent stimulus, does not induce plasma cell differentiation, but causes
proliferation of naive and memory B cells. During childhood, the production of
plasmablasts in response to CpG increases with age mirroring the development of
memory B cells. The response to CD40L does not change with age. In patients with
selective IgA deficiency (SIgAD), we observed that switched memory B cells are
reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells
are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients
show a reduced proliferative response to CD40L. Our results demonstrate that
functional tests are an important tool to assess the functions of the humoral
immune system.
Osteopontin (OPN) is a protein, generally considered to play a pro-tumorigenic
role, whereas several reports have demonstrated the anti-tumorigenic function of
OPN during tumor development. These opposing anti-and pro-tumorigenic functions are
not fully understood. Here, we report that host-derived OPN plays an anti-
tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP)
model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in
Rag2(-/-) mice suggests that OPN is dispensable in the adaptive immune response. We
found that host-derived OPN enhanced infiltration of natural killer (NK) cells into
TRAMP tumors. The requirement of OPN in NK cell migration towards TRAMP cells was
confirmed by an ex vivo cell migration assay. In contrast to TRAMP cells, in vivo
B16 tumor development was not inhibited by OPN, and B16 tumors did not show OPN-
mediated cell recruitment. It is possible that low levels of chemokine expression
by B16 cells do not allow OPN to enhance immune cell recruitment. In addition to
demonstrating the anti-tumorigenic role of OPN in TRAMP tumor development, this
study also suggests that the contribution of OPN to tumor development depends on
the type of tumor as well as the source and isoform of OPN.
Design and implementation of a low cost grid-connected 5kVA solar photovoltaic (PV)
system is proposed in this paper. Since the inverter is a major component of the PV
system, the B4 inverter used in this paper reduces the total cost of the PV system.
In order to eliminate the massive transformer, the PV system is connected to the
grid through IGBT switches. In addition to injection of active power into the grid,
the B4 inverter can compensate reactive power and reduce harmonics of the nonlinear
loads. A TMS320F28335 DSP processor is used for effective control of the B4
inverter. Various features of this processor enable the implementation of the
necessary control algorithms. As a first step, the PV system is simulated and
evaluated in Matlab/Simulink. In the second step, hardware circuits are designed
and implemented based on the simulation results. The operation of the PV system has
been evaluated under balanced, unbalanced, linear and nonlinear loads which proves
its accuracy and efficiency.
B7-homolog 4 (B7-H4), one of the costimulatory molecules of the B7 family, has been
reported to be widely expressed in multiple types of cancer tissues, and to be
important in tumor progression and poor prognosis. However, the role of B7-H4 in
esophageal precancerous lesions has not been elucidated yet. In the present study,
a model of esophageal squamous cell carcinogenesis was established in 208 C57BL/6
mice by 4-nitroquinoline-1-oxide (4NQO) drinking water of mice, and the changes in
the expression of B7-H4 during the whole pathological process were investigated.
Hematoxylin and eosin staining results demonstrated that the pathological stage was
exacerbated with the increase in time of 4NQO-mediated carcinogenesis induction,
and the pathological features were similar to those observed in humans.
Immunohistochemistry results revealed that B7-H4 expression was upregulated and
positively correlated with pathological stage (P < 0.0001) as well as with
infiltration of cluster of differentiation (CD) 11b(+) macrophage cells (P=0.0002).
In addition, B7-H4 messenger RNA expression increased in the esophagi of model mice
compared with that of control mice, which was positively associated with the gene
expression of interleukin (IL)-6 and signal transducer and activator of
transcription 3 (STAT3), according to the results of reverse transcription-
quantitative polymerase chain reaction analysis. Similarly, B7-H4 protein
expression was upregulated in the esophageal tissues of model mice in comparison
with that of control mice, and was positively associated with IL-6 expression and
STAT3 phosphorylation. In conclusion, the present data suggested that B7-H4
expression increased during esophageal squamous cell carcinogenesis in mice in
association with IL-6/STAT3 signaling pathway activation.
Background: Babesiosis is a socioeconomically important tick- borne disease of
animals (including humans) caused by haemoprotozoan parasites. The severity of
babesiosis relates to host and parasite factors, particularly
virulence/pathogenicity. Although Babesia bovis is a particularly pathogenic
species of cattle, there are species of Babesia of ruminants that have limited
pathogenicity. For instance, the operational taxonomic unit Babesia sp. Xinjiang
(abbreviated here as Bx) of sheep from China is substantially less
virulent/pathogenic than B. bovis is in cattle. Although the reason for this
distinctiveness is presently unknown, it is possible that Bx has a reduced ability
to adhere to cells or evade/suppress immune responses, which might relate to
particular proteins, such as the variant erythrocyte surface antigens (VESAs).
Results: We sequenced and annotated the 8.4 Mb nuclear draft genome of Bx and
compared it with those of B. bovis and B. bigemina by synteny analysis; we also
investigated the genetic relationship of Bx with selected Babesia species and
related apicomplexans for which genomic datasets are available, and explored the
VESA complement in Bx. Conclusions: The availability of the Bx genome now provides
unique opportunities to elucidate aspects of the molecular biology, biochemistry
and physiology of Bx, and to explore the reason(s) for its limited virulence and/or
apparent ability to evade immune attack by the host animal. Moreover, the present
genomic resource and an in vitro culture system for Bx raises the prospect of
establishing a functional genomic platform to explore essential genes as new
intervention targets against babesiosis.
The apicoplast (ap) is a unique, non-photosynthetic organelle found in most
apicomplexan parasites. Due to the essential roles that this organelle has, it has
been widely considered as target for drugs against diseases caused by
apicomplexans. Exploring the ap genomes of such parasites would provide a better
understanding of their systematics and their basic molecular biology for
therapeutics. However, there is limited information available on the ap genomes of
apicomplexan parasites. In the present study, the ap genomes of two operational
taxonomic units of Babesia (known as Babesia sp. Lintan [Bl] and Babesia sp.
Xinjiang [Bx]) from sheep were sequenced, assembled and annotated using a massive
parallel sequencing based approach. Then, the gene content and gene order in these
ap genomes (similar to 30.7 kb in size) were defined and compared, and the genetic
differences were assessed. In addition, a phylogenetic analysis of ap genomic data
sets was carried out to assess the relationships of these taxonomic units with
other apicomplexan parasites for which complete ap genomic data sets were publicly
available. The results showed that the ap genomes of Bl and Bx encode 59 and 57
genes, respectively, including 2 ribosomal RNA genes, 25 transfer RNA genes and 30-
32 protein-encoding genes, being similar in content to those of Babesia bovis and
B. orientalis. Ap gene regions that might serve as markers for future
epidemiological and population genetic studies of Babesia species were identified.
Using sequence data for a subset of six protein-encoding genes, a close
relationship of Bl and Bx with Babesia bovis from cattle and B. orientalis from
water buffalo was inferred. Although the focus of the present study was on Babesia,
we propose that the present sequencing-bioinformatic approach should be applicable
to organellar genomes of a wide range of apicomplexans of veterinary importance.
(C) 2016 Elsevier B.V. All rights reserved.
Baby factories are new systematic abuse structures that are promoting infant
trafficking, neo-slavery and the exploitation of young women with unwanted
pregnancies in Nigeria. Since this practice was first described in 2006, it has
been growing rather than abating. This paper reviews the scientific literature,
along with media reports, and critiques this phenomenon from a children's rights'
perspective. Children born into baby factories are denied various civil rights.
They also suffer abuse in the baby factories and as a consequence of being born in
such places. This abuse can be classified into immediate and long term. Immediate
abuse includes inadequate care and its repercussions, denial of birth registration,
illegal adoption and murder. Long-term or delayed abuse that they may be exposed to
includes health-related consequences, neglect, death, child labour, prostitution
and other sexual abuse, organ trafficking and recruitment as child soldiers.
Various factors are thought to drive the baby factory phenomenon which include
poverty, high infertility rates and the profitability of local and inter-country
adoptions. Programmes directed at addressing the root cause of the problem are
needed in order to eliminate infant trafficking. Also, clear laws that delineate
inter-country adoption and infant trafficking need to be enacted. Most importantly,
baby factories need to be recognised as child trafficking routes. Copyright (c)
2015 John Wiley & Sons, Ltd.
Baby factories and baby harvesting are relatively new terms that involve breeding,
trafficking, and abuse of infants and their biological mothers. Since it was first
described in a United Nations Educational, Scientific and Cultural Organization
report in Nigeria in 2006, several more baby factories have been discovered over
the years. Infertile women are noted to be major patrons of these baby factories
due to the stigmatization of childless couples in Southern Nigeria and issues
around cultural acceptability of surrogacy and adoption. These practices have
contributed to the growth in the industry which results in physical, psychological,
and sexual violence to the victims. Tackling baby factories will involve a
multifaceted approach that includes advocacy and enacting of legislation barring
baby factories and infant trafficking and harsh consequences for their patrons.
Also, programs to educate young girls on preventing unwanted pregnancies are
needed. Methods of improving awareness and acceptability of adoption and surrogacy
and reducing the administrative and legal bottlenecks associated with these options
for infertile couples should be explored to diminish the importance of baby
factories.
Clostridium haemolyticum causes bacillary hemoglobinuria (BH), an infectious and
usually fatal disease that occurs mostly in cattle, which is clinically
characterized by jaundice, hemoglobinuria, and anemia. The trematode Fasciola
hepatica has been commonly reported as the main predisposing factor that triggers
this condition. The authors evaluated 20 naturally occurring cases of bovine BH to
characterize the pathology and pathogenesis of the disease. Grossly, the most
consistent finding was a large, frequently single focus of necrosis surrounded by a
red to purple halo, observed most frequently on the parietal surface of the right
and left hepatic lobes. Other findings were jaundice, dark-brown discoloration of
kidneys, and red urine in the urinary bladder. Microscopically, characteristic
lesions were locally extensive, necrotizing hepatitis with thrombosis and numerous
intralesional Gram-positive rod-shaped bacteria, and acute renal tubular necrosis.
By immunohistochemistry, many hepatocytes outside the necrotic focus in the liver
were positive for activated caspase 3, suggesting that those cells were undergoing
apoptosis. Ultrastructural evaluation revealed hepatocyte necrosis, hemolysis, and
clumps of vegetative and sporulating bacilli within the liver. Polymerase chain
reaction for the C. haemolyticum beta toxin gene was positive in randomly selected
liver samples. No gross or microscopic lesions indicative of fascioliasis were
detected in the liver of any animal, suggesting that other yet undetermined
predisposing factors were associated with these cases of BH.
Deeper understanding of plant-endophyte interactions under abiotic stress would
provide new insights into phytoprotection and phytoremediation enhancement. Many
studies have investigated the positive role of plant-endophyte interactions in
providing protection to the plant against pollutant stress through auxin (indole-3-
acetic acid (IAA)) production. However, little is known about the impact of
endophytic colonization patterns on plant stress response in relation to reactive
oxygen species (ROS) and IAA levels. Moreover, the possible effect of pollutant
phase on plant stress response is poorly understood. Here, we elucidated the impact
of endophytic colonization patterns on plant stress response under airborne
formaldehyde compared to formaldehyde-contaminated soil. ROS, tryptophan and IAA
levels in the roots and shoots of endophyte-inoculated and non-inoculated plants in
the presence and absence of formaldehyde were measured. Strain-specific
quantitative polymerase chain reaction (qPCR) was used to investigate dynamics of
endophyte colonization. Under the initial exposure to airborne formaldehyde, non-
inoculated plants accumulated more tryptophan in the shoots (compared to the roots)
to synthesize IAA. However, endophyte-inoculated plants behaved differently as they
synthesized and accumulated more tryptophan in the roots and, hence, higher levels
of IM accumulation and exudation within roots which might act as a signaling
molecule to selectively recruit B. cereus ERBP. Under continuous airborne
formaldehyde stress, higher levels of ROS accumulation in the shoots pushed the
plant to synthesize more tryptophan and IAA in the shoots (compared to the roots).
Higher levels of IAA in the shoots might act as the potent driving force to
relocalize B. cereus ERBP from roots to the shoots. In contrast, under
formaldehyde-contaminated soil, B. cereus ERBP colonized root tissues without
moving to the shoots since there was a sharp increase in ROS, tryptophan and IAA
levels of the roots without any significant increase in the shoots. Pollutant phase
affected endophytic colonization patterns and plant stress responses differently.
(C) 2017 Elsevier Masson SAS. All rights reserved.
To isolate and identify DNA-binding protein(s) with affinity for the mobile
chromosomal repeat element bcr1 in Bacillus cereus group bacteria. A biotinylated
bcr1 element was immobilized to streptavidin-coated magnetic beads and used to pull
out a 20 kDa DNA-binding protein from a whole cell protein extract of B. cereus
ATCC 14579. The protein was identified as the product of ORF 2 encoded by the
bacteriophage-related autonomously replicating linear genetic element pBClin15
carried by the strain. DNA binding was not bcr1-specific. By Northern blotting ORF
2 was co-transcribed with ORF 1, and also in certain instances with ORF 3 by
transcriptional readthrough of the terminator located between ORF 2 and ORF 3. ORF
2 from pBClin15 encodes a DNA-binding protein. ORF 2 is co-transcribed with its
upstream gene ORF 1, and in a subset of the transcripts also with the downstream
gene ORF 3 through alternative transcription termination. The B. cereus group
contains bacterial species of medical and economic importance. Bacteriophages or
phage-encoded proteins from these bacteria have been suggested as potential
therapeutic agents. Understanding the biology of bacteriophage-related genetic
elements through functional characterization of their genes is of high relevance.
Effects of reactive oxygen species (ROS) on cell growth and poly(-glutamic acid) (-
PGA) synthesis were studied by adding hydrogen peroxide to a medium of Bacillus
subtilis NX-2. After optimizing the addition concentration and time of H2O2, a
maximum concentration of 33.9g/L -PGA was obtained by adding 100 mu M H2O2 to the
medium after 24H. This concentration was 20.6% higher than that of the control. The
addition of diphenyleneiodonium chloride (ROS inhibitor) can interdict the effect
of H2O2-induced ROS. Transcriptional levels of the cofactors and relevant genes
were also determined under ROS stress to illustrate the possible metabolic
mechanism contributing to the improve -PGA production. The transcriptional levels
of genes belonging to the tricarboxylic acid cycle and electron transfer chain
system were significantly increased by ROS, which decreased the NADH/NAD(+) ratio
and increased the ATP levels, thereby providing more reducing power and energy for
-PGA biosynthesis. The enhanced -PGA synthetic genes also directly promoted the
formation of -PGA. This study was the first to use the ROS control strategy for -
PGA fermentation and provided valuable information on the possible mechanism by
which ROS regulated -PGA biosynthesis in B. subtilis NX-2. (C) 2015 International
Union of Biochemistry and Molecular Biology, Inc.
Many food and feed additives result from fermentation of genetically modified (GM)
microorganisms. For vitamin B2 (riboflavin), GM Bacillus subtilis production
strains have been developed and are often used. The presence of neither the GM
strain nor its recombinant DNA is allowed for fermentation products placed on the
EU market as food or feed additive. A vitamin B2 product (80% feed grade) imported
from China was analysed. Viable B. subtilis cells were identified and DNAs of two
bacterial isolates (LHL and LGL) were subjected to three whole genome sequencing
(WGS) runs with different devices (MiSeq, 454 or HiSeq system). WGS data revealed
the integration of a chloramphenicol resistance gene, the deletion of the
endogenous riboflavin (rib) operon and presence of four putative plasmids
harbouring rib operons. Event- and construct-specific real-time PCR methods for
detection of the GM strain and its putative plasmids in food and feed products have
been developed. (C) 2017 The Authors. Published by Elsevier Ltd.
To explore the influence of the direct repeat sequence (DRS) in Bacillus chitinase
genes on heterogonous expression in Escherichia coli, we cloned and sequenced the
entire open reading frame (ORF) and upstream sequences of the chitinase B (chiB)
and chitinase MY75 (chiMY75) from Bacillus thuringiensis and Bacillus
licheniformis. A pair of 8-bp DRS was found upstream of each chi gene. Chi ORFs
with a series of truncated DRS were cloned and transformed into E. coli XL-Blue.
The activity of the transformants without the DRS were significantly higher in
chitinase assays than transformants containing the DRS. SOS-PAGE showed that part
and full deletion of the DRS increased chi gene expression by approximately 1.7 and
3.8-fold, respectively. Northern blotting revealed deletion of the DRS regions
increased chiB and chiMY75 mRNA expression. Specific binding of DNA-binding factors
in the E. coli cell lyaste was observed to both the chiB and chiMY75 promoter
regions and DRS elements. This is the first investigation to demonstrate that
heterologous expression of Bacillus chi genes in E. coli is negatively regulated by
their upstream DRS regions, which act as cis-acting elements. (C) 2012 Elsevier
Inc. All rights reserved.
In recent years, model predictive control (MPC) has been successfully used for the
control of power electronics converters with different topologies and for different
applications. MPC offers many advantages over more traditional control techniques
such as the ability to avoid cascaded control loops, easy inclusion of constraint,
and fast transient response. On the other hand, the controller computational burden
increases exponentially with the system complexity and may result in an unfeasible
realization on modern digital control boards. This paper proposes a novel
distributed MPC (DMPC), which is able to achieve the same performance of the
classical MPC while reducing the computational requirements of its implementation.
The proposed control approach is tested on a ac/ac converter in a back-to-back
configuration used for power flow management. Simulation results are provided and
validated through experimental testing in several operating conditions.
This work presents a fully FPGA based deadbeat-like predictive control scheme for
back-to-back converter PMSG wind turbine systems with space vector modulator (SVM).
A deadbeat-like predictive torque/current controller is used to control the machine
side converter, while a deadbeat power control method in alpha beta frame is used
to control the grid side converter. Both sides achieve nice steady state
performances requiring few tuning efforts. Both the machine and grid side
predictive controllers are realized on a commercial-off-the-shelf FPGA based
platform. By using a single-cycle-timed-loop (SCTL) technique, the whole
computation time is quite short (less than 4 mu s), which makes the calculation
time compensation not required. The effectiveness of the presented method is
verified through experimental data.
The use of power converters has considerably grown up, in part, because refined
control strategies have been recently proposed, including nonlinear schemes such as
predictive control. This approach is used in this work considering a variable grid
frequency environment in order to get an appropriate response for a wide ac mains
frequency range. Indeed, in order to achieve appropriate, both dynamic and static,
responses for all operating frequencies, the number of samples per period is kept
constant and independent of the ac mains frequency. This allows a fixed resolution
of the sensed voltages and/or currents, which is preferable if high-performance
digital control schemes are required. However, imposing a constant number of
samples per period requires a variable sampling time in systems that feature
variable ac mains frequency. On the other hand, predictive control has been
developed and well documented just for a constant sampling frequency. This work
presents how to extend the predictive control algorithms for variable sampling time
allowing high-performance waveforms and wider ac mains frequency range. Simulated
and experimental results show the feasibility of the proposed control strategy
which corroborates the mathematical and model analysis.
This paper presents a three-phase back-to-back transformerless inverter for online
uninterruptible power supply applications. The inverter consists of a three-phase
three-wire input rectifier stage and a three-phase four-wire output inverter stage
with their ground wires tied together. Both of the two stages are with sinusoidal
pulse width modulation based division-summation (D-Sigma) digital control. The
input stage controls the power flow between utility grid and dc link, regulates the
dc-link voltage, and fulfills power factor correction. While the output stage
tracks three-phase ac reference voltages. The proposed control laws derived based
on the D-Sigma digital approach take into account the effects of dc-link voltage
fluctuation, grid-voltage distortion, and inductance variation due to different
current levels. Thus, distortion of input current and output voltage, and filter
inductor core size can be reduced significantly. Moreover, circulating current
through their common ground can be suppressed effectively. Simulated and
experimental results from a three-phase back-to-back transformerless inverter have
confirmed the analysis and discussion of the proposed control approach.
The aim of this study was to evaluate the occurrence of Toxoplasma gondii in
backyard pigs destined for human consumption in Pernambuco state, Brazil. Blood and
tissue samples (liver, heart, brain, lung and diaphragm) were collected from 224
pigs from legal slaughterhouses and tested for T. gondii infection. Antibodies to
T. gondii were found in the sera of 37.9% (85/224) by using the immunofluorescence
antibody test (cut-off -1: 64). Tissue samples from seropositive pigs were
bioassayed in mice. Tissue samples from seropositive pigs and from mice of the
bioassay were submitted to histopathology, immunohistochemistry, polymerase chain
reaction (PCR) and sequencing; 14.1% of pig tissue samples and 27.7% of bioassayed
mouse samples were positive for T. gondii DNA, but all pig and mouse tissues were
negative in histopathology analysis and immunochemistry. By using a risk assessment
questionnaire, there was significant difference (p< 0.001) in seroprevalence of
21.2% (reproducer) and 3.1% (finishing pig). These data serve as indicative of the
sanitary conditions and risk of T. gondii infection for backyard pigs. Preventive
measures must be implemented by health services to avoid toxoplasmosis human cases
due to ingestion of pig meat.
Waterborne diseases have emerged as global health problems and their rapid and
sensitive detection in environmental water samples is of great importance.
Bacterial identification and enumeration in water samples is significant as it
helps to maintain safe drinking water for public consumption. Culture-based methods
are laborious, time-consuming, and yield false-positive results, whereas viable but
nonculturable (VBNCs) microorganisms cannot be recovered. Hence, numerous methods
have been developed for rapid detection and quantification of waterborne pathogenic
bacteria in water. These rapid methods can be classified into nucleic acid-based,
immunology-based, and biosensor-based detection methods. This review summarizes the
principle and current state of rapid methods for the monitoring and detection of
waterborne bacterial pathogens. Rapid methods outlined are polymerase chain
reaction (PCR), digital droplet PCR, real-time PCR, multiplex PCR, DNA microarray,
Next-generation sequencing (pyrosequencing, Illumina technology and genomics), and
fluorescence in situ hybridization that are categorized as nucleic acid-based
methods. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are
classified into immunology-based methods. Optical, electrochemical, and mass-based
biosensors are grouped into biosensor-based methods. Overall, these methods are
sensitive, specific, time-effective, and important in prevention and diagnosis of
waterborne bacterial diseases.
A repetitive sequence-based (rep)-polymerase chain reaction (PCR) and inter-simple
sequence repeat (ISSR)-PCR were used to molecular type Pseudomonas syringae pv.
syringae (PSS) strains isolated from barley and wheat plants with bacterial black
node symptoms grown in 22 different locations and six different seed-production
districts in Japan. Eighteen genomic fingerprinting (GF) genotypes were obtained
from the combined results of BOX-, REP-, and GTG(5)-PCR, indicating that the PSS
population in Japan has high genetic diversity. The result based on logistic
regression indicated that the population of GF genotype A was significantly related
to a seed-producing district and that the epidemic of PSS strains in fields
originated mainly from seed infection. This study will be applicable to future
studies of the molecular epidemiology of bacterial plant diseases that have
multiple infection routes.
The objective of this study was to assess the effect of dietary probiotics on rumen
fermentation and the bacterial community in dairy calves. Twelve Holstein calves
were randomly allocated to three treatments: a basal diet, the basal diet
supplemented with Lactobacillus plantarum GF103 (LB) or basal diet supplemented
with a mixture of Lactobacillus plantarum GF103 and Bacillus subtilis B27 (LBS). A
milk replacer was fed to calves from 8days of age. A starter and alfalfa hay was
offered ad libitum from 21 and 28days of age, respectively, and the orts were
weighted daily. The ruminal fluid was sampled at 56 and 83days of age to determine
the rumen fermentation characteristics. The bacterial community was analyzed by
denaturing gradient gel electrophoresis (DGGE) and the number of certain bacteria
was quantified by real-time polymerase chain reaction. The ratio of total dry
matter intake to average body wieght was higher in the control (P<0.05). The DGGE
fingerprint of the 16S ribosomal RNA gene was affected by the blended probiotics at
83days of age. The number of Ruminococcus albus was lower in the LB and LBS
treatment (P<0.05). Oral administration of the probiotics affected the rumen
bacterial community and the numbers of cellulolytic bacteria decreased.
To determine the effect of oxytetracycline on the anaerobic biological treatment of
livestock wastewater, we studied the removal efficiency of chemical oxygen demand
(determined by K2Cr2O7, CODCr), methane production, and bacterial diversity under
the stress of different concentrations of oxytetracycline. Results indicated that
the removal of COD and the yield of methane were inhibited by oxytetracycline. With
an increase in oxytetracycline concentration, methane production decreased from 392
to 207mL (the control group was 448 mL) and COD removal efficiency fell from 92% to
84% (the control group was 94%). Results of PCRDGGE (polymerase chain reaction and
denaturing gradient gel electrophoresis) indicated that, with an increase in
oxytetracycline concentration, the richness values of the bacterial community fell
from 0.86 to 0.45 (the control group was 1). In addition, oxytetracycline reduced
COD removal efficiency, methane production, and bacterial diversity in livestock
wastewater. Results presented in this study provide important information about
bacterial diversity in livestock wastewater treated using oxytetracycline.
Watermelon (Citrullus lanatus) is an important crop of the Cucurbitaceae family in
fruit production worldwide. During its production, bacterial fruit blotch (BFB)
caused by Acidovorax citrulli (Acidovorax avenae subsp. citrulli) is an important
limiting factor on the volume and value of crops. This pathogen is known as a seed-
borne pathogen, and the infested seeds can be a primary source of inoculum. Hence,
a rapid and sensitive method for detecting A. citrulli on seeds would be an
important tool in the management of BFB. In this study, we sought to develop a
method to detect A. citrulli bacterial cells based on a TaqMan probe-based
insulated isothermal PCR (TiiPCR) assay. Firstly, the specific primers and probe
were designed based on a specific DNA fragment from the genome of A. citrulli.
Then, PCR amplification was performed with the plasmid DNA to adjust the components
of the PCR reagents, such as the concentrations of primers, magnesium chloride, and
Taq DNA polymerase. Results revealed that 10 copies of plasmid DNA were detectable
within the modified reagents by TiiPCR. Moreover, 10 bacterial cells in each
reaction tube were detectable at a 100 % detection rate in this condition with a
fluorescent signal intensification over 1.8. Based on these results, we concluded
that a specific, rapid, and sensitive method based on TiiPCR had been successfully
developed to detect bacterial cells of A. citrulli.
The targeting of bacterial type III secretion systems (T3SSs), which are critical
virulence factors in most Gram-negative pathogens, is regarded as an alternative
strategy for the development of novel anti-microbial drugs. Xanthomonas oryzae pv.
oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc) are two of the most important
bacterial pathogens on rice, which cause leaf blight and leaf streak diseases,
respectively. To identify potential anti-virulence drugs against these two
pathogens, we screened a library of plant phenolic compounds and derivatives for
their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the
promoter activity of a harpin gene, hpa1. These inhibitors were further tested for
their impact on the hypersensitive response (HR) caused by Xoo on non-host tobacco
plants. The results showed that pretreatment of Xoo with TS006 (o-coumaric acid,
OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without
affecting bacterial growth or survival. In addition, Cya translocation assays
demonstrated that the translocation of two T3 effectors was suppressed by the four
inhibitors. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
analysis showed that mRNA levels of representative genes in the hrp (hypersensitive
response and pathogenicity) cluster, as well as the regulatory genes hrpG and hrpX,
were reduced by treatment with the four inhibitors, suggesting that expression of
the Xoo T3SS was suppressed. The expression of other virulence factors was not
suppressed, which indicated possible T3SS-specific inhibition. Finally, we
demonstrated that these inhibitors reduced the disease symptoms of Xoo and Xoc on
the rice cultivar (Oryza sativa) IR24 to varying extents.
Objective. -To determine if bacterial vaginosis is a marker for risk of spontaneous
preterm delivery and if its detection and treatment can reduce this risk. Methods.
-Consultation of the database Pubmed/Medline, Science Direct, and international
guidelines of medical societies. Results. -Bacterial vaginosis (BV) is a dysbiosis
resulting in an imbalance in the vaginal flora through the multiplication of
anaerobic bacteria and jointly of a disappearance of well-known protective
Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain
with establishment of the Nugent score. The prevalence of the BV extraordinarily
varies according to ethnic and/or geographical origin (4-58 %), in France, it is
close to 7 % in the first trimester of pregnancy (EL2). The link between BV and
spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the
most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV
(EL3). It is recommended to prescribe one of these antibiotics in the case of
symptomatic BV (Professional Consensus). The testing associated with the treatment
of BV in the global population showed no benefit in the prevention of the risk of
spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population
(defined by the absence of antecedent of premature delivery), it has been failed
profit to track and treat the BV in the prevention of the risk of spontaneous
preterm delivery (ELI). Concerning the high-risk population (defined by a history
of preterm delivery), it has been failed profit to track and treat the VB in the
prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub
population of patients with a history of preterm delivery occurred in a context of
materno-fetal bacterial infection, there may be a benefit to detect and treat early
and systematically genital infection, and in particular the BV (Professional
Consensus). Conclusion. -The screening and treatment of BV during pregnancy in
asymptomatic low-risk population is not recommended in the prevention of the risk
of spontaneous preterm delivery (grade A): In the population at high risk with the
only notion of antecedent of premature delivery, screening and treatment of the BY
is not recommended (grade C). (C) 2016 Elsevier Mason SAS.
In 2016, the British Journal of Biomedical Science published 36 reports outlining
specific advances in each of the various disciplines within biomedical science.
These were one review, 25 original articles, 9 'In Brief' reports and one letter to
the Editor. Of these, the majority were in blood science (5 in biochemistry, 7 in
haematology and 2 in immunology) and infection science (8 in microbiology, 2 in
virology) with a smaller number in cellular sciences (6 in cellular pathology and 2
in cytopathology). Three reports considered both biochemistry and immunology, while
another reported an advance in the identification of chromosomal abnormalities. The
present report will summarise key aspects of these publications that are of
greatest relevance to laboratory scientists.
The Dutch microbiologist/biochemist Albert Jan Kluyver (1888-1956) was an early
proponent of the idea of biochemical unity, and how that concept might be
demonstrated through the careful study of microbial life. The fundamental
relatedness of living systems is an obvious correlate of the theory of evolution,
and modern attempts to construct phylogenetic schemes support this relatedness
through comparison of genomes. The approach of Kluyver and his scientific
descendants predated the tools of modern molecular biology by decades. Kluyver
himself is poorly recognized today, yet his influence at the time was profound.
Through lens of today however, it has been argued that the focus by Kluyver and
others to create taxonomic and phylogenetic schemes using morphology and
biochemistry distorted and hindered progress of the discipline of microbiology,
because of a perception that the older approaches focused too much on a
reductionist worldview. This essay argues that in contrast the careful
characterization of fundamental microbial metabolism and physiology by Kluyver made
many of the advances of the latter part of the twentieth century possible, by
offering a framework which in many respects anticipated our current view of
phylogeny, and by directly and indirectly training a generation of scientists who
became leaders in the explosive growth of biotechnology.
In this article we compare the efficacy of different pharmacological agents
( ranitidine, and omeprazole) to support phage transit from stomach to distal
portions of the gastrointestinal tract in rats. We show that a temporal
modification of environment in the animal stomach may protect Twort-like
therapeutic antistaphylococcal phage A5/80 ( from bacteriophage collection of the
Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland)
from the inactivation by gastric juice effectively enough to enable a significant
fraction of orally administered A5/80 to pass to the intestine. Interestingly, we
found that yogurt may be a relatively strong in enhancing phage transit. Given the
immunomodulating activities of phages our data may suggest that phages and yogurt
can act synergistically in mediating their probiotic activities and enhancing the
effectiveness of oral phage therapy. We also demonstrate that orally applied phages
of similar size, morphology, and sensitivity to acidic environment may differ in
their translocation into the bloodstream. This was evident in mice in which a
therapeutic staphylococcal phage A5/80 reached the blood upon oral administration
combined with antacid agent whilst T4 phage was not detected even when applied in
103 times higher dose. Our findings also suggest that phage penetration from
digestive tract to the blood may be species-specific.
The Poisson distribution played a key role in experiments that had a historic role
in the development of molecular biology. In particular, the interpretation and
design of experiments elucidating the actions of bacteriophages and their host
bacteria during the infection process were based on the parameters of the Poisson
distribution. I briefly review three of the most important of these experiments and
offer suggestions on the use of the Poisson distribution in statistical
calculations in biology laboratory exercises reflecting the use of the Poisson
distribution in current biological investigations.
His-Asn-His (HNH) proteins are a very common family of small nucleic acid-binding
proteins that are generally associated with endonuclease activity and are found in
all kingdoms of life. Although HNH endonucleases from mesophiles have been widely
investigated, the biochemical functions of HNH endonucleases from thermophilic
bacteriophages remain unknown. Here, we characterized the biochemical properties of
a thermostable HNH endonuclease from deep-sea thermophilic bacteriophage GVE2. The
recombinant GVE2 HNH endonuclease exhibited non-specific cleavage activity at high
temperature. The optimal temperature of the GVE2 HNH endonuclease for cleaving DNA
was 60-65 A degrees C, and the enzyme retained its DNA cleavage activity even after
heating at 100 A degrees C for 30 min, suggesting the enzyme is a thermostable
endonuclease. The GVE2 HNH endonuclease cleaved DNA over a wide pH spectrum,
ranging from 5.5 to 9.0, and the optimal pH for the enzyme activity was 8.0-9.0.
Furthermore, the GVE2 HNH endonuclease activity was dependent on a divalent metal
ion. While the enzyme is inactive in the presence of Cu2+, the GVE2 HNH
endonuclease displayed cleavage activity of varied efficiency with Mn2+, Mg2+,
Ca2+, Fe2+, Co2+, Zn2+, and Ni2+. The GVE2 HNH endonuclease activity was inhibited
by NaCl. This study provides the basis for determining the role of this
endonuclease in life cycle of the bacteriophage GVE2 and suggests the potential
application of the enzyme in molecular biology and biotechnology.
Bacteriophages represent a simple viral model of basic research with many
possibilities for practical application. Due to their ability to infect and kill
bacteria, their potential in the treatment of bacterial infection has been examined
since their discovery. With advances in molecular biology and gene engineering, the
phage application spectrum has been expanded to various medical and
biotechnological fields. The construction of bacteriophages with an extended host
range or longer viability in the mammalian bloodstream enhances their potential as
an alternative to conventional antibiotic treatment. Insertion of active
depolymerase genes to their genomes can enforce the biofilm disposal. They can also
be engineered to transfer various compounds to the eukaryotic organisms and the
bacterial culture, applicable for the vaccine, drug or gene delivery. Phage
recombinant lytic enzymes can be applied as enzybiotics in medicine as well as in
biotechnology for pathogen detection or programmed cell death in bacterial
expression strains. Besides, modified bacteriophages with high specificity can be
applied as bioprobes in detection tools to estimate the presence of pathogens in
food industry, or utilized in the control of food-borne pathogens as part of the
constructed phage-based biosorbents.
Secretory immunoglobulin A (SIgA) antibody-secreting cells (ASCs) are the major
effector cells of mucosal immunity, and immunoglobulin G (IgG) ASCs are also
associated with mucosal immunity. This study aimed to explore the distribution of
these 2 ASC populations in the palatine tonsils of Bactrian camels of different
ages. Eighteen Bactrian camels were divided into the following three age groups:
pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). SIgA and IgG
ASCs within different sites of the palatine tonsils were observed through
histological and immunohistochemical techniques, and their densities were analyzed
using statistical methods. The results from all age groups showed that both the
SIgA and IgG ASCs were primarily distributed in the subepithelial compartments of
the reticulated crypt epithelium and secondarily distributed in the subepithelial
compartments of the stratified surface squamous epithelium, with a few ASCs located
in the extrafollicular region. Their densities in these three areas were
significantly decreased in turn (P<0.05). However, the densities of SIgA ASCs were
significantly higher than IgG ASCs in the same regions (P<0.05), and the densities
of both ASC populations decreased with age. The results confirmed that Bactrian
camel palatine tonsils are the primary mucosal immune organ producing SIgA ASCs,
and the subepithelial compartment of the reticulated crypt epithelium is the
primary region for the colonization and functional activity of SIgA and IgG ASCs.
In the present study, we reveal for the first time that the Bactrocera oleae
chorion peroxidase (bPxd) participates essentially in B. oleaechorion formation and
clearly represents the homologous member of Drosophila melanogaster chorion
peroxidase (Pxd). Comparative sequence analysis disclosed that the bPxd cDNA semi-
central region,which encodes for the putative catalytic domain of the enzyme,
exhibits great homology (98%) with its Pxd counterpart. Thus, it is very likely
that bPxd is highly responsible for the chorion hardening process, through protein
cross-linking mediated by the formation of di- and tri-tyrosine bonds. Distinct
molecular weight bPxd RNA transcripts were detected in Northern blotting analysis
of total RNA extracts of adult flies (2.9 and 1.7 kb) and ovaries (2.2 kb). The
ovarian-specific bPxd RNA transcript is selectively expressed in the follicle cell
layer during the late stages of oogenesis 12-14, as revealed by in situ
hybridization. Moreover, reverse transcription reactions confirmed the stage-
specific developmental regulation of the bPxd gene, which is maximally expressed
during stage 13. Western blotting with the rabbit anti-rAePO polyclonal antibody
revealed three immunoreactive bands of 76, 66 and 54 kDa in crude protein extracts
from adult flies, while in larva and purified chorion preparations, a unique 54 kDa
band was clearly detected. Immunolocalization experiments revealed that bPxd
peroxidase constitutes an essential structural chorionic component, being
abundantly localized in all the successive chorionic layers and vitelline membrane
as well.
The genus Potexvirus is one of the eight genera belonging to the family
Alphaflexiviridae according to the Virus Taxonomy 2015 released by International
Committee on Taxonomy of Viruses (www. ictvonline. org/index. asp). Currently, the
genus contains 35 known species including many agricultural important viruses,
e.g., Potato virus X (PVX). Members of this genus are characterized by flexuous,
filamentous virions of 13 nm in diameter and 470-580 nm in length. A potexvirus has
a monopartite positive-strand RNA genome, encoding five open-reading frames (ORFs),
with a cap structure at the 5 0 end and a poly(A) tail at the 3 0 end. Besides PVX,
Bamboo mosaic virus (BaMV) is another potexvirus that has received intensive
attention due to the wealth of knowledge on the molecular biology of the virus. In
this review, we discuss the enzymatic activities associated with each of the
functional domains of the BaMV replication protein, a 155kDa polypeptide encoded by
ORF1. The unique cap formation mechanism, which may be conserved across the
alphavirus superfamily, is particularly addressed. The recently identified
interactions between the replication protein and the plant host factors are also
described.
We constructed a SSH (suppression subtractive hybridization) library based on two
populations (Rs-C and Rs-P) of Radopholus similis from different host plants and
exhibiting differences in pathogenicity on Musa paradisiaca and Anthurium
andraeanum plants. In order to screen the clones with significant expression
differences from the SSH library, a total of 2,400 clones was randomly selected and
reverse northern blotting was performed on them. Out of the 2,400 clones, 89 clones
showed significant expression differences. Out of sequencing these 89 clones,
distinct sequences from 87 clones were obtained. Aligning the 87 distinct sequences
against the non-redundant nucleotide database (nr) in NCBI, we found that five
sequences were highly conserved with Rs-eng-1b. Two of five sequences with lengths
of 467 base pairs (bp) (GW395922) and 742 bp (GW395923) were further employed to
perform 5' RACE-PCR and 3' RACE-PCR, respectively. Subsequently, the complete
length of Rs-eng-1b (EU414839) was obtained (1,427 bp). Our qPCR result showed that
expression of Rs-eng-1b in the population Rs-C with high pathogenicity on host
plants was approximately 2.7 times as much as the expression of Rs-eng-1b in the
population Rs-P with low pathogenicity on host plants. Furthermore, the gene Rs-
eng-1b from the Rs-C population also showed expression differences amongst four
different development stages. The order of Rs-eng-1b relative expression abundance
from high to low was females, juveniles, males, and eggs. We further used RNAi to
test whether Rs-eng-1b of Rs-C population was responsible for pathogenicity which
was the first RNAi work about Rs-eng-1b. The RNAi results showed that Rs-eng-1b
expression had a positive correlation to pathogenicity of the population. The
longer the RNAi treatment, the less pathogenic the nematode population was. Non-
endogenous gfp dsRNA had no significant influence on the expression of Rs-eng-1b
and pathogenicity of R. similis Rs-C population. In conclusion, all our evidence
indicated Rs-eng-1b might be a crucial pathogenicity-related gene in R. similis.
Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is among the most
destructive diseases of banana (Musa spp.). Because no credible control measures
are available, development of resistant cultivars through genetic engineering is
the only option. We investigated whether intron hairpin RNA (ihpRNA)-mediated
expression of small interfering RNAs (siRNAs) targeted against vital fungal genes
(velvet and Fusarium transcription factor 1) in transgenic banana could achieve
effective resistance against Foc. Partial sequences of these two genes were
assembled as ihpRNAs in suitable binary vectors (ihpRNA-VEL and ihpRNA-FTF1) and
transformed into embryogenic cell suspensions of banana cv. Rasthali by
Agrobacterium-mediated genetic transformation. Eleven transformed lines derived
from ihpRNA-VEL and twelve lines derived from ihpRNA-FTF1 were found to be free of
external and internal symptoms of Foc after 6-week-long greenhouse bioassays. The
five selected transgenic lines for each construct continued to resist Foc at 8
months postinoculation. Presence of specific siRNAs derived from the two ihpRNAs in
transgenic banana plants was confirmed by Northern blotting and Illumina sequencing
of small RNAs derived from the transgenic banana plants. The present study
represents an important effort in proving that host-induced post-transcriptional
ihpRNA-mediated gene silencing of vital fungal genes can confer efficient
resistance against debilitating pathogens in crop plants.
A low-voltage bandgap reference implemented in 0.18 mu m CMOS process is designed.
The bandgap reference circuit is optimized by adjusting the ratio of the resistors,
and reducing the working voltage of operational amplifier. It achieves the
performance of a temperature coefficient of 25 ppm/degrees C in the range of 0
similar to 100 degrees C which works under the voltage of 0.8V. The simulated power
supply rejection ratio is 46.3dB @1Hz and the line regulation is 1.5mV/V in the
range from 0.8V to 1.8V.
This article designed a bandgap voltage reference source with a low temperature
drift, high power supply rejection ratio for the TCXO chips, and design the
sensitive reaction of thermal protection circuit is used to protect TCXO chips. The
structure of self-biased current source and differential operational amplifier is
used in the bandgap reference, And the over temperature protection circuit
controlled oscillator on or off by a NPN transistor to detection the circuit
current. The simulation results show that the range of the voltage output is not
more than 0.78 mV when the temperature changes at -40 to 125, The power supply
rejection ratio in the circuit is as high as 95dB; the oscillator is turned off
When the temperature is greater than 150 degrees, and it's restart when the
temperature is less than 130 degrees, and it turn off needs less than 0.071 S,
restart needs less than 0.064 S. The circuit can provide a stable reference and
good temperature protection effect, which has great practical value for the TCXO
chip.
This paper presents a new curvature-compensated CMOS bandgap reference topology
with a high power supply reject ratio (PSRR). A dual-differential input amplifier
(DDIA) is used to generate a complementary to absolute temperature voltage. This
voltage and the DDIA are then used to fine-tune its curvature compensation.
Experimental characterization of the bandgap reference circuit implemented on a 0.5
A mu m CMOS process yielded a bandgap reference voltage with a temperature
coefficient (TC) of 4.1 ppm/A degrees C across the temperature range of -40 to 125
A degrees C. A PSRR of 82 dB was also realized with a high output load current
driving ability without the use of an external buffer amplifier.
This paper proposes a new CMOS based Bandgap voltage reference generator (BGR)
circuit by using polysilicon resistors in 32nm CMOS technology. This reference
generator uses a three stage operational amplifier for improved performance over
previously proposed BGR circuits. The proposed design is simulated in Synopsys
HSPICE simulator. This circuit produces an output reference voltage of 0.725V at
the room temperature (25 degrees C) for the supply voltage of 1.8V. Analysis shows
that, a very low temperature coefficient (TC) of 13ppm/degrees C is obtained in the
output reference voltage for the temperature range of-40 degrees C to 100 degrees
C. Using poly-silicon resistor the area is reduced, without losing too much control
over current consumption.
This paper presents a novel low power bandgap reference circuit, the bandgap
reference adopts half a period working mechanism. The operational amplifier doesn't
work during the switched capacitor network sampling. And the operational amplifier
works after the charge balanced. The bandgap reference runs discontinuously. The
design implements in standard 0.18um CMOS process. The simulation result shows
that, the circuit consumes 19.8 uAat 3.3V. The noise of the circuit in low
frequency achieves 3.9 mu V/root Hz and the temperature coefficient is 21
ppm/degrees C.
Grid voltage feedforward is extensively used for controlling grid-connected
converters. However, the conventional voltage feedforward control reduces the
stability margins of the converter connected to a high-impedance grid. The effect
mechanism of voltage feedforward on the grid-connected converter control under
high-inductive conditions of the grid impedance is clearly explained in this study
using the equivalent transformations of control block diagrams. Results show that
the delay produced by the digital control is the root cause of this effect. An
improved voltage feedforward strategy, in which a bandpass filter (BPF) is
introduced into the feedforward path, is proposed to strengthen the converter's
robust stability against grid impedance variations. The selection method of the
BPF's bandwidth is also provided considering the tradeoff between the response
speed to the grid voltage sag and the system's robust stability. The converter can
work stably over a wide range of the grid impedance through the proposed approach.
Simulation and experimental results fully verify the effectiveness of the BPF-based
voltage feedforward strategy.
In this paper a DVCC based operational amplifier has been proposed. A pole has been
introduced in transfer characteristic of DVCC by an integrated capacitor. The op
amp is composed of an on chip DVCC, one integrated NMOS resistor, a capacitor and a
CMOS voltage follower. The bandwidth of DVCC op amp can be adjusted by voltage
tuning of the resistor. Conventional voltage mode operational amplifiers suffer
from introduction of second pole at high frequencies, thus rendering the circuits
suitable for low frequency applications only. The proposed DVCC op amp has large
signal bandwidth and can operate for wide range of frequencies. A bandpass filter
has been tested using the reported op amp in PSPICE and theoretical analysis has
been presented.
A low component sensitivity band-pass filter has been proposed. The filter has only
one operational amplifier as active component and three resistors and one grounded
capacitor as passive components. Two resistors provide the positive feedback and
one resistor is used for independent tuning of Q factor. The capacitor is grounded
which is an advantage in integrated technology. The circuit uses the pole frequency
of the operational amplifier for its working and can be operated at high frequency
range. PSpice simulations have been presented to verify theoretical analysis.
This paper presents the design and characterization of a fully-differential
intermediate frequency (IF) filter based on an operational transconductance
amplifier (OTA) with 6th order Butterworth bandpass characteristic. The designed 2-
stage BiCMOS OTA can be treated as an operational amplifier (OPAmp) together with
its output resistance. The combination exhibits an open-loop voltage gain of 75 dB
and high gainbandwidth product (GBP) of 5.8 GHz, while stability is achieved with a
worst case phase margin (PM) of 54 degrees from a low bias-current of only 520 mu
A. The multiple-feedback filter (MFB) elements for the target Butterworth frequency
response are determined with circuit analysis based on an ideal OTA transfer
function. The filter center frequency is set to 60 MHz, whereby a measured -3 dB-
bandwidth of 15.5MHz is achieved. To enable the operation within an on-time of 200
ns the filter is able to settle at +/- 1 dB of its steady state amplitude in less
than 115 ns. The filter was fabricated in the IHP 130nm BiCMOS technology and
requires a current of only 1.6mA from a 2.5V-supply including all bias circuits.
Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in
traditional Chinese medicine, is widely distributed in South China, especially in
Fujian. Recent studies about B. cusia mainly focus on its chemical composition and
pharmacological effects, but further analysis of the plant's gene functions and
expression is required to better understand the synthesis of its effective
compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful
method for gene expression analysis. It is necessary to select a suitable reference
gene for expression normalization to ensure the accuracy of RT-qPCR results. Ten
candidate reference genes were selected from the transcriptome datasets of B. cusia
in this study, and the expression stability was assessed across 60 samples
representing different tissues and organs under various conditions, including
ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and
abscisic acid), and in different plant organs. By employing different algorithms,
such as geNorm, NormFinder, and BestKeeper, which are complementary approaches
based on different statistical procedures, 18S rRNA was found to be the most stable
gene under UV irradiation and hormonal stimuli, whereas ubiquitin-conjugating
enzyme E2 was the best suitable gene for different plant organs. This novel study
aimed to screen for suitable reference genes and corresponding primer pairs
specifically designed for gene expression studies in B. cusia, in particular for
RT-qPCR analyses.
This study had the aim to identify and relat the occurrence of billfish larvae and
eggs in the Southeastern coast of Brazil. During the summer in two seasons
(2012/2013 and 2013/2014) 74 surface trawls were done using an ichthyoplankton net
off the coast of Vitoria-ES, Rio de Janeiro-RJ and Ilhabela-SP and 391 fish larvae
were collected. The identification of the billfish larvae was done by molecular
biology using the DNA barcode (COI gene). During the 2012/2013 season, five
sailfish and two white marlin larvae were identified and in the 2013/2014 season,
two sailfishes, two white marlin larvae and two swordfish eggs were identified. The
occurrence of billfish larvae shall be further studied, so that inferences about
the area and period of spawning and development of early life stages of these fish
can be made more accurately.
This article has three aims. First, it reacts to the doubts expressed recently
about the possibility of making generalizations about Catholicism after the Council
of Trent. Second, it discusses the different uses of the term "Catholic
Reformation" and proposes a definition that involves a movement toward the
universalization of divine love. And third, it also discusses the success of
confessionalization in some parts of Europe and the reasons why it was not a top-
down process. The emphasis on disciplining endeavors in the analysis of the history
of confessionalization misses the integrative character of various devotional
practices in Baroque Europe and fails to pay sufficient attention to the religious
constraints affecting political actors.
Functional genomic screening of the rat enamel organ (EO) has led to the
identification of a number of secreted proteins expressed during the maturation
stage of amelogenesis, including amelotin (AMTN) and odontogenic ameloblast-
associated (ODAM). In this study, we characterise the gene, protein and pattern of
expression of a related protein called secretory calcium-binding phosphoprotein-
proline-glutamine-rich 1 (SCPPPQ1). The Scpppq1 gene resides within the secretory
calcium-binding phosphoprotein (Scpp) cluster. SCPPPQ1 is a highly conserved, 75-
residue, secreted protein rich in proline, leucine, glutamine and phenylalanine. In
silico data mining has revealed no correlation to any known sequences. Northern
blotting of various rat tissues suggests that the expression of Scpppq1 is
restricted to tooth and associated tissues. Immunohistochemical analyses show that
the protein is expressed during the late maturation stage of amelogenesis and in
the junctional epithelium where it localises to an atypical basal lamina at the
cell-tooth interface. This discrete localisation suggests that SCPPPQ1, together
with AMTN and ODAM, participates in structuring the basal lamina and in mediating
attachment of epithelia cells to mineralised tooth surfaces.
High metabolic activity and low levels of antioxidant enzymes make neurons
particularly prone to damage by reactive oxygen species. Thus, repair of oxidative
DNA damage is essential for normal brain function. Base excision repair is the
major pathway for repair of oxidative DNA damage, and is initiated by DNA
glycosylases recognizing and removing the damaged base. In mammalian cells at least
five different DNA glycosylases with overlapping substrate specificity, NEIL1,
NEIL2, NEIL3, OGG1 and NTH1, remove oxidative DNA base lesions. Here we report mRNA
expression and distribution of these five DNA glycosylases in human and rodent
brains using in situ hybridization and Northern blotting supported by glycosylase
activity assays. NEIL1, NEIL2, OGG1 and NTH1 showed widespread expression at all
ages. in situ hybridization studies in mouse brain showed that expression of mNeil1
increased with age. In newborn mouse brain, mNeil3 revealed a discrete expression
pattern in brain regions known to harbour stem cell populations, i.e., the
subventricular zone, the rostral migratory stream, and the hilar region of the
hippocampal formation. Expression of mNeil3 decreased with age, and in old mice
brains could be detected only in layer V of neocortex. MNth1 was constitutively
expressed during lifespan. in Northern blots, mOgg1 expression showed a transient
decrease followed by an increase after 8 weeks of age. Assays for faPy DNA
glycosylase activity revealed increased activity level with age in all brain
regions analyzed.
Currently there is no effective approach for monitoring early -cell loss during
islet graft rejection following human islet transplantation (HIT). Due to ethical
and technical constraints, it is difficult to directly study biomarkers of islet
destruction in humans. Here, we established a humanized mouse model with induced
human -cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of
ALT-treated mice had perigraft lymphocyte infiltration, fewer insulin(+) cells, and
increased -cell apoptosis. Islet-specific miR-375 was used to validate our model,
and expression of miR-375 was significantly decreased in the grafts and increased
in the circulation of ALT-treated mice before hyperglycemia. A NanoString
expression assay was further used to profile 800 human miRNAs in the human islet
grafts, and the results were validated using quantitative real-time polymerase
chain reaction. We found that miR-4454 and miR-199a-5p were decreased in the human
islet grafts following ALT and increased in the circulation prior to hyperglycemia.
These data demonstrate that our in vivo model of induced human -cell destruction is
a robust method for identifying and characterizing circulating biomarkers, and
suggest that miR-4454 and miR-199a-5p can serve as novel biomarkers associated with
early human -cell loss following HIT.
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded exvivo is
currently being investigated clinically by us and others as a means of reducing
allograft rejection following organ transplantation. Data from animal models has
demonstrated that adoptive transfer of allospecific Tregs offers greater protection
from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR)
are clinically translatable synthetic fusion proteins that can redirect the
specificity of T cells toward designated antigens. We used CAR technology to
redirect human polyclonal Tregs toward donor-MHC class I molecules, which are
ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were
engineered: one comprising a CD28-CD3 signaling domain (CAR) and one lacking an
intracellular signaling domain (CAR). CAR Tregs were specifically activated and
significantly more suppressive than polyclonal or CAR Tregs in the presence of HLA-
A2, without eliciting cytotoxic activity. Furthermore, CAR and CAR Tregs
preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers.
In a human skin xenograft transplant model, adoptive transfer of CAR Tregs
alleviated the alloimmune-mediated skin injury caused by transferring allogeneic
peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our
results demonstrated that the use of CAR technology is a clinically applicable
refinement of Treg therapy for organ transplantation.
Basic fibroblast growth factor (bFGF) regulates pluripotent marker expression and
cellular differentiation in various cell types. However, the mechanism by which
bFGF regulates REX1 expression in stem cells, isolated from human exfoliated
deciduous teeth (SHEDs) remains unclear. The aim of the present study was to
investigate the regulation of REX1 expression by bFGF in SHEDs. SHEDs were isolated
and characterized. Their mRNA and protein expression levels were determined using
real-time polymerase chain reaction and enzyme-linked immunosorbent assay,
respectively. In some experiments, chemical inhibitors were added to the culture
medium to impede specific signaling pathways. Cells isolated from human exfoliated
deciduous tooth dental pulp tissue expressed mesenchymal stem cell surface markers
(CD44, CD73, CD90, and CD105). These cells differentiated into osteogenic and
adipogenic lineages, when appropriately induced. Treating SHEDs with bFGF induced
REX1 mRNA expression and this effect was attenuated by pretreatment with FGFR or
Akt inhibitors. Cycloheximide pretreatment also inhibited the bFGF-induced REX1
expression, implying the involvement of intermediate molecule(s). Further, the
addition of an IL-6 neutralizing antibody attenuated the bFGF-induced REX1
expression by SHEDs. In conclusion, bFGF enhanced REX1 expression by SHEDs via the
FGFR and Akt signaling pathways. Moreover, IL-6 participated in the bFGF-induced
REX1 expression in SHEDs. (C) 2016 Wiley Periodicals, Inc.
Rationale, aims and objectivesThe purpose of medical education is to produce
competent and capable professional practitioners who can combine the art and
science of medicine. Moreover, this process must prepare individuals to practise in
a field in which knowledge is increasing and the contexts in which that knowledge
is applied are changing in unpredictable ways. The basic sciences' are important in
the training of a physician. The goal of basic science training is to learn it in a
way that the material can be applied in practice. Much effort has been expended to
integrate basic science and clinical training, while adding many other topics to
the medical curriculum. This effort has been challenging. The aims of the paper are
(1) to propose a unifying conceptual framework that facilitates knowledge
integration among all levels of living systems from cell to society and (2)
illustrate the organizing principles with two examples of the framework in action -
cybernetic systems (with feedback) and distributed robustness. MethodsLiterature
related to hierarchical and holarchical frameworks was reviewed. ResultsAn
organizing framework derived from living systems theory and spanning the range from
molecular biology to health systems management was developed. The application of
cybernetic systems to three levels (regulation of pancreatic beta cell production
of insulin, physician adjustment of medication for glycaemic control and
development and action of performance measures for diabetes care) was illustrated.
Similarly distributed robustness was illustrated by the DNA damage response system
and principles underlying patient safety. ConclusionsEach of the illustrated
organizing principles offers a means to facilitate the weaving of basic science and
clinical medicine throughout the course of study. The use of such an approach may
promote systems thinking, which is a core competency for effective and capable
medical practice.
The feruloyl esterase (FAE) gene EST1 from the basidiomycete Pleurotus sapidus was
heterologously expressed in Escherichia coli and Pichia pastoris. Catalytically
active recombinant Est1 was secreted using P. pastoris as a host. For expression in
P. pastoris, the expression vector pPIC9K was applied. The EST1 gene was cloned
with an N-terminal a-mating factor pre-pro sequence and expressed under the control
of a methanol inducible alcohol oxidase 1 promotor. Est1 was purified to
homogeneity using ion exchange and hydrophobic interaction chromatography. The
recombinant Est1 showed optima at pH 5.0 and 50 degrees C, and released ferulic
acid from saccharide esters and from the natural substrate destarched wheat bran.
Substrate specificity profile and descriptor-based analysis demonstrated unique
properties, showing that Est1 did not fit into the current FAE classification
model. Transferuloylation synthesis of feruloyl-saccharide esters was proven for
mono- and disaccharides. (C) 2015 International Union of Biochemistry and Molecular
Biology, Inc. Volume 63, Number 6, Pages 852-862, 2016
Large collections of data in studies on cancer such as leukaemia provoke the
necessity of applying tailored analysis algorithms to ensure supreme information
extraction. In this work, a custom-fit pipeline is demonstrated for thorough
investigation of the voluminous MILE gene expression data set. Three analyses are
accomplished, each for gaining a deeper understanding of the processes underlying
leukaemia types and subtypes. First, the main disease groups are tested for
differential expression against the healthy control as in a standard case-control
study. Here, the basic knowledge on molecular mechanisms is confirmed
quantitatively and by literature references. Second, pairwise comparison testing is
performed for juxtaposing the main leukaemia types among each other. In this case
by means of the Dice coefficient similarity measure the general relations are
pointed out. Moreover, lists of candidate main leukaemia group biomarkers are
proposed. Finally, with this approach being successful, the third analysis provides
insight into all of the studied subtypes, followed by the emergence of four
leukaemia subtype biomarkers. In addition, the class enhanced DEG signature
obtained on the basis of novel pipeline processing leads to significantly better
classification power of multi-class data classifiers. The developed methodology
consisting of batch effect adjustment, adaptive noise and feature filtration
coupled with adequate statistical testing and biomarker definition proves to be an
effective approach towards knowledge discovery in high-throughput molecular biology
experiments.
The aim of this study is to optimize the production of optically pure D (-) lactic
acid (DLA) employing a cost-effective production medium. Based on the designed
biomass approach, Sporolactobacillus inulinus NBRC 13595 was found to exhibit high
DLA titer (19.0 g L-1) and optical purity (99.6%). A cost-effective medium was
constituted using Palmyra palm jaggery (PJ) from Borassus flabellifer and whey
protein hydrolysate (WPH) as carbon and nitrogen sources, respectively. Plackett-
Burman design indicated that PJ, WPH, and MnSO4 as significant variables influence
DLA production. A rotatable central composite design and response surface
methodology were used to optimize the PJ and WPH concentrations. A maximum DLA
titer (170.14 g L-1) was predicted for 222.24 g L-1 of PJ and 11.99 g L-1 of WPH,
respectively. Fermentation experimental results exhibited a maximum DLA titer
(189.0 +/- 8.53 g L-1) and productivity (5.25 +/- 0.24 g L-1 H-1), which is the
highest ever reported for DLA production from a renewable feedstock in the batch
process. The present investigation substantiates that the potential application of
economically viable raw feedstocks (PJ and WPH) for enhanced DLA production, which
is attributed to 2.5-fold reduction in DLA production cost compared with
conventional medium. (C) 2015 International Union of Biochemistry and Molecular
Biology, Inc.
Selection on floral traits in hermaphroditic plants is determined by both male and
female reproductive success. However, predictions regarding floral trait and mating
system evolution are often based solely on female fitness. Selection viamale
fitness has the potential to affect the outcomes of floral evolution. In this
study, we used paternity analysis to assess individual selfing rates and selection
on floral traits via male and female fitness in an experimental population of
Clarkia xantiana where pollen limitation of seed set was strong. We detected
selection through both female and male fitness with reinforcing or noninterfering
patterns of selection through the two sex functions. For female fitness, selection
favored reduced herkogamy and protandry, traits that promote increased autonomous
selfing. For male fitness, selection on petal area was disruptive, with higher
trait values conferring greater pollinator attraction and outcross siring success
and smaller trait values leading to higher selfed siring success. Combining both
female and male fitness, selection on petal area and protandry was disruptive
because intermediate phenotypes were less successful as both males and females.
Finally, functional relationships among male and female fertility components
indicated that selfing resulted in seed discounting and pollen discounting. Under
these functional relationships, the evolutionarily stable selfing rate can be
intermediate or predominantly selfing or outcrossing, depending on the segregating
load of deleterious mutations.
This report describes the case of a 10-month-old infant, who was delivered to our
hospital by the emergency physician intubated and in an unclear unconscious state.
The father reported that the child had fallen from the couch to the ground. The
consulted ophthalmologist reported venous stasis in both eyes including
intraretinal and preretinal bleeding in all four quadrants, a diffuse vitreous
hemorrhage in the right eye and temporal retinal wrinkling in both eyes. Based on
these particular clinical findings a shaken baby syndrome was suspected. This
report demonstrates the importance of recognizing and correctly interpreting the
typical ophthalmological signs of physical child abuse in order to detect and
prevent further mistreatment of children; moreover, the increasing importance of
photographic documentation and histological work-up of the findings for forensic
reasons are emphasized.
The objective of this study was to examine factors facilitating and constraining
the identification and management of intimate partner violence (IPV) at an
emergency department (ED). Semi-structured interviews were conducted with 18 ED
employees of a university hospital in the Netherlands. All interviews were
audiotaped, transcribed verbatim, and analyzed by using qualitative content
analysis in Atlas. ti. Constraining factors were lack of knowledge, awareness, and
resources at the ED. ED employees felt many barriers to bringing up IPV.
Facilitating factors were good cooperation among staff, the involvement of one team
member in producing an IPV protocol, having received training on child abuse, and
private consulting rooms. The ED setting and the ED employees' task perception and
attitude contained both constraining and facilitating factors: ED employees saw it
as their task and responsibility to help IPV victims, but their priorities were to
secure a high turnover and treat acute physical problems. Although ED employees
expressed openness and willingness to help, they also took the view that victims
had a considerable responsibility of their own in disclosing and managing IPV,
which led to ambivalent feelings. In conclusion, ED employees faced tensions in IPV
identification and management caused by lack of awareness, knowledge and resources,
conflicting priorities at the ED, and ambivalent feelings. Improvements can be made
by supporting ED employees with guidelines in the form of a protocol and with
training that also addresses the tensions ED employees face.
In the United States, the judicial system response to violence between intimate
partners, or intimate partner violence (IPV), typically mandates that adjudicated
perpetrators complete a batterer intervention program (BIP). The social science
data has found that these programs, on the whole, are only minimally effective in
reducing rates of IPV. The authors examined the social science literature on the
characteristics and efficacy of BIPs. More than 400 studies were considered,
including a sweeping, recently conducted survey of BIP directors across the United
States and Canada. Results of this review indicate that the limitations of BIPs are
due, in large part, to the limitations of current state standards regulating these
programs and, furthermore, that these standards are not grounded in the body of
empirical research evidence or best practices. The authors, all of whom have
considerable expertise in the area of domestic violence perpetrator treatment,
conducted an exhaustive investigation of the following key intervention areas:
overall effectiveness of BIPs; length of treatment/length of group sessions; number
of group participants and number of facilitators; group format and curriculum;
assessment protocol and instruments; victim contact; modality of treatment;
differential treatment; working with female perpetrators; working with perpetrators
in racial and ethnic minority groups; working with lesbian, gay, bisexual, and
transgender (LGBT) perpetrators; perpetrator treatment and practitioner-client
relationships; and required practitioner education and training. Recommendations
for evidence-based national BIP standards were made based on findings from this
review.
Treatment of perpetrators is tried and tested albeit little researched for the
prevention of recidivism in domestic violence in Germany. This study investigated
the evidence of batterer programs on the risk of domestic violence recidivism and
the risk of child maltreatment reported by fathers on 161 perpetrators of domestic
violence. Based on the indicators for a high risk for reassault that were confirmed
in international longitudinal studies, a risk inventory for domestic violence was
developed and implemented in three German program sites. A shortened German version
of the Child Abuse Potential Inventory and the Interpersonal- Reactivity- Index
were used for perpetrators' self report. The study showed that the child abuse
potential of program dropouts was significantly higher compared to program
completers at baseline (n = 92). Longitudinal results showed significant
improvements with moderate effect sizes in all risk indicators assessed by
specialists (n = 78) and battered women (n = 44). Perpetrators' self report on
cognitive empathy improved too (n = 62). However, selfreported risk of child
maltreatment did not change (n = 46). No evidence of selective questioning of
victims was found. A classification of the results as well as the implications for
the treatment of perpetrators and research on recidivism in Germany are discussed.
The deployment of renewable energy technologies, such as solar photovoltaics and
wind turbines, poses challenges in terms of electricity grid stability due to the
intermittent nature of such energy sources, which creates a need for innovative
storage solutions. We demonstrate a metal hydride-based hybrid electrochemical
system that enables a solid-oxide fuel cell to operate in both fuel cell mode and
battery mode, allowing for un-interrupted electricity generation. In the fuel cell
mode, the device acts as a conventional fuel cell and converts the chemical energy
stored in fuels into electrical energy. In the battery mode, the metal hydride near
the anode releases hydrogen and quickly responds to fuel supply interruption or
power demand surges. The concept demonstrated here is a promising way to provide a
robust and economical solution for balancing power supply and demand for the
electrical grid of the future.
This paper introduces a module-integrated distributed battery energy storage and
management system without the need for additional battery equalizers and
centralized converter interface. This is achieved by integrating power electronics
onto battery cells as an integrated module. Compared with the conventional
centralized battery system, the modular design brings several advantages such as
reduced power rating and voltage stress of power electronics, no extra equalizers
or centralized converters, active thermal distribution control ability, enhanced
safety and reliability, etc. The battery system can now be built by simply
attaching integrated modules together. The integrated module is implemented by a
synchronous bidirectional dc/dc converter with digital control techniques. The
design considerations and control strategy of the system are discussed. A prototype
is built that the power electronics are integrated onto the battery cell.
Experimental results of a three-module system verified that the module-integrated
distributed system provides satisfied functional performance without extra
equalizers, centralized charger, or bidirectional dc/dc converter.
The battery energy storage systems (BESSs) have been increasingly installed in the
power system, especially with the growing penetration rate of the renewable energy
sources. However, it is difficult for BESSs to be profitable due to high capital
costs. In order to boost the economic value of BESSs, this paper proposes a
hierarchical energy management system (HiEMS) to aggregate multiple BESSs, and to
achieve multimarket business operations. The proposed HiEMS optimizes the
multimarket bids considering a realistic BESS performance model, and coordinates
the BESSs and manages their state of charge values, according to their price
penalties based on dynamically generated annualized cost. By taking part in the
energy market and regulation market at the same time, the cost-performance index
(CPI) of the BESS aggregation is greatly improved. The impact of photovoltaic
generation on system performance and CPI is also studied.
Battery energy storage (BES) plays an important role in the integration of
intermittent renewable power and distributed generation. The price arbitrage is a
major source of energy storage income. In China, the electricity price is tightly
regulated by the government. It's interesting to find out whether the BES is
economic viability in such a special electricity market, and what's the optimal
response of the grid (or regulator) when facing the arbitrage activities of BES.
This research starts with a price arbitrage model to evaluate the feasibility of
energy storage in China's electricity market, which can be used to determine the
optimal investment scale and operation mode of energy storage. A quantitative
assessment is also implemented to discuss the influence when factors change.
Following this, an optimal pricing strategy for grid is established. The results
reveal that the storage investment can realize positive profit in some districts
where the price gap between peak/off-peak periods is high. Appropriate subsidies
can be quantitatively described by sensitivity analysis. In terms of social
welfare, the energy storage can be deployed on a large-scale at a low social cost
under a suitable price mechanism. (C) 2017 Elsevier Ltd. All rights reserved.
This paper proposes a supervisory power management system (PMS) for a grid
interactive microgrid with a hybrid energy storage system. The key feature of the
proposed PMS is reduced number of sensors required to implement the PMS. The PMS
considers renewable power variation, grid availability, electricity pricing, and
changes in local loads. It can detect the operating mode of system without
measuring load currents and powers. A single-phase voltage source converter (VSC)
transfers real power between dc grid and utility grid besides offering ancillary
services such as harmonic mitigation, reactive power support, and unity power
factor at the point of common coupling (PCC). In the proposed system, a better dc-
link voltage regulation is achieved and the usage of supercapacitors reduces the
current stress on the battery. The PMS also addresses extreme operating conditions
such as load shedding, off-maximum power point tracking operation of photovoltaic,
elimination of critical oscillation of hybrid energy storage systems power,
islanded operation, and resynchronization with grid. The performance of the
proposed PMS is verified by digital simulation and experimental studies.
In order to reduce the stress on fuel cell based hybrid source fed electric drive
system the controller design is made through active current sharing (ACS)
technique. The effectiveness of the proposed ACS technique is tested on a dc drive
system fed from fuel cell and battery energy sources which enables both load
current sharing and source power management. High efficiency and reliability of the
hybrid system can be achieved by proper energy conversion and management of power
to meet the load demand in terms of required voltage and current. To overcome the
slow dynamics feature of FC, a battery bank of adequate power capacity has to be
incorporated as FC voltage drops heavily during fast load demand. The controller
allows fuel cell to operate in normal load region and draw the excess power from
battery. In order to demonstrate the performance of the drive using ACS control
strategy different modes of operation of the hybrid source with the static and
dynamic behavior of the control system is verified through simulation and
experimental results. This control scheme is implemented digitally in LabVIEW with
PCI 6251 DAQ I/O interface card. The efficacy of the controller performance is
demonstrated in system changing condition supplemented by experimental validation.
(C) 2016 Elsevier Ltd. All rights reserved.
Herein, we present a fully integrated electronic product code (EPC) Gen-2
compatible battery-assisted passive (BAP) radio-frequency identification sensor tag
integrated circuit (IC) with efficient power management. The key components of the
tag IC include an adaptive radio-frequency (RF) energy harvester, a battery access
controller (BAC), a storage capacitor charger, and a power-gated sensor block.
External RF energy is efficiently harvested using dynamically controlled rectifying
stages and a threshold-compensation technique. The BAC tightly controls the power
path, cutting off leakage current from the battery. The power-gated sensor block
supports multiplexed sensing operations in a power efficient manner. The sensor
interface includes a chopper amplifier, a programmable gain amplifier,
multiplexers, and an 8-bit ADC. For sensing data logging, custom designed
nonvolatile memory is employed via one-time programmable memory. The digital
control block is based on an EPCglobal Gen-2 standard that is modified to support
the sensing operation. The tag chip was fabricated in a 1-poly 6-metal standard
0.18-mu m standard CMOS process. The tag IC consumes 1 mu A for leakage and active
operation (0.1% duty), and the estimated lifespan of the BAP tag IC is about 0.2
year/mA.h.
Suppose that, to assess the joint distribution of a random vector (X-1,...,X-n),
one selects the kernels Q(1),...,Q(n) with Q(1) to be regarded as a possible
conditional distribution for X-i, given (X, : j not equal i);,Q(n) are compatible
if there exists a joint distribution for (X-1,...,X-n) with conditionals
Q(1),...,Q(n). Similarly, are improperly compatible if they can be obtained,
according to the usual rule, with an improper distribution in place of a
probability distribution. In this paper, compatibility and improper compatibility
of Q(1),...,Q(n) are characterized under some assumptions on their functional form.
The characterization applies, in particular, if each Q(i) belongs to a one
parameter exponential family. Special attention is paid to Gaussian conditional
autoregressive models. (C) 2017 Elsevier B.V. All rights reserved.
Efficient performance modeling is an extremely important task for yield analysis
and design optimization of analog circuits. In this paper, a novel regression
modeling method based on hierarchical shrinkage priors is proposed to construct
hybrid performance models with both high accuracy and low computational cost. In
particular, the user-defined model templates derived from design equations and the
general-purpose orthogonal polynomials are combined together to set up a hybrid
dictionary. Next, in order to avoid over-shrinking large model coefficients, a
novel regression method based on hierarchical shrinkage priors and variational
Bayesian inference is adopted for model fitting. A rail-to-rail operational
amplifier example demonstrates that the proposed method achieves up to 40% error
reduction over other state-of-the-art approaches without increasing the modeling
cost.
We routinely observe others' choices and use them to guide our own. Whose choices
influence us more, and why? Prior work has focused on the effect of perceived
similarity between two individuals (self and others), such as the degree of overlap
in past choices or explicitly recognizable group affiliations. In the real world,
however, any dyadic relationship is part of a more complex social structure
involving multiple social groups that are not directly observable. Here we suggest
that human learners go beyond dyadic similarities in choice behaviors or explicit
group memberships; they infer the structure of social influence by grouping
individuals (including themselves) based on choices, and they use these groups to
decide whose choices to follow. We propose a computational model that formalizes
this idea, and we test the model predictions in a series of behavioral experiments.
In Experiment 1, we reproduce a well-established finding that people's choices are
more likely to be influenced by someone whose past choices are more similar to
their own past choices, as predicted by our model as well as dyadic similarity
models. In Experiments 2-5, we test a set of unique predictions of our model by
looking at cases where the degree of choice overlap between individuals is equated,
but their choices indicate a latent group structure. We then apply our model to
prior empirical results on infants' understanding of others' preferences,
presenting an alternative account of developmental changes. Finally, we discuss how
our model relates to classical findings in the social influence literature and the
theoretical implications of our model. Taken together, our findings demonstrate
that structure learning is a powerful framework for explaining the influence of
social information on decision making in a variety of contexts.
In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine
Immunol 24: e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16) describe a dual-
purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine
(AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures
to SIV to become infected relative to nonimmunized animals. The authors
hypothesized that augmented susceptibility to SIV was due to activation of CD4(+) T
cells through trained immunity. This commentary explores the possible relationship
between trained immunity, enhanced CD4 T cell responses, and increased
susceptibility to human immunodeficiency virus (HIV).
Objective. Conventional, multi-channel scalp electroencephalography (EEG) allows
the identification of the attended speaker in concurrent-listening ('cocktail
party') scenarios. This implies that EEG might provide valuable information to
complement hearing aids with some form of EEG and to install a level of neuro-
feedback. Approach. To investigate whether a listener's attentional focus can be
detected from single-channel hearing-aid-compatible EEG configurations, we recorded
EEG from three electrodes inside the ear canal ('in-Ear-EEG') and additionally from
64 electrodes on the scalp. In two different, concurrent listening tasks,
participants (n = 7) were fitted with individualized in-Ear-EEG pieces and were
either asked to attend to one of two dichotically-presented, concurrent tone
streams or to one of two diotically-presented, concurrent audiobooks. A forward
encoding model was trained to predict the EEG response at single EEG channels. Main
results. Each individual participants' attentional focus could be detected from
single-channel EEG response recorded from short-distance configurations consisting
only of a single in-Ear-EEG electrode and an adjacent scalp-EEG electrode. The
differences in neural responses to attended and ignored stimuli were consistent in
morphology (i.e. polarity and latency of components) across subjects. Significance.
In sum, our findings show that the EEG response from a single-channel, hearing-aid-
compatible configuration provides valuable information to identify a listener's
focus of attention.
In current brain computer interfacing (BCI) system is used for many applications.
This technology also used for capturing brain signals in the form of EEG. This
technique have intensive applications in non-invasive technique of signal
capturing, Due to its temporal resolution, low set-up cost, easy portability
compared to all other techniques. In the EEG technique, as we are dealing with very
low frequency signals, these signals have plagued with various noise and
interferences, so there is an urge for designing and implementing an accurate and
stabilized system for acquiring these low frequency signals. This paper is aiming
for VLSI design and testing of EEG acquisition system to acquire brain signals.
Initially the low power and high gain generalized operational amplifier is
designed. Later a suitable filter is designed to eliminate the noise signals
produced in low frequency operations, in order to capture EEG signals. The
generalized amplifier design of this system consists of differential amplifier
followed with voltage follower circuit. The above circuit is designed using the
Cadence tool which facilitates the capturing of transient response and generation
of virtual layouts. Each and every blocks of the system is designed and tested
individually, for each blocks virtual layouts are generated. And the transient
response of the system which contains EEG signals with different voltage levels and
frequencies are captured.
Embryo implantation is a complex initial step in establishment of a successful
pregnancy. Many mRNAs have been shown to be differentially expressed in the rat
uterus during embryo implantation. However, the expression profiles of microRNAs
(miRNAs), a key post-transcriptional regulator of gene expression, in the rat
uterus between the pre-receptive and receptive phases are still unknown. Here, an
miRNA microarray was used to examine differential expression of miRNAs in the rat
uterus between the pre-receptive and receptive phases. Twenty-eight miRNAs were up-
regulated and 29 miRNAs were down-regulated at least twofold during the receptive
phase in rat uterus; these results were confirmed by Northern blotting. miR-29a was
only highly expressed in rat uterus during the implantation period, and activation
of delayed implantation and artificial decidualization enhanced the miR-29a level.
Further investigation revealed that both the pro-apoptotic factor genes Bak1 and
Bmf and the anti-apoptotic factor gene Bcl-w are targets of miR-29a. There was weak
binding between miR-29a and the 3 UTR of the anti-apoptotic factor gene Mcl1. Over-
expression of miR-29a inhibited the late apoptosis of endometrial stromal cells,
which may be due to the stronger binding capacity between miR-29a and the 3 UTR of
pro-apoptotic factors than that between miR-29a and the 3 UTR of anti-apoptotic
factors. Collectively, miR-29a plays an important role during embryo implantation
by regulating both pro-apoptotic and anti-apoptotic factors. miR-29a may
predominantly bind pro-apoptotic factors, leading to inhibition of cell apoptosis.
Sequential measurement of BCR-ABL1 mRNA levels by reverse transcription
quantitative polymerase chain reaction (RT-qPCR) is embedded in the management of
patients with chronic myeloid leukaemia (CML), and has played an important role in
the remarkable improvement in patient outcomes seen in this disease. As a provider
of external quality assessment (EQA) in this area, UK NEQAS for Leucocyte
Immunophenotyping (UKNEQAS LI) has a unique perspective on the changing face of
BCR-ABL1 testing in CML. To assess the impact of technical standardisation and the
development of the International Scale (IS) upon the accuracy of BCR-ABL1 testing,
we reviewed EQA trial data from 2007 to 2015. Comparison of participant results
identified considerable variability at both high and low levels of disease,
including therapeutically important decision points; however, results converted to
the IS showed less variability compared to unconverted data sets. We also found
that different methods of converting to the IS produce consistently different
median results within UKNEQAS LI IS data sets. This data suggests that whilst the
development of the IS has improved the comparability of results between centres,
there is still the need for further improvement in the processes of converting raw
results to the IS in order to fully realise the benefits of molecular monitoring of
CML.
What is known and objectiveThe role of CYP3A5 in drug metabolism has been receiving
attention because CYP3A5 may be more involved in the metabolism of CYP3A substrates
in vivo than previously thought. The polymorphism of transporters, such as P-gp (P-
glycoprotein) and breast cancer-related protein (BCRP), influences the metabolism
of these substrates, and felodipine is a substrate of P-gp. The aim of this study
was to evaluate the pharmacogenetic variability in the disposition of felodipine in
healthy Chinese subjects. MethodsA single dose of 5 mg felodipine was orally
administered to 45 healthy Chinese subjects. The serum concentration of felodipine
was measured by using LC/MS/MS. We detected the SNPs of cytochromes P450 enzymes
and transporters, which play vital roles in drug metabolism and have a high
frequency of mutation in Chinese population. Results and discussionThe area under
the plasma concentration-time curve (AUC) within the time points 0 to 72 h (AUC((0-
72))) after felodipine administration was significantly higher in subjects
possessing the BCRP421AA alleles than in those with the BCRP421 CC or CA genotype
(P = 0034). The subjects with CYP3A5*3/*3 (n = 27) had higher felodipine exposure
than CYP3A5*1/*3 (n = 15) (P = 0035). What is new and conclusionThis study showed
that the genetic polymorphisms of CYP3A5*3 and BCRPC421A might explain the
variability in the pharmacokinetics of felodipine in the Chinese population.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated
with cortisol responses to stress with gender differences reported, although the
findings are not entirely consistent. To evaluate the role of Val66Met genotype and
gender on cortisol responses to stress, we conducted a 45-min mental stress
protocol including four tasks and four rest periods. Blood cortisol was collected
for assay immediately before and after each task and rest period. A significant
two-way interaction of Val66Met genotype x gender (P= 0.022) was observed on the
total area under the curve (AUC), a total cortisol response over time, such that
the Val/Val genotype was associated with a larger cortisol response to stress as
compared to the Met group in women but not in men. Further contrast analyses
between the Val/Val and Met group for each stress task showed a similar increased
cortisol pattern among women Val/Val genotype but not among men. The present
findings indicate the gender differences in the effect of Val66Met genotype on the
cortisol responses to stress protocol, and extend the evidence for the importance
of gender and the role of Va166Met in the modulation of stress reactivity and
subsequent depression prevalence. Further studies and the underlying mechanism need
to be investigated, which may provide an insight for prevention, intervention, and
treatment strategies that target those at high risk. (C) 2017 Elsevier Ltd. All
rights reserved.
Aims Epidemiological studies strongly suggest a link between stress, depression,
and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly
understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met),
associated with depression and anxiety, has been proposed as a genetic risk factor
for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which
phenocopies psychiatric-related symptoms found in humans, we investigated the
impact of this SNP on thrombosis. Methods and results BDNFMet/Met mice displayed a
depressive-like phenotype concomitantly with hypercoagulable state and platelet
hyper-reactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-
type (WT) mice showed differential expression of proteins involved in the
coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid
artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection.
Interestingly, transfection with BDNFMet construct induced a
prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using
resveratrol and/or CAY10591, prevented thrombus formation and restored the
physiological levels of coagulation and of platelet markers in BDNFMet/Met mice
and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by
sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory
phenotype in WT mice and cells. Finally, we found that BDNF Met homozygosity is
associated with increased risk of acute myocardial infarction (AMI) in humans.
Conclusion Activation of platelets, alteration in coagulation pathways, and changes
in vessel wall protein expression in BDNFMet/Met mice recapitulate well the
features occurring in the anxiety/depression condition. Furthermore, our data
suggest that the BDNFVal66Met polymorphism contribute to the individual propensity
for arterial thrombosis related to AMI.
A number of measures to increase the quality of data recorded with an improved
Balzers Eldigraph KD-G2 gas-phase electron diffractometer are discussed. The beam-
stop has been decoupled from the sector enabling us recording the current of the
primary beam and scattered electrons during the experiment. Different beam-stops
were tested for use in the present setup. Modifications of the nozzle tip of an
earlier described medium temperature nozzle are reported. The measures lead to
reduced exposure times and reduced amount of sample necessary for complete data
collection.
Bearingless permanent magnet synchronous motors (BPMSMs) have been received more
and more attention during the past few decades. To realize the high-performance
control for rotation and levitation, we will first need to obtain the accurate
suspension force model of a BPMSM. In this work, different from conventional
suspension force models, a modeling scheme for the suspension force of a BPMSM is
presented by taking into account rotor eccentricity with the Maxwell stress tensor
modeling scheme. The theoretical value of a suspension force model is compared by
the two-dimensional finite element (FE) analysis, and calculation results reveal
that the theoretical value closely agree with the FE computed one. Furthermore, the
digital control system is devised by taking advantage of TMS320F2812, and a test
platform for experiments is then set up. In accordance with the corresponding
findings of the experiments, the rotor stabilization with magnetic levitation can
be achieved. The results lay a theoretical and experimental foundation for further
study of the BPMSM.
Recently, bearingless switched reluctance motor (BLSRM) has been received more and
more attention. To realize the stable levitation and rotation, the corresponding
suspending force and torque should be controlled. In this paper, different from the
conventional bearingless SRM control, one independent control scheme for levitation
force and torque is presented. In the control, a complex control algorithm based on
a lookup table is not needed. Torque control is separated from radial force
control, and each channel of radial force is independently controlled. Therefore,
the control is very simple to be implemented. First, based on the brief
introduction of the BLSRM structure and operating principle, the mathematical
relationship of levitation force with respect to current and displacement is
derived. Furthermore, the rotor dynamics model, in which levitation force in four
degrees of freedom is considered, is established. Based on the given analysis, the
digital control system, which includes torque and suspending force, is designed by
means of TMS320F28335, and an experimental platform is established. According to
the experimental results, the proposed BLSRM can be steadily levitated in the
static and rotating conditions.
Power electronic converters are single input multiple output (SIMO) systems in
frequency domain. In distributed power system (DPS), one converter's switching
frequency ripples are another converter's perturbations, and beat frequency
components are generated due to their SIMO characteristics. As the control loops of
power converters always take high gains in low-frequency regions if the beat
frequency components are relatively low, they may be magnified and presented as
oscillations, which will introduce system instability. This paper proposes a
matrix-based multifrequency output impedance model to describe the SIMO
characteristics of power converters and to analyze the stability of DPS. The buck
converter is specifically illustrated as demonstration. The proposed model
indicates that the variation of switching frequency, as well as those traditionally
discussed parameters of control loops and passive components, could also change
output impedance characteristics and introduce system instability. In DPS, the beat
frequency oscillation that traditional models fail to explain could be accurately
predicted by the proposed model. In addition, based on the proposed model, the
switching frequencies for power converters can be optimized to improve the
stability of power electronic-based systems. Simulation and experimental results
validate the accuracy and the effectiveness of the proposed method.
Current ambitions to limit climate change to no more than 1.5 degrees C-2 degrees C
by the end of the 21st century rely heavily on the availability of negative
emissions technologies (NETs)-bioenergy with CO2 capture and storage (BECCS) and
direct air capture in particular. In this context, these NETs are providing a
specific service by removing CO2 from the atmosphere, and therefore investors would
expect an appropriate risk-adjusted rate of return, varying as a function of the
quantity of public money involved. Uniquely, BECCS facilities have the possibility
to generate both low carbon power and remove CO2 from the atmosphere, but in an
energy system characterised by high penetration of intermittent renewable energy
such as wind and solar power plants, the dispatch load factor of such BECCS
facilities may be small relative to their capacity. This has the potential to
significantly under utilise these assets for their primary purpose of removing CO2
from the atmosphere. In this study, we present a techno-economic environmental
evaluation of BECCS plants with a range of operating efficiencies, considering
their full-and part-load operation relative to a national-scale annual CO2 removal
target. We find that in all cases, a lower capital cost, lower efficiency BECCS
plant is superior to a higher cost, higher efficiency facility from both
environmental and economic perspectives. We show that it may be preferable to
operate the BECCS facility in base-load fashion, constantly removing CO2 from the
atmosphere and dispatching electricity on an as-needed basis. We show that the use
of this 'spare capacity' to produce hydrogen for, e.g. injection to a natural gas
system for the provision of low carbon heating can add to the overall environmental
and economic benefit of such a system. The only point where this hypothesis appears
to break down is where the CO2 emissions associated with the biomass supply chain
are sufficiently large so as to eliminate the service of CO2 removal.
Introduction: Depressive symptoms are common in patients assessed by
neuropsychologists, and these symptoms can have an effect on cognitive functioning.
Discrepancies between patient- and informant-reported depressive symptoms have been
found in some diagnostic groups, raising concerns as to the value of assessing
depressive symptoms via self-report alone. This study aimed to examine the
relationship between these discrepancies and cognitive functioning in a
heterogeneous outpatient neuropsychological sample. Method: Sixty-two patients with
a variety of diagnoses (e.g., stroke, mild cognitive impairment) completed a
measure of depressive symptoms and a battery of neuropsychological tests.
Informants also rated the patients' depressive symptoms and completed a measure of
the patients' functional abilities. Results: Patient and informant reports of
depressive symptoms were moderately correlated; larger differences between patient-
and informant-reported symptoms were associated with poorer verbal learning and
memory and greater functional impairments. Conclusions: The moderate level of
agreement found for depressive symptoms is consistent with past studies using
specific neuropsychological patient groups and other studies in both clinical and
non-clinical populations. These results highlight the utility of collecting
informant reports of depressive symptoms in neuropsychological evaluations.
Aim: The aim of this study was to determine Nigerian parents' views about the
causes and treatment of childhood enuresis. Methods: Parents of children aged 5-17
years were individually interviewed in an urban community in Nigeria using a
pretested questionnaire. Their responses about the causes and treatment of enuresis
were grouped under common themes. Results: We included 448 respondents in the
study: 75.5% were mothers, 44.2% had at least one child with enuresis and only 1.3%
had spoken to a doctor about it. Enuresis was thought to be due to playing too much
and drinking too much fluid at night by 69.7% and 21.2% of the respondents,
respectively. The two most common treatment methods that parents were aware of for
enuresis were waking to void (23.7%) and urinating on hot charcoal (20.8%). The
most common methods that parents actually employed included waking to void (49.0%),
punishing the child (36.9%) and doing nothing (28.8%). Conclusion: Most of the
respondents believed that playing too much and drinking or eating too much were
responsible for childhood enuresis. Parents rarely discussed childhood enuresis
with their doctors and some of the self-help measures that were employed may be
harmful and could constitute child abuse.
A full-length Beet black scorch virus (BBSV) cDNA clone (pUBF52) was constructed by
RT-PCR. The clone contains an upstream T7 RNA polymerase promoter designed for in
vitro transcription of infectious RNAs from the linearized plasmid that faithfully
represent the viral cDNA. Leaves of Chenopodium amaranticolor inoculated with in
vitro transcripts developed the same symptoms and disease phenotype as the wild
type virus. The presence of BBSV RNA and coat protein in the leaves was confirmed
respectively by Northern blotting and Western blotting. Comparisons of specific
immunoreactions between the expression product of the BBSV p24 gene in E. coli and
antiserum against purified BBSV virions demonstrated that the p24 gene encodes the
coat protein. Based on the sequence of the pUBF52 cDNA, a frame-shift mutant and
two deletion mutants were generated. One of the deletions encompasses the entire CP
ORF and the other truncates 174 amino acids from the central region of the protein.
Transcripts derived from the frame-shift CP mutant, which terminates the CP after
the first 23 amino acids, elicited the same symptom phenotype and levels of RNA
accumulation as the wild type virus, but the leaves infected with the CP deletion
mutants exhibited greatly reduced RNA accumulation. In addition, leaves inoculated
with in vitro transcripts of the mutant in which the entire CP gene was deleted had
lower local lesions than wild type virus transcripts. Two expression vectors, pBGFP
and pBGUS, were constructed by fusing the GFP and GUS genes to the 23 N-terminal
amino acids of the CP gene, respectively. Leaves infected with in vitro transcripts
of pBGFP and pBGUS exhibited expression of GFP and GUS proteins as assessed by
laser confocal microscopy and histochemical staining, respectively. The high levels
of expression of the GFP and GUS proteins provide tools that can be used for
studies of replication and movement of the virus, and indicate that BBSV has
considerable biotechnology potential as a plant virus expression vehicle.
Co-infection of none-coding satellite RNAs (sat-RNAs) usually inhibits replication
and attenuates disease symptoms of helper viruses. However, we find that the sat-
RNA of Beet black scorch virus (BBSV) and low temperature (18 degrees C) additively
enhance the systemic infection of BBSV in Nicotiana benthamiana. Northern blotting
hybridization revealed a relatively reduced accumulation of BBSV-derived small
interfering RNAs (siRNAs) in presence of sat-RNA as compared to that of BBSV alone.
Cloning and sequencing of total small RNAs showed that more than 50% of the total
small RNAs sequenced from BBSV-infected plants were BBSV-siRNAs, whereas the
abundance of sat-siRNAs were higher than BBSV-siRNAs in the sat-RNA co-infected
plants, indicating that the sat-RNA occupies most of the silencing components and
possibly relieves the RNA silencing-mediated defense against BBSV. Interestingly,
the 5' termini of siRNAs derived from BBSV and sat-RNA were dominated by Uridines
(U) and Adenines (A), respectively. Besides, the infection of BBSV alone and with
sat-RNA induce down-regulation of miR168 and miR403, respectively, which leads to
high accumulation of their targets, Argonaute 1 (AGO1) and AGO2. Our work reveals
the profiles of siRNAs of BBSV and sat-RNA and provides an additional clue to
investigate the complicated interaction between the helper virus and sat-RNA
This study examines whether the delivery of three components, (a) exercise
training, (b) behavior management skill building, and (c) dementia-related
education, in an evidence-based program are differentially associated with changes
in outcomes for individuals with dementia (IWDs) after 3 months. Data come from 508
IWDs participating in the community replication of the evidence-based Reducing
Disability in Alzheimer's Disease program. Regression results indicate that after 3
months, more exercise sessions are associated with improvements in physical
functioning, mobility, minutes exercising, and symptoms of depression; more
dementia education sessions are related to fewer restricted activity days; and more
behavior management sessions are related to more symptoms of depression. As
resource-strapped agencies look to best serve participants, further analysis and
consideration is needed to determine the ideal balance of program efficacy,
feasibility, and resources, as well as program benefits for IWDs and caregivers.
Depression is associated with decreased engagement in behavioural activities. A
wide range of activities can be promoted by simulating them via mental imagery.
Mental imagery of positive events could thus provide a route to increasing adaptive
behaviour in depression. The current study tested whether repeated engagement in
positive mental imagery led to increases in behavioural activation in participants
with depression, using data from a randomized controlled trial (Blackwell et al. in
Clin Psychol Sci 3(1):91-111, 2015. doi:10.1177/2167702614560746). Participants (N
= 150) were randomized to a 4-week positive imagery intervention or an active non-
imagery control condition, completed via the internet. Behavioural activation was
assessed five times up to 6 months follow-up using the Behavioural Activation for
Depression Scale (BADS). While BADS scores increased over time in both groups,
there was an initial greater increase in the imagery condition. Investigating
mental imagery simulation of positive activities as a means to promote behavioural
activation in depression could provide a fruitful line of enquiry for future
research.
We propose a simulation-based analog equivalence boundary search methodology for
high level Simulink models and their low level HSpice counterparts. The equivalence
of high and low level designs is determined by comparing a set of predefined
performance parameters measured during the simulation of both models. Our
methodology investigates the search space to obtain boundary of input parameters,
where both models have equivalent performance parameters. We build an optimization
problem, where the error percentage between the performance parameters of both
models being less than a specified threshold is defined as success criteria. In
this problem, input parameters are determined by utilizing evolutionary
computation. At the end of the optimization, the border of equivalence for the
models is found for input parameters satisfying the success criteria. We
demonstrate the validity of our approach on three designs, an inverter, an
operational amplifier, and a buck converter, where our approach proves to be an
efficient tool in finding an equivalence boundary of analog circuits and models.
(C) 2016 Elsevier B.V. All rights reserved.
Symbolically generated network functions for an analog integrated circuit are
complicated in general. For this reason a variety of simplification methods have
been proposed in the literature. In this work a novel topology-based symbolic
simplification method is proposed, which is capable of generating a simplified
symbolic network function together with a simplified small-signal circuit. The
technique is developed by applying the recently proposed graph-pair decision
diagram (GPDD) algorithm that generates a symbolic network function stored in a
binary decision diagram (BDD). Two types of element elimination can directly be
operated on such a GPDD data structure. The performance variation by eliminating
each symbol from the original circuit is assessed by the means of two monitored
response metrics (dc gain and phase margin). After sorting the performance loss,
those circuit elements with less performance loss are eliminated, resulting in a
reduced GPDD which is automatically a simplified network function. A simplified
small-signal circuit is available simultaneously after reduction. Applications to
two operational amplifier examples confirm the effectiveness of the proposed
methodology.
A model of the operational amplifier based on VHDL-AMS is proposed. According to
needs of simulating the total ionizing dose (TED) radiation effect, parameters of
operational amplifier are taken into account when the performance is specified. The
operational amplifier model used for the TID radiation effect simulation is
completed after verifying each modeled parameter. And a parameter for describing
the external environment is introduced to make the model combined with TID.
Finally, an example is used to illustrate the TID effect on the operational
amplifier of MC14573, proving the validity of the model.
Introduction. Behavioral changes often occur after moderate-to-severe traumatic
brain injury (TBI) and can lead to poor health, psychosocial functioning, and
quality of life. Challenges in evaluating these behaviors often result from the
complexity and variability in the way they are conceptualized and defined. We
propose and test a conceptual model that is specific to behavioral symptoms after
TBI, to serve as a basis for better assessment and treatment. We hypothesized that
clusters of individuals, with unique emotional, cognitive, and behavioral
characteristics, would emerge that would illustrate this conceptual model. Methods.
We conducted model-based cluster analyses in two cohorts, 6-months post-injury
(n=79) and >6months post-injury (n=62), of adults with moderate-to-severe TBI to
explore the face validity of our conceptual model by evaluating how participants
clustered with regard to emotional (Patient Health Questionnaire 9, Positive and
Negative Affect Schedule), cognitive (neuropsychological test battery), and frontal
behavioral (Frontal Systems Behavior Scale) symptoms. Results. In each cohort,
unique clusters of participants emerged that differed significantly with regard to
emotional state, cognition, and behavior (ps6months) demonstrated a more complex
pattern of symptoms; the most severe behavioral symptoms occurred in the context of
severe emotional symptoms, even in the absence of cognitive impairment. However,
problematic behavioral symptoms were also present in the context of severe
cognitive impairment, even in the absence of emotional symptoms. Conclusions.
Emotional, cognitive, and behavioral characteristics were represented as expected,
based on the proposed conceptual model of behavior. This conceptual model provides
the basis for evaluating behavioral changes after moderate-to-severe TBI and
identifying modifiable targets and relevant subpopulations for behavioral
intervention, with the goal of improved evidence-based personalized medicine for
this population.
Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD),
subtypes of frontotemporal dementia, are characterized by distinct clinical
symptoms and neuroimaging features, with predominant left temporal grey matter (GM)
atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential
hemispheric predilection may also be reflected by other neuroimaging features, such
as brain connectivity. This study investigated white matter (WM) microstructure and
functional connectivity differences between SD and bvFTD, focusing on the
hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and
17 controls underwent diffusion tensor imaging and resting state functional MRI at
3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts
affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization
indices were calculated. Functional connectivity was established for GM regions
affected in early stage SD or bvFTD. Results of a direct comparison between SD and
bvFTD are reported. Whole-brain WM microstructure abnormalities were more
pronounced in the left hemisphere in SD and bilaterally-with a slight predilection
for the right-in bvFTD. Lateralization of tract-specific abnormalities was seen in
SD only, toward the left hemisphere. Functional connectivity of disease-specific
regions was mainly decreased bilaterally in SD and in the right hemisphere in
bvFTD. SD and bvFTD show WM microstructure and functional connectivity
abnormalities in different regions, that are respectively more pronounced in the
left hemisphere in SD and in the right hemisphere in bvFTD. This indicates
differential hemispheric predilection of brain connectivity abnormalities between
SD and bvFTD.
Aims: To conduct a pilot trial to test the feasibility of a guided self-help
intervention for chronic orofacial pain. Methods: A pilot randomized controlled
trial was conducted to compare the intervention with usual treatment. A total of 37
patients with chronic orofacial pain were randomized into either the intervention
group (n = 19) or the usual treatment (control) group (n = 18). Validated outcome
measures were used to measure the potential effectiveness of the intervention over
a number of domains: physical and mental functioning (Short Form 36 [SF-36]);
anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); pain
intensity and interference with life (Brief Pain Inventory [BPI]); disability
(Manchester Orofacial Pain Disability Scale [MOPDS]); and illness behavior (Revised
Illness Perceptions Questionnaire [IPQr]). Bootstrap confidence intervals were
computed for the treatment effect (ES) posttreatment and at 3 months follow-up and
adjusted for baseline values of the outcome measure by using analysis of
covariance. Results: At posttreatment and the 3-month follow-up, 11 participants in
the intervention group and 7 in the control group failed to complete outcome
measures. The intervention was acceptable and could be feasibly delivered face to
face or over the telephone. Although the pilot trial was not powered to draw
conclusions about the effectiveness, it showed significant (P <.05) effects of the
intervention on physical and mental functioning and treatment control. Conclusion:
The self-help intervention was acceptable to patients and allowed them to better
understand and self-manage chronic orofacial pain. It showed potential
effectiveness on outcome domains related to functioning and illness perception.
Further research is needed to understand the cost effectiveness of the intervention
for chronic orofacial pain.
Imagination pushes humanity well beyond its natural biological capacities. An
approach of co-evolution, between molecular biology and behaviour, is thus required
to explain these combined processes. Technological performances define spiritual
conquests and formulas whose sole function is cultural. Humanity operates according
to intentional social modes defined by the group, but these immediately become
conditions for their own evolution. These choices are the motor for the history of
humanity, and thus humanity can itself choose its own path. Anatomic modernisation
is only a distant reflection of bipedalism, but freeing the hands leads to the
development of abstract thought. The relationship between anatomy and awareness
allows infinite variations in the harmonious adaptation to nature, animals and
other societies. In Europe, humanity arrived in abrupt bursts because it was the
result of external evolution, continuous and distant, dispersed across Asia. By its
unceasing audacity, humanity combats biological determinism, imposing "moral"
rules, or imperatives. The balance between biology and culture is reflected in the
rules for sharing food: the biological life itself is coded by social sharing.
These systems take on ternary values as soon as they include animal behaviours.
Built shelters integrate societies with the cosmos because they delimit cultural
spaces within natural chaos. Mastery of cognitive mechanisms gives humanity an
entirely new responsibility, that of being able to define its destiny. Our united
disciplines are transformed into ethical requirements. (C) 2016 Published by
Elsevier Masson SAS on behalf of Academie des sciences.
Faces play an integral role in day-to-day functioning, particularly for social
interactions where dynamic and rapid processing of information is vital. Analysis
of faces allows an individual to ascertain a wide range of information including
deciphering mood and identity, with these assessments directing an individual's
subsequent response and behaviours. The prominent social and emotional deficits
observed in frontotemporal dementia (FTD), a youngeronset dementia syndrome, may in
part reflect a breakdown of the face processing network. Different subtypes of FTD
present with divergent patterns of atrophy, although damage is predominantly
confined to the frontal and temporal lobes. Specific predictions regarding the role
of frontal and temporal regions in face processing have been proposed in the model
outlined by Haxby et al. Trends in Cognitive Sciences, 4(6), 223-233 (2000). This
model presents a parsimonious method by which to understand face processing in FTD
while concurrently allowing assessment of the predictive value and applicability of
such a model. By applying the Haxby model to the existing FTD literature, this
review presents both direct and indirect evidence of a breakdown in key elements of
the face processing network. The type and degree of breakdown appears to differ as
a function of FTD subtype and associated brain atrophy. The evidence presented in
this review and its relationship with predictions of the Haxby model provides
impetus and direction for future research investigating face processing in FTD.
Transforming Growth Factor (TGF)-beta inhibitors have been in development for
decades with the outmost results of being promising candidates. From the latest
clinical results at the 2016 ASCO meeting converging evidences suggest that we have
moved from promising to effective drug nominees.
Beliefs about the unacceptability of experiencing and expressing emotions have been
found to be related to worse outcomes in people with persistent physical symptoms.
The current study tested mediation models regarding emotional suppression, beliefs
about emotions, support-seeking and global impact in fibromyalgia. One hundred
eighty-two participants took part in an online questionnaire testing potential
mechanisms of this relationship using mediation analysis. The model tested
emotional suppression and affective distress as serial mediators of the
relationship between beliefs about emotions and global impact. In parallel paths,
two forms of support-seeking were tested (personal/emotional and symptom-related
support-seeking) as mediators. Emotional suppression and affective distress
significantly serially mediated the relationship between beliefs about emotions and
global impact. Neither support-seeking variable significantly mediated this
relationship. Results indicate a potential mechanism through which beliefs about
emotions and global impact might relate which might provide a theoretical basis for
future research on treatments for fibromyalgia.
The prostate is composed mainly of epithelial and stromal cells, whose dynamic
interaction is vital to a broad array of cellular processes, including
proliferation, differentiation, growth, and apoptosis. To understand intercellular
communication in the development and progression of prostatic diseases, we examined
gene expression in tissues from five patients diagnosed with benign prostatic
hyperplasia (BPH). Fibroblasts and epithelial cells derived from these tissues were
grown in a primary co-culture system that retains many characteristics of the
intact human prostate. The mRNA levels of expressed genes as assessed by
differential-display reverse transcription-PCR revealed that 110 genes were
differentially expressed in co-cultured fibroblasts and epithelial cells, compared
with expression in separately cultured cells. Eighty-four of these were confirmed
by reverse Northern blotting, and 68 were successfully sequenced. Of the sequenced
genes, 43 were differentially expressed in epithelial cells (37 upregulated, 6
downregulated), and 25 were differentially expressed in fibroblasts (6 upregulated,
19 downregulated) in co-cultures versus separate cultures. Semi-quantitative RT-PCR
analysis of 12 genes with known functions showed that five of these were
differentially expressed in co-cultured cells. Human kallikrein gene 7 (KLK7) was
markedly upregulated in co-cultured compared with separately cultured epithelial
cells (P<0.001), whereas S100 calcium binding protein All, tyrosine 3-
monooxygenase/tryptophan 5-monooxygenase activation protein, cyclin I, and latexin
were significantly downregulated in co-cultured fibroblasts (P<0.05). Quantitative
real-time RT-PCR and Western blot analysis confirmed KLK7 up-regulation at both the
mRNA and protein levels, respectively. Thus, epithelial-stromal cell interaction
and communication are likely to be important in BPH. Epithelial cells and
fibroblasts may interplay coordinately or collaboratively to influence cellular
growth and death through dynamically differential gene expression in response to
physiological and pathophysiological changes.
All clinically-used antipsychotics display similar affinity for both D-2 (D2R) and
D-3 (D3R) receptors, and they likewise act as 5-HT2A receptor antagonists. They
provide therapeutic benefit for positive symptoms, but no marked or consistent
improvement in neurocognitive, social cognitive or negative symptoms. Since
blockade of D-3 and 5-HT6 (5-HT6R) receptors enhances neurocognition and social
cognition, and potentially improves negative symptoms, a promising approach for
improved treatment for schizophrenia would be to develop drugs that preferentially
act at D3R versus D2R and likewise recognize 5-HT6R. Starting from the high
affinity 5-HT6R ligands I and II, we identified compounds 11a and 14b that behave
as 5-HT6R ligands with significant selectivity for D3R over D2R. (C) 2016 Elsevier
Ltd. All rights reserved.
Selective inhibitors of histone deacetylase 6 (HDAC6) are an emerging class of
pharmaceuticals due to the involvement of HDAC6 in different pathways related to
neurodegenerative diseases, cancer, and immunology. Herein, the synthesis of ten
new benzohydroxamic acids, constructed by employing the tetrahydrobenzothiazepine
core as a privileged pharmacophoric unit, is described. This is the first report on
the synthesis and isolation of octahydrodibenzothiazepines and octahydro-6H-
benzocycloheptathiazepines, which were then used to develop a new class of HDAC6
inhibitors. Evaluations of their HDAC-inhibiting activity resulted in the
identification of cis-N-(4-hydroxycarbamoyl-benzyl)-1,2,3,4,4a, 5,11,11a-
octahydrodibenzo[b, e] [1,4]thiazepine-10,10-dioxide and cis-N-(4-hydroxycarbamoyl-
benzyl)-7-trifluoromethyl-1,2,3,4,4a, 5,11,11a-octahydrodibenzo[b,e]
[1,4]thiazepine-10,10-dioxide as highly potent and selective HDAC6 inhibitors with
activity in the low nanomolar range, which also show excellent selectivity on the
enzymatic and cellular levels. Furthermore, four promising inhibitors were
subjected to an Ames fluctuation assay, which revealed no mutagenic effects
associated with these structures.
Berberine is traditionally used to treat gastrointestinal (GI) motility disorders.
The interstitial cells of Cajal (ICCs) are the pacemaker cells of the
gastrointestinal tract, which are responsible for the production of gut movements.
The present study aimed to investigate the effects of berberine on pacemaker
potentials (PPs) in cultured ICC clusters from the mouse small intestine, and
sought to identify the receptors involved and the underlying mechanisms of action.
All experiments were performed on cultured ICCs, and a whole-cell patch-clamp
configuration was used to record PPs from ICC clusters (current clamp mode). Under
current clamp mode, berberine was shown to decrease the amplitude and frequency of
PPs. However, these effects were suppressed by treatment with glibenclamide, a
specific ATP-sensitive K+ channel blocker. Nor-binaltorphimine dihydrochloride (a
kappa opioid receptor antagonist) did not suppress berberine-induced PP inhibition,
whereas ICI 174,864 (a delta opioid receptor antagonist) and CTOP (a mu opioid
receptor antagonist) did suppress the inhibitory effects of berberine. Pretreatment
with SQ-22536 (an adenylate cyclase inhibitor) or with KT-5720 (a protein kinase A
inhibitor) did not suppress the effects of berberine; however, pretreatment with
1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (a guanylate cyclase inhibitor) or
KT-5823 [a protein kinase G (PKG) inhibitor] did. In addition, berberine stimulated
cyclic guanosine monophosphate (cGMP) production in ICCs. These observations
indicate that berberine may inhibit the pacemaker activity of ICC clusters via ATP-
sensitive K+ channels and the cGMP-PKG-dependent pathway by stimulating mu and
delta opioid receptors. Therefore, berberine may provide a basis for the
development of novel agents for the treatment of GI motility dysfunction.
Psychological adaptation following homicide loss can prove more challenging for
grievers than other types of losses. Although social support can be beneficial in
bereavement, research is mixed in terms of identifying whether it serves as a
buffer to distress following traumatic loss. In particular, studies have not parsed
out specific domains of social support that best predict positive bereavement
outcomes. Recruiting a sample of 47 African Americans bereaved by homicide, we
examined six types of social support along with the griever's perceived need for or
satisfaction with each and analyzed them in relation to depression, anxiety,
complicated grief, and posttraumatic stress disorder outcomes. Results of
multivariate analyses revealed that the griever's level of satisfaction with
physical assistance at the initial assessment best predicted lower levels of
depression, anxiety, and posttraumatic stress disorder levels 6 months later, while
less need for physical assistance predicted lower complicated grief at follow-up.
Clinical implications and suggestions for future research are discussed.
Mental health issues have been increasingly recognized as public health problems
globally. Their burden is projected to increase over the next several decades.
Additional therapies for mental problems are in urgent need worldwide due to the
limitations and costs of existing healthcare approaches. Essential oil aromatherapy
can provide a cost-effective and safe treatment for many mental problems. This
pilot study observed the effects of bergamot essential oil inhalation on mental
health and well-being, as measured by the Positive and Negative Affect Scale, in a
mental-health treatment center located in Utah, USA. Fifty-seven eligible
participants (50 women, age range: 23-70years) were included for analysis. Fifteen
minutes of bergamot essential oil exposure improved participants' positive feelings
compared with the control group (17% higher). Unexpectedly, more participants
participated in experimental periods rather than control periods, suggesting even
brief exposure to essential oil aroma may make people more willing to enroll in
clinical trials. This study provides preliminary evidence of the efficacy and
safety of bergamot essential oil inhalation on mental well-being in a mental health
treatment center, suggesting that bergamot essential oil aromatherapy can be an
effective adjunct treatment to improve individuals' mental health and well-being.
(c) 2017 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
It has been shown in vitro that only specific dietary fibers contribute to
immunity, but studies in vivo are not conclusive. Here, we investigated degree of
polymerization (DP) dependent effects of beta 2 ->1-fructans on immunity via
microbiota-dependent and-independent effects. To this end, conventional or germ-
free mice received short-or long-chain beta 2 ->1-fructan for 5 days. Immune cell
populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs)
were analyzed with flow cytometry, genome-wide gene expression in the ileum was
measured with microarray, and gut microbiota composition was analyzed with 16S rRNA
sequencing of fecal samples. We found that beta 2 ->1-fructans modulated immunity
by both microbiota and microbiota-independent effects. Moreover, effects were
dependent on the chain-length of the beta 2 ->1-fructans type polymer. Both short-
and long-chain beta 2 ->1-fructans enhanced T-helper 1 cells in PPs, whereas only
short-chain beta 2 ->1-fructans increased regulatory T cells and
CD11b(-)CD103(-)dendritic cells (DCs) in the MLN. A common feature after short-and
long-chain beta 2 ->1-fructan treatment was enhanced 2-alpha-L-fucosyltransferase 2
expression and other IL-22-dependent genes in the ileum of conventional mice. These
effects were not associated with shifts in gut microbiota composition, or altered
production of short-chain fatty acids. Both short-and long-chain beta 2 ->1-
fructans also induced immune effects in germ-free animals, demonstrating direct
effect independent from the gut microbiota. Also, these effects were dependent on
the chain-length of the beta 2 ->1-fructans. Short-chain beta 2 ->1-fructan induced
lower CD80 expression by CD11b(-)CD103(-) DCs in PPs, whereas long-chain beta 2 -
>1-fructan specifically modulated B cell responses in germ-free mice. In
conclusion, support of immunity is determined by the chemical structure of beta 2 -
>1-fructans and is partially microbiota independent.
Interferon beta (IFNb) preparations are commonly used as first-line therapy in
relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by
limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.
In this pilot study, we assessed with the ELISA method the presence of the binding
antibodies (BAbs) against interferon beta after 2 years of therapy with
subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were
established again within 1 year after treatment withdrawal. We used 3 interferons
that are commercially available for MS therapy, namely Avonex (Biogen Idec
Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens. BAbs
reacting with Rebif were found in 24.4% to 55% of patients, depending on the units
of their expression. The levels of anti-ebif antibodies remained high in 8 patients
and in 4 patients they dropped significantly. Strong correlations were obtained in
all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-
anti-Avonex) and the existence of cross-reactivity in the formation of antibodies
against all the tested formulations of interferon beta was confirmed. The levels of
BAbs remain significant in the clinical context, and their assessment is the first
choice screening; however, methods of BAbs evaluation can be crucial for further
decisions. More studies are needed to confirm our results; specifically it would be
of interest to evaluate methods of neutralizing antibodies identification, as we
only assessed the binding antibodies. Nevertheless, our results support the concept
that in interferon nonresponders, that are positive for binding antibodies,
switching the therapy to alternative disease-modifying agent (for example
glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to
another interferon formulation will probably be of no benefit.
Plant beta-1, 3-glucanases are involved in plant defense and in development. Very
little data are available on the expression of rice glucanases both in
developmental tissues and under various stresses. In this study, we cloned and
characterized twenty-seven rice beta-1, 3-glucanases (OsGlu) from at total of 71
putative glucanases. The OsGlu genes were obtained by PCR from a cDNA library and
were classified into seven groups (Group I to VII) according to their DNA or amino
acid sequence homology. Analysis of the expression of the twenty-seven OsGlu genes
by Northern blotting revealed that they were differentially expressed in different
developmental tissues as Well as in response to plant hormones, biotic stress, high
salt etc. OsGlu11 and 27 in Group IV were clearly expressed only in stem and leaf
and were also induced strongly by SA (5 mM), ABA (200 mu M), and M. grisea. OsGlu1,
10, 11, and 14 were induced earlier and to higher levels in incompatible M. grisea
interaction than in compatible one. Taken together, our findings suggest that the
twenty-seven rice OsGlu gene products play diverse roles not only in plant defense
but also in hormonal responses and in development.
Backgound: beta-Carotene exhibits biological activity as provitamin A. Key step in
vitamin A formation is the cleavage of beta-carotene to retinal by an enzyme
designated as beta-carotene 15,15'-monooxygenase (BCM). Recently, it is reported
that expression of BCM gene in the intestine is under feedback regulation by
retinoic acid (RA). However, the regulation of BCM gene expression in various other
tissues is still unknown. Aim of the study: In the present study, we identified the
full-length cDNA encoding the rat BCM gene and investigated the regulation of its
expression in several tissues by RA in the presence of vitamin A deficiency.
Methods: We cloned the full-length cDNA encoding BCM gene from a rat intestinal
cDNA library by hybridization screening. The BCM gene expression was examined using
Northern blotting and reverse transcription-PCR analysis. We also investigated
whether BCM gene expression was regulated by retinoids in several tissues of
vitamin A-deficient rats. Results: Sequence analysis of this clone revealed an open
reading frame of 1,701 bases encoding a protein of 566 amino acids. The predicted
polypeptide showed 94%, 81%, and 66% identity with mouse, human, and chicken BCM,
respectively. Rat BCM mRNA was highly expressed in the intestine and liver, while
there was weak expression in the testes, kidneys, and lungs. Immunoblotting
revealed that rat BCM is a 64-kDa protein. BCM gene expression was increased in the
small intestine by vitamin A deficiency compared with that in rats on a control
diet, while this upregulation was suppressed by all-trans RA (ATRA) or 9-cis RA (9-
cis RA). BCM gene expression in the lungs and testes was also suppressed by ATRA or
9-cis RA in rats with vitamin A deficiency. However, hepatic BCM gene expression
was only decreased by ATRA and renal expression was not affected by either
retinoid. As the small intestine is the major site of beta-carotene conversion,
intestinal BCM gene expression may be more tightly regulated. Conclusion: These
data suggest that BCM gene expression in several tissues may be down-regulated by
RA at the level of conversion of beta-carotene to retinal. To prevent an excess of
retinol, homeostasis may occur at the level of conversion of beta-carotene to
retinal in several tissues.
To efficiently express a gene of interest in transgenic plants, the choice of
promoter is a crucial factor as it directly affects the expression of the transgene
that will yield the desired phenotype. The Arabidopsis beta-carotene hydroxylase 1
gene (AtBch1) shows constitutive and ubiquitous expression and was thus selected as
one of best candidates for constitutive promoter analysis by both in silico
northern blotting and semi-quantitative RT-PCR analysis. To investigate AtBch1
promoter activity, the 1,981-bp 5'-upstream region of this gene was fused with
beta-glucuronidase (GUS) and transformed into Arabidopsis. Through the molecular
characterization of transgenic leaf tissues, the AtBch1 promoter generated strong
activity that drives 1.8- and 2-fold higher GUS expression than the cauliflower
mosaic virus 35S (35S) promoter at the transcriptional and translational levels,
respectively. Furthermore, the GUS enzyme activity driven by the AtBch1 promoter
was 2.8-fold higher than that produced by the 35S promoter. By histochemical GUS
staining, the ubiquitous expression of the AtBch1 promoter was observed in all
tissues of Arabidopsis. Semi-quantitative RT-PCR analysis with different tissues
further showed that this promoter serves as a strong constitutive driver of
transgene expression in dicot plants.
This work was conducted to prepare beta-caryophyllene-hydroxypropyl-beta-
cyclodextrin inclusion complex (HP beta CD/BCP) and investigate its effects and
mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HP beta
CD/BCP was prepared, optimized, characterized, and evaluated. HP\CD/BCP and AM630
were then administered to VD rats to upregulate and downregulate the cannabinoid
receptor type 2 (CB2). Results showed that HP beta CD/BCP can significantly
increase the bioavailability of BCP. Through the Morris water maze test, HP beta
CD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow
(CBF) monitoring results indicated that HP beta CD/BCP can promote the recovery of
CBF. Moreover, molecular biology experiments showed that HP beta CD/BCP can
increase the expression levels of CB2 in brain tissues, particularly the
hippocampus and white matter tissues, as well as the expression levels of PI3K and
Akt. Overall, the findings demonstrated the protective effects of HP beta CD/BCP
against cognitive deficits induced by chronic cerebral ischemia and suggested the
potential of HP beta CD/BCP in the therapy of vascular dementia in the future.
A novel type of pH-responsive star polymer based on beta-cyclodextrin (beta-CD) was
synthesized and further covalently conjugated with enzyme. The impact of its self-
assembly behavior on enzyme activity was investigated. In our design, azide
containing the polymer (N-3)(7)-beta-CD-(PtBA)(14) was synthesized via atom
transfer radical polymerization of tert-butyl acrylate using (N-3)(7)-beta CD-(Br)
(14) as the multifunctional initiator. The final product (N-3)(7)-beta-CD-(PAA)(14)
was obtained via hydrolysis and covalently conjugating pectinase onto pH-responsive
polyacrylic acid (PAA) arms. PAA can change its conformation with the self-assembly
by altered pH, leading its nanostructure into micellar nanoparticles in aqueous
solution and further affecting the activity of immobilized pectinase. The results
were proved by fluorescence spectroscopy and dynamic light scattering. This system
proves that the activity of immobilized enzyme can be tailored predictably, and
this pH-responsive polymer holds great potential for controllable delivery of
enzymes. (C) 2016 International Union of Biochemistry and Molecular Biology, Inc.
Aims: We investigated the mechanism(s) by which valsartan, a selective antagonist
of angiotensin subtype 1 (AT(1)) receptor, decreased plasma glucose in
streptozotocin (STZ)-induced diabetic rats. Methods: The plasma glucose
concentration was assessed by the glucose oxidase method. The concentration of
beta-endorphin in plasma or medium incubating adrenal medulla was measured using an
enzyme-linked immunosorbent assay. The mRNA levels of the subtype 4 form of glucose
transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK)
in the liver were detected by Northern blotting analysis, while the protein levels
of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using
Western blotting analysis. Results: A single intravenous injection of valsartan
dose-dependently increased plasma beta-endorphin-like immunoreactivity (BER) in
parallel with the lowering of plasma glucose concentration in STZ-induced diabetic
rats. Naloxone and naloxonazine inhibited the plasma glucose-lowering action of
valsartan at doses sufficient to block opioid mu-receptors. In contrast to its
action in wild-type diabetic mice, valsartan failed to modify plasma glucose in
opioid mu-receptor knockout diabetic mice. Bilateral adrenalectomy in STZ-induced
diabetic rats eliminated both the plasma glucose-lowering action and the plasma
BER-elevating action of valsartan. In the isolated adrenal medulla of STZ-induced
diabetic rats, angiotensin II (Ang II) or valsartan did not affect spontaneous BER
secretion. Activation of cholinergic receptors by 1.0 mu mol/l acetylcholine (ACh)
enhanced BER secretion from the isolated adrenal medulla of STZ-induced diabetic
rats, but not in the presence of 1.0 nmol/l Ang II, while valsartan reversed this
inhibition by Ang II in a concentration-dependent manner. Treatment of STZ-induced
diabetic rats with valsartan (0.2 mg/kg) three times daily for 3 days resulted in
an increase in gene expression of GLUT4 in soleus muscle and impeded the reduction
of elevated mRNA or protein level of hepatic PEPCK. Both of these effects were
blocked by opioid mu-receptor antagonist. Conclusions: The results suggest that
blockade of AT(1) receptor by valsartan may enhance the adrenal beta-endorphin
secretion induced by ACh, activating the opioid mu-receptors to increase glucose
utilization and/or to decrease hepatic gluconeogenesis, resulting in the reduction
of plasma glucose in STZ-induced diabetic rats.
Endonuclease cleavage is the rate-limiting step in the decay of nonsense-containing
human beta-globin mRNA in erythroid cells. The 5'-truncated intermediates thus
generated are polyadenylated and more stable than the parent mRNA. Northern
blotting is commonly used to measure the decay rate of full-length mRNA, and S1
nuclease protection is used to assay the fate of decay intermediates. We have
adapted the more sensitive and facile MBRACE assay (Lasham et al., Nucleic Acids
Res 38: e19, 2010) to quantitatively monitor the decay process by detecting full-
length beta-globin and its decay intermediates.
Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine
widely used for improving sports performance. Although limp is recognized to
promote anabolic or anti-catabolic effects on protein metabolism, the impact of its
long-term use on skeletal muscle and/or genes that control the skeletal protein
balance is not fully known. This study aimed to investigate whether chronic HM beta
treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and
myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or
vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected
for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of
pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected
for total RNA or protein extraction to evaluate the expression of pituitary growth
hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I)
mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR,
or Western blotting. Results: Chronic HM beta treatment increased the content of
pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No
changes were detected on skeletal muscle IGF-I and myostatin mRNA expression.
However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia.
Conclusions: The data presented herein extend the body of evidence on the potential
role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this
effect, HM beta supplementation also induces an apparent insulin resistance state
which might limit the beneficial aspects of the former results, at least in rats
under normal nutritional status and health conditions. (C) 2010 Growth Hormone
Research Society. Published by Elsevier Ltd. All rights reserved.
Although large numbers of long noncoding RNAs (IncRNAs) expressed in the mammalian
nervous system have been detected, their functions and mechanisms of regulation
remain to be fully clarified. It has been reported that the IncRNA antisense
transcript for beta-secretase-1 (BACE1-AS) is elevated in Alzheimer's disease (AD)
and drives the rapid feed-forward regulation of p-secretase, suggesting that it is
critical in AD development. In the present study, the senile plaque (SP) AD SH-SY5Y
cell model was established using the synthetic amyloid beta-protein (A beta) 1-42
in vitro. Using this model, the potential of siRNA-mediated silencing of IncRNA
BACE1-AS expression to attenuate the ability of beta-secretase-1 (BACE1) to cleave
amyloid precursor protein (APP) and to reduce the production of A beta(1-42)
oligomers was investigated. MTT assays demonstrated that exogenous A beta(1-42)
suppressed SH-SY5Y cell proliferation and induced APP-related factor expression and
SP formation: Furthermore, quantitative polymerase chain reaction and western blot
analysis revealed that the mRNA and protein expression of A beta(1-42) and A
beta(1-40) was significantly increased in the AD model group, with a marked
decrease in Ki-67 expression at day six. RNase protection assays (RPA) and northern
blotting analysis confirmed that exogenous A beta(1-42) not only promoted the
expression of the APP-cleaving enzyme BACE1, but also induced IncRNA BACE1-AS
expression. Furthermore, IncRNA BACE1-AS formed RNA duplexes and increased the
stability of BACE1 mRNA. Downregulation of IncRNA BACE1-AS expression in SH-SY5Y
cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to
cleave APP and delayed the induction of SP formation in the SP AD SH-SY5Y cell
model.
Recently, we discovered that beta-thujaplicin (BT) induces metallothionein (MT)
expression in mouse ker- atinocytes, both in vivo and in vitro. However, the
molecular mechanisms by which BT exerts its biological effects have not been
elucidated. The purpose of this study is to explore the signal transduction pathway
involved in the MT mRNA induction by BT. Using a HaCaT keratinocyte cell line,
Northern blotting was performed for analyzing the human MT-IIA mRNA expression
levels in combination with BT and a number of protein kinase (PK) in hibitors
including H7, HA1004 and a PKC-specific inhibitor chelerythrin. CAT assays with the
MT-IIA gene promorter-CAT construct were conducted for examining the
transcriptional regulation by BT of MT. A free radical scavenger N-acetylcysteine
(NAC) was used for analyzing a role of oxidative stress for the MT gene induction
by BT. BT increased MT-IIA gene transcript levels and CAT activity in a dose-
dependent fashion in HaCaT cells. The increase in MT-IIA mRNA levels and CAT
activity were completely suppressed by H7 but not by HA1004. In addition,
chelerythrin prevented BT-inducible MT-IIA promoter activation. Furthermore, NAC
suppressed BT4 inducible MT-IIA promoter activation. These results demonstrate that
BT is a potent activator of the MT-IIA gene promoter and that PKC activation and
reactive oxygen species are implicated in BT-inducible MT-IIA gene expression. BT
may be a useful tool for dissecting the signal transduction pathway mediating MT-
IIA promoter activation.
BackgroundRetinoblastoma is the most common malignant cancer of the eye in
children. Although metastatic retinoblastoma is rare, cure rates for this advanced
disease remain below 50%. High-level polo-like kinase 1 expression in
retinoblastomas has previously been shown to be correlated with adverse outcome
parameters. Polo-like kinase 1 is a serine/threonine kinase involved in cell cycle
regulation at the G2/M transition. Polo-like kinase 1 inhibition has been
demonstrated to have anti-tumour effects in preclinical models of several
paediatric tumours. Here, we assessed its efficacy against retinoblastoma cell
lines. MethodsExpression of polo-like kinase 1 was determined in a panel of
retinoblastoma cell lines by polymerase chain reaction and western blot analysis.
We analysed viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) (MTT assay), proliferation (5-bromo-2'-deoxyuridine enzyme-linked
immunosorbent assay), cell cycle progression (propidium iodid staining) and
apoptosis (cell death enzyme-linked immunosorbent assay) in three retinoblastoma
cell lines after treatment with two adenosine triphosphate-competitive polo-like
kinase 1 inhibitors, BI6727 or GSK461364. Activation of polo-like kinase 1
downstream signalling components including TP53 were assessed. ResultsTreatment of
retinoblastoma cells with either BI6727 or GSK461364 reduced cell viability and
proliferative capacity and induced both cell cycle arrest and apoptosis. Polo-like
kinase 1 inhibition also induced the p53 signalling pathway. Analysis of key
players in cell cycle control revealed that low nanomolar concentrations of either
polo-like kinase 1 inhibitor upregulated cyclin B1 and increased activated cyclin-
dependent kinase 1 (phosphorylated at Y15) in retinoblastoma cell lines.
ConclusionsThese preclinical data indicate that polo-like kinase 1 inhibitors could
be useful as components in rationally designed chemotherapy protocols to treat
patients with metastasized retinoblastoma in early phase clinical trials.
The paper aims to determine the day-ahead market bidding strategies for retailers
with flexible demands to maximize the short-term profit. It proposes a short-term
planning framework to forecast the load under dynamic tariffs and construct biding
curves. Stochastic programming is applied to manage the uncertainties of spot
price, regulating price, consumption behaviors, and responsiveness to dynamic
tariffs. A case study based on data from Sweden is carried out. It demonstrates
that a real-time selling price can affect the aggregate load of a residential
consumer group and lead to load shift toward low-price periods. The optimal bidding
curves for specific trading periods are illustrated. Through comparing the bidding
strategies under different risk factors, the case study shows that a risk-averse
retailer tends to adopt the strategies with larger imbalances. The benefit lies in
the reduction of low-profit risk. However, the aversion to risk can only be kept in
a certain level. A larger imbalance may lead to a quick reduction of profit in all
scenarios.
This paper presents a new approach for determining the day-ahead bidding strategies
of a large-scale hybrid electric energy company. The company has both energy
generation and energy retailing businesses in a competitive electricity market.
Demand response programs are also considered in the retail side of the company in
order to hedge the risk of participation in wholesale market. This paper introduces
a max-min bilevel mathematical programming with equilibrium constraint model for
offering a strategy that manages the risk of uncertain forecasted rivals' bids by
robust optimization. The max-min bilevel model is converted to its equivalent
single-level optimization using Karush-Kuhn-Tucker optimality conditions. The
duality theory is utilized to find the equivalent ordinary maximization model of
the max-min problem. Strong duality theory and big M method are also used to
linearize the final model of offering strategy. Applicability of the proposed
approach is shown by implementing it on the IEEE 118-bus test system.
This paper presents a novel interleaved high-conversion-ratio bidirectional dc-dc
converter based on switched capacitors and coupled inductors. Series-connected
switched capacitor and inductor cells were used to increase the voltage conversion
ratio, reduce voltage stresses on power switches, realize soft-charging/discharging
of switched capacitors, and achieve autocurrent-sharing in parallel inductors. The
interleaved structure combined with switched capacitors was adopted to reduce
current ripple at the side having lower voltage, thus enabling applications that
require high power levels. In this paper, we first review the status of high-
voltage-ratio bidirectional dc-dc converters. Then, the evolution of the proposed
extensible topologies and the steady-state operating principle under the inductor
current continuous conduction mode is presented. Finally, the performance and
features such as voltage gain, voltage and current stress, and the autocurrent-
sharing mechanism that are realized by switched capacitors are verified; the
optimal design of coupled-inductors, switched-capacitors, and the chip size of
switches are given. A specific design of the driving circuit that facilitates
actual applications is described. A 1-kW prototype converter, employing a hybrid
configuration of SiC and Si MOSFETs, was constructed to verify the theoretical
analysis, and achieved an optimal compromise between conversion efficiency and low
cost.
The two-stage 48 V-12 V-1.8 V voltage regulator module (VRM) structure is gaining
more and more attention in high-end server applications. The LLC converter is the
preferred choice for the first conversion stage because it provides the isolated
12-V output efficiently, which is then converted to 1.8 V by the multi-phase Buck
converter. Since the CPU works in sleep-mode most of the time, the light-load
efficiency is very important for energy saving. This paper proposes to change the
primary side of the LLC converter from the full-bridge (FB) configuration into the
half-bridge (HB) configuration dynamically in the light-load condition, so that the
output of the LLC dc transformer (DCX) can be changed from 12 to 6 V. This will
increase the overall light-load efficiency significantly due to the reduced core
loss of the LLC DCX and the reduced switching loss of the multiphase Buck
converter. To achieve a fast transition of the bus voltage between 12 and 6 V, the
capacitance for the intermediate bus is properly selected and the optimal
trajectory control for transition between the FB configuration and HB configuration
is proposed. A high-efficiency high-density 48-12 /6 V LLC DCX is designed, and
experiments on the two-stage VRM demonstrate that there is a fast transient
response and a more than 10% light-load efficiency improvement.
This paper proposes a bidirectional three-level LLC resonant converter with a new
pulse width and amplitude modulation control method. With different control
signals, it has three different operation modes with different voltage gains.
Therefore, it can achieve wide voltage gain range by switching among these three
modes, which is attractive for energy storage system applications needing wide
voltage variation. The proposed topology operates with constant switching
frequency, which is easy to implement with digital control, and it can achieve soft
switching for all the switches and diodes in the circuit as a conventional LLC
resonant converter. The performance of the proposed converter is validated by the
experimental results from a 1-kW prototype with 20 A maximum output current.
Bifenthrin (BF) is a chiral pesticide with two enantiomers. In this work, its
stereoselective degradation was investigated in plants and domesticated active
sludge. Considering that the degradation to pesticides of plants was effected by
external conditions, hence, nanometer materials (gothite) were added into soil to
explore the effect of sorption on enantioselectivity in degradation of BF. The
microbial community that was responsible for BF-biodegrading in active sludge was
studied by polymerase chain reaction and denaturing gradient gel electrophoresis
(PCR-DGGE). In plant researches, chiral difference was discovered in the
degradation of pesticides that onions resulted in. The existence of gothite in soil
not only reduced the amount of BF that plants uptake from the environment, but it
also enlarged the chiral difference during the process, indicating that the
absorption of gothite to pesticides had enantioselectivity, which may be generated
by that adsorption site where BF combined with gothite located in the chiral center
of the pesticide. In studies of sludge, BF can be effectively degraded and decline
of both isomers followed first-order kinetics. However, there was no obvious
stereoselective degradation in domesticated sludge. The analysis of DGGE revealed
that active sludge maintained the rich microbial community in the whole process (H
>3). The H index increased in the early domestication, which may because BF had no
direct toxicity to the bacteria. The bacteria were able to degrade the small dose
of the pesticide and absorbed it as nutrition. The sequence results demonstrated
that the variety of bacteria grew, instead of Acidobacteria, Betaproteobacteria,
Sphingobacteriia and Alphaproteobacteria, Flavobacteria also appearing in sludge
after domestication.
The paper reviews the circuitry of differential stages (DSs) based on the elements
of radiation-hardened bipolar and field effect analog gate-array master chip
"AGAMC-1.3" (OJSC "Integral", Minsk city, Belarus). It suggests architectures of op
amps (OAs) realized on the base of BJTs-JFETs. Their feature lies in the absence of
classical reference current source setting a steady-state behavior of the input
transistors. It increases the radiation stability. The parameters of experimental
circuit of OA of this class IC-3, oriented for the use in sensor systems of
demanding application, are given.
The architectures of the operational amplifiers (OA), implemented on the basis on
bipolar and field (JFET) transistors, are offered. Their feature - the use of
transistors operating on different physical principles, precision in the input
circuits of differential stages (DS). This allows you to set a static DS mode due
to the choice of the geometric dimensions of field-effect transistors and to
exclude from structure of the classical sources of the reference current. The
circuit engineering and the basic circuits of inclusion of the differential
difference operational amplifiers (DDA), based on the analog gate-array master chip
AGAMC (OJSC "Integral", Minsk) with low offset voltages, are provided. Parameters
and topology of the experimental chip of OA of this class (IC-3) oriented on use in
the sensor systems of responsible application are given.
Efficiency in a light load dc-dc converter is improved by reducing the switching
frequency with the load current. Further, a bifrequency operation (BFO) using pulse
train (PT) control can achieve spread spectrum. Using discrete-time models, this
paper shows that a stable periodic BFO is generally not achievable in existing PT
control methods. Thereafter, a unified multimode digital control technique is
proposed, in which a voltage-mode digital pulse-width-modulator (DPWM) is used to
control a predefined periodic BFO. Beside the fixed-frequency DPWM, an extra
multiplexer is considered for real-time configuration to: 1) bifrequency pulse
frequency modulation; 2) PT control; or 3) pulse regulation control; or 4) pulse
skipping control with smooth transition. Analysis and design methods are discussed
to ensure periodic BFO and to customize the power spectrum with predictable ripple
parameters. A buck converter prototype is made, and the proposed control is
implemented using an FPGA device.
In order to find new insect resistance genes, four homologous cDNAs, hta-a, hta-b,
hta-c and hta-d with lengths of 775, 718, 784 and 752 bp, respectively (GenBank
accession numbers AF477031-AF477034), were isolated from a tuber cDNA expression
library of Helianthus tuberosus L. Sequence analysis revealed that all four cDNAs
contain an open reading frame of 444 bp, coding a polypeptide of 147 amino acid
residues, and that the sequences of the cDNAs are very similar to those of the
mannose-binding agglutinin genes of the jacalin-related family. In hemagglutination
reactions and hapten inhibition assays, affinity-purified HTA (Helianthus tuberosus
agglutinin) from induced Escherichia coli BL21(DE3) expressing GST-HTA shows
hemagglutination ability and a higher carbohydrate-binding ability for mannose than
other tested sugars. Trypsin inhibitory activity was detected in the crude extracts
of induced E. coli BL21(DE3) expressing HTA, and was further verified by trypsin
inhibitory activity staining on native polyacrylamide gel. The mechanism of
interaction between HTA and trypsin was studied by molecular modeling. We found
that plenty of hydrogen bonds and electrostatic interactions can be formed between
the supposed binding sites of HTA-b and the active site of trypsin, and that a
stable HTA/trypsin complex can be formed. The results above imply that HTA might be
a bifunctional protein with carbohydrate-binding activity and trypsin inhibitory
activity. Moreover, Northern blotting analysis demonstrated that hta is
predominantly expressed in tubers of H. tuberosus, very weakly expressed in stems,
but not expressed at all in other tissues. Southern blotting analysis indicated
that hta is encoded by a multi-gene family. The insect resistance traits have been
described in another paper.
DC distribution power systems are vulnerable to instability because of the
destabilizing effect of converter-controlled constant power loads (CPLs) and input
filters. Standard stability analysis tools based on averaging linearization
techniques can be used only when the switching frequency of the converter is
significantly higher than the cutoff frequency of the filter. However, dc
distribution systems with a reduced size filter, and consequently a high cutoff
frequency, are common in transportation applications. Conventional methods fail to
detect instabilities in the system because they do not take into account the
switching effect. To overcome this drawback, this paper proposes a discrete-time
method to analyze the stability of dc distribution systems. This model is applied
here to a dc power system with a CPL. The switching effects and the nonlinearities
of the system model are taken into account with a simple discretization approach.
The proposed method is able to predict the dynamic properties of the system, such
as slow-scale and fast-scale instabilities. An active stabilizer is also included
in the system model in order to extend the stability margin of the system. Finally,
these observations are validated experimentally on a laboratory test bench.
We report a five-component autonomous chaotic oscillator of jerky type, hitherto
the simplest of its kind, using only one operational amplifier. The key component
of the circuit is a junction field-effect transistor operating in its triode
region, which provides a nonlinear resistor of antisymmetrical current-voltage
characteristic, emulating a Colpitts-like chaotic circuit. We describe the
experimental results illustrating the dynamical behavior of the circuit. In
addition, we report numerical simulations of a model of the circuit which display
good agreement with our measurements.
Smart meters play vital roles in the aspects of the management and operation of
smart grids such as demand response, energy efficiency improvement, and electricity
pricing. Massive amounts of data are being collected owing to the popularity of
smart meters. Two main issues should be addressed in this context. One is the
communication and storage of big data from smart meters at reduced cost. The other
is the effective extraction of useful information from this massive dataset. In
this paper, the K-SVD sparse representation technique, which includes two phases
(dictionary learning and sparse coding), is used to decompose load profiles into
linear combinations of several partial usage patterns (PUPs), which allows the
smart meter data to be compressed and hidden electricity consumption patterns to be
extracted. Then, a linear support vector machine (SVM) based method is used to
classify the load profiles into two groups, residential customers and small and
medium-sized enterprises (SMEs), based on the extracted patterns. Comprehensive
comparisons with the results of k-means clustering, the discrete wavelet transform
(DWT), principal component analysis (PCA), and piecewise aggregate approximation
(PAA) are conducted on real datasets in Ireland. The results show that our proposed
technique outperforms these methods in both compression ratio and classification
accuracy.
Precision medicine is a new strategy that aims at preventing and treating human
diseases by focusing on individual variations in people's genes, environment and
lifestyle. Precision medicine has been used for cancer diagnosis and treatment and
shows evident clinical efficacy. Rapid developments in molecular biology, genetics
and sequencing technologies, as well as computational technology, has enabled the
establishment of "big data", such as the Human Genome Project, which provides a
basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an
aggressive cancer with a high incidence rate and low survival rate. Current
therapies are often aggressive and carry considerable side effects. Much research
now indicates that precision medicine can be used for HNSCC and may achieve
improved results. From this perspective, we present an overview of the current
status, potential strategies, and challenges of precision medicine in HNSCC. We
focus on targeted therapy based on cell the surface signaling receptors epidermal
growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human
epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and
RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of
HNSCC is also discussed.
Disease has an effect on crop yields, causing significant losses. As the worldwide
demand for agricultural products increases, there is a need to pursue the
development of new methods to protect crops from disease. One mechanism of plant
protection is through the activation of the plant immune system. By exogenous
application, 'plant activator molecules' with elicitor properties can be used to
activate the plant immune system. These defence-inducing molecules represent a
powerful and often environmentally friendly tool to fight pathogens. We show that
the secondary bile acid deoxycholic acid (DCA) induces defence in Arabidopsis and
reduces the proliferation of two bacterial phytopathogens: Erwinia amylovora and
Pseudomonas syringae pv. tomato. We describe the global defence response triggered
by this new plant activator in Arabidopsis at the transcriptional level. Several
induced genes were selected for further analysis by quantitative reverse
transcription-polymerase chain reaction. We describe the kinetics of their
induction and show that abiotic stress, such as moderate drought or nitrogen
limitation, does not impede DCA induction of defence. Finally, we investigate the
role in the activation of defence by this bile acid of the salicylic acid
biosynthesis gene SID2, of the receptor-like kinase family genes WAK1-3 and of the
NADPH oxidase-encoding RbohD gene. Altogether, we show that DCA constitutes a
promising molecule for plant protection which can induce complementary lines of
defence, such as callose deposition, reactive oxygen species accumulation and the
jasmonic acid and salicylic acid signalling pathways.
Accumulation of hydrophobic bile acids in the liver contributes to cholestatic
liver injury. Inflammation induced by excessive bile acids is believed to play a
crucial role, however, the mechanisms of bile acids triggered inflammatory response
remain unclear. Recent studies have highlighted the effect of NLRP3 inflammasome in
mediating liver inflammation and fibrosis. In this study, we for the first time
showed that chenodeoxycholic acid (CDCA), the major hydrophobic primary bile acid
involved in cholestatic liver injury, could dose-dependently induce NLRP3
inflammasome activation and secretion of pro-inflammatory cytokine-IL-1 beta in
macrophages by promoting ROS production and K+ efflux. Mechanistically, CDCA
triggered ROS formation in part through TGR5/EGFR downstream signaling, including
protein kinase B, extracellular regulated protein kinases and c-Jun N-terminal
kinase pathways. Meanwhile, CDCA also induced ATP release from macrophages which
subsequently causes K+ efflux via P2X7 receptor. Furthermore, in vivo inhibition of
NLRP3 inflammasome with caspase-1 inhibitor dramatically decreased mature IL-1 beta
level of liver tissue and ameliorated liver fibrosis in bile duct ligation (BDL)
mouse model. In conclusion, excessive CDCA may represent an endogenous danger
signal to activate NLRP3 inflammasome and initiate liver inflammation during
cholestasis. Our finding offers a mechanistic basis to ameliorate cholestatic liver
fibrosis by targeting inflammasome activation.
Worldwide natural gas consumption has increased significantly, especially for power
generation in electricity systems with the gas-to-power (G2P) process of natural
gas fired units. Supply for both natural gas and electricity systems should be
dispatched economically and simultaneously due to their firm interconnection. This
paper proposes a security-constrained bi-level economic dispatch (ED) model for
integrated natural gas and electricity systems considering wind power and power-to-
gas (P2G) process. The upper level is formulated as an ED optimization model for
electricity system, while the lower level is an optimal allocation problem for
natural gas system. Natural gas system is modeled in detail. In addition, the
security constraints and coupling constraints for the integrated energy systems are
considered. The objective function is to minimize the total production cost of
electricity and natural gas. The lower model is converted and added into the upper
model as Karush-Kuhn-Tucher (KKT) optimality conditions, thus the bi-level
optimization model is transformed into a mix-integer linear programming (MILP)
formulation. Numerical case studies on the PJM-5bus system integrated with a seven-
node gas system and IEEE 118-bus system integrated with a modified Belgian high-
calorific gas system demonstrate the effectiveness of the proposed bi-level ED
model. (C) 2016 Elsevier Ltd. All rights reserved.
This paper describes a variable output voltage, multi-phase switched capacitor
step-up DC-DC converter with a digital voltage regulation scheme, implemented in
CMOS VLSI technology. The number of conversion ratios generated using n flying
capacitors is of the order of 2(n). A scheme for selection of switch is presented.
Expressions for equivalent series resistance (Req), conduction, switching power
loss and efficiency are obtained and compared with the cadence spectre simulation
results. The step-up open loop converter circuit for one of the gain is described
and analysed by varying the switching frequency. An open loop converter efficiency
of about 78% is achieved with 4% bottom plate parasitic capacitance for a load
current of 1 mA and input voltage of 0.6 V at 4 MHz of switching frequency for a
gain of 4/3. The voltage regulation scheme for a desired output voltage is designed
with a digital control circuit using inherent capacitive DAC which can interpolate
through various gain configuration for n = 2 flying capacitor and is simulated in
Cadence Analog-Mixed Signal Flow using 180nm CMOS technology. The layout design
using MIM cap has been done and back annotation results are presented.
Destination memory refers to the ability to remember to whom a piece of information
was previously transmitted. Our paper assessed this ability in schizophrenia.
Twenty-five patients with schizophrenia and 25 control participants told proverbs
(e.g., "send a thief to catch a thief") to pictures of celebrities (e.g., Elvis
Presley). Afterward, participants had to indicate to which celebrity they had
previously said the proverbs. Participants also completed a binding task in which
they were required to associate letters with their corresponding context (i.e.,
location). Analysis revealed worse destination memory and binding in patients with
schizophrenia than in controls. In both populations, destination memory was
significantly correlated with performances on the binding task. Our findings
suggest difficulty in the ability to attribute information to its appropriate
destination in schizophrenia. This difficulty may be related to compromise in
binding separate cues together to form a coherent representation of an event in
memory.
Background: A 12-month, open-label extension study assessed the long-term safety
and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating
disorder (BED). Methods: Adults (aged 18-55 y) with BED who completed 1 of 3
antecedent studies were enrolled in a 52-week, open-label extension study (dose
optimization, 4 weeks [initial titration dose, 30-mg LDX; target doses, 50-or 70-mg
LDX]; dose maintenance, 48 weeks). Safety evaluations included the occurrence of
treatment-emergent adverse events (TEAEs), vital sign and weight assessments, and
Columbia-Suicide Severity Rating Scale responses. Results: Of the 604 enrolled
participants, 599 (521 women and 78 men) comprised the safety analysis set, and 369
completed the study. Mean (SD) LDX exposure was 284.3 (118.84) days; cumulative LDX
exposure duration was 12 months or longer in 344 participants (57.4%). A total of
506 participants (84.5%) reported TEAEs (TEAEs leading to treatment
discontinuation, 54 [9.0%]; severe TEAEs, 42 [7.0%]; serious TEAEs, 17 [2.8%]).
Treatment-emergent adverse events reported in greater than or equal to 10% of
participants were dry mouth (27.2%), headache (13.2%), insomnia (12.4%), and upper
respiratory tract infection (11.4%). Mean (SD) changes from antecedent study
baseline in systolic and diastolic blood pressure, pulse, and weight at week
52/early termination (n = 597) were 2.19 (11.043) and 1.77 (7.848) mm Hg, 6.58
(10.572) beats per minute, and -7.04 (7.534) kg, respectively. On the Columbia-
Suicide Severity Rating Scale, there were 2 positive responses for any active
suicidal ideations; there were no positive responses for suicidal behavior or
completed suicides. Conclusions: In this 12-month, open-label, extension study, the
long-term safety and tolerability of LDX in adults with BED were generally
consistent with its established profile for attention-deficit/hyperactivity
disorder.
ObjectiveThis study aims to evaluate the theory of mind ability in a sample of
obese patients with and without binge eating disorder (BED) and to explore the
correlations between emotional and clinical assessments. MethodsOverall, 20 non-
BED, 16 under-threshold BED and 22 BED obese patients completed a battery of tests
assessing social cognition and eating disorder psychopathology. ResultsBinge eating
disorder, non-BED and under-threshold-BED obese patients showed similar ability to
recognise others' emotions, but BED obese patients exhibited a deficit in
recognising their own emotions as demonstrated by more impaired levels of
alexithymia and interoceptive awareness and were more depressed. High positive
correlations were evident between binging, depression, interoceptive awareness and
alexithymia. ConclusionsBinge eating disorder patients have a comparable ability to
understand others' emotions but a more impaired capacity to understand and code
their own emotions compared with non-BED obese patients. This impairment is highly
correlated with depression. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating
Disorders Association.
This study presents a bioacoustic sensor system developed for early detection of
the recovery of bowel activity after abdominal surgery and to perform analysis on
bowel sounds. Different than other studies, in order to be able to attenuate noise,
two capacitive microphones oriented in opposite directions are used. Bowel sounds
are typically observed at a frequency between 100 Hz and 1500 Hz and amplitude
between 0 and 20mV. The signal strength is boosted 48 times with an amplifying
circuit. The second microphone is used to observe environmental noise such as
examination room noise. Both signals are digitized using an ADC (NI DAQ Data
Acquisition USB 6009). Finally, we developed a software that can extract spectral
properties of the signal and present the results in real time.
Reclamation of wastewater (WW) for irrigation, after treatment represents a
challenge that could alleviate pressure on water resources and address the
increasing demand for agriculture. However, the risks to human health must be
assessed, particularly those related to human enteric viruses that resist standard
treatments in most wastewater treatment plants (WWTP). The risks associated with
exposure to viral bioaerosols near WWTP and near agricultural plots irrigated with
WW are poorly documented. The objectives of this study were to 1) better
characterize human enteric viruses found in bioaerosols near a "standardWWTP" and
over fields irrigated with treated WW and 2) propose a numeric model to assess the
health risk to populations located close to the irrigated areas, with particular
attention to norovirus, which is responsible for most viral gastroenteritis in
France. Water and air samples were collected at various locations in the largest
French WW-irrigated site near Clermont-Ferrand, at the WWTP entrance and after
treatment, in the air above activated sludge basins, and above fields irrigated
with WW. Various enteric viruses were found in the water samples collected both
before and after treatment. Norovirus was the most abundant with >10e4 genome
copies/l (GC/L) before treatment and similar to 10e3 GC/L after treatment. Low
quantities (= 3 m/s) and a constant emission rate of 8e3 GC/m(3)/s. This
probability decreases by 3 log when the distance to the emission source is doubled.
This information can aid development of safe water reuse policies in terms of local
setback distance and wind conditions for wastewater reuse. (C) 2017 Elsevier B.V.
All rights reserved.
Synergistic effects of multiple plant secondary metabolites on upper trophic levels
constitute an underexplored but potentially widespread component of coevolution and
ecological interactions. Examples of plant secondary metabolites acting
synergistically as insect deterrents are not common, and many studies focus on the
pharmaceutical applications of natural products, where activity is serendipitous
and not an evolved response. This review summarizes some systems that are ideal for
testing synergistic plant defenses and utilizes a focused meta-analysis to examine
studies that have tested effects of multiple compounds on insects. Due to a dearth
of ecological synergy studies, one of the few patterns for synergy that we are able
to report from the meta-analysis is that phytochemical mixtures have a larger
overall effect on generalist herbivores than specialist herbivores. We recommend a
focus on synergy in chemical ecology programs and suggest future hypothesis tests
and methods. These approaches are not focused on techniques in molecular biology to
examine mechanisms at the cellular level, rather we recommend uncovering the
existence of synergy first, by combining the best methods in organic synthesis,
isolation, chemical ecology, bioassays, and quantitative analyses. Data generated
by our recommended methods should provide rigorous tests of important hypotheses on
how intraclass and interclass compounds act synergistically to deter insects,
disrupt the immune response, and ultimately contribute to diversification. Further
synergy research should also contribute to determining if antiherbivore synergy is
widespread among plant secondary metabolites, which would be consistent with the
hypothesis that synergistic defenses are a key attribute of the evolved diverse
chemical mixtures found in plants.
The l-alanine dehydrogenase of Bacillus subtilis (BasAlaDH), which is strictly
dependent on NADH as redox cofactor, efficiently catalyzes the reductive amination
of pyruvate to l-alanine using ammonia as amino group donor. To enable application
of BasAlaDH as regenerating enzyme in coupled reactions with NADPH-dependent
alcohol dehydrogenases, we alterated its cofactor specificity from NADH to NADPH
via protein engineering. By introducing two amino acid exchanges, D196A and L197R,
high catalytic efficiency for NADPH was achieved, with k(cat)/K-M=54.1 mu M(-
1)Min(-1) (K-M=32 +/- 3 mu M; k(cat)=1,730 +/- 39Min(-1)), almost the same as the
wild-type enzyme for NADH (k(cat)/K-M=59.9 mu M(-1)Min(-1); K-M=14 +/- 2 mu M;
k(cat)=838 +/- 21Min(-1)). Conversely, recognition of NADH was much diminished in
the mutated enzyme (k(cat)/K-M=3 mu M(-1)Min(-1)). BasAlaDH(D196A/L197R) was
applied in a coupled oxidation/transamination reaction of the chiral dicyclic
dialcohol isosorbide to its diamines, catalyzed by Ralstonia sp. alcohol
dehydrogenase and Paracoccus denitrificans -aminotransferase, thus allowing
recycling of the two cosubstrates NADP(+) and l-Ala. An excellent cofactor
regeneration with recycling factors of 33 for NADP(+) and 13 for l-Ala was observed
with the engineered BasAlaDH in a small-scale biocatalysis experiment. This opens a
biocatalytic route to novel building blocks for industrial high-performance
polymers. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Chromatin immunoprecipitation (ChIP) is an indispensable tool in the fields of
epigenetics and gene regulation that isolates specific protein-DNA interactions.
ChIP coupled to high throughput sequencing (ChIP-seq) is commonly used to determine
the genomic location of proteins that interact with chromatin. However, ChIP-seq is
hampered by relatively low mapping resolution of several hundred base pairs and
high background signal. The ChIP-exo method is a refined version of ChIP-seq that
substantially improves upon both resolution and noise. The key distinction of the
ChIP-exo methodology is the incorporation of lambda exonuclease digestion in the
library preparation workflow to effectively footprint the left and right 5 ' DNA
borders of the protein-DNA crosslink site. The ChIP-exo libraries are then
subjected to high throughput sequencing. The resulting data can be leveraged to
provide unique and ultra-high resolution insights into the functional organization
of the genome. Here, we describe the ChIP-exo method that we have optimized and
streamlined for mammalian systems and next-generation sequencing-by-synthesis
platform.
N-6-Methyladenosine (m(6)A) modifications of RNA are diverse and ubiquitous amongst
eukaryotes. They occur in mRNA, rRNA, tRNA, and microRNA. Recent studies have
revealed that these reversible RNA modifications affect RNA splicing, translation,
degradation, and localization. Multiple physiological processes, like circadian
rhythms, stem cell pluripotency, fibrosis, triglyceride metabolism, and obesity are
also controlled by m(6)A modifications. Immunoprecipitation/sequencing, mass
spectrometry, and modified northern blotting are some of the methods commonly
employed to measure m(6)A modifications. Herein, we present a northeastern blotting
technique for measuring m6A modifications. The current protocol provides good size
separation of RNA, better accommodation and standardization for various
experimental designs, and clear delineation of m(6)A modifications in various
sources of RNA. While m(6)A modifications are known to have a crucial impact on
human physiology relating to circadian rhythms and obesity, their roles in other
(patho) physiological states are unclear. Therefore, investigations on m6A
modifications have immense possibility to provide key insights into molecular
physiology.
Considerable effort has recently been directed toward the implementation of
molecular bioassays on digital-microfluidic biochips (DMFBs). However, today's
solutions suffer from the drawback that multiple sample pathways are not supported
and on-chip reconfigurable devices are not efficiently exploited. As a result,
impractical manual intervention is needed to process protocols for gene-expression
analysis. To overcome this problem, we first describe our benchtop experimental
studies to understand gene-expression analysis and its relationship to the biochip
design specification. We then introduce an integrated framework for quantitative
gene-expression analysis using DMFBs. The proposed framework includes: 1) a
spatial-reconfiguration technique that incorporates resource-sharing specifications
into the synthesis flow; 2) an interactive firmware that collects and analyzes
sensor data based on quantitative polymerase chain reaction; and 3) a real-time
resource-allocation scheme that responds promptly to decisions about the protocol
flow received from the firmware layer. This framework is combined with
cyberphysical integration to develop the first design-automation framework for
quantitative gene expression. Simulation results show that our adaptive framework
efficiently utilizes on-chip resources to reduce time-to-result without sacrificing
the chip's lifetime.
Various grafts or combination of bone substitute materials have been used in sinus
lift procedures. Currently, ongoing developments in several disciplines, from
molecular biology and chemistry to computer science and engineering, have
contributed to the understanding of biological processes leading to bone healing
after the use of bone substitute materials (BSBs) and therefore of the behavior of
BSBs. The understanding of the properties of each graft enables individual
treatment concepts and therefore allows shift from a simple replacement material to
the modern concept of an individually created composite biomaterial. Indeed, the
choice of the best BSB still remains crucial for success in maxillary sinus
augmentation procedures. The present article provides an overview of most of the
materials currently available for sinus lift, with a specific focus on their
histological, molecular, cellular and pharmaceutical aspects.
Biochemical analysis of biological substances found at a crime scene is an
important aspect of forensic investigations, where the objective is to determine
the identification of crime victims and suspects/persons-of-interest. One
particular biochemistry/molecular biology-based area of interest in forensic
analysis is forensic serology; this area focuses on the complex task of gathering
information regarding the type, age, ethnicity, and/or gender of the sample
originator from the biological fluids (blood, saliva, etc.) found at a crime scene.
In this review, we cover various studies involving biocomputing techniques used for
the analysis of biological samples namely blood - in different forensic
applications. The studies covered include the differentiation of gender and
ethnicity using a biocomputing system that produces a binary result, as well as the
determination of blood spot age. Each of the applications showcased in this review
produces sometimes ambiguous results that would normally pose major problems for a
study, however, the addition of biocomputing logic provides an extra level of
certainty and clarity. We hope to convey the advantages of utilizing biocomputing
methods in various forms of forensic analysis.
Adverse social conditions in early life have been linked to increased expression of
proinflammatory genes and reduced expression of antiviral genes in circulating
immune cells-the conserved transcriptional response to adversity (CTRA). However,
it remains unclear whether such effects are specific to the Western, educated,
industrialized, rich, and democratic (WEIRD) cultural environments in which
previous research has been conducted. To assess the roles of early adversity and
individual psychological resilience in immune system gene regulation within a non-
WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child
soldiers and matched noncombatant civilians 5 y after the People's War in Nepal.
CTRA gene expression was up-regulated in former child soldiers. These effects were
linked to the degree of experienced trauma and associated distress-that is,
posttraumatic stress disorder (PTSD) severity-more than to child soldier status per
se. Self-perceived psychological resilience was associated with marked buffering of
CTRA activation such that PTSD-affected former child soldiers with high levels of
personal resilience showed molecular profiles comparable to those of PTSD-free
civilians. These results suggest that CTRA responses to early life adversity are
not restricted to WEIRD cultural contexts and they underscore the key role of
resilience in determining the molecular impact of adverse environments.
In recent years, there has been increasing concern over public health threat
presented by introduction of petroleum hydrocarbon pollutants in environment due to
anthropogenic activities to a greater extent and natural processes to some extent.
Many countries all over the world are currently facing severe problem due to these
pollutants as they are one of the persistent organic pollutants (POPs). Remediation
of polluted sites by biodegradation is a viable option as conventional physico-
chemical methods for remediation seems technically as well as economically
challenging. Biodegradation is non-invasive and could be cost-effective in removal
of petroleum hydrocarbon pollutants. It is considered as ultimate mechanism for
pollutants removal. Immobilized microbial cells give advantage over free microbial
cells to improve the survival and retention of the bioremediation agents in
polluted sites. However, current biodegradation approaches suffer from a number of
limitations, which include pollutant characteristics, poor capabilities of
microbial communities in the field, lesser bioavailability of pollutants, growth
conditions, etc. Understanding the factors affecting microbial degradation is of
great research interest in present scenario. This review selectively examines and
provides a critical view on bioavailability of the substrates, microorganisms in
petroleum hydrocarbon pollutants degradation and the molecular techniques for their
characterization, degradation mechanisms under aerobic and anaerobic conditions,
commercially available bioremediation agents and factors affecting biodegradation
of these pollutants. Role of genetically modified organisms and biodegradation of
petroleum hydrocarbon pollutants by immobilized will also be discussed. (C) 2017
Elsevier Ltd. All rights reserved.
Microbiological deterioration was observed on a historic collection of retouched
glass plate negatives. The collection came from a burnt manor house that belonged
to the Brandys family before World War Ilnd. The photographs were taken at the end
of 19th century. The collection consists of 35 glass plate negatives, 4 of which
were examined for possible presence of microorganisms. The current state of the
negatives indicated that the collection may have been flooded. Initially, the
viability of the microorganisms on the plates was examined using luminescence
adenosine phosphate assay. The fungi were isolated and identified with molecular
biology methods as Trichoderma longibrachiatum, Hypocrea Aspergillus versicolor,
Penicillium sp. As the historic negatives were covered with a protective varnish
layer, the impact of the isolated fungi on test negative plates covered with dammar
and sandarac varnishes, and on a gelatine image layer were examined. The most
effective in degradation of gelatine emulsion was T. longibrachiatum. All of the
investigated microorganisms quickly decomposed silver image in gelatine layer not
covered with varnish in opposite to slower decomposition of silver image in
gelatine layer covered with sandarac and dammar varnishes. UV-induced luminescence
observation confirmed that the microorganisms quickly decomposed gelatin layer not
covered with varnish. The cracking of varnish was the result of fungal activity
within gelatin, however, some fungi also attacked the varnish itself. (C) 2016
Elsevier Ltd. All rights reserved.
The present study deals with the exposure of four different mortar formulations in
the headspace of two distinct sewer networks prone to biodeterioration phenomenon
due to the presence of hydrogen sulphide. Cylindrical specimens composed of two
cements, ordinary Portland cement ( OPC) and calcium aluminate cement ( CAC), with
or without a substitution of 75 % of cement by blast furnace slag ( BFS) were
prepared and exposed. During the exposure, the evolution of cement materials was
monitored. After 4 years exposure, OPC materials without BFS are deeply
deteriorated at high speed. Best performances have been observed with CAC mortars
correlated to their higher content in aluminium ion ( Al3+). The rank of durability
observed on site is OPC < OPC+BFS<CAC+BFS<CAC. Molecular biology analysis revealed
that microbial diversity is varying according to binder type as well as during the
exposure duration.
Humans have drastically altered the abundance of animals in marine ecosystems via
exploitation. Reduced abundance can destabilize food webs, leading to cascading
indirect effects that dramatically reorganize community structure and shift
ecosystem function. However, the additional implications of these top-down changes
for biogeochemical cycles via consumer-mediated nutrient dynamics (CND) are often
overlooked in marine systems, particularly in coastal areas. Here, we review
research that underscores the importance of this bottom-up control at local,
regional, and global scales in coastal marine ecosystems, and the potential
implications of anthropogenic change to fundamentally alter these processes. We
focus attention on the two primary ways consumers affect nutrient dynamics, with
emphasis on implications for the nutrient capacity of ecosystems: (1) the storage
and retention of nutrients in biomass, and (2) the supply of nutrients via
excretion and egestion. Nutrient storage in consumer biomass may be especially
important in many marine ecosystems because consumers, as opposed to producers,
often dominate organismal biomass. As for nutrient supply, we emphasize how
consumers enhance primary production through both press and pulse dynamics. Looking
forward, we explore the importance of CDN for improving theory (e.g., ecological
stoichiometry, metabolic theory, and biodiversity-ecosystem function
relationships), all in the context of global environmental change. Increasing
research focus on CND will likely transform our perspectives on how consumers
affect the functioning of marine ecosystems.
Plant virus ecology mainly focuses upon populations and their interactions with
host plants within environment. The subject includes interesting insights as many
factors which affect the virus behavior, population, virus-vector interactions,
biodiversity and host plants genotypes are involved in it. Moreover the
achievements in the field of molecular ecology by application of recent molecular
biology techniques are included which enhance the strength in understanding the
economically important virus populations, growth and their world wide spread. Virus
infection results direct and indirect effect on insect vectors by evolution of
changes in their life cycles, health and interacting behaviors that support their
spread. Similarly, the description of the recent information about how plant
viruses disseminate towards the important agro-ecological zones in naturally
managed vegetations and which factors play important role in ecological aspects are
also included in this review. The modern era of science and technology requires a
better understanding about movement of viruses in both directions which has become
a highly important issue to levitate such kinds of aspects thus making plant virus
ecology an exciting research discipline in future.
In the biorefinery context, thermochemical processes have attracted a significant
attention in recent years. Such processes generally consist of three main steps:
pretreatment, thermochemical treatment, and post-treatment. In these developing
processes, drying and feeding of biomass feedstock remain a significant and costly
challenge. The moisture content of biomass feedstock must be decreased to an
economic level at pretreatment step otherwise it has to have a detrimental effect
on the process efficiency and quality of products. This work addresses the drying
of biomass feedstock using novel but practical technology, called biodrying. It is
a green technology that offers an opportunity for biomass drying without using an
external heat source or fossil fuels, since drying energy is generated through
exothermic microbial activity in the biomass that enhances the drying rate. This
paper focuses on technoeconomic assessment of continuous biodrying technology
integrated to gasification-based biorefinery and investigates the conditions that
make such novel technology viable in conjunction with gasification process. Fixed
capital investment and operating cost of different biodrying scenarios were
estimated as M$4.3-21 and M$0.85/y-3.6/y, respectively, and potential benefits
(sludge landfilling cost, energy savings, and carbon credit) from integration of
the continuous biodrying system in gasification process implemented in pulp and
paper mill were calculated, and ultimately economic performances of the scenarios
were assessed. Furthermore, the viable biodrying conditions were specified as 4-day
residence time and the major viability risk was found to be bound moisture of
biomass.
Bioelectrochemical systems (BESs) may be used to upgrade anaerobic digester biogas
by directly converting CO2 to CH4. The objective of this study was to evaluate gas
(N-2, CO2, CH4, and H-2) and carbon transport within a methanogenic BES. Four BES
configurations were evaluated: abiotic anode with abiotic cathode (AAn-ACa),
bioanode with abiotic cathode (BAn-ACa), abiotic anode with biocathode (AAn-BCa),
and bioanode with biocathode (BAn-BCa). Transport of N-2, a gas commonly used for
flushing anoxic systems, out of the anode headspace ranged from 3.7 to 6.2L/d-atm-
m(2), normalized to the proton exchange membrane (PEM) surface area and net driving
pressure (NDP). CO2 was transported from the cathode to the anode headspace at
rates from 3.7 to 5.4L/d-atm-m(2). The flux of H-2 from cathode to anode headspace
was 48% greater when the system had a biocathode (AAn-BCa) than when H-2 was
produced at an abiotic cathode (BAn-ACa), even though the abiotic cathode headspace
had 75% more H-2 than the AAn-BCa biocathode at the end of 1 day. A 7-day carbon
balance of a batch-fed BAn-BCa BES showed transient microbial carbon storage and a
net transport of carbon from anode to cathode. After a 7-day batch incubation, the
CH4 production in the biocathode was 27% greater on a molar basis than the initial
CO2 supplied to the biocathode headspace, indicating conversion of CO2 produced in
the anode. This research expands the current understanding of methanogenic BES
operation, which may be used in improving the assessment of BES performance and/or
in the development of alternative BES designs and mathematical models. Biotechnol.
Bioeng. 2017;114: 961-969. (C) 2016 Wiley Periodicals, Inc.
In this work, the performance of dual-chamber microbial fuel cells (MFCs)
constructed either with commonly used Nafion (R) proton exchange membrane or
supported ionic liquid membranes (SILMs) was assessed. The behavior of MFCs was
followed and analyzed by taking the polarization curves and besides, their
efficiency was characterized by measuring the electricity generation using various
substrates such as acetate and glucose. By using the SILMs containing either
[C(6)mirn][PF6] or [Bmiml[NTf2] ionic liquids, the energy production of these MFCs
from glucose was comparable to that obtained with the MFC employing polymeric
Nafion (R) and the same substrate. Furthermore, the MFC operated with [Bmim]
[NTf2]-based SILM demonstrated higher energy yield in case of low acetate loading
(80.1 J g(-1) CODin m(-2) h(-1)) than the one with the polymeric Nafion N115 (59 J
g(-1) CODin m(-2) h(-1)). Significant difference was observed between the two SILM-
MFCs, however, the characteristics of the system was similar based on the cell
polarization measurements. The results suggest that membrane-engineering applying
ionic liquids can be an interesting subject field for bioelectrochemical system
research. (C) 2017 Elsevier Ltd. All rights reserved.
Bio-electrochemical systems (BESs) are the microbial systems which are employed to
produce electricity directly from organic wastes along with some valuable chemicals
production such as medium chain fatty acids; acetate, butyrate and alcohols. In
this review, recent updates about value-added chemicals production concomitantly
with the production of gaseous fuels like hydrogen and methane which are considered
as cleaner for the environment have been addressed. Additionally, the bottlenecks
associated with the conversion rates, lower yields and other aspects have been
mentioned. In spite of its infant stage development, this would be the future trend
of energy, biochemicals and electricity production in greener and cleaner pathway
with the win-win situation of organic waste remediation. Henceforth, this review
intends to summarise and foster the progress made in the BESs and discusses its
challenges and outlook on future research advances. (C) 2017 Elsevier Ltd. All
rights reserved.
Limiting global warming to well below 2 degrees C requires the transformation of
the global energy system at a scale unprecedented since the industrial revolution.
To meet this 2 degrees C goal, 87% of integrated assessment models opt for using
bioenergy with carbon capture and storage (BECCS). Without BECCS, the models
predict that the goal will be either unachievable or substantially more costly to
meet. While the modeling literature is extensive, studies of how key climate policy
actors perceive and prioritize BECCS are sparse. This article provides a unique
intercontinental mapping of the prioritization of BECCS for the long term
transition of the electricity supply sector. Based on survey responses from 711 UN
climate change conference delegates, the article reports the low prioritization of
BECCS relative to alternative technologies, indicating an urgent need for studies
of the sociopolitical preconditions for large-scale BECCS deployment.
Exposure to air pollution claimed the lives of about seven million people worldwide
in 2010, largely from combustion of solid biomass fuels. Bioenergy is an
alternative renewable source which can mitigate a climate change. Little is known
about the human health and ecosystem effects of bioenergy, mainly in the
electricity sector. This research applied a life cycle assessment approach to
examine the human health and ecosystem effects of four bioenergy pathways: direct
combustion of wood biomass, direct combustion of forest residue, direct combustion
of pellets, and biomass integrated gasification and combined cycle (BIGCC). All
pathways showed some variability of impacts; therefore, no single bioenergy pathway
was the best absolute option. With the exception of the slightly higher human
health impact, BIGCC has the least impact for all impact categories. However, all
bioenergy systems implied lower ecosystem impact but higher human health impact as
compared to climate change impact. Electricity generation from wood-biomass would
improve the environmental sustainability of Alberta's electricity grid system
because it reduces the human health and ecosystem impacts, as compared to the
existing electricity production mix of the province. (C) 2017 Elsevier Ltd. All
rights reserved.
Coal-fired power plants produce nearly 40% of the electricity in the United States,
contributing more than three-quarters of all carbon dioxide emissions from the
electricity sector. While many European coal-fired power plants have been
transitioning to wood pellets to abate carbon dioxide emissions, such a changeover
has not occurred in the United States electricity sector. This analysis examines
the environmental implications of co-firing coal and wood pellets in the
Southeastern United States, where the vast majority of wood pellet exports to
Europe originate. Utilizing primary data from existing wood pellet manufacturers, a
life cycle inventory is presented that characterizes the full cradle-to-grave
environmental performance of co-firing coal and wood pellets for electricity
generation. Furthermore, the avoided life cycle emissions related to shipping wood
pellets to Europe are calculated. Life cycle assessment modeling scenarios for co-
firing wood pellets in existing coal-fired power plants within the Southeastern
United States result in reductions in eight of nine impact categories. The results
presented here indicate that co-firing with wood pellets could be a viable interim
solution for the aging fleet of coal-fired power plants within the Southeastern
United States, particularly if stricter emission regulations and renewable
portfolio standards are implemented. (C) 2017 Published by Elsevier Ltd.
Substrate nanotopography has been shown to be a potent modulator of cell phenotype
and function. To dissect nanotopography modulation of cell behavior, a large area
of nanopatterned substrate is desirable so that enough cells can be cultured on the
nanotopography for subsequent biochemical and molecular biology analyses. However,
current nanofabrication techniques have limitations to generate highly defined
nanopatterns over a large area. Herein, we present a method to expand nanopatterned
substrates from a small, highly defined nanopattern to a large area using stitch
technique. The method combines multiple techniques, involving soft lithography to
replicate poly(dimethylsiloxane) (PDMS) molds from a well-defined mold, stitch
technique to assemble multiple PDMS molds to a single large mold, and
nanoimprinting to generate a master mold on polystyrene (PS) substrates. With the
PS master mold, we produce PDMS working substrates and demonstrate
nanotopographical modulation of cell spreading. This method provides a simple,
affordable yet versatile avenue to generate well-defined nanopatterns over large
areas, and is potentially extended to create micro-/nanoscale devices with hybrid
components.
Biofouling is a pervasive challenge in industrial and medical settings with
enormous economic and health impacts. Use of quorum-quenching phages is a potential
solution in either combating the biofilm or inhibiting biofilm formation when an
engineered phage is designed for a specific bacterial system. In the event of a
real-life application of synthetic phage, it is necessary to consider the effect of
environmental conditions on the synthetic phage. This study focused on both (1)
stability of phage lysate under different types of carbon sources and (2)
competition of the engineered phage in comparison to a wild-type (wt) phage.
Optimal results were found (in plaque forming units [PFUs]) with glucose as a
carbon source and were kept stable for almost 30 days. Results suggested that
competition happens before 4h. After that time, polymerase chain reaction results
from PFU samples showed an increase in T7aiiA, which indicates that these
conditions favored the phage replication of the engineered phage over the wt at 27h
in a monoculture system. When both stability and competition were combined, the mix
of phages showed a trend similar to T7aiiA only primarily after 8 days.
Biofuels have transitioned from a technology expected to deliver numerous benefits
to a highly contested socio-technical solution. Initial hopes about their potential
to mitigate climate change and to deliver energy security benefits and rural
development, particularly in the Global South, have unravelled in the face of
numerous controversies. In recognition of the negative externalities associated
with biofuels, the European Union developed sustainability criteria which are
enforced by certification schemes. This paper draws on the literature on
stewardship to analyse the outcomes of these schemes in two countries: the UK and
Guatemala. It explores two key issues: first, how has European Union biofuels
policy shaped biofuel industries in the UK and Guatemala? And second, what are the
implications for sustainable land stewardship? By drawing attention to the outcomes
of European demand for biofuels, we raise questions about the ability of European
policy to drive sustainable land practices in these two cases. The paper concludes
that, rather than promoting stewardship, the current governance framework
effectively rubberstamps existing agricultural systems and serves to further embed
existing inequalities.
The present research study presents the optimization of Solid Oxide Fuel Cell
(SOFC) power plants directly fed by biogas. By considering energy and exergy
balances for such a system, a detailed thermodynamic model (THERMAS) was designed
and implemented. A specific SOFC-based system was selected as case study, equipped
with three heat exchangers (preheaters), a reformer, a SOFC-stack system and an
afterburner. The use of the simulation tool THERMAS give us the opportunity to
investigate all the appropriate parameters that affect system's efficiency based on
exergy analysis while incorporating a detailed parametric analysis regarding the
whole system. The optimization process relies on the difference between the energy
and exergy efficiency by considering an innovative Optimization Factor (OPF) for
each simulated system, which is dynamically affected by operational parameters,
such as fuel composition, extension of chemical reactions and temperatures. It is
found that the use of a pure fuels seems to be meaningless without optimization.
(C) 2017 Elsevier Ltd. All rights reserved.
Herein a techno-economic assessment was performed on an energy-crop-based biogas
plant coupled with a greenhouse for utilizing thermal energy produced by
cogeneration. Seven energy crops were evaluated: triticale, maize, alfalfa,
sunflower, clover, barley and wheat. According to the evaluation, triticale was the
most competitive energy crop under selected climate conditions for northern Greece.
Although maize displays higher biomass yield and biogas potential than the drought-
resistant crop triticale, it has high irrigation demand that contributes
significantly to total production costs. For a triticale-based biogas production to
become economically feasible, agricultural arable area larger than 500 ha, or
biogas plant size larger than 1000 kW(el), is required. However, with public
funding, biogas production becomes feasible at smaller area (>250 ha) or biogas
plant size (>500 kW(el)). The inclusion of a greenhouse into the design of the
biogas plant contributes positively to the economic viability of the entire system.
Under this scenario, greenhouse financial income accounts for about 17-18% of total
income. Results of a sensitivity analysis suggest that the selection of an
appropriate energy crop for biogas production should be based principally on both
digestibility (specific methane yield) and biomass yield per hectare, these factors
being more critical than biomass production costs.
Many recent studies have reported that microRNA (miRNA) biogenesis and function are
related to the molecular mechanisms of various clinical diseases. Several methods,
including northern blotting and DNA chip analyses, are capable of assessing miRNA-
production patterns in cells. However, the development of repetitive monitoring of
the miRNA-production profile in a noninvasive manner is demanded for the
application of miRNAs to human medicine. Here, we describe a noninvasive system for
monitoring miRNA biogenesis, from the stage of primary transcripts to that of
mature miRNA regulation. We review the optical methods that have been developed to
image miRNA production at each step of the miRNA-processing pathway in living
subjects. We propose that an optical miRNA-imaging strategy, based on molecular
imaging, can be used as an miRNA imaging detector to monitor various miRNAs, by
using different reporters, simultaneously, for high-throughput screening, and will
provide potential application for the diagnosis and therapeutics of multiple
diseases.
Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs
(mRNAs) involved in the growth and development of a variety of cells, including
primordial germ cells (PGCs) which play an essential role in germ cell development.
However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs
remain unclear. Here, we demonstrate a novel miRNAs control PGC development through
targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched
expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -
127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA
microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs
are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ
hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA
microarray analysis and miRNA target prediction demonstrates the regulatory
networks through which these miRNAs regulate their potential target genes during
PGC development. The elucidated networks of miRNAs disclose a coordinated molecular
mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that
determine germ cell development.
Tripterygium wilfordii Hook. F. is one of the most valuable medicinal plants
because it contains a large variety of active terpenoid compounds, including
triptolide, celastrol, and wilforlide. All of the pharmacologically active
secondary metabolites are synthesized from the 2-C-methyl-D-erythritol 4-phosphate
and mevalonate pathway in the isoprenoid biosynthetic system. The key step in this
pathway is the isomerization of dimethylallyl diphosphate and isopentenyl
diphosphate, which is catalyzed by isopentenyl diphosphate isomerase (IPI). In the
present study, a full-length cDNA encoding IPI (designate as TwIPI, GenBank
accession no. KT279355) was cloned from a suspension of cultured cells from T.
wilfordii. The full-length cDNA of TwIPI was 1,564 bp and encoded a polypeptide of
288 amino acids. The bioinformatics analysis showed that the deduced TwIPI sequence
contained the TNTCCSHPL and WGEHELDY motif. The transcription level of the TwIPI in
the suspension cells increased almost fivefold after treatment with methyl
jasmonate as an elicitor. A functional color assay in Escherichia coli indicated
that TwIPI could promote the accumulation of lycopene and encoded a functional
protein. (C) 2015 International Union of Biochemistry and Molecular Biology, Inc.
Volume 63, Number 6, Pages 863-869, 2016
It is assumed that resistance to ionizing radiation, as well as cross-resistance to
other abiotic stresses, is a side effect of the evolutionary-based adaptation of
anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can
withstand prolonged desiccation as well as high doses of ionizing radiation
exposure. For a further understanding of the mechanisms of cross-tolerance to both
types of stress exposure, we profiled genome-wide mRNA expression patterns using
microarray techniques on the chironomid larvae collected at different stages of
desiccation and after exposure to two types of ionizing radiation-70 Gy of high-
linear energy transfer (LET) ions (He-4) and the same dose of low-LET radiation
(gamma rays). In expression profiles, a wide transcriptional response to
desiccation stress that much exceeded the amount of up-regulated transcripts to
irradiation exposure was observed. An extensive group of coincidently up-regulated
overlapped transcripts in response to desiccation and ionizing radiation was found.
Among this, overlapped set of transcripts was indicated anhydrobiosis-related
genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock
proteins. The most overexpressed group was that of protein-L-isoaspartate/D-
aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins,
were the most represented. Performed functional analysis showed strongly enriched
gene ontology terms associated with protein methylation. In addition, active
processes of DNA repair were detected. We assume that the cross-tolerance of the
sleeping chironomid to both desiccation and irradiation exposure comes from a
complex mechanism of adaptation to anhydrobiosis.
Background: Hepatitis B virus (HBV) DNA sequence data from thousands of samples are
present in the public sequence databases. No publicly available, up-to-date,
multiple sequence alignments, containing full-length and subgenomic fragments per
genotype, are available. Such alignments are useful in many analysis applications,
including data-mining and phylogenetic analyses. Results: By issuing a query, all
HBV sequence data from the GenBank public database was downloaded (67,893
sequences). Full-length and subgenomic sequences, which were genotyped by the
submitters (30,852 sequences), were placed into a multiple sequence alignment, for
each genotype (genotype A: 5868 sequences, B: 4630, C: 7820, D: 8300, E: 2043, F:
985, G: 189, H: 108, I: 23), according to the results of offline BLAST searches
against a custom reference library of full-length sequences. Further curation was
performed to improve the alignment. Conclusions: The algorithm described in this
paper generates, for each of the nine HBV genotypes, multiple sequence alignments,
which contain full-length and subgenomic fragments. The alignments can be updated
as new sequences become available in the online public sequence databases. The
alignments are available at http://hvdr.bioinf.wits.ac.za/alignments.
Human multipotent mesenchymal stromal cells (hMSCs) possess the ability to
differentiate into osteoblasts, and they can be utilized as a source for bone
regenerative therapy. Osteoinductive pretreatment, which induces the osteoblastic
differentiation of hMSCs in vitro, has been widely used for bone tissue engineering
prior to cell transplantation. However, the molecular basis of osteoblastic
differentiation induced by osteoinductive medium (OIM) is still unknown. Therefore,
we used a next-generation sequencer to investigate the changes in gene expression
during the osteoblastic differentiation of hMSCs. The hMSCs used in this study
possessed both multipotency and self-renewal ability. Whole-transcriptome analysis
revealed that the expression of zinc finger and BTB domain containing 16 (ZBTB16)
was significantly increased during the osteoblastogenesis of hMSCs. ZBTB16 mRNA and
protein expression was enhanced by culturing the hMSCs with OIM. Small interfering
RNA (siRNA)-mediated gene silencing of ZBTB16 decreased the activity of alkaline
phosphatase (ALP); the expression of osteogenic genes, such as osteocalcin (OCN)
and bone sialoprotein (BSP), and the mineralized nodule formation induced by OIM.
siRNA-mediated gene silencing of Osterix (Osx), which is known as an essential
regulator of osteoblastic differentiation, markedly downregulated the expression of
ZBTB16. In addition, chromatin immunoprecipitation (ChIP) assays showed that Osx
associated with the ZBTB16 promoter region containing the GC-rich canonical Sp1
sequence, which is the specific Osx binding site. These findings suggest that
ZBTB16 acts as a downstream transcriptional regulator of Osx and can be useful as a
late marker of osteoblastic differentiation. J. Cell. Biochem. 117: 2423-2434,
2016. (c) 2016 Wiley Periodicals, Inc.
Recent developments in single-cell transcriptomics have opened new opportunities
for studying dynamic processes in immunology in a high throughput and unbiased
manner. Starting from a mixture of cells in different stages of a developmental
process, unsupervised trajectory inference algorithms aim to automatically
reconstruct the underlying developmental path that cells are following. In this
review, we break down the strategies used by this novel class of methods, and
organize their components into a common framework, highlighting several practical
advantages and disadvantages of the individual methods. We also give an overview of
new insights these methods have already provided regarding the wiring and gene
regulation of cell differentiation. As the trajectory inference field is still in
its infancy, we propose several future developments that will ultimately lead to a
global and data-driven way of studying immune cell differentiation.
Bioinformatics field has now solidly settled itself as a control in molecular
biology and incorporates an extensive variety of branches of knowledge from
structural biology, genomics to gene expression studies. Bioinformatics is the
application of computer technology to the management of biological information.
Genomic signal processing (GSP) techniques have been connected most all around in
bioinformatics and will keep on assuming an essential part in the investigation of
biomedical issues. GSP refers to using the digital signal processing (DSP) methods
for genomic data (e.g. DNA sequences) analysis. Recently, applications of GSP in
bioinformatics have obtained great consideration such as identification of DNA
protein coding regions, identification of reading frames, cancer detection and
others. Cancer is one of the most dangerous diseases that the world faces and has
raised the death rate in recent years, it is known medically as malignant neoplasm,
so detection of it at the early stage can yield a promising approach to determine
and take actions to treat with this risk. GSP is a method which can be used to
detect the cancerous cells that are often caused due to genetic abnormality. This
systematic review discusses some of the GSP applications in bioinformatics
generally. The GSP techniques, used for cancer detection especially, are presented
to collect the recent results and what has been reached at this point to be a new
subject of research.
The tertiary structure of the proteins determines their functions. Therefore, the
predicting of protein's tertiary structure, based on the primary amino acid
sequence from long time, is the most important and challenging subject in
biochemistry, molecular biology, and biophysics. One of the most popular protein
structure prediction methods, called Hydrophobic-Polar (HP) model, is based on the
observation that in polar environment hydrophobic amino acids are in the core of
the molecule-in contact between them and more polar amino acids are in contact with
the polar environment. In this study, we present a new mixed integer programming
formulation, exact algorithm, and two heuristic algorithms to solve the protein
folding problem stated as a combinatorial optimization problem in a simple cubic
lattice. The results from computational runs on a set of benchmarks are favorably
compared to known algorithms for solving the 3D lattice HP model as genetic
algorithms, ant colony optimization algorithm, and Monte Carlo algorithm.
The chances of raising crop productivity to enhance global food security would be
greatly improved if we had a complete understanding of all the biological
mechanisms that underpinned traits such as crop yield, disease resistance or
nutrient and water use efficiency. With more crop genomes emerging all the time, we
are nearer having the basic information, at the gene-level, to begin assembling
crop gene catalogues and using data from other plant species to understand how the
genes function and how their interactions govern crop development and physiology.
Unfortunately, the task of creating such a complete knowledge base of gene
functions, interaction networks and trait biology is technically challenging
because the relevant data are dispersed in myriad databases in a variety of data
formats with variable quality and coverage. In this paper we present a general
approach for building genomescale knowledge networks that provide a unified
representation of heterogeneous but interconnected datasets to enable effective
knowledge mining and gene discovery. We describe the datasets and outline the
methods, work flows and tools that we have developed for creating and visualising
these networks for the major crop species, wheat and barley. We present the global
characteristics of such knowledge networks and with an example linking a seed size
phenotype to a barley WRKY transcription factor orthologous to TTG2 from
Arabidopsis, we illustrate the value of integrated data in biological knowledge
discovery. The software we have developed (www.ondex.org) and the knowledge
resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source
and provide a first step towards systematic and evidence-based gene discovery in
order to facilitate crop improvement. (C) 2016 The Authors. Published by Elsevier
B.V. This is an open access article under the CC BY license.
Hepatocellular carcinoma is the major form of primary liver cancer, which is the
second and sixth leading cause of cancer-related death in men and women,
respectively. Extensive research indicates that Wnt/beta-catenin signaling pathway,
which plays a pivotal role in growth, development, and differentiation of
hepatocellular carcinoma, is one of the major signaling pathways that is
dysregulated in hepatocellular carcinoma. Cyclin D1 is a proto-oncogene and is one
of the major regulators of Wnt signaling pathway, and its overexpression has been
detected in various types of cancers including hepatocellular carcinoma. Using
several validated bioinformatic databases, we predicted that the microRNAs are
capable of targeting 3'-untranslated region of Cyclin D1 messenger RNA. According
to the results, miR-20a was selected as the highest ranking microRNA targeting
Cyclin D1 messenger RNA. Luciferase assay was recruited to confirm bioinformatic
prediction results. Cyclin D1 expression was first assessed by quantitative real-
time polymerase chain reaction in HepG2 cell line. Afterward, HepG2 cells were
transduced by lentiviruses containing miR-20a. Then, the expression of miR-20a and
Cyclin D1 was evaluated. The results of luciferase assay demonstrated targeting of
3'-untranslated region of Cyclin D1 messenger RNA by miR-20a. Furthermore, 238-fold
decline in Cyclin D1 expression was observed after lentiviral induction of miR-20a
in HepG2 cells. The results highlighted a considerable effect of miRNA-20a
induction on the down-regulation of Cyclin D1 gene. Our results suggest that miR-
20a can be used as a novel candidate for therapeutic purposes and a biomarker for
hepatocellular carcinoma diagnosis.
Eucheuma denticulatum, an economically and industrially important red alga, is a
valuable marine resource. Although microRNAs (miRNAs) play an essential role in
gene post-transcriptional regulation, no research has been conducted to identify
and characterize miRNAs in E. denticulatum. In this study, we identified 134 miRNAs
(133 conserved miRNAs and one novel miRNA) from 2,997,135 small-RNA reads by high-
throughput sequencing combined with bioinformatics analysis. BLAST searching
against miRBase uncovered 126 potential miRNA families. A conservation and
diversity analysis of predicted miRNA families in different plant species was
performed by comparative alignment and homology searching. A total of 4 and 13
randomly selected miRNAs were respectively validated by northern blotting and stem-
loop reverse transcription PCR, thereby demonstrating the reliability of the miRNA
sequencing data. Altogether, 871 potential target genes were predicted using
psRobot and TargetFinder. Target genes classification and enrichment were conducted
based on Gene Ontology analysis. The functions of target gene products and
associated metabolic pathways were predicted by Kyoto Encyclopedia of Genes and
Genomes pathway analysis. A Cytoscape network was constructed to explore the
interrelationships of miRNAs, miRNA-target genes and target genes. A large number
of miRNAs with diverse target genes will play important roles for further
understanding some essential biological processes in E. denticulatum. The uncovered
information can serve as an important reference for the protection and utilization
of this unique red alga in the future.
Sclerospora graminicola (Sacc.) Schroet., an oomycete pathogen of Pennisetum
glaucum (L.) R. Br. infects the meristematic tissues of young seedlings. The motile
zoospores from the sporangia encyst, germinate and penetrate the plant tissue.
Resistance to the invading pathogen is governed by the specific recognition of
conserved pathogen-associated proteins or elicitors. In the present study, a
zoospore protein was isolated and purified to homogeneity by a combination of size
exclusion and high-performance liquid chromatography ( HPLC). The crude
fractionated protein was able to elicit an array of defence responses in resistant
and susceptible cells of pearl millet. Treatment of cultured cells of pearl millet
with partially purified elicitor protein resulted in a rapid loss of cell viability
in the resistant cells and the percentage of cell death was higher in the resistant
than in the susceptible cells. Cultures of resistant cells showed a sharp increase
in the extra cellular pH compared with susceptible cells when treated with the
crude elicitor. Increased oxidative burst was also recorded in the cells treated
with the crude elicitor. The purified elicitor showed unique properties. The
purified protein was acidic with a pI of 5.6 as revealed by isoelectric focusing
(IEF) and matrix-assisted laser desorption ionisation (MALDI) analysis showed that
the elicitor had a molecular mass of 7040 daltons. The primary structure determined
by N-terminal Edman degradation and searches with BLAST did not reveal similarities
to any known plant pathogenic or oomycete elicitor. Higher activities of the
important defence-related enzymes phenylalanine ammonia lyase ( PAL) and peroxidase
in the resistant cell cultures than in the susceptible cell cultures treated with
the purified elicitor were clearly evident. Studies of gene expression by northern
blotting with heterologus peroxidase, PAL and oxalate oxidase probes showed that
the mRNA transcripts were strongly up-regulated in resistant cell cultures within
30 min of elicitor treatment. The purified elicitor also demonstrated a very strong
concentration-dependent sterol binding. The purified elicitor protein belongs to a
class of low molecular weight oomycete elicitors with sterol carrier properties.
The identified low molecular weight protein elicitor displays unique properties
that can be exploited for synthesis of novel molecules for eco-friendly crop
protection.
Whereas significant advances have been made in understanding how exposure to early
adversity gets under the skin of children to result in long term changes in
developmental outcomes, the processes by which positive social relationships become
biologically embedded remain poorly understood. The aim of this study was to
understand the pathways by which maternal and infant social environments become
biologically embedded in infant cortisol reactivity. Two hundred seventy-two
pregnant women and their infants were prospectively assessed during pregnancy and
at 6 months postpartum. In serial mediation analyses, higher perceived social
support from partners during pregnancy was associated with lower infant cortisol
reactivity or larger decreases in cortisol in response to a stressor at 6 months of
age via lower self-reported prenatal maternal depression and higher mother-infant
interaction quality. The findings add to our understanding of how perinatal social
relationships become biologically embedded in child development.
The fast growth of the human population forces us to produce more food, but higher
crop production also leads to the fast spread of diseases. Plant pathology deploys
a wide range of methods that do not provide an adequate solution to all disease
losses. In the case of viroids, therapeutic means of control are not available;
therefore control strategies are more focused on the development of reliable
detection methods to quickly exclude the infected plant material. Although viroids
are the smallest and simplest plant pathogens, their identification and detection
is not straightforward. Each viroid-host combination is specific, and for reliable
identification, all steps from sampling to final detection must be performed
accurately. In this review, several methods for viroid detection in various host
plants are discussed, including their advantages and disadvantages. Even though
relatively new molecular methods enable fast and sensitive detection of viroids, a
combination of different methods gives the most reliable identification. Techniques
based on nucleic acids may be the future for viroid detection but they still cannot
replace biological indexing, which is usually essential in epidemiological and
aetiological studies.
The definition of biological individuality is one of the most discussed topics in
philosophy of biology, but current debate has focused almost exclusively on
evolution-based accounts. Moreover, several participants in this debate consider
the notions of a biological individual and an organism as equivalent. In this
paper, I show that the debates would be considerably enriched and clarified if
philosophers took into account two elements. First, physiological fields are
crucial for the understanding of biological individuality. Second, the category of
biological individuals should be divided into two subcategories: physiological
individuals and evolutionary individuals, which suggests that the notions of
organism and biological individual should not be used interchangeably. I suggest
that the combination of an evolutionary and a physiological perspective will enable
biologists and philosophers to supply an account of biological individuality that
will be both more comprehensive and more in accordance with scientific practices.
Salivary biomarkers could be helpful to characterize breast cancer. Therefore, this
review was performed to evaluate the capability of salivary biological markers in
the diagnosis and monitoring of breast cancer. Studies were eligible for inclusion
if they assessed the potential diagnostic value or other discriminatory properties
of biological markers in saliva of patients with breast cancer. The search was
performed in six electronic databases (Cochrane, LILACS, PubMed, Science Direct,
Scopus, Web of Science). In addition the biomarkers were classified according to
their potential clinical application. We identified 567 pertinent studies, of which
13 met the inclusion criteria. Combined biomarker approaches demonstrated better
ability to predict breast cancer patients than individual biomarkers. As single
biomarlcer, namely proline, reported great capacity in both early and late stage
breast cancer diagnosis. Taurine showed interesting capability to identify early
breast cancer individuals. Furthermore, valine also demonstrated excellent
diagnostic test accuracy for advanced stages of breast cancer. Only seven studies
reported sensitivity and specificity (Zhang et al., 2010; Streckfus et al., 2000a;
Brooks et al., 2008; Cheng et al., 2015; Bigler et al., 2002; Zhong et al., 2016;
Streckfus, 2009), which varied considerably from 50% to 100%, and from 51% to 97%,
respectively. In general, salivary biomarkers identified advanced stages of breast
cancer better than early stages. There is currently limited evidence to confirm the
putative implementation of salivary biomarkers as diagnostic tools for breast
cancer. However, current review provides new research directions. (C) 2016 Elsevier
Ireland Ltd. All rights reserved.
Background and Aim: In our previous study, we demonstrated that four microRNAs
(miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in
both plasma and tumor tissues were confirmed to be promising non-invasive
diagnostic biomarkers for gastric cancer (GC). Methods: We used the quantitative
reverse transcription polymerase chain reaction to assess the expression levels of
the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan-
Meier curves and log-rank test were applied to predict the correlation between
miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we
performed in vitro assays including cell proliferation, migration, invasion and
colony formation, and apoptosis. Results: The median of miRNA expression in
paraffin-embedded tissues were used as the cutoff value to classify patients into
high or low expression groups. Down-regulation of miR-26a and miR-148a was
significantly associated with shorter OS of GC patients either in the test set
(miR-26a: P=0.009; miR-148a: P=0.005) or the validation set (miR-26a: P=0.011; miR-
148a: P=0.024). When two sets were combined, Cox regression analysis demonstrated
that both of miR-26a and miR-148a were independent prognostic factors for
predicting OS of patients with GC (miR-26a: HR=0.76, 95% CI=0.61-0.94; miR-148a:
HR=0.73, 95% CI=0.58-0.91). Furthermore, elevated expression of miR-26
significantly suppressed cell proliferation, migration, invasion and colony
formation, and induced apoptosis of MGC-803 cells compared with negative control
groups (P<0.05). Conclusion: These findings supported miR-26a and miR-148a could
serve as potential prognostic biomarkers for GC.
Power to gas (P2G) may be used to store curtailed electricity whilst converting the
energy vector to gas. To be economically viable these systems require cheap
electricity and a cheap concentrated source of CO2. Biogas produced from anaerobic
digestion typically comprises of 60% methane and 40% CO2. The P2G system
substitutes for the conventional upgrading system by using hydrogen (derived from
surplus wind electricity) to react with CO2 and increases the methane output. The
potential CO2 production from biogas in Ireland associated with typical wet
substrates is assessed as more than 4 times greater than that required by the
potential level of H-2 from curtailed electricity. Wind energy curtailment in 2020
in Ireland is assessed conservatively at 2175GW(e)h/a. Thus P2G is limited by
levels of curtailment of electricity rather than biogas systems. It is shown that 1
GW(e)h of electricity used to produce H-2 for upgrading biogas in a P2G system can
affect a savings of 97 tonnes CO2. The cost of hydrogen is assessed at
(sic)0.96/m(3) renewable methane when the price of electricity is (sic)c5/kW(e)h.
This leads to a cost of compressed renewable gas from grass of (sic)1.8/m(3). This
drops to (sic)1.1/m(3) when electricity is purchased at (sic)c0.2/1cW(e)h. (C) 2016
Elsevier Ltd. All rights reserved.
The beamline BL19U2 is located in the Shanghai Synchrotron Radiation Facility
(SSRF) and is its first beamline dedicated to biological material small-angle X-ray
scattering (BioSAXS). The electrons come from an undulator which can provide high
brilliance for the BL19U2 end stations. A double flat silicon crystal (111)
monochromator is used in BL19U2, with a tunable monochromatic photon energy ranging
from 7 to 15 keV. To meet the rapidly growing demands of crystallographers,
biochemists and structural biologists, the BioSAXS beamline allows manual and
automatic sample loading/unloading. A Pilatus 1M detector (Dectris) is employed for
data collection, characterized by a high dynamic range and a short readout time.
The highly automated data processing pipeline SASFLOW was integrated into BL19U2,
with help from the BioSAXS group of the European Molecular Biology Laboratory
(EMBL, Hamburg), which provides a user-friendly interface for data processing. The
BL19U2 beamline was officially opened to users in March 2015. To date, feedback
from users has been positive and the number of experimental proposals at BL19U2 is
increasing. A description of the new BioSAXS beamline and the setup characteristics
is given, together with examples of data obtained.
Biologics, both monoclonal antibodies (mAbs) and fusion proteins, have
revolutionized the practice of medicine. This year marks the 30th anniversary of
the Food and Drug Administration approval of the first mAb for human use. In this
review, we examine the biotechnological breakthroughs that spurred the explosive
development of the biopharmaceutical mAb industry, as well as how critical lessons
learned about human immunology informed the development of improved biologics. We
also discuss the most common mechanisms of action of currently approved biologics
and the indications for which they have been approved to date. (C) 2016 Elsevier
Inc. All rights reserved.
Background: Distinguishing recipient cells from donor ligament cells is difficult
in the early graft-healing phase after anterior cruciate ligament (ACL)
reconstruction. The ability to track the distribution and differentiation of
recipient cells using genetically engineered transgenic (Tg) animals would have
significant clinical and research effects on graft healing after ACL
reconstruction. Hypothesis: Kusabira-Orange Tg pigs may allow the tracking of
recipient cells infiltrating the graft after ACL reconstruction. The repopulation
of recipient cells within the graft would be apparent even in the early graft-
healing phase when necrotic donor cells are still present. Study Design:
Descriptive laboratory study. Methods: In 17 genetically engineered Tg pigs, which
carried the red fluorescent protein Kusabira-Orange, ACL reconstruction was
performed on the right knee using a digital flexor tendon harvested from wild-type
pigs. Tissue samples harvested at different time points were subjected to
histological, immunohistochemical, and electron microscopic analyses. Results: At 3
weeks postoperatively, recipient cells expressing red fluorescence embraced the
graft and were infiltrating the central part of the graft. These cells with oval
nuclei gradually infiltrated the gap of collagen fibers, losing their regular
orientation. At 6 weeks, cellularity within the graft had doubled to match that of
the native ACL, while acellular necrotic regions still existed centrally.
Ubiquitous cellular distributions resembling the native ACL were observed at 24
weeks. Electron microscopic analysis showed that the mean collagen fibril diameter
and density gradually decreased over 24 weeks. Conclusion: Genetically engineered
pigs carrying the Kusabira-Orange gene were useful animal models for analyzing
intrinsic and extrinsic cellular dynamics during the course of graft healing after
ACL reconstruction. Cellular repopulation by recipient cells occurred in the very
early stage, and the cellular distribution within the graft resembled that in the
native ACL by 24 weeks, but the reconstructed graft had not restored the
ultrastructure of the native ACL by that stage. Clinical Relevance: In allograft
ACL reconstruction in a pig model, cellular repopulation was completed by 24 weeks
after surgery, but the collagen matrix had not resumed the ultrastructure of the
native ACL. Surgeons should be aware that risks may remain with returning to sports
activities at 24 weeks after surgery.
Food poisoning by Staphylococcus aureus is a result of ingestion of Staphylococcal
enterotoxins (SEs) produced by this bacterium and is a major source of foodborne
illness. Staphylococcal enterotoxin D (SED) is one of the predominant enterotoxins
recovered in Staphylococcal food poisoning incidences, including a recent outbreak
in Guam affecting 300 children. Current immunology methods for SED detection cannot
distinguish between the biologically active form of the toxin, which poses a
threat, from the inactive form, which poses no threat. In vivo bioassays that
measure emetic activity in kitten and monkeys have been used, but these methods
rely upon expensive procedures using live animals and raising ethical concerns. A
rapid (5 h) quantitative bioluminescence assay, using a genetically engineered T-
cell Jurkat cell line expressing luciferase under regulation of nuclear factor of
activated T cells response elements, in combination with the lymphoblastoid B-cell
line Raji for antigen presentation, was developed. In this assay, the detection
limit of biologically active SED is 100 ng/mL, which is 10 times more sensitive
than the splenocyte proliferation assay, and 105 times more sensitive than monkey
or kitten bioassay. Pasteurization or repeated freeze-thaw cycles had no effect on
SED activity, but reduction in SED activity was shown with heat treatment at 100
degrees C for 5 min. It was also shown that milk exhibits a protective effect on
SED. This bioluminescence assay may also be used to rapidly evaluate antibodies to
SED for potential therapeutic application as a measurement of neutralizing
biological effects of SED.
Background: Disease surveillance in patients with bladder cancer is important for
early diagnosis of progression and metastasis and for optimised treatment.
Objective: To develop urine and plasma assays for disease surveillance for patients
with FGFR3 and PIK3CA tumour mutations. Design, setting, and participants: Droplet
digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from
two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort
included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other
cohort included 468 patients with bladder cancer undergoing radical cystectomy
(Cx). Urine supernatants (NMIBC n = 216, Cx n = 27) and plasma samples (NMIBC n =
39, Cx n = 27) from patients harbouring mutations were subsequently screened using
ddPCR assays. Outcome measurements and statistical analysis: Progression-free
survival, recurrence-free survival, and overall survival were measured. Fisher's
exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied.
Results and limitations: In total, 36% of the NMIBC patients (129/363) and 11% of
the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening
of DNA from serial urine supernatants from the NMIBC cohort revealed that high
levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC
(p = 0.003). Furthermore, high levels of tDNA in plasma samples were associated
with recurrence in the Cx cohort (p = 0.016). A positive correlation between tDNA
levels in urine and plasma was observed (correlation coefficient 0.6). The
retrospective study design and low volumes of plasma available for analysis were
limitations of the study. Conclusions: Increased levels of FGFR3 and PIK3CA mutated
DNA in urine and plasma are indicative of later progression and metastasis in
bladder cancer. Patient summary: Urine and plasma from patients with bladder cancer
may be monitored for diagnosis of progression and metastasis using mutation assays.
(C) 2016 European Association of Urology. Published by Elsevier B.V. All rights
reserved.
OBJECTIVE The incidence of posttraumatic ventriculomegaly (PTV) and shunt-dependent
hydrocephalus after nonaccidental head trauma (NAHT) is unknown. In the present
study, the authors assessed the timing of PTV development, the relationship between
PTV and decompressive craniectomy (DC), and whether PTV necessitated placement of a
permanent shunt. Also, NAHT/PTV cases were categorized into a temporal profile of
delay in admission and evaluated for association with outcomes at discharge.
METHODS The authors retrospectively reviewed the cases of patients diagnosed with
NAHT throughout a 10-year period. Cases in which sequential CT scans had been
obtained (n = 28) were evaluated for Evans' index to determine the earliest time
ventricular dilation was observed. Discharge outcomes were assessed using the
King's Outcome Scale for Childhood Head Injury score. RESULTS Thirty-nine percent
(11 of 28) of the patients developed PTV. A low admission Glasgow Coma Scale (GCS)
score predicted early PTV presentation (within1 week). A majority of PTV/NAHT
patients presented with a subdural hematoma (both convexity and interhemispheric)
and ischemic stroke, but subarachnoid hemorrhage was significantly associated with
PTV/NAHT (p = 0.011). Of 6 patients undergoing a DC for intractable intracranial
pressure, 4 (67%) developed PTV (p = 0.0366). These patients tended to present with
lower GCS scores and develop ventriculomegaly early. Only 2 patients developed
hydrocephalus requiring shunt placement. CONCLUSIONS PTV presents early after NAHT,
particularly after a DC has been performed. However, the authors found that only a
few PTV/NAHT patients developed shunt-dependent hydrocephalus.
Recent innovations in molecular biology and colorectal cancer (CRC) genetics have
facilitated the understanding of the pathogenesis of sporadic and hereditary CRC
syndromes. The development of technology has enabled data collection for a number
of genetic factors, which lead to understanding of the molecular mechanisms
underlying CRC. The incidence and the nature of CRC is a mixture of genetic and
environmental factors. The current field of interest is to understand how molecular
basis could shape predisposition for developing CRC, disease progression and
response to chemotherapy. In this article, we summarize new and developing genetic
markers, and assess their clinical value for inherited and sporadic CRC.
Introduction: Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading
cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to
improve median overall survival in comparison with gemcitabine. Based on better
understanding of tumor molecular biology and of the role of tumor microenvironment,
monoclonal antibodies (mAbs) could be an interesting and new type of targeted
treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated
the efficacy of several mAbs in pancreatic cancer treatment. This review will
underline the most important targeted pathways by mAbs involved in this disease,
including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints.
Expert opinion: Despite the promising results of preclinical and phase I trials,
the addition of mAbs to standard chemotherapy or in association with other target
agents seems not to confirm these results in the following phase II and III trials
in pancreatic cancer patients. However, an improved patient selection before
treatment based on molecular characteristics in association with reliable
predictive biomarkers can identified more efficacious treatment approaches,
minimizing toxicity profile of these drugs.
Flexible multi-generation systems (FMGs) consist of integrated and flexibly
operated facilities that provide multiple links between the different sectors of
the energy system. The present study treated the design optimization of a
conceptual FMG which integrated a methanol-producing biorefinery with an existing
combined heat and power (CHP) unit and industrial energy utility supply in the
Danish city of Horsens. The objective was to optimize economic performance and
minimize total CO2 emission of the FMG while it was required to meet the local
district heating demand plus the thermal utility demand of the butchery. The design
optimization considered: Selection, dimensioning, location and integration of
processes; operation optimization with respect to both hourly variations in
Operating conditions over the year as well as expected long term energy system
development; and uncertainty analysis considering both investment costs and
operating conditions. Applying a previously developed FMG design methodology,
scalable models of the considered processes were developed and the system design
was optimized with respect to hourly operation over the period 2015-2035. The
optimal design with respect to both economic and environmental performance involved
a maximum-sized biorefinery located next to local industry rather than in
connection with the existing CHP unit. As the local industry energy demands were
limited when compared to the biorefinery dimensions considered, process integration
synergies were found to be marginal when compared to the economic and environmental
impact of the biorefinery for the present case. Assessing the impact of
uncertainties on the estimated FMG performances, the net present value (NPV) of the
optimal design was estimated to vary within the range 252.5-1471.6 ME in response
to changes of 25% in investment costs and methanol price, and considering two
different electricity price scenarios. In addition, a change in the interest rate
from 5% to 20% was found to reduce the lower bound of the NPV to 181.3 ME for
reference operating conditions. The results suggest that the applied interest rate
and operating conditions, in particular the methanol price, would have a much
higher impact on the economic performance of the designs than corresponding
uncertainties in investment costs. In addition, the study outcomes emphasize the
importance of including systematic uncertainty analysis in the design optimization
of FMG concepts. (C) 2016 Elsevier Ltd. All rights reserved.
This paper first reviews the potential causality from biomass energy to CO2
emissions and economic development within relevant literature. Later, the paper
examines statistically the impacts of biomass energy consumption on CO2 emissions
and GDP in the US. To this end, paper observes environmental and economic
implications of biomass fuel usage throughout energy literature and launches
asymmetric causality test to confirm/disconfirm the literature output. The findings
of the tests indicate that biomass energy consumption per capita mitigates CO2
emissions per capita and increases GDP per capita. Eventually, upon its output,
this research asserts that biomass energy consumption can be an efficient policy
tool for environmentally sustainable development in the US, and, that, hence,
biomass production technologies and biomass consumption need to be promoted in
other countries as well as in the US. On the other hand, analyses underline the
fact that policy makers should consider as well some potential constraints of
biomass energy usage such as land use constraints and carbon leakage from biomass
production. Therefore, although this paper explores the remedial impact of biomass
on environment and growth, one may suggest also that further possible works
consider the effects of biomass sources in detail to minimize the some worsening
influence of biomass usage on climate change.
The quality and composition of biomass as used in Portugal's thermal power plants
is highly variable. The biomass consists mainly of residual forest biomass derived
from forestry operations and wood waste from industrial processes, in particular
paper and pulp industry. Its quality and composition is influenced by the presence
of moisture and inert fragments, the latter being incorporated during collection or
as a consequence of adherence to the biomass prior to collection. This variability
presents difficulties for the thermal power plants; besides being an additional
operational cost, the presence of large amounts of water and inerts in biomass used
as a fuel, can result in problems related to the instability of the combustion and
the accumulation of ash or rock that have to be removed and discarded. The
objective of this paper is to review the main parameters that influence the quality
of biomass, while analysing the current state-of-the-art power generation from the
biomass sector in Portugal, as a new contribution to earlier studies.
Biomass is the most widely used renewable energy source in the world today. It is
used mostly in solid form and, to a lesser extent, in the form of liquid fuels and
gas. The utilization of biomass for energy production has increased at only a
modest rate in modern times. Biomass is the major source of energy in rural Turkey.
Biomass is used to meet a variety of energy needs, including generating
electricity, heating homes, fueling vehicles and providing process heat for
industrial facilities. Biomass potential includes wood, animal and plant wastes.
Among the biomass energy sources, fuel wood seems to be the most interesting
because its share of the total energy production of Turkey is high at 14%. The
total biomass energy potential of Turkey is about 33 million tons of oil
equivalents (Mtoe). The amount of usable biomass potential of Turkey is
approximately 17 Mtoe. The electrical production potential from usable bioenergy
sources are 73 MW in 2010 and corporate income and represent more than 280,000
jobs. This study shows that there is important biomass energy potential for climate
change mitigation and energy sustainability in Turkey. (C) 2017 Elsevier Ltd. All
rights reserved.
Three-dimensional (3D) carbon materials derived from waste biomass have been
attracted increasing attention in catalysis and materials science because of their
great potential of catalyst supports with respect to multi-functionality, unique
structures, high surface area, and low cost. Here, we present a facile and
efficient way for preparing 3D heterogeneous catalysts based on vertical MnO2 wires
deposited on hemp-derived 3D porous carbon. The 3D porous carbon materials are
fabricated by carbonization and activation processes using hemp (Cannabis Sttiva
L). These 3D porous carbon materials are employed as catalyst supports for direct
deposition of vertical MnO2 wires using a one-step hydrothermal method. The XRD and
XPS results reveal the crystalline structure of alpha-MnO2 wires. The resultant
composites are further employed as a catalyst for glycolysis of poly(ethylene
terephthalate) (PET) with high conversion yield of 98%, which is expected to be
expressly profitable for plastics recycling industry. (C) 2017 Elsevier B.V. All
rights reserved.
Greenhouse gas emissions in the transport sector can significantly be reduced by
replacing fossil based fuels with green alternatives. Various alternative fuel
concepts have been developed differing in used sustainable feedstock, synthesis
technology and final fuel characteristics. Whether these fuels can succeed in the
market will depend on the fuel net production costs, the expected cost reduction
potentials and the political intention to mitigate climate change. Results of
previous studies for the techno-economic assessment of alternative fuels are
difficult to compare due to significant differences in the applied methodology,
level of detail and key assumptions in terms of economic factors and market prices.
In this work, a standardized methodology for techno-economic analysis of fuel
production processes is presented and exemplarily applied on sustainable fuels from
Fischer-Tropsch (FT) synthesis. The methodology was adapted from a best practice
approach from chemical industry and consists of three main steps: (A) literature
survey on feasible production designs, (B) flowsheet simulation and (C) techno-
economic assessment with the in-house software tool TEPET (Techno-Economic Process
Evaluation Tool). It is shown that the standardized approach enables qualitative
and quantitative statements regarding the technical and economic feasibility of
fuel synthesis concepts including the identification of the appropriate fuel
production concept due to predefined framework conditions. Results from the case
study on green FT fuels reveal that Biomass-to-Liquid (BtL) concepts have lowest
production costs at high electricity costs, whereas the Power-to-Liquid (PtL) and
Power and Biomass-to-Liquid (PBtL) concepts are superior at low electricity prices.
Fuel production costs in the range of 1.2 and 2.8 (sic)(2014)/1 were estimated. (C)
2016 Elsevier Ltd. All rights reserved.
Controversy exists regardingwhether violent shaking is harmful to infants in the
absence of impact. In this study, our objective was to characterize the
biomechanical response of the infant head during shaking through use of an
instrumented anthropomorphic test device (commonly referred to as a "crash test
dummy'' or surrogate) representing a human infant and having improved biofidelity.
A series of tests were conducted to simulate violent shaking of an infant
surrogate. The Aprica 2.5 infant surrogate represented a 5th percentile Japanese
newborn. A 50th percentile Japanese adult male was recruited to shake the infant
surrogate in the sagittal plane. Triaxial linear accelerometers positioned at the
center of mass and apex of the head recorded accelerations during shaking. Five
shaking test series, each 3-4 sec in duration, were conducted. Outcome measures
derived from accelerometer recordings were examined for trends. Head/neck
kinematics were characterized during shaking events; mean peak neck flexion was
1.98 radians (113 degrees) and mean peak neck extension was 2.16 radians (123
degrees). The maximum angular acceleration across all test series was 13,260
radians/sec 2 (during chin-to-chest contact). Peak angular velocity was 105.7
radians/sec (during chin-to-chest contact). Acceleration pulse durations ranged
from 72.1 to 168.2ms. Using an infant surrogate with improved biofidelity, we found
higher angular acceleration and higher angular velocity than previously reported
during infant surrogate shaking experiments. Findings highlight the importance of
surrogate biofidelity when investigating shaking.
This brief presents a submicrowatt, offset-free, and implantable system for a
biomedical capacitive sensor. The system is powered by a 13.56-MHz radio frequency
signal and performs sensor signal amplification, analog-to-digital conversion, and
load-shift keying uplink data transmission within 640 mu s. An ultralow-power
capacitance-to-digital converter (CDC) is designed by replacing a power-hungry
operational amplifier with a subthreshold inverter in a switched-capacitor
amplifier (SC-amp). A fast-response-gain compensation method is employed to reduce
the gain error of the SC-amp while achieving high energy efficiency for the CDC. To
eliminate the offset, a two-step autocalibration is applied. The application-
specific integrated circuit is implemented in the Taiwan Semiconductor
Manufacturing Company 90-nm complementary metal-oxide-semiconductor technology, and
the whole system achieves an 8.02 effective number of bits with 9-bit linearity
while consuming only 5.5 mu W.
Background: The Drug Ontology (DrOn) is an OWL2-based representation of drug
products and their ingredients, mechanisms of action, strengths, and dose forms. We
originally created DrOn for use cases in comparative effectiveness research,
primarily to identify historically complete sets of United States National Drug
Codes (NDCs) that represent packaged drug products, by the ingredient(s),
mechanism(s) of action, and so on contained in those products. Although we had
designed DrOn from the outset to carefully distinguish those entities that have a
therapeutic indication from those entities that have a molecular mechanism of
action, we had not previously represented in DrOn any particular therapeutic
indication. Results: In this work, we add therapeutic indications for three
research use cases: resistant hypertension, malaria, and opioid abuse research. We
also added mechanisms of action for opioid analgesics and added 108 classes
representing drug products in response to a large term request from the Program for
Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM)
project. The net result is a new version of DrOn, current to May 2016, that
represents three major therapeutic classes of drugs and six new mechanisms of
action. Conclusions: A therapeutic indication of a drug product is represented as a
therapeutic function in DrOn. Adverse effects of drug products, as well as other
therapeutic uses for which the drug product was not designed are dispositions. Our
work provides a framework for representing additional therapeutic indications,
adverse effects, and uses of drug products beyond their design. Our work also
validated our past modeling decisions for specific types of mechanisms of action,
namely effects mediated via receptor and/or enzyme binding. DrOn is available at:
http://purl. obolibrary. org/obo/ dron. owl. A smaller version without NDCs is
available at: http://purl. obolibrary. org/obo/dron/dron-lite. owl
In the present paper, an operational amplifier (Op-Amp) topology that achieves
high-gain and low- power dissipation is designed and analyzed. The design uses a
current mirror with a class-A output stage having capacitive Miller compensation.
The low power operational amplifier is the main active power consuming block. The
proposed Op-Amp operates at +/- 0.75V supply voltage and consumes a total power of
1.83mW with the gain >= 90dB. The proposed design has been implemented using Tanner
EDA Tools for 90nm CMOS technology node.
Finger vein recognition has drawn increasing attention from biometrics community
due to its security and convenience. In this paper, a novel discriminative binary
codes (DBC) learning method is proposed for finger vein recognition. First of all,
subject relation graph is built to capture correlations among subjects. Based on
the relation graph, binary templates are transformed to describe vein
characteristics of subjects. To ensure that templates are discriminative and
representative, graph transform is formulated into an optimization problem, in
which the distance between templates from different subjects is maximized and
templates provide maximum information about subjects. At last, supervised
information for training instances is provided by the obtained binary templates,
and SVMs are trained as the code learner for each bit. Compared with existing
binary codes for finger vein recognition, DBC are more discriminative and shorter.
In addition, they are generated with considering the relationships among subjects
which may be useful to improve performance. Experimental results on PolyU database
and MLA database demonstrate the effectiveness and efficiency of DBC for finger
vein recognition and retrieval.
Calcium carbonate skeletal tissues in metazoans comprise a small quantity of
occluded organic macromolecules, mostly proteins and polysaccharides that
constitute the skeletal matrix. Because its functions in modulating the
biomineralization process are well known, the skeletal matrix has been extensively
studied, successively via classical biochemical approaches, via molecular biology
and, in recent years, via transcriptomics and proteomics. The optimistic view that
the deposition of calcium carbonate minerals requires a limited number of
macromolecules has been challenged, in the last decade, by high throughput
approaches. Such approaches have made possible the rapid identification of large
sets of mineral-associated proteins, i.e., 'skeletal repertoires' or 'skeletomes',
in several calcifying animal models, ranging from sponges to echinoderms. One of
the consequences of this expanding set of data is that a simple definition of the
skeletal matrix is no longer possible. This increase in available data, however,
makes it easier to compare skeletal repertoires, shedding light on the fundamental
evolutionary mechanisms affecting matrix components. (C) 2016 Elsevier Inc. All
rights reserved.
In this paper a detailed mathematical and physical model is presented in order to
calculate the impedance of a tooth. The proposed model is based in an op-amp
balanced Wien bridge oscillator and a voltage divider. From the amplitude of the
signal and the phase shift we can calculate the resistance and the capacitance of a
tooth.
The discovery of the importance of kinase activity and its relationship to the
emergence and proliferation of cancer cells, due to changes in normal physiology,
opened a remarkable pathway for the treatment of chronic myelogenous leukemia
through intense search of drug candidates. Six Abl kinase inhibitors have received
the US FDA approval as chronic myelogenous leukemia treatment, and continuous
efforts in obtaining new, more effective and selective molecules are being carried
out. Herein we discuss the mechanisms of Abl inhibition, structural features and
ligand/protein interactions that are important for the design of new Abl kinase
inhibitors. This review provides a broad overview of binding mode predictions,
through molecular docking, which can be an approach to discover novel Abl kinase
inhibitors.
Sialic acid sugars that terminate cell-surface glycans form the ligands for the
sialic acid binding immunoglobulin-like lectin (Siglec) family, which are
immunomodulatory receptors expressed by immune cells. Interactions between sialic
acid and Siglecs regulate the immune system, and aberrations contribute to
pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between
living cells are difficult to study owing to a lack of specific tools. Here, we
report a glycoengineering approach to remodel the sialic acids of living cells and
their binding to Siglecs. Using bioorthogonal chemistry, a library of cells with
more than sixty different sialic acid modifications was generated that showed
dramatically increased binding toward the different Siglec family members. Rational
design reduced cross-reactivity and led to the discovery of three selective Siglec-
5/14 ligands. Furthermore, glyco-engineered cells carrying sialic acid ligands for
Siglec-3 dampened the activation of Siglec-3(+) monocytic cells through the NF-
kappa B and IRF pathways.
AimsThe aim of this study was to develop and evaluate a real-time PCR technology
for microbiological control methods to examine individualized cell therapeutics, an
emerging class of pharmaceutical formulations. Methods and ResultsOligonucleotide
primers and hybridization probe for bacterial detection targeting the 16SrRNA gene
were adapted based on Nadkarni etal. [Microbiology148 (2002) 257]. For detection of
yeast and moulds, primers and probe were designed from conserved sequences of the
18SrRNA gene in this study. The real-time PCR assays were tested on genomic DNA of
Escherichia coli and Candida albicans to assess efficiency and linear dynamic
range. After successful establishment of robust real-time PCRs, applicability of
the assays was evaluated by extracting microbial target DNA from cell-based
preparations. Different commercial DNA extraction methods were compared identifying
the MagNA Pure DNA Isolation Kit III as the method of choice. Sensitivity was
examined for different strains and a detection limit of 10(2)-10(3) CFU per ml in a
sample containing similar to 10(6) mammalian cells per ml was achieved.
ConclusionsThis study reports the successful establishment of two qualitative real-
time PCR assays, enabling in general the broad-range detection of microbial
contaminants in a cell-based sample matrix. Significance and Impact of the
StudyIndividualized cell therapeutics tend to have a short shelf life. Due to
lengthy incubation periods, compendial testing according to current pharmacopoeial
guidelines may not be applicable. We report a suitable alternative method upon
which future microbiological quality control methods for such products could be
based on. However, to implement valid rapid microbiological testing methods using
real-time PCR technology, further challenges need to be addressed.
During embryogenesis, the spherical inner cell mass (ICM) proliferates in the
confined environment of a blastocyst. Embryonic stem cells (ESCs) are derived from
the ICM, and mimicking embryogenesis in vitro, mouse ESCs (mESCs) are often
cultured in hanging droplets. This promotes the formation of a spheroid as the
cells sediment and aggregate owing to increased physical confinement and cell-cell
interactions. In contrast, mESCs form two-dimensional monolayers on flat substrates
and it remains unclear if the difference in organization is owing to a lack of
physical confinement or increased cell-substrate versus cell-cell interactions.
Employing microfabricated substrates, we demonstrate that a single geometric degree
of physical confinement on a surface can also initiate spherogenesis. Experiment
and computation reveal that a balance between cell-cell and cell-substrate
interactions finely controls the morphology and organization of mESC aggregates.
Physical confinement is thus an important regulatory cue in the three-dimensional
organization and morphogenesis of developing cells.
Context: Hypericum perforatum L., commonly known as St. John's wort, is practised
as an alternative medicine against depression. Conversely, its remedial efficacy is
indulged by various adverse effects that are recuperated in formulating nanoscaled
commercial capsules encased by the biopolymer chitosan. A potential application of
nanoencapsulation with regards to polymer enhances a slow controlled release of the
targeted drug to achieve the desired delay until the right stimulus is obtained.
Aims: To value synthesizing biopolymeric nanocomposites encapsulating St. John's
wort commercial capsules substantiating it with a study of animal model of
depression to endorse the effect of nanocapsulated drug as an effective brain drug.
Methods The nanoparticulated suspension was prepared by ionic gelation technique
and characterized to attest its antidepressant activity by in vivo studies.
Results: The drug binding efficiency was endorsed by FT-IR studies and the
nanoparticles were characterized by an average particle size of 211.4 nm with a
positive zeta potential of 45.9 mV. The animal despair studies on depression
induced mice models displayed a significant difference in the immobility time
during force swimming and tail suspension test. The commercial capsules were
administed orally (p.o., 50 and 100 mg/kg). The animal despair studies were
substantiated with affirmative biochemical assessments like SOD, CAT, GP(x), GSH
and LPO and compared with control groups. Conclusions: The outcomes of this work
manifest the calibre of St. John's wort nanocomposites in a lower dosage that can
alleviate depression and reduce side effects.
Building blocks made from renewable sources attract increasing attention for the
design of new polymer systems. Recently, in this particular context, cellulose
nanocrystals (CNCs) have gained great interest in both academic research and
industry, mainly on account of their ability to reinforce range of polymer matrices
and afford nanocomposites with attractive mechanical properties. The limited
thermal stability of conventionally produced cellulose nanocrystals (CNCs) has,
however, so far limited the range of polymers that could be used as basis for melt-
processed CNC nanocomposites. We herein show that a commercially accessible
nanocrystal source, a particular grade of microcrystalline cellulose (MCC), can
easily be converted into thermally stable CNCs by ultrasonication in phosphoric
acid. A scalable melt-mixing process was used to produce nanocomposites of these
CNCs with a thermoplastic polyurethane (TPU) elastomer. A significant improvement
of the room temperature storage modulus from 40 MPa (neat polymer) to 120 MPa (10%
w/w CNC) was observed. The introduction of CNCs not only increased the stiffness of
the polymer matrix, but also improved the shape memory properties of the
nanocomposite. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134,
45033.
In this paper, a new low power, low noise operational amplifier dedicated to
implantable biomedical applications is introduced. The amplifier is designed to
minimize input referred noise and power consnmption. To rednce inpnt thermal noise,
we use the EKV Model to set the bias currents of the transistors. To rednce the
flicker noise, PMOS inpnt transistors with large gate areas and operating in weak
inversion are used. The noise rednction techniqne of switched biasing is then
applied, which involves switching the transistor periodically between accnmnlation
(cntoff) and inversion region. This helps to fnrther reduce the flicker noise of
the transistors. The use of switched biasing allows ns to rednce the inpnt noise,
withont having to increase the current and thus allows us to avoid the problem of
trading power with noise. Using this techniqne, we are able to achieve an extremely
low input noise of 2.89/mu V-rms in the desired bandwidth, at a small snpply
cnrrent of 4.8/mu A. The additional circuitry required for switched biasing
consumes minimal power, and the average power consnmption of the amplifier is
15.174/mu W, which makes it ideal for implantable applications. The gain of the
amplifier is 76.2dB in the required frequency range, with a phase margin of 74
degrees and a CMRR greater than 120dB at all frequencies. The circuit is designed
using the TSMC 0.18/mu m process, in the Analog Design Environment of Cadence
Virtuoso. The performance of the circuit is studied at all process corners, namely
TT, FF, SS, SF and FS. The simulations are carried out at 36.9 degrees C, the
normal human body temperature.
Industrialization of mammalian cell culture has been achieved by integrating
knowledge from several applying core concepts of chemical engineering, cellular and
molecular biology, and biochemistry. Modeling has been applied to biological and
physical processes to gain additional insights into such processes. This article
covers modeling of the bioreactor and metabolic processes as it applies to
bioprocess. Hydrodynamics of a bioreactor is briefly described while additional
focus is given to gas-liquid mass transfer. Biological modeling is presented in the
order of increasing complexity. First steady state models are presented followed by
dynamic models, cybernetic models, and finally bioreactor integrated models. The
closing discussion summarizes challenges of implementation of model-based
approaches in the biopharmaceutical industry. (c) 2016 American Institute of
Chemical Engineers AIChE J, 63: 398-408, 2017
Recombinant consensus interferon (CIFN) is a therapeutic protein with molecular
weight of 19.5kDa having broad spectrum antiviral activity. Recombinant human CIFN
(rhCIFN) has previously been expressed in Escherichia coli using isopropyl--d-
thiogalactopyranoside (IPTG), a non-metabolizable and expensive compound, as
inducer. For economical and commercial-scale recombinant protein production, it is
greatly needed to increase the product yield in a limited time frame to reduce the
processing cost. To reduce the cost of production of rhCIFN in E. coli, induction
was accomplished by using lactose instead of IPTG. Lactose induction (14g/L) in
shake flask experiment resulted in higher yield as compared with 1mM IPTG. Finally,
with single-step purification on DEAE sepharose, 150mg/L of >98% pure rhCIFN was
achieved. In the present study, an attempt was made to develop a low cost process
for producing quality product with high purity. Methods devised may be helpful for
pilot-scale production of recombinant proteins at low cost. (C) 2015 International
Union of Biochemistry and Molecular Biology, Inc.
We analyzed 115 iliac crest bone marrow biopsy specimens from 101 patients with
metastatic castration resistant prostate cancer, divided into a test (n = 57) and a
validation (n = 58) set. We developed a score based on computed tomography
Hounsfield units and lactate dehydrogenase levels, which were associated with a
positive biopsy result. The score can be used to select patients for whom a bone
marrow biopsy will provide tissue for molecular characterization. Background: The
urgent need for castration-resistant prostate cancer molecular characterization to
guide treatment has been constrained by the disease's predilection to metastasize
primarily to bone. We hypothesized that the use of clinical and imaging criteria
could maximize tissue acquisition from bone marrow biopsies (BMBs). We aimed to
develop a score for the selection of patients undergoing BMB. Materials and
Methods: A total of 115 BMBs were performed in 101 patients: 57 were included in a
derivation set and 58 were used as the validation set. The clinical and laboratory
data and prebiopsy computed tomography parameters (Hounsfield units [HUs]) were
determined. A score for the prediction of biopsy positivity was developed from
logistic regression analysis of the derivation set and tested in the validation
set. Results: Of the 115 biopsy specimens, 75 (62.5%) were positive; 35 (61.4%) in
the test set and 40 (69%) in the validation set. On univariable analysis,
hemoglobin (P = .019), lactate dehydrogenase (P = .003), prostate specific antigen
(P = .005), and mean HUs (P = .004) were selected. A score based on the LDH level
(>= 225 IU/L) and mean HUs (>= 125) was developed in multivariate analysis and was
associated with BMB positivity in the validation set (odds ratio, 5.1; 95%
confidence interval, 1.9%-13.4%; P = .001). The area under the curve of the score
was 0.79 in the test set and 0.77 in the validation set. Conclusion: BMB of the
iliac crest is a feasible technique for obtaining tumor tissue for genomic analysis
in patients with castration-resistant prostate cancer metastatic to the bone. A
signature based on the mean HUs and LDH level can predict a positive yield with
acceptable internal validity. Prospective studies of independent cohorts are needed
to establish the external validity of the score. (C) 2016 The Author(s). Published
by Elsevier Inc.
Background: Driven by a range of sustainability challenges, e.g. climate change,
resource depletion and expanding populations, a circular bioeconomy is emerging and
expected to evolve progressively in the coming decades. South Africa along with
other BRICS countries (Brazil, Russia, India and China) represents the emerging
bioeconomy and contributes significantly to global sugar market. In our research,
South Africa is used as a case study to demonstrate the sustainable design for the
future biorefineries annexed to existing sugar industry. Detailed techno-economic
evaluation and Life Cycle Assessment (LCA) were applied to model alternative routes
for converting sugarcane residues (bagasse and trash) to selected biofuel and/or
biochemicals (ethanol, ethanol and lactic acid, ethanol and furfural, butanol,
methanol and Fischer-Tropsch synthesis, with co-production of surplus electricity)
in an energy self-sufficient biorefinery system. Results: Economic assessment
indicated that methanol synthesis with an internal rate of return (IRR) of 16.7%
and ethanol-lactic acid co-production (20.5%) met the minimum investment criteria
of 15%, while the latter had the lowest sensitivity to market price amongst all the
scenarios. LCA results demonstrated that sugarcane cultivation was the most
significant contributor to environmental impacts in all of the scenarios, other
than the furfural production scenario in which a key step, a biphasic process with
tetrahydrofuran solvent, had the most significant contribution. Conclusion:
Overall, the thermochemical routes presented environmental advantages over
biochemical pathways on most of the impact categories, except for acidification and
eutrophication. Of the investigated scenarios, furfural production delivered the
inferior environmental performance, while methanol production performed best due to
its low reagent consumption. The combined techno-economic and environmental
assessments identified the performance- limiting steps in the 2G biorefinery design
for sugarcane industry and highlighted the technology development opportunities
under circular bioeconomy context.
Bioremediation plays an important role in oil spill management and bio-
electrochemical treatment systems are supposed to represent a new technology for
both effective remediation and energy recovery. Diesel removal rate increased by
four times in microbial fuel cells (MFCs) since the electrode served as an electron
acceptor, and high power density (29.05 W m(-3)) at current density 72.38 A m(-3)
was achieved using diesel (v/v 1%) as the sole substrate. As revealed by Scanning
electron microscope images, carbon fibres in the anode electrode were covered with
biofilm and the bacterial colloids which build the link between carbon fibres and
enhance electron transmission. Trace metabolites produced during the anaerobic
biodegradation were identified by gas chromatography-mass spectrometry. These
metabolites may act as emulsifying agents that benefit oil dispersion and play a
vital role in bioremediation of oil spills in field applications. (C) 2017 Elsevier
Ltd. All rights reserved.
Here, we aimed our attention at the synthesis of carbon dots (C-dots) with the
ability to interact with DNA to suggest an approach for the detection of DNA
damage. Primarily, C-dots modified with amine moieties were synthesized using the
one-step microwave pyrolysis of citric acid in the presence of diethylenetriamine.
The C-dots showed strong photoluminescence with a quantum yield of 4%. In addition,
the C-dots (2.8 +/- 0.8 nm) possessed a good colloidal stability and exhibited a
positive surface charge (zeta=36 mV) at a neutral pH. An interaction study of the
C-dots and the DNA fragment of lambda bacteriophage was performed, and the DNA
binding resulted in changes to the photoluminescent and absorption properties of
the C-dots. A binding of the C-dots to DNA was also observed as a change to DNA
electrophoretic mobility and a decreased ability to intercalate ethidium bromide
(EtBr). Moreover, the Forster (or fluorescence) resonance energy transfer (FRET)
between the C-dots and EtBr was studied, in which the C-dots serve as an excitation
energy donor and the EtBr serves as an acceptor. When DNA was damaged using
ultraviolet (UV) radiation (lambda=254 nm) and hydroxyl radicals, the intensity of
the emitted photoluminescence at 612 nm significantly decreased. The concept was
proved on analysis of the genomic DNA from PC-3 cells and DNA isolated from
melanoma tissues.
This paper presents a low-power, low-noise CMOS instrumentation amplifier intended
for use in wireless bio-potential monitoring system. It employs a capacitively-
coupled topology to achieve high power efficiency. In order to depress the noise,
chopper-stabilized technique is used and a transconductance-boost technique is
introduced in low-noise amplifier (LNA). All MOS transistors implemented in LNA are
biased in subthreshold region with a supply voltage of 0.5 V to reduce the power
consumption. Moreover, a DC-servo loop (DSL) is implemented to realize a high-pass
corner for electrode offset cancellation. Implemented in a 0.18 mu m CMOS process,
the front-end circuit occupies 0.48 mm(2) and draws 1.5 mu A. The capacitively-
coupled chopper-stabilized instrumentation amplifier (CCIA) draws 800 nA and its
input-referred noise is 3.5 mu V-rms integrated from 0.5 to 1 kHz, which results in
a NEF of 3.8 and a PEF of 7.2 respectively. The whole circuit achieves 98 dB CMRR
and 73 dB PSRR. The total input-referred noise of the front-end instrumentation
amplifier including the DSL is 4.3 mu V-rms integrated from 0.5 to 1 kHz. (C) 2016
Elsevier Ltd. All rights reserved.
Foodborne pathogens have been a cause of a large number of diseases worldwide and
more so in developing countries. This has a major economic impact. It is important
to contain them, and to do so, early detection is very crucial. Detection and
diagnostics relied on culture-based methods to begin with and have developed in the
recent past parallel to the developments towards immunological methods such as
enzyme-linked immunosorbent assays (ELISA) and molecular biology-based methods such
as polymerase chain reaction (PCR). The aim has always been to find a rapid,
sensitive, specific and costeffective method. Ranging from culturing of microbes to
the futuristic biosensor technology, the methods have had this common goal. This
review summarizes the recent trends and brings together methods that have been
developed over the years.
Unwanted immune responses to therapeutic proteins can severely impact their safety
and efficacy. Studies show that the presence of trace amounts of host cells and
process-related impurities that stimulate pattern recognition receptors (PRR) can
cause local inflammation and enhance product immunogenicity. Here we used purified
PRR agonists as model impurities to assess the minimal level of individual innate
immune response modulating impurities (IIRMIs) that could activate a local immune
response. We show that levels of endotoxin as low as 10 pg (0.01 EU), 1 ng for
polyinosinic: polycytidylic acid (PolyI: C), 100 ng for synthetic diacylated
liopprotein, thiazoloquinolone compound, or muramyl dipeptide, 1 mg for flagellin
or b-glucan, or 5 mg for CpG-oligodeoxynucleotide increased expression of genes
linked to innate immune activation and inflammatory processes in the skin of
rhesusmacaques. Furthermore, spiking studies using rasburicase as a model
therapeutic showed that the levels of PRR agonists that induced detectable gene
upregulation in the skin were associated with increased immunogenicity for
rasburicase. This study underscores the need for testing multiple IIRMIs in
biologics, strengthening the connection between the local mRNA induction in skin,
innate immune activation, and antibody development in primates, and provides an
indication of the levels of IIRMI in therapeutic products that could impact product
immunogenicity. Published by Elsevier Inc. on behalf of the American Pharmacists
Association.
In the nearly 20 years since Rabinow's 1996 "Artificiality and Enlightenment: From
Sociobiology to Biosociality," scholarly attention to biosociality and related
concepts such as biological citizenship have expanded Foucault's theories of
biopolitics, updating them-as it were-for the 21st century. In this commentary, I
explicate these "new biopolitical theories" and propose a schema for
operationalizing them for deductive analyses in ethnographic research. I illustrate
the way this schema may be applied with examples from an ethnographic study on
autism in Italy. In doing so, I provide a model of new biopolitical theory that can
be used in future projects in a variety of research settings and put scholarship on
biosocialities and biological citizenships in more explicit conversation with each
other. Such robust conversation will further scholarly understanding of biopolitics
in general and of the local particularity of biologies, biomedicines, and politics
that affect them.
Innovations in novel enzyme discoveries impact upon a wide range of industries for
which biocatalysis and biotransformations represent a great challenge, i. e., food
industry, polymers and chemical industry. Key tools and technologies, such as
bioinformatics tools to guide mutant library design, molecular biology tools to
create mutants library, microfluidics/microplates, parallel miniscale bioreactors
and mass spectrometry technologies to create high-throughput screening methods and
experimental design tools for screening and optimization, allow to evolve the
discovery, development and implementation of enzymes and whole cells in (bio)
processes. These technological innovations are also accompanied by the development
and implementation of clean and sustainable integrated processes to meet the
growing needs of chemical, pharmaceutical, environmental and biorefinery
industries. This review gives an overview of the benefits of highthroughput
screening approach from the discovery and engineering of biocatalysts to cell
culture for optimizing their production in integrated processes and their
extraction/ purification.
Biocatalysis is a fundamental concept in biotechnology. The topic integrates
knowledge of several disciplines; therefore, it was included in the course " design
and optimization of biological systems" which is offered in the biochemistry
curricula. We selected the ciliate tetrahymena as an example of a eukaryotic system
with potential for the biotransformation of sterol metabolites of industrial
interest; in particular, we focused on the conversion of cholesterol to provitamin
D-3. The students work with wild type and recombinant strains and learn how sterol
pathways could be modified to obtain diverse sterol moieties. During the course the
students identify and measure the concentration of sterols. They also search for
related genes by bioinformatic analysis. Additionally, the students compare
biotransformation rates, growing the ciliate in plate and in a bioreactor. Finally,
they use fluorescence microscopy to localize an enzyme involved in
biotransformation. The last day each team makes an oral presentation, explaining
the results obtained and responds to a series of key questions posed by the
teachers, which determine the final mark. In our experience, this course enables
undergraduate students to become acquainted with the principles of biocatalysis as
well as with standard and modern techniques, through a simple and robust laboratory
exercise, using a biological system for the conversion of valuable pharmaceutical
moieties. (C) 2016 by The International Union of Biochemistry and Molecular
Biology, 45(2): 105- 114, 2017.
This study questions the presumed relation between formal schooling and scientific
literacy about biotechnologies. Comparing science and nonscience majors ' knowledge
of and attitudes toward biotechnological applications, conclusions are drawn if
their formal learnings improve pupils ' understandings of and attitudes toward
biotechnology applications. Sample of the study consists of 403 undergraduate and
graduate students, 198 nonscience, and 205 science majors. The Biotechnology
Knowledge Questionnaire and the Biotechnology Attitude Questionnaire were
administered. Descriptive statistics ( mean and percentages), t test, and
correlations were used to examine the participants ' knowledge of biotechnology and
attitudes toward biotechnological applications and differences as regards their
majors. Although the science majors had higher knowledge and attitude scores than
the nonscience majors, it is not possible to say that they have sufficient
knowledge of biotechnologies. Besides, the participants ' attitudes toward
biotechnological applications were not considerably related to their knowledge of
biotechnology. (C) 2016 by The International Union of Biochemistry and Molecular
Biology, 45( 2): 115- 125, 2017.
This study evaluated the effect of an aluminosilicate mineral additive-Biotite V
(BV) on growth performance, the immunological and adrenal responses in weaned pigs
after Escherichia coli lipopolysaccharide (LPS) challenge. Thirty-two crossbred
weaned pigs were used in this 2x2 factorial experiment, with dietary treatment
(basal diet with or without 0.45% BV supplementation) and LPS challenge (challenged
or not challenged) as two main factors. On day 14 and 21, pigs were injected
intraperitoneally with either 100 mu g/kg body weight of LPS or an equivalent
amount of sterile saline. Blood samples were collected 3 h after the first
challenge followed by total and differential leukocyte counts and analysis of
plasma tumor necrosis factor-alpha (TNF-alpha), prostaglandin E-2 (PGE(2)),
cortisol, insulin, and biochemical parameters. Body weight and feed intake were
measured weekly throughout the 4-week experiment. The results showed that both LPS
challenges reduced average daily gain (ADG) (P < 0.05) and increased feed/gain (P <
0.001), and BV decreased feed/gain (P < 0.05) of immunology challenged pigs. The
LPS challengexdiet interactions were observed for ADG (P < 0.05) and feed/gain (P <
0.05) during both challenge. LPS challenge reduced the number of white blood cells,
lymphocytes, monocytes, and neutrophils (P < 0.05). LPS challengexdiet interaction
was observed for plasma TNF-alpha (P < 0.05) concentration, showing decreased
plasma TNF-alpha response to LPS challenged in pigs receiving BV. But no LPS
challenge x diet interaction was observed for plasma cortisol or PGE(2). There was
a diet effect for plasma insulin (P < 0.05) and glucose (P < 0.05), showing
increased plasma insulin and decreased glucose with BV supplementation, but no LPS
challengexdiet interaction was observed. We conclude that BV improved the weight
gain and feed efficiency of weaned pigs during an immunological challenge by
suppressing the proinflammatory cytokine release.
The synergistic effect between displacement damage dose (DDD) and analog transient
radiation effects on electronics (ATREE) in an operational amplifier (LM124)
(opamp) from three different manufacturers is investigated. Pulsed X-ray
experiments have highlighted ATREE sensitivity on devices significantly more
important following exposure to fission neutrons than for unirradiated devices. A
previously developed simulation tool is used to model ATREE responses taking into
account the electrical parameters degradation due to displacement damage
phenomenon. A good agreement is observed between model outputs and experimental
ATREE results.
The influence of external circuit designs on ASET shapes in a high speed current
feedback amplifier (CFA) (AD844) is investigated by means of the pulsed laser
single event effect (PLSEE) simulation technique. Changes of the feedback resistors
modify circuit's electrical parameters such as closed-loop gain and bandwidth,
affecting amplifier stability and so ASET shapes. Qualitative explanations based on
general electronic rules and feedback theories enable the understanding of a CFA
operation establishing a correlation between the evolution of external feedback
resistor values and ASET parameters. TID effects on the ASET sensitivity in AD844
CFA are also investigated in this work highlighting different behaviors according
to the impacted bipolar transistor in the integrated circuit.
The propagation of Analog Single Event Transients (ASETs) to multiple outputs of
Bipolar Junction Transistor (BJTs) Integrated Circuits (ICs) is reported for the
first time. The results demonstrate that ASETs can appear at several outputs of a
BJT amplifier or comparator as a result of a single ion or single laser pulse
strike at a single physical location on the chip of a large-scale integrated BJT
analog circuit. This is independent of interconnect cross-talk or charge-sharing
effects. Laser experiments, together with SPICE simulations and analysis of the
ASET's propagation in the s-domain are used to explain how multiple-output
transients (MOTs) are generated and propagate in the device. This study
demonstrates that both the charge collection associated with an ASET and the ASET's
shape, commonly used to characterize the propagation of SETs in devices and
systems, are unable to explain quantitatively how MOTs propagate through an
integrated analog circuit. The analysis methodology adopted here involves combining
the Fourier transform of the propagating signal and the current-source transfer
function in the s-domain. This approach reveals the mechanisms involved in the
transient signal propagation from its point of generation to one or more outputs
without the signal following a continuous interconnect path.
Objective: To examine emotion processing in euthymic bipolar patients (EBP)
compared to healthy controls. In addition, to determine whether or not there is an
association between emotion processing and psychosocial functioning. Material and
methods: A sample of 60 EBP and 60 healthy controls matched for age, gender,
education level, and premorbid intelligence were studied. All subjects were
assessed using the MATRICS Consensus Cognitive Battery (MCCB) and two additional
executive function measures: the Trail Making Test-Part B and the Stroop Test.
Emotion processing was examined using the Mayer-Salovey-Caruso Emotional
Intelligence Test (MSCEIT). Psychosocial functioning was assessed using the
Functional Assessment Short Test (FAST). Results: Euthymic bipolar patients
obtained lower scores than controls in all MSCEIT measures except for the using
emotions branch. Likewise, EBP obtained a worse performance than healthy controls
in all neurocognitive domains. Correlation between MSCEIT strategic area measures
and FAST total score was found (r = -0.311; P < 0.016). Regression analysis showed
that residual depressive symptomatology explains a 9.1% of the variance in
functional outcome. MSCEIT strategic area score explained an additional 8.6%.
Neurocognition did not increase the percentage of the variance explained by emotion
processing. Conclusions: Euthymic bipolar patients exhibit deficits in emotion
processing. Emotion processing is associated with social functioning in these
patients.
Background: Up to 60% of patients with bipolar disorder (BD) have a history of
traumatic events, which is associated with greater episode severity, higher risk of
comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD
are thus necessary but studies are currently scarce. The aim of this study is to
examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy
focusing on adherence, insight, de-idealisation of manic symptoms, prodromal
symptoms and mood stabilization can reduce episode severity and relapse rates and
increase cognitive performance and functioning in patients with BD. Methods/
design: This is a single-blind, randomized controlled, multicentre trial in which
82 patients with BD and a history of traumatic events will be recruited and
randomly allocated to one of two treatment arms: EMDR therapy or supportive
therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min
each, during 6 months. The primary outcome is a reduction of affective episodes
after 12 and 24 months in favour of the EMDR group. As secondary outcome we
postulate a greater reduction in affective symptoms in the EMDR group (as measured
by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the
Clinical Global Impression Scale modified for BD), and a better performance in
cognitive state, social cognition and functioning (as measured by the Screen for
Cognitive Impairment in Psychiatry, The Mayer-SaloveyCaruso Emotional Intelligence
Test and the Functioning Assessment Short Test, respectively). Traumatic events
will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-
administered PTSD Scale and the Impact of Event Scale. Discussion: The results of
this study will provide evidence whether a specific EMDR protocol for patients with
BD is effective in reducing affective episodes, affective symptoms and functional,
cognitive and trauma
Objectives: Emotional processing abnormalities have been implicated in bipolar
disorder (BD) but studies are typically small and uncontrolled. Here, facial
expression recognition was explored in a large and naturalistically recruited
cohort of BD patients. Methods: 271 patients with BD completed the facial
expression recognition task. The effects of current medication together with the
influence of current mood state and diagnostic subtype were assessed whilst
controlling for the effects of demographic variables. Results: Patients who were
currently receiving treatment with lithium demonstrated significantly poorer
accuracy in recognising angry faces, an effect that held in a monotherapy sub-
analysis comparing those participants on lithium only and those who were
medication-free. Accuracy in recognising angry faces was also lower amongst
participants currently taking dopamine antagonists (antipsychotics). Higher levels
of current depressive symptoms were linked to poorer accuracy at identifying happy
faces. Conclusion: Use of lithium and possibly dopamine antagonists may be
associated with reduced processing of anger cues in BD. Findings support the
existence of mood-congruent negative biases associated with depressive symptoms in
BD. Observational cohort studies provide opportunities to explore the substantial
effects of demographic, psychometric and clinical variables on cognitive
performance and emotional processing.
In patients with major depressive disorder or bipolar disorder, abnormalities in
excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to
aberrant functional connectivity patterns within large brain networks. Network
dysfunction in association with altered brain levels of glutamate and gamma-
aminobutyric acid have been identified in both animal and human studies of
depression. In addition, evidence of an antidepressant response to subanesthetic-
dose ketamine has led to a collection of studies that have examined neurochemical
(e.g., glutamatergic and gamma-aminobutyric acidergic) and functional imaging
correlates associated with such an effect. Results from these studies suggest that
an antidepressant response in association with ketamine occurs, in part, by
reversing these neurochemical/physiological disturbances. Future studies in
depression will require a combination of neuroimaging approaches from which more
biologically homogeneous subgroups can be identified, particularly with respect to
treatment response biomarkers of glutamatergic modulation.
Most theoretical frameworks regarding the role of life stress in bipolar disorders
(BD) do not incorporate the possibility of a changing relationship between
psychosocial context and episode initiation across the course of the disorder. The
kindling hypothesis theorizes that over the longitudinal course of recurrent
affective disorders, the relationship between major life stressors and episode
initiation declines (Post, 1992). The present study aimed to test an extension of
the kindling hypothesis in BD by examining the effect of early life adversity on
the relationship between proximal life events and prospectively assessed mood
episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and
mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-
Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II;
33 Cyclothymic disorder). Participants completed a self-report measure of early
adversity at baseline and interview-assessed mood episodes and life events at
regular 4-month follow-ups. Results indicate that early childhood adversity
sensitized bipolar participants to the effects of recent stressors only for
depressive episodes and not hypomanic episodes within BD. This was particularly the
case with minor negative events. The current study extends prior research examining
the kindling model in BD using a methodologically rigorous assessment of life
stressors and mood episode occurrence. Clinicians should assess experiences of
early adversity in individuals with BD as it may impact reactivity to developing
depressive episodes in response to future stressors.
Background: Bipolar disorder is a common chronic illness characterized by high
levels of morbidity and all-cause mortality. Lithium is one of the gold standard
mood stabilizer treatments, but the identification of good, partial and non-
responders in clinical settings is inconsistent. Methods: We used an established
rating scale (the Alda scale) to classify the degree of lithium response (good
response, partial response, non-response) in a large, multicentre clinically
representative sample of well-characterized cases of bipolar disorders I and II.
Next, we examined previously reported clinical predictors of response to determine
which factors significantly differentiated between the three response groups.
Results: Of 754 cases, 300 received lithium, for at least 6months, as a treatment
for bipolar disorder (40%). Of these cases, 17% were classified as good response,
52% as partial response and 31% as non-response. Lifetime history of mixed episodes
(p=0.017) and alcohol use disorders (p=0.015) both occurred in >20% of partial
response and non-response groups but <10% of good response cases. Family history of
bipolar disorder I was of borderline statistical significance, being more frequent
in the good response group (38%) compared with the non-response group (18%). There
was a trend (p=0.06) for bipolar disorder II to be associated with non-response.
Conclusions: Only three factors previously identified as predictors of lithium
response significantly differentiated the response groups identified in our sample.
Interestingly, these factors have all been found to co-occur more often than
expected by chance, and it can be hypothesized that they may represent a shared
underlying factor or dimension. Further prospective studies of predictors and the
performance of the Alda scale are recommended.
Background: The relationship between Toxoplasma gondii infection and the
development of bipolar disorder (BD) has long been investigated, yet to date it is
still poorly understood and documented. The aim of this review is to derive a
summary estimate of the strength of the association between infection with T.
gondii and BD from the available published studies. Methods: A systematic review
was performed using PubMed, LILACS, PsycINFO, and Embase databases. Studies which
included a proportion of seropositive BD patients and controls were further
examined in a meta analysis. Results: One hundred eighteen citations were initially
retrieved. Thirteen studies were included in our systematic review. Eight out of
these thirteen studies were included in our meta-analysis. Statistical analyses
showed that T. gondii infection is associated with with BD (OR=1.26). Limitations:
Small sample size was the major limitation among the studies that carried out
serological analyses. In addition, the available studies did not have enough
information on disease status/severity or type of bipolar disorder. Also, it was
not possible to analyze pregnancy status or perinatal infection. Future studies
addressing the aforementioned topics are clearly needed. Conclusions: Despite
heterogeneous results, patients with BD are more likely to be infected by T. gondii
than controls. Early T. gondii infection might predispose the development of BD.
T.gondii infection is becoming clinically relevant in psychiatric disorders and
future mechanistic studies are required to elucidate the underlying
pathophysiological mechanisms.
Sleep disruptions represent a core feature of bipolar disorders and have been
widely studied through the use of actigraphy, which is an objective measure of
motor activity and sleep. Finding objective outcomes, which reliably measure sleep
in bipolar disorders, is essential in developing better therapies and improving
follow-up monitoring strategies. Our aim is to understand the role of actigraphy as
an objective measure of sleep in bipolar disorder. We undertook a systematic review
and meta-analysis on studies using actigraphy to detect changes in activity and
sleep patterns in bipolar patients versus healthy controls. The primary outcome
measures were the analyses of 'activity mean' and 'sleep duration'. As secondary
outcomes we analysed 'sleep onset latency', 'sleep efficiency', and 'time awake
after sleep onset'. Thirteen studies comprising 821 subjects met quality criteria
for inclusion. The results show a decrease in activity mean and an altered pattern
of sleep in bipolar patients. Further analyses suggest that the results might be
generalized to a bipolar condition which underlies manic and depressed episodes as
well as euthymic phases. This study highlights the role of actigraphy as an
important objective tool for the ambulatory monitoring of sleep and activity in
bipolar disorders. (C) 2016 Elsevier Ltd. All rights reserved.
Background. The different patterns of Emotional Intelligence (EI) deficits in
schizophrenia and bipolar I disorder are are not yet well understood. This study
compares EI levels among these groups and highlights the potential impact of non-
social cognition on EI. Method. Fifty-eight schizophrenia and 60 bipolar
outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence
Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS).
Analyses of covariance were performed with adjustment for the BACS composite score.
Results. Compared to bipolar subjects, schizophrenia patients showed significantly
lower levels in both EI and nonsocial cognition. After adjustment for the BACS
composite score, the difference in EI was lost. The mediation analysis revealed
that differences between schizophrenia and bipolar patients in strategic EI are
almost fully attributable to the mediating effect of non-social cognition.
Conclusions. Our findings suggest that in both schizophrenia and bipolar patients
EI is strongly influenced by nonsocial cognitive functioning. This has to be taken
into account when interpreting MSCEIT data in comparative studies in serious mental
illness and emphasizes the importance of cognitive remediation.
The degradation of LM124J operational amplifier under the gamma-irradiation is
studied for different dose rates and temperatures during irradiation. The results
show that degradation of studied devices due to total ionizing dose effects
continues to increase significantly, if the dose rate decreases below 0.01
rad(Si)/s, that is not typical for the most of bipolar devices. It can complicate
the use of criteria of enhanced low dose rate sensitivity (ELDRS), which are
defined by existing standards for radiation tests. The paper shows how to take into
account such effects during radiation testing considering ELDRS.
Objective: Bipolar disorder (BD) is highly heritable. Neuroimaging studies
comparing unaffected youth at high familial risk for BD (i.e., those with a first-
degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR)
youth (i.e., those without a first-degree relative with BD) and to patients with BD
may help identify potential brain-based markers associated with risk (i.e., regions
where BR+BD not equal LR), resilience (HR not equal BD+LR), or illness (BD not
equal HR+LR). Method: During functional magnetic resonance imaging (fMRI), 99
youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR,
41 LR) performed a task probing face emotion labeling, previously shown to be
impaired behaviorally in youth with BD and HR youth. Results: We found three
patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared
deficits) included dysfunction in higher-order face processing regions (e.g.,
middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience
markers and disorder sequelae (where HR and BD, respectively, show unique
alterations relative to the other two groups) included different patterns of neural
responses across other regions mediating face processing (e.g., fusiform),
executive function (e.g., inferior frontal gyrus), and social cognition (e.g.,
default network, superior temporal sulcus, temporoparietal junction). Conclusion:
If replicated in longitudinal studies and with additional populations, neural
patterns suggesting risk endophenotypes could be used to identify individuals at
risk for BD who may benefit from prevention measures. Moreover, information about
risk and resilience markers could be used to develop novel treatments that recruit
neural markers of resilience and attenuate neural patterns associated with risk.
Urban habitats are described as having an overall negative influence on many
fitness-related traits in several bird species, but a vital function such as
immunity remains poorly studied. The immune response is strongly linked to
individual condition, which partly depends on resource availability and the
parasitic context that often differ between urban and natural habitats. A
difference between the immunity of populations dwelling in urban areas and
populations from more natural habitats can, therefore, be hypothesized. We
conducted a 2-year experimental study on great tits (Parus major) in urban and
forest areas. We stimulated the constitutive immunity of nestlings and assessed
both the inflammatory response by measuring the plasma levels of haptoglobin, an
inflammatory marker, and its activation cost through the loss of body mass. In
addition, we checked the nestlings for ectoparasites and assessed haemosporidian
prevalence in adults. Nestlings from urban sites produced relatively less
haptoglobin and lost more body mass than those from forest sites, which suggests
that the activation of constitutive immunity is more costly for birds living in
urban sites than for those living in the forest. We detected no ectoparasite in
birds in both habitats. However, urban adults showed lower haemosporidian
prevalence than forest ones, suggesting a reduced exposure to these parasites and
their vectors in towns. Overall, our study provides evidence for an immune
difference between urban and forest populations. Because immunity is crucial for
organism fitness, it is of prime interest to identify causes and processes at the
origin of this difference.
Introducing an animal into a new location could be hazardous in the form of disease
transmission, especially with respect to infections that are often overlooked. Such
introduced infectious agents, including parasitic ones, then pose potential danger
to the native animal population. Within the conservation program, the European
bison was introduced into many European countries. However, this largest European
herbivore was recognized as a new host for an invasive parasitic nematode,
Ashworthius sidemi, in Poland in 1998. Since then, the prevalence of this non-
native parasite in Poland has increased not only in bison but also in other wild
ruminants. In 2011 five European bison individuals were transported from Poland to
the Czech Republic. In the current study, we examined the gastrointestinal tracts
of two European bison and two red deer culled in the Z. idlov game reserve. A.
sidemi was identified in all investigated animals using both morphological and
molecular methods; infection intensity was higher in bison than in deer. Our
findings represent the first record of this invasive parasite in European bison at
the Czech territory. The results of this study indicate changes in epidemiological
patterns of Ashworthius infections in the climatic condition of Central Europe as
well as the need to verify the reliability of ashworthiosis intravital diagnostics.
One can expect A. sidemi to spread gradually in the Czech Republic and colonize
other native ruminant hosts.
In the present study, sediment was spiked with bisphenol A (BPA) solution to
explore the interaction between indigenous bacterial communities and BPA
biodegradation in sediment. Results showed that BPA could be adsorbed to the
sediment and then biodegraded rapidly. Biodegradation efficiency of BPA in
treatments with 10 and 50 mg/L BPA reached 64.3 and 61.8% on the first day,
respectively. Quantitative polymerase chain reaction and denaturing gradient gel
electrophoresis analysis indicated that BPA affected the densities, species, and
diversities of bacteria significantly. The response of bacterial community to BPA
favored BPA biodegradation by promoting the growth of BPA-reducing bacteria and
inhibiting other competitors. According to the results of sequencing, Pseudomonas
and Sphingomonas played vital roles in the degradation of BPA. They presented over
73% of the original bacterial community, and both of them were promoted by BPA
comparing with controls. Laccase and polyphenol oxidase contributed to the
degradation of BPA and metabolic intermediates, respectively. This paper
illustrates the rapid biodegradation of BPA induced by the response of indigenous
bacterial communities to the BPA stress, which will improve the understandings of
BPA degradation in sediment.
Aberrant expression of EPH receptors and their ligands, ephrins, has been reported
in a large variety of human cancers, including epithelial cancers from the colon
and ovary. Due to the recently reported decrease or loss of EPHBs expression in
colorectal carcinomas and the abundance of CpG sites in their promoters, we
analyzed the promoter methylation status of three members of the EPHB family,
EPHB2, EPHB3 and EPHB4, in a series of 22 colon cancer cell lines, as well as in
four ovarian cancer cell lines and 56 ovarian tumor samples. The promoters of the
three receptor genes were unmethylated in the vast majority of samples as assessed
by methylation-specific polymerase chain reaction (MSP). These results were
confirmed by direct bisulphite sequencing. Furthermore, from RT-PCR analyzes and
Northern blotting, EPHB2 showed only small variation in RNA expression across
ovarian cancer cell lines and clinical samples. We conclude that promoter
hypermethylation of EPHB2, EPHB3 and EPHB4 is not a common event in colon and
ovarian cancers and therefore plays no major role in these tumors.
Children represent a population at risk, because of their short size, their naivety
and their attraction to animals. The face and hands are the most specific locations
in young children. Wounds are often multiple. In more than half the cases, the
child knows the animal, which are dogs and cats by frequency argument. The bite
episode occurs mostly when the child is alone with the pet without direct
supervision, while playing or stroking the animal. As in all bites, pediatric
lesions are infectious, functional and aesthetic emergencies, but the goal of this
work was primarily to make a point on principles of surgical management of animal
bites in children, highlighting pediatric specificities. Animal bites require
psychological, anesthetic and surgical treatment, adapted to the child, in a
specialized structure. Hospitalization and general anesthesia are more frequent in
children. Any suspicion of mistreatment (and/or abuse) should lead to the child's
hospitalization, even if wounds do not justify monitoring in a surgical
environment. Emergency surgery is essential to limit functional and aesthetic
consequences. The healing capacities of the child and the frequent lack of co-
morbidity allow a conservative surgical treatment with suture, repositioning skin
flaps and controlled healing in the first place. Immobilization, drainage, and
antibiotics will complete the surgery. The healing process, however, leads to a
specific management during scar remodeling phase and growth. Psychological care of
the child and parents should not be forgotten, and has to start at the same time as
surgical treatment at in acute phase. (C) 2016 Elsevier Masson SAS. All rights
reserved.
BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant
patient. Soon after its identification, BKPyV was characterized as a kidney-tropic
virus, which is responsible of a significant fraction of the rejection of
transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able
to transform different types of animal and human cells and to induce tumors of
different histotypes in experimental animals. BKPyV DNA sequences have been
detected in healthy individuals and cancer patients using polymerase chain
reaction/Shouthern blot hybridization methods. Serum antibodies against this
polyomavirus were revealed using immunological techniques, which, however, cross-
react with other polyomaviruses such as JC (JCPyV) and Simian Virus 40. These non-
specific data indicate the need of novel immunological methods and new
investigations to check in a specific manner, BKPyV spread in humans. To this aim,
mimotopes from BKPyV structural capsid protein 1 (VP1) were employed for specific
immunological reactions to IgG antibodies of human serum samples. An indirect
enzyme-linked immunosorbent assay with synthetic peptides mimicking immunogenic
epitopes of BKPyV VP1 was set up and employed to test sera of healthy adult
subjects. Data from this innovative immunological assay indicate that serum
antibodies against BKPyV VP1 mimotopes are detectable in healthy subjects ranging
from 18 to 90 years old. The overall prevalence of serum samples that reacted to
BKPyV VP1 mimotopes was 72%. The strong points from this investigation are the
novelty of the immunological method, its simplicity of the approach, and the
specificity of BKPyV antibody reaction to VP1 mimotopes.
Infections and malignancies are the expected complications of immunosuppressive
therapy, which non-specifically impairs cellular and humoral immune responses in
renal transplant recipients. Infections were usually frequent and severe during the
early post-transplant period (first year). Recent diagnostic methods (molecular
biology) and availability of new antivirals, antifungal and. antibiotic drugs made
rapid diagnosis and systematic preventive strategies much easier and this resulted
in a significant reduction of infections and infectious death in this population.
However, new infectious agents like BK polyomavirus, hepatitis E virus, parvovirus
(as well as Chigunkunya, West Nile and others in particular areas) were recently
recognized as responsible of aggressive infections in the immunocompromised host.
Malignancies are also common after transplantation, due to the intensity and
duration of immunosuppression. Skin cancers and lymphoproliferative disorders are
the most common and are undoubtedly caused by viral infections, but incidence of
non-skin cancers is also increased. After reduction of immunosuppression, treatment
is similar to non-transplant patients: Results are usually poor and cancer is now
the third cause of death in transplant recipients. Due to their anti-proliferative
and anti-tumoral properties, incidence of de novo cancer significantly decreased in
patients receiving mTor inhibitors as maintenance immunosuppression; furthermore,
in patients already diagnosed with Kaposi sarcoma or recurrent skin cancers,
introduction of mTor was associated with stabilisation and/or regression of
malignant lesions. (C) 2016 Association Societe de nephrologie. Published by
Elsevier Masson SAS. All rights reserved.
Objective: The purpose of the present, prospective, cohort study was to monitor
urine cytology samples from recipients of renal transplants to search for the
occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to
correlate the existence of these cells with molecular detection of polyomavirus BK
(BKV) DNA in urine. Material and methods: This study included patients who
underwent renal transplantation. Patients had their urine tested quarterly, during
the first year post-transplantation, for the presence of decoy cells and
degenerated cells, as well as by quantitative determination of BKV load in the
urine and plasma. Results: Three hundred and sixty-one examinations were performed
on 101 patients within 12 months of attendance. Urine cytology results were: 198
(54.9%) negative and 60 (16.6%) positive for the presence of viral cytopathic
effects depending on the presence of BKV infection, 72 (19.9%) positive for the
manifestation of degenerated cells and 31 (8.6%) unsatisfactory for analysis. There
was a subtle tendency towards the presence of degenerated inclusion-bearing cells
in cases in which the virus was detected in voided urine. However, the presence of
degenerated cells exhibited a tendency to BKV positivity in months 3, 6 and 9 and,
exclusively in month 12, this trend was statistically significant. Conclusions:
There were not enough strong morphological and staining elements to state the
origin of the degenerated cells or to describe the nature of the infection (viral
or bacterial), given that these cells were undergoing an apoptotic process in post
renal transplant patients.
Background. Although trichinellosis is known to cause thrombotic disease, serious
thrombotic events are rare and have not been previously associated with Trichinella
nativa infection. Methods. Patient interviews and medical chart reviews were
conducted on 10 men who became ill following consumption of a common source of
black bear meat. Trichinella serology on patient sera as well as polymerase chain
reaction (PCR) and larval identification of the meat samples was conducted.
Results. All 10 exposed individuals developed an acute illness clinically
compatible with trichinellosis, characterized by fever, abdominal pain, and
diarrhea, along with eosinophilia ranging from 0.9 x 10(9)/L to 6.1 x 10(9)/L.
Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed
individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-
elevation myocardial infarction and sinus venous tract thrombosis occurred as a
complication of trichinellosis in 2 patients. Acute serology was nonreactive in all
patients, though convalescent serology was reactive in 6 of 8 (75%) patients for
whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and
was corroborated by microscopic larval identification. Conclusions. We report a
100% attack rate of T. nativa from bear meat among those who were exposed, and
demonstrate that this species can cause serious thrombotic complications of
trichinellosis in humans. Education of hunters and the public regarding the
importance of proper preparation of wild game prior to ingestion is warranted.
Black rot, caused by Xanthomonas campestris pv. campestris (Pammel) Dowson (Xcc),
is one of the most damaging diseases of cauliflower and other crucifers. In order
to investigate the molecular resistance mechanisms and to find the genes related to
black rot resistance in cauliflower, a suppression subtractive hybridization (SSH)
cDNA library was constructed using resistant line C712 and its susceptible near-
isogenic line C731 as tester and driver, respectively. A total of 280 clones were
obtained from the library by reverse northern blotting. Sequencing analysis and
homology searching showed that these clones represent 202 unique sequences. The
library included many defense/disease-resistant related genes, such as plant
defensin gene PDF1.2, lipid transfer protein, thioredoxin h. Gene expression
profiles of 12 genes corresponding to different functional categories were
monitored by real-time RT-PCR. The results showed that the expression induction of
these genes in the susceptible line C712 in response to Xcc was quicker and more
intense, while in C731 the reaction was delayed and limited. Our results imply that
these up-regulated genes might be involved in cauliflower responses against Xcc
infection. Information obtained from this study could be used to understand the
molecular mechanisms of disease response in cauliflower under Xcc stress.
Instrumental test of black tea samples instead of human panel test is attracting
massive attention recently. This study focused on an investigation of the
feasibility for estimation of the color sensory quality of black tea samples using
the VIS-NIR spectroscopy technique, comparing the performances of models based on
the spectra and color information. In model calibration, the variables were first
selected by genetic algorithm (GA); then the nonlinear back propagation-artificial
neural network (BPANN) models were established based on the optimal variables. In
comparison with the other models, GA-BPANN models from spectra data information
showed the best performance, with the correlation coefficient of 0.8935, and the
root mean square error of 0392 in the prediction set. In addition, models based on
the spectra information provided better performance than that based on the color
parameters. Therefore, the VIS-NIR spectroscopy technique is a promising tool for
rapid and accurate evaluation of the sensory quality of black tea samples. (C) 2017
Elsevier B.V. All rights reserved.
Possible altered gene expression patterns in bladder tumour carcinogenesis in rat
bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined
by cDNA microarray analysis of gene expression profiles. Thirty Sprague-Dawley rats
were given drinking water containing 0.05% BBN ad libitum for 24 to 28 weeks. Equal
numbers of control rats were given tap water without BBN. After treatment, the rat
bladders were excised for RNA extraction and histopathological examinations. Total
RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-
dissected normal rat bladder epithelia. The atlas glass rat microarray was used,
which included oligonucleotides of 1081 rat genes. Some of the up-regulated genes
in rat bladder TCCs were further confirmed by Northern blotting. Our results showed
that the transcriptions of 30 genes were significantly elevated in the rat bladder
TCCs, and these included fly proto-oncogene, Lipocortin 2, COX IV, COX V a, and
cathepsin D. Also, 15 genes were significantly down-regulated in the rat bladder
TCCs and they included B7.1, TNFr1, APOA1 and VHL. The results of cDNA microarray
analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited
different and specific gene statement profiles. The increased expressions of the
identified genes may play an important role in the chemically induced bladder
carcinogenesis.
To date, molecular evidence studies for bladder cancer, using the microarray
technology, are focusing on the transitional cell carcinoma, however, similar
fingerprinting studies have rarely been performed on the other molecular phenotypes
of bladder cancer, squamous cell carcinoma (SCC). This study was conducted to
monitor the gene expression profiles for bilharzial-related SCC of the bladder to
be able to compare its data with transitional cell carcinoma microarray data. A
total of 17 paired bilharzial urinary bladder SCC specimens and their corresponding
normal urothelium were analyzed using the complementary deoxyribonucleic acid
microarray hybridization approach to study the molecular basis of the development
of SCC of the urinary bladder. Validation of the microarray results was performed
using the Northern blotting technique. After supervised analysis of the microarray
data, there was at least a 3-fold difference in the expression between SCC of the
bladder and normal urothelium in 82 genes. A total of 38 genes were up-regulated in
SCC of the bladder, including matrix degradation-related genes, growth factors,
different oncogenes, and immunology related genes. Conversely, 44 genes were down-
regulated in SCC of the bladder, including integrins, laminins, cadherins,
nonmetastatic cell 1 (NM23) and apoptosis-related genes. Our findings can explain
the aggressive behavior of SCC of the bladder. Such gene profiling studies will add
to our understanding of the mechanisms of carcinogenesis, and may also improve our
ability to diagnose and treat bladder cancer. (c) 2007 Elsevier Inc. All rights
reserved.
Objective. - Comment the new WHO histological classification of tumors of the
urinary system and male genital organs 2016 and expose the state of art about
urothelial carcinogenesis and molecular modifications of bladder cancer, with the
consequences on the treatments. Material and method. - A systematic review of the
literature search was performed from the data base PubMed, focused on the following
keywords: "bladder cancer", "molecular", "subtypes". Results. - The new WHO
histological classification of tumors of the urinary system 2016 confirm the
importance of pathology in determining the care of patients, especially the grade,
the histological type and the infiltration, while taking into account the
difficulties. In 2014, the Cancer Genome Atlas reported genetic modifications of
bladder cancer. Recently, several studies explored molecular anomalies of bladder
cancer and elaborated molecular classifications, analyzing their predictive value.
According to the groups, different molecular subtype had been defined: Urobasal A,
Urobasal B, genomically unstable, infiltrated, squamous cell carcinoma-like and
p53-like luminal bladder cancers. This latter subgroup seems to be chemoresistant.
Conclusions. - The molecular biology and classifications allow a better
understanding of bladder cancer and could complete in near future histological data
to improve patient management. (C) 2016 Elsevier Masson SAS. All rights reserved.
Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein
that has been recently found to play a role in cancer cell proliferation,
angiogenesis, and invasion. Due to its potential responsibility in cancer
aggressiveness, the main objective of this work was to investigate its expression
in bladder cancer and the biological functions in bladder cancer cells. Using
immunohistochemistry, western blot, and reverse transcription polymerase chain
reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein
B in bladder cancer tissues and bladder cancer cell lines. The effects of
glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and
invasion were tested after knocking down the glycoprotein nonmetastatic melanoma
protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell,
and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma
protein B protein was highly expressed in the bladder cancer tissues and cell
lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress
the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein
nonmetastatic melanoma protein B expression was related to the poor differentiation
and recurrence by immunohistochemistry analysis. The survival analysis also showed
that glycoprotein nonmetastatic melanoma protein B was related to the patient
prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was
highly expressed in the bladder cancer, which was related to the poor prognosis in
bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the
proliferation, migration, and invasion in bladder cancer cells.
We sought to identify and validate a novel urinary autophagy transcript signature
in patients with bladder cancer and evaluate its clinical utility. We performed an
initial screening for seven autophagy transcript-based panel (autophagy-related
protein 12 (ATG12); WD repeat domain, phosphoinositide interacting 2 (WIPI2); FYVE
and coiled-coil domain-containing protein 1 (FYCO1); microtubule-associated protein
light chain (MAPLC3); RB1-inducible coiled-coil 1 (RB1CC1); tachylectin-II-like
beta-propeller domain 1 (TECPR1); and Unc-51-like kinase (ULK1)) that was
identified based on bioinformatics analysis followed by SYBR Green-based polymerase
chain reaction array validation in paired tissue and urine samples. Afterward, we
evaluated the expression of differentially expressed autophagy transcripts in an
independent validation set with reverse transcription quantitative real-time
polymerase chain reaction in urine sediments of 140 patients with bladder cancer,
68 patients with benign urological lesions, and 74 healthy controls (age and sex
matched). The expression levels of ATG12, FYCO1, TECPR1, and ULK1 in paired bladder
tissue and urine samples were significantly lower in bladder cancer than in control
group (p < 0.001). In the validation set, the receiver-operating characteristic
curve analyses demonstrated that each urinary autophagy transcripts showed high
sensitivity and specificity for distinguishing bladder cancer from non-bladder
cancer patients (ATG12, 75.4% and 86.1%; FYCO1, 87% and 75.7%; ULK1, 85.5% and
75.6%; and TECPR1, 90% and 81.9%). We document and validate a novel autophagy
transcript signature for human bladder cancer diagnosis: bilharzial and non-
bilharzial types.
Background: Bladder cancer is a leading cause of morbidity and mortality. Despite
recent advances in understanding its molecular biology, the 5-year survival for
muscle-invasive disease (muscle-invasive bladder cancer [MIBC]) remains
approximately 50%. Although neoadjuvant chemotherapy (NAC) offers an established 5%
absolute survival benefit at 5 years, only the 40% of patients with a major tumor
response appear to benefit. There remains, therefore, a critical unmet need for
predictive markers to determine which patients are best managed with NAC, as well
as for novel targeted therapies to overcome resistance to NAC. Methods: The NAC
paradigm offers the optimal clinical context for developing precision therapy for
MIBC. Abundant tissue is available for analysis before NAC in all patients and
after NAC in patients with residual MIBC. Technologic advances have enabled next-
generation sequencing and gene expression microarray analysis of routinely
collected and even archived tissue specimens. These technologies provide a
foundation for the identification of markers of chemoresistance and for the
development of rational cotargeting strategies. Results: Modern computational
methods allow for some measure of target validation, which can be enhanced by the
use of patient-derived primary xenografts (PDX). These PDX can be established at
the time of radical cystectomy after NAC if there is residual MIBC. By the time a
patient recurs clinically, candidate drugs targeting specific molecular changes in
the patient tumor and corresponding PDX would have been tested in the PDX model,
and only the most efficacious drug(s) would be administered to the patient. Liquid
biopsies in the form of circulating tumor DNA and circulating tumor cells allow
noninvasive longitudinal monitoring of the molecular landscape of an advanced tumor
as it is being treated with successive courses of systemic therapy. Conclusions:
These tools combined form the foundation of an evidence-based precision oncology
strategy for MIBC. (C) 2016 Elsevier Inc. All rights reserved
Objective: This study examined symptom reporting related to the 10th Edition of the
International Statistical Classification of Diseases and Related Health Problems
(ICD-10) criteria for postconcussional syndrome (PCS) in Operation Enduring Freedom
(OEF) and Operation Iraqi Freedom (OIF) Veterans. Our aims were to: (a) examine
relationships among PCS symptoms by identifying potential subscales of the British
Columbia Postconcussion Symptom Inventory (BC-PSI); and (b) examine group
differences in BC-PSI items and subscales in Veterans with and without blast
exposure, mild traumatic brain injury (mTBI), and posttraumatic stress disorder
(PTSD). Method: Our sample included Veterans with blast-related mTBI history
(n=47), with blast exposure but no mTBI history (n=20), and without blast exposure
(n=23). Overall, 37 Veterans had PTSD, and 53 did not. We conducted an exploratory
factor analysis (EFA) of the BC-PSI followed by multivariate analysis of variance
to examine differences in BC-PSI subscale scores by blast exposure, mTBI history,
and PTSD. Results: BC-PSI factors were interpreted as cognitive, vestibular,
affective, anger, and somatic. Items and factor scores were highest for Veterans
with blast exposure plus mTBI, and lowest for controls. Vestibular, affective, and
somatic factors were significantly higher for Veterans with blast exposure plus
mTBI than for controls, but not significantly different for those with blast
exposure but no mTBI. These results remained significant when PTSD symptom severity
was included as a covariate. Cognitive, anger, and somatic subscales were
significantly higher for Veterans with PTSD, though there was no interaction effect
of PTSD and mTBI or blast history. Conclusions: EFA-derived subscales of the BC-PSI
differentiated Veterans based on blast exposure, mTBI history, and PTSD.
The extraction of molten iron and slag in the liquid phase from the lower part of a
blast furnace (hearth) is usually accomplished according to operational experience
and involves a high degree of uncertainty, mainly because the liquid level cannot
be directly measured. This study presents a methodology for obtaining multistep
models to forecast the hearth liquid level by measuring a voltage generated on the
blast furnace shell, which is strongly correlated with the hearth liquid level. The
results show that this electrical signal is a nonstationary and nonlinear time-
series that, after appropriate treatment, can be represented by a time-delay neural
network (TDNN) model. Some comparisons are made with linear time-series models
represented by an autoregressive moving average model and a seasonal autoregressive
integrated moving average model, and the results indicate that the TDNN model
provides better forecasting performance up to one hour ahead. Note to
Practitioners-This work was motivated by the need for better knowledge regarding
the liquid level in a blast furnace hearth because this information affects the
strategy of the opening and closing of tapholes in the blast furnace and,
consequently, the production control and operational quality. Due to the
difficulties of measuring the liquid level in the hearth directly, a system was
installed that uses a voltage generated in the hearth shell as a liquid-level
sensor in the hearth. In this study, the analysis and treatment of this signal is
performed by achieving a stationary, nonlinear signal strongly correlated with the
level of molten iron and slag inside the blast furnace hearth. A mathematical model
that represents this signal was developed and implemented online in the blast
furnace digital control system to enable forecasting of the liquid level up to one
hour ahead. This computational tool aids operators and engineers in deciding in
advance the instants to open or close the tapholes, thereby increasing safety and
financial gains.
The aims of this study were to observe the effects of vacuum sealing drainage (VSD)
with three different negative pressures on the wound healing rate, macrophage count
and the expression of hyaluronic acid (HA) as well as its receptor CD44 in
seawater-immersed blast-injury wounds (SIBIW) and to determine the optimal negative
pressure value. In a minipig SIBIW model, different suction pressures and routine
dressing were applied. Histological and immunohistochemical comparisons as well as
molecular biology methods were performed to compare the wound healing conditions,
macrophage count and the levels of HA and CD44. The wound healing rate of the VSD
group was significantly higher than that of the control group, with the -120 mmHg
group exhibiting the best effects. The macrophage count of the VSD group was higher
than that of the control group. The HA level fluctuation was higher in the VSD
group, with the -120 mmHg and the -180 mmHg groups showing the most significant
fluctuation (P < 005). CD44 was expressed in the full-thickness wound-limbic
tissues and was higher in the treatment group than that in the control group, with
the -120 mmHg group having the most obvious expression. VSD significantly improved
the healing ability and increased the macrophage count and the HA content. It also
promoted CD44 expression. -120 mmHg is the optimal negative pressure value.
Blastocystis, a genetically diverse intestinal parasite with controversial
pathogenic potential, has increasingly been incriminated for diarrheal illness in
immunocompromised individuals including colorectal cancer (CRC) patients. The aim
of the current study was to assess the possible association between Blastocystis
infection and CRC condition in Makkah, Saudi Arabia (KSA). Methods: Stool samples
were collected from 80 non-cancer (NC) and 138 cancer subjects including 74 CRC
patients and 64 patients with other cancers outside gastrointestinal tract (COGT).
Molecularly confirmed Blastocystis isolates were genetically grouped and subtyped
using multiplex polymerase chain reaction with restriction fragment length
polymorphism (PCR-RFLP) and sequence-tagged site primers-based PCR (PCR-STS),
respectively. Results: Blastocystis hominis were confirmed in 29.7, 25 and 15%
among CRC, COGT and NC patients, respectively. Obtained Blastocystis isolates were
initially categorized into 2 groups (A and C), which were subsequently subtyped
into 3 different subtypes; subtype-I (38%), subtype-II (44%) and subtype-V (22%).
Interestingly, subtype-I was the most predominantly detected subtype (54.5%) among
CRC patients with a significant association risk (COR 7.548; 95% CI: 1.629-34.987;
P = 0.004). Conclusion: To the best of our knowledge, the current study is the
first to provide genetic insights on the prevalence of Blastocystis hominis among
CRC patients in Makkah, KSA. Moreover, the study suggests for a possible
association between subtype-I of Blastocystis hominis and CRC, which could indicate
a potential influence of Blastocystis on CRC condition. Further studies are
required to confirm this association risk and to investigate the possible
underlying mechanism of postulated carcinogenic influence of Blastocystis hominis
subtype-I.
Purpose of review In the last nine decades, large advances have been made toward
the characterization of the pathogenic basis and clinical management of von
Willebrand disease (VWD), the most prevalent inherited bleeding disorder.
Pathological variations at the von Willebrand factor (VWF) locus present as a range
of both quantitative and qualitative abnormalities that make up the complex
clinical spectrum of VWD. This review describes the current understanding of the
pathobiological basis of VWD. Recent findings The molecular basis of type 2
(qualitative abnormalities) and type 3 VWD (total quantitative deficiency) have
been well characterized in recent decades. However, knowledge of type 1 VWD
(partial quantitative deficiency) remains incomplete because of the allelic and
locus heterogeneity of this trait, and is complicated by genetic variability at the
VWF gene, interactions between the VWF gene and the environment, and the
involvement of external modifying loci. Recent genome wide association studies and
linkage analyses have sought to identify additional genes that modify the type 1
VWD phenotype. Summary Understanding the pathogenic basis of VWD will facilitate
the development of novel treatment regimens for this disorder, and improve the
ability to provide complementary molecular diagnostics for type 1 VWD.
The objective was to investigate a family from Argentina. The proposita was a 51-
year-old woman who had a moderate bleeding tendency. Some of her children showed a
mild bleeding tendency. Her mother and the husband were asymptomatic. Clotting,
immunological and molecular biology techniques were used. Partial thromboplastin,
prothrombin, Russell Viper venom-clotting times were moderately prolonged in the
proposita, whereas they were slightly prolonged in the children and in her mother.
Factor X (FX) activity was about 2-3% of normal in all assay systems. FX antigen
was less than 5%. Other clotting factors and platelet were normal. Genetic analysis
showed a compound heterozygosis: combination of a 'new' mutation (Gln138Arg) with
an already known mutation (Glu350Lys). The children had intermediate FX levels (35-
63% of normal) and were carriers of one of the two mutations present in the
proposita. This is the first observation of a FX deficiency in Argentina. Copyright
(C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
According to the Huaxi Group 2# blind inclined shaft hoisting machine adopts TKD-A
control system in speed control performance is poor, the control circuit is
complex, high noise, stability and low reliability, this paper proposes a SCR-D
system to replace the original scheme of reforming the electric control system. The
paper introduces the structure and working principle of SCR-D system, shows the
main equipment selection of the main circuit, and gives the system installation and
adjustment. The result shows, the reformed electric control system has
characteristics of perfect protection, control with high precision, good energy
saving effect. It achieved the expected goal.
Clavibacter michiganensis ssp. michiganensis (Cmm) causes substantial economic
losses in tomato production worldwide. The disease symptoms observed in plants
infected systemically by Cmm are wilting and canker on the stem, whereas blister-
like spots develop in locally infected leaves. A wide repertoire of serine
proteases and cell wall-degrading enzymes has been implicated in the development of
wilt and canker symptoms. However, virulence factors involved in the formation of
blister-like spots, which play an important role in Cmm secondary spread in tomato
nurseries, are largely unknown. Here, we demonstrate that Cmm virulence factors
play different roles during blister formation relative to wilting. Inoculation with
a green fluorescent protein (GFP)-labelled Cmm382 indicates that penetration occurs
mainly through trichomes. When spray inoculated on tomato leaves, the wild-type
Cmm382 and Cmm100 (lacking plasmids pCM1 and pCM2) strains form blister-like spots
on leaves, whereas Cmm27 (lacking the chp/tomA pathogenicity island) is non-
pathogenic, indicating that plasmid-borne genes, which have a crucial role in
wilting, are not required for blister formation. Conversely, mutations in
chromosomal genes encoding serine proteases (chpC and sbtA), cell wall-degrading
enzymes (pgaA and endX/Y), a transcriptional regulator (vatr2), a putative perforin
(perF) and a putative sortase (srtA) significantly affect disease incidence and the
severity of blister formation. The transcript levels of these genes, as measured by
quantitative reverse transcription-polymerase chain reaction, showed that, during
blister formation, they are expressed early at 8-16 h after inoculation, whereas,
during wilting, they are expressed after 24-72 h or expressed at low levels. Plant
gene expression studies suggest that chpC is involved in the suppression of host
defence.
DNA nanotechnology enables the synthesis of nanometer-sized objects that can be
site-specifically functionalized with a large variety of materials. For these
reasons, DNA-based devices such as DNA origami are being considered for
applications in molecular biology and nanomedicine. However, many DNA structures
need a higher ionic strength than that of common cell culture buffers or bodily
fluids to maintain their integrity and can be degraded quickly by nucleases. To
overcome these deficiencies, we coated several different DNA origami structures
with a cationic poly(ethylene glycol)-polylysine block copolymer, which
electrostatically covered the DNA nanostructures to form DNA origami polyplex
micelles (DOPMs). This straightforward, cost-effective, and robust route to protect
DNA-based structures could therefore enable applications in biology and
nanomedicine where unprotected DNA origami would be degraded.
Canine brucellosis caused by Brucella canis is a neglected zoonosis worldwide and
is a leading cause of reproductive failure in dogs, often causing substantial
economic losses in breeding kennels. This study aimed to investigate the occurrence
of B.canis infection in dogs of commercial breeding kennels located in SAo Paulo
State, Brazil. A total of 753 dogs (183 males and 570 females) from 38 commercial
kennels were clinically examined, and blood samples were collected for brucellosis
diagnosis through blood culture. The association between clinical manifestations
suggestive of brucellosis and positive results through blood culture was
determined. Of the 753 dogs tested, 166 (22.0%) had at least one clinical sign
suggestive of brucellosis and 158 (20.9%) had positive blood cultures. Seventy-two
dogs had positive blood culture and had at least one clinical sign suggestive of
brucellosis, while 91 dogs showed at least one clinical manifestation suggestive of
brucellosis although blood culture was negative. Of the 38 kennels, 16 (42.1%) had
at least one positive dog. The prevalence of infection in each kennel varied from
3.8% to 62.6%. Abortion/stillbirth, failure to conceive and enlargement of lymph
nodes were significantly associated with brucellosis in female. No association of
clinical signs and positive results in blood culture was observed in males. None of
the kennels has been carrying out programmes to control brucellosis, and the sale
of infected dogs was considered a common practice yielding risks to the public
health, in view of the zoonotic potential of the infection.
Invasive candidiasis remains one of the most serious community and healthcare-
acquired infections worldwide. Conventional Candida detection methods based on
blood and plate culture are time-consuming and require at least 2-4 days to
identify various Candida species. Despite considerable advances for candidiasis
detection, the development of simple, compact and portable point-of-care
diagnostics for rapid and precise testing that automatically performs cell lysis,
nucleic acid extraction, purification and detection still remains a challenge.
Here, we systematically review most prominent conventional and nonconventional
techniques for the detection of various Candida species, including Candida
staining, blood culture, serological testing and nucleic acid-based analysis. We
also discuss the most advanced lab on a chip devices for candida detection.
Eccentric exercise training is effective for increasing muscle mass and strength,
and improving insulin sensitivity and blood lipid profiles. However, potential
muscle damage symptoms such as prolonged loss of muscle function and delayed onset
of muscle soreness may restrict the use of eccentric exercise, especially in
clinical populations. Therefore, strategies to reduce eccentric exercise-induced
muscle damage (EIMD) are necessary, and an extensive number of scientific studies
have tried to identify potential intervention modalities to perform eccentric
exercises without adverse effects. The present paper is based on a narrative review
of current literature, and provides a novel hypothesis by which an ischemic
preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an
intermittent application of short time non-lethal ischemia to an extremity (e.g.
using a tourniquet) followed by reperfusion and was discovered in clinical settings
in an attempt to minimize inflammatory responses induced by ischemia and ischemia-
reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on
morphological and biochemical similarities in the pathophysiology of skeletal
muscle damage during clinical surgery and EIMD. Even though the primary origin of
stress differs between I/R-Injury and EIMD, subsequent cellular alterations
characterized by an intracellular accumulation of Ca2+, an increased production of
reactive oxygen species or increased apoptotic signaling are essential elements for
both. Moreover, the incipient immune response appears to be similar in I/R-Injury
and EIMD, which is indicated by an infiltration of leukocytes into the damaged
soft-tissue. Thus far, IPC is considered as a potential intervention strategy in
the area of cardiovascular or orthopedic surgery and provides significant impact on
soft-tissue protection and downregulation of undesired excessive inflammation
induced by I/R-Injury. Based on the known major impact of IPC on skeletal muscle
physiology and immunology, the present paper aims to illustrate the potential
protective effects of IPC on EIMD by discussing possible underlying mechanisms. (C)
2016 Elsevier Ltd. All rights reserved.
Objective-Systemic lupus erythematosus (SLE) is associated with the premature
development of cardiovascular disease. The platelet-endothelium interaction is
important in the pathogenesis of cardiovascular disease. In this study, we
investigated the platelet phenotype from patients with SLE and matched controls,
and their effect on endothelial cells. Approach and Results-Platelet aggregability
was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.112.8 years;
82% female; 37% white) with age- and sex-matched controls. Platelets were
coincubated with human umbilical vein endothelial cells (HUVECs) and changes to
gene expression assessed by an RNA array and quantitative reverse transcription
polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1
+/- 3.9). Compared with controls, patients with SLE had significantly increased
monocyte and leukocyte-platelet aggregation and platelet aggregation in response to
submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with
SLE platelets found a platelet-mediated effect on endothelial gene pathways
involved in cell activation. Sera from SLE versus control subjects significantly
increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3)
platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion
molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by
interleukin-1-dependent pathway. Incubation of SLE-activated platelets with an
interleukin-1-neutralizing antibody or HUVECs pretreated with interleukin-1
receptor antibodies attenuated the platelet-mediated activation of endothelial
cells. Conclusions-Platelet activity measurements and subsequent interleukin-1-
dependent activation of the endothelium are increased in subjects with SLE.
Platelet-endothelial interactions may play a role in the pathogenesis of
cardiovascular disease in patients with SLE.
We previously reported the secretion of C-type natriuretic peptide (CNP) from
vascular endothelial cells and proposed the existence of a vascular natriuretic
peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B
(GC-B), the CNP receptor, and involved in the regulation of vascular tone,
remodeling, and regeneration. In this study, we assessed the functional
significance of this system in the regulation of blood pressure in vivo using
vascular endothelial cell-specific CNP knockout and vascular smooth muscle cell-
specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor
the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial
cell-specific CNP knockout mice exhibited significantly increased blood pressures
and an enhanced acute hypertensive response to nitric oxide synthetase inhibition.
Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings
of mesenteric artery isolated from endothelial cell-specific CNP knockout mice. In
addition, endothelin-1 gene expression was enhanced in pulmonary vascular
endothelial cells from endothelial cell-specific CNP knockout mice, which also
showed significantly higher plasma endothelin-1 concentrations and a greater
reduction in blood pressure in response to an endothelin receptor antagonist than
their control littermates. By contrast, vascular smooth muscle cell-specific GC-B
knockout mice exhibited blood pressures similar to control mice, and acetylcholine-
induced vasorelaxation was preserved in their isolated mesenteric arteries.
Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in
mesenteric arteries from vascular smooth muscle cell-specific GC-B knockout mice.
These results demonstrate that endothelium-derived CNP contributes to the chronic
regulation of vascular tone and systemic blood pressure by maintaining endothelial
function independently of vascular smooth muscle GC-B. Online Data Supplement
Ehrlichiosis in lung transplant (LT) recipients is associated with severe outcomes.
Ehrlichia ewingii is a less frequent cause of symptomatic ehrlichiosis,
characterized by cytoplasmic inclusions (morulae) within circulating neutrophils.
We report a case of E.ewingii infection in an LT recipient diagnosed promptly by
blood smear exam and confirmed with molecular studies.
The social isolation rearing of young adult rats is a model of psychosocial stress
and provides a nonpharmacological tool to study alterations reminiscent of symptoms
seen in psychosis. We have previously demonstrated that social isolation in rats
leads to increased oxidative stress and to cerebral NOX2 elevations. Here, we
investigated early alterations in mRNA expression leading to increased NOX2 in the
brain. Rats were exposed to a short period of social isolation (1 week) and real-
time polymerase chain reaction (PCR) for mRNA expression of genes involved in
blood-brain barrier (BBB) formation and integrity (ORLs, Vof 21 and Vof 16, Leng8,
Vnr1, and Trank 1 genes) was performed. Real-time PCR experiments,
immunohistochemistry, and Western blotting analysis showed an increased expression
of these genes and related proteins in isolated rats with respect to control
animals. The expression of specific markers of BBB integrity, such as matrix
metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), occludin 1, and
plasmalemmal vesicle associated protein-1 (PV-1), was also significantly altered
after 1 week of social isolation. BBB permeability, evaluated by quantification of
Evans blue dye extravasation, as well as interstitial fluid, was significantly
increased in rats isolated for 1 week with respect to controls. Isolation-induced
BBB disruption was also accompanied by a significant increase of Interleukin 6 (IL-
6) expression. Conversely, no differences in NOX2 levels were detected at this time
point. Our study demonstrates that BBB disruption precedes NOX2 elevations in the
brain. These results provide new insights in the interplay of mechanisms linking
psychosocial stress to early oxidative stress in the brain, disruption of the BBB,
and the development of mental disorders.
Since the lacZ alpha-based blue/white screening system was introduced to molecular
biology, several different visual reporter systems were developed and used for
various purposes in Escherichia coli. A common limit to the existent visual
reporter systems is that an extracellular chromogenic substrate has to be added for
the visible pigment production. In this study, we developed a new blue/white
screening system based on a non-ribosomal peptide synthetase encoded by idgS from
Streptomyces and a phosphopantetheinyl transferase encoded by sfp from Bacillus.
When IdgS is activated from an apo-form to a holo-form via a posttranslational
modification catalyzed by Sfp, it can synthesize a blue pigment indigoidine using
L-glutamine, the amino acid abundant in cells, as a substrate. The new blue/white
screening system contains a recipient E. coli strain with an optimized idgS gene
cassette and a cloning vector harboring an sfp gene with an in-frame insertion of a
multiple cloning site close to its N-terminal. We demonstrated that the IdgS/Sfp-
based blue/white screening system is a powerful alternative to the lacZ alpha-based
screening system, which does not require any external substrate addition.
Bluetongue is a non-contagious, haemorrhagic, Culicoides-borne disease of
ruminants. The causative agent, bluetongue virus (BTV), is a member of the
Orbivirus genus of the Reoviridae family. So far, 26 BTV serotypes have been
identified worldwide. The global distribution of bluetongue has been expanding, and
rapid detection of BTV, preferably in the field, is critical for timely
implementation of animal movement restrictions and vector control measures. To
date, many laboratory-based, molecular assays for detection of BTV have been
developed. These methods require the samples to be shipped to a central laboratory
with sophisticated instruments and highly skilled technicians to perform the
assays, conduct analyses and interpret the results. Here, we report the development
and evaluation of a rapid, portable, user-friendly, pan-BTV reverse transcription-
insulated isothermal polymerase chain reaction (RT-iiPCR) assay that can
potentially be used in low-resource field conditions. The total length of the assay
was < 60 min, and at the end of the assay, the results were automatically displayed
as `+' or '_' without the need for data interpretation. The RT-iiPCR assay detected
36 BTV isolates and two in vitro transcribed RNA samples representing all 26 BTV
serotypes. The assay did not cross-react with other animal viruses tested,
including two closely related orbiviruses. The analytical sensitivity of the assay
was as low as nine copies of in vitro transcribed double-stranded BTV RNA. Analysis
of BTVinfected whole blood samples showed that the BTV RT-iiPCR assay was as
sensitive as real-time RT-PCR. The assay can potentially be used for rapid
screening of animals for BTV in routine diagnostics and for monitoring bluetongue
outbreaks both in ruminants and in Culicoides vectors in the field and in the
laboratory.
Small intestinal injury is seldom described in the context of child abuse. Signs
and symptoms are subtle, often leading to delays in diagnosis. We describe a 3-
year-old boy initially admitted with severe blunt abdominal trauma from physical
child abuse. He was successfully managed nonoperatively. The child was then
hospitalized several times for nonspecific abdominal symptoms until diagnostic
laparoscopy discovered a jejunal stricture with a proximal jejuno-jejunal fistula.
Symptoms fully resolved after resection. Delayed presentation of small intestinal
injury should remain on the differential diagnosis in the evaluation of persistent
abdominal symptoms in a child with a prior history of physical abuse, even if
imaging studies do not reveal specific abnormalities.
Background. Blunted facial affect is a common negative symptom of schizophrenia.
Additionally, assessing the trustworthiness of faces is a social cognitive ability
that is impaired in schizophrenia. Currently available pharmacological agents are
ineffective at improving either of these symptoms, despite their clinical
significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects
when administered intranasally to healthy individuals and shows promise in
decreasing negative symptoms and enhancing social cognition in schizophrenia.
Although two small studies have investigated oxytocin's effects on ratings of
facial trustworthiness in schizophrenia, its effects on facial expressivity have
not been investigated in any population. Method. We investigated the effects of
oxytocin on facial emotional expressivity while participants performed a facial
trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched
healthy controls using a double-blind, placebo-controlled, cross-over design.
Participants rated the trustworthiness of presented faces interspersed with
emotionally evocative photographs while being video-recorded. Participants' facial
expressivity in these videos was quantified by blind raters using a well-validated
manualized approach (i.e. the Facial Expression Coding System; FACES). Results.
While oxytocin administration did not affect ratings of facial trustworthiness, it
significantly increased facial expressivity in individuals with schizophrenia (Z=-
2.33, p=0.02) and at trend level in healthy controls (Z=-1.87, p=0.06).
Conclusions. These results demonstrate that oxytocin administration can increase
facial expressivity in response to emotional stimuli and suggest that oxytocin may
have the potential to serve as a treatment for blunted facial affect in
schizophrenia.
We previously reported that higher education protects against executive dysfunction
related to higher body mass index (BMI) in younger, but not older, adults. We now
extend the previous analyses to verbal and nonverbal memory. Fifty-nine healthy,
dementia-free community-dwelling adults ranging in age from 18 to 81years completed
the Hopkins Verbal Learning Test - Revised (HVLT-R) and the Brief Visuospatial
Memory Test - Revised (BVMT-R). Self-reported years of education served as a proxy
for cognitive reserve. We found that more highly educated individuals maintained
their BVMT-R immediate recall performance across the range of BMI, but in less
educated individuals, higher BMI was associated with worse performance. Our
findings suggest that education may play a protective role against BMI-related
nonverbal learning deficits, similar to previous reports for verbal memory and
executive functioning. Results highlight the importance of considering educational
background when determining the risk for BMI-related cognitive impairment in
clinical settings.
NS3 protease plays a vital role in the replication of the hepatitis C virus (HCV).
BMS-605339 is a novel linear tetra-peptide alpha-ketoamide inhibitor of NS3
protease and shows specificity for HCV NS3 protease genotype 1a and genotype 1b.
Mutation at the key site 168 of the HCV NS3 protease can induce resistance to BMS-
605339, which greatly affects the antiviral therapy efficacy to hepatitis C. In the
present study, we employed molecular dynamics simulations, free energy
calculations, and free energy decomposition to explore the drug resistance
mechanism of BMS-605339 due to the three representative mutations D168C/Y/V. The
free energy decomposition analysis indicates that the decrease in the binding
affinity is mainly attributed to the decrease in both van der Waals and
electrostatic interactions. After detailed analysis of our calculated results, we
observed that the break of the salt bridge between residues 155 and 168 caused by
the mutations D168C/Y/V is the original reason for the decrease in the binding
ability between BMS-605339 and the mutant NS3 proteases. The obtained results will
reveal the drug resistance mechanism between BMS-605339 and the mutant NS3
proteases, and provide valuable clue for designing novel and more potent drugs to
HCV NS3 protease. (C) 2016 International Union of Biochemistry and Molecular
Biology, Inc.
The Kruppel-associated box (KRAB)-containing zinc finger proteins (ZFPs) comprise
the largest family of zinc finger transcription factors that function as
transcriptional repressors. In the study of glial cell line-derived neurotrophic
factor (GDNF)-RET signaling, we have identified bone marrow zinc finger 3 (BMZF3),
encoding a KRAB-ZFP, as a GDNF-inducible gene by differential display analysis. The
expression of BMZF3 transcripts in the human neuroblastoma cell line TGW increased
I h after GDNF stimulation, as determined by Northern blotting and quantitative
reverse-transcriptase polymerase chain reaction. The BMZF3 possesses
transcriptional repressor activity in the KRAB domain. BMZF3 interacts with a co-
repressor protein, KRAB-associated protein I (KAP-1), through the KRAB domain and
siRNA-mediated knockdown of KAP-1 abolished the transcriptional repressor activity
of BMZF3, indicating that KAP-1 is necessary for BMZF3 function. Furthermore,
siRNA-mediated silencing of BMZF3 inhibited cell proliferation. These findings
suggest that BMZF3 is a transcriptional repressor induced by GDNF that plays a role
in cell proliferation. (c) 2007 Elsevier Inc. All rights reserved.
We present a generalization of the Bode integral formula for discrete-time linear
periodic systems. It is shown that similar to the classical Bode integral formula,
the sensitivity integral for a discrete-time linear periodic system depends only on
the open-loop dynamics of the system; in particular, on the open-loop
characteristic multipliers outside the unit circle in the complex plane. The
integral is derived by using an asymptotic eigenvalue distribution theorem for
block Toeplitz matrices, which does not require the open loop system to be stable
or the disturbance to be Gaussian. The result is demonstrated through application
to a class of multi-rate sampled data systems with commensurate rates.
Bodily knowledge has attracted significant attention within the humanities and
other related fields over the last two decades. Although theoretical discussion on
bodily knowledge in the context of physical education has been active over the past
10 years, these discussions lack clear conceptual analyses of bodily knowledge.
Using a phenomenological approach, the purpose of this paper is to clarify the
notion of bodily knowledge, furthering epistemological discussions of the topic
within reflective, embodied practices. Instead of seeing bodily knowledge
inherently connected to the acquisition of motor skills or improving physical
fitness, we will discuss physical training as a reflective, embodied process that
can turn sensuous information about the moving body into knowledge. Using outdoor
running as an example, we describe the process of forming bodily knowledge, which
includes: (1) the exploring and identifying of movement qualities, (2) developing
capabilities of registering changes in the body and (3) directing and modifying
one's own training processes based on bodily findings. Contextualizing this
epistemological discussion with adults' recreational physical activity, this paper
argues that bodily knowledge can cultivate individuals to trust their own body
awareness and embodied responses to take more responsibility for their own physical
exercise. When biomedical knowledge of the body in sport sciences tends to shrink
the body to physiological attributes, such as muscle mass and fat percentage, our
analysis stresses the agency of the lived body as a source of knowledge in physical
activity.
The prevalence of weight problems is increasing worldwide. There is growing
evidence that high body mass index (BMI) is associated with frontal lobe
dysfunction and cognitive deficits concerning mental flexibility and inhibitory
control efficiency. The present study aims at replicating and extending these
observations. We compared cognitive control performance of normal weight (BMI= 25)
university students on a task tapping either inhibitory control (Experiment 1) or
interference control (Experiment 2). Experiment 1 replicated previous findings that
found less efficient inhibitory control in overweight individuals. Experiment 2
complemented these findings by showing that cognitive control impairments
associated with high BMI also extend to the ability to resolve stimulus-induced
response conflict and to engage in conflict-driven control adaptation. The present
results are consistent with and extend previous literature showing that high BMI in
young, otherwise healthy individuals is associated with less efficient cognitive
control functioning. (C) 2017 Elsevier Ltd. All rights reserved.
This study investigated the association between child maltreatment and body mass
index (BMI) using data from four waves (wave 2 in 2011 through 5 in 2014) of the
Korean Children & Youth PanelSurvey collected by the South Korean National Youth
Policy Institute. We employed a latent growth curve modeling approach to estimate
an unobserved latent trajectory and to test the longitudinal effects of child abuse
and neglect on BMI. Our results indicate that child abuse is significantly
associated with BMI and children who report higher levels of abuse tend to have
higher rates of increase in their BMI. This study addresses a gap in the literature
by demonstrating that a parent's maltreatment of their child has a long-term effect
on the rate of change in their BMI over time.
The aim of this study was to explore the significant predictors associated with
electroconvulsive therapy (ECT) outcome for patients with major depressive
disorder. Major depressive disorder inpatients (N=130) requiring ECT were recruited
from a major psychiatric center in South Taiwan. ECT was generally performed for a
maximum of 12 sessions. Symptom severity was assessed using the 17-item Hamilton
Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-
S) before ECT, after every three ECT sessions, and after the last ECT. The
generalized estimating equations method was used to analyze the influence of
potential variables over time on the HAMD-17 and CGI-S, respectively. Fourteen
patients not completing the first three sessions of ECT were excluded. The
remaining 116 patients were included in the analysis. Patients with treatment-
resistant depression, longer duration of the current depressive episode, and higher
levels of pain were more likely to have less symptom reduction after acute
treatment with ECT, irrespective of how the depressive symptoms were rated using
HAMD-17 or CGI-S. To improve efficacy, earlier application of ECT and pain control
should be considered during an acute course of ECT. Other clinical predictors
related to ECT outcome require further investigation in future studies.
The majority of human neuroscience research has focussed on understanding
functional organisation within segregated patches of cortex. The ventral visual
stream has been associated with the detection of physical features such as faces
and body parts, whereas the theory-of-mind network has been associated with making
inferences about mental states and underlying character, such as whether someone is
friendly, selfish, or generous. To date, however, it is largely unknown how such
distinct processing components integrate neural signals. Using functional magnetic
resonance imaging and connectivity analyses, we investigated the contribution of
functional integration to social perception. During scanning, participants observed
bodies that had previously been associated with trait-based or neutral information.
Additionally, we independently localised the body perception and theory-of-mind
networks. We demonstrate that when observing someone who cues the recall of stored
social knowledge compared to non-social knowledge, a node in the ventral visual
stream (extrastriate body area) shows greater coupling with part of the theory-of-
mind network (temporal pole). These results show that functional connections
provide an interface between perceptual and inferential processing components, thus
providing neurobiological evidence that supports the view that understanding the
visual environment involves interplay between conceptual knowledge and perceptual
processing.
For young birds in a nest, body size may have implications for other aspects of
development such as telomere length and immune function. However, it is possible to
predict associations in either direction. On the one hand, there may be trade-offs
between growth and telomere maintenance, and growth and investment in immune
function, suggesting there will be negative correlations. On the other hand,
relatively larger individuals might be advantaged in competition with their nest-
mates, allowing them to garner more resources overall, leading to positive
correlations. We studied development over the nestling period in 34 nests of wild
European starlings, Sturnus vulgaris. Intrabrood competition is typically more
intense in larger broods. Hence, we predicted that body size should become an
increasingly positive predictor of telomere length and immune functioning as brood
size increases. In partial support of our prediction, there were significant
interactions between brood size and body size in predicting both erythrocyte
telomere length change and plasma levels of the cytokine interleukin-6. The
associations between body size and these outcomes went from negative in the
smallest broods to positive in the largest. A further immune marker, high-
sensitivity C-reactive protein, showed no systematic patterning with body size or
brood size. Our results confirm that the size to which a nestling grows is
important for telomere dynamics and the development of the immune system, but the
phenotypic associations are moderated by the competitive context.
Background: Small non-coding RNAs (ncRNAs) are important regulators of gene
expression in eukaryotes. Previously, only microRNAs (miRNAs) and piRNAs have been
identified in the silkworm, Bombyx mori. Furthermore, only ncRNAs (50-500nt) of
intermediate size have been systematically identified in the silkworm. Results:
Here, we performed a systematic identification and analysis of small RNAs (18-50nt)
associated with the Bombyx mori argonaute2 (BmAgo2) protein. Using RIP-seq, we
identified various types of small ncRNAs associated with BmAGO2. These ncRNAs
showed a multimodal length distribution, with three peaks at similar to 20nt,
similar to 27nt and similar to 33nt, which included tRNA-, transposable element
(TE)-, rRNA-, snoRNA-and snRNA-derived small RNAs as well as miRNAs and piRNAs. The
tRNA-derived fragments (tRFs) were found at an extremely high abundance and
accounted for 69.90% of the BmAgo2-associated small RNAs. Northern blotting
confirmed that many tRFs were expressed or up-regulated only in the BmNPV-infected
cells, implying that the tRFs play a prominent role by binding to BmAgo2 during
BmNPV infection. Additional evidence suggested that there are potential cleavage
sites on the D, anti-codon and T psi C loops of the tRNAs. TE-derived small RNAs
and piRNAs also accounted for a significant proportion of the BmAgo2-associated
small RNAs, suggesting that BmAgo2 could be involved in the maintenance of genome
stability by suppressing the activities of transposons guided by these small RNAs.
Finally, Northern blotting was also used to confirm the Bombyx 5.8 s rRNA-derived
small RNAs, demonstrating that various novel small RNAs exist in the silkworm.
Conclusions: Using an RIP-seq method in combination with Northern blotting, we
identified various types of small RNAs associated with the BmAgo2 protein,
including tRNA-, TE-, rRNA-, snoRNA-and snRNA-derived small RNAs as well as miRNAs
and piRNAs. Our findings provide new clues for future functional studies of the
role of small RNAs in insect development and evolution.
The larval pigment pattern in the silkworm, Bombyx mori, is formed by melanin,
ommochromes and pteridines. During development all these pigments are synthesized
autonomously, and possibly also with mutual interaction between them, to yield
unique pigment patterns. In order to find the key trigger for such pigment pattern
formation, developmental changes in pteridine biosynthesis were studied using the
quail mutant (q/q), which has darker larval marks formed by melanin and an
abundance of ommochromes in the integument. In the current study, emphasis has been
placed on the analysis of GTP-cyclohydrolase I (GTP-CH I), which is a key enzyme
for the biosynthesis of pteridines, during the development of the silkworm. Results
of Northern blotting showed that in the quail mutant strong signals of GTP-CH I
mRNA appeared around each period of ecdysis, while no such signals appeared in the
background strain (+q/q) used. Also, both GTP-CH I activities and pteridine content
were higher in the quail mutant compared with the background strain. These results
strongly suggest that pteridine biosynthesis is closely linked to the formation of
melanin and ommochromes. It is also suggested here that in the silkworm a recessive
gene (q) may be involved in the regulation of its pigment pattern formation.
Transforming growth factor (TGF)-beta are strongly associated with osteoblast
differentiation. Mechanical stress including compressive force (CF) also involve in
osteoblast differentiation via the alteration of the expression of bone-specific
transcription factors, namely Runx2 and Osterix. However, the role of TGF-beta s in
mediating the effects of CF on osteoblasts remains unclear. In the present study,
we examined the effects of CF on the expression of TGF-beta 1, TGF-beta 2, TGF-beta
type 1 and 2 receptor (T beta r1 and T beta r2), and Runx2 and Osterix in
osteoblasts: We also investigated the effects of CF on the phosphorylation of
Smad2, Smad3 and p38; which were located on the downstream of T beta rs. Effect of
T beta r inhibitor (LY2109761) on expression of Runx2 and Osterix, and
phosphorylation of Smad2, Smad3 and p38 were additionally examined Cultured MC3T3-
E1 osteoblast-like cells were subjected, or not, to continuous CF (1.0 g/ cm(2) or
2.0 g/cm(2)) for 1-9 h. TGF-beta 1, TGF-beta 2, T beta r1, T beta r2, Runx2 and
Osterix expression were measured by real-time polymerase chain reaction and Western
blot analysis. Phosphorylation levels of Smad2, Smad3 and p38 were determined by
Western blot analysis. The mRNA and protein expression of TGF-beta 1 and TGF-beta 2
were significantly increased by 1.0 g/cm(2), but not 2.0 g/cm(2), CF for 3-6 h,
relative to control cells; T beta r1 and T beta r2 expression were unaffected by
either CF condition. The 1.0 g/cm(2) CF also increased the phosphorylation of
Smad2, Smad3 and p38 and the expression of Runx2 and Osterix, and these increases
were attenuated by pretreatment with LY2109761. The present findings indicate that
1.0 g/cm(2) CF can induce bone-specific transcription factors via autocrine action
of CF-induced TGF-beta signaling in osteoblasts.
Chimerism associated with placental sharing in marmosets has been traditionally
analysed using conventional chromosome staining on metaphase spreads or polymerase
chain reaction. However, the former technique requires the presence of
proliferating cells, whereas the latter may be associated with possible blood cell
contamination. Therefore, we aimed to develop a single-cell analysis technique for
sexing marmoset cells. We applied fluorescent in situ hybridisation (FISH) to cell
nuclei using differentially labelled X and Y chromosome-specific probes. Herein we
present the validation of this method in metaphase cells from a marmoset
lymphoblastoid cell line, as well as application of the method for evaluation of
cross-sex chimerism in interphase blood lymphocytes and haematopoietic bone marrow
cells from marmosets of same- and mixed-sex litters. The results show conclusively
that haematopoietic cells of bone marrow and leucocytes from blood are cross-sex
chimeric when the litter is mixed sex. In addition, single samples of liver and
spleen cell suspensions from one individual were tested. Cross-sex chimerism was
observed in the spleen but not in liver cells. We conclude that FISH is the method
of choice to identify cross-sex chimerism, especially when combined with
morphological identification of nuclei of different cell types, which will allow a
targeted tissue-specific analysis.
Background Diamond-Blackfan anemia and Shwachman-Diamond syndrome are inherited
bone marrow failure syndromes linked to defects in ribosome synthesis. The purpose
of this study was to determine whether yeast models for Diamond-Blackfan anemia and
Shwachman-Diamond syndrome differed in the mechanism by which ribosome synthesis
was affected. Design and Methods Northern blotting, pulse-chase analysis, and
polysome profiling were used to study ribosome synthesis in yeast models.
Localization of 60S ribosomal subunits was assessed using RPL25eGFP. Results
Relative to wild-type controls, each disease model showed defects in 60S subunit
maturation, but with distinct underlying mechanisms. In the model of Diamond-
Blackfan anemia, 60S subunit maturation was disrupted at a relatively early stage
with abortive complexes subject to rapid degradation. 5S ribosomal RNA, unlike
other large subunit ribosomal RNA in this model, accumulated as an extra-ribosomal
species. In contrast, subunit maturation in the Shwachman-Diamond syndrome model
was affected at a later step, giving rise to relatively stable pre-60S particles
with associated 5S ribosomal RNA retained in the nucleus. Conclusions These
differences between the yeast Diamond-Blackfan anemia and Shwactiman-Diamond
syndrome models have implications for signaling mechanisms linking abortive
ribosome. assembly to cell fate decisions and may contribute to the divergent
clinical presentations of Diamond-Blackfan anemia and Shwachman-Diamond syndrome.
Background: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent
cells with a high constitutive level of autophagy and low expression of CD99. Under
certain conditions, MSCs may develop tumorigenic properties. However, these
transformation-induced conditions are largely unknown. Recently, we have identified
an association between Hsp70, a main participant in cellular stress response and
tumorigenesis, and CD99. Preliminary observations had revealed upregulation of both
proteins in stressed long-term cultured MSCs. And so we hypothesized that CD99 is
implicated in stress-induced mechanisms of cellular transformation in MSCs. Hence,
we investigated the effects of prolonged stress on MSCs and the role of CD99 and
autophagy in their survival. Methods: Human telomerase reverse transcriptase
(hTERT) overexpressing immortalized MSCs and primary bone marrow stromal cells were
used to investigate the influence of long-term serum deprivation and hypoxia on
growth and differentiation of MSCs. Cell proliferation and apoptosis were evaluated
using flow cytometry, differentiation capabilities of MSCs were assessed by
immunohistochemical staining followed by microscopic examination. CD99, Hsp70
expression were analyzed using flow cytometry, western blotting, and reverse
transcriptase polymerase chain reaction. Autophagy was explored with specific
inhibitors using cell morphology examination and western blotting. Results: Chronic
stress factors are able to change the morphology of MSCs and to inhibit spontaneous
differentiation into adipocyte lineage. Furthermore, CD99 elevation and
downregulation of p53 and p21 accompanied defective autophagy, which is usually
associated with tumor formation. We found that inhibition of autophagy by
chloroquine promoted cell detachment and modulated CD99 expression level whereas
incorporation of CD99 recombinant protein into the cells suppressed autophagy.
Conclusions: Obtained results provide a model for chronic stress-induced
transformation of MSCs via CD99 and may therefore be highly relevant to mesenchymal
tumorigenesis.
Immunodeficient mice play a critical role in hematology research as in vivo models
of hematopoiesis and immunology. Multiple strains have been developed, but
hematopoietic stem cell engraftment and immune reconstitution have not been
methodically compared among them. Four mouse strains were transplanted with human
fetal bone marrow or adult peripheral blood CD34(+) cells: NSG, NSG-3GS, hSCF-Tg-
NSG, and hSIRP alpha-DKO. Hematopoietic engraftment in the bone marrow, blood,
spleen, and liver was evaluated by flow cytometry 12 weeks after transplant. The
highest levels of human engraftment were observed in the liver, spleen, and bone
marrow, whereas peripheral blood cell chimerism was notably less. The highest
levels of tissue engraftment were in hSCF-Tg-NSG mice, but NSG mice exhibited the
highest blood leukocyte engraftment. hSCF-Tg-NSG mice also exhibited the highest
levels of CD133(+)CD34(++) stem cells. hSIRPa-DKO engrafted poorly and exhibited
poor breeding. Myelopoiesis was greatest in NSG-3GS mice, followed by hSCF-Tg-NSG
and NSG mice, whereas B cell engraftment exhibited the opposite pattern.
Engraftment of CD3(+) T cells, CD3(+)CD161(+)T cells, and CD3(-)CD56(+) NK cells
was greatest in NSG-3GS mice. Mast cell engraftment was highest in hSCF-Tg-NSG
mice, but was also elevated in spleen and livers of NSG-3GS mice. Basophils were
most abundant in NSG-3GS mice. Overall, hSCF-Tg-NSG mice are the best recipient
mice for studies requiring high levels of human hematopoiesis, stem cell
engraftment, and an intermediate level of myelopoiesis, whereas NSG and NSG-3GS
mice offer select advantages in the engraftment of certain blood cell lineages.
Aim: To test the hypothesis that genistein stimulates the osteoblastic
differentiation through the p38 mitogen activated protein kinase (MAPK)-core-
binding factor 1 (Cbfa1) pathway. Methods: The activation of p38 MAPK was detected
by Western blotting. Alkaline phosphatase (ALP) activity and calcium deposition
were assessed for osteoblastic differentiation of bone marrow-derived mesenchymal
stem cell (BMSC) cultures. The expression of Cbfa1 was analyzed at both the mRNA
and protein levels. The activity of Cbfa1 was detected by electrophoretic mobility
shift assay. Bone sialoprotein (BSP), ALP, osteocalcin (OC), and osteopontin (OPN)
gene transcription were also evaluated by either RT-PCR or Northern blotting.
Results: Genistein (0.01-1 mu mol/L) dose dependently led to the rapid and
sustained activation of the p38 MAPK pathway in mouse BMSC cultures. Treatment with
genistein (1 mu mol/L) resulted in increased ALP activity and calcium deposition of
BMSC cultures as a function of time. Genistein also enhanced Cbfa1 DNA binding
activity and promoted the expressions of Cbfa1 itself as well as several Cbfa1-
regulated genes, including ALP, BSP, OC, and OPN. Concurrent treatment with p38
MAPK inhibitor (SB203580) diminished the genistein-induced osteoblastic maturation
and p38 MAPK-Cbfa1 activation in mouse BMSC cultures. Conclusion: These results
indicated that genistein could stimulate the osteoblastic differentiation of BMSC
cultures through the p38 MAPK-Cbfa1 pathway.
Background: Novel therapies for men with castration-resistant prostate cancer
(CRPC) are needed, particularly for cancers not driven by androgen receptor (AR)
activation. Objectives: To identify molecular subgroups of PC bone metastases of
relevance for therapy. Design, setting, and participants: Fresh-frozen bone
metastasis samples from men with CRPC (n = 40), treatment-nai " ve PC (n = 8), or
other malignancies (n = 12) were characterized using whole-genome expression
profiling, multivariate principal component analysis (PCA), and functional
enrichment analysis. Expression profiles were verified by reverse transcription-
polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77)
and compared to levels in malignant and adjacent benign prostate tissue from
patients with localized disease (n = 12). Selected proteins were evaluated using
immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral
resection with long follow-up was used for prognostic evaluation. Results and
limitations: The majority of CRPC bone metastases (80%) was defined as AR driven
based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1,
HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were
non-AR-driven. Functional enrichment analysis indicated high metabolic activity and
low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and
CD68+ cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell
HLA class I ABC immunoreactivity was inversely correlated with nuclear AR
immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1,
and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate
tissue and bone metastases of other origins. In primary PC, low HLA class I ABC
immunoreactivity was associated with high Gleason score, bone metastasis, and short
cancer-specific survival. Limitations include the limited number of patients
studied and the single metastasis sample studied per patient. Conclusions: Most
CRPC bone metastases show high AR and metabolic activities and low immune
responses. A subgroup instead shows low AR and metabolic activities, but high
immune responses. Targeted therapy for these groups should be explored. Patient
summary: We studied heterogeneities at a molecular level in bone metastasis samples
obtained from men with castration-resistant prostate cancer. We found differences
of possible importance for therapy selection in individual patients. (C) 2016
European Association of Urology. Published by Elsevier B. V.
Bone morphogenetic protein-2 (BMP-2) participates significantly in vascular
development and pathophysiological processes. Angiotensin II (AngII) has been
demonstrated to be critical in the initiation and progression of atherosclerosis.
However, the effects of AngII on BMP-2 expression and of probucol on the AngII-
induced BMP-2 expression in human umbilical vein endothelial cells (HUVECs) are
unknown. The aim of our study was to investigate these effects. HUVECs were
cultured and stimulated with various agents. The total superoxide dismutase (SOD)
activity and the concentrations of malondialdehyde (MDA) and BMP-2 were measured by
standard methods. Northern blotting was used to detect the expression of BMP-2
mRNA. The activation of NF-kappa B in the HUVECs was also determined. The AngII
treatment significantly increased BMP-2 expression levels and activated NF-kappa B.
These effects were suppressed by treatment with pyrrolidine dithiocarbamate (PDTC)
or probucol. Furthermore, the increased levels of MDA in the conditioned medium and
the decrease in the total SOD activity caused by the AngII treatment were reversed
by treatment with probucol or PDTC. Probucol downregulated the AngII-nduced BMP-2
expression. These effects of probucol may be mediated by the inhibition of NF-kappa
B activation.
Alveolar bone resorption caused by trauma or periodontal diseases has represented a
challenge for both dental clinicians and researchers. In this study, we evaluate
the osteogenic potential of human gingival fibroblasts (HGFs) through a direct
transdifferentiation from HGFs to functional osteoblasts via epigenetic
modification and osteogenic signaling with bone morphogenetic protein 2 (BMP2) in
vitro and in vivo. HGF treatment with 5-aza-2'-deoxycytidine (5-aza-dC) induced
demethylation in the hypermethylated CpG islands of the osteogenic lineage marker
genes RUNX2 and ALP, and subsequent BMP2 treatment successfully drove the
fibroblasts to the osteoblasts' lineage. Cell morphological changes viewed under
microscopy and alkaline phosphatase (ALP) and alizarin red S (ARS) staining
confirmed the osteoblastic change mediated by epigenetic modification as did real-
time polymerase chain reaction (PCR), methylation-specific PCR (MSP), and chromatin
immunoprecipitation (ChIP) assay, which demonstrated the altered methylation
patterns in the RUNX2 and ALP promoter regions and their effect on gene expression.
Furthermore, micro-computed tomography (CT) analysis of in vivo mouse cell
transplantation experiments showed high-density signal in the epigenetically
modified HGF group; in addition, a significant amount of bone formation was
observed in the transplanted material using hematoxylin and eosin (H&E) staining as
well. Collectively, our results indicate that epigenetic modification permits the
direct programming of HGFs into functional osteoblasts, suggesting that this
approach might open a novel therapeutic avenue in alveolar bone regeneration.
Objective: The objective of this study was to determine the contribution of
lymphatic tissue to heterotopic ossification (HO). Background: HO is the pathologic
development of ectopic bone within soft tissues often following severe trauma.
Characterization of the tissue niche supporting HO is critical to identifying
therapies directed against this condition. Lymphangiogenesis is upregulated during
incidents of trauma, thereby coincident with the niche supportive of HO. We
hypothesized that lymphatic tissues play a critical role in HO formation. Methods:
Mice underwent hindlimb Achilles' tendon transection and dorsal burn injury
(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised
ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to
quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Results:
Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon
transection sites when compared with the contralateral, intact tendon based on
LYVE1+ tubules (10.9% vs 0.8%, P < 0.05). Excision of the inguinal and popliteal
nodes with draining popliteal lymphatic vessel significantly decreased the presence
of mature lymphoendothelium 2 weeks after injury (10.9% vs 3.3%, P < 0.05). Bone-
cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2-/CD45-/CD90-/BP1-) were
also significantly decreased after lymph node excision (10.2% vs 0.5%, P < 0.05). A
significant decrease was noted in the volume of de novo HOpresent within the soft
tissues (0.12 mm(3) vs 0.02 mm(3)). Conclusion: These findings suggest that
lymphatic vessels are intimately linked with the de novo formation bone within soft
tissues following trauma, and their presence may facilitate bone formation.
Growth recovery lines, also known as growth arrest lines, are transverse radiodense
metaphyseal bands that develop due to a temporary arrest of endochondral
ossification caused by local or systemic insults. To determine if growth recovery
lines are more common in infants at high risk versus low risk for abuse. Reports of
American College of Radiology compliant skeletal surveys (1999-2013) were reviewed
with clinical records. Infants at low risk for abuse had a skull fracture without
significant intracranial injury, history of a fall and clinical determination of
low risk (child protection team/social work assessment). Infants at high risk had
significant intracranial injury, retinal hemorrhages, other skeletal injuries and
clinical determination of high risk. There were 52 low-risk infants (mean: 4.7
months, range: 0.4-12 months) and 21 high-risk infants (mean: 4.2 months, range:
0.8-9.1 months). Two blinded radiologists independently evaluated the skeletal
survey radiographs of the knees/lower legs for the presence of at least one growth
recovery line. When growth recovery lines are scored as probably present or
definitely present, their prevalence in the low-risk group was 38% (standard
deviation [SD] = 8%; reader 1 = 17/52, reader 2 = 23/52) vs. 71% (SD = 7%; reader 1
= 16/21, reader 2 = 14/21) in the high-risk group (P < 0.001; odds ratio 4.0, 95%
CI: 1.7-9.5). Growth recovery lines are encountered at a significantly higher rate
in infants at high risk vs. low risk for abuse. This suggests that abused infants
are prone to a temporary disturbance in endochondral ossification as a result of
episodic physiological stresses.
Determining individual health status is of great importance for a better
understanding of life history trade-offs between growth, reproduction, and
maintenance. However, existing immunological methods are invasive and therefore not
suitable for investigating health status in wild populations. Thus, there is an
urgent need for non-invasive methods to assess the immune status of animals.
Neopterin is involved in the cell-mediated pathway of the immune response (Th1-
type), secreted during the activation of monocytes and macrophages. We investigated
if urinary neopterin could serve as a biomarker of health status in bonobos and
chimpanzees. First, we performed a chemical validation of a commercial neopterin
enzyme immune assay (EIA) for bonobo and chimpanzee urine. We then examined if
urinary neopterin levels in bonobos increase during the acute period of respiratory
infections. We found that neopterin levels can be reliably measured in urine of the
two species with a commercial EIA. Stability experiments revealed considerable
changes in urinary neopterin levels in relation to multiple freezethaw cycles and
extended exposure to room temperature. Exposure to sunlight led to a degradation of
urinary neopterin, whereas sample storage up to two years did not affect urinary
neopterin levels. There was no detectable diurnal variation in neopterin levels,
and levels remained very stable across several days in healthy individuals. While
urinary neopterin levels were independent of sex, nonadult individuals had higher
urinary neopterin levels than adults. Most importantly, there was a significant
increase in urinary neopterin levels during a period of respiratory infection. Our
results demonstrate that regular urine sample collection would allow for the
monitoring of individual health status and disease progression with minimal
disturbance of the subjects. In combination with behavioral, life history, and
endocrinological parameters, the method can be used to investigate questions
related to immunocompetence handicaps or life history trade-offs.
Conventionally, a high accuracy operational amplifier (OPA)-based current sensor is
used for sensing current message under a full load range, which increases the cost
characteristic. Instead of a high accuracy OPA-based current sensor, this paper
describes using a switching inductor quasi-V-2 hysteretic control boost dc-dc
regulator with a proposed current-sensing technique named emulated-ramp feedback
(ERF), which can improve transfer efficiency under a full load range. Two control
systems are presented in this paper. The first system, a hysteretic voltage control
switching boost converter with ERF, achieves the hysteretic voltage control in a
boost regulator and lowers the cost characteristic without using compensator. The
second system, a quasi-V-2 hysteretic voltage control switching boost converter
with ERF, demonstrates the compatibility of ERF technique in rippled-based control
boost converters. The regulator was implemented with TSMC 0.25-mu m HV CMOS
process. Experimental results show the second system can work under the
specification of 5-12V with a 0 to 300-mA load range. Additionally, this system
attained a recovery time is 27/95 mu s for step-up/step-down in a 100 to 300-mA
continuous conduction mode load current, and a peak efficiency of 92.1% with a chip
area of only 1.014mm(2). Copyright (c) 2016 John Wiley & Sons, Ltd.
Monte Carlo (MC) techniques are widely applied to check a design on its robustness
and for estimating the production yield of integrated circuits. Using standard
random MC and the sample yield for estimation, a very large number of samples is
required for accurate verification, especially if a high yield is desired. This can
make MC extremely time consuming, but if the data follows a normal Gaussian
distribution a much faster yield prediction is possible by using the well-known C-
PK method. We extended this specification-distance-based scheme for the far more
difficult general non-normal case by three different means, ending up in a new
generalized process capability index named C-GPK. First, we apply parametric
modeling only to the specification-sided distribution part. This way any
difficulties in distribution parts that actually have little yield impact do not
degrade the model fit anymore. Second, to improve the parametric model we introduce
a new tail parameter t. Third, to allow modeling of difficult asymmetrical,
multimodal or flat distributions we also introduce a new reference location
parameter instead of using the mean. An advantage of improving MC this way is that-
in opposite to many other MC enhancements (like importance sampling)-the
performance of the C-GPK is not negatively impacted by design complexity. We
described the formulation of the C-GPK and derived confidence intervals using an
advanced bootstrap scheme. We verified the performance against the sample yield and
C-PK for a representative set of distributions, including real production data and
MC data from the design of a CMOS operational amplifier and other circuits.
ObjectivesBorderline personality disorder (BPD) is characterized by emotional
instability, interpersonal dysfunction, and other features that typically develop
before a background of insecure attachment and traumatic experiences. Dialectical
behaviour therapy (DBT) has proven highly effective in reducing self-harm and
improving emotion regulation, whereby problems concerning social cognition, which
are also characteristic of BPD, may need additional approaches such as
mentalization-based treatment (MBT). MethodsHere, we examined, in a pilot study,
the effectiveness of MBT given adjunct to DBT, compared to DBT alone, in an
inpatient sample with BPD, whereby mentalization was measured using a novel
cartoon-based task. ResultsBoth treatments were highly effective in reducing
symptom severity. The combination of DBT and MBT was superior in reducing fearful
attachment and in improving affective mentalizing. ConclusionsMentalization-based
treatment in combination with DBT may improve certain aspects of social cognitive
skills and attachment security, as compared to DBT alone, although the exact
mechanisms that led to these changes need to be studied further. Practitioner
points Clinical implications Dialectical behaviour therapy (DBT) can usefully be
combined with mentalization-based treatment (MBT). The combination of DBT and MBT
reduces self-harm more than DBT alone. DBT plus MBT may lead to a reduction in
fearful attachment and improvement of affective mentalizing. Short-term
combinations of evidence-based borderline treatments may enrich psychiatric
inpatient care. Therefore, such approaches deserve further research. Limitations
The treatment condition was therapeutically more intense than the control
condition. The study lacked a follow-up assessment. The impact of comorbid
conditions on treatment response was not taken into account. Adherence to the
manualized approach was not measured.
Borderline personality disorder (BPD) has been shown to be a valid and reliable
diagnosis in adolescents and associated with a decrease in both general and social
functioning. With evidence linking BPD in adolescents to poor prognosis, it is
important to develop a better understanding of factors and mechanisms contributing
to the development of BPD. This could potentially enhance our knowledge and
facilitate the design of novel treatment programs and interventions for this group.
In this paper, we outline a theoretical model of BPD in adolescents linking the
original mentalization-based theory of BPD, with recent extensions of the theory
that focuses on hypermentalizing and epistemic trust. We then provide clinical case
vignettes to illustrate this extended theoretical model of BPD. Furthermore, we
suggest a treatment approach to BPD in adolescents that focuses on the reduction of
hypermentalizing and epistemic mistrust. We conclude with an integration of theory
and practice in the final section of the paper and make recommendations for future
work in this area.
Impairments in interpersonal relationships are a core feature of borderline
personality disorder (BPD). Social cognition dysfunction, like false recognition of
others' emotions and intentions, may lead to emotional disturbances, self-injury,
and impulsive aggression behaviors in patients with BPD. This study explored the
extent to which social cognition, including emotional recognition and theory of
mind (ToM), can predict the ability of social awareness in patients with BPD.
Emotion recognition tasks (matching emotional facial expressions to prosody),
verbal and nonverbal theory of mind tasks, and the awareness of social inference
test were assessed. Results of a stepwise multiple regression showed that the
quality of the early parent-child relationship, anger prosody recognition, and ToM
were significantly related to the ability to be aware of social interactions in the
patients with BPD.
Canine respiratory diseases are commonly seen in dogs along with co -infections
with multiple respiratory pathogens, including viruses and bacteria. Virus
infections in even vaccinated dogs were also reported. The clinical signs caused by
different respiratory etiological agents are similar, which makes differential
diagnosis imperative. An oligonucleotide microarray system was developed in this
study. The wild type and vaccine strains of canine distemper virus (CDV), influenza
virus, canine herpesvirus (CHV), Bordetella bronchiseptica and Mycoplasma cynos
were detected and differentiated simultaneously on a microarray chip. The detection
limit is 10, 10, 100, 50 and 50 copy numbers for CDV, influenza virus, CHV, B.
bronchiseptica and M. cynos, respectively. The clinical test results of nasal swab
samples showed that the microarray had remarkably better efficacy than the
multiplex PCR-agarose gel method. The positive detection rate of microarray and
agarose gel was 59.0% (n=33) and 41.1% (n =23) among the 56 samples, respectively.
CDV vaccine strain and pathogen co -infections were further demonstrated by the
microarray but not by the multiplex PCR-agarose gel. The oligonucleotide microarray
provides a highly efficient diagnosis alternative that could be applied to clinical
usage, greatly assisting in disease therapy and control. (C) 2017 Elsevier B.V. All
rights reserved.
Obesity is a major global public health concern. Immune responses implicated in
obesity also control certain infections. We investigated the effects of high-fat
diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia
burgdorferi in mice. DIO was associated with systemic suppression of neutrophil-
and macrophage-based innate immune responses. These included bacterial uptake and
cytokine production, and systemic, progressive impairment of bacterial clearance,
and increased carditis severity. B.burgdorferi-infected mice fed normal diet also
gained weight at the same rate as uninfected mice fed high-fat diet, toll-like
receptor 4 deficiency rescued bacterial clearance defects, which greater in female
than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone
marrow-derived macrophages from obese, B.burgdorferi-infected mice was also
affected. Importantly, innate immune suppression increased with infection duration
and depended on cooperative and synergistic interactions between DIO and
B.burgdorferi infection. Thus, obesity and B.burgdorferi infection cooperatively
and progressively suppressed innate immunity in mice.
Tick-borne borreliae include Lyme disease and relapsing fever agents, and they are
transmitted primarily by ixodid (hard) and argasid (soft) tick vectors,
respectively. Tick-host interactions during feeding are complex, with host immune
responses influenced by biological differences in tick feeding and individual
differences within and between host species. One of the first encounters for
spirochetes entering vertebrate host skin is with local antigen-presenting cells,
regardless of whether the tick-associated Borrelia sp. is pathogenic. In this
study, we performed a basic comparison of cytokine responses in THP-1-derived
macrophages after exposure to selected borreliae, including a nonpathogen. By using
THP-1 cells, differentiated to macrophages, we eliminated variations in host
response and reduced the system to an in vitro model to evaluate the extent to
which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells
were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi
(B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides
(LPS) (activated) or media (no treatment) controls. Intracellular and secreted
interferon (IFN)-gamma, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor
(TNF)-alpha were measured using flow cytometric and Luminex-based assays,
respectively, at 6, 24, and 48 h postexposure time points. Using a general linear
model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no
treatment) had a significant effect on secreted TNF-alpha only. Time point had a
significant effect on intracellular IFN-gamma, TNF-alpha and IL-6. However, we did
not see significant differences in selected cytokines among Borrelia spp.
treatments. Thus, in this model, we were unable to distinguish pathogenic from
nonpathogenic borreliae using the limited array of selected cytokines. While unique
immune profiles may be detectable in an in vitro model and may reveal predictors
for pathogenicity in borreliae of unknown pathogenicity, a larger panel of
cytokines would be desirable to test.
The translationally controlled tumor protein (TCTP) is an important component of
the target of rapamycin (TOR) signaling pathway, the major regulator of cell growth
in animals and fungi. Despite its relevance, knowledge on plant TCTP homologs is
still limited. In the present study, the full-length BoTCTP cDNA was isolated from
a cabbage (Brassica oleracea L.) cDNA library. The BoTCTP cDNA encodes a
polypeptide of 168 amino acids and shared the highly conserved GTPase binding
surface in all of the species analyzed. Northern blotting analysis showed that
BoTCTP was specifically expressed in the root and stem. Furthermore, the expression
of BoTCTP could be obviously enhanced by stress stimuli, including high temperature
and salt stresses, while no significant changes in the BoTCTP expression were
observed under ABA stress. Functional analysis of BoTCTP was performed by the
silencing of BoTCTP using RNA interference (RNAi) and the BoTCTP RNAi plants
exhibited reduced vegetative growth rate and decreased tolerance of the cold, high
temperature, and salt stresses. The reported results clearly suggest that the
BoTCTP gene is involved in the regulation of both growth and stress response in
cabbage.
Introduction: Botulinum toxin (BT) is used in many medical specialties to treat
muscle hyperactivity, exocrine gland hyperactivity and pain disorders. BT drugs
consist of botulinum neurotoxin (BNT), complexing proteins (CP) and excipients.
Antibodies can be formed against BNT and CP. When they are formed against BNT
(BTAB) they can block BT's therapeutic efficacy thus producing antibody induced
therapy failure (ABTF).Areas covered: BT applied and BTAB are in a functional
balance within the body. ABTF is rare, but influences the treatment algorithms of
BT therapy considerably. ABTF risk factors include BT doses given, interinjection
intervals, booster injections and immunological quality of the BT drug. Testing for
BTAB and interpretation of ABTF is complicated. As management of ABTF is
frustrating, prevention of ABTF is of major importance. Improved antigenicity of
new BT drugs may improve treatment algorithms of BT therapy, substandard
antigenicity may very likely be their end.Expert commentary: Concern about ABTF has
influenced the treatment algorithms of BT therapy considerably. Better
understanding of ABTF may improve them and, thus, the outcome of BT therapy. New BT
drugs may have further improved antigenicity, especially when their CP are removed.
They may, however, fail because of antigenicity problems.
Conventional phase leading input current (PLIC) compensation techniques have
focused on a continuous conduction mode (CCM) boost power factor corrector (PFC).
In precedent studies, the causes of the PLIC have been investigated by analyzing
the current control loop and the input impedance of a boost PFC. However, in a
boundary conduction mode (BCM) boost PFC, the current flowing through the input
filter capacitor becomes a main cause due to its large ripple current. Despite
that, there has not been any effort to compensate the current in the input filter
capacitor (IFC) in a BCM boost PFC. In this paper, a new digital control method is
proposed to compensate PLIC in a BCM boost PFC, by minimizing the effect of the
IFC. The proposed method uses only the derivative of the input voltage, without any
additional component. Also, the proposed method improves the displacement factor,
but does not affect the distortion factor, resulting in a high power quality in the
entire input and output conditions. The derivation of the proposed method is
presented based on time-domain analysis, and the effectiveness of the proposed
method is experimentally verified with a 60-Hz, 90-230 V-rms input and 395-V/0.5-A
output prototype.
This paper presents a novel predictive digital control method for boundary
conduction mode PFC converters without the need for detecting the inductor current.
In the proposed method, the inductor current is predicted by analytical equations
instead of being detected by a sensing-resistor. The predicted zero-crossing point
of the inductor current is determined by the values of the input voltage, output
voltage and predicted inductor current. Importantly, the prediction of zero-
crossing point is achieved in just a single switching cycle. Therefore, the errors
in predictive calculation caused by parameter variations can be compensated. The
prediction of the zero-crossing point with the proposed method has been shown to
have good accuracy. The proposed method also shows high stability towards
variations in both the inductance and output power. Experimental results
demonstrate the effectiveness of the proposed predictive digital control method for
PFC converters.
In boost converters and other indirect energy transfer topologies, transient-
oriented controllers are designed to facilitate a dynamic response that may range
from minimum time up to minimum output voltage deviation. Since analytical
definitions for these control laws can become quite complex, a large-signal
stability verification is not immediate. This paper explores the existence of
stability of indirect energy transfer converters that are controlled by either
boundary or hybrid controllers and introduces a new simplified procedure for
examination of large-signal stability of a given converter and load type using a
graphical-analytical approach. The stability analysis and examination method are
demonstrated on a boost converter loaded by resistive load and constant current
load. The stability conditions are verified using a 30 W 3.3-to-12 V boost
converter prototype, controlled by a programmable-deviation controller and time-
optimal controller, verifying their large-signal stability.
This article explores socially withdrawn young Finnish people on an Internet forum
who identify with the Japanese hikikomori phenomenon. We aim to overcome the
dualism between sociology and psychology found in earlier research by referring to
Pierre Bourdieu, who provides insights into how individual choices are constructed
in accordance with wider social settings. We focus on the individual level and
everyday choices, but we suggest that psychological factors (anxiety, depression)
can be seen as properties of social relations rather than as individual states of
mind, as young adults have unequal access to valued resources. We scrutinise young
people's specific reasoning related to the social and psychological factors and
contingent life events that influence their choice to withdraw. An experience of
inadequacy, a feeling of failure and a lack of self-efficacy are common experiences
in the data. This indicates that young adults who identify with the hikikomori
phenomenon find external society demanding and consider themselves lacking
resources such as education, social networks or the personality type that they see
as valued in society and as essential to survival'. They also feel that they cannot
control their life events, which may mean that they receive little help in their
everyday lives.
We have previously shown that there is high Na(+)/Ca(2+) exchange (NCX) activity in
bovine adrenal chromaffin cells. In this study, by monitoring the [Ca(2+)](i)
change in single cells and in a population of chromaffin cells, when the reverse
mode of exchanger activity has been initiated, we have shown that the NCX activity
is enhanced by K(+). The K(+)-enhanced activity accounted for a significant
proportion of the Na(+)-dependent Ca(2+) uptake activity in the chromaffin cells.
The results support the hypothesis that both NCX and Na(+)/Ca(2+)-K(+) exchanger
(NCKX) are co-present in chromaffin cells. The expression of NCKX in chromaffin
cells was further confirmed using PCR and northern blotting. In addition to the
plasma membrane, the exchanger activity, measured by Na(+)-dependent (45)Ca(2+)
uptake, was also present in membrane isolated from the chromaffin granules enriched
fraction and the mitochondria enriched fraction. The results support that both NCX
and NCKX are present in bovine chromaffin cells and that the regulation of [Ca(2+)]
(i) is probably more efficient with the participation of NCKX.
Background: In this study we evaluated the RespoCheck Mycoplasma triplex real-time
PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.)
dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory
disease (BRD). Primers and probes of the RespoCheck Mycoplasma triplex real-time
PCR are based on the V3/V4 region of the 16S rRNA gene of the three Mycoplasma
species. Results: The analytical sensitivity of the RespoCheck triplex real-time
PCR was, as determined by spiking experiments of the Mycoplasma strains in
Phosphate Buffered Saline, 300 colony forming units (cfu)/mL for M. dispar, and 30
cfu/mL for M. bovis or M. bovirhinis. The analytical sensitivity of the RespoCheck
Mycoplasma triplex real-time PCRwas, as determined on purified DNA, 10 fg DNA per
assay for M. dispar and 100 fg fo rM. bovis and M. bovirhinis. The analytical
specificity of the RespoCheck Mycoplasma triplex real-time PCR was, as determined
by testing Mycoplasmas strains (n = 17) and other bacterial strains (n = 107), 100,
98.2 and 99.1% for M. bovis, M. dispar and M. bovirhinis respectively. The
RespoCheck Mycoplasma triplex real-time PCR was compared with the PCR/DGGE analysis
for M. bovis, M. dispar and M. bovirhinis respectively by testing 44 BALF samples
from calves. Conclusion: In conclusion, the RespoCheck PCR assay can be a valuable
tool for timely and accurate detection of three Mycoplasma species associated with
in bovine respiratory disease.
Background: Bovine respiratory disease (BRD) is caused by growth of single or
multiple species of pathogenic bacteria in lung tissue following stress and/or
viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons
(NGS 16S amplicon analysis) is a powerful culture-independent open reference method
that has recently been used to increase understanding of BRD-associated bacteria in
the upper respiratory tract of BRD cattle. However, it has not yet been used to
examine the microbiome of the bovine lower respiratory tract. The objective of this
study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung
and lymph node tissue samples harvested from fatal BRD cases and clinically healthy
animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue
samples were collected from calves diagnosed as BRD cases by veterinary laboratory
pathologists and from clinically healthy calves. NGS 16S amplicon libraries,
targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and
sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology
(QIIME) was used to determine operational taxonomic units (OTUs) which corresponded
to the 16S rRNA gene sequences. Results: Leptotrichiaceae, Mycoplasma,
Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the
lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae,
Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative
abundances in post-mortem lung samples collected from fatal cases of BRD in dairy
calves, compared with clinically healthy calves without lung lesions.
Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances
in post-mortem lymph node samples collected from fatal cases of BRD in dairy
calves, compared with clinically healthy calves without lung lesions. Two
Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-
enriched shotgun sequences. Conclusions: The microbiomes of the cranial lung lobe
and mediastinal lymph node from calves which died from BRD and from clinically
healthy H-F calves have been characterised. Contigs corresponding to the abundant
Leptotrichiaceae OTU were sequenced and found not to be identical to any known
bacterial genus. This suggests that we have identified a novel bacterial species
associated with BRD.
Extrafetal tissues are a noncontroversial and inexhaustible source of mesenchymal
stem cells that can be harvested noninvasively at low cost. In the veterinary
field, as in man, stem cells derived from extrafetal tissues express plasticity,
reduced immunogenicity, and have high anti-inflammatory potential making them
promising candidates for treatment of many diseases. Umbilical cord mesenchymal
cells have been isolated and characterized in different species and have recently
been investigated as potential candidates in regenerative medicine. In this study,
cells derived from bovine Wharton jelly (WJ) were isolated for the first time by
enzymatic methods, frozen/thawed, cultivated for at least 10 passages, and
characterized. Wharton jelly-derived cells readily attached to plastic culture
dishes displaying typical fibroblast-like morphology and, although their
proliferative capacity decreased to the seventh passage, these cells showed a mean
doubling time of 34.55 +/- 6.33 hours and a mean frequency of one colony-forming
unit fibroblast like for every 221.68 plated cells. The results of molecular
biology studies and flow cytometry analyses revealed that WJ-derived cells showed
the typical antigen profile of mesenchymal stem cells and were positive for CD29,
CD44, CD105, CD166, Oct-4, and c-Myc. They were negative for CD34 and CD14.
Remarkably, WJ-derived cells showed differentiation ability. After culture in
induced media, WJ-derived cells were able to differentiate into osteogenic,
adipogenic, chondrogenic, and neurogenic lines as shown by positive staining and
expression of specific markers. On polymerase chain reaction analysis, these cells
were negative for MHC-II and positive for MHC-I, thus reinforcing the role of
extrafetal tissue as an allogenic source for bovine cell-based therapies. These
results provide evidence that bovine WJ-derived cells may have the potential to
differentiate to repair damaged tissues and reinforce the importance of extrafetal
tissues as stem cell sources in veterinary regenerative medicine. A more detailed
evaluation of their immunologic properties is necessary to better understand their
potential role in cellular therapy. (C) 2016 Elsevier Inc. All rights reserved.
Objective: Skeletal dysplasia with bowing long bones is a rare group of multiple
characterized congenital anomalies. Materials and Methods: We introduce a simple,
practical diagnostic flowchart that may be helpful in identifying the appropriate
pathway of obstetrical management. Results: Herein, we describe four fetal cases of
bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests,
distinctive X-ray features, and chondral growth plate histology. The first case was
a typical campomelic dysplasia resulting from a de novo mutation in the SOX9 gene.
The second fetus was affected by osteogenesis imperfecta Type II carrying a
mutation in the COLA1 gene. The third case was a rare presentation of campomelic
dysplasia, Cumming type, in which SOX9 examination was normal. Subsequently, a
femoral hypoplasia unusual fades syndrome is also discussed. Conclusion: Targeted
molecular tests and genetic counseling are required for supplementing ultrasound
imaging in order to diagnose the correct skeletal disorders. Copyright (C) 2016,
Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
OBJECTIVE: To define the increased mRNA expression of Bpifb1, a member of the
bactericidal/permeability-increasing protein family, in parotid acinar cells from
non-obese diabetic (NOD) mice, an animal model for Sjogren's syndrome. MATERIALS
AND METHODS: Parotid acinar cells were prepared from female NOD (NOD/ShiJcl) mice
with or without diabetes, as well as from control (C57BL/6JJcl) mice. Total RNA and
homogenate were prepared from the parotid acinar cells. Embryonic cDNA from a Mouse
MTC (TM) Panel I kit was used. The expression of Bpifb1 was determined by cDNA
microarray analysis, RT-PCR, real-time PCR, northern blotting and in situ
hybridization. RESULTS: The expression of Bpifb1 mRNA was high in parotid acinar
cells from diabetic and non-diabetic NOD mice at 5-50 weeks of age. Acinar cells in
the C57BL/6 mice had a low expression of Bpifb1 mRNA at an age >8 weeks, but had a
relatively high expression in the foetus and infantile stages. CONCLUSIONS: Bpifb1
mRNA is upregulated in parotid acinar cells in NOD mice, but its expression is not
related to the onset of diabetes. These findings suggest that high expression
levels of Bpifb1 might predict disease traits before the onset of autoimmunity.
Previous studies have demonstrated that targeting bradykinin receptors is a
promising strategy to counteract the cognitive impairment related with aging and
Alzheimer's disease (AD). The hippocampus is critical for cognition, and
abnormalities in this brain region are linked to the decline in mental ability.
Nevertheless, the impact of bradykinin signaling on hippocampal function is
unknown. Therefore, we sought to determine the role of hippocampal bradykinin
receptors B1R and B2R on the cognitive decline of middle-aged rats. Twelve-month-
old rats exhibited impaired ability to acquire and retrieve spatial information in
the Morris water maze task. A single intra-hippocampal injection of the selective
B1R antagonist des-Arg(9)-[Leu(8)]-bradykinin (DALBK, 3 nmol), but not the
selective B2R antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-BK (Hoe 140, 3
nmol), reversed the spatial learning and memory deficits on these animals. However,
both drugs did not affect the cognitive function in 3-month-old rats, suggesting
absence of nootropic properties. Molecular biology analysis revealed an up-
regulation of B1R expression in the hippocampal CA1 sub-region and in the pre-
frontal cortex of 12-month-old rats, whereas no changes in the B2R expression were
observed in middle-aged rats. These findings provide new evidence that
inappropriate hippocampal B1R expression and activation exert a critical role on
the spatial learning and memory deficits in middle-aged rats. Therefore, selective
B1R antagonists, especially orally active non-peptide antagonists, may represent
drugs of potential interest to counteract the age-related cognitive decline. (C)
2016 Elsevier B.V. All rights reserved.
OBJECTIVE Recent advancements in molecular biology have identified the BRAF
mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor
(BRAFi) in patients with metastatic melanoma has been established. The objective of
this study was to examine the impact of BRAF mutation status and use of BRAFi in
conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center
retrospective study. Patient's charts and electronic records were reviewed for date
of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date
of the diagnosis of CNS metastases, date of SRS, survival, local tumor control
after SRS, and adverse events. Patients were divided into 3 groups: Group A, those
with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant
BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35
patients). Within a cohort of 65 patients with the known BRAF mutation status and
treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were
identified. Kaplan-Meier methodology was then used to compare survival based on
each binary parameter. RESULTS Median survival times after the diagnosis of
melanoma BM and after SRS were favorable in patients with a BRAF mutation and
treated with SRS in conjunction with BRAFi (Group B) compared with the patients
with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p <
0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the
entire cohort of patients. Furthermore, the local control rate was improved in the
patients treated with SRS in conjunction with BRAFi (Group B) compared with
patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as
an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an
important role as a potent prognostic factor in patients harboring melanoma BM.
BRAFi in conjunction with SRS may benefit this group of patients in terms of BM
survival and SRS with an acceptable safety profile.
Aim: Little is known about molecular biology of brain metastasis (BM) from
colorectal cancer and its concordance with matched primary tumors. Materials &
methods: We identified 56 consecutive colorectal cancer patients who underwent
neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and
PIK3CA. The molecular profile of the brain lesion was compared with the
corresponding primary tumor. Results: The molecular profile concordance rate was
95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median
overall survival was 24.0 months (95% CI: 15.6-32.4). Conclusion: In this cohort,
we report a high frequency of KRAS mutations and a very high concordance rate
between the molecular status of BM and that of matched primary tumors.
BackgroundThe role of BRAF mutations in cancerogenesis has been demonstrated in
several solid tumor types. However, in salivary gland tumors, this genetic
alteration is very uncommon, and its role still remains unclear. Thus, the aim of
this study was to analyze BRAF V600E (VE1) protein expression with BRAF mutation
status in codon 600, in malignant and benign salivary gland tumors. MethodsStudies
were performed on archived formalin-fixed paraffin-embedded tissue sections derived
from 95 patients who underwent surgery for tumors of the salivary gland.
Immunohistochemical staining (IHC) on tissue microarray slides was performed for
evaluation of BRAF V600E (VE1) protein expression, and the automatic molecular
diagnostics platform was used for the evaluation of mutations in codon 600 of BRAF
gene. ResultsIHC cytoplasmic expression of BRAF V600E (VE1) protein was found in
two of 95 cases: one case of adenocarcinoma NOS (one of three; 33%) and one case of
carcinoma ex pleomorphic adenoma (one of five; 20%). Although, in IHC studies,
nuclear BRAF V600E (VE1) protein expression was found in 14 (15%) of the analyzed
cases: nine of 28 (32%) cases of pleomorphic adenoma, three of five (60%) cases of
ductal carcinoma, one of nine (11%) case of mucoepidermoid carcinoma, and in one of
five (20%) case of carcinoma ex pleomorphic adenoma. All cases were negative for
polymerase chain reaction PCR-based analyses of BRAF mutations in codon 600.
ConclusionsIn studied salivary gland cancers, no PCR-based prove mutations of BRAF
V600 were detected. Further molecular analyses are necessary to rapid molecular
arrays for the identification of specific mutations, optimal for individualized
targeted therapies.
To examine molecular events in hippocampus associated with aging and acupuncture
effect, we employed cDNA arrays providing data of 588 genes to define
transcriptional patterns. Male 8-month-old SAMP 10 and its homologous SAMR1 were
selected and randomly divided into four groups: RI control group (Rc), P10 control
group (PC), P10 acupuncture group (Pa) and PIO non-acupoint group (Pn). The points
consisted Shanzhong (CV17), Zhongwan (CV12), Qihai (CV6), Zusanli (ST36) and Xuehai
(SPIO). In Pa, we found that points stimuli could completely or partly reverse some
genes expression profiles in hippocampus with aging. Simultaneously, some genes not
related with brain aging were affected by acupuncture as well. Meanwhile, non-
acupoint had some effect on aging-unrelated genes expression and little or negative
effect on aging-related genes. We verified array results with RT-PCR and Northern
blotting for three genes which are related to oxidative damage closely, including
Hsp84, Hsp86 and YB-1. In conclusion, acupuncture Could be a potential intervention
to retard molecular events with aging in mammals. (c) 2006 Elsevier Ireland Ltd.
All rights reserved.
As the most fascinating, complex, and dynamic part of our organism, the human brain
is shaped by many interacting factors that not only are of neurobiological
(including sex hormones) and environmental origin but are also sociocultural in
their very nature (such as social roles). Gender is one of these factors. Most
neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders are
characterized by impairments in visual social cognition (primarily body language
reading and face perception) and a skewed sex ratio: females and males are affected
differently in terms of clinical picture, prevalence, and severity. Is the social
brain sex specific? This is still an open question. For a long time and for many
reasons, sex differences have been overlooked or entirely ignored in neuroscience
and biomedical research: there is a paucity of neuroimaging work examining sex
differences in the social brain. However, the pattern of experimental behavioral
data in both healthy, typically developing individuals and patients with deficient
social cognition is beyond simple interpretation: contrary to popular wisdom,
females are not always more proficient in understanding social signals, and their
social abilities may be particularly affected by disease. Clarification of how
neurobiological sex and sociocultural gender affect the social brain would provide
novel insights into understanding gender-specific vulnerability to neuropsychiatric
disorders. This interaction is far beyond simplicity. Although sex differences
represent a rather delicate topic, underestimation or exaggeration of possible
effects retards progress in the field. (C) 2016 Wiley Periodicals, Inc.
Objective. Brain-computer interfaces (BCIs) can help patients who have lost control
over most muscles but are still conscious and able to communicate or interact with
the environment. One of the most popular types of BCI is the P300-based BCI. With
this BCI, users are asked to count the number of appearances of target stimuli in
an experiment. To date, the majority of visual P300-based BCI systems developed
have used the same character or picture as the target for every stimulus
presentation, which can bore users. Consequently, users attention may decrease or
be negatively affected by adjacent stimuli. Approach. In this study, a new stimulus
is presented to increase user concentration. Honeycomb-shaped figures with 1-3 red
dots were used as stimuli. The number and the positions of the red dots in the
honeycomb-shaped figure were randomly changed during BCI control. The user was
asked to count the number of the dots presented in each flash instead of the number
of times they flashed. To assess the performance of this new stimulus, another
honeycomb-shaped stimulus, without red dots, was used as a control condition. Main
results. The results showed that the honeycomb-shaped stimuli with red dots
obtained significantly higher classification accuracies and information transfer
rates (p < 0.05) compared to the honeycomb-shaped stimulus without red dots.
Significance. The results indicate that this proposed method can be a promising
approach to improve the performance of the BCI system and can be an efficient
method in daily application.
Social cognition refers to the ability to use social cues to infer the meaning and
intentions behind the behaviour of others in order to respond in a socially
adaptive manner. It is increasingly recognised that disorders of social cognition,
including problems with emotion perception, theory of mind, conversational
inference, morality judgements, decision making and social inhibition, characterise
many developmental and psychiatric disorders and are highly relevant to many with
acquired brain injuries or diseases, especially the frontotemporal dementias. This
review provides an introduction and overview of the papers in this special edition
on social cognition and places these in the context of other recent research. In
doing so, several current issues in the clinical management of social cognition are
delineated. Given that social cognition seems to be a sensitive predictor of
psychosocial function, the assessment of social cognition is seen by many
clinicians to be important although which profession is responsible is yet to be
resolved. Issues in how social cognition are assessed are discussed, including the
importance of context to social cognition, its interactive nature and the need to
recognise influences such as family upbringing, gender and emotional state on
social cognitive performance. There also needs to be development of tests that
address all aspects of social cognition, including decision making and inhibition.
Finally, this review discusses intervention research. Interventions are especially
well developed in relation to schizophrenia, and less well developed in brain
injury. These appear to be generally effective although treatments for emotional
self-awareness are yet to be developed.
Confronted with brain metastases (BM), pathologists aim to rule out a primary
central nervous system (CNS) tumor and to identify or verify the primary tumor site
to guide the clinician to specific therapies. Apart from morphological features,
ancillary immunohistochemical analysis is the most effective tool for
characterizing a metastatic neoplasm of unknown origin. A limited array of
antibodies is used, taking into account relevant clinical information and the known
brain tropism of lung cancer, breast cancer and melanoma. Recently, targeted
therapies have enriched the therapeutic arsenal, in particular for patients with
non-small cell lung cancer or melanoma and for patients carrying molecular
anomalies. These therapies can lead to a substantial tumor response, brain
metastases included, which justifies rapid determination of a molecular profile. To
combine different tools and provide timely results, good tumor sample management
and careful attention at the pre-analytical phase are critical. Appropriate
strategies for molecular and immunohistochemical analysis are needed to identify
theranostic markers. This article aims to review the anatomopathological diagnostic
approach for BM in the age of targeted therapies.
Background: Lung cancer is the leading cause of brain metastases (BM). The
identification of driver oncogenes and matched targeted therapies has improved
outcome in non-small cell lung cancer (NSCLC) patients; however, a better
understanding of BM molecular biology is needed to further drive the process in
this field. Methods: In this observational study, stage IV NSCLC patients tested
for EGFR and KRAS mutations were selected, and BM incidence, recurrence and
patients' outcome were assessed. Results: A total of 144 patients (142 Caucasian
and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with
KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more
frequent in patients with EGFR mutation according to multivariate analyses (MVA)
(Odds ratio OR = 8.745 [1.743-43.881], p = 0.008). Among patients with treated BM,
recurrence after local treatment was less frequent in patients with KRAS mutation
(OR = 0.234 [0.078-0.699], p = 0.009). Among patients with untreated BM, overall
survival (OS) was shorter for patients with KRAS mutation according to univariate
analysis (OR = 7.130 [1.240-41.012], p = 0.028), but not MVA. Conclusions: EGFR and
KRAS mutations have a predictive role on BM incidence, recurrence and outcome in
Caucasian NSCLC patients. These results may impact the routine management of
disease in these patients. Further studies are required to assess the influence of
other biomarkers on NSCLC BM.
Brain single-photon emission computerized tomography (SPECT), in particular, with
perfusion agents or with neuroreceptor imaging radiopharmaceuticals, is rapidly
becoming a clinical tool in many neurologic and psychiatric conditions. This
imaging modality has been used for diagnosis, prognosis assessment, evaluation of
response to therapy, risk stratification, detection of benign vs. malignant viable
tissue, and the choice of medical or surgical therapy. We will present our
institutional experience in this area, formatting a pictorial review of brain
perfusion SPECT on more than 20 types of different neurologic and psychiatric
diseases, such as dementia, epilepsy, cerebral palsy, head injury, brain tumor,
herpes encephalitis, hypoxic brain damage, vacuities, depression, carbon monoxide
(CO) poisoning, and cocaine abuse. This is a demanding procedure as far as the need
for trained and experienced physicians and personnel as well as advanced equipment
are concerned. However, extraordinary useful clinical information achieved by this
technology outweighs the existing challenge. More routine use of this procedure
which is unfortunately underutilized in many countries including ours should be
encouraged.
Numerous findings demonstrate that there is a strong association between maternal
health during pregnancy and cardiovascular disease in adult offspring. The purpose
of the present study was to test whether maternal gestational hypertension
modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory
cytokines that sensitizes angiotensin II-elicited hypertensive response in adult
offspring. In addition, the role of renal nerves and the RAAS in the sensitization
process was investigated. Reverse transcription polymerase chain reaction analyses
of structures of the lamina terminalis and paraventricular nucleus indicated
upregulation of mRNA expression of several RAAS components and proinflammatory
cytokines in 10-week-old male offspring of hypertensive dams. Most of these
increases were significantly inhibited by either renal denervation performed at 8
weeks of age or treatment with an angiotensin-converting enzyme inhibitor,
captopril, in drinking water starting at weaning. When tested beginning at 10 weeks
of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA
expression of RAAS components and proinflammatory cytokines in the lamina
terminalis and paraventricular nucleus and an augmented pressor response in male
offspring of hypertensive dams. The augmented blood pressure change and most of the
increases in gene expression in the offspring were abolished by either renal
denervation or captopril. The results suggest that maternal hypertension during
pregnancy enhances pressor responses to angiotensin II through overactivity of
renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS
and proinflammatory cytokines in these offspring may contribute to maternal
gestational hypertension-induced sensitization of the hypertensive response to
angiotensin II.
Basic helix-loop-helix PAS domain proteins form a growing family of transcription
factors. These proteins are involved in the process of adaptation to cellular
stresses and environmental factors such as a change in oxygen concentration. We
describe the identification and characterization of a recently cloned PAS domain
protein termed Npas4 in ischemic rat brain. Using gene expression profiling
following middle cerebral artery occlusion, we showed that the Npas4 mRNA is
differentially expressed in ischemic tissue. The full-length gene was cloned from
rat brain and its spatial and temporal expression characterized with in situ
hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in
the brain and is highly up-regulated in ischemic tissues following both focal and
global cerebral ischemic insults. Immunohistochemistry revealed a strong expression
in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of
the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a
protein of similar to 100 kDa. In brain samples, however, in addition to the 100
kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic
challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the
100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for
activation and/or deactivation of this protein in response to ischemic brain
injury.
Although, overwhelmingly, behavior is similar in males and females, and,
correspondingly, the brains are similar, sex differences permeate both brain and
behavioral measures, and these differences have been the focus of increasing
scrutiny by neuroscientists. This Review describes milestones from more than 3
decades of research in brain and behavior. This research was necessarily bound by
available methodology, and we began with indirect behavioral indicators of brain
function such as handedness. We proceeded to the use of neuropsychological
batteries and then to structural and functional neuroimaging that provided the
foundations of a cognitive neuroscience-based computerized neurocognitive battery.
Sex differences were apparent and consistent in neurocognitive measures, with
females performing better on memory and social cognition tasks and males on spatial
processing and motor speed. Sex differences were also prominent in all major brain
parameters, including higher rates of cerebral blood flow, higher percentage of
gray matter tissue, and higher interhemispheric connectivity in females, compared
with higher percentage of white matter and greater intrahemispheric connectivity as
well as higher glucose metabolism in limbic regions in males. Many of these
differences are present in childhood, but they become more prominent with
adolescence, perhaps linked to puberty. Overall, they indicate complementarity
between the sexes that would result in greater adaptive diversity. (C) 2016 Wiley
Periodicals, Inc.
One-third of cancer patients undergoing chemotherapy treatment often display
symptoms of depression leading to poor adherence and decreased quality of life.
Thus, this study aimed to investigate the possible protective effect of nebivolol
against cisplatin-associated depressive symptoms in adult male rats. Nebivolol is a
highly cardioselective -adrenergic receptor blocker that possesses endothelium-
dependent vasodilator properties and antioxidant capacities. Animals were allocated
into four groups. Group one was given aqueous solution of carboxymethyl cellulose
and served as control, group two was given nebivolol (10mg/kg p.o., daily), group
three was given cisplatin (2mg/kg i.p. once per week) for 10 consecutive weeks and
group four was treated with cisplatin concomitantly with nebivolol as per above
schedule. Cisplatin-treated rats showed an increase in both depressive-like
behaviors in open-field and forced swimming tests. In addition, histopathological
examination revealed cortical encephalomalacia along with hippocampal neuronal
degeneration and kidney dysfunction. In parallel, cisplatin administration
prominently reduced GABA and elevated glutamate levels in the cortical and
hippocampal tissues. Furthermore, it resulted in a significant decline in cortical
and hippocampal brain-derived neurotrophic factor and nitric oxide contents
concomitantly with a marked decrease in endothelial- and an increase in inducible-
nitric oxide synthase genes expression. On the other hand, treatment with nebivolol
effectively mitigated the aforementioned cisplatin-associated behavioral,
biochemical, and histopathological alterations without changing its antitumor
activity as evidenced by sulforhodamine B cell survival assay. Taken together, our
results suggest that nebivolol may offer a promising approach for alleviating
depressive symptoms associated with the use of cisplatin.
Background: Preclinical and clinical evidence supports the concept of bidirectional
brain-gut microbiome interactions. We aimed to determine if subgroups of irritable
bowel syndrome (IBS) subjects can be identified based on differences in gut
microbial composition, and if there are correlations between gut microbial measures
and structural brain signatures in IBS. Methods: Behavioral measures, stool
samples, and structural brain images were collected from 29 adult IBS and 23
healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used
to profile stool microbial communities, and various multivariate analysis
approaches were used to quantitate microbial composition, abundance, and diversity.
The metagenomic content of samples was inferred from 16S rRNA gene sequence data
using Phylogenetic Investigation of Communities by Reconstruction of Unobserved
States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T
scanner, and morphological measures were computed for 165 brain regions. Results:
Using unweighted Unifrac distances with hierarchical clustering on microbial data,
samples were clustered into two IBS subgroups within the IBS population (IBS1 (n =
13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95,
specificity 0.67). A Random Forest classifier provided further support for the
differentiation of IBS1 and HC groups. Microbes belonging to the genera
Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification.
Clinical features distinguishing the groups included a history of early life trauma
and duration of symptoms (greater in IBS1), but not self-reported bowel habits,
anxiety, depression, or medication use. Gut microbial composition correlated with
structural measures of brain regions including sensory-and salience-related
regions, and with a history of early life trauma. Conclusions: The results confirm
previous reports of gut microbiome-based IBS subgroups and identify for the first
time brain structural alterations associated with these subgroups. They provide
preliminary evidence for the involvement of specific microbes and their predicted
metabolites in these correlations.
(R)ecent advances in deep brain stimulators and brain -machine interfaces have
greatly expanded the possibilities of neuroprosthetics and neuromodulation.
Together with advances in neuroengineering, nanotechnology, molecular biology and
material sciences, it is now possible to address fundamental questions in
neuroscience in new, more powerful ways. It is now possible to apply these new
technologies in ways that range from augmenting and restoring function to
neuromodulation modalities that treat neuropsychiatric disorders. Recent
developments in neuromodulation methods offer significant advantages and potential
clinical benefits for a variety of disorders. Here we describe the current state of
the art in neuromodulation methods, and some advances in brain -machine interfaces,
describing the advantages and limitations of the clinical applications of each
method. The future applications of these new methods and how they will shape the
future of psychiatry and medicine, along with safety and ethical implications, are
also discussed. (c) 2017 Elsevier Inc. All rights reserved.
Introduction. - Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all
brain tumors in the pediatric population; currently prognosis remains poor, with an
overall survival of 7-14 months. Recently the indication of DIPG biopsy has been
enlarged due to the development of molecular biology and various ongoing clinical
and therapeutic trials. Classically a biopsy is performed using a stereotactic
frame assisted procedure but the workflow may sometimes be heavy and more complex
especially in children. In this study the authors present their experience with
frameless robotic-guided biopsy of DIPG in a pediatric population. Patients and
methods. - Retrospective study on a series of five consecutive pediatric patients
harboring DIPG treated over a 4-year period. All patients underwent frameless
robotic-guided biopsy via a transcerebellar approach. Results. - Among the 5
patients studied 3 were male and 2 female with a median age of 8.6 years [range 5
to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve
palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of
them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on
T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56
minutes (range 45 to 67 minutes). No new postoperative neurological deficits were
recorded. Histological diagnosis was achieved in all cases as follows: two
anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma
(grade III). Conclusion. - Frameless robotic assisted biopsy of DIPG in pediatric
population is an easier, effective, safe and highly accurate method to achieve
diagnosis. (C) 2016 Elsevier Masson SAS. All rights reserved.
Diffuse intrinsic pontine glioma (DIPG) is a malignant brain tumor of childhood
that carries an extremely poor prognosis. There are similar to 200-300 new cases
diagnosed each year, [1, 2] and little progress has been made in changing the
prognosis and outcome of the tumor since it was first documented in the literature
in 1926 [3]. The median overall survival is 8-11 months [4], with an overall
survival rate of 30% at 1 year, and less than 10% at 2 years [4]. This review will
provide background information on DIPGs, a historical look at the trends in caring
for DIPG, and current trends in diagnosis and treatment. By changing the way we
care for these terminal tumors, we can work towards having a better understanding
of the underlying molecular biology, and attempt to develop better chemotherapeutic
tools to combat the disease.
We study the energy dispatch of power distribution networks (PDNs) coupled with
urban transportation networks. The electricity demand at each charging/swapping
facility is influenced by the arrival rates and charging requests of electric
vehicles, which further depends on the spatial distribution of traffic flows over
the entire transportation system. We consider the impact of the road congestion on
route choices of vehicles from a system-level perspective. The traffic flow pattern
in steady state is characterized by the Wardrop user equilibrium. We consider the
PDN load perturbation caused by the traffic demand uncertainty, and propose a
robust dispatch method that maintains the feasibility of an alternating current
power flow constraints. By applying the convex relaxation to nonlinear branch power
flow equations, the proposed model yields a two-stage robust convex optimization
problem with an implicit uncertainty set. Moreover, a decomposition framework is
proposed, in which the first phase determines the uncertainty set of electricity
demand by solving two traffic assignment problems associated with the extreme
scenarios, and the second phase solves a two-stage robust second-order cone program
following a delayed constraint generation framework. Several issues regarding the
scalability and conservatism are elaborated. Case studies corroborate the
applicability and efficiency of the proposed method.
Three genes, gnd, pgl, and fbp, relevant to the pentose phosphate pathway (PPP)
were overexpressed in Corynebacterium glutamicum IWJ001, leading to increase of L-
isoleucine production. The transcriptional levels of gnd, pgl, and fbp
significantly increased in IWJ001/pDXW-8-gnd-fbp-pgl. Compared with the control
strain IWJ001/pDXW-8, intracellular NADPH/NADP(+) ratios in IWJ001/pDXW-8-gnd and
IWJ001/pDXW-8-gnd-fbp cells grown for 36 H increased threefold and fourfold,
respectively, indicating that overexpression of gnd and fbp redirected the carbon
flux to PPP. Intracellular NADPH/NADP(+) ratio in IWJ001/pDXW-8-gnd-fbp-pgl grown
for 36 H was similar to IWJ001/pDXW-8, suggesting that the NADPH produced by PPP
could be quickly consumed for L-isoleucine production. 10.9 and 28.96 g/L of L-
isoleucine was produced in IWJ001/pDXW-8-gnd-fbp-pgl in shake flask cultivation and
fed-batch fermentation, respectively. In addition, IWJ001/pDXW-8-gnd-fbp-pgl grew
fast, its dry cell weight reached 49 g/L after 48 H, whereas the start strain
IWJ001/pDXW-8 reached only 40 g/L. After 96 H fermentation, L-isoleucine yield on
glucose in IWJ001/pDXW-8-gnd-fbp-pgl reached 0.138 g/g. The results demonstrate
that carbon flux redirection to PPP is an efficient approach to enhance L-
isoleucine production in C. glutamicum. (C) 2015 International Union of
Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 877-885, 2016
Background: During embryogenesis, tight regulation of retinoic acid (RA)
availability is fundamental for normal development. In parallel to RA synthesis, a
negative feedback loop controlled by RA catabolizing enzymes of the cytochrome P450
subfamily 26 (CYP26) is crucial. In vertebrates, the functions of the three CYP26
enzymes (CYP26A1, CYP26B1, and CYP26C1) have been well characterized. By contrast,
outside vertebrates, little is known about CYP26 complements and their biological
roles. In an effort to characterize the evolutionary diversification of RA
catabolism, we studied the CYP26 genes of the cephalochordate amphioxus
(Branchiostoma lanceolatum), a basal chordate with a vertebrate-like genome that
has not undergone the massive, large-scale duplications of vertebrates. Results: In
the present study, we found that amphioxus also possess three CYP26 genes (CYP26-1,
CYP26-2, and CYP26-3) that are clustered in the genome and originated by lineage-
specific duplication. The amphioxus CYP26 cluster thus represents a useful model to
assess adaptive evolutionary changes of the RA signaling system following gene
duplication. The characterization of amphioxus CYP26 expression, function, and
regulation by RA signaling demonstrated that, despite the independent origins of
CYP26 duplicates in amphioxus and vertebrates, they convergently assume two main
roles during development: RA-dependent patterning and protection against
fluctuations of RA levels. Our analysis suggested that in amphioxus RA-dependent
patterning is sustained by CYP26-2, while RA homeostasis is mediated by CYP26-1 and
CYP26-3. Furthermore, comparisons of the regulatory regions of CYP26 genes of
different bilaterian animals indicated that a CYP26-driven negative feedback system
was present in the last common ancestor of deuterostomes, but not in that of
bilaterians. Conclusions: Altogether, this work reveals the evolutionary origins of
the RA-dependent regulation of CYP26 genes and highlights convergent functions for
CYP26 enzymes that originated by independent duplication events, hence establishing
a novel selective mechanism for the genomic retention of gene duplicates.
BACKGROUND: Glutamine synthetase (GS; EC 6.3.1.2) is a key enzyme of nitrogen (N)
assimilation, catalysing the synthesis of glutamine from ammonium and glutamate.
Plants have two types of GS isoenzyme that are localised in different compartments:
one in the cytosol (GS1) and the other in the chloroplast (G52). GS1 is the major
form of GS in plant roots and directly converts ammonium taken up by plant roots to
glutamine. RESULTS: The GS1 gene cDNA of non-heading Chinese cabbage (Brassica
campestris ssp. chinensis Makino) cultivar 'Suzhouqing' was isolated by RT-PCR
(real-time polymerase chain reaction) and (5'/3')-RACE (rapid amplification of cDNA
ends) techniques. It was classified as GS1 by sequence alignment and motif search
and named B. campestris ssp. chinensis Makino GS1 (BcGS1). Subcellular localisation
analysis showed that BcGS1 was distributed in the cytoplasm of cells. BcGS1 was
expressed in all parts, but mainly in the roots, which was verified by northern
blotting analysis. Additionally, its expression was influenced by the N source
concentration. CONCLUSION: These results suggest that BcGS1 is a novel member of
the GS family in plants. BcGS1 was significantly related to N assimilation in non-
heading Chinese cabbage, demonstrating that this gene plays an important role in
plant growth and development. (C) 2010 Society of Chemical Industry
FLOWERING LOCUS C (FLC), which encodes a MADS-box domain protein, is a flowering
repressor involved in the key position of Arabidopsis (Arabidopsis thaliana)
flowering network. In Brassica species, several FLC homologues are involved in
flowering time like Arabidopsis FLC. Here, we report the analysis of splicing
variation in BrpFLC1 and the expression of BrpFLC homologues associated with early
flowering of Purple Flowering Stalk (Brassica campestris L. ssp. chinensis L. var.
purpurea Bailey). It was indicated that a splice site mutation happened in intron 6
with G to A at the 5' splice site. Three alternative splicing patterns of BrpFLC1,
including the entire exon 6 excluded and 24 bp or 87 bp of intron 6 retained, were
identified in Purple Flowering Stalk. But there was only one normal splicing
pattern in Pakchoi (Brassica campestris ssp. chinensis var. communis). Northern
blotting and semi-quantitative RT-PCR revealed that the expression levels of the
three FLC homologues in Purple Flowering Stalk were lower than that in Pakchoi.
However, the expression levels of downstream genes, SUPPRESSOR OF OVEREXPRESSION OF
CONSTANS 1 (SOC1) and FLOWERING LOCUS T (FT), were higher in Purple Flowering
Stalk. These results suggest that a natural splicing site mutation in BrpFLC1 gene
and repressed expression of all BrpFLC genes contribute significantly to flowering
time variation in Purple Flowering Stalk.
The polygalacturonase (PG) gene family has been found to be enriched in pollen of
several species; however, little is currently known about the function of the PG
gene in pollen development. To investigate the exact role that the PG gene has
played in pollen development and about this family in general, one putative PG
gene, Brassica campestris Male Fertility 9 (BcMF9), was isolated from Chinese
cabbage (Brassica campestris ssp. chinensis, syn. B. rapa ssp. chinensis) and
characterized. RT-PCR, northern blotting and in situ hybridization were used to
analyse the expression pattern of BcMF9, and antisense RNA technology was applied
to study the function of this gene. BcMF9 is expressed in particular in the tapetum
and microspore during the late stages of pollen development. Antisense RNA
transgenic plants that displayed decreased expression of BcMF9 showed pollen
morphological defects that resulted in reduced pollen germination efficiency.
Transmission electron microscopy revealed that the homogeneous pectic exintine
layer of pollen facing the exterior was over-developed and predominantly occupied
the intine, reversing the normal proportional distribution of the internal
endintine layer and the external exintine in transgenic pollen. Inhibition of BcMF9
also resulted in break-up of the previously formed tectum and baculae from the
beginning of the binucleate stage, as a result of premature degradation of tapetum.
Several lines of evidence, including patterns of BcMF9 expression and phenotypic
defects, suggest a sporophytic role in exine patterning, and a gametophytic mode of
action of BcMF9 in intine formation. BcMF9 might act as a co-ordinator in the late
stages of tapetum degeneration, and subsequently in the regulation of wall material
secretion and, in turn, exine formation. BcMF9 might also play a role in intine
formation, possibly via regulation of the dynamic metabolism of pectin.
Based on the significant differences in the resistance to Sclerotinia sclerotiorum
between two Brassica napus cultivars, ZhongR888 and Zhongyou821, near isogenic
lines (NILs) were established. The resistance differences between Zhongyou821 and
BC5 progeny (the fifth generation from a cross between Zhongyou821 and ZhongR888
with Zhongyou821 as successive backcross parent) was displayed by cDNA-AFLP and
differential transcripts-derived fragments (TDFs). The full-length cDNA of 1,707 bp
with 1,323 bp open reading frame (ORF, open box), named Rsk was identified by RT-
RACE from the resistance related fragment 40-2 in Zhongyou821. It encoded a protein
of 440 amino acid residues, which contained a putative extracellular domain, a
transmembrane domain, and an intracellular domain. Analysis of the deduced amino
acid sequence of Rsk revealed that it had high homology to Arabidopsis thaliana
kinase involved in protein binding, and had a conserved region of LRR-RI,
indicating it might be a member of leucine-rich repeats, ribonuclease inhibitor-
like subfamily. DNA sequences of 1,685 bp and 1,703 bp without an intron were also
identified from Zhongyou821 and BC5, respectively. Expression analysis showed that
Rsk might play a role in disease resistance pathways.
Oilseeds of the plant family Brassicaceae are important for providing both lipid
and protein contents to human nutrition. Cruciferins (12S globulins) are seed
storage proteins, which are getting attention due to their allergenic and
pathogenicity related nature. This study describes the purification and
characterization of a trimeric (similar to 190 kDa) cruciferin protein from the
seeds of Brassica nigra (L). Cruciferin was first partially purified by ammonium
sulfate precipitation (30% saturation constant) and further purified by size
exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82%
sequence homology with cruciferin from Arabidopsis thaliana. The 50-55 kDa
monomeric cruciferin produced multiple bands of two major molecular weight ranges
(a-polypeptides of 28-32 kDa and (beta-polypeptides of 17-20 kDa) under reduced
conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further
separation of the bands into their isoforms with major pI ranges between 5.7 and
8.0 (a-poly peptides) and 5.5-8.5 (beta-polypeptides). The Dynamic Light Scattering
(DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of
5.8 +/- 0.1 nm confirming the trimeric nature of the protein. The Circular
Dichroism (CD) spectra showed both a-helices and beta-sheets in the native
conformation of the trimeric protein. The pure cruciferin protein (40 mg/m1) was
successfully crystallized; however, the crystals diffracted only to low resolution
data (8 A). Small-angle x-ray scattering (SAXS) was applied to gain insights into
the three-dimensional structure in solution. SAXS showed that the radius of
gyration is 4.24 +/- 0.25 nm and confirmed the nearly globular shape. The SAXS
based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins
(PDB ID: 3KGL) of B. napus which further confirmed a highly similar molecular
weight and globular shape indicating a conserved trimerization of B. nigra
cruciferin. The comparison of the scattering patterns of both proteins showed a
minimized x(2)-value of 1.337 confirming a similar molecular structure. This is the
first report describing the purification and characterization of a cruciferin
protein from seeds of B. nigra. (C) 2017 Elsevier B.V. All rights reserved.
The species Brassica rapa includes various vegetable crops. Production of these
vegetable crops is usually impaired by heat stress. Some microRNAs (miRNAs) in
Arabidopsis have been considered to mediate gene silencing in plant response to
abiotic stress. However, it remains unknown whether or what miRNAs play a role in
heat resistance of B. rapa. To identify genomewide conserved and novel miRNAs that
are responsive to heat stress in B. rapa, we defined temperature thresholds of non-
heading Chinese cabbage (B. rapa ssp. chinensis) and constructed small RNA
libraries from the seedlings that had been exposed to high temperature (46 degrees
C) for 1 h. By deep sequencing and data analysis, we selected a series of conserved
and novel miRNAs that responded to heat stress. In total, Chinese cabbage shares at
least 35 conserved miRNA families with Arabidopsis thaliana. Among them, five miRNA
families were responsive to heat stress. Northern hybridization and real-time PCR
showed that the conserved miRNAs bra-miR398a and bra-miR398b were heat-inhibitive
and guided heat response of their target gene, BracCSD1; and bra-miR156h and bra-
miR156g were heat-induced and its putative target BracSPL2 was down-regulated.
According to the criteria of miRNA and miRNA* that form a duplex, 21 novel miRNAs
belonging to 19 miRNA families were predicted. Of these, four were identified to be
heat-responsive by Northern blotting and/or expression analysis of the putative
targets. The two novel miRNAs bra-miR1885b.3 and bra-miR5718 negatively regulated
their putative target genes. 5'-Rapid amplification of cDNA ends PCR indicated that
three novel miRNAs cleaved the transcripts of their target genes where their
precursors may have evolved from. These results broaden our perspective on the
important role of miRNA in plant responses to heat.
Recent advances in our understanding of the molecular biology of epithelial ovarian
cancer have led to the development of a number of targeted therapies, including
poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of
therapeutic agents that target tumors with deficiencies in the homologous
recombination DNA repair pathway. Early studies have shown significant efficacy for
PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident
that BRCA wild-type patients with other defects in the homologous recombination
repair pathway benefit from this therapeutic approach. Importantly, companion
homologous recombination deficiency scores are being developed to help guide the
selection of patients most likely to gain clinical benefit from PARP inhibition.
Olaparib, the first and most extensively investigated PARP inhibitor, is now
licensed in Europe for maintenance treatment of patients with platinum-sensitive
relapsed BRCA-mutated (germ-line or somatic) high-grade serous ovarian cancer who
have responded to platinum-based chemotherapy. In the United States, olaparib is
licensed for treatment of patients with germline BRCA-mutated ovarian cancer who
have received 3 or more lines of chemotherapy. There are a number of other PARP
inhibitors in late phase clinical development in ovarian cancer including
rucaparib, niraparib, veliparib, and talazoparib. This review will focus on the
current evidence for PARP inhibitors in ovarian cancer and discuss ongoing clinical
trials and future research directions in this rapidly evolving area.
Germline BRCA2 mutations are the first known cause of inherited (familial)
pancreatic ductal adenocarcinoma (PDAC). This tumor is the third most frequent
cancer in carriers of germline BRCA2 mutations, as it occurs in around 10% of BRCA2
families. PDAC is known as one of the most highly lethal cancers, mainly because of
its chemoresistance and frequently late diagnosis. Based on recent developments in
molecular biology, a subgroup of BRCA2-associated PDAC has been created, allowing
screening, early surgical treatment and personalized systemic treatment. BRCA2
germline mutation carriers who have >= 1 first-degree relative, or >= 2 blood
relatives with PDAC, should undergo screening and regular follow-up based on
magnetic resonance imaging and endoscopic ultrasound. The goal of screening is to
detect early invasive PDAC and advanced precancerous lesions suitable for a
stepwise surgical complete (R0) resection. Increasing evidence on the molecular
role of the BRCA2 protein in the homologous recombination of DNA damages suggest
that BRCA2-related PDAC are sensitive to agents causing DNA cross-linking damage,
such as platinum salts, and treatments targeting rescue DNA repair pathways, such
as poly(ADP-ribose) polymerase inhibitors that are currently under investigation.
Aims: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive
carcinoma that locates characteristically to the midline of the head and neck, and
mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at
15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a
fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline
Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly
rare, and we report a case series of seven cases. Methods and results: We searched
for cases in files of different hospitals as well as a thorough search of the
English language literature. The diagnosis of NMC is made by demonstration of NUT
rearrangement either by immunohistochemistry, fluorescence in-situ hybridization
(FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three
previously published cases, and in this series add four cases of our own.
Conclusions: NMC consists of monomorphic, often discohesive, cells with an
epithelioid appearance and distinct nucleoli. The tumours typically show abrupt
squamous differentiation. The mean age of the patients was 34 years, hence
significantly lower than that for conventional laryngeal carcinoma. All tumours
were located in the supraglottis and five patients died of the disease after 3, 7,
8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness
among pathologists is warranted. NMC has characteristic morphological features, and
positive immunostaining with the NUT antibody is diagnostic. Its aggressive
behaviour demands a very intense treatment strategy and the need for its
recognition is emphasized further by new promising treatment strategies.
Irinotecan is a natural alkaloid agent widely used in cancer therapy. High-mobility
group protein B1 as a non-histone chromosomal protein plays a fundamental role in
gene expression and inflammation. In this study, the effect of irinotecan on high-
mobility group protein B1 and MMP9 content, gene expression, cell cycle, and cell
growth in human breast cancer cells (MCF-7) was investigated. The cells were
exposed to various concentrations of irinotecan and the viability determined by
trypan blue exclusion and 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazolium
bromide assays. High-mobility group B proteins were extracted from the control and
drug-treated cells and analyzed by immunoblot. High-mobility group protein B1 and
MMP9 messenger RNA expression was studied by reverse transcription polymerase chain
reaction. The results demonstrated reduction of cell viability upon increasing
irinotecan concentration, up-regulated high-mobility group protein B1 gene
expression, and down-regulated MMP9 mRNA. Although the content of high-mobility
group protein B1 was decreased in chromatin extract upon drug action, no high-
mobility group protein B1 release to extracellular space was detected by immunoblot
analysis. Irinotecan decreased H3K9 acetylation and increased poly ADP-ribose
polymerase fragmentation to 89 kDa and anion superoxide production suggesting
induction of apoptosis in these cells. Propidium iodide staining of the cells 24 h
after the drug treatment revealed arrest of the cells in S-phase. From the results,
it is concluded that overexpression of high-mobility group protein B1 in the
presence of irinotecan precedes breast cancer cells into apoptosis and in this
response the binding of irinotecan to chromatin or high-mobility group protein B1
may condense/aggregate chromatin, preventing high-mobility group protein B1 release
from chromatin.
Neoadjuvant chemotherapy, that is, the administration of chemotherapy before
surgery, has been commonly used for locally advanced breast cancer to improve the
surgical outcomes and increase the opportunity for breast-conserving therapy. Women
with breast cancer often receive an anthracycline-based regimen as the neoadjuvant
chemotherapy, which is associated with a high risk of emesis. Despite the
development of novel antiemetics, chemotherapy-induced nausea and vomiting (CINV)
has been commonly reported as a major adverse effect, affecting the quality of life
of the patients. However, the factors predicting CINV in women with breast cancer
undergoing neoadjuvant chemotherapy remain unclear. In this single-institution,
prospective, observational study conducted at an outpatient cancer centre in the
Republic of Korea from November 2013 to March 2016, we analysed women with breast
cancer who planned to be treated with neoadjuvant chemotherapy before surgery.
Candidate factors associated with CINV were assessed before neoadjuvant
chemotherapy using the Munich Chronotype Questionnaire, Pittsburgh Sleep Quality
Index and Hospital Anxiety and Depression Scale. CINV was assessed after
chemotherapy by using the Multinational Association of Supportive Care in Cancer
Antiemesis Tool. Of a total of 143 participants, 7 patients were lost to follow-up
and 2 patients were excluded due to changes in their treatment plan; thus, 134
patients were finally included in the analyses. Overall, 48.5% of the participants
experienced CINV, with delayed CINV prevalence (42.5%) being more common than acute
(39.6%). In the univariate analyses, overall CINV was significantly associated with
late chronotypes (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.37-8.87; p
= 0.009), a history of nausea/vomiting (OR, 2.19; 95% CI, 1.10-4.37; p = 0.026) and
anxiety (OR, 2.25; 95% CI, 1.05-4.81; p = 0.036). In the multivariate analyses,
late chronotypes (OR, 3.53; 95% CI, 1.27-9.79; p = 0.015) and a history of
nausea/vomiting (OR, 2.83; 95% CI, 1.31-6.13; p = 0.008) remained significantly
associated with CINV. In conclusion, in women with breast cancer undergoing
neoadjuvant chemotherapy before surgery, late chronotypes were found to have an
increased risk of CINV; these data suggest that clinicians need to assess and
consider the chronotype in the management of CINV.
The present study tested the supposition that greater levels of couple identity (or
we-ness) increase a woman's coping self-efficacy in relation to breast cancer,
which, in turn, predicts better psychosocial adjustment. Women (N = 112) in
committed relationships completed surveys assessing their levels of couple
identity, cancer coping self-efficacy, and aspects of their psychosocial adjustment
(specifically, depression, anxiety and functional well-being) during one of their
outpatient visits to the cancer centre. As predicted, the more women identified
with their relationships, the lower their levels of depression and anxiety were and
the greater their functional well-being was. This relationship was mediated by
coping self-efficacy: greater identification with one's relationship predicted
greater confidence in one's ability to cope, which, in turn, predicted better
adjustment. The role intimate relationships play in women's adjustment to breast
cancer, as well as directions for further research, are discussed.
Background: High levels of distress are expected shortly after the diagnosis breast
cancer. The Distress Thermometer (DT) is commonly used to screen for distress,
using a cutoff score of 4 or 5; however, this score might not be appropriate for
detecting distress in women with recently diagnosed breast cancer. Objectives: The
aims of this study were to establish the optimal DT cutoff score for detecting high
distress shortly after breast cancer diagnosis and to correlate this score with the
reported problems. Methods: We selected for this study Dutch women who completed
the DT and the Hospital Anxiety and Depression Scale within 1 month after breast
cancer diagnosis. Receiver operating characteristic analysis of DT scores was
performed, with the Hospital Anxiety and Depression Scale being used as the
criterion standard for the level of distress. The sensitivity, specificity,
positive predictive value, and negative predictive value of each DT score were
calculated. Results: In total, 181 women participated in the study. The optimal DT
cutoff score for detecting distress was 7 with a sensitivity of 0.73, specificity
of 0.84, positive predictive value of 69%, and negative predictive value of 87%.
Emotional problems were the most frequently reported concerns. Conclusion: We
consider a cutoff score of 7, shortly after breast cancer is diagnosed, optimal to
identify those women with high distress and therefore at risk of chronic distress.
Implications for Practice: The findings are clinically important because they can
enable healthcare professionals to direct their time and resources to those most in
need of their assistance.
Treatment strategies in oncology are nowadays largely based on the "target therapy
model", which allows to personalize the cure of each patient depending on
distinctive host and disease features. As a general concept "targeted drugs" are
effective only when the tumor exhibits the "target", which in breast cancer
pathology may correspond to the expression of estrogen receptors and/or of HER2.
These biomarkers are evaluated on breast cancer tissues by companion diagnostic
tests, however, evidence suggests that the first step in breast cancer predictive
pathology is still represented by morphology. For instance, histological types,
such as tubular and cribriform carcinomas, define patients who may not need any
treatments other than surgical excision. Neoadjuvant studies have shown that
patients affected by lobular carcinomas are not likely to have any beneficial
effects from chemotherapy. The second step in prediction is represented by
immunophenotyping. If the immunohistochemical evaluation of four markers (estrogen
and progesterone receptors, HER2 and Ki67) remains the best practice for breast
cancer predictive pathology, molecular pathology has certainly reshaped the way we
approach breast cancer diagnosis. The aim of this review is to discuss current
knowledge in predictive pathology for the management of breast cancer patients,
focusing on the benefits and drawbacks of traditional tools and of novel
improvements of molecular biology.
Although breast cancer is becoming more prevalent in Africa, few epidemiologic
studies have been undertaken and appropriate methodologic approaches remain
uncertain. We therefore conducted a population-based case-control study in Accra
and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer
and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy
(if given), blood, saliva and fecal samples were sought for study subjects.
Response rates, risk factor prevalences and odds ratios for established breast
cancer risk factors were calculated. A total of 54.5% of the recruited cases were
diagnosed with malignancies, 36.0% with benign conditions and 9.5% with
indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9%
in controls, with the vast majority of interviewed subjects providing saliva (97.9%
in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower
proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences
were unique as compared to women in other countries (e.g., less education, higher
parity), cancer risk factors resembled patterns identified elsewhere (elevated
risks associated with higher levels of education, familial histories of breast
cancer, low parity and larger body sizes). Subjects with benign conditions were
younger and exhibited higher socioeconomic profiles (e.g., higher education and
lower parity) than those with malignancies, suggesting selective referral
influences. While further defining breast cancer risk factors in Africa, this study
showed that successful population-based interdisciplinary studies of cancer in
Africa are possible but require close attention to diagnostic referral biases and
standardized and documented approaches for high-quality data collection, including
biospecimens. What's new? Breast cancer incidence is rising rapidly throughout
Africa, but few epidemiologic or molecular studies have been undertaken there. Best
practices for study design are yet to be established. In this study, the authors
discuss factors such as recruitment, data collection and biological sample
collection. They found that the prevalence of various risk factors differed but the
magnitudes of associations were similar to those observed elsewhere. These methods
and results indicate that successful studies in Africa are possible, despite many
challenges.
Background: Breast cancer is the most common type of cancer among females. Genetic
polymorphisms might have a role in carcinogenesis. The aim of this study was to
determine whether C to T base substitution within TaqI Vitamin D receptor (VDR)
gene (rs731236) in exon 9 was a risk factor among patients with breast cancer.
Methods: Peripheral blood was drawn from 122 Jordanian breast cancer patients and
100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months
(from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase
chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification
of serum 25-hydroxy Vitamin D (25[OH] D) level was determined by competitive
immunoassay Elecsys. Results: Genotypic frequencies for TaqI TT, Tt, and tt
genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for
control, respectively. Vitamin D serum level was significantly lower in the breast
cancer patients (8.1 +/- 0.3 ng/ml) compared to the control group (21.2 +/- 0.6
ng/ml; P = 0.001). This study showed an inverse association between 25(OH) D serum
level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI],
10.06-51.29). Conclusions: An inverse association was found between 25(OH)D serum
level and breast cancer risk. Statistical difference was also found between
different VDR TaqI genotypes and circulating levels of 25(OH) D among Jordanian
females with breast cancer.
Breast carcinogenesis is a multistep process, involving both genetic and epigenetic
modification process of genes, involved in diverse pathways ranging from DNA repair
to metabolic processes. This study was undertaken to assess the role of promoter
methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes,
in relation to its expression, polymorphism, and clinicopathological parameters.
Tissue samples were taken from breast cancer patients and paired with their normal
adjacent tissues. A total of 51 subjects were studied, in which the frequency of
promoter methylation in cancerous tissue was 37.25% as against 11% in the normal
tissues (p = 0.001). The hypermethylated status of the gene was significantly
associated with the loss of the protein expression (r = -0.449, p = 0.001, odds
ratio = 7.42, 95% confidence interval = 2.05-26.92). Furthermore, when compared
with the clinical parameters, the significant association was found between the
promoter hypermethylation and lymph node metastasis (p = 0.001), tumor stage (p =
0.039), tumor grade (p = 0.028), estrogen receptor status (p = 0.018), and
progesterone receptor status (p = 0.046). Our study is the first of its kind in
Kashmiri population, which indicates that GSTP1 shows aberrant methylation pattern
in the breast cancer with the consequent loss in the protein expression.
Furthermore, it also shows that the gene polymorphism (Ile105Val) at codon 105 is
not related to the promoter methylation and two are the independent events in
breast cancer development.
Keratins are fibrous proteins. Hair keratins constitute hard structures such as the
hair and nails, and cytokeratins have been used as markers of breast carcinoma.
However, the expression and function of full-size hair keratin genes have not been
previously demonstrated in breast cancer. We investigated the expression of the
hair keratin, KRT81, and its function in human breast cancer and normal mammary
epithelial cells. Western blotting showed full size 55-kDa KRT81 expression in the
human breast cancer cell lines, MCF7, SKBR3 and MDA-MB-231, normal human mammary
epithelial cells (HMEC), and non-neoplastic cells (MCF10A). Reverse transcription-
polymerase chain reaction revealed that the full size KRT81, including its 5'
region is expressed in breast cells. Immunohistochemical and immunofluorescence
analyses showed that KRT81 was located in the cytoplasm. To investigate the
function of KRT81, we knocked down KRT81 by siRNA in MCF10A cells. Microarray
analysis revealed that the expression of genes related to invasion such as matrix
metallopeptidase (MMP)9 was decreased. In KRT81-knockdown MDA-MB231 cells,
zymography revealed a decrease in MMP9 activity, while scratch and invasion assays
revealed that KRT81-knockdown decreased cell migration and invasion abilities. This
is the first study showing that full size KRT81 is expressed in normal breast
epithelial cells and breast cancer cells. Moreover, our results indicate that KRT81
contributes to the migration and invasion of breast cancer cells.
Breast cancer is a disease of unknown etiology; however, the major risk factors are
genetic alterations. Studies have demonstrated an association between insulinlike
growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced
apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two
polymorphic variants of the IGF-1 gene are highlighted in association with breast
cancer, rs6220 and rs7136446, although controversy exists as to this relationship.
The current study included 137 women (68 breast cancer cases and 69 controls
without breast cancer) who had 3 ml of peripheral blood drawn for the study of
genomic DNA extracted from leukocytes using the genotyping technique by real-time
polymerase chain reaction. The CC genotype (rs7136446) was present in 4 women
(5.9%) from the case group and in 2 (3.0%) women from the control group (p = 0.67),
while the GG genotype (rs6220) occurred in 8 (11.5%) women from the case group and
in 5 (7.2%) women from the control group (p = 0.75). No statistically significant
difference was observed between the CC genotype of variant rs7136446 in
premenopausal case and control women (p = 0.31), thus as there was also no
significant difference between case and control postmenopausal women (p = 1.00).
Concerning the GG genotype of rs6220, it occurred in 6 (14.2%) premenopausal case
and 4 (8%) control women (p = 0.71) and no difference was found in postmenopausal
women (p = 1.00). In the current study, IGF-1 gene polymorphism of SNP variants
rs6220 and rs7136446 had no statistically significant association with breast
cancer, both in premenopausal and postmenopausal women.
Breast cancer is the most commonly diagnosed cancer among women. Therapeutic
treatments for breast cancer generally include surgery, chemotherapy, radiotherapy,
endocrinotherapy and molecular targeted therapy. With the development of molecular
biology, immunology and pharmacogenomics, immunotherapy becomes a promising new
field in breast cancer therapies. In this review, we discussed recent progress in
breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and
immune checkpoint inhibitors. Several additional immunotherapy modalities in early
stages of development are also highlighted. It is believed that these new
immunotherapeutic strategies will ultimately change the current status of breast
cancer therapies.
Breast cancer is the most frequent cancer among women worldwide. Tumor immunology
suggests relationships between the immune system, chronic inflammation, and cancer.
The immune system may either prevent or promote carcinogenesis. Here, we evaluated
molecular signaling pathways common in inflammation and cancer and detected the
microRNAs which play pivotal roles in mediating these pathways. Using
bioinformatics assays, signaling pathways common in inflammation and cancer, and
microRNAs mediating these pathways were identified. MiR-590 was selected and cloned
into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines.
The expression level of microRNA and the candidate genes was evaluated by real-time
quantitative reverse transcription polymerase chain reaction, and the apoptosis
level in transfected cells was measured by Annexin V-7AAD assay. The cell migration
was tested by real-time quantitative reverse transcription polymerase chain
reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes
(i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While
miR-590 showed an over-expression, the genes were significantly down-regulated. A
significant increase was observed in apoptosis level in both cell lines and
MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as
a microRNA which triggers and down-regulates critical genes of signaling pathways
similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K,
MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast
cancer cell lines. Apparently, some microRNAs can be good candidates for novel
treatments of cancer. Although miR-590 showed good results in this study, further
studies are required to investigate the role of miR-590 in breast cancer therapy.
Studies have demonstrated low expression of miR-145 associated with cell
proliferation and migration in a wide variety of tumors. Here, we studied the
expression of miR-145 in relation to the occurrence and development of breast
cancer. Total RNA from breast cancer tissue and corresponding adjacent normal
tissue was extracted and used to detect miR-145 expression by quantitative real-
time polymerase chain reaction (qRT-PCR). We also transfected breast cancer cells
with hsa-miR-145 mimics, hsa-miR-145 inhibitor, mimics negative control (mimics NC)
or inhibitor negative control (inhibitor NC). Cell proliferation was analyzed by
colony formation assays and methyl thiazolyl tetrazolium assays. Cell proliferation
in breast cancer cells was decreased after overexpression of miR-145 and increased
following miR-145 suppression. Cell migration and invasion were assessed using
Transwell and wound healing assays, respectively, and were also decreased after
overexpression of miR-145 and increased after miR-145 suppression in breast cancer
cells. Finally, western blot assays showed that over expression of miR-145
inhibited expression of transforming growth factor-beta 1 (TGF-beta 1).
Collectively, these data suggest that miR-145 may inhibit TGF-beta 1 protein
expression which may in turn contribute to tumor formation.
We here report identification and characterization of Required for Cell
Differentiation I homolog (RQCD1) as a potential therapeutic target for breast
cancer. Gene-expression profiling analysis of breast cancer cells, semi-
quantitative RT-PCR, Northern blotting and Western blotting confirmed RQCD1 to be
frequently up-regulated in breast cancer specimens and breast cancer cell lines. On
the other hand, its expression was very weak or hardly detectable in normal human
tissues except testis, indicating this molecule to be a novel cancer-testis
antigen. Treatment of breast cancer cell lines with siRNA targeting RQCD1
drastically suppressed cell proliferation. Concordantly, introduction of exogenous
RQCD1 into HEK293 cells significantly enhanced cell growth, implying RQCD1 to have
an oncogenic activity. Co-immunoprecipitation experiments and immunocytochemical
staining revealed an interaction of RQCD1 protein with Grb10 interacting GYF
protein I (GIGYF1) and 2 (GIGYF2) proteins, involved in regulation of Akt
activation, in breast cancer cells. Interestingly, knockdown of either of RQCD1,
GIGYF1 or GIGYF2 resulted in significant reduction of the phosphorylation of Akt at
Ser 473 in breast cancer cell lines. Our findings suggest that RQCD1 is a potential
molecular target for treatment of breast cancer.
Background: Elevation of fatty acid synthase (FAS) in human cancers is often
associated with increased tumor aggression. The basic genetic mechanisms leading to
increased enzyme content in cancer cells were investigated using cell lines derived
from human metastatic breast carcinomas (T47D, Zr75 and SKBr3) and normal human
breast epithelium (184A1). Materials and Methods: Western analysis, Northern
blotting, [2-C-14]malonyl-CoA incorporation assays, nuclear run-off transcription
assays, mRNA decay assays, and poly(A) tail assays were used to measure and compare
transcription rates of the FAS gene among the four cell lines. Results: By Western
analysis, FAS levels in T47D were 2.6 times lower than ZR75 and SK-Br3, but 6.7
times greater than non-neoplastic 184A1 cells. FAS mRNA levels and specific
activity correlated with protein content. In contrast, relative rates of FAS gene
transcription were significantly higher in non-neoplastic 184A1 cells than T47D,
ZR75 and SKBr3. Stability of message was investigated to explain this discrepancy.
The half-life of FAS mRNA in 184A1 cells was 5.6 h, or 4-5-fold less than ZR75 and
SKBr3. Poly(A) tail assays showed that FAS mRNA species from 184A1 cells tended to
be longer than those of breast cancer cell lines (500-1500 nt versus 500-800 nt,
respectively). Conclusion: Breast cancer cell lines contained significantly more
FAS enzyme, message and activity than nonneoplastic 184A1 cells. Yet, 184A1 cells
exhibited higher rates of FAS gene activation. The discrepancy is explained by
faster decay of FAS message in 184A1 cells, suggesting that stabilization of FAS
mRNA plays a major role in overexpression of the protein in breast cancer.
Increased stability could not be explained simply by degree of polyadenylation.
Therefore, some other mechanism (s) must be responsible for conferring stability to
FAS RNA species in breast cancer cells.
Breast cancer (BC) is a disease with different clinical, histological and molecular
characteristics, frequently presenting mutated tumour-suppressing genes and
oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several
mutations in p53 inhibit its role as a transcriptional repressor of several
oncogenes. Topoisomerase 2 alpha (TOP2 alpha) is a gene target of p53, and it is
also a known target for anthracyclines. The aim of the present study, was to
analyse the genetic alterations of p53 and TOP2 alpha genes and their levels of
protein expression, as well as their association with survival in Mexican women
with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from
patients with BC. To identify point mutations and deletions in the p53 gene, the
Sanger sequencing method was carried out. Deletions or amplifications for TOP2
alpha gene were determined using quantitative polymerase chain reaction (qPCR). In
addition, the expression of the TOP2 alpha and p53 proteins was evaluated by
western blotting. Furthermore, p53 protein expression was analysed by proximity
ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-
negative breast cancer (TNBC); the average age at the time of diagnosis of these
patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III
(p=0.0089). No differences in point mutations or deletions in p53, and deletions or
amplifications as well as protein expression level of TOP2 alpha were observed
between patients with TNBC and non-TNBC patients. However, patients with TNBC
showed p53 protein overexpression as determined by PLA-qPCR and western blotting
(p<0.0001). Furthermore, we found an association between TOP2 alpha amplification
and over expression of its protein in patients with TNBC (p<0.0001). Concerning
p53, overexpression resulted in a lower survival in patients with BC.
Women with breast cancer frequently report distressing symptoms during and after
treatment that can significantly erode quality of life (QOL). Symptom burden among
women with breast cancer is of complex etiology and is likely influenced by
disease, treatment, and environmental factors as well as individual genetic
differences. The purpose of the present study was to examine the relationships
between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1
(NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-
methyltransferase (COMT) and patient symptom burden of QOL, pain, fatigue, anxiety,
depression, and sleep disturbance before, during, and after treatment for breast
cancer in a subset of participants (N = 51) in a randomized clinical trial of a
novel symptom-management modality for women with breast cancer undergoing
chemotherapy. Patients were recruited at the time of initial breast cancer
diagnosis and completed all survey measures at the time of recruitment, after the
initiation of treatment (surgery and/or chemotherapy), and then following treatment
conclusion. Multiple linear regression analyses revealed significant associations
between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom
burden. Two COMT variants were associated with the specific symptoms of anxiety and
QOL measures prior to the initiation of chemotherapy as well as pain interference
and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was
associated with both sleep disturbance and fatigue. These findings, while
exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to
relative risk for symptom burden during and shortly after the period of
chemotherapy in women with early stage breast cancer.
Breast cancer is the second most common cause of mortality in women; therefore, the
identification of novel putative markers is required to improve its diagnosis and
prognosis. Selenium is known to protect mammary epithelial cells from oxidative DNA
damage, and to inhibit the initiation phase of carcinogenesis by stimulating DNA
repair and apoptosis regulation. Consequently, the present study has focused
attention on the selenoprotein family and their involvement in breast cancer. The
present study performed a global analysis of the seleno-transcriptome expression in
human breast cancer MCF-7 and MDA-MB231 cell lines compared with healthy breast
MCF-10A cells using reverse transcription-quantitative polymerase chain reaction.
The present data revealed the presence of differently expressed genes in MCF-7 and
MDA-MB231 cells compared with MCF-10A cells: Four downregulated [glutathione
peroxidase (GPX) 1, GPX4, GPX5 and GPX7] and three upregulated (deiodinase
iodothyronine, type II, GPX2 and GPX3) genes. Additionally, interactomic
investigation were performed by the present study to evaluate the association
between the downregulated and upregulated genes, and to identify putative HUB
nodes, which represent the centers of association between the genes that are
capable of direct control over the gene networks. Network analysis revealed that
all differentially regulated genes, with the exception of selenoprotein T, are
implicated in the same network that presents three HUB nodes interconnected to the
selenoprotein mRNAs, including TP53, estrogen receptor 1 and catenin-beta 1
(CTNNB1). Overall, these data demonstrated for the first time, a profile of seleno-
mRNAs specific for human breast cells, indicating that these genes alter their
expression on the basis of the ER-positivity or negativity of breast cancer cells.
It has recently become apparent that it is possible to characterize productively
recombined, T-cell receptor (TcR) gene segments in tumor exome files, which
presumably include representations of the DNA of other cells in the
microenvironment. Similar characterizations have been done for TcR recombinations
in tumor specimen RNASeq files. While exome files have been used to characterize
immunoglobulin gene segment recombinations for tumors closely related to B-cells,
immunoglobulin recombinations have yet to be characterized for putative
microenvironment cells for solid tumors. Here we report a novel scripted algorithm
that detects productive and unproductive immunoglobulin recombinations in both B-
cell related tumor exome files and in solid tumor exome files, with the most
important result being the relatively high level B-cell infiltrate in breast
cancer. This analysis has the potential of streamlining and dramatically augmenting
the knowledge base regarding B-cell infiltrates into solid tumors; and leading to
antibody reagents directed against tumor antigens and tissue resident, infectious
pathogens.
Purpose This study was conducted to investigate the role of four polymorphic
variants of DNA methyltransferase genes as risk factors for radiation-induced
fibrosis in breast cancer patients. We also assessed their ability to improve
prediction accuracy when combined with mitochondrial haplogroup H, which we
previously found to be independently associated with a lower hazard of radiation-
induced fibrosis. Materials and Methods DNMT1 rs2228611, DNMT3A rs1550117, DNMT3A
rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain
reaction in 286 Italian breast cancer patients who received radiotherapy after
breast conserving surgery. Subcutaneous fibrosis was scored according to the Late
Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA)
scale. The discriminative accuracy of genetic models was assessed by the area under
the receiver operating characteristic curves (AUC). Results Kaplan-Meier curves
showed significant differences among DNMT1 rs2228611 genotypes in the cumulative
incidence of grade 2 subcutaneous fibrosis (log-rank test p-value= 0.018).
Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent
protective factor for moderate to severe radiation -induced fibrosis (GG vs. M;
hazard ratio, 0.26; 95% confidence interval [Cl], 0.10 to 0.71; p=0.009). Adding
DNMT1 rs2228611to haplogroup H increased the discrimination accuracy (AUC) of the
model from 0.595 (95% Cl, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710).
Conclusion DNMT1 rs2228611 may represent a determinant of radiation-induced
fibrosis in breast cancer patients with promise for clinical usefulness in genetic-
based predictive models.
Aim: Aim of the present study is to evaluate the risk of residual neoplastic foci,
in patients treated with breast conservative surgery, based on duct carcinoma in
situ (DCIS) grading. Materials and methods: The study is based on a retrospective
analysis of 419 resection specimens relative to 161 patients. All these patients
underwent surgical re-excision when the first specimen had shown one or more
margins involved by DCIS. Margins were oriented and the side of margin involved was
recorded. Clonal analysis, using the mitochondrial DNA (mtDNA) technique, was
obtained in selected cases. Results: Residual neoplastic foci were found in 145 out
of 419 (34.6%) re-excised specimens. Specifically, residual foci of DCIS grade 2
and 3 were found more frequently in the margin facing the nipple (33.3% and 51.6%,
respectively). On the contrary foci of DCIS grade 1 did not show any specific
distribution. Clonal mt DNA analysis evidenced that DCIS grade 3 foci present in
the re-excision specimens were genetically similar to the tumor removed in the
first specimen, while DCIS grade 1 foci were not clonally related each other.
Conclusions: The present data further confirm that DCIS grade 3 is characterized by
a circumscribed neoplastic process extending along the large ducts probably of a
single mammary lobe. On the contrary DCIS grade 1 is characterized by multiple
independent neoplastic foci,, dispersed through several lobes indicating a field
where multiple independent foci of cancer harbor. (C) 2016 Elsevier Ltd, BASO
similar to The Association for Cancer Surgery, and the European Society of Surgical
Oncology. All rights reserved.
The sialidase gene from Brevibacterium casei was cloned in pET28a and overexpressed
as a histidine-tagged protein in Escherichia coli BL21(DE3). The histidine-tagged
sialidase protein was purified and characterized from the crude cell extracts of
isopropyl-beta-D-thiogalactopyranoside-induced cells using Ni-NTA agarose
chromatography. SDS-PAGE using the purified sialidase indicated a single band at
116 kDa. This sialidase showed maximum activity at a pH of 5.5 and temperature of
37 degrees C. The kinetic parameters K-m and V-max for the artificial substrate 2'-
(4-methylumbelliferyl)-alpha-D-N-acetyl-neuraminic acid sodium salt hydrate were
1.69 x 10(-3) mM and 244 mmol.Min(-1)center dot mg(-1), respectively. The sialidase
may catalyze the hydrolysis of terminal sialic acids linked by the alpha-(2,3) and
alpha-(2,8) linkage of polysialogangliosides, but it does not act on
monosialotetrahexosylganglioside (GM1), which offers it a great potential for
commercially producing GM1 from polysialogangliosides. (C) 2016 International Union
of Biochemistry and Molecular Biology, Inc.
This paper presents a scheme to improve the line current distortion of power factor
corrector (PFC) topology at the zero crossing point using a predictive control
algorithm in both the continuous conduction mode (CCM) and discontinuous conduction
mode (DCM). The line current in single-phase PFC topology is distorted at the zero
crossing point of the input AC voltage because of the characteristic of the general
proportional integral (PI) current controller. This distortion degrades the line
current quality, such as the total harmonic distortion (THD) and the power factor
(PF). Given the optimal duty cycle calculated by estimating the next state current
in both the CCM and DCM, the proposed predictive control algorithm has a fast
dynamic response and accuracy unlike the conventional PI current control method.
These advantages of the proposed algorithm lower the line current distortion of PFC
topology. The proposed method is verified through PSIM simulations and experimental
results with 1.5 kW bridgeless PFC (BLPFC) topology.
The present paper summarizes the results of some numerical calculations carried out
on the basis of a recent wide experimental research. The calculations are performed
on axisymmetric specimens weakened by V notches consisting of a large bulk of
different shapes. The specimens are subjected to multiaxial fracture loading
(tension + torsion). Stress and strain fields in the whole specimens are evaluated
herein by using the finite element method (FEM). Special attention is paid to the
changing distribution of stresses induced by loading and notch shape. By taking
advantage of the numerical calculations carried out in the present investigation, a
new non-local fracture criterion for notched specimens under multiaxial loading is
proposed and successfully employed and compared with some data taken from the
recent literature. (C) 2017 Published by Elsevier Ltd.
AimsThe aim of this study was to investigate potential molecular mechanisms
associated with loss of BRM expression in poorly differentiated clear cell renal
cell carcinoma (ccRCC). Methods and resultsNineteen previously selected BRM-
negative RCC tissues were examined by DNA sequencing, fluorescence in-situ
hybridization (FISH) and methylation-specific polymerase chain reaction (PCR) of
the BRM gene. BRM mutation was identified in 78.9% (15 of 19) cases, chromosome 9
monosomy or BRM deletion in 43.8% (seven of 16) and BRM promoter region cytosine-
phosphate-guanine (CpG) methylation in 42.8% (six of 14). These results indicated
that 89.5% (17 of 19) of the cases harboured at least one type of BRM genetic
alteration, with two or more types of alteration in 47.4% (nine of 19). Such
alterations were found rarely in adjacent non-neoplastic tissues and low-grade
areas of composite tumours. ConclusionsBRM gene mutation, chromosome 9 monosomy or
BRM deletion and CpG methylation contribute collectively to the loss of BRM
expression in ccRCC. This work focusing on composite tumours indicated that BRM
abnormality occurred during tumour progression.
Multifunction RF systems which can operate with different RF functions like radar,
communication and electronic warfare offer a variety of benefits beyond the well-
known AESA (Active Electronically Steerable Antenna) features. To reach a
sufficient technology maturity to start product development a series of challenges
most stemming from the large required operation bandwidth have to be resolved.
Dual-polarised low-loss apertures with array grids designed for a grating lobe and
scan blindness free 60 conical Field of View (FoV) at the highest operational
frequency have to be considered. The active components of the AESA and especially
the T/R-M are required to be power efficient over the whole multifunction bandwidth
and they shall be miniaturised to fit the array grid. RF functions like high speed
datalink require linear high power amplification with low harmonics generation and
interference suppression in receive is essential in order to maintain performance.
Enablers for such broadband AESA are the GaN technology for T/R-M front-end
components and SiCe BiCMOS technology for core chip and digital control of the T/R-
M. The paper shows the state-of-the-art technology in Europe for multifunction RF
Systems.
Multifunction RF systems which can operate with different RF functions like radar,
communication and electronic warfare offer a variety of benefits beyond the well-
known AESA (Active Electronically Steerable Antenna) features. To reach a
sufficient technology maturity to start product development a series of challenges
most stemming from the large required operation bandwidth have to be resolved.
Dual-polarised low-loss apertures with array grids designed for a grating lobe and
scan blindness free 60 conical Field of View (FoV) at the highest operational
frequency have to be considered. The active components of the AESA and especially
the T/R-M are required to be power efficient over the whole multifunction bandwidth
and they shall be miniaturised to fit the array grid. RF functions like high speed
datalink require linear high power amplification with low harmonics generation and
interference suppression in receive is essential in order to maintain performance.
Enablers for such broadband AESA are the GaN technology for T/R-M front-end
components and SiGe BiCMOS technology for core chip and digital control of the T/R-
M. The paper shows the state-of-the-art technology in Europe for multifunction RF
Systems.
Ventilator-associated pneumonia (VAP) is the most common infection in critically
ill patients. Initial antibiotic therapy is often broad spectrum, which promotes
antibiotic resistance so new techniques are under investigation to obtain early
microbiological identification and quantification. This trial compares the
performance of a new real-time quantitative molecular-based method with
conventional culture in patients with suspected VAP. Patients with suspected VAP
who were ventilated for at least 48 h were eligible. An endotracheal aspirate (ETA)
and a bronchoalveolar lavage (BAL) were performed at each suspected VAP episode.
Both samples were analysed by conventional culture and molecular analysis. For the
latter, bacterial DNA was extracted from each sample and real-time PCR were run. In
all, 120 patients were finally included; 76% (91) were men; median age was 65
years, and clinical pulmonary infection score was >= 6 for 73.5% (86) of patients.
A total of 120 BAL and 103 ETA could be processed and culture results above the
agreed threshold were obtained for 75.0% (90/120) of BAL and 60.2% (62/103) of ETA.
The main isolated bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and
Haemophilus influenzae. Performancewas 89.2% (83.2% e93.6%) sensitivity and 97.1%
(96.1% e97.9%) specificity for BAL samples and 71.8% (61.0% e81.0%) sensitivity and
96.6% (95.4% e97.5%) specificity for ETA samples when the molecular biology method
was compared with conventional culture method (chosen as reference standard). This
new molecular method can provide reliable quantitative microbiological data and is
highly specific with good sensitivity for common pathogens involved in VAP. (C)
2016 European Society of Clinical Microbiology and Infectious Diseases. Published
by Elsevier Ltd. All rights reserved.
Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly
vascularized and innervated, and can be activated in adult humans. Brown adipocytes
are responsible for performing non-shivering thermogenesis, which is exclusively
mediated by uncoupling protein (UCP)-1 (a protein found in the inner mitochondrial
membrane), the hallmark of BAT, responsible for the uncoupling of the proton
leakage from the ATP production, therefore, generating heat (i.e. thermogenesis).
Besides UCP1, other compounds are essential not only to thermogenesis, but also to
the proliferation and differentiation of BAT, including peroxisome proliferator-
activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-
BF-1-RIZ1 homologous domain protein containing protein (PRDM)-16. The sympathetic
nervous system centrally regulates thermogenesis through norepinephrine, which acts
on the adrenergic receptors of BAT. This bound leads to the initialization of the
many pathways that may activate thermogenesis in acute and/or chronic ways. In
summary, this mini-review aims to demonstrate the latest advances in the knowledge
of BAT. (C) 2016 Elsevier Ltd. All rights reserved.
We quantitatively examined the transcript levels of ten fatty acid-binding protein
(FABP) isoforms in the brown adipose tissue (BAT) of rats kept at room temperature
and of rats exposed to the cold by Northern blotting using the synthesized RNA of
each isoform as an external standard. FABP3-5 were expressed in BAT of both rats
maintained at room temperature and those exposed to the cold. FABP4 was the most
abundantly expressed isoform, but its transcript level was not significantly
affected by cold exposure. FABP3 was slightly expressed in the BAT of rats
maintained at room temperature and its transcript level was elevated ten fold by
cold exposure. FABP5 was also elevated four fold by cold exposure but the amount of
its mRNA in BAT was negligible.
Brown spiders are venomous arthropods that use their venom for predation and
defense. In humans, bites of these animals provoke injuries including dermonecrosis
with gravitational spread of lesions, hematological abnormalities and impaired
renal function. The signs and symptoms observed following a brown spider bite are
called loxoscelism. Brown spider venom is a complex mixture of toxins enriched in
low molecular mass proteins (4-40 kDa). Characterization of the venom confirmed the
presence of three highly expressed protein classes: phospholipases D,
metalloproteases (astacins) and insecticidal peptides (knottins). Recently, toxins
with low levels of expression have also been found in Loxosceles venom, such as
serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like
toxins and histamine-releasing factors. The toxin belonging to the phospholipase-D
family (also known as the dermonecrotic toxin) is the most studied class of brown
spider toxins. This class of toxins single-handedly can induce inflammatory
response, dermonecrosis, hemolysis, thrombocytopenia and renal failure. The
functional role of the hyaluronidase toxin as a spreading factor in loxoscelism has
also been demonstrated. However, the biological characterization of other toxins
remains unclear and the mechanism by which Loxosceles toxins exert their noxious
effects is yet to be fully elucidated. The aim of this review is to provide an
insight into brown spider venom toxins and toxicology, including a description of
historical data already available in the literature. In this review article, the
identification processes of novel Loxosceles toxins by molecular biology and
proteomic approaches, their biological characterization and structural description
based on x-ray crystallography and putative biotechnological uses are described
along with the future perspectives in this field.
Brownian motion with adaptive drift has attracted much attention in prognostics
because its first hitting time is highly relevant to remaining useful life
prediction and it follows the inverse Gaussian distribution. Besides linear
degradation modeling, nonlinear-drifted Brownian motion has been developed to model
nonlinear degradation. Moreover, the first hitting time distribution of the
nonlinear-drifted Brownian motion has been approximated by time-space
transformation. In the previous studies, the drift coefficient is the only hidden
state used in state space modeling of the nonlinear-drifted Brownian motion.
Besides the drift coefficient, parameters of a nonlinear function used in the
nonlinear-drifted Brownian motion should be treated as additional hidden states of
state space modeling to make the nonlinear-drifted Brownian motion more flexible.
In this paper, a prognostic method based on nonlinear-drifted Brownian motion with
multiple hidden states is proposed and then it is applied to predict remaining
useful life of rechargeable batteries. 26 sets of rechargeable battery degradation
samples are analyzed to validate the effectiveness of the proposed prognostic
method. Moreover, some comparisons with a standard particle filter based prognostic
method, a spherical cubature particle filter based prognostic method and two
classic Bayesian prognostic methods are conducted to highlight the superiority of
the proposed prognostic method. Results show that the proposed prognostic method
has lower average prediction errors than the particle filter based prognostic
methods and the classic Bayesian prognostic methods for battery remaining useful
life prediction. (C) 2017 Elsevier Ltd. All rights reserved.
The cDNA encoding brain protein 44-like (Brp44l) was identified from the brain and
spinal cord cDNA library of Gekko japonicus. It contains a 324 bp open reading
frame corresponding to a deduced protein of 107 amino acids. The molecular weight
of the BRP44L protein is 12.2664 kDa and its theoretical pI is 9.67. At amino acid
level, the BRP44L from gecko shares 85-89% similarity with those from other
species. Northern blotting showed that Brp44l was ubiquitously expressed in the
major organs of Gekko japonicus including brain, spinal cord, heart, lung, liver,
and kidney, suggesting a fundamental biological role of this gene. In situ
hybridization (ISH) revealed that positive hybridization signals were present in
gray matter of spinal cord. The change of Brp44l expression in spinal cord after
tail amputation was examined by reverse transcription polymerase chain reaction
(RT-PCR). The expression level of this gene increased in the spinal cord after tail
amputation, and reached the highest value at 1 week after tail amputation, which
indicated that the expression level of Brp44l might be associated with the process
of spinal cord injury and regeneration.
We evaluated the capacity of the Brucella sp. eryC gene as a diagnostic marker for
brucellosis by quantitative real-time PCR. eryC gene encodes the enzyme d-
erythrulose-1-phosphate dehydrogenase that plays an important role in the
erythritol metabolism and is related with the Brucella survival in the
intracellular environment of the macrophage. The assay includes an internal
amplification control (IAC) in order to avoid false negative results. It was 100%
specific, with an analytical sensitivity of 1 genome equivalent (GE) in 43% of the
reactions, being the quantification highly linear (R (2) >0.9953) and efficient
(PCR efficiency >0.8820) over a 6-log dynamic range, down to 10 GE. Finally, the
applicability of this assay was evaluated with artificially contaminated biological
matrices implicated in the transmission of this bacterium such as sheep raw milk
and pig blood. The eryC-IAC real-time PCR assay allowed detection of as few as ten
Brucella cells per 25 ml of sheep raw milk or per 1 ml of pig blood. In conclusion,
we present an alternative for the detection of Brucella genus and therefore
facilitate the establishment of preventive and prophylactic measures in food and
farm environments.
The genus Brucella causes significant economic losses due to infertility, abortion,
stillbirth or weak calves, and neonatal mortality in livestock. Brucellosis is
still a zoonosis of public health importance worldwide. The study was aimed to
optimize and evaluate PCR assays used for the diagnosis of Brucella infections. For
this aim, several primers and PCR protocols were performed and compared with
Brucella cultures and biological material inoculated with Brucella. In PCR assays,
genus- or species-specific oligonucleotide primers derived from 16S rRNA sequences
(F4/R2, Ba148/928, IS711, BruP6-P7) and OMPs (JPF/JPR, 31ter/sd) of Brucella were
used. All primers except for BruP6-P7 detected the DNA from reference Brucella
strains and field isolates. In spiked blood, milk, and semen samples, F4-R2 primer-
oriented PCR assays detected minimal numbers of Brucella. In spiked serum and fetal
stomach content, Ba148/928 primer-oriented PCR assays detected minimal numbers of
Brucella. Field samples collected from sheep and cattle were examined by
bacteriological methods and optimized PCR assays. Overall, sensitivity of PCR
assays was found superior to conventional bacteriological isolation. Brucella DNA
was detected in 35.1, 1.1, 24.8, 5.0, and 8.0% of aborted fetus, blood, milk,
semen, and serum samples by PCR assays, respectively. In conclusion, PCR assay in
optimized conditions was found to be valuable in sensitive and specific detection
of Brucella infections of animals.
Careful examination of the skin and soft tissues is a routine part of the forensic
autopsy to identify and characterise traumatic lesions. Three cases are reported
where benign vascular lesions presented as bruises. In case 1, a 44-year-old man
with a history of epilepsy was found dead on the floor. Dissection of the neck
revealed a haemorrhagic area 15mmx1.5mm, deep to the left thyrohyoid muscle. In
case 2, an 87-year-old man was found dead with a plastic bag over his head attached
to an opened cylinder of nitrogen gas. On the mucosal surface of his upper lip,
there was an apparent 5mm blue/purple bruise. In case 3, examination of the back of
a 16-month-old girl revealed an apparent 15mm bruise. Histological examination of
all three lesions revealed benign vascular lesions. In the absence of microscopy,
these lesions would have been considered traumatic in origin, raising the
possibility of inflicted trauma.
Bruxism (BRX) is a condition of great interest for researchers and clinicians in
dental and medical areas. BRX has two circadian manifestations; it can occur during
sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, WB). However, it
can be suffered together. Recent investigations suggest that central nervous system
neurotransmitters and their genes could be involved in the genesis of BRX.
Serotonin is responsible for the circadian rhythm, maintaining arousal, regulating
stress response, muscle tone and breathing. Thus, serotonin could be associated
with BRX pathogenesis. The aim of this work was to evaluate the frequency of
genetic polymorphisms in the genes HTR1A (rs6295), HTR2A (rs1923884, rs4941573,
rs6313, rs2770304), HTR2C (rs17260565) and SLC6A4 (rs63749047) in subjects
undergoing BRX treatment. Patients included were classified according to their
diagnosis in awake bruxism (61 patients), sleep bruxism (26 patients) and both (43
patients). The control group included 59 healthy patients with no signs of BRX.
Data showed significant differences in allelic frequencies for the HTR2A rs2770304
polymorphism, where the C allele was associated with increased risk of SB (odds
ratio = 213, 95% confidence interval: 108-421, P = 003). Our results suggest that
polymorphisms in serotonergic pathways are involved in sleep bruxism. Further
research is needed to clarify and increase the current understanding of BRX
physiopathology.
Background: Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in
traditional medicine of India and of other countries for curing various infections,
bowel diseases, healing wounds and other ailments. However, its anticancer
properties are poorly defined. In view of broad spectrum therapeutic potential of
B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus
(HPV) activities in its leaf extracts and tried to isolate its active principle.
Methods: A chloroform extract derived from a bulk of botanically well-characterized
pulverized B. pinnata leaves was separated using column chromatography with step-
gradient of petroleum ether and ethyl acetate. Fractions were characterized for
phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the
fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility
Shift Assay, Northern blotting and assay of apoptosis related proteins by
immunoblotting in human cervical cancer cells. Results: Results showed presence of
growth inhibitory activity in the crude leaf extracts with IC50 at 552 mu g/ml
which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50: 50) and showed
IC50 at 91 mu g/ml. Investigations of anti-viral activity of the extract and its
fraction revealed a specific anti-HPV activity on cervical cancer cells as
evidenced by downregulation of constitutively active AP1 specific DNA binding
activity and suppression of oncogenic c-Fos and c-Jun expression which was
accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth,
fraction F4 strongly induced apoptosis as evidenced by an increased expression of
the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2,
and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of
fraction F4 by HPTLC and NMR indicated presence of activity that resembled
Bryophyllin A. Conclusions: Our study therefore demonstrates presence of anticancer
and anti-HPV an activity in B. pinnata leaves that can be further exploited as a
potential anticancer, anti-HPV therapeutic for treatment of HPV infection and
cervical cancer.
The eco-toxicological effects of Bacillus thuringiensis (Bt) maize on earthworm
life-history traits were widely studied and the results were controversial, while
their effects on earthworm bacterial community have been rarely studied. Here,
effects of two hybrids of Bt maize [5422Bt1 (event Bt11) and 5422CBCL (MON810)]
straw return on Eisenia fetida bacterial community were investigated by the
terminal restriction fragment length polymorphism (T-RFLP) and polymerase chain
reaction-denaturing gradient gel electrophoresis (PCR-DGGE) combing with DNA
sequencing, compared to near-isogenic non-Bt maize (5422). Bt maize straw return
had significant effects on soil nutrients, especially for available nitrogen (N).
The significant differences were shown in soil bacterial community between Bt and
non-Bt maize treatments on the 75th and 90th d, which was closely correlated with
soil available N, P and K rather than CrylAb protein. There was no statistically
significant difference in the bacterial community of earthworm gut contents between
Bt and non-Bt maize treatments. The significant differences in the bacterial
community of earthworm casts were found among three maize varieties treatments,
which were closely correlated with CrylAb protein and N levels. The differentiated
bacterial species in earthworm casts mainly belonged to Proteobacteria, including
Brevundimonas, Caulobacter, Pseudomonas, Stenotrophomonas, Methylobacterium,
Asticcacaulis and Achromobacter etc., which were associated with the
mineralization, metabolic process and degradation of plants residues. Therefore, Bt
maize straw return caused changes in the bacterial community of E. fetida casts,
which was possibly caused by the direct (CrylAb protein) and non-expected effects
(N levels) of Bt maize straw. (C) 2017 Elsevier Ltd. All rights reserved.
In digitally controlled circuits for power electronic circuits, sampling data are
important because the digital control circuit is operated on the basis of these
data. If the sampled values have been affected by switching noise from the power
circuit, the control stability of the circuit would be disturbed. This paper
proposes a noiseless sampling method that can sample a value without being affected
by the switching noise. The synchronous sampling method may be affected by the
switching noise depending on the duty ratio of the circuit. The noiseless sampling
method does not obtain data immediately after turn-on and turn-off switching. The
control circuit can avoid the switching noise by using noiseless sampling, which
leads to a disturbance in the control circuit and enhances the robustness of the
circuit when applying the multisampling method. Experimental results are presented
to verify that the current control of the proposed sampling method is not disturbed
by the switching noise even in the absence of a noise filter.
This paper presents the design of a digital control strategy for a dc-dc type Buck
converter used as an efficient lead acid battery charger in isolated electric,
photovoltaic systems. The strategy is designed to be implemented in a digital
signal processor (DSP). The control acts depending on the state of charge of the
batteries by regulating the drive duty cycle with the proper combination of
incremental conductance MPPT technique and precise control of the battery current
according to three charging stages, providing a joint solution which on one hand
maximizes the production of solar energy available in the PV array, and on the
other ensures a long battery lifetime, both aspects, which are generally
investigated independently in technical literature, are treated simultaneously in
our approach. The work explains in detail the converter modeling, the project of
the compensator, as well as the development of MPPT used. Validation simulations
are done via Matlab and experimental results from a prototype low power TMS320F2812
using a DSP from Texas Instruments, are provided and discussed, which show
satisfactory performance of the proposed control system. (C) 2016 Elsevier Ltd. All
rights reserved.
Implantable devices like artificial cardiac pacemakers are generally used to
control irregular pulses of heart. For 10-year usage, high accuracy supply voltage
is essential with the unavoidable aging of the power system to achieve near-natural
beat rhythm. A Self-Calibration DC-DC Buck converter (SC-Buck) is proposed to
achieve high output voltage accuracy by eliminating offset caused by mismatch of
process, voltage and temperature (PVT). Furthermore, the discontinuity which
affects transient performance in conventional offset cancellation is also overcome.
Large area occupation, which is required to decrease mismatch in conventional
operational amplifier, can be largely decreased according to Monte Carlo analysis.
Without trimming process, the proposed SC-Buck technique achieves high accuracy for
long-term usage (years) and low cost. The test chip fabricated in UMC 28nm CMOS
process proves the output voltage accuracy of 97% since the mismatch of error
amplifier can be suppressed from 122% to 1%.
A new hysteresis window method is proposed as a solution for avoiding the
operational dead zone that exists at the transition between buck and boost
operating modes in all noninverting buck-boost converters. In addition, this method
also eliminates the discontinuities in the converter's steady-state output voltage
transfer characteristic, which is a function of the duty cycle. The converter's
output voltage function is surjective and, therefore, smooth mode transitions are
achieved. The negative effects of operating within the dead zone are shown by the
presence of subharmonics in the output voltage, increased output voltage ripple,
poor regulation, and the instability of the converter during the transition between
buck and boost operating modes. The dead-zone avoidance technique proposed in this
paper eliminates all these issues while at the same time ensures highly efficient
operation of the converter. An additional advantage of the technique is its
simplicity, which allows for implementation into low-cost digital signal
controllers, as well as into analog control circuits. The advantageous features of
the proposed approach were evaluated on the basis of comparisons with three other
dead-zone avoidance approaches and the initial case, which does not utilize any
dead-zone avoidance technique. All the experiments were carried out on a purpose-
built prototype of a noninverting buck-boost converter with magnetically coupled
inductors.
To explore the effects of bufalin on inhibiting proliferation, up-regulating
methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human
erythroid leukemic (HEL) cells. The HEL cells were treated with bufalin at various
concentrations to observe cellular morphology, proliferation assay and cell cycle.
The mRNA and protein expression levels of WT1 were detected by reverse
transcription polymerase chain reaction (RT-PCR), Western blot and
immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA
methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR,
and Western blot respectively. The bufalin was effective to inhibit proliferation
of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%+/-
2.1% to 87.2%+/- 5.4% with an half maximal inhibit concentration (IC50) of 0.046 mu
mol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The
proliferation index of cell cycle decreased from 76.4%+/- 1.9% to 49.7%+/- 1.3%.
The expression levels of WT1 mRNA and its protein reduced gradually with increasing
doses of bufalin, meanwhile, the methylation status of WT1 gene changed from
unmethylated into partially or totally methylated. While, the expression levels of
DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-
dependent manner. Bufalin can not only significantly inhibit the proliferation of
HEL cells and arrest cell cycle at G(0)/G(1) phase, but also induce cellular
apoptosis and down-regulate the expression level of WT1. Our results provide the
evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1
methylation status which is related to the up-regulation of DNMT3a and DNMT3b
proteins in erythroid leukemic HEL cells.
Information security and customers' privacy in smart grid are significant concerns.
Existing security and privacy preserving schemes consider that the consumption
reports for electricity consumption aggregation and billing purposes are sent
periodically. These periodic messages increase the computation and communication
burden on restricted-capabilities smart meters. In this paper, we propose a
lightweight security and privacy preserving scheme that is based on forecasting the
electricity demand for a cluster of houses in the same residential area; it limits
the cluster's connection with electricity utility only when the cluster needs to
adjust its total demand. The scheme efficiently satisfies the security and privacy
requirements in customer-side networks, i.e., communication between customers and
power utility. At the same time, it significantly reduces the communication and
computation overhead. Moreover, the proposed scheme utilizes NTRU cryptosystem to
further reduce the computation complexity.
Building-integrated photovoltaic (BIPV) windows provide the benefits of generating
electricity, reducing building cooling and heating energy consumption, and
efficiently utilizing daylight simultaneously. In this paper, the overall energy
performance of a PV double skin facade (PV-DSF) and a PV insulating glass unit (PV-
IGU) is studied through comparative experiments on a test rig in Hong Kong. The PV-
DSF means ventilated PV-DSF by default, if not special mentioned. It is found that
the average solar heat gain coefficients (SHGCs) of the PV-DSF and the PV-IGU are
0.152 and 0.238, while the U-values are 2.535 W/m(2) K and 2.281 W/m(2) K. The
results indicate that the PV-DSF has better performance than PV-IGU in reducing
solar heat gains, while it has worse performance regarding thermal insulation. With
a lower PV module temperature, the energy conversion efficiency of PV-DSF is 1.8%
better than PV-IGU. Simulation models for the PV-DSF and the PV-IGU are developed
and validated against experimental data. Using the validated models, the overall
energy performances of PV-DSF and PV-IGU in five different climates of China are
investigated. The results show that the average energy saving potential of the PV-
DSF and the PV-IGU are 28.4% and 30%, respectively, compared to the commonly used
insulating glass window in five different climates. On average, the performance of
PV-IGU was 2% better performance than the ventilated PV-DSF in the five
representative cities. However, if an appropriate ventilation control scheme was
adopted, PV-DSF can have a much better performance than the PV-IGU. The models
developed in this study can be used for selecting suitable PV windows in the design
process, and the results achieved can be used as a guideline for utilizing PV
windows in different climates. (C) 2017 Elsevier Ltd. All rights reserved.
Understanding the energy demand of cities is a challenge especially in countries
such as Brazil where the lack of building energy consumption benchmarks makes it
hard to decide upon interventions in the building stock, as neither the existing
nor the attainable energy performance are known. Aiming to overcome these
difficulties this study develops a framework to estimate the Energy Use Intensity
(EUI) baseline of an existing building stock category based on the investigation of
land use regulations, a land tax database and field surveys. These offer a starting
point to estimate current energy consumption and promising interventions without
having to study specific buildings in depth. A case study of the high-rise
commercial building stock took place in the city of Belo Horizonte, Brazil. Three
representative typologies were identified. For each of these, archetype energy
models were created in order to assess EUI. The analysis of the EUI baselines
highlights differences between archetypes, explaining the impact of technical
choices on the overall electricity consumption and indicating a growing tendency of
energy consumption for forthcoming buildings. The archetype analysis also provides
knowledge to identify the most promising energy savings potential and thus to
support further energy policies in the city. (C) 2017 Elsevier B.V. All rights
reserved.
This study provides understanding of the influence of outside temperature on
intuitional buildings in an urban landscape. We derive heating and cooling degree
days for each of the buildings by identifying an appropriate choice of balance
point temperatures and perform multiple linear regression seasonally to
characterize the temperature-electricity use relations. Our study reveals
considerable differences in temperature-electricity relationships based on building
use and characteristics. In addition to outside temperature, the weekday effect has
large influences on electricity consumption of buildings. Summer months have
greater influence of outside temperature on electricity consumption followed by
transition months and winter as an increase in one cooling degree day (CDD)
increases daily electricity consumption by 0.124 kW/m2 whereas during winter, one
heating degree day (HDD) increases daily electricity consumption by 0.025 kW/m2 and
by 0.099 kW/m2 during transition months. We apply two kinds of models to project
electricity demand for projected temperature profiles in 2030. Both cases strongly
suggest higher electricity demand not just in summer months but also during
transition periods in spring and fall. Overall, electricity demand increases by
0.95% under a low emission scenario (RCP 4.5) and 2.03% under a high emission
scenario (RCP 8.5), which is likely to put immense pressure on the United States
electric grid system and an overall increase in the energy cost by 2030. (C) 2017
Elsevier B.V. All rights reserved.
This study aims to conduct the nonlinearity analysis of the shading effect on the
technical-economic performance of the building-integrated photovoltaic blind
(BIPB), which is designed as a preliminary study to evaluate the feasibility of the
BIPB before its implementation. First, in terms of the technical performance of the
BIPB, the shading effect due to the blind's slat in the BIPB can have a nonlinear
effect on the amount of electricity generation per unit area (AEGunit) from the
BIPB. Particularly, as the width of the PV panel increases, the AEG(unit) from the
BIPB tends to decrease. Second, in terms of the economic performance of the BIPB,
the feasibility of the BIPB depends on the type of investment values. Specifically,
as' the width of the PV panel increases, the NPV25 (net present value at year 25)
tends to increase; however, the SIR25 (saving-to-investment ratio at year 25) tends
to decrease. That is, while the NPV25 is determined to be highest at US$82,869 when
the width of the PV panel is 50 mm, the SIR25 is determined to be highest at 2.90
times when the width of the PV panel is 10 mm. The main findings of this study can
be used to clearly define the design specifications of the BIPB before its
implementation, which ensure to meet the client expectations on various objectives,
such as technical performance (e.g., the AEG(unit) from the BIPB) and economic
performance (e.g., NPV25 and SIR25). (C) 2016 Elsevier Ltd. All rights reserved.
Electricity generators of varying capacities are popularly utilized in Nigeria as
alternative source of power owing to the unreliability of electricity supply
through the national grid. This study evaluated the impact of emissions from
generating sets on air quality and human health in selected areas of Abeokuta city,
Nigeria. The levels of particulates (PM1, PM3), carbon monoxide, carbon dioxide,
sulphur oxides, nitrogen oxides, nitrogen dioxide, hydrogen sulphide and methane
were monitored using portable samplers. Copies of questionnaire were administered
to generator operators and nearby residents so as to collect additional
information. The capacities of sampled generators ranged from 1 to 25 kVA. The
range of mean concentrations of PM1 (4.7-219.2 mu g/m(3)), PM3 (7.8-251.6 mu
g/m(3)), carbon dioxide (4.5-10.9%), methane (0.0-1.2 ppm), carbon monoxide (141.1-
4167.0 ppm), NOx (4.0-85.7 ppm), methane (2.3-31.0 ppm), sulphur oxides (3.5-65.6
ppm) and hydrogen sulphide (0.0-0.7 ppm) was highest at generator sites. The
distance of sample sites to generator locations accounted for 14-66% variation of
pollutants levels. Ailments frequently suffered by the exposed residents included
nasal congestion (66%), cough (33%), headache (24%) and fever (12%). A national
policy on appropriate use of electricity generator is urgently needed in Nigeria.
Improvement in noise performance and transconductance using positive feedback
approach in bulk driven operational amplifier is proposed in this paper.
Downscaling of CMOS technology has compelled the supply voltage to reduce, which in
turn demands the reduction in threshold voltage. To overcome the barrier of
threshold, bulk driven technique is a good non-conventional approach because it
require no modification in the existing structure of MOSFET. The limitation with
bulk driven approach is that the transconductance of operational amplifier get
reduced almost three to four times. Thanks to loop of positive feedback. The
resulting transconductance is boosted to a higher value; thus, increasing the
voltage gain and decreasing the input referred noise. So, concept of positive
feedback is used in the design of low voltage (LV) low Power (LP) building blocks
of operational amplifier using standard CMOS technology. Though amplifier is
designed for power supply of 1V, it is also capable to operate at supply of less
than 1V. The simulation is carried out using Mentorgraphics tools of 180 nm
technology.
A simple realization of a 0.5V bulk-driven voltage follower/direct current (DC)
level shifter designed in a 0.18 mu m CMOS technology is presented in the paper.
The circuit is characterized by large input and output voltage swings and a DC
voltage gain close to unity. The DC voltage shift between input and output
terminals can be regulated in a certain interval around zero, by means of biasing
current sinks. An application of the proposed voltage follower circuit for
realization of a low-voltage class AB output stage has also been described in the
paper. Finally, the operational amplifier exploiting the proposed output stage has
been presented and evaluated in detail. Copyright (c) 2014 John Wiley & Sons, Ltd.
The effective transconductance (G(m)) of a bulk-driven operational amplifier opamp)
can significantly vary with the input common-mode voltage. This variation of G(m)
complicates frequency compensation and creates harmonic distortion. Thus, this
brief presents a G(m)-stabilizing technique to reduce the variation of G(m) across
the input common-mode range (ICMR). The idea is to use a variable positive feedback
structure to adaptively control G(m) to the input common-mode voltage. A low-
voltage bulk-driven opamp with the proposed G(m)-stabilizing technique has been
implemented in a 0.18-mu m n-well CMOS process. The opamp consumes 261 mu W from a
900-mV supply voltage. The variation of G(m) is reduced from 132% to 25% across the
rail-to-rail ICMR. The measured dc gain is 76.8 dB and the unity-gain bandwidth is
7.11 MHz when the opamp is loaded with 17 pF parallel to 1 M Omega.
A new solution for an ultra-low-voltage, low-power, bulk-driven operational
amplifier is presented in the paper. The amplifier is based on a new input stage,
exploiting the concept of partial positive feedback. As compared with prior work,
the proposed input stage offers improvement of all basic performance metrics,
including such important parameters as input-referred noise and offset voltage. In
order to improve the DC voltage gain of the overall op-amp, a novel solution for an
ultra-low-voltage, high-input-resistance common-mode amplifier has also been
proposed. Simulated performance of the overall operational amplifier for a 50 nm
CMOS process and supply voltage of 0.4 V shows power dissipation of 24 W, the open-
loop voltage gain of 60dB, and the gain-bandwidth product of 2.18 MHz for 20 pF
load capacitance.
This paper presents a 0.25-V supplied bulk-driven symmetrical OTA implemented in
130-nm CMOS process. By operating in weak inversion, and using a distributed layout
approach, the OTA can benefit from the voltage reduction and high linearity enabled
by halo-implanted transistors. The proposed circuit consumes only 10-nW, features a
low transconductance of 22-nS, and a total harmonic distortion of 0.53 % for a 100-
mV(pp) input voltage, thus making it suitable for low-frequency and low-power -C
applications.
A design solution for bulk-driven tunable transconductor capable of working under
extremely low supply/consumption with rail-to-rail input common-mode range is
presented in this work. The proposed transconductor topology consists of six bulk-
driven CMOS inverters, and it uses a very simple biasing circuit for the
transconductance tuning. The design robustness was verified for 0.5 and 0.25 V
power supplies offering the advantages of the current-controlled input
transconductance. For 0.5 V power supply, the proposed transconductor has 0.075-
10.2 transconductance tuning range, input-referred intercept point IP3 = 1.81 V,
and 4.62 MHz bandwidth for 3 current consumption. The design robustness of the
tunable transconductor was verified by means of computer simulation using triple-
well 0.18 CMOS process.
In this paper by using Gm-C compensation technique, an ultra-low-power two-stage
operational transconductance amplifier (OTA) with full rail-to-rail input/output
swing is presented. The proposed configuration consists of composite transistors,
improved bulk-driven folded cascode (FC) structure, feed-forward compensation path
and high-speed current mirrors. In comparison with the typical FC, the proposed
input stage structure has the benefit of transconductance enhancement with the same
power consumption without adversely affecting the noise and offset performance. The
presented OTA is simulated in 0.18 mu m CMOS technology and the simulation results
confirm the theoretical analyses. The proposed amplifier exhibits a DC gain
enhancement of 9.5 dB as well as 100 % improvement in gain-bandwidth compared to
the conventional FC input stage structure. Finally, the amplifier consumes 400 nW @
0.6 V supply voltage which makes it suitable for ultra-low-power applications.
The characterization and quantitative analyses of the key transcription factors for
spermiogenesis are necessary in the identification of causal factors for the
production of the seemingly normal sperm with dysfunctions in Japanese Black bulls
and further elucidation of whole aspect of molecular mechanisms for spermiogenesis
in livestock. The objective of this study was to obtain the information regarding
the characterization and individual changes of an activator cAMP-responsive element
modulator (CREM), which is necessary to the normal progress of spermiogenesis and
is required for the transcriptional activity of genes coding essential factors for
the sperm fertilization ability in rodents, using testes from 21 Japanese Black
bulls with the ability to produce sperm indicating the normal motility and
morphology. The bull CREM Tay (one of activator variants) was detected in testes
more strongly than livers by reverse transcription-polymerase chain reaction and
Northern blotting. This variant was localized in the nuclei of spermatids as shown
by indirect immunofluorescence with the homemade mouse antiserum. The motility and
morphology of the cauda epididymal sperm from 16 Japanese Black bulls were examined
before the quantitative analyses of testicular activator CREM to confirm the
ability to produce sperm with normal motility and morphology in these males. The
percentages of the motile sperm, those of the sperm with the normal acrosomes, and
those of morphologically normal sperm were 60.0% to 90.0%, 88.0% to 100%, and 83.0%
to 97.9%, respectively. The quantitative analyses with real-time polymerase chain
reaction using the testicular RNA from the same bulls revealed that the relative
expression levels of activator CREM variants in testes varied significantly among
these bulls in the range from 0.56 to 1.64 (P < 0.05). These results are consistent
with the suggestions that CREM Tay are involved in the spermiogenesis in the testes
of Japanese Black bulls and that the expression levels of the activator CREM
variant mRNAs in the testes are varied significantly among individual bulls that
have the ability to produce sperm with the normal motility and morphology. (c) 2014
Elsevier Inc. All rights reserved.
This retrospective investigation examined the association among childhood bullying
victimization, multiple forms of victimization, and psychological functioning in a
college sample. Four hundred-and-eighty-two undergraduate students participated in
the study (M = 19.98 years, SD = 1.82). The sample included 65 % women. For
race/ethnicity, 66.4 % were European-American (N = 320), 16.8 % African-American (N
= 81). For grade level, 21.6 % were freshmen (N = 104), followed by 38.2 %
sophomores (N = 184), 16.2 % juniors (N = 78), and 23.4 % seniors (N = 113).
Participants completed a survey packet of measures assessing childhood bullying
victimization experiences and current levels of psychological functioning. Findings
indicated that bullying victimization significantly predicted greater levels of
depression, anxiety, and post-traumatic stress (PTS) after controlling for other
childhood victimization experiences. PTS symptoms were predicted by exposure to
community violence and child abuse with bullying victimization was found to be the
strongest predictor. College-level practitioners need to assess for a wide range of
childhood victimization experiences, including bullying victimization.
BACKGROUND: Generic health status quality of life (QoL) instruments have been used
in patients with common variable immune deficiency (CVID). However, by their
nature, these tools may over-or underestimate the impact of diseases on an
individual's QoL. OBJECTIVE: The objective of this study was to develop and
validate a questionnaire to measure specific-health-related QoL for adults with
CVID (CVID_QoL). METHODS: The 32-item content of the CVID_QoL questionnaire was
developed using focus groups and individual patient interviews. Validation studies
included 118 adults with CVID who completed Short Form-36, Saint George Respiratory
Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a
single session. Principal component and factor analysis solutions identified 3
scores to be similar in number and content for each solution. Validation of 3
factor scores was performed by construct validity. Reproducibility, reliability,
convergent validity, and discriminant validity were evaluated. Matrices consisting
of correlations between the 32 items in the CVID_QOL were calculated. RESULTS:
Factor analysis identified 3 dimensions: emotional functioning (EF), relational
functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had
good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n
= 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for
RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity
correlating with conceptually similar dimensions of other study scales. Acute and
relapsing infections had a significant impact on EF and RF. CONCLUSIONS: This study
provides evidence of the reliability and construct validity of the CVID_QoL to
identify QoL issues in patients with CVID that may not be addressed by generic
instruments. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the
American Academy of Allergy, Asthma & Immunology. This is an open access article
under the CC BY-NC- ND license.
Since communal violence erupted in Myanmar's Rakhine State in 2012 between Buddhist
and Muslim communities, the plight of the Rohingya Muslims has received much media
attention both inside and outside of the country. Rarely, however, do we get
critical analyses of how such reporting is constructed. Research on communal
conflict and journalism tends to focus on the how-to of conflict-sensitive
reporting and the dangers of employing local fixers and interpreters whose
influence is seen to reduce the objectivity of news, rather than on the actual news
gathering strategies used in specific conflicts. Based on personal observations of
a freelance reporter in Myanmar, and interviews with journalists and fixers working
in the country, this article analyses the news production processes in reporting on
the conflict. The article maps out the various actors involved in the production of
news, such as foreign and local journalists, local producers (the fixers) and
interpreters, and the various challenges and limitations they face. These
challenges function to perpetuate a familiar set of reporting routines and us vs
them or binary narratives, with consequences for the de-escalation or perpetuation
of the conflict.
Plastic encapsulated microcircuits (PEMs) have been used tremendously in commercial
and industrial fields due to their cost, weight, availability and performance
advantages. However, the inherent structures and materials of PEMs introduce high
risks of failures and limit their use in high reliability field. Screening test for
package-level plays an important part in improving reliability of PEMs by
eliminating marginal components and early time failures. Failure analysis of the
microcircuits failed in screening test contributes to find out failure mechanisms
and helps improve design for package reliability. However, during screening test,
after screening out failed components, failure analysis is not conducted to figure
out the root cause of failure and does not contribute to the conclusion of the
screening test or to the advice for design. In this paper, dynamic burn-in of
screening test on plastic encapsulated components is presented. An integrated
circuit OPA134UA (single operational amplifier) fails in the electrical test after
24hrs. Failure analysis is carried out on the failed components to discover the
root causes. It turns out that OPA134UA fails because of the delamination between
the mold compound/die pad interface. The result of failure analysis proves that
thermal mismatch in PEMs causes delamination, which suggests that other components
also have delamination and that the design for packaging reliability require lower
difference of coefficients of thermal expansion (CTE) of different materials in
PEMs.
Curious eroded depressions, most resembling an eye shedding an elongate tear, are
found in gently sloping, intertidal, carbonate-rich arenite outcropping on the sea
coast near Lakes Entrance, Victoria, southeast Australia. The depressions, known
locally as Tears of the Virgin, are evidently formed by multiple generations of a
barnacle, Chthamalus antennatus Darwin, 1854 in association with cyanobacteria.
While the round part of a depression offers the barnacle a modicum of protection
from impacts during high tides, it is also partially inhabited by cyanobacteria,
which extend into and tend to fill the elongate tear. As such, this appears to be
the first case of mutualism between a higher invertebrate and cyanobacteria, with
the cyanobacteria reducing the barnacle's risk of desiccation while receiving
metabolic wastes from it during low tides. It is also the first record of a
balanomorph barnacle eroding calcareous arenite beneath its shell, the net effect
of which would be expected to reduce its adhesion to the substrate. However, the
siliceous residue, resulting from the barnacle's dissolution of the more than 80%
of the calcite-rich sedimentary rock, is sequestered in delicate folds on the
inside of the shell wall as it grows. A brief review of cirripedes capable of
excavation includes the first photographic documentation of excavation of a mollusc
shell by a verrucomorph.
The digital low dropout regulator (D-LDO) has drawn significant attention recently
for its low-voltage operation and process scalability. However, the tradeoff
between current efficiency and transient response speed has limited its
applications. In this brief, a coarse-fine-tuning technique with burst-mode
operation is proposed to the D-LDO. Once the voltage undershoot/overshoot is
detected, the coarse tuning quickly finds out the coarse control word in which the
load current should be located, with large power MOS strength and high sampling
frequency for a fixed time. Then, the fine-tuning, with reduced power MOS strength
and sampling frequency, regulates the D-LDO to the desired output voltage and takes
over the steady-state operation for high accuracy and current efficiency. The
proposed D-LDO is verified in a 65-nm CMOS process with a 0.01-mm(2) active area.
The measured voltage undershoot and overshoot are 55 and 47 mV, respectively, with
load steps of 2 to 100 mA with a 20-ns edge time. The quiescent current is 82 mu A,
with a 0.43-ps figure of merit achieved. Moreover, the reference tracking speed is
1.5 V/mu s.
This paper presents a new driving method for a sulfur plasma lamp in low-power
applications. The newly developed magnetron power supply (MPS) is a series-
resonance type with a full-bridge topology controlled by the phase shift to track
the beam current of the magnetron. To drive the sulfur plasma lamp optimally, the
MPS should: 1) provide peak power above a discharge condition to excite the sulfur
plasma lamp, and 2) allow average power control of the light dimmer while
satisfying condition 1. The newly developed driving method uses the burst mode,
which enables both peak and average power controls to satisfy these conditions.
Furthermore, a magnetizing current offset balancer is developed; it guarantees
zero-voltage switching of all field-effect transistors, although the MPS operates
in the burst mode. Thus, the proposed method provides easy lighting and relighting
under optimized conditions with high efficiency. The power of the MPS delivered by
the proposed method reached 1.6 kW with variable average power of 200 similar to
400 W by adjusting burst-on time proportionally. Experimental results proved the
feasibility of the proposed driving method.
Objective: Gut microbial translocation is a major driving force behind chronic
immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis,
including increases in mucosa-associated pathobionts, may influence microbial
translocation and contribute to mucosal and systemic inflammation. Thus, it is
critical to understand the mechanisms by which gut microbes and their metabolic
products, such as butyrate, influence immune cell function during HIV-1 infection.
Design: A cross-sectional study was performed to compare the relative abundance of
butyrate-producing bacterial (BPB) species in colonic biopsies and stool of
untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study
participants. The effect of exogenously added butyrate on gut T-cell activation and
HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model.
Methods: Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo
isolated lamina propria mononuclear cells were infected with C-C chemokine receptor
type 5-tropic HIV-1Bal, cultured with enteric gram-negative bacteria and a range of
butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels
measured. Results: Relative abundance of total BPB and specifically of Roseburia
intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-
uninfected individuals. In HIV-1-infected study participants, R. intestinalis
relative abundance inversely correlated with systemic indicators of microbial
translocation, immune activation, and vascular inflammation. Exogenous butyrate
suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation
and HIV-1 infection levels in vitro. Conclusion: Reductions in mucosal butyrate
from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation
and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.
Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
The paradigmatic system of societal abuse occurs in totalitarian state systems. The
relational systems of subjugation that maintain such states of terror must, of
necessity, destroy any authentic civic space in which individuals can flourish.
Similar dynamics characterize child abuse within families. Survival requires the
use of varied strategies, the most extreme of which are dissociative in nature, and
that result in marked distortions of developmental trajectories across all
psychological domains. Such dynamics are mirrored in dissociative systems that, in
the absence of intervention, perpetuate the trauma of non-recognition by
subjugation and self-objectification, or by omnipotent denial of others'
subjectivity. All abusive systems are facilitated by bystanders, whose awareness of
what is disavowed is always partial, resulting in a state of knowing and not-
knowing. As dynamics shift, bystanders may behave like victimspassive, helpless,
frightened and frozen, or like perpetratorstaking vicarious and voyeuristic
pleasure in abuse or actively aiding and abetting the abusers.
Background: The Clostridium difficile rate in symptomatic patients represents both
those with C difficile infection (CDI) and those with colonization. To predict the
extent of CDI overdiagnosis, we compared the asymptomatic colonization rate to the
symptomatic positivity rate in hospitalized patients using nucleic acid testing.
Methods: Between July 2014 and April 2015, formed stool samples were collected from
asymptomatic patients after admission to 3 hospital wards at the Stanford Hospital.
Stool samples from symptomatic patients with suspected CDI in the same wards were
collected for testing per provider order. The GeneXpert C. difficile tcdB
polymerase chain reaction (PCR) assay (Cepheid, Sunnyvale, CA, USA) was performed
on all stool samples and PCR cycle threshold was used as a measure of genomic
equivalents. Chart review was performed to obtain clinical history and medication
exposure. Results: We found an asymptomatic C. difficile carriage rate of 11.8%
(43/365) (95% confidence interval [CI], 8.515.1%) and a positivity rate in
symptomatic patients of 15.4% (54/351) (95% CI, 11.6-19.2%; P = 0.19). The median
PCR cycle thresholds was not significantly different between asymptomatic carriers
and symptomatic positives (29.5 versus 27.3; P = 0.07). Among asymptomatic
patients, 11.6% (5/43) of carriers and 8.4% (27/322; P = 0.56) of noncarriers
subsequently became symptomatic CDI suspects within the same hospitalization.
Single and multivariate analysis did not identify any demographic or clinical
factors as being significantly associated with C difficile carriage. Conclusions:
Asymptomatic C difficile carriage rate was similar to symptomatic positivity rate.
This suggests the majority of PCR-positive results in symptomatic patients are
likely due to C. difficile colonization. Disease specific biomarkers are needed to
accurately diagnose patients with C difficile disease. (C) 2017 Elsevier Inc. All
rights reserved.
ScopeNaturally occurring isothiocyanates (ITCs) have been investigated for their
chemopreventive actions. However, limited studies have determined the potential for
regulation of hepatic glutathione S-transferase A2 (GSTA2) by arylalkyl or alkyl
ITCs. Methods and resultsThe present study was designed to investigate the effects
of ITCs on GSTA2 expression and upstream signaling analyzed by Northern blotting,
RT-PCR, immunoblotting, and promoter-luciferase assay. A single dose of ethyl
isothiocyanate and phenethyl isothiocyanate (PEITC) enhanced GSTA2 mRNA levels in
rats. The three consecutive injections of arylalkyl ITCs resulted in the gene
induction. PEITC was the most potent and sustained inducer of GSTA2 in vivo. PEITC
induced GSTA2 mRNA and protein expression in H4IIE cells. PEITC increased the
levels of nuclear factor erythroid 2 related factor 2 and CCAAT/enhancer binding
protein (C/EBP). The cells transfected with a pGL-ARE or pGL-C/EBP-deleted promoter
construct failed to increase GSTA2 promoter activity by PEITC. These effects of
PEITC were downstream of multiple cellular signaling, including phosphoinositide 3-
kinase (PI3K), c-jun N-terminal kinase (JNK), and/or protein kinase A (PKA).
ConclusionThese results demonstrated that PEITC is the most efficacious of the
arylalkyl ITCs for the induction of GSTA2 in vivo and in vitro, and that
transactivation of C/EBP and nuclear factor erythroid 2 related factor 2 downstream
of multiple signaling pathways is involved in this induction.
In this study, we report the identification and characterization of a novel C2H2
zinc finger protein, ZNF552, from a human embryonic heart cDNA library. ZNF552 is
composed of three exons and two introns and maps to chromosome 19q13.43. The cDNA
of ZNF552 is 2.3 kb, encoding 407 amino acids with an amino-terminal KRAB domain
and seven carboxyl-terminal C2H2 zinc finger motifs in the nucleus and cytoplasm.
Northern blotting analysis indicated that a 2.3 kb transcript specific for ZNF552
was expressed in liver, lung, spleen, testis and kidney, especially with a higher
level in the lung and testis in human adult tissues. Reporter gene assays showed
that ZNF552 was a transcriptional repressor, and overexpression of ZNF552 in the
COS-7 cells inhibited the transcriptional activities of AP-1 and SRE, which could
be relieved through RNAi analysis. Deletion studies showed that the KRAB domain of
ZNF552 may be involved in this inhibition. [BMB reports 2010; 43(3): 193-198]
The chronic inflammation plays an important role in heart failure and complement
components might be useful markers of the prognosis. We set out to evaluate their
predictive value in the clinical outcomes of patients with cardiac
resynchronization therapy (CRT). We determined the complement levels C3, C3a, sC5b-
9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP)
of 126 heart failure patients in a prospective, single-center observational study
before and 6 months after CRT implantation. CRT reduced the C3a [212.5 (148.2-
283.6) vs. 153 (119.8-218.3) ng/mL, p165 ng/mL hazard ratio = 4.21 (1.65-10.72), p
= 0.003] independent of the NT-proBNP and other factors. After reclassification, we
observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p
< 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p =
0.0002]. In patients with CRT, elevated C3a levels increase the risk of mortality
independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory
effect by reducing the complement activation.
This review summarizes biogenesis, composition, intracellular transport, and
possible functions of trichocysts. Trichocyst release by Paramecium is the fastest
dense core-secretory vesicle exocytosis known. This is enabled by the crystalline
nature of the trichocyst "body" whose matrix proteins (tmp), upon contact with
extracellular Ca2+, undergo explosive recrystallization that propagates
cooperatively throughout the organelle. Membrane fusion during stimulated
trichocyst exocytosis involves Ca2+ mobilization from alveolar sacs and tightly
coupled store-operated Ca2+-influx, initiated by activation of ryanodine receptor-
like Ca2+-release channels. Particularly, aminoethyldextran perfectly mimics a
physiological function of trichocysts, i.e. defense against predators, by vigorous,
local trichocyst discharge. The tmp's contained in the main "body" of a trichocyst
are arranged in a defined pattern, resulting in crossstriation, whose period
expands upon expulsion. The second part of a trichocyst, the "tip", contains
secretory lectins which diffuse upon discharge. Repulsion from predators may not be
the only function of trichocysts. We consider ciliary reversal accompanying
stimulated trichocyst exocytosis (also in mutants devoid of depolarization-
activated Ca2+ channels) a second, automatically superimposed defense mechanism. A
third defensive mechanism may be effectuated by the secretory lectins of the
trichocyst tip; they may inhibit toxicyst exocytosis in Dileptus by crosslinking
surface proteins (an effect mimicked in Paramecium by antibodies against cell
surface components). Some of the proteins, body and tip, are glycosylated as
visualized by binding of exogenous lectins. This reflects the biogenetic pathway,
from the endoplasmic reticulum via the Golgi apparatus, which is also supported by
details from molecular biology. There are fragile links connecting the matrix of a
trichocyst with its membrane; these may signal the filling state, full or empty,
before and after tmp release upon exocytosis, respectively. This is supported by
experimentally produced " frustrated exocytosis", i.e. membrane fusion without
contents release, followed by membrane resealing and entry in a new cycle of
reattachment for stimulated exocytosis. There are some more puzzles to be solved:
Considering the absence of any detectable Ca2+ and of acidity in the organelle,
what causes the striking effects of silencing the genes of some specific Ca2+-
release channels and of subunits of the H+-ATPase? What determines the inherent
polarity of a trichocyst? What precisely causes the inability of trichocyst mutants
to dock at the cell membrane? Many details now call for further experimental work
to unravel more secrets about these fascinating organelles.
This study aimed to evaluate the recovery of structurally intact human norovirus
(NoV) during Kimchi fermentation at varying temperatures. Lactic acid bacteria
(LAB), pH, and acidity during storage and fermentation were also measured to assess
the correlation between NoV reduction and microbial or physicochemical property
alterations. LAB number, NoV G titer, pH, acidity, and the ability of NoV GII.4 to
persist in Kimchi stored at 4 degrees C and 10 degrees C (survivability) as
determined using nano magnetic beads conjugated with poly(methyl vinyl ether-maleic
anhydride) combined with quantitative real-time reverse transcription-polymerase
chain reaction amplification were investigated up to 28 days post inoculation. NoV
was detected in all test samples after 28 days although the NoV recovery quantity
was reduced to 1.31 (4 degrees C) and 1.66 (10 degrees C ) login genomic
copies/reaction. The time required to reduce the amount of virus by 2.57 logic,
(t(d)) on survival plots of NoV determined using a modified Weibull model was 2445
days at 4 degrees C and 138 days at 10 degrees C. These results indicate that NoV
from food preparation or processing is able to persistently survive in Kimchi.
Therefore, preventing NoV transmission is important for protecting Kimchi against
NoV contamination. (C) 2016 Elsevier Ltd. All rights reserved.
An attributional life cycle assessment (LCA) was conducted to provide a
comprehensive picture of the environmental burdens associated with cacao production
and primary processing in the Philippines. The analysis considered the entire
system, from agricultural operations in the field until storage of the dried beans,
required to produce and process 1 ton of dried cacao beans. The inputs include
fertilizer, pesticides, diesel, electricity and biodegradable plastics while the
outputs include the dried beans, emissions of lambda-cyhalothrin, mancozeb, CO2,
SO2, CH4, N2O, NO and CO, and solid wastes. The following impacts were found to be
associated with the production of 1 ton dried cacao beans-0.163 kg 1,4-DB-eq.
(human toxicity), 0.180 kg 1,4-DB-eq. (terrestrial ecotoxicity), 0.796 kg SO2 eq.
(atmospheric acidification) and 629.93 kg CO2 eq. (climate change). Transportation,
harvesting, pest management, and nutrient management contributed the most to the
environmental impact categories considered in the study. As such, it is suggested
that improvement measures be focused on the reduction of fossil fuel consumption
and judicious application of fertilizers and pesticides to minimize the adverse
environmental impacts of cacao production and primary processing. The amount of
harmful emissions released and the impact scores of cacao production and primary
processing are generally low. This may be an indication of the cleaner production
and eco-efficiency of the system. The results of this LCA study serves as a
feedback mechanism that will assist the Philippine cacao industry in identifying
the options for improving the environmental management of its production and
primary processing system.
Brazil, the Cadastro Ambiental Rural (CAR) is currently being implemented. This
policy aims to geo-reference all properties and promote monitoring of, and
compliance with, natural vegetation conservation requirements. Scholarly efforts
and policy attention have so far concentrated on possible environmental impacts
hereof, while the attention devoted to how the CAR might affect farmers'
livelihoods has been limited. In this paper, we evaluate potential livelihood
impacts of the CAR and programs that facilitate CAR registration. We do so by
developing a conceptual framework and using evidence from semi-structured
interviews with key stakeholders including farmers, governments, and funding
agencies. We find that while the CAR and programs facilitating CAR do not have
explicit livelihood impact goals, they nonetheless affect livelihoods, both
positively and negatively, depending on the initial amount of natural vegetation on
farmers' properties, farmers' access to credit and infrastructure, and changing
market conditions. We argue that environmental interventions and policies need to
consider potential livelihood impacts, especially if the policy intervention area
has high poverty rates. (C) 2017 The Authors. Published by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license
Objective: To examine a possible association between maternal-request caesarean
section (CS) and two intrapsychic psychoanalytic personality variables: object
relations (OR) and unconscious defences.Background: While maternal-request CS is a
growing phenomenon, studies are lacking regarding personality variables that may be
associated with it.Methods: A cross-sectional questionnaire was conducted in one
delivery ward. During 2009, 59 primigravida, healthy women were recruited; 28 who
had requested and delivered by CS without an obstetrical indication and 31 who
opted for a spontaneous vaginal delivery. Due to missing data for some measures,
only 27 participants were analysed in each group. All women completed the fear of
childbirth (FOC) questionnaire, and the object relations (SCORS) and unconscious
defences (DMM) measures of the Thematic Apperception Test (TAT), as well as
questionnaires assessing background variables. Multivariate analysis of variance
(MANOVA) and a logistic hierarchical multiple regression were performed.Results:
Preliminary MANOVA showed significant differences between groups in age, FOC and
use of the defence mechanism projection. Hence, these variables entered as
predictors of maternal-request CS to a logistic hierarchical multiple regression
model. The model was found to have a good fit [(2)((4)) = 38.19, p<0.001]. Age, FOC
and projection defence were found to be significant factors associated with
maternal-request CS.Conclusion: Maternal-request CS was found to be strongly
associated with age and FOC. Except for unconscious defence of projection,
intrapsychic variables were not found to be associated with maternal-request CS.
Possible implications are discussed.
There are numerous reports on intronic miRNAs from plants, most of which are
involved in the regulation of unrelated genes. Some of the target genes are
antagonistic to the host genes. Intronic miRNAs in animal systems, however, are
known to have synergistic effects. This article is the first to report a similar
regulatory effect of a miRNA originating from an intron in plants. NMT genes
involved in caffeine biosynthesis were silenced to obtain transformants with
reduced caffeine. Transcript analysis revealed the accumulation of transcripts for
a related NMT gene (CaMTL1) in transformants bearing either antisense or RNAi
constructs. The altered expression was assumed to relate to the silencing of the
NMT genes. Bioinformatics analysis of the genes involved in biosynthesis revealed
the presence of an intronic miRNA originating from the intron of the theobromine
synthase gene targeting CaMTL1. The putative miRNA was cloned and sequenced.
Modified 5'-RLM-RACE mapping of the cleavage site and subsequent Northern blotting
experimentally demonstrated the presence and activity of such a miRNA in Coffee
canephora. This novel regulatory mechanism previously unreported in plants will
shed more light onto the evolution of multigene families and the role of introns in
this process. (c) 2013 Elsevier B.V. All rights reserved.
Background: Analysis of residual gene expression of the nuclear factor of activated
T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to
monitor therapy with calcineurin inhibitors. The availability of commercial primer
sets (Search-LC) and the well-established assay protocol makes this biomarker a
promising candidate to be used clinically in different laboratories. However,
implementation of the method in routine practice requires analytical robustness and
comparable results across laboratories. Therefore, a protocol originally
established at the Institute of Immunology, Heidelberg was verified at the
Institute of Laboratory Medicine, Klinikum Stuttgart, and a comparison study was
conducted between the 2 laboratories. Methods: For the analytical verification,
whole blood samples of healthy individuals were incubated with tacrolimus in vitro.
Linearity, imprecision, and limit of quantification, as well as sample stability,
were investigated. For interlaboratory comparison, samples of patients under
cyclosporine A therapy were analyzed in Heidelberg and then reanalyzed in Stuttgart
within 24 hours. Results: Tacrolimus (6.25-50 mcg/L) decreased the expression of
NFAT-regulated genes in vitro dose dependently (15%-89%). Within-and between-assay
coefficient of variations (n = 6 each) were <17%. The limit of quantification
was,200 cDNA copies for each of the interleukin-2, interferon-g, and granulocyte-
macrophage colony-stimulating factor genes. Samples were stable for 24 hours.
Interlaboratory comparison using patient samples correlated well (r = 0.951) but
showed an inconsistent bias depending on the magnitude of residual gene expression.
Conclusions: The assay can be set up with a satisfactory analytical performance in
a routine molecular biological laboratory and shows comparable results between
laboratories. The reproducibility of the NFAT-regulated gene expression assay
across laboratories can facilitate the implementation of this assay for
pharmacodynamic routine monitoring of calcineurin inhibitors in different centers.
Hormonal responses to acute stress rely on the rapid induction of
corticotropinreleasing hormone (CRH) production in the mammalian hypothalamus, with
subsequent instructive steps culminating in corticosterone release at the
periphery. Hypothalamic CRH neurons in the paraventricular nucleus of the
hypothalamus are therefore considered as 'stress neurons'. However, significant
morphological and functional diversity among neurons that can transiently produce
CRH in other hypothalamic nuclei has been proposed, particularly as histochemical
and molecular biology evidence associates CRH to both GABA and glutamate
neurotransmission. Here, we review recent advances through single-cell RNA
sequencing and circuit mapping to suggest that CRH production reflects a state
switch in hypothalamic neurons and thus confers functional competence rather than
being an identity mark of phenotypically segregated neurons. We show that CRH mRNA
transcripts can therefore be seen in GABAergic, glutamatergic and dopaminergic
neuronal contingents in the hypothalamus. We then distinguish 'stress neurons' of
the paraventricular nucleus that constitutively express secretagogin, a Ca2+ sensor
critical for the stimulus-driven assembly of the molecular machinery underpinning
the fast regulated exocytosis of CRH at the median eminence. Cumulatively, we infer
that CRH neurons are functionally and molecularly more diverse than previously
thought.
Voltage-gated calcium (Ca-v) channels serve dual roles in the cell, where they can
both depolarize the membrane potential for electrical excitability, and activate
transient cytoplasmic Ca2+ signals. In animals, Ca-v channels play crucial roles
including driving muscle contraction (excitation-contraction coupling), gene
expression (excitation transcriptioncoupling), pre-synaptic and neuroendocrine
exocytosis (excitation-secretion coupling), regulation of flagellar/ciliary
beating, and regulation of cellular excitability, either directly or through
modulation of other Ca2+-sensitive ion channels. In recent years, genome sequencing
has provided significant insights into the molecular evolution of Ca-v channels.
Furthermore, expanded gene datasets have permitted improved inference of the
species phylogeny at the base of Metazoa, providing clearer insights into the
evolution of complex animal traits which involve Ca-v channels, including the
nervous system. For the various types of metazoan Ca-v channels, key properties
that determine their cellular contribution include: Ion selectivity, pore gating,
and, importantly, cytoplasmic protein-protein interactions that direct sub-cellular
localization and functional complexing. It is unclear when these defining features,
many of which are essential for nervous system function, evolved. In this review,
we highlight some experimental observations that implicate Ca-v channels in the
physiology and behavior of the most early-diverging animals from the phyla
Cnidaria, Placozoa, Porifera, and Ctenophora. Given our limited understanding of
the molecular biology of Ca-v channels in these basal animal lineages, we infer
insights from better-studied vertebrate and invertebrate animals. We also highlight
some apparently conserved cellular functions of Ca-v channels, which might have
emerged very early on during metazoan evolution, or perhaps predated it.
The ipomoelin gene (IPO) was identified to be a wound-inducible gene from Ipomoea
batatas, and its expression was stimulated by methyl jasmonate (MeJA) and hydrogen
peroxide. IPO protein was also characterized as a defence-related protein, and it
is also a carbohydrate-binding protein. In this study, the expression of IPO was
used as a molecular probe to study the effects of Ca2+ on the signal transduction
of ethylene. A confocal microscope monitored the Ca2+ within cells, and Northern
blotting examined IPO expression. The presence of Ca2+ channel blocker, including
diltiazem, neomycin or ruthenium red, abolished the increase of cytosolic Ca2+, and
reduced the IPO expression in the cells induced by ethylene. Furthermore, both Ca2+
influxes and IPO expression stimulated by ethylene were prohibited in the presence
of 10 mM ethylene glycol-bis(2-aminoethyl ether)-N, N, N', N'-tetraacetic acid
(EGTA). These results indicated that Ca2+ influxes into the cytosol induced by
ethylene are from both apoplast and organelles, and are required for activating IPO
expression. However, in the presence of 1 mM EGTA, ethylene can still stimulate IPO
expression, but mechanical wounding failed to do it. Therefore, Ca2+ channels in
the plasma membrane induced by ethylene have higher affinity to Ca2+ than that
stimulated by wounding. Moreover, the addition of A23187, an ionophore, raised
cytosolic Ca2+, but was unable to stimulate IPO expression. These findings showed
that IPO induction did not solely depend on Ca2+, and Ca2+ elevation in cytosol is
necessary but not sufficient for IPO expression. The application of PD98059, a
mitogen-activated protein kinase kinase (MAPKK) inhibitor, did not prevent Ca2+
from increasing in the cytosol induced by ethylene, but inhibited the IPO
expression stimulated by staurosporine (STA), a protein kinase inhibitor.
Conclusively, elevation of cytosolic Ca2+ by ethylene may stimulate protein
phosphatase and MAPKK, which finally activates IPO expression.
A low energy- noise switched-capacitor (SC) sensor interface for resistive bridge
sensor is presented. The SC amplifier achieves low-power metric with two operating
modes using operation-phase-dependent biasing and compensation scheme in the op-amp
design. This novel op-amp works in high-bandwidth high-power mode to sample the
bridge signal for 13 mu s twice and in low-bandwidth low-power mode for 474 mu s
over 500 mu s measurement interval. To further reduce the power of the SC amplifier
in system level, a SC level-shift design is adopted. Regarding offset calibration,
a capacitor divider based trimming scheme is implemented to generate the mid-point
DC output voltage under the constraint of the feedback capacitor size. Implemented
in 65 nm CMOS, the SC interface together with the regulator, voltage reference and
trimming circuit occupies an area of 0.358 mm(2). For the first test setup
utilizing Half Wheatstone Bridge, the proposed SC amplifier consumes 12.3 mu W at 1
V regulated supply with a 2 kHz system clock. The measured Signal-to-Noise Ratio
(SNR) of SC circuit is 55.6 dB. In the second test setup using a commercial sensor
with 0.092 mV/kPa sensitivity, the interface has demonstrated the sensing function
with sensitivity of 3.52 mV/kPa. Finally, compared to the representative prior-
arts, this work has achieved the best energy-noise figure-of-merit at identical
fractional resistance change.
Food restriction affects the activation of the immune system although the metabolic
cost associated with mounting such a response has rarely been examined except in
model animals. Wild animals are constantly exposed to variations in the
availability of food resources and they need to balance their energy budget to
fight against pathogens. We examined the effect of food restriction in the fish
eating Myotis (Myotis vivesi), a species of bat that experiences periods in which
foraging is limited due to ambient conditions. We tested the hypothesis that acute
food restriction (similar to 65% restriction for 1 night) would reduce the caloric
response to lipopolysaccharidae (LPS) injection compared to bats fed ad libitum. We
also measured a proxy for body temperature (T-skin) and expected reduced fever
development when food intake was limited. Bats on the restricted diet had similar
resting metabolic rate, total caloric cost and Tskin after the LPS challenge than
when fed ad libitum. However, there was a delay in the metabolic and pyrogenic
responses when bats were on the restricted diet. The effect of acute food
restriction in delaying the hyperthermia development in fish eating Myotis might be
of importance for its capacity to fight pathogens. Similar to other bats, the fish
eating Myotis can fast for several consecutive days by entering torpor and future
work is warranted to understand the effect of long periods of food restriction on
bat immune response. (C) 2016 Deutsche Gesellschaft fur Saugetierkunde. Published
by Elsevier GmbH. All rights reserved.
Calprotectin is composed of two proteins, S100A8 and S100A9, which are S100 family
members, and is detected in gingival crevicular fluid and gingival tissue with
inflammation. The release and production of calprotectin are regulated by
lipopolysaccharides of periodontopathic bacteria and cytokines. Emotional or
psychological stress, a risk factor of periodontal disease, is transmitted by
stress modulators including norepinephrine and cortisol. The aim of the present
study was to investigate the effect of stress on calprotectin expression using
norepinephrine and cortisol. U-937 cells, a human monocytic cell line, were
incubated with norepinephrine in the presence or absence of beta- or alpha-
adrenergic receptor antagonists, or with cortisol. The expression of S100A8/S100A9
mRNAs was examined by northern blotting and the amount of calprotectin was measured
by enzyme-linked immunosorbent assay (ELISA). The DNA binding activity of C/EBP
alpha (CCAAT enhancing binding protein), a transcription factor, was examined by
electrophoretic mobility shift assay. Norepinephrine stimulated the expression of
S100A8/S100A9 mRNAs via beta-adrenergic receptors in U-937 cells and significantly
increased calprotectin production to about 3.6-fold that of the control. However,
cortisol had no effect on calprotectin expression at the mRNA and protein levels.
Norepinephrine elevated C/EBP alpha DNA binding activity, but cortisol did not
increase the activity. Norepinephrine, a stress modulator, stimulated calprotectin
expression in human monocytic cells. Calprotectin expression may be regulated by
stress in addition to inflammatory factors.
Calprotectin is an antimicrobial complex composed of the S100A8 and S100A9 protein
family subunits. Contributing to innate immunity, calprotectin expression is
increased by interleukin-1 alpha (IL-1 alpha), which modulates keratinocyte
differentiation. Keratinocyte growth factor (KGF) is produced by mesenchymal cells
and has a mitogenic activity for epithelial cells. In this study, we investigated
the effect of KGF on calprotectin expression in keratinocytes and modulation by IL-
1 alpha. Human keratinocytes were cultured with KGF in the presence or absence of a
KGF receptor (KGFR) inhibitor or mitogen-activated protein kinase (MAPK)
inhibitors. Calprotectin (S100A8/S100A9) expression was determined by northern
blotting and enzyme-linked immunosorbent assay, respectively, whereas MAPK
phosphorylation was analyzed by western blot analysis. KGF significantly decreased
the expression of S100A8/S100A9-specific mRNAs and calprotectin protein. In the
presence of KGF, KGFR inhibitor or extracellular-regulated kinase inhibitor
restored KGF-downregulated expression of S100A8/S100A9. KGF increased IL-1 alpha
expression in keratinocytes, whereas IL-1 alpha increased KGF expression in
fibroblasts. Cocultured fibroblast and keratinocytes showed lower S100A8/S100A9
mRNA expression than keratinocytes alone in the presence or absence of IL-1 alpha
or KGF. These results suggest that fibroblast-derived KGF reduces or restricts
calprotectin expression in keratinocytes, which supports our hypothesis that
calprotectin expression in keratinocytes is modulated by factors associated with
epithelial mesenchymal interactions. Immunology and Cell Biology (2010) 88, 328-
333; doi: 10.1038/icb.2009.104; published online 12 January 2010
Background: The rapid increase of extended-spectrum beta-lactamase (ESBL) producing
bacteria are a potential health hazard. Development of antimicrobial resistance in
animal pathogens has serious implications for human health, especially when such
strains could be transmitted to human. In this study, the antimicrobial resistance
due to ESBL producing Pseudomonas aeruginosa in the camel meat was investigated.
Methods: In this study meat samples from 200 healthy camels at two major abattoirs
in Egypt (Cairo and Giza) were collected. Following culture on cetrimide agar,
suspected P. aeruginosa colonies were confirmed with a Vitek 2 system
(bioMe'rieux). P. aeruginosa isolates were phenotypically identified as ESBL by
double disk synergy test. Additionally antimicrobial susceptibility testing of ESBL
producing P. aeruginosa isolates were done against 11 antimicrobial drugs and
carried out by disk diffusion method. The ESBL genotypes were determined by
polymerase chain reaction according to the presence of the bla(PFR-1), bla(CTX-M),
bla(SHV), and bla(TFM). Results: Pseudomonas aeruginosa was isolated from 45 camel
meat sample (22.5%). The total percentage of ESBL producing P. aeruginosa was 45%
(21/45) from camel meat isolates. Antibiogram results revealed the highest
resistance was for c, ceftriaxone and rifampicin followed by cefepime and
aztreonam. The prevalence rates of beta-lactamase genes were recorded (bla(PER-1)
28.5%, bla(CTX-M) 38%, bla(SHV) 33.3% and bla(TEM) 23.8%). Conclusions: This study
illustrates the presence of high rates of ESBL-P. aeruginosa in camels that
represents an increasing alarming for the risk of transmission to human and opens
the door for current and future antibiotics therapy failure. Livestock associated
ESBL-P. aeruginosa is a growing disaster, therefore, attention has to be fully
given to livestock associated ESBL-bacteria which try to find its way to human
beings.
The major aim of made tea identification is to identify the variety and provenance
of the tea plant. The present experiment used 113 tea plants [Camellia sinensis
(L.) O. Kuntze] housed at the Tea Research and Extension Substation, from which 113
internal transcribed spacer 2 (ITS2) fragments, 104 trnL intron, and 98 trnL-trnF
intergenic sequence region DNA sequences were successfully sequenced. The
similarity of the ITS2 nucleotide sequences between tea plants housed at the Tea
Research and Extension Substation was 0.379-0.994. In this polymerase chain
reaction-amplified noncoding region, no varieties possessed identical sequences.
Compared with the trnL intron and trnL-trnF intergenic sequence fragments of
chloroplast cpDNA, the proportion of ITS2 nucleotide sequence variation was large
and is more suitable for establishing a DNA barcode database to identify tea plant
varieties. After establishing the database, 30 imported teas and 35 domestic made
teas were used in this model system to explore the feasibility of using ITS2
sequences to identify the varieties and provenances of made teas. A phylogenetic
tree was constructed using ITS2 sequences with the unweighted pair group method
with arithmetic mean, which indicated that the same variety of tea plant is likely
to be successfully categorized into one cluster, but contamination from other tea
plants was also detected. This result provides molecular evidence that the
similarity between important tea varieties in Taiwan remains high. Wesuggest a
direct, wide collection of made tea and original samples of tea plants to establish
an ITS2 sequence molecular barcode identification database to identify the
varieties and provenances of tea plants. The DNA barcode comparison method can
satisfy the need for a rapid, low-cost, frontline differentiation of the large
amount of made teas from Taiwan and abroad, and can provide molecular evidence of
their varieties and provenances. Copyright (C) 2016, Food and Drug Administration,
Taiwan. Published by Elsevier Taiwan LLC.
In higher plants, P450s participate in the biosynthesis of many important secondary
metabolites. Here we reported for the first time the isolation of a new cytochrome
P450 cDNA that expressed in a stem-specific manner from Camptotheca acuminata
(designated as CaSS), a native medicinal plant species in China, using RACE-PCR.
The full-length cDNA of CaSS was 1735 bp long containing a 1530 bp open reading
frame (ORF) encoding a polypeptide of 509 amino acids. Bioinformatic analysis
revealed that CASS contained a heme-binding domain PFGXGRRXCX and showed homology
to other plant cytochrome P450 monooxygenases and hydroxylases. Southern blotting
analysis revealed that there was only one copy of the CaSS present in the genome of
Camptotheca acuminata. Northern blotting analysis revealed that CaSS expressed, in
a tissue-specific manner, highly in stem and lowly in root, leaf and flower. Our
study suggests that CaSS is likely to be involved in the phenylpropanoid pathway.
The aim of this study was to reveal the molecular mechanism involved in multidrug
resistance and virulence of Campylobacter jejuni isolated from broiler chickens.
The virulence of six multidrug resistant C. jejuni was determined by in vitro and
in vivo methods. The de novo whole genome sequencing technology and molecular
biology methods were used to analyze the genomic features associated with the
multidrug resistance and virulence of a selected isolate (C. jejuni 1655). The
comparative genomic analyses revealed a large number of single nucleotide
polymorphisms, deletions, rearrangements, and inversions in C. jejuni 1655 compared
to reference C. jejuni genomes. The co-emergence of Thr-86-1Ie mutation in gyrA
gene, A2075G mutation in 23S rRNA gene, tetO, aphA and aadE genes and pTet plasmid
in C. jejuni 1655 contributed its multidrug resistance to fluoroquinolones,
macrolides, tetracycline, and aminoglycosides. The combination of multiple
virulence genes may work together to confer the relative higher virulence in C.
jejuni 1655. The co-existence of mobile gene elements (e.g., pTet) and CRISPR-Cas
system in C. jejuni 1655 may play an important role in the gene transfer and immune
defense. The present study provides basic information of phenotypic and genomic
features of C. jejuni 1655, a strain recently isolated from a chicken displaying
multidrug resistance and relatively high level of virulence.
Background: Campylobacter species are widespread zoonotic pathogens. Campylobacter
jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter
drug resistance is considered a serious threat. In order to better understand
national and international research output on Campylobacter, we conducted this
bibliometric overview of publications on Campylobacter. This study can be used to
assess extent of interaction and response of researchers, food regulators, and
health policy makers to global burden of campylobacateriosis. Methods: Scopus
database was used to retrieve publications with the following keywords
(Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set
from 2000 to 2015. All types of journal documents, excluding errata, were
considered. Bibliometric indicators such as annual growth of publications, country
contribution, international collaboration, and citation analysis were presented.
The quality of retrieved data was indirectly assessed by Hirsch index and impact
factor of journals. Results: A total of 5522 documents were retrieved with median
(Q1-Q3) citations of 9 (2-23) and h-index of 113. Annual number of publications
showed a fluctuating increase. The core leading journals were Applied and
Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%)
publications for each. The USA (1309; 23.6%) was the most productive country while
Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half
of the top ten productive countries were European. France had the lowest percentage
(33.5%) of articles with international collaboration while Netherlands (57.7%) had
the highest percentage of articles with international collaboration. Approximately
half (50.1%) of retrieved articles were published in journals under the subject
area of "immunology/microbiology". Main themes in highly cited articles were
molecular biology/genetics and public health burden of campylobacteriosis. There
were 728 (13.1%) articles on campylobacter-related drug resistance, and the top
cited articles focused mainly on increasing resistance to quinolones and
fluoroquinolones. Conclusions: There was a clear increase in number of publications
on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is
highly recommended. International collaboration is highly required particularly in
implementing new diagnostic screening technologies to minimize global health burden
of Campylobacter and ensure food safety.
Objective: To increase the level of awareness that Ehlers-Danlos/hypermobility
syndrome (EDS) and vitamin D deficiency are associated with infantile fragility
fractures and radiologic features that may be mistakenly reported to be caused by
non-accidental trauma due to Child Abuse and Neglect (CAN). Patients and Methods:
We constructed a case series, the largest to date, of infants with EDS who were
vitamin D sufficient, insufficient and deficient and infants without EDS but with
documented vitamin D deficiency and radiologic evidence of rickets who presented
with multiple fractures originally diagnosed as being non-accidental and caused by
child abuse. These infants were referred to the outpatient Bone Health Care Clinic
at Boston University Medical Campus over a 6-year (2010-2015) period. We also
present 6 index cases in which the court concluded that there was no convincing
evidence of child abuse and the infants were returned to their parents.
Institutional Review Board (IRB) approval was obtained. Results: We present 72
cases of infants with multiple fractures diagnosed to be caused by non-accidental
trauma. All infants were younger than one year of age. Among them, 93%(67) had
clinical evidence of EDS and/or a family history with a confirmed clinical
diagnosis of at least one parent having EDS and the other 7%(5) without evidence of
EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were
diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common
fractures noted at diagnosis were ribs and extremity fractures (including classic
metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH) D] were reported
in 48 infants (18.0 +/- 8.5 ng/ml) and in 30 mothers (21.3 +/- 11.7 ng/ml). Sixty-
three percent (27) of the EDS infants who had their serum 25(OH) D measured were
vitamin D deficient 25(OH) D30 ng/ml. The mean serum level for infants with vitamin
D deficiency/rickets was (10.2 +/- 3.0 ng/ml) Conclusion: EDS, OI/EDS and vitamin D
deficiency/infantile rickets are associated with fragility fractures in infants
that can be misinterpreted as caused by non-accidental trauma due to child abuse.
This article uses an intersectionality lens to explore how experiences of race,
gender, sexuality, class and their intersections are associated with depression and
unmet need for mental healthcare in a population of 704 women and
transgender/gender liminal people from Ontario, Canada. A survey collecting
demographic information, information about mental health and use of mental
healthcare services, and data for the Everyday Discrimination Scale and the PHQ-9
Questionnaire for Depression was completed by 704 people via Internet or pen-and-
paper between June 2011 and June 2012. Bivariate and regression analyses were
conducted to assess group differences in depression and discrimination experiences,
and predictors of depression and unmet need for mental healthcare services.
Analyses revealed that race, gender, class and sexuality all corresponded to
significant differences in exposure to discrimination, experiences of depression
and unmet needs for mental healthcare. Use of interaction terms to model
intersecting identities and exclusion contributed to explained variance in both
outcome variables. Everyday discrimination was the strongest predictor of both
depression and unmet need for mental healthcare. The results suggest lower income
and intersections of race with other marginalised identities are associated with
more depression and unmet need for mental healthcare; however, discrimination is
the factor that contributes the most to those vulnerabilities. Future research can
build on intersectionality theory by foregrounding the role of structural
inequities and discrimination in promoting poor mental health and barriers to
healthcare.
Polycomb group proteins regulate chromatin structure and have an important
regulatory role on gene expression in various cell types. Two polycomb group
complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified
in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone
modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2
catalyzes methylation of histone H3 on lysine 27. These alterations of histones can
lead to altered gene expression patterns by regulating chromatin structure.
Numerous studies have highlighted the role of the PRC2 catalytic component enhancer
of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2
mutations have been identified in various malignancies. Through modulating the
expression of critical genes, EZH2 is actively involved in fundamental cellular
processes such as cell cycle progression, cell proliferation, differentiation and
apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the
differentiation and function of T effector and T regulatory cells. In this review
we summarize the recent progress regarding the role of EZH2 in human malignancies,
highlight the molecular mechanisms by which EZH2 aberrations promote the
pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via
activating direct anti-cancer mechanisms and anti-tumor immunity.
Measuring cell proliferation can be performed by a number of different methods,
each with varying levels of sensitivity, reproducibility and compatibility with
high-throughput formatting. This protocol describes the use of three different
methods for measuring cell proliferation in vitro including conventional
hemocytometer counting chamber, a luminescence-based assay that utilizes the change
in the metabolic activity of viable cells as a measure of the relative number of
cells, and a multi-mode cell imager that measures cell number using a counting
algorithm. Each method presents its own advantages and disadvantages for the
measurement of cell proliferation, including time, cost and high-throughput
compatibility. This protocol demonstrates that each method could accurately measure
cell proliferation over time, and was sensitive to detect growth at differing
cellular densities. Additionally, measurement of cell proliferation using a cell
imager was able to provide further information such as morphology, confluence and
allowed for a continual monitoring of cell proliferation over time. In conclusion,
each method is capable of measuring cell proliferation, but the chosen method is
user-dependent.
Molecular imaging agents have the ability to non-invasively visualize,
characterize, and quantify the molecular biology of disease. Recent advances in
nuclear probe development, particularly in PET radiotracers, have generated many
new imaging agents with precise molecular targets. With such specificity, PET
probes may be utilized as biomarkers to objectively interrogate and evaluate
pathology. Whereas the current indications for PET imaging are predominately
confined to staging and restaging of malignancy, the utility of PET greatly expands
when utilized as a biomarker, the topic of this review. As an imaging biomarker,
PET may be used to (1) measure target expression to select subsets of patients who
would most benefit from targeted therapy; (2) measure early treatment response to
predict therapeutic efficacy; and (3) relate tumor response to survival. This
review will discuss the application of radiotracers to targeted cancer therapy.
Particular attention is given to new radiotracers evaluated in recently completed
clinical trials and those with current or potential clinical utility. The diverse
roles of PET in clinical trails for drug development are also examined. (C) 2016
Elsevier Ireland Ltd. All rights reserved.
In order to study the impact of nucleus accumbens-1 (NAC1) expression on survival
in cancer cell and the molecular mechanism involved. NAC1 has been observed to be
up-regulated in human cancer, and to play an important role in progression and
recurrence of ovarian cancer. In this study, we investigated the regulatory role of
NAC1 in glycolysis and the effect of the NAC1-mediated glycolysis on cancer cell
survival. Cell biology, molecular biology, and pharmacology approaches and methods
were used in this study. We demonstrated: 1) NAC1 is a critical regulator of cancer
cell survival under hypoxic condition. Silencing of NAC1 leads to increase in the
cleaved caspase-3 and cleaved PARP, and a decline in cell viability and colony
formation when the cells were subjected to hypoxia; 2) NAC1 is a novel regulator of
glycolysis. Depletion of NAC1 leads to an increase in the concentration of glucose
in the culture medium, a decrease in the level of intercellular lactate; 3) NAC1
enhances the stability and protein level of HIF-1 alpha. Under hypoxia, NAC1
promotes cancer cell survival and glycolysis through strengthening the stability of
HIF-1 alpha.
Since molecular biology studies began, researches in biological science have
centered on proteins and genes at molecular level of a single cell. Cancer research
has also focused on various functions of proteins and genes that distinguish cancer
cells from normal cells. Accordingly, most contemporary anticancer drugs have been
developed to target abnormal characteristics of cancer cells. Despite the great
advances in the development of anticancer drugs, vast majority of patients with
advanced cancer have shown grim prognosis and high rate of relapse. To resolve this
problem, we must reevaluate our focuses in current cancer research. Cancer should
be considered as a systemic disease because cancer cells undergo a complex
interaction with various surrounding cells in cancer tissue and spread to whole
body through metastasis under the control of the systemic modulation. Human body
relies on the cooperative interaction between various tissues and organs, and each
organ performs its specialized function through tissue-specific cell networks.
Therefore, investigation of the tumor-specific cell networks can provide novel
strategy to overcome the limitation of current cancer research. This review
presents the limitations of the current cancer research, emphasizing the necessity
of studying tissue-specific cell network which could be a new perspective on
treating cancer disease, not cancer cells.
Myeloid-derived suppressor cells (MDSCs) cause paraneoplastic leukemoid reactions
and facilitate tumor cell metastasis. However, the interaction of MDSCs with tumor
cells in live tissue has not been adequately visualized. To accomplish this task,
we developed an intravital imaging protocol to observe metastasized tumor cells in
mouse lungs. For visualization of the activation of MDSCs, bone marrow cells
derived from transgenic mice expressing a Forster resonance energy transfer
biosensor for ERK were implanted into host mice. Under a two-photon excitation
microscope, numerous polymorphonuclear cells (PMNs) were found to infiltrate the
lungs of tumor-bearing mice in which 4T1 mammary tumor cells were implanted into
the footpads. By Forster resonance energy transfer imaging, we found ERK activation
in PMNs around the 4T1 tumor emboli in the lungs. Because antibody array analysis
implied the involvement of osteopontin (OPN) in the metastasis of 4T1 cells, we
further analyzed the effect of OPN knockdown. The OPN knockdown in 4T1 cells did
not affect the cell growth, but markedly suppressed lung metastasis of 4T1 cells
and ERK activation in PMNs in the lung. Intravenous injection of recombinant OPN
restored the lung metastasis of OPN-deficient 4T1 cells, suggesting that OPN
functioned in a paracrine manner. It has been reported that ERK activation of
neutrophils causes NETosis and that PMNs promote metastasis of tumor cells by
NETosis. In agreement with previous reports, the NETosis inhibitor DNase I
inhibited lung metastasis of 4T1 cells. These observations suggest that OPN
promotes metastasis of 4T1 cells by activating PMNs and inducing NETosis.
The lymph node (LN) is an important immune system in which a number of antigen-
presenting cells are present that induce rapid immune responses to foreign
antigens. While a great number of macrophages exist in lymph nodes, recent studies
using animal models have shown that lymph node sinus macrophages are associated
with the induction of anti-tumor immunity, playing a significant role in host
immune responses against tumor cells. In colorectal tumor, malignant melanoma, and
endometrial tumor, it was shown that a high density of CD169-positive macrophages
in the LN sinus was a predictive factor for better clinical prognosis. The
observations that the density of CD169-positive macrophages in the LN sinus was
positively associated with the density of infiltrating T or NK cells in tumor
tissues, indicates the significance of CD169-positive macrophages in anti-tumor
immune reactions of tumor patients. Moreover, antigen delivery targeting LN
macrophages is also considered to be promising approach for vaccination. In this
article, we have summarized the significance of CD169-positive LN macrophages in
anti-tumor immunity.
Objective: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing
to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK)
cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers.
CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study
aimed to determine whether treatment with CIK cells combined with valproic acid
(VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model
of HCC. Methods: Upregulation of natural killer group 2D (NKG2D) ligands (retinoic
acid early inducible 1 [RAE-1], mouse; major histocompatibility complex class I
polypeptide-related sequence A [MIC-A], human) were evaluated by FACS. VPA
concentrations that did not reduce tumor volume were calculated to avoid VPA
cytotoxicity in a C3H mouse model of HCC. CIK cells were generated from mouse
splenocytes using interferon gamma, a CD3 monoclonal antibody, and interleukin 2.
The potential synergistic effect of CIK cells combined with VPA was evaluated in
the mouse model and tissue pathology was investigated. Results: After 40h of
incubation with VPA, RAE-1 and MIC-A expression were increased in 4 HCC cell lines
compared with that in control (2.3-fold in MH-134, 2.4-fold in Huh-7, 3.7-fold in
SNU-761, and 6.5-fold in SNU-475). The maximal in vivo VPA dosage that showed no
significant cytotoxicity compared with control was 10mg/kg/day. CIK cells were well
generated from C3H mouse splenocytes. After 7d of treatment with CIK cells plus
VPA, a synergistic effect was observed on relative tumor volume in the mouse model
of HCC. While the relative tumor volume in untreated control mice increased to
11.25, that in the combination treatment group increased to only 5.20 (P = 0.047).
Conclusions: The VPA-induced increase in NKG2D ligands expression significantly
enhanced the effects of CIK cell therapy in a mouse model of HCC.
The progressive growth and spread of tumour cells in the form of metastases
requires an interaction of healthy host cells, such as endothelial cells,
fibroblasts, and other cells of mesenchymal origin with immune cells taking part in
innate and adaptive responses within the tumour lesion and entire body. The host
cells interact with tumour cells to create a dynamic tumour microenvironment, in
which healthy cells can both positively and negatively influence the growth and
spread of the tumour. The balance of cellular homeostasis and the effect of
substances they secrete on the tumour microenvironment determine whether the tumour
has a tendency to grow or disappear, and whether the cells remain within the lesion
or are capable of metastasis to other regions of the body. Intercellular
interactions also determine the tumour's susceptibility to radiation or other types
of cancer treatment. They may also be a rational explanation for differences in
treatment outcomes, in which some metastases regress and others progress in
response to the same treatment method.
Hanahan and Weinberg described six distinct biological properties of cancer cells
that enable tumor growth and metastasis. These properties were referred to as the
traditional hallmarks of cancer. Recent discoveries further elucidated hallmarks
including evasion of immune destruction by tumor cells that disrupt anticancer
response pathways. This review discusses cancer immunology and new treatment
strategies aimed at restoration of antitumor immune responses.
Introduction: Regulatory T cells (Treg) play an important role in suppressing anti-
immunity and their depletion has been linked to improved outcomes. To better
understand the role of Treg in limiting the efficacy of anti-cancer immunity, we
used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and
deplete Treg. Methods: Tumor bearing BALB/c FoxP3.dtr transgenic mice were
subjected to different treatment protocols, with or without Treg depletion and
tumor growth and survival monitored. Results: DTX specifically depleted Treg in a
transient, dose-dependent manner. Treg depletion correlated with delayed tumor
growth, increased effector T cell (Teff) activation, and enhanced survival in a
range of solid tumors. Tumor regression was dependent on Teffs as depletion of both
CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity
following Treg depletion was only observed, when consecutive doses of DTX were
given during peak CD8 T cell activation, demonstrating that Treg can be depleted on
multiple occasions, but only when CD8 T cell activation has returned to base line
levels. Finally, we show that even minimal Treg depletion is sufficient to
significantly improve the efficacy of tumor-peptide vaccination. Conclusions:
BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic
potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg
depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and
complete tumor regression at high doses, while enhancing the efficacy of tumor-
specific vaccination at low doses. Together this data highlight the importance of
Treg manipulation as a useful strategy for enhancing current and future cancer
immunotherapies.
The crosstalk between NK cells and M1 macrophages has a vital role in the
protection against infections and tumor development. However, macrophages in the
tumor resemble an M2 phenotype, and, at present, their effect on NK cells is less
clear. This study investigated whether tumor-associated macrophages (TAMs) have a
role in altering NK cell function and phenotype using in vitro cocultures of murine
NK cells with peritoneal or bone marrow-derived, M2-polarized macrophages or TAMs
isolated from spontaneous mouse breast tumors. We report here that both peritoneal
and bone marrow-derived M2 macrophages, as well as TAMs, substantially inhibit NK
cell activation and concordant cytotoxicity against tumor cells. The mechanism for
this inhibition was found to require contact between the respective cell types.
Both M2 macrophages and TAMs are producers of the immunosuppressive cytokine TGF-
beta. The inhibition of TGF-beta restored the cytotoxicity of NK cells in contact
with M2 macrophages, implicating TGF-beta in the mechanism for NK cell inhibition.
In addition to affecting NK cell function, TAMs also induced a
CD27(low)CD11b(high)-exhausted NK cell phenotype, which corresponds with the
reduced activation and cytotoxicity observed. This study reveals a novel
implication of TAMs in the tumor-associated inhibition of NK cell function by
demonstrating their capacity to directly alter NK cell cytotoxicity and phenotype
in a contact-dependent mechanism involving TGF-beta. These findings identify the
interaction between NK cells and TAMs as a prospective therapeutic target to
enhance NK cell effector function for effective NK cell cancer therapies.
The field of immune-oncology is rapidly progressing with new data being generated
across all research areas of this field. The American Association for Cancer
Research (AACR)'s Tumor Immunology and Immunotherapy meeting, the sixth in this
series, provides a forum for researchers from academia and industry, as well as
clinicians, to present their work to a global audience to enhance the understanding
of the immune response to cancer and to focus on how this response can be used for
disease treatment and prevention.
Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst
the most characterized tumour types. Hence, patients with PPGL have greatly
benefited from precision medicine for more than two decades. According to current
molecular biology and genetics-based taxonomy, PPGL can be divided into three
different clusters characterized by: Krebs cycle reprogramming with oncometabolite
accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling
pathway with increased tumour cell proliferation, invasiveness and migration (group
1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic
state (group 2). Categorization into these clusters is highly dependent on mutation
subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes
and outcomes have been described. Genetic screening tests have a documented
benefit, as different PPGL syndromes require specific approaches for optimal
diagnosis and localization of various syndrome-related tumours. Genotype-tailored
treatment options, follow-up and preventive care are being investigated. Future new
developments in precision medicine for PPGL will mainly focus on further
identification of driver mechanisms behind both disease initiation and malignant
progression. Identification of novel druggable targets and prospective validation
of treatment options are eagerly awaited. To achieve these goals, we predict that
collaborative large-scale studies will be needed: Pheochromocytoma may provide an
example for developing precision medicine in orphan diseases that could ultimately
aid in similar efforts for other rare conditions.
Background: Fatigue is highly prevalent after hematopoietic stem cell
transplantation (HCT). It has been described as intense and may last for years
following treatment. Objective: The aim of this study is to compare fatigue,
physical activity, sleep, emotional distress, cognitive function, and biological
measures in HCT survivors with persistent fatigue (n = 25) with age-and gender-
matched healthy controls with occasional tiredness (n = 25). Methods: Data were
collected using (a) objective, real-time assessments of physical activity and sleep
over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective
testing of cognitive functioning; and (d) biological measures. Differences between
groups were examined using multivariate analysis of variance. Results: Survivors of
HCT reported increased physical (P <.001), mental (P <.001), and overall (P <.001)
fatigue as well as increased anxiety (P <.05) and depression (P <.01) compared with
healthy controls. Red blood cell (RBC) levels were significantly lower in HCT
survivors (P <.001). Levels of RBC for both groups, however, were in the normal
range. Tumor necrosis factor-! (P <.001) and interleukin-6 (P <.05) levels were
significantly higher in HCT survivors. Conclusions: Persistent fatigue in HCT
survivors compared with healthy controls with occasional tiredness is accompanied
by increased anxiety and depression along with decreased RBC counts. Elevated tumor
necrosis factor-alpha and interleukin-6 levels may be important biomarkers.
Implications for Practice: This study provides preliminary support for the
conceptualization of fatigue as existing on a continuum, with tiredness anchoring
one end and exhaustion the other. Persistent fatigue experienced by HCT survivors
is more severe than the occasional tiredness of everyday life.
Many Siglecs function as inhibitory receptors on innate and adaptive immune cells
and may contribute to the attenuation of immune responses to tumors. Siglec 9 on
neutrophils and Siglec 7 on NK cells are prominent examples of inhibitory Siglecs
that can potentially dampen anti-tumor immunity. CD169 is a Siglec that may
function as an adhesion molecule and a facilitator of the recognition and
internalization of sialic acid decorated apoptotic bodies and exosomes derived from
tumors. It can potentially contribute to both the attenuation as well as the
facilitation of anti-tumor immunity. Siglecs have been best studied in the tumor
context in animal models of cancer. Modulators of Siglec function are likely to be
developed and investigated clinically in a cancer context over the next few years.
Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark
regulating gene transcription, alternative splicing and DNA repair. Genes encoding
H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved
in chromosomal translocations in cancer. Molecular biology studies have
demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs.
Structural studies of the catalytic SET domain of H3K36 KMTases have revealed
intriguing opportunities for design of small molecule inhibitors. Nevertheless,
potent inhibitors for most H3K36 KMTases have not yet been developed, underlining
the challenges associated with this target class. As we now have strong evidence
linking H3K36 KMTases to cancer, drug development efforts are predicted to yield
novel compounds in the near future.
Background: Adults, 65 years or older, are the most common age group diagnosed with
cancer. However, little is known about their beliefs (representations) regarding
treatment-related symptoms or how they make decisions to manage those symptoms at
home. Objective: The aim of this study is to explore symptom representation of
treatment-related symptoms in older adults with cancer. Methods: A total of 100
older adults in treatment for cancer completed a standardized measure of symptom
representation. Demographic and other patient variables were also collected.
Analysis of variance, t tests, and Pearson correlations were used for analysis.
Results: Fatigue was both the most common and most noted symptom; however, several
most noted symptoms were not common. Overall, older adults believed symptoms were
caused by either their cancer or treatment and were unsure if symptoms would last a
long time. They were able to recognize symptom consequences but were unsure about
their ability to control symptoms. Adults who reported more comorbid illnesses and
a higher number of symptoms believed that treatment-related symptoms had higher
consequences. Conclusions: Findings suggest that older adults experience symptom-
related consequences but question the impact that their actions will have on
symptom severity. This may contribute to older adult's lack of active symptom self-
management. Implications for Practice: Patient education strategies need to address
these representations and new interventions may need to be developed to reinforce
symptom consequences and empower older adults to self-manage symptoms.
Herein we report the synthesis and activity of an enzyme-directed immunostimulant
with immune cell activation mediated by -galactosidase, either exogenously added,
or on B16 melanoma cells. Covalent attachment of a -galactopyranoside to an
imidazoquinoline immunostimulant at a position critical for activity resulted in a
pro-immunostimulant that could be selectively converted by -galactosidase into an
active immunostimulant. The pro-immunostimulant exhibited -galactosidase-directed
immune cell activation as measured by NF-B transcription in RAW-Blue macrophages or
cytokine production (TNF, IL-6, IL-12) in JAWSII monocytes. Conversion of the pro-
immunostimulant into an active immunostimulant was also found to occur using -
galactosidase-enriched B16 melanoma cells. In co-culture experiments with either
immune cell line, -galactosidase-enriched B16 cells effected activation of
bystander immune cells.
Cancer is a complex disease: its pathology cannot be properly understood in terms
of independent players-genes, proteins, molecular pathways, or their simple
combinations. This is similar to many-body physics of a condensed phase that many
important properties are not determined by a single atom or molecule. The rapidly
accumulating large 'omics' data also require a new mechanistic and global
underpinning to organize for rationalizing cancer complexity. A unifying and
quantitative theory was proposed by some of the present authors that cancer is a
robust state formed by the endogenous molecular-cellular network, which is
evolutionarily built for the developmental processes and physiological functions.
Cancer state is not optimized for the whole organism. The discovery of crucial
players in cancer, together with their developmental and physiological roles, in
turn, suggests the existence of a hierarchical structure within molecular biology
systems. Such a structure enables a decision network to be constructed from
experimental knowledge. By examining the nonlinear stochastic dynamics of the
network, robust states corresponding to normal physiological and abnormal
pathological phenotypes, including cancer, emerge naturally. The nonlinear
dynamical model of the network leads to a more encompassing understanding than the
prevailing linear-additive thinking in cancer research. So far, this theory has
been applied to prostate, hepatocellular, gastric cancers and acute promyelocytic
leukemia with initial success. It may offer an example of carrying physics
inquiring spirit beyond its traditional domain: while quantitative approaches can
address individual cases, however there must be general rules/laws to be discovered
in biology and medicine.
Patients with cancer often experience a high symptom burden prior to the start of
treatment. As disease and treatment-related neurotoxicities appear to be additive,
targeting disease-related symptoms may attenuate overall symptom burden for cancer
patients and improve the tolerability of treatment. It has been hypothesized that
disease-related symptoms are a consequence of tumor-induced inflammation. We tested
this hypothesis using a syngeneic heterotopic murine model of human papilloma virus
(HPV)related head and neck cancer. This model has the advantage of being mildly
aggressive and not causing cachexia or weight loss. We previously showed that this
tumor leads to increased IL-6, IL-1 beta, and TNF-alpha expression in the liver and
increased 1L-1 beta expression in the brain. The current study confirmed these
features and demonstrated that the tumor itself exhibits high inflammatory cytokine
expression (e.g., IL-6, IL-1 beta, and TNF-alpha) compared to healthy tissue. While
there is a clear relationship between cytokine levels and behavioral deficits in
this model, the behavioral changes are surprisingly mild. Therefore, we sought to
confirm the relationship between behavior and inflammation by amplifying the effect
using a low dose of lipopolysaccharide (LPS, 0.1 mg/kg). In tumor-bearing mice LPS
induced deficits in nest building, tail suspension, and locomotor activity
approximately 24 h after LPS. However, these mice did not display an exacerbation
of LPS-induced weight loss, anorexia, or anhedonia. Further, while heightened serum
IL-6 was observed there was minimal priming of liver or brain cytokine expression.
Next we sought to inhibit tumor-induced burrowing deficits by reducing inflammation
using minocycline. Minocycline (similar to 50 mg/kg/day in drinking water) was able
to attenuate tumor-induced inflammation and burrowing deficits. These data provide
evidence in favor of an inflammatory-like mechanism for the behavioral alterations
associated with tumor growth in a syngeneic murine model of HPV-related head and
neck cancer. However, the inflammatory state and behavioral changes induced by this
tumor clearly differ from other forms of inflammation-induced sickness behavior.
(C) 2017 Elsevier Ltd. All rights reserved.
Cancer is a serious hazard to human health all around the world; however, many
current therapies remain toxic and poor. In view of the understanding of immunology
and tumor biology, cancer immunotherapy with minimal toxicity has been regarded as
a promising strategy for cancer treatment because of immune surveillance.
Unfortunately, the efficacy of immunotherapy was impeded and resisted due to the
tumor immune evasion mechanism. Hence, targeted cancer immunotherapy has been
proposed to tackle the tumor immune suppression and complexity of malignant tumor
cells. Nanotechnology-based immunotherapy has improved the limitations and enhanced
the therapeutic efficiency of traditional immunotherapy. This review illustrates
the recent progresses in immunotherapy based on nanotechnology, and reveals that
nanodevices could be utilized for active and passive cancer immunotherapy.
The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as
important regulators of tissue homeostasis, inflammation and repair, raise
questions regarding the presence and role of these cells in cancer tissues. In
addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC
family comprises non-cytolytic, cytokine-producing cells that are classified into
ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently
from natural killer cells, which are the prototypical members of ILC1 and whose
role in tumors is better established, the involvement of other ILC subsets in
cancer progression or resistance is still fuzzy and in several instances
controversial, since current studies indicate both context-dependent beneficial or
pathogenic effects. Here, we review the current knowledge regarding the involvement
of these novel ILC subsets in the context of tumor immunology, highlighting how ILC
subsets might behave either as friends or foes. (C) 2016 European Federation of
Immunological Societies. Published by Elsevier B.V. All rights reserved.
The purpose of this study is to evaluate if locus of control (LOC) predicts various
quality of life (QOL) and mental well-being measures among terminally ill cancer
patients at the time of palliative care consult. Multi-site analysis of patients
with advanced cancer being seen as new patients in a Palliative and Supportive Care
outpatient clinic. Patients completed the following surveys: locus of control (LOC)
scale, Functional Assessment of Chronic Illness Therapy-General (FACT-G),
Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital
Anxiety Depression Scale (HADS), and Herth Hope Index (HHI). Regression models were
created to examine the effect of LOC upon QOL, symptoms, and other measures of
mental well-being. These models adjusted for the effect of age, gender, race,
partnership status, education, and months since diagnosis as potential confounders.
This study enrolled 100 patients. After adjusting for site, race, and partnership
status, higher levels of LOC chance predicted decreased QOL (FACT-G) (p < 0.01).
Higher levels of LOC chance also correlated with increased depression and anxiety
(p < 0.01) and decreased meaning/peace and faith (p < 0.01). Additionally, higher
levels of LOC chance predicted decreased hope (HHI) (p < 0.001). Terminally ill
cancer patients with a high LOC chance may be at risk for decreased physical and
mental well-being at the end of life. Efforts should be made to identify these
patients and design interventions to increase their feeling of control over the
situation in order to improve physical and mental well-being at the end of life.
Metal complexes have been the subject of numerous investigations in oncology but,
despite the plethora of newly synthesized compounds, their precise mechanisms of
action remain generally unknown or, for the best, incompletely determined. The
continuous development of efficient and sensitive techniques in analytical
chemistry and molecular biology gives scientists new tools to gather information on
how metal complexes can be effective toward cancer. This review focuses on recent
findings about the anticancer mechanism of action of metal complexes and how the
ligands can be used to tune their pharmacological and physicochemical properties.
microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene
expression. Disturbance of microRNA expression may play a role in the initiation
and progression of certain diseases. A microRNA expression signature has been
identified that is associated with pancreatic cancer. This has been accomplished
with the application of real-time PCR profiling of over 200 microRNA precursors on
specimens of human pancreatic adenocarcinoma, paired benign tissue, normal
pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical
clustering was able to distinguish tumor from normal pancreas, pancreatitis and
cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal
pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were
aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including
microRNAs previously reported as differentially expressed in other human cancers
(miR-155, miR21, miR-221 and miR-222) as well as those not previously reported in
cancer (miR-376a and miR-301). Most of the top aberrantly expressed miRNAs
displayed increased expression in the tumor. Expression of the active, mature
microRNA was validated using a real-time PCR assay to quantify the mature microRNA
and Northern blotting. Reverse transcription in situ PCR showed that three of the
top differentially expressed miRNAs (miR-221, -376a and -301) were localized to
tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA
expression may offer new clues to pancreatic tumorigenesis and may provide
diagnostic biomarkers for pancreatic adenocarcinoma. (c) 2006 Wiley-Liss, Inc.
Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in
cancer survivors and decrease quality of life; however, the impact of the co-
occurrence of these conditions has garnered little attention. This study
investigated differences between obese and non-obese cancer survivors with CIPN and
predictors of symptom burden and pain. Patients with CIPN were administered the MD
Anderson Symptom Inventory and a modified version of pain descriptors from the
McGill Pain Inventory. Independent t tests assessed group differences between obese
and non-obese survivors, and linear regression analyses explored predictors of
patient outcomes. Results indicated a significant difference in symptom severity
scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08)
patients (t(37.86) = -2.49, p = .02). Significant differences were also found for a
total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus
non-obese (M = 2.42, SD = 2.69) participants (t(74) = -2.53, p = .01). Obesity was
a significant predictor of symptom severity and total pain descriptors endorsed.
Other significant predictors included age and months since treatment. Cancer
survivors with CIPN and co-occurring obesity may be more at risk for decreased
quality of life through increased symptom severity and pain compared to non-obese
survivors. This paper identified risk factors, including obesity, age, and months
since treatment, that can be clinically identified for monitoring distress in CIPN
patients. Future research should focus on the longitudinal relationship between
obesity and CIPN, and robust interventions to address the multifaceted issues faced
by cancer survivors.
BackgroundUDP-glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17) encodes
for an enzyme that modifies carcinogens, C19 steroids, xenobiotics, and anticancer
chemotherapeutic agents by glucuronidation. Pediatric cancers are much more
sensitive to anticancer agents than adult cancers. The aim of this study was
therefore to examine the effects of UGT2B17 deletion polymorphism on prognosis in
pediatric cancer. MethodsA total of 145 DNA samples were collected from children
with malignant disease. UGT2B17 copy number variant was determined on polymerase
chain reaction. Survival analysis was carried out to analyze the effects of UGT2B17
deletion on relapse-free rate in lymphoblastic and non-lymphoblastic malignancy.
ResultsUGT2B17 was deleted in 64% of children with lymphoblastic malignancy, but in
83% of children with non-lymphoblastic malignancy. Moreover, in non-lymphoblastic
malignancy, children without UGT2B17 deletion polymorphism had significantly higher
relapse rates than those with the deletion polymorphism (HR, 16.1; 95%CI: 1.67-154;
P = 0.016), which remained significant after adjustment for age, sex, underlying
disease, advanced stage, and adverse events (HR, 22.4; 95%CI: 1.10-454; P = 0.043).
There was a significant interaction between UGT2B17 deletion and non-lymphoblastic
malignancy. In the early subgroup, that is, stages 1-3 or standard/intermediate
risk, children without UGT2B17 deletion polymorphism had a higher relapse rate than
children with more advanced disease (log-rank test: P = 0.0004). ConclusionsUGT2B17
deletion polymorphism may improve the relapse-free rate in children with non-
lymphoblastic malignancy.
Precision medicine (PM) can be defined as a predictive, preventive, personalized,
and participatory healthcare service delivery model. Recent developments in
molecular biology and information technology make PM a reality today through the
use of massive amounts of genetic, 'omics', clinical, environmental, and lifestyle
data. With cancer being one of the most prominent public health threats in
developed countries, both the research community and governments have been
investing significant time, money, and efforts in precision cancer medicine (PCM).
Although PCM research is extremely promising, a number of hurdles still remain on
the road to an optimal integration of standardized and evidence-based use of PCM in
healthcare systems. Indeed, PCM raises a number of technical, organizational,
ethical, legal, social, and economic challenges that have to be taken into account
in the development of an appropriate health policy framework. Here, we highlight
some of the more salient issues regarding the standards needed for integration of
PCM into healthcare systems, and we identify fields where more research is needed
before policy can be implemented. Key challenges include, but are not limited to,
the creation of new standards for the collection, analysis, and sharing of samples
and data from cancer patients, and the creation of new clinical trial designs with
renewed endpoints. We believe that these issues need to be addressed as a matter of
priority by public health policymakers in the coming years for a better integration
of PCM into healthcare.
Major advances in the knowledge of cancer biology and its interactions with tumor
immune environment led to the emergence, in the last five years of new
immunotherapy-based treatment strategies in cancer patients. At the same time,
improvement in radiation technique and progress in radiobiology allowed in the last
decade to expand the applications of radiotherapy in a growing number of settings.
At present, there are strong theoretical basis to propose immune-enhanced radiation
therapy that may represent in the future a new paradigm of treatment, combining the
intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed
immune response with modern highly conformal and precise dose delivery, in order to
maximize response at the major site of disease and obtain durable disease control.
The aim of this review is to describe the principal mechanisms of immune modulation
of response to radiation and investigational strategies to harness the potential of
radiation-inducible immune response: radiation therapy is expected to be not just a
local treatment but the cornerstone of a multimodal strategy that might achieve
long-lasting tumor remission at the primary site and systemic efficacy metastatic
lesions. (C) 2017 Elsevier B.V. All rights reserved.
Background: Fatigue is one of the most debilitating adverse effects of cancer
therapy. Identifying biomarkers early during cancer therapy may help us understand
the biologic underpinnings of the persistence of fatigue following therapy.
Objective: We aimed to identify early biomarkers of fatigue by examining
correlations of levels of cytokines during external beam radiation therapy (EBRT)
with persistence of fatigue 1 year following treatment completion in men with
nonmetastatic prostate cancer (NM-PC). Methods: A sample of 34 men with
nonmetastatic prostate cancer scheduled to receive EBRT were followed up at
baseline (T1), midpoint of EBRT (T2), and 1 year following EBRT (T3). Demographic
and clinical data were obtained by chart review. The Functional Assessment of
Cancer TherapyYFatigue was administered to measure fatigue levels. Plasma cytokine
levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits.
Results: Significant correlations were observed between levels of interleukin 2
(IL-3), IL-8, IL-9, IL-10, IL-16, interferon + Yinduced protein 10, interferon
alpha 2, interferon +, and stromal cell-derived factor 1 alpha at T2 with worsening
of fatigue from T1 to T3. Conclusions: Immunological changes prior to chronic
fatigue development may reflect the long-term response to radiation therapyYinduced
damage. Implications for Practice: Early biomarkers for chronic fatigue related to
cancer therapy will help advance our understanding of the etiology of this
distressing symptom and will help nurses identify patients at risk of developing
chronic fatigue after cancer treatment. This information will also aid in patient
education, as well as symptom management.
In this paper, cotton seed oil deodorizer distillate (CSODD), was recovered to
obtain fatty acid sterol ester (FASE), which is one of the biological activated
substances added as human therapeutic to lower cholesterol. Esterification
reactions were carried out using Candida rugosa lipase as a catalyst, and the
conversion of phytosterol was optimized using response surface methodology. The
highest conversion (90.8 +/- 0.4%) was reached at 0.84 wt% enzyme load, 1: 25
solvent/CSODD mass ratio, and 44.2 degrees C after 12 H reaction. A kinetic model
based on the reaction rate equation was developed to describe the reaction process.
The activation energy of the reaction was calculated to be 56.9 kJ/mol and the
derived kinetic parameters provided indispensable basics for further study. The
optimization and kinetic research of synthesizing FASE from deodorizer distillate
provided necessary information for the industrial applications in the near future.
Experimental results showed that the proposed process is a promising alternative to
recycle sterol esters from vegetable oil deodorizer distillates in a mild,
efficient, and environmental friendly method. (C) 2016 International Union of
Biochemistry and Molecular Biology, Inc.
In the absence of steroid receptors and any known mechanism of gene regulation by
steroid hormones in Candida albicans, we did a genome-wide analysis of C. albicans
cells treated with progesterone using Eurogentec cDNA microarrays to find the
complete repertoire of steroid responsive genes. Northern blotting analysis was
employed to validate the genes that were differentially regulated by progesterone
in the microarray experiments. A total of 99 genes were found to be significantly
regulated by progesterone, among them 60 were up-regulated and 39 were down-
regulated. It was observed that progesterone considerably enhanced the expression
of multi-drug resistance (MDR) genes belonging to ATP Binding Cassette (CDR1 and
CDR2) super-family of multidrug transporters, suggesting a possible relationship
between steroid stress and MDR genes. Several genes associated with hyphal
induction and the establishment of pathogenesis were also found up-regulated. In
silico search for various transcription factor (TF) binding sites in the promoter
of the affected genes revealed that EFG1, CPH1, NRG1, TUP1, MIG1 and AP-1 regulated
genes are responsive to progesterone. The stress responsive elements (STRE; AG(4)
or C4T) were also found in the promoters of several responsive genes. Our data
sheds new light on the regulation of gene expression in C. albicans by human
steroids, and its correlation with drug resistance, virulence, morphogenesis and
general stress response. A comparison with drug induced stress response has also
been discussed.
In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During
this time, a 10-year-old German Shepherd dog presented to the referring
veterinarian with lethargy and coughing that quickly progressed to death. This
report describes the macroscopic and microscopic lesions and the molecular testing
performed to identify the novel North American H3N2 strain of canine influenza. The
larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane.
Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes
with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius
was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase
chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung
lobes. The neuraminidase gene sequence from the influenza virus isolated obtained
from this dog had 98% homology to the strain circulating in the Chicago area.
Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a
systemic disease, which can present with variable clinical signs, and
clinicopathological abnormalities. Clinical manifestations can range from
subclinical infection to very severe systemic disease. Leishmaniosis is categorized
as a neglected tropical disease and the complex immune responses associated with
Leishmania species makes therapeutic treatments and vaccine development challenging
for both dogs and humans. In this review, we summarize innate and adaptive immune
responses associated with L. infantum infection in dogs, and we discuss the
problems associated with the disease as well as potential solutions and the future
direction of required research to help control the parasite.
Canine parvovirus type 2 (CPV-2) comprises three antigenic subtypes (2a, 2b and 2c)
that have been reported in many countries. These subtypes cause serious disease in
dogs with characteristic gastroenteritis signs. Little information has been
documented in Africa about the genetic characterization of CPV-2. The aim of this
study was to detect and to characterize the CPV-2 subtypes circulating in dogs
admitted to Veterinary Clinics from two cities of Mozambique, Maputo and Matola, in
2010. A total of 40 field fecal samples were collected and tested for CPV-2 by
polymerase chain reaction assay. The partial length VP2 gene of the positive
samples were sequenced and genetically analyzed. Twenty-six (65%) fecal samples
were positive for CPV-2. The restriction fragment length polymorphism analysis was
also performed from positive samples and did not reveal the presence of CPV-2c
subtype. The results of the sequencing revealed the presence of CPV-2a (n = 9) and
CPV-2b (n = 17). No CPV-2 and CPV-2c were detected. Sequence analysis comparison
showed nucleotide identities of 99.6-100% among our CPV-2 isolates. Amino acid
analysis showed predicted amino acid changes. Phylogenetically, all of the CPV-2a
strains isolated formed a cluster together with South African and Nigerian
isolates. Most of Mozambican CPV-2b isolates also tended to cluster together with
South African isolates; however, four were more closely related to French strain
and one isolates to the American strain. The present study was the first to
characterize the CPV-2 circulating in the Mozambican dog population.
Aims: Recent evidence indicates that the defective ability to clear apoptotic cells
by macrophages (efferocytosis) and the resultant apoptotic cells accumulation in
atherosclerotic plaques play an important role during the progression of unstable
plaques. The cannabinoid type 2 receptor (CB2), has recently been emerging as a new
target to reduce vulnerability and promote stability of plaques, however, the
underlying mechanisms have not been studied in detail. In the present study, we
investigated whether selective activation of CB2 improves efferocytosis of
macrophages. Main methods: RAW264.7 macrophage line and primary-isolated peritoneal
lavage macrophages from C57bI/6J mice were cultured. The efferocytosis of
macrophages was analyzed by using flow cytometry or confocal microscopy; and the
possible mechanisms involved in regulation of efferocytosis were also explored by
using molecular biology methods. Key findings: We found that JWH-133 and HU-308,
selective agonists of CB2 receptor, concentration-dependently increased the
phagocytosis of apoptotic cells in normal-cultured and oxidative low density
lipoprotein (OxLDL) - loaded RAW264.7 and primary macrophages. JWH-133 and HU-308
also up-regulated expressions of tyrosine kinase family phagocytic receptors MerTK,
Tyro3 and Axl, reduced levels of TNF-alpha and reactive oxygen species (ROS)
induced by OxLDL, and inhibited activation of RhoA GTPase. Significance: The
selective activation of CB2 improves efferosytosis of normal-cultured and OxLDL-
loaded macrophages, which might provide a novel mechanism on how CB2 activation
reduces vulnerability and promotes stability of atherosclerotic plaques. (C) 2016
Elsevier Inc All rights reserved.
Animal and human studies suggest that initial expression of maternal behaviour
depends on oxytocin and dopamine systems. However, the mechanism by which these
systems affect parenting behaviours and the timing of these effects are not well
understood. This article explores the role of mothers' executive function in
mediating the relation between oxytocin and dopamine gene variants and maternal
responsiveness at 48 months post-partum. Participants (n= 157) were mothers
recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study,
which assesses longitudinally two cohorts of mothers and children in Canada. We
examined single nucleotide polymorphisms (SNPs) related to the dopamine and
oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298),
assessed mothers' decision-making at 48 months using the Cambridge Neurological
Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from
videotaped interactions during the Etch-A-Sketch co-operation task. Mediation
analyses showed that OXTR rs2254298 A-carriers had an indirect effect on positive
parenting which was mediated by mothers' performance on decision-making task
(estimate= 0.115, P < 0.005), while OXTR rs2254298 A-carriers had both direct and
indirect effects on physically controlling parenting, also mediated through
enhanced performance on decision-making (estimate=-0.059, P0.05). While oxytocin
has previously been associated with only the early onset of maternal behaviour, we
show that an OXTR polymorphism is involved in maternal behaviour at 48 months post-
partum through mothers' executive function. This research highlights the importance
of the oxytocin system to maternal parenting beyond infancy.
A novel weak capacitance measurement system is proposed to measure the gas-solid
two-phase flows. The system is mainly consist of capacitance sensor, Micro-
programmed Control Unit (MCU), Direct Digital Synthesizer (DDS), operational
amplifier, analogue multiplier and low-pass filter. Since the stray capacitance is
much larger than the variation of measured capacitance, the stray capacitance
should be eliminate by the measurement system. The experimental results show that
the system meets the application requirement, and has good linearity, high
measurement accuracy and stray-immune. The result of the percentage error is about
0.6% and the non-linear error is less than 1.5%. The sampling rate which is related
to the frequency of the signal generator and the MCU clock can reach 500 kps.
In this work, capacitance multiplier is designed by using negative current feedback
operational amplifier. The proposed circuit has low sensitivity to temperature
variations. The simulation results are obtained by PSPICE simulations verify the
theoretical analysis between 100KHz-6MHz.
Phase-sensitive detection circuit tests signals according to the correlation of the
reference signal and the input signal. The noise is eliminated by the independence
between the reference signal and the noise signal. The sensitivity of the detector
is improved significantly by the suppression of the noise. In this work, a phase-
sensitive detection circuit is designed for seismometer, which possesses the
characteristics of low-input noise, variable-output gain and high sensitivity. The
feasibility of this phase-sensitive detection circuit is verified by the Multisim
and the signal-to-noise ratio is satisfactory.
Vapor detection using highly sensitive miniaturized resonant sensors is of great
interest for many applications, including consumer, industrial, and environmental
applications. An operational-amplifier-based multichannel oscillator that
interfaces with a 50-MHz capacitive micromachined ultrasonic transducer array is
presented for chemical sensing applications. The circuit was implemented in a 0.18-
mu m CMOS technology to reduce power consumption, number of wires, and active area
per channel. The presented integrated circuit also addresses the potential-
frequency-locking problem between channels by allowing the open-loop gain to be
adjustable off-chip. The feasibility of the developed oscillator for the chemical
sensing application is demonstrated. Two channels that were operated simultaneously
achieved excellent volume sensitivities of 8.5 x 10(-4)%/Hz and 3.9 x 10(-4)%/Hz,
respectively, to relative humidity in N-2.
This paper presents a capacitive sensing system, addressing the issue of collision
avoidance in partially modelled or unknown robot-assisted industrial environment by
means of object distance measurement, motion tracking, and surface profile
detection. The sensor consists of a mesh of multiple electrodes, a digital control
module, a capacitance to digital converter, and a data processing module. The mesh
is composed of 16 metal squares organized to form a 4x4 capacitor matrix. The
electrode connections within the matrix can be reconfigured at run time by the
digital control logic to provide multiple sense functionalities. Statistical
regression models are applied to derive the distance and track the motion. A
machine learning algorithm (Support Vector Machine, SVM) is applied to measured
data to classify surface profiles. The fabricated sensing system has the ability of
detecting objects at distances up to 20 cm from the sensor, and shows accuracy over
90% in profile recognition.
This brief presents an ultra-low-power low-noise chopped capacitively coupled
instrumentation amplifier (CCIA) that is suitable for neural recording
applications. An active high-pass filter is embedded in the ripple reduction loop
(RRL) to suppress the residual noise and relax the capacitor size. Multiple
chopping is employed to further reduce the residual output ripple due to the RRL
offsets. A dc servo loop (DSL) using a 14-nA pseudofeedback amplifier is proposed
to achieve a subhertz high-pass corner while using only a 15-pF on-chip capacitor.
The complete CCIA is implemented in a standard 0.18-mu m CMOS process. It occupies
an area of 0.23 mm(2) (including the DSL) and consumes 1.7 mu A froma 1.25-V
supply, achieving a noise efficiency factor of 2.9 that compares favorably with the
state of the art.
Optimal sizing of residential photovoltaic (PV) generation and energy storage (ES)
systems is a timely issue since government polices aggressively promote installing
renewable energy sources in many countries, and small-sized PV and ES systems have
been recently developed for easy use in residential areas. We in this paper
investigate the problem of finding the optimal capacities of PV and ES systems in
the context of home load management in smart grids. Unlike existing studies on
optimal sizing of PV and ES that have been treated as a part of designing hybrid
energy systems or polygeneration systems that are stand-alone or connected to the
grid with a fixed energy price, our model explicitly considers the varying
electricity price that is a result of individual load management of the customers
in the market. The problem we have is formulated by a D-day capacity planning
problem, the goal of which is to minimize the overall expense paid by each customer
for the planning period. The overall expense is the sum of expenses to buy
electricity and to install PV and ES during D days. Since each customer wants to
minimize his/her own monetary expense, their objectives look conflicting, and we
first regard the problem as a multi-objective optimization problem. Additionally,
we secondly formulate the problem as a D-day noncooperative game between customers,
which can be solved in a distributed manner and, thus, is better fit to the pricing
practice in smart grids. In order to have a converging result of the best-response
game, we use the so-called proximal point algorithm. With numerical investigation,
we find Pareto-efficient trajectories of the problem, and the converged game-
theoretic solution is shown to be mostly worse than the Pareto-efficient solutions.
Capripoxviruses (CaPVs), consisting of Sheeppox virus (SPV), Goatpox virus (GPV),
and Lumpy skin disease virus (LSDV) species, cause economically significant
diseases in sheep, goats, and cattle, respectively. Quantitative real-time
polymerase chain reaction (qPCR) assays are routinely used for rapid detection of
CaPVs in surveillance and outbreak management programs. We further modified and
optimized 2 previously published CaPV qPCR assays, referred to as the Balinsky and
Bowden assays, by changing commercial PCR reagents used in the tests. The modified
assays displayed 100% analytical specificity and showed no apparent changes in
analytical sensitivities for detection of CaPVs compared with the original assays.
Diagnostic sensitivities, assessed using 50 clinical reference samples from
experimentally infected sheep, goats, and cattle, improved from 82% to 92% for the
modified Balinsky assay and from 58% to 82% for the modified Bowden assay. The
modified qPCR assays were multiplexed for detection of beta-actin as an indicator
for potential false-negative results. The multiplex modified qPCR assays exhibited
the same diagnostic sensitivities as the singleplex assays suggesting their utility
in the detection of CaPVs.
Lentivirus-mediated transduction of autologous T cells with a chimeric antigen
receptor (CAR) to confer a desired epitope specificity as a targeted immunotherapy
for cancer has been among the first human gene therapy techniques to demonstrate
widespread therapeutic efficacy. Other approaches to using gene therapy to enhance
antitumor immunity have been less specific and less effective. These have included
amplification, marking, and cytokine transduction of tumor infiltrating
lymphocytes, recombinant virus-based expression of tumor antigens as a tumor
vaccine, and transduction of antigen-presenting cells with tumor antigens. Unlike
any of those methods, the engineering of CAR T cells combine specific monoclonal
antibody gene sequences to confer epitope specificity and other T-cell receptor and
activation domains to create a self-contained single vector approach to produce a
very specific antitumor response, as is seen with CD19-directed CAR T cells used to
treat CD19-expressing B-cell malignancies. Recent success with these therapies is
the culmination of a long step-wise iterative process of improvement in the design
of CAR vectors. This review aims to summarize this long series of advances in the
development of effective CAR vector since their initial development in the 1990s,
and to describe emerging approaches to design that promise to enhance and widen the
human gene therapy relevance of CAR T-cell therapy in the future.
Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-
2), has affected the commercial production of the goldfish Carassius auratus and
gibelio carp Carassius auratus gibelio. High water temperature treatments are
reported to reduce the mortality rate of infected goldfish and elicit immunity in
the survivors. To define the mechanism by which this intervention induces
resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related
to both species and has been used in fish immunology, may represent a promising
model species. In this study, we investigated the susceptibility of clonal ginbuna
strains to CyHV-2 and the effect of high water temperature treatment on infected
ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25
degrees C caused 100% mortality in ginbuna strains, which was accompanied by
histopathological changes typical of HVHN. Both infected ginbuna S3n strain and
goldfish, exposed to high temperature for 6 days [shifting from 25 degrees C
(permissive) to 34 degrees C (non-permissive)], showed reduced mortalities after
the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction
of immunity. It was concluded that ginbuna showed a similar susceptibility and
disease development in CyHV-2 infection compared to goldfish, suggesting that
ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.
Background: Antimicrobial resistance is a global public health challenge and
carbapenem resistance, in particular, is considered an urgent global health threat.
This study was carried out to give a bibliometric overview of literature on
carbapenem resistance. In specific, number of publications, top productive
countries and institutes, highly cited articles, citation analysis, co-authorships,
international collaboration, top active authors, and journals publishing articles
on carbapenem resistance were analyzed and discussed. Methods: Specific keywords
pertaining to carbapenem resistance were used in Scopus database. Quantitative and
qualitative analysis of retrieved data were presented using appropriate
bibliometric indicators and visualization maps. Results: A total of 2617 journal
articles were retrieved. The average number of citations per article was of 21.47.
The growth of publications showed a dramatic increase from 2008 to 2015.
Approximately 9 % of retrieved articles on carbapenem resistance were published in
Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by
102 different countries. The United States of America (USA) contributed most with
437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When
productivity was stratified by population size, Greece ranked first followed by
France. Greece also ranked first when data were stratified by gross domestic
product (GDP). Asian countries have lesser international collaboration compared
with other countries in the top ten list. Five of top ten productive institutes
were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians
(China and South Korea). Other active institutes included an Israeli and a
Brazilian institute. Four of the top ten cited articles were published in
Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet
Infectious Diseases. Conclusion: There was a dramatic increase in number of
publications on carbapenem resistance in the past few years. These publications
were produced from different world regions including Asia, Europe, Middle East, and
Latin America. International collaboration needs to be encouraged particularly for
researchers in Asia. Molecular biology and epidemiology dominated the theme of the
top ten cited articles on carbapenem resistance. This bibliometric study will
hopefully help health policy makers in planning future research and allocating
funds pertaining to carbapenem resistance.
The objective of this study was to reveal the molecular mechanism involved in
carbapenem resistance and virulence of a K2 Klebsiella pneumoniae clinical isolate
24835. The virulence of the strain was determined by in vitro and in vivo methods.
The de novo whole-genome sequencing technology and molecular biology methods were
used to analyze the genomic features associated with the carbapenem resistance and
virulence of K. pneumoniae 24835. Strain 24835 was highly resistant to carbapenems
and belonged to ST14, exhibited hypermucoviscous and unique K2-aerobactin-kfu-rmpA
positive phenotype. As the only carbapenemase gene in strain 24835, bla(NDM -5) was
located on a 46-kb IncX3 self-transmissible plasmid, which is a very close relation
of pNDM-MGR194 from India. Genetic context of blaNDM 5 in strain 24835 was closely
related to those on IncX3 plasmids in various Enterobacteriaceae species in China.
The combination of multiple virulence genes may work together to confer the
relative higher virulence in K. pneumoniae 24835. Significantly increased
resistance to serum killing and mice mortality were found in the virulent New Delhi
metallo-beta -lactamase ( NDM)-producing K. pneumoniae strain compared to the other
NDM-producing K. pneumoniae strain. Our study provides basic information of
phenotypic and genomic features of K. pneumoniae 24835, a strain displaying
carbapenem resistance and relatively high level of virulence. These findings are
concerning for the potential of NDM-like genes to disseminate among virulent K.
pneumoniae isolates.
Background: Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have
been continuously growing and pose challenge to health institution globally.
Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB
which has limited treatment options and higher mortality compared to those of
sensitive strains. We report an increased burden of CRE fecal carriage at a
hospital in the North-eastern region of Malaysia. Methods: A retrospective
descriptive study from August 2013 to December 2015 was conducted in the Medical
Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which
is a tertiary teaching hospital with more than 700 beds. This hospital treats
patients with various medical and surgical conditions. Suspected CRE from any
clinical specimens received by the laboratory was identified and confirmed using
standard protocols. Polymerase chain reaction (PCR) assay was performed to
determine the genotype. Results: Altogether, 8306 Enterobacteriaceae was isolated
from various clinical specimens during the study period and 477/8306 (5.74%) were
CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which
Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly
isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%);
blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-
six isolates were subjected to genotype determination and., 112/136 (82.4%) showed
positive detection of New Delhi metallo-beta-lactamase 1 (NDM-1) gene (bla(NDM1)).
Conclusion: The study noted a high numbers of CRE isolated especially from rectal
swabs. Active screening results in significant cost pressures and therefore should
be revisited and revised, especially in low resource settings.
The physicochemical properties of anode material are important for the electron
transfer of anode bacteria and electricity generation of microbial fuel cells
(MFCs). In this work, carbon cloth anode was pretreated with isopropanol, hydrogen
peroxide (H2O2) and sodium hypochlorite (NaOCl) in order to reduce the anode
functional groups. The influence of functional groups on the electrochemical
properties of carbon cloth anode and power generation of MFCs was investigated. The
anode pretreatments removed the surface sizing layer of carbon cloth and
substantially reduced the contents of C-O and pyridinic/pyrrolic N groups on the
anode. Electrochemical impedance spectroscopy and cyclic voltammetry analyses of
the biofilm-matured anodes revealed an enhanced electrochemical electron transfer
property because of the anode pretreatments. As compared with the untreated control
(612 +/- 6mWm(-2)), the maximum power density of an acetate-fed single-chamber MFC
was increased by 26% (773 +/- 5mWm(-2)) with the isopropanol treated anode.
Additional treatment with H2O2 and NaOCl further increased the maximum power output
to 844 +/- 5mWm(-2) and 831 +/- 4 mWm(-2). A nearly inverse liner relationship was
observed between the contents of C-O and pyridinic/pyrrolic N groups on anodes and
the anodic exchange current density and the power output of MFCs, indicating an
adverse effect of these functional groups on the electricity production of anodes.
Results from this study will further our understanding on the microbial interaction
with carbon-based electrodes and provide an important guidance for the modification
of anode materials for MFCs in future studies. Copyright (c) 2016 John Wiley &
Sons, Ltd.
China is currently the world's largest emitter of carbon dioxide. Considered as a
large agricultural country, carbon emission in China's agriculture sector keeps on
growing rapidly. It is, therefore, of great importance to investigate the driving
forces of carbon dioxide emissions in this sector. The traditional regression
estimation can only get "average" and "global" parameter estimates; it excludes the
"local" parameter estimates which vary across space in some spatial systems.
Geographically weighted regression embeds the latitude and longitude of the sample
data into the regression parameters, and uses the local weighted least squares
method to estimate the parameters point-by-point. To reveal the nonstationary
spatial effects of driving forces, geographically weighted regression model is
employed in this paper. The results show that economic growth is positively
correlated with emissions, with the impact in the western region being less than
that in the central and eastern regions. Urbanization is positively related to
emissions but produces opposite effects pattern. Energy intensity is also
correlated with emissions, with a decreasing trend from the eastern region to the
central and western regions. Therefore, policymakers should take full account of
the spatial nonstationarity of driving forces in designing emission reduction
policies.
As the world's fastest growing major economy and home to nearly one-fifth of the
worlds population, India a vibrant democracy is in the midst of a profound
transformation and rapid urbanization. Urbanization improves the quality of life of
people while promoting economic growth; however it also increases energy
consumption and is capable of generating an energy crisis. Urbanization has a
significant impact on Carbon Dioxide (CO,) emissions as well. This paper
empirically investigates the temporal, dynamic and causal relationships between
urbanization, energy consumption and emissions. The study also aims to understand
the urbanization process in India, in terms of the level and tempo of urbanization
and the urban growth morphology, by utilizing the census data of 1901-2011. The
rise in energy consumption and resulting emissions in the context of rapid
urbanization is also reviewed. To address these problems the study recommends a
series of measures and a set of strategies that include energy intensity and
emission intensity reduction measures through continuous monitoring, information
feedback systems, introduction of industrial energy quota management, incentives
for energy efficient facilities, shutting down of inefficient facilities, and
setting up of smart residential buildings. Reduction of distribution and
transmission losses by investing in smart grids is also highly recommended.
Power-to-X concepts promise a reduction of greenhouse gas emissions simultaneously
guaranteeing a safe energy supply even at high share of renewable power generation,
thus becoming a cornerstone of a sustainable energy system. Power-to-syngas, that
is, the electro-chemical conversion of steam and carbon dioxide with the use of
renewably generated electricity to syngas for the production of synfuels and high-
value chemicals, offers an efficient technology to couple different energy-intense
sectors, such as "traffic and transportation" and "chemical industry". Syngas
produced by co-electrolysis can thus be regarded as a key-enabling step for a
transition of the energy system, which offers additionally features of CO2-
valorization and closed carbon cycles. Here, we discuss advantages and current
limitations of low-and high-temperature co-electrolysis. Advances in both
fundamental understanding of the basic reaction schemes and stable high-performance
materials are essential to further promote co-electrolysis.
Climate models predict increased frequency and intensity of storm events, but it is
unclear how extreme precipitation events influence the dynamics of soil fluxes for
multiple greenhouse gases (GHGs). Intact soil mesocosms (0-10 cm depth) from a
temperate forested watershed in the piedmont region of Maryland [two upland forest
soils, and two hydric soils (i.e., wetland, creek bank)] were exposed to
experimental water pulses with periods of drying, forcing soils towards extreme wet
conditions under controlled temperature. Automated measurements (hourly resolution)
of soil CO2, CH4, and N2O fluxes were coupled with porewater chemistry analyses
(i.e., pH, Eh, Fe, S, NO3 (-)), and polymerase chain reaction-denaturing gradient
gel electrophoresis to characterize changes in microbial community structure.
Automated measurements quantified unexpected increases in emissions up to 245% for
CO2 (Wetland), >23,000% for CH4 (Creek), and >110,000% for N2O (Forest Soils)
following pulse events. The Creek soil produced the highest soil CO2 emissions, the
Wetland soil produced the highest CH4 emissions, and the Forest soils produced the
highest N2O emissions during the experiment. Using carbon dioxide equivalencies of
the three GHGs, we determined the Creek soil contributed the most to a 20-year
global warming potential (GWP; 30.3%). Forest soils contributed the most to the
100-year GWP (up to 53.7%) as a result of large N2O emissions. These results
provide insights on the influence of extreme wet conditions on porewater chemistry
and factors controlling soil GHGs fluxes. Finally, this study addresses the need to
test biogeochemical thresholds and responses of ecosystem functions to climate
extremes.
Luminescent carbon nanodots (CDots) have attracted much attention, but their
luminescence is usually quenched in solid state. Efficient green or yellow emissive
CDot-based phosphors are scarce. In this work, green emissive CDot@NaCl composite
phosphors were fabricated through a convenient, low cost and eco-friendly way by
embedding green emissive CDots (g-CDot) in NaCl crystals. With the protection of
NaCl host, the g-CDot@NaCl composite phosphors exhibit good photostability,
significant resistance to organic solvents, and improved photoluminescence quantum
yields up to 25%. White light-emitting diodes with tunable color temperatures
(3944-5478 K) and CIE coordinates have been realized based on the g-CDot@NaCl
composite phosphors. (C) 2017 Elsevier Inc. All rights reserved.
In this study a pseudo comprehensive carbon footprint model for fossil fuel power
plants is presented. Parameters which their effects are considered in this study
include: plant type, fuel type, fuel transmission type, internal consumption of the
plant, degradation, site ambient condition, transmission and distribution losses.
Investigating internal consumption, degradation and site ambient condition effect
on carbon footprint assessment of fossil fuel power plant is the specific feature
of the proposed model. To evaluate the model, a sensitivity analysis is performed
under different scenarios covering all possible choices for investigated
parameters. The results show that carbon footprint of fossil fuel electrical energy
that is produced, transmitted and distributed, varies from 321 g CO(2)eq/kWh to 980
g CO2 equivalent /kWh. Carbon footprint of combined cycle with natural gas as main
fuel is the minimum carbon footprint. Other factors can also cause indicative
variation. Fuel type causes a variation of 28%. Ambient condition may change the
result up to 13%. Transmission makes the carbon footprint larger by 4%. Internal
consumption and degradation influence the result by 2 and 2.5%, respectively.
Therefore, to minimize the carbon footprint of fossil fuel electricity, it is
recommended to construct natural gas ignited combined cycles in low lands where the
temperature is low and relative humidity is high. And the internal consumption is
as least as possible and the maintenance and overhaul is as regular as possible.
This paper presents an enhancement of a previous Conventional Carbon Nanotube Field
Effect Transistor (C-CNTFET) compact model proposed by Raychowdhury et al. This
improvement consists in three new extensions to the previous work: first, by adding
adequate electronic noise sources to the C-CNTFET modelling the electronic noise at
the source and drain access regions; i.e., thermal noise and the electronic noise
in the device channel; i.e., flicker and shot noise, second by adopting a simple
and a fast analytical calculating approach that models the Schottky barrier (SB) at
the source and drain metal access and the semiconducting carbon nanotube (CNT)
interface by including adequate noise sources, and finally by proposing a generic
compact model that is suitable for circuit simulation purpose. In order to validate
the proposed SB-CNTFET compact model, electrical simulation results are compared
with literature reported experimental results. Good agreement is observed over a
large range of the device biases. For the SB assessment, an operational amplifier
(Op Amp) circuit has been designed and simulated using the SB-CNTFET compact model.
A significant degradation on the Op Amp's performances is observed for large SB. As
SB proprieties is associated with the CNT geometry; i.e., diameter, and to prevent
circuit's performances degradation, an optimization work has been carried out to
provide the circuit design community with the suitable CNT diameters that should be
made.
This paper presents a computationally efficient Raychowdhury compact model for the
Schottky barrier (SB) carbon nanotube field-effect transistor (CNTFET). In order to
achieve an accurate compact model, shot noise sources is added. Then, for the
assessment of the SB on circuit performances, an operational amplifier (Op-Amp) is
designed using the SB-CNTFET compact model, and results are compared with a
conventional CNTFET.
Carbonaceous stationary phases have gained much attention for their peculiar
selectivity and robustness. Herein we report the fabrication and application of a
graphene-coated polymeric stationary phase for anion exchange chromatography. The
graphene-coated particles were fabricated by a facile evaporation reduction method.
These hydrophilic particles were proven appropriate substrates for grafting of
hyperbranched condensation polymers (HBCPs) to make pellicular anion exchangers.
The new phase was characterized by zeta potentials, Fourier transform infrared
spectroscopy, thermogravimetry and scanning electron microscope. Frontal
displacement chromatography showed that the capacities of the anion exchangers were
tuned by both graphene amount and HBCPs layer count. The chromatographic
performance of graphene-coated anion exchangers was demonstrated with separation of
inorganic anions, organic acids, carbohydrates and amino acids. Good
reproducibility was obtained by consecutive injections, indicating high chemical
stability of the coating. (C) 2017 Published by Elsevier B.V.
The innate immune system, which includes toll-like receptor (TLR) signaling, plays
an important role in inflammation and oncogenesis. Although TLR common adaptor
myeloid differentiation factor 88 (MyD88) is known to have multiple effects on
carcinogenesis, the role of MyD88 in hepatocarcinogenesis remains unknown. In this
study, MyD88 expression was examined in 105 samples of human hepatocellular
carcinoma (HCC) tissue by immunohistochemistry, Western blot, and quantitative
reverse-transcriptase polymerase chain reaction methods. The relationships between
MyD88 expression and clinical and pathological parameters were analyzed. The
results showed that attenuated expression of MyD88 in HCC tissue tumor cells was
significantly related to hepatitis B virus infection, large tumor size, positive
vascular invasion, and intrahepatic metastasis (P<0.05). Western blot analysis of
MyD88 protein in nine normal livers and 28 HCCs showed gender disparity (P<0.01,
P<0.05), and attenuated expression in cirrhotic livers (P<0.05). Low expression of
MyD88 mRNA was evident in HCCs with vascular invasion (P<0.01). In contrast to
previous reports, these results suggest that attenuated expression of MyD88 in HCC
is associated with tumor progression.
Background: Gene polymorphisms are associated with sensitivity to platinum drugs.
This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2
rs717620 locus, and the sensitivity of patients with advanced non-small cell lung
cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. Material/Methods:
The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients
were assessed by polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients
and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using
progression-free survival (PFS) and overall survival (OS) as the major outcome
indicators. Results: The median PFS of patients with advanced NSCLC was 6.9 months
and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier
survival analysis indicated that survival time of patients with GSTP1 AG + GG was
significantly longer than in patients with AA gene (P<0.05), and survival time of
patients with ABCC2 CT + TT was significantly longer than in patients with the CC
gene (P<0.05). Conclusions: Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be
used to predict the outcomes of Uygur patients with advanced NSCLC who have
received platinum-based chemotherapy. Additionally, this information could be used
to guide the individualized treatment of Uygur patients with advanced NSCLC.
Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the
growth, invasion and metastasis of tumor cells. However, to date little is known
about the oncogenic mechanisms of CAFs. This study aimed to identify the
microenvironmental factors involved in tumor development and progression directed
by CAFs in liver metastases. Tissue samples collected from 20 patients with
colorectal liver metastases were used in this study. Histological and morphological
characterization of the samples was performed using hybridization and
immunohistological assays. The m RNA expression of a-smooth muscle actin (alpha-
SMA) was measured by northern blotting. The expression of plasminogen activator
inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA).
As a result, co-expression of Thy-1 (CD90) and alpha-SMA was identified in CAFs,
while normal liver samples were negative for alpha-SMA and Thy-1. Compared with
epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the
expression of alpha-SMA increased significantly following transforming growth
factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF)
caused a significant suppression of alpha-SMA expression (P<0.05). PAI-1 expression
was significantly lower in unstimulated fibroblasts compared to TGF-1-treated
fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher
in CAFs from the patient samples compared with the healthy controls. Taken
together, our findings suggest that CAFs may be important in migration, matrix
degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the
activation of PAI-1 transcription in CAFs.
The opportunity to distinguish an accurate set of genes associated with multigenic
diseases such as cardiomyopathies or cardiac arrhythmias was very limited before
the genomic era. Numerous methods of measuring RNA abundance exist, including
northern blotting, multiplex polymerase chain reaction (PCR), and quantitative
real-time reverse transcriptase-PCR. However, these techniques might be used to
assess the expression levels of only 10-50 genes at time. Today, DNA microarrays
provide us with opportunity to simultaneously analyze tens of thousands of genes,
giving a remarkable possibility to investigate the genomic contribution to
cardiovascular diseases. A particular tissue at any stage of health or disease may
be used to generate a genomic profile. Microarray techniques are already used in
infectious diseases, oncology, and pharmacology to facilitate clinicians, risk-
stratify patients, as well as to predict and assess therapeutic responses to drugs.
In this paper, we describe recent advances in the use of various types of
microarray technique in the diagnosis of arrhythmogenic heart disease. We also
highlight other strategies and methods of differential gene typing comparing with
pros and cons of microarray analysis.
Background: An impairment of cardiovascular function in streptozotocin (STZ)-
diabetic rats has been mentioned within 5 days to 3 months of induction. ATP
sensitive potassium (K-ATP) channels are expressed on cardiac sarcolemmal
membranes. It is highly responsive to metabolic fluctuations and can have effects
on cardiac contractility. The present study attempted to clarify the changes of
cardiac K-ATP channels in diabetic disorders. Methods: Streptozotocin-induced
diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of
glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24
hr) were used to examine the effect of hyperglycemia on cardiac function and the
expression of K-ATP channels. K-ATP channels expression was found to be linked to
cardiac tonic dysfunction, and we evaluated the expression levels of K-ATP channels
by Western blot and Northern blot analysis. Results: The result shows diazoxide
produced a marked reduction of heart rate in control group. Furthermore, the
methods of Northern blotting and Western blotting were employed to identify the
gene expression of K-ATP channel. Two subunits of cardiac K-ATP channel (SUR2A and
kir 6.2) were purchased as indicators and showed significantly decreased in both
diabetic rats and high glucose treated rat cardiac myocytes. Correction of
hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K-ATP
in these diabetic rats. Conclusions: Both mRNA and protein expression of cardiac K-
ATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This
phenomenon leads to result in desensitization of some K-ATP channel drugs.
The morbidity and mortality of heart failure with preserved left ventricular
ejection fraction (HFpEF) were similar to those of systolic heart failure, but the
pathogenesis of HFpEF remains poorly understood. It was demonstrated that, in
systolic heart failure, microRNA-21 (miR-21) could inhibit the apoptosis of cardiac
fibroblasts, leading to cardiac hypertrophy and myocardial fibrosis, but the role
of miR-21 in HFpEF remains unknown. By employing cell culture technique, rat
myocardiocytes and cardiac fibroblasts were obtained. The expression of miR-21 in
the two cell types under different conditions was compared and we found that the
miR-21 expression was significantly higher in cardiac fibroblasts than in
myocardiocytes. We established a rat HFpEF model and harvested the tissues of
cardiac apex for pathological examination, Northern blotting and so forth. We found
that miR-21 expression was significantly higher in model rats than in sham-operated
rats, and the model rats developed the cardiac atrophy and cardiac fibrosis. After
injection of miR-21 antagonist, the the cardiac atrophy and cardiac fibrosis were
conspicuously ameliorated. Both in vivo and in vitro, inhibition of miR-21
expression resulted in reduced Bcl-2 expression while over-expression of miR-21 led
to elevation of Bcl-2 expression. Our study suggested that miR-21 promoted the
development of HFpEF by up-regulating the expression of anti-apoptotic gene Bcl-2
and thereby suppressing the apoptosis of cardiac fibrosis.
Growing evidence suggests that microRNAs (miRNAs) play key roles in cardiac
hypertrophy. To measure the expression of endogenous miRNAs is very conducive to
understanding the importance of miRNAs in cardiac hypertrophy. However, current
methods to monitor endogenous miRNA levels, such as Northern blotting, quantitative
real-time polymerase chain reaction (qRT-PCR), and microarrays cannot provide real-
time information on miRNA biogenesis in vivo. We constructed a miRNA reporter
imaging system to monitor miR-22 expression in isoproterenol-induced cardiac
hypertrophy repetitively and noninvasively. There were three copies of the
antisense of miR-22 (3xPT_miR-22) cloned into the 3' untranslated region (UTR) of
the Gaussia luciferase (Gluc) reporter genes under the control of the
cytomegalovirus (CMV) promoter in this miRNA reporter system (CMV/Gluc/3xPT_miR-
22). CMV/firefly luciferase (Fluc) was used as a positive control for imaging of
miR-22 expression. Meanwhile, quantifications of miR-22 in cardiomyocyte
hypertrophy and in mouse cardiac hypertrophy induced by isoproterenol stimulation
were measured by qRT-PCR. Furthermore, we used this miRNA reporter imaging system
to appraise the antihypertrophic effect of antagomir-22 in vitro and in vivo. The
bioluminescence signals of the CMV/Gluc/3xPT_miR-22 were gradually decreased with
prolongation of isoproterenol intervention in vitro and in vivo. Overexpression of
miR-22 was observed in cardiac hypertrophy, and markedly administration of
antagomir-22 could reverse the upregulation of miR-22 and its prohypertrophic
effects. Furthermore, knockdown of miR-22 by antagomir-22 could markedly reverse
the repressed Gluc activities in vitro and in vivo. However, the Fluc activity of
CMV/Fluc was not affected with isoproterenol treatment. This study elucidates the
feasibility of using our constructed miRNA reporter imaging system to monitor the
location and magnitude of expression levels of miR-22 in cardiac hypertrophy in
vitro and in vivo.
Rationale: Direct reprogramming of cardiac fibroblasts to cardiomyocytes has
recently emerged as a novel and promising approach to regenerate the injured
myocardium. We have previously demonstrated the feasibility of this approach in
vitro and in vivo using a combination of 4 microRNAs (miR-1, miR-133, miR-208, and
miR-499) that we named miR combo. However, the mechanism of miR combo mediated
direct cardiac reprogramming is currently unknown. Objective: Here, we investigated
the possibility that miR combo initiated direct cardiac reprogramming through an
epigenetic mechanism. Methods and Results: Using a quantitative polymerase chain
reaction array, we found that histone methyltransferases and demethylases that
regulate the trimethylation of H3K27 (H3K27me3), an epigenetic modification that
marks transcriptional repression, were changed in miR combo-treated fibroblasts.
Accordingly, global H3K27me3 levels were downregulated by miR combo treatment. In
particular, the promoter region of cardiac transcription factors showed decreased
H3K27me3 as revealed by chromatin immunoprecipitation coupled with quantitative
polymerase chain reaction. Inhibition of H3K27 methyltransferases or of the PRC2
(Polycomb Repressive Complex 2) by pharmaceutical inhibition or siRNA reduced the
levels of H3K27me3 and induced cardiogenic markers at the RNA and protein level,
similarly to miR combo treatment. In contrast, knockdown of the H3K27 demethylases
Kdm6A and Kdm6B restored the levels of H3K27me3 and blocked the induction of
cardiac gene expression in miR combo-treated fibroblasts. Conclusions: In summary,
we demonstrated that removal of the repressive mark H3K27me3 is essential for the
induction of cardiac reprogramming by miR combo. Our data not only highlight the
importance of regulating the epigenetic landscape during cell fate conversion but
also provide a framework to improve this technique.
Optogenetics is a technique exploded in the last 10 years, which revolutionized
several areas of biological research. The brightest side of this technology is the
use of light to modulate non-invasively, with high spatial resolution and
millisecond time scale, excitable cells genetically modified to express light-
sensitive microbial ion channels (opsins). Neuroscience has first benefited from
such fascinating strategy, in intact organisms. By shining light to specific
neuronal subpopulations, optogenetics allowed unearth the mechanisms involved in
cell-to-cell communication within the context of intact organs, such as the brain,
formed by complex neuronal circuits. More recently, scientists looked at
optogenetics as a tool to answer some of the questions, remained in the dark, of
cardiovascular physiology. In this review, we focus on the application of
optogenetics in the study of the heart, a complex multicellular organ, homing
different populations of excitable cells, spatially and functionally
interconnected. Moving from the first proof-of-principle works, published in 2010,
to the present time, we discuss the in vitro and in vivo applications of
optogenetics for the study of electrophysiology of the different cardiac cell
types, and for the dissection of cellular mechanisms underlying arrhythmias. We
also present how molecular biology and technology foster the evolution of cardiac
optogenetics, with the aim to further our understanding of fundamental questions in
cardiac physiology and pathology. Finally, we confer about the therapeutic
potential of such biotechnological strategy for the treatment of heart rhythm
disturbances (e.g. cardiac pacing, cardioversion). (C) 2016 Elsevier Inc. All
rights reserved.
Objective: The aim of this study was to examine physical and heart rhythm
management device malfunction complications after participating in a cardiac
rehabilitation program intervention compared with usual care. Method: This study
was a clinical trial of 100 patients. After randomization, intervention group
patients received 8 cardiac rehabilitation program sessions for 8 weeks and follow-
up phone calls. Each session consisted of exercise training, education, and
psychological interventions. Data were collected at 3 points in both groups-
baseline and 8 and 12 weeks after the first day of the intervention-using a
researcher-designed case report form. Data were analyzed using descriptive and
nonparametric tests. Results: Of the participants, 59% were men, and the sample was
aged 40 to 60 years. At the 8- to 12-week follow-up, there were less physical
complications among the cardiac rehabilitation group (P < .001) and no between-
group differences in complications related to device malfunction. By heart rhythm
device type, cardiac rehabilitation had the greatest efficacy in reducing physical
complications in patients with cardioverter/defibrillators. Conclusions: Cardiac
rehabilitation reduced physical complications in patients with cardiac rhythm
management devices, especially in patients with cardioverter/defibrillators.
Cardiac clinical nurse specialists should recommend rehabilitation programs as part
of postimplantation rhythm device treatment to decrease the risk of physical
complications.
Implantable cardiac pacemakers play a vital role in extending the lives of patients
with cardiovascular diseases. The technique of wireless power transfer (WPT) via
magnetic coupling resonance (MCR) makes it possible to wirelessly and
uninterruptedly supply electricity for pacemakers from external. However, the eddy
current in the metallic pacemaker shell seriously impacts the electric energy
receiving by receiving coils, making the WPT system operate at low efficiency. To
decrease eddy current effect and increase WPT efficiency, the precise implant
position of receiving coils is theoretically and experimentally investigated in
this paper. The electromagnetic model of pacemaker WPT system is built and the
analytical solution of induced voltage across receiving coils is derived, which is
verified by experiments. Accordingly, the minimum distance between the receiving
coil and the pacemaker shell is reversely calculated for enough induced voltage.
Experimental results show that supplied by a power source of 5.66 V/300 kHz, the
pacemaker charging system successfully charged Lithium-ion battery from 3.98 (80%
residual capacity) to 4.2 V within 30 min by a 0.15 mm thickness receiving coil
implanted into 4 mm subcutaneously. On the safety of charging system,
electromagnetic and thermal simulation results show that the maximum SAR and
temperature rise in tissues are 36.8 W/kg and 0.66. degrees C, respectively. The
results provide a theoretical and practical support for design of a wireless
charging system.
Objective: To establish the transgenic mouse of cTnT(R141W) gene to make an animal
model of dilated cardiomyopathy. Methods: A transgenic plasmid was constructed by
inserting the cTnT(R141W) gene driven by the alpha-MHC promoter. The expression
level of the gene was determined with Northern blotting. Pathologic changes were
observed by light microscopy and transmission electronic microscopy and analyzed
with echocardiography. The localization of the mutant human cTnT protein was
detected by immunohistochemistry. The hypertrophy markers were analyzed by RT-PCR.
Results: Transgenic mice carrying the cTnT(R141W) mutation were established. The
cTnT(R141W) was expressed by 1.5- to 2.0-fold that of the endogenous cTnT gene and
was showed to assemble in the sarcomere. The transgenic heart exhibited a thinner
ventricular wall and an enlarged ventricular chamber. Interstitial fibrosis and the
elongated and lysed myofrils were also observed in the transgenic heart tissue. The
function on EF%, FS% and movement of the ventricular wall was significantly
decreased. The immature death occurred after 4 months of age and the immature death
rate was 11.1% before 8 months of age in the cTnT(R141W) mice. The increased NPPB,
ACTA1 and decreased ATP2A2 were detected in the transgenic heart. Conclusions: The
expression of mutant cTnT(R141W) in the mouse heart caused ventricular chamber
enlargement, systolic dysfunction, myocardial hypertrophy, and interstitial
fibrosis, suggesting that the cTnT(R141W) gene is a causal factor for DCM and that
the cTnT(R141W) transgenic mouse is a useful animal model for the study of human
DCM. (C) 2008 Published by Elsevier Ireland Ltd.
Rationale: Mammalian heart has minimal regenerative capacity. In response to
mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure
and volume overload in the heart cause increased size (hypertrophic growth) of
cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy
have been well-established, the molecular events that inhibit or repress cardiac
hypertrophy are less known. Objective: To identify and investigate novel regulators
that modulate cardiac hypertrophy. Methods and Results: Here, we report the
identification, characterization, and functional examination of a novel cardiac
Isl1-interacting protein (CIP). CIP was identified from a bioinformatic search for
novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear
protein without recognizable motifs. Northern blotting, in situ hybridization, and
reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes
of developing and adult hearts. Yeast two-hybrid screening identified Isl1, a
LIM/homeodomain transcription factor essential for the specification of cardiac
progenitor cells in the second heart field, as a cofactor of CIP. CIP directly
interacted with Isl1, and we mapped the domains of these two proteins, which
mediate their interaction. We show that CIP represses the transcriptional activity
of Isl1 in the activation of the myocyte enhancer factor 2C. The expression of CIP
was dramatically reduced in hypertrophic cardiomyocytes. Most importantly,
overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy.
Conclusions: Our studies therefore identify CIP as a novel regulator of cardiac
hypertrophy. (Circ Res. 2012; 110: 818-830.)
Endothelin, a vasoconstrictor peptide, plays important roles not only in the
mammalian circulatory system but also in non-mammalian systems, such as the gill
lamellar vascular network with complex structural characteristics. Here, we show
that (i) the contraction of pillar cells that delimit the lamellar vasculature is
controlled by endothelin through the type A endothelin receptor (ETA) linked to the
intracellular calcium signaling system and (ii) ETA receptor is also highly
expressed on fugu erythrocytes, a hitherto unexpected finding. Database mining
revealed the presence of five endothelin receptor (ETR) sequences in the fugu
genome. By Northern blotting, cDNA cloning, and fura-2 monitoring, the branchial
ETR subtype was shown to be ETA able to induce a Ca2+ transit. Immunohistochemistry
revealed its pillar cell and erythrocyte localization. These results suggest an
endothelin/ETA-Mediated coordinated regulation of the pillar cell shape and
erythrocyte membrane flexibility. (c) 2007 Elsevier Inc. All rights reserved.
Endomyocardial biopsy (EMB) has been established in parallel with the development
of percutaneous catheter technology for the diagnosis of cardiac diseases. It was
developed in the early 1960 s in Japan by Drs. Konno, Sakakibara and Sekiguchi of
Tokyo Women's Medical University. EMB is a valuable and useful, but invasive,
modality for making a definite diagnosis in diseases such as myocarditis and
secondary cardiomyopathies, which are often difficult to diagnose by imaging
modality alone. In the field of heart transplantation, the histology of EMB helps
monitor rejection to allografts. In cases of chronic heart failure, fibrosis and
degeneration of cardiomyocytes are very important findings of heart remodeling.
Recently, molecular biology technology has been applied to EMB specimens to get
more detailed information. However, we must also recognize that EMB is an invasive
examination that should not be performed without skillful cardiac catheterization
experience to avoid complications. In this review as a message from pathologists,
we present key cardiac histopathology using EMB, in a way that allows one to
imagine whole cardiac pathological conditions. We also describe the current role of
EMB and its significance in order to encourage young cardiologists to perform EMB
to see another world of pathology.
Objective: In flammation may contribute to an increased risk of cardiovascular
disease (CVD) in HIV-1 infection. MicroRNAs (miRNAs) are involved in the regulation
of inflammation. In treated HIV-1-infected individuals, we aimed to identify
differentially expressed miRNAs with known roles in inflammation and CVD risk and
to investigate associations between these and systemic inflammation. Methods: In a
screening cohort including 14 HIV-1-infected individuals and 9 uninfected controls,
microarray profiling was performed using peripheral blood mononuclear cells
(PBMCs). Differentially regulated miRNAs previously related to inflammation and CVD
were validated using real-time quantitative reverse-transcription polymerase chain
reaction in 26 HIV-1-infected individuals and 20 uninfected controls. Validated
miRNAs were measured in PBMCs, CD4+ and CD8+ T cells. Interleukin-6, tumor necrosis
factor-alpha, high-sensitivity C-reactive protein, lipopolysaccharide (LPS),
cytomegalovirus immunoglobulin G, lipids, and fasting glucose were measured, and
associations with validated miRNAs were assessed with multiple linear regression
analysis. Results: Upregulation of miR-210, miR-7, and miR-331 was found in PBMCs
from HIV-1-infected individuals when compared with those from uninfected controls
(P, 0.005). In contrast, miR-210 and miR-331 were downregulated in CD8(+) T cells.
In multivariate analysis, miR-210 in CD8(+) T cells was negatively associated with
LPS (P = 0.023) and triglycerides (P = 0.003) but positively associated with tumor
necrosis factor-alpha (P = 0.004). MiR-7 in PBMC was positively associated with
interleukin-6 (P = 0.025) and fasting glucose (P = 0.005), whereas miR-331 was
negatively associated with LPS (P = 0.006). In PBMCs from HIV-1-infected
individuals with low cytomegalovirus immunoglobulin G, miR-7, miR-29a, miR-221, and
miR-222 were downregulated. Conclusion: In 2 independent cohorts, miR-210, miR-7,
and miR-331 were differentially regulated in treated HIV-1-infected individuals and
associated with markers of systemic inflammation.
Background and Purpose There is increasing interest in extracellular RNAs (ex-
RNAs), with numerous reports of associations between selected microRNAs (miRNAs)
and a variety of cardiovascular disease phenotypes. Previous studies of ex-RNAs in
relation to risk for cardiovascular disease have investigated small numbers of
patients and assayed only candidate miRNAs. No human studies have investigated
links between novel ex-RNAs and stroke. Methods We conducted unbiased next-
generation sequencing using plasma from 40 participants of the FHS (Framingham
Heart Study; Offspring Cohort Exam 8) followed by high-throughput polymerase chain
reaction of 471 ex-RNAs. The reverse transcription quantitative polymerase chain
reaction included 331 of the most abundant miRNAs, 43 small nucleolar RNAs, and 97
piwi-interacting RNAs in 2763 additional FHS participants and explored the
relations of ex-RNAs and prevalent (n=63) and incident (n=51) stroke and coronary
heart disease (prevalent=286, incident=69). Results After adjustment for multiple
cardiovascular disease risk factors, 7 ex-RNAs were associated with stroke
prevalence or incidence; there were no ex-RNA associated with prevalent or incident
coronary heart disease. Statistically significant ex-RNA associations with stroke
were specific, with no overlap between prevalent and incident events. Conclusions
This is the largest study of ex-RNAs in relation to stroke using an unbiased
approach in an observational cohort and the first large study to examine human
small noncoding RNAs beyond miRNAs. These results demonstrate that when studied in
a large observational cohort, extracellular miRNAs are associated with stroke risk
We investigated the physicochemical properties (size, shape, elemental composition,
and endotoxin) of size resolved particulate matter (PM) collected from the indoor
and corridor environments of classrooms. A comparative hazard profiling of these PM
was conducted using human microvascular endothelial cells (HMVEC). Oxidative
stress-dependent cytotoxicity responses were assessed using quantitative reverse
transcriptase polymerase chain reaction (RT-PCR) and high content screening (HCS),
and disruption of monolayer cell integrity was assessed using fluorescence
microscopy and transwell assay. Scanning electron microscopy (SEM) coupled with
energy-dispersive X-ray spectroscopy (EDX) analysis showed differences in the
morphology and elemental composition of PM of different sizes and origins. While
the total mass of PM collected from indoor environment was lower in comparison with
those collected from the corridor, the endotoxin content was substantially higher
in indoor PM (e.g., ninefold higher endotoxin level in indoor PM8.1-20). The
ability to induce oxidative stress-mediated cytotoxicity and leakiness in cell
monolayer were higher for indoor PM compared to those collected from the corridor.
In conclusion, this comparative analysis suggested that indoor PM is relatively
more hazardous to the endothelial system possibly because of higher endotoxin
content.
Objectives. - The link parent-child is central in the construction of the young
subject. This link can be put in distress when the adult suffers from psychiatric
disorders and become toxic. This article proposes a reflection on the impacts of
adult's serious psychological troubles on the child and a discussion about the
existing tension between psychiatric care for the parent and the measures of help
and protection towards the child. Method. - To try to define all the elements of
answer, the authors lean on their experience in a multidisciplinary team compound
of social workers, psychologists, a jurist and doctors (pediatrician and child
psychiatrist) asked for 30 years to realize the diagnostic and therapeutic care of
situations of ill-treatments of children and teenagers. We met different situations
involving parents and children within the framework of our process of
multidisciplinary evaluation. We also base ourselves on a work of network,
discussing with our colleagues in charge of the therapeutic support of the adult
patients. Results. - The processes of evaluation between the looks of the
professionals close to the child and those who meet the parents in their adult's
suffering allowed to seize all the relevance to go out of an simplistic reading to
understand the ins and outs which led to ill treatment. Discussion. - In spite, of
the concern of the respect for every protagonist concerned in a holistic
understanding of his course of life, we are confronted with the limits of our
mission, on one hand, and what bases the therapeutic link on the other hand. It is
so, for example, that the question of the shared professional secretly represents a
stumbling block which can affect the process of evaluation and support in his
purpose. Conclusion. - The clinical experience and the theoretical reflections
confirm the interest of a complex multidisciplinary work, integrating the
contributions of the visions of the professional asked to estimate and to
accompany, on one hand, the child, and on the other hand, the parent. (C) 2016
Elsevier Masson SAS. All rights reserved.
Anxiety is common among postpartum women and can have adverse effects on mother's
and child's somatic and psychological health if left untreated. In the UK, nurses
or midwifes with a specialisation in community public health nursing, also called
health visitors (HVs), work with families who have children younger than 5 years of
age and are therefore in a key position to identify and support women with
postpartum mental health issues. Until recently, postpartum mental health support
provided by HVs mainly focused on identifying and managing depression, but the
updated clinical guidance by the National Institute for Health and Care Excellence
also includes guidance regarding screening and psychological interventions for
perinatal anxiety. This study therefore aimed to explore HVs' experiences of
supporting women with postpartum anxiety and their views on currently available
care. Using a qualitative approach, in-depth semi-structured interviews were
conducted with 13 HVs from the UK between May and October 2015. Participants were
interviewed in person at their workplace or on the phone/Skype. Using thematic
analysis, four main themes emerged: identification and screening issues; importance
of training; service usage; and status of current service provision. Women with
postpartum anxiety were commonly encountered by HVs in their clinical practice and
described as often heavily using their or other related healthcare services, which
puts additional strain on HVs' already heavy workload. Issues with identifying and
screening for postpartum anxiety were raised and the current lack of perinatal
mental health training for HVs was highlighted. In addition, HVs described a
current lack of good perinatal mental health services in general and specifically
for anxiety. The study highlights the need for HV perinatal mental health training
in general and postpartum anxiety specifically, as well as better coverage of
specialist mental health services and the need for development of interventions
targeted at postpartum anxiety.
The objectives of this study were to describe illness representations in dementia
caregiving and examine the relationship between illness perceptions and carers'
sense of coherence. Illness perceptions were assessed by the Brief Illness
Perception Questionnaire. We measured sense of coherence, symptoms of anxiety and
depression and carer burden. Regression analyses indicated that after controlling
for demographic factors, burden and psychological distress in carers, illness
coherence and emotional responses to the disease independently contributed towards
explaining variance in carers' sense of coherence. Results provide support for the
usefulness of the self-regulation model in understanding dementia caregiving.
Considerable research has examined infants' understanding and evaluations of social
agents, but two questions remain unanswered: First, do infants organize observed
social relations into larger structures, inferring the relationship between two
social beings based on their relations to a third party? Second, how do infants
reason about a type of social relation prominent in all societies: the caregiving
relation between parents and their babies? In a series of experiments using
animated events, we ask whether 15- to 18-month-old infants infer that two babies
who were comforted by the same adult, or two adults who comforted the same baby,
will affiliate with one another. We find that infants make both of these
inferences, but they make no comparable inferences when presented with the same
visible events with voices that specify a peer context, in which one adult responds
to another laughing adult. Thus, infants are sensitive to at least one aspect of
caregiving and organize relations between infants and adults into larger social
structures. (C) 2016 Elsevier B.V. All rights reserved.
In this paper, we use a car-following model to study each electric vehicle's trip
cost and the total trip cost allowing late arrival. The numerical result show that
the electricity cost has great effects on each commuter's trip cost and the total
trip costs and that these effects are dependent on each commuter's time headway at
the origin, but the electricity cost has no prominent impacts on the minimum value
of total trip cost under each commuter's different time headway at the origin. (C)
2017 Elsevier B.V. All rights reserved.
While the US Food and Drug Administration has not approved the use of 3% papain gel
in the United States, the authors feel this study adds to the literature regarding
its use. Introduction. The aim of this study was to evaluate the effect of 3%
papain gel on wounds in mice. Materials and Methods. Thirty healthy C57BL mice (25-
30 g) aged 10 weeks were randomly divided into 2 groups: mice treated with 3%
papain gel and mice treated with placebo gel. Skin incisions were performed with a
6-mm metallic punch with a cutting blade edge. On days 3 and 7 after creating the
lesion, the mice were euthanized and lesion samples were collected. The lesion
samples were processed and sectioned into 3 fragments of skin to be stained with 3
types of dye: hematoxylin and eosin, Picrosirius red, and Weigert. In addition,
immunohistochemical analysis (alpha-SM actin and Ki67) followed by real-time
polymerase chain reaction (PCR) protocol was performed on the samples. Results. On
gross examination, the 3% papain-treated group took less time to heal the wounds
compared with the control. On day 7, microscopic examination showed the 3% papain-
treated group had lower numbers of inflammatory cells, increased
neovascularization, and improved organization of collagen and elastic fibers. Using
PCR analysis, the 3% papain-treated group showed a significant increase in
transforming growth factor beta and interleukin-6 expression compared with the
control (P < .05). Conclusion. Due to a reduced local inflammatory response,
increased angiogenesis, and improved organization of collagen deposition, these
findings demonstrate 3% papain gel can improve cutaneous wound healing in mice.
CarNAC3 contains 285 amino acids and a conserved NAC domain. NAC genes, including
NAM, ATAF1, ATAF2, and CUC2, are members of one of the largest transcription factor
families in plants. CarNAC3, a member of the NAP group, plays an important role in
plant development and responses to abiotic stresses. In this study, CarNAC3 was
transformed into hybrid poplar plants (Populus deltoides x P. euramericana
'Nanlin895') using Agrobacterium tumefaciens. PCR analysis confirmed integration of
the introduced T-DNA into the target genome. Reverse transcription PCR confirmed
the transformation, and Southern and northern blotting verified the transgene copy
number and gene expression, respectively. Fourteen lines of positive transformants
were transplanted into a greenhouse to verify their drought and salt tolerances.
Under normal conditions, transgenic poplar plants were shorter than the wild-type,
but under drought and salt stresses, they maintained their normal rooting and stem
growth rates, while those of the wild-type plants were suppressed. Under stress
conditions, CarNAC3 expression caused increases in proline and photosynthetic
pigment levels and in antioxidant enzyme activities. Furthermore, the expression of
CarNAC3 lowered malondialdehyde concentrations compared with the wild-type control.
Overall, our results indicated that the CarNAC3 transgene enhanced drought and salt
tolerance in transgenic poplar plants.
Phase noise correction is crucial to exploit full advantage of orthogonal
frequency-division multiplexing (OFDM) in modern high-data-rate communications.
OFDM channel estimation with simultaneous phase noise compensation has therefore
drawn much attention and stimulated continuing efforts. Existing methods, however,
either have not taken into account the fundamental properties of phase noise or are
only able to provide estimates of limited applicability owing to considerable
computational complexity. In this paper, we have reformulated the joint phase noise
and channel estimation problem in the time domain as opposed to existing frequency-
domain approaches, which enables us to develop much more efficient algorithms using
the majorization-minimization technique. In addition, we propose two methods based
on dimensionality reduction and regularization, respectively, that can adapt to
various phase noise levels and signal-to-noise ratio and achieve much lower
estimation errors than the benchmarks without incurring much additional
computational cost. Several numerical examples with phase noise generated by free-
running oscillators or phase-locked loops demonstrate that our proposed algorithms
outperform existing methods with respect to both computational efficiency and mean
squared error within a large range of SNRs.
Adoptive transfer of antigen-specific T cells has been adapted by investigators for
treatment of cancer. This technology is becoming popular in the aspects of cell in
vitro preparation and T cell proliferation. In addition, it also does well in
enhancing immunity effect and reducing cytotoxicity. A major advantage for this
adoptive T-cell therapy (ACT) is its ability to efficiently endow patient's T cells
with reactivity for tumor antigens through stable or regulated introduction of
genes that encode high affinity tumor-targeting T-cell receptors (TCRs) or
synthetic chimeric antigen receptors (CARs). To overcome issues of immune tolerance
which limit the endogenous adaptive immune response to tumor-associated antigens
(TAAs), robust systems for genetic modification and characterization of T cells
that express the chimeric antigen receptors (CARs) for redirecting their
specificity have been produced. More and more cases have indicated that the CAR-T
cells are excellent in cancer treatment. However, they still have many limitations
in the treatment of solid malignancies. In addition, the toxicity of CARs T cells
is also a serious problem in the CAR therapy as well. At present, the CAR therapy
has been developed through four generations. This review thus focuses on the
opportunities and challenges facing the CAR-T cells.
The design, construction, and experimental evaluation of a cascade thermoacoustic
engine are presented in this paper. The system was designed and built under the
constraint of an inexpensive device to meet the energy needs of the people based in
remote and rural areas. From the cost and straightforward system point of view, the
air at atmospheric pressure was applied as a working fluid, and the main resonator
tubes were then constructed of conventional polyvinyl chloride (PVC) pipes. Such
device consists of one standing-wave unit and one traveling-wave unit connected in
series. This topology is preferred because the traveling-wave unit provides an
efficient energy conversion, and a straight-line series configuration is easy to
build and allows no Gedeon streaming. The system was designed to operate at a low
frequency of about 57 Hz. The measured results were in a reasonably good agreement
with the predicted results. So far, this system can deliver up to 61W of acoustic
power, which was about 17% of the Carnot efficiency. In the further step, the
proposed device will be applied as the prime mover for driving the thermoacoustic
refrigerator.
Leakage current reduction of the single-phase transformerless cascaded H-bridge PV
inverter is investigated in this paper. The high-frequency common-mode loop model
of a typical single-phase cascaded H-bridge PV system is established. Based on the
model, the main factors that affect the leakage current are discussed. The reason
why the typical single-phase cascaded H-bridge inverter fails to reduce the leakage
current is explained. In order to solve the problem, a cascaded topology based on
the H5 inverter is presented, along with a new modulation strategy, which can
ensure that the stray capacitor voltage is free of high-frequency components. In
this way, the leakage current can be effectively reduced. Finally, a prototype with
TMS320F28335DSP+XC3S400FPGA digital control is built. The performance tests of
cascaded H-bridge and the proposed topologies are carried out. The experimental
results verify the effectiveness of the proposed solution.
This paper proposes a modified cascaded multilevel grid-connected inverter (MCM-
GCI) suitable for photovoltaic grid-connected generation system, which considers
wide operation range, low grid current total harmonics distortion (THD), and high
European efficiency. In the proposed topology, a bidirectional power switch is
added to the standard single-phase cascaded multilevel inverter (CMI) to implement
the transformation between CMI mode and H-bridge inverter (HBI) mode. An online
topology transformation approach of the MCM-GCI is proposed to guarantee the
topology modes transformed safely and smoothly. The proposed MCM-GCI operates in
CMI mode when the PV arrays' output voltage and power are low, and transforms into
HBI mode when the PV arrays' output voltage and power are high. Experimental
results of five-level MCM-GCI are represented to validate the feasibility of the
proposed topology and it is also compared with other three classic grid-connected
inverters to highlight its advantages. Furthermore, more structures based on hybrid
CMI, which possess the topology transformation ability, are shown to further
improve the generation range and obtain a higher efficiency of the system.
Background: Colorectal cancer (CRC) is one of the most common cancers. As in other
cancer locations, the involvement of human papillomaviruses (HPV) has been
suggested but remains highly debated with wide differences among reported
prevalence of HPV infection in CRCs. Aim: To determine the actual prevalence of
high risk HPV16 and 18 in a large case-control study. Methods: CRC specimens were
used for analysis of both tumor and distant healthy tissue. As a nonmalignant
control group, samples from sigmoid diverticulosis resections were studied.
Detection of HPV16 and HPV18 DNA was performed using a real time polymerase chain
reaction (qPCR). Ten percent of tumor samples were also randomly subjected to a
complete HPV genotyping using the INNO-LiPA technique. Results: 467 samples were
analyzed: 217 tumor samples from 210 CRCs, 210 distant healthy tissue samples, and
40 sigmoid samples. HPV18 DNA was never amplified and HPV16 was amplified only
three times in tumor tissues with viral loads under or at the limit of
quantification. New extraction from the same tumor blocks for these samples
revealed no HPV with qPCR and INNO-Lipa assays. Conclusion: With adequate
procedures and reliable techniques, no HPV was detected in the largest case-control
study so far, bringing more evidence on the absence of involvement of HPV in CRCs.
(C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All
rights reserved.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and
the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely.
Genetic variability affecting the host response may also influence the
susceptibility to MPP. Several studies have investigated the association between
single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however,
the results were inconsistent. Here, we investigated the association of 5
functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del), IL-
6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715 subjects
(415 cases, 300 controls) by using tetra-primer allele-specific polymerase chain
reaction (PCR) and Sanger sequencing. The gene-gene interactions were analyzed
using the Multifactor Dimensionality Reduction and cumulative genetic risk score
approaches. Our results showed that 3 SNPs of ACE rs4340, IL-6 rs1800795, and NOS3
rs1799983 were significantly associated with the risks of MPP, while no differences
were observed in genotype frequencies of GSTM1 (Ins/del) and CYP1A1 rs2606345
between both groups. The combinations of ACE rs4340D/NOS3 rs1799983T/CYP1A1
rs2606345G and ACE rs4340D/NOS3 rs1799983T contribute to the genetic susceptibility
of MPP in Chinese children.
BACKGROUNDCurrent research on the gastrointestinal digestion of milk-casein
strongly suggests the existence of novel bioactive peptides with antiviral
activities that are attributable to their immunostimulatory effects. In the present
study, we investigated the antiviral activity of casein peptides rich in phosphate
groups, such as casein phosphopeptide (CPP-III). RESULTSWe prepared two types of
CPP with different phosphorylation levels to clarify the role of the phosphate
group. Further phosphorylation of CPP-III was conducted by dry heating with sodium
pyrophosphate, whereas dephosphorylation was performed enzymatically using alkaline
phosphatase and alkaline treatment. Feline calicivirus (FCV) strain F9, a typical
norovirus surrogate, and Crandell Rees feline kidney cells were used as the target
virus and host cells, respectively. Antiviral activity was determined based on the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and quantitative
polymerase chain reaction quantification of antiviral cytokine mRNA expression.
Higher cell viability was observed in the host cells treated with phosphorylated
CPP-III, and a significant up-regulation of type 1 interferon expression was
induced compared to that treated with native CPP-III. However, dephosphorylation of
CPP-III resulted in a decrease in the anti-FCV effect. CONCLUSIONThe CPP effect was
enhanced by the introduction of additional phosphates and conversely weakened by
their elimination. Therefore, CPP-III phosphorylation represents an emerging
approach for the production of food-grade antiviral agents. (c) 2016 Society of
Chemical Industry
Caspian horse, a rare horse breed found in 1965 by Louise Firouz in northern Iran,
is a small horse which is reported to be in danger of extinction in its original
homeland. There seems to be a great need to prevent extinction of this valuable
horse. In this study, 51 fibroblast cell lines from Caspian horse ear marginal
tissue were successfully established by sampling 60 horses using primary explant
technique. Cells were authenticated and growth curve was plotted. According to
results obtained, population doubling time (PDT) was calculated 23 +/- 0.5 h for
all cell lines. Multiplex polymerase chain reaction (multiplex PCR) revealed that
cell lines had no cross-contamination with other species. Bacteria, fungi, and
mycoplasma contamination were checked using standard methods such as PCR, direct
culture, and Hoechst staining. In addition to providing a valuable source for
genomic, postgenomic, and somatic cloning researches, the established cell lines
would preserve Caspian horse genetic resources. It will also create an accessible
database for researchers.
Although millions of cats live among humans worldwide the scientific community
knows relatively little about cat behavior and cognition. Olfaction is an important
perceptual sense for many members of Carnivora, however the role of chemical
signals in cat social relationships is not fully understood. Research indicates
chemical signals play an important role in many areas of cat behavior including
mother offspring and conspecific interactions and exploration of their environment.
Chemical cues appear to play a role in stress and anxiety reduction, allowing cats
to feel secure in their environment. A better understanding of cat chemical
signals, especially as it relates to within and between species communication, may
lead to an increase in cat wellbeing as humans can utilize this knowledge in
applied settings. Therefore, the purpose of this review is to investigate how cats
process and use chemical signals in social contexts and identify ways this
information can be applied to address cat behavioral issues, such as inappropriate
litter box and scratching behavior, and improve cat welfare, including species-
appropriate ways of reinforcing the human-cat bond. (C) 2016 Elsevier B.V. All
rights reserved.
Abiotic stresses, such as drought, high salinity, and cold/freezing, lead plants to
produce excess reactive oxygen species. Catalase, a unique hydrogen peroxide-
scavenging enzyme, plays a very important role in plants. To characterize the
catalase involved in plant response to abiotic stresses, we constructed a cDNA
library from 4 degrees C-treated Festuca arundinacea Schreb seedlings and isolated
a catalase gene from this library. The cDNA (FaCat1, 1 735 bp) contained an open
reading frame of 1 479 bp. BLAST analysis indicated that the deduced amino acid
sequence showed 96% identity with that from wheat TaCat1 and 87% identity with that
from maize ZmCat2. Northern blotting analysis showed an obvious increase of FaCat1
transcripts in leaves in contrast with roots. Time-course analysis of the
expression of FaCat1 in F. arundinacea leaves showed that FaCat1 expression was
upregulated in cold- and salt-stressed leaves, with the FaCat1 transcripts
accumulating mostly at 4 or 2 h after cold or salt stress, respectively. No
significant changes in FaCat1 transcription were observed in dried leaves and
inhibition of FaCat1 transcription was found in abscisic acid (ABA)-treated leaves,
indicating that the FaCat1 gene is differentially expressed during cold, high salt,
drought, and ABA treatment in F. arundinacea leaves.
OBJECTIVE: To examine the association of pain catastrophizing to pain experience
and a history of childhood sexual abuse in women with chronic pelvic pain (CPP) of
gynecologic origin. STUDY DESIGN: Cross-sectional study of women with CPP (N=273)
attending a tertiary care obstetrics and gynecology pain clinic. Subjects completed
standardized questionnaires to assess pain intensity, pain interference with daily
activity, pain catastrophizing, severity of depressive symptoms, and a history of
childhood sexual abuse. RESULTS: Correlational analysis indicated, that pain
catastrophizing, pain intensity, pain interference and depression scores all shared
significant association. Multiple regression analysis indicated that, after
controlling for the influence of depressive symptoms on both pain intensity and
pain interference, pain catastrophizing significantly predicted both pain outcome
measures. After controlling for pain catastrophizing, depressive symptoms were
found to significantly influence pain interference but not pain intensity. Of the
abuse measures, only women who reported major sexual abuse in childhood were found
to endorse more severe pain catastrophizing. CONCLUSION: Pain catastrophizing
appears to be an important variable in understanding the pain experience of women
with chronic pelvic pain. More over, the presence of a history of major sexual
abuse in childhood may be an additional risk factor for pain catastrophizing in
this population, contributing to further pain morbidity.
Major histocompatibility complex (MHC) class I molecules present antigenic peptides
to cytotoxic T cells. During an adaptive immune response, MHC molecules are
regulated by several mechanisms including lipopolysaccharide (LPS) and interferon
gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G
(CatG), which is generally secreted by neutrophils at the site of inflammation,
might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and
lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of
immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules
are reduced on dendritic cells from CatG deficient mice compared to their wild type
counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B
cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism
for CatG to facilitate intercellular communication between infiltrating cells and
the respective target cell. Subsequently, our findings highlight the pivotal role
of CatG as a checkpoint protease which might force target cells to display their
intracellular MHC I: antigen repertoire.
This brief comment explores the significance of a number of current lawsuits
brought against Catholic Church leaders in Ballarat, Victoria, Australia, in the
context of enduring failures of justice for Australian victims of Catholic clerical
child sexual abuse. It examines the obstacles to criminal and civil justice that
have prevented Church superiors from being held to account for child sexual abuse
perpetrated in Catholic institutions, and explains the responsibility of Australian
governments, courts and the Catholic Church to further justice for survivors(1) in
this context.
Cationic copolymer emulsions of St, BA, AA, and GMA were successfully synthesized
via semi-continuous emulsion polymerization. The properties of synthesized cationic
emulsions were characterized by monomer conversion and solid content, differential
scanning calorimeter, particle size and distribution, zeta potential, and
centrifugal stability. The film performance of the cationic emulsions formed on
cotton fiber surface was observed by scanning electricity microscopy. The influence
of cationic emulsions on the color data, K/S values and rubbing fastness of dyed
cotton fabrics was also investigated. The results show that P (St-BA-AAGMA)
emulsion had larger particle size and higher zeta potential than P (St-BA-AA)
emulsion. When the films were formed at room temperature, P (St-BA-AA-GMA) emulsion
film had better performance than P (St-BA-AA) emulsion film. The addition of GMA
monomers improved the film performance. P (St-BA-AA-GMA) emulsion films formed at
120 degrees C after acetic acid solution treatment had the best water resistance.
Dyed cotton fabrics pretreated with P (St-BA-AA-GMA) emulsion had better pigment
dyeing performance than those pretreated with P (St-BA-AA) emulsion. It
demonstrates that the addition of GMA monomers further improved the effect of
pigment dyeing for cotton fabrics with cationic emulsions as binders. With the
increase of P (St-BA-AA-GMA) concentration, the color performance of dye fabrics
improved while the rubbing fastness decreased a little. But, the handle and
fastness still meets the use standards for consumers. (C) 2017 Wiley Periodicals,
Inc.
The control of Rhipicephalus microplus is essential to prevent cattle discomfort
and economic losses. However, increased resistance and acaricides inefficiency lead
producers to adopt strategies that could result in the accumulation of chemical
residues in meat and milk with possibilities of poisoning in animals and people.
This scenario demonstrates the necessity of research into the identification of
novel, effective and environmentally safe therapeutic options for cattle tick
control. The objectives of this study were to develop and assess the efficacy of R.
microplus biotherapic and of 5% eugenol for the control of R. microplus in
artificially infested calves. Eighteen male 6-month-old Holstein calves were
divided into three groups of six animals. In Group 1, the animals did not receive
medication (control group); in Group 2, the animals received 1 mL of R. microplus
biotherapic at dilution 6CH (centesimal Hahnemannian), orally administered twice
daily. And in Group 3, they received a single application of eugenol 5% in the
pour-on formulation. The median efficacy for biotherapy and eugenol 5% was
respectively 10.13 and 13.97%; however, upon analyzing reproductive efficiency, it
is noteworthy that the biotherapic had 45.86% efficiency and was superior to the
action of eugenol (12.03%) after 37 days of treatment. The ultrastructural study
provided information about the effects of R. microplus biotherapic on the ovaries
of engorged females and showed disorganization in the deposition of the oocyte
exochorion. The results suggest hatchability inhibition of larvae, interference in
R. microplus reproduction and future possibilities for eco-friendly control of R.
microplus with biotherapic 6CH.
A full-length cDNA of an immunogenic protein was cloned from a cDNA library of the
local Egyptian cattle tick Boophilus annulatus. Antibodies raised against B.
annulatus larval proteins were used to screen a cDNA expression library. A 936 bp
cloned fragment was sequenced and showed an open reading frame of 516 bp encoding a
protein of 171 amino acids. Comparison of the deduced amino acid sequence with
protein data bank revealed that the sequence is related to a sequence isolated from
the hard tick Haemaphysalis qinghaiensis (Hq05). Southern blot analysis of B.
annulatus genomic DNA showed that the cloned cDNA hybridized to double bands per
restriction digest, suggesting that the cloned cDNA is a double copy gene. Amino
acid analysis of the cloned gene revealed the presence of two casein kinase 11
phosphorylation sites in the N-terminal domain suggesting that this molecule may be
involved in the signal transduction or gene expression pathways. RT-PCR and
northern blotting revealed the presence of two isoforms of the Ba05 gene in
salivary glands and in the 3-day-old eggs. The cloned gene without the signal
peptide, was expressed in Escherichia coli under T7 promotor of pET-30b vector, and
purified under denaturation conditions. The purified protein appeared as a single
band on 12% SDS-PAGE with a molecular weight around 22.8 kDa including the
histidine tag of the vector. Antibodies raised against the purified molecule were
used to detect the B. annulatus homologue to the Hq05 gene in whole tick, larvae
and gut protein extracts. Immunoblotting revealed the presence of this molecule
Ba05 only in whole tick and larval protein extracts and not in the gut protein
extract. Using the same antibodies, homologues to the Ba05 gene were detected in
other tick species as Hyalomma dromedarii and Rhipicephalus sp. but not in
Ornithodoros moubata. (c) 2007 Elsevier B.V. All rights reserved.
The objective of this study was to assess the immune and stress responsiveness of
cows identified as extremely high and low feed conversion efficiency phenotypes.
The study utilised 16 Holstein-Friesian cows in their third to fourth lactation,
and identified as having either extremely high (n = 8) or extremely low (n = 8)
feed conversion efficiency. A commercial vaccine was used to induce measurable
antibody-and cell-mediated adaptive immune responses and assess general immune
responsiveness. Stress responsiveness was assessed by measuring changes in plasma
cortisol concentrations in response to yarding and handling. No significant
differences in antibody-or cell-mediated immune responsiveness were observed
between the extreme high and low feed conversion efficiency phenotypes (P = 0.343
and 0.546, respectively). However, results suggested that plasma cortisol
concentrations trended higher in the low feed conversion efficiency phenotype cows
than their high feed conversion efficiency counterparts (P = 0.079) 48 h post-
yarding and handling. A significant negative correlation was observed between
antibody-mediated immune responsiveness and stress responsiveness (r = -0.44, P =
0.043) but not with cell-mediated immune responsiveness (r = 0.135, P = 0.309).
This study provides preliminary evidence that cows selected for feed conversion
efficiency may have improved stress-coping abilities and immune responsiveness.
The association between transportation and the occurrence of the bovine respiratory
disease complex (BRDC) has long been recognised. Many hypotheses regarding this
association have been declared through the past decades, and it is agreed upon by
most researchers that the multiple stressors that calves experience during
transportation result in an overall immunosuppression that allows the respiratory
tract to be invaded by numerous opportunistic pathogens. Furthermore, the innate
immune cells, neutrophils, may be trapped in a paradox whereby their crucial
defence and pathogen-killing activities are counteracted by excessive inflammation
and tissue damage that may exacerbate disease, including the BRDC. Neutrophilia in
response to glucocorticoids has been attributed to an influx of immature
neutrophils newly released from the bone marrow, a decrease in neutrophil
margination along endothelial walls, and a decrease in neutrophil apoptosis.
Several of these explanations have been confirmed by altered expression of genes
and proteins important for neutrophil margination and apoptosis.
The genetically dystonic rat (SD-dt:JFL) is an autosomal recessive model of
generalized dystonia. Without cerebellectomy, the dt rat dies prior to Postnatal
Day 40. The dt locus was mapped to a 4.2 Mb region on Chr 7q11 and candidate genes
were screened with semi-quantitative RT-PCR. Then, Southern blotting and genomic
DNA sequencing identified the Y-long terminal repeat portion of an intracisternal A
particle element inserted into Intron I of Atcay, the gene which encodes caytaxin.
Northern and Western blotting and quantitative real-time RT-PCR defined the Atcay
allele in dt rats (Atcay(dt)) as hypomorphic. To establish a framework for
functional studies of caytaxin, the developmental expression of rat Atcay
transcript was analyzed with Northern blotting, relative quantitative multiplex
real-time RT-PCR (QRT-PCR) and in situ hybridization. With a multiple tissue
Northern blot, three Atcay transcripts were identified in brain but none were
present in heart, spleen, lung, liver, muscle, kidney or testis. With a multiple
time-point Northern blot, the same three transcripts were present in cerebellum at
Embryonic Day (E15), Postnatal Day 1 (P1), P7, P14, P36 and 8 months. During early
development (E15 to P14), the relative proportion of the smallest transcript was
increased. QRT-PCR was performed with total RNA from cerebral cortex, striatum,
thalamus, hippocampus and cerebellum. Transcript levels peaked at P7 in
hippocampus, increased linearly from PI to P36 in cerebellum, and showed minimal
developmental regulation in cerebral cortex. Radioactive in situ hybridization
localized Atcay transcript to seemingly all neuronal populations in brain. In
cerebellum, Atcay transcript was present in the molecular, Purkinje and granular
layers; transcript density in the molecular layer peaked at P14. In the background
of previous biochemical, behavioral and electrophysiological studies in the dt rat,
our data are compatible with a vital role for caytaxin in the development and
neurophysiology of cerebellar cortex. (c) 2005 Elsevier B.V. All rights reserved.
Background: The psychological literature suggests that therapist perfectionism is
common and potentially detrimental to client recovery. Little is known about the
relationship between therapist perfectionism and client outcomes. Aims: This study
aimed to measure perfectionism in High Intensity Cognitive Behavioural therapists,
and establish any relationships between dimensions of therapist perfectionism,
client outcomes and drop-out rates in treatment. Method: Thirty-six therapists took
part in the study; levels of perfectionism were measured using a self-report
questionnaire and these were analysed in relation to the clinical outcomes from a
sample of their clients. Results: The results indicated that therapist
perfectionism may be less common than previously suggested. Overall, a number of
significant negative associations were observed between aspects of therapist
perfectionism (e.g. having high standards for others), treatment efficacy and
client retention in treatment. Conclusions: Therapist perfectionism is associated
with CBT treatment outcomes; tentative recommendations for therapists managing
their own schema as part of their clinical practice have been made, although
further investigation is required.
Background: Eotaxin/CCL11 plays an important role in asthma. It acts through the
chemokine receptor CCR3 expressed on hematopoietic and nonhematopoietic cells in
the lung. Objective: To determine whether eotaxin/CCL11 modulates lung and
bronchial fibroblast properties and thereby might contribute to airway remodeling.
Methods: CCR3 expression was characterized on a lung fibroblast line (MRC-5; flow
cytometry, fluorescent microscopy, RT-PCR, and Northern blotting), on primary
bronchial fibroblasts (flow cytometry), and on fibroblasts in human lung tissue
(confocal laser microscopy). The effects of eotaxin/CCL11 on lung fibroblast
migration (Boyden chamber), proliferation (tritiated thymidine incorporation), a-
smooth muscle actin expression (ELISA), 3-dimensional collagen gel contraction
(floating gel), pro-alpha 1(I) collagen mRNA (Northern blotting), total collagen
synthesis (tritiated proline incorporation), matrix metalloproteinase activity
(gelatin zymography), and TGF-beta(1) release (ELISA) were evaluated. The
contribution of eotaxin/CCL11/CCR3 binding on lung fibroblasts was also
investigated by neutralizing experiments. Results: CCR3 is constitutively expressed
in cultured lung and primary bronchial fibroblasts and colocalizes with specific
surface markers for human fibroblasts in lung tissue. Eotaxin/CCL11 selectively
modulates fibroblast activities by increasing their proliferation, matrix
metalloproteinase 2 activity, and collagen synthesis but not their differentiation
into myofibroblasts, contractility in collagen gel, or TGF-beta(1) release.
Eotaxin/CCL11 enhances migration of lung fibroblasts in response to nonspecific
chemoattractants, and this effect is completely inhibited by anti-CCR3-neutralizing
antibodies. Conclusion: These data demonstrate that eotaxin/CCL11 has a direct and
selective profibrogenic effect on lung and bronchial fibroblasts, providing a novel
mechanism whereby eotaxin/CCL11 can participate in airway remodeling in asthma.
Background and Objectives: Calprotectin, a heterodimer of S100A8 and S100A9 with
antimicrobial properties, is expressed in gingival keratinocytes and plays an
important role in innate immunity. Because calprotectin expression is localized in
the spinous cell layer of the gingival epithelium, we hypothesized that the
expression of calprotectin in keratinocytes is related to the differentiation
stage. The aim of the present study was to investigate the relationship between
calprotectin expression and keratinocyte differentiation using some factors that
regulated its differentiation. Material and Methods: Normal human gingival
keratinocytes were isolated from gingival tissues obtained at the extraction of
wisdom teeth, and were cultured in serum-free keratinocyte medium supplemented with
interleukin-1 alpha or calcium, which promote keratinocyte differentiation, and
transforming frowth factor-beta (TGF-beta) or retinoic acid, which suppress its
differentiation. The expression of S100A8/A9 mRNA and the production of
calprotectin in normal human gingival keratinocytes were examined by northern
blotting and enzyme-linked immunosorbent assay, respectively. The expression of
cytokeratin 14, involucrin and filaggrin (marker proteins of keratinocyte
differentiation) was investigated by immunohistochemical staining, and the DNA-
binding activity of CCAAT/enhancer binding protein alpha (C/EBP alpha), a
transcription factor, was examined by electrophoretic mobility shift assay.
Results: The expression of S100A8/A9 mRNA and the production of calprotectin were
increased by interleukin-1 alpha and calcium, but decreased by TGF-beta. RA
inhibited the expression of S100A8/A9 and keratinocyte differentiation, which were
induced by interleukin-1 alpha. C/EBP alpha DNA-binding activity in normal human
gingival keratinocytes was enhanced by interleukin-1 alpha and calcium, but
suppressed by TGF-beta. Conclusion: The present study suggests that calprotectin
expression is related to keratinocyte differentiation and that C/EBP alpha is a
regulator of calprotectin expression in keratinocytes.
DREB transcription factors usually play important regulatory roles in the responses
of plants to abiotic stress. In this study, a novel SlDREB1 transcription factor
from tomato was isolated by yeast-one-hybrid system. Bioinformatics analysis showed
that the SlDREB1 is a single copy gene with typical AP2 conserved domain, and
located on the #6 chromosome of the tomato genome. The SlDREB1 protein was
confirmed to be localized to the cell nucleus. To profile the physiological and
molecular responses of the SlDREB1 gene to drought stress, we transferred the
SlDREB1 gene into the Arabidopsis plants, and functionally characterized the
SlDREB1 gene by molecular detection in vitro and drought stress experiments. The
data showed that accumulation of the SlDREB1 mRNA in the roots of the tomato was
higher than that in the shoots, and strongly induced by drought, salt or exogenous
abscisic acid. Both transcriptional activation and gel mobility shift assay
indicated that the SlDREB1 protein exhibited specific mechanism recognizing the
CCGAC motif in the promoters of the stress-resistant genes in the transgenic
Arabidopsis. The data exhibited that the transgenic Arabidopsis revealed obvious
up-regulations in accumulations of the SlDREB1 and ERD15 mRNA in response to
drought stress. Physiological measurements demonstrated that the transgenic
Arabidopsis overexpressing the SlDREB1 gene remarkably increased accumulation of
osmolytes, such as soluble sugar and free proline, but reduced the contents of
malondialdehyde in the leaves, suggesting that overexpression of the SlDREB1 gene
in the transgenic Arabidopsis plays crucial regulatory roles in maintaining the
balance of osmotic potentials and alleviating physiological damage in response to
drought stress. Northern blotting also provided evidence that the tomato SlDREB1
apparently up-regulated the expressions of the drought-resistant ERD15 gene through
a transcriptional activation pathway recognizing the CCGAC motifs, such as the
NNCCGACNN element in the promoter of the ERD15 instead of limiting to the specific
DRE element in the promoter of the RD29A, and led to an enhanced tolerance of the
transgenic Arabidopsis to drought stress.
Objective: Understanding how treatments work is a goal of psychotherapy research,
however the strength of relationships between therapy processes and outcomes is
inconsistent. DeRubeis, Cohen, et al. (2014) proposed that process-outcome
relationships are moderated by patient characteristics. These "patient response
patterns" (PRPs) indicate individuals' responsiveness to the active ingredients of
treatment. Given the same quality of therapy, one individual may receive more
benefit than another depending on their PRP. The "prognosis moderation hypothesis"
states that PRPs can be defined by pretreatment prognostic indicators. Medium
prognosis groups ("pliant-like") will have stronger process-outcome relationships
than good ("easy-like") or poor ("challenging-like") groups. Method: N = 190
individuals received unguided computerized CBT. They were 58% women, aged 44.7
years. Engagement with the cCBT program was the process variable. PRPs were defined
by predicted scores from a prognostic regression model. Outcomes were BDI scores at
3, 6, and 12 months. "Easy-like," "pliant-like" and "challenging-like" groups were
created and the engagement-outcome relationship was assessed as a function of
group. Results: Engagement-outcome correlations by PRP were: easy-like, r = -.27 (p
< 05); pliant-like, r = -.36 (p < .01); and challenging-like, r = .05 (p = .70).
The pliant-like group was found to be the only moderator of the engagement-outcome
relationship. Results were similar at 6 months but faded at 12. Conclusions: The
engagement-outcome relationship varied as a function of prognosis, providing
support for the prognosis moderation hypothesis. The "pliant-like" group appeared
most sensitive to treatment procedures. Future research is needed to refine the
methods for identifying PRPs.
The immense work presented in this paper is a high frequency sinusoidal oscillator
using positive second generation current controlled conveyor (CCCII+) with minimum
passive components. CCCII is implemented using single Current Feedback Operational
Amplifier (CFOA) and single Operational Trans-conductance Amplifier (OTA). The
frequency (time period) of CCCII is tuned to a maximum of 4 MHz using external bias
current. The performance of the proposed circuit is practically verified using ICs
AD844 (CFOA) and LM 13700 (OTA) and its results are incIuded. The topology is
suitable for monolithic IC fabrication.
Combined cooling, heating and power (CCHP) system plays a significant role in
efficient usage of energy in field of small scale power system for application
ranging from residence to utilities. In the paper, a new CCHP system is proposed
which consists of a power generation unit (PGU), an absorption chiller, a storage
tank and a ground source heat pump (GSHP) to substitute conventional electric
chiller and auxiliary boiler to supply the deficient cooling or heating load. In
the study, three basic load following strategies: following electric load (FEL),
following thermal load (FTL) and following hybrid load (FHL) are employed to
analyze the annual total cost (ATC), operational cost (COST), carbon dioxide
emissions (CDE) and primary energy consumption (PEC) based on a case study of a
regional energy system in Sino-Singapore eco-city. For the evaluated case, carbon
tax and electricity feed in tariff are both considered to compare with the
performances of following maximum electric efficiency of the PGU (Max-eff)
strategy. The results show that the proposed system performed well on COST, CDE and
PEC reduction and the ATC are all increased except that of Max-eff strategy with
carbon tax and electricity feed in tariff. When carbon tax and electricity feed in
tariff are considered, performances of the Max-eff strategy is the best. Otherwise,
the application of FEL is better. Finally, for the Max-eff and FEL strategy,
sensitivity analysis is performed and results are presented with varying of
electricity and gas price. (C) 2016 Elsevier Ltd. All rights reserved.
This paper presents a new topology for waveform-generation using two current
conveyors, and a grounded capacitor or a resistor for tuning. It uses current-
conveyors in place of voltage op-amps to offer better linearity, bandwidth, slew
rate and thermal stability. Measured results obtained using commercially available
devices AD844AN and passive components show excellent linearity and tunability for
both grounded resistor and capacitor topologies over the range of interest.
Component sensitivity and temperature-sensitivity from -150 degrees C to +150
degrees C are studied. A comparison with existing candidate-designs shows
superiority of the proposed design on all aspects. Grounded-connection of tuning
components makes digital control easy.
Methods. The expression of Cyr61 and NF-kappa B pathway molecules was examined by
western blotting. CCL2 expression was assessed by northern blotting and ELISA.
Interaction between NF-kappa B and Cyr61 promoter was evaluated by electrophoretic
mobility shift assay. In rat CIA, osteoblastic expression of Cyr61 was examined by
immunohistochemistry and disease progression was assessed by clinical, radiographic
and histological examinations. Results. EGCG inhibited Cyr61 expression stimulated
by cytokines in primary human osteoblasts and human osteoblastic cell line U2OS. In
U2OS, oncostatin M (OSM) induced I kappa B-alpha degradation through the
mTOR/rictor/Akt pathway, and EGCG attenuated the action. Electrophoretic mobility
shift assay revealed that the OSM-enhanced NF-kappa B/DNA binding was reduced by
EGCG, possibly through abrogating nucleus localization of p65 and p50. Cyr61
enhanced OSM-induced expression of CCL2. Moreover, EGCG diminished OSM-stimulated
CCL2 expression at least partially via suppressing Cyr61 induction. Co-distribution
of CD68(+) macrophages and Cyr61(+) osteoblasts in osteolytic areas was obvious in
the CIA model. Clinical, radiographic and immunohistochemical analyses revealed
that administration of EGCG markedly diminished the severity of CIA, macrophage
infiltration, and the number of Cyr61-synthesizing osteoblasts. Conclusion. By
modulating the mTOR/rictor/Akt/NF-kappa B pathway, EGCG attenuated Cyr61 production
in osteoblastic cells and in turn diminished macrophage chemotaxis. Our data
support the therapeutic potential of EGCG on arthritis.
This study examined the effect of resistance exercise on the production,
recruitment, percentage, and adhesion characteristics of granulocytes with
andwithout polyphenol (PPB) supplementation. Thirty-eight untrained men were
randomized into three groups: PPB (n=13, 21.8 +/- 2.5 years, 171.2 +/- 5.5cm, 71.2
+/- 8.2kg), placebo (PL; n=15, 21.6 +/- 2.5years, 176.5 +/- 4.9cm, 84.0 +/-
15.7kg), or control (CON; n=10, 23.3 +/- 4.3years, 173.7 +/- 12.6cm, 77.3 +/-
16.3kg). Blood samples were obtained pre (PRE), immediately (IP), 1h (1H), 5h (5H),
24h (24H), 48h (48H), and 96h (96H) postresistance exercise (PPB/PL) or rest (CON).
Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and
48H. Plasma concentrations and intramuscular content of interleukin-8 (IL-8),
granulocyte (G-CSF), and granulocyte-macrophage colony stimulating factor (GM-CSF)
were analyzed via multiplex assays. Changes in relative number of circulating
granulocytes and adhesion receptor (CD11b) were assessed using flow cytometry.
Intramuscular IL-8 was significantly elevated at 1H, 5H, and 48H (P<0.001). Area
under the curve analysis indicated a greater intramuscular IL-8 content in PL than
PPB (P=0.011). Across groups, circulating G-CSF was elevated from PRE at IP
(P<0.001), 1H (P=0.011), and 5H (P=0.025), while GM-CSF was elevated at IP
(P<0.001) and 1H (P=0.007). Relative number of granulocytes was elevated at 1H
(P<0.001), 5H (P<0.001), and 24H (P=0.005, P=0.006) in PPB and PL, respectively.
Across groups, granulocyte CD11b expression was upregulated from PRE to IP
(P<0.001) and 1H (P=0.015). Results indicated an increase in circulating CD11b on
granulocytes, and IL-8 within the muscle following intense resistance exercise.
Polyphenol supplementation may attenuate the IL-8 response, however, did not affect
granulocyte percentage and adhesion molecule expression in peripheral blood
following resistance exercise.
Most immune cell communication takes place by intercellular transfer of cytokines
or the contact-dependent interaction of surface receptors in immunological
synapses. In this issue of the European Journal of Immunology, Gardell and Parker
(Eur. J. Immunol. 2017, 47, 41-50) point to a new, hybrid mechanism for Th1-cell
delivery of help to B cells, based on contact-dependent CD40L transfer. The
transfer process and its specificity are both cell contact dependent and antigen
dependent. CD40 expression is also required on the B-cell surface to capture the
CD40L presented by the Th1 cell. While further studies are needed to confirm the
phenomenon in vivo and to test the role of transferred CD40L in other aspects of T-
cell help, this study provides an exceptional take-off point and makes excellent
use of mouse genetics to work out some possible rules for B cells being able to
order help 'to go'.
Background: Abnormal expression of some CD44 molecules in tumor tissues can induce
the degradation of the extracellular matrix, and is closely associated with
axillary lymph node metastasis, angiogenesis, cancer progression, and drug
resistance. Patients and Methods: We measured and confirmed the expression of
CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal
tissues of postoperative non-small cell lung cancer (NSCLC) patients with either
adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative
reverse transcription polymerase chain reaction, gene sequencing, and
immunohistochemical analysis. Results: CD44st and MMP2 expression were closely
associated with the histopathological classification, lymph node metastasis, and
TNM stage of the tumors, and the difference was statistically significant (p <
0.05). The median overall survival (OS) for the high CD44st expression group was
30.52 months (95% confidence interval (Cl) 24.02-36.15); for the low expression
group it was 43.23 months (95% Cl 31.81-52.02) (p = 0.020). The median OS for the
high MMP-2 expression group was 30.53 months (95% Cl 26.69-33.31); for the low
expression group it was 40.06 months (95% Cl 33.55-46.45) (p = 0.022). Conclusion:
The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas
than in adenocarcinomas, were closely associated with lymph node metastasis and TNM
stage, and affected patients' prognoses. (C) 2017 S. Karger GmbH, Freiburg
alpha 1-antitrypsin (AAT), a circulating glycoprotein that rises during acute phase
responses and healthy pregnancies, exhibits immunomodulatory properties in several
T-cell-dependent immune pathologies. However, AAT does not directly interfere with
T-cell responses; instead, it facilitates polarization of macrophages and dendritic
cells towards M2-like and tolerogenic cells, respectively. AAT also allows NK cell
responses against tumor cells, while attenuating DC-dependent induction of
autoimmune NK cell activities. Since AAT-treated macrophages bear resemblance to
cancer-promoting tumor-associated macrophages (TAMs), it became imperative to
examine the possible induction of tumor permissive conditions by AAT. Here, AAT
treatment is examined for its effect on tumor development, metastatic spread, and
tumor immunology. Systemic AAT treatment of mice inoculated with B16-F10 melanoma
cells resulted in significant inhibition of tumor growth and metastatic spread.
Using NK cell-resistant RMA cells, we show that AAT interferes with tumor
development in a CD8(+) T-cell-dependent manner. Unexpectedly, upon analysis of
tumor cellular composition, we identified functional tumor-infiltrating CD8(+) T-
cells alongside M1-like TAMs in AAT-treated mice. Based on the ability of AAT to
undergo chemical modifications, we emulated conditions of elevated reactive
nitrogen and oxygen species. Indeed, macrophages were stimulated by treatment with
nitrosylated AAT, and IFN gamma transcripts were significantly elevated in tumors
extracted soon after ischemia-reperfusion challenge. These context-specific changes
may explain the differential effects of AAT on immune responses towards tumor cells
versus benign antigenic targets. These data suggest that systemically elevated
levels of AAT may accommodate its physiological function in inflammatory
resolution, without compromising tumor-targeting immune responses.
Proliferation of endometrial cells is a prerequisite step for functional
differentiation in the uterus A tumor suppressor gene Cyclin dependent kinase 2
associated protein 1 (Cdk2ap1) mRNA was detected in the pregnant uterus and was
suggested to be involved in cell proliferation However its roles and the mechanisms
regulating its expression are largely unknown In this study the role of steroid
hormones in the expression of Cdk2ap1 was examined using RT PCR Northern blotting
and in situ hybridization methods Cdk2ap1 mRNA was highly expressed during the
proestrus phase and was mainly localized in the epithelium and subepithelium Its
expression was induced by a single injection of estradiol and progesterone but the
effect of progesterone was stronger than that of estradiol Injections of
progesterone (P1 2) on 2 consecutive days induced Cdk2ap1 expression in the
endometrium with the same patterns ob served in the proestrus phase but injections
of estradiol (El 2) on 2 consecutive days did not induce expression The Cdk2ap1
mRNA level was decreased by combined treatment of progesterone and estradiol (E1+P2
3) RU486 suppressed completely the Cdk2ap1 mRNA expression in P1,2 while ICI 182
780 did not in E1+P2 3 In the uteri on day 4 of gestation expression of Cdk2ap1
also was regulated by progesterone as expected Cdk2ap1 mRNA expression was totally
suppressed by RU486 but not by ICI 182 780 Thus it is suggested that Cdk2ap1
expression is primarily regulated by progesterone and the progesterone receptor in
uterus and is mainly localized to proliferating tissues (J Endocrinol Invest 33 650
656 2010) (c) 2010 Editrice Kurtis
Background: Tumour-initiating cells (TICs) account for chemoresistance, tumour
recurrence and metastasis, and therefore represent a major problem in tumour
therapy. However, strategies to address TICs are limited. Recent studies indicate
Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been
associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in
TICs has not been described yet. Methods: Expression of Cdk5 in human cancer tissue
was analysed by staining of a human tissue microarray (TMA). Functional effects of
Cdk5 overexpression, genetic knockdown by siRNA and shRNA, and pharmacologic
inhibition by the small molecule roscovitine were tested in migration, invasion,
cell death, and tumorsphere assays and in tumour establishment in vivo. For
mechanistic studies, molecular biology methods were applied. Results: In fact, here
we pin down a novel function of Cdk5 in TICs: knockdown and pharmacological
inhibition of Cdk5 impaired tumorsphere formation and reduced tumour establishment
in vivo. Conversely, Cdk5 overexpression promoted tumorsphere formation which was
in line with increased expression of Cdk5 in human breast cancer tissues as shown
by staining of a human TMA. In order to understand how Cdk5 inhibition affects
tumorsphere formation, we identify a role of Cdk5 in detachment-induced cell death:
Cdk5 inhibition induced apoptosis in tumorspheres by stabilizing the transcription
factor Foxo1 which results in increased levels of the pro-apoptotic protein Bim.
Conclusions: In summary, our study elucidates a Cdk5-Foxo1-Bim pathway in cell
death in tumorspheres and suggests Cdk5 as a potential target to address TICs.
CDK8, a member of the transcriptional subtype of the cyclin-dependent kinases
(CDKs) family, shows remarkable cancer tissue specific expression profile and
rather more selective contribution to the regulation of gene expression levels
involved in some signaling pathways. However, the effect of CDK8 on the malignant
phenotype of human laryngeal squamous cell carcinoma (LSCC) cells and the potential
molecular mechanisms remain unclear. In the present study, we evaluated the
expression levels of CDK8 by quantitative real-time reverse-transcriptase
polymerase chain reaction (qRT-PCR) and immunohistochemistry in tissue samples of
60 LSCC patients. Then we analyzed and correlated the results with
clinicopathological features. We demonstrated that CDK8 was significantly
overexpressed in LSCC tissues compared with normal controls, and this
overexpression was correlated with lymph node metastasis and advanced clinical
stages. Kaplan-Meier analysis showed that high expression levels of CDK8 miRNA
significantly correlated with short OS survival. In addition, down-regulation of
CDK8 using small interfering RNA(siRNA) reduced the proliferation and migration of
LSCC in vitro. To explore the potential mechanism, we investigated the effect of
CDK8 on Wnt signaling pathway and found that CDK8 was involved in the EMT progress
by regulating beta-catenin of the Wnt signaling. In summary, our data suggest for
the first time that CDK8 appears to contribute to the malignant mechanism of LSCC
and may represent a significant prognostic marker for LSCC patients.
4-Coumarate: coenzyme A ligase (4CL) is one of the key enzymes in phenylpropanoid
metabolism leading to series of phenolics, including water-soluble phenolic acids,
which are important compounds determining the medicinal quality of Danshen (Salvia
miltiorrhiza Bunge), a traditional Chinese medicinal herb. To investigate the
function of 4CL in the biosynthesis of water-soluble phenolic acid in Danshen, we
have cloned two cDNAs (Sm4CL1 and Sm4CL2) encoding divergent 4CL members by
applying nested reverse transcription-polymerase chain reaction (RT-PCR) with
degenerate primers followed by 5'/3' rapid amplification of cDNA ends (RACE) (Note,
these sequence data have been submitted to the GenBank database under accession
numbers AY237163 and AY237164). Either of the coding regions was inserted into a
pRSET vector and a kinetic assay was performed with purified recombinant proteins.
The substrate utilization profile of Sm4CL1 was distinct from that of Sm4CL2. The
K(m) values of Sm4CL1 and Sm4CL2 to 4-coumaric acid were (72.20 +/- 4.10) and (6.50
+/- 1.45) mu mol/L, respectively. These results, in conjunction with Northern
blotting and other information, imply that Sm4CL2 may play an important role in the
biosynthesis of water-soluble phenolic compounds, whereas Sm4CL1 may play a minor
role in the pathway. Southern blotting analysis suggested that both Sm4CL1 and
Sm4CL2 genes are present as a single copy and are located at different sites in the
genome.
Fresh-cut papaya fruit undergo rapid tissue deterioration during storage. A
comparative gene expression study was conducted to isolate genes differentially
expressed upon fresh-cut processing by means of mRNA differential display RT-PCR.
Differential display analysis was performed on intact and fresh-cut papaya fruit
stored in parallel for 12h at 5 degrees C with three different one-base-anchored
oligo dT and eight arbitrary primers. Confirmation of true positive bands was
performed by northern blotting. Fourteen differentially expressed cDNAs ranging
from 154 to 777 bp were cloned, sequenced and compared to GenBank sequences. The
partial cDNAs showed significant homologies to signaling pathway genes, membrane
proteins, cell-wall enzymes, proteases, ethylene biosynthetic enzymes, and enzymes
involved in plant defense responses. Northern blot analysis with probes of each of
the partial clones revealed that most of the genes corresponding to partial cDNAs
were expressed in a fresh-cut dependent manner during 8 days storage. The
transcripts for PC18-5, PA19-3 and PC17 were not detectable on northern blots. The
results suggest that fresh-cut processing induces the expression of proteins
involved in membrane degradation, free radical generation, and enzymes involved in
global stress responses. (c) 2006 Elsevier B.V. All rights reserved.
The cDNA encoding a protease of Perinereis aibuhitensis Grube (PPA) was cloned. The
deduced amino acid sequence analysis showed that the protein had 49% identity to
the C-terminal amino acid 169-246 of serine protease of Heterodera glycines.
Northern blotting analysis indicated that the cDNA could hybridize with mRNA of
approximately 260 bases isolated from the marine earthworm. The cDNA was amplified
by polymerase chain reaction and cloned into pMAL-p2 to construct expression vector
pMAL-PPA. pMAL-PPA was introduced into Escherichia coli BL21(DE3) and
overexpression of PPA fused with maltose binding protein was achieved by isopropyl-
beta-D-thiogalactopyranoside induction. The fusion protein was purified by affinity
chromatography on an amylose resin column and ion-exchange chromatography on a
diethylaminoethyl-Sepharose 4B column. Rabbits were immunized with the purified
protein and antiserum was prepared. The antibody could react with a protein of
approximately 9 kDa extracted from the marine earthworm as shown by Western
blotting analysis. The activity analysis of the recombinant PPA suggested that it
was probably a plasminogen activator.
The basic helix-loop-helix transcription factor Math1, which is transiently
expressed in proliferating neural precursors in multiple domains of the developing
nervous system, is also related to the cell fate decision of enteroendocrine,
goblet, and Paneth cells in the intestine. On the other hand, the transcription
factor Cdx2, which is normally confined to intestinal epithelial cells, is related
to the differentiation of these cells. Therefore, we investigated the relationship
between Math1 and Cdx2 in intestinal epithelial cells. The Math1 and Cdx2
expressions in normal intestinal mucosa and intestinal metaplastic mucosa from
mouse and human stomachs, as well as an intestinal crypt-derived cell line, were
analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction
and Northern blotting, and Math1 enhancer element was analyzed by luciferase
reporter assays. Math1-positive epithelial cells co-expressing Cdx2 were found in
normal intestinal mucosa from humans and mice. Furthermore, Math1-producing
epithelial cells that showed positive immunostaining for Cdx2 were also observed in
intestinal metaplastic mucosa from human and Cdx2 transgenic mouse stomachs,
although they were not detected in normal gastric mucosa of humans and mice.
Expression of Cdx2 stimulated endogenous Math1 mRNA expression in the intestinal
crypt-derived cell line IEC-6, corroborating observations in Cdx2-expressing
intestinal metaplastic mucosa. Furthermore, expression of Cdx2 in IEC-6 cells
conferred the ability to express a Math1 reporter gene containing a Math1 enhancer.
Based on these results, we hypothesize that Cdx2 is involved in activating Math1
expression in intestinal epithelial cells.
As bacterial resistance becomes increasingly common, a new hybrid peptide,
cecropinA-magainin (KWALSKEGPGKFLGKKKKF), has been developed that can kill a broad
spectrum of bacteria without damaging human cells. The mechanism of antibacterial
toxicity for the hybrid peptides is unknown. Herein, we investigate the
localization of the hybrid peptide in methicillin-resistant Staphylococcus aureus
(MRSA). The minimum inhibitory concentration was 64 mu g/mL. The hybrid peptides
could enhance the hydrophobicity of MRSA. Dye leakage experiments showed that the
hybrid peptides caused dye leakage from liposomes. The hybrid peptides influenced
the permeability of the outer membrane and plasma membrane of MRSA. After
cecropinA-magainin treatment of MRSA, the membrane ultrastructure was damaged and
the concentration of K+ increased. Ultimately, the peptide destroyed the integrity
of the bacterial cell membrane, allowing the dye propidium iodide to enter the
cytoplasm. Therefore, the hybrid antibacterial peptide can kill MRSA. (C) 2015
International Union of Biochemistry and Molecular Biology, Inc. Volume 63, Number
6, Pages 805-811, 2016
Squamous cell carcinoma of the head and neck is one of the most common cancer types
worldwide. It initiates on the epithelial lining of the upper aerodigestive tract,
at most instances as a consequence of tobacco and alcohol consumption. Treatment
options based on conventional therapies or targeted therapies under development
have limited efficacy due to multiple genetic alterations typically found in this
cancer type. Natural products derived from plants often possess biological
activities that may be valuable in the development of new therapeutic agents for
cancer treatment. Several genera from the family Celastraceae have been studied in
this context. This review reports studies on chemical constituents isolated from
species from the Celastraceae family targeting cancer mechanisms studied to date.
These results are then correlated with molecular characteristics of head and neck
squamous cell carcinoma in an attempt to identify constituents with potential
application in the treatment of this complex disease at the molecular level.
Background: Celiac disease (CD) is an immune-mediated disorder characterized by an
accumulation of immune cells in the duodenal mucosa as a consequence of both
adaptive and innate immune responses to undigested gliadin peptides. Mast cells
(MCs) are innate immune cells that are a major source of costimulatory signals and
inflammatory mediators in the intestinal mucosa. Although MCs have previously been
associated with CD, functional studies have never been performed. Objective: We
aimed at evaluating the role of MCs in the pathogenesis of CD. Methods: Intestinal
biopsy specimens of patients with CD were scored according to the Marsh
classification and characterized for leukocyte infiltration and MC distribution.
Moreover, MC reactivity to gliadin and its peptides was characterized by using in
vitro assays. Results: Infiltrating MCs were associated with the severity of
mucosal damage, and their numbers were increased in patients with higher Marsh
scores. MCs were found to directly respond to nonimmunodominant gliadin fragments
by releasing proinflammatory mediators. Immunohistochemical characterization of
infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an
increase in proinflammatory MC function in advanced stages of the disease. This was
also associated with increased neutrophil accumulation, the prevalence of M1
macrophages, and the severity of tissue damage. Conclusion: We provide a
description of the progressive stages of CD, in which MCs are the hallmark of the
inflammatory process. Thus the view of CD should be revised, and the contribution
of MCs in the onset and progression of CD should be reconsidered in developing new
therapeutic approaches.
AimTo investigate the effect of simvastatin on lipopolysaccharide (LPS)-stimulated
inflammatory cytokines, cell adhesion molecules and nuclear factor-B (NF-B)
transcription factors in human dental pulp cells (HDPCs). MethodologyThe effect of
LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using
a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The
expression of inflammatory cytokines and cell adhesion molecules was evaluated by
reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked
immunosorbent assay (ELISA) and Western blot analysis. NF-B transcription factors
were evaluated by Western blot analysis. Statistical analysis was performed with
analysis of variance (anova). ResultsThe viability of cells exposed to different
concentrations of E.coli LPS, P.gingivalis LPS and simvastatin was not
significantly different compared with that of control cells (P>0.05). LPS
significantly increased interleukin (IL)-1 (P<0.05) and IL-6 mRNA expression
(P<0.05) and vascular cell adhesion molecule-1 (VCAM-1) (P<0.05) and intercellular
adhesion molecule-1 (ICAM-1) protein expression (P<0.05) in HDPCs. Treatment with
simvastatin significantly attenuated LPS-stimulated production of IL-1, IL-6, VCAM-
1 and ICAM-1 (P<0.05). Treatment with simvastatin decreased LPS-induced expression
of p65 and phosphorylation of IB and also significantly decreased the
phosphorylation of p65 and IB in the cytoplasm and the level of p65 in the nucleus
(P<0.05). ConclusionsSimvastatin has a suppressing effect on LPS-induced
inflammatory cytokine, cell adhesion molecules and NF-B transcription factors in
HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent
in vital pulp therapy.
Background and Aim: Pulmonary monocyte infiltration plays a significant role in the
development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after
common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL,
but the origins remain unclear. Splenic reservoir monocytes have been identified as
a major source of monocytes that accumulate in injured tissues. Whether splenic
monocytes contribute to monocyte alterations after CBDL is unknown. This study
evaluates monocyte distributions and assesses effects of splenectomy on monocyte
levels and pulmonary vascular and hepatic abnormalities in experimental HPS.
Methods: Splenectomy was performed in CBDL animals. Monocyte levels in different
tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were
evaluated with vascular endothelial growth factor-A (VEGF-A) levels, angiogenesis,
and alveolar-arterial oxygen gradient (AaPO(2)). Liver abnormalities were evaluated
with fibrosis (Sirius red), bile duct proliferation (CK-19), and enzymatic changes.
Results: Monocyte levels increased in the lung and liver after CBDL and were
accompanied by elevated circulating monocyte numbers. Splenectomy significantly
decreased monocyte accumulation, VEGF-A levels, and angiogenesis in CBDL animal
lung and improved AaPO(2) levels. In contrast, hepatic monocyte levels, fibrosis,
and functional abnormalities were further exacerbated by spleen removal.
Conclusions: Splenic reservoir monocytes are a major source for lung monocyte
accumulation after CBDL, and spleen removal attenuates the development of
experimental HPS. Liver monocytes may have different origins, and accumulation is
exacerbated after depletion of splenic reservoir monocytes. Tissue specific
monocyte alterations, influenced by the spleen reservoir, have a significant impact
on pulmonary complications of liver disease.
Background: In previous studies by the authors, it was demonstrated that a
fibronectin ( FN)- derived oligopeptide, termed F20, stimulates osteoblast
differentiation in vitro and bone formation in vivo. However, the fundamental
molecular mechanism by which F20 stimulates osteogenesis remains unknown.
Therefore, in this study the molecular mechanism underlying the effect of F20 in
osteoblast differentiation is investigated. Methods: The role of F20 in osteoblast
differentiation was examined using mouse bone- marrow- derived ST2 cell line. The
effect of Smad1/ 5 was determined following small interfering RNA knockdown. Runt-
related transcription factor ( Runx) 2, alkaline phosphatase ( Alp), and
osteocalcin ( Oc) mRNA levels were determined by quantitative real- time polymerase
chain reaction, and their transcriptional activation was assessed using luciferase
reporter assays. Extracellular signalregulated kinase ( ERK) phosphorylation was
visualized via immunoblotting. Results: Synthetic oligopeptide F20 stimulated
expression of bone marker genes Runx2, Alp, and Oc in ST2 cells via Smad and ERK or
mitogen- activated protein kinase signaling pathways as did bone morphogenic
protein 2 ( BMP2). Furthermore, Runx2 acted as a transcription factor during
F20induced osteoblast differentiation. Conclusions: Collectively, these results
indicate that F20 induces osteoblast differentiation with a pattern similar to that
mediated by BMP2 signaling pathway. The authors' previous data also showed that FN-
derived oligopeptide improved wound healing, and it is suggested that F20 might
serve as a therapeutic biomolecule to facilitate periodontal tissue regeneration.
Life is driven by a set of biological events that are naturally dynamic and tightly
orchestrated from the single molecule to entire organisms. Although biochemistry
and molecular biology have been essential in deciphering signaling at a cellular
and organismal level, biological imaging has been instrumental for unraveling life
processes across multiple scales. Imaging methods have considerably improved over
the past decades and now allow to grasp the inner workings of proteins, organelles,
cells, organs and whole organisms. Not only do they allow us to visualize these
events in their most-relevant context but also to accurately quantify underlying
biomechanical features and, so, provide essential information for their
understanding. In this Commentary, we review a palette of imaging (and biophysical)
methods that are available to the scientific community for elucidating a wide array
of biological events. We cover the most-recent developments in intravital imaging,
light-sheet microscopy, super-resolution imaging, and correlative light and
electron microscopy. In addition, we illustrate how these technologies have led to
important insights in cell biology, from the molecular to the whole-organism
resolution. Altogether, this review offers a snapshot of the current and state-of-
the-art imaging methods that will contribute to the understanding of life and
disease.
Perennial monoculture forming grasses are very important natural remediators of
pollutants. Their genetic improvement is an important task because introduction of
key transgenes can dramatically improve their remediation potential. Transfer of
key genes for mercury phytoremediation into the salt marsh cordgrass (Spartina
alterniflora) is reported here. S. alterniflora plays an important role in the salt
marsh by cycling of elements, both nutrients and pollutants, protects the coastline
from erosion, is a keystone species in the salt marsh supporting a large food web,
which in turn supports a significant segment of economy, including tourism, has an
impact on cloud formation and consequently on global weather, and is thus an
ecologically important species relevant for our life-support systems. Embryogenic
callus of S. alterniflora was co-inoculated with a pair of Agrobacterium strains
LBA4404 carrying the organomercurial lyase (merB) and mercuric reductase (merA)
genes, respectively, in order to co-introduce both the merA and the merB genes.
Seven stable geneticin resistant lines were recovered. The presence of merA and
merB genes was verified by PCR and Southern blotting. All but one transgenic lines
contained both the merA and the merB sequences proving that co-introduction into
Spartina of two genes from separate Agrobacterium strains is feasible and frequent,
although the overall frequency of transformation is low. Northern blotting showed
differences in relative expression of the two transgenes among individual
transformants. The steady-state RNA levels appeared to correlate with the
phenotype. Line #7 showed the highest resistance to HgCl2 (up to 500 mu M), whereas
line #3 was the most resistant to phenylmercuric acetate (PMA). Wild-type (WT)
callus is sensitive to PMA at 50 mu M and to HgCl2 at 225 mu M.
Viruses must continuously evolve to hijack the host cell machinery in order to
successfully replicate and orchestrate key interactions that support their
persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of
viral persistence within the host, having plagued the human population for decades.
In recent years, advances in cellular imaging and molecular biology have aided the
elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis.
Super-resolution imaging techniques such as stimulated emission depletion (STED)
and photoactivation and localization microscopy (PALM) have been instrumental in
studying viral assembly and release through both cell-cell transmission and cell-
free viral transmission. Moreover, powerful methods such as Forster resonance
energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have
shed light on the protein-protein interactions HIV-1 engages within the host to
hijack the cellular machinery. Specific advancements in live cell imaging in
combination with the use of multicolor viral particles have become indispensable to
unravelling the dynamic nature of these virus-host interactions. In the current
review, we outline novel imaging methods that have been used to study the HIV-1
lifecycle and highlight advancements in the cell culture models developed to
enhance our understanding of the HIV-1 lifecycle.
Growing leaves do not expand at a constant rate but exhibit pronounced diel growth
rhythms. However, the mechanisms giving rise to distinct diel growth dynamics in
different species are still largely unknown. As a first step towards identifying
genes controlling rate and timing of leaf growth, we analysed the transcriptomes of
rapidly expanding and fully expanded leaves of Populus deltoides Bartr. ex. Marsh
at points of high and low expansion at night. Tissues with well defined temporal
growth rates were harvested using an online growth-monitoring system based on a
digital image sequence processing method developed for quantitative mapping of
dicot leaf growth. Unlike plants studied previously, leaf growth in P. deltoides
was characterised by lack of a base-tip gradient across the lamina, and by maximal
and minimal growth at dusk and dawn, respectively. Microarray analysis revealed
that the nocturnal decline in growth coincided with a concerted down-regulation of
ribosomal protein genes, indicating deceleration of cytoplasmic growth. In a
subsequent time-course experiment, Northern blotting and real-time RT-PCR confirmed
that the ribosomal protein gene RPL12 and a cell-cycle gene H2B were down-regulated
after midnight following a decrease in cellular carbohydrate concentrations. Thus,
we propose that the spatio-temporal growth pattern in leaves of P. deltoides
primarily arises from cytoplasmic growth whose activity increases from afternoon to
midnight and thereafter decreases in this species.
The tigrina (tig)-d.12 mutant of barley is impaired in the negative control
limiting excess protochlorophyllide (Pchlide) accumulation in the dark. Upon
illumination, Pchlide operates as photosensitizer and triggers singlet oxygen
production and cell death. Here, we show that both Pchlide and singlet oxygen
operate as signals that control gene expression and metabolite accumulation in tig-
d.12 plants. In vivo labeling, Northern blotting, polysome profiling, and protein
gel blot analyses revealed a selective suppression of synthesis of the small and
large subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (RBCSs and
RBCLs), the major light-harvesting chlorophyll a/b-binding protein of photosystem
II (LHCB2), as well as other chlorophyll-binding proteins, in response to singlet
oxygen. In part, these effects were caused by an arrest in translation initiation
of photosynthetic transcripts at 80S cytoplasmic ribosomes. The observed changes in
translation correlated with a decline in the phosphorylation level of ribosomal
protein S6. At later stages, ribosome dissociation occurred. Together, our results
identify translation as a major target of singlet oxygen-dependent growth control
and cell death in higher plants.
Exogenous short biologically active peptides epitalon (Ala-Glu-Asp-Gly), bronchogen
(Ala-Glu-Asp-Leu), and vilon (Lys-Glu) at concentrations 10(-7)-10(-9) M
significantly influence growth, development, and differentiation of tobacco
(Nicotiana tabacum) callus cultures. Epitalon and bronchogen, in particular, both
increase growth of calluses and stimulate formation and growth of leaves in plant
regenerants. Because the regulatory activity of the short peptides appears at low
peptide concentrations, their action to some extent is like that of the activity of
phytohormones, and it seems to have signaling character and epigenetic nature. The
investigated peptides modulate in tobacco cells the expression of genes including
genes responsible for tissue formation and cell differentiation. These peptides
differently modulate expression of CLE family genes coding for known endogenous
regulatory peptides, the KNOX1 genes (transcription factor genes) and GRF (growth
regulatory factor) genes coding for respective DNA-binding proteins such as
topoisomerases, nucleases, and others. Thus, at the level of transcription, plants
have a system of short peptide regulation of formation of long-known peptide
regulators of growth and development. The peptides studied here may be related to a
new generation of plant growth regulators. They can be used in the experimental
botany, plant molecular biology, biotechnology, and practical agronomy.
Background and Objectives: Early growth response-1 is a nuclear transcription
factor implicated in regulating cell proliferation. Fibroblast growth factor-1 is
the prototypic fibroblast growth factor involved in the proliferation and
differentiation of various cell types. Expression of early growth response-1
induced by fibroblast growth factor-1 thus may be very important for cell growth,
during both development and wound healing in oral tissue. However, little is known
about the expression and kinetics of early growth response-1 in fibroblast growth
factor-1-stimulated oral cells. The aim of this study was to investigate the
effects of fibroblast growth factor-1 on the expression of early growth response-1
in human periodontal ligament cells. Material and Methods: Periodontal ligament
cells were cultured in medium containing 1, 10 or 100 ng/mL of fibroblast growth
factor-1 for 45 min or with 10 ng/mL of fibroblast growth factor-1 for 15, 30, 45,
60 or 120 min. The proliferation of periodontal ligament cells was evaluated by
measuring 5-bromo-2'-deoxyuridine incorporation. The expression of early growth
response-1 mRNA and protein, and the localization of early growth response-1
protein, were examined by western blotting, northern blotting and
immunocytostaining. Results: 5-Bromo-2'-deoxyuridine incorporation correlated
directly with increases in fibroblast growth factor-1 concentration, and 5-bromo-
2'-deoxyuridine incorporation peaked 45 min after starting treatment. Early growth
response-1 protein was expressed in response to a concentration of fibroblast
growth factor-1 as low as 1 ng. Peak expression of early growth response-1 mRNA was
observed at 15 min and that of early growth response-1 protein at 60 min. The 140-
kDa early growth response-1 protein was not detected in the nuclear fraction, and
the peak expression of the 80-kDa early growth response-1 protein occurred at 60
min. Early growth response-1 localized in or around the nucleus at 30 min.
Conclusion: These results show that a concentration of fibroblast growth factor-1
as low as 1 ng induces the expression of early growth response-1 protein, and that
the 80-kDa early growth response-1 protein functions in the nucleus of periodontal
ligament cells treated with fibroblast growth factor-1.
The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the
rapidly activating delayed rectifier potassium channel (I-Kr), which is important
for cardiac repolarization. Dysfunction of hERG causes long QT syndrome and sudden
death, which occur in patients with cardiac ischemia. Cardiac ischemia is also
associated with activation, up-regulation, and secretion of various proteolytic
enzymes. Here, using whole-cell patch clamp and Western blotting analysis, we
demonstrate that the hERG/I-Kr channel was selectively cleaved by the serine
protease, proteinase K (PK). Using molecular biology techniques including making a
chimeric channel between protease-sensitive hERG and insensitive human ether-a-go-
go (hEAG), as well as application of the scorpion toxin BeKm-1, we identified that
the S5-pore linker of hERG is the target domain for proteinase K cleavage. To
investigate the physiological relevance of the unique susceptibility of hERG to
proteases, we show that cardiac ischemia in a rabbit model was associated with a
reduction in mature ERG expression and an increase in the expression of several
proteases, including calpain. Using cell biology approaches, we found that calpain-
1 was actively released into the extracellular milieu and cleaved hERG at the S5-
pore linker. Using protease cleavage-predicting software and site-directed
mutagenesis, we identified that calpain-1 cleaves hERG at position Gly-603 in the
S5-pore linker of hERG. Clarification of protease-mediated damage of hERG extends
our understanding of hERG regulation. Damage of hERG mediated by proteases such as
calpain may contribute to ischemia-associated QT prolongation and sudden cardiac
death.
Aim: To enhance survival and generation of definitive endoderm cells from human
embryonic stem cells in a simple and reproducible system. Main methods: Definitive
endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced
under a chemical-defined condition withdrawn insulin supplement and serum albumin.
We dissected influence of "alternative growth factors", WNT3A, BMP4 and bFGF in
activin A-driven differentiation by detection of DE-associated genes expression and
cell viability. Expression of DE-associated SOX17 and FOXA2 genes was analyzed by
real time reverse transcription polymerase chain reaction (RT-PCR) and Western blot
assays. Quantitative evaluation of DE efficiency was performed by flow cytometry
analysis of CXCR4-expressed cell population. Cell viability during DE
differentiation was analyzed by an Annexin V/PI double staining test. Key findings:
Supplementation with WNT3A, BMP4 or bFGF promoted DE generation in a dose- and
time-dependent manner. Cell apoptosis elicited by activin A was significantly
ameliorated by a cocktail with WNT3A, BMP4 and bFGF. This allowed for sustained
cell viability without insulin-containing supplements, thereby indirectly improving
the efficiency of DE generation. Therefore, the cocktail containing is optimal for
efficient DE generation in the presence of activin A and an insulin/albumin-free
condition. Significance: This optimal condition facilitates the balance between the
productivity and the viability maintenance, and could be valuable for mass
production of DE with minimal variation. (C) 2017 Elsevier Inc. All rights
reserved.
Background. Hepatocyte nuclear factor-4 (HNF-4) plays a central role in the
differentiation process of hepatic cells. We investigated the effects of an
overexpression of HNF-4 on hepatic progenitor cells isolated from a fetal mouse
liver and transplantation of the cells in a mouse model of liver fibrosis. Methods.
Hepatic progenitor cells were isolated from the embryonic day 14.0 fetal mouse
livers and were purified by magnetic cell sorting to remove the hematopoietic
cells. We transfected adenovirus-mediated HNF-4 into the cells, and analyzed the
expressions of the liver-specific functions using reverse-transcription polymerase
chain reaction and Northern blotting. HNF-4-overexpressing hepatic progenitor cells
were then injected into recipient mice, which were treated with dimethylnitrosamine
and 30% partial hepatectomy. Results. After 5 days of culture, the cells located in
the center of the aggregates were stained positive for albumin, but the peripheral
cells for cytokeratin 19. Adenovirus-mediated HNF-4 gene transfer resulted in
increases in the expressions of HNF-4, apolipoprotein (Apo)A1, ApoC3, and pregnane
X receptor messenger RNA. The mice treated with HNF-4-transfected progenitor cells
survived significantly longer than the control mice (P=0.004). The plasma levels of
albumin, total cholesterol, and glucose were higher in the mice treated with cells
transfected by HNF-4 than in the control mice. Conclusions. These findings
demonstrate that adenovirus-mediated HNF-4 transfection induces the differentiation
from hepatic progenitor cells to hepatic parenchymal cells in vitro. These cells
may be useful as a source for cell transplantation in liver diseases.
Nutritional immunology, immunometabolism and identification of novel
immunotherapeutic targets are areas of active investigation in parasitology. There
is a well-documented crosstalk among immune cells and cells in metabolically active
tissues that is important for homeostasis. The numbers and function of these cells
are altered by obesity leading to inflammation. A variety of helminths spend some
part of their life cycle in the gastrointestinal tract and even entirely enteral
nematode infections exert beneficial effects on glucose and lipid metabolism. The
foundation of this review is the ability of enteric nematode infections to improve
obesity-induced type 2 diabetes and the metabolic syndrome, which are significant
health issues in developed areas. It considers the impact of nutrition and specific
nutritional deficiencies, which are occur in both undeveloped and developed areas,
on the host's ability mount a protective immune response against parasitic
nematodes. There are a number of proposed mechanisms by which parasitic nematodes
can impact metabolism including effects gastrointestinal hormones, altering
epithelial function and changing the number and/or phenotype of immune cells in
metabolic tissues. Nematodes can also exert their beneficial effects through Th2
cytokines that activate the transcription factor STAT6, which upregulates genes
that regulate glucose and lipid metabolism.
Pollination is composed of cell-cell communication and complicated signaling
cascades that regulate pollen tube growth and guidance toward the ovules for double
fertilization, and is critical for successful sexual reproduction. Exploring
expression profiles of in vivo grown pollen tubes is important. Nevertheless, it is
difficult to obtain accessible pollen tubes for profiling studies in most model
plants. By taking advantage of the hollow styles of lily (Lilium longiflorum), in
vivo pollen tubes harvested from pollinated styles which had been cut open were
used here to study their protein and transcript profiles. Pollination
quantitatively and qualitatively altered the total protein composition of
elongating pollen tubes. cDNAs generated and amplified from total RNAs of 24 h in
vivo grown and 12 h in vitro cultured pollen tubes were used for suppression
subtractive hybridization analyses and preparation of home-made array chips.
Microarray analyses conducted with different probe sets revealed 16 transcripts
specifically present and/or enriched in in vivo pollen tubes. Reverse
transcription-PCR (RT-PCR), in situ hybridization and Northern blotting were
applied to validate their unique pollination-induced expression features.
Interestingly, several transcripts were simultaneously detected on the stylar
transmitting tract epidermis, where in vivo pollen tubes tightly adhered during
pollination. Their deduced amino acid sequences showed that most of them encoded
small proteins and could be classified into several families. Transient assay
revealed filament-like structures decorated by these proteins and one probably
localized in the generative cell. These small peptides might be critical for pollen
tube growth during pollination, and further exploration of their biological
functions and mechanisms of action are of great interest.
In this paper, we propose a new floor field Cellular Automaton (CA) model with
considering the swapping behaviors of pedestrians. The neighboring pedestrians in
opposite directions take swapping in a probability decided by the linear density of
pedestrian flow. The swapping which happens simultaneously with the normal movement
is introduced to eliminate the gridlock in low density region. Numerical results
show that the fundamental diagram is in good agreement with the measured data. Then
the model is applied to investigate the counterflow and four typical states such as
free flow, lane, intermediate and congestion states are found. More attention is
paid on the intermediate state which lane-formation and local congestions switch in
an irregular manner. The swapping plays a vital role in reducing the gridlock.
Furthermore, the influence of the corridor size and individual's eyesight on
counterflow are discussed in detail. (C) 2017 Elsevier B.V. All rights reserved.
The development of methods for the detection of aflatoxin BI (AFB(1)) in foods is a
very important practice for ensuring food quality and safety. Most tests of AFB(1)
are still conducted with conventional methods (i.e. antibody-based ELISA tests,
high performance liquid chromatography HPLC); however biosensor methods are being
developed to date as screening tools for 'field analysis. Compared to
immunology/ELISA-like tests or chromatography methods, biosensors are able to
provide rapid, sensitive, robust and cost effective quantitative methods for on-
site testing. In this work we propose a cellular biosensor based on Vero cells,
membrane engineered with anti-AFB1 antibody as the biological recognition element
reacting with AFBi molecules on gold nanoparticle/screen printed electrodes (SPEs)
(three electrode system). In order to culture the cells on the SPEs surfaces the
working electrodes were coated with poly L-lysine to facilitate cell adhesion. The
SPEs were connected to a potentiostat device through a transducer and
chronoamperometric (CA) and cyclic voltammetric (CV) measurements were performed.
Quantitative results obtained using the cellular biosensor method for AFB(1) were
compared to those obtained using the HPLC method in pistachio samples spiked with
AFB(1). The method displayed good sensitivity (r(2) = 0.87) and detection limit
(0.5 ng/mL). (C) 2016 Elsevier Ltd. All rights reserved.
The adaptive growth of the uterus during pregnancy is a critical event that
involves increased synthesis of extracellular matrix (ECM) proteins and dynamic
remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a
dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and
its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since
the myometrium at term is exposed to considerable mechanical stretching of the
uterine wall by the growing fetus(es), the objective of the present study was to
examine its role in the regulation of FN and ITGA5 expression at late gestation and
during labor. Using myometrial tissues from unilaterally pregnant rats, we
investigated the temporal changes in Itga5 gene expression in gravid and empty
uterine horns by Northern blotting and real-time PCR, in combination with
immunoblotting and immunofluorescence analyses of the temporal/spatial
distributions of the FN and ITGA5 proteins. In addition, we studied the effects of
early progesterone (M) withdrawal on Itga5 mRNA levels and ITGA5 protein detection.
At all time-points examined, the Itga5 mRNA levels were increased in the gravid
uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed
higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P
< 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle
layer, increased with gestational age in the circular muscle layer of the gravid
horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid
horn exhibited a continuous layer of variable thickness associated directly with
the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not
appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-
ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during
late pregnancy; and 2) facilitates force transduction during the contractions of
labor by anchoring hypertrophied SMCs to the uterine ECM.
This paper analyses the changing conceptualisation of cellular differentiation
during the twentieth century. This involved a move away from a view of this process
as irreversible to an understanding of it as contingent. We examine the import of
this shift for the transformation of stem cell biology, including the therapeutic
promise attributed to this field, and how it came to challenge historical
conceptions of both the cell and stem cell. We take as our starting point the 2012
Nobel Prize for Physiology and Medicine awarded jointly to John Gurdon and Shinya
Yamanaka. In the view of the Nobel Committee, their work delineates a paradigm
shift in the understanding of cellular differentiation, one that incorporates the
concept of 'plasticity'. We explore the emergence, uses and meanings of this
concept within this specific biological context, examining and emphasising its role
as an epistemological tool. In this setting, 'plasticity' was introduced by cell
biologist Helen Blau in the course of research undertaken in the 1980s into the
genetics of cell differentiation. We argue that Blau's experimental and theoretical
contributions were seminal to a reconceptualisation of this process and provide a
crucial link between the work of Gurdon and Yamanaka. Overall, the paper highlights
the contested process of conceptual change within the biomedical sciences. It also
draws attention to the dynamic and reciprocal relationship between conceptual and
technical change, exemplified here in the changing conceptions of cell
differentiation following from the analysis of gene expression using new cell
fusion and cloning techniques. More broadly, the paper also affords a window onto
the shifting priorities, goals and values within late twentieth-century biomedical
research.
Background and ObjectivePeriodontitis is an infectious disease in which the host
immune and inflammatory responses play essential roles in resistance to bacterial
infection, as well as the induction of tissue destruction if the immune response is
dysregulated. The triggering receptor expressed on myeloid cells (TREMs) modulates
inflammatory and innate immune signaling. TREM-1 is considered as an amplifier of
the immune response, while TREM-2 is a negative regulator that has yet to be
explored in periodontal disease before. We hypothesized that TREMs participated in
the innate immune responses during the pathogenesis of periodontitis. Therefore,
the aim of this study was to evaluate TREM-1 and TREM-2 expression in the gingival
tissues from patients with chronic periodontitis and healthy subjects as well as
their correlation with clinical periodontal parameters. This study is the first to
identify TREM-2 in periodontal tissue, as well as the protein expression changes of
TREM-1 and TREM-2 in periodontal tissues. Material and MethodsGingival tissue
sections were collected from 31 healthy subjects and 53 patients with chronic
periodontitis. Immunohistochemistry and quantitative real-time polymerase chain
reaction were employed to evaluate the protein and mRNA expression of these
receptors in gingival tissues. The recorded clinical parameters were probing depth,
clinical attachment loss, plaque index and bleeding on probing. ResultsIn addition
to myeloid cells in gingival connective tissues, TREM-1 and TREM-2 were also found
expressed in gingival epithelial cells. In particular, TREM-1 was detected in
almost all gingival epithelium from both healthy and inflamed biopsies. The
expression levels of TREM-1 and TREM-2 were significantly increased in the
periodontitis group compared to the healthy group. Increased levels of these
receptors are to be positively correlated with site-specific periodontal
parameters. ConclusionThe increased expression of TREM-1 and TREM-2 levels in
periodontitis may confer diagnostic and potential therapeutic targets as well as
indicating their association with the clinical severity of the disease.
We used PCR-based methods to clone and sequence four previously unidentified
cellulase cDNAs: cbhI-I, cbhI-II, cbhII-I and egII. CbhI-I, cbhI-II and cbhII-I
consist of 1710, 1610 and 1453 bp, respectively, and encode for 512, 458 and 442
amino acids, respectively. EgII consists of 1180bp encoding for 310 amino acids,
and belongs to family 61 of the glycosyl hydrolases. CbhI-I, cbhII-I and egII all
have a modular structure, with the catalytic domain (CD) and cellulose-binding
domain (CBD) located at the C-terminus in cbhI-I and egII, and at the N-terminus in
cbhII-I. CbhI-II shows high homology to cbhI-I but lacks a CBD. Northern blotting
revealed that cbhI-I, cbhI-II and cbhII-I were coordinately expressed at various
stages of the mushroom developmental cycle (substrate colonization to mature fruit
body), although the number of cbhI-I transcripts was much smaller. No egII
expression was detectable during the substrate colonization phase but transcription
levels increased as fruit body morphogenesis progressed.
Background and ObjectivesAmelogenin proteins are the major constituent of
developing extracellular enamel matrix and are believed to have an exclusively
epithelial origin. Recent studies have suggested that amelogenins might induce the
differentiation and maturation of various cells, including cementoblast lineage
cells. However, the residues comprising the active site of amelogenin remain
unclear. The purpose of this study was to identify the active site region of
amelogenin by studying the effects of amelogenin fragments on the osteogenic
differentiation of cementoblasts. Material and MethodsAmelogenin fragments lacking
the C-terminus (rh163) and N-terminus (rh128) and a fragment consisting of the C-
terminal region of rh174 (C11 peptide) were synthesized and purified. Human
cementoblast lineage cells were cultured in osteogenic differentiation medium and
treated with 0, 10, 100 or 1000 ng/mL of rh163, rh128 or C11 peptide. The mRNA
levels of bone markers were examined by real-time polymerase chain reaction
analysis. Alkaline phosphatase activity and calcium deposition were also
determined. Mineralization was evaluated by alizarin red staining. ResultsThe
osteogenic differentiation of human cementoblast lineage cells was significantly
enhanced by treatment with rh128 or C11 peptide, whereas rh163 had no significant
effect as compared with untreated controls. ConclusionsThe C-terminus of amelogenin
promotes the osteogenic differentiation of human cementoblast lineage cells,
indicating the possible utility of C11 peptide in periodontal tissue regeneration.
This paper assesses the feasibility of determining key household characteristics
based on temporal load profiles of household electricity demand. It is known that
household characteristics, behaviours and routines drive a number of features of
household electricity loads in ways which are currently not fully understood. The
roll out of domestic smart meters in the UK and elsewhere could enable better
understanding through the collection of high temporal resolution electricity
monitoring data at the household level. Such data affords tremendous potential to
invert the established relationship between household characteristics and temporal
load profiles. Rather than use household characteristics as a predictor of loads,
observed electricity load profiles, or indicators based on them, could instead be
used to impute household characteristics. These micro level imputed characteristics
could then be aggregated at the small area level to produce 'census-like' small
area indicators. This work briefly reviews the nature of current and future census
taking in the UK before outlining the household characteristics that are to be
found in the UK census and which are also known to influence electricity load
profiles. It then presents descriptive analysis of a large scale smart meter-like
dataset of half-hourly domestic electricity consumption before reviewing the
correlation between household attributes and electricity load profiles. The paper
then reports the results of multilevel model-based analysis of these relationships.
The work concludes that a number of household characteristics of the kind to be
found in UK census-derived small area statistics may be predicted from particular
load profile indicators. A discussion of the steps required to test and validate
this approach and the wider implications for census taking is also provided. (C)
2016 The Authors. Published by Elsevier Ltd.
The central carbon metabolism (glycolysis, the pentose phosphate pathway [PPP], and
the tricarboxylic acid [TCA] cycle) plays an essential role in the supply of
biosynthetic precursors and energy. How the central carbon metabolism changes with
the varying growth rates in the in vitro cultivation of rapidly proliferating
mammalian cells, such as cancer cells and continuous cell lines for recombinant
protein production, remains elusive. Based on relationships between the growth rate
and the activity of seven key enzymes from six cell clones, this work reports
finding an important metabolic characteristic in rapidly proliferating glutamine
synthetase-Chinese hamster ovary cells. The key enzymatic activity involved in the
TCA cycle that is responsible for the supply of energy became elevated as the
growth rate exhibited increases, while the activity of key enzymes in metabolic
pathways (glycolysis and the PPP), responsible for the supply of biosynthetic
precursors, tended to decreasesuggesting that rapidly proliferating cells still
depended predominantly on the TCA cycle rather than on aerobic glycolysis for their
energetic demands. Meanwhile, the growth-limiting resource was most likely
biosynthetic substrates rather than energy provision. In addition, the multifaceted
role of glucose-6-phosphate isomerase (PGI) was confirmed, based on a significant
correlation between PGI activity and the percentage of G2/M-phase cells. (C) 2015
International Union of Biochemistry and Molecular Biology, Inc.
Ask any neuroscientist to name the most profound discoveries in the field in the
past 60years, and at or near the top of the list will be a phenomenon or technique
related to genes and their expression. Indeed, our understanding of genetics and
gene regulation has ushered in whole new systems of knowledge and new empirical
approaches, many of which could not have even been imagined prior to the molecular
biology boon of recent decades. Neurochemistry, in the classic sense, intersects
with these concepts in the manifestation of neuropeptides, obviously dependent upon
the central dogma (the established rules by which DNA sequence is eventually
converted into protein primary structure) not only for their conformation but also
for their levels and locales of expression. But, expanding these considerations to
non-peptide neurotransmitters illustrates how gene regulatory events impact
neurochemistry in a much broader sense, extending beyond the neurochemicals that
translate electrical signals into chemical ones in the synapse, to also include
every aspect of neural development, structure, function, and pathology. From the
beginning, the mutability - yet relative stability - of genes and their expression
patterns were recognized as potential substrates for some of the most intriguing
phenomena in neurobiology - those instances of plasticity required for learning and
memory. Near-heretical speculation was offered in the idea that perhaps the very
sequence of the genome was altered to encode memories. A fascinating component of
the intervening progress includes evidence that the central dogma is not nearly as
rigid and consistent as we once thought. And this mutability extends to the
potential to manipulate that code for both experimental and clinical purposes.
Projection neurons play a key role in carrying long-distance information between
spatially distant areas of the nervous system and in controlling motor circuits.
Little is known about how projection neurons with distinct anatomical targets are
organized, and few studies have addressed their spatial organization at the level
of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric
nervous system of the crab Cancer borealis, projection neurons convey sensory,
motor, and modulatory information to several distinct anatomical regions. While the
functions of descending projection neurons (dPNs) which control downstream motor
circuits in the stomatogastric ganglion are well characterized, their anatomical
distribution as well as that of neurons projecting to the labrum, brain, and
thoracic ganglion have received less attention. Using cell membrane staining, we
investigated the spatial distribution of CoG projection neurons in relation to all
CoG neurons. Retrograde tracing revealed that somata associated with different
axonal projection pathways were not completely spatially segregated, but had
distinct preferences within the ganglion. Identified dPNs had diameters larger than
70% of CoG somata and were restricted to the most medial and anterior 25% of the
ganglion. They were contained within a cluster of motor neurons projecting through
the same nerve to innervate the labrum, indicating that soma position was
independent of function and target area. Rather, our findings suggest that CoG
neurons projecting to a variety of locations follow a generalized rule: for all
nerve pathway origins, the soma cluster centroids in closest proximity are those
whose axons project down that pathway.
There is evidence that both the centrality of a loss-event as well as reduced self-
concept clarity are involved in emotional problems after the death of a loved one.
One issue that is still unexplored is the relative importance of these two concepts
in predicting bereavement outcome. The current study examined the degree to which
both concepts contribute to emotional distress after loss, both concurrently and
longitudinally. Data were available from 124 individuals, all bereaved within the
previous half year, who completed measures of prolonged grief, posttraumatic
stress, and depression at inclusion into the study and again 6 months later. Loss-
centrality and self-unclarity were associated with all three outcome measures, in
cross-sectional analyses. Longitudinal analyses indicated that loss-centrality
predicted symptom levels of prolonged grief, self-unclarity predicted symptom
levels of depression, and both loss-centrality and self-unclarity were associated
with posttraumatic stress 6 months after baseline. Implications of these findings
are discussed.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by multiple alterations in
the TGF-beta signaling pathway. Yes-associated protein (YAP65) interacts with Smad7
thereby influencing TGF-beta signaling. In the present study, the expression of
YAP65 in PDAC was analyzed in order to elucidate the potential role of this
molecule in the pathogenesis of pancreatic cancer. YAP65 mRNA expression levels in
human pancreatic tissue samples and cell lines were analyzed by Northern blotting
and quantitative RT-PCR. Immunohistochemistry was carried out to localize and
quantify YAP65 expression in relation to Smad7 expression and Smad4 mutations. The
effects of TGF-beta 1 on Smad7 and YAP65 mRNA expression were analyzed by
quantitative RT-PCR. Enhanced expression of YAP65 mRNA was identified by Northern
blotting and quantitative RT-PCR in PDAC in comparison to the normal pancreas (2.5-
fold increase) and to chronic pancreatitis (1.3-fold increase). In the normal
pancreas, YAP65 was absent in acinar cells, large ducts and islet cells, but
exhibited moderate to strong immunoreactivity in centro-acinar cells and ductules.
Tubular complexes in CP and CP-like lesions in PDAC also exhibited strong staining.
In contrast, weak to moderate YAP65 immunoreactivity was present in the cancer
cells. There was no correlation between YAP65 immunostaining and Smad7 staining or
Smad4 mutations in the cancer samples. TGF-beta 1 strongly induced Smad7 mRNA in
Colo-357 and in Panc-1 cells, but only slightly induced YAP65 rnRNA in Colo-357
cells. In conclusion, YAP65 is expressed mainly in centroacinar and small ductal
cells in the normal pancreas. In PDAC, YAP65 is present in tubular complexes and to
a lesser extent in cancer cells. Together with the known function of YAP65 in
different growth and differentiation regulating pathways, it is suggested that this
gene plays a role in the normal and diseased pancreas.
The neural basis of autism spectrum disorder (ASD) is not yet understood. ASD is
marked by social deficits and is strongly associated with cerebellar abnormalities.
We studied the organization and cerebellar connectivity of the temporoparietal
junction (TPJ), an area that plays a crucial role in social cognition. We applied
localized independent component analysis to resting-state fMRI data from autistic
and neurotypical adolescents to yield an unbiased parcellation of the bilateral TPJ
into 11 independent components (ICs). A comparison between neurotypical and
autistic adolescents showed that the organization of the TPJ was not significantly
altered in ASD. Second, we used the time courses of the TPJ ICs as spatially
unbiased "seeds" for a functional connectivity analysis applied to voxels within
the cerebellum. We found that the cerebellum contained a fine-grained, lateralized
map of the TPJ. The connectivity of the TPJ subdivisions with cerebellar zones
showed one striking difference in ASD. The right dorsal TPJ showed markedly less
connectivity with the left Crus II. Disturbed cerebellar input to this key region
for cognition and multimodal integration may contribute to social deficits in ASD.
The findings might also suggest that the right TPJ and/or left Crus II are
potential targets for noninvasive brain stimulation therapies.
Autism spectrum disorders (ASDs) are known to be characterized by restricted and
repetitive behaviors and interests and by impairments in social communication and
interactions mainly including "theory of mind" (ToM) processes. The cerebellum has
emerged as one of the brain regions affected by ASDs. As the cerebellum is known to
influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits,
it has been proposed that cerebello-cortical "disconnection" could in part underlie
autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging
(fMRI) to investigate the potential RS connectivity changes between the cerebellar
dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD
pathophysiology. When comparing ASD patients to controls, we found decreased
connectivity between the left DN and cerebral regions known to be components of the
ToM network and the default mode network, implicated in specific aspects of
mentalizing, social cognition processing, and higher order emotional processes.
Further, a pattern of overconnectivity was also detected between the left DN and
the supramodal cerebellar lobules associated with the default mode network. The
presented RS-fMRI data provide evidence that functional connectivity (FC) between
the dentate nucleus and the cerebral cortex is altered in ASD patients. This
suggests that the dysfunction reported within the cerebral cortical network,
typically related to social features of ASDs, may be at least partially related to
an impaired interaction between cerebellum and key cortical social brain regions.
Over the past three decades, insights into the role of the cerebellum in emotional
processing have substantially increased. Indeed, methodological refinements in
cerebellar lesion studies and major technological advancements in the field of
neuroscience are in particular responsible to an exponential growth of knowledge on
the topic. It is timely to review the available data and to critically evaluate the
current status of the role of the cerebellum in emotion and related domains. The
main aim of this article is to present an overview of current facts and ongoing
debates relating to clinical, neuroimaging, and neurophysiological findings on the
role of the cerebellum in key aspects of emotion. Experts in the field of
cerebellar research discuss the range of cerebellar contributions to emotion in
nine topics. Topics include the role of the cerebellum in perception and
recognition, forwarding and encoding of emotional information, and the experience
and regulation of emotional states in relation to motor, cognitive, and social
behaviors. In addition, perspectives including cerebellar involvement in emotional
learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the
cerebellum in mood disorders are briefly discussed. Results of this consensus paper
illustrate how theory and empirical research have converged to produce a composite
picture of brain topography, physiology, and function that establishes the role of
the cerebellum in many aspects of emotional processing.
The metabolic pathophysiology underlying ischemic stroke remains poorly understood.
To gain insight into these mechanisms, we performed a comparative metabolic and
transcriptional analysis of the effects of cerebral ischemia on the metabolism of
the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model.
Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear
separation between the ischemia and control group. The decreases of fructose 6-
phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate
pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion.
Transcriptional profiling by microarray hybridization indicated that the Toll-like
receptor and mitogen-activated protein kinase (MAPK) signaling pathways were
upregulated during cerebral ischemia without reperfusion. In relation to the PPP,
upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling
pathway and was confirmed through real-time polymerase chain reaction.
Immunoblotting showed a slight increase in HSP27 protein expression and a marked
increase in HSP27 phosphorylation at serine 85 after 60-min and 120-min MCAO
without reperfusion. Corresponding upregulation of glucose 6-phosphate
dehydrogenase (G6PD) activity and an increase in the NADPH/NAD(+) ratio were also
observed after 120-min MCAO. Furthermore, intracerebroventricular injection of
ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly
reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein
kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently,
G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be
part of an endogenous antioxidant defense neuroprotection mechanism during the
earliest stages of ischemia. These findings have important therapeutic implications
for the treatment of stroke. (C) 2017 IBRO. Published by Elsevier Ltd. All rights
reserved.
Objective Cerebral palsy (CP) is the most common cause of chronic disability that
restricts participation in areas of occupations for children. The main aim of
rehabilitation is enhancement of their clients for participation in occupations.
The aim of this study was to overview of the factors influencing the participations
of children with CP in Iran. Materials & Methods A systematic, evidence-based
process (Duffy 2005) was used. For data gathering electronic databases including
Google scholar and Iranian and foreigner famous journals in the fields of
pediatrics, were used. The main key words for search were Activity of Daily Living
(ADL),Instrumental Activity of Daily Living (IADL), play, leisure, work,
rest/sleep, social participation, and education. All the papers of this study were
about the factors influencing the participation of Iranian CP children during 2000-
2016. Totally, 156 articles were found eligible as for Iranian CP children study,
of which 100 articles were discarded. Because of repetitive and duplicability of
some articles, 17 articles were removed as well. Results The most studies about
Iranian CP children participations in life areas were in the ADL area of
participation (N=12), and the lowest articles were in the area in the field of:
Work (N=2), play (N=2), and sleep/rest (N=2). Most of the occupational therapists
do not focus on the all life areas. Conclusion In Iran, many researchers do not pay
attention to the participation of CP children. Many articles just paid attention to
the sensory, motor or cognitive components of their clients.
Anatase (A) TiO2 is widely used as a support of the supported vanadium-based and
non-vanadium-based catalysts for NH3-SCR reaction. However, there is lack of enough
attention for brookite (B) and rutile (R) TiO2. Therefore, in the present work, we
synthesize a series of TiO2-A, TiO2-B, and TiO2-R, and then used as supports to
prepare CeO2/TiO2-A, CeO2/TiO2-B, and CeO2/TiO2-R catalysts with the purpose of
clarifying the crystal form effect of TiO2 supports on the physicochemical
properties and catalytic performance of these supported ceria-based catalysts for
NH3-SCR reaction. Characterization results exhibit that H-2 consumption (responding
to reduction property), acid amounts, surface Ce3+ content, surface adsorbed oxygen
species, and catalytic performance of these supported ceria-based catalysts give
the order of CeO2/TiO2-R>CeO2/TiO2-B >CeO2/TiO2-A, which is related to the
interaction (i.e., Ce3+ Ti4+Ce4+Ti3+) between CeO2 and TiO2 (anatase, brookite, and
rutile). Especially, CeO2/1102-R catalyst exhibits the optimal catalytic
performance for NH3-SCR reaction among these supported ceria-based catalysts owing
to the most excellent reduction property as well as the largest amounts of acid
sites, surface Ce3+ content, and surface adsorbed oxygen species. (C) 2017 Elsevier
B.V. All rights reserved.
Despite widespread applications of tetravalent cerium compounds in organic
synthesis and catalysis, the coordination and organometallic chemistry of
cerium(IV) complexes has not been well explored, due, in part, to the high
oxidizing power of Ce(IV). Using chelating O-donor supporting ligands, stable
tetravalent cerium complexes bearing various ligand functionalities have been
isolated, thus making it possible to investigate the reaction chemistry of
cerium(IV) complexes systematically. This review summarizes the recent developments
of the coordination chemistry of cerium(IV) complexes bearing O-, N-, and C-donor
ligands. Special attention will be directed to cerium(IV) complexes supported by a
tripodal oxygen ligand. (C) 2016 Elsevier B.V. All rights reserved.
Objective: By primary cultivation of clinical specimens of human cervical cancer,
the main and side population cells were isolated and their biological
characteristics were analyzed. Methods: Clinical specimens of human cervical tissue
were cultured to get the primary cells. After staining by Hoechst33342, flow
cytometry was used for sorting to get the main and side population cells. Their
molecular biology, morphology and tumorigenicity were compared with that of Hela
cells. Results: The primary cervical cancer and side population cells were isolated
successfully, and the two cells have obvious tumor cell morphology. CK17, CK19, P63
and beta 1-integrin and other related markers were expressed. Tumorigenicity of
side population cells was significantly higher than the main group of cells.
Distribution of the cytoskeleton and expression associated tumor markers were not
affected before and after tumorigenesis of the two cells. Conclusion: Side
population cells which were cultured and isolated from clinical specimens of human
cervical cancer have the characteristics of tumor stem cell, which can be used for
further study of targeted therapy for cervical cancer.
We aimed to explore the correlations between eukaryotic translation initiation
factor 3, subunit A (eIF3a) polymorphisms and susceptibility to and
chemoradiotherapy efficacy in cervical carcinoma. Between August 2007 and August
2011, 176 patients with cervical carcinoma were enrolled as the case group, and 180
healthy individuals were selected as the control group. elF3a Arg803Lys C >T
genotypes were detected by hemi-nested polymerase chain reaction restriction
fragment length polymorphism. All patients received chemoradiotherapy and were
evaluated for efficacy. Compared with carriers of the CC genotype, carriers of the
T genotype of the elF3a Arg803Lys C >T polymorphism had a higher risk of cervical
carcinoma. The elF3a Arg803Lys C >T polymorphism was associated with tumor size,
differentiation degree, Federation of Gynecology and Obstetrics (FIGO) stage, and
lymph node metastasis (LNM). The overall response rate of the case group was 69.32%
(122/176). The response rate of CC genotype carriers was higher compared to
patients with the CM+TT genotypes. Binary-logistic regression analysis showed that
tumor size, FIGO stage, LNM, and the e1F3a Arg803Lys C >T polymorphism were
influencing factors for chemoradiotherapy efficacy. Univariate analysis revealed
that age, e1F3a Arg803Lys C >T polymorphism, differentiation degree, FIGO stage,
and LNM were prognostic factors of cervical carcinoma, and multivariate analysis
showed that age >= 60 years, higher FIGO stage, and LNM, as well as the CT and TT
genotypes of the elF3a Arg803Lys C >T polymorphism, were risk factors related to
the prognosis of cervical carcinoma. The e1F3a Arg803Lys C >T polymorphism is
connected with a higher susceptibility to cervical carcinoma and may affect
chemoradiotherapy efficacy in and prognosis of cervical carcinoma. Copyright (C)
2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.
It is known that high-risk human papillomavirus infection is the main etiological
factor in cervical carcinogenesis. However, human papillomavirus screening is not
sufficient for early diagnosis. In this study, we aimed to identify potential
biomarkers common to cervical carcinoma and human papillomavirus infection by
proteomics for human papillomavirus-based early diagnosis and prognosis. To this
end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-
embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical
intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han
women. Human papillomavirus infection by eight oncogenic human papillomavirus types
was detected in tissue DNA samples using a quantitative polymerase chain reaction.
The protein profile of cervical specimens from human papillomavirus 16-positive
squamous cell carcinoma and human papillomavirus-negative normal controls was
analyzed by proteomics and bioinformatics. The expression of candidate proteins was
further determined by quantitative reverse transcriptase-polymerase chain reaction
and immunohistochemistry. We identified 67 proteins that were differentially
expressed in human papillomavirus 16-positive squamous cell carcinoma compared to
normal cervix. The quantitative reverse transcriptase-polymerase chain reaction
analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1,
ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix (p <
0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was
also significantly increased in cervical intraepithelial neoplasia II-III compared
to normal cervix. Immunohistochemistry staining further confirmed the
overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and
cervical intraepithelial neoplasia II-III compared to normal controls (p < 0.05).
Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and
possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical
carcinogenesis and potentially associated with human papillomavirus infection.
Further validation studies of the profile will contribute to establishing auxiliary
diagnostic markers for human papillomavirus-based cancer prognosis.
Objective: To quantify cell free fetal DNA (cffDNA) with fetal specific epigenetic
marker, hypermethylated RASSF1A, in maternal plasma of normal pregnant women from
20 weeks of gestation and to assess its relationship with maternal age, height,
pre-pregnancy weight and body mass index (BMI). Methods: Hundred normal pregnant
women within the gestational age of 21-40 weeks were randomly selected and grouped
into five (n = 20). Group 1: 21-24, Group 2: 25-28, Group 3: 29-32, Group 4: 33-36
and Group 5: 37-40 weeks. Maternal plasma DNA was extracted, digested with
methylation-sensitive restriction enzyme, BstUI and the fetal specific DNA (cffDNA)
was quantified by Real-time polymerase chain reaction (qRT-PCR). Results: The mean
hypermethylated RASSF1A concentrations in different gestational groups were Group
1: 30.1 +/- 14.9, Group 2: 52.6 +/- 22.18, Group 3: 93.2 +/- 19.08, Group 4: 172.8
+/- 26.81 and Group 5: 337.8 +/- 52.9 copies/ml. Pearson's correlation analysis
showed highly significant positive correlation between cffDNA and gestational age
(r = 0.899, p < 0.001). BMI was also found to be positively related to cffDNA (r =
0.217, p < 0.05). However, it did not show any correlation with maternal age,
height and pre-pregnancy weight. Conclusions: The gestational age-dependent
increase of hypermethylated RASSF1A; the fetal specific epigenetic marker in
maternal plasma was demonstrated, in an Indian study group of normal pregnant
women. Findings would form the basis of future studies involving pregnancy
complications that would aid in the early diagnosis of placental pathologies with
hypermethylated RASSF1A.
The current feedback instrumentation amplifier (CFIA) designed for EEG detection
systems is presented. This CFIA includes two digitally programmable operational
transconductance amplifiers (DPOTAs) and a current feedback operational amplifier
(CFOA) where the digital control of DPOTA is done using 4-bit current division
network (CDN). PSpice simulation results are carried out using 0.25 mu m IBM CMOS
process under +/- 0.8V supply voltage. The CFIA reaches 126.6dB common mode
rejection ratio (CMRR), consumes 695 mu W, and has 9.4777 mu V/root Hz input
referred noise. The achieved gain is from 22.236dB to 45.386dB. These results make
the CFIA suitable for the EEG detection systems.
In this work, the low-voltage current feedback operational amplifier (CFOA) with
bulk-driven, quasi-floating-gate (QFG) transistor and bulk-driven-quasi-floating-
gate (QFG) transistor techniques to operate under low supply voltage is proposed.
The proposed circuits were design based on the voltage follower and current
follower while the output stages are designed base on the voltage follower. The
CFOA circuits are designed by using the 0.18 mu m CMOS technology and supply
voltage operated 1 V. Simulation results shows output impedance of CFOA with bulk-
driven, quasi-floating-gate (QFG) MOS transistor and bulk-driven-quasi-floating-
gate (BD-QFG) MOS transistor are 55.72 Omega dB, 43.88 Omega dB, and 41.63 Omega
dB, respectively. Finally, the proposed BD, QFG and BD-QFG MOS transistors
techniques can used before the ultra-low voltage and low-power CFOA circuits.
Protein based therapeutics have started to dominate the pharmaceutical landscape
primarily due to the high efficacy that they have demonstrated against complex
diseases. Despite the significant success, issues with regards to safety, efficacy
and quality of biotherapeutics have been a point of considerable debate and concern
among the various stakeholders. The correlation between the glycoform profile and
the safety and efficacy of a drug, in particular, has garnered significant
attention of researchers worldwide. An escalated emphasis is presently given to
develop an understanding of how the various process parameters as well molecular
biology considerations contribute to glycan heterogeneity. This paper aims to
review the major developments that have occurred in this area over the last decade.
The impact of the various process parameters on glycan expression, methods for
obtaining a pre-determined glycan levels/profiles of a protein therapeutic and
developments in the area of real-time glycan monitoring and control are discussed.
(c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1091-1102,
2016
Symptomatic chronic Chagas disease affects up to 40% of patients infected with
Trypanosoma cruzi. The lack of reliable early markers of cure after therapy hinders
disease management and clinical trials with new drugs. We performed a study with 18
months of follow-up to compare changes in immune parameters and T. cruzi-specific
immune responses as surrogate markers of response to therapy between patients
treated with benznidazole and untreated patients. This was a pilot, open-label,
randomised clinical trial of treatment with benznidazole versus no treatment in
patients with indeterminate chronic T. cruzi infection. In both groups we
investigated changes in T-cell activation, T-cell subpopulations, regulatory T-cell
counts, 16, and sCD14 levels, and T. cruzi-specific immune responses (Th1, Th2, and
Th17 responses). Fourteen patients were included in the study (seven in each
group). Median age was 35 years (F25-75 31-43), 57% were female, and 93% were
Bolivian. Benznidazole was administered at 5 mg/kg/day for 60 days. Three patients
discontinued benznidazole owing to adverse reactions and were not evaluated. At the
end of the follow-up period, treated patients showed significantly less immune
activation and lower regulatory T-cell counts, with an increased Th17 and Thl
response. This randomised pilot clinical trial administering benznidazole to
patients with indeterminate chronic Chagas disease brings about changes in the
adaptive immunity, leading to a general decrease in inflammatory status. This
apparently beneficial response could act as the basis for monitoring new
antiparasitic drugs. (C) 2016 Elsevier B.V. All rights reserved.
The parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas disease,
is widely distributed throughout the Americas, from the southern United States (US)
to northern Argentina, and infects at least 6 million people in endemic areas. Much
remains unknown about the dynamics of T. cruzi transmission among mammals and
triatomine vectors in sylvatic and peridomestic eco-epidemiological cycles, as well
as of the risk of transmission to humans in the US. Identification of T. cruzi DTUs
among locally-acquired cases is necessary for enhancing our diagnostic and clinical
prognostic capacities, as well as to understand parasite transmission cycles. Blood
samples from a cohort of 15 confirmed locally-acquired Chagas disease patients from
Texas were used for genotyping T. cruzi. Conventional PCR using primers specific
for the minicircle variable region of the kinetoplastid DNA (kDNA) and the highly
repetitive genomic satellite DNA (satDNA) confirmed the presence of T. cruzi in
12/15 patients. Genotyping was based on the amplification of the intergenic region
of the miniexon gene of T. cruzi and sequencing. Sequences were analyzed by BLAST
and phylogenetic analysis by Maximum Likelihood method allowed the identification
of non-TcI DTUs infection in six patients, which corresponded to DTUs TcII, TcV or
TcVI, but not to TcIII or TcIV. Two of these six patients were also infected with a
TcI DTU, indicating mixed infections in those individuals. Electrocardiographic
abnormalities were seen among patients with single non-TcI and mixed infections of
non-TcI and TcI DTUs. Our results indicate a greater diversity of T. cruzi DTUs
circulating among autochthonous human Chagas disease cases in the southern US,
including for the first time DTUs from the TcII-TcV-TcVI group. Furthermore, the
DTUs infecting human patients in the US are capable of causing Chagasic cardiac
disease, highlighting the importance of parasite detection in the population. (C)
2017 Elsevier B.V. All rights reserved.
The flotation response of chalcopyrite and molybdenite when using a novel compound,
acetic acid-[(h ydrazinylthioxomethypthiol-sodium (AHS), as the depressant was
investigated through micro-flotation and batch flotation in this study. The
depressing mechanisms were studied by means of zeta potential, MR and XPS
measurements. The micro and bench flotation results indicated that AHS exhibited a
strong influence on the depression of chalcopyrite and had little effect on the
flotation of molybdenite minerals; these results might be attributed to the
significant improvement of the molybdenite/chalcopyrite selectivity index after the
addition of AHS. The results of the FTIR spectra, zeta potential and XPS
measurements indicated that AHS chemisorbs onto the chalcopyrite surface through
its S and N atoms, forming a five-membered cheat ring. A possible depressant
mechanism along with a postulated adsorption mode for the surface interaction
between AHS and chalcopyrite are provided. (C) 2017 Elsevier BN. All rights
reserved.
In this, study, a type-2 fuzzy chance-constrained programming (TFCP) method is
developed for supporting energy systems planning (ESP) under uncertainty. TFCP
incorporates chance-constrained programming within a type-2 fuzzy programming
framework to handle uncertainties (i.e. type-2 fuzzy sets and probabilistic
distributions) in the objective and constraints, as well as to examine the
reliability of satisfying (or risk of violating) system constraints. A TFCP-based
energy system (TFCP-ES) model is then formulated for energy systems planning of
Shanghai, where multi-energy resources, multi-processing technologies, multi-
conversion technologies and multi-end users are considered. Solutions of energy
supply, electricity generation, capacity expansion, and air-pollutant emission
associated with different constraint-violation risks are obtained. Results reveal
that (i) natural gas is one of the major energy-supply sources for the city in the
future (increasing by 13.0%); (ii) the city's electricity-generation structure
tends to the transition from coal-dominated into clean energy-dominated (e.g.,
natural gas, onshore wind, offshore wind, and photovoltaic power); (iii) the city's
energy-supply security is enhanced by provoking the utilization of renewable
energies (increasing by 1.0%). The results are helpful for managers to adjust the
city's current energy structure, enhance the energy supply security, as well as
make tradeoff between system cost and constraint-violation risk. (C) 2017 Elsevier
Ltd. All rights reserved.
The sociological interpretation of reality and the processes occurring in it is
determined by various approaches to understanding its nature. The diversity of
these approaches is eventually reduced to its definition as a reality of the social
world, which reflects, on the one hand, objectively existing phenomena and
processes and, on the other hand, people's subjective perceptions about the
objective reality. Social actuality as objective social reality exists beyond the
subject of social cognition, i.e. objectively. Each new generation inherits from
their parent generations a complex system of economic, social and political
structures, institutions, organizations and t5he established relationships which
form the social infrastructure of objective reality (social reality). But people
perceive directly only the part of objective reality in which they have their own
knowledge. Due to knowledge of its particular sphere or different objects of
reality, people get its more or less adequate subjective perception. Therefore, the
study of social reality focuses on the process of formation of subjective ideas
about the objects of social actuality and attitudes to it, which is included in the
subject area of sociology of knowledge. That is, from the standpoint of sociology
of knowledge, the research object is not reality, but ideas about the reality.
Based on subjective perceptions of reality, people construct their own reality.
These perceptions change under the influence of various factors affecting the
changes in social reality in the process of its formation. A significant change
factor is the crisis which affects all spheres of the Russian society. The article
analyzes the impact of the crisis on the changes in social reality in different
population groups in Russia and the way it is reflected on people's attitudes to
each other, to family, work and education. Based on analysis of data from
nationwide studies it has been revealed that there is a contradiction between
Russians' traditional attitudes to each other, family, work and education and the
emerging modern attitudes. Amid crisis, this contradiction tends to exacerbate due
to the impossibility of maintaining the traditional principles underlying the old
way of life, which leads to uncertainty and formation of new forms of certainty
through the change in life paradigm.
The multidirectional multiscroll chaotic attractors generated by second-generation
current conveyor (CCII) are investigated. A fourth-order and a fifth-order grid
multiscroll chaotic system are presented by designing staircase function and
shifted voltage sign functions in the high-order Jerk system. Using the CCIIs, a
chaotic circuit is designed and implemented, which can generate 4 x 2 x 2 x 2- and
4 x 2 x 2 x 2 x 2-scroll chaotic attractors, respectively, via switching control.
Compared with the voltage operational-amplifier-based circuit, the proposed circuit
has better performance in terms of circuit structure and bandwidth. Numerical
simulations and experimental results are accordant.
As an important signal source, chaotic circuit can play key blocks of Codec in
fields of weak signal detection and high speed security communication and non-
linear control. First we review the chaotic circuit design methodology into three
kinds of methods like blocks stickiness with 3-blocks, decreasing- or increasing-
type, for root cause of period three implying chaos. Then two new chaotic circuits
are designed and demonstrated in core features of 1L-1C plus 1 multiplier and 1
operational amplifier, and 2L-3C plus 1T-MOSFET. The phase diagrams and FFT
spectrums of tested independent variables show that new circuits are chaotic with
the greatest Lyapunov's Exponents more than zero. At last our conclusions throw up
both the birth of Lee's circuits under logic steps and deep thinking of precision
measurements based on chaos in voltage-or current-mode.
Calnexin (IP90/P88) is an integral membrane protein of the endoplasmic reticulum
that binds newly synthesized N-linked glycoproteins during their folding in the ER
including MHC class I molecule. This manuscript reports the identification of two
unique cDNA clones of calnexin in rainbow trout. Both encode putative mature
proteins of 579 and 592 aa respectively in addition to a 24 aa signal peptide.
Sequence analysis revealed that only one of the two cDNA clones encodes a putative
ER retention signal, K/QEDDL, followed by a serine phosphorylation site conserved
with mammalian homologs. Amino acid sequence alignment illustrated conservation of
the calnexin luminal domain, which consists of a globular and a P domain, in both
copies. Southern blotting revealed that there are at least two copies of the
calnexin gene in the trout genome and northern blotting showed a wide tissue
distribution of an estimated 3 kbp calnexin transcript with an additional minor
transcript of 2.3 kbp expressed only in head kidney, spleen PBLs and strongly in
RTS11. Importantly, the smaller transcript was predominantly upregulated in RTS11
after a 24 h treatment with the calcium ionophore A23187. In western blots,
calnexin was detected primarily as a 120 kDa protein and upon A23187 treatment; a
100 kDa band was most prominently expressed. These results suggest that in
salmonids there are two differentiated versions of the calnexin gene which encode
proteins that may have diverged to perform unique biological functions. (C) 2013
Elsevier Ltd. All rights reserved.
Interspecific aggression between sibling species may enhance discrimination of
competitors when recognition errors are costly, but proximate mechanisms mediating
increased discriminative ability are unclear. We studied behavioral and neural
mechanisms underlying responses to conspecific and heterospecific vocalizations in
Alston's singing mouse (Scotinomys teguina), a species in which males sing to repel
rivals. We performed playback experiments using males in allopatry and sympatry
with a dominant heterospecific (Scotinomys xerampelinus) and examined song-evoked
induction of egr-1 in the auditory system to examine how neural tuning modulates
species-specific responses. Heterospecific songs elicited stronger neural responses
in sympatry than in allopatry, despite eliciting less singing in sympatry. Our
results refute the traditional neuroethological concept of a matched filter and
instead suggest expansion of sensory sensitivity to mediate competitor recognition
in sympatry.
Considering the importance of mother's support in the adaptation of a sexually
abused child, it is relevant to determine if the mothers and children involved in
an intergenerational cycle of child sexual victimization differ from dyads in which
only the child has been abused. The purpose of this study was to compare mother-
child dyads with sexually abused children according to whether the mother had
herself been victim of child sexual abuse. The sample included 87 dyads with
sexually abused children aged 3-18years old and their mothers (44 reporting
maternal and child abuse), followed by social welfare services of the province of
Quebec (Canada). The two groups of mothers were compared on their past family abuse
experiences and past family relations, their mental health history, their current
psychological distress, their parenting behaviors, and their current levels of
family functioning. Children were compared on their adaptation. Multivariate
analyses indicated that mothers reporting child sexual abuse were more likely to
report more other maltreatments in their childhood and greater prevalence of
lifetime history of alcohol abuse disorders, dysthymia, and panic disorder compared
with mothers who had not experienced CSA. Compared to children whose mothers had
not experienced CSA, those whose mothers had experienced CSA showed higher rates of
problems behaviors and were more likely to report having been sexually abused by a
trusted person. These results highlight the specific clinical needs for the
assessment and treatment for sexually abused children whose mothers experienced
child sexual abuse.
The measurement and analysis of low level vibrations and Acoustic Emissions in
components, fabrications and structures, is often accomplished by the utilisation
of multiple distributed piezoelectric sensors. The frequencies of interest usually
commence in the upper audio range above 2 kHz, but are more typically ultrasonic
frequencies (up to 1MHz). Such measurements are intrinsically limited in terms of
their dynamic range due to the signal to noise ratio of the overall system
(comprising the transducer and front end signal amplification, together with
associated interconnection cables). This paper demonstrates that the latest bipolar
operational amplifier technologies (rather than traditional FET technologies) can
provide a better solution at higher frequencies in these ultra low noise systems,
whilst still delivering the high gain bandwidth needed. This paper also presents a
comparative noise analysis for the three principle operational amplifier circuit
topologies commonly utilised for piezoelectric sensors: (single ended charge
amplifiers, differential charge amplifiers and voltage mode amplifiers). The
effects of transducer cables and system configuration are also considered from the
noise perspective. The theoretical analysis has been verified by practical
experiment.
This paper presents a standalone 5.6 nV/root Hz chopper op-amp that operates from a
2.1-5.5 V supply. Frequency compensation is achieved in a power-and area-efficient
manner by using a current attenuator and a dummy differential output. As a result,
the overall op-amp only consumes 1.4 mA supply current and 1.26 mm(2) die area. Up-
modulated chopper ripple is suppressed by a local feedback technique, called auto
correction feedback (ACFB). The charge injection of the input chopping switches can
cause residual offset voltages, especially with the wider switches needed to reduce
thermal noise. By employing an adaptive clock boosting technique with NMOS input
switches, the amount of charge injection is minimized and kept constant as the
input common-mode voltage changes. This results in a 0.5 mu V maximum offset and
0.015 mu V/degrees C maximum drift over the amplifier's entire rail-to-rail input
common-mode range and from -40 degrees C to 125 degrees C. The design is
implemented in a 0.35 mu m CMOS process augmented by 5 V CMOS transistors.
The aim of this research is to design a charge pump to improve current matching,
wide range of output voltage, fast switching operation and reduce charge sharing in
transistor. The design of charge pump is proposed and simulated in cadence virtuoso
ADE and ADXL tools at 90nm CMOS technology. Current mismatching is analysed with
Monte Carlo simulation and output variation is calculated on PVT. The designed
charge pump achieves wide output voltage swing 0.5 similar to 1V, improve current
mismatching approximate 0.5% and power dissipation of 320 mu W.
The paper deals with the design of a charge pump circuit after analyzing the
current mismatch problem. Charge sharing problem is eliminated by using
transistors. For enhancing the matching characteristics a cascode type current
mirror circuit is used. This design provides a technique by which the value of I-UP
and I-DN is matched in way that there is no time mismatch between the UP and DN
signals. The proposed design has a added advantage of low power consumption. All
simulations are done at 1.8v power supply.
A power and area efficient metal-oxide semiconductor field-effect transistor
(MOSFET)-only 1.5-bit fully differential pipelined analog-to-digital converter
(ADC) stage is proposed and designed in TSMC 0.18 mu m digital CMOS technology with
supply voltage of 1.8 V. It is based on charge pump based technique to achieve the
stage voltage gain of 2. Various capacitances are implemented by MOSCAPs
(capacitance offered by the MOSFET), offering compatibility with cheaper digital
complimentary metal-oxide semiconductor (CMOS) process in order to reduce the much
required manufacturing cost. The proposed stage suffers from only linear gain error
with full signal swing of 2 V peak-to-peak (p-p) differential. Using the proposed
stage, un-calibrated signal-to-noise and distortion ratio (SNDR) and spurious-free
dynamic range (SFDR) for 10-bit, 100 MS/s pipelined ADC are 40.11 and 40.86 dB,
respectively, which can be further increased by using a simple digital calibration
technique. Comparison between the proposed stage and conventional operational
amplifier based stage shows insensitivity towards capacitor mismatch along with
power savings and design simplicity.
A simple low-power and low-area metal-oxide-semiconductor field-effect transistor-
only fully differential 1.5-bit pipelined analog-to-digital converter stage is
proposed and designed in Taiwan Semiconductor Manufacturing Company 0.18m-
technology using BSIM3v3 parameters with supply voltage of 1.8V in inexpensive
digital complementary metal-oxide semiconductor (CMOS) technology. It is based on
charge pump technique to achieve the desired voltage gain of 2, independent of
capacitor mismatch and avoiding the need of power hungry operational amplifier-
based architecture to reduce the power, Si area and cost. Various capacitances are
implemented by metal-oxide semiconductor capacitors, offering compatibility with
cheaper digital CMOS process in order to reduce the much required manufacturing
cost.
To draw an accurate relationship between power dissipation and speed is a
challenging problem in operational Amplifier with switch capacitance. However,
transformation of current steer circuit into charge steer is an efficient technique
to reduce power dissipation even at higher speed. In this paper, an efficient model
is proposed to estimate the 1st and 2nd stage operational Amplifier's power
dissipation and delay, which can further used to design higher order Operational
Amplifier, Voltage controlled Oscillator, Analog to Digital converters and other
efficient power CMOS circuits. Analysis of 1st and 2nd stage Amplifier with BSIM4
model for CMOS in Tanner environment is done. The result shows that the power
dissipation is reduced approximately 63% for 1st stage and 53: 5% for 2nd stage
Amplifier using charge steering technique at 90nm.
A differential-hybrid charge sensitive preamplifier (CSP) was designed by taking a
monolithic dual N-Channel Junction Field-effect Transistor (JFET) and a high-speed,
low-noise, operational amplifier as the core parts. Input-stage of the circuit
employs low-noise differential dual JFET, which ensures high input impedance and
low noise. The differential dual transistor makes the quiescent point of the first-
stage differential output stable, which is convenient for connecting with the post
stage high-speed operational amplifier. Broadband could be amplified by connecting
to the double differential dual transistors through the folded cascode-bootstrap.
The amplifying circuit which replaces the interstage and post stage discrete
components of a traditional CSP with integrated operational amplifier is simpler
and more reliable. It simplifies the design of the quiescent point, gives full play
to advantages of releasing large open-loop gain, and improves charge-voltage
conversion gain stability. Particularly, the charge-voltage conversion gain is
larger under a smaller feedback capacitor, thus enabling to gain better signal-
noise ratio. The designed CSP was tested, reporting 3.3 x10(13) V/C charge
sensitivity, about 90 ns rise time of signals, 35:1 signal-noise ratio to gamma-
rays of Cs-137 (662 keV) and a 0.023 fC/pF noise slope. Gamma-rays of Am-241 (59.5
keV) were measured by the BPX66 detector and the designed CSP under room
temperature, providing 1.97% energy resolution.
In today's world power consumption is a burning issue. Research is going on to find
out various new power efficient design techniques. Power dissipation could be
reduced by transforming continuous-time current-steering circuits into discrete-
time charge-steering circuits. Charge steering shows all potential to emerge as an
effective technique to reduce power dissipation for high-speed circuits. This
technique can be exploited in the design of both analog and semi-analog circuits
such as an op-amp, latches and clock-data recovery (CDR) circuits. This paper
discusses the design techniques of charge steering circuits like op-amp and
latches. Both 1st stage and 2nd stage op-amp circuits and different type of latches
in a single stage and cascade forms are designed. The power and performances of the
charge steering circuits are also compared with conventional design techniques like
current mode logic (CML) circuits to show the improvements. The results show that
the op-amp power dissipation is reduced by approximately 87% with better gain. All
circuits have been designed using UMC's 180 nm CMOS technology.
Objectives This study aimed to develop a performance assessment tool for the
history-taking components of the medical evaluation of physical abuse in young
children by (1) determining the consensus-based injury history and social
components for documentation, (2) identifying preliminary performance standards,
(3) assessing current level-specific performance using the created tools, and (4)
evaluating reliability and validity of the created tools. Methods The Physical
Abuse Assessment Tool (PHAAT) was developed in 2 steps: (1) a modified Delphi
survey was used to identify the injury history and social components for
documentation in a medical evaluation for physical abuse, and (2) level-specific
(novice, competent, expert) practice standards (minimum passing scores) were
created using the identified components via the Angoff method. To evaluate
validity, reliability, and level-specific performance of the PHAAT, a chart review
of 50 consecutive cases from each of the 3 levels was performed. Results Seventy-
one child abuse pediatricians and 39 social workers participated in the modified
Delphi survey, and 67 child abuse pediatricians and 27 social workers participated
in the Angoff method. The resulting PHAAT included 2 checklists for use based on
presence or absence of a history of an injurious event. One-way analysis of
variance shows significant differences in performance based on team level (P <
0.001), indicating construct validity. Intrarater and interrater reliability
evaluations showed strong (r(s) = 0.64-0.92) and moderate to strong (intraclass
correlation coefficient = 0.81-0.98) correlations, respectively. Conclusions
Initial evaluation suggests the PHAAT may be a reliable and valid practice
assessment tool for the medical evaluation of physical abuse.
Evidence suggests that exosomes can transfer genetic material between cells.
However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we
report that exosomes present in the sera of chronic hepatitis B (CHB) patients
contained both HBV nucleic acids and HBV proteins, and transferred HBV to
hepatocytes in an active manner. Notably, HBV nucleic acids were detected in
natural killer (NK) cells from both CHB patients and healthy donors after exposure
to HBV-positive exosomes. Through real-time fluorescence microscopy and flow
cytometry, 1,1'-dioctadecyl-3,3,3', 3',-tetramethylindodicarbocyanine, 4-
chlorobenzenesulfnate salt (DiD)-labeled exosomes were observed to interact with NK
cells and to be taken up by NK cells, which was enhanced by transforming growth
factor-beta treatment. Furthermore, HBV-positive exosomes impaired NK-cell
functions, including interferon (IFN)-gamma production, cytolytic activity, NK-cell
proliferation and survival, as well as the responsiveness of the cells to poly (I:
C) stimulation. HBV infection suppressed the expression of pattern-recognition
receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells,
resulting in the dampening of the nuclear factor kappa B (NF-kappa B) and p38
mitogen-activated protein kinase pathways. Our results highlight a previously
unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during
CHB infection. Cellular & Molecular Immunology (2017) published online 30 May 2016
Objectives: To develop and provide validity evidence for a performance checklist to
evaluate the child abuse screening behaviors of prehospital providers. Methods:
Checklist Development: We developed the first iteration of the checklist after
review of the relevant literature and on the basis of the authors' clinical
experience. Next, a panel of six content experts participated in three rounds of
Delphi review to reach consensus on the final checklist items. Checklist
Validation: Twenty-eight emergency medical services (EMS) providers (16 EMT-Basics,
12 EMT-Paramedics) participated in a standardized simulated case of physical child
abuse to an infant followed by one-on-one semi-structured qualitative interviews.
Three reviewers scored the videotaped performance using the final checklist.
Light's kappa and Cronbach's alpha were calculated to assess inter-rater
reliability (IRR) and internal consistency, respectively. The correlation of
successful child abuse screening with checklist task completion and with
participant characteristics were compared using Pearson's chi squared test to
gather evidence for construct validity. Results: The Delphi review process resulted
in a final checklist that included 24 items classified with trichotomous scoring
(done, not done, or not applicable). The overall IRR of the three raters was 0.70
using Light's kappa, indicating substantial agreement. Internal consistency of the
checklist was low, with an overall Cronbach's alpha of 0.61. Of 28 participants,
only 14 (50%) successfully screened for child abuse in simulation. Participants who
successfully screened for child abuse did not differ significantly from those who
failed to screen in terms of training level, past experience with child abuse
reporting, or self-reported confidence in detecting child abuse (all p >0.30). Of
all 24 tasks, only the task of exposing the infant significantly correlated with
successful detection of child abuse (p < 0.05). Conclusions: We developed a child
abuse checklist that demonstrated strong content validity and substantial inter-
rater reliability, but successful item completion did not correlate with other
markers of provider experience. The validated instrument has important potential
for training, continuing education, and research for prehospital providers at all
levels of training.
The western blotting technique for transfer and detection of proteins, named
following the discovery of southern and northern blotting for DNA-and RNA-blotting,
respectively, has traditionally relied on the use of X-ray films to capture
chemiluminescence. Recent advancements use super-cooled charge coupled devices
(CCD) cameras to capture both chemiluminescence and fluorescence images, which
exhibit a greater dynamic range compared to traditional X-ray film.
Chemiluminescence detected by a CCD camera records photons and displays an image
based on the amount of light generated as a result of a dynamic chemical reaction.
Fluorescent detection with a CCD camera, on the other hand, is measured in a static
state. Despite this advantage, researchers continue to widely use chemiluminescent
detection methods due to the generally poor performance of fluorophores in the
visible spectrum. Infrared imaging systems offer a solution to the dynamic
reactions of chemiluminescence and the poor performance of fluorophores detected in
the visible spectrum, by imaging fluorophores in the infrared spectrum. Infrared
imaging is static, has a wide linear range, high sensitivity, and reduced
autofluorescence and light scatter. A distinct advantage of infrared imaging is the
ability to detect two target proteins simultaneously on the same blot which
increases accuracy of quantification and comparison, while minimizing the need for
stripping and reprobing. Here, we compare the methodology for chemiluminescent (UVP
BioChemi) and infrared (UVP Odyssey) detection of salivary total and phosphorylated
fetuin-A, a multifunctional protein associated with cardio-metabolic risk, and
discuss the advantages and disadvantages of these methodologies.
Background. Although human stromal vascular fraction (SVF) has been regarded as an
attractive stem cell source, its therapeutic mechanism in wound healing has not
been fully elucidated. Aims. In this study, we investigated the molecular
characteristics and therapeutic property of SVF for wound healing. Methods.
Microarray data showed that SVF cells are enriched with a higher level of wound
healing or epithelium development related genes and micro RNA. Results.
Quantitative polymerase chain reaction (PCR) and reverse transcriptase PCR results
revealed that the epithelialization growth factor, epidermal growth factor (EGF),
chemokines, stromal cell derived factor (SDF-1 or CXCL12), neutrophil-activating
protein-2 (NAP-2 or CXCL7), chemokine receptors (CXCR1, CCR2 and CCR3) and wound
healing genes were up-regulated in SVF compared with those in adipose-derived
mesenchymal stem cells (ASCs). An in vitro scratch wound closure experiment
demonstrated that co-culture with SVF substantially accelerated the wound closure
of fibroblasts. Wounds in nude mice were created by skin excisions followed by
injections of SVF with Pluronic hydrogel. SVF implantation highly accelerated wound
closure and increased cellularity and re-epithelialization. In addition, the
transplanted SVF exhibited high engraftment rates in the wound area, suggesting
direct benefits for cutaneous closure. Conclusions. Taken together, these data
suggest that SVF possesses high therapeutic capability for wound healing via the
secretion of epithelialization and chemotactic growth factors and enhanced
engraftment properties.
Stromal derived factor-alpha (SDF-1-alpha) is a CXC chemokine which has been
demonstrated as a recruitment factor for leukocytes to the site of inflammation,
infection, injury and following stress. This chemokine has been shown to be
expressed by liver cells and in liver diseases. Hence, the aim of this study was to
examine the expression of SDF-1 by hepatocytes in responses to the stress Imposed
during isolation by collagenase perfusion and under heat shock Stimulation. In this
study hepatocytes (2-5 x 10(6)) were isolated from male Sprague Dawley rat liver
and Cultured in plates that were pre-coated with collagen Type-I matrix. The
western and northern blotting analysis were employed to detect SDF-1 at protein and
mRNA levels in isolated and cultured hepatocytes in response to isolation and heat
shock stresses. The SDF-1 is expressed by isolated rat hepatocytes immediately
after isolation and early culture and decreased with time. SDF-1 protein was highly
expressed in freshly isolated cells and decreased by time (27h) (P<0.05). mRNA was
also expressed in freshly isolated cells (0h) but decreased after 24h of culture
(P<0.01). This results also demonstrated that expression of SDF-1 by hepatocytes
was increased in response to heat shock at different time points comparing with
control (P<0.01). These results demonstrated that the isolation and heat shock
stresses induced the expression of SDF-1 in hepatocytes in a time-dependent manner.
Accordingly, it seems that hepatocytes mimic the experiences that fiver experience
after injury in vivo and therefore, produce stress related agents like chemokines
to overcome such a injurious condition.
Background and ObjectivePeriodontal disease pathogenesis is comprised of the
complex inflammatory immune response to oral bacterial dysbiosis. Like other
inflammatory diseases, there is sexual dimorphism evident in periodontal diseases.
During periodontitis, inflammatory chemokines direct neutrophils to migrate to the
site of infection to neutralize the pathogen. Interestingly, these same chemokines
are also involved in regulating pathogen-induced osteoclast formation. Previous
reports show differences in bone turnover and lymphocyte recruitment between sexes.
We hypothesize that chemokine expression is differentially regulated by sex and
thus results in differential osteoclast formation. Material and MethodsMale and
female mice were utilized to isolate neutrophils based on expression of Ly6G-
specific, as well as defined osteoclast progenitors. Cells were stimulated with
lipopolysaccharide (LPS; 100 ng/mL) then analyzed for neutrophil infiltration and
gene expression. Defined osteoclast progenitors were primed: macrophage-colony
stimulating factor (25 ng/mL), receptor activator of NF-B ligand (50 ng/mL), then
stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated
for gene expression analysis via quantitative polymerase chain reaction. ResultsIn
response to LPS, male neutrophils in vitro respond with increased chemokine
expression and significantly more osteoclast formed in response to LPS compared to
females. ConclusionsFindings support observations in humans regarding a sexual
dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong
inflammatory response to bacterial infection, resulting in increased inflammatory
microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-
driven bone loss in response to differential expression of key chemokines.
Thiocyanate is a C1 compound containing carbon, nitrogen, and sulfur. It is a (by)
product in a number of natural and industrial processes. Because thiocyanate is
toxic to many organisms, including humans, its removal from industrial waste
streams is an important problem. Although a number of bacteria can use thiocyanate
as a nitrogen source, only a few can use it as an electron donor. There are two
distinct pathways to use thiocyanate: (i) the "carbonyl sulfide pathway," which has
been extensively studied, and (ii) the " cyanate pathway," whose key enzyme,
thiocyanate dehydrogenase, was recently purified and studied. Three species of
Thioalkalivibrio, a group of haloalkaliphilic sulfur-oxidizing bacteria isolated
from soda lakes, have been described as thiocyanate oxidizers: (i) Thioalkalivibrio
paradoxus ("cyanatepathway"), (ii) Thioalkalivibrio thiocyanoxidans (" cyanate
pathway") and (iii) Thioalkalivibrio thiocyanodenitrificans (" carbonyl sulfide
pathway"). In this study we provide a comparative genome analysis of these
described thiocyanate oxidizers, with genomes ranging in size from 2.5 to 3.8
million base pairs. While focusing on thiocyanate degradation, we also analyzed the
differences in sulfur, carbon, and nitrogen metabolism. We found that the
thiocyanate dehydrogenase gene is present in 10 different Thioalkalivibrio strains,
in two distinct genomic contexts/genotypes. The first genotype is defined by having
genes for flavocytochrome c sulfide dehydrogenase upstream from the thiocyanate
dehydrogenase operon (present in two strains including the type strain of Tv.
paradoxus), whereas in the second genotype these genes are located downstream,
together with two additional genes of unknown function (present in eight strains,
including the type strains of Tv. thiocyanoxidans). Additionally, we found
differences in the presence/absence of genes for various sulfur oxidation pathways,
such as sulfide: quinone oxidoreductase, dissimilatory sulfite reductase, and
sulfite dehydrogenase. One strain (Tv. thiocyanodenitrificans) lacks genes encoding
a carbon concentrating mechanism and none of the investigated genomes were shown to
contain known bicarbonate transporters. This study gives insight into the genomic
variation of thiocyanate oxidizing bacteria and may lead to improvements in the
application of these organisms in the bioremediation of industrial waste streams.
Neuropathy target esterase (NTE) was proposed as the initial target during the
process of organophosphate-induced delayed neuropathy (OPIDN) in human and some
sensitive animals. Adult hens are usually the animal model for experimental studies
of OPIDN. However, little is known about the sequence and characteristics of
chicken NTE. We report here the cloning of the 5' and 3' cDNA ends of chicken NTE
through rapid amplification of cDNA ends (RACE) and their expression profiles in
different tissues with northern blotting. The cloned 3' cDNA end of chicken NTE is
801 base pair (bp) in length with an open reading frame (ORF) of 379 bp. It
contains a termination codon (TAG) and a 422-nucleotide noncoding sequence with the
polyA sequence (GenBank accession no. DQ126678). The chicken NTE 5'cDNA end is 665
bp in length with an ORF of 552 bp. It contains an iniation codon (ATG) and a 113-
bp untranslated region (GenBank accession no. DQ 126677). The deduced proteins from
5' and 3'cDNA ends have a high degree of homology to humans and mouse NTE at the
amino acid level. Chicken NTE is suggested to be a transmembrane protein by the
transmembrane helix prediction of the deduced N-terminal sequence. The chicken NTE
gene is expressed as a 4.5 kb transcript in different tissues, including brain,
kidney, liver and testis. Moreover, the mRNA expression of chicken NTE is highest
in brain, and the mRNA levels of chicken NTE in testis, kidney and liver are about
75%, 47% and 24% of that in brain, respectively. These results should be helpful in
cloning chicken full-length NTE gene. (C) 2007 Elsevier Ireland Ltd. All rights
reserved.
MHM is a chicken Z chromosome-linked locus that is methylated and transcriptionally
silent in male cells, but is hypomethylated and transcribed into a long non-coding
RNA in female cells. MHM has been implicated in both localised dosage compensation
and sex determination in the chicken embryo, but direct evidence is lacking. We
investigated the potential role of MHM in chicken embryonic development, using
expression analysis and retroviral-mediated mis-expression. At embryonic stages,
MHM is only expressed in females. Northern blotting showed that both sense and
antisense strands of the MHM locus are transcribed, with the sense strand being
more abundant. Whole mount in situ hybridization confirmed that the sense RNA is
present in developing female embryos, notably in gonads, limbs, heart, branchial
arch and brain. Within these cells, the MHM RNA is localized to the nucleus. The
antisense transcript is lowly expressed and has a cytoplasmic localization in
cells. Mis-expression of MHM sense and antisense sequences results in overgrowth of
tissues in which transcripts are predominantly expressed. This includes altered
asymmetric ovarian development in females. In males, MHM mis-expression impairs
gonadal expression of the testis gene. DMRT1. Both MHM sense and antisense mis-
expression cause brain abnormalities, while MHM sense causes an increase in male-
biased embryo mortality. These results indicate that MHM has a role in chicken
normal embryonic development, including gonadal sex differentiation. (C) 2012
Elsevier Inc. All rights reserved.
Interferon-inducible transmembrane protein (IFITM) family proteins are antivirus
factors. In the present study, we examined the expression pattern of chicken
IFITM10 using quantitative reverse transcription-polymerase chain reaction. In
adult chickens, IFITM10 levels were markedly lower than those of IFITM3, which
exhibits antivirus activity. On the other hand, IFITM10 was expressed in levels
similar to those of IFITM3 in embryonic organs. Primordial germ cells in 2.5-d
embryos expressed high levels of IFITM10, which gradually decreased with time. The
interferon- stimulation of embryonic fibroblast cells did not enhance the
expression of IFITM10. The forced expression of IFITM10 slightly inhibited the
infectivity of the VSV-G-pseudotyped lentiviral vector. Furthermore, cell fusion
was inhibited by IFITM10 when HeLa cells transfected with the VSV-G expression
vector were treated with low pH buffer. Although it remains unclear whether IFITM10
inhibits viral infections under physiological conditions, these results suggest
that chicken IFITM10 exhibits antivirus activity.
Twenty chickpea accessions belonging to ten different countries of the world have
been subjected to phylogeny and length variations from nuclear ribosomal DNA (nr
DNA). ITS1-5.8S-ITS2 regions of Cicer accessions were used for amplification in two
sets, each comprising a reverse and forward ITS primers. Lengths of ITS-1 of C.
arietinum and C. reticulatum ranged from 340 to 350bp whereas that of ITS-2 from
400 to 410bp. In all the 20 accessions investigated, GC content in ITS-1 ranged
from 40 to 55% and in ITS-2 from 42 to 55%. Sequencing of polymerase chain reaction
product from ITS-1 showed variability in 278 and 290bp due to adenine and guanine
nucleotide base pairs. BLAST search for ITS-1 region revealed highest homology
(99%) with four strains of C. arietinum accessions. Whereas, ITS2 showed 100%
homology with C. arietinum and 99% homology with that of C. echinospermum.
In the late 1920s the government of the Federal Territory of Quintana Roo
introduced the cooperative system in the chicle industry, which was controlled by
U.S. chewing-gum companies and its contratistas, intermediaries between the
companies and the chicle producers. However, the project ended in failure, because
of various factors, including the impact of the Great Depression, U.S. companies'
boycott, the competition between chicle and other raw materials for chewing-gum,
the corruption and inefficiencies in the government, or the discord between the
local and federal governments.
Research examining child abuse and neglect (CAN) profiles among adult offender
populations is lacking. Therefore, the primary aim of the present study was to
address this limitation by using latent class analysis (LCA) to identify meaningful
classes of individuals who have experienced physical abuse, emotional abuse, sexual
abuse, as well as neglect. Another aim was to estimate the association between CAN
class membership and external criteria (psychopathy factors, self-esteem, attitudes
towards male sexual violence in dating relationships, child sexual abuse myth
acceptance, violent offending, and age). Data were collected among a large
systematically selected sample of adult male inmates (N=1261). Based on LCA, three
unique classes of CAN were distinguished, including a 'low abuse' group (43.4% of
the sample), a 'high physical and emotional abuse' group (51.3%), and a 'poly-
victimized' group (5.3%). The analysis revealed that the CAN classes were
differentially associated with affective responsiveness, cognitive responsiveness,
personal self-esteem, prison self-esteem, attitudes towards male sexual violence in
dating relationships, and violent offending. Findings highlight the unique nature
of CAN constellations among criminal justice involved participants. The
significance of the present results is discussed in relation to past and future
research. Potential contributions to treatment strategies are also presented. (C)
2016 Elsevier Ltd. All rights reserved.
Across the United States, child abuse law is governed by state statute.
Pediatricians must report suspected child abuse/neglect in accordance with their
state's specific reporting requirements; failure to make a timely report creates
civil liability exposures and triggers criminal penalties. The pediatrician's
initial report may instigate further investigation by child protective services,
and the reporting pediatrician may later become involved as a critical fact witness
in ensuing legal proceedings, including criminal prosecutions, custody
determinations, and medical malpractice controversies. The reporting pediatrician's
testimony may influence the disposition of those matters and significantly affect
the well-being of the involved children. As such, dutifully reporting pediatricians
promulgate and engage in peerless child advocacy.
Research suggests that early care and education (ECE) services, particularly
center-based ECE, may help prevent child maltreatment and also mitigate some of the
negative developmental outcomes associated with child maltreatment. There is also
preliminary evidence to suggest that ECE could reduce the likelihood that
maltreatment allegations will be substantiated by child welfare authorities and/or
result in children being placed in out-of home care. However, little is known about
rates of ECE participation among children receiving child welfare services, nor the
factors that determine ECE participation for this population. Data from the first
wave of the National Survey of Child and Adolescent Wellbeing II, a nationally
representative sample of children referred to the United States (U.S.) child
welfare system (CWS) for suspected maltreatment, were used to measure the frequency
with which 0-5 year olds participate in center-based ECE. Additionally, logistic
regression analyses explored the effects of maltreatment type, substantiation, and
children's living arrangements (Le., with parents, relatives, or foster parents) on
this outcome, controlling for a range of child and family covariates associated
with ECE participation in the general population. Results indicate that less than a
third of 0-5 year olds receiving child welfare services in the U.S. are
participating in center-based ECE. Among the various categories of maltreatment
type measured, being reported to the CWS for suspected physical abuse was
associated with decreased odds of center based ECE participation; however, other
types of maltreatment, substantiation, and living arrangement were unrelated to
center-based ECE participation. These findings suggest that, despite recent efforts
by the U.S. federal government to promote ECE participation for CWS-supervised
children, the vast majority of young children in the U.S. CWS are not receiving
center-based ECE, and physically abused children are particularly disadvantaged
when it comes to accessing these services. (C) 2016 Elsevier Ltd. All rights
reserved.
Background and Aim: Child maltreatment, i.e. abuse and neglect, is a significant
problem worldwide and can cause impaired physical and mental health throughout
life. The true extent still remains unknown in all countries, including Turkey. The
aim of this study was to apply the two versions of the International Society for
the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool of
ICAST-C and ICAST-P, which are used to assess child and parent feedback and to
compare reports given by children and those given by parents. This is the first
study of its kind conducted in Turkey. Methods: First, ICAST was translated into
Turkish by bilingual experts. Students and their parents were asked to complete
ICAST-C and ICAST-P respectively, with the help of trained researchers. In total,
data from 2,608 matched reports (2,608 children and 2,608 parents) was obtained.
Descriptive statistics were used to evaluate demographical variables, and chi-
square tests were employed to investigate the statistical significance of
comparisons. Results: The present study demonstrated that Turkish parents consider
rebukes, insults and corporal punishment effective ways of disciplining children.
According to parents' reports, the use of psychological abuse was most prevalent
against boys aged 16, while the use of physical abuse was most prevalent against
boys aged 13. A statistically significant relationship was found between parents'
economic conditions and child abuse (p0.05). However, the relationship between
paternal educational background and psychological abuse was observed to be
significant (p < 0.05). A comparison of children's and parents' reports shows that
parents tended to under-report child maltreatment. Conclusions: The results show
that there is a significant healthcare problem in Turkey, since child maltreatment
is prevalent, but parents are not generally aware of its extent. Possible
approaches to changing this situation include efforts to increase education levels,
promoting public awareness, and strengthening political commitments.
Most victims of child abuse have experienced more than one type of maltreatment,
yet there is a lack of understanding of the impact of specific combinations of
types of maltreatment. This study aimed to identify meaningful classes of
maltreatment profiles and to associate them with short-term clinical outcomes. A
total of 358 German children and adolescents aged 4-17 with a known history of
child maltreatment were included in the study. Through interviews and
questionnaires, information was obtained from participants and their primary
caregivers on history of maltreatment, sociodemographics, psychopathology, level of
psychosocial functioning, and health-related quality of life. Types of abuse were
categorized into six major groups: sexual abuse in general, sexual abuse with
penetration, physical abuse, emotional abuse, neglect, and exposure to domestic
violence. A latent class analysis (LCA) was performed to determine distinct multi-
type maltreatment profiles, which were then assessed for their associations with
the sociodemographic and clinical outcome variables. The LCA revealed that
participants could be categorized into three meaningful classes according to
history of maltreatment: (1) experience of multiple types of maltreatment excluding
sexual abuse (63.1%), (2) experience of multiple types of maltreatment including
sexual abuse (26.5%), and (3) experience of predominantly sexual abuse (10.3%).
Members of Class 2 showed significantly worse short-term outcomes on
psychopathology, level of functioning, and quality of life compared to the other
classes. Three distinct profiles of multiple types of maltreatment were empirically
identified in this sample. Exposure to multiple types of abuse was associated with
poorer outcomes. (C) 2016 Elsevier Ltd. All rights reserved.
Child maltreatment and other adverse childhood experiences adversely influence
population health and socioeconomic outcomes. Knowledge of the risk factors for
child maltreatment can be used to identify children at risk and may represent
opportunities for prevention. We examined a range of possible child, parent and
family risk factors for child maltreatment in a prospective 27-year population-
based birth cohort of 2443 Australians. Physical abuse, sexual abuse, emotional
abuse, neglect and witnessing of domestic violence were recorded retrospectively in
early adulthood. Potential risk factors were collected prospectively during
childhood or reported retrospectively. Associations were estimated using bivariate
and multivariate logistic regressions and combined into cumulative risk scores.
Higher levels of economic disadvantage, poor parental mental health and substance
use, and social instability were strongly associated with increased risk of child
maltreatment. Indicators of child health displayed mixed associations and infant
temperament was uncorrelated to maltreatment. Some differences were observed across
types of maltreatment but risk profiles were generally similar. In multivariate
analyses, nine independent risk factors were identified, including some that are
potentially modifiable: economic disadvantage and parental substance use problems.
Risk of maltreatment increased exponentially with the number of risk factors
experienced, with prevalence of maltreatment in the highest risk groups exceeding
80%. A cumulative risk score based on the independent risk factors allowed
identification of individuals at very high risk of maltreatment, while a score that
incorporated all significant risk and protective factors provided better
identification of low-risk individuals. (C) 2016 Elsevier Ltd. All rights reserved.
Social support by family, friends and significant others is known to buffer the
impact of adverse life events on children's well-being and functioning, however
little is known about pathways explaining this association. We investigated whether
maltreatment-related cognitions mediate the association between social support and
posttraumatic stress symptoms (PTSS). Furthermore, age was introduced as moderator.
We assessed the history of maltreatment in 200 maltreated children and adolescents
(age 8-17 years) using a semi-structured interview. Participants' perceived current
social support, maltreatment-related negative cognitions related to the
subjectively "worst" experience of maltreatment and PTSS during the past month were
assessed using self-report questionnaires. A set of mediation analyses
demonstrated, that negative maltreatment-related appraisals mediated the relation
between perceived social support and PTSS. The hypothesized negative associations
of social support with PTSS and dysfunctional cognitions did not differ between
children (8-11:11 years) and adolescents (12-17;11 years). Thus, the protective
function of social support after maltreatment can be explained by fewer negative
beliefs maltreated youth have about themselves and the world. These results provide
support to models of social-cognitive processing and emphasize the importance of
cognitive coping in regard to episodes of maltreatment which can be shaped within
social interactions with non-abusive caregivers, friends, and significant others.
(C) 2016 Elsevier Ltd. All rights reserved.
Child abuse and neglect occur in epidemic numbers in the United States and around
the world, resulting in major physical and mental health consequences for abused
children in the present and future. A vast amount of information is available on
the signs and symptoms and short- and long-term consequences of abuse. A limited
number of instruments have been empirically developed to screen for child abuse,
with most focused on physical abuse in the context of the emergency department,
which have been found to be minimally effective and lacking rigor. This literature
review focuses on physical, sexual, and psychological abuse and neglect, occurring
in one or multiple forms (polyabuse). A systematic, in-depth analysis of the
literature was conducted. This literature review provides information for
identifying children who have been abused and neglected but exposes the need for a
comprehensive screening instrument or protocol that will capture all forms of child
abuse and neglect. Screening needs to be succinct, user-friendly, and amenable for
use with children at every point of care in the healthcare system.
Child abuse is a global public health problem and a serious social issue in Japan.
Social support is beneficial for parents faced with childrearing challenges. The
aim of this study was to clarify the association between social support and child
abuse potential. A cross-sectional study was conducted using a structured
questionnaire. The target population was mothers of children at nine public nursery
schools. Bivariate and multiple linear regression analysis were performed to
examine the effects of socio-demographic, social support and psychological distress
factors on child abuse potential. Among 309 mothers, 29 (9.4%) had a high child
abuse potential score. Bivariate analysis indicated that mothers with a higher
child abuse potential score were more likely to be divorced or unmarried (P <
0.001); living in single-female-parent households (P < 0.001); have low perceived
economic status (P < 0.001); have a low level of child care support (P = 0.01);
have a low Multidimensional Scale of Perceived Social Support (MSPSS) score (P <
0.001); and/or a high General Health Questionnaire -12 score (GHQ -12) (P < 0.001).
Important predictors of child abuse potential among the mothers surveyed included
living in single-female-parent households, having low perceived economic status,
low MSPSS score, and high GHQ -12 score. Improving approaches that help mothers
build social support relationships and ease them into child rearing in a
psychologically healthy condition is recommended to prevent child abuse. (C) 2016
Elsevier Ltd. All rights reserved.
The current study presents a preliminary evaluation of a Spanish adaptation of an
implicit analog procedure, the Parent-child Aggression Acceptability Movie task
(Spanish Parent-CAAM). Based on Social Information Processing theory, Spanish
Parent-CAAM scores were expected to relate to self-reported PCA attitudes, negative
child attributions, and child abuse risk in Spanish students; 245 undergraduates in
Spain completed the Spanish Parent-CAAM along with self-report measures of PCA
attitudes, negative children attributions, inclination to punish misbehavior, and
child abuse risk. Findings indicate Spanish Parent-CAAM scores were significantly
related to explicit measures of PCA, attributions of intentional child misbehavior,
propensity to punish such misbehavior, and increased child abuse potential. Results
are considered within the cultural context of Spain's corporal punishment ban and
PCA attitudes.
The objective of this study was to investigate whether acute pain in abused
children was under recognized by doctors and nurses compared to children evaluated
for accidental injuries. We hypothesize that an abused child's reaction to physical
pain could be an additional symptom of this challenging diagnosis. For the
observational prospective case control study in an emergency department, children
were eligible when: younger than six years old, the reported trauma occurred within
the previous seven days, the trauma comprised a bone injury or burn, and the child
was able to express his or her pain. The case group comprised children for whom the
medical team reported their abuse suspicions and supporting information to a court,
and whose cases Of abuse were subsequently confirmed. The control group consisted
of children with a plausible cause for their injury and no obvious signs of abuse.
The children were matched according to their age and type of trauma. The pain was
assessed by doctors and nurses before analgesic administration using a certified
pain scale. Among the 78 included children, pain was significantly less recognized
in the abused children vs. the controls (relative risk = 0.63; 95% CI: 0.402-0.986;
p=0.04). We observed a discrepancy between the nurses' and doctors' scores for the
pain assessments (Kappa coefficient = 0.59, 95% CI: 0.40-0.77). Our results
demonstrate that pain expression in abused children is under recognized by medical
staff. They also suggest that abused children may have reduced pain expression
after a traumatic event. Paying particular attention to the pain of abused children
may also optimize the analgesic treatment. (C) 2017 Elsevier Ltd. All rights
reserved.
This article compares multiple types of child maltreatment among Puerto Rican
youth. We seek to expand the limited knowledge of the effects of multiple types of
maltreatment on depressive symptoms in a specific Latino population as emerging
studies indicate that children who are exposed to one type of maltreatment are
often exposed to other types. This study examines the predictive strength of
different and multiple types of lifetime child maltreatment (i.e., physical,
sexual, and emotional abuse; and neglect), and the effect of youth support from
parents, youth coping, youth self-esteem, and place of residence on depressive
symptoms among Puerto Rican youth. Secondary data analyses were performed using
three annual waves (2000-2004) of data from the Boricua Youth Study. The analytic
sample consists of 1041 10-13 year old Puerto Rican youth living in New York and
Puerto Rico. Results indicate that: (1) youth who experienced 'sexual abuse only',
'multiple maltreatment' (2 or more types of maltreatment), 'physical abuse only'
have a significant increase in depressive symptoms (75.1%, 61.6%, and 40.5%
respectively) compared to those without maltreatment; and (2) place of residence,
exposure to violence, and mental disorders were significant risk factors. When
developing psychosocial interventions, professionals should particularly focus on
youth who report past lifetime experience with child maltreatment. Particular
attention should be given to children living in the Bronx, New York and similar
urban low-income areas who report past lifetime experience with multiple types of
child maltreatment and who present symptoms or a diagnosis of co-occurring mental
health problems. (C) 2016 Elsevier Ltd. All rights reserved.
Background: Smoking behavior and smoking cessation are complex. Interpersonal
factors such as childhood adversity are associated with smoking, especially in
women. Identifying how and in whom these individual factors contribute to smoking
behavior may support individualized smoking cessation strategies. Attachment
insecurity (attachment avoidance and attachment anxiety) involves biological and
psychological processes in close relationships and is associated with both
childhood adversity, and in select populations, smoking. This study aims to
identify an association between attachment insecurity and smoking in adults and to
determine if attachment insecurity is a plausible mediator between childhood
adversity and smoking.Methods: In a cross-sectional survey, 348 primary care
patients reported childhood adversity, attachment insecurity and smoking status.
Statistical analyses were performed using regression and PRODCLIN.Results: Sixty-
one percent of participants had experienced childhood adversity and 20% were
current smokers. In women, attachment anxiety was associated with both childhood
adversity (p=.002) and current smoking (p=.04). The PRODCLIN test indicated that
attachment anxiety may be a mediator between childhood adversity and current
smoking in women (95%CI 0.003, 0.236). In men, current smoking was not associated
with childhood adversity (p=.673) or attachment anxiety (p=.29). Attachment
avoidance was not related to current smoking in men (p=.31) or in women
(p=.16).Conclusions: In women but not in men, attachment anxiety is associated with
current smoking and may mediate the relationship between childhood adversity and
current smoking. Childhood adversity and attachment anxiety may be factors to
consider in the design of cessation strategies for women.
Research has begun to explore the relationship between cancer and child abuse. Thus
far, work has shown that child abuse is associated with higher odds of cancer in
adulthood. Unfortunately, the current research is plagued by three interrelated
issues: (1) there is no agreement as to what actions constitute abuse and how abuse
types (i.e., physical, sexual, and emotional abuse) are distinct or interrelated;
(2) analytic strategies limit the types of conclusions that can be drawn because of
how they treat or measure abuse and related concepts; and (3) few theories exist to
explain the connection between abuse and cancer. Each of these issues and their
implications is described. Then an integrated theoretical framework that attempts
to address current shortcomings is proposed. Going forward, abuse research should
carefully consider the measures and mechanisms linking abuse to disease in order to
test meaningful hypotheses and advance our theoretical understanding of these
connections.
Increasing research efforts are exploring the racial/ethnic composition of the
population served by the U.S. child welfare system (CWS); however, only limited
research has examined the unique experiences of CWS-involved Latino/Latina children
and families, particularly those reported for child sexual abuse (CSA). This lack
of research is troubling given that Latinos/Latinas are this country's largest and
fastest growing minority group. To address this knowledge gap, this secondary data
analysis uses data from the 2012 National Child Abuse and Neglect Data System Child
File to examine a sample of children reported to the CWS (N = 2,401,304) and
subsample of children involved in CSA reports (n = 179,199). Using descriptive and
bivariate analyses, we describe a national profile of CWS-involved Latino/Latina
children reported for CSA. This profile is developed based on the child
characteristics of the analytic sample, rates of case substantiation, report
sources, perpetrator characteristics, and caretaker risk factors. We then compare
the profile of this subgroup of Latino/Latina children with the profiles of
children who are non-Latino/Latina Black or non-Latino/Latina White. Results
indicate several significant differences exist between the profiles of CWS-involved
Latino/Latina children with a CSA report as compared with their counterparts in
other racial/ethnic groups. Findings are discussed with the aim of informing
practice, policy, and research on sexual abuse prevention and intervention
strategies for Latino/Latina populations. (C) 2016 Elsevier Ltd. All rights
reserved.
This study examined the patterns and correlates of the types of maltreatment
experienced by adolescents aged 9-12, participating in an ongoing longitudinal
study on the impact of neglect on children's development. Using case record
abstraction, the study compared the child protection classification and findings
from the case record abstraction with regard to the rates of four types of
maltreatment (i.e. physical, sexual, emotional abuse and neglect) as well as co-
occurrence across multiple types of maltreatment. Next, the study examined the
frequently observed patterns of child maltreatment. Finally, the study investigated
whether aspects of caretaker functioning and the detailed incident characteristics
in the cases of neglect differed by the number of different types of maltreatment
the children experienced. Results showed significant discrepancies between the
Child Protective Service classification and case record abstraction. Child
Protective Service classification considerably underestimated the rate of co-
occurrence across multiple types of maltreatment. Neglect accompanied by physical
and emotional abuse was the most common form. Some of the caretaker functioning
variables distinguished the number of types of maltreatment. Based on the findings,
future-research directions and practice implication were discussed.
OBJECTIVE. Physicians have an ethical and legal mandate to identify abused children
so that they may be protected from further harm and are simultaneously required to
think broadly and objectively about differential diagnoses. The medical literature
is replete with examples of medical diseases that mimic abuse, potentially leading
to misdiagnoses and subsequent harm to children and families. CONCLUSION. This
review highlights some of the common and uncommon diseases that mimic physical and
sexual abuse of children.
Responding to Ross E. Cheit's Witch-Hunt Narrative, this article is a commentary
chronicling the emergence of child sexual abuse as a social issue in Los Angeles
County in the 1980s. Based on the responses to child sexual abuse in Los Angeles
County as experienced by one social worker during the McMartin years, it discusses
the impact of the McMartin case on the identification and intervention in child
sexual abuse cases and tracks the evolution and changes that took place in the
1980s and 1990s in Southern California. It offers some insight into a rationale for
the denial of child sexual abuse which continues to this day.
Psychiatrists are mandated to report suspicions of child abuse in America.
Potential for harm to children should be considered when one is treating parents
who are at risk. Although it is the commonly held wisdom that mental illness itself
is a major risk factor for child abuse, there are methodologic issues with studies
purporting to demonstrate this. Rather, the risk from an individual parent must be
considered. Substance abuse and personality disorder pose a separate risk than
serious mental illness. Violence risk from mental illness is dynamic, rather than
static. When severe mental illness is well-treated, the risk is decreased. However,
these families are in need of social support.
Across the eight jurisdictions of Australia, mandatory reporting obligations and
thresholds for reporting vary. Teachers are one group of the professionals who are
mandated to report child maltreatment, yet some teachers are still reluctant to
make such a report. This paper examines the barriers that discourage teachers from
reporting child maltreatment and also whether teachers consider it necessary to
question a child about the maltreatment before they decide if a report should be
made. Thirty semi-structured interviews with Victorian primary school teachers were
thematically analysed and revealed that inadequate and inconsistent mandatory
reporting training, the need for certainty before initiating a report and the
ambiguous concept of neglect were barriers to teachers identifying and reporting
child maltreatment. Analyses further revealed that teachers gather evidence to
confirm or disconfirm their suspicions of maltreatment by questioning the suspected
child victim. The consequences of this practice are discussed along with
recommendations to help overcome the barriers to making a formal report when child
maltreatment is suspected.
Using administrative child welfare data from the Ontario Child Abuse and Neglect
Data System (OCANDS), this study compared the profiles of Asian-Canadian and White-
Canadian children and families that experienced a case closure after an
investigation instead of being transferred to ongoing child protection services
(CPS). Child protection investigations involving Asian-Canadian and White-Canadian
children and families that were transferred to ongoing CPS presented a different
profile of case characteristics and caregiver and child clinical needs. Asian-
Canadian children and families received ongoing CPS for over a month longer than
White-Canadian children and families and were less likely (odds ratio [OR] = 0.39)
to be reinvestigated for any form of maltreatment-related concerns within 1 year
after case closure. It appears that child protection investigations involving
Asian-Canadian children and families are less likely to be closed prematurely than
White-Canadian children and families, and the child protection system may be
meeting the needs of Asian-Canadian communities. Alternatively, it is possible
there is unaccounted biases that may be reflective of systemic problem of
discriminative practices in the child protection system. Further research is needed
to explore this phenomenon.
Introduction: Numerous data sources suggest a decline in child sexual abuse (CSA)
in the United States since the early 1990s. Some evidence also indicates that an
earlier period of higher CSA incidence began following World War II. This study
examines prevalence estimates of sexual abuse reported retrospectively as having
occurred in childhood (ChSA) in two nationally representative surveys of the
Canadian population. Methods: Data are from 13 931 respondents aged 18 to 76 years
from the 2004/2005 Canadian Gender, Alcohol, and Culture: An International Study
(GENACIS), and from 22 169 household residents aged 18 years or older who
participated in the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH).
We present inter-and intrasurvey comparisons of ChSA prevalence specific to sex and
age groups. Results: Findings from both surveys suggest a decline in CSA since
1993, consistent with declines observed in the United States. Results also suggest
that 1946 to 1992 was a period of higher risk of CSA, relative to the period before
1946. The evidence was more robust for women. Conclusion: Evidence of a decline in
CSA in Canada since the early 1990s is encouraging, given the long-term
debilitating effects with which it is associated. Continued monitoring is critical.
The long-term negative effects associated with CSA underscore the importance of
continuing to move from lower risk to zero risk.
To develop a prediction model for the first recurrence of child maltreatment within
the first year after the initial report, we carried out a historical cohort study
using administrative data from 716 incident cases of child maltreatment (physical
abuse, psychological abuse, or neglect) not receiving support services, reported
between April 1, 1996 through March 31, 2011 to Shiga Central Child Guidance
Center, Japan. In total, 23 items related to characteristics of the child, the
maltreatment, the offender, household, and other related factors were selected as
predictive variables and analyzed by multivariate logistic regression model for
association with first recurrence of maltreatment. According to the stepwise
selection procedure six factors were identified that include 9-13 year age of child
(AOR =3.43/95%CI = 1.52-7.72), <40 year age of the offender (AOR= 1.65/95%CI =
1.09-2.51), offender's history of maltreatment during childhood (AOR = 2.56/95%Cl =
1.31-4.99), household financial instability or poverty (AOR= 1.64/95%Cl =1.10-
2.45), absence of someone in the community who could watch over the child (AOR=
1.68/95%Cl = 1.16-2.44), and the organization as the referral source (AOR =
2.21/95%CI = 1.24-3.93). Using these six predictors, we generated a linear
prediction model with a sensitivity and specificity of 45.2% and 82.4%,
respectively. The model may be useful to assess the risk of further maltreatment
and help the child and family welfare administrations to develop preventive
strategies for recurrence. (C) 2016 The Author(s). Published by Elsevier Ltd.
Recognizing the clinical presentation of a child with abusive injuries is crucial.
This review article gives an updated summary on inflicted intraoral, esophageal,
and abdominal visceral injuries, including current recommendations on recognition,
evaluation, screening value, and management of at risk children. Physical abuse
should be suspected in precruising infants with intraoral injuries. When sexual
abuse is suspected, referral to specialized centers equipped to conduct
comprehensive examination and forensic testing by an experienced provider adhering
to chain of evidence protocol is recommended. Abdominal trauma is the second most
common cause of death in children who have been abused. The diagnosis and
management of these injuries require careful consideration. Routine screening
hepatic transaminases should be guided by the age of child and clinical scenario. A
definitive confirmatory computed tomography scan of the abdomen and pelvis should
be performed for those with transaminase levels more than 80 IU/L, or in all
concerning cases with history and examination consistent with abusive abdominal
trauma.
We examine associations between childhood sexual abuse (CSA) and substance abuse,
the role of mental health indicators as mediators in these associations and whether
or not associations differ by gender. Data are from 14,063 respondents aged 18-76
years from the 2004-2005 Canadian Gender, Alcohol, and Culture: An International
Study (GENACIS). Multiple logistic regression models were used to examine
associations between CSA and substance abuse variables, controlling for socio-
demographic factors. Odds were adjusted by indicators of mental health to assess if
these variables mediated associations between CSA and substance abuse. Tests of
interactions between sex and CSA were conducted to see if gender differences exist
in associations. In 2004/2005, CSA was reported by 14% of women and 5% of men. CSA
was associated with heavy drinking, hazardous drinking, and the use of marijuana,
other illicit drugs, and off-label drugs. Associations were only very marginally
attenuated when controlling for depression and self-perceived emotional/mental
health. In all cases previously observed significant associations persisted.
Evidence of gender differences in associations between CSA and substance abuse was
negligible. Preventing CSA may also reduce substance abuse. Crown Copyright (C)
2016 Published by Elsevier Ltd.
Background: In recent years, a number of government-sponsored initiatives have been
implemented in Germany that are focused on early preventive intervention in child
protection. In response to the need for interdisciplinary training in this area,
the internet-based e-learning program "Early Preventive Intervention and Child
Protection" was developed for professionals in the child welfare and health care
systems working with families with infants and toddlers. The program is currently
undergoing evaluation for effectiveness and user satisfaction. Methods: In a pre-
post design, users are requested to complete questionnaires that assess three
measures of expertise: theoretical knowledge of relevant fields, the ability to
correctly identify subtle signals of infant communication, and the ability to
assess maternal sensitivity. This article presents the contents of the program and
the pre-training results (N = 1.294 participants). Descriptive analyses as well as
Pearson correlations and Bonferroni corrections of error were conducted using the
statistical program SPSS v. 21.0. Results: The findings show that a wide range of
professionals are making use of the program, and that their existing theoretical
knowledge about early preventive intervention, as well as their ability to identify
subtle signals of infant communication, is relatively good. However, their ability
to assess maternal sensitivity, which is considered a crucial indicator for the
risk of child abuse, was low. Conclusions: The outcome of the pre-training results
indicates that professionals working in the area of child protection need to
develop more capability in recognizing maternal sensitivity, in order to ensure
early detection of families who are at risk and thus in need of support. Finally,
the number of years of professional experience did not correlate with the scores on
any of the three measures, which emphasizes the importance of providing
interdisciplinary training in this area for all those working in child and family
services, regardless of background.
In high-conflict divorce cases, the emotional toll on the family unit is
unquestionably destructive. While the physical and mental health of the children
should be the primary focus, the emotional turmoil of a high-conflict divorce often
moves the focus away from the children as parents struggle emotionally and
financially. Although the best interests of the children are always in the judicial
purview, the repeated, lengthy, and hostile litigation process often associated
with high-conflict dissolution has lasting effects on the physical and mental
health of children, similar to those associated with physical abuse and neglect.
Child Protective Services (CPS) must step in and protect the emotional well-being
of children during high-conflict divorce cases.
Interest in child maltreatment research has been growing in the last two decades.
The main approach underlying this research has relied upon self and family reports.
These methods may be problematic because they often require conscious awareness,
generate socially desirable over accurate responses or can be biased by parents'
unrealistic expectations, misattributions and perceptual errors. Simultaneously,
research has been adapting methods from social cognition research in an attempt to
access the implicit and spontaneous processes underlying the information processing
related to parent-child interactions, exploring parental cognitions and emotions
that may constitute important contributions to explain abusive and neglectful
parenting. In this paper we review the research on child abuse and neglect using
implicit measures. Using combinations of words related with child abuse and
neglect, and with autonomic and affective variables assessed by the implicit
measures, we have conducted a systematic review of 33 studies, and we examined the
variables explored, the type of measures used and the results obtained. The
research reviewed points out the importance of assessing parental representations
in parent-child interactions and analyzing the differences between maltreating and
non-maltreating parents. Specifically, physically abusive parents tend to show more
difficulties in recognizing children's emotions, reveal more biases in their
perceptions and attributions about children and behave more aggressively. Further
research with maltreating parents, namely neglectful, using implicit measures is
still required. (C) 2016 Elsevier Ltd. All rights reserved.
Parental maltreatment of children has been steadily increasing in Korea despite
national efforts to curb it. Children and adolescents who experience maltreatment
develop psychological and social maladjustment. Therefore, mediating variables
alleviating the negative effects of parental maltreatment on child development
should be investigated to develop effective intervention programs. We identified
the direct effects of parental abuse and neglect on adolescents' school adjustment
and the mediating effects of adolescents' self-esteem and peer attachment on the
relationships between parental abuse and neglect and their school adjustment. We
used data from 2351 middle school students who participated in the Korean Children
and Youth Panel Survey. Structural equation modeling revealed the following: child
neglect directly and negatively related with adolescents' school adjustment,
whereas child abuse did not. Further, while adolescents' self-esteem and peer
attachment mediated the relationship between child neglect and school adjustment,
adolescents' self-esteem alone mediated the relationship between child abuse and
school adjustment. These findings imply that there is a need to develop different
intervention programs based on child maltreatment types. Finally, we suggested that
the negative effects of parental neglect on adolescents' school adjustment could be
alleviated by adolescents' self-esteem recovery resulting from peer support. On the
other hand, in the case of adolescents experiencing parental abuse, self-esteem
recovery through education and counseling provided by teachers or respected adults
could be prioritized.
This study systematically reviews research on child maltreatment and risk of
gambling problems in adulthood. It also reviews adult problem gamblers' risk of
abusing or neglecting their own children. Multiple database searches were conducted
using pre-defined search terms related to gambling and child abuse and neglect. We
identified 601 unique references and excluded studies if they did not report
original research, or did not specifically measure child maltreatment or gambling.
Twelve studies that included multivariable analysis of childhood maltreatment
exposure and problem gambling were identified. Six of seven studies examining
childhood sexual abuse and four of five examining physical abuse showed a
significant positive association between abuse and later gambling problems (odds
ratios for sexual abuse 2.01-3.65; physical abuse 2.3-2.8). Both studies examining
psychological maltreatment and two of three examining neglect identified positive
associations with problem gambling. In most studies, risks were reduced or
eliminated when controlling for other mental health disorders. The three studies
measuring risk of child abuse and neglect among current problem gamblers suggest an
increased risk for child physical abuse and medical conditions indicative of
neglect although there is a considerable amount of variation among studies. Child
abuse is associated with increased risk of gambling problems - gambling treatment
providers should ask about maltreatment history as part of their clinical
assessment. Problem gamblers may be more likely to physically abuse or neglect
their children, but data here are more limited. Child welfare professionals should
consider asking questions about parental gambling when assessing family risk. (C)
2016 Elsevier Ltd. All rights reserved.
Child maltreatment most often occurs within the family and is often an expression
of the inability of parents to cope with the child's needs. Parental distress
results in inadequate, conscious or unconscious but never accidental overreactions,
resulting in severe physical and psychological sequelae. Furthermore, the
individual and healthcare costs to society are extensive; therefore, early
identification of children and adolescents at risk is of paramount importance and
due to the position of trust in relationship to families, pediatricians play an
important role. The recommended preventive medical check-ups are regular contacts,
which provide the opportunity for early recognition of child maltreatment and
implementation of measures to prevent further harm. Knowledge of risk factors,
potential triggers and availability of community programs and resources to help
affected families are indispensable prerequisites.
Despite wide recognition that increased social support is associated with positive
parenting behaviors, there is limited understanding regarding the mechanisms
through which the neighborhood context can increase or hinder social connections.
In a sample of 1,050 parents in Franklin County, OH, this study examines the role
of availability of social services in child maltreatment. Through negative binomial
regression, the study finds that greater availability of social services is
associated with lower levels of child abuse and neglect. Additionally, the
availability of social services moderates the relationship between social support
and child maltreatment, such that the relationship between social support and child
maltreatment is weaker for parents in neighborhoods with greater availability of
services. The findings suggest that increasing services and awareness of such
services might be an opportunity for child maltreatment prevention.
Background: It is well established that childhood maltreatment (CM) is a risk
factor for various mental and substance use disorders. To date, however, little
research has focused on the possible long-term physical consequences of CM.
Diabetes is a chronic disease, for which an association with CM has been
postulated. Methods: Based on data from a sample of 21,878 men and women from the
2012 Canadian Community Health Survey - Mental Health (CCHS - MH), this study
examines associations between three types of CM (childhood physical abuse (CPA),
childhood sexual abuse (CSA), and childhood exposure to intimate partner violence
(CEIPV)) and diabetes in adulthood. Multiple logistic regression models were used
to examine associations between CM and diabetes controlling for the effects of
socio-demographic characteristics and risk factors for type 2 diabetes. Results:
When controlling socio-demographic characteristics, diabetes was significantly
associated with reports of severe and frequent CPA (OR = 1.8) and severe and
frequent CSA (OR = 2.2). A dose-response relationship was observed when co-
occurrence of CSA and CPA was considered with the strongest association with
diabetes being observed when both severe and frequent CSA and CPA were reported (OR
= 2.6). Controlling for type 2 diabetes risk factors attenuated associations
particularly for CPA. CEIPV was not significantly associated with having diabetes
in adulthood. Conclusion: CPA and CSA are risk factors for diabetes. For the most
part, associations between CPA and diabetes are mediated via risk factors for type
2 diabetes. Failure to consider severity and frequency of abuse may limit our
understanding of the importance of CM as a risk factor for diabetes.
Adult victims of child physical abuse (CPA) are more likely to perpetrate intimate
partner violence (IPV) than are nonvictims. However, not all CPA victims go on to
become violent toward their partners, suggesting that other factors moderate risk
for IPV perpetration. Drawing on the background-situational model (Riggs & O'Leary,
1989, 1996), this study examines the independent and interactive effects of CPA
history and negative affect arising during conflict with an intimate partner in
predicting physical IPV perpetration. Fifty-three heterosexual dating couples
completed questionnaires assessing CPA history and perpetration of physical IPV.
Couples discussed the largest source of conflict in their relationship for 10 min.
Videos of these discussions were coded for negative affect. Using an actor partner
interdependence model approach to account for the dyadic interdependence of the
data, findings revealed that at average levels of negative affect, CPA severity
predicted greater IPV perpetration for both men and women. However, at average
levels of CPA, negative affect during conflict was positively predictive of IPV
perpetration for men only. Findings further revealed an interaction such that for
men, the positive association between CPA severity and IPV perpetration became
stronger as their negative affect during conflict increased.
BackgroundThere have been no previous studies on the adequacy of combined
evaluation of possible abusive head trauma cases by frontline medical personnel,
hospital-based child protection teams, and child protective services in local
districts of Japan. MethodsWe conducted a questionnaire survey of hospitalized
patients under 24months old with a diagnosis of intracranial hemorrhage (ICH) from
January 2011 to December 2013. Eleven large-scale general hospitals in Yokohama,
Japan were surveyed, which provide centralized inpatient care to moderately-
severely ill children. ResultsA total of 51 ICH patients were listed from eight
hospitals. Median patient age was 7months, and 84% were younger than 12months. The
most common diagnosis on computed tomography was subdural hematoma (n=26; 51%). Of
a total of 51 cases, 31 (61%) occurred inside the home; the injury scene was
unknown in six cases (12%). We reviewed these 37 cases from the viewpoint of
evaluation with concern for suspected child abuse. Three out of 37 patients (8%)
were not examined for inflicted skin lesions, and skeletal surveys and funduscopy
were not conducted in 14 (38%) and 15 (41%), respectively. Thirteen out of 37 cases
(35%) were not reported to hospital-based child protection teams and 22 (59%) were
not reported to regional child protective services. ConclusionThe sociomedical
evaluation of possible child abuse appears to be systematically inadequate in
Yokohama.
Removing a child from parental care is an important and difficult decision to make.
There are far reaching consequences for the child and family. Whilst there is a
plethora of literature in relation to child protection practice generally, research
on decision making is minimal. In this practice paper, I present 12 decision-making
criteria to assist practitioners make decisions about child removal. It is
important for child protection practitioners to apply the same set of principles
and consider the same factors when making these decisions. These criteria are as
follows: the severity of the abusive incident; the presence of cumulative harm;
whether the perpetrator has access to the child; the functioning of the parent;
whether the perpetrator has been responsible for child abuse or intimate partner
violence in the past; the cooperation of the parent; the intent of the perpetrator;
the age of the child; the functioning of the child; the voice and expressed wishes
of the child; protective relationships available to the child and the statutory
requirement to cause no further harm. Referring to these criteria will assist
practitioners be clear and explicit about how they reach a decision, and result in
greater consistency of outcome for children and families.
Children participating in research, like other children, may be being maltreated.
There is also potential for exposure to abuse during research. Research training,
practices and protocols to respond to disclosure and discovery of abuse to protect
both researchers and children may not be sufficiently robust. Our aim was to
compare and contrast research practices reported in the literature related to
protecting children and to recommend safer ways to conduct research. The
simultaneous increase in research with children, along with an increased
willingness to listen to child victims of abuse, means that researchers must
consider the protection of children in the research setting. Twenty-three papers
were identified in a literature review. These studies reported a wide variation of
ethical considerations, methods, methodology and came from different disciplines.
From the 23 papers, two overarching themes were identified: social justice and
research and safer research. To make research safer teams should consider training,
safety protocols and support for child protection, which includes support to report
safeguarding concerns to social care. Further work is required to ensure that
training, protocols and support are effective in facilitating researchers to
identify and make appropriate child abuse referrals. Ethics practices in abuse
research need further debate.
The role of teachers in safeguarding the welfare of children is long acknowledged.
However, recent research in Ireland found that the training provided to teachers on
child protection issues was lacking (Buckley and McGarry, ). The frequent
interactions that teachers have with children and their expertise in terms of
typical child development place them in an ideal position for identifying possible
signs of abuse. Yet despite this advantage, research indicates that schools fail to
report a substantial proportion of suspected child abuse cases (Kenny, ). The oft-
cited reasons for this may be conceptualised as: explicit reasons, such as a lack
of knowledge about child abuse issues; and implicit reasons, such as the individual
teacher's belief system about abuse. The current paper discusses implicit as well
as explicit obstacles to teachers' engagement' with, and consequent barriers to
their responding to, child protection issues. The current changes in initial
teacher education and the introduction of mandatory reporting for professionals in
Ireland, offer an opportune time to raise this issue and highlight the need for
holistic education in child protection for teachers. Copyright (c) 2015 John Wiley
& Sons, Ltd.
There is convincing evidence that many young people who are in the justice system
have had contact with child protection services and that victims of childhood
maltreatment are at increased risk of subsequent youth justice involvement. In
Australia, however, there have been few longitudinal studies that have examined
these associations and relatively less is known in this area. This study examines
the overlap between the child protection and youth justice involvement in South
Australia, and determines how substantiated maltreatment and variations in these
experiences (e.g., the type, timing and recurrence of maltreatment) relate to
criminal convictions as a youth. The results show that although the majority of
child-protection involved youth do not become convicted offenders, the odds of
subsequent convictions are significantly greater both for those with notifications
and substantiated maltreatment and for those who had been placed in out-of-home
care. Multivariate analyses revealed that the strongest predictors for receiving a
conviction among maltreated youth were: male gender, Aboriginal and Torres Strait
Islander ethnicity, experiences of physical abuse and emotional abuse, a greater
number of substantiations (recurrence), experiencing maltreatment that commenced in
childhood and continued into adolescence, and placement in out-of-home care. The
mechanisms through which maltreatment might be linked with behavior are then
considered, along with directions for future research in this area. (C) 2016
Elsevier Ltd. All rights reserved.
AimChildhood maltreatment (CM) has been related to a persistent reprograming of
stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis
activation; however, few studies have examined copeptin levels in children exposed
to CM. The aim of this study was to compare serum copeptin levels in children
reporting child abuse and/or neglect and children with no history of CM.
MethodsThis study included 65 children with a positive history of moderate to
severe CM, as reported by themselves and their parent(s) during a clinical
interview, and 71 children with no history of CM as a comparison group. CM was
considered moderate to severe based on the child-reported frequency of being
exposed to events related to sexual abuse, physical abuse, emotional abuse,
emotional neglect, and/or physical neglect. Child psychopathology symptoms were
assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin
concentration using enzyme-linked immunosorbent assay. ResultsChildren exposed to
CM exhibited higher levels of serum copeptin compared to children without CM when
controlling for sex, age, and psychiatric morbidity. The CBCL total score,
including internalizing and externalizing symptoms, was higher in children with CM.
We found no correlation between copeptin and CBCL scores for internalizing symptoms
and externalizing symptoms. Conclusion CM is associated with copeptin serum levels
independently of age, sex, and symptom severity. Copeptin is a promising new
biomarker for children with a history of abuse and/or neglect.
A growing awareness of child sexual exploitation (CSE) in the United Kingdom and
throughout the world has prompted human service and legal/policy professionals to
seek ways of engaging young people experiencing sexual exploitation, although much
remains unknown regarding effective practice, and whether or not current knowledge
regarding best practices with young people can be expanded to address CSE. This
paper considers how principles of harm reduction, a public health approach widely
used to engage adults and young people in help-seeking behaviours, can be
considered as part of a children's rights-centred approach to policy and practice
with young people experiencing CSE. (C) 2015 The Authors. Children & Society
published by National Children's Bureau and John Wiley & Sons Ltd.
While the link between educational attainment and future health and wellness is
well understood, little investigation has considered the potential impacts of
distinct forms of childhood maltreatment on high school completion. In the present
study, the relationship between five categories of childhood maltreatment
(physical, emotional, and sexual abuse, and physical and emotional neglect) and
completion of high school education were examined using the Childhood Trauma
Questionnaire (CTQ). From September 2005 to May 2013, data were collected for the
At-Risk Youth Study (ARYS), a cohort of street-involved young people who use
illicit drugs in Vancouver, Canada. We used logistic regression to examine the
relationship between childhood maltreatment and high school completion, while
controlling for a range of potential confounding variables. Specifically, five
separate models for each category of maltreatment and two combined models were
employed to examine the relative associations between, and cumulative impact of,
different forms of childhood maltreatment and educational attainment. Among 974
young people, 737 (76%) reported not completing high school. In separate
multivariable analyses physical abuse, emotional abuse, physical neglect, and
emotional neglect remained positively and independently associated with an
incomplete high school education. In a combined multivariable model with all forms
of childhood maltreatment considered together, emotional abuse (adjusted odds
ratio=2.08; 95% confidence interval: 1.51-2.86) was the only form of maltreatment
that remained significantly associated with an incomplete high school education.
The cumulative impact assessment indicated a moderate dose-dependent trend where
the greater the number of different forms of childhood maltreatment the greater the
risk of not completing a high school education. These findings point to the need
for trauma-informed interventions to improve educational attainment among
vulnerable young people, as well as evidence-based prevention programmes, such as
the Nurse-Family Partnership, aimed at supporting at-risk families before
maltreatment occurs.
Children often need help before their parents are ready to stop fighting. Children
at the center of high-conflict disputes, particularly those who resist contact with
a parent, face extraordinary risks of maladjustment. Years of investigation and
litigation may precede any meaningful attempt at intervention, based on the
questionable belief that all elements of causality (or blame) must be established
before any effective treatment can occur. Children's functioning may continue to
deteriorate during this time, undermining their future adjustment and reducing the
chance of successful intervention later. We illustrate the application of the
coping-focused, multisystemic Child Centered Conjoint Therapy model to assisting
these families. Methods to assist children without compromising external
investigations are discussed.
Among children visiting child and adolescent mental health care (CAM), the
prevalence of exposure to family violence (FV) is reported to exceed prevalence in
community samples, as are potentially traumatic interpersonal events (IPE) outside
the family. The aim of the study was to relate CAM patients' self-reported
experiences of violence exposure to their current psychiatric symptoms and to
compare patients exposed to violence with patients who reported no exposure. We
asked 305 consecutive 9- to 17-year-old patients in CAM about their current and
previous exposure to violence in and outside of the family. Prevalence of exposure
to any kind of violence was 67%. Reported exposures were 19% to IPE, 21% to FV, and
27% to both. Children exposed to both FV and IPE were more negatively affected by
the events than children exposed to FV or IPE only. Children in the FV + IPE group
reported more mental health symptoms than those in the no violence (33%) group. In
general, IPE was related to the outcome measures only in combination with FV.
Degree of violence exposure seemed to have a dose-response relationship with the
diagnosis of post-traumatic stress disorder.
It is widely accepted that the classic metaphyseal lesion (CML) is a traumatic
lesion, strongly associated with abuse in infants. Nevertheless, various non-
traumatic origins for CMLs continue to be suggested in medical and legal settings.
No studies to date systematically describe the association of CMLs with other
traumatic injuries. The primary objective of this study is to examine the
association of CMLs with other traumatic injuries in a large data set of children
evaluated for physical abuse. This was a retrospectively planned secondary analysis
of data from a prospective, observational study of children < 120 months of age who
underwent evaluation by a child abuse physician. For this secondary analysis, we
identified all children a parts per thousand currency sign12 months of age with an
identified CML and determined the number and type of additional injuries
identified. Descriptive analysis was used to report frequency of additional
traumatic injuries. Among 2,890 subjects, 119 (4.1%) were identified as having a
CML. Of these, 100 (84.0%) had at least one additional (non-CML) fracture. Thirty-
three (27.7%) had traumatic brain injury. Nearly half (43.7%) of children had
cutaneous injuries. Oropharyngeal injuries were found in 12 (10.1%) children.
Abdominal/thoracic injuries were also found in 12 (10.1%) children. In all, 95.8%
of children with a CML had at least one additional injury; one in four children had
three or more categories of injury. CMLs identified in young children are strongly
associated with traumatic injuries. Identification of a CML in a young child should
prompt a thorough evaluation for physical abuse.
Missing a fracture in a child on skeletal surveys for suspected non-accidental
trauma can have devastating results. Double-read has the potential to improve
fracture detection. However the yield of double-read is unknown. To determine the
advantage of double-read versus single-read of radiographic skeletal surveys for
suspected non-accidental trauma. The study was performed in two phases. In the
first phase (April 2013 to September 2013), double-read was performed for all
skeletal surveys obtained during weekday working hours. Because we had no new
double-read findings in studies initially read as negative, we conducted a second
phase (January 2014 to March 2014). In the second phase we limited double-reads to
skeletal surveys found positive on the first read. At the end of this period, we
retrospectively performed double-read for all initially negative skeletal surveys.
We excluded follow-up skeletal surveys. The difference in discrepancy (new fracture
or false diagnosis of a fracture) ratio between negative and positive skeletal
surveys was evaluated using the Fisher exact test, and change in discrepancy ratio
between the first and second study phases was evaluated using the stratified
Cochran-Mantel-Haenszel test. Overall in the two phases, 178 skeletal surveys were
performed in 178 children (67 girls) with mean age of 9 months (range 3 days to 3.7
years). Double-read found 16 discrepancies in 8/178 (4.5%) skeletal surveys. Seven
of these studies showed additional fractures (n=15). In one study, an initial read
of a skull fracture was read as a variant on the second read. There was a
significant (P=0.01) difference between rate of disagreement in negative skeletal
surveys (1/104, 1.0%) and positive skeletal surveys (7/74, 9.5%). No significant
change in disagreement rate was demonstrated between the two phases of the study
(P=0.59). Double-read of skeletal survey for suspected non-accidental trauma found
false-negative fractures in a few cases and rarely found false-positive diagnosis
of a fracture. Double-read uncommonly found discrepancies in an initially normal
skeletal survey. Limiting double-read to initially positive studies improves the
yield of the double-read.
Aim: To assess plasma levels of cortisol and cytokines between cocaine-dependent
women with and without childhood maltreatment (CM) history during cocaine
detoxification treatment. Method: We assessed immunoendocrine and clinical
parameters of 108 crack cocaine female users during 3 weeks of inpatient
detoxification treatment, and 24 healthy women to obtain reference values. Women
with (CM+, n = 53) or without (CM-, n = 55) CM history were identified answering
the Childhood Trauma Questionnaire (CTQ). Blood samples and clinical assessment
were collected before lunch during the first, second and third week post-treatment
admission. Flow cytometry was used to assess TNF-alpha, IFN-gamma, IL-2, IL-4, IL-
6, IL-10, IL-17A plasma levels and ELISA assay was used to measure plasma cortisol
levels. Results: At baseline, lower Th1 and Thl 7-related cytokines levels and
higher Th2 cytokines levels were observed in crack cocaine users compared with
reference values. Cytokines levels of cocaine dependents gradually became closer to
reference values along detoxification treatment. However, when CM+ and CM groups
were compared, increased levels of IL-6, IL-4 and TNF-alpha across time were
observed in CM+ group only. Additionally, a Th1/Th2 immune imbalance was observed
within CM+ group, which was negatively correlated with the severity of the crack
withdrawal. Finally, loading trauma exposure severity, immunoendocrine and clinical
parameters in factor analysis, we identified three clusters of observed variables
during detoxification: (1) systemic immunity and trauma exposure, (2) pro-
inflammatory immunity and (3) behavior Conclusion: Our results suggest the
existence of an immunological phenotype variant associated with CM exposure during
crack cocaine detoxification of women. (C) 2016 Elsevier Ireland Ltd. All rights
reserved.
Commercial sexual exploitation of children (CSEC) is associated with child abuse,
neglect, poverty, homelessness, and societal causes. Sex trafficking is the
participation in commercial sex acts in which force, fraud, or coercion occur. This
article discusses the scope of CSEC and sex trafficking, and the necessary
identification skills and medical evaluations needed to help these patients.
The perceptions and judgments of social workers who interview the child and family
are especially significant factors in child abuse assessment process. The current
study describes and compares child protection workers' assessment processes in
Korea and the USA through the use of case vignettes and in-depth interview. The
responses from social workers in these two countries were compared and discussed in
the areas of: risk assessment; perception of the main problems; tolerance of
corporal punishment; and judgments about appropriateness of interventions. Most
revealing was that Korean social workers determined abuse based on their child
abuse definition and the US Army FAP social workers determined abuse based on their
definition, which was affected by legal standards and cultural differences. Korean
social workers are more likely to remove a child from the home, even in mild cases,
but US FAP social workers would recommend child removal from the home as a last
option. The social workers that participated in this survey play a vital role in
the safety of children in child protective services. Both countries can benefit
from sharing information to improve the child protection services delivered. Social
workers' professional judgment leads to objective and consistent outcomes and are
less likely to compromise child safety in the decision making process.
Primary prevention programs of pediatric abusive head trauma (PAHT) exist and early
screening is proposed, but negative effects of mislabeling parents as abusers, an
important issue, are not well documented. The aim of our study was to simulate the
possible impact of programs for the primary prevention and screening of PAHT. We
developed Markov models that simulate the life histories of PAHT with no
intervention, with primary prevention program only, with screening program, and
with both programs in a hypothetical cohort of 800,000 newborns in a high-income
country. Screening program would be addressed to all families until children are 2
years old, during repeated consultations. Potential side effects for parents being
mislabeled as abusers were supposed to increase the probability of PAHT and
decrease participation in screening. Time horizon was 2 years with cycles of 15
days. Outcomes were number of deaths and abused children avoided. Uncertainty was
specified with probability distributions. After 2 years, the median number of
deaths avoided through primary prevention would vary from 6 (95% confidence
interval [CI] 2-11) to 28 (95% CI 6-51) per 100,000 newborns. Screening could
prevent up to 6 (95% CI 0-29) or cause up to 66 (95% CI 0-361) deaths per 100,000
children born alive. The impact of both programs was uncertain. Our model confirmed
the potential benefits of primary prevention and documented the uncertainty
associated with screening of PAHT.
The domestic violence against children (DVAC) interferes in the psychological
development leading to sequels that manifest and persist up to the adulthood. The
physical evidences of domestic violence are more easily observed in the orofacial
complex, becoming eventually detected by dentists. The present systematic
literature review aimed to investigate the perception, knowledge and attitude of
dentists towards the detection and management of DVAC cases. A systematic search
was performed in 6 data-bases: PubMed, ScienceDirect, LILACS, SciELO,
GoogleScholar, and OpenGrey. Cross-sectional articles assessing the perception,
knowledge, and attitude of dentists facing potential cases of DVAC were selected.
No restriction of language, time, and publication status was considered. The search
resulted in 1.024 articles, of which 18 fit the eligibility criteria. The knowledge
for detecting cases of DVAC obtained during the undergraduation course was
classified by the dentists (in 39% of the articles) as "insufficient". When
suspecting of cases involving domestic violence, most of the dentists (in 77.75% of
the articles) considered reporting to the competent authorities. However, the
dentists are not sure about who these authorities are (in 31.25% of the articles).
More attention must be given to the Forensic education in Dentistry. Specifically,
proper training is necessary to support the dentists on the detection and
management of pediatric patients under domestic violence. (C) 2016 Elsevier Ltd and
Faculty of Forensic and Legal Medicine. All rights reserved.
All paediatricians and health professionals working with young children need to be
aware of the potential for child abuse to be a cause of physical injuries, such as
fractures. Clinical experience, Serious Case Reviews and research show us that
maltreatment should be kept in mind, in order for investigations to be carried out
where appropriate and to prevent further harm. Whilst accidental fractures are
common, fractures may also be the sentinel injury that alerts professionals to the
possibility of child abuse, presenting clinically or detected as an occult injury
on imaging for other reasons or when investigating a case of suspected
maltreatment. The health professional evaluating a child with any fracture should
be aware of features that raise the suspicion of abuse as a cause and be familiar
with current recommendations for further investigations. This article outlines the
current research concerning abusive fractures in children. It offers guidance on
how to optimize radiological investigations and avoid common pitfalls in clinical
practice.
Background: A psychosocial phenotype of interstitial cystitis/bladder pain syndrome
(IC/BPS), a urogenital condition without known organic causes, was proposed. While
psychosocial variables, including interpersonal maltreatment and negative affect,
were studied in association with IC/BPS, the specificities of the relationships
between childhood trauma by close others, psychiatric dysfunctions (negative affect
and post-traumatic psychopathology), and urogenital symptoms have not been
established. Methods: 94 IC/BPS patients were recruited together with 47 patients
with acute cystitis who served as clinical controls. Standardized scales were used
to assess various potentially traumatizing events in childhood and adulthood as
well as psychiatric (dissociation and negative affect) and urogenital symptoms.
Results: Among the potentially traumatizing events, those perpetrated by close
others during childhood were found to be the most salient features discriminating
the IC/BPS group from the control group. When divided into 2 subgroups according to
their history of childhood trauma by close others, only IC/BPS patients with
childhood trauma by close others had more dissociative and anxiety symptoms
compared with the control group. These two subgroups did not differ in urogenital
symptom severity. Conclusions: Childhood trauma by close others, rather than other
types of interpersonal trauma, was a differentiating characteristic in IC/BPS
patients, and a childhood trauma related psychosocial phenotype with a distinct
clinical profile of dissociation and anxiety proneness was identified. Future
studies should investigate whether a distinct set of pathogenic factors exists in
IC/BPS patients with a history of childhood trauma by close others, even if this
subgroup is not readily differentiated by urogenital symptoms. (C) 2016 Elsevier
Inc. All rights reserved.
The introduction of the concept of child abuse has radically changed the mode of
interaction between pediatricians and children, but also the practice of sanitary
personnel in primary care centers, who are often the first to see victims of
maltreatment. This study aims at illustrating the results of a questionnaire sent
to family doctors, pediatricians and hospitals in Milan and surrounding areas.
concerning child abuse. Among all the operators, 273 returned the questionnaires.
The results show scarce knowledge on how to report to judicial authority in cases
of child abuse (51.5%), mainly because of lack of basilar information concerning
the manner of reporting. For what concerns specific training, almost half the
subjects recruited for the study admitted not to have attended any congress or
meeting concerning child maltreatment in the last three years. In the same time
span, more than one third has not read any scientific articles concerning child
abuse. In addition, 75.6% admit to not ever having attended any professional
training course concerning child maltreatment. This study highlights the scarce
knowledge on the behalf of pediatricians and general practitioners regarding how to
deal with child abuse and the importance of proper training programs.
Background: Prehospital care providers are in a unique position to provide initial
unadulterated information about the scene where a child is abusively injured or
neglected. However, they receive minimal training with respect to detection of
Child Abuse and Neglect (CAN) and make few reports of suspected CAN to child
protective services. Aims: To explore barriers and facilitators to the recognition
and reporting of CAN by prehospital care providers. Design/Methods: Twenty-eight
prehospital care providers participated in a simulated case of infant abusive head
trauma prior to participating in one-on-one semi-structured qualitative debriefs.
Researchers independently coded transcripts from the debriefing and then
collectively refined codes and created themes. Data collection and analysis
continued past the point of thematic saturation. Results: Providers described 3 key
tasks when caring for a patient thought to be maltreated: (1) Medically managing
the patient, which included assessment of the patient's airway, breathing, and
circulation and management of the chief complaint, followed by evaluation for CAN;
(2) Evaluating the scene and family interactions for signs suggestive of CAN, which
included gathering information on the presence of elicit substances and observing
how the child behaves in the presence of caregivers; and (3) Creating a safety
plan, which included, calling police for support, avoiding confrontation with the
caregivers and sharing suspicion of CAN with hospital providers and child
protective services. Reported barriers to recognizing CAN included discomfort with
pediatric patients; uncertainty related to CAN (accepting parental story about
alternative diagnosis and difficulty distinguishing between accidental and
intentional injuries); a focus on the chief complaint; and limited opportunity for
evaluation. Barriers to reporting included fear of being wrong; fear of caregiver
reactions; and working in a fast-paced setting. In contrast, facilitators to
reporting included understanding of the mandated reporter role; sharing thought
processes with peers; and supervisor support. Conclusions: Prehospital care
providers have a unique vantage point in detecting CAN, but limited resources and
knowledge related to this topic. Focused education on recognition of signs of
physical abuse; increased training on scene safety; real-time decision support; and
increased follow-up related to cases of CAN may improve their detection of CAN.
Background: Children exposed to maltreatment show neural sensitivity to facial cues
signalling threat. However, little is known about how maltreatment influences the
processing of social threat cues more broadly, and whether atypical processing of
social threat cues relates to psychiatric risk. Methods: Forty-one 10- to 14-year-
old children underwent a social rejection-themed emotional Stroop task during
functional magnetic resonance imaging: 21 children with a documented history of
maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F).
Groups were matched on age, pubertal status, gender, IQ, socioeconomic status,
ethnicity and reading ability. Classic colour Stroop stimuli were also administered
in the same paradigm to investigate potential differences in general cognitive
control. Results: Compared with their peers, children who had experienced
maltreatment showed reduced activation in the Rejection versus Neutral condition,
across circuitry previously implicated in abuse-related posttraumatic stress
disorder (PTSD), including the left anterior insula, extending into left
ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior
parietal cortex (STS); and bilateral visual association cortex, encompassing the
cuneus and lingual gyrus. No group differences in neural or behavioural responses
were found for the classic colour Stroop conditions. Significant negative
associations between activity in bilateral cuneus and STS during the rejection-
themed Stroop and higher self-reported PTSD symptomatology, including dissociation,
were observed in children exposed to maltreatment. Conclusion: Our findings
indicate a pattern of altered neural response to social rejection cues in
maltreated children. Compared to their peers, these children displayed relative
hypoactivation to rejection cues in regions previously associated with PTSD,
potentially reflecting an avoidant coping response. It is suggested that such
atypical processing of social threat may index latent vulnerability to future
psychopathology in general and PTSD in particular.
IntroductionNo previous study has investigated the association between early trauma
and suicidal behavior in Zonguldak. The aim of this study was to investigate the
incidence of childhood abuse and neglect in the general population living in
Zonguldak province and the relationship between childhood trauma and suicidal
ideations and attempts. MethodsThe present study was carried out with 897 people in
the general population, as assessed in a representative sample from Zonguldak
province. The cluster sampling method was used. After obtaining written consent
from the people who agreed to participate in the study, the Socio-demographic
Information Form, Suicide Probability Scale, Childhood Trauma Questionnaire, Beck
Depression Inventory, and Beck Anxiety Inventory were administered. ResultsThe
lifetime prevalence of suicidal ideations was 18.3% among those who experienced at
least one type of early trauma, and it was 9.6% among those without a history of
childhood trauma (P<0.001). Only emotional abuse exhibited a significantly high
odds ratio for lifetime suicidal ideations (odds ratio [OR]=3.168, 95% confidence
interval [CI]=1.731-5.798) and attempts (OR=3.467, 95% CI=1.343-8.952). Emotional
neglect showed a high odds ratio only for lifetime suicidal attempts (OR=3.282, 95%
CI=1.287-8.371). There were significant correlations among the Beck Depression
Inventory, Beck Anxiety Inventory, and Suicidal Probability Scale sub-scores and
all six Childhood Trauma Questionnaire scores. DiscussionEmotional abuse and
neglect in childhood are significantly associated with lifetime suicidal ideations
and attempts in the general population living in Zonguldak province. Therefore,
clinicians should be aware of the importance of the childhood trauma in the
patients with suicidal ideations and attempts.
Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological
and psychological adversities that have been linked to reduced social functioning
across the lifespan. However, the joint effects of being born preterm and being
exposed to CSA on adult social outcomes remains unclear. We sought to determine the
impact of exposure to both preterm birth and CSA on adult social functioning in a
group of 179 extremely low birth weight (ELBW;2500 g) participants in the fourth
decade of life. Social outcome data from a prospective, longitudinal, population-
based Canadian birth cohort initiated between the years of 1977 and 1982 were
examined. At age 29-36 years, ELBW survivors who experienced CSA reported poorer
relationships with their partner, worse family functioning, greater loneliness,
lower self-esteem and had higher rates of avoidant personality problems than those
who had not experienced CSA. Birth weight status was also found to moderate
associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family
functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW
survivors. Exposure to CSA appears to augment the adult social risks associated
with perinatal adversity. Individuals born preterm and exposed to CSA appear to be
a group at particularly high risk for adverse social outcomes in adulthood.
The present study aimed to examine professionals' experiences, perceptions, and
knowledge regarding violence-exposed children in order to clarify the status and
opportunities these children have in the Swedish legal system. A questionnaire was
distributed to 63 professionals, representing police, prosecutors, social
personnel, and treatment personnel. Findings revealed several problems that
hindered effective work. Routines and guidelines were lacking and knowledge gaps
regarding these children were found among all professions. Perceptions that
children remember and tell were widely held, although conditions enabling
sufficient reports are seldom met. Results can be used to guide necessary changes
in national routines and guidelines to ensure recovery and maintaining of societal
rights of this group of psychologically abused victims.
Child maltreatment can lead to acute and long-term consequences, and it is
important that at-risk children are identified early. Child healthcare (CHC) nurses
in Sweden are in a position to identify child maltreatment, as they follow children
and their parents from the child's birth to school age. Therefore, the aim was to
describe CHC nurses' experiences when encountering families in which child
maltreatment was identified or suspected. Individual open interviews with eight CHC
nurses were performed and analysed using a qualitative content analysis. Findings
revealed that keeping the child in focus, while supporting the family was essential
for the nurses. This family-centred approach was assumed to benefit the child's
interests. Meeting families where child maltreatment was identified or suspected
influenced the nurses, emotionally in different ways. Nevertheless, it was
important to keep an open mind and communication build on honesty. Furthermore, the
nurses requested professional supervision in order to help them learn from the
situation ahead of the next time. This knowledge about CHC nurses' experiences may
form a basis for the development of interventions that aim to support the CHC
nurses in their professional role, and thereby improve support to children and
parents in the future.
Over the last 3 decades, researchers have elucidated the cognitive and motivational
conditions that affect the capacity and willingness of young alleged victims to
describe their experiences to forensic interviewers. Applied researchers have also
studied the contents and features of training programs designed to help
interviewers take advantage of the research on developmentally appropriate
interviewing. The latter studies have highlighted a knowledge transfer problem-
scientists understand best-practice techniques well, many interviewers believe that
they both understand and employ those practices, but widespread training has had a
limited impact on the actual quality of interviews conducted in the field. There is
now clear evidence that improvements in interviewing practice occur reliably only
when training courses involve multiple modules, distributed over time, with
repeated opportunities for interviewers to consolidate learning and to obtain
feedback on the quality of the interviews they do conduct. Barriers to the
implementation of such training are discussed.
Forensic medical evaluation rates for child abuse victims in Texas are low relative
to national rates. In exploring reasons, researchers collected quantitative and
qualitative interview and focus group data from multidisciplinary child abuse
response team members across the state. This paper presents results of a secondary
analysis of (N = 19) health care providers' interview and focus group transcripts,
looking specifically at experiences with conducting forensic evaluations thoughts,
struggles, and ethical issues. The analysis was conducted from a critical realist
perspective using content and discourse analysis. A theme of ambivalence was
identified and explored. Three discursive themes were identified: ambivalence about
the legal role, the health care role, and about unintended outcomes of evaluations.
Extra-discursive elements related to the physical body, resource distribution, and
funding policy were examined for their interaction with discursive patterns.
ImplicatiOns of findings include addressing issues in the current approach to
responding to child abuse (e.g., uniting around common definitions of abuse;
refining parameters for when FME is helpful; shoring up material resources for the
abuse response infrastructure) and considering modification of providers' roles and
activities relative to forensic work (e.g., deploying providers for prevention
activities versus reactive activities). (C) 2017 Elsevier Ltd. All rights reserved.
The current article reports on perpetrator characteristics gathered in the first
large-scale prevalence study on interpersonal violence against children in sport in
the Netherlands and Belgium. Using retrospective web survey design, 4043 adults
answered questions on their experiences in youth sport. The study looks at the
number of perpetrators as well as individual descriptive characteristics (sex, age,
and role in the sport organization) of perpetrators of psychological, physical and
sexual violence as reported retrospectively by victim-respondents. This information
was then clustered to provide an overview of the most common perpetrator profiles.
Results show that in all types of interpersonal violence in sport, perpetrators are
predominantly male peer athletes who frequently operate together in (impromptu)
groups. Several differences between the three types of interpersonal violence are
highlighted. While incidents of physical violence perpetrated by coaches tend to be
less severe compared to those by other perpetrators, acts of sexual violence
committed by a coach are significantly more severe. The presented findings shed new
light on perpetrators of interpersonal violence in sport, nuancing the predominant
belief that the male coach is the main perpetrator while providing nuanced
information that can be utilized to improve prevention and child protection
measures and other safeguarding initiatives in sport. (C) 2016 Elsevier Ltd. All
rights reserved.
Little is known about the link between child abuse and health risk behaviors among
Chinese college students. This cross-sectional study examined the prevalence of
child abuse and its relations with individual and clusters of health risk behaviors
among Chinese college students. A total of 507 students participated in this
survey. The prevalence of child abuse from the highest to the lowest was emotional
neglect (53.9%), physical neglect (49.0%), emotional abuse (21.8%), physical abuse
(18.3%), and sexual abuse (18.1%), respectively. Males were more likely to report
child abuse than females (p < 0.01). For males, emotional abuse was associated with
internet addiction [OR = 2.28; 95%CI (1.00, 5.20)] and suicidal behavior [OR =
12.47, 95%CI (2.61, 59.54)]; while sexual abuse was associated with internet
addiction [OR = 2.30, 95%CI (1.14, 4.66)]. For females, emotional abuse was
significantly associated with increased risks for self-harm behavior [OR = 15.03,
95%CI (3.59, 63.07)] and suicidal behavior [OR = 5.16, 95%CI (1.63, 16.40)].
Physical abuse was related to risks for internet addiction [OR = 2.50, 95%CI (1.03,
6.04)] significantly. Two-step cluster analysis showed that participants in
clusters with more health risk behaviors reported higher scores of child abuse.
These findings suggest that child abuse was associated with both individual and
clustering of health risk behaviors among Chinese college students.
Child Protective Services (CPS) identifies over 700,000 victims of child
maltreatment in the United States annually. Research shows that risk factors for
these children may persist despite CPS intervention. Mothers have unique and often
untapped perspectives on the experiences and consequences of CPS intervention that
may inform future practice. We explored these perspectives through interviews with
24 mothers after a first-time CPS finding of maltreatment not resulting in out-of-
home placement. Male partners were primary perpetrators in 21 cases, with mothers
or sitters identified as perpetrators in remaining cases. Data were analyzed using
grounded theory. Mothers described risk factors or Roots of maltreatment prior to
CPS involvement and reported variable experiences with Recognition of and Response
to maltreatment. Divergent Outcomes emerged: I Feel Stronger and We're No Better.
These findings provide an understanding of household experiences around child
maltreatment that may support practice and policy changes to improve outcomes for
vulnerable children.
Child abuse includes all forms of physical and emotional ill treatment, sexual
abuse, neglect, and exploitation that results in actual or potential harm to the
child's health, development, or dignity. In Taiwan, the Child Protection Medical
Service Demonstration Center (CPMSDC) was established to protect children from
abuse and neglect. We further analyzed and compared the trends and clinical
characteristics of cases reported by CPMSDC to evaluate the function of CPMSDC in
approaching child abuse and neglect in Taiwan. We prospectively recorded children
with reported child abuse and neglect in a CPMSDC in a tertiary medical center from
2014 to 2015. Furthermore, we analyzed and compared age, gender, scene, identifying
settings, time of visits, injury type, injury severity, hospital admission,
hospitalization duration, and outcomes based on the different types of abuse and
the different settings in which the abuse or neglect were identified. Of 361 child
abuse cases (mean age 4.8 +/- 5.36 years), the incidence was highest in 1- to 6-
year-old children (n=198, 54.85%). Physical abuse and neglect were predominant in
males, while sexual abuse was predominant in females (P<0.001). Neglect was most
common (n=279, 75.85%), followed by physical (n=56, 15.51%) and sexual abuse (n=26,
7.2%). The most common identifying setting was the emergency department (n=320,
88.64%), with neglect being most commonly reported. Head, neck, and facial injuries
were more common in physically abused children than in neglected and sexual abused
children (P<0.005), leading to longer hospitalization (P=0.042) and a higher Injury
Severity Score (P=0.043). There were more skin injuries in neglect (P<0.001). The
mortality rate was 2.49% (n=9). The CPMSDC could enhance the ability, alertness,
and inclination of professionals to identify suspected cases of child abuse, and to
increase the rate of registry. Cases of physical abuse had a higher Injury Severity
Score, longer duration of hospitalization, and more injuries of head, face, and
neck compared with other types of abuse. The reported rate of neglect was highly
elevated after the CPMSDC established during the study period. Recognition of
neglect is not easy, but the consequent injury, especially asphyxia, may lead to
mortality.
Aim In the Netherlands, preventive child healthcare workers (PCHWs) have an
important role in identifying signs of abuse, because they reach virtually all
children. A closer cooperation of PCHWs and forensic physicians could improve the
detection of child abuse. The aim of the study was to evaluate the use of forensic
expertise by PCHWs. Subjects and methods In November 2013, a survey was distributed
among PCHWs employed by the Amsterdam Public Health Service (n = 221). Results
Forty-nine percent of PCHWs indicated suspicions of physical abuse during the last
6 months (response rate: 43 %). In all, 89 % rated the consultation of forensic
physicians as useful. In a 1-year period, only three respondents sought advice from
a forensic doctor. Conclusions Although PCHWs regularly have suspicions of physical
child abuse and have a very positive attitude towards consulting a forensic
physician, consultation rates are very low. More research is needed to understand
barriers to consultation of forensic physicians.
Background: Childhood maltreatment is an important risk factor for mental and
physical health problems. Adolescents living in residential youth care (RYC) have
experienced a high rate of childhood maltreatment and are a high-risk group for
psychiatric disorders. Quality of life (QoL) is a subjective, multidimensional
concept that goes beyond medical diagnoses. There is a lack of research regarding
the associations between childhood maltreatment and QoL. In the present study, we
compare self-reported QoL between adolescents in RYC in Norway with and without
maltreatment histories, and adolescents from the general population. We also study
the impact of number of types of adversities on QoL. Methods: Adolescents aged 12-
23 years living in RYC in Norway were invited to participate in the study; 400
participated, yielding a response rate of 67 %. Maltreatment histories were
assessed through interviews with trained research assistants, and completed by 335
adolescents. Previous exposure to maltreatment was reported by 237 adolescents. The
Questionnaire for Measuring Health-Related Quality of Life in Children and
Adolescents (KINDL-R) was used. Nonexposed peers in RYC (n = 98) and a sample of
adolescents from the general population (n = 1017) were used for comparison.
General linear model analyses (ANCOVA) were conducted with five KINDL-R life
domains as dependent variables. Linear regression was used to study the effect of
number of types of adversities. Results: Exposed adolescents in RYC reported poorer
QoL than peers in control groups. Compared with nonexposed peers in RYC, the 95 %
confidence intervals for mean score differences on the KINDL-R subdomains (0-100
scale) were 1.9-11.4 (Physical Well-being), 2.2-11.1 (Emotional Well-being), -0.7-
10.0 (Self-esteem), and 1.8-10.9 (Friends). Compared with the general population
sample, the 95 % confidence intervals for mean score differences were 9.7-17.6
(Physical Well-being), 7.9-15.3 (Emotional Well-being), 3.6-12.5 (Self-esteem), and
5.3-12.8 (Friends). Number of types of adversities was associated with a poorer QoL
score on all subdomains (Physical-and Emotional Well-being, Self-esteem, Friends,
and School). Conclusions: Childhood maltreatment was associated with a poorer QoL
score. We suggest the use of QoL and maltreatment measures for all children and
adolescents in RYC.
Background: Childhood maltreatment is a potent predictor of poor mental health
across the life span. We argue that there is a need to improve the understanding of
the mechanisms that confer psychiatric vulnerability following maltreatment, if we
are to progress from simply treating those with a manifest disorder, to developing
effective preventative approaches that can help offset the likelihood that such
disorders will emerge in the first place. Methods: We review extant functional
neuroimaging studies of children and adolescents exposed to early neglect and/or
maltreatment, including physical, sexual and emotional abuse across four
neurocognitive domains: threat processing, reward processing, emotion regulation
and executive control. Findings are discussed in the context of 'latent
vulnerability', where alterations in neurocognitive function are considered to
carry adaptive value in early adverse caregiving environments but confer long-term
risk. Results: Studies on threat processing indicate heightened as well as
depressed neural responsiveness in maltreated samples, particularly in the
amygdala, thought to reflect threat hypervigilance and avoidance respectively.
Studies on reward processing generally report blunted neural response to
anticipation and receipt of rewards, particularly in the striatum, patterns
associated with depressive symptomatology. Studies on emotion regulation report
increased activation of the anterior cingulate cortex (ACC) during active emotion
regulation, possibly reflecting greater effortful processing. Finally, studies of
executive control report increased dorsal ACC activity during error monitoring and
inhibition. Conclusions: An emerging body of work indicates that altered
neurocognitive functioning following maltreatment: (a) is evident even in the
absence of overt psychopathology; (b) is consistent with perturbations seen in
individuals presenting with psychiatric disorder; (c) can predict future
psychiatric symptomatology. These findings suggest that maltreatment leads to
neurocognitive alterations that embed latent vulnerability to psychiatric disorder,
establishing a compelling case for identifying those children at most risk and
developing mechanistically informed models of preventative intervention. Such
interventions should aim to offset the likelihood of any future psychiatric
disorder.
Child abuse refers to the actions or non-actions which, mediated or immediately,
affect the physical or psychic integrity of an infant, and negatively influence his
normal physical, emotional and social development. Neglect represents the willful
failure of either parent or tutor to assure to the child access to a healthcare
system, thus jeopardizing his growth and evolution. In the field of pediatric
dentistry, both abuse and neglect ultimately lead to complex dento-facial
disabilities, with long-term consequences. The pediatric dentist is expected to
establish complex professional medical relations, based on clearly-defined
deontological principles, continuously targeting child superior interest. In this
way, the dental practitioner may identify quite various situations which, according
to the fundamental principle of a medical good action, require the involvement, in
the medical relation, of a third responsible person. Accordingly, child's superior
interest will represent a priority, granting all his rights to life and health, as
well as - if such be the case his special protection. When potentially or really
dangerous situations for child security and well-being are to be faced, the medical
staff is obliged to announce the specialized structures of child assistance and
protection; in such cases, the secondary principles on professional medical
confidentiality and interdiction of making public the professional medical secret
should be left aside. Such type of intervention in the physician-patient relation
is characterized by both risks and advantages, most of them derived from the
promptness with which the general and even forceful methods for protection of
children in a civilized community are to be applied.
Gene-environment interactions that moderate aggressive behavior have been
identified independently in the serotonin transporter (5-HTT) gene and monoamine
oxidase A gene (MAOA). The aim of the present study was to investigate epistasis
interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked
polymorphism (LPR) and child abuse and the effects of these on aggressive
tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male
adolescents completed the Child Trauma Questionnaire and Youth self-report of the
Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects
of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-
environmental effects on aggressive behavior were analyzed using a linear
regression model. The effect of child maltreatment was significant, and a three-way
interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive
behaviors was identified. Chinese male adolescents with high expression of the
MAOA-VNTR allele and 5-HTTLPR SS genotype exhibited the highest aggression
tendencies with an increase in SA during childhood. The findings reported support
aggression being a complex behavior involving the synergistic effects of gene-gene-
environment interactions.
Background: Child abuse is often unrecognized at out-of-hours primary care (OOH-PC)
services. The aim of our study was to evaluate the clinical outcome of the
screening instrument SPUTOVAMO-R2 for child abuse (checklist), followed by a
structured approach (reporting code), at OOH-PC services. The reporting code with
five steps should ensure consistent action in case of a suspicion. Methods: All
children attending one of the five participating OOH-PC services in the region of
Utrecht, the Netherlands, in a year time, were included. The checklist is an
obligatory field in the electronic patient file and was filled in for all children.
In case of a positive checklist, the steps in the reporting code were followed.
Additionally, the case was evaluated in a multidisciplinary team to determine the
probability of child abuse. Results: The checklist was filled in for 50671
children; 108 (0.2 %) were positive. The multidisciplinary team diagnosed child
abuse in 24 (22 %) of the 108 positive checklists, and no child abuse in 36 (33 %).
Emotional neglect was the most frequent type of abuse diagnosed. For all abused
children, care was implemented according to the protocol. The most frequent care
given was a referral to the hospital (N = 7) or contact with child's own general
practitioner (N = 6). Conclusion: A checklist followed by a reporting code
guarantees consistent actions and care for children with a suspicion of child
abuse. The percentage of positive checklists is lower than expected. Validity of
the checklist should be assessed in a diagnostic study.
This study uses large, longitudinal, multisector administrative datasets of
families investigated by child welfare services for maltreatment to explore which
children are more likely to later enter psychiatric residential treatment
facilities. This question is grounded in a pressing interest to understand these
costly, highly restrictive mental health treatment settings. We use statewide data
from one Southeastern state linked from multiple systems (child welfare services,
income maintenance, and Medicaid). We use Cox regression analyses to develop models
predicting psychiatric residential treatment facilities entry among children 5-17
years, whose families were investigated for maltreatment between 2003 and 2012 (n =
182,676). Findings show children from these families who enter foster care have a
heightened risk for psychiatric residential treatment facilities entry (hazard
ratio = 11.63), after controlling for other factors. Study findings build on a body
of research underscoring the importance of the overlap of child welfare and mental
health systems to child well-being.
Objective: Child abuse can have devastating mental health consequences.
Fortunately, not all individuals exposed to child abuse will suffer from poor
mental health. Understanding what factors are related to good mental health
following child abuse can provide evidence to inform prevention of impairment. Our
objectives were to 1) describe the prevalence of good, moderate, and poor mental
health among respondents with and without a child abuse history; 2) examine the
relationships between child abuse and good, moderate, and poor mental health
outcomes; 3) examine the relationships between individual- and relationship-level
factors and better mental health outcomes; and 4) determine if individual- and
relationship-level factors moderate the relationship between child abuse and mental
health. Method: Data were from the nationally representative 2012 Canadian
Community Health Survey: Mental Health (n = 23,395; household response rate =
79.8%; 18 years and older). Good, moderate, and poor mental health was assessed
using current functioning and well-being, past-year mental disorders, and past-year
suicidal ideation. Results: Only 56.3% of respondents with a child abuse history
report good mental health compared to 72.4% of those without a child abuse history.
Individual- and relationship-level factors associated with better mental health
included higher education and income, physical activity, good coping skills to
handle problems and daily demands, and supportive relationships that foster
attachment, guidance, reliable alliance, social integration, and reassurance of
worth. Conclusions: This study identifies several individual- and relationship-
level factors that could be targeted for intervention strategies aimed at improving
mental health outcomes following child abuse.
The identification of potential child maltreatment using reliable and valid
screening instruments is of particular importance in high risk populations. The
current study investigates the psychometric properties of the Brief Child Abuse
Potential (BCAP) Inventory in mothers enrolled in opioid substitution therapy. The
BCAP Risk Abuse scale had strong internal reliability. Comparisons between valid
and invalid protocols (ae4 on the Lie scale, >1 Random Responding) failed to find
systematic differences across most variables although those with a faking good
profile had significantly lower scores on psychological well being. A six-factor
solution was obtained and was conceptually strong. Subsequent analyses suggested
Rigidity may be an independent subscale that needs further investigation. These
results add further evidence for the potential utility of the BCAP as a measure of
child abuse potential. Replication studies are needed to ascertain whether the
subscales derived have convergent and predictive utility.
Practitioners and researchers alike face the challenge that different sources
report inconsistent information regarding child maltreatment. The present study
capitalizes on concordance and discordance between different sources and probes
applicability of a multisource approach to data from three perspectives on
maltreatmentChild Protection Services (CPS) records, caregivers, and children. The
sample comprised 686 participants in early childhood (3- to 8-year-olds; n = 275)
or late childhood/adolescence (9- to 16-year-olds; n = 411), 161 from two CPS sites
and 525 from the community oversampled for psychosocial risk. We established three
components within a factor-analytic approach: the shared variance between sources
on presence of maltreatment (convergence), nonshared variance resulting from the
child's own perspective, and the caregiver versus CPS perspective. The shared
variance between sources was the strongest predictor of caregiver- and self-
reported child symptoms. Child perspective and caregiver versus CPS perspective
mainly added predictive strength of symptoms in late childhood/adolescence over and
above convergence in the case of emotional maltreatment, lack of supervision, and
physical abuse. By contrast, convergence almost fully accounted for child symptoms
for failure to provide. Our results suggest consistent information from different
sources reporting on maltreatment is, on average, the best indicator of child risk.
The evolution of the concept of child abuse leads to consider new types of
maltreatment that in the future will certainly be taken into account with a new era
of social pediatrics. Pediatric care has been based on the increased awareness of
the importance of meeting the psychosocial and developmental needs of children and
of the role of families in promoting the health.
ObjectiveTo determine whether staff responses to abuse disclosures had improved
since the introduction of a trauma policy and training programme. MethodThe files
of 250 clients attending four New Zealand mental health centres were audited.
ResultsThere was a significant improvement, compared to an audit prior to the
introduction of the policy and training, in the proportion of abuse cases included
in formulations, and, to a lesser extent, in treatment plans. There was no
significant improvement in the proportion referred for relevant treatment, which
remained at less than 25% across abuse categories. The proportion of neglect
disclosures responded to was significantly lower than for abuse cases. Fifty
percent of the files in which abuse/neglect was recorded noted whether the client
had been asked about previous disclosure, and 22% noted whether the client thought
there was any connection between the abuse/neglect and their current problems. Less
than 1% of cases were reported to legal authorities. People diagnosed with a
psychotic disorder were significantly less likely to be responded to appropriately.
ConclusionFuture training may need to focus on responding well to neglect and
people diagnosed with psychosis, on making treatment referrals, and on initiating
discussions about reporting to authorities.
Background. Child abuse and neglect (CAN) is a risk factor for the development of
psychiatric disorders. Untreated, disorders can sustain into adulthood. Objectives.
This study compares rates of psychiatric disorders to mental health care
utilization in victims of CAN. Methods. From three regions in Germany, 322 children
and adolescents aged between 4 and 17 and a non-abusive caregiver were assessed for
the child's history of CAN, mental health and mental health care utilization via
semi-structured interviews. Results. Approximately two thirds of the participants
(present state 64.29 %; lifetime 69.57 %) suffered from a psychiatric disorder
classifiable with ICD-10. Posttraumatic stress disorder (25.16 %), conduct
disorders (21.34%) and attention and hyperactivity disorders (16.15 %) were most
frequently diagnosed. Merely 19.88% were using mental health care at the time of
the assessment. Conclusions. The provision of mental health care for victims of CAN
is insufficient. To improve access to appropriate services for this vulnerable
clientele, cooperation between psychiatrists and psychotherapists and the child
welfare system is essential. The implementation and dissemination of evidence-based
diagnostic methods and treatments must be further advanced.
International estimates of the incidence of non-accidental burns (NAB) in children
admitted to burn centres vary from 1% to 25%. Hardly any data about Dutch figures
exist. The aim of this study was to evaluate the incidence, treatment and outcome
of burns due to suspected child abuse in paediatric burns. We described the process
of care and outcome, including the accuracy of the SPUTOVAMO screening tool and
examined child, burn and treatment characteristics related to suspicions of child
abuse or neglect. A retrospective study was conducted in children aged 0-17 years
with a primary admission after burn injuries to the burn centre Rotterdam in the
period 2009-2013. Data on patient, injury and treatment characteristics were
collected, using the Dutch Burn Repository R3. In addition, medical records were
reviewed. In 498 paediatric admissions, suspected child abuse or neglect was
present in 43 children (9%). 442 screening questionnaires (89%) were completed. In
52 out of 442 questionnaires (12%) the completed SPUTOVAMO had one or more positive
signs. Significant independent predictors for suspected child abuse were burns in
the genital area or buttocks (OR = 3.29; CI: 143-7.55) and a low socio-economic
status (OR = 2.52; 95%CI: 1.30-4.90). The incidence of suspected child abuse
indicating generation of additional support in our population is comparable to
studies with a similar design in other countries. (C) 2016 Elsevier Ltd and ISBI.
All rights reserved.
Partial or complete division of the parietal bones resulting in anomalous cranial
sutures is a rare entity and may raise concern for fracture and potential abuse
when identified on radiological examination in young children. We present a case of
a 4-week-old male found to have anomalous intraparietal sutures originally
interpreted as fractures during a comprehensive evaluation for nonaccidental
trauma. Our goal is to raise awareness of a complex branching pattern of accessory
intraparietal sutures, which has not been previously described. Additionally, we
will review the characteristics that aid in the radiologic differentiation of
accessory cranial sutures and fractures. (C) 2016 Elsevier Inc. All rights
reserved.
Introduction: The social developmental processes by which child maltreatment
increases risk for marijuana use are understudied. This study examined hypothesized
parent and peer pathways linking preschool abuse and sexual abuse with adolescent
and adult marijuana use. Methods: Analyses used data from the Lehigh Longitudinal
Study. Measures included child abuse (physical abuse, emotional abuse, domestic
violence, and neglect) in preschool, sexual abuse up to age 18, adolescent (average
age = 18 years) parental attachment and peer marijuana approval/use, as well as
adolescent and adult (average age = 36 years) marijuana use. Results: Confirming
elevated risk due to child maltreatment, path analysis showed that sexual abuse was
positively related to adolescent marijuana use, whereas preschool abuse was
positively related to adult marijuana use. In support of mediation, it was found
that both forms of maltreatment were negatively related to parental attachment,
which was negatively related, in turn, to having peers who use and approve of
marijuana use. Peer marijuana approval/use was a strong positive predictor of
adolescent marijuana use, which was a strong positive predictor, in turn, of adult
marijuana use. Conclusions: Results support social developmental theories that
hypothesize a sequence of events leading from child maltreatment experiences to
lower levels of parental attachment and, in turn, higher levels of involvement with
pro-marijuana peers and, ultimately, to both adolescent and adult marijuana use.
This sequence of events suggests developmentally-timed intervention activities
designed to prevent maltreatment as well as the initiation and progression of
marijuana use among vulnerable individuals. (C) 2016 Elsevier Ltd. All rights
reserved.
Background: An estimated one billion children experience child abuse each year,
with the highest rates in low- and middle-income countries. The Sinovuyo Teen
programme is part of Parenting for Lifelong Health, a WHO/UNICEF initiative to
develop and test violence-prevention programmes for implementation in low-resource
contexts. The objectives of this parenting support programme are to prevent the
abuse of adolescents, improve parenting and reduce adolescent behavioural problems.
This trial aims to evaluate the effectiveness of Sinovuyo Teen compared to an
attention-control group of a water hygiene programme. Methods/Design: This is a
pragmatic cluster randomised controlled trial, with stratified randomisation of 37
settlements (rural and peri-urban) with 40 study clusters in the Eastern Cape of
South Africa. Settlements receive either a 14-session parenting support programme
or a 1-day water hygiene programme. The primary outcomes are child abuse and
parenting practices, and secondary outcomes include adolescent behavioural
problems, mental health and social support. Concurrent process evaluation and
qualitative research are conducted. Outcomes are reported by both primary
caregivers and adolescents. Brief follow-up measures are collected immediately
after the intervention, and full follow-up measures collected at 3-8 months post-
intervention. A 15-24-month follow-up is planned, but this will depend on the
financial and practical feasibility given delays related to high levels of ongoing
civil and political violence in the research sites. Discussion: This is the first
known trial of a parenting programme to prevent abuse of adolescents in a low- or
middle-income country. The study will also examine potential mediating pathways and
moderating factors.
Musculoskeletal manifestations of child maltreatment represent common presentations
to the emergency department. The recognition of child maltreatment is an essential
role for the practicing emergency physician, as it can directly prevent further
serious injury. Orthopedic trauma in children presents very differently than that
in adults. Understanding of the unique properties of pediatric bone as well as the
developmental capabilities of children in relation to injury mechanism is essential
in the interpretation of these injuries. Children younger than 3 years are most
vulnerable to bony injury from child maltreatment. Common presenting findings
include complex skull fractures, rib fractures, long bone fractures, and
metaphyseal corner fractures. Skeletal survey remains the mainstay of detection for
injuries, but recent work has also elucidated a role for other modalities in
fracture detection. Management should include proper orthopedic interventions,
along with mandatory reporting of possible maltreatment to the local child
protective services or other equivalent agency.
Child abuse in its various types such as physical, emotional, sexual, and neglect
has been document throughout history. However, before the mid-20th century,
inflicted injuries to children was overlooked in part because children were often
viewed as property. According to the World Health Organization, 57,000 children
were the victims of homicide in the year 2000. In this paper we present the
skeletal and radiological manifestation of physical abuse and fatal neglect and
provide recommendations to assess child maltreatment from past populations.
Pediatric biomechanical factors and healing are discussed as it is important to
keep in mind that children are not just small adults. Skeletal and radiological
indicators of nonaccidental or inflicted injuries are reviewed from the literature.
Inflicted injuries are presented based on specificity to identify child abuse. In
addition, skeletal indicators that could help assess fatal starvation are also
reviewed and metabolic diseases are proposed as potential evidence of neglect. A
recent child homicide is presented and used to illustrate the difficulty in
assessing child maltreatment. Present-day clinical child abuse protocols are used
to provide recommendations to assess child abuse in a bioarchaeological context.
Clin. Anat. 29:844-853, 2016. (c) 2016 Wiley Periodicals, Inc.
Over the past two decades there has been a growing awareness that sport may not be
a positive experience for all children. For example, we know that some children
experience sexual abuse in the context of organised sport, and that these offences
are often committed by trusted adults, including coaches and club officials.
However, less attention has been given to the physical abuse of child athletes.
This paper presents a study that explored children's experiences of organised
sport, as recounted by young people between the ages of 18 and 25 years in
Australia. The study explored the experience of child physical abuse in organised
sport including violence, overtraining, and training while injured. A mixed methods
research design produced 107 survey responses and 10 in-depth interviews with young
adults. Most respondents reported the positive impact that participating in sport
had had on their development, but more than a third of the respondents also
described experiences of overtraining, being forced to train when injured or of
direct physical violence. Drawing upon a thematic analysis of the qualitative data,
a conceptual model has been developed and is presented to assist in the
understanding of the dynamic of secrecy, which may facilitate ongoing physical harm
to children in this context.
Ross Cheit's book The Witch-Hunt Narrative highlights the difficulties of
prosecuting child sexual abuse. Drawing examples from a single case, Alex A., we
examine the ways in which false acquittals of sexual abuse are likely to occur.
First, prosecutors tend to question children in ways that undermine their
productivity and credibility. Second, prosecutors have difficulty in explaining to
juries the dynamics of sexual abuse and disclosure, making children's acquiescence
to abuse and their failure to disclose when abuse first occurs incredible. Third,
attorneys undermine children's credibility by pushing them to provide difficult to
estimate temporal and numerical information. A post-script to the Alex A. case
illustrates the costs of wrongful acquittals.
Much of the fabric in today's society is at odds with planning a robust and
generative public health response to child maltreatment prevention. A critical
component of this problem is the absence of a public policy framework and related
infrastructure that can create common ownership of the problem while recognizing
the vast differences in individual willingness and capacity to alter their
parenting behaviors. To address this challenge, it seems prudent to begin building
a universal system of assessment and support that will touch all children and all
families at multiple points in the developmental process. Such a system would not
simply identify those at highest risk. Rather this system would be built on the
premise that all parents have issues and concerns and differ only in the extent to
which they have the capacity to address these issues. This commentary outlines the
key elements of such a system and its benefits in strengthening both the impacts of
interventions and the collective will to support all children.
To compare the nature and determinants of child discipline in Qatar and Palestine
among young adults through retrospective survey to develop legislation, policies
and interventions for effective prevention of child maltreatment, and educational
materials to promote positive discipline among parents and caregivers. Cross-
sectional random household surveys were conducted in each country (Qataris N = 697,
Palestinians N = 2064) using ISPCAN Child Abuse Screening Tool -Retrospective
(ICAST-R) for young adults (18-24 years), to investigate child discipline methods
into the maltreatment range. Qatari young adults were more educated (p < 0.001) and
had more full-time employment (p = 0.004) than Palestinian young adults. Qatar
reported lower physical and emotional abuse compared to their counterparts in
Palestine, e.g. Hit/Punch, Kick (p < 0.001) and Insult/Criticize, Threaten to be
hurt/killed (p < 0.001). Qatari participants found any harsh discipline they
received in childhood was not reasonable and not justified compared to Palestinian
participants. The more advantaged Qatari population was less likely to experience
disciplinary methods that experts developing the ICAST-R defined as abuse compared
to Palestinians where the higher incidence of child abuse could be attributed to
lower economic advantage, lower level of education and greater exposure to
violence. Suggestions are made for future studies in Qatar and Palestine to develop
survey methodology with a more culturally appropriate level of intrusion, such as
indirect yet meaningful child maltreatment questions. (C) 2016 Elsevier Ltd. All
rights reserved.
Recognition of physical child abuse is imperative for ensuring children's safety.
Screening tools (ST) may increase identification of physical abuse; however, the
extent of their use is unknown. This study assessed use of STs for physical abuse
in children's hospitals and determined attitudes regarding STs. A web-based survey
was sent to child abuse program contacts at 103 children's hospitals. The survey
assessed institutional use of a ST for physical abuse and characteristics of the ST
used. Respondents were asked to identify benefits and liabilities of STs used or
barriers to ST use. Seventy-two respondents (70 %) completed the survey; most (64
%) were child abuse pediatricians. Nine (13 %) respondents reported using a ST for
physical abuse; STs varied in length, population, administration, and outcomes of a
positive screen. Most respondents (86 %) using a ST felt that it increased
detection of abuse. Barriers noted included lack of time for development and
provider completion of a ST. While few respondents endorsed use of a ST for
physical abuse, most believed that it increased detection of abuse. Future research
should focus on development of a brief, uniform ST for physical abuse which may
increase detection in at-risk children.
Objective: Traumatic brain injury causes substantial morbidity and mortality in
children. Posttraumatic seizures may worsen outcomes after traumatic brain injury.
Posttraumatic seizures risk factors are not completely understood. Our objective
was to clarify posttraumatic seizures risk factors in a large cohort of children
with severe traumatic brain injury. Design: Retrospective cohort study of a
probabilistically linked dataset from the National Trauma Data Bank and the
Pediatric Health Information Systems database, 2007-2010. Setting: Twenty-nine U.S.
children's hospitals. Patients: A total of 2,122 children (age, < 18 yr old at
admission) with linked National Trauma Data Bank and Pediatric Health Information
Systems records, severe (emergency department Glasgow Coma Scale, < 8) traumatic
brain injury, hospital length of stay more than 24 hours, and nonmissing
disposition. Interventions: None. Measurements and Main Results: The outcome was
posttraumatic seizures, identified using validated International Classification of
Diseases, 9th Revision, Clinical Modification diagnosis codes. Prespecified
candidate predictors of posttraumatic seizures included age, injury mechanism,
emergency department Glasgow Coma Scale, intracranial hemorrhage type, hypoxia,
hypotension, and cardiac arrest. Posttraumatic seizures were diagnosed in 25.2% of
children with severe traumatic brain injury. In those without abuse/assault or
subdural hemorrhage, the posttraumatic seizures rate varied between 36.6% in those
less than 2 years old and 16.4% in those 14-17 years old. Age, abusive mechanism,
and subdural hemorrhage are each significant predictors of posttraumatic seizures.
The risk of posttraumatic seizures has a complex relationship with these
predictors. The estimated odds of posttraumatic seizures decrease with advancing
age, odds ratio equal to 0.929 (0.905-0.954) per additional year of age with no
abuse/assault and no subdural hemorrhage; odds ratio equal to 0.820 (0.730-0.922)
per additional year of age when abuse and subdural hemorrhage are present. An
infant with accidental traumatic brain injury and subdural hemorrhage has
approximately the same estimated probability of posttraumatic seizures as an abused
infant without subdural hemorrhage (47% [95% CI, 39-55%] vs 50% [95% CI, 41-58%]; p
= 0.69). The triad of young age, injury by abuse/assault, and subdural hemorrhage
confers the greatest estimated probability for posttraumatic seizures (60% [95% CI,
53-66%]). Conclusions: Posttraumatic seizures risk in children with severe
traumatic brain injury is greatest with a triad of younger age, injury by
abuse/assault, and subdural hemorrhage. However, posttraumatic seizures are common
even in the absence of these factors.
Many studies have explored the negative outcomes of childhood maltreatment,
including psychopathology, risk-taking behaviors, and death by suicide. Being male
may exacerbate negative symptoms following maltreatment and result in a decreased
sense of psychological well-being. Much remains unexamined when exploring factors
that may buffer the negative outcomes of maltreatment. Self-compassion has been
suggested to aid in the improvement of psychological well-being and in the recovery
of traumatic events. This study examined the relationship between self-compassion
and psychological well-being among a sample of men who had and had not experienced
childhood maltreatment. Testing a model of mediation, findings reflected that self-
compassion, while not a full mediator between maltreatment and psychological well-
being, served as partial mediator. Implications and future directions are explored.
Physical, emotional and sexual child abuse are major problems in South Africa. This
study investigates whether children know about post-abuse services, if they
disclose and seek services, and what the outcomes of help-seeking behaviour are. It
examines factors associated with request and receipt of services. Confidential
self-report questionnaires were completed by adolescents aged 10-17 (n = 3515) in
South Africa. Prevalence of frequent (>weekly) physical abuse was 7.4%, frequent
emotional abuse 12.4%, and lifetime contact sexual abuse 9.0%. 98.6% could name one
suitable confidante or formal service for abuse disclosure, but only 20.0% of abuse
victims disclosed. Of those, 72% received help. Most common confidantes were
caregivers and teachers. Of all abuse victims, 85.6% did not receive help due to
non-disclosure or inactivity of services, and 14.4% received help: 4.9% from formal
health or social services and 7.1% through community vigilante action. Emotional
abuse, sexual abuse and female gender were associated with higher odds of help-
seeking. While children in South Africa showed high knowledge of available
services, access to and receipt of formal services among abused children was low.
Notably fewer children received help from formal services than through community
vigilante action. Urgent action is needed to improve service access for child abuse
victims.
Objective To identify areas of deficiencies and gaps in child protection services
in Northern Sri Lanka. Also, to help in recommending strategies, programmes of
interventions for addressing issues of child abuse and advice the legal system.
Methods A retrospective study was done to determine the socio-demographic details,
type of abuse, clinical profile, relationship of the perpetrator and nature of
abuse among children admitted to a tertiary care centre from 2009 through 2014, a
period after cessation of a 60-y conflict. Data were obtained from hospital based
records and records maintained at the district probation office. Results Seven
hundred twenty cases were referred to the tertiary care centre with abuse. Majority
of the children were from the Jaffna district, the northern city of the war
affected area and mean age of the children affected was 14.5 +/- 2.6 y. Females
were affected more than the males and 352 children were seen following sexual
abuse. The clinical examination showed penetrative injury in 15 %. The perpetrator
was known in 70 % of the situations and the victim was coerced into a relationship
for abuse. Attempted suicide was seen in significant numbers during the immediate
post war period and school dropout and delinquent behaviour was seen in later
years. Conclusions The problem of child abuse is considerable in this region and
there is an urgent need to strengthen the services offered to the victims. Urgent
steps are needed to safeguard these children, especially in the war affected areas.
The high prevalence of child sexual abuse (CSA) is concerning, particularly as
survivors are at increased risk for multiple adverse outcomes, including poor
mental health across the lifespan. Children born at an extremely low birth weight
(ELBW;2500 g) participants at ages 22-26 and 29-36. At age 22-26, CSA was
associated with increased odds of clinically significant internalizing (OR= 7.32,
95% CI: 2.31-23.23) and externalizing (OR = 4.65, 95% CI: 1.11-19.51) problems
among ELBW participants exposed to CSA compared to those who did not, though
confidence intervals were wide. At age 29-36, CSA was linked to increased odds of
any current (OR = 3.43, 95% CI: 1.08-10.87) and lifetime (OR= 7.09, 95% CI: 2.00-
25.03) non -substance use psychiatric disorders, however, this did not hold after
adjustment for covariates. Statistically significant differences in mental health
outcomes were not observed in NBW participants exposed to CSA compared to NBW
participants who were not exposed. Survivors of significant perinatal adversity who
are also exposed to CSA may be at higher risk for psychopathology through the
fourth decade of life. (C) 2016 Elsevier Ltd. All rights reserved.
Child sexual abuse (CSA) affects over 62,000 children annually in the United
States. A primary obstacle to the success of a public health prevention strategy is
the lack of knowledge around community level risk factors for CSA. We evaluated
community level characteristics for children seeking care for suspected CSA in the
Greater Houston area for 2009. There was a total incidence rate of medical
evaluations for suspected CSA of 5.9/1000 children. We abstracted the medical
charts of 1982 (86 %) children who sought a medical evaluation for suspected CSA at
three main medical systems in the Greater Houston area for 2009. We evaluated 18
community level variables from the American Community Survey for the 396 zip codes
these children lived in. The mean number of cases per Greater Houston zip code was
2.77 (range 0-27), with 62 % of zip codes not having a case at any of the three
sites surveyed. Zip codes with a higher than Houston average rate of vacant houses,
never married females and unemployed labor force with high family poverty rate,
were associated with an increased rate of children seeking care for suspected CSA.
We demonstrated zip codes level characteristics which were associated with an
increased rate of children seeking care for suspected CSA. Our modelling process
and our data have implications for community based strategies aimed at improved
surveillance or prevention of CSA. The process of identifying locally specific
community level factors suggests target areas which have particular socioeconomic
characteristics which are associated with increased rate of seeking CSA
evaluations.
Fractures are the second most common presentation of child abuse following soft-
tissue bruising and burns. It is often difficult to determine potential abuse in a
child presenting with a non-rib fracture(s) and without soft-tissue injuries. One
hundred and fifteen consecutive patients aged a parts per thousand currency sign2
years who presented with a fracture between January 2010 and June 2012 to our
emergency department (ED) or pediatric fracture clinic were retrospectively
analyzed. Statistical analyses were carried out for non-accidental fractures based
on age (< 1 year vs 1-2 years), location of presentation (ED vs pediatric fracture
clinic), type of long bone fracture, number of fractures, and patient demographics.
Fractures in 19 of 115 (17 %) patients were reported as non-accidental trauma
(NAT). Eighty (70 %) of the 115 patients first reported to the ED. Thirty-two
percent of fractures in children aged < 1 year and 5 % of fractures in children
aged 1-2 years were reported as NAT (p < 0.001). Sixteen of 19 (84 %) patients
reported for abuse had multiple fractures; 15 of these patients were aged < 1 year.
Eight of 11 (73 %) reported femoral fractures were transverse fractures. Corner
fractures (12) only occurred in children aged < 1 year and never occurred in
isolation; all of them were reported as NAT. Four of 60 patients (7 %) with
commercial insurance and 15 of 55 patients (28 %) with Medicaid were reported as
NAT. Age less than 1 year, multiple fractures, corner fractures, transverse
fractures, and covered by Medicaid were the most common factors associated with
reporting of NAT.
Objective: Child abuse exerts a deleterious impact on a broad array of mental
health outcomes. However, the neurobiological mechanisms that mediate this
association remain poorly characterized. Here, we use a longitudinal design to
prospectively identify neural mediators of the association between child abuse and
psychiatric disorders in a community sample of adolescents. Method: Structural
magnetic resonance imaging (MRI) data and assessments of mental health were
acquired for 51 adolescents (aged 13-20; M=16.96; SD=1.51), 19 of whom were exposed
to physical or sexual abuse. Participants were assessed for abuse exposure (time
1), participated in MRI scanning and a diagnostic structured interview (time 2),
and 2 years later were followed-up to assess psychopathology (time 3). We examined
associations between child abuse and neural structure, and identified whether
abuse-related differences in neural structure prospectively predicted psychiatric
symptoms. Results: Abuse was associated with reduced cortical thickness in medial
and lateral prefrontal and temporal lobe regions. Thickness of the left and right
parahippocampal gyrus predicted antisocial behavior symptoms, and thickness of the
middle temporal gyrus predicted symptoms of generalized anxiety disorder. Thickness
of the left parahippocampal gyrus mediated the longitudinal association of abuse
with antisocial behavior. Conclusion: Child abuse is associated with widespread
disruptions in cortical structure, and these disruptions are selectively associated
with increased vulnerability to internalizing and externalizing psychopathology.
Identifying predictive biomarkers of vulnerability following childhood maltreatment
may uncover neurodevelopmental mechanisms linking environmental experience with the
onset of psychopathology.
With government's response to child abuse and neglect seen as one of the most
daunting challenges for public policy and law, legislative reform on this issue
struggles to adequately protect children while preserving the integrity of family.
The authors utilize the Child Abuse Prevention and Treatment Act (CAPTA) as an
example of the funding and policy challenges in reforming federal child welfare
law, as well as a lens through which advocates can locate both conventional and
unconventional tools to move forward. CAPTA is examined as an important but weak
and flawed federal statute. Authors present an array of opportunities to improve
CAPTA during the next reauthorization cycle. Noting exemplary successes, in other
recent and related legislation reforms, are suggested for CAPTA to more effectively
address ongoing challenges of child welfare.
Child and adolescent abuse and neglect of children is a growing social problem that
is not limited to medical, legal or social services professions; Dental
professionals must be able to identify, document, report and often help treat these
patients and their families. This study is descriptive with retrospective Cross-
sectional design, with a population consisting of all children and adolescents
treated in Forensic Medicine of the CICPC ( Merida, Venezuela) during the period
from January 2010 to June 2013 with the aim of describing the clinical findings of
dental interest in child and adolescent victims of abuse. Information was collected
on a tab and the results are presented in tables and graphs of percentage bar. The
findings showed that physical injuries caused by violent events are usually
unnoticed, the most susceptible age group was 14-16 years, wounds located in lips
were the most frequent injuries, most of present dental lesions required general
dental treatment. It is recommended to promote more research in order to know the
magnitude of the impact of child and adolescent abuse.
Attachment theory promoted an impressive body of research on the psychic
developmental processes, resulting in studies on both typical and atypical
development. Much of the diffusion of the attachment theory in the clinical field
was related to the design of reliable instruments to evaluate the organization of
attachment in infancy as well as in adulthood. Until recently, the lack of a
suitable instrument to assess attachment in middle childhood as well as in
adolescence hindered the expansion of research in these developmental phases during
which the parent-child relationship takes on a different, albeit still crucial,
role. The Child Attachment Interview (CAI), a measure that was recently designed to
assess attachment at a representational level in middle childhood and adolescence,
filled the measurement gap. The aim of the current review was to summarize previous
empirical investigations concerning CAI in order to (a) provide an overview of the
state of current research, (b) identify unanswered questions, and (c) propose
future research directions. A narrative review was conducted to map the current
research findings by searching for the term "Child Attachment Interview" in the
Medline, Scopus, Web of Science, and PsychINFO databases, followed by a search in
Mendeley. Limits were set to exclude dissertations, chapters in books, and
qualitative or theoretical papers, while empirical studies were included if they
used the CAI and were published in English language, peer-reviewed journals by
July, 2016. The review, which ultimately included 39 studies meeting the criteria,
showed that the CAI is a reliable instrument to assess attachment organization in
clinical and non-clinical samples, thus providing a worthwhile contribution to the
investigation of the influence of the parent-child relationship beyond infancy and
early childhood. Nevertheless, the review pointed out a number of relevant open
issues, the most critical of which concerned the CAI coding and classification
system. In particular, some relevant questions arose about (a) how opportune it
would be to maintain a distinct classification for mother and father, (b) coding
challenges regarding both the father and the Preoccupied and Disorganized
classification, and finally (c) the advantage of a dimensional vs. a categorical
approach.
This research examines how victim and offender characteristics, as well as
contextual factors are related to the lethality of assaults for children less than
5 years old. The National Incident-Based Reporting System (NIBRS) data for 2006 to
2011 were analyzed using logistic regression techniques to estimate two models
designed to explore factors associated with the death of preschoolers. Results
indicate that the probability of fatality is significantly influenced by victim and
offender characteristics, victim-offender relationship, weapon used, time of
incident, and region of the United States in which the incident occurred.
Previous research has investigated the deleterious effects of child maltreatment on
child development; however, little research has examined the development of
children who live with caregivers who are at risk of maltreatment on child
development outcomes. This study utilized self-report data from caregivers that
included the Child Abuse Potential Inventory (CAPI), Parenting Stress Inventory-
Short Form (PSI/SF), and Adaptive Behavior Assessment System-2nd Edition (ABAS-II)
for 116 children ages 3-12 from a rural, Appalachian community. Caregivers with
lower child abuse potential, children who used fewer school services, older
children, and caregivers with lower household income had better total adaptive
skills. Caregivers with lower child abuse potential, children who used fewer school
services and older children had better functioning on the academic skills subscale.
Children who used fewer school services, were older, and had lower family income
had greater self-care skills. Finally, children who used fewer school services had
greater communication skills. Parent-child dysfunction was not related to child
development outcomes. The findings demonstrate that educators are in a unique
position to intervene and support children at risk of maltreatment.
A maternal history of childhood maltreatment is thought to be a potent risk factor
for child abuse and neglect, yet the extent of continuity across generations is
unclear, with studies reporting vastly different rates of intergenerational
transmission. Disparate findings may be due to lack of attention to the nature of
maltreatment experiences in each generation. We sought to expand the current
literature by examining the role of maltreatment type, perpetrator identity, and
substantiation status of reports to child protective services (CPS) on
intergenerational maltreatment among adolescent mothers (n = 417) and their
children. We found that when mothers had at least one report of childhood
maltreatment (substantiated or not), the odds that they maltreated their children
increased by 72% (OR = 2.52), compared to mothers who are not maltreated, but the
odds were considerably lower when we limited analysis to substantiated reports.
Both a maternal history of substantiated neglect and multiple type maltreatment
(neglect and physical or sexual abuse) were associated with increased risk of child
maltreatment, yet the likelihood of children experiencing multiple maltreatment
perpetrated with their mothers identified as perpetrators increased over 300% when
mothers had a childhood history of multiple maltreatment. (C) 2016 Elsevier Ltd.
All rights reserved.
Aim: Although considerable efforts have been made to improve relationships between
professionals and parents suspected of child maltreatment, little research has been
conducted to examine the ways in which parents escalate their negative cognition
and behavior involving professionals. This study developed a model of parents'
negative reinforcement of their cognitive behavior and the factors influencing
reductions in this reinforcement. Method: Interview data were collected from 21
parents, who had experienced outreach and child protection issues, and analyzed
using the grounded theory approach. Result: In the outreach phase, the analysis
initially produced the negative image of help-seeking behavior category, followed
by the dissatisfaction with outreach and reinforcement of negative cognition
categories. In this phase, the analysis also identified the social support and
support groups step as a means of reducing negative cognition. In contrast, in the
child protection phase, the analysis produced the anger and psychological conflict
with child protection services and unwilling consent categories. In this phase, the
analysis also identified the psychoeducation and timely feedback step as an
acceptable means of minimizing the escalation of negative cognition. Conclusion:
The hypothetical model revealed the ways in which parents changed their cognition
and behavior and demonstrated the factors influencing reductions in the
reinforcement of negative cognition and behavior. These results could be useful for
practice in child maltreatment cases. (C) 2016 The Authors. Published by Elsevier
Ltd.
A correlation between socioeconomic disadvantage and child maltreatment has long
been observed, but the drivers of this association are poorly understood. We sought
to estimate the effects of economic factors on risk of child maltreatment after
adjusting for other known influences using the Australian Temperament Project, a
population-based birth cohort of 2443 individuals and their parents. We used
logistic regression to estimate associations of childhood economic factors
(parental education, occupation, and unemployment; type of housing; and
retrospective perception of poverty) with retrospective reports of perceived child
maltreatment (physical abuse, sexual abuse, emotional abuse, neglect, and
witnessing of domestic violence), controlling for demographic factors, parental
mental health and substance use, and child health. We then used these estimates to
approximate the proportions of child maltreatment population attributable fractions
that are theoretically preventable by addressing childhood economic disadvantage.
Economic factors were associated with all types of child maltreatment. For the most
part, these associations diminished only partially when controlling for noneconomic
con-founders, supporting hypotheses of causal relationships. Jointly, economic
factors were significant predictors of physical abuse, sexual abuse, and witnessing
of domestic violence but not of emotional abuse or neglect. Retrospective
perceptions of childhood poverty were, in particular, strongly associated with most
forms of child maltreatment but not with sexual abuse after accounting for other
economic factors. We estimated that 27% of all child maltreatment was jointly
attributable to economic factors. These findings suggest that strategies that
reduce economic disadvantage are likely to hold significant potential to reduce the
prevalence of child maltreatment. (C) 2016 Elsevier Ltd. All rights reserved.
Crime is a major public health and safety threat. Many studies have suggested that
early exposure to child maltreatment increases an individual's risk for persistent
serious crime in adulthood. Despite these findings about the connection between
child maltreatment and criminal behavior, there is a paucity of empirically-based
knowledge about the processes or pathways that link child maltreatment to later
involvement in crime. Using a community sample of 337 young adults (ages 18-25) in
a U.S. metropolitan area, the present study examined the role of various facets of
impulsivity in linking child maltreatment to crime. A series of factor analyses
identified three types of crime including property crime, violent crime, and fraud.
Structural equation modelings were conducted to examine the associations among
childhood maltreatment, four facets of impulsivity, and criminal behavior,
controlling for sociodemographic information, family income and psychological
symptoms. The present study found that child emotional abuse was indirectly related
to property crime and fraud through urgency while a lack of premeditation mediates
the relationship between child neglect and property crime. Child physical abuse was
directly related to all three types of crime. Personality traits of urgency and
lack of premeditation may play a significant role in the maltreatment-crime link.
Preventive interventions targeting impulsivity traits such as urgency and a lack of
premeditation might have promising impacts in curbing criminal behavior among
maltreatment victims. (C) 2016 Elsevier Inc. All rights reserved.
A cost of illness (COI) study was undertaken to estimate the magnitude and range of
lifetime effects associated with child maltreatment in Australia, using an
incidence-based approach. Costs were primarily estimated through calculation of
population attributable fractions (PAFs) to determine the marginal effects of child
maltreatment on a range of outcomes. PAFs were then applied to estimates of
expenditure, inflated to 2014-15 Australian dollars, projected over the life
course, according to a baseline age of incident cases for child maltreatment in
2012-13, and discounted at 7% per annum. Sensitivity analysis was conducted using a
best and lower bound estimate of incidence of child abuse. The best estimate of the
total estimated lifetime financial costs for incident cases of child maltreatment
in 2012-13 was $9.3 billion (a cost per child maltreated of $176,437), with a lower
bound of $5.8 billion. The best estimate of lifetime costs associated with reduced
quality of life and premature mortality (non-financial costs) for all incident
cases of child maltreatment in 2012-13 was $17.4 billion, or $328,757 per child
maltreated. The considerable lifetime costs associated with child maltreatment
warrants an expansion of existing investment in primary and secondary prevention
and targeted support services for children and families at risk. (C) 2016 Elsevier
Ltd. All rights reserved.
In cases of maltreatment involving children of U.S. Army service members, the U.S.
Army Family Advocacy Program (FAP) is responsible for providing services to
families and ensuring child safety. The percentage of cases of maltreatment that
are known to FAP, however, is uncertain. Thus, the objective of this retrospective
study was to estimate the percentage of U.S. Army dependent children with child
maltreatment as diagnosed by a military or civilian medical provider who had a
substantiated report with FAP from 2004 to 2007. Medical claims data were used to
identify 0-17 year old child dependents of soldiers who received a medical
diagnosis of child maltreatment. Linkage rates of maltreatment medical diagnoses
with corresponding substantiated FAP reports were calculated. Bivariate and
multivariable analyses examined the association of child, maltreatment episode, and
soldier characteristics with linkage to substantiated FAP reports. Across 5945
medically diagnosed maltreatment episodes, 20.3% had a substantiated FAP report.
Adjusting for covariates, the predicted probability of linkage to a substantiated
FAP report was higher for physical abuse than for sexual abuse, 25.8%, 95% CI
(23.4, 28.3) versus 14.5%, 95% CI (11.2, 17.9). Episodes in which early care was
provided at civilian treatment facilities were less likely to have a FAP report
than those treated at military facilities, 9.8%, 95% CI (7.3, 12.2) versus 23.6%,
95% CI (20.8, 26.4). The observed low rates of linkage of medically diagnosed child
maltreatment to substantiated FAP reports may signal the need for further
regulation of FAP reporting requirements, particularly for children treated at
civilian facilities. (C) 2016 Elsevier Ltd. All rights reserved.
The study examines family characteristics that put adolescent girls at increased
risk of abuse, mainly physical, sexual and emotional abuse and neglect. Stratified
random sampling was done among classes 7th to 12th of government girls' schools of
a semi-urban area of Delhi, and a total of 1060 adolescent girls participated.
Majority were in mid-adolescence. Approximately 70% study subjects faced at least
one form of maltreatment. Physical abuse was faced by 42.6%, sexual abuse by 26.6%,
emotional abuse by 37.9% and neglect by 40.1% of study subjects. The most frequent
perpetrator of physical and emotional abuse was mother, and of sexual abuse were
friends, relatives or neighbours. No or low education of father increased odds of
physical and emotional abuse, while odds of physical abuse and neglect were lower
if mothers were housewives. Excessive arguments between parents and history of
maltreatment in parents increased odds of child maltreatment in study subjects.
Although people with a history of child abuse are known to be at elevated risk for
later difficulties in relationships, there is debate over whether these effects are
enduring and relatively immutable or are moderated by characteristics and behaviors
of the partner. To reconcile these competing perspectives, we conducted a
longitudinal study of 414 newlywed couples living in low-income neighborhoods,
testing whether the association between abuse history and relationship satisfaction
is dependent on the partners' aggression, depression, substance abuse, observed
communication, and other demographic risk factors. Spouses who had been abused as
children (25% of husbands, 31% of wives) reported more symptoms of depression and
substance abuse and, among husbands, displayed more negative communication. Spouses
with a history of child abuse were also less satisfied with their marriage, even as
newlyweds; abused wives also declined in satisfaction over time compared to those
without this history. However, interactions between abuse history and all of the
proposed moderators were not significant, indicating that partner and relationship
characteristics failed to strengthen or weaken the association between abuse
history and relationship satisfaction. Childhood experiences of abuse appear to
have lasting and broad effects on individual and relational outcomes, and these
effects are neither heightened nor mitigated by the partner's characteristics or
behaviors.
Objective: Early victimization elevates children's risk for developing
psychopathology. Recent findings suggest that disruptions in developmental
processes related to symptoms of posttraumatic stress (PTS) may partially account
for the association between early victimization and subsequent psychopathology. The
present study prospectively tested the temporal sequencing of these associations
using, multiinformant measurements in a large, diverse sample of children at high
risk for victimization. Method: This study measured victimization (i.e., direct,
indirect, familial, and nonfamilial violence), PTS, externalizing, and
internalizing problems among 1154 children (561 girls and 593 boys) who
participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN).
Results: Structural equation modeling revealed that, in addition to directly
impacting psychopathology, childhood victimization contributed to escalations in
internalizing and externalizing problems as children transitioned from middle to
late childhood indirectly through PTS. The mediational role of PTS was largely
similar for girls and boys and for those who were investigated for early reports of
maltreatment and those identified early as at-risk for victimization. Conclusions:
This study delineated the role of PTS in the development of psychopathology
following early victimization. These findings highlight the importance of carefully
assessing for underlying trauma symptoms when considering diverse presentations of
psychopathology among youth who have been victimized.
Educators periodically encounter the need to report a suspicion of child abuse or
neglect. Studies show that school professionals recognize more than half of
maltreated children. Because of uncertainty with reporting policies, practices, and
procedures, this experience may be difficult for the educator before, during, or
after a report is made, which precipitates a variety of emotions and a need for
support. Many educators often encounter challenges and barriers with reporting
procedures within the school settings. Educators who lack support in their
educational institution may fail to report their suspicion of child maltreatment.
This article explores child maltreatment reporting practices from the point of view
of an educator in a school setting and proposes strategies to address reporting
practices effectively. Appropriate intervention and services are required to meet
the needs of children when there is a suspicion of abuse and neglect and are built
into a model that can shape training, policies, and procedures. Therefore,
strategies that cultivate immediately and legally responsive environments are
imperative in the educational setting to begin to reduce the number of maltreated
child cases that are unreported.
There is strong evidence that poverty and economic disadvantage are associated with
child maltreatment; however, research in this area is underdeveloped in Canada. The
purpose of this paper is to examine the relationship between economic hardship and
maltreatment for families and children identified to the Ontario child protection
system for a maltreatment concern. Secondary analyses of the Ontario Incidence
Study of Reported Child Abuse and Neglect-2013 (OIS-2013) were conducted. The OIS-
2013 examines the incidence of reported maltreatment and the characteristics of
children and families investigated by child welfare authorities in Ontario in 2013.
Descriptive and bivariate chi-square analyses were conducted in addition to a
logistic regression predicting the substantiation of maltreatment. In 9% of
investigations, the household had run out of money for food, housing, and/or
utilities in the past 6 months. Children in these households were more likely to
have developmental concerns, academic difficulties, and caregivers with mental
health concerns and substance use issues. Controlling for key clinical and case
characteristics, children living in families facing economic hardship were almost 2
times more likely to be involved in a substantiated maltreatment investigation (OR
= 1.91, p < 0.001). The implications in regard to future research and promoting
resilience are discussed.
Background: The Texas Department of Family and Protective Services (DFPS) created a
statewide network of child abuse pediatricians working at 6 academic centers in
2006. Methods: Case data for the period 9/1/2012-8/31/2014 were reviewed for child
demographics, risk factors, physician determinations, injury descriptors, and
information made available to the physician. Results: 8061 of 410,315 DFPS cases
(2%) were referred during the period. Network utilization rates ranged from 7.5% in
counties served by San Antonio to 1.4% in Austin-served counties. Cases from
outlying counties were less likely to involve older children. African American
children were over-represented in referrals, and Caucasian and Asian children were
underrepresented. Prevalent risk factors included prior DFPS history, single
parent-household, mental illness, substance abuse, and domestic violence. Network
providers found no or only nonspecific evidence for maltreatment in 45% of cases.
Determinations were hindered by poor quality photographs in 188 cases and
inadequate skeletal surveys in 121. Insufficient information precluded case
completion for 65 cases of children <2 years. Conclusions: Our data indicate that
child abuse centers in Texas are underutilized, and there are practice differences
with respect to medical referrals across different regions. Our findings concerning
ethnic differences and risk factors are consistent with national trends. The
problems of inadequate photographs and case information may improve with better
training of workers; the issue of poor quality skeletal surveys requires further
study. Standard DFPS criteria for referrals to child abuse pediatricians should
mitigate some of the problems identified by this study. (C) 2016 Elsevier Ltd. All
rights reserved.
Criminal justice research frequently investigates relationships between punishment
decisions and demographic characteristics of the accused, such as gender, race, and
age. While there are many similarities between criminal justice and child welfare
cases, research on child maltreatment has yet to examine potential demographic
influences on case outcomes. The current study examines relationships between
parent gender, type of maltreatment, and child removal among agency responses to
child maltreatment cases. Using data collected by the National Data Archive on
Child Abuse and Neglect Data System (NCANDS), we identify differences in the
likelihood of child removal from the parental home across type of maltreatment and
perpetrator gender. Our results indicate that mother perpetrators of physical abuse
not only face significantly higher likelihood of removal than mother perpetrators
of neglect, but are more at risk for losing their children than father perpetrators
of both physical abuse and neglect. Findings suggest that gendered attributions and
stereotypes regarding parenting can shape assessments of parents' blameworthiness,
dangerousness, and rehabilitative potential. We propose that future research on
child maltreatment cases adapt and apply justice concepts and frameworks to uncover
potential unwarranted demographic disparities in agency decision-making. (C) 2016
Elsevier Ltd. All rights reserved.
The current study tested the hypothesis that mothers who have experienced child
maltreatment and aggression within their adult relationships may be at particular
risk for misinterpreting infant emotions, leading to less sensitive parenting
behaviors. Participants were 120 pregnant women recruited for a larger,
longitudinal study investigating the role of psychosocial and environmental risk on
women and their young children. Data were collected during the third trimester of
pregnancy, and when children were 1 and 2 years of age. Participants completed a
projective test designed to elicit individual differences in perceptions of infant
emotions and an observer-rated assessment of parenting behaviors was conducted in
the family home. Using structural equation modeling, we tested associations between
maternal interpersonal aggression exposure and perceptions of infant emotion and
parenting behaviors. Results demonstrated that a history of child abuse and
intimate partner conflict were associated with a maternal tendency to view
ambiguous infant facial expressions as negative (i.e., negative attribution bias),
and in turn, with less parenting sensitivity over time. Findings suggest that
negative attributions of infant emotion may be 1 mechanism by which a history of
trauma and violence exposure contributes to less sensitive parenting for some
mothers. Implications for intervention include the need for trauma-informed
clinical services and psychoeducational methods that help mothers more accurately
read and respond to infant emotional expression and bids for connection.
Although Child Protective Services (CPS) and other child welfare agencies aim to
prevent further maltreatment in cases of child abuse and neglect, recidivism is
common. Having a better understanding of recidivism predictors could aid in
preventing additional instances of maltreatment. A previous study identified two
CPS interventions that predicted recidivism: psychotherapy for the parent, which
was related to a reduced risk of recidivism, and temporary removal of the child
from the parent's custody, which was related to an increased recidivism risk.
However, counter to expectations, this previous study did not identify any other
specific risk factors related to maltreatment recidivism. For the current study, it
was hypothesized that (a) cumulative risk (i.e., the total number of risk factors)
would significantly predict maltreatment recidivism above and beyond intervention
variables in a sample of CPS case files and that (b) therapy for the parent would
be related to a reduced likelihood of recidivism. Because it was believed that the
relation between temporary removal of a child from the parent's custody and
maltreatment recidivism is explained by cumulative risk, the study also
hypothesized that that the relation between temporary removal of the child from the
parent's custody and recidivism would be mediated by cumulative risk. After
performing a hierarchical logistic regression analysis, the first two hypotheses
were supported, and an additional predictor, psychotherapy for the child, also was
related to reduced chances of recidivism. However, Hypothesis 3 was not supported,
as risk did not significantly mediate the relation between temporary removal and
recidivism. (C) 2016 Elsevier Ltd. All rights reserved.
Parental criminal justice involvement is prevalent in the United States and
potentially associated with a range of negative outcomes for children including
child abuse and neglect. However, the association between prior parental criminal
justice involvement and child maltreatment is not well understood. This paper
reviewed the existing literature regarding maltreatment victimization among
children of parents with prior criminal justice involvement. Results from ten
reviewed studies demonstrated an association between prior parental criminal
justice involvement and child maltreatment, but did not provide sufficient evidence
to determine whether parental criminal justice involvement is an independent risk
factor for child maltreatment or of the specific mechanisms through which this
association occurs. Recommendations for future research include use of multivariate
analysis methods that account for variations in the type and timing of parental
criminal justice involvement and child maltreatment. Implications for practice
include the development of strategies to address the adverse family contexts
commonly found among these parents and children. (C) 2016 Elsevier Ltd. All rights
reserved.
Child maltreatment has been demonstrated to. have many short- and long-term harmful
consequences for victims, but whether or not child abuse is associated with an
increased risk of peer victimization during adolescence is unclear. This study
analyzed prospective data from 831 children and parents participating in the
Longitudinal Studies on Child Abuse and Neglect (LONGSCAN) to investigate the
relationships between child physical and sexual abuse and adolescent victimization
by peers, as well as the potential for gender to moderate these relationships.
Results from ordinal logit regression models indicated that children who were
physically abused prior to age 12, based on official reports, parent reports, and
child reports, had a greater risk of experiencing more intimidation and physical
assault by peers at age 16. Having a history of sexual abuse predicted more
physical assault but not intimidation. There was no evidence that gender moderated
these relationships; in all cases, the relationship between abuse and
revictimization was similar for boys and girls. The findings emphasize the need to
provide victims of abuse with assistance to help prevent a cycle of victimization.
(C) 2016 Elsevier Ltd. All rights reserved.
We reviewed and meta-analyzed 10 studies (N = 492) that examined the association
between (risk for) child maltreatment perpetration and basal autonomic activity,
and 10 studies (N = 471) that examined the association between (risk for) child
maltreatment and autonomic stress reactivity. We hypothesized that maltreating
parents/at-risk adults would show higher basal levels of heart rate (HR) and skin
conductance (SC) and lower levels of HR variability (HRV) and would show greater HR
and SC stress reactivity, but blunted HRV reactivity. A narrative review showed
that evidence from significance testing within and across studies was mixed. The
first set of meta-analyses revealed that (risk for) child maltreatment was
associated with higher HR baseline activity (g = 0.24), a possible indication of
allostatic load. The second set of meta-analyses yielded no differences in
autonomic stress reactivity between maltreating/at-risk participants and
nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that
positive effects for sympathetic stress reactivity as a risk factor for child
maltreatment were found in a few early studies, whereas each subsequently
aggregated study reduced the combined effect size to a null effect, an indication
of the winner's curse. Most studies were underpowered. Future directions for
research are suggested.
Although cases of child abuse among migrant families are often reported by social
media, the issue of child maltreatment among migrant families in China has received
little empirical attention. This study investigated both the prevalence of child
maltreatment by parents among migrant families, and the individual, family and
community-level risk factors associated with child abuse in this context. A survey
was conducted with 667 migrant and 496 local adolescents in Shenzhen, South China,
with a stratified two-stage cluster sampling design. Logistic regression analysis
was conducted to compare the prevalence of maltreatment between migrant and local
adolescents, and also to explore risk factors associated with the psychological and
physical maltreatment in both groups. The results showed that parent-to-child abuse
was more prevalent among migrant than local adolescents, with migrant adolescents
1.490 and 1.425 times more likely to be psychologically and physically abused by
their parents than their local counterparts. Low academic performance, delinquent
behavior, family economic adversity and low parent attachment put migrant
adolescents at increased risk of both psychological and physical maltreatment, and
neighborhood disorganization was significantly related to psychological aggression
among migrant adolescents. The findings confirm that child abuse perpetuated by
parents is a serious problem in Mainland China, especially among migrant families,
and implications for policy and practice are discussed. (C) 2017 Elsevier Ltd. All
rights reserved.
The experience of maltreatment during childhood is associated with chronic low-
grade inflammation in adulthood. However, the molecular mechanisms underlying this
pro-inflammatory phenotype remain unclear. Mitochondria were recently found to
principally coordinate inflammatory processes via both inflammasome activation and
inflammasome-independent pathways. To this end, we hypothesized that alterations in
immune cell mitochondrial functioning and oxidative stress might be at the
interface between the association of maltreatment experiences during childhood and
inflammation. We analyzed pro-inflammatory biomarkers (levels of C-reactive
protein, cytokine secretion by peripheral blood mononuclear cells (PBMC) in vitro,
PBMC composition, lysophosphatidylcholine levels), serum oxidative stress levels
(arginine:citrulline ratio, L-carnitine and acetylcarnitine levels) and
mitochondrial functioning (respiratory activity and density of mitochondria in
PBMC) in peripheral blood samples collected from 30 women (aged 22-44 years) with
varying degrees of maltreatment experiences in form of abuse and neglect during
childhood. Exposure to maltreatment during childhood was associated with an
increased ROS production, higher levels of oxidative stress and an increased
mitochondria! activity in a dose-response relationship. Moreover, the increase in
mitochondrial activity and ROS production were positively associated with the
release of pro-inflammatory cytokines by PBMC. Decreased serum levels of
lysophosphatidylcholines suggested higher inflammasome activation with increasing
severity of child maltreatment experiences. Together these findings offer
preliminary evidence for the association of alterations in immune cell
mitochondrial functioning, oxidative stress and the pro-inflammatory phenotype
observed in individuals with a history of maltreatment during childhood. The
results emphasize that the early prevention of child abuse and neglect warrants
more attention, as the experience of maltreatment during childhood might have life-
long consequences for physical health. (C) 2016 Elsevier B.V. and Mitochondria
Research Society. All rights reserved.
A social information processing (SIP) theory of parenting risk posits that social-
cognitive and neuro-cognitive incapacities characterize at-risk parents, and that
these cognitive difficulties operate across relational domains. This study focused
on highly disadvantaged mothers of preschoolers and compared mothers with histories
of perpetrating child neglect (n = 69) to demographically similar mothers without
such histories (n = 76). Participants completed measures of unrealistic
expectations for children and other adults, social problem-solving in parenting and
nonparenting situations, executive functioning (EF), and attributions for children
and other adults. As predicted, associations among these measures were found within
and across relational domains. Exploratory factor analysis revealed two distinct
clusters that distinguished the two groups. The first included measures of
expectations and attributions (for both children and other adults) and the second
included problem-solving difficulties and EF. When group differences were examined
on individual variables, mothers with histories of perpetrating neglect exhibited
more unrealistic expectations of children and other adults, more hostile
attributions toward children and other adults, and poorer performance on tests of
EF than comparisons. Only interpersonal problem-solving (in both parenting and
nonparenting situations) failed to differentiate the neglect group from
comparisons. In regression analyses, both parenting and nonparenting social
cognition and EF contributed significantly to child neglect. These findings provide
some support for this cognitive model of parenting risk and suggest widespread
disturbances in parenting and nonparenting social cognition and neurocognition, may
play a role in child neglect.
In relation to child abuse, child neglect has been understudied even though it is
more common and causes at least as much harm. While child maltreatment (in a single
category) has been linked to substance use disorders (SUD), and while child abuse
alone (without neglect) has been linked to SUD, it remains unclear whether
differences exist in the link between SUD and child abuse alone (without neglect)
versus SUD and child neglect alone (without abuse). Utilising the National Survey
of Child and Adolescent Well-Being II (NSCAW II, 2014): Wave I - 2008-09; Wave II -
18months later: N=5872), we used logistic regression to longitudinally assess
whether past-year abuse versus past-year neglect in Wave I are equally influential
in predicting newly diagnosed substance dependence in Wave II (among youth without
SUD in Wave I). After adjusting for several factors, we found that past-year child
neglect in Wave I was a significant predictor of newly diagnosed substance
dependence in Wave II among youth who did not have SUD in Wave I. Other forms of
youth maltreatment were unrelated. The findings suggest that child welfare and
substance abuse professionals could pay special attention to youth with past-year
neglect in order to help prevent the emergence of new substance dependence
disorders. Copyright (c) 2015 John Wiley & Sons, Ltd.
Objectives: It is hypothesized that parents who have physically abused a child or
who are at high risk to physically abuse a child form more negative/less positive
impressions about children than nonabusive/low-risk-for-abuse parents. However, to
date, the overall evidence from the several individual studies testing this
hypothesis has been inconclusive. Method: The current meta-analysis compared the
impressions that abusive/high-risk-for-abuse parents and nonabusive/low-risk-for-
abuse parents form about children (k = 27, N = 1,645). Results: Overall, we
estimated the difference in parents' impressions of children to be about 1/3 of 1
standard deviation in the hypothesized direction (d = 0.32, 95% confidence interval
[0.19, 0.44]). This difference was found among studies using a variety of
procedures and a variety of dependent variables. Further, an analysis of the
distribution of p values from the published studies corroborated this finding.
Conclusions: Collectively, the current meta-analysis confirms differences between
abusive/high-risk-for-abuse parents' and nonabusive/low-risk-for-abuse parents'
impressions of children. However, despite the clear evidence for the existence of
an effect, the current results suggest the magnitude of this effect is modest.
Future research should determine whether parents' impressions are meaningfully
related to parents' child-directed behaviors. Such research would be informative as
to whether parents' impressions of children should be targeted in interventions
aimed at reducing physically abusive parenting behaviors.
Aims To assess the knowledge, attitudes and experience of a group of Malaysian
dental health care providers regarding child physical abuse (CPA) cases in terms of
frequency of occurrence, diagnosis, risk factors and reporting. Methods A
questionnaire was distributed to all dental health care providers attending a
national paediatric dentistry conference in Kuantan, Malaysia, and demographical
variables, knowledge, attitudes and experience about CPA, risk factors and the
reasons for not reporting abuse cases were collected. Descriptive statistics and
bivariance analysis were performed. A 5 % level of statistical significance was
applied for the analyses (p <= 0.05). Results The response rate was 74.7 %. Half of
the respondents (52.8 %) stated that the frequency of occurrence of CPA is common
in Malaysia. Full agreement between dental health care providers was not determined
concerning the identification of signs of CPA and its risk factors. Although 83.3 %
were aware that reporting CPA is a legal requirement in Malaysia, only 14.8 % have
reported such cases. Lack of adequate history was the main reason for not
reporting. Virtually two-thirds of the respondents (62 %) indicated that they had
not received sufficient information about CPA and were willing to be educated on
how to diagnose and report child abuse cases (81.5, 78.7 %, respectively).
Conclusions There were considerable disparities in respondents' knowledge and
attitudes regarding the occurrence, signs of suspected cases, risk factors and
reporting of CPA. Despite being aware of such cases, only a handful was reported.
Enhancement in the education of Malaysian dental health care providers on
recognising and reporting CPA is recommended.
This paper addresses child abuse and the Social Services protection and builds upon
a study of verdicts concerning 2 Care of Young Persons Act (CYPA). The aim was to
explore the extent of, and what characterised, the violence the children were being
subjected to. A central finding was that of all the applications of 2 CYPA during
one year concerning 196 children, 13-18 years, 70% concerned children reported as
subjected to violence. The violence was in most cases described as severe and
systematically exerted over many years with intimidating tactics of power and
control. More girls than boys were in question for care because of violence. Girls
were also to a greater extent reported as having been subjected to sexual abuse or
coercive control of their sexuality in relation to standards regarding honour and
virginity. In an international perspective the findings can be said to confirm the
need to analyse such factors as gender, power and control when research and
interventions concerns children abused by their parents. In a Swedish context the
findings can be said to suggest that the 2 CYPA is a crucial intervention to
protect children from violence.
Children in Scotland who are subject to child protection interviews should be
interviewed jointly by specially trained police officers and social workers who
have attended training based on a national curriculum. This study, which was
conducted in two Strands, explores the effectiveness of the training, focusing
specifically on the free narrative phase of the interview. Strand A explores
respondents' self-evaluation, obtained through semi-structured interviews with 16
participants, while Strand B comprises an analysis of 21 role-play interviews. The
findings show a considerable discrepancy between perceived practitioner confidence
in ability and actual skill levels observed in role-plays, where interviewers
showed a persistent overuse of specific and closed questions, while neglecting the
use of open prompts and open questions to encourage free narrative. The study
concludes that the national curriculum is not as effective in preparing
participants for the free narrative phase of the interview as perceived by
participants. Possible reasons are explored. Copyright (c) 2015 John Wiley & Sons,
Ltd.
Child protection and welfare have become international issues in a globalized
world. Ideas about childhood and the upbringing of children vary widely, depending
upon the prevailing economic, socio-cultural, religious, and political contexts.
These have had dramatic effects on the way societies value children, and the role
acquired by the state in their protection and advancing their well-being. Children,
however, remain at risk. They are placed at risk by the breakdown of extended
family systems as a result of urbanization, and as a result of impaired functioning
of some nuclear families, in the absence of kinship safety nets. Some traditional
cultural practices place children at risk, especially girl children. Poverty
creates risks for all children but it can create specific catastrophic risks for
girls. Countries can enact visionary laws intended to protect children, but they
will be ineffective against entrenched social attitudes, especially if only limited
resources can be provided to implement and enforce them. This is the ultimate
challenge that the world community must address if the vision of the United Nations
Convention on the Rights of the Child is to be realized.
The risk for using child abuse images (CAI) is difficult to assess, especially as
it mostly remains undetected by legal authorities. The present study investigates
the association of aspects of sexual preference and dynamic risk factors with CAI
only and mixed offending (CAI and child sexual abuse) over lifetime and within six
months prior to assessment. A sample of 190 undetected, self-identified pedo-
and/or hebephiles was investigated. Multinomial logistic regression analyses
revealed that sexual preoccupation is of great importance, especially for recent
CAI only and mixed offending, as well as lifetime mixed offending. Although
inconclusive, a sexual preference for early-pubescent children seems to be of
interest for recent and lifetime offending. A sexual preference for prepubescent
children, additional paraphilias and sexualised coping have shown some, although no
statistically meaningful association with lifetime offending. Gender preference,
exclusivity of pedohebephilia and offence-supportive attitudes did not show any
significant relation with offending behaviour.
The view of what constitutes child abuse and neglect is dependent on the laws,
cultural context, local thresholds and the availability. Since 1982, the
International Society for the Prevention of Child Abuse and Neglect (ISPCAN) has
conducted surveillance of child maltreatment and child protection every two years,
published in World Perspectives on Child Abuse. It is hoped that up to date
information will inform the development of laws, policies and programs to better
address child abuse and neglect. This article is based on data on child sexual
abuse and exploitation from 73 countries gathered online in 2015-16 for the 12
edition of World Perspectives. Respondents were key informants who were
knowledgeable professionals in the child protection field. They were encouraged to
consult with colleagues so as to provide accurate information. Countries were
grouped into different regions of the world and into income level categories. The
findings focus on definitions of abuse and neglect, laws, policies and programs to
address and prevent maltreatment and barriers to prevention. It is evident that
there is considerable variability across regions and country income categories, and
that programs and services need to be considerably strengthened, even in high
income countries. (C) 2017 Published by Elsevier Ltd.
Interpreters play a crucial role in many investigative interviews with child
complainants of sexual abuse; however, little has been written about the
interpreting process from the perspective of the interviewers. This study elicited
interviewers' perspectives about the challenges of using interpreters, with the aim
of understanding how investigative interviews could be improved. The participants
consisted of 21 investigative interviewers and prosecutors of child abuse cases
(from a range of jurisdictions) who use interpreters on a regular basis. Thematic
analysis of semi-structured interviews with the professionals about the
interpreting process revealed two main challenges particular to child abuse
interviews, namely the interpreters' lack of preparedness to deal with the
traumatic and sensitive nature of children's abuse histories, and an insufficient
understanding of best-practice' child interview process. The recommendations focus
on the need for more specialised training for, and screening of, interpreters, and
more extensive use of pre-conferencing to familiarise children with the
interpreter-mediated interview process.
The present pilot study sought to identify predictors of delays in child sexual
abuse (CSA) disclosure, specifically whether emotional and physical abuse by a
parental figure contributes to predicting delays over and above other important
victim factors. Alleged CSA victims (N= 79), whose parental figures were not the
purported sexual abuse perpetrators, were interviewed and their case files
reviewed, across two waves of a longitudinal study. Regression analyses indicated
that experiencing both emotional and physical abuse by a parental figure was
uniquely predictive of longer delays in disclosure of CSA perpetrated by someone
other than a parental figure. Victim-CSA perpetrator relationship type and sexual
abuse duration also significantly predicted CSA disclosure delay, whereas victim
age at the time of the police report, victim gender, and victims' feelings of
complicity were not significant unique predictors. Child abuse victims'
expectations of lack of parental support may underlie these findings. Parent-child
relationships are likely crucial to timely disclosure of CSA, even when a parent is
not the CSA perpetrator. (C) 2016 Elsevier Ltd. All rights reserved.
In the past three decades, there has been an exponential increase in the worldwide
availability of Internet access and devices that are able to access online
materials. This literature review investigated whether increased accessibility of
Internet child pornography (CP) increases the risk of in-person child sexual
exploitation. The current review found little to no evidence that availability of
the Internet has increased the worldwide incidence or prevalence of in-person child
sexual abuse. In fact, during the time period in which the Internet has flourished,
international crime statistics have shown a steady decrease of in-person child
sexual abuse. The only exception to this trend is an increase in Internet child
pornography or luring offenses (e.g., Stats Can, 2014), which involves child abuse
by definition. This article reviews the impact of the Internet on child sexual
abuse. It also reviews the characteristics of online CP offenders. Treatment of
these offenders and prevention of such offenses is also discussed.
Introduction: Estimating the national prevalence of child sexual abuse (CSA) and
its association with health and developmental outcomes is the first step in
developing prevention strategies. While such data are available from many
countries, less is known about the epidemiology of CSA in Japan. Methods: For this
systematic review, we searched English databases: Embase, Ovid MEDLINE(R) In-
Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R),
Ovid OLDMEDLINE(R), PsycINFO, and Japanese databases: Cinii, J-Stage, Children's
Rainbow Center Japan, Japan Child and Family Research Institute, Japanese Journal
of Child Abuse and Neglect to identify articles published before July 2015
examining the lifetime prevalence of CSA in Japan using non-clinical samples. Data
were extracted from published reports. Results: We initially identified 606
citations and after abstract review, retrieved 120 publications. Six studies that
met the selection criteria and additional two relevant studies were reviewed. The
range of contact CSA for females was 10.4%-60.7%, and the prevalence of this type
of CSA for males was 4.1%. The range of penetrative CSA for females was 1.3%-8.3%
and that for males was 0.5%-1.3%. A number of methodological issues were
identified, including a lack of validated measures of CSA, and low response rates.
Conclusion: In contrast to a lower prevalence of penetrative CSA, the prevalence of
contact CSA among Japanese females may be comparable or higher in relation to
international estimates. Future research on children's perceptions of and exposure
to sexual abuse, crime and exploitation in Japan is discussed. (C) 2017 Elsevier
Ltd. All rights reserved.
The population of potential child abuse offenders has largely been unstudied. In
the current study, we examine whether a six-component model used for primary
diabetes prevention could be adapted to child sexual abuse pre-offenders, whereby
individuals who are prone to sexual abuse but have not yet committed an offense can
be prevented from committing a first offense. The six components include: define
and track the magnitude of the problem, delineate a well-established risk factor
profile so that at-risk persons can be identified, define valid screening tests to
correctly rule in those with the disease and rule out those without disease, test
effectiveness of interventionsthe Dunkelfeld Project is an example, produce and
disseminate reliable outcome data so that widespread application can be justified,
and establish a system for continuous improvement. By using the diabetes primary
prevention model as a model, the number of victims of child sexual abuse might be
diminished.
Although researchers have found that child welfare placement disruptions are
associated with elevated youth physical and mental health problems, the mechanisms
that explain this association have not been previously studied. The present study
built on a previous investigation of the physical and behavioral consequences of
long-term permanent placement patterns among youth who participated in the
Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). The current
investigation (n = 251) aimed to (a) report the early adolescent living situations
of youth with different long-term placement patterns, and (b) to delineate the
roles of adverse childhood experiences (ACEs) and post-traumatic stress (PTS)
reactions in the association between unstable long-term placement patterns and
physical and mental health problems during the transition to adolescence.
Information about youth's living situations, ACEs, and physical and mental health
was gathered prospectively from child protective services records and biannual
caregiver and youth interviews when youth were 4-14 years old. The majority of
youth remained with the same caregiver during early adolescence, but youth with
chronically unstable permanent placement patterns continued to experience
instability. Path analyses revealed that ACEs mediated the association between
unstable placement patterns and elevated mental, but not physical, health problems
during late childhood. Additionally, late childhood PTS mediated the association
between unstable placement patterns and subsequent escalations in physical and
mental health problems during the transition to adolescence. Findings highlight the
importance of long-term permanency planning for youth who enter the child welfare
system and emphasize the importance of trauma-focused assessment and intervention
for these youth. (C) 2016 Elsevier Ltd. All rights reserved.
Amendments made to the Child Abuse Prevention and Treatment Act in 2003 and the
Individuals with Disabilities Education Improvement Act in 2004 opened the door to
a promising partnership between child welfare services and early intervention (EI)
agencies by requiring a referral to EI services for all children under age 3
involved in a substantiated case of child abuse, neglect, or illegal drug exposure.
However, little research has been conducted to assess the implications of these
policies. Using data drawn from a nationally representative study conducted in
2008-2009, we observed less than a fifth of all children in substantiated cases to
receive a referral to developmental services (18.2%) approximately 5 years after
the passage of the amendments. Of children in contact with the U.S. child welfare
system, Hispanic children of immigrants demonstrated the greatest developmental
need yet were among the least likely to receive EI services by the end of the study
period. Implications for policy and practice are discussed.
The purpose of this article was to examine the potential impact of child welfare
services on the risk for fatal child maltreatment. This was conducted using a
subsample of children who were identified as prior victims in the National Child
Abuse and Neglect Data System from 2008 to 2012. At the multivariate level, the
analyses show that case management services act to protect children from death as
do family support services, family preservation services, and foster care, but that
the results vary by type of maltreatment experienced. The author recommends that
before strong conclusions are drawn, additional research in this area is warranted.
Child wellbeing is identified as one of the three primary goals for child welfare
outcomes, thus strong wellbeing assessment tools are crucial to the monitoring of
child welfare success. Data from wellbeing measures can serve to identify child
needs, inform case planning, monitor change over time, and evaluate intervention
impact at the individual, local, state, and national levels. This paper examines
the goals, strengths, and challenges of four wellbeing measures currently used with
child welfare populations, namely: the Child and Adolescent Functional Assessment
Scale (CAFAS), the Child and Adolescent Needs and Strengths Assessment Tool (CANS),
the Child Behavior Checklist and related tools from the Achenbach System of
Empirically Based Assessment (CBCL/ASEBA), and the Treatment Outcomes Package
(TOP). For each measure, we describe the content, practical attributes, clinical
applications, and evidence of reliability and validity. We explore implementation
considerations and provide recommendations for system changes to ensure the optimal
use of each instrument. Agencies are encouraged to carefully consider their needs,
goals, capacities, and implementation infrastructure to inform selection of tools
that will aid them in successfully supporting and monitoring child wellbeing over
time. (C) 2016 Elsevier Ltd. All rights reserved.
David Stoesz offers a sweeping critique of the Children's Bureau and social work
education by claiming the existence of a child welfare cartel. He also attacks the
quality of social work education and research, which he claims has poorly invested
government funding and helped create the unmitigated failures of the American child
welfare system. However, closer examination reveals that many of his claims, while
dramatic, are actually ill conceived and unsupportable. We attempt to clarify and
inform readers about some significant aspects of the field of child welfare and the
contemporary responses being made by the federal government in partnership with
social work educators and researchers.
Childhood and adolescence coincide with rapid structural and functional maturation
of brain networks implicated in Theory of Mind (ToM); however, the impact of
paediatric traumatic brain injury (TBI) on the development of these higher order
skills is not well understood. ToM can be partitioned into conative ToM, defined as
the ability to understand how indirect speech acts involving irony and empathy are
used to influence the mental or affective state of the listener; and affective ToM,
concerned with understanding that facial expressions are often used for social
purposes to convey emotions that we want people to think we feel. In a sample of 84
children with mild-severe TBI and 40 typically developing controls, this study
examined the effect of paediatric TBI on affective and conative ToM; and evaluated
the respective contributions of injury-related factors (injury severity/lesion
location) and non-injury-related environmental variables (socio-economic status
(SES)/family functioning) to long-term ToM outcomes. Results showed that the
poorest ToM outcomes were documented in association with mild-complicated and
moderate TBI, rather than severe TBI. Lesion location and SES did not significantly
contribute to conative or affective ToM. Post-injury family affective
responsiveness was the strongest and most significant predictor of conative ToM.
Results suggest that clinicians should exercise caution when prognosticating based
on early clinical indicators, and that group and individual-level outcome
prediction should incorporate assessment of a range of injury-and non-injury-
related factors. Moreover, the affective quality of post-injury family interactions
represents a potentially modifiable risk factor, and might be a useful target for
family-centred interventions designed to optimise social cognitive outcomes after
paediatric TBI.
AimTo identify nurses' role and experiences of keeping children safe.
BackgroundApproaches to preventing, identifying and responding to child abuse and
neglect have moved towards a multidisciplinary approach where all professionals are
expected to contribute to the goal of keeping children safe. Frequently in contact
with children and families, nurses well positioned to contribute to keeping
children safe from abuse and neglect. Much has been published around nurses'
experiences of their role in keeping children safe, but this literature has not yet
been synthesized to determine the challenges and potential scope of this role.
DesignIntegrative review following an Integrative Review framework. Data
sourcesStudies were identified through a search of the electronic databases CINAHL,
Medline, Web of Science, Scopus and Informit to identify literature published
between 2005-2015. Review methodsAll the studies were critically appraised for
methodological quality using the Critical Skills Appraisal Programme. Data from
each study were extracted and categorized according to the review aims and the
study's major findings. ResultsInclusion criteria were met in 60 studies. Three
main findings were identified including nurses' insufficient knowledge, need for
validation and improved communication and balancing surveillance and support for
vulnerable families. ConclusionsNurses have many roles and experiences in keeping
children safe but often felt they did not have the knowledge, skills and support to
take action in this area. Further research is needed to understand why nurses feel
inadequate and disempowered to advocate and intervene on the behalf of children at
risk of abuse or neglect.
Sexual abuse perpetrated by a parent particularly the mother creates turmoil in the
child who has to depend on the very person who betrays their trust. A review of the
literature confirms that there are only a few case studies of mother-child incest
reported in the psychoanalytic literature; the incidence of such incest, however,
is unknown. Considerably, more information is available in the forensic and child
abuse literatures along with an increase in research; yet, there is a paucity of
data. Child sexual abuse by women as highly prevalent is described in early
societies, and that there is a bias in peoples' minds about the capacity of females
to sexually abuse children is raised by many writers. The fact of being abused by
one's mother brings up specific issues for survivors of maternal incest. Shame and
the fear of not being believed, which was the experience of my female patient and a
sense of specialness and failure of recognition of incest by the males, created
particular difficulties which had to be dealt with in psychotherapy. This paper
describes three teenagers, one female and two males who were sexually abused by
their mothers. I have condensed several years of treatment to provide an account of
the female patient and a summary of each of the males, and I attempt to explore the
dynamics of relatedness in the abused and the abuser.
Objective: To understand effective ways for EMS providers to interact with
distressed family members during a field intervention involving a recent or
impending out-of-hospital ( OOH) pediatric death. Methods: Eight focus groups with
98 EMS providers were conducted in urban and rural settings between November 2013
and March 2014. Sixty-eight providers also completed a short questionnaire about a
specific event including demographics. Seventy-eight percent of providers were
males, 13% were either African American or Hispanic, and the average number of
years in EMS was 16 years. They were asked how team members managed the family
during the response to a dying child, what was most helpful for families whose
child suddenly and unexpectedly was dead in the OOH setting, and what follow up
efforts with the family were effective. Results: The professional response by the
EMS team was critical to family coping and getting necessary support. There were
several critical competencies identified to help the family cope including: ( 1)
that EMS provide excellent and expeditious care with seamless coordination, ( 2)
allowing family to witness the resuscitation including the attempts to save the
child's life, and ( 3) providing ongoing communication. Whether the child is
removed from the scene or not, keeping the family appraised of what is happening
and why is critical. Exclusion of families from the process in cases of suspected
child abuse is not warranted. Giving tangible forms of support by calling friends,
family, and clergy, along with allowing the family time with the child after death,
giving emotional support, and follow-up gestures all help families cope.
Conclusion: The study revealed effective ways for EMS providers to interact with
distressed family members during an OOH pediatric death
Background Children that living with addicted parents are at risk for intentionally
and unintentionally poisoning. Present study aimed to evaluate the effect of
parental addiction on unintentional childhood poisoning. Materials and Methods:
Totally, 140 admitted children with poisoning in Loghman hospital, Tehran-Iran, as
referral center were recruited from March 2013 to July 2014. Cases were matched
with 280 controls by age (within a caliper of six months), gender, and date of
hospital attendance in Tehran, Iran. Parents were interviewed using an objective
checklist about the risk factors of childhood poisoning. Conditional logistic
regression with within-group varying weights was used to adjust for measured
confounders. Vary weights within the matched set was defined by inverse probability
weighting (IPW). Results: Sixty-two of cases (74.7%) were poisoned with Methadone.
The odds ratio [OR] 95% confidence interval [CI] of having addicted parents in
poisoned children compared to the controls in three scenarios of ordinary, un-
stabilized weighted and stabilized weighted conditional regression logistic ORs
(95% CI) were 17.3 (8.7, 34.6), 2.6 (1.9, 3.3) and 3.6 (2.9, 4.3) respectively.
Conclusion The results indicate that child abuse and neglect have been linked to
parental substance abuse. Education on preventive interventions such as safe
storage of methadone and store poisoning product out of reach and sight of children
are necessary in substance abusing families.
Facial traumas are common in children but often unconsidered. Facial injury is
responsible of impressive bleeding because of the rich vascularization of the face;
this bleeding is often underestimated because of the immediate arterial
vasoconstriction that is very strong for children. The blood volume is 80 ml/kg for
a newborn, with a total of 250 ml, reaching 70 ml/kg at one year of age. The
evaluation must be rigorously performed due to the risk of a sudden decompensation.
Regarding the wounds, the primary repair must be performed directly neat or optimal
in case of damaged tissues. The rule is to keep maximum of the integrity and to
limit debridement. Careful repair often requires general anesthesia, especially in
young children, to facilitate a perfect joining of the edges and of the
mucocutaneous lines. Losses of substance should be treated by directed
cicatrization. Flaps are never performed in children as a first intention for
reasons developed below. Given the elasticity of the facial skeleton, fractures
require a brutal shock to occur, but the clinical signs can be misleading. For
instance, too specific and sometimes ignored, fractures can show weakly symptomatic
signs : the fractures of the condylar and the orbital floor, with their respective
complication that are temporomandibular bone ankylosis and definitive diplopia.
Possible children abuse should be suspected in case of different age lesions and
discrepancies between the told story and types of injuries. Once the vital urgency
is eliminated, the orbital emergency should be first considered in facial traumas
within the ophthalmology specialty because wounds and contusions of the globe are
often under-evaluated and threaten the vision. The second emergency is the orbital
floor fracture in its 'trapdoor' type, specific to the child. Combined with a
motionless eye and uncontrollable vomiting, this is the second true urgency because
it involves the prognosis of the oculomotricity and requires emergency surgery.
Finally, dental trauma should not be overlooked because of their functional and
aesthetic consequences. Primary cicatrization is usually rapid but scars remain
inflammatory during a long time. The risk of hypertrophy exists in case of
contusions and lacerations associated with wounds but also during puberty and in
some locations. Age interfere with the result because growth will either improve or
worsen the initial result, depending on the location and mechanism. The secondary
specialized and prolonged managing and monitoring is capital on the functional,
aesthetic and psychological points of view. (C) 2016 Elsevier Masson SAS. All
rights reserved.
Background: The relation between viral load and disease severity in childhood acute
respiratory tract infections (ARI) is not fully understood. Objectives: To assess
the clinical relevance of the relation between viral load, determined by cycle
threshold (CT) value of real-time reverse transcription-polymerase chain reaction
assays and disease severity in children with single-and multiple viral ARI. Study
design: 582 children with ARI were prospectively followed and tested for 15
viruses. Correlations were calculated between CT values and clinical parameters.
Results: In single viral ARI, statistically significant correlations were found
between viral loads of Respiratory Syncytial Virus (RSV) and hospitalization and
between viral loads of Human Coronavirus (HCoV) and a disease severity score. In
multiple-viral ARI, statistically significant correlations between viral load and
clinical parameters were found. In RSV-Rhinovirus (RV) multiple infections, a low
viral load of RV was correlated with a high length of hospital stay and a high
duration of extra oxygen use. The mean CT value for RV, HCoV and Parainfluenza
virus was significantly lower in single-versus multiple infections. Conclusion:
Although correlations between CT values and clinical parameters in patients with
single and multiple viral infection were found, the clinical importance of these
findings is limited because individual differences in host-,viral and laboratory
factors complicate the interpretation of statistically significant findings. In
multiple infections, viral load cannot be used to differentiate between disease
causing virus and innocent bystanders. (C) 2017 Elsevier B.V. All rights reserved.
Introduction: It is important to elucidate the psychologically positive aspects of
childbirth for mothers, and not only the negative aspects such as perinatal
depression. This study aimed to examine psychological growth after childbirth and
its related variables by focussing on five factors of posttraumatic growth:
relating to others, new possibilities, personal strength, spiritual change and
appreciation of life.Methods: Pregnant women during mid-pregnancy were
consecutively recruited at a women's hospital in Japan and followed up 1 month
after childbirth. Psychological growth was assessed by the Posttraumatic Growth
Inventory.Results: Among 177 participants, 117 (66.1%) completed follow-up
assessments 1 month after childbirth. Multivariable regression analysis revealed
that primipara, higher resilience and less fear at childbirth were associated with
posttraumatic growth factors of relating to others and new possibilities. High
resilience and less fear at childbirth were also associated with personal strength.
On the other hand, being primiparous and high depressive symptoms were associated
with greater appreciation of life. No variables were associated with spiritual
change.Discussion: These findings suggest that giving birth for the first time
could be a highly challenging life event as well as an opportunity which leads to
PTG, and that giving birth with low fear might lead to mothers' psychological
growth. On the other hand, appreciation of life might need attention as it might
signify some sorts of coping response. These findings contribute to our
understanding of the psychological changes experienced by mothers.
Background: Recent studies have suggested that the interactions among several
factors affect the onset, progression, and prognosis of major depressive disorder.
This study investigated how childhood abuse, neuroticism, and adult stressful life
events interact with one another and affect depressive symptoms in the general
adult population. Subjects and methods: A total of 413 participants from the
nonclinical general adult population completed the Patient Health Questionnaire-9,
the Child Abuse and Trauma Scale, the neuroticism subscale of the shortened Eysenck
Personality Questionnaire - Revised, and the Life Experiences Survey, which are
self-report scales. Structural equation modeling (Mplus version 7.3) and single and
multiple regressions were used to analyze the data. Results: Childhood abuse,
neuroticism, and negative evaluation of life events increased the severity of the
depressive symptoms directly. Childhood abuse also indirectly increased the
negative appraisal of life events and the severity of the depressive symptoms
through enhanced neuroticism in the structural equation modeling. Limitations:
There was recall bias in this study. The causal relationship was not clear because
this study was conducted using a cross-sectional design. Conclusion: This study
suggested that neuroticism is the mediating factor for the two effects of childhood
abuse on adulthood depressive symptoms and negative evaluation of life events.
Childhood abuse directly and indirectly predicted the severity of depressive
symptoms.
Objective: To investigate whether individual differences in coping self-efficacy
mediated the association of child abuse and symptoms of ADHD in young adults.
Method: Self-reported measures of coping self-efficacy, child abuse, and ADHD were
obtained from 66 adults. Results: Adults who reported childhood physical or sexual
abuse (prior to the age of 17) had significantly higher levels of ADHD than those
who did not. Individual differences in coping self-efficacy fully mediated the
association between child abuse and ADHD symptoms in adulthood, such that
individuals who endorsed child abuse had lower coping self-efficacy, and coping
self-efficacy negatively predicted ADHD symptoms. Discussion: The findings suggest
a potential causal mechanism by which childhood physical and sexual abuse may
result in ADHD symptoms later in life. Interventions that improve coping skills may
be useful in preventing later ADHD symptoms among adults with a childhood history
of physical and sexual abuse.
Violence against children is a human rights problem that cuts across gender, race,
geographical, religious, socio-economic status and cultural boundaries. The risk of
violence towards disabled children during their lifetime is three to four times
greater than towards non-disabled children. It starts in early childhood, is more
severe and linked to disablist structures in society. Violence is perpetrated by
individuals and through institutional practices that are part of disabled
children's everyday life. Violence is often misdiagnosed as related to individual
impairment, and not recognised by professionals or the victims themselves.
Presenting disabled women's reflections of childhood violence, help-seeking and
responses to disclosure, this article seeks to raise an awareness of violence
towards disabled girls and the need for these to be recognised as a serious child
protection issue to be included in official definitions of child abuse.
Objective We aimed to find the prognostic factors to detect the patients who fail
the treatment of epilepsy, in the early stages of the disease. Materials&Methods
This study was done on the epileptic patients attending the Neurology Clinic of
Mofid Children's Hospital, Tehran, Iran from September 2013 to October 2014. After
defining the criteria for exclusion and inclusion, the patients were divided to two
groups based on responding to the medical treatment for their epilepsy and indices
were recorded for all the patients to be used in the statistical analyses. Results
The patients' age ranged from 1 to 15 yr. There was 188 patients with refractory
seizure in group 1 (experimental group) and 178 patient with well controlled
seizure in group 2(control group). There was a significant different between serum
drug level in both groups and patients with refractory seizure group had a lower
serum drug level than control group. In both groups tonic-clonic was the most
common type of seizure. Also the prevalence of brain imaging Abnormalityand other
neurologic disorders was significantly higher in patients with refractory seizure
in compare with control group. Conclusion Children with seizure who suffer from
refractory epilepsy need more attention and exact observation by the medical staff.
The increase of violence against children is a diagnosed social problem in the
Costa Rican society. This article focuses on the presence of an ideological bias in
the opinion writings of the local newspapers: La Nacion and Diario Extra. It
explains how some visions of the sources are ideological and do not contribute to
the end of the violence, nor to an effective promotion of childrens Human Rights.
In order to avoid violence we must develop a pro-children cultural change, complex
multi-institutional social networking, children autonomy and a critic to the family
institution.
This study explored the influences on living arrangements of orphans and vulnerable
children (OVC) housed at a community-based home in Johannesburg, South Africa. A
total of 50 OVC (males = 36%, females = 64%; age range 11 to 18 years) completed an
open-ended questionnaire, while some of them also participated in individual
interviews and focus group discussions on how they became residents of the
community-based home. The data were thematically analysed. Findings suggest their
choice to live in a community-based care setting to have been influenced by
homelessness with accompanying poverty, health issues, experiences of child abuse
and neglect, discrimination, and domestic violence. School psychologists working
with OVC from community-based homes should consider pathways by which the children
could be provided with needed support for resilient health and wellness.
Background: Obesity is genetically heterogeneous and highly heritable, although
polymorphisms explain the phenotype in only a small proportion of obese children.
We investigated the presence of copy number variations (CNVs) in "classical" genes
known to be associated with (monogenic) early-onset obesity in children. Methods:
In 194 obese Caucasian children selected for early-onset and severe obesity from
our obesity cohort we screened for deletions and/or duplications by multiplex
ligation-dependent probe amplification reaction (MLPA). As we found one MLPA probe
to interfere with a polymorphism in SIM1 we investigated its association with
obesity and other phenotypic traits in our extended cohort of 2305 children.
Results: In the selected subset of most severely obese children, we did not find
CNV with MLPA in POMC, LEP, LEPR, MC4R, MC3R or MC2R genes. However, one SIM1 probe
located at exon 9 gave signals suggestive for SIM1 insufficiency in 52 patients.
Polymerase chain reaction (PCR) analysis identified this as a false positive result
due to interference with single nucleotide polymorphism (SNP) rs3734354/rs3734355.
We, therefore, investigated for associations of this polymorphism with obesity and
metabolic traits in our extended cohort. We found rs3734354/rs3734355 to be
associated with body mass index-standard deviation score (BMI-SDS) (p = 0.003), but
not with parameters of insulin metabolism, blood pressure or food intake.
Conclusions: In our modest sample of severely obese children, we were unable to
find CNVs in well-established monogenic obesity genes. Nevertheless, we found an
association of rs3734354 in SIM1 with obesity of earlyonset type in children,
although not with obesity-related traits.
There is a growing interest in English-speaking jurisdictions, including Australia,
North America, Canada, the United Kingdom and New Zealand, about the prevention of
sexual abuse perpetrated by children against other children. The aim of this review
was to identify opportunities for research, policy and practice which could enhance
the prevention agenda relating to the perpetration of sexual abuse by children
through conducting a Critical Interpretive Synthesis. Eleven electronic databases
were searched in the period from 22 April to 23 May 2013 and included: SocINDEX,
Social Services Abstracts, Applied Social Sciences Index and Abstracts, Family and
Society Studies Worldwide, Project Muse, PsychINFO, Family and Society Plus, Jstor,
Expanded Academic ASAP, Web of Science and Google Scholar. Key individual journals
were also searched, including Child Abuse and Neglect and the Journal of
Interpersonal Violence, as well as the grey literature. The search was guided by
the research question: How could the prevention agenda relating to sexual abuse
perpetrated by children be enhanced? The systematic literature search yielded 3323
titles, and 34 of these papers were included in the final synthesis. The authors
identified five domains operating in the evidence base: characteristics, causes,
communications, interventions and treatments. A synthesising construct emerged from
the review: prevention-enhancing interactions. This construct referred to the
potential for enhancing the prevention agenda which exists as the evidence domains
interact with one another, and with the public health model of prevention. The
authors consider this review to be a timely contribution to the current agenda
pertaining to sexual abuse perpetrated by children. It provides researchers, policy
makers and practitioners in the field with an evidence-informed conceptualisation
of opportunities for enhancing prevention work.
Immigrants from East Asia make up 14.21% of the total number of immigrants in
Canada. These families face many challenges as they acculturate to North America,
but, sadly, some of these children may be at risk for sexual abuse. In this
article, we outline the ways in which East Asian children, compared with Western
nonimmigrant children, are at a particular disadvantage when considering
prosecution of those who perpetrate abuse. We focus specifically on 3 areas of
concern: (1) cultural differences that can shape children's memory recall, (2)
cultural differences that can impact the path of disclosure of sexual abuse, and
(3) language differences that reduce the chances that perpetrators will be
prosecuted for sexual abuse. The consequences for East Asian immigrant youth who
allege (or are suspected) that they are victims of abuse are serious. East Asian
children face an uphill battle to see justice in sexual abuse cases. Thus, a
significant portion of immigrant children will not see their abusers punished, and,
worse, the knowledge that prosecution is unlikely may make East Asian immigrant
children vulnerable.
Introduction: The success of the vaccines available on the market has significantly
increased interest in vaccine development.Areas covered: The main aim of this paper
is to discuss the most important vaccines of pediatric interest that are currently
being developed. New pneumococcal vaccines and vaccines against group B
Streptococcus, Staphylococcus aureus and respiratory syncytial virus are analyzed
in detail.Expert commentary: Advances in understanding human immunology, including
human monoclonal antibody identification, sequencing technology, and the ability to
solve atomic level structures of vaccine targets have provided tools to guide the
rational design of future vaccines. It is likely that some of these vaccines will
reach the market in the future and will thus partially contribute to the prevention
of very severe diseases that significantly affect the morbidity and mortality of
children. However, further studies in animals and several clinical trials in
children must be performed before new vaccines become licensed.
Children in pre-school age present a limited cognitive development, a restricted
vocabulary and a short attention span, which do not allow conducting classical
taste sensitivity measures as developed for adults. The aim of this study was to
develop and validate an age-appropriate protocol for sensitivity testing of the
five basic tastes with pre-schoolers. One hundred and forty children aged 3-4 years
(mean age 46.3 months, SD 3.4) performed a paired comparison task consisting of
discriminating water from "magic water" by relying on their affect. In order to
accommodate the age group, the task was gamified and did not require verbal
responses. Sweet (sucrose, ranging from 0.94 to 4.32 g/l), sour (citric acid
monohydrate, 0.20-0.38 g/l), umami (monosodium glutamate, 0.17-0.49 g/l), salty
(sodium chloride, 0.34-0.98 g/l), and bitter (quinine hydrochloride dihydrate,
0.0014-0.0038 g/l) water dilutions were tested at four levels. Subsets of about 20
children per taste participated in retest sessions. Individual sensitivity scores
were derived in two manners, following the experimenter's success criterion (water
with taste is classified as magic) and the child's criterion for "magic water"
(children's individual magic-labelling strategies). Results show that the protocol
was highly engaging, that the children performed the task consistently, and that
the children's performances were not dependent on cognitive level differences, thus
validating the protocol for this study. On average, the children were clearly more
sensitive to sour stimuli selected dilutions were not equivalent across tastes.
Different sensitivity distributions of the children were obtained across taste
modalities and scoring criteria. The key elements of an age-appropriate protocol
for pre-schoolers are discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: This study examines how socio-demographic and clinical characteristics
influence suicide risk among a large, urban sample of children (ages 12 and
younger) receiving Psychiatric Emergency Services (PES). Methods: Bivariate and
binomial logistic regression analyses were employed to analyze data for a sample of
951 urban children presenting for pediatric PES. Results: Approximately 17.2% of
patients presented had a history of suicidal thought and behavior. Despite the
larger number of black children presenting for PES, we found no significant
difference in suicide risk across ethnic group, though the prevalence rates were
increasingly higher in Whites, Latinos, and Black respectively. Of those presenting
with suicidality: 65.1% were diagnosed with a behavioral disorder, 263% were
diagnosed with a mood disorder, 3.8% with a psychotic disorder, and 4.8% with
another disorder. About one in ten suicidal cases admitted to prior child abuse.
Furthermore, patients admitted to the hospital for suicidality were more likely to
be female, to have a mood disorder, and to be appropriately discharged to an
inpatient setting following initial hospital care. Conclusions: The study points to
the importance of screening publically insured (Medicaid) urban children
experiencing psychological distress regardless of ethnicity and age for suicide
risk. Clinicians should consider these findings when working with children in
psychiatric crisis. (C) 2016 Published by Elsevier Ltd.
The aim of this article is to systematically review the literature studying the
association between television viewing and children's executive function, academic
performance, attention, language and play. Using keywords: television, children,
infants, attention, language, education and cognition, five online databases were
searched. Seventy-six studies that met all the inclusion criteria were reviewed.
The findings suggest the relationship between television viewing and children's
development is complex. First, the likely effects of television may depend on
children's individual characteristics, family and social context. Second, the
features of television, such as content and editing pace, and the type of exposure
(foreground or background) may affect outcomes. Specifically, watching high-quality
educational content during preschool years improves children's basic academic
skills and predicts subsequent positive academic performance. Conversely,
television viewing in infancy is disruptive to play; it reduces the quality and
quantity of child-parent interactions and is associated with
inattentive/hyperactive behaviours, lower executive functions, and language delay,
at least in the short-term. It remains unclear whether these interactions between
television and cognition are long lasting. Future research should focus on the
systematic investigation of the pathways that link particular components of
television and the type of exposure with individual and contextual factors, to
investigate their potential unique and combined effects on development. Researchers
must also address the challenge of investigating the diverse and rapidly changing
technologies to which the current generation of children are exposed.(C) 2017
Elsevier Inc. All rights reserved.
In European industrial countries severe underweight children due to malnutrition
are uncommon. The case of a 7aEuromonth-old infant girl hospitalized with severe
underweight is presented. The child suffered from considerable chronic malnutrition
with a severe reduction of body weight (3470 g) and reduced growth as well as
general retardation. In hospital the infant quickly recovered after adequate food
supply. A predisposition to disease could be clinically excluded. In such cases the
degree of malnutrition as well as the duration of food shortage has to be estimated
with a classification as acute or chronic malnutrition.
Background: Vernal keratoconjunctivitis (VKC) is a chronic and often severe
bilateral conjunctivitis. VKC etiology still remains unclear although endocrine,
genetic, neurogenic and environmental factors have been implicated. Vitamin D is a
fat-soluble prohormone whose main function is the regulation of calcium and
phosphate metabolism. The aim of this study was to evaluate serum vitamin D in
children affected by VKC compared to the healthy children and investigate the
relationship between its levels and disease severity. Methods: A total of 110
children, 47 affected by VKC, aged between 5 and 12 years were enrolled at the
Department of Pediatrics, Division of Allergy and Immunology, "Sapienza" University
of Rome. Used as controls were 63 healthy children with negative skin prick test
(SPT), without allergic, ocular and systemic disease. Serum samples were obtained
in April from all the children included in the study. Vitamin D dosage was repeated
in October in 20 patients after therapy and in 20 controls. A conjunctival scraping
was performed in all children affected by VKC. Results: Children affected by VKC
had lower vitamin D levels compared to healthy controls and we found an increase in
vitamin D levels after therapy with cyclosporine eye drops 1% although this
increase was lower than that of healthy controls. Moreover we found significant
correlations between vitamin D level and the severity of the disease. Conclusions:
The study shows that children affected by VKC have lower vitamin D levels when
compared to healthy controls and highlights a significant correlation between its
levels and disease severity.
Objectives: To test the performance of a single 3D IR T2-Weighted sequence compared
to a Whole-body MRI protocol including DWI, T1-Weighted and STIR 3D IR (3S) in a
pediatric population. Methods: Two radiologists (15 and 30 years of
experience),reviewed WBMRIs: first the STIR alone and 2 weeks later the 3S
protocol. The indications were variable. Only positive findings were explicitly
reported. A third reader compared the results to gold standard (GS) exams specific
for the pathology. Agreement between the two readers, sensitivity and positive
predictive value of STIR were calculated. Results: fifty-four WBMRIs were included
(16 suspected child abuse, 8 chronic recurrent multifocal osteomyelitis (CRMO), 11
lymphomas, 4 osteosarcomas, 9 neuroblastomas, 6 histiocytosis). The mean age was 6
years 10 months, range: 1 month to 15 years. Agreement between readers was of 0.87
[0.82-0.91] for 3D STIR, and 0.89 [0.83-0.93] for the 3S protocol. For reader 1
sensitivity of 3D STIR was 81.6% and of 3S 81.0%. For reader 2 it was 74.1% for 3D
STIR and 74.7% for 3S. For both readers and for both protocols, the positive
predictive value (PPV) depended on the type of disease (for example 100%
histocytosis and osteosarcomas, >90% for child abuse, >85% CRMO but <70% for
lymphoma and neuroblastoma). Conclusions: Sensitivities were not different between
the 2 protocols, for each reader and were different between the 2 readers for each
protocol. (C) 2017 Elsevier B.V. All rights reserved.
Familiarising researchers and practitioners with different countries' policies for
police interviews with children contributes to an exchange of knowledge and
strengthens global approaches against child abuse. We start by describing the
system of videotaped testimonies in Cyprus during the first 10years of this
system's implementation. We then continue on to the effects of tourism on police
interviews with children. Police forces in destinations with high tourist numbers
need to comprehend how tourist seasons could influence police interviews with
children. No studies investigated whether children of tourists testified in police
departments during their holidays. We explored how tourist seasons affected the
number of testimonies obtained by Cyprus police forces, taking into account the
presence of non-Cypriot and non-native speaking children, the number of testimonies
taken in languages other than Greek, and the presence of translators during the
interviews. We analysed the national sample of police interviews with children for
a period of a decade using official police records and copies of transcripts of
children's testimonies. As expected, the results revealed no significant
differences in police interviews with children during tourist seasons but show a
slight increase in the number of interviews with non-Cypriot children during
tourist seasons. Copyright (c) 2016 John Wiley & Sons, Ltd.
Patients with B-cell hematologic malignancies who progress through first-or second-
line chemotherapy have a poor prognosis. Early clinical trials with autologous
anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising
results for patients who have relapsed or refractory disease. Lymphodepleting
conditioning regimens, including cyclophosphamide, fludarabine, pentostatin,
bendamustine, interleukin-2, and total body irradiation, are often administered
before the infusion of CAR T cells, allowing for greater T-cell expansion. The
major toxicity associated with CAR T-cell infusions is cytokine release syndrome
(CRS), a potentially life-threatening systemic inflammatory disorder. The quick
onset and progression of CRS require rapid detection and intervention to reduce
treatment-related mortality. Management with tocilizumab can help ameliorate the
symptoms of severe CRS, allowing steroids, which diminish the expansion and
persistence of CAR T cells, to be reserved for tocilizumab-refractory patients.
Other toxicities of CAR T-cell therapy include neutropenia and/or febrile
neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A
review of patients' medications is imperative to eliminate medications that may
contribute to treatment-related toxicities. Studies are ongoing to help optimize
patient selection, preparation, safety, and management of individuals receiving CAR
T cells. Long-term follow-up will help establish the place of CAR T cells in
therapy.
Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more
accurate and meaningful classifications, improved pathogenetic concepts and
expanded therapeutic options. This requires considerations of the immunologic
concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR)
affinities and signaling. Scientists from various disciplines established the
CONTROL-T research unit and in an international conference on MTCL they brought
together experts from T-cell immunity, oncology, immunotherapy and systems biology.
We report here meeting highlights on the covered topics of diagnostic pitfalls,
implications by the new WHO classification, insights from discovered genomic
lesions as well as TCR-centric concepts of cellular dynamics in host defense, auto-
immunity and tumorigenic clonal escape, including predictions to be derived from in
vivo imaging and mathematical modeling. Presentations on novel treatment approaches
were supplemented by strategies of optimizing T-cell immunotherapies. Work
packages, that in joint efforts would advance the field of MTCL more efficiently,
are identified.
In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have
been identified. The mechanisms and association of chimeric transcripts arising
from chromosomal rearrangements with cancer are well established, but much remains
unknown regarding the biogenesis and importance of other chimeric transcripts that
arise from nongenomic alterations. Recently, a SLC45A3-ELK4 chimera has been shown
to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate
tumors relative to local prostate cancers. Here, we characterize the expression of
a KLK4 cis sense-antisense chimeric transcript, and show other examples in prostate
cancer. Using non-protein-coding microarray analyses, we initially identified an
androgen-regulated antisense transcript within the 3' untranslated region of the
KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-
mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5'
and 3' rapid amplification of cDNA ends (RACE) revealed that this transcript forms
multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter
activity using reporter assays suggests that these transcripts are unlikely to
arise from a trans-splicing mechanism. 59 RACE and analyses of deep sequencing data
from LNCaP cells treated +/- androgens revealed six high-confidence sense-antisense
chimeras of which three were supported by the cDNA databases. In this study, we
have shown complex gene expression at the KLK4 locus that might be a hallmark of
cis sense-antisense chimeric transcription.
Background: In cat visual cortex, critical period neuronal plasticity is minimal
until approximately 3 postnatal weeks, peaks at 5 weeks, gradually declines to low
levels at 20 weeks, and disappears by 1 year of age. Dark rearing slows the entire
time course of this critical period, such that at 5 weeks of age, normal cats are
more plastic than dark reared cats, whereas at 20 weeks, dark reared cats are more
plastic. Thus, a stringent criterion for identifying genes that are important for
plasticity in visual cortex is that they show differences in expression between
normal and dark reared that are of opposite direction in young versus older
animals. Results: The present study reports the identification by differential
display PCR of a novel gene, alpha-chimaerin, as a candidate visual cortex critical
period plasticity gene that showed bidirectional regulation of expression due to
age and dark rearing. Northern blotting confirmed the bidirectional expression and
5'RACE sequencing identified the gene. There are two alternatively-spliced alpha-
chimaerin isoforms: alpha 1 and alpha 2. Western blotting extended the evidence for
bidirectional regulation of visual cortex alpha-chimaerin isoform expression to
protein in cats and mice. alpha 1- and alpha 2-Chimaerin were elevated in dark
reared compared to normal visual cortex at the peak of the normal critical period
and in normal compared to dark reared visual cortex at the nadir of the normal
critical period. Analysis of variance showed a significant interaction in both cats
and mice for both alpha-chimaerin isoforms, indicating that the effect of dark
rearing depended on age. This differential expression was not found in frontal
cortex. Conclusions: Chimaerins are RhoGTPase-activating proteins that are EphA4
effectors and have been implicated in a number of processes including growth cone
collapse, axon guidance, dendritic spine development and the formation of
corticospinal motor circuits. The present results identify alpha-chimaerin as a
candidate molecule for a role in the postnatal critical period of visual cortical
plasticity.
In this paper, we reviewed four key themes in the study of clean power transition
in China, the resources potential, the technology advancement, the air pollution
control, and the policy and reform of the power sector. In each theme, we
summarized the ongoing research development and highlighted some key areas for
further study. Given that China's power sector transition is a huge task, we hope
this review will add some discussions into the ongoing conversation. (C) 2016
Elsevier B.V. All rights reserved.
Much attention is being given to estimating cement-related CO2 emissions in China.
However, scant explicit and systematical exploration is being done on regional and
national CO2 emission volumes. The aim of this work is therefore to provide an
improved bottom-up spatial-integration system, relevant to CO2 emissions at factory
level, to allow a more accurate estimation of the CO2 emissions from cement
production. Based on this system, the sampling data of cement production lines were
integrated as regional- and national-level information. The integration results
showed that each ton of clinker produced 883 kg CO2, of which the process, fuel,
and electricity emissions accounted for 58.70%, 35.97%, and 5.33%, respectively.
The volume of CO2 emissions from clinker and cement production reached 1202 Mt and
1284 Mt, respectively, in 2013. A discrepancy was identified between the clinker
emission factors relevant to the two main production processes (i.e., the new
suspension preheating and pre-calcining kiln (NSP) and the vertical shaft kiln
(VSK)), probably relevant to the energy efficiency of the two technologies. An
analysis of the spatial characteristics indicated that the spatial distribution of
the clinker emission factors mainly corresponded to that of the NSP process. The
discrepancy of spatial pattern largely complied with the economic and population
distribution pattern of China. The study could fill the knowledge gaps and provide
role players with a useful spatial integration system that should facilitate the
accurate estimation of carbon and corresponding regional mitigation strategies in
China.
With the global environmental pollution and fossil energy shortage problems getting
increasingly serious, renewable energy sources (RES) are drawing more and more
attention. In China, RES are experiencing rapid development. However, because of
the randomness of RES and the volatility of power output, energy storage technology
is needed to chip peak off and fill valley up, promoting RES utilization and
economic performance. So to speak, energy storage is the precondition of large-
scale integration and consumption of RES. However, China's energy storage industry
is at the exploration stage and far from commercialization. This restricts the
development of RES to certain extent. For this reason, this paper will concentrate
on China's energy storage industry. First, it summarizes the developing status of
energy storage industry in China. Then, this paper analyzes the existing problems
of China's energy storage industry from the aspects of technical costs, standard
system, benefit evaluation and related policies. Finally, solutions are proposed
based on the above problems to promote the sound development of China's energy
storage industry.
Chinese cherry (Prunus pseudocerasus L) is an allotetraploid species and exhibits
natural self-compatibility However, the full-length cDNA sequences, functional
analysis and the transcripts of S-RNase alleles in Chinese cherry cultivars are not
known. In the two cultivars Taixiaohongying and Laiyang Short Cherry with
S(1)S(2)S(3)S(4) genotypes, two S-RNases were transcribed in Northern blotting, and
the two full-length cDNAs of S-RNase were cloned and analyzed. As the result, the
transcribed S-RNases were S(1)-RNase and S(2)-RNase The two complete cDNA sequences
of S(1)-RNase and S(2)-RNase were registered as EU073938 and EU073939,
respectively, and had characteristic structure of rosaceous S-RNases based on their
sequences indicating that they had normal function for S-RNase in the style The
S(3)-RNase and S(4)-RNase were not transcribed in the style and were nonfunctional
for S-RNase, so S(3m) and S(4m) could be used to represent the nonfunctional S(4)-
RNase and S(4)-RNase. The phylogenetic analysis implied that the S-RNases of
Prunus. including Chinese cherry, had lower intra-specific similarity and diverged
earlier than the divergence of species in Prunus
Sialic acid is a sugar typically found at the N-glycan termini of glycoproteins in
mammalian cells. Lec3 CHO cell mutants are deficient in,epimerase activity, due to
a defect in the gene that encodes a bifunctional UDP-GlcNAc 2-epimerase/ManNAc
kinase (GNE). Sialic acid modification on the cell surface is partially affected in
these cells. We have mutagenized Lec3 CHO cells and isolated six mutants (termed
C2m) deficient in the cell surface expression of polysialic acid (PSA). Mutant C2m9
was partially defective in expression of cell-surface PSA and wheat germ agglutinin
(WGA) binding, while in the other five mutants, both cell-surface PSA and WGA
binding were undetectable. PSA expression was restored by complementation with the
gene encoding the CMP-sialic acid transporter (CST), indicating that CST mutations
were responsible for the phenotypes of the C2m cells. We characterized the CST
mutations in these cells by Northern blotting and RT-PCR. C2m9 and C2m45 carried
missense mutations resulting in glycine to glutamate substitutions at amino acids
217 (G217E) and 256 (G256E), respectively. C2m13, C2m39 and C2m31 had nonsense
mutations that resulted in decreased CST mRNA stability, and C2m34 carried a
putative splice site mutation. PSA and CD15s expression in CST-deficient Lec2 cells
were partially rescued by G217E CST, but not by G256E CST, although both proteins
were expressed at similar levels, and localized to the Golgi. These results
indicate that the novel missense mutations isolated in this study affect CST
activity.
Chinese tallow (Sapium sebiferum L.) is a promising landscape and bioenergy plant.
Measuring gene expression by quantitative real-time polymerase chain reaction (qRT-
PCR) can provide valuable information on gene function. Stably expressed reference
genes for normalization are a prerequisite for ensuring the accuracy of the target
gene expression level among different samples. However, the reference genes in
Chinese tallow have not been systematically validated. In this study, 12 candidate
reference genes (185, GAPDH, UBQ, RPS15, SAND, TIP41, 60S, ACT7, PDF2, APT, TBP and
TUB) were investigated with qRT-PCR in 18 samples, including those from different
tissues, from plants treated with sucrose and cold stresses. The data were
calculated with four common algorithms, geNorm, BestKeeper, NormFinder, and the
delta cycle threshold (Delta Ct). TIP41 and GAPDH were the most stable for the
tissue-specific experiment, GAPDH and 60S for cold treatment, and GAPDH and UBQ for
sucrose stresses, while the least stable genes were 60S, TIP41, and 18S
respectively. The comprehensive results showed APT, GAPDH, and UBQ to be the top-
ranked stable genes across all the samples. The stability of 60S was the lowest
during all experiments. These selected reference genes were further validated by
comparing the expression profiles of the chalcone synthase gene in Chinese tallow
in different samples. The results will help to improve the accuracy of gene
expression studies in Chinese tallow.
To improve the quality of Chinese traditional Paocai, two psychrotolerant lactic
acid bacteria (LAB) strains were isolated from Paocai, and the quality of Chinese
Paocai product using these two strains as starter cultures was compared to a
control sample fermented with aged brine at 10 degrees C. The results suggested
that the physicochemical and sensory features of Paocai fermented with
psychrotolerant LAB were more suitable for industrial applications. The nitrite
content of Paocai fermented with psychrotolerant LAB was 1 mg/kg, which was
significantly lower than that of the control Paocai (P < 0.05). Low temperature
fermentation with the starter cultures of psychrotolerant LAB could effectively
prevent overacidity and over-ripening of the Paocai products. Additionally, Paocai
fermented with psychrotolerant LAB harbored relatively simple microbial flora as
revealed by polymerase chain reaction-denaturing gradient gel electrophoresis. This
study provides a basis for improving the quality of Chinese traditional Paocai and
the large-scale production of low-temperature Chinese traditional Paocai products.
Vector-borne diseases (VBD) are of major importance to human and animal health. In
recent years, VBD have been emerging or re-emerging in many geographical areas,
alarming new disease threats and economic losses. The precise diagnosis of many of
these diseases still remains a major challenge because of the lack of comprehensive
data available on accurate and reliable diagnostic methods. Here, we conducted a
systematic and in-depth review of the former, current, and upcoming techniques
employed for the diagnosis of VBD.
Chromatin immunoprecipitation followed by qPCR analysis (ChIP-qPCR) is a widely
used technique to study gene expression. A large number of students in molecular
biology and more generally in life sciences will be confronted with the use of this
technique, which is quite difficult to set up and can lead to misinterpretation if
not carefully managed. This article describes a four-session laboratory practical
designed for Masters students to introduce this technique. During the practical,
students work in pairs. They extract chromatin from MCF-7 culture cells stimulated
or not by estrogens, then immunoprecipitate the transcription factor estrogen
receptor alpha using an antibody directed against it. Students then measure the
enrichment of promoter DNA target sequences from the chromatin that coprecipitates
by qPCR. These are two estrogen responsive genes, pS2 (trefoil factor one) and PGR
(the progesterone receptor). They learn how to analyze their ChIP-qPCR data by two
methods: percent input and fold enrichment, and are taught about the interpretation
limits of these two calculation methods. Thus, this practical is a good framework
for an in-depth discussion of how this technique can be used to study gene
expression and for raising awareness of the importance of careful interpretation of
results. (C) 2016 by The International Union of Biochemistry and Molecular Biology,
45(2): 152-160, 2017.
Radiation hardness of different samples of the same ICs can vary greatly from lot
to lot, depending on the year or the country of production. However, it is assumed
that radiation hardness of the samples from the same lot is the same too. The new
chip uniformity test method based on ionization response comparison is offered.
Fusarium head blight (FHB) and Fusarium seedling blight (FSB) of wheat, caused by
Fusarium pathogens, are devastating diseases worldwide. We report the expression of
RNA interference (RNAi) sequences derived from an essential Fusarium graminearum
(Fg) virulence gene, chitin synthase (Chs) 3b, as a method to enhance resistance of
wheat plants to fungal pathogens. Deletion of Chs3b was lethal to Fg; disruption of
the other Chs gene family members generated knockout mutants with diverse impacts
on Fg. Comparative expression analyses revealed that among the Chs gene family
members, Chs3b had the highest expression levels during Fg colonization of wheat.
Three hairpin RNAi constructs corresponding to the different regions of Chs3b were
found to silence Chs3b in transgenic Fg strains. Co-expression of these three RNAi
constructs in two independent elite wheat cultivar transgenic lines conferred high
levels of stable, consistent resistance (combined type I and II resistance) to both
FHB and FSB throughout the T-3 to T-5 generations. Confocal microscopy revealed
profoundly restricted mycelia in Fg-infected transgenic wheat plants. Presence of
the three specific short interfering RNAs in transgenic wheat plants was confirmed
by Northern blotting, and these RNAs efficiently down-regulated Chs3b in the
colonizing Fusarium pathogens on wheat seedlings and spikes. Our results
demonstrate that host-induced gene silencing of an essential fungal chitin synthase
gene is an effective strategy for enhancing resistance in crop plants under field
test conditions.
The asymptomatic nature of most Chlamydia trachomatis infections and the lack of
appropriate effects by current prevention and management call for vaccine
development. We evaluated a recombinant subunit vaccine candidate based on the
major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve
maximal immunogenicity and ease of production and purification, MOMP VS2/4 was
constructed by using highly immunogenic sequences of MOMP only, thereby minimizing
the presence of hydrophobic regions, and spacing the immunogenic epitopes with a
flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was
given intranasally, with or without intravaginal boost, with cholera toxin (CT)
adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection
against a live challenge infection with C. trachomatis serovar D. Bacterial
shedding, cell-mediated responses, and antibody responses were monitored. Immunized
mice exhibited significantly less bacterial shedding and were better protected
against infertility as compared to unimmunized control mice. Immunizations
stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA)
responses, and primed T cells that produced interferon-c and interleukins 13 and 17
upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT
adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective
immunity associated with less pathology. We regard MOMP VS2/4 as a promising
candidate for further development into a mucosal chlamydial vaccine.
Chlamydia trachomatis genital infection is the most common sexually transmitted
bacterial disease, causing a significant burden to females due to reproductive
dysfunction. Intensive screening and antibiotic treatment are unable to completely
prevent female reproductive dysfunction, thus, efforts have become focused on
developing a vaccine. A major impediment is identifying a safe and effective
adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes
capable of halting genital infection and inflammation. Previously, we described a
natural nanocapsule called the vault which was engineered to contain major outer
membrane protein (MOMP) and was an effective vaccine which significantly reduced
early infection and favored development of a cellular immune response in a mouse
model. In the current study, we used another chlamydial antigen, a polymorphic
membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate,
in depth, the vault vaccine for its protective capacity in the absence of an added
adjuvant. We found PmpG-vault immunized mice significantly reduced the genital
bacterial burden and histopathologic parameters of inflammation following a C.
muridarum challenge. Immunization boosted antigen-specific CD4 cells with a
multiple cytokine secretion pattern and reduced the number of inflammatory cells in
the genital tract making the vault vaccine platform safe and effective for
chlamydial genital infection. We conclude that vaccination with a Chlamydia-vault
vaccine boosts antigen-specific immunities that are effective at eradicating
infection and preventing reproductive tract inflammation.
Chlamydia suis infections are endemic in domestic pigs in Europe and can lead to
conjunctivitis, pneumonia, enteritis and reproductive failure. Currently, the
knowledge on the zoonotic potential of C.suis is limited. Moreover, the last
decades, porcine tetracycline resistant C.suis strains have been isolated, which
interfere with treatment of chlamydial infections. In this study, the presence of
C.suis was examined on nine Belgian pig farms, using Chlamydia culture and a C.suis
specific real-time PCR in both pigs and farmers. In addition to diagnosis for
C.suis, the farmers' samples were examined using a Chlamydia trachomatis PCR.
Additionally, the Chlamydia isolates were tested for the presence of the tet(C)
resistance gene. C. DNA was demonstrated in pigs on all farms, and eight of nine
farmers were positive in at least one anatomical site. None of the farmers tested
positive for C. trachomatis. Chlamydia suis isolates were obtained from pigs of
eight farms. Nine porcine C.suis isolates possessing a tet(C) gene were retrieved,
originating from three farms. Moreover, C.suis isolates were identified in three
human samples, including one pharyngeal and two rectal samples. These findings
suggest further research on the zoonotic transfer of C.suis from pigs to humans is
needed.
The objective of the present study was to characterize the pattern of gene
expression at the last stage of ovarian maturation in Chlamys farreri. Dynamic
transcriptomic analysis of ovaries was performed at four time points prior to
ovulation, using the Illumina HiSeq 2500 platform. A total of 174,928 unigenes were
obtained, among which 42,534 were annotated according to bioinformatics databases,
such as NT, NR, Swiss-Prot, KOG, GO, and KEGG. Results from the transcriptome
analysis revealed a time-dependent pattern of global transcriptional responses.
When compared to the 0 d library, 99, 152, and 3248 differently expressed genes
(DEGs) were obtained in the 3, 10, and 21 d libraries, respectively. Those three
libraries shared only 10 DEGs, the majority of which were time-specific. Pairwise
comparisons of each profile demonstrated that DEGs were related to hormone
metabolism and receptors, cell division, gametogenesis, and vitellogenesis
pathways. Notably, when adjacent sampling time point groups were compared, the only
DEG throughout the experimental period was related to the G protein-coupled
receptor signaling pathway. The present study provides the first dynamic
transcriptomic analysis of C. farreri for evaluation of the molecular basis of
gonadal maturation. (C) 2016 Elsevier Inc. All rights reserved.
The present report describes a 13 month pilot remediation study that consists of a
combination of Cr(VI) (4.4 to 57 mg/l) geofixation and dechlorination of
chlorinated ethenes (400 to 6526 mu g/l), achieved by the sequential use of
nanoscale zerovalent iron (nZVI) particles and in situ biotic reduction supported
by whey injection. The remediation process was monitored using numerous techniques,
including physical-chemical analyses and molecular biology approaches which enabled
both the characterization of the mechanisms involved in pollutant transformation
and the description of the overall background processes of the treatment. The
results revealed that nZVI was efficient toward Cr(VI) by itself and completely
removed it from the groundwater (LOQ 0.05 mg/l) and the subsequent application of
whey resulted in a high removal of chlorinated ethenes (97 to 99%). The persistence
of the reducing conditions, even after the depletion of the organic substrates,
indicated a complementarity between nZVI and the whey phases in the combined
technology as the subsequent application of whey phase partially assisted the
microbial regeneration of the spent nZVI by promoting its reduction into Fe(II),
which further supported remediation conditions at the site. Illumina sequencing and
the detection of functional vcrA and bvcA genes documented a development in the
reducing microbes (iron-reducing, sulfate-reducing and chlororespiring bacteria)
that benefited under the conditions of the site and that was probably responsible
for the high dechlorination and/or Cr(VI) reduction. The results of this study
demonstrate the feasibility and high efficiency of the combined nano-
biotechnological approach of nZVI and whey application in-situ for the removal of
Cr(VI) and chlorinated ethenes from the groundwater of the contaminated site. (C)
2016 Elsevier B.V. All rights reserved.
Thermal tetrachloroethene (PCE) remediation by steam injection in a sandy aquifer
led to the release of dissolved organic carbon (DOC) from aquifer sediments
resulting in more reduced redox conditions, accelerated PCE biodegradation, and
changes in microbial populations. These changes were documented by comparing data
collected prior to the remediation event and eight years later. Based on the
premise that dual C-Cl isotope slopes reflect ongoing degradation pathways, the
slopes associated with PCE and TCE suggest the predominance of biotic reductive
dechlorination near the source area. PCE was the predominant chlorinated ethene
near the source area prior to thermal treatment. After thermal treatment, cDCE
became predominant. The biotic contribution to these changes was supported by the
presence of Dehalococcoides sp. DNA (Dhc) and Dhc targeted rRNA close to the source
area. In contrast, dual C-CI isotope analysis together with the almost absent VC C-
13 depletion in comparison to cDCE C-13 depletion suggested that cDCE was subject
to abiotic degradation due to the presence of pyrite, possible surface-bound iron
(II) or reduced iron sulphides in the downgradient part of the plume. This
interpretation is supported by the relative lack of Dhc in the downgradient part of
the plume. The results of this study show that thermal remediation can enhance the
biodegradation of chlorinated ethenes, and that this effect can be traced to the
mobilisation of DOC due to steam injection. This, in turn, results in more reduced
redox conditions which favor active reductive dechlorination and/or may lead to a
series of redox reactions which may consecutively trigger biotically induced
abiotic degradation. Finally, this study illustrates the valuable complementary
application of compound-specific isotopic analysis combined with molecular biology
tools to evaluate which biogeochemical processes are taking place in an aquifer
contaminated with chlorinated ethenes. (C) 2016 Elsevier B.V. All rights reserved.
Chloroplast development is regulated by many biological processes. However, these
processes are not fully understood. Leaf variegation mutants have been used as
powerful models to elucidate the genetic network of chloroplast development since
the degree of leaf variegation is regulated by developmental and environmental
cues. The thylakoid formation 1 (thf1) mutant is unique for its variegation in both
leaves and cotyledons. Here, we reported a new suppressor gene of thf1 leaf
variegation, designated sot8. Map-based cloning and DNA sequencing results showed
that a single nucleotide mutation from G to A was detected in the second exon of
the gene encoding the ribosomal protein small subunit 9 (PRPS9) in sot8-1,
resulting in an amino acid change and a partial loss of PRPS9 function. However,
sot8-1 was unable to rescue the thf1 phenotype in low photosystem II activity
(Fv/Fm). In addition, we identified two T-DNA insertion mutants defective in
plastid-specific ribosomal proteins (PSRPs), psrp2-1, and psrp5-1. Genetic analysis
showed that knockdown of PSRP5 expression but not PSRP2 expression suppressed leaf
variegation. Northern blotting results showed that precursors of plastid rRNAs
over-accumulated in prps9-1 and psrp5-1, indicating that mutations in PRPS9 and
PSRP5 cause a defect in rRNA processing. Consistently, inhibition of plastid
protein synthesis by spectinomycin led to increased levels of plastid rRNA
precursors in wild-type plants, suggesting that rRNA processing and plastid
ribosomal assembly are coupled. Taken together, our data indicate that
downregulating the expression of specific plastid ribosomal proteins suppresses
thf1 leaf variegation, and provide new insights into a role of THF1 in plastid gene
expression.
The plastid genome of plants is the smallest and most gene-rich of the three
genomes in each cell and the one generally present in the highest copy number. As a
result, obtaining plastid DNA sequence is a particularly cost-effective way of
discovering genetic information about a plant. Until recently, the sequence
information gathered in this way was generally limited to small portions of the
genome amplified by polymerase chain reaction, but recent advances in sequencing
technology have stimulated a substantial rate of increase in the sequencing of
complete plastid genomes. Within the last year, the number of complete plastid
genomes accessible in public sequence repositories has exceeded 1000. This sudden
flood of data raises numerous challenges in data analysis and interpretation, but
also offers the keys to potential insights across large swathes of plant biology.
We examine what has been learnt so far, what more could be learnt if we look at the
data in the right way, and what we might gain from the tens of thousands more
genome sequences that will surely arrive in the next few years. The most exciting
new discoveries are likely to be made at the interdisciplinary interfaces between
molecular biology and ecology.
Objectives. TNF-alpha, IL-1 and IL-6 are known to have primary roles in the
pathogenesis of rheumatoid arthritis and other inflammatory diseases. The anti-
rheumatic drug chloroquine has been shown to inhibit TNF-alpha, IL-1 and IL-6
production from mononuclear phagocytes. We examined the underlying mechanisms
involved in the chloroquine-induced inhibition of cytokine production. Methods.
Human peripheral blood mononuclear cells and monocytes/macrophages and monocytic U-
937 and THP-1 cells were stimulated with lipopolysaccharide, and TNF-alpha, IL-1
beta and IL-6 production was measured by ELISA. Levels of mRNA were measured by
northern blotting and reverse transcription-polymerase chain reaction. Synthesis of
26-kDa TNF-alpha precursor was measured by metabolic labelling and
immunoprecipitation analysis. Transcription rate was determined by nuclear run-on
assay. Results. TNF-alpha release from the cells was inhibited by chloroquine,
whereas the steady-state level of TNF-alpha mRNA and synthesis of 26-kDa TNF-alpha
precursor were not changed by chloroquine. In contrast, chloroquine-induced
inhibition of IL-1 beta and IL-6 release was accompanied by a decrease in their
steady-state mRNA levels. The transcription rates of the IL-1 beta and IL-6 genes
were not changed by chloroquine, whereas the stability of IL-1 beta and IL-6 mRNA
was decreased by chloroquine. Weak-base amines such as methylamine and ammonium
chloride had no effect on the production of TNF-alpha, whereas they partially
blocked the production of IL-1 beta and IL-6. Conclusions. Our results indicate
that chloroquine-mediated inhibition of TNF-alpha, IL-1 beta and IL-6 synthesis
occurs through different modes in lipopolysaccharide-stimulated human
monocytes/macrophages: it blocks the conversion of cell-associated TNF-alpha
precursor to mature soluble protein, whereas it reduces the levels of IL-1 beta and
IL-6 mRNA, at least in part, by decreasing their stability and by a pH-dependent
mechanism.
Mammalian cell cultures are the preferred expression systems for the production of
biopharmaceuticals requiring posttranslational processing. Usually, cell cultures
are cultivated in medium supplemented with serum, which supports cell
proliferation, viability, and productivity. However, due to scientific and
regulatory concerns, serum-free conditions are required in recombinant protein
production. Cell lines that are intended for commercial recombinant protein
production have to adapt to serum- or protein-free conditions early in their
development. This is a labor- and time-consuming process because of the specific
cell requirements related to their adaptation in new microenvironment. In the
present study, a Chinese hamster ovary (CHO) cell line producing glycosylated
recombinant human erythropoietin (rhEPO) was adapted for growth and rhEPO
production in serum- and protein-free conditions. The physiology, growth
parameters, and morphology of the CHO cells and rhEPO biosynthesis and structure
were closely monitored during the adaptation process to avoid unwanted selection of
cell subpopulations. The results showed that the CHO cells were successfully
adapted to suspension growth and rhEPO production in the protein-free conditions
and that the structure of rhEPO remained nearly unchanged. In addition, during
rhEPO production in the protein-free suspension conditions, the agitation rate seem
to be significant for optimal process performance in contrast to the initial cell
concentration, evaluated through evolutionary operation method. (C) 2015
International Union of Biochemistry and Molecular Biology, Inc.
Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it
is more common in Asia, its incidence in Europe and North America has significantly
increased in recent decades. The prognosis of CCA is dismal. Surgery is the only
potentially curative treatment, but the majority of patients present with advanced
stage disease, and recurrence after resection is common. Over the last two decades,
our understanding of the molecular biology of this malignancy has increased
tremendously, diagnostic techniques have evolved, and novel therapeutic approaches
have been established. This review discusses the changing epidemiologic trends and
provides an overview of newly identified etiologic risk factors for CCA.
Furthermore, the molecular pathogenesis is discussed as well as the influence of
etiology and biliary location on the mutational landscape of CCA. This review
provides an overview of the diagnostic evaluation of CCA and its staging systems.
Finally, new therapeutic options are critically reviewed, and future therapeutic
strategies discussed.
Cholangiocarcinoma (CC) is an intrahepatic bile duct carcinoma with a high
mortality rate and a poor prognosis. Sarcomatous change/epithelial mesenchymal
transition (EMT) of CC frequently leads to aggressive intrahepatic spread and
metastasis. The aim of this study was to identify the genetic alterations and gene
expression pattern that might be associated with the sarcomatous change in CC.
Previously, we established 4 human CC cell lines (SCK, JCK1, Cho-CK, and Choi-CK).
In the present study, we characterized a typical sarcomatoid phenotype of SCK, and
classified the other cell lines according to tumor cell differentiation (a poorly
differentiated JCK, a moderately differentiated Cho-CK, and a well differentiated
Choi-CK cells), both morphologically and immunocytologically. We further analyzed
the genetic alterations of two tumor suppressor genes (p53 and FHIT) and the
expression of Fas/FasL gene, well known CC-related receptor and its ligand, in
these four CC cell lines. The deletion mutation of p53 was found in the sarcomatoid
SCK cells. These cells expressed much less Fas/FasL mRNAs than did the other
ordinary CC cells. We further characterize the gene expression pattern that is
involved in the sarcomatous progression of CC, using cDNA microarrays that
contained 18,688 genes. Comparison of the expression patterns between the
sarcomatoid SCK cells and the differentiated Choi-CK cells enabled us to identify
260 genes and 247 genes that were significantly over-expressed and under-expressed,
respectively. Northern blotting of the 14 randomly selected genes verified the
microarray data, including the differential expressions of the LGALS1, TGFBI, CES1,
LDHB, UCHL1, ASPH, VDAC1, VIL2, CCND2, S100P, CALB1, MAL2, GPX1, and ANXA8 mRNAs.
Immunohistochemistry also revealed in part the differential expressions of these
gene proteins. These results suggest that those genetic and gene expression
alterations may be relevant to the sarcomatous change/EMT in CC cells.
The purpose of this study was to determine whether the superior colliculus (SC) of
the microbat has the same neurochemical makeup as that of other mammals. We
examined the organization of choline acetyltransferase (ChAT)- and tyrosine
hydroxylase-immunoreactive (TH-IR) fibers/cells using standard immunohistochemistry
with antibodies against ChAT and TH. ChAT-IR fibers observed in the superficial
layers were denser than those in the deeper layers, and these fibers were
classified into two types: small varicose fibers and large varicose fibers. ChAT-IR
cells were predominantly located in the superficial layers with diverse
morphologies. Among the well-known sources of cholinergic fibers in the mammalian
SC, pedunculopontine tegmental nucleus (PPTN) and laterodorsal tegmental nucleus
(LDTN) contained strongly labeled ChAT-IR cells, while no cholinergic structures
were found in the parabigeminal nucleus (PBG) in the microbat brain. TH-
immunoreactivity was found within fibers but not within cells. The density of TH-IR
fibers was high in the zonal layer, moderate in the superficial gray and optic
layers, and low in the deeper layers. Well-labeled TH-IR cells were also observed
within area 13 and the locus coeruleus, known as the sources of catecholaminergic
fibers in other mammalian SC. Although there are some cytoarchitectural variations
among species, our results clearly showed elaborately organized ChAT-IR and TH-IR
fibers/cells in the microbat SC. Our findings will contribute significantly to the
understanding of actively constructed microbat visual systems.
Osteosarcoma has a well-recognized bimodal distribution, with the first peak in
adolescence and another in the elderly age-group. The elderly patients have
different clinical features and a poorer prognosis as compared to adolescents. To
better understand the biological features of osteosarcoma in the elderly
population, we established a new human osteosarcoma cell line from a 58-year-old
man with primary chondroblastic osteosarcoma. After 6 months of continuous culture
in vitro for over 50 passages, an immortalized cell line CHOS was established. The
cell line was well-characterized by cytogenetic, biomarker, functional, and
histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a
doubling time of 36h. Cytogenetic analysis of CHOS cells revealed the loss of
chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain
reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the
expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS
cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be
more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate.
The cell line was highly tumorigenic and maintained the histological
characteristics and invasive nature of the original tumor. Furthermore, on
immunohistochemical analysis, the xenografts and metastases were found to co-
express collagen II, aggrecan, vimentin and S100A4 that resembled the original
tumor cells. Our results indicate, the potential of CHOS cell line to serve as a
useful tool for further studies on the molecular biology of osteosarcoma,
especially in the elderly patients. (c) 2016 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016.
The input offset voltage is a quit important performance parameter for operational
amplifiers, and the low frequency l/f noise has a great effect on the offset
voltage. In this paper, chopping technology which is an efficient approach to
decrease the l/f noise and offset voltage of CMOS amplifiers is adopted. In the low
pass filter, the multiplier composed of R and C is used to filter out the
modulation noise. The circuit of the presented chopper amplifier is designed and
simulated with 45nm CMOS process and a 1V supply. Simulated results show that the
total harmonic distortion of chopper amplifier is 54.1dB and the chopper frequency
is 10 kHz. The input referred noise is 2.54 nV/root Hz @1kHz, and the average power
consumption is 65.5 mu W. The proposed technology has a pleasurable preference.
The paper presents three approaches for frequency compensation in chopper offset-
stabilized amplifiers with symmetrical passive RC notch filter with two cutoff
frequencies. The filter has two cutoff frequencies: the chopping frequency itself
and the fifth harmonic of the chopping frequency. The frequency compensation
network is connected either at the input of the notch filter, or at its output, or
between its two sections. The large signal transient response is evaluated in terms
of the overshoot/undershoot and the settling time. Three circuits using these
techniques were fabricated and evaluated. The approach that uses the frequency
compensation network connected between the sections of the filter has the best
results, except for the chopping ripple rejection.
This paper deals with the susceptibility of analog integrated circuits to radio
frequency interferences (RFI) and it concentrates on the effects induced by RFI on
the operation of offset compensated chopped CMOS operational amplifiers. The first
part of the work explains the causes of the additional output DC offset induced by
input RF disturbances in chopped systems. Afterwards, the design of a chopped CMOS
operational transconductance amplifier (OTA) is briefly treated and in the final
part of the paper the results of some simulations performed on such OTA are
presented in order to highlight the concepts discussed in the first and second
paragraphs.
This paper presents a thyristor-based tap changing transformer and a diode
rectifier for variable-voltage high-current dc applications. Back-to-back
thyristors are connected in series with the transformer taps on the primary side.
Thyristors are phase controlled in a continuous manner to achieve variable ac
voltage at the secondary side of the transformer. This leads to a variable voltage
at the output of the three-phase diode rectifier connected at the secondary side of
the transformer. A passive filter is added at the primary side to achieve power
factor improvement over the range of output voltage. This scheme is optimized to
determine optimum turns ratio of the transformer and optimum reactive power rating
of the passive filter. Design guidelines are presented for various values of power
factor along with optimum turns ratios and passive filter rating. A 62.5-kW
experimental system with a passive filter of 17.5 kVA (reactive) is developed to
verify the system performance. In the end, a comparison of the proposed topology
with other state-of-the-art topologies is also presented.
This paper presents a chopper instrumentation amplifier designed in 28nm CMOS
technology. The operational amplifier has a rail-to-rail folded cascode input
stage, which ensures a constant gm over the available common-mode range. It is
characterized by a Nested Miller compensation. All transistors operate in sub-
threshold region; thus the opamp has been designed through a specific procedure for
sub-threshold operation. The chopper technique is exploited to reduce the input
referred offset and noise. The circuit operates with 0.9V supply voltage and
exhibits a simulated 106dB DC gain and 329kHz GBW. Montecarlo simulations
demonstrate an offset distribution with 2.2 mu V standard deviation. The input
noise spectral density is equal to 27nV/Hz, giving a noise efficiency factor of 8.
Background: Chordoma are malignant tumors of the axial skeleton, which arise from
remnants of the notochord. The Notochord (chorda dorsalis) is an essential
embryonic structure involved in the development of the nervous system and axial
skeleton. Therefore, the notochord seems to be the most biologically relevant
control tissue to study chordoma in molecular biology research. Nevertheless, up to
now mainly different tissues but not the notochord have been used as control for
chordoma, due to difficulty of isolating notochordal tissue. Here, we describe a
fast and precise method of isolating notochordal cells. Methods: Examination of
human fetuses, with a gestation of 9, 11 and 13 weeks, using (immuno) histochemical
methods was performed. To isolate pure notochord cells for further molecular
biology investigation five flash frozen fetuses between 9 and 10 weeks of gestation
were dissected by microtome slicing. Thereafter pure notochord cells for further
molecular biology investigation where harvested by using laser capture
microdissection (LCM). RNA was extracted from these samples and used in
quantitative PCR. Results: This study illustrates notochord of embryonic spines in
three different stages of gestation (9-1113 weeks). Immunohistochemical staining
with brachyury showed strong staining of the notochord, but also weak staining of
the intervertebral disc and vertebral body. LCM of notochord slices and subsequent
total RNA extraction resulted in a good yield of total RNA. qPCR analysis of two
housekeeping genes confirmed the quality of the RNA. Conclusion: LCM is a fast and
precise method to isolate notochord and the quality and yield RNA extracted from
this tissue is sufficient for qPCR analysis. Therefore early embryo notochord
isolated by LCM is suggested to be the gold standard for future research in
chordoma development, classification and diagnosis. (C) 2016 Elsevier B.V. All
rights reserved.
Chorioamnionitis is an acute inflammation of the gestational (extraplacental)
membranes, most commonly caused by ascending microbial infection. It is associated
with adverse neonatal outcomes including preterm birth, neonatal sepsis, and
cerebral palsy. The decidua is the outermost layer of the gestational membranes and
is likely an important initial site of contact with microbes during ascending
infection. However, little is known about how decidual stromal cells (DSCs) respond
to microbial threat. Defining the contributions of individual cell types to the
complex medley of inflammatory signals during chorioamnionitis could lead to
improved interventions aimed at halting this disease. We review available published
data supporting the role for DSCs in responding to microbial infection, with a
special focus on their expression of pattern recognition receptors and evidence of
their responsiveness to pathogen sensing. While DSCs likely play an important role
in sensing and responding to infection during the pathogenesis of chorioamnionitis,
important knowledge gaps and areas for future research are highlighted.
Background. Although Ureaplasma species are the most common organisms associated
with prematurity, their effects on the maternal and fetal immune system remain
poorly characterized. Methods. Rhesus macaque dams at approximately 80% gestation
were injected intra-amniotically with 10(7) colony-forming units of Ureaplasma
parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later. We
performed comprehensive assessments of inflammation and immune effects in multiple
fetal and maternal tissues. Results. Although U. parvum grew well in amniotic
fluid, there was minimal chorioamnionitis. U. parvum colonized the fetal lung, but
fetal systemic microbial invasion was limited. Fetal lung inflammation was mild,
with elevations in CXCL8, tumor necrosis factor (TNF) alpha, and CCL2 levels in
alveolar washes at day 7. Inflammation was not detected in the fetal brain.
Significantly, U. parvum decreased regulatory T cells (Tregs) and activated
interferon gamma production in these Tregs in the fetus. It was detected in uterine
tissue by day 7 and induced mild inflammation and increased expression of connexin
43, a gap junction protein involved with labor. Conclusions. U. parvum colonized
the amniotic fluid and caused uterine inflammation, but without overt
chorioamnionitis. It caused mild fetal lung inflammation but had a more profound
effect on the fetal immune system, decreasing Tregs and polarizing them toward a T-
helper 1 phenotype.
Background/aims To assess the efficacy and safety of dexamethasone (DEX)
intravitreal implant in patients with active serpiginous choroiditis (SC) already
receiving maximal tolerated systemic immunosuppressive therapy. Methods In this
retrospective longitudinal study we evaluated patients receiving 0.7mg DEX
intravitreal implant for active SC despite maximal systemic immunosuppression.
Medical history was reviewed over a period of 18months for each patient. We
diagnosed SC activity using direct fundus examination and blue-light fundus
autofluorescence. Primary outcomes were the rate of disease control and functional
changes at end of follow-up. Secondary outcomes were the incidence of injection-
related adverse events and the success of immunosuppression tapering at the last
examination. Results We examined eight eyes of seven patients. We controlled SC
activity with one injection in five eyes, two injections in one eye, and three
injections in two eyes (total of 13 implants). Best-corrected visual acuity at the
end of the investigational period improved in two eyes (25%), remained stable in
four eyes (50%) and decreased in two eyes (25%). Three eyes showed transient
intraocular pressure increase and two eyes disclosed cataract progression. The
average dosage of systemic prednisone at baseline and after DEX intravitreal
implant decreased from 8.8 to 2.8mg/day. Conclusions Dexamethasone intravitreal
implant may be an effective treatment option to control active serpiginous lesions
in patients in whom increased systemic corticosteroid therapy is contraindicated.
Sliced ready-to-eat traditional meat products presented in individual packaging
with more convenience to the consumer is the way that food industry tries to adapt
to the new consumer tendencies. The current work assessed the survival of Listeria
monocytogenes in a contaminated sliced vacuum packed chourico with different sugar
concentrations, two salt levels, and presence/absence of Lactobacillus sakei as
starter culture along the storage period at two temperatures (8 degrees C and 22
degrees C). Neither the inoculation with L. sakei, nor the addition of
carbohydrates influenced the survival of the pathogen. Higher amount of salt
resulted in a signifi cant reduction of L. monocytogenes, and storage at the higher
temperature displayed a safer product. After 7 days, L. monocytogenes was not
detected in any samples. The study of the association of the factors contributing
for L. monocytogenes survival by logistic regression showed that increasing the
level of salt addition from 1.5% to 3% reduces the odds of survival of L.
monocytogenes to about one fifth (0.174). Worthy of attention is the signifi cant
reduction in the odds (OR=0.028) of fi nding viable L. monocytogenes when the
samples are stored at room temperature (22 degrees C), when compared to low
temperature (8 degrees C). The general and indiscriminate use of refrigeration for
meat products might increase the risk of presence of L. monocytogenes. The
competitive advantage that L. monocytogenes has at low temperatures, as the
potential inhibition of LAB activity, is probably the reason of the observed
behaviour. The amount of salt was an important hurdle to control L. monocytogenes
growth, so, manufacturing meat products with lower salt contents to meet the
demands of healthy products might represent a risk for safety, since high levels of
salt together with low a w are the keys for their conservation.
Background: The local recurrence rate in oral squamous cell cancer (OSCC) hardly
decreases. This is partly due to the presence of (pre) malignant cells in the
remaining tissue after resection, that may lead to the development of a new tumor
in time. Detection of histologically (pre) malignant cells in the tumor resection
margins should predict these patients at risk for recurrence, however this appears
to be difficult in routine practice. Purpose of this study was to apply easy-to-use
molecular tests for more accurate detection of (pre) malignant cells in
histopathologically tumor-free margins, to improve diagnosis of patients at risk.
Methods: 42 patients with firstly diagnosed, radically resected primary OSCC with
histopathologically confirmed tumor-free resection margins (treated between 1994
and 2003) were included. Inclusion criteria comprised of follow-up >= 5 years, and
radical surgery without postoperative treatment. Formalinf-ixed paraffine-embedded
tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were
subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and
7 copy number variations (CNV), and to p53 immunohistochemistry (IHC). Results: 11
out of the 42 patients developed a local recurrence within 5 years. FISH analysis
showed that nine of eleven recurrences exhibited CI in at least one of the
resection margins (p = 0.008). P53 overexpression and routine histopathologic
classification were not correlated with recurrent disease. The presence of CI in
the resection margins revealed a significantly worse progression-free survival
(log-rank p = 0.012). Conclusions: CI in the resection margins of OSCC can reliably
identify patients at risk for developing a local recurrence. (C) 2016 Elsevier Ltd.
All rights reserved.
We conducted a prospective study to assess the prognostic impact of selected copy
number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer.
A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8
selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q,
ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase
chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point
was the impact of the CNVs on the 4-year disease-free survival (DFS). The
recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus
31% Stage III patients (p<0.0001). The 4-year DFS was significantly decreased in
patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041).
The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain
at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q
and ERBB2/17q was also associated with relapse, with the hazard ratio increasing
from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in
the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q
and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon
cancer.
Increasing evidence suggests that regular physical exercise suppresses chronic
inflammation. However, the potential inhibitory effects of swimming on dextran
sulfate sodium (DSS)-induced chronic colitis, and its underlying mechanisms, remain
unclear. In this study, rats were orally administered DSS to induce chronic
colitis, and subsequently treated with or without swimming exercise. A 7-week
swimming program (1 or 1.5 hours per day, 5 days per week) ameliorated DSS-caused
colon shortening, colon barrier disruption, spleen enlargement, serum LDH release,
and reduction of body weight gain. Swimming for 1.5 hours per day afforded greater
protection than 1 hour per day. Swimming ameliorated DSS-induced decrease in crypt
depth, and increases in myeloperoxidase activity, infiltration of Ly6G(+)
neutrophils and TNF-alpha- and IFN-gamma-expressing CD3(+) T cells, as well as
fecal calprotectin and lactoferrin. Swimming inhibited pro-inflammatory cytokine
and chemokine production and decreased the protein expression of phosphorylated
nuclear factor-kappa B p65 and cyclooxygenase 2, whereas it elevated interleukin-10
levels. Swimming impeded the generation of reactive oxygen species,
malondialdehyde, and nitric oxide; however, it boosted glutathione levels, total
antioxidant capacity, and superoxide dismutase and glutathione peroxidase
activities. Additionally, swimming decreased caspase-3 activity and expression of
apoptosis-inducing factor, cytochrome c, Bax, and cleaved-caspase- 3, but increased
Bcl-2 levels. Overall, these results suggest that swimming exerts beneficial
effects on DSS-induced chronic colitis by modulating inflammation, oxidative
stress, and apoptosis.
BACKGROUND: Fractional exhaled nitric oxide (FENO) is a safe and convenient test
for assessing T(H)2 airway inflammation, which is potentially useful in the
management of patients with chronic cough. OBJECTIVE: To summarize the current
evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid
(ICS) responsiveness in patients with chronic cough. METHODS: A systematic
literature review was conducted to identify articles published in peer-reviewed
journals up to February 2015, without language restriction. We included studies
that reported the usefulness of FENO (index test) for predicting ICS responsiveness
(reference standard) in patients with chronic cough (target condition). The data
were extracted to construct a 2 3 2 accuracy table. Study quality was assessed with
Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: We identified 5
original studies (2 prospective and 3 retrospective studies). We identified
considerable heterogeneities in study design and outcome definitions, and thus were
unable to perform a meta-analysis. The proportion of ICS responders ranged from 44%
to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%,
respectively. The reported area under the curve ranged from about 0.60 to 0.87;
however, studies with a prospective design and a lower prevalence of asthma had
lower area under the curve values. None measured placebo effects or objective cough
frequency. CONCLUSIONS: We did not find strong evidence to support the use of FENO
tests for predicting ICS responsiveness in chronic cough. Further studies need to
have a randomized, placebo-controlled design, and should use validated measurement
tools for cough. Standardization would facilitate the development of clinical
evidence. (C) 2016 Published by Elsevier Inc. on behalf of the American Academy of
Allergy, Asthma & Immunology
The number of times a scientific article has been cited reflects its impact on a
specific field. Highly cited articles are known as citation classics. Here, we aim
to characterize the most frequently cited articles in chronic granulomatous disease
(CGD). We searched the ISI Web of Science in Aug 2016 for articles that were cited
100 times or more and evaluated them for several characteristics. The most
frequently cited article received 955 citations. The citations mean was 221.6
citations (SD = 162.7). The most recent article was published in 2011. The articles
were published in 36 journals, led by The New England Journal of Medicine. Overall
authors came from 17 countries, with the United States of America (USA)
contributing to 91 (80%) articles. The National Institute of Health was the most
common institution of origin for the corresponding author. The most common type of
articles was basic science with 77 (67%) articles. These results provide some
insights into the most cited research articles in CGD since its first description
60 years ago.
Chronic granulomatous disease (CGD), a disease characterized by inadequate
neutrophil killing of microbial pathogens, affects 4 to 5 per million live births.
For many decades following its description, CGD was a fatal disease in childhood.
With the development of effective preventive therapies and the early recognition of
infectious complications, 90% of children with CGD now survive into adulthood. The
management of CGD in adults includes unique challenges and potential disease
manifestations. In this article, the authors discuss the current approach to the
management of CGD in both children and adults. This includes a focus on the
importance of a comprehensive multidisciplinary approach in the care of CGD and its
potential complications. In addition, a novel approach to improving education about
CGD, and subsequently improving adherence to preventive therapies, is discussed.
(C) 2016 American Academy of Allergy, Asthma & Immunology.
Chronic granulomatous disease is a rare, inherited immunodeficiency disorder that
reduces the superoxide generation ability of phagocytes, leading to recurrent
infections and granulomatous inflammation. We report the case of a previously
healthy 3-year-old boy who presented with classic features of Crohn disease.
Suspicion from histopathologiclogic assessment allowed early diagnosis and
treatment for chronic granulomatous disease before the onset of infections.
Little is known about the association between chronic illness and suicidal ideation
(SI) among Dominicans living in the United States. This study used data from a
community survey of 2753 Dominican adults in New York City. SI included thoughts of
self-harm or being better off dead in the past month. Chronic physical illness
burden was categorized as having 0, 1, or 2+ diagnosed conditions. Adjusted
logistic regressions evaluated the association between number of conditions and SI,
overall and stratified by sex and age. Adjusted models yielded a strong association
between chronic illness burden and SI among men [odds ratio (OR) 5.57, 95 %
confidence interval (CI) 2.19-14.18] but not women (OR 0.80, 95 % CI 0.50-1.29;
interaction p = 0.011). The association of interest did not differ significantly
between younger and older adults. Screening for SI in health care practice,
particularly among Dominican men with multiple chronic health conditions, may be
warranted.
Purpose of review Altered differentiation and activation of T-cell subsets occur in
patients with chronic kidney disease (CKD), but the impact on graft rejection and
protective immunity during transplantation are not fully understood. Recent
findings Patients with CKD have decreased frequency of naive T cells, accumulation
of activated, terminally differentiated memory cells, and skewed regulatory versus
T helper 17 ratio. Naive and memory T-cell subsets do not appear to improve
following kidney transplantation. Retained thymic output is associated with acute
rejection, whereas naive lymphopenia and accumulation of CD8(+) TEMRA cells
correlate with long-term graft dysfunction. CD28(null) memory cells accumulate
during CKD and appear to confer protection against acute rejection under standard
immunosuppression and possibly costimulation blockade. T cells bearing CD57 are
also increased in patients with CKD and may underlie rejection during costimulation
blockade. Summary The mechanisms by which CKD alters the differentiation and
activation status of T-cell subsets is poorly understood. Further research is also
needed to understand which cell populations mediate rejection under various
immunosuppressive regimens. To date, there is little use of animal models of organ
failure in transplant immunology research. CKD mouse models may help identify novel
pathways and targets to better control alloimmunity in posttransplant.
Endothelial dysfunction and impaired endothelial regenerative capacity are key
contributors to the high incidence of cardiovascular disease in patients with
chronic kidney disease (CKD). Uremic toxins are associated with this pathogenesis.
Previous studies have revealed that a uremic toxin, para-cresol (p-cresol), exerts
an antiproliferation effect on human endothelial progenitor cells (EPCs), but the
mechanism remains unclear. In the present study, reactive oxygen species (ROS) were
confirmed to function as signaling molecules that regulate growth factor-dependent
EPC proliferation. EPCs were treated with p-cresol for 72 h, using a concentration
range typically found in CKD patients. ROS production was analyzed by fluorescence
microscopy and flow cytometry, and protein expression levels of nicotinamide
adenine dinucleotide phosphate oxidase, a major source of ROS, were analyzed by
western blot analysis. mRNA expression levels of antioxidant genes were assessed by
reverse transcription-quantitative polymerase chain reaction analysis. The results
revealed that p-cresol partially inhibits ROS production, and this effect may be
associated with a significant reduction in cytochrome b-245 alpha and beta chain
expression in EPCs. An increase of glutathione peroxidase 4 mRNA expression was
also detected. In conclusion, the present study revealed that the antiproliferation
effect of p-cresol on EPCs might act via its antioxidant activity. The results of
the present study may facilitate understanding of uremic toxin toxicity on the
cardiovascular system.
ObjectivesThis study investigates whether achieving complete remission (CR) with
undetectable minimal residual disease (MRD) after allogeneic stem cell
transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome.
MethodsWe retrospectively studied 46 patients transplanted for CLL and evaluated
for post-transplant MRD by flow cytometry. ResultsAt transplant time, 43% of the
patients were in CR, including one with undetectable MRD, 46% were in partial
response, and 11% had refractory disease. After transplant, 61% of the patients
achieved CR with undetectable MRD status. By multivariate analysis, reaching CR
with undetectable MRD 12 months after transplant was the only factor associated
with better progression-free survival (P = 0.02) and attaining undetectable MRD,
independently of the time of negativity, was the only factor that correlated with
better overall survival (P = 0.04). ConclusionThus, achieving undetectable MRD
status after allo-SCT for CLL is a major goal to improve post-transplant outcome.
Chemotherapy is the main treatment method for patients with chronic myeloid
leukemia (CML) and has achieved marked results. However, the acquisition of
multidrug resistance (MDR) has seriously affected the quality of life and survival
rate of patients. The overexpression of the inhibitors of apoptosis proteins (IAPs)
and the adenosi ne triphosphate (ATP) dependent binding cassette (ABC) transporters
are the two main causes of MDR. Apollon and MDR1 are the most important and
representative members, respectively, among the IAPs and ABC transporters. In the
present study, we investigated the role of Apollon and MDR1 in chemotherapy
resistance and their mechanism of interaction. We respectively knocked down the
expression of Apollon and MDR1 using short hairpin RNA (shRNA) in adriamycin (ADM)
resistant human CML K562 cells and examined the drug sensitivity, the consequences
with regard to ADM accumulation and the alterations in the expression of Apollon
and MDR1. The expression levels of Apollon and MDR1 mRNA were higher in the
K562/ADM cells compared with the parental K562 cells as determined by reverse
transcription-polymerase chain reaction (RT-PCR). The plasmids of Apollon and MDR1
shRNA were respectively stably transfected into K562/ADM cells using Lipofectamine
2000. The transfection efficiency was detected by fluorescence microscopy. Cell
Counting Kit-8 (CCK-8) assay revealed that Apollon or MDR1 knockdown significantly
increased the chemosensitivity of the K562/ADM cells to ADM. Flow cytometric assay
revealed that K562/ADM/shMDR1 cells exhibited a significantly increased
intracellular accumulation of ADM, and that changes were not found in the
K562/ADM/shApollon cells. Compared with the parental K562/ADM cells, a
significantly decreased expression of Apollon mRNA and protein was determined in
the K562/ADM/shApollon cells without affecting the expression of MDR1 as determined
by RT-PCR and western blotting. Likewise, the expression levels of MDR1 mRNA and
protein also markedly downregulated in the K562/ADM/shMDR1 cells had no effect on
Apollon expression. Collectively, our findings demonstrated, for the first time,
that downregulation of Apollon or MDR1 through stable transfection with the
Apollon- or MDR1-targeting shRNA induced MDR reversal through respective inhibition
of Apollon or MDR1 expression and function. However, the reversal mechanism of
Apollon and MDR1 revealed no direct interaction with each other.
Several clinical trials have demonstrated that some patients with chronic myeloid
leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses
on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt
treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-
treated patients; however, the feasibility of TFR following nilotinib or dasatinib
has also been demonstrated. In this review, we discuss available data from TFR
trials and what these data reveal about the molecular biology of TFR. With an
increasing number of ongoing TFR clinical trials, TFR may become an achievable goal
for patients with CML-CP.
Imatinib mesylate (IM) is considered as a highly effective therapy for chronic
myeloid leukemia (CML) patients. However, a minority of patients fail to achieve
optimal response due to impaired bioavailability of IM. The human organic cation
transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter
involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression
changes may influence IM response. In this study, we aimed to investigate the
impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the
clinical outcome in CML patients. hOCT1 expression profile was determined using the
quantitative real-time polymerase chain reaction in 69 CML patients treated with IM
(35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69
cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing
after amplification of exon7. Our results showed that the hOCT1 gene was
significantly downregulated in the samples of the IM-resistant group when compared
with the IM-responder group (p = 0.0211). Moreover, sequencing data show an
association in all cases between the SNP 408V >M (g.1222G >A) and an intronic 8 bp
(base pairs) insertion of GTAAGTTG (rs36056065) at the 3' end of exon 7. The
genotype and allele distribution of the different SNPs did not differ significantly
between the two groups of patients. hOCT1 mRNA expression may serve as a clinical
biomarker of response to imatinib and could be useful to predict IM therapy outcome
of CML patients.
Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
(APECED, APS-I) suffer from chronic candidosis caused mainly by Candida albicans,
and repeated courses of azole antifungals have led to the development of resistance
in the APECED patient population in Finland. The aim of our study was to address
whether the patients are persistently colonized with the same or genetically
closely related strains, whether epidemic strains are present and which molecular
mechanisms account for azole resistance. Sets of C. albicans (n = 19) isolates from
nine APECED patients reported with decreased susceptibility to fluconazole isolated
up to 9years apart were included. The strains were typed by multilocus sequence
typing. CDR1/2, MDR1 and ERG11 mRNA expression was analysed by northern blotting
and Cdr1, Cdr2 and Mdr1 protein expression by western blotting, and TAC1 and ERG11
genes were sequenced. All seven patients with multiple C. albicans isolates
analysed were persistently colonized with the same or a genetically closely related
strain for a mean of 5 years. All patients were colonized with different strains
and no epidemic strains were found. The major molecular mechanisms behind the azole
resistance were mutations in TAC1 contributing to overexpression of CDR1 and CDR2.
Six new TAC1 mutations were found, one of which (N740S) is likely to be a gain-of-
function mutation. Most isolates were found to have gained multiple TAC1 and ERG11
point mutations. Despite clinically successful treatment leading to relief of
symptoms, colonization by C. albicans strains is persistent within APECED patients.
Microevolution and point mutations occur within strains, leading to the development
of azole-resistant isolates.
Introduction: Brain-derived neurotrophic factor (BDNF) disturbances and life
stress, both independently and in interaction, have been hypothesized to induce
chronic pain. We examined whether (a) the BDNF pathway (val (66)met genotype, gene
expression, and serum levels), (b) early and recent life stress, and (c) their
interaction are associated with the presence and severity of chronic multi-site
musculoskeletal pain. Methods: Cross-sectional data are from 1646 subjects of the
Netherlands Study of Depression and Anxiety. The presence and severity of chronic
multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG)
questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF
serum levels were measured. Early life stress before the age of 16 was assessed by
calculating a childhood trauma index using the Childhood Trauma Interview. Recent
life stress was assessed as the number of recent adverse life events using the List
of Threatening Events Questionnaire. Results: Compared to val(66)val, BDNF met
carriers more often had chronic pain, whereas no differences were found for BDNF
gene expression and serum levels. Higher levels of early and recent stress were
both associated with the presence and severity of chronic pain (p<0.001). No
interaction effect was found for the BDNF pathway with life stress in the
associations with chronic pain presence and severity. Conclusions: This study
suggests that the BDNF gene marks vulnerability for chronic pain. Although life
stress did not alter the impact of BDNF on chronic pain, it seems an independent
factor in the onset and persistence of chronic pain.
Objectives: Interleukin-36 (IL-36) is a recently described proinflammatory
cytokine, characterized by the induction of inflammatory mediators. In the present
study, we investigated the biological activity and the signal transduction of IL-36
alpha in human pancreatic myofibroblasts. Methods: The mRNA and protein expression
of inflammatory mediators was evaluated using real-time polymerase chain reaction
and enzyme-linked immunosorbent assay, respectively. The expression of IL-36 alpha
and its receptor in the pancreatic tissue was evaluated using immunohistochemical
technique. Intracellular signaling pathways were evaluated using immunoblotting and
specific small interference RNA-transfected cells. Results: Interleukin-36 alpha
and its receptor complex IL-36R/IL-1RAcP were detected in fibrotic tissue of
chronic pancreatitis. Interleukin-36 alpha dose-and time-dependently induced the
mRNA expression and protein secretion of CXCL1, CXCL8, MMP-1, and MMP-3 from human
pancreatic myofibroblasts. Interleukin-36 alpha assembled MyD88 adaptor proteins
(MyD88, TRAF6, IRAK1, and TAK1) into a complex. Furthermore, IL-36 alpha induced
the phosphorylation of mitogen-activated protein kinases and the activation of
nuclear factor kappa B and activator protein 1. Mitogen-activated protein kinase
inhibitors and small interference RNAs specific for nuclear factor kappa B and
activator protein 1 significantly suppressed the protein secretion of inflammatory
mediators induced by IL-36 alpha stimulation. Conclusions: It was suggested that
IL-36 alpha plays an important role in the pathophysiology of inflammation and
fibrosis in the pancreas via an autocrine function.
Background and ObjectiveMore than 100 salivary constituents have been found to show
levels significantly different in patients with oral squamous cell carcinoma (OSCC)
from those found in healthy controls, and therefore have been suggested to be
potential salivary biomarkers for OSCC detection. However, many of these potential
OSCC salivary biomarkers are also involved in chronic inflammation, and whether the
levels of these biomarkers could be affected by the presence of chronic
periodontitis was not known. The objective of this pilot study was therefore to
measure the levels of seven previously reported potential OSCC salivary mRNA
biomarkers in patients with chronic periodontitis and compare them to levels found
in patients with OSCC and healthy controls. The seven salivary mRNAs were
interleukin (IL)-8, IL-1, dual specificity phosphatase 1, H3 histone family 3A,
ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and
spermidine/spermine N1-acetyltransferase 1. Material and MethodsUnstimulated whole
saliva samples were collected from a total of 105 human subjects from the following
four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree,
non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and
healthy controls. Levels of each mRNA in patient groups (OSCC or chronic
periodontitis) relative to the healthy controls were determined by a pre-
amplification reverse transcription-quantitative polymerase chain reaction approach
with nested gene-specific primers. Results were recorded and analyzed by the Bio-
Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs.
control groups were analyzed by the Mann-Whitney U-test with Bonferroni
corrections. ResultsOnly S100P showed significantly higher levels in patients with
OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The
difference in S100P levels between patients with OSCC and healthy controls was also
marginally significant (p = 0.009). There was no significant difference in the
levels of salivary IL-8, IL-1 and dual specificity phosphatase 1 mRNAs between
patients with OSCC and patients with CPNS (p = 0.510, 0.058 and 0.078,
respectively); no significant difference in levels of salivary ornithine
decarboxylase antizyme 1 and spermine N1-acetyltransferase mRNAs between patients
with OSCC and patients with CPS (p = 0.318 and 0.764, respectively); and no
significant difference in levels of the H3 histone family 3A mRNA between patients
with OSCC and either CPS (p = 0.449) or healthy controls (p = 0.107).
ConclusionsSalivary S100P mRNA could be a reliable biomarker for OSCC detection,
regardless of the presence of chronic periodontitis. The presence of chronic
periodontitis could significantly affect the levels of the other six mRNAs, and
negatively influence reliability for using them as biomarkers for oral cancer
detection.
Chronic stress is a precipitating factor for disorders including depression. The
basolateral amygdala (BLA) is a critical substrate that interconnects with stress-
modulated neural networks to generate emotion and mood-related behaviors. The
current study shows that 3 h per day of restraint stress for 14 days caused mice to
exhibit long-term depressive behaviors, manifested by disrupted sociality and
despair levels, which were rescued by fluoxetine. These behavioral changes
corresponded with morphological and molecular changes in BLA neurons, including
chronic stress-elicited increases in arborization, dendritic length, and spine
density of BLA principal neurons. At the molecular level, calcium-permeable alpha-
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) within the
synaptosome exhibited an increased GluR1:GluR2 subunit ratio. We also observed
increased GluR1 phosphorylation at Ser 845 and enhanced cyclic AMP-dependent
protein kinase (PICA) activity in the BLA. These molecular changes reverted to the
basal state post-treatment with fluoxetine. The expression of synaptophysin (SYP)
and postsynaptic density protein 95 (PSD-95) at BLA neuronal synapses was also
enhanced by chronic stress, which was reversed post-treatment. Finally, chronic
stress-provoked depressive behavior was overcome by local blockage of CP-AMPARs in
the BLA via stereotaxic injection (IEM-1460). Chronic stress-elicited depressive
behavior may be due to hypertrophy of BLA neuronal dendrites and increased of PICA-
dependent CP-AMPAR levels in BLA neurons. Furthermore, fluoxetine can reverse
chronic stress triggered cytoarchitectural and functional changes of BLA neurons.
These findings provide insights into depression-linked structural and functional
changes in BLA neurons. (C) 2017 Elsevier Inc. All rights reserved.
Introduction: Chronic rhinosinusitis (CRS) is a common disease of the upper airways
and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients
suffer from sleep disruption at a significantly higher proportion (60 to 75%) than
in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL
and is linked to poor functional outcomes such as impaired cognitive function and
depression.Areas covered: A systematic PubMed/Medline search was done to assess the
results of studies that have investigated sleep and sleep disturbances in
CRS.Expert commentary: These studies reported sleep disruption in most CRS
patients. The main risk factors for sleep disruption in CRS include allergic
rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent
with regard to the prevalence of sleep-related disordered breathing (e.g.
obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to
sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that
expected from physical blockage of the upper airways alone. Despite the high
prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the
literature contains a paucity of studies that have investigated the mechanisms
underlying this major problem in CRS.
ObjectiveDetermine whether the elimination of pain improves accuracy of clinical
diagnostic criteria for adult chronic rhinosinusitis. Study DesignRetrospective
cohort study. MethodsHistory, symptoms, nasal endoscopy, and computed tomography
(CT) results were analyzed for 1,186 adults referred to an academic otolaryngology
clinic with presumptive diagnosis of chronic rhinosinusitis. Clinical diagnosis was
rendered using the 1997 Rhinosinusitis Taskforce (RSTF) Guidelines and a modified
version eliminating facial pain, ear pain, dental pain, and headache. ResultsFour
hundred seventy-nine subjects (40%) met inclusion criteria. Among subjects positive
by RSTF guidelines, 45% lacked objective evidence of sinonasal inflammation by CT,
48% by endoscopy, and 34% by either modality. Applying modified RSTF diagnostic
criteria, 39% lacked sinonasal inflammation by CT, 38% by endoscopy, and 24% by
either modality. Using either abnormal CT or endoscopy as the reference standard,
modified diagnostic criteria yielded a statistically significant increase in
specificity from 37.1% to 65.1%, with a nonsignificant decrease in sensitivity from
79.2% to 70.3%. Analysis of comorbidities revealed temporomandibular joint
disorder, chronic cervical pain, depression/anxiety, and psychiatric medication use
to be negatively associated with objective inflammation on CT or endoscopy.
ConclusionClinical diagnostic criteria overestimate the prevalence of chronic
rhinosinusitis. Removing facial pain, ear pain, dental pain, and headache increased
specificity without a concordant loss in sensitivity. Given the high prevalence of
sinusitis, improved clinical diagnostic criteria may assist primary care providers
in more accurately predicting the presence of inflammation, thereby reducing
inappropriate antibiotic use or delayed referral for evaluation of primary headache
syndromes. Level of Evidence4. Laryngoscope, 127:1011-1016, 2017
Farming systems can expose animals to chronic mild stress which is known to induce
negative affective state. Affective state in animals, as in humans, can be assessed
through behavioral cues. This study aimed to describe the effect of a chronic mild
stress, known to induce a negative affective state, on sheep health through their
response to vaccination. The study used 15 lambs subjected to a model of chronic
mild stress for 15 weeks and 15 lambs reared under conventional farming as a
control group. After 7 weeks of stressful treatment, the lambs were individually
exposed to a judgment bias test to assess a putative stress-induced pessimism.'
After 15 weeks of stressful treatment, antibody immune response was measured after
an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine
strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment
bias test, revealing a negative affective state. Stressed and control animals
showed different immunological reactions to vaccine challenge: stressed sheep had
lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase
protein concentrations. Antibody response induced by the vaccine strain was not
different between stressed and control sheep. Our results suggest that negative
affective state induced by chronic stress treatment may induce a stronger
inflammatory response to vaccine challenge in sheep. Improvement of animal health
may be achieved through consideration of stressors that may affect the emotional
and immunological state of sheep.
Brain imaging and postmortem studies have indicated that white matter abnormalities
may contribute to the pathology and pathogenesis of depression. However, until now,
no study has quantitatively investigated white matter changes in depression in
rats. The current study used the chronic unpredictable stress (CUS) model of
depression. Body weight and sucrose preference test (SPT) scores were assessed
weekly. Upon successfully establishing the CUS animal model, all animals were
tested using the SPT and the open field test (OFT). Then, transmission electron
microscopy and unbiased stereological methods were used to investigate white matter
changes in the rats. Compared with the control group, the body weight and sucrose
preference of the CUS rats were significantly decreased (p<.001, p<.001,
respectively). In the OFT, the total time spent and the total distance traveled in
the inner area by the CUS rats were significantly lower than those of the control
group (p=.002, p=.001, respectively). The stereological results revealed that white
matter volume, the total volume, and the total length and mean diameter of
myelinated fibers in the white matter of the CUS rats were significantly decreased
compared to the control rats (p= .042, p= .038, p= .035, p= .019, respectively).
The results of this study suggested that white matter atrophy and disruption of
myelinated fibers in the white matter may contribute to the pathophysiology
underlying depression, which might provide new targets for the development of novel
therapeutic interventions for depression.
BACKGROUND: Patients who have failed traditional treatment of chronic urticaria may
require trials of alternative medications. Safety profiles, continuous laboratory
monitoring, and physician comfort are often barriers to treatment. OBJECTIVES: To
evaluate the safety of alternative agents used in chronic urticaria. METHODS: A
retrospective chart review of electronic medical records from a single-center
allergy and immunology clinic in a major academic hospital was conducted. One
hundred twenty-six charts of patients with chronic urticaria treated with
alternative agents were reviewed. RESULTS: Adverse effects were reported in 39 of
73 (53%) patients on dapsone, 19 of 47 (40%) patients on sulfasalazine, 15 of 36
(42%) patients on tacrolimus, 7 of 45 (16%) patients on hydroxychloroquine, 9 of 27
(33%) patients on mycophenolate, 6 of 8 (75%) patients on cyclosporine, and 3 of 24
(4%) patients on omalizumab. Most of these adverse effects were mild, did not
require discontinuation of the medication, and resolved after stopping the
medication or decreasing the dose. CONCLUSIONS: The use of alternative agents for
the treatment of chronic urticaria angioedema is generally safe when proper
laboratory and clinical monitoring is observed. (C) 2016 American Academy of
Allergy, Asthma & Immunology
Social jet lag is a term describing misalignment between social and biological
times. In this article, it is argued that the currently used formula for social jet
lag captures not only this misalignment, but also sleep debt resulting from sleep
deprivation during workdays. It is proposed to adopt the sleep-corrected formula
for social jet lag, which takes the form of the difference between the sleep onset
on free days and workdays in the case of subjects with longer sleep and later (or
equal) sleep onset on free days compared to workdays; it takes the form of the
difference between the sleep offset on free days and workdays for subjects with
longer sleep and earlier (or equal) sleep offset on workdays compared to free days.
Chronotype is an emerging predictor of health and longevity, and understanding its
influence on chronic diseases is important for constructing conceptual models of
long-term pathways to health. We assessed the associations of chronotype with
health status in the general Finnish adult population. Our population-based data
were derived from the National FINRISK 2012 study and consisted of 4414
participants, aged 25-74 years, living in Finland. As part of their health
examination, participants were asked about their circadian preference to the daily
activities (morningness-eveningness) and a diagnosis or treatment for a set of
common noncommunicable medical conditions and chronic diseases during the past 12
months. We found that there were 1935 (43.8%) morning types (MTs) and 595 (13.5%)
evening types (ETs) and that 1884 (42.7%) were intermediates. As compared with the
MTs, the ETs had significantly greater odds for depression (OR = 2.44, 95% CI =
1.52-3.90, p < 0.001) and other mental disorders (OR = 5.18, 95% CI = 2.32-11.52, p
< 0.001). The odds were also increased for gallstones, and chronic obstructive
pulmonary disease, but these did not remain significant after controlling for
multiple testing. Responses to the single-item subjective estimation on the
chronotype yielded the association of the definitely evening type of persons with
the diagnosis or treatment of cardiac insufficiency (OR = 1.99, 95% CI = 1.02-3.88,
p = 0.044) that was corroborated as the greater the eveningness score was, the more
common the diagnosis or treatment of cardiac insufficiency was (beta= 0.92, 95% CI
= 0.85-0.98, p = 0.013). This exploratory study adds further support to the role of
evening chronotype in chronic disease risk, albeit underlying mechanisms remain to
be elucidated.
Agroinfiltration was tested as a method of inoculation of chrysanthemum plants with
chrysanthemum stunt viroid (CSVd). Binary vectors harboring dimeric CSVd sequences
in sense and antisense orientations were constructed, and Agrobacterium transfected
with these binary vectors was infiltrated into chrysanthemum leaves. Northern
blotting and reverse transcription polymerase chain reaction analysis showed that
local infection was established within 7 days and systemic infection within 20
days. CSVd polarities showed no difference in infectivity. This study showed that
agroinfiltration of chrysanthemum plants is an easy, rapid, and cost-effective
method for CSVd inoculation. (C) 2016 Elsevier B.V. All rights reserved.
A full-length cDNA (Slctlp2) encoding a chymotrypsin-like serine protease was
cloned from Spodoptera litura. This cDNA encoded a putative serine protease with a
predicted molecular mass of 30.6 kDa, which contained a serine protease catalytic
motif GDSGGPL. Temporal and spatial expression of Slctlp2 mRNA and protein detected
by Northern blotting, RT-PCR, qPCR and Western blotting analyses revealed that both
Slctlp2 mRNA and protein were mainly present in the foregut and midgut of the 5th
and 6th instar larvae during the feeding stages. In situ hybridization and
immunohistochemistry confirmed that both Slctlp2 mRNA and protein were
predominately present in the midgut. Expression of the gene was not induced by
bacterial infection. Juvenile hormone III induced the gene expression, while 20-
hydroxyecdysone had no impact on the expression. The expression of Slctlp2 mRNA and
protein was down-regulated by starvation but up-regulated by re-feeding. The
SlCTLP2 protein was detected in the lumen residues of the anterior, middle and
posterior midgut and feces of the feeding 6th instar larvae, suggesting that it was
secreted from the epithelium into the lumen of the gut. The results suggest that
this Slctlp2 gene may be involved in digestive process of food proteins during the
feeding stages of the larval development. (C) 2010 Elsevier Ltd. All rights
reserved.
Two dehydrin genes were identified from a Cichorium intybus EST database. They were
among the most abundant sequences obtained from 10 cDNA libraries constructed from
chicory roots grown under field conditions. The full length cDNA sequences,
designated CiDHN1 and CiDHN2, were 1,176 and 1,055 bp long and encoded predicted
polypeptides of 262 and 261 amino acids, respectively. The deduced CiDHN1 protein
contains a S-segment and four lysine-rich consensus motifs (K-segments) which
represent a typical SK(4) structure of dehydrins. The CiDHN2 sequence contains two
Y motifs and two K-segments classifying CiDHN2 as Y(2)K(2)-type dehydrin. Southern-
blotting analysis suggested that CiDHN1 and CiDHN2 are single copy genes. Northern-
blotting analysis revealed that both CiDHN genes are expressed in roots and leaves,
with seasonal variations in transcript accumulation. The effect of cold on the
CiDHN1 and CiDHN2 transcript level was demonstrated. CiDHN1 and CiDHN2 promoter
analysis revealed the presence of low temperature-responsive and ABA-responsive
elements.
In the present article we report europium-doped strontium ortho-silicates, namely
Sr2SiO4:xEu(3+) (x=1.0, 1.5, 2.0, 2.5 or 3.0mol%) phosphors, prepared by solid
state reaction method. The crystal structures of the sintered phosphors were
consistent with orthorhombic crystallography with a Pmna space group. The chemical
compositions of the sintered phosphors were confirmed by energy dispersive X-ray
spectroscopy (EDS). Thermoluminescence (TL) kinetic parameters such as activation
energy, order of kinetics and frequency factors were calculated by the peak shape
method. Orange-red emission originating from the D-5(0)-F-7(J) (J=0, 1, 2, 3)
transitions of Eu3+ ions could clearly be observed after samples were excited at
395nm. The combination of these emissions constituted orange-red light as indicated
on the Commission Internationale de l'Eclairage (CIE) chromaticity diagram.
Mechanoluminescence (ML) intensity of the prepared phosphor increased linearly with
increasing impact velocity of the moving piston that suggests that these phosphors
can also be used as sensors to detect the stress of an object. Thus, the present
investigation indicates that the piezo-electricity was responsible for producing ML
in the prepared phosphor.
Cigarette smoke has been considered a major contributor to the pathogenesis of
chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth
muscle layer has been observed to be markedly thickened and the proliferation of
airway smooth muscle cells (ASMCs) was therefore used by the present study as a
model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to
various concentrations of CSE and the proliferation of the cells was analyzed by an
MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-
binding protein alpha (C/EBP-) in CSE-stimulated ASMCs were determined by
polymerase chain reaction and western blot analyses. In addition, the effects of
RNA interference (RNAi) to knockdown calreticulin and/or C/EBP- on ASMC
proliferation were studied. CSE was found to promote the proliferation of ASMCs,
which was associated with increased expression of calreticulin and decreased
expression of C/EBP-. Knockdown of calreticulin resulted in the upregulation of
C/EBP- and inhibition of cell proliferation, while simultaneous knockdown of C/EBP-
promoted cell proliferation. The present study revealed that CSE promoted the
proliferation of ASMCs, which was mediated by inhibition of C/EBP-. These findings
shed new light on airway remodeling in COPD and may provide novel approaches for
therapies.
Using data from the state and national Youth Risk Behavior Surveys for the period
1991-2005, Carpenter and Cook (2008) find a strong, negative relationship between
cigarette taxes and youth smoking. We revisit this relationship using four extra
waves of YRBS data (from 2007, 2009, 2011, and 2013). Our results suggest that
youths have become much less responsive to cigarette taxes since 2005. In fact, we
find little evidence of a negative relationship between cigarette taxes and youth
smoking when we restrict our attention to the period 2007-13. We conclude that
policy makers interested in reducing youth smoking may have to adopt alternative
strategies.
The stearoyl-acyl carrier protein desaturase (SAD) is a key enzyme that determines
the ratio of saturated to unsaturated fatty acids in higher plants. Using reverse
transcriptase polymerase chain reaction and rapid amplification of cDNA ends, a
full-length cDNA of SAD was obtained from developing leaves of Cinnamomum
longepaniculatum. Sequence analysis showed that the deduced amino acid sequence had
high similarity to other reported SADs. The CSAD gene was functionally expressed in
Escherichia coli, and the desaturating activity of the recombinant protein was
markedly detected when assayed in vitro by adding spinach ferredoxin. Southern blot
analysis indicated that the gene was a member of a small gene family. Northern
blotting revealed that the CSAD gene was highly expressed in developing leaves of
C. longepaniculatum. These results would provide opportunities for modifying fatty
acid composition in C. longepaniculatum.
Although it has long been established that estrogen alters circadian rhythms in
behavior, physiology, and reproductive functions in mammals, the molecular
mechanism for these effects remains unknown. To explore the possibility that
estrogen affects circadian rhythms by changing the expression of clock-related
genes, we investigated the effects of chronic treatment with 17 beta-estradiol (E2)
on the expression of Per1 and Per2 genes in the brain (suprachiasmatic nucleus and
cerebral cortex) and periphery (liver, kidney, and uterus) of ovariectomized rats
by means of in situ hybridization and northern blotting. In the brain, E2 treatment
advanced the peak of Per2 mRNA expression in the SCN; however, it failed to affect
the rhythm of Per2 mRNA expression in the CX and Per1 mRNA expression in both the
SCN and the CX. In nonreproductive peripheral tissues (liver and kidney), E2
delayed the phase and increased the amplitude of Per1 mRNA expression. In the
reproductive tissues (uterus), biphasic rhythms in Per1 and Per2 mRNA were observed
after E2 treatment. These findings suggest that the effects of estrogen are
different between central and peripheral clock in the brain, and between
reproductive and nonreproductive tissues in the periphery. (c) 2005 Wiley-Liss,
Inc.
Objective: Symptoms of airway diseases are often associated with specific times of
the day. For example, midnight worsening of cough is a frequent complaint of
patients with laryngitis and bronchitis. We speculate that these symptoms are under
the control of the circadian clock, and the clock genes in the airway epithelium
play some important roles. In the present study, we tried to prove the time
specific expressions of clock oscillating genes in the murine larynx. Materials and
methods: Adult wild-type C57/B16 mice and mCry1(-/-)mCry2(-/-) mutant mice were
used for this study. We employed immunohistochemistyr and/or Northern blotting for
examining the circadian expression of mPer1, mPer2, C/EBPbeta, HNF3beta, and MUC5b.
Results: The expression of mPer2 mRNA showed a strong day-night expression
difference, which was abolished after the lesion of the suprachiasmatic nucleus,
and in mCry1(-/-)mCry2(-/-) mutant mice. mPER1 and mPER2 proteins both showed very
similar expression profiles in the epithelium and submucosal glands with a peak in
the evening and a trough in the early morning. Other nuclear proteins such as
C/EBPbeta and HNF3beta did not show the rhythms. MUC5b protein showed circadian
oscillation in the laryngeal submucosal gland. Conclusion: In this study, we
confirmed the existence of a local laryngeal clock which is controlled by the
central clock in the suprachiasniatic nucleus. MUC5b protein in the submucosal
mucous gland also showed circadian rhythm. We consider that these rhythmic
expressions may cause the time specific symptoms among laryngeal diseases. (C) 2008
Elsevier Ireland Ltd. All rights reserved.
A switchable operational amplifier (opamp) is examined in this brief. It is based
on a current-mirror opamp with switchable transconductance values. Contrary to
switched opamp (SO) and partial SO, it can be used to realize both half-delay and
full-delay switched-capacitor integrators. The added circuit design complexity is
shown to be minimal. Optimal switching is developed in this brief. It is also shown
in this brief that the absolute average power consumption can be less as compared
with an SO design. The experimental results of a delta-sigma modulator prototype
(designed in 1-V 65-nm CMOS), employing the designated switchable-opamp technique,
show power reduction without any degradation in SNDR (58.5 dB) or SFDR (67 dB).
Circulating tumor cells (CTC) have become a field of interest for oncologists based
on the premise that they constitute the underpinning for metastatic dissemination.
The lethal nature of cancer is no longer attributed to solid tumor formation, but
rather to the process of metastasis; shifting the focus of current studies towards
the isolation and identification of metastatic progenitors, such as CTCs. CTCs
originate from primary tumor masses that undergo morphologic and genetic
alterations, which involve the release of mesenchymal-like cancer cells into the
bloodstream, capable of invading nearby tissues for secondary tumor development.
Cancerous cells contained in the primary tumor mass acquire the motile mesenchymal
phenotype as a result of the Epithelial-to-Mesenchymal Transition, where
substantial variations in protein expression and signaling pathways take place.
CFCs that migrate from the primary tumor, intravasate into the systemic
vasculature, are transported through the bloodstream, and invade tissues and organs
suitable for secondary tumor development. While only a limited number of CTCs are
viable in the bloodstream, their ability to elude the immune system, evade
apoptosis and successfully metastasize at secondary tumor sites, makes CTCs
promising candidates for unraveling the triggers that initiates the metastatic
process. In this article, these subjects are explored in greater depth to elucidate
the potential use of CFCs in the detection, disease staging and management of
metastatic melanoma. (C) 2017 Elsevier B.V. All rights reserved.
Patient-Reported Outcomes Measurement Information System (PROMIS) tools can
identify health-related quality of life (HRQOL) domains that could differentially
affect disease progression. Cirrhotics are highly prone to hospitalizations and re-
hospitalizations, but the current clinical prognostic models may be insufficient,
and thus studying the contribution of individual HRQOL domains could improve
prognostication. Analyze the impact of individual HRQOL PROMIS domains in
predicting time to all non-elective hospitalizations and re-hospitalizations in
cirrhosis. Outpatient cirrhotics were administered PROMIS computerized tools. The
first non-elective hospitalization and subsequent re-hospitalizations after
enrollment were recorded. Individual PROMIS domains significantly contributing
toward these outcomes were generated using principal component analysis. Factor
analysis revealed three major PROMIS domain groups: daily function (fatigue,
physical function, social roles/activities and sleep issues), mood (anxiety, anger,
and depression), and pain (pain behavior/impact) accounted for 77% of the
variability. Cox proportional hazards regression modeling was used for these groups
to evaluate time to first hospitalization and re-hospitalization. A total of 286
patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were
enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths
(IQR 22-47), during which 31% were hospitalized [median IQR mths 12.5 (3-27)] and
12% were re-hospitalized [10.5 mths (3-28)]. Time to first hospitalization was
predicted by HE, HR 1.5 (CI 1.01-2.5, p = 0.04) and daily function PROMIS group HR
1.4 (CI 1.1-1.8, p = 0.01), independently. In contrast, the pain PROMIS group were
predictive of the time to re-hospitalization HR 1.6 (CI 1.1-2.3, p = 0.03) as was
HE, HR 2.1 (CI 1.1-4.3, p = 0.03). Daily function and pain HRQOL domain groups
using PROMIS tools independently predict hospitalizations and re-hospitalizations
in cirrhotic patients.
Patients with decompensated cirrhosis have high morbidity and are commonly
hospitalized with acute kidney injury. We examined serum levels of Siglec-7, a
transmembrane receptor that regulates immune activity, as a biomarker for mortality
in patients with cirrhosis and acute kidney injury. Serum Siglec-7 was measured in
hospitalized patients with cirrhosis and acute kidney injury, as well as in
reference groups with acute liver injury/acute kidney injury, cirrhosis without
acute kidney injury, and sepsis without liver disease. Clinical characteristics and
subsequent outcomes were examined using univariate and multivariable analyses
according to initial Siglec-7 levels. Primary outcome was death by 90 days. One
hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute
kidney injury and were used in the primary analysis. Average Model for End-Stage
Liver Disease (MELD) score was 24 [95 % CI 23, 26], and serum creatinine was 2.5
[2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and
MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of
1.96 [1.04, 3.69; p = 0.04]. There was no difference in Siglec-7 levels by etiology
of AKI (p = 0.24). Addition of serum Siglec-7 to MELD score improved discrimination
for 90-day mortality [category-free net reclassification index = 0.38 (p = 0.04);
integrated discrimination increment = 0.043 (p = 0.04)]. Serum Siglec-7 was
associated with increased mortality among hospitalized patients with cirrhosis and
acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination
to predict 90-day mortality.
Platinum drugs remain the backbone of many antineoplastic regimens. Among the
numerous chemical or pharmacological effects of platinum drugs, some aspects tend
to be under-reported. Thus, this perspective paper intends to stress some neglected
properties of platinum drugs: first, the physico-chemical characteristics (aquation
reaction kinetics) that determine site-specific toxicity; second, the impact on RNA
molecules. Knowledge of the RNA world' has dramatically changed our understanding
of cellular and molecular biology. The inherent RNA-crosslinking properties should
make platinum-based drugs interact with coding and non-coding RNAs. Third, we will
discuss the impact on the immune system, which is now recognized to substantially
contribute to chemotherapy efficacy. Together, platinum drugs are in fact old
drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave
the way to new drugs or an improved application of the already existing compounds.
The newly discovered Citrus leprosis virus cytoplasmic type 2 (CiLV-C2) is one of
the causal virus of citrus leprosis disease complex; which leads to substantial
loss of citrus production in the states of Meta and Casanare of Colombia. Specific
and sensitive detection methods are needed to monitor the dissemination of CiLV-C2
in Colombia, and to prevent introduction of CiLV-C2 to other citrus growing
countries. Toward this end, putative coat protein gene (CPG) of CiLV-C2 was
amplified from CiLV-C2 infected citrus tissues. The CPG was cloned, expressed and
purified a recombinant coat protein of 31 kDa which used to generate monoclonal
antibodies and polyclonal antisera. Four monoclonal antibodies and two polyclonal
antisera were selected as being specific following Western blotting. The monoclonal
antibody MAb E5 and polyclonal antiserum PAb UF715 were selected testing with an
extract of CiLV-C2 infected leaves using triple antibody sandwich enzyme-linked
immunosorbent assay (TAS-ELISA). In addition, an immunocapture RT-PCR was
standardized using MAb E5 for specific and sensitive detection of CiLV-C2. The
standardized TAS-ELISA and IC-RT-PCR were able to detect CiLV-C2 in the extracts of
symptomatic citrus leprosis tissues up to the dilutions of 1:160 and 1:2580,
respectively. Result demonstrated that CiLV-C2 is present in citrus orchards in
Meta and Casanare citrus growing areas of Colombia. TAS-ELISA could be used for
routine detection of CiLV-C2, epidemiological studies, and for border inspections
for quarantine purposes. IC-RT-PCR could be valuable for CiLV-C2 validation and
viral genome analysis. (C) 2017 Elsevier B.V. All rights reserved.
Citrus tristeza virus (CTV) is a major pathogen of Citrus. A single dominant gene
Ctv present in the trifoliate relative of Citrus, Poncirus trifoliata confers broad
spectrum resistance against CTV. Refinement of genetic maps has delimited this gene
to a 121 kb region, comprising of ten candidate Ctv resistance genes. The ten
candidate genes were individually cloned in Agrobacterium based binary vector and
transformed into three CTV susceptible grapefruit varieties. Two of the candidate
R-genes, R-2 and R-3 are exclusively expressed in transgenic plants and in Poncirus
trifoliata, while five other genes are also expressed in non-transformed Citrus
controls. Northern blotting with a CTV derived probe for assessment of infection in
virus inoculated plants over a span of three growth periods, each comprising of six
to eight weeks, indicates either an absence of initiation of infection or it's slow
spread in R-2 plant lines or an initial appearance of infection and it's subsequent
obliteration in some R-1 and R-4 plant lines. Limited genome walk up- and
downstream form R-1 gene, based on it's 100% sequence identity between Poncirus and
Citrus, indicates promoter identity of 92% between the two varieties. Further
upstream and downstream sequencing indicates the presence of an O-methyl
transferase and a Copia like gene respectively in Citrus instead of the amino acid
transporter like gene upstream and a sugar transporter like gene downstream in
Poncirus. The possibility of recombinations in the resistance locus of Citrus and
the need for consistent monitoring for virus infection and gene expression in the
transgenic Citrus trees is discussed.
MicroRNAs (miRNAs) are a new family of small RNA molecules found in plants and
animals. We developed a comprehensive strategy for identifying new miRNA homologues
by mining the repository of available citrus expressed sequence tags (ESTs). By
adopting a range of filtering criteria, we identified a total of 38 potential
miRNAs - nine, five, nine and 15 miRNAs in Citrus trifoliata (ctr-miRNAs), C.
clementina (ccl-miRNAs), C. reticulata (crt-miRNAs) and C. sinensis (csi-miRNAs),
respectively - from more than 430,000 EST sequences in citrus. Using the potential
miRNA sequences, we conducted a further BLAST search of the mRNA database and found
six potential target genes in these citrus species. Eight miRNAs were selected in
order to verify their existence in citrus using Northern blotting, and the
functions of several miRNAs in miRNA-mediated gene regulation are experimentally
suggested. It appears that all these miRNAs regulate expression of their target
genes by cleavage, which is the most common situation in gene regulation mediated
by plant miRNAs. Our achievement in identifying new miRNAs in citrus provides a
powerful incentive for further studies on the important roles of these miRNAs.
The study of microRNA (miRNA), a component of low molecular weight RNA (LMW RNA),
has received increasing attention in recent years. A critical prerequisite in miRNA
studies is acquisition of high quality LMW RNA. LMW RNA is generally obtained from
total RNA or from total nucleic acids solutions. Most traditional methods for LMW
RNA isolation involve many steps and chemical reagents which upon degradation may
negatively affect results. We employed a simple and quick method involving trizol
for total RNA extraction from citrus tissues, then generation of LMW RNA using 4M
LiCl, which have been successfully utilized in studies in our laboratory. Compared
with traditional methods, this method is less expensive and produced high RNA
yields while avoiding the use of phenol or other toxic reagents. In addition, the
entire procedure can be completed within 4 hours with many samples being processed
simultaneously. Therefore, this is a practical and efficient method for LMW RNA
extraction from woody fruit crops containing high levels of polysaccharide and
polyphenolics. Using the extracted LMW RNA, miRNAs were successfully detected and
characterized by reverse transcriptase polymerase chain reaction (RT-PCR) and
Northern blotting.
MicroRNAs (miRNAs) are a class of non-protein-coding small RNAs. Considering the
conservation of many miRNA genes in different plant genomes, the identification of
miRNAs from non-model organisms is both practicable and instrumental in addressing
miRNA-guided gene regulation. Citrus is an important staple fruit tree, and
publicly available expressed sequence tag (EST) database for citrus are increasing.
However, until now, little has been known about miRNA in citrus. In this study, 27
known miRNAs from Arabidopsis were searched against citrus EST databases for miRNA
precursors, of which 13 searched precursor sequences could form fold-back
structures similar with those of Arabidopsis. The ubiquitous expression of those 13
citrus microRNAs and other 13 potential citrus miRNAs could be detected in citrus
leaf, young shoot, flower, fruit and root by northern blotting, and some of them
showed differential expression in different tissues. Based on the fact that miRNAs
exhibit perfect or nearly perfect complementarity with their target sequences, a
total of 41 potential targets were identified for 15 citrus miRNAs. The majority of
the targets are transcription factors that play important roles in citrus
development, including leaf, shoot, and root development. Additionally, some other
target genes appear to play roles in diverse physiological processes. Four target
genes have been experimentally verified by detection of the miRNA-mediated mRNA
cleavage in Poncirus trifoliate. Overall, this study in the identification and
characterization of miRNAs in citrus can initiate further study on citrus miRNA
regulation mechanisms, and it can help us to know more about the important roles of
miRNAs in citrus.
This paper introduces the adaptive slope compensation method into the digital
clamping current control at various input voltages to improve the power factor (PF)
and the total harmonic distortion (THD) of the universal input. The controller
conducts a phase-management mechanism for various input voltages and load
conditions to raise the circuit conversion efficiency. The optimal switching timing
for one-and two-phase operations can be determined from the power loss
distribution. A digital signal processor chip TMS320F28035 is used to implement the
digital platform. A 300-W laboratory prototype with a universal line voltage 80-V
dc output voltage is designed and tested to verify the feasibility. The values of
efficiency from light load (10% of rated power) to full load at 115- and 230-V
inputs are greater than 95%. PF values from medium to full load are greater than
0.94. Input current harmonics also meet the norm of IEC 61000-3-2 Class D.
In this paper, a three-stage class AB operational transconductance amplifier (OTA)
with large slew rate is presented. The reversed nested Miller compensation
technique is used to stabilize the proposed OTA, allowing the slew rate enhancement
to be achieved by using class AB input and output stages. A flipped-voltage
follower cell in the first stage in combination with a switched-capacitor level
shifter in the last stage are utilized to implement the class AB operation. Circuit
level simulation results are provided using HSPICE and a 90 nm CMOS technology
which show 306 % enhancement in the large-signal FoM with approximately the same
power dissipation compared to the class A OTA. The achieved settling time with 0.02
% accuracy for the proposed class AB and conventional class A OTAs are 7.5 and 15.3
ns, respectively.
In this paper we extend the figures of merit for class AB symmetrical OTAs to the
fully differential case and compare topologies from the literature. This analysis
shows that the power consumption of the CMFB can have a significant role in
determining the efficiency of the OTA, but on the other hand a CMFB is needed both
to set the desired output common mode voltage and to improve the CMRR. We propose
the complementary triode CMFB, i.e. a triode CMFB applied both at the NMOS and PMOS
current mirrors, as suitable for class AB symmetrical OTAs, and show some case
studies in deep submicron CMOS technology to assess the effectiveness of the
proposed solution. Copyright (C) 2015 John Wiley & Sons, Ltd.
In recent years, it is desired that the bandwidth of a class-D amplifier is widened
using sampling frequencies as low as possible. For example, it is expected in the
application of the power amplifier of vibration generator that the bandwidth is
kept 5[kHz] within the load impedance infinity similar to 2 [Omega]. In this paper,
it is shown that this demand to the class-D amplifier can be attained by an A2DOF
(Approximate 2-Degree-Of-Freedom) digital controller with 200[kHz] switching and
sampling frequencies. The controller is implemented by a FPGA and it is shown from
experiments that this demand is attained enough.
The present study reports US independent classic articles published by American
scientists from 1900 to 2014. We examined those articles that had been cited at
least 1000 times since publication to the end of 2014 using the Science Citation
Index Expanded in the Web of Science (WoS). We also applied a bibliometric
indicator, the Y-index, to assess the contributions of the authors of these
articles. The results showed that 4909 classic articles were published between 1916
and 2013, and that the most productive categories from the WoS were
multidisciplinary sciences, biochemistry and molecular biology, and general and
internal medicine. Science published most of these articles, and the three most
productive institutions were Harvard University, Massachusetts Institute of
Technology and Stanford University. The physicist, Edward Witten was the most
prolific author and an article written by the biochemist, Marion Bradford at
University of Georgia in 1976 had the highest number of citations. In addition, the
article by Perdew, Burke and Ernzerhof at Tulane University had the highest number
of citations in 2014.
Renewable energy projects in Korea have two avenues that provide subsidies to
increase their financial viability. Feed-in-Tariffs (FITs) offer cost based prices
for renewable electricity to compete with conventional energy producers. The Clean
Development Mechanism (CDM) issues certified emission reduction (CER) credits that
generate additional revenues, enhancing renewable projects' return on investment.
This study investigated how these subsidies impact the financial returns on Korea's
CDM projects. An investment analysis was performed on four cases including solar,
hydropower, wind and landfill gas projects. Revenues from electricity sales, FITs
and CERs were compared using financial indicators to measure their relative
contributions on profitability. Results indicate that CDM is partial towards large
scale projects with high emission reductions. Moreover, conflicts with FIT schemes
can deter small scale, capital intensive projects from pursuing registration. The
analysis highlights CDM's bias for particular project types, which is in part due
to its impartiality towards carbon credit prices. It also reveals that Korea, a key
benefactor of CDM, is susceptible to such biases, as demonstrated by the
disproportionate distribution of issued CERs. Improving incentives for bundled,
small scale projects, CER price differentiation, and excluding domestic subsidies
during additionality testing are proposed as possible reforms.
This review attempts to put together the sequential pathogenesis of VHL mutant
metastatic ccRCC with links between driver pathways, epigenetics, biochemistry and
immune evasion, with a translational perspective. We reflect on the gap between our
understanding of the molecular pathogenesis and currently accepted standard of care
in metastatic RCC, and present ideas to bridge the gap with better translational
research.Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all RCC, and
biallelic Von Hippel-Lindau (VHL) gene defects occur in 75% of sporadic ccRCC. The
etiopathogenesis of VHL mutant metastatic RCC, based on our understanding to date
of molecular mechanisms involved, is a sequence of events which can be grouped
under the following: (i) loss of VHL activity (germline/somatic mutation +
inactivation of the wild-type copy); (ii) constitutive activation of the hypoxia-
inducible factor (HIF) pathway due to loss of VHL activity and transcription of
genes involved in angiogenesis, epithelial-mesenchymal transition, invasion,
metastasis, survival, anaerobic glycolysis and pentose phosphate pathway; (iii)
interactions of the HIF pathway with other oncogenic pathways; (iv) genome-wide
epigenetic changes (potentially driven by an overactive HIF pathway) and the
influence of epigenetics on various oncogenic, apoptotic, cell cycle regulatory and
mismatch repair pathways (inhibition of multiple tumor suppressor genes); (v)
immune evasion, at least partially caused by changes in the epigenome. These
mechanisms interact throughout the pathogenesis and progression of disease, and
also confer chemoresistance and radioresistance, making it one of the most
difficult metastatic cancers to treat. This article puts together the sequential
pathogenesis of VHL mutant ccRCC by elaborating these mechanisms and the interplay
of oncogenic pathways, epigenetics, metabolism and immune evasion, with a
perspective on potential therapeutic strategies. We reflect on the huge gap between
our understanding of the molecular biology and currently accepted standard of care
in metastatic ccRCC, and present ideas for better translational research involving
therapeutic strategies with combinatorial drug approach, targeting different
aspects of the pathogenesis.
This paper analyzes the impacts of flexible demands on day-ahead market outcomes in
a system with significant wind power production. We use a two-stage stochastic
market-clearing model, where the first stage represents the day-ahead market and
the second stage represents the real-time operation. On one hand, flexibility of
demands is beneficial to the system as a whole since such flexibility reduces the
operation cost, but on the other hand, shifts in demands from peak periods to off-
peak periods may influence prices in such a way that demands may not be willing to
provide flexibility. Specifically, we investigate the impacts of different degree
of demand flexibility on day-ahead prices. A number of scenarios modeling the
uncertainty associated with wind production at the operation stage, and
nonconvexities due to start-up costs of generators and their minimum power outputs
are taken into account.
The changes in endopolygalacturonase (endo-PG) levels and endo-PG expression in
nonmelting flesh (NMF) and melting flesh (MF) peach fruits (Prunus persica) during
softening were studied. The endo-PG gene was analysed to identify polymorphisms
exploitable for early marker-assisted selection WAS) of flesh texture. The role of
endo-PG in softening was assessed by western and northern blotting and by
biochemical analyses. Polymorphisms in the endo-PG gene were revealed by reverse
transcription-polymerase chain reaction (RT-PCR) and sequencing. An endo-PG protein
was detected in both NMF and MF fruits. The levels of this endo-PG protein were
higher and increased with softening in MF fruits, but remained lower and were
constant in NMF fruits. The different levels of endo-PG appeared to be caused by
the differential expression of an endo-PG gene, whose open-reading frame (ORF)
showed five single nucleotide polymorphisms (SNPs) in NMF 'Oro A' compared with MF
'Bolero'. One of these SNPs allowed us to determine the allelic configuration at
the melting flesh M locus and also seemed to be exploitable for early MAS in other
NMF/MF phenotypes. The NMF phenotype does not seem to be caused by a large deletion
of the endo-PG gene.
Background: Carbohydrates, also called glycans, play a crucial but not fully
understood role in plant health and development. The non-template driven formation
of glycans makes it impossible to image them in vivo with genetically encoded
fluorescent tags and related molecular biology approaches. A solution to this
problem is the use of tailor-made glycan analogs that are metabolically
incorporated by the plant into its glycans. These metabolically incorporated probes
can be visualized, but techniques documented so far use toxic copper-catalyzed
labeling. To further expand our knowledge of plant glycobiology by direct imaging
of its glycans via this method, there is need for novel click-compatible glycan
analogs for plants that can be bioorthogonally labelled via copper-free techniques.
Results: Arabidopsis seedlings were incubated with azido-containing monosaccharide
analogs of N-acetylglucosamine, N-acetylgalactosamine, L-fucose, and L-
arabinofuranose. These azido-monosaccharides were metabolically incorporated in
plant cell wall glycans of Arabidopsis seedlings. Control experiments indicated
active metabolic incorporation of the azido-monosaccharide analogs into glycans
rather than through non-specific absorption of the glycan analogs onto the plant
cell wall. Successful copper-free labeling reactions were performed, namely an
inverse-electron demand Diels-Alder cycloaddition reaction using an incorporated N-
acetylglucosamine analog, and a strain-promoted azide-alkyne click reaction. All
evaluated azido-monosaccharide analogs were observed to be non-toxic at the used
concentrations under normal growth conditions. Conclusions: Our results for the
metabolic incorporation and fluorescent labeling of these azido-monosaccharide
analogs expand the possibilities for studying plant glycans by direct imaging.
Overall we successfully evaluated five azido-monosaccharide analogs for their
ability to be metabolically incorporated in Arabidopsis roots and their imaging
after fluorescent labeling. This expands the molecular toolbox for direct glycan
imaging in plants, from three to eight glycan analogs, which enables more extensive
future studies of spatiotemporal glycan dynamics in a wide variety of plant tissues
and species. We also show, for the first time in metabolic labeling and imaging of
plant glycans, the potential of two copper-free click chemistry methods that are
bio-orthogonal and lead to more uniform labeling. These improved labeling methods
can be generalized and extended to already existing and future click chemistry-
enabled monosaccharide analogs in Arabidopsis.
Aim: The purpose of this study was to examine clients' perspectives regarding the
helpful aspects of pluralistic therapy for depression. Method: Thirty-nine clients
received psychological treatment in a multi-site study exploring alternative
interventions to standardised 'evidence-based' approaches. Eighteen of them
consented to a face-to-face or telephone change interview at the end of their
treatment. Change interviews aim to elicit clients' perspective regarding changes
that they noticed during, and after, therapy and also the possible causes of these
changes. Their descriptions were transcribed and analysed thematically using
explicit coding of themes which were audited by the research team. Findings: The
data were categorised in three a priori domains consisting of specific themes. The
first domain constitutes of client-originated helpful factors including clients'
positive perspectives of therapy, clients' overall effort to change and clients'
contribution in the decision-making process of therapy. Therapists were perceived
as helpful when they were accepting and respectful, empathic, responding to
clients' needs, making clients feel comfortable, challenging, empowering, using
techniques, flexible and reassuring. Treatment outcomes such as change in
perspectives, behaviour and response to problems as well as increased insight were
also considered helpful factors of therapy. Conclusion: These findings suggest that
clients in pluralistic therapy are active agents of change and their willingness to
engage with treatment is crucial. Helping clients feel comfortable by creating a
safe therapeutic environment, challenging dysfunctional patterns associated with
depression and empowering them to believe that change is possible through
reassurance and non-intrusive guidance were considered beneficial.
Although species traits have the potential to disentangle long-term effects of
multiple, potentially confounded drivers in ecosystems, this issue has received
very little attention in the literature. We aimed at filling this gap by assessing
the relative effects of hydroclimatic and water quality factors on the trait
composition of invertebrate assemblages over 30 years in the Middle Loire River
(France). Using a priori predictions on the long-term variation of trait-based
adaptations over the three decades, we evaluated the ability of invertebrate traits
to indicate the effects of warming, discharge reduction and water quality
improvement. Hydroclimatic and water quality factors contributed to up to 65% of
the variation in trait composition. More than 70% of the initial trait response
predictions made according to observed long-term hydroclimatic changes were
confirmed. They supported a general climate-induced trend involving adapted
resistance and resilience strategies. A partial confounding effect of water quality
improvement acting on trophic processes was also highlighted, indicating that
improved water quality management can significantly help to reduce some adverse
effects of climate change. This trait-based approach can have wider implications
for investigating long-term changes driven by multiple, potentially confounded
factors, as frequently encountered in the context of global change.
Electricity is the basic tool that drives industrialization, technological
advancement, engineering transformation and economic growth all over the world. The
situation of Nigeria's electricity power sector is one that has defied virtually
every effort made to resurrect it from its state of dilapidation. A major concern
is "can there ever be stable and cost effective electricity in Nigeria?" The
authors are positive this can be realised, but not without considering other forms
of electricity energy resources available in Nigeria other than the conventional
sources of electricity which is currently the mainstay. A deliberate transition
from conventional sources of electricity energy to renewable and environmental
friendly sources is critical for national development, even though recent
development show the Nigerian government is backsliding in adopting renewable
energy technologies. This paper will be used to highlight the different sources of
renewable energy which is critical to solve the lingering problem of electricity
generation in Nigeria. Hence, based on the literature, modeled scenarios and field
experience, the authors discovered it is much easier for individuals to drive this
transition to 100% renewable energy than to continue to depend on government
forever.
This paper focuses on the effectiveness of passive adaptation measures against
climate change, in the medium (2036-2065) and long term (2066-2095), for three case
studies located in Florence (central Italy). In order to identify and highlight the
passive measures which can provide comfort conditions with the lowest net heating
and cooling energy demand, the input assumptions consider a constant thermal
comfort level and don't take into account either the effect of HVAC system's
performance and the degradation of the materials by ageing. The study results show
that, in case of poorly insulated buildings, on the medium term, the reduction of
energy needed for heating could be bigger than the increase for cooling, resulting
in a total annual net energy need decrease, while in the long term the opposite
happens. Conversely, considering a high level of thermal insulation, due to the
large increase in cooling demand, the total annual energy need rises in both
periods. Furthermore, attention should be paid to internal loads and solar gains
that, due to the projected climate change, could become main contributors to the
energy balance. In general, since the magnitude of energy need increase for cooling
and decrease for heating is very significant on the long term, and varies in
function of the type of building, the passive measure adopted and the level of
thermal insulation, the research results lead to pay close attention to different
types of energy refurbishment interventions, that should be selected in function of
their effectiveness over time.
Introduction: There are now more than 50,000 hospitalists working in the United
States. Limited empiric research has been performed to characterize clinical
excellence in hospital medicine. We conducted a qualitative study to discover
elements judged to be most pertinent to excellence in clinical care delivered by
hospitalists. Methods: The chiefs of hospital medicine at five hospitals were asked
to identify their "clinically best" hospitalists. Data collection, in the form of
one-on-one interviews, was directed by an interview guide. Interviews were
transcribed verbatim, and the informants' perspectives were analyzed using editing
analysis to identify themes. Results: A total of 26 hospitalists were interviewed.
The mean age of the physicians was 38 years, 13 (50%) were women, and 16 (62%) were
non-white. Seven themes emerged that related to clinical excellence in hospital
medicine: communicating effectively, appreciating partnerships and collaboration,
having superior clinical judgment, being organized and efficient, connecting with
patients, committing to continued growth and development, and being professional
and humanistic. Discussion: This qualitative study describes how respected
hospitalists think about excellence in clinical care in hospital medicine. Their
perspectives can be used to guide continuing medical education, so that offered
programs can pay attention to enhancing the skills of learners so they can develop
towards excellence, rather than using only competence as the desired target
objective.
The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs)
and the relationship of RVs to lung function, acute rejection (AR) and
opportunistic infections in these patients are not well known. We performed a
prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPSs) from
asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory
tract infectious disease (URTID), lower respiratory tract infectious disease
(LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall,
1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean
follow-up of 3.4 years (interquartile range 2.5-4.0 years). Approximately half of
URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused
by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of
nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function
changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case-
control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas
aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV)
replication or disease was associated with URTID (HR 2.53) in the previous 3 mo.
There was no association between RVs and Aspergillus spp. colonization or infection
(HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs.
LRTID produced significant lung function abnormalities. Associations were observed
between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and
between CMV replication or disease and URTID. A large prospective study of the
epidemiology of respiratory viruses in lung transplant recipients using molecular
assays demonstrates a very high incidence of respiratory viral infection and an
association between respiratory virus infectious diseases, immediate allograft
dysfunction, and the development of acute rejection and opportunistic infection.
DNA-encoded chemical library technology was developed with the vision of its
becoming a transformational platform for drug discovery. The hope was that a new
paradigm for the discovery of low-molecular-weight drugs would be enabled by
combining the vast molecular diversity achievable with combinatorial chemistry, the
information-encoding attributes of DNA, the power of molecular biology, and a
streamlined selection-based discovery process. Here, we describe the discovery and
early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase
(sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally
bioavailable, potent and selective inhibitor of sEH that has a long half life and
produced no serious adverse events in a first-time-in-human clinical study. To our
knowledge, GSK2256294 is the first molecule discovered from this technology to
enter human clinical testing and represents a realization of the vision that DNA-
encoded chemical library technology can efficiently yield molecules with favorable
properties that can be readily progressed into high-quality drugs.
The recent outbreak of Ebola virus disease in West Africa has led to more than
11,000 deaths, with a peak in mortality from August through December of 2014. A
meeting convened by the World Health Organization (WHO) in September 2014,
concluded that an urgent unmet need exists for efficacy and safety testing of the
Ebola virus vaccine candidates and that clinical trials should be expedited. These
vaccines could be used both in an outbreak setting and to provide long-term
protection in populations at risk of sporadic outbreaks. A number of vaccines have
been evaluated in phase 1 trials, but the two most advanced first-generation Ebola
vaccine candidates are the live replicating vesicular stomatitis virus (rVSV) and
the replication-defective chimpanzee adenovirus 3 (ChAd3). This review focuses on
these two vaccines in clinical development and discusses the future opportunities
and challenges faced in the licensure and deployment of Ebola virus vaccines. Crown
Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.
Breast cancer is the second leading cause of cancer death in women, affecting 1.7
million patients every year worldwide. As a result of its heterogeneous nature, the
genetic profile and associated clinical feature varies greatly among different
breast cancer subtypes. With the advancement of molecular biology, our
understanding of breast cancer has improved greatly in recent years. In this
review, we examine different types of breast cancer and summarize their clinical
features, current treatment schemes, and potential drug resistance profiles in
response to treatments. We believe that the understanding of the molecular
mechanisms of each treatment and subsequent drug resistance development will
eventually lead to the discovery of more effective and efficient second-line
therapeutics.
We have isolated the cDNA of Ca2+/H+ antiporter which was designated as Suaeda
salsa cation exchanger 1 (SsCAX1) from the C-3 halophyte S. salsa L. To ascertain
the location of SsCAX1 in the cell, a peptide-specific antibody to SsCAX1 was
prepared, and Western blotting analysis showed that it reacted only with a 48.8-kDa
protein from S. salsa vacuolar membrane. Furthermore, SsCAX1 could resume yeast
vacuolar Ca2+ transport mutants growth in high Ca2+ concentration (200 mM) culture
medium. Northern blotting analysis showed that SsCAX1 expression was mainly found
in the leaves and stems and slightly in the roots of S. salsa seedlings. Moreover,
SsCAX1 expression levels and the protein amounts were significantly upregulated by
CaCl2 and NaCl treatment, respectively. In addition, the upregulation of the
expression levels of V-H+-ATPase subunit c coordinated with the expression levels
of the Ca2+/H+ antiporter under salinity. These results suggested that SsCAX1 from
halophyte S. salsa might be a Ca2+ transporter at tonoplast and plays a key role in
maintaining cytosolic Ca2+ homeostasis under saline condition.
It is known that the neutral/cytosolic alpha-mannosidase (Man2c1) which can cleave
alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues, is stimulated by
cobalt and is inhibited by furanose analogues swainsonine (SW) and 1,4-dideoxy-1,4-
imino-D-mannitol (DIM). The enzyme is involved in the degradation of
oligomannosides derived from dolichol intermediates and the degradation of newly
synthesized glycoproteins. An immunological relationship has been demonstrated
between the rat endoplasmic reticulum alpha-mannosidase and the cytosolic alpha-
mannosidase. In fact antibodies raised against the soluble alpha-mannosidase
recognized the membrane form of the ER alpha-mannosidase. A cDNA encoding the mouse
cytosolic alpha-mannosidase was obtained by RZPD (Deutsches Ressourcenzentrum fur
Genomforschung GmbH), Berlin, Germany. Comparison of the mouse genomic sequence
with the cDNA sequence revealed the presence of 25 introns within the cytosolic
alpha-mannosidase gene. The gene spans 11.5 kb from the major transcription
initiation site to the RNA cleavage site. The transcription initiation site of
mouse cytosolic alpha-mannosidase was mapped to 170 bases upstream of the ATG codon
using 5' RACE. Northern blotting analysis revealed expression of a major transcript
of 3.8 kb in all tissues examined. COS cells transfected with the cDNA showed a 20-
fold increase in cytosolic alpha-mannosidase activity. This enzyme activity was
stimulated by cobalt and inhibited by DIM and EDTA. Furthermore we demonstrated
that the expressed enzyme was active towards the radiolabeled substrate Man9GlcNAc1
giving the final product Man5GlcNAc1 through the formation of Man8GlcNAc1 isomer C
as intermediate. (c) 2006 Elsevier B.V. All rights reserved.
Parasites are significant groups for carcinogenesis among which liver flukes,
including Opisthorchis viverrini and Clonorchis sinensis, are typical
representatives causing cholangiocarcinoma (CCA), the second most common primary
hepatic malignancy with dismal prognosis. O. viverrini is prevalent in Southeast
Asia, infecting 10 million people while C. sinensis has a wider distribution in
East Asia and several Southeast Asian countries, affecting more than 35 million
people's health. These two worms have some common characteristics and/or
discrepancies in life cycle, genome, and transcriptome. As hot spots in recent
years, genome and transcriptome research has extracted numerous novel fluke worm-
derived proteins, which are excellent for carcinogenic exploration. However, just a
handful of these studies have focused on the metabolic pathway. In this study, the
main mechanisms of carcinogenesis of both worms, in terms of mechanical damage,
metabolic products and immunopathology, and other possible pathways, will be
discussed in detail. This review retrospectively describes the main traits of C.
sinensis and O. viverrini, their molecular biology and core carcinogenic mechanisms
in a contrast pattern.
Clopidogrel resistance in patients with acute coronary syndrome (ACS) is one of the
key causes of recurrent cardiovascular disease (CVD) events after percutaneous
coronary intervention (PCI). Clopidogrel targets the platelet membrane receptor
P2RY12 to inhibit platelet aggregation via adenosine diphosphate (ADP). This study
aimed to investigate the relationships between P2RY12 polymorphisms and the risk of
clopidogrel resistance and adverse CVD events after PCI. From January 2015 to
December 2014, patients who had been diagnosed with ACS undergoing PCI and treated
with clopidogrel were recruited for this prospective cohort study (N=498). Data
regarding demographics, medication intake, and ACS lesion were recorded, and whole
blood samples were collected for biochemical tests, ADP-induced platelet
aggregation ratio detection, and P2RY12 genotyping. P2RY12 genotyping was performed
by polymerase chain reaction. The left ventricular ejection fraction was calculated
by echocardiography. After 3 to 12 months of follow-up, data regarding any adverse
CVD event or death were recorded. The allele frequencies for the T variation
alleles in C34T and G52T of P2RY12 were 20.3% and 11.6%, respectively. Patients
with T variations at C34T or G52T of P2RY12 had a significantly higher risk of
clopidogrel resistance (C34T: P<0.001; G52T: P=0.003) and total cardiovascular
events (C34T: P=0.013; G52T: P=0.018) compared to those with the wild-type
genotype. Moreover, multivariable logistic regression showed that patients with the
T variations in C34T (odds ratio [OR]: 2.89 (95% confidence interval [CI]: 1.48-
5.64), P=0.002) and G52T (OR: 3.68 [95% CI: 1.71-7.92], P=0.001) also had a
significantly higher risk of clopidogrel resistance. Also, the T variations in C34T
(OR: 2.68 [95% CI: 1.07-6.73], P=0.035) and G52T (OR: 5.64 [95% CI: 1.52-20.88],
P=0.010) significantly increased the risk of post-PCI CVD events after accounting
for confounding factors. The P2RY12 gene polymorphisms C34T and G52T were
significantly associated with a higher risk of clopidogrel resistance and
sequential cardiovascular events in Chinese ACS patients after PCI.
Due to the higher attenuation of switching frequency current harmonics, the LCL
filter has been widely used in grid-connected inverters. To deal with the resonance
of the LCL filter, the capacitor current is usually fed back to damp the resonance
actively. However, the computation and pulsewidth modulation (PWM) delays in the
digital control system have a significant influence on the active damping method,
resulting in poor system robustness. Meanwhile, these delays also reduce the
control bandwidth greatly and thus impose a severe limitation on the low-frequency
gains. In this paper, a real-time computation method with dual sampling mode is
proposed to remove the computation delay from the inner active damping loop and the
outer grid-current control loop simultaneously; thus, the system robustness and the
control performance can be greatly improved. Moreover, the time duration between
the sampling instant and the switching transition of the inverter bridge is
extended by the proposed method, which effectively prevents the switching noise
distorting the sampled signals. Therefore, the noise immunity of the inverter is
also improved greatly. Experimental results from a 6-kW LCL-type single-phase grid-
connected inverter confirm the theoretical expectations and the effectiveness of
the proposed method.
Preventing voltage waveform distortion in multifrequency current control during
saturated operation is a difficult problem, which so far has been only partially
solved. In this paper, a scheme based on the principle of realizable references is
proposed. As the converter enters saturated operation, an algorithm recalculates
the converter-current reference such that unsaturated operation returns, i.e., the
converter-voltage reference does not exceed the space-vector-modulation hexagon.
Distortion is thereby avoided, as is integrator windup.
Plant residues are one of the main sources of soil organic matter in paddy fields,
and elucidation of the bacterial communities decomposing plant residues was
important to understand their function and roles, as the microbial decomposition of
plant residues is linked to soil fertility. We conducted a DNA stable isotope
probing (SIP) experiment to elucidate the bacterial community assimilating 13-
carbon (C-13) derived from plant residue under an anoxic soil condition. In
addition, we compared the bacterial community with that under the oxic soil
condition, which was elucidated in our previous study (Lee et al. in Soil Biol
Biochem 43:814-822, 2011). We used the C-13-labeled dried rice callus cells as a
model of rice plant residue. A paddy field soil was incubated with unlabeled and C-
13-labeled callus cells. DNA extracted from the soils was subjected to buoyant
density gradient centrifugation to fractionate C-13-enriched DNA. Then, polymerase
chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) analysis of
bacterial 16S rDNA band patterns and band sequencing method were used to evaluate
bacterial community. DGGE analysis showed that the band patterns in the C-13-
enriched fractions were distinctly changed over time, while the changes in the
community structure before fractionation were minor. Sequencing of the C-13-labeled
DGGE bands revealed that Clostridia were a major group in the bacterial communities
incorporating the callus-derived carbon although Gram-negative bacteria, and
Actinobacteria also participated in the carbon flow from the callus under the
anoxic condition. The proportion of Gram-negative bacteria and Actinobacteria
increased on 14 days after the onset of incubation, suggesting that the callus was
decomposed by diverse bacterial members on this phase. When the bacterial groups
incorporating the C-13 were compared between under anoxic and oxic soil conditions,
the composition was largely different under the two opposite conditions. However,
some members of Gram-negative bacteria were commonly found under the anoxic and
oxic soil conditions. The majority of bacterial members assimilating the callus
carbon was Clostridia in the soil under anoxic conditions. However, several Gram-
negative bacterial members, such as Acidobacteria, Bacteroidetes, and
Proteobacteria, also participated in the decomposition of callus under anoxic soil
conditions. Our study showed that carbon flow into the diverse bacterial members
during the callus decomposition and the distinctiveness of the bacterial
communities was formed under the anoxic and oxic soil conditions.
A mutant strain of Clostridium beijerinckii, with high tolerance to ferulic acid,
was generated using atmospheric pressure glow discharge and high-throughput
screening of C. beijerinckii NCIMB 8052. The mutant strain M11 produced 7.24g/L of
butanol when grown in P2 medium containing 30g/L of glucose and 0.5g/L of ferulic
acid, which is comparable to the production from non-ferulic acid cultures (8.11g/L
of butanol). When 0.8g/L of ferulic acid was introduced into the P2 medium, C.
beijerinckii M11 grew well and produced 4.91g/L of butanol. Both cell growth and
butanol production of C. beijerinckii M11 were seriously inhibited when 0.9g/L of
ferulic acid was added into the P2 medium. Furthermore, C. beijerinckii M11 could
produce 6.13g/L of butanol using non-detoxified hemicellulosic hydrolysate from
diluted sulfuric acid-treated corn fiber (SAHHC) as the carbon source. These
results demonstrate that C. beijerinckii M11 has a high ferulic acid tolerance and
is able to use non-detoxified SAHHC for butanol production. (C) 2015 International
Union of Biochemistry and Molecular Biology, Inc.
Purpose of reviewNorovirus infection is an emerging chronic infection in
immunocompromised hosts. The aim of this review is to discuss the pathophysiology
of Norovirus infection and explore mechanistic models for chronic infection/shedder
state, especially in patients with immune deficiency diseases.Recent
findingsChronic Norovirus infection is increasingly associated with enteropathy
associated with both primary and secondary immune deficiency diseases. There is an
ongoing debate in the immune deficiency community whether it is truly a causative
agent for the enteropathy or it is an innocent bystander.We describe the historic
aspects of Norovirus infection, its immunology and viral structure and the basis
for preventive and vaccination strategies.We also postulate in this review a
disease model in immune deficiency subjects which creates a milieu for it to become
a chronic and explore newer frontiers for disease modification and
prevention.SummaryNorovirus is the most common cause of acute gastroenteritis in
general population but the factors that lead to its persistence in patients with
immune deficiency need further holistic studies. This should include host
assessment, microbiome signatures, and viral pathogenic factors assessment.
Background: Diarrhea, a common complication after solid organ transplant (SOT), is
associated with allograft failure and death. No evidence-based guidelines exist for
the evaluation of diarrhea in SOT recipients. We performed a cost analysis to
derive a testing algorithm for the diagnosis of community-onset diarrhea that
minimizes costs without compromising diagnostic yields. Design: A cost analysis was
performed on a retrospective cohort of 422 SOT admissions for community-onset
diarrhea over an 18-month period. A stepwise testing model was applied on a
population level to assess test costs relative to diagnostic yields. Results: Over
an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned
positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests
with the lowest cost per decrease in the false-omission rate (FOR) were stool
Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus
quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture
($6804). A time-to-event analysis found no significant difference in the length of
hospital stay between patients with and without NV testing (P=.520). Conclusions: A
stepwise testing strategy can reduce costs without compromising diagnostic yields.
In the first-stage testing, we recommend assessment for C.difficile,
cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal
episodes, second-stage evaluation should include stool NV PCR,
Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in
immunosuppressive therapy, and possibly endoscopy. Although NV testing had a
relatively low cost per FOR, we recommend NV testing during second-stage
evaluation, as an NV diagnosis may not lead to changes in clinical management or
further reductions in length of hospital stay.
Health care-onset health care facility-associated Clostridium difficile infection
(HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C.
difficile colonization and the inability of hospitals to limit testing to patients
with clinically significant diarrhea. We conducted a quasiexperimental study from
22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test
orders at an academic hospital. Real-time electronic patient data tracking was used
by the laboratory to enforce testing criteria (defined as the presence of diarrhea
[>= 3 un-formed stools in 24 h] and absence of laxative intake in the prior 48 h).
Outcome measures included C. difficile test utilization, HO-CDI incidence, oral
vancomycin utilization, and clinical complications. During the intervention, 7.1%
(164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence
of diarrhea and receipt of laxative therapy, respectively. C. difficile test
utilization decreased upon implementation from an average of 208.8 tests to 143.0
tests per 10,000 patient-days (P < 0.001). HO-CDI incidence rate decreased from an
average of 13.0 cases to 9.7 cases per 10,000 patient-days (P = 0.008). Oral
vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per
1,000 patient-days (P = 0.009). Clinical complication rates were not significantly
different in patients with 375 canceled orders compared with 869 episodes with
diarrhea but negative C. difficile results. Real-time electronic clinical data
tracking is an effective tool for verification of C. difficile clinical testing
criteria and safe reduction of inflated HO-CDI rates.
Clostridium kluyveri is unique in fermenting ethanol and acetate to butyrate,
caproate, and H-2. The genes encoding butyrate-producing enzymes, including
electron-bifurcating butyryl-CoA dehydrogenase/electron transfer flavoprotein
complex and NADH-dependent reduced ferredoxin:NADP(+) oxidoreductase, form a
cluster, which is preceded by a gene annotated as the transcriptional regulator
Rex. Northern blotting and RT-PCR experiments indicated that the gene cluster forms
a large transcriptional unit that possibly includes several small transcriptional
units. The deduced Rex protein contains a winged helix DNA-binding domain and a
Rossmann fold potentially interacting with NAD(H). Bioinformatics analysis revealed
that Rex can bind the promoter regions of numerous genes, which are involved in
carbon and energy metabolism, including NADH oxidation, hydrogen production, ATP
synthesis, butyrate formation, and succinate metabolism. Rex may regulate the
transcription of genes encoding certain transcriptional regulators and
transporters. Electrophoretic mobility shift and isothermal titration calorimetry
assays revealed that Rex specifically formed protein-DNA complexes with the
promoter regions of target genes, which could be inhibited by NADH but restored by
an excess amount of NAD(+). These results suggest that Rex plays a key role in the
carbon and energy metabolism of C. kluyveri as a global transcriptional regulator
in response to the cellular NADHINAD' ratio. (C) 2016 Elsevier B.V. All rights
reserved.
A load estimation algorithm based on k-means cluster analysis was developed. The
algorithm applies cluster centres - of previously clustered load profiles - and
distance functions to estimate missing and future measurements. Canberra,
Manhattan, Euclidean, and Pearson correlation distances were investigated. Several
case studies were implemented using daily and segmented load profiles of aggregated
smart meters. Segmented profiles cover a time window that is less than or equal to
24 h. Simulation results show that Canberra distance outperforms the other distance
functions. Results also show that the segmented cluster centres produce more
accurate load estimates than daily cluster centres. Higher accuracy estimates were
obtained with cluster centres in the range of 16-24 h. The developed load
'estimation algorithm can be integrated with state estimation or other network
operational tools to enable better monitoring and control of distribution networks.
(C) 2016 The Authors. Published by Elsevier Ltd.
Background: Bipolar disorder (BD) and schizophrenia (SZ) show substantial overlap.
It has been suggested that a subgroup of patients might contribute to these
overlapping features. This study employed a cross diagnostic cluster analysis to
identify subgroups of individuals with shared cognitive phenotypes. Method: 143
participants (68 BD patients, 39 SZ patients and 36 healthy controls) completed a
battery of EEG and performance assessments on perception, nonsocial cognition and
social cognition. A K-means cluster analysis was conducted with all participants
across diagnostic groups. Clinical symptoms, functional capacity, and functional
outcome were assessed in patients. Results: A two-cluster solution across 3 groups
was the most stable. One cluster including 44 BD patients, 31 controls and 5 SZ
patients showed better cognition (High cluster) than the other cluster with 24 BD
patients, 35 SZ patients and 5 controls (Low cluster). BD patients in the High
cluster performed better than BD patients in the Low cluster across cognitive
domains. Within each cluster, participants with different clinical diagnoses showed
different profiles across cognitive domains. Limitations: All patients are in the
chronic phase and out of mood episode at the time of assessment and most of the
assessment were behavioral measures. Conclusions: This study identified two
clusters with shared cognitive phenotype profiles that were not proxies for
clinical diagnoses. The finding of better social cognitive performance of BD
patients than SZ patients in the Lowe cluster suggest that relatively preserved
social cognition may be important to identify disease process distinct to each
disorder.
Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal
tissues, but seldom in healthy adult tissues. While PTN has been reported to be
expressed in many types of tumors as well as at high serum concentrations in
patients with many types of cancer, to date, there has been no report that PTN is
expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+)
subset of B cells from peripheral blood from healthy adults, B-cell acute
lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-
CLL) patients and examined these cells for PTN mRNA and protein expression. We used
immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to
show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL
patients, but barely expressed in B cells from healthy adults. We also examined PTN
expression at the nucleic acid level using reverse transcription polymerase chain
reaction (RT-PCR) and northern blotting and detected a high levels of PTN
transcripts in the CD19(+) B cells from both groups of leukemia patients, but very
few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity
of the PTN transcripts correlated with the severity of disease. Moreover,
suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells
from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN
antibody suggests that PTN may be a new target for the treatment of lymphocytic
leukemia.
Existing and dominant perspectives on determinants of firm internationalization
have focused on the firm-specific and country-specific factors, paying less
attention to the question if and how can clusters foster internationalization of
cluster firms'. To investigate this issue, we conducted the study focused on the
Polish clusters. First, we conceptualize the impact of clusters on the
internationalization of cluster firms by introducing the concepts of the propensity
of internationalization and intensity of internationalization. Second, we assess
the internationalization intensity of clusters in Poland and check how cluster
managers facilitated the internationalization of cluster firms. The results
obtained show that clusters play an important role in neutralizing the liability of
foreignness suffered by cluster entities. The findings confirm that the need of
internationalization which is related to the internationalization propensity
emerges over the time as a cluster matures and internationalization intensity is
higher in case of more dense clusters. By combining meso- and microeconomic
perspectives, this study offers a more holistic approach for studying
internationalization processes.
The ongoing deployment of residential smart meters in numerous jurisdictions has
led to an influx of electricity consumption data. This information presents a
valuable opportunity to suppliers for better understanding their customer base and
designing more effective tariff structures. In the past, various clustering methods
have been proposed for meaningful customer partitioning. This paper presents a
novel finite mixture modeling framework based on C-vine copulas (CVMM) for carrying
out consumer categorization. The superiority of the proposed framework lies in the
great flexibility of pair copulas toward identifying multidimensional dependency
structures present in load profiling data. CVMM is compared to other classical
methods by using real demand measurements recorded across 2613 households in a
London smart-metering trial. The superior performance of the proposed approach is
demonstrated by analyzing four validity indicators. In addition, a decision tree
classification module for partitioning new consumers is developed and the improved
predictive performance of CVMM compared to existing methods is highlighted. Further
case studies are carried out based on different loading conditions and different
sets of large numbers of households to demonstrate the advantages and to test the
scalability of the proposed method.
Cytokines and chemokines play a crucial role in regulating the immune system.
Understanding how these molecules are co-regulated is important to understand
general immunology, and particularly their role in clinical applications such as
development and evaluation of novel drug therapies. Cytokines are today widely used
as therapeutic targets and as biomarkers to monitor effects of drug therapies and
for prog-nosis and diagnosis of diseases. Therapies that target a specific cytokine
are also likely to affect the pro-duction of other cytokines due to their cross-
regulatory functions and because the cytokines are produced by common cell types.
In this study, we have perturbated the production of 17 different cyto-kines in a
preclinical rat model of autoimmune arthritis, using 55 commercially available
immunomodula-tory drugs and clinical candidates. The majority of the studied drugs
was selected for their anti-inflammatory role and was confirmed to inhibit the
production of IL-2 and IFN-gamma in this model but was also found to increase the
production of other cytokines compared to the untreated control. Correlation
analysis identified 58 significant pairwise correlations between the cytokines. The
strongest correlations found in this study were between IL-2 and IFN-gamma (r =
0.87) and between IL-18 and EPO (r = 0.84). Cluster analysis identified two robust
clusters: (1) IL-7, IL-18 and EPO, and (2) IL-2, IL-17 and IFN-gamma. The results
show that cytokines are highly co-regulated, which provide valuable information for
how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine
that is used as a ther-apeutic biomarker could be combined with its related
cytokines into a biomarker panel to improve diag-nostic accuracy. (C) 2016 Elsevier
Ltd. All rights reserved.
Introduction: The identification of BCR-ABL expression as the defining leukemogenic
event in chronic myeloid leukemia (CML) and the introduction of BCR-ABL tyrosine
kinase inhibitors in 2001 have revolutionized disease management, leading to a
reduction in mortality rates and accordingly an increase in the estimated
prevalence of CML. Case report : Based on medical records and clinical follow-up,
the authors present the case of a Philadelphia chromosome-positive CML patient who
developed resistance to imatinib. Quantitative reverse transcription-polymerase
chain reaction testing revealed a V280G BCR-ABL mutation. Discussion and
conclusions: This is the first report describing a new BCR-ABL kinase domain
mutation-V280G-that might be associated with resistance to imatinib. Approximately
15% to 30% of patients treated with imatinib discontinue treatment due to
resistance or intolerance. More than 90 BCR-ABL mutations were detected so far,
conferring variable degrees of drug resistance, with consequent clinical,
therapeutic, and prognostic impact.
The aim of the study was to examine the relation between additional chromosomal
aberrations (ACAs) with major molecular response (MMR) and BCR-ABL kinase domain
(KD) mutations in the long-term follow-up of the chronic myeloid leukemia (CML)
disease. The study design was cross-sectional observational and used the CML
patients' data of Izmir Ataturk Education and Research Hospital from 2011 to 2015.
Conventional cytogenetic, fluorescence in situ hybridization (FISH), quantitative
real-time polymerase chain reaction (RQ-PCR) test results from 89 CML patients' and
pyrosequencing analysis results from 17 patients' were set up for comparison
analysis. The chi-square test was used in statistical analysis of the experimental
data. There were no statistically significant correlations between ACAs and MMR
(p=.361, p>.05) groups or BCR-ABL KD mutations (p=.576, p>.05) groups observed in
the study. This study has revealed that MMR and BCR-ABL KD mutations did not
correlate with ACAs.
In this paper, we elaborate a program based on multi-objective genetic algorithms
(MOGAs) to allow automated optimization of analog circuits. The proposed
methodology is used to find the optimal transistors sizes (length and width) in
order to obtain operational amplifier performances for analog and mixed CMOS-based
circuit applications. Eight performances are considered in this study, direct
current (DC) gain, unity-gain bandwidth (GBW), phase margin (PM), power consumption
(P), area (A), slew rate (SR), thermal noise and signal to noise ratio (SNR). The
program is solved using MATLAB Optimization Toolbox (TM) solvers. Also by using
variables obtained from genetic algorithms, the operational transconductance
amplifier (OTA) is simulated by using Cadence Virtuoso Spectre circuit simulator in
standard TSMC (Taiwan Semiconductor Manufacturing Company) RF 0.18 mu m CMOS
technology. A good agreement is observed between the program optimization and
electric simulation.
This paper presents a novel adaptive bias technique based on the use of squaring
circuits. Here, the tail current of an operational amplifier (OpAmp) is controlled
using an auxiliary circuit. By design, it generates a well-controlled tail current
which - to a first order approximation-is independent of the OpAmp's common-mode
input voltage. As a result, parameters like common-mode rejection ratio (CMRR) and
power supply rejection ratio (PSRR) are enhanced. However, when a differential
input signal is applied, it generates a tail current proportional to the square of
the OpAmp's differential input voltage. In this way, the currents of the OpAmp's
input pairs are boosted, thus improving slew rate. Experimental results in 0.5 mu m
CMOS technology verify current and slew rate enhancement factors between 10 and 15
with less than 20% static current increase.
A design methodology for three-stage CMOS OTAs operating in the subthreshold region
is presented. The procedure is focused on the development of ultra-low-power
amplifiers requiring low silicon area but being able to drive high capacitive
loads. Indeed, by following the presented methodology we designed a CMOS OTA in a
0.35-mu m technology that occupies only 4.4 . 10(-3) mm(2), is powered with a 1-V
supply, exhibits 120-dB DC gain and is able to drive a capacitive load up to 200
pF. Thanks to proposed methodology, the OTA is able to provide a 20-kHz unity gain
bandwidth while consuming 195 nW, even under the high load considered. Moreover,
the slew rate enhancer circuit in addition to the class AB output stage allows an
average slew rate higher than 5 mV/mu s with the 200 pF load. Comparison with prior
art shows an improvement factor in the figures of merit higher than 5.
This paper presents a compact, reliable 1.2 V low-power rail-to-rail class AB
operational amplifier (OpAmp) suitable for integrated battery powered systems which
require rail-to-rail input/output swing and high slew-rate while maintaining low
power consumption. The OpAmp, fabricated in a standard 0.18 mu m CMOS technology,
exhibits 86 dB open loop gain and 97 dB CMRR. Experimental measurements prove its
correct functionality operating with 1.2 V single supply, performing very
competitive characteristics compared with other similar amplifiers reported in the
literature. It has rail-to-rail input/output operation, 5 MHz unity gain frequency
and a 3.15 V/mu s slew-rate for a capacitive load of 100 pF, with a power
consumption of 99 mu W. (C) 2014 Elsevier Ltd. All rights reserved.
This paper presents a current driver for an integrated angular acceleration sensor
readout circuit. The architecture of the proposed amplifier consists of a voltage
follower and an inverting amplifier to achieve a differential output. The amplifier
and the follower are based on a three-stage class AB operational amplifier with a
power output stage. The output current of current driver is controlled by input
voltage and has a maximum value of 80 mA. The proposed circuit is designed in 0.18
mu m CMOS technology. The typical output current flow in an equivalent sensor load
of 50 Ohm is 10 rnA with a rise time of 40 ns.
A new simulation based automated CMOS analog circuit design method which applies a
multi-objective non-Darwinian-type evolutionary algorithm based on Learnable
Evolution Model (LEM) is proposed in this article. The multi-objective property of
this automated design of CMOS analog circuits is governed by a modified Strength
Pareto Evolutionary Algorithm (SPEA) incorporated in the LEM algorithm presented
here. LEM includes a machine learning method such as the decision trees that makes
a distinction between high- and low-fitness areas in the design space. The learning
process can detect the right directions of the evolution and lead to high steps in
the evolution of the individuals. The learning phase shortens the evolution process
and makes remarkable reduction in the number of individual evaluations. The expert
designer's knowledge on circuit is applied in the design process in order to reduce
the design space as well as the design time. The circuit evaluation is made by
HSPICE simulator. In order to improve the design accuracy, bsim3v3 CMOS transistor
model is adopted in this proposed design method. This proposed design method is
tested on three different operational amplifier circuits. The performance of this
proposed design method is verified by comparing it with the evolutionary strategy
algorithm and other similar methods.
A 60frames/s CMOS image sensor with column-parallel inverter-based sigma-delta
(Sigma Delta) ADCs is proposed in this paper. In order to improve the robustness of
the inverter, instead of constant power supply, two buffers are designed to provide
power supply for inverters. Instead of using of an operational amplifier, an
inverter-based switch-capacitor (SC) circuit is adopted to low-voltage low-power
Sigma Delta modulator. Detailed analysis and design optimization are provided. Due
to the use of the inverter-based Sigma Delta ADCs, the conversion speed is improved
while reducing the area and power consumption. The proposed CMOS image sensor has
been fabricated with 0.18 mu m CMOS process. The measurement results show that the
random noise (RN) is 7e(rms)(-), the pixel conversion gain is 100 mu V/e(-). Since
the measured full well capacity of the pixel is 25000e(-), the CMOS image sensor
achieves a 71 dB dynamic range (DR). The total power consumption at 60frame/s is
58.2 mW. (C) 2015 Elsevier Ltd. All rights reserved.
This paper presents an ultra-low-power low-voltage Class-AB Fully Differential
Operational Amplifier designed in 45-nm CMOS technology. The proposed circuit uses
transistors operating in sub-threshold region for low-power and low-voltage
operation. The proposed Op Amp offers an open-loop gain of 74.6 dB, 1 MHz unity
gain frequency, 50-degrees Phase Margin, and 91.55 dB common-mode rejection ratio
for 10 pF loads with a power consumption of 0.39 mu W at a +/-0.4 V supply.
Simulation results illustrate a Slew Rate of 0.013 V/us and a rail-to-rail output
swing, demonstrating its correct functionality.
This paper deals with low offset operational amplifiers. It shows an innovative
approach to design an operational amplifier (OpAMP) which combines two different
techniques that make it able to handle both the technological and the radio
frequency interference (RFI) induced offset.
This paper proposes a novel analog circuit verification approach using causal
reasoning. To verify analog circuits, the flow begins with mining the causal
reasoning steps (design plan) that produced the circuit, including starting ideas,
design step sequence, and their justification [1]. Then, topological structures
corresponding to the starting ideas and design step sequences are verified
individually by replacing the related devices with ideal amplifier model. Circuit
performance is evaluated through Spectre simulation. Comparing simulation results
reveals incorrect functional issues and/or performance drawbacks (negative causes)
of certain starting ideas or design steps, which might have been omitted during the
design process. The paper discusses three operational amplifier designs realized in
0.2-mu m CMOS technology to illustrate the verification approach.
A gain boosted operational amplifier designed using positive feedback technique is
presented in this paper. In this design, a differential output differential
amplifier merged with a single output differential amplifier is used so that
positive feedback can be applied appropriately. The proposed Op-Amp is designed in
0.18 mu m CMOS process using gpdk45nm library in Cadence virtuoso analog design
environment. The simulation of proposed circuit results in 116.2dB gain, 281MHz
UGB, 72 degree phase margin and 620 mu W power consumption. The Monte Carlo
analysis of the circuit indicates that the variation of power supply voltage
produces minimal effect on the gain and phase of the circuit.
In this paper a novel high gain Op-Amp design is presented. This Proposed circuit
also exhibits high linearity. The Architecture of the Op-Amp presented in this
paper is based on cross-coupled differential pair and positive feedback. The
proposed Op-Amp is designed in 0.18 mu m CMOS process using UMC90nm library in
Cadence virtuoso analog design environment. The simulation of proposed circuit
results in 124dB gain, 307MHz UGB and 69 degree phase margin while dissipating 221
mu W power. The THD analysis of the circuit shows a maximum distortion of 63dB at
2V output peak-to peak voltage and 1KHz frequency.
An ultra low power Op-Amp design is presented in this paper. In the proposed
design, a gm enhancement technique is used to obtain sufficient gain and bandwidth.
In the Op-Amp design, all transistors have been operated in weak inversion region.
The proposed Op-Amp has been designed using UMC90nm library and simulated in
Cadence analog design environment. The proposed circuit generates a 31dB gain,
52KHz UGBW and 69 degrees phase margin upon simulation, while the resultant power
consumption is just 6nW.
This paper describes the design and results of a low-voltage high-gain CMOS
operational amplifier (op-amp) which is very appropriate for low-voltage analog and
mixed-signal applications. The design is based on folded architecture. The
amplifier was designed using standard 180 nm digital n-well CMOS technology to
operate with a 1.8 V single supply. The simulated small-signal AC gain of the
amplifier is 90.79 dB and slew rate is 11.5 V/us with a 10 pF capacitive and 1 M
ohm resistive load. For the same load, the gain bandwidth is 14.23 MHz with a phase
margin of 54.8 degree. The amplifier consumes total DC power of 167 uW. The input-
referred noise is 110 nV/sqrt(Hz). Furthermore, the presented operational amplifier
works perfectly at supply voltage of 1 V.
This work presents a rail-to-rail operational amplifier hardened by design against
ionizing radiation at circuit level, using only standard layout techniques. Not
changing transistor layout, for instance by using enclosed layout structures,
allows design and simulation using the standard models provided by the foundry. The
circuit was fabricated on a standard 035 mu m CMOS process, and submitted to a
total ionizing dose (TID) test campaign using a Co-60 radiation source, at a dose
rate of 0.5 rad((Si)/s, reaching a final accumulated dose of 500 krad(Si). The
circuit proved to be radiation tolerant for the tested accumulated dose. The design
practices used to mitigate TID effects are presented and discussed in detail. (C)
2016 Elsevier Ltd. All rights reserved.
This article presents a design concept of a time gain-compensation (TGC) amplifier
integrated circuit (IC) for ultrasonic echo signal processing. The TGC chain
contains pre-amplification, attenuation, filtering and comparison circuit blocks.
An on-chip oscillator, bias circuit and digital control core are also included. The
presented TGC IC concept blocks are designed and modeled using Cadence's IC design
tools using a 250 nm CMOS process. The operational amplifier implemented in the TGC
IC has a gain of 35 dB with a -3 dB bandwidth of 750 kHz, which corresponds to
ultrasonic signal frequency range. The second order active band pass filter is of a
Sallen-Key topology with a 274 MHz center frequency and a filter quality factor of
Q = 1.018. A ring oscillator with external tuning capability is modeled at 448 kHz
and has a 0.09 % frequency deviation. The ultrasonic echo processing chain has a
digital output where the length of the pulse corresponds to the received signal
strength. This makes the presented TGC IC concept suitable for both simple and
complex ultrasonic, medical, industrial or research equipment.
Due to the compl ex growth in very large scale integration circuits, the task of
optimal analog integrated circuit design by hand is very difficult. Optimization is
a time consuming process having many conflicting criteria and a wide range of
design parameters. Characterization of complex tradeoffs between nonlinear
objectives while assuring required specifications makes analog circuit design a
tedious process. The design and optimization processes have to be automated with
high accuracy. Evolutionary technique may be a proficient implement for automatic
design of analog integrated circuits that has been one of the most challenging
topics in VLSI design process. This paper presents a competent approach for optimal
designs of two analog circuits, namely, complementary metal oxide semiconductor
two-stage comparator with P-type metal oxide semiconductor input driver and n-
channel input, folded-cascode operational amplifier. The evolutionary technique
used is particle swarm optimization (PSO) with an aging leader and challenger (ALC-
PSO). The main aim is to optimize the MOS transistors' sizes using ALC-PSO in order
to reduce the areas occupied by the circuits and to get better performance
parameters of the circuits. To exhibit the performance parameters of the circuits,
simulation program with integrated circuit emphasis simulation has been carried out
by using the optimal values of MOS transistor sizes and other design parameters.
Simulation results demonstrate that design specifications are closely met and
required functionalities are accommodated. The simulation results also show that
the ALC-PSO is superior to the other algorithms in terms of MOS area, and
performance parameters like gain, power dissipation, etc. for the examples
considered.
This paper presents the optimal designs of two analogue complementary metal-oxide-
semiconductor (CMOS) amplifier circuits, namely differential amplifier with current
mirror load and two-stage operational amplifier. A modified Particle Swarm
Optimization (PSO), called Craziness-based Particle Swarm Optimization (CRPSO)
technique is applied to minimize the total MOS area of the designed circuits. CRPSO
is a highly modified version of conventional PSO, which adopts a number of random
variables and has a better and faster exploration and exploitation capability in
the multidimensional search space. Integration of craziness factor in the
fundamental velocity term of PSO not only brings diversity in particles but also
pledges convergence close to global best solution. The proposed CRPSO-based circuit
optimization technique is reassured to be free from the intrinsic disadvantages of
premature convergence and stagnation, unlike Differential Evolution (DE), Harmony
Search (HS), Artificial Bee Colony (ABC) and Particle Swarm Optimization (PSO). The
simulation results achieved for the two analogue CMOS amplifier circuits establish
the efficacy of the proposed CRPSO-based approach over those of DE, HS, ABC and PSO
in terms of convergence haste, design conditions and design goals. The optimally
designed analogue CMOS amplifier circuits occupy the least MOS area and show the
best performance parameters like gain and power dissipation, in compared with the
other reported literature. Copyright (c) 2016 John Wiley & Sons, Ltd.
In this paper, a hybrid population based metaheuristic search algorithm named as
gravitational search algorithm (GSA) combined with particle swarm optimization
(PSO) (GSA-PSO) is proposed for the optimal designs of two commonly used analog
circuits, namely, complementary metal oxide semiconductor (CMOS) differential
amplifier circuit with current mirror load and CMOS two-stage operational amplifier
circuit. PSO and GSA are simple, population based robust evolutionary algorithms
but have the problem of suboptimality, individually. The proposed GSA-PSO based
approach has overcome this disadvantage faced by both the PSO and the GSA
algorithms and is employed in this paper for the optimal designs of two amplifier
circuits. The transistors' sizes are optimized using GSA-PSO in order to minimize
the areas occupied by the circuits and to improve the design/performance parameters
of the circuits. Various design specifications/performance parameters are optimized
to optimize the transistor's sizes and some other design parameters using GSA-PSO.
By using the optimal transistor sizes, Simulation Program with Integrated Circuit
Emphasis simulation has been carried out in order to show the performance
parameters. The simulation results justify the superiority of GSA-PSO over
differential evolution, harmony search, artificial bee colony and PSO in terms of
convergence speed, design specifications and performance parameters of the optimal
design of the analog CMOS amplifier circuits. It is shown that GSA-PSO based design
technique for each amplifier circuit yields the least MOS area, and each designed
circuit is shown to have the best performance parameters like gain, power
dissipation etc., as compared with those of other recently reported literature.
Still the difficulties and challenges faced in this work are proper tuning of
control parameters of the algorithms GSA and PSO, some conflicting
design/performance parameters and design specifications, which have been partially
overcome by repeated manual tuning. Multiobjective optimization may be the proper
alternative way to overcome the above difficulties.
This paper proposes a novel hybrid optimisation algorithm which combines the
recently proposed evolutionary algorithm Backtracking Search Algorithm (BSA) with
another widely accepted evolutionary algorithm, namely, Differential Evolution
(DE). The proposed algorithm called BSA-DE is employed for the optimal designs of
two commonly used analogue circuits, namely Complementary Metal Oxide Semiconductor
(CMOS) differential amplifier circuit with current mirror load and CMOS two-stage
operational amplifier (op-amp) circuit. BSA has a simple structure that is
effective, fast and capable of solving multimodal problems. DE is a stochastic,
population-based heuristic approach, having the capability to solve global
optimisation problems. In this paper, the transistors' sizes are optimised using
the proposed BSA-DE to minimise the areas occupied by the circuits and to improve
the performances of the circuits. The simulation results justify the superiority of
BSA-DE in global convergence properties and fine tuning ability, and prove it to be
a promising candidate for the optimal design of the analogue CMOS amplifier
circuits. The simulation results obtained for both the amplifier circuits prove the
effectiveness of the proposed BSA-DE-based approach over DE, harmony search (HS),
artificial bee colony (ABC) and PSO in terms of convergence speed, design
specifications and design parameters of the optimal design of the analogue CMOS
amplifier circuits. It is shown that BSADE- based design technique for each
amplifier circuit yields the least MOS transistor area, and each designed circuit
is shown to have the best performance parameters such as gain, power dissipation,
etc., as compared with those of other recently reported literature.
To minimize the power consumption of an analog sigma-delta modulator (SDM), a
fifth-order loop filter of the SDM has been realized with only three operational
amplifiers (op-amp). The analog SDM with shared op-amp is applied to a class-D
amplifier for a digital hearing aid. The class-D amplifier with the analog SDM has
been realized in a standard 0.13-mu m CMOS process. The maximum output power level
of the class-D amplifier is 1.13-mW for a load with 46.5-Omega DC resistance. The
total harmonic distortion+noise (THD+N) and the dynamic range (DR) of the class-D
amplifier are 0.0038-% and 96-dB, respectively. The fifth-order analog SDM with
shared op-amp consumes only 0.2-mW from a 1.2-V power supply.
The paper represents a design procedure of basic two stage CMOS operational
amplifier using Miller compensation technique. The LtSpice simulation tool is used
to present system result at low capacitive load with different characteristics. The
Miller capacitor creates an undesirable right-half-plane (RHP) zero due a non
inverting feedforward signal path is induced in the input of the second stage
towards its output, which can be eliminated by using voltage buffer. My work shows
the two stage amplifier with Miller compensation techniques, simulated using
LtSpice simulation tool for 180, 130 and 90 nm CMOS technology process. When a 10-
pF capacitive load is drive, the amplifier achieves voltage gain approximate 20 %
more with exactly double gain bandwidth (GBW) which shows phase margin of 44.8
degrees, 49.06 degrees, and 53.70 degrees, slew rate of 44.48, 10.29, and 9.77 V/mu
s, with dissipating power value of 830 mu W at 2.5 V, 504.06 mu W at 1.5 V, 486 mu
W at 1.2 V supply voltage for 180 nm, 130 nm, 90 nm CMOS technology, respectively.
In this paper, a 40 M-1000 MHz 77.2-dB spurious free dynamic range (SFDR) CMOS RF
variable gain amplifier (VGA) has been presented for digital TV tuner applications.
The proposed RFVGA adopts a wideband operational-amplifier-based VGA and a wideband
buffer with differential multiple gated transistor linearization method for
wideband operation and high linearity. The SFDR of the proposed RFVGA is also
analyzed in detail. Fabricated in a 0.13-mu m CMOS process, the RFVGA provides 31-
dB gain range with 1-dB gain step, a minimum noise figure of 7.5 dB at a maximum
gain of 27 dB, and maximum in-band output-referred third-order intercept point of
27.7 dBm, while drawing an average current of 27.8 mA with a supply voltage of 3.3
V. The chip core area is 0.54mmx0.4mm. Copyright (c) 2014 John Wiley & Sons, Ltd.
This paper explores the modeling and design of Miller-based operational amplifier
structures that are highly immune to electromagnetic interference (EMI). The
proposed CMOS Miller-based operational amplifier is derived using the present
modeling. It provides higher immunity to EMI that is injected into the amplifier's
input over a wide range of frequencies; moreover, the frequency response is
comparable to that of a Miller operational amplifier. Simulation results show that
the maximum EMI-induced input offset voltage for the proposed CMOS operational
amplifier is 5 mV at an EMI frequency of 40 MHz, when a 900 mVpp EMI signal is
applied at its input. In contrast, the standard Miller operational amplifier
generates an input offset voltage of 32 mV under the same operating conditions. The
developed mathematical modeling of the EMI-induced offset correlates with the
circuit simulations, providing superior accuracy when designing for high EMI
robustness.
In practical printed circuit board (PCB) designs, electromagnetic interference
(EMI) is coupled from the ground plane, which is commonly shared among the analog,
digital, and mixed-signal integrated circuits. This noisy ground plane couples
interference capacitively to all the IC pins, including the output: this effect is
exacerbated when the IC is connected to long wires and traces that are routed close
to the conductive ground plane. This paper reports on the effect of interference,
which is coupled capacitively from the PCB ground plane into all the IC pins of an
opamp connected as a voltage buffer. Simulations illustrate the susceptibilities in
custom operational amplifier designs, and are corroborated by measurements on
several commercial devices. These measurements show that the EMI-induced offset can
attain considerable values for the most critical EMI frequencies, which lie between
10 and 100 MHz. Moreover, these illustrate that there is a considerable
susceptibility of operational amplifiers to electromagnetic interference coupled to
their output pins.
In this paper an operational amplifier of general purpose is presented. The unified
current-control model is used to synthesize a standard, two-stage topology based
circuit. The design procedure is discussed thoroughly and every step is explained
in details. The results obtained include open loop gain of 74 dB, the gain-
bandwidth product of 100 MHz and the phase margin higher than 46 degrees. Supply
voltage and temperature coefficients are analyzed and discussed within the paper.
Process variations are investigated through corner analysis. The results presented
are obtained through schematic level simulations using the Spectre Simulator from
Cadence Design System and a standard 130 nm CMOS technology process.
This paper presents an efficient and robust circuital implementation of a rail-to-
rail input stage with transconductance control, tailored for low-noise operational
amplifiers based on differential pairs biased in the sub-threshold region. The
proposed g (m) -control circuit design is indeed based on transistors ratio only,
and allows efficient control with scaled currents and dimensions. The architecture
guarantees nearly constant performance in terms of bandwidth and power consumption
over the whole common mode input range in a power- and area-efficient way. The
achievable precision of the transconductance control is also analyzed with
transistor equations and its deviation predicted with a simple analytical model,
which suggests also a strategy for the minimization of the error by proper tuning.
A prototype of the input-output rail-to-rail operational amplifier has been
fabricated in a standard 0.35 mu m CMOS technology, confirming the validity of the
g (m) -control loop. The amplifier consumes 597 mu A from a 3.3 V supply, with an
open-loop gain of 107 dB and a gain-bandwidth product of 42.6 MHz.
This paper describes the design of Two Stage Operational Amplifier using three
structures and calculation of its various parameters. The three basic designs
include CMOS, Hybrid of CMOS and DTMOS, and full DTMOS, which operate at 2.5V power
supply and 0.18um technology. In this paper, simulation curves are computed for its
different characteristics such as Gain, PM, ICMR, CMRR. Simulation has been carried
out in PSPICE tool. All the three design are application specific. The basic CMOS
based 2 stage op-amp provides high open loop voltage gain and rail to rail output
swing. First proposed design is the Hybrid of CMOS and DTMOS which provides
additional gain, increased CMRR and higher phase margin. The second proposed design
is Full DTMOS based 2 Stage op-amp which can be used for low power applications as
DTMOS is the best alternative for implementation of low power circuits.
Despite the clear need, progress toward a vaccine for congenital cytomegalovirus
(CMV) has been slow. However, recent events have provided new interest, and several
vaccine candidates are either in clinical trials or the trials are close to
starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues
show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored
vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and
improves pup survival in a guinea pig model of congenital CMV infection (Clin
Vaccine Immunol 24: e00300-16, 2017, https://doi.org/10.1128/CVI.00300-16). The
combination vaccine appeared to be the most effective.
Purpose: To evaluate the morphological characteristics of posterior corneal regions
including keratic precipitates in eyes with cytomegalovirus (CMV) corneal
endotheliitis using anterior segment spectral domain optical coherence tomography
(SD-OCT). Methods: Thirteen eyes of 13 patients with polymerase chain reaction-
proven CMV corneal endotheliitis were included in this study. Slit-lamp images and
anterior segment SD-OCT images of the posterior cornea were obtained to analyze the
clinical characteristics of corneal structures and keratic precipitates.
Morphological changes in the posterior cornea throughout the course of an antiviral
treatment were also investigated. Results: Anterior SD-OCT images showed protruding
structures at the posterior cornea. These protruding structures exhibited
dendritic, dome-shaped, quadrangular, or saw-tooth appearance, and reflectivity of
these structures was high. Reflectivity of posterior corneal images including the
endothelium and deep stromal corneal regions were also high (76.9%). Because
corneal inflammation and corneal edema improved, the protruding structures and
high-intensity regions of posterior corneal images were resolved after a course of
antiviral treatment. Conclusions: The anterior segment SD-OCT examination
represents a useful noninvasive alternative to diagnose and monitor CMV corneal
endotheliitis.
Lanzhou lily (Lilium davidii var. unicolor) with symptoms of severe fasciation or
dwarfing was observed in the central region of Gansu province, and the disease
caused a serious loss in production of the bulb edible crop. In order to determine
possible virus infections involved in the described disease, a set of enzyme-linked
immunosorbent assays and immunoelectron microscopy had been performed to test the
naturally infected plants. A mixed infection which includes Lily symptomless virus
(LSV: Flexiviridae, Carlavirus), Cucumber mosaic virus (CMV: Bromoviridae,
Cucumovirus) and Lily mottle virus (LMoV: Potyviridae; Potyvirus) has been
confirmed by serologic and morphologic evidences. The subsequent thin sectioning
observation with a transmission electron microscope on different tissues from
infected samples showed that cytopathologic damages happened. Total RNA extracted
from different tissues of infected plants was used in the Northern-blotting assays
with probes of coat protein gene of each virus, then hybridization data showed a
symptomatic infection of related virus. Thus, the study gives reliable serologic,
morphologic, cytopathologic and molecular evidences for the diagnosis of the
systemic infections. This study is hoped to be useful in prevention of certain
viral diseases and to increase the quality and production of this crop in the
future.
The transformation of polyp into medusa is one of the most interesting processes in
the life cycle of cnidarians. In the polyps of the class Scyphozoa this
transformation occurs in the form of strobilation, which is the transverse fission
of polyps with the formation of discoidal ephyrae. At present, the endogenous
regulation of strobilation in one of scyphozoans, Aurelia aurita, is being
investigated by the methods of molecular biology (Fuchs et al., 2014). However, it
is still unclear which key environmental factors induce this process. The main
purposes of this review are to summarize the literature data on the conditions in
which strobilation in A. aurita occurs in nature and in the laboratory and to try
to identify the environmental factors that are most likely to play a signaling role
in strobilation.
VLSI technology is being adopted widely nowadays for biomedical applications to
improve healthcare diagnosis, monitoring and cure. Analog devices such as A/D
converters for biomedical applications can be of modest precision but need to be
very energy efficient in order to operate for decades. CNTFET can be the future
alternative to be used in various high performance, low power devices. In this
paper we have presented a low power CNTFET based two stage Op-Amp for biomedical
A/D converters. A sample and hold circuit is also implemented using CNTFET based
Op-Amp to be used in biomedical ADCs. Simulation results of CNTET based circuits
are compared with MOSFET circuits. Results indicate improvement of power
consumption up to 80%. The proposed circuit simulations are carried out in HSPICE.
It is concluded that CNTFET based circuits can be prime choice for low power
applications.
This paper presents an extension of the ballistic carbon nanotube field-effect
transistor (CNTFET) Raychowdhury [1] compact model with adding acoustic phonon (AP)
and optical phonon scattering (OP) mechanisms. These mechanisms cause noise in the
device. To obtain an accurate compact model, the flicker and thermal noise-models
should be included. This model can be easily implemented with a hardware
description language (HDL)-like Verilog-A in the Agilent Advanced Design System
simulation tool ADS. The impact of the AP scattering mechanism on operational
amplifier (Op Amp) circuit performances is investigated and the simulation results
are compared with respect to Op Amp including both AP and OP scattering and to Amp
Op using ballistic model. Hence, degradation in the Op Amp performances with AP and
OP scattering models is observed especially in gain and bandwidth figure of merits
in addition to the increase of the flicker noise in the device.
Germany appears set to miss its CO2 reduction target in 2020. As a result, ideas
for additional political measures have been put forward. One such idea involves an
early phase-out of coal-fired power plants. However, the possible impacts of such a
phase-out on the energy system have not yet been fully analyzed. We therefore apply
a German energy system model to analyze these impacts. To do so, we calculate three
different scenarios. The first represents a business-as-usual scenario, while the
second takes a coal phase-out into account. The third scenario has to achieve the
same CO2 reduction as the second without being forced to implement a coal phase-
out. Our three scenarios show that a definitive coal phase-out by 2040 would result
in only a relatively small amount of additional CO2. However, an equal CO2
reduction can be obtained using a different strategy and slightly lower costs. In
the latter scenario, the additional costs are also distributed more evenly across
the sectors. The sensitivities analyzed show the robustness of the conclusions
drawn. In summary, this analysis outlines what consequences could arise by
excluding several options in parallel from a technology portfolio. (C) 2017
Elsevier Ltd. All rights reserved.
Conversion of coal into dedicated hydrocarbons has been developed in the beginning
of the last century and is still practiced in areas of the world with scarcity or
insecure oil and gas supply. Given the need for carbon in chemistry, possible
political disruptions in oil and gas producing regions and the rise of renewable
energy, lignite, as a secure domestic raw material, can serve as a chemical feed-
stock. Furthermore, it can serve as an energy storage using polygeneration, i.e.
the ratio between power and hydrocarbon products can follow the fluctuating grid
requirements. In North-Rhine Westphalia (NRW), a committee for inquiry regarding
the future of the chemical industry advocates this idea in its final report
released in April 2015. This is in line with the position of RWE Generation (RWEG),
which has been pursuing an alternative use of lignite besides the generation of
electricity and has been expediting the related technology development for decades.
So far, economical reasons prevented this option to be realized in commercial scale
in Germany during the last 30 years. Together with partners from science, as well
as industry and partly government-funded, RWEG develops innovative plant concepts
and technologies for Coal-to-Product concepts. Especially the challenges and
chances are taken into consideration resulting from the given circumstances, a
changing market situation and shifting political goals. To meet the challenge of
high investment costs, RWEG pursues a so called annex approach to improve the
economic viability of the alternative use of lignite. Annex means to use synergies
on infrastructure at established power plant or chemical sites, when planning a
CtL/CtG plant. In addition, the process steps are critically questioned, here the
gas treatment plant, whether amine scrubbing can be applied as a less costly
alternative to the commonly used Rectisol scrubbing. To reduce the CO2 footprint
and to use renewable energy for hydrocarbon products, there is, next to the way of
integrating electrolytically produced H-2 into the process, another way, to
substitute carbon consumption needed for the gasification temperatures by
electrical heating. (C) 2017 Elsevier Ltd. All rights reserved.
The electrochemical detection of ascorbic acid (AA) was investigated using a
cobalt(III)-ferritin immobilized on a self-assembled monolayer modified gold
electrode in phosphate buffer solution (pH7.5). The modified electrode showed
excellent electrochemical activity for oxidation of AA. The response to AA on the
modified electrode was examined using cyclic and differential pulse voltammetry
techniques. The resulting biosensor showed a linear response to AA in a
concentration range from 6.25x10(-6) to 2.31x10(-5) M with sensitivity of 86,437
AM(-1) and detection limit of 4.65 x 10(-6) M based on a signal-to-noise ratio of
3. Electrochemical parameters including the charge transfer coefficient () and the
apparent heterogeneous electron transfer rate constant (k(s)) for AA were found to
be 0.52 and 1.054 Sec(-1), respectively. It has been shown that, using this
modified electrode, AA can be determined with high sensitivity, low detection
limit, and high selectivity. (C) 2015 International Union of Biochemistry and
Molecular Biology, Inc.
Cobalt-containing metal-on-metal hip replacements are associated with adverse
reactions to metal debris (ARMD), including inflammatory pseudotumours, osteolysis,
and aseptic implant loosening. The exact cellular and molecular mechanisms leading
to these responses are unknown. Cobalt ions (Co2+) activate human Toll-like
receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses
to Gram negative bacterial lipopolysaccharide (LPS). We investigated the effect of
Co2+-mediated TLR4 activation on human microvascular endothelial cells (HMEC-1),
focusing on the secretion of key inflammatory cytokines and expression of adhesion
molecules. We also studied the role of TLR4 in Co2+-mediated adhesion molecule
expression in MonoMac 6 macrophages. We show that Co2+ increases secretion of
inflammatory cytokines, including IL-6 and IL-8, in HMEC-1. The effects are TLR4-
dependent as they can be prevented with a small molecule TLR4 antagonist. Increased
TLR4-dependent expression of intercellular adhesion molecule 1 (ICAM1) was also
observed in endothelial cells and macrophages. Furthermore, we demonstrate for the
first time that Co2+ activation of TLR4 upregulates secretion of a soluble adhesion
molecule, sICAM-1, in both endothelial cells and macrophages. Although sICAM-1 can
be generated through activity of matrix metalloproteinase-9 (MMP-9), we did not
find any changes in MMP9 expression following Co2+ stimulation. In summary we show
that Co2+ can induce endothelial inflammation via activation of TLR4. We also
identify a role for TLR4 in Co2+-mediated changes in adhesion molecule expression.
Finally, sICAM-1 is a novel target for further investigation in ARMD studies.
While chronic cocaine use is associated with abnormalities in both brain structure
and function within and interactions between regions, previous studies have been
limited to interrogating structure and function independently, and the detected
neural differences have not been applied to independent samples to assess the
clinical relevance of results. We investigated consequences of structural
differences on resting-state functional connectivity in cocaine addiction and
tested whether resting-state functional connectivity of the identified circuits
predict relapse in an independent cohort. Subjects included 64 non-treatment-
seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent
treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the
end of a 30-day residential treatment programme. Differences in cortical thickness
and related resting-state functional connectivity between NTSCUs and healthy
control subjects were identified. Survival analysis, applying cortical thickness of
the identified regions, resting-state functional connectivity of the identified
circuits and clinical characteristics to the treatment cohort, was used to predict
relapse. Lower cortical thickness in bilateral insula and higher thickness in
bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole
brain resting-state functional connectivity analyses with these four different
anatomical regions as seeds revealed eight weaker circuits including within the
salience network (insula seeds) and between temporal pole and elements of the
default mode network in NTSCUs. Applying these circuits and clinical
characteristics to the independent cocaine-dependent treatment cohort, functional
connectivity between right temporal pole and medial prefrontal cortex, combined
with years of education, predicted relapse status at 150 days with 88% accuracy.
Deficits in the salience network suggest an impaired ability to process
physiologically salient events, while abnormalities in a temporal pole-medial
prefrontal cortex circuit might speak to the social-emotional functional
alterations in cocaine addiction. The involvement of the temporal pole-medial
prefrontal cortex circuit in a model highly predictive of relapse highlights the
importance of social-emotional functions in cocaine dependence, and provides a
potential underlying neural target for therapeutic interventions, and for
identifying those at high risk of relapse.
ObjectiveTo compare counts of Aggregatibacter actinomycetemcomitans, Prevotella
intermedia, Porphyromonas gingivalis and Fusobacterium nucleatum between crack
users and non-users. Materials and methodsA cross-sectional study was conducted
involving seventy-four crack cocaine users and eighty-one non-users matched for
age, gender and tobacco use. Demographic and clinical variables were analysed.
Subgingival bacterial samples were collected from four sites with the greatest
probing depths and were analysed using real-time polymerase chain reaction.
ResultsNo significant difference was found in the prevalence of total counts for
each bacterial species analysed between groups. However, crack users had a 1.85
(95% CI: 1.03-3.31), 2.19 (95% CI 1.24-3.88), 2.53 (95% CI 1.27-5.04) and 2.40 (95%
CI 1.22-4.75) greater probability of having the higher counts (75th percentile) for
Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
intermedia and Fusobacterium nucleatum, respectively. ConclusionAlthough some crack
users had higher (>75th percentile) bacterial counts for Aggregatibacter
actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and
Fusobacterium nucleatum, total counts did not differ between crack users and non-
users, leading to the hypothesis that the higher occurrence of periodontitis on
crack users may be related to other non-bacterial factors.
Knowledge of putative insect species vectors of the coconut lethal yellowing
disease (CLYD) in Mozambique is crucial to develop an effective disease management
plan. Hemiptera specimens from the families Derbidae and Pentatomidae were
collected in the Inhambane and Zambezia provinces of the coastal region of
Mozambique in 2014, covering the two main growing seasons. Sequence analyses of the
16S rRNA gene were used for phytoplasma clustering. Polymerase chain reaction (PCR)
amplification was performed employing three different primer sets specific for
phytoplasma. BLAST sequence comparison and phylogenetic analysis of the 16S rDNA
PCR products revealed that collected specimens of Derbidae Diostrombus mkurangai
Wilson were carrying the CLYD phytoplasma. Virtual RFLP analyses of the obtained
sequences confirmed this assigning the detected phytoplasmas to the 16SrXX-A
subgroup, confirming that they are 'Candidatus Phytoplasma palmicola'-related
strains. This is the first detection of a 'Candidatus Phytoplasma palmicola'-
related strain in D. mkurangai.
Background and ObjectiveThe goal of periodontal therapy is to
regenerate/reconstruct the damaged supporting tissues of diseased teeth and to
facilitate recovery of their physiological functions. Combination of stem cell
transplantation and gene therapy offers a viable method for accelerating
periodontal repair and regeneration. In this study, the role of the ephrinB2/EphB4
signaling pathway in regulating osteogenic differentiation of periodontal ligament
stem cells (PDLSCs) and crosstalk between PDLSCs and pre-osteoblasts within co-
culture was investigated through ephrinB2 transgenic expression in PDLSCs. Material
and MethodsPDLSCs isolated from premolar teeth of teenage patients undergoing
orthodontic treatment were transfected with transgenic (hEfnB2-GFP-Bsd) vector or
empty vector (GFP-Bsd). Vector-PDLSCs, EfnB2-PDLSCs, MC3T3-E1 and co-cultures of
vector-PDLSCs with MC3T3-E1, and EfnB2-PDLSCs with MC3T3-E1 were subjected to
osteogenic induction. The osteogenic differentiation of EfnB2-PDLSCs, vector-PDLSCs
and co-cultures were assessed by reverse transcription-polymerase chain reaction,
alkaline phosphatase (ALP) assay and Alizarin-red S staining. Protein expression
levels of ephrinB2, EphB4, phosphorylated ephrinB2 and EphB4 were analyzed by
western blot, immunoprecipitation and co-immunoprecipitation assays. ResultsALP
assay and Alizarin-red S staining demonstrated higher ALP activity and increased
mineralization with EfnB2-PDLSCs vs. vector-PDLSCs and with co-culture of EfnB2-
PDLSCs and MC3T3-E1 vs. vector-PDLSCs and MC3T3-E1. Reverse transcription-
polymerase chain reaction revealed that the expression of human odonto/osteogenic
markers were significantly enhanced in EfnB2-PDLSCs compared to vector-PDLSCs, and
that the expression of mouse odonto/osteogenic markers were significantly higher in
co-culture of EfnB2-PDLSCs with MC3T3-E1 vs. vector-PDLSCs with MC3T3-E1. The EphB4
receptor was activated through phosphorylation during osteogenic differentiation.
ConclusionOur data indicate that transgenic expression of ephrinB2 in PDLSCs could
promote osteogenic differentiation via stimulation of the phosphorylation of
ephrinB2 and EphB4, which regulates cell communication between PDLSCs and between
PDLSCs and pre-osteoblasts within co-culture.
Varying chemical oxygen demand (COD) and sulphate concentrations in substrate were
used to determine reaction kinetics and mass balance of organic matter and sulphate
transformation in a microbial fuel cell (MFC). MFC with anodic chamber volume of 1
L, fed with wastewater having COD of 500 mg/L and sulphate of 200 mg/L, could
harvest power of 54.4 mW/m(2), at a Coulombic efficiency of 14%, with respective
COD and sulphate removals of 90 and 95%. Sulphide concentration, even up to 1500
mg/L, did not inhibit anodic biochemical reactions, due to instantaneous abiotic
oxidation to sulphur, at high inlet sulphate. Experiments on abiotic oxidation of
sulphide to sulphur revealed maximum oxidation taking place at an anodic potential
of -200 mV. More than 99% sulphate removal could be achieved in a MFC with inlet
COD/sulphate of 0.75, giving around 1.33 kg/m(3) day COD removal.
Bioelectrochemical conversion of sulphate facilitating sulphur recovery in a MFC
makes it an interesting pollution abatement technique.
The use of information and communication technologies (ICTs) in developing regions
has gained momentum due to their increasing affordability, particularly in rural
areas where other ICT infrastructures for information management are often non-
existent. Giving potential technology users, the opportunity to actively engage and
contribute to the design of an artefact increases adoption and sustainable use. In
this paper, we illustrate our application of community-based codesign (CBCD) that
led to the development of an ICT intervention to support water management in three
rural communities in Uganda. The community-based system helps water managers to
track water users, payments and expenditures in a bid to improve transparency,
accountability and trust. We present research learnings of the method and how
engagement with rural communities can be improved through the use of intermediaries
and paying more attention to community values as well as exercising ethics of
reciprocity in community-based ICT initiatives.
Objectives Growing evidence supports the view that the diagnosis of coeliac disease
(CD) can be made by serological tests alone, although this approach is still not
widely accepted. We previously showed in retrospective and prospective studies that
in adults an IgA-tissue transglutaminase antibody cut-off can be defined above
which the positive predictive value for CD is 100%. Following a change in the
analytical method for measuring the antibody, our objectives were to re-examine
this finding in a larger series of adults to ascertain whether a diagnosis of CD
can be reliably made in a proportion of patients without the need for small bowel
biopsy and to re-evaluate the diagnostic guidelines used in our centre. Patients
and methods A retrospective analysis was done in an unselected series of 270 adult
patients who had small bowel biopsies and serum IgA-tissue transglutaminase
antibody levels measured from 2009 to 2014. Results At an IgA-tissue
transglutaminase antibody cut-off greater than 45 U/ml (>8 x upper limit of normal
+ 2SDs) the positive predictive value for CD in this cohort was 100%; 40% of cases
were above this cut-off. Conclusion We have verified that a diagnosis of CD can be
reliably made in a high proportion of adults based on serology alone using the IgA-
tissue transglutaminase antibody method specified. These results add to the body of
evidence that small bowel biopsy should no longer be considered mandatory for the
diagnosis of CD. On the basis of these results the diagnostic guidelines in our
centre have been modified. Copyright (C) 2017 Wolters Kluwer Health, Inc. All
rights reserved.
Research about the Chinese film industry is far behind the actual development of
practice, especially considering its evolution and main influential factors.
Furthermore, existing research on the film industry in economic geography is mostly
conducted from the perspective of cluster theory, with lesser attention to
institutions or culture. In this paper, the theory of co-evolution is used to
tackle these two gaps. The role of institutions, culture and industrial
organization as three fundamental elements of co-evolution is pointed out and
discussed in the theoretical section. The phenomena of co-evolution in the Shanghai
film industry as important examples of the Chinese film industry are analysed in
the empirical part. We phase the development process in four periods and
differentiate identified effects of co-evolution between institutions, culture and
industrial organization based on the specific setting in each particular period.
The reductionist approach of dissecting biological systems into their constituents
has been successful in the first stage of the molecular biology to elucidate the
chemical basis of several biological processes. This knowledge helped biologists to
understand the complexity of the biological systems evidencing that most biological
functions do not arise from individual molecules; thus, realizing that the emergent
properties of the biological systems cannot be explained or be predicted by
investigating individual molecules without taking into consideration their
relations. Thanks to the improvement of the current -omics technologies and the
increasing understanding of the molecular relationships, even more studies are
evaluating the biological systems through approaches based on graph theory. Genomic
and proteomic data are often combined with protein-protein interaction (PPI)
networks whose structure is routinely analyzed by algorithms and tools to
characterize hubs/bottlenecks and topological, functional, and disease modules. On
the other hand, co-expression networks represent a complementary procedure that
give the opportunity to evaluate at system level including organisms that lack
information on PPIs. Based on these premises, we introduce the reader to the PPI
and to the co-expression networks, including aspects of reconstruction and
analysis. In particular, the new idea to evaluate large-scale proteomic data by
means of co-expression networks will be discussed presenting some examples of
application. Their use to infer biological knowledge will be shown, and a special
attention will be devoted to the topological and module analysis.
Caffeine biosynthesis involves sequential methylation of the purine ring by the
transfer of methyl group from the methyl donor S-adenosyl methionine. Genes that
code for the individual methyl transferase have a high degree of sequence homology.
To achieve decaffeination by genetic engineering of coffee, the effect and
efficiency of different post-transcriptional gene silencing (PTGS) constructs were
evaluated. Sense, antisense and invert repeat constructs were developed using a 339
bp fragment from the conserved region of the coffee N-methyltransferase genes
involved in caffeine biosynthesis. The silencing constructs were mobilized into
Agrobacterium tumefaciens (EHA101). Sonication assisted Agrobacterium-mediated
transformation of the somatic embryos of C. canephora was performed, followed by
regeneration of the transformants. Molecular analysis and identification of
flanking regions confirmed the stable integration of the transgenes in the
transformants and their integration in non coding regions of the genome,
respectively. Effectiveness of the silencing constructs was evaluated by transcript
analysis of the targeted genes by RT-PCR and northern blotting. The silencing
efficiency was further evaluated by estimation of the purine alkaloid content in
the transgenic lines using HPLC. The three constructs differed in their silencing
efficiencies and specificity. Though the constructs were not specific to a single
N-methyltransferase, transformants obtained were mainly affected in one of the N-
methyltransferases. Results show that the use of homologous coding sequence in the
PTGS constructs results in a much higher efficiency in silencing the caffeine
biosynthetic pathway. Further, the lowering of caffeine content should be the
preferred over complete decaffeination due to extremely low survival rate of
transgenic plants with extremely low levels of caffeine.
To response to the increasing demands for clean water, a large pressurized water
reactor (PWR) with a desalination capability has been studied and demonstrated its
potential so far. However, the electricity production of the large nuclear reactor
decreases by 10% due to steam bypass for desalination. In this study, the authors
evaluate the possibility of a large PWR with a capability of producing both
electric power and clean water by using the supercritical CO2 (S-CO2) Brayton cycle
technology. The S-CO2 power technology is adopted to minimize the decrease in the
electricity production capacity due to desalination process. Two concepts which
replace the existing steam based power conversion system with a S-CO2 Brayton cycle
were proposed. The first concept is that the low pressure steam turbine section of
the power conversion system is replaced with the S-CO2 Brayton cycle. The second
concept is that the whole steam based power conversion system is replaced with the
S-CO2 Brayton cycle. Several S -CO2 cycle options were considered in terms of power
production and the desalination capacity and conducted a comparative analysis of
selected layouts and the optimal operating conditions of the suggested layouts were
identified. (C) 2017 Elsevier B.V. All rights reserved.
Background. Functional decline among patients with mental illness is not unique to
individuals with psychotic disorders. Despite this, research on early predictors of
functional outcome mainly focused on individuals thought to have an 'at risk mental
state' (ARMS) for psychosis. There is evidence suggesting that certain early
vulnerability markers, such as neurological soft signs (NSS), may explain
variability in functional outcomes independent of the level of psychosis risk and
the traditional diagnostic classification. Method. Structural equation modeling was
applied to baseline data from a prospective longitudinal study of 138 young
individuals in treatment with secondary services for non-psychotic disorders. We
evaluated theoretically based models of pathways to functional outcome starting
from NSS. The intervening variables were established according to previous evidence
and drawn from two general categories: cognition (neuro-and social-) and negative
symptoms (expressive and experiential). Results. A final trimmed model was a single
path running from NSS to neurocognition to experiential negative symptoms to
outcome. It could not be improved by adding or dropping connections that would
change the single path to multiple paths. The indirect effect from NSS to outcome
was significant. The validity of the model was independent of the ARMS status and
the psychiatric diagnosis. Conclusions. Our results provide evidence for a single
pathway model in which the starting and intervening variables represent modifiable
trans-diagnostic therapeutic targets to improve functional trajectories in young
individuals with a recent-onset psychiatric diagnosis and different levels of
psychosis risk.
Learning objectives: After participating in this activity, learners should be
better able to: Evaluate the evolution of social cognitive abilities as a
developmental process Assess the evidence regarding social cognition difficulties
in youth at clinical high risk for psychosis Individuals at clinical high risk
(CHR) for psychosis exhibit a broad range of difficulties, including impaired
social cognition, which may represent a target for early identification and
intervention. Several studies have examined various domains of social cognition in
CHR individuals. Most focus on adolescent and young adult populations, but given
the accumulating evidence that impairment exists before the onset of psychotic
disorders, it is critically important to begin to look for these risk markers in
younger children. The present article reviews 25 studies on CHR that examine any of
the following four domains of social cognition: emotion processing, theory of mind,
social perception, or attribution bias. Eligible studies were identified through a
comprehensive literature search, conducted using electronic databases, including
PubMed/MEDLINE and PsycINFO, and combinations of key social-cognition and CHR
search terms. Despite some mixed results, the existing literature establishes that
CHR individuals display social-cognitive impairment, though it remains unclear as
to how and when that impairment develops. Thus, by using the literature on social
cognition in typically developing children as a model and reference, and by looking
at the evolution of social-cognitive abilities as a developmental process, our
review presents a valuable new perspective that indicates the necessity of further
investigation in younger, at-risk populations. Implications for treatment and
future research are discussed.
Objectives: In this proof-of-concept trial, we examined the feasibility and
preliminary efficacy of Understanding Social Situations (USS), a new social
cognitive intervention that targets higher level social cognitive skills using
methods common to neurocognitive remediation, including drill and practice and
hierarchically structured training, which may compensate for the negative effects
of cognitive impairment on learning. Method: Thirty-eight individuals with
schizophrenia spectrum disorders completed the same baseline assessment of
cognitive and social cognitive functioning twice over a 1-month period to minimize
later practice effects, then received 7-10 sessions of USS training, and then
completed the same assessment again at posttreatment. Results: USS training was
well tolerated and received high treatment satisfaction ratings. Large improvements
on the USS Skills Test, which contained items similar to but not identical to
training stimuli, suggest that we were effective in teaching specific training
content. Content gains generalized to improvements on some of the social cognitive
tasks, including select measures of attributional bias and theory of mind.
Importantly, baseline neurocognition did not impact the amount of learning during
USS (as indexed by the USS Skills Test) or the amount of improvement on social
cognitive measures. Conclusions and Implications for Practice: USS shows promise as
a treatment for higher level social cognitive skills. Given the lack of
relationship between baseline cognition and treatment effects, it may be
particularly appropriate for individuals with lower range cognitive function.
Alterations in general intellectual ability and social cognition in schizophrenia
are core features of the disorder, evident at the illness' onset and persistent
throughout its course. However, previous studies examining cognitive alterations in
siblings discordant for schizophrenia yielded inconsistent results. Present study
aimed to investigate the nature of the association between facial emotion
recognition and general IQ by applying genetically sensitive cross-trait cross-
sibling design. Participants (total n=158; patients, unaffected siblings, controls)
were assessed using the Benton Facial Recognition Test, the Degraded Facial Affect
Recognition Task (DFAR) and the Wechsler Adult Intelligence Scale-III. Patients had
lower IQ and altered facial emotion recognition in comparison to other groups.
Healthy siblings and controls did not significantly differ in IQ and DFAR
performance, but siblings exhibited intermediate angry facial expression
recognition. Cross-trait within-subject analyses showed significant associations
between overall DFAR performance and IQ in all participants. Within-trait cross-
sibling analyses found significant associations between patients' and siblings' IQ
and overall DFAR performance, suggesting their familial clustering. Finally, cross-
trait cross-sibling analyses revealed familial covariation of facial emotion
recognition and IQ in siblings discordant for schizophrenia, further indicating
their familial etiology. Both traits are important phenotypes for genetic studies
and potential early clinical markers of schizophrenia-spectrum disorders. (C) 2016
Elsevier Ireland Ltd. All rights reserved.
Background: There is a lack of treatment plurality at step 2 of Improving Access to
Psychological Therapies (IAPT) services. This project therefore sought to develop
and pilot a cognitive analytic informed guided self-help treatment for mild-to-
moderate anxiety for delivery by Psychological Wellbeing Practitioners (PWPs).
Method: Medical Research Council treatment development guidelines were used. Phase
I included development of the six-session treatment manual using practice
guidelines, small-scale modelling (n = 3) and indicated manual iterations. Phase II
consisted of a mixed methods case series design (n = 11) to index feasibility,
uptake and clinical outcomes. Results: Cognitive analytic guided self-help (CAT-SH)
met established quality parameters for guided self-help. A high treatment
completion rate was observed, with 10/11 patients who attended the first treatment
session subsequently completing full treatment. Six out of ten patients completing
full treatment met reliable recovery criteria at follow-up. Effect sizes and
recovery rates equate with extant PWP outcome benchmarks. Practitioner feedback
indicated that delivery of CAT-SH was feasible. Conclusion: CAT-SH shows promise as
a low-intensity treatment for anxiety, and so further, larger and more controlled
evaluations are indicated.
The current paper provides an overview of the cultural and religious background of
Pakistan; the current situation of mental health in Pakistan with special emphasis
on cultural adaptation of cognitive behaviour therapy (CBT) in Pakistan. In the
context of Sufism-Islamic Mindfulness, it is interesting to note that it has been
easy to explain the concepts of CBT to the therapists and clients in Pakistan, but
the process to culturally adapt CBT in Pakistani culture, had to be based on
patience while generating evidence for it. Our group has taken the responsibility
to do that and so far, have been successful in the endeavours pertaining to
research and service development, described in this paper.
According to recent theories, social cognition is based on two different types of
information-processing; an implicit or action-based one and an explicit or verbal
one. The present study examined whether implicit and explicit social-cognitive
information processing interact with each other by investigating young children's
and adults' use of verbal (i.e., explicit) information to predict others' actions.
Employing eye tracking to measure anticipatory eye-movements as a measure of
implicit processing, Experiment 1 presented 1.5-, 2.5-, and 3.5-year-old children
as well as adults with agents who announced to move to either of two possible
targets. The results show that only the 3.5-year-old children and adults, but not
the 1.5-and 2.5-year-old children were able to use verbal information to correctly
anticipate others' actions. Yet, Experiments 2 and 3 showed that 2.5-year-old
children were able to use explicit information to give a correct explicit answer
(Experiment 2) and that they were able to use statistical information to anticipate
the other's actions (Experiment 3). Overall, the study is in line with theoretical
claims that two types of information-processing underlie human social cognition. It
shows that these two inform each other by 3 years of age.(C) 2016 Elsevier B.V. All
rights reserved.
Substantial evidence indicates that infants expect agents to move directly to their
goals when no obstacles block their paths, but the representations that articulate
this expectation and its robustness have not been characterized. Across three
experiments (total N = 60), 6-month-old infants responded to a novel, curvilinear
action trajectory on the basis of its efficiency, in accord with the expectation
that an agent will move to its goal on the least costly path that the environment
affords. Infants expected minimally costly action when presented with a novel
constraint, and extended this expectation to agents who had previously acted
inefficiently. Infants' understanding of goal-directed action cannot be explained
alone by sensitivity to specific features of agent's actions (e.g. agents tend to
move on straight paths, along supporting surfaces, when facing their goals
directly) or extrapolations of agents' past actions to their future ones (e.g. if
an agent took the shortest path to an object in the past, it will continue to do so
in the future). Instead, infants' reasoning about efficiency accords with the
overhypothesis that agents minimize the cost of their actions. (C) 2016 Elsevier
B.V. All rights reserved.
When do descriptive regularities (what characteristics individuals have) become
prescriptive norms (what characteristics individuals should have)? We examined
children's (4-13years) and adults' use of group regularities to make prescriptive
judgments, employing novel groups (Hibbles and Glerks) that engaged in morally
neutral behaviors (e.g., eating different kinds of berries). Participants were
introduced to conforming or non-conforming individuals (e.g., a Hibble who ate
berries more typical of a Glerk). Children negatively evaluated non-conformity,
with negative evaluations declining with age (Study 1). These effects were
replicable across competitive and cooperative intergroup contexts (Study 2) and
stemmed from reasoning about group regularities rather than reasoning about
individual regularities (Study 3). These data provide new insights into children's
group concepts and have important implications for understanding the development of
stereotyping and norm enforcement.
The challenge of studying human cognitive evolution is identifying unique features
of our intelligence while explaining the processes by which they arose. Comparisons
with nonhuman apes point to our early-emerging cooperative-communicative abilities
as crucial to the evolution of all forms of human cultural cognition, including
language. The human self-domestication hypothesis proposes that these early-
emerging social skills evolved when natural selection favored increased in-group
prosociality over aggression in late human evolution. As a by-product of this
selection, humans are predicted to show traits of the domestication syndrome
observed in other domestic animals. In reviewing comparative, developmental,
neurobiological, and paleoanthropological research, compelling evidence emerges for
the predicted relationship between unique human mentalizing abilities, tolerance,
and the domestication syndrome in humans. This synthesis includes a review of the
first a priori test of the self-domestication hypothesis as well as predictions for
future tests.
In natural situations, speech perception often takes place during the concurrent
execution of other cognitive tasks, such as listening while viewing a visual scene.
The execution of a dual task typically has detrimental effects on concurrent speech
perception, but how exactly cognitive load disrupts speech encoding is still
unclear. The detrimental effect on speech representations may consist of either a
general reduction in the robustness of processing of the speech signal ('noisy
encoding'), or, alternatively it may specifically influence the temporal sampling
of the sensory input, with listeners missing temporal pulses, thus underestimating
segmental durations ('shrinking of time'). The present study investigated whether
and how spectral and temporal cues in a precursor sentence that has been processed
under high vs. low cognitive load influence the perception of a subsequent target
word. If cognitive load effects are implemented through 'noisy encoding',
increasing cognitive load during the precursor should attenuate the encoding of
both its temporal and spectral cues, and hence reduce the contextual effect that
these cues can have on subsequent target sound perception. However, if cognitive
load effects are expressed as 'shrinking of time', context effects should not be
modulated by load, but a main effect would be expected on the perceived duration of
the speech signal. Results from two experiments indicate that increasing cognitive
load (manipulated through a secondary visual search task) did not modulate temporal
(Experiment 1) or spectral context effects (Experiment 2). However, a consistent
main effect of cognitive load was found: increasing cognitive load during the
precursor induced a perceptual increase in its perceived speech rate, biasing the
perception of a following target word towards longer durations. This finding
suggests that cognitive load effects in speech perception are implemented via
'shrinking of time', in line with a temporal sampling framework. In addition, we
argue that our results align with a model in which early (spectral and temporal)
normalization is unaffected by attention but later adjustments may be attention-
dependent. (C) 2016 Elsevier Inc. All rights reserved.
Cognitive behavioral approaches have been able to demonstrate some of the
underlying and perpetuating factors of depression such as cognitive reactivity
(CR). The association of CR and the severity of depression is yet to be reported.
We aimed to compare the CR of a group of outpatients based on their self-reported
severity of depression (SRSD), and to identify the role of specific CR
vulnerability markers in depression. The study population consisted of 221
outpatients diagnosed with Major Depressive Disorder. We used the Mini
International Neuropsychiatric Interview, and completed a demographic and clinical
data form. The participants completed the Leiden Index of Depression Sensitivity-
Revised (LEIDS-R), and the Hospital Anxiety and Depression Scale. To identify how
well CR, as measured by the scores of the LEIDS-R, could discriminate the groups
based on the SRSD, one-way analysis of variance was used. To examine the unique
associations between the CR and the SRSD, a hierarchical linear regression analysis
was performed. To identify group membership to severe depression, the scores of the
LEIDS-R were entered in a logistic regression model. Large, and small group
differences emerged on the rumination, and control scores, respectively. The other
group differences were all in the medium range. The control, risk aversion, and
rumination scores were the subscales which explained a significant proportion of
the variance in the SRSD. Overall, the logistic regression model classified 93.7 %
of the severely depressed patients correctly. These results indicated that
rumination, risk aversion, and perfectionism were particularly associated with
severe depression.
Background: Anxiety disorders are the leading cause of mental illness in
adolescence. While anxious adolescents show impairments in emotion processing and
deficits in emotion regulation, few studies have attempted to improve emotion
regulation within these populations. Method: This study used a multi-method design
to test a newly developed emotion regulation training aimed at improving insight
into emotions and instructing cognitive reappraisal. The efficacy of cognitive
reappraisal was investigated in 27 clinically anxious youth (Age: M=12.36, SD=2.59)
and 43 healthy controls (Age: M=13.07, SD=2.19) using psychophysiological measures.
Specifically, heart rate variability, pupil dilation, and visual fixations were
recorded while youth had to up-or downregulate their emotions in response to
affective pictures in the Psychophysiological Indicators of Emotion Regulation
(PIER) task. Results: The novel training effectively improved self-reported emotion
regulation and momentary anxiety in both groups. Moreover, initial group
differences in emotional reactivity mostly disappeared when participants were
instructed to apply emotion regulation in the task. However, pupil dilation data
suggested that participants with anxiety disorders required more cognitive
resources for the upregulation of negative affect to counteract this effect.
Limitations: The relatively small sample size and large age range could hamper
detection of additional group differences that may exist. Conclusions: The current
study provides evidence that anxious youth can apply cognitive reappraisal to a
similar extent as healthy adolescents after emotion regulation training but may
need to exert more effort to do so. This training could be a valuable addition to
current treatment programs.
Psychosocial rehabilitation programs received mental health professional support in
addition to traditional medication therapy. Many psychosocial programs were
developed since the 1990s, including cognitive remediation therapy. In this review,
we focus on cognitive remediation therapy in Korea since the 1990s. We review
several cognitive rehabilitation programs developed in Korea and their outcome
studies and suggest future research directions and prospects. We reviewed cognitive
rehabilitation programs including social cognitive training as well as more recent
forms of computerized cognitive rehabilitation. Although there are differences in
cognitive domains by training targets, almost all neurocognitive remediation
trainings in Korea have beneficial effects on early visual processing, various
attention types, and executive function. Future studies need to investigate the
mechanisms and various mediators underlying the relationships between cognitive
functions and functional outcomes. With more comprehensive cognitive and social
cognitive programs, we can enhance both cognition and functional outcomes of the
patients with schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Objective: This pilot project was designed to develop procedures for and test the
feasibility of implementing Cognitive Enhancement Therapy (CET) in a group home
environment, with a goal of maximizing treatment efficacy by augmenting social
engagement in group CET sessions with ongoing social interaction. Methods: Six
participants who met criteria including chronic schizophrenia were recruited in a
group home with 30 residents. After two months of CET, pre- and posttest measures,
including cognitive tests, were administered and qualitative interviews were
conducted periodically. Interaction was observed in the house and staff members
were interviewed in a focus group. Results: Five of the initial six participants
completed the intervention-which continued for a total of 45 weeks-engaging in
weekly group CET sessions and computer exercises outside of the formal sessions.
All participants liked the computer exercises, and all but one participated in and
reported enjoying the group exercises. Observations and staff comments indicated
increased social interaction and sustained impact for some residents. Some aspects
of cognitive functioning improved for some participants during the initial two
months. Conclusions: CET now needs to be tested more formally to determine if it
can be delivered successfully in other group homes with a manualized procedure. The
idea should be tested that feedback effects due to the sustained social contact may
enhance the effectiveness of CET in group homes and lead to larger, sustained gains
in community functioning. Clinicians who provide cognitive interventions should
focus attention on the social context in which treatment is delivered and consider
providing treatment to patient groups whose daily, ongoing social interaction can
enhance its effects. (C) 2016 Elsevier B.V. All rights reserved.
Objective: Individuals with schizophrenia demonstrate cognitive, social cognitive,
and motivational deficits that contribute to impairment in real-world functioning.
In the current study, we investigated the effects of supplementing computerized
neurocognitive training with social cognitive exercises, as compared with
neurocognitive training alone. Method: In this ongoing, double-blind, randomized
controlled trial of 111 participants with psychosis, we compare the effects of
supplementing intensive targeted cognitive training with social cognitive training
exercises (TCT + SCT) with the effects of targeted cognitive training alone (TCT-
only). Participants were assessed on cognition, symptoms, functional capacity, and
functional outcomes, as well as social cognition and measures related to reward
processing. Results: Both treatment groups showed significant improvement in
multiple cognitive domains and improvement in functional capacity. However, as
predicted, TCT + SCT group participants showed significant improvement in prosody
identification and reward processing relative to TCT-only participants. Conclusions
and Implications for Practice: Our findings indicate that supplementing intensive
computerized cognitive training with social cognitive exercises in people with
psychosis confers greater benefits in prosody identification and reward processing
relative to cognitive training alone, even though both approaches drive significant
improvements in cognition and functional capacity. Impairments in both prosody
identification and reward processing have been associated with greater negative
symptoms and poorer functional outcomes in schizophrenia, raising the possibility
that this form of treatment may lead to better long-term outcomes than traditional
cognitive training approaches. Follow-up assessments will determine whether results
are durable and generalize over time to improvements in symptoms and functioning.
Objective: Cognitive remediation programs often have larger effects on cognition
compared with everyday outcomes. We compared changes across cognitive, functional
competence, and vocational domains in 2 cognitive remediation programs. Method: A
sequential enrollment, nonrandom design with 50 individuals with serious mental
illnesses (psychotic and mood disorders) from a community vocational rehabilitation
program. Action-Based Cognitive Remediation (ABCR), a new program that combines
traditional cognitive training techniques with simulated workplace situations and
goal setting for engaging with cognitively demanding activities (N = 24; 19
completers) was compared with traditional cognitive remediation (tCR; N = 26; 15
completers). Both groups met twice-weekly for 2-hr sessions over 10 weeks. Repeated
measures analysis of variance was used to examine effects pre-and posttreatment and
10 weeks after treatment. Univariate analysis of variance and chi-square tests were
used to compare work outcomes 6 months after intervention. Results: Significantly
more ABCR participants (83%) were retained in the intervention compared with tCR
(57%) and reported greater increases in perceived competence with cognitively
challenging tasks (eta(2) =.23). ABCR effects were significantly larger than tCR on
functional competence (eta(2) =.53), with smaller, nonsignificant differences in
social cognition (eta(2) =.14) and neurocognition (eta(2) =.16). ABCR participants
were marginally more likely to be competitively employed (68.4% vs. 40%) and, among
those employed, ABCR participants experienced less job-related stress (eta(2)
=.37). Conclusions and Implications for Practice: Cognitive rehabilitative programs
for serious mental illness that rely on computer -based training for
neuroplasticity should ensure opportunities for active skill development and
therapist supported techniques to overcome challenges with generalizing cognitive
effects to everyday outcomes.
Objective: Cognitive challenges are prominent features of individuals diagnosed
with schizophrenia, impairing occupational, social, and economic functioning. These
challenges are predictive of social and work outcomes. Cognitive remediation has
been shown to be effective in improving both cognitive and social functions.
However, cognitive remediation does not produce improvement in all participants. We
investigated demographic, neurocognitive, and psychopathological predictors
associated with improvement following cognitive remediation interventions in
service recipients with severe mental illnesses. Method: One hundred thirty-seven
adult participants with a diagnosis of schizophrenia, schizoaffective disorder, or
bipolar disorder according to the Diagnostic and Statistical Manual of Mental
Disorders (4th ed., text rev.) were enrolled in 12-week cognitive remediation
programs. Assessments of demographic and illness variables, together with baseline
and end point assessment of psychopathology (Positive and Negative Syndrome Scale
[PANSS]), neurocognition (Measurement and Treatment Research to Improve Cognition
in Schizophrenia [MATRICS] Consensus Cognitive Battery [MCBB]), and social
functions (Personal and Social Performance Scale [PSP]) were conducted. Change in
cognitive domains was calculated using the reliable change index. Logistic
regression analysis was used to assess predictors of cognitive improvement after
the intervention. Results: Sixty-two percent of participants improved on at least 1
of the MCCB domains. Higher baseline speed of processing, attention or vigilance,
and working memory predicted a positive response to cognitive remediation. Younger
age, higher education level, shorter length of stay, and lower PANSS Negative and
Disorganized factors were additional predictors. Conclusions and Implications for
Practice: Our results indicate the clinical usefulness of cognitive remediation and
identified a pattern of clinical and cognitive predictors of good response to the
intervention. Identification of these predictive factors by clinicians may enhance
the outcome and aid in the development of individualized rehabilitative cognitive
remediation treatment plans.
Background: The objective of this study was to validate the Turkish version of the
Quick Mild Cognitive Impairment (Qmci-TR) screen. Methods: In total, 100 patients
aged 65 years referred to a geriatric outpatient clinic with memory loss were
included. The Qmci was compared to the Turkish versions of the standardized Mini-
Mental State Examination and the Montreal Cognitive Assessment (MoCA). Results: The
Qmci-TR had higher accuracy than the MoCA in discriminating subjective memory
complaints (SMCs) from cognitive impairment (mild cognitive impairment [MCI] or
dementia), of borderline significance after adjusting for age and education (P
= .06). The Qmci-TR also had higher accuracy than the MoCA in differentiating MCI
from SMC, which became nonsignificant after adjustment (P = .15). A similar pattern
was shown for distinguishing MCI from dementia. Test reliability for the Qmci-TR
was strong. Conclusion: The Qmci-TR is a reliable and useful screening tool for
discriminating MCI from SMC and dementia in a Turkish population.
Background: Evidence in the literature suggests that there is an impairment of
social cognition in schizophrenia. Theory of Mind (ToM) is defined as one's ability
to understand others' wishes, beliefs, intentions, and other psychological states
and thereby to judge others' behavior, as an essential component of social
cognition. However, there have been limited studies on social cognition, especially
ToM in adolescent onset schizophrenia (AOS). The current study aims to investigate
ToM abilities in adolescent schizophrenia according to various ToM subcomponents
(cognitive ToM and affective ToM) and various ToM orders (first order and second
order). Methods: This study examines ToM in 35 adolescent schizophrenic patients
and 35 healthy adolescents using the "Yoni task" and "Faux Pas Recognition test" to
assess their affective and cognitive ToM abilities. Results: In the Yoni task,
patients with AOS showed differences in ToM abilities either on a different order
or under different conditions. The Faux Pas Recognition task results revealed that
AOS patients were not always able to recognize a faux pas or understand complicated
emotions under the faux pas scenario. Furthermore, as indicated by the correlation
analysis, neither cognitive ToM nor affective ToM was related to the patients'
symptoms, disease duration, dose of medication, or intelligence quotient (IQ).
Conclusion: Our findings showed AOS impairment in the performance of ToM tasks. It
seemed that impairment in second-order-ToM is more serious. Moreover, these
deficits are largely independent of symptom clusters, disease duration, dose of
medication, and IQ. It can be speculated that ToM dysfunction may be a hallmark of
adolescent schizophrenia.
The swarm cognitive behavior of bees readily translates to swarm intelligence with
"social cognition," thus giving rise to the rapid promotion of survival skills and
resource allocation. This paper presents a novel cognitively inspired artificial
bee colony clustering (ABCC) algorithm with a clustering evaluation model to manage
the energy consumption in cognitive wireless sensor networks (CWSNs). The ABCC
algorithm can optimally align with the dynamics of the sensor nodes and cluster
heads in CWSNs. These sensor nodes and cluster heads adapt to topological changes
in the network graph over time. One of the major challenges with employing CWSNs is
to maximize the lifetime of the networks. The ABCC algorithm is able to reduce and
balance the energy consumption of nodes across the networks. Artificial bee colony
(ABC) optimization is attractive for this application as the cognitive behaviors of
artificial bees match perfectly with the intrinsic dynamics in cognitive wireless
sensor networks. Additionally, it employs fewer control parameters compared to
other heuristic algorithms, making identification of optimal parameter settings
easier. Simulation results illustrate that the ABCC algorithm outperforms particle
swarm optimisation (PSO), group search optimization (GSO), low-energy adaptive
clustering hierarchy (LEACH), LEACH-centralized (LEACH-C), and hybrid energy-
efficient distributed clustering (HEED) for energy management in CWSNs. Our
proposed algorithm is increasingly superior to these other approaches as the number
of nodes in the network grows.
Background: Antiretroviral therapy (ART) improves the survival and quality of life
of HIV-positive individuals, but the effects of long-term ART use do eventually
manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in
Uganda (CoLTART) was established to investigate the metabolic and renal
complications of long-term ART use among Ugandan adults. We describe the CoLTART
study set-up, aims, objectives, study methods, and also report some preliminary
cross-sectional study enrolment metabolic and renal complications data analysis
results. Methods: HIV-positive ART naive and experienced adults (18 years and
above) in Uganda were enrolled. Data on demographic, dietary, medical, social
economic and behaviour was obtained; and biophysical measurements and a clinical
examination were undertaken. We measured: fasting glucose and lipid profiles, renal
and liver function tests, full blood counts, immunology, virology and HIV drug
resistance testing. Plasma samples were stored for future studies. Results: Between
July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were
ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on
ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females,
608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a
Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction
between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients
on PI regimens had higher total cholesterol, lower high density lipoprotein, higher
low density lipoprotein, higher triglycerides, and a high atherogenic index for
plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens
had higher mean diastolic hypertension than patients on PI regimens, p < 0.001.
Conclusions: Our finding of no differences in renal dysfunction between patients on
Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir
based first line ART can safely be initiated even in settings without routine renal
function monitoring. However, integration of cardiovascular risk assessment,
preventive and curative measures against cardiovascular disease are required. The
CoLTART cohort is a good platform to investigate the complications of long-term ART
use in Uganda.
Background: Although discovery research has identified the importance of dozens of
pro-and anti-inflammatory immune mediators in the pathogenesis, maintenance,
exacerbation and resolution of inflammatory diseases, most human cohort studies
have incorporated few or no immunological intermediate phenotypes in their
analyses. Significant hindrances have been (1) the limited panel of biomarkers
known to be readily detected in healthy human populations and (2) the stability,
hence utility, of such biomarkers to repeated analysis. Methods: The frequency and
stability of 14 plasma biomarkers linked to in vivo immune regulation of allergic
and autoimmune inflammatory disorders was determined in 140 healthy pediatric and
adult participants. The impact of initial and multiple subsequent freeze/thaw
cycles on pro-inflammatory (CCL2, CXCL10, IL-18, TNF alpha, IL-6), anti-
inflammatory (IL-10, sTNF-RII, IL-1Ra), acute phase proteins (CRP, PTX3) and other
biomarkers (sST2, IL-1RAcP) was subsequently quantified. Results: Multiple
biomarkers capable of providing an innate immune signature of inflammation were
readily detected directly ex vivo in healthy individuals. These biomarker levels
were unaffected when comparing paired data sets from freshly obtained, never frozen
plasma or serum and matched aliquots despite extensive freeze/thaw cycles. Neither
age nor sex affected stability. Similarly, no quantitative differences were found
following repetitive analysis of inflammatory biomarkers in culture samples
obtained following in vitro stimulation with TLR and RLR ligands. Conclusions: A
broad panel of in vivo and ex vivo cytokine, chemokine and acute phase protein
biomarkers that have been linked to human chronic inflammatory disorders are
readily detected in vivo and remain stable for analysis despite multiple freeze
thaw cycles. These data provide the foundation and confidence for large scale
analyses of panels of inflammatory biomarkers to provide better understanding of
immunological mechanisms underlying health versus disease.
Purpose Keratoconus (KC) is thinning of the central cornea. Its etiology is
unknown, but it may result from degrading of collagen type IV. The major protein in
the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade
collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9
enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1
(TIMP-1). In the present study, we sought to investigate and evaluate the effects
of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC
in an Iranian population sample. Methods This case-control study was performed on
140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-
9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification
refractory mutation system polymerase chain reaction (ARMS-PCR). Result Our
findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR =
0.26, 95% CI = 0.08-0.82, P = 0.022). rs17576A/G, associated with KC and the A
allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-
chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06-4.76, P =
0.036). In males, the allele frequency was not associated with KC risk/protection.
Conclusions This study indicates that in our population, the COL4A3 rs55703767
polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism
was associated with an increased risk of KC.
Affordable and portable indirect impedance measurement techniques with minimum
hardware and post-processing requirements are necessary for various applications,
and in particular for bioimpedance measurements. In this paper, a new method to
extract the single-dispersion Cole bioimpedance model parameters is presented using
a simple circuit consisting of a operational amplifier and a set of resistors. We
examine the theory behind this magnitude-only method and demonstrate its
application for the extraction of impedance data from a number of different fruit
samples. Three means to compute the single-dispersion Cole model parameters are
given and discussed under different measurement scenarios, and compared with
experimental results. (C) 2015 Elsevier B.V. All rights reserved.
Study Design. A three-level rat tail caudal intervertebral disc (IVD) degeneration
(IVDD) model was established to study effects of static compression on
extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD.
Objective. The aim of this study was to investigate the effect of compression force
on ECM remodeling and integrin signaling in IVDs during IVDD. Summary of Background
Data. Integrins sense mechanical environment alteration via binding to ECM ligands
and trigger intracellular signaling for pathological ECM remodeling during IVDD.
However, the role of compression force in ECM remodeling and integrin signaling
during IVDD remains elusive. Methods. Compared with the classical one-level rat
tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies,
a three-level model was established by using an Ilizarovtype apparatus to exert
stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To
exclude side effects from surgical stab injury on manipulated discs, intact
coccygeal (Co) disc Co8-9 was analyzed. Results. In three-level IVDD model,
significant degeneration of the Co8-9 disc was observed. Quantitative real-time
polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen
types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and
decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading
altered the expression of integrin alpha 2 beta 1 (upregulated) and alpha 10 beta 1
(downregulated) in NP cells, and activated integrin downstream signaling. By
contrast, one-level model showed more severe disc degeneration and ECM remodeling.
Integrin alpha 1, alpha 2, alpha 11, and beta 1 were upregulated, whereas alpha 10
was downregulated. Similar activation of integrin signaling was observed.
Conclusion. Static compression altered collagen and MMP expression, and promoted
beta 1 integrin expression and signaling in IVD. Compared with one-level rat tail
IVDD model, three-level model showed milder effects on disc degeneration, ECM
remodeling, and integrin expression, suggesting one-level model might involve other
causes that induce IVDD via mechanisms independent of compression force.
OBJECTIVE Spontaneous subaponeurotic fluid collection (SSFC) is an uncommon and
newly described entity of unknown etiology, observed in infants less than 1 year of
age. The authors report on series of infants who presented to the Hospital for Sick
Children (HSC) with SSFC, focusing on the natural history of this condition.
METHODS Data from the Hospital for Sick Children were retrospectively reviewed for
the period between January 2004 and June 2015. Patient age and sex, birth history,
medical history, laboratory findings, and symptoms were reviewed. SSFC location,
imaging characteristics, management, and outcome were also analyzed. A MEDLINE and
Embase literature search was performed on the condition, yielding previously
reported cases of SSFC in the English language. RESULTS Nine cases involving
patients who presented with SSFC during the study period were identified. The
patients were 4 male and 5 female infants (age range 5 weeks to 11 months). All
cases of SSFC developed spontaneously over a period of days, and the infants had no
history of injuries, trauma, or hair manipulation in the immediate period preceding
the development of the subgaleal collections. Six patients underwent remote
forceps- or vacuum-assisted instrumented births, although none of the patients
developed scalp collections or skin discoloration immediately after birth. All of
the cases were managed conservatively on an outpatient (6 cases) or inpatient (3
cases) basis. In 1 case, the size of the fluid collection fluctuated over 4 months,
but in all of the cases, the collections resolved spontaneously without structural
or infectious complications. CONCLUSIONS This is the largest series describing SSFC
to date and summarizes 9 cases managed at a large academic neurosurgical center.
Although the specific pathophysiology of SSFC remains unknown, in some cases the
condition may be associated with a remote history of instrumented delivery. SSFC
occurs spontaneously without immediate preceding trauma, and an extensive
hematology or child abuse workup is not necessary. A conservative approach with
outpatient follow-up is advocated.
The on-line measurement of high-power IGBT collector current is important for the
hierarchical control and short-circuit and overcurrent protection of its driver and
the sensorless control of the converter. The conventional on-line measurement
methods for IGBT collector current are not suitable for engineering measurement due
to their large-size, high-cost, low-efficiency sensors, current transformers or
dividers, etc. Based on the gate driver, this paper has proposed a current
measuring circuit for IGBT collector current. The circuit is used to conduct non-
intervention on-line measurement of IGBT collector current by detecting the voltage
drop of the IGBT power emitter and the auxiliary emitter terminals. A theoretical
analysis verifies the feasibility of this circuit. The circuit adopts an
operational amplifier for impedance isolation to prevent the measuring circuit from
affecting the dynamic performance of the IGBT. Due to using the scheme for
integration first and amplification afterwards, the difficult problem of achieving
high accuracy in the transient-state and on-state measurement of the voltage
between the terminals of IGBT power emitter and the auxiliary emitter (u(Ee)) has
been solved. This is impossible for a conventional detector. On this basis, the
adoption of a two-stage operational amplifier can better meet the requirements of
high bandwidth measurement under the conditions of a small signal with a large
gain. Finally, various experiments have been carried out under the conditions of
several typical loads (resistance-inductance load, resistance load and inductance
load), different IGBT junction temperatures, soft short-circuits and hard short-
circuits for the on-line measurement of IGBT collector current. This is aided by
the capacitor voltage which is the integration result of the voltage uEe. The
results show that the proposed method of measuring IGBT collector current is
feasible and effective.
Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid
synthesis, which is important in the development of colon carcinoma. The high
expression of FASN is considered a promising molecular target for colon cancer
therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect
in various types of human cancer, including colon cancer; however, the molecular
mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell
Counting Kit-8 assay. The apoptosis rate of cells was quantified via flow cytometry
following AnnexinV/ propidium iodide staining. FASN activity was measured by
monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength
of 340nm, and intracellular free fatty acid levels were detected using a Free Fatty
Acid Quantification kit. Western blot analysis and reverse transcription-polymerase
chain reaction were used to detect target gene and protein expression. The present
study was performed to investigate whether the gene expression of FASN and its
enzymatic activity are regulated by emodin in a human colon cancer cell line.
Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein
level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU-C5 cells.
Emodin significantly downregulated the protein expression of FASN in HCT116 cells,
which was caused by protein degradation due to elevated protein ubiquitination.
Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels
of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis
in a dose-and time-dependent manner. The combined treatment of emodin and
cerulenin, a commercial FASN inhibitor, had an additive effect on these activities.
Palmitate, the final product of the FASN reaction, rescued emodin-induced viability
and apoptosis. In addition, emodin altered FASN-involved signaling pathways,
including phosphatidylinositol3-kinase/Akt and mitogen-activated protein
kinases/extracellular signal-regulated kinases1/2. These results suggested that
emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and
provide a molecular basis for colon cancer therapy.
Changes in the colonic microbiota are critical to the pathogenesis of diverticular
complications such as diverticulitis and peridiverticular abscesses. However, more
subtle changes in microbiota composition may well be important to the more chronic
manifestations of diverticulosis. Some studies have shown the presence of bacterial
overgrowth in subgroups of patients with diverticular disease and recent studies,
using molecular biology techniques, found an increase of proteobacteria and
actinobacteria in patients with symptomatic uncomplicated diverticular disease
(SUDD), compared with healthy controls. The use of probiotics to modulate
intestinal microecology in SUDD appears therefore rational. Although several
investigations evaluating the clinical efficacy of probiotics have been performed,
no definitive results have yet been achieved, mainly due to the heterogeneity of
the available studies. Most of the studies used probiotics in combination with
poorly absorbed antimicrobials or anti-inflammatory drugs. In only 4 studies, there
was a harm using probiotics alone, but only 1 was a placebo-controlled, double-
blind trial. The analysis of the available evidence reveals a poor quality of the
published studies, whose design was heterogeneous, with only 2 out of 11 trials
being double-blind and randomized. Therefore, available data can only suggest a
benefit of probiotics in SUDD, but do not allow any evidence-based definite
conclusion. As a consequence, current guidelines state that there is insufficient
evidence to recommend probiotics for symptom relief in patients with diverticular
disease.
Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in
colon and rectal cancer samples, correlated with their age at diagnosis,
histological subtype, value of pretreatment CEA, TNM staging and clinical outcome.
Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor
samples obtained from surgical treatment of 50 patients. Results: An increased
expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor
samples was found. There was no statistically significant difference between the
expression of these genes and microRNAs when compared to age at diagnosis and
histological subtype. The EGFR gene showed higher expression in relation to the
value of CEA diagnosis. The expression of microRNA-203 was progressively lower in
relation to the TNM staging and was higher in the patient group in clinical
remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs
remains under investigation reserving huge potential for future applications and
clinical interventions in conjunction with existing therapies. We expect, based on
the exposed data, to stimulate the development of new therapeutic possibilities,
making the treatment of these tumors more effective.
High-power white light-emitting diodes (LEDs) have attracted much attention due to
their versatility in a variety of applications and growing demand in markets such
as general lighting, automotive lamps, communications devices, and medical devices.
In particular, the need for high reliability and long lifetime poses new challenges
for the research and development, production, and application of LED lighting.
Accurate and effective prediction of the lifetime or reliability of LED lighting
has emerged as one of the key issues in the solid-state lighting field. Prognostic
is an engineering technology that predicts the future reliability or determines the
remaining useful lifetime of a product by assessing the extent of deviation or
degradation of a product from its expected normal operating conditions. Prognostics
bring benefits to both LED developers and users, such as optimizing system design,
shortening qualification test times, enabling condition-based maintenance for LED-
based systems, and providing information for return-on-investment analysis. This
paper provides an overview of the prognostic methods and models that have been
applied to both LED devices and LED systems, especially for use in long-term
operational conditions. These methods include statistical regression, static
Bayesian network, Kalman filtering, particle filtering, artificial neural network,
and physics-based methods. The general concepts and main features of these methods,
the advantages and disadvantages of applying these methods, as well as LED
application case studies, are discussed. The fundamental issues of prognostics and
photoelectrothermal theory for LED systems are also discussed for clear
understanding of the reliability and lifetime concepts for LEDs. Finally, the
challenges and opportunities in developing effective prognostic techniques are
addressed.
Color is a common channel for displaying data in surface visualization, but is
affected by the shadows and shading used to convey surface depth and shape.
Understanding encoded data in the context of surface structure is critical for
effective analysis in a variety of domains, such as in molecular biology. In the
physical world, lightness constancy allows people to accurately perceive shadowed
colors; however, its effectiveness in complex synthetic environments such as
surface visualizations is not well understood. We report a series of crowdsourced
and laboratory studies that confirm the existence of lightness constancy effects
for molecular surface visualizations using ambient occlusion. We provide empirical
evidence of how common visualization design decisions can impact viewers' abilities
to accurately identify encoded surface colors. These findings suggest that
lightness constancy aids in understanding color encodings in surface visualization
and reveal a correlation between visualization techniques that improve color
interpretation in shadow and those that enhance perceptions of surface depth. These
results collectively suggest that understanding constancy in practice can inform
effective visualization design.
Expanding from remote areas of Mexico to a worldwide scale, the ten-striped insect,
the Colorado potato beetle (CPB, Leptinotarsa decemlineata Say), has risen from
being an innocuous beetle to a prominent global pest. A diverse life cycle,
phenotypic plasticity, adaptation to adverse conditions, and capability to detoxify
or tolerate toxins make this insect appear to be virtually indestructible. With
increasing advances in molecular biology, tools of biotechnological warfare were
deployed to combat CPB. In the last three decades, genetically modified potato has
created a new challenge for the beetle. After reviewing hundreds of scientific
papers dealing with CPB control, it became clear that even biotechnological means
of control, if used alone, would not defeat the Colorado potato beetle. This
control measure once again appears to be provoking the potato beetle to exhibit its
remarkable adaptability. Nonetheless, the potential for adaptation to these
techniques has increased our knowledge of this pest and thus opened possibilities
for devising more sustainable CPB management programs.
On a broader scale, T cell density and localization in colorectal cancer liver
metastases have prognostic and predictive implications. As T cell distribution at
higher resolutions has not been fully investigated, a detailed resolution analysis
of T cell distribution was performed. Patient tissues were divided into 10 mu m
distance classes between the tumor border and adjacent normal liver. Thereby,
distinct density patterns of T cell localization in relation to the malignant
tissue could be detected. At a distance of 20 to 30 mu m to the tumor, a decrease
of CD3 T cells is common. Within this area, cytotoxic Granzyme B and CD8(+) T cells
were found to be significantly reduced as well as CD163 macrophages were increased
and identified to be in close contact with T cells. Our data suggests a physical or
functional border within this region. Survival analysis revealed improved overall
survival in patients with high T cells numbers at the direct tumor border.
Interestingly, the decreased T cells in the 20 to 30 mu m region were also found to
be significantly associated with improved survival. Consequently, the detailed
localization of T cells, despite blockade, could be associated with improved
clinical outcome. The high-resolution analysis represents new insights into
relevant heterogenous T cell distributions especially related to clinical
responses. As the paradoxical observation of localization-dependent prognostic
relevance of T cell densities is only detectable by detailed spatial analyses, this
investigation of spatial profiles at higher resolutions is suggested as a new
biomarker for survival and response to therapies.
AIM To investigate the use of droplet digital polymerase chain reaction (ddPCR) for
detecting host mRNA markers in stools as a non-invasive test for colorectal cancer
screening. METHODS ddPCR and quantitative PCR were compared side by side for their
performance in the detection of ITGA6 and ITGA6A transcripts in stool samples
obtained from patients with various types of colorectal lesions (advanced adenomas
and stage II - IV colorectal cancers) and control (patients displaying no
pathological findings) using duplex TaqMan reactions for both methods. ITGA6 and
ITGA6A were chosen for this proof-of-concept study based on their relative medium
and low abundance in stool samples, respectively, as established in a previous
study. RESULTS We found that the ddPCR and qPCR methods performed equally well in
this TaqMan duplex assay for the detection of ITGA6 and ITGA6A transcripts in
stools of patients with colorectal lesions. For ITGA6, receiver operating
characteristic (ROC) curve analysis showed comparable areas under the curve of 0.91
(P < 0.0001) and 0.89-0.90 (P < 0.0001) for the prediction of advanced adenomas and
colorectal cancers, respectively. ITGA6A, which was detected at very low levels in
control patients, was found to be significantly elevated (over 40 times) in stage.
and. colorectal cancers (P < 0.0002). Comparison of the two sets of data revealed a
strong correlation of the copy numbers obtained by ddPCR and qPCR for both ITGA6
and ITGA6A. CONCLUSION We found that ITGA6 and ITGA6A detection in stools of
patients with colorectal cancers with ddPCR is comparable to that of qPCR using
TaqMan assays.
Background and Aim: Long intergenic noncoding RNAs (lincRNAs) have critical roles
in elevating efficacy of anticancer therapy and tumor progression. Recent studies
show that Regulator of Reprogramming (ROR) is aberrantly expressed in several types
of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a
standard preoperative treatment. However, a considerable number of CRCs are
resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in
radiotherapy for CRC and detected the underlying molecular mechanism. Methods:
Real-time polymerase chain reaction was employed to quantify the expression level
of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and
apoptosis assays were used to confirm the radiotherapy-mediated effects by lincRNA-
ROR altered expression. The direct impact of lincRNA-ROR on the expression of
p53/miR-145 by loss-of-function and gain-of-function strategy was also analyzed. A
xenograft mouse model was used to evaluate the role of linc-ROR in CRC treatment.
Results: We discovered that lincRNA-ROR was upregulated in CRC cell lines and
tissue samples. We further showed that knockdown of lincRNA-ROR enhanced the
sensitivity to radiotherapy for CRC by inhibiting cell viability and promoting
apoptosis. Activity of the p53/miR-145 pathway may help explain the role of
lincRNA-ROR for stress-induced regulation in CRC therapy. Combined specific
knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model resulted in
a significant reduction in the tumor growth. Conclusion: LincRNA-ROR decreases
sensitivity to radiotherapy via the negative regulation of p53/miR-145 and may
represent a potential target for the treatment of CRC.
Serrated polyps have long been thought to lack malignant potential in the human
colorectum. However, identification of the serrated pathway to colorectal cancer
based on molecular biology has improved our understanding of the pathogenesis of
colorectal cancers. Accordingly, serrated polyps such as traditional serrated
adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be
precursor lesions of the serrated pathway. Recently, serrated polyps were
classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and
traditional serrated adenoma, according to the World Health Organization
classification. It has been suggested that SSA/P in the proximal colon are a
precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF
mutation and a CpG island methylator phenotype with or without microsatellite
instability. However, SSA/P is more challenging to detect by colonoscopy and is
likely to account for some interval cancers, particularly in the proximal colon
because it presents flat or sessile, isochroous appearance, and occasionally has a
mucous cap. Furthermore, the possibility has been raised that pathologists
misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to
recognize the endoscopic features of serrated polyps to facilitate their detection
and removal and also to establish postpolypectomy surveillance guidelines. In this
review, we discuss the recent classification of serrated polyps; the molecular
characteristics of the serrated pathway; appropriate diagnostic methods using
endoscopy, including a new image-enhanced endoscopic technique; and management of
these lesions.
People living nowadays with HIV and AIDS may be treated effectively regarding virus
replication and immunology. However, non-AIDS-defining cancer is of growing
relevance due to high incidence and unfavorable outcome. The aim of this review is
to summarize current knowledge on gastrointestinal (GI) carcinoma. Although
literature on GI cancer is rare, an increased incidence of esophageal, gastric,
pancreatic, hepatocellular, and colorectal carcinoma has been demonstrated.
However, there are only few reports on therapy strategies and outcome, so that,
despite increased occurrence of many GI carcinomas, only little is known about
individualized treatment options and outcome in HIV-positive patients. More efforts
have to be undertaken to close this gap. (C) 2017 S. Karger GmbH, Freiburg
Purpose of reviewDespite the large investment of resources from screening, the fact
that colorectal cancer remains the second leading cause of cancer deaths among
Americans underscores the need for alternative strategies. Thus, a major clinical
and research imperative is personalize clinical care, while focusing on risk
stratification for screening, surveillance, chemoprevention, and therapeutic
intervention.Recent findingsA complicating factor that colorectal cancer is
biologically heterogeneous for at least four consensus molecular subtypes presents
clear challenges for developing robust molecular biomarkers.SummaryThe purpose of
the review is to discuss the genetics and molecular biology of colonic neoplasia,
high and low penetrance, and racial disparities in colonic neoplasia. Finally, we
put forth the emerging concept of greater genomic landscape and the idea of
chromatin protection therapy as a novel adjuvant to chemotherapy.
Purpose: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in
China and fourth worldwide. Metastatic dissemination of primary tumors is
considered main cause for CRC related mortality. The serine-threonine kinase 31
(STK31) gene is a novel cancer testis (CT) antigen. It was found significantly
highly expressed in gastrointestinal cancers. In our study we aimed to analyze the
correlation between STK31 expression patterns and metastasization, tumor stage and
grade in CRC patients. Results: Relative STK31 expression level was significantly
higher in patients with lymph node metastasis. STK31 expression levels in primary
tumorous tissues of metastatic patients were significantly higher than in ANCTs and
in lymph nodes samples, both at the RNA level and the protein level. Materials and
Methods: Surgical specimens of cancerous tissues, paired with adjacent noncancerous
tissues, and lymph nodes from 44 CRC cases with different clinicopathological
features were collected. Expression of STK31 was detected and measured by
immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-
PCR). Conclusions: Our data suggest that STK31 might be a potential biomarker in
detecting, monitoring and predicting the metastatic risk of colorectal cancer.
UNC5C is a member of the UNC5H family of transmembrane receptors and functions as a
dependence receptor. The expression of UNC5C is lost or markedly reduced in a large
proportion of cancers at the messenger RNA level. However, there is little
information available regarding the protein expression of UNC5C, the relationship
between UNC5C protein expression and UNC5C methylation, and the correlation between
patient clinical features and UNC5C protein expression in colorectal cancer. In
this study, the methylation and protein expression of UNC5C were examined in 36
adenomatous polyps, 73 colorectal cancers, and 28 corresponding normal mucosa, and
the correlation between the methylation, as well as protein expression status, and
the clinicopathologic features was evaluated. Furthermore, the relationship between
the methylation and protein expression of UNC5C, and correlation between UNC5C
protein expression and overall survival were analyzed. The results showed that
aberrant methylation of UNC5C was observed in colorectal cancers (78%) and
adenomatous polyps (64%). The methylation-specific polymerase chain reaction
results were confirmed by bisulfite sequencing of UNC5C promoter region. UNC5C
methylation was significantly higher in early tumor, node, metastasis stage (I +
II) of colorectal cancers. Compared with the corresponding normal tissues, protein
expression of UNC5C was significantly lower in colorectal cancers (42%) and
adenomatous polyps (81%). Protein expression of UNC5C was significantly higher in
early tumor, node, metastasis stage (I + II) of colorectal cancers compared with
advanced tumor, node, metastasis stage. Furthermore, patients with UNC5C-negative
expression had a poorer prognosis than those with UNC5C-positive expression through
Kaplan-Meier survival analysis (p = 0.038), univariate (p = 0.044) and multivariate
analysis (p = 0.045). According to Spearman rank correlation analysis, UNC5C
methylation and protein expression were negatively correlated (r = -0.461, p <
0.001). Together, these results suggest that UNC5C methylation may be an earlier
event in the development of colorectal cancer, which was negatively correlated with
protein expression. UNC5C may have a critical role in the pathogenesis of
colorectal cancers and be a valuable prognostic factor of colorectal cancers
patients. UNC5C may be identified as an attractive therapeutic target for the
treatment of colorectal cancers in the further studies.
Background miR-338-3p is a recently discovered miRNA and is involved in cell
differentiation. However, few data are yet available on the aberrant expression of
miR-338-3p in human colorectal carcinoma (CRC). This work aimed to investigate the
relationship between miR-338-3p expression pattern and clinicopathological features
of human CRC and the possible regulative mechanisms. Methods The 40 CRC, adjacent
nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were
collected, respectively, and the total RNA and protein were isolated routinely. The
miR-338-3p expression pattern was detected by real-time reverse transcription-
polymerase chain reaction (RT-PCR) and Northern blotting. Smoothened (SMO, possible
target of miR-338-3p) mRNA and corresponding protein expression pattern were
detected by semiquantitative RT-PCR and Western blotting. nniR-338-3p expression
patterns were compared between nontumor mucosa and CRC samples, graded by
progression-related factors. Disease outcome was calculated by Kaplan-Meier
survival analysis to determine whether miR-338-3p was related to disease-free
survival (DFS) and overall survival (OS) of patients. Moreover, SMO 3'-UTR fragment
was PCR amplified from genome DNA of human colon and inserted into a luciferase
reporter plasmid. The luciferase reporter plasmid construct was then transfected
into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase
activity in the transfected cells was detected. Results The expression of miR-338-
3p was significantly downregulated in CRCs than those in the adjacent nontumorous
tissues, and the value was negatively related to advanced TNM stage and local
invasion (P <0.01). Furthermore, miR-338-3p value was decreased markedly in SW-620
cell line relative to SW-480 (P <0.01). Low expression of miR-338-3p was associated
with unfavorable outcome in DFS but not in OS independent of clinical covariates.
Moreover, RT-PCR and Western blotting analysis demonstrated that there was no
significant difference in SMO mRNA expression between the corresponding CRCs and
nontumorous tissues, whereas SMO protein markedly increased in CRCs (P <0.01). A
significant increase in luciferase activity was detected in CRC cells, which were
cotransfected with the luciferase reporter plasmid construct and anti-miR-338-3p (P
<0.01). Conclusions nniR-338-3p is expressed differentially in CRC and associated
with progression and prognosis of CRC. SMO might be a possible target of miR-338-
3p, which made it a potential antitumor candidate for treatment and prevention of
CRC.
Molecular pathological epidemiology (MPE) is an integrative field that utilizes
molecular pathology to incorporate interpersonal heterogeneity of a disease process
into epidemiology. In each individual, the development and progression of a disease
are determined by a unique combination of exogenous and endogenous factors,
resulting in different molecular and pathological subtypes of the disease. Based on
"the unique disease principle," the primary aim of MPE is to uncover an interactive
relationship between a specific environmental exposure and disease subtypes in
determining disease incidence and mortality. This MPE approach can provide
etiologic and pathogenic insights, potentially contributing to precision medicine
for personalized prevention and treatment. Although breast, prostate, lung, and
colorectal cancers have been among the most commonly studied diseases, the MPE
approach can be used to study any disease. In addition to molecular features, host
immune status and microbiome profile likely affect a disease process, and thus
serve as informative biomarkers. As such, further integration of several
disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and
microbial MPE), to provide novel insights into underlying etiologic mechanisms.
With the advent of high-throughput sequencing technologies, available genomic and
epigenomic data have expanded dramatically. The MPE approach can also provide a
specific risk estimate for each disease subgroup, thereby enhancing the impact of
genome-wide association studies on public health. In this article, we present
recent progress of MPE, and discuss the importance of accounting for the disease
heterogeneity in the era of big-data health science and precision medicine.
In the present work, a solid chemical sensor using mesoporous silica nanospheres as
scaffold, was applied for preconcentration and spectrophotometric determination of
the Hg(II), Ag(I), Au(III), and Pd(II) in electronic wastes. Digital Image-Based
Colorimetric Analysis was also used for determination of the concentrations of the
metal ions as a fast and low-cost colorimetric detections for quantitative chemical
analysis. At the optimum conditions, the analytical characteristics of the two
methods (e.g., limit of detection and linear range) were evaluated. Linearity was
obeyed.in the range of 0.5-10 ng m1(-1) of Au(III) with a linear correlation
coefficient of 0.999. The new sensor displayed high sensitivity for very low
concentrations of the detectable metals analytes up to 10(-10) mol L-1 in solution.
Results showed evidence that Thiomichler's Ketone (TMK) sensor will attract
worldwide attention as a promising technological means of recovering and recycling
silver, gold and palladium. (C) 2017 Elsevier B.V. All rights reserved.
Compressed air energy storage technologies can improve the supply capacity and
stability of the electricity grid, particularly when fluctuating renewable energies
are massively connected. While incorporating the combined cooling, heating and
power systems into compressed air energy storage could achieve stable operation as
well as efficient energy utilization. In this paper, a novel combined cooling,
heating and power based compressed air energy storage system is proposed. The
system combines a gas engine, supplemental heat exchangers and an ammonia-water
absorption refrigeration system. The design tradeoff between the thermodynamic and
economic objectives, i.e., the overall exergy efficiency and the total specific
cost of product, is investigated by an evolutionary multi-objective algorithm for
the proposed combined system. It is found that, with an increase in the exergy
efficiency, the total product unit cost is less affected in the beginning, while
rises substantially afterwards. The best trade-off solution is selected with an
overall exergy efficiency of 53.04% and a total product unit cost of 20.54
cent/kWh, respectively. The variation of decision variables with the exergy
efficiency indicates that the compressor, turbine and heat exchanger preheating the
inlet air of turbine are the key equipment to cost-effectively pursuit a higher
exergy efficiency. It is also revealed by an exergoeconomic analysis that, for the
best trade-off solution, the investment costs of the compressor and the two heat
exchangers recovering compression heat and heating up compressed air for expansion
should be reduced (particularly the latter), while the thermodynamic performance of
the gas engine need to be improved significantly. (C) 2017 Elsevier Ltd. All rights
reserved.
Recent energy policy has favored a massive introduction of Renewable Energy Sources
on electricity markets, which has greatly impacted their performance. First, the
electricity price has decreased as a consequence of the so-called merit-order
effect. Another relevant effect is associated to the intermittent nature of
Renewable Energy, which has increased the cost of ancillary services. A third and
important aspect, less addressed in the literature, is the induced change in the
strategic behavior of the conventional electricity producers. In principle, the
entry of new generators in a concentrated market would make it more competitive and
change the strategic behavior of the incumbents. We test this hypothesis for the
Spanish wholesale market. While we find no significant change in behavior for
Nuclear, Hydropower and Coal, a change is observed in Combined Cycle bidding
strategies after the entry of renewable generators. Our analysis shows that the
massive entry of Renewable Energy Sources made other generators' behavior more
competitive in the short run, but the effect was not persistent.
Active demand side response (DSR) will provide a significant opportunity to enhance
the power system flexibility in the Great Britain (GB). Although electricity peak
shaving has a clear reduction on required investments in the power system, the
benefits on the gas supply network have not been examined. Using a Combined Gas and
Electricity Networks expansion model (CGEN+), the impact of DSR on the electricity
and gas supply systems in GB was investigated for the time horizon from 2010 to
2050s. The results showed a significant reduction in the capacity of new gas-fired
power plants, caused by electricity peak shaving. The reduction of gas-fired power
plants achieved through DSR consequently reduced the requirements for gas import
capacity up to 90 million cubic meter per day by 2050. The cost savings resulted
from the deployment of DSR over a 50-year time horizon from 2010 was estimated to
be around 60 billion for the GB power system. Although, the cost saving achieved in
the gas network was not significant, it was shown that the DSR will have a crucial
role to play in the improvement of security of gas supply. (C) 2016 The Authors.
Published by Elsevier Ltd.
Purpose: Combined modality therapy is a mainstay option for thoracic malignancies
and head and neck cancers. The integration of different strategies is based on the
multidisciplinary approach of modern clinical oncology. Radiation oncologists have
to be educated, trained, and updated to provide state-of-the-art care to cancer
patients and thus educational meetings are crucial. Methods: The Italian
Association of Radiation Oncology Young Members Working Group (AIRO Giovani)
organized its 8th national meeting, focused on combination therapy in lung,
esophageal, and head and neck cancer (with a specific focus on larynx-preservation
strategies for larynx/hypopharynx tumors), involving young professionals working in
Italy. The meeting was addressed to young radiation oncologists, presenting state-
of-the-art knowledge, based on the latest evidence in this field. We performed a
review of the current literature based on the highlights of the Congress. Results:
The multimodality approach of head and neck and thoracic malignancies includes
surgery, chemotherapy, and radiotherapy, but also has to take into account new
information and data coming from basic and translational research and including
molecular biology, genetics, and immunology. All these aspects are crucial for the
treatment of non-small-cell lung cancer and esophageal, esophagogastric junction,
and larynx/hypopharynx malignancies. The integration of different treatments in the
clinical decision-making process to combine therapies is crucial. Conclusions:
Combination therapy has proved to be a consolidated approach in these specific
oncologic settings, highlighting the importance of multimodality management in
modern clinical oncology. Dedicated meetings on specific topics are helpful to
improve knowledge and skills of young professionals in radiation oncology.
The widespread overuse of antibiotics in aquaculture has led to the emergence of
antibiotic-resistance shrimp pathogens, the negative impact on shrimp gut
microbiota, and the presence of antimicrobial residues in aquaculture products,
with negative consequences on human health. Alternatively, probiotics have positive
effects on immunological responses and productive performance of aquatic animals.
In this study, three probiotic bacteria, (Bacillus licheniformis MAt32, B. subtilis
MAt43 and B. subtilis subsp. subtilis GAtB1), isolated from the Anadara tuberculosa
were included in diets for juvenile shrimp, Litopenaeus vannamei, to evaluate their
effects on growth, survival, disease prevalence, and immune-related gene
expression. Shrimp naturally infected with WSSV and IHHNV were fed with the basal
diet (control, T1) and diets supplemented with four levels of bacilli probiotic mix
(1:1:1) at final concentration of (T2) 1 x 10(6), (T3) 2 x 10(6), (T4) 4 x 10(6),
and (T5) 6 x 10(6) CFU g(-1) of feed. The specific growth rate of shrimp was
significantly higher in T2 than in Tl (control) treatment, and the final growth as
well as the survival were similar among treated groups. The prevalence of WSSV and
IHHNV infected shrimp was reduced in T2 and T4 treatments, respectively, compared
with control. The mRNA expression of proPO gene was higher in treatment T4 than
control. The LvTo111 gene was significantly up-regulated in treatments T4 and T5
compared to control. The SOD gene was up-regulated in treatment T5 compared to
control. In contrast, the mRNA expression of the Hsp70 gene was down -regulated in
treatments T4 and T5 respect to control, and the TGase gene remained unaffected by
the level of bacillus probiotic mix. As conclusion, the bacilli probiotic mix
(Bacillus spp.) enhanced immune-related gene expression in WSSV and IHHNV naturally
infected shrimp. This is the first report of probiotic potential of bacteria
isolated from A. tuberculosa on the immune response and viral prevalence in shrimp
Litopenaeus vannamei. (C) 2016 Elsevier Ltd. All rights reserved.
An increasing body of evidence indicates the relevance of microbiota for pulmonary
health and disease. Independent investigations recently demonstrated that the lung
harbors a resident microbiota. Therefore, it is intriguing that a lung microbiota
can shape pulmonary immunity and epithelial barrier functions. Here, we discuss the
ways how the composition of the microbial community in the lung may influence
pulmonary health and vice versa, factors that determine community composition.
Prominent microbiota at other body sites such as the intestinal one may also
contribute to pulmonary health and disease. However, it is difficult to
discriminate between influences of lung vs. gut microbiota due to systemic
mutuality between both communities. With focuses on asthma and respiratory
infections, we discuss how microbiota of lung and gut can determine pulmonary
immunity and barrier functions.
Energy storage resources (ESRs) inherent in building structures are a viable,
attractive option to improve power system operation by providing demand-side
flexibility. This paper proposes a two-stage optimisation framework for price-based
demand response of commercial buildings that include variable speed heat pumps
(VSHPs). The proposed framework aims at assisting commercial building aggregators
to devise a beneficial strategy for exploiting thermal ESRs in response to
electricity prices. Specifically, in this paper, the thermal dynamics of VSHPs are
modelled in detail using a set of piecewise linear equations for two different
methods of room temperature control. The energy consumption and reserve provision
of VSHPs, as well as plug-in electric vehicles, are then co-optimised considering
the operating conditions of distribution networks (DNs) for the pre- and post-
contingency states of wind power generation. Simulation case studies are performed
to estimate the effects of building ESRs on the optimal operation of power systems
and commercial buildings under various conditions characterised by: (1) temperature
control methods, (2) ESR penetration levels, and (3) DN operational constraints.
(C) 2017 Elsevier Ltd. All rights reserved.
Traffic flow in cities is affected by numerous factors, including land use
(especially commercial land use because of its trip-making nature). This phenomenon
can be more effective when combined with accessibility factors and street
connectivity. The case of Bojnourd has been selected for this study. The most
important reason to choose this case is that the municipality gives commercial
construction permits to developers in this city without paying attention to traffic
consequences. Bojnourd is a medium-sized city and the capital of the North Khorasan
province. The ultimate goal of this study is to determine the effectiveness of both
commercial land use and route configuration on number of trips. For this purpose,
analysis of secondary data has been used as the method of study. Findings showed
that there is a significant relationship between commercial land use and trip
volume in Bojnourd city. Findings also indicated a strong correlation between the
syntax of routes and traffic flow in the case of Bojnourd. The combined effect of
both commercial land use and route configuration on the number of trips was
examined and both factors that influence the number of trips were significant. (C)
2016 American Society of Civil Engineers.
Identifying parasitized nests and eggs is a prerequisite for studying conspecific
brood parasitism. Previous studies on the effectiveness of egg morphology to
identify parasitic eggs of different species have produced mixed results. Brood
parasitism and egg measurements (length, width and weight) were monitored in Common
Coot (Fulica atra; n = 85) nests. Maximum Euclidean distance was calculated for
each nest. Results indicated that maximum Euclidean distance values of non -
parasitized and parasitized nests were significantly different (t(83) = 9.747, P <
0.01). The optimal split value of recursive partitioning analysis for Common Coot
nests was 2.98 (R-2 = 0.65), which can identify 93.3% non-parasitized and 88.0%
parasitized nests successfully. However the most dissimilar egg in parasitized
nests calculated by maximum average Euclidean distance only identified 39.3% of the
parasitic eggs correctly. Egg morphology is effective for detecting conspecific
brood parasitism of Common Coot nests, but is not accurate enough to determine
parasitic eggs. As a result, this method should be used with caution and combined
with observational or molecular biology methods.
Primary antibody deficiencies (PADs) are the most common form of primary
immunodeficiency and predispose to severe and recurrent pulmonary infections, which
can result in chronic lung disease including bronchiectasis. Chronic lung disease
is among the most common complications of PAD and a significant source of morbidity
and mortality for these patients. However, the development of lung disease in PAD
may not be solely the result of recurrent bacterial infection or a consequence of
bronchiectasis. Recent characterization of monogenic immune dysregulation disorders
and more extensive study of common variable immunodeficiency have demonstrated that
interstitial lung disease (ILD) in PAD can result from generalized immune
dysregulation and frequently occurs in the absence of pneumonia history or
bronchiectasis. This distinction between bronchiectasis and ILD has important
consequences in the evaluation and management of lung disease in PAD. For example,
treatment of ILD in PAD typically uses immunomodulatory approaches in addition to
immunoglobulin replacement and antibiotic prophylaxis, which are the stalwarts of
bronchiectasis management in these patients. Although all antibody-deficient
patients are at risk of developing bronchiectasis, ILD occurs in some forms of PAD
much more commonly than in others, suggesting that distinct but poorly understood
immunological factors underlie the development of this complication. Importantly,
ILD can have earlier onset and may worsen survival more than bronchiectasis.
Further efforts to understand the pathogenesis of lung disease in PAD will provide
vital information for the most effective methods of diagnosis, surveillance, and
treatment of these patients. (C) 2016 American Academy of Allergy, Asthma &
Immunology.
Intergeneric hybridization is an important strategy to introgress alien genes into
common wheat for its improvement. But presence of crossability barrier mechanism
regulated by Kr1 gene played a major destructive role for hybridization than other
reported genes. In order to know the underlying molecular mechanism and to dissect
out this barrier, cDNA-AFLP (Amplified Fragment Length Polymorphism)
transcriptional analysis was carried out using chromosome 5B RIL (Recombinant
Inbred Line) population. Totally 14 differentially expressed fragments for Kr1 gene
were identified, cloned and sequenced. Further the expression was confirmed by
northern blotting analysis. Sequence analysis of the resulted clones revealed
several classes of putative genes, including stress responsive, signal transduction
and flowering related genes. The probable relation between other genes, Vrn1 and
Ph1, located along with Kr1 gene was discussed.
A loop stability compensation technique for continuous-time common-mode feedback
(CMFB) circuits is presented. A Miller capacitor and nulling resistor in the
compensation network provide a reliable and stable operation of the fully-
differential operational amplifier without any performance degradation. The
amplifier is designed in a 130 nm CMOS technology, achieves simulated performance
of 57 dB open loop DC gain, 1.3-GHz unity-gain frequency and 65 degrees phase
margin. Also, the loop gain, bandwidth and phase margin of the CMFB are 51 dB, 27
MHz, and 76 degrees, respectively.
This paper proposes a gravity heat pipe exchanger used for cooling the
communication base station to replace the traditional air conditioning system
during winter and transition seasons. Tests were conducted on a commercial
available gravity heat pipe exchanger. The experiment was performed to study the
effects of the air flow rate and temperature on the cooling capacity, the heat
transfer unit number (NTU) and cooling efficiency of the heat pipe exchanger. The
results showed that the larger the air flow rate, the smaller the NTU and the
larger the cooling capacity. Based on the analysis of the experimental data, it
proved that the gravity heat pipe exchanger could reduce running time and operating
cost of air conditioning system. According to the practical applications, the
yearly cooling loads of a typical communication base station were further
calculated for five typical cities which represent the five climatic zones of
China. The results validated that the energy saving by using the gravity heat pipe
exchanger is significant. The highest annual electricity-saving rate is achieved by
Kunming, about 48.6%, while the lowest annual electricity-saving rate is obtained
in Guangzhou, about 18.7% among the five climatic zones. The fitted correlation of
cooling capacity in term of outdoor temperature is generic to evaluate
approximately the performance of applying the gravity heat pipe exchanger in the
actual applications subject to various outdoor temperatures. (C) 2016 Elsevier Ltd.
All rights reserved.
The Door-in-the-Face (DITF) sequential message strategy was investigated in a
threestudy analysis of existing experimental findings. The current study predicted
there would be a positive relationship between concession size and compliance rates
in DITF studies. Study 1 included 25 comparisons where size of concession was
quantifiable as measured by percentage reduction from initial to target request in
the DITF condition. Study 2 data relied on a panel of undergraduate students to
provide an index of concession size in 12 additional observations. A third study
validated the panel procedure of rating concession size and also provided 9
additional independent observations from the pool of published studies on DITF.
Results from each study indicated a positive relationship between concession size
and effect size (r = 0.35, 0.55, 0.68, respectively). Study findings provide
support for reciprocal concessions explanation for DITF effects.
A method for determining mRNA half-lives in the polymorphic fungus Candida albicans
is described. It employs growth in a defined medium, the inhibition of
transcription with thiolutin (10-20 mu g/mL), and quantitative Northern blotting.
The method is effective for the A72, SC5314, and CAI-4 strains of C. albicans, and
for mRNAs that have a wide variety of decay rates and steady-state abundances. The
range of half-lives detected (from 4-168 min) shows that this method is effective
for mRNAs with widely varying half-lives. The mRNA decay rates obtained are
compared with those for orthologous mRNAs from Saccharomyces cerevisiae. This
procedure should work for a broad range of C. albicans strains and can be adapted
to other fungal species.
This paper describes a high temperature voltage comparator and an operational
amplifier (op-amp) in a 1.2-mu m silicon carbide (SiC) CMOS process. These circuits
are used as building blocks for designing a high-temperature SiC low-side over
current protection circuit. The over current protection circuit is used in the
protection circuitry of a SiC FET gate driver in power converter applications. The
op-amp and the comparator have been tested at 400 degrees C and 550 degrees C
temperature, respectively. The op-amp has an input common-mode range of 0-11.2 V, a
dc gain of 60 dB, a unity gain bandwidth of 2.3 MHz, and a phase margin of 48
degrees at 400 degrees C. The comparator has a rise time and a fall time of 38 and
24 ns, respectively, at 550 degrees C. The over current protection circuit,
implemented with these analog building blocks, is designed to sense a voltage
across a sense resistor up to 0.5 V.
In the context of a doubly fed induction generator (DFIG) connected to the utility
grid under unbalanced voltage conditions, the controller design needs to ensure
additional challenges such as restricting the total harmonic distortion (THD) in
grid current, minimizing the pulsations in generated power, torque, dc-link
voltage, etc., apart from facilitating the generator power control. In this study,
a negative-sequence compensation scheme for the magnetizing current in a DFIG is
investigated. The reference currents are modified to include the negative-sequence
compensating component for the magnetizing current. A rotor-side converter is
employed to compensate the pulsations in magnetizing current thereby minimizing the
ripple in power and torque. A grid-side converter is used to maintain unity power
factor and a constant dc-link voltage. It is revealed that controlling the
magnetizing current as a single control target enables simultaneous reduction of
pulsations in torque, power, and dc-link voltage and also minimizes unbalance in
currents. The effectiveness of the scheme is validated through detailed analysis
and numerical simulations in PSCAD/EMTDC for a practical 250 kW DFIG wind
generation system and further, through experimental results for a 2.3 kW DFIG test
setup. Typical experimental results for the laboratory test setup show an improved
performance.
The digital low dropout regulator (D-LDO) has drawn significant attention recently
for its low-voltage operation and process-scalability. However, the D-LDO
inherently suffers from limit cycle oscillation (LCO). To address this issue, the
modes and amplitudes of LCO are calculated in this work and verified by SPICE
simulation in a 65-nm CMOS process. An LCO reduction technique for the D-LDO is
then proposed, by adding two unit power transistors in parallel with the main power
MOS array as a feedforward path. This technique sets the LCO mode to 1 and
effectively reduces the ripple amplitude for a wide (0.5-20 mA) load current range.
When compared with the dead-zone scheme, this technique minimizes LCO with
negligible circuit complexity and design difficulty.
Numerous breast cancer patients experience cognitive changes during and after
chemotherapy. Chemotherapy-related cognitive impairment can significantly affect
quality of life. This pilot study attempted to determine the effects of a
compensatory cognitive training on the objective and subjective cognitive
functioning of breast cancer patients receiving adjuvant chemotherapy. Fifty-four
patients were assigned to either a compensatory cognitive training or waitlist
condition. They were assessed at baseline (T1), the completion of the 12-week
intervention (T2), and 6 months after intervention completion (T3). Outcomes were
assessed using the standardized neuropsychological tests and the Functional
Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), version 3. Raw data
were converted to T-scores based on baseline scores, and a repeated-measures
ANCOVA, adjusting for age, intelligence, depression, and treatment, was used for
analysis. The effect sizes for differences in means were calculated. The
intervention group improved significantly over time compared to the waitlist group
on objective cognitive function. Among ten individual neuropsychological measures,
immediate memory, delayed memory, verbal fluency in category, and verbal fluency in
letter showed significant group x time interaction. In subjective cognitive
function, scores of the waitlist group significantly decrease over time on
perceived cognitive impairments, in contrast to those of the intervention group.
The 12-week compensatory cognitive training significantly improved the objective
and subjective cognitive functioning of breast cancer patients. Because this was a
pilot study, further research using a larger sample and longer follow-up durations
is necessary.
Chen J-K, Chen J, Thomas G, Kozma SC, Harris RC. S6 kinase 1 knockout inhibits
uninephrectomy- or diabetes-induced renal hypertrophy. Am J Physiol Renal Physiol
297: F585-F593, 2009. First published May 27, 2009;
doi:10.1152/ajprenal.00186.2009. - Removal of one kidney stimulates synthesis of
RNA and protein, with minimal DNA replication, in all nephron segments of the
remaining kidney, resulting in cell growth (increase in cell size) with minimal
cell proliferation (increase in cell number). In addition to the compensatory renal
hypertrophy caused by nephron loss, pathophysiological renal hypertrophy can occur
as a consequence of early uncontrolled diabetes. However, the molecular mechanism
underlying renal hypertrophy in these conditions remains unclear. In the present
study, we report that deletion of S6 kinase 1 (S6K1) inhibited renal hypertrophy
seen following either contralateral nephrectomy or induction of diabetes. In wild-
type mice, hypertrophic stimuli increased phosphorylation of 40S ribosomal protein
S6 (rpS6), a known target of S6K1. Immunoblotting analysis revealed that S6K1(-/-)
mice exhibited moderately elevated basal levels of rpS6, which did not increase
further in response to the hypertrophic stimuli. Northern blotting indicated a
moderate upregulation of S6K2 expression in the kidneys of S6K1(-/-) mice.
Phosphorylation of the eukaryotic translation initiation factor 4E-binding protein
1, another downstream target of the mammalian target of rapamycin (mTOR), was
stimulated to equivalent levels in S6K1(-/-) and S6K1(+/+) littermates during renal
hypertrophy, indicating that mTOR was still activated in the S6K1(-/-) mice. The
highly selective mTOR inhibitor, rapamycin, inhibited increased phosphorylation of
rpS6 and blocked 60-70% of the hypertrophy seen in wild-type mice but failed to
prevent the similar to 10% hypertrophy seen in S6K1(-/-) mice in response to
uninephrectomy (UNX) although it did inhibit the basal rpS6 phosphorylation. Thus
the present study provides the first genetic evidence that S6K1 plays a major role
in the development of compensatory renal hypertrophy as well as diabetic renal
hypertrophy and indicates that UNX- and diabetes-mediated mTOR activation can
selectively activate S6K1 without activating S6K2.
ObjectiveClinical supervision is fundamental to the training of psychologists.
Neuropsychology (NP) is recognised as a distinct discipline of psychology and is an
area of endorsement; however, specific training in NP supervision has received
limited attention. Reflective practice is a supervisor competency required by the
Psychology Board of Australia (PBA) and is one element of NP foundational
competencies. Reflective practice can be described as the process of consciously
analysing decision-making, and drawing upon theory and experience, in order to
improve clinical practice. This discussion paper aims to improve the supervision of
neuropsychologists in Australia by providing an explicit framework to incorporate
reflective practice into NP supervision. MethodAs a discussion paper, the first
stage is to review the NP supervision literature; and second to provide a practical
supervision framework to integrate reflective practice in accordance with current
research, NP-specific requirements, and the PBA. ResultsThe extant literature on NP
supervision is exceedingly limited. NP supervision training frameworks were based
upon developmental and competency-based models and indicate that reflective
practice is a core element. A practical framework for the implementation of
reflective practice was effectively developed. ConclusionsThe reflective approach
allows supervisees to attain core functional and foundational neuropsychological
competencies, and is flexible to allow for different contexts and potentially new
supervision training requirements. Importantly, the reflective practice framework
supports ongoing professional development and competency throughout the
neuropsychologists' professional career span.
A recent theoretical model suggests that intraspecific competition is an important
determinant of the severity of inbreeding depression. The reason for this is that
intraspecific competition is density dependent, leading to a stronger negative
effect on inbred individuals if they are weaker competitors than outbred ones. In
support of this prediction, previous empirical work shows that inbred individuals
are weaker competitors than outbred ones and that intraspecific competition often
exacerbates inbreeding depression. Here, we report an experiment on the burying
beetle Nicrophorus vespilloides, in which we recorded the outcome of competition
over a small vertebrate carcass between an inbred or outbred male resident caring
for a brood and a size-matched inbred or outbred male intruder. We found that
inbred males were more successful as intruders in taking over a carcass from a male
resident and were injured more frequently as either residents or intruders.
Furthermore, inbred males gained less mass during the breeding attempt and had a
shorter adult life span than outbred males. Finally, successful resident males
reared a substantially smaller brood comprised of lighter larvae when the intruder
was inbred than when it was outbred. Our results shows that inbred males increased
their competitive effort, thus contradicting previous work suggesting that inbred
males are weaker competitors. Furthermore, our results shows that inbred intruders
impose a greater cost to resident males, suggesting that outbred individuals can
suffer fitness costs as a result of competition with inbred ones.
Wind power integration in an existing power system needs more attention due to its
uncertain nature. If a difference creates between the actual and forecasted wind
speeds and the power delivery contract is signed between the Generation Companies
(GENCOs) and Distribution Companies (DISCOs) as per the forecasted speed, then the
GENCOs may be awarded or penalized by the Independent System Operator (ISO) for
their surplus or deficit power supply. This paper proposes an approach to assess
the uncertainties of wind speed of the wind integrated electrical system within a
completely deregulated environment. In this work, twelve spots in India have been
chosen randomly for the application of the proposed approach and to verify the
outcome of the proposed approach. The real time data for actual wind speed (AWS)
and forecasted wind speed (FWS) of all selected spots have been also considered.
The imbalance cost due to mismatch between the forecasted and actual wind speeds is
evaluating by formulation of surplus charge rate and deficit charge rate. Modified
IEEE 14-bus and modified IEEE 30-bus systems are considered for analyzing the
effectiveness of the proposed approach. (C) 2017 Elsevier Ltd. All rights reserved.
Reproduction is energetically costly, and females frequently trade off their
reproductive effort with allocation to other physiological processes. One of these
processes is the maintenance of a functional immune defence. However, such
interactions between immunity and reproduction have rarely been explored in mammals
under natural conditions. In our study on females of an individually marked
European rabbit Oryctolagus cuniculus colony, we measured different components of
the maternal immune system from peripheral blood and serum 1day after parturition,
and we associated variation in these measures with differences in mothers'
reproductive effort. We used total litter mass as a measure of the mother's current
reproductive effort. In addition, we recorded whether or not mothers gave birth and
nursed another litter shortly before and considered this a measure of prior
reproductive effort. Mothers with higher current or prior reproductive effort
showed generally lower concentrations of white blood cells, in particular
neutrophils and lymphocytes, but a higher activity of the complement system and
higher IgG serum concentrations than females with lower reproductive effort. We
obtained similar results when comparing individual changes in immune parameters
measured post-partum across repeated reproductive events. Cell concentrations of
neutrophils and lymphocytes increased when individual females decreased their
reproductive effort. In contrast, IgG serum concentrations and the activity of the
complement system increased when mothers increased their reproductive effort. In
conclusion, the results underline differential responses of different branches of
the maternal post-partum immune system to variation in reproductive effort. On the
one hand, our study indicates that females might compromise at least some cellular
immune parameters for reproduction. On the other hand, the positive association
between IgG concentrations and reproductive effort could be adaptive as a higher
litter mass and higher number of pups requires an intensified transfer of this
immune parameter via placenta or colostrum and milk. This positive association
might constitute an additional, immunological component of the energetic costs of
reproduction.
Complement is the major humoral component of the innate immune system. It
recognizes pathogen- and damage-associated molecular patterns, and initiates the
immune response in coordination with innate and adaptive immunity. When activated,
the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and
thus its tight control is crucial to prevent damage to host tissues and allow
restoration of immune homeostasis. Factor H is the major soluble inhibitor of
complement, where its binding to self markers (i.e., particular glycan structures)
prevents complement activation and amplification on host surfaces. Not
surprisingly, mutations and polymorphisms that affect recognition of self by factor
H are associated with diseases of complement dysregulation, such as age-related
macular degeneration and atypical haemolytic uremic syndrome. In addition,
pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor
H to evade the immune response. Here we review recent (and not so recent)
literature on the structure and function of factor H, including the emerging roles
of this protein in the pathophysiology of infectious diseases and cancer.
Immunology is the science of biological warfare between the defenses of our immune
systems and offensive pathogenic microbes and cancers. Over the course of his
scientific career, Eckhard R. Podack made several seminal discoveries that
elucidated key aspects of this warfare at a molecular level. When Eckhard joined
the complement laboratory of Muller-Eberhard in 1974, he was fascinated by two
questions: (1) what is the molecular mechanism by which complement kills invasive
bacteria? and (2) which one of the complement components is the killer molecule?
Eckhard's quest to answer these questions would lead to the discovery C9 and later,
two additional pore-forming killer molecules of the immune system. Here is a brief
account of how he discovered poly-C9, the pore-forming protein of complement in
blood and interstitial fluids: Perforin-1, expressed by natural killer cells and
cytotoxic T lymphocytes; and Perforin-2 (MPEG1), expressed by all cell types
examined to date. All the three killing systems are crucial for our survival and
health.
There is a large body of experimental and clinical evidence that complement
activation contributes to glomerular injury in multiple different diseases.
However, the underlying mechanisms that trigger complement activation vary from
disease to disease. Immune complexes activate the classical pathway of complement
in many types of glomerulonephritis, whereas the alternative pathway and mannose-
binding lectin pathways are directly activated in some diseases. Eculizumab is an
inhibitory antibody to C5 that has been approved for the treatment of atypical
hemolytic uremic syndrome, and case reports suggest that it is also effective in
other types of glomerulonephritis. Furthermore, new complement-inhibitory drugs are
being developed that target additional proteins within the complement cascade,
raising the possibility of blocking the specific complement proteins involved in a
given disease. This review examines the rationale for targeting different proteins
within the complement cascade, the new anti-complement drugs currently in
development and some of the challenges that investigators will face in bringing
these drugs to the clinic.
We develop and fabricate a 0.5-V rail-to-rail operational amplifier (op-amp) with
ultralow-power operation in a 0.18-mu m standard complementary metal-oxide-
semiconductor process. The op-amp has a two-stage structure that comprises a
complementary input stage and a novel cross-coupled output stage. The cross-coupled
output stage increases the transconductances of the metal-oxide-semiconductor
field-effect transistors of the output stage without requiring an additional chip
area. Hence, it increases the gain of the op-amp and drivability for a capacitive
load. Our experimental results showed that the dc gain was 77 dB at the common-mode
input voltage of 0.25 V with a supply voltage of 0.5 V. DC gains of more than 40 dB
were obtained for common-mode input voltages ranging 50-450 mV. Furthermore, the
unitygain frequency was 4.0 kHz and the phase margin was 56 degrees, with a
capacitive load of 40 pF. The power consumption was 70 nW, including all bias
circuits.
An upper bound for the roots of X-d + a(1) Xd-1 + ... + a(d-1) X + a(d) is given by
the sum of the largest two of the terms This bound by Lagrange has gained attention
from different sides recently, while a succinct proof seems to be missing. We
present a short, original proof of Lagrange's bound. Our approach leads to some
definite improvements. To benefit computationally from these improvements, we
construct a modified Lagrange bound which at the same asymptotic computational
complexity is at most 11 per cent from optimal for degrees d >= 16. (C) 2017
Elsevier Ltd. All rights reserved.
Metal hydrides have received much attention due to the flourishing concept of a
hydrogen economy. In addition, recent studies of metal hydride materials have shown
that technological implementation of these compounds not only lies in the storage
of hydrogen, but for a range of multi-functional applications; including, smart
optical windows, energy storage materials in fuel cells for both stationary and
mobile devices, and as thermal energy storage materials for concentrating solar
thermal plants. This review concentrates on the molecular structures, thermodynamic
properties and other physical properties of the complexes of [NiH4](4), [FeH6](4),
[CoH5](4) and [RuH6](4). The synthesized derivatives of these compounds have also
been reviewed to give a full overview on the advancement of these systems and will
allow for a fresh prospective for future studies to fully understand the physical
and chemical nature of these complex transition metal hydrides. (C) 2017 Elsevier
B.V. All rights reserved.
Life is so remarkable, and so unlike any other physical system, that it is tempting
to attribute special factors to it. Physics is founded on the assumption that
universal laws and principles underlie all natural phenomena, but is it far from
clear that there are 'laws of life' with serious descriptive or predictive power
analogous to the laws of physics. Nor is there (yet) a 'theoretical biology' in the
same sense as theoretical physics. Part of the obstacle in developing a universal
theory of biological organization concerns the daunting complexity of living
organisms. However, many attempts have been made to glimpse simplicity lurking
within this complexity, and to capture this simplicity mathematically. In this
paper we review a promising new line of inquiry to bring coherence and order to the
realm of biology by focusing on 'information' as a unifying concept.
Objective: To compare the outcomes of percutaneous nephrolithotomy (PCNL) in
immunocompromised patients with those of PCNL in healthy population. Patients and
Methods: A matched case-control study was performed from January 2009 through
December 2014 using our prospectively collected kidney stone database. Patients
with positive serology to human immunodeficiency virus (HIV), hepatitis C (cellular
immune dysfunction), and patients on high dose of immunosuppressive drugs for
treatment of autoimmune diseases composed the case group. Control group included
patients with kidney stones and no other comorbidity. Patients were randomly
matched based on Guy's score as a surrogate of case complexity. Results: Sixty-two
patients were enrolled in this study, 21 cases and 42 controls. There were no
significant differences in age, gender, and body mass index between groups.
Regarding PCNL technique, there were no differences in patient positioning, number
of accesses, and operative time. Complication rate was higher in the case group
(38.1% vs 14.3%; p = 0.032); however, major complications, defined by Clavien score
>= 3, were not statistically different (4.8% vs 2.4%; p = 0.611). There was a
tendency of more postoperative urinary tract infection in the case group (19% vs
4.8%; p = 0.069). Mean decrease in hemoglobin level (3.3 vs 2.4 mg/dL; p = 0.037)
and blood transfusion rate (23.8% vs 4.8%; p = 0.036) was significantly higher in
the case group. Immunocompromised patients had a 2.8-fold increased risk of
complications (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.01, 7.74) and
a 5.8-fold increased risk of blood transfusion (OR = 5.8, 95% CI 1.29, 26.55).
There were no differences in stone-free rate, nephrostomy tube time, and length of
hospital stay. Conclusion: Immunocompromised patients are at higher risk for
complications such as bleeding after PCNL.
In many applications, offset of the OP-AMPs should be canceled to high accuracy be
accomplished. In this work, an asymmetrical differential input circuit with active
DC offset rejection circuit was implemented to minimize the systematic offset of
the amplifier. The proposed OP-AMPs show that the systematic offset voltages is
less than 80 mu V.
Soybean oil is an important carbon source in kitasamycin fermentation by
Streptomyces kitasatoensis. In this study, three different surfactants, Tween 80,
Tween 85, and sodium dodecyl sulfate (SDS), were added in the fermentation medium
to improve soybean oil utilization. Results indicated that all of these surfactants
promote kitasamycin biosynthesis. When 0.5 g/L SDS was added at the beginning of
fermentation, kitasamycin production increased by 55% and A(5) content improved by
12%, compared with the control treatment (i.e., no surfactant added). Oil
consumption rate and lipase activity were also improved in the presence of SDS,
producing more organic acids benefiting kitasamycin biosynthesis. High butyric acid
concentration in the fermentation medium containing SDS repressed C-3 acetylation
and promoted A(5) component accumulation. Additionally, utilization of oil
components by S. kitasatoensis was altered. Specifically, linoleic acid was
primarily used in the fermentation process with SDS, whereas oleic acid was
primarily used in the fermentation process where no surfactant had been added. (C)
2015 International Union of Biochemistry and Molecular Biology, Inc. Volume 63,
Number 6, Pages 895-900, 2016
This paper describes macromodeling of operational amplifiers for overdrive circuit
design. Macromodels have been applied to operational amplifier simulations with
good convergence. Also, macromodels allow the accurate simulation with not only
double-power supply but also single-power supply. In this study, a macromodel has
been applied to an overdrive circuit for sound effect design. Output waveform using
the macromodel is compared with that using a pre-set model only with double-power
supply and experiment. The output of the macromodel shows more accurate in
amplitude, a frequency, and distortion than that of the pre-set model. From this
result, the macromodel of the operational amplifier is suitable than the pre-set
model in the overdrive circuit design.
This paper highlights the digital control problems and issues during the controller
design and suggests the solutions to resolve them. For this purpose, digital
controller designed on the basis of digital redesign or emulation technique is
applied to a buck converter working in continuous conduction mode. Nonlinearities
due to the ADC and DAC quantizers, loop-delay, etc. are introduced into the control
loop and their adverse effects on performance are interrogated. The nonlinearities
are suppressed by retuning the digital controller. The order of the controller may
increase and require more resources for its implementation. The quantizers'
nonlinearities add quantization noise into the loop and may cause offsets and limit
cycle oscillations (LCOs). The overall phase margin gets reduced due to the delay
thus keeping the bandwidth limited and leading the system towards instability. The
well-tuned loop remains asymptotically stable if the nonlinearities are neglected.
MATLAB/Simulink environment is used to address all the issues.
Composite lymphomas (CLs) are defined as two unrelated lymphomas occurring at the
same time within the same tissue. The incidence of these tumors is low. Of all
possible combinations between lymphomas, the least frequent are the ones combining
peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma (HL). We recently identified
five cases of CL composed of PTCL and classical HL, mixed cellularity type. We
investigated histological and clinical features of these cases. Immunostaining was
performed on paraffin sections. PTCL cells were positive for CD8 and TIA-1 in four
of the five cases. Hodgkin and Reed-Sternberg (HRS) cells were positive for CD30
and weakly positive for PAX5 in all cases, positive for CD15 in three of five
cases, positive for CD20 in one of five cases, and negative for EBER. Monoclonal
rearrangement of the T-cell receptor (TCR) and immunoglobulin heavy chain (IGH)
genes was confirmed by polymerase chain reaction (PCR) using whole paraffin
sections. We concluded more precisely the monoclonality of the IGH rearrangement of
HRS cells based on single-cell PCR for IGH and DNA sequencing analysis after laser
microdissection of single cells in one case. HL can occur in CD8-positive and TIA-
1-positive PTCL. Clinicians should recognize the possibility of these CL.
Carbon fiber-reinforced polymers (CFRPs) have attracted attention from the
aerospace industry due to their light weight, excellent mechanical properties, and
resistance to corrosion. However, CFRP composites are difficult to recycle as their
recycling process must be performed under extreme conditions; end-of-life
regulations do not directly address the problem with reusing these composites.
Thus, the objective of this study is to explore solutions that minimize the use of
CFRPs and prolong their useful life in the airline industry. To achieve this goal,
this work conducted a review of the state of the art of CFRP fiber recycling,
emphasizing the recycling processes, restrictions, and regulations. One solution is
to develop a CFRP recycling market that would allow the sequential use of recycled
materials among industries in descending order of the required structural
performance of the composite.
In recent years, compressed sensing has received considerable attention from the
signal processing community because of its ability to represent sparse signals with
a number of samples much less than that is required by the Nyquist sampling
theorem. -minimization is a powerful tool for sparse signal reconstruction from few
measured samples, but its computational complexity is a burden for real
applications. Recently, a number of greedy algorithms based on orthogonal matching
pursuit (OMP) have been proposed, and they have near -minimization performance with
much less processing time. In this work, a new OMP-type two-stage sparse signal
reconstruction algorithm, namely data-driven forward-backward pursuit (DD-FBP), is
proposed. It is based on a former work called forward-backward pursuit (FBP). DD-
FBP iteratively expands and shrinks the estimated support set, and these constitute
the forward and backward stages. In DD-FBP, unlike FBP, the forward and backward
step sizes are not constants, but they are dependent on the correlation and
projection values, respectively, which are calculated in each iteration. The
recovery performance by using noiseless and noisy sparse signal ensembles, as well
as a natural sparse image, indicates that DD-FBP surpasses the other methods in
terms of success rate and processing time.
Sequential estimation of the delay and Doppler parameters for sub-Nyquist radars by
analog-to-information conversion (AIC) systems has received wide attention
recently. However, the estimation methods reported are AIC-dependent and have poor
performance for off-grid targets. This paper develops a general estimation scheme
in the sense that it is applicable to all AICs regardless whether the targets are
on or off the grids. The proposed scheme estimates the delay and Doppler parameters
sequentially, in which the delay estimation is formulated into a beamspace
direction-of-arrival problem and the Doppler estimation is translated into a line
spectrum estimation problem. Then the well-known spatial and temporal spectrum
estimation techniques are used to provide efficient and high-resolution estimates
of the delay and Doppler parameters. In addition, sufficient conditions on the AIC
to guarantee the successful estimation of off-grid targets are provided, while the
existing conditions are mostly related to the on-grid targets. Theoretical analyses
and numerical experiments show the effectiveness and the correctness of the
proposed scheme.
Strategic bidding problems in electricity markets are widely studied in power
systems, often by formulating complex bi-level optimization problems that are hard
to solve. The state-of-the-art approach to solve such problems is to reformulate
them as mixed-integer linear programs (MILPs). However, the computational time of
such MILP reformulations grows dramatically, once the network size increases,
scheduling horizon increases, or randomness is taken into consideration. In this
paper, we take a fundamentally different approach and propose effective and
customized convex programming tools to solve the strategic bidding problem for
producers in nodal electricity markets. Our approach is inspired by the Schmudgen's
Positivstellensatz Theorem in semi-algebraic geometry; but then we go through
several steps based upon both convex optimization and mixed-integer programming
that results in obtaining close to optimal bidding solutions, as evidenced by
several numerical case studies, besides having a huge advantage on reducing
computation time. While the computation time of the state-of-the-art MILP approach
grows exponentially when we increase the scheduling horizon or the number of random
scenarios, the computation time of our approach increases rather linearly.
This paper presents a method to evaluate the computational cost of a function in
embedded systems. This method, which uses the Least Squares method, is useful to
see the sample time choice feasibility, in control applications. In this work, the
developed method is used to evaluate the computational cost of the model-based
predictive control to speed control of a shunt direct current motor. The method was
tested using two embedded devices allowing to find the correct sample time for each
device evaluated.
In three-phase induction motor drives, addition of certain zero-sequence signal
which divides the null vector time equally between the two zero states is known to
improve the harmonic performance over sinusoidal modulation. Similarly, in split-
phase induction motor (SPIM) drives also, addition of such a zero-sequence signal
to each set of three-phase sinusoidal modulating waves leads to reduction in total
harmonic distortion (THD) in a motor current. However, the above method known as
double zero-sequence injection pulse width modulation (DZIPWM) is significantly
inferior to four-dimensional 24-sector space vector pulse width modulation (4D24SEC
PWM) in terms of THD. This paper investigates and attempts to determine the zero-
sequence signal, if any, whose injection could result in a harmonic performance
comparable to that of 4D24SEC PWM. Such a zero-sequence signal is determined and is
shown to be quite different from that used in DZIPWM. The analytical findings are
used to propose a computationally efficient, carrier-based approach to implement
the 4D24SEC PWM, whose implementation is otherwise highly resource intensive. The
feasibility, computational efficiency, and accuracy of the proposed approach are
demonstrated and validated on a 6-kW split-phase motor drive, controlled from a
field programmable gate array platform. This paper enables good harmonic
performance of the split-phase drive with low computational effort and resources.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that act as efficient post-
transcriptional regulators of gene expression. In 2012, the first cross-kingdom
miRNA-based interaction had been evidenced, demonstrating that exogenous miRNAs act
in a manner of mammalian functional miRNAs. Starting from this evidence, we defined
the concept of cross-kingdom functional homology between plant and mammalian miRNAs
as a needful requirement for vegetal miRNA to explicit a regulation mechanism into
the host mammalian cell, comparable to the endogenous one. Then, we proposed a new
dedicated algorithm to compare plant and mammalian miRNAs, searching for functional
sequence homologies between them, and we developed a web software called
MirCompare. We also predicted human genes regulated by the selected plant miRNAs,
and we determined the role of exogenous miRNAs in the perturbation of intracellular
interaction networks. Finally, as already performed by Pirro` and coworkers, the
ability of MirCompare to select plant miRNAs with functional homologies with
mammalian ones has been experimentally confirmed by evaluating the ability of mol-
miR168a to downregulate the protein expression of SIRT1, when its mimic is
transfected into human hepatoma cell line G2 (HEPG2) cells. This tool is
implemented into a user-friendly web interface, and the access is free to public
through the website http://160.80.35.140/MirCompare
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene
expression at posttranscriptional level. They might regulate tolerance to abiotic
stress. However, this has not been studied in Tradescantia (BNL clone 3340), an
important bio-indicator for measuring the effect of radiation. Up to date, gamma
irradiation (gamma-IR) responsive miRNAs and their expressions patterns in plants
in response to gamma-IR stress have not been reported yet. Therefore, putative
gamma-IR responsive miRNAs from a cDNA library of Tradescantia after radiation
stress were predicted in this study by using comprehensive genomic approaches.
Here, we identified 37 miRNAs belonged to 36 different miRNA families. The
quantitative real-time polymerase chain reaction (qRT-PCR) analysis of five
randomly selected miRNAs were confirmed that their responsiveness to gamma-IR
stress. Target prediction revealed that 37 miRNAs targeted 149 genes involved in
stress tolerance regulation, light response, redox systems, signaling pathways, DNA
repair, and transcription factors. A coordinated reverse expression changes between
miRNAs and their target genes further validated that these predicted miRNAs could
be gamma-IR responsive and likely to be directly involved in stress regulatory
networks of Tradescantia. Altogether, these results will provide novel insights to
the understanding of molecular mechanisms of miRNAs involved in plant response to
gamma-IR.
New contributions that aim to accelerate the development or to improve the efficacy
and safety of vaccines arise from many different areas of research and technology.
One of these areas is computational science, which traditionally participates in
the initial steps, such as the pre-screening of active substances that have the
potential to become a vaccine antigen. In this work, we present another promising
way to use computational science in vaccinology: mathematical and computational
models of important cell and protein dynamics of the immune system. A system of
Ordinary Differential Equations represents different immune system populations,
such as B cells and T cells, antigen presenting cells and antibodies. In this way,
it is possible to simulate, in silico, the immune response to vaccines under
development or under study. Distinct scenarios can be simulated by varying
parameters of the mathematical model. As a proof of concept, we developed a model
of the immune response to vaccination against the yellow fever. Our simulations
have shown consistent results when compared with experimental data available in the
literature. The model is generic enough to represent the action of other diseases
or vaccines in the human immune system, such as dengue and Zika virus.
Young children with suspected abusive head trauma often receive skull radiographs
to evaluate for fractures as well as computed tomography (CT) of the head to assess
for intracranial injury. Using a CT as the primary modality to evaluate both
fracture and intracranial injury could reduce exposure to radiation without
sacrificing performance. To evaluate the sensitivity of CT head with (3-D)
reconstruction compared to skull radiographs to identify skull fractures in
children with suspected abusive head trauma. This was a retrospective (2013-2014)
cross-sectional study of infants evaluated for abusive head trauma via both skull
radiographs and CT with 3-D reconstruction. The reference standard was skull
radiography. All studies were read by pediatric radiologists and neuroradiologists,
with ten percent read by a second radiologist to evaluate for interobserver
reliability. One hundred seventy-seven children (47% female; mean/median age: 5
months) were included. Sixty-two (35%) had skull fractures by radiography. CT with
3-D reconstruction was 97% sensitive (95% confidence interval [CI]: 89-100%) and
94% specific (CI: 87-97%) for skull fracture. There was no significant difference
between plain radiographs and 3-D CT scan results (P-value = 0.18). Kappa was 1 (P-
value < 0.001) between radiologist readings of CTs and 0.77 (P = 0.001) for skull
radiographs. CT with 3-D reconstruction is equivalent to skull radiographs in
identifying skull fractures. When a head CT is indicated, skull radiographs add
little diagnostic value.
The increasing levels of criminal media being shared in peer-to-peer (P2P) networks
pose a significant challenge to law enforcement agencies. One of the main
priorities for P2P investigators is to identify cases where a user is actively
engaged in the production of child sexual abuse (CSA) media - they can be
indicators of recent or on-going child abuse. Although a number of P2P monitoring
tools exist to detect paedophile activity in such networks, they typically rely on
hash value databases of known CSA media. As a result, these tools are not able to
adequately triage the thousands of results they retrieve, nor can they identify new
child abuse media that are being released on to a network. In this paper, we
present a new intelligent forensics approach that incorporates the advantages of
artificial intelligence and machine learning theory to automatically flag
new/previously unseen CSA media to investigators. Additionally, the research was
extensively discussed with law enforcement cybercrime specialists from different
European countries and Interpol. The approach has been implemented into the iCOP
toolkit, a software package that is designed to perform live forensic analysis on a
P2P network environment. In addition, the system offers secondary features, such as
showing on-line sharers of known CSA files and the ability to see other files
shared by the same GUID or other IP addresses used by the same P2P client. Finally,
our evaluation on real CSA case data shows high degrees of accuracy, while hands-on
trials with law enforcement officers demonstrate the toolkit's complementarity to
extant investigative workflows. (C) 2016 The Authors. Published by Elsevier Ltd.
In the last years, there is a greater interest in using computers in education, and
in particular, in engineering education. Software programs have a great impact on
studying many physical phenomena that otherwise could be described only using very
complex mathematical algorithms. Furthermore, by computer simulation it can be
studied the behavior of many engineering systems before its launching in
production. However, the focus many times exclusively could be a handicap for the
future engineers from a different perspective: lack of real measurement and future
data manipulation and interpretation. At the same time, experimental stands could
be often very expensive for many university laboratories. In this article, the
author presents a methodology that could be a compromise between the use of
software dedicated programs and of really electrical systems. The use of electronic
simulators releases the university laboratory of expensive acquisitions and does
not put a very large gap between practice and theoretical concepts. Based on the
block system diagram of a real system, it is constructed the electronic simulator
using basic Operational Amplifier structures' circuits. The result is an electronic
system simulator.
Background: Computer-delivered cognitive behavioural therapy (cCBT) is an effective
alternative to provider-delivered treatment for depression and anxiety, but high
attrition poses a significant challenge to its use. Peer support is a feasible
approach to improving cCBT engagement, but less is known about its acceptability
among Veterans. Aims: To obtain feedback from Veterans (n = 24) with depression
and/or anxiety on their preferences for (a) activities of Veterans Administration
Peer Support Specialists (VA PSS) in helping Veterans use Moving Forward, a cCBT-
based protocol developed by VA, and (b) methods for delivering support to Veterans
using this programme. Method: Four focus groups (5-7 Veterans per group) provided
feedback to be used in the development of a peer-supported engagement intervention
to help Veterans with depression and anxiety use Moving Forward. Content areas
included roles that a VA PSS might play in supporting the use of and engagement in
Moving Forward, as well as methods of delivering that support. Results: Veteran
preferences for PSS activity focused on practical aspects of using Moving Forward,
including orientation to the programme, technical support, and monitoring progress.
Feedback also suggested that Veterans preferred more personal roles for the PSS,
including emotional support, as well as application of Moving Forward to real life'
problems. Conclusions: The findings extend the literature on online, patient-facing
mental health protocols by identifying emotional support and real life' skills
application as Veteran-preferred components of a peer-support protocol designed to
enhance use of and engagement in cCBT for depression and anxiety.
How do older adults mobilize social support, with and without digital media? To
investigate this, we focus on older adults 65+ residing in the Toronto locality of
East York, using 42 interviews lasting about 90 minutes done in 2013-2014. We find
that digital media help in mobilizing social support as well as maintaining and
strengthening existing relationships with geographically near and distant contacts.
This is especially important for those individuals (and their network members) who
have limited mobility. Once older adults start using digital media, they become
routinely incorporated into their lives, used in conjunction with the telephone to
maintain existing relationships but not to develop new ones. Contradicting fears
that digital media are inadequate for meaningful relational contact, we found that
these older adults considered social support exchanged via digital media to be real
support that cannot be dismissed as token. Older adults especially used and valued
digital media for companionship. They also used them for coordination, maintaining
ties, and casual conversations. Email was used more with friends than relatives;
some Skype was used with close family ties. Our research suggests that policy
efforts need to emphasize the strengthening of existing networks rather than the
establishment of interventions that are outside of older adults' existing ties. Our
findings also show that learning how to master technology is in itself a form of
social support that provides opportunities to strengthen the networks of older
adults.
Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability
factor for several psychiatric diseases as well as aggressive behavior, either
directly, or in interaction with an adverse environment. The present study aimed at
investigating the susceptibility properties of COMT genotype to adverse and
favorable environment in relation to physical and verbal aggressive behavior. The
COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort
including 1,783 individuals, ages 20-24 years (47% males). A significant three-way
interaction was found, after correction for multiple testing, between COMT
genotype, exposure to violence, and parent-child relationship in association with
physical but not verbal aggressive behavior. Homozygous for the Val allele reported
lower levels of physical aggressive behavior when they were exposed to violence and
at the same time experienced a positive parent-child relationship compared to Met
carriers. Thus, susceptibility properties of COMT genotype were observed in
relation to physical aggressive behavior supporting the hypothesis that COMT
genotypes are modifying the sensitivity to environment that confers either risk or
protection for aggressive behavior. As these are novel findings, they warrant
further investigation and replication in independent samples. (C) 2016 Wiley
Periodicals, Inc.
Backround: Previous studies have demonstrated the contributions of genetic variants
and positive psychological traits (e.g. gratitude and forgiveness) to well-being.
However, little is known about how genes interact with positive traits to affect
well-being. Methods: To investigate to what extent the COMTVa1158Met polymorphism
modulates well-being and to what extent dispositional gratitude and forgiveness
mediate the individual differences in well-being, 445 participants were recruited
and required to complete a battery of questionnaires. Results: We found that
individuals with a smaller number of the Met alleles reported greater well-being,
less depressive symptoms, and greater tendencies for gratitude and forgiveness.
Moreover, dispositional gratitude and forgiveness mediated the genotype effects on
well-being and depressive symptoms. These results remained significant after
controlling for non-genetic factors (socioeconomic status, religious beliefs,
romantic relationship status, parenting style). Limitation: The sample size limits
the generalizability of results. Conclusion: This study demonstrates the
contribution of the COMT Va1158Met polymorphism to individual differences in well-
being and suggests a potential psychobiological pathway from dopaminergic and
noradrenergic systems to happiness.
Solar Tower Technology is a promising way to generate sustainable electricity from
concentrated solar radiation. In one of the most effective variants of this
technology, a so called volumetric air receiver is used to convert concentrated
radiation into heat. This component consists of a high temperature resistant
cellular material which absorbs radiation and transfers the heat to an air flow
which is fed from the ambient and from recirculated air. It is called volumetric,
because the radiation may penetrate into the "volume" of the receiver through the
open, permeable cells of the material. In this way a larger amount of heat transfer
surface supports the solid to gaseous heat transfer in comparison to a tubular
closed receiver. Finally the heated air is directed to the steam generator of a
conventional steam turbine system. In this study an advanced cellular metal
honeycomb structure has been designed, manufactured and tested for use as an open
volumetric receiver. It consists of winded pairs of flat and corrugated metal
foils. The technology is based on a one which has been primarily developed for the
treatment of combustion engine exhaust gases. A number of variations of the pure
linear honeycomb structure have been introduced to increase local turbulence and
radial flow. Firstly, a set of samples has been tested in laboratory scale
experiments to determine effective properties and the solar-to-thermal efficiency.
After that, results have been compared with theoretical predictions. Finally, the
three most promising materials have been used for a 500 kW test on the research
platform of the Solar Tower Julich. Air outlet temperatures of more than 800
degrees C have been achieved with efficiencies of about 80%, which is about 5% more
than the state-of-the-art technology, which is currently used at the main receiver
of the Solar Tower. Next to this, lifetime models will be developed to increase the
overall reliability of the technology. (C)2017 Elsevier Ltd. All rights reserved.
High concentration photovoltaics, equipped with high efficiency multijunction solar
cells, have great potential in achieving cost-effective and clean electricity
generation at utility scale. Such systems are more complex compared to conventional
photovoltaics because of the multiphysics effect that is present. Modelling the
power output of such systems is therefore crucial for their further market
penetration. Following this line, a multiphysics modelling procedure for high
concentration photovoltaics is presented in this work. It combines an open source
spectral model, a single diode electrical model and a threedimensional finite
element thermal model. In order to validate the models and the multiphysics
modelling procedure against actual data, an outdoor experimental campaign was
conducted in Albuquerque, New Mexico using a high concentration photovoltaic
monomodule that is thoroughly described in terms of its geometry and materials. The
experimental results were in good agreement (within 2.7%) with the predicted
maximum power point. This multiphysics approach is relatively more complex when
compared to empirical models, but besides the overall performance prediction it can
also provide better understanding of the physics involved in the conversion of
solar irradiance into electricity. It can therefore be used for the design and
optimisation of high concentration photovoltaic modules. (C) 2017 Elsevier Ltd. All
rights reserved.
One of the possible research lines for improving the Concentrated Solar Power (CSP)
technology is the enhancement of the thermophysical properties of the Heat Transfer
Fluids (HTF) used. This enhancement leads to reduce costs for producing electricity
using this technology. So, this study presents the preparation of nanofluids in
which Ag nanoparticles were added to a base fluid composed of a eutectic mixture of
diphenyl oxide and biphenyl. The base fluid is a heat transfer fluid commonly used
in concentrating solar power plants. The nanofluids were shown to have improved
thermal properties, the heat transfer coefficient increasing by up to 6% compared
with the base fluid. Thus, their use could lead to enhancements in the overall
efficiency of CSP plants. Accordingly, nanofluids were prepared with varying
nanoparticle concentrations and their properties were characterized, including
their physical and chemical stability, viscosity, isobaric specific heat and
thermal conductivity. In addition, molecular dynamic calculations were performed to
reach a better understanding of the nanofluid system at a molecular level. The
isobaric specific heat and thermal conductivity values followed the same
experimental tendency. An analysis of the radial distribution functions (RDFs) and
spatial distribution functions (SDFs) shows that there is a first layer of base
fluid molecules around the metal in which the oxygen atoms play an important role.
This first layer encourages the directionality of the movement in the heart of the
nanofluid, which leads to enhanced thermal properties. (C) 2017 Elsevier Ltd. All
rights reserved.
The main aim of this study was to conduct preliminary analysis on the performance
of two conceptual designs that integrate the production of potable water,
electricity, and salt. We used reverse osmosis (RO), pressure-retarded osmosis
(PRO), and electrodialysis (ED) to produce potable water, electricity, and salt,
respectively. The objective of the analysis is to observe how the relative
positions of RO and PRO in the integrated process affect the five key parameters,
i.e. the total dissolved solids (TDS) of potable water, permeate rate, the total
energy requirement of the RO and ED units, net delivered power, and salt potential.
We simulated each integrated design using previously validated mathematical
expressions of RO, PRO, and ED. We found that the net delivered power is higher
When the RO unit is located before the PRO unit. The same sequence also results in
lower energy requirement for producing potable water, although the permeate rate is
smaller than that of the rival sequence. On the other hand, the salt potential is
not affected by the relative positions of the RO and PRO units. (C) 2017 Elsevier
B.V. All rights reserved.
Adhesively bonding fiber-reinforced polymer (FRP) composites to reinforced concrete
members is a simple and highly effective method to restore strength, increase
loading capacities, and extend the service life of structures. With growing demand
and wider applications of these strengthening systems, it is their durability that
has recently received significant attention from the research community, largely in
the form of laboratory testing of deteriorated FRP-to-concrete joints. To develop
generalized deterioration factors, a database of shear tests has been collected to
quantitatively assess the change in bond characteristics across a number of
environmental conditions. It has been identified that a major shortcoming of
existing test data is that reporting of the full-range load-displacement behavior
is very limited. To supplement existing data, an experimental study is devised to
further assess the deterioration of carbon FRP bonded systems under three aqueous
conditions. The investigation consists of continually immersing specimens in water,
a 5% salt solution, and, for the first time, a sulfuric acid solution of pH 4.0 to
simulate the pooling of acid rain. Results show that sulfuric acid attack is most
detrimental to the durability of the bond. Then, using a mechanics-based numerical
model, bond properties are extracted from the present results as well those in
published literature, to determine conservative deterioration factors for the
change in bond characteristics with environmental exposure. (C) 2017 American
Society of Civil Engineers.
Objective: A previous study conducted by our group found theory of mind (ToM)
differences in preschool children who sustained mild traumatic brain injury (mTBI)
compared with typically developing peers, 6 months postinjury. The goals of the
current longitudinal study were to determine whether these findings are the result
of a brain-injury-specific effect or rather a general-injury effect, to examine the
long-term evolution of ToM skills following preschool mTBI, as well as to
investigate the links between ToM abilities and general social functioning. Method:
Seventy-two children who sustained mTBI between the ages of 18 and 60 months were
evaluated 6 and 18 months postinjury on ToM tasks including desires and emotions
reasoning and false belief understanding. They were compared with 58 participants
who sustained an orthopedic injury (OI) and 83 typically developing children (TDC).
Results: The 3 groups did not differ on demographic and baseline characteristics.
The mTBI group obtained poorer scores relative to both comparison groups on the
desires and emotions reasoning task, both at 6 and 18 months injury. No
correlations were found between injury characteristics and ToM performance. For the
mTBI group, associations were found between ToM performance and global social
competence. Conclusion: These findings suggest a brain-injury-specific effect that
persists in the long-term following mTBI in preschool children.
Background: The density of a host population is a key parameter underlying disease
transmission, but it also has implications for the expression of disease through
its effect on host physiology. In response to higher densities, individuals are
predicted to either increase their immune investment in response to the elevated
risk of parasitism, or conversely to decrease their immune capacity as a
consequence of the stress of a crowded environment. However, an individual's health
is shaped by many different factors, including their genetic background, current
environmental conditions, and maternal effects. Indeed, population density is often
sensed through the presence of info-chemicals in the environment, which may
influence a host's interaction with parasites, and also those of its offspring. All
of which may alter the expression of disease, and potentially uncouple the presumed
link between changes in host density and disease outcomes. Results: In this study,
we used the water flea Daphnia magna and its obligate bacterial parasite Pasteuria
ramosa, to investigate how signals of high host density impact on host-parasite
interactions over two consecutive generations. We found that the chemical signals
from crowded treatments induced phenotypic changes in both the parental and
offspring generations. In the absence of a pathogen, life-history changes were
genotype-specific, but consistent across generations, even when the signal of
density was removed. In contrast, the influence of density on infected animals
depended on the trait and generation of exposure. When directly exposed to signals
of high-density, host genotypes responded differently in how they minimised the
severity of disease. Yet, in the subsequent generation, the influence of density
was rarely genotype-specific and instead related to ability of the host to minimise
the onset of infection. Conclusion: Our findings reveal that population level
correlations between host density and infection capture only part of the complex
relationship between crowding and the severity of disease. We suggest that besides
its role in horizontal transmission, signals of density can influence parasite
epidemiology by modifying mechanisms of resistance across multiple generations, and
elevating variability via genotype-by-environment interactions. Our results help
resolve why some studies are able to find a positive correlation between high
density and resistance, while others uncover a negative correlation, or even no
direct relationship at all.
The efforts for more reliable power conversion systems have been gaining momentum
in recent years. The majority of the studies concerning reliability of power
switches focus on the package-related failures, mainly caused by the cyclic thermal
stress. The basic failure precursor for this type of stress has been identified as
increased on-state resistance for power MOSFETs in the recent literature. On-state
resistance monitoring during converter operation is a challenging and costly task
as it requires current and voltage sensing circuits, which can block the high
voltage across the switch during off-state to protect the measurement or control
unit. This paper proposes a software frequency response analysis method to
determine the health status of high-voltage power MOSFETs with high on-state
resistance. This is achieved by analyzing and evaluating the variation in the plant
model at double pole frequency using the same DSP that is used for control
purposes. The proposed concept is analyzed for boost converter; however, it can be
used to detect the on-state resistance variation in other types of converters
operating in continuous condition mode (CCM). The proposed algorithm is embedded in
a low cost DSP and experimentally verified on a dc/dc boost converter.
This paper presents a new stochastic operation scheduling model for microgrid in
day-ahead electricity market considering the forecast uncertainties of wind
generations, microgrid's load, and locational marginal price of the point of common
coupling, as well as the uncertainties pertaining to availability of generation
units of the microgrid. The financial risk caused by these uncertainties is modeled
by conditional value-at-risk criterion. The proposed approach is formulated as a
risk-minimizing two-stage stochastic model based on mixed-integer linear
programming framework. This model minimizes the expected scheduling cost together
with the cost of financial risk. The impacts of different uncertainty sources on
the model's results in both grid-connected and islanded operation modes are
extensively studied. Additionally, higher effectiveness of the proposed stochastic
model compared with common deterministic approach, regarding total operation cost
and convergence behavior, is illustrated through an out-of-sample analysis.
Early-life stress has long-lasting effects on the stress response, emotions, and
behavior throughout an individual's life. Clinical reports have demonstrated that
child abuse victims exhibit impairments in reward-associated behavior; yet, the
mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled
with social isolation (SI) (MS + SI) is widely used as a model for early-life
stress in rodent studies. We employed mice subjected to MS + SI to clarify the
long-term effect of early-life stress on reward-seeking involving palatable foods
by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience
decreased exploration time in a chocolate-paired compartment in adult female mice,
but not in male mice. We then focused on the mesolimbic dopamine pathway associated
with reward seeking behavior and measured both mRNA and protein levels of tyrosine
hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2
receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly
lower D1 receptor mRNA and protein levels than controls, whereas the expression of
TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels
were unchanged in MS + SI male mice. When attempting to elucidate the mechanism
underlying downregulation of the Dl receptor in the NAc of MS + SI females, we
found hypermethylation of the Drd1a promoter region. These results suggest that
early-life stress affects reward-seeking behavior in female mice, which may be
associated with the downregulation of D1 receptor in the NAc via epigenetic
modification of its promoter region. (C) 2017 Elsevier B.V. All rights reserved.
This paper proposes a predictive control algorithm that includes conduction-mode
detection for power factor correction (PFC) converter. In PFC converters, the line
current is usually distorted because of the characteristics of the proportional-
integral (PI) current controller. To improve the quality of the current, the PI
current controller requires additional circuits or algorithms. However, because of
the optimal duty cycle determined by estimating the next-state current in both the
continuous-conduction mode and the discontinuous-conduction mode, the proposed
predictive control method has a fast dynamic response and accuracy compared to the
PI current-control method. Moreover, the proposed algorithm can detect the
conduction mode without any additional circuitry or mode-detection algorithm using
the characteristic of the optimal duty cycle calculated by the predictive control.
These advantages of the proposed algorithm improve the quality of the line current
for PFC converters. We verify the proposed method by performing experiment using a
1.5-kW PFC converter.
Condyloma acuminata (CA) are warty lesions caused by human papilloma virus (HPV)
that generally affect the external genitalia and mucocutaneous junctions.
Involvement of the urinary tract is rare, and involvement of the urinary bladder is
thought to be due to immunosuppression. A 30-year-old woman was diagnosed with
urethral CA 12 months after renal transplantation. She underwent transurethral
resection (TUR) of the urethral lesions. During the operation, multiple sessile
warty lesions were found incidentally inside the bladder and were also removed by
TUR. The patient's postoperative course was uneventful. Pathological examination
confirmed that the lesions were CA. Multiplex real-time polymerase chain reaction
was performed to confirm the HPV genotype and revealed type 45 HPV DNA. CA of the
urethra are uncommon, and bladder involvement is extremely rare. This case is the
first reported, to our knowledge, to involve HPV type 45 in bladder condyloma. TUR
may be the preferred option for the management of CA in the urinary bladder.
Introduction: National conference didactic lectures have traditionally featured
hour-long lecture-based presentations. However, there is evidence that longer
lectures can lead to both decreased attention and retention of information. The
authors sought to identify trends in lecture duration, lecture types, and number of
speakers at four national emergency medicine (EM) conferences over a 6-year period.
Methods: The authors performed a retrospective analysis of the length, number of
speakers, and format of didactic lectures at four different national EM conferences
over 6 years. The authors abstracted data from the national academic assemblies for
the four largest not-for-profit EM organizations in the United States: American
Academy of Emergency Medicine, American College of Emergency Physicians, Council of
Emergency Medicine Residency Directors, and Society for Academic Emergency
Medicine. Results: There was a significant yearly decrease in the mean lecture
lengths for three of the four conferences. There was an increase in the percentage
of rapid fire sessions over the preceding 2 years with a corresponding decrease in
the percentage of general educational sessions. There was no significant difference
in the mean number of speakers per lecture. Discussion: An analysis of 4210
didactic lecture sessions from the annual meetings of four national EM
organizations over a 6-year period showed significant decreases in mean lecture
length. These findings can help to guide EM continuing medical education conference
planning and research.
Expectation of reward can be shaped by the observation of actions and expressions
of other people in one's environment. A person's apparent confidence in the likely
reward of an action, for instance, makes qualities of their evidence, not observed
directly, socially accessible. This strategy is computationally distinguished from
associative learning methods that rely on direct observation, by its use of
inference from indirect evidence. In twenty-three healthy human subjects, we
isolated effects of first-hand experience, other people's choices, and the
mediating effect of their confidence, on decision-making and neural correlates of
value within ventromedial prefrontal cortex (vmPFC). Value derived from first-hand
experience and other people's choices (regardless of confidence) were
indiscriminately represented across vmPFC. However, value computed from agent
choices weighted by their associated confidence was represented with specificity
for ventromedial area 10. This pattern corresponds to shifts of connectivity and
overlapping cognitive processes along a posterior-anterior vmPFC axis. Task
behavior and self-reported self-reliance for decision-making in other social
contexts correlated. The tendency to conform in other social contexts corresponded
to increased activation in cortical regions previously shown to respond to social
conflict in proportion to subsequent conformity (Campbell-Meiklejohn et al., 2010).
The tendency to self-monitor predicted a selectively enhanced response to
accordance with others in the right temporoparietal junction (rTPJ). The findings
anatomically decompose vmPFC value representations according to computational
requirements and provide biological insight into the social transmission of
preference and reassurance gained from the confidence of others.
Three studies examined the hypothesis that bilinguals can more rapidly disengage
attention from irrelevant information than monolinguals by investigating the impact
of previous trial congruency on performance in a simple flanker task. In Study 1,
monolingual and bilingual young adults completed two versions of a flanker task.
There were no differences between language groups on mean reaction time using
standard analyses for congruent or incongruent trials or the size of the flanker
effect. Sequential congruency effects (SCEs) however, which account for previous
trial congruency, were smaller for bilinguals than for monolinguals. This finding
was strongest at the shortest response-to-stimulus interval (RSI). Study 2
replicated this effect using a slightly different flanker task and a shorter RSI
than study 1. Study 3 showed that at long RSIs, where behavioral SCE differences
between groups disappear because of sufficient time to recover from the previous
trial, event-related potentials demonstrated a continued influence of previous
trial congruency for monolinguals but not bilinguals at both the N2 and the P3,
replicating the reaction time effects in Studies 1 and 2. Together, these studies
demonstrate that bilinguals experience less influence from previous trial
congruency and have greater ability to disengage attention from the previous trial
in order to focus attention on the current trial than is found for monolinguals.
(C) 2017 Elsevier B.V. All rights reserved.
The immigration of Latin American women of childbearing age has spread the
congenital transmission of Chagas disease to areas of nonendemicity, and the
disease is now a worldwide problem. Some European health authorities have
implemented screening programs to prevent vertical transmission, but the lack of a
uniform protocol calls for the urgent establishment of a new strategy common to all
laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in
the newborn by means of five serological tests for the diagnosis and follow-up of
congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques
for diagnosing a congenital transmission, and (iii) propose a strategy for a
prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In
noninfected newborns, a continuous decreasing trend of passive IgG antibodies was
observed, but none of the serological assays seroreverted in any the infants before
12 months. From 12 months onwards, serological tests achieved negative results in
all the samples analyzed, with the exception of the highly sensitive
chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally
infected infants, the antibody decline was detected only after treatment
initiation. In order to improve the diagnosis of congenital T. cruzi infection, we
propose a new strategy involving fewer tests that allows significant cost savings.
The protocol could start 1 month after birth with a parasitological test and/or a
PCR. If negative, a serological test would be carried out at 9 months, which if
positive, would be followed by another at around 12 months for confirmation.
Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based
on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether
simultaneous vaccination with both antigens enhances protection. We undertook
evaluation of a novel bivalent vaccine based on nonreplicating lymphocytic
choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB
[gB(dCt)] and full-length pp65 from human CMV in mice. Immunization with the
gB(dCt) vector alone elicited a comparable gB-binding antibody response and a
superior neutralizing response to that elicited by adjuvanted subunit gB.
Immunization with the pp65 vector alone elicited robust T cell responses.
Comparable immunogenicity of the combined gB(dCt) and pp65 vectors with the
individual monovalent formulations was demonstrated. To demonstrate proof of
principle for a bivalent rLCMV-based HCMV vaccine, the congenital guinea pig
cytomegalovirus (GPCMV) infection model was used to compare rLCMV vectors encoding
homologs of pp65 (GP83) and gB(dCt), alone and in combination versus Freund's
adjuvanted recombinant gB. Both vectors elicited significant immune responses, and
no loss of gB immunogenicity was noted with the bivalent formulation. Combined
vaccination with rLCMV-vectored GPCMV gB(dCt) and pp65 (GP83) conferred better
protection against maternal viremia than subunit or either monovalent rLCMV
vaccine. The bivalent vaccine also was significantly more effective in reducing pup
mortality than the monovalent vaccines. In summary, bivalent vaccines with rLCMV
vectors expressing gB and pp65 elicited potent humoral and cellular responses and
conferred protection in the GPCMV model. Further clinical trials of LCMV-vectored
HCMV vaccines are warranted.
Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide,
with an estimated incidence in developed countries of 0.6-0.7% of all live births.
The burden of disease related to congenital CMV in substantial, as it is the
leading non-genetic cause of sensorineural hearing loss and an important cause of
neurodevelopmental disabilities in children. Despite its clinical significance,
congenital CMV infection often goes undetected because the majority of infected
infants are asymptomatic at birth and screening programs have not been
substantially implemented. Other than behavioral measures, effective interventions
aimed at the prevention of maternal infection and of mother-to-child transmission
are lacking. Due to a convergence of recent advances in both diagnostic and
therapeutic strategies in infants with congenital CMV, though, the field likely
will be changing rapidly over just the next few years. Specifically, a highly-
sensitive screening test with high throughput potential has been developed, and
treatment of infants symptomatically infected with congenital CMV has proven to be
well-tolerated and effective in improving long-term hearing and neurodevelopmental
outcomes. This review highlights the clinical importance of congenital CMV
infection, the developments in laboratory diagnostics, and the benefits of
antiviral therapy. It also identifies the global efforts still required in the
prevention of maternal infection and in the optimization of antiviral therapy to
further reduce the burden of congenital CMV disease.
Background: Erythropoietin (EPO), an essential stimulator of erythropoiesis
produced by the fetal liver, is important both in vascular remodeling and
modulation of the endothelial response in the pulmonary vasculature. In addition,
EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct
target of RA, and the retinoid pathway is altered in the nitrofen-induced
congenital diaphragmatic hernia (CDH) model. In the present study, we tested the
hypothesis that the synthesis of EPO is suppressed in a rat model of CDH. Materials
and Methods: Pregnant rats were treated with either nitrofen or vehicle on
gestational day 9 (D9). Fetuses were sacrificed on D19 and D21 and divided into
control and CDH groups. Immunohistochemistry and quantitative real-time polymerase
chain reaction (RT-PCR) were performedto determine the expression ofEPOin the fetal
liver and kidney. We also estimated the expression of EPO receptor in the fetal
lung. Results: The relative EPO mRNA expression in the liver on D19 and in the
kidney on D21 were significantly lower in the CDH group than in the controls (P =
0.0008 and P = 0.0064, respectively). In addition, the results of
immunohistochemistry supported the findings from the RT-PCR analysis. No
significant changes were noted in the expression pattern or EPO receptor levels in
the fetal lungs of the CDH group compared to the controls. Conclusions: Our results
reveal the suppressed EPO synthesis in the CDH fetus, which may contribute to the
pathogenesis of lung hypoplasia and modification of pulmonary vasculature in the
CDH rat model. (C) 2016 Wiley Periodicals, Inc.
Super-majorities have occurred frequently in Congress but have escaped scholarly
attention. This paper employs new measures of positive agenda control and a unique
data set of 3,407 nontrivial bills from 1981 to 2008 to answer two questions: how
did legislative leaders construct veto-proof coalitions, and what did presidents do
with them? Legislative leaders, we argue, deployed procedures to expand and sustain
veto-proof coalitions, despite increasing polarization. The resulting history,
which signaled members' commitment to a bill, provided information to the president
that reduced uncertainty about possibilities for interbranch bargaining and the
likely success of a veto. We find that positive agenda control increased the
probability of vote tallies of two-thirds or more, especially after the 1994
election. In addition, we demonstrate that presidents concentrated veto activity on
bills with outcomes of less than two-thirds, rejected some veto-proof bills for
reputational gains, and deployed signing statements strategically. The analysis
suggests that congressional leaders paradoxically gained capacity for nurturing
large, bipartisan alliances as the institution became more polarized. Moreover, it
demonstrates that strategic activity by legislative leaders is critical to
explaining variation in presidential options for veto bargaining and signing
statements.
Human judgment often violates normative standards, and virtually no judgment error
has received as much attention as the conjunction fallacy. Judgment errors have
historically served as evidence for dual-process theories of reasoning, insofar as
these errors are assumed to arise from reliance on a fast and intuitive mental
process, and are corrected via effortful deliberative reasoning. In the present
research, three experiments tested the notion that conjunction errors are reduced
by effortful thought. Predictions based on three different dual-process theory
perspectives were tested: lax monitoring, override failure, and the Tripartite
Model. Results indicated that participants higher in numeracy were less likely to
make conjunction errors, but this association only emerged when participants
engaged in two-sided reasoning, as opposed to one-sided or no reasoning. Confidence
was higher for incorrect as opposed to correct judgments, suggesting that
participants were unaware of their errors.
In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2)
is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast
proliferation, its pathophysiological effects in cardiac myocytes remain to be
elucidated. In this study, we examined the biological effects of CTGF in rat
neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its
C-terminal region peptide showed the increase in cell surface area. Similar to
hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF
activated amino acid uptake; however, CTGF-induced hypertrophy is not associated
with the increased expression of skeletal actin or BNP, analyzed by Northern-
blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of
Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell
size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy.
These findings indicate that CTGF is a novel hypertrophic factor in cardiac
myocytes. (C) 2008 Elsevier Inc. All rights reserved.
Functional neuroimaging studies have suggested the existence of 2 largely distinct
social cognition networks, one for theory of mind (taking others' cognitive
perspective) and another for empathy (sharing others' affective states). To address
whether these networks can also be dissociated at the level of brain structure, we
combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla
MRI cortical thickness and structural covariance analysis in 270 healthy adults,
recruited across 2 sites. Regional thickness mapping only provided partial support
for divergent substrates, highlighting that individual differences in empathy
relate to left insular-opercular thickness while no correlation between thickness
and mentalizing scoreswas found. Conversely, structural covariance analysis showed
clearly divergent network modulations by socio-cognitive and -affective phenotypes.
Specifically, individual differences in theory of mind related to structural
integration between temporo-parietal and dorsomedial prefrontal regions while
empathy modulated the strength of dorsal anterior insula networks. Findings were
robust across both recruitment sites, suggesting generalizability. At the level of
structural network embedding, our study provides a double dissociation between
empathy and mentalizing. Moreover, our findings suggest that structural substrates
of higher-order social cognition are reflected rather in interregional networks
than in the the local anatomical markup of specific regions per se.
Human brain asymmetries have been well described. Intriguingly, a number of
asymmetries in brain phenotypes have been shown to change throughout the lifespan.
Recent studies have revealed topological asymmetries between hemispheric white
matter networks in the human brain. However, it remains unknown whether and how
these topological asymmetries evolve from adolescence to young adulthood, a
critical period that constitutes the second peak of human brain and cognitive
development. To address this question, the present study included a large cohort of
healthy adolescents and young adults. Diffusion and structural magnetic resonance
imaging were acquired to construct hemispheric white matter networks, and graph-
theory was applied to quantify topological parameters of the hemispheric networks.
In both adolescents and young adults, rightward asymmetry in both global and local
network efficiencies was consistently observed between the 2 hemispheres, but the
degree of the asymmetry was significantly decreased in young adults. At the nodal
level, the young adults exhibited less rightward asymmetry of nodal efficiency
mainly around the parasylvian area, posterior tempo-parietal cortex, and fusiform
gyrus. These developmental patterns of network asymmetry provide novel insight into
the human brain structural development from adolescence to young adulthood and also
likely relate to the maturation of language and social cognition that takes place
during this period.
Adverse conditions during fetal life have been associated to both structural and
functional changes in neurodevelopment from the neonatal period to adolescence. In
this study, connectomics was used to assess the evolution of brain networks from
infancy to early adolescence. Brain network reorganization over time in subjects
who had suffered adverse perinatal conditions is characterized and related to
neurodevelopment and cognition. Three cohorts of prematurely born infants and
children (between 28 and 35 weeks of gestational age), including individuals with a
birth weight appropriated for gestational age and with intrauterine growth
restriction (IUGR), were evaluated at 1, 6, and 10 years of age, respectively. A
common developmental trajectory of brain networks was identified in both control
and IUGR groups: network efficiencies of the fractional anisotropy (FA)-weighted
and normalized connectomes increase with age, which can be related to maturation
and myelination of fiber connections while the number of connections decreases,
which can be associated to an axonal pruning process and reorganization. Comparing
subjects with or without IUGR, a similar pattern of network differences between
groups was observed in the three developmental stages, mainly characterized by IUGR
group having reduced brain network efficiencies in binary and FA-weighted
connectomes and increased efficiencies in the connectome normalized by its total
connection strength (FA). Associations between brain networks and neurobehavioral
impairments were also evaluated showing a relationship between different network
metrics and specific social cognition-related scores, as well as a higher risk of
inattention/hyperactivity and/or executive functional disorders in IUGR children.
Objective: The aim of this study was to evaluate the association between two
haplotype-tag single nucleotide polymorphisms (SNPs) (rs6658835 and rs10495098) of
TGF-2 and conotruncal heart defects (CTDs).Methods: Two polymorphisms of TGF-2 gene
were genotyped by polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP) from 259 CTDs patients and 310 control subjects.Results:
The association between SNP rs6658835 in TGF-2 and CTDs has been found. The
frequency of G allele in CTDs patients was significantly higher than that in
control subjects (52.7% versus 40.3%, p<0.001, OR =1.649).Conclusion:TGF-2 gene
polymorphisms may serve as a novel genetic marker for the risk of CTDs.
Introduction. The aim of this study was to evaluate the effects of consecutive
night shifts (CNS) and shift length on cognitive performance and sleepiness.
Materials and methods. This study evaluated the sleepiness and performance of 30
control room operators (CROs) working in 7 nights, 7 days, 7 days off (7N7D7O) and
30 CROs working in 4 nights, 7 days, 3 nights, 7 days off (4N7D3N7O) shift patterns
in a petrochemical complex on the last night shift before swinging into the day
shift. To assess cognitive performance, the n-back test, continuous performance
test and simple reaction time test were employed. To assess sleepiness, the
Karolinska sleepiness scale was used. Results. Both schedules indicated that the
correct responses and response times of working memory were reduced (p=0.001),
while intentional errors and sleepiness increased during the shift work (p=0.001).
CNS had a significant impact on reaction time and commission errors (p=0.001).
Conclusion. The main duty of CROs at a petrochemical plant is checking hazardous
processes which require appropriate alertness and cognitive performance. As a
result, planning for appropriate working hours and suitable number of CNS in a
rotating shift system is a contribution to improving CRO performance and enhancing
safety.
Introduction: The high success rate in the management medulloblastoma achieved in
the western world is not exactly mirrored in developing countries including India.
Socio-demographic differences, health-care disparity, and lack in uniformity of
care with resultant widespread variations in the clinical practice are some of the
reasons that may partly explain this difference in outcomes. Patients with
medulloblastoma require a multi-disciplinary team approach involving but not
limited to neuro-radiology, neurosurgery; neuropathology, molecular biology,
radiation oncology, pediatric medical oncology and rehabilitative services for
optimizing outcomes. Methods: The Indian Society of Neuro-Oncology (ISNO)
constituted an expert multi-disciplinary panel with adequate representation from
all stakeholders to prepare national consensus guidelines for the contemporary
management of medulloblastoma. Results: Minimum desirable, as well as preferable
though optional recommendations (as appropriate), were developed and adopted for
the pre-surgical work-up including neuroimaging; neurosurgical management including
surgical principles, techniques, and complications; neuropathology reporting and
molecular testing; contemporary risk-stratification in the molecular era;
appropriate adjuvant therapy (radiotherapy and chemotherapy); and follow-up
schedule in medulloblastoma. Conclusions: The current document represents a broad
consensus reached amongst various stakeholders within the neuro-oncology community
involved in the contemporary curative-intent management of children with
medulloblastoma. It provides both general as well as specific guidelines and
recommendations to be adopted by physicians and health care providers across India
to achieve uniformity of care, improve disease-related outcomes, and compare
results between institutions within the country.
The optimal use of biomass from a global warming mitigation perspective depends
upon numerous factors, including competition for land and other constraints. The
goal of this study is identifying optimal uses of domestic biomass resources for
the case of Denmark, with the objectives of minimizing global warming contribution
and fossil energy resource consumption. For this purpose, consequential life cycle
assessment of the different options for biomass was performed. Optimal solutions
were identified, given specific national environmental targets, using linear
programming. Results highlighted that utilizing the energy potential of manure and
straw represents the primary opportunity for further global warming mitigation. For
this purpose, co-digestion (for manure) and combustion with heat-and-power
production (for straw) appear as the most promising technologies. The utilization
of biomass (or biogas) for electricity/heat is generally preferred, as long as
coal/oil is still used within the energy system. Yet, to fulfill environmental
targets for renewable energy in the transport sector, the diversion of a
significant share of biogas (and/or other biofuels) from these more beneficial uses
is necessary. To completely phase out coal/oil, additional biomass (to current
domestic resources) must be included, either through domestic energy crops
cultivation or biomass/biofuel import; alternatively, natural gas could be used.
(C) 2017 Elsevier Ltd. All rights reserved.
Research indicates that inducing high-level construal (processing that highlights
invariant, essential features) relative to low-level construal (processing that
highlights idiosyncratic, peripheral features) promotes self-control (Fujita &
Carnevale, 2012). In the present work, we investigate to what extent people
recognize the self-control benefits of high-level construal, and explore the
consequences of this knowledge. Studies 1 and 2 provide initial evidence that
individuals are aware that high-level relative to low-level construal promotes
self-control in the dieting domain. Studies 3 and 4 find that individual
differences in this knowledge predict self-control success outcomes (i.e., body
mass index) among those who are motivated by dieting goals. Examining academics as
a domain of self-control, Study 5 demonstrates that those with higher knowledge of
construal level's impact on self-control earned higher end-of-semester grades to
the extent that they were motivated to do well academically. Theoretical and
practical implications of these findings are discussed.
The aim of this study was to assess the environmental impact of microbial fuel
cells (MFCs) implerriented in constructed wetlands (CWs). To this aim a life cycle
assessment (LCA) was carried out comparing three scenarios: 1) a conventional CW
system (without MFC implementation); 2) a CW system coupled with a gravel-based
anode MFC, and 3) a CW system coupled with a graphite-based anode MFC. All systems
served a population equivalent of 1500 p.e. They were designed to meet the same
effluent quality. Since MFCs implemented in CWs improve treatment efficiency, the
CWs coupled with MFCs had lower specific area requirement compared to the
conventional CW system. The functional unit was 1 m(3) of wastewater. The LCA was
performed with the software SimaPro (R) 8, using the CML-IA baseline method. The
three scenarios considered showed similar environmental performance in all the
categories considered, with the exception of Abiotic Depletion Potential. In this
impact category, the potential environmental impact of the CW system coupled with a
gravel-based anode MFC was around 2 times higher than that generated by the
conventional CW system and the CW system coupled with a graphite based anode MFC.
It was attributed to the large amount of less environmentally friendly materials
(e.g. metals, graphite) for MFCs implementation, especially in the case of gravel-
based anode MFCs. Therefore, the CW system coupled with graphite-based anode MFC
appeared as the most environmentally friendly solution which can replace
conventional CWs reducing system footprint by up to 20%. An economic assessment
showed that this system was around 1.5 times more expensive than the conventional
CW system. (C) 2017 Elsevier B.V. All rights reserved.
Roofers have long suffered from low back disorders (LBDs), which are a primary
nonfatal injury in construction. Ergonomic studies have identified several risk
factors associated with LBDs in workplaces and developed biomechanical models for
general LBD risk assessments. However, these models cannot be directly used for
assessments in roof workplaces because they are designed for general tasks without
considering roofers' posture variance and effects of working on slanted roof
surfaces. This paper examined the relationship between roofing work-related factors
and LBD risk among roofers using a laboratory assessment. A pitch-configurable wood
platform was built to mimic the rooftop. The maximum trunk flexion angle and
normalized electromyography (EMG) signals were measured as indicators using a
motion capture system and a skeletal muscle signal recording system under different
settings, i.e., different roof slopes, postures, facing directions, and working
paces. The results indicated the measured factors with significant effects on the
LBD development and revealed unfavorable conditions (e.g., using a stooped posture
to work on low-pitch rooftops at a fast pace) where the work on rooftops needs
particular attention. Such information is useful for systematic understanding of
roofing nonfatal LBD developments among construction professionals and may enable
development of interventions and guidelines for reducing the prevalence of LBDs at
roofing jobsites. (C) 2017 American Society of Civil Engineers.
Many animal toxins may target the same molecules that need to be controlled in
certain pathologies; therefore, some toxins have led to the formulation of drugs
that are presently used, and many other drugs are still under development.
Nevertheless, collecting sufficient toxins from the original source might be a
limiting factor in studying their biological activities. Thus, molecular biology
techniques have been applied in order to obtain large amounts of recombinant toxins
into Escherichia coli. However, most animal toxins are difficult to express in this
system, which results in insoluble, misfolded, or unstable proteins. To solve these
issues, toxins have been fused with tags that may improve protein expression,
solubility, and stability. Among these tags, the SUMO (small ubiquitin-related
modifier) has been shown to be very efficient and can be removed by the Ulp1
protease. However, removing SUMO is a labor- and time-consuming process. To enhance
this system, here we show the construction of a bicistronic vector that allows the
expression of any protein fused to both the SUMO and Ulp1 protease. In this way,
after expression, Ulp1 is able to cleave SUMO and leave the protein interest-free
and ready for purification. This strategy was validated through the expression of a
new phospholipase D from the spider Loxosceles gaucho and a disintegrin from the
Bothrops insularis snake. Both recombinant toxins showed good yield and preserved
biological activities, indicating that the bicistronic vector may be a viable
method to produce proteins that are difficult to express.
Over recent decades, water conservation have become increasingly an utmost
important issue for debate, and this includes the domestic sector. Reducing demand
water by improving the efficiency of water use in domestic sector requires an
understanding of how water is used and in what ways water savings can be realized.
The focus of this global, web-based, consumer questionnaire survey was to analyze
individual consumer attitudes towards using water in manual dishwashing and
understand the likelihood of a prospect of changing the daily manual dishwashing
method resulting to a more efficient domestic usage of water. This study was
designed to investigate the manual dishwashing technique used in the 5249
households of nine different countries - China, Germany, Italy, Russia, Indonesia,
Brazil, India, South Africa and Argentina. Besides socio-demographics, technical
questions like cleaning steps, hygiene questions motivational question,
environmental awareness questions, questions on payment for water and electricity,
questions on information sources about household work were included in the study.
It was found that the awareness to conserve water was common among the Asian
participants but it necessarily was not practiced in the households as individual
washing of dishes was found to be quite high. Among the many outcomes, important
one was that running tap method' was found to be most prevalent (86%) among Russian
participants, complimenting their detached approach towards conserving domestic
water usage. In South American countries like Brazil (66%) and Argentina (51%),
high occurrence of running tap rinse' was found to be a common practice, confirming
the lack of conscious use of water in manual dishwashing in the subcontinent. Based
on the overall responses, awareness of a new and efficient technique of manual
dishwashing could be propagated through the most voted mediums of Internet (81%)
and TV (69%).
Research question: Scholars have paid little attention to consumer response to the
termination of a sponsorship. The purpose of this study was to examine the reaction
of fans of a professional cycling team to a sponsorship terminating, which
ultimately led to the team disbanding.Research methods: The research purpose was
pursued through digital ethnography (via message boards and weblog), examining the
case of Basque professional cycling fans. Comments were analysed to understand
fans' reaction to the 2013 cessation of Euskaltel-Euskadi, a Basque professional
cycling team, after its sponsor, Euskaltel, exited the partnership.Results and
findings: Fan reaction to Euskaltel ending its sponsorship was somewhat
paradoxical, in that the terminated sponsorship ultimately led to the team
disbanding, yet fans appeared to be appreciative of Euskaltel. They continued to
celebrate the team's corporate sponsor colour as they mourned the end of Euskaltel-
Euskadi and questioned the future of Basque cycling. This reaction is made more
logical by understanding the long-term duration of the partnership, and how
Euskaltel's support of the team for nearly two decades led to the intermeshing of
the team and its sponsor, thus avoiding negative sentiment.Implications: This study
makes a meaningful contribution to the sponsorship literature, particularly
sponsorship termination. This study is one of the first to examine consumer
response to sponsorship termination in a real-world setting, and suggests a
potential legacy effect of long-term sponsorship, such that fan reaction to a long-
term sponsorship terminating may not be negative, especially if fans understand the
sponsor's contribution over time.
Green energy has gained significant research attention across the globe due to its
ability to reduce environmental damage. However, for complete acceptance of green
energy, only government regulations are not enough; the willingness to use green
energy and contribute to the wellbeing of the environment should spring from within
consumers. Such willingness may be developed by enhancing consumers' perceived
value of green energy. However, in order to do so, it is necessary to assess
existing levels of consumers' perceived value towards green energy. The present
study develops a multidimensional green perceived value scale to measure existing
levels of consumers' perceived value. The scale considers green perceived value as
a multidimensional second order construct comprising functional value, social
value, conditional value and emotional value dimensions. Such an attempt has not
been made before which highlights the originality value of the present study. The
scale can be used to assess consumers' perception towards green energy. Such
information would help in formulating strategies that encourage consumers to
voluntarily adopt green energy. The study also reveals that it is not only the
financial aspects that lead consumers to decide on adoption of green energy;
consumers are also driven by emotional and social considerations. Thus, policy
makers could formulate pro-green energy programmes and mass messages that appeal to
consumers' sense of responsibility to voluntarily adopt green energy without having
to rely on financial incentives. Researchers could examine the considered
dimensions of the scale further with respect to other constructs related to
consumer behaviour. (C) 2017 Elsevier Ltd. All rights reserved.
Effective HIV prevention requires knowledge of the structure and dynamics of the
social networks across which infections are transmitted. These networks most
commonly comprise chains of sexual relationships, but in some populations, sharing
of contaminated needles is also an important, or even the main mechanism that
connects people in the network. Whereas network data have long been collected
during survey interviews, new data sources have become increasingly common in
recent years, because of advances in molecular biology and the use of partner
notification services in HIV prevention and treatment programmes. We review current
and emerging methods for collecting HIV-related network data, as well as modelling
frameworks commonly used to infer network parameters and map potential HIV
transmission pathways within the network. We discuss the relative strengths and
weaknesses of existing methods and models, and we propose a research agenda for
advancing network analysis in HIV epidemiology. We make the case for a combination
approach that integrates multiple data sources into a coherent statistical
framework. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
The present study focuses on measuring the effects of industrial wastewater
disposed from thermal electricity power plant as by-product on the geotechnical
properties of sandy soil and applying washing process to remediate the contaminated
soil samples and measure the efficiency of washing technique. The disturbed sandy
soil samples were obtained from Al-Kufa City located to the southwest of Iraq and
the industrial wastewater obtained from Al-Musayib thermal electricity power plant.
The intact sandy soil was contaminated in the laboratory with four percentages of
industrial wastewater (10, 20, 40 and 100%) calculated according to the weight of
dry soil. The industrial wastewater is mixed with distilled water to constitute the
solution used in the contamination process of soil through soaking the soil by this
solution for 30 days. The study results showed that with increasing the percentages
of the contaminant, there was a slight increase in both the liquid limit and
particle size, while there was a significant increase in the optimum water content.
Nevertheless, a slight decrease was observed in the specific gravity, maximum dry
unit weight, and void ratio, while, a considerable decrease was noticed in the
angle of the internal friction and coefficient of permeability of soil. The
proposed remediation technique "soil washing" is efficient, economical, and time
saving when used to remediate sandy soils. After remediation, the results showed an
increase in the cohesion, angle of internal friction and maximum dry unit weight.
Also, a slight increase was observed in the specific gravity, void ratio and
permeability coefficient of remediated soil samples when compared with that of
contaminated samples. The removal efficiencies of contaminant from soil were
(97.63, 96.79, 96.58, and 93.87%) for the soil samples contaminated with industrial
wastewater by (10, 20, 40 and 100%), respectively.
Starting with a computational analysis of brightness matching, we develop a novel
variational framework able to model perceptual context-driven effects that may be
extended to non-physical judgments as well. The most important feature of the
variational framework is the description of these phenomena as a suitable balance
between contrast and dispersion. The optimal balance is defined through the
simultaneous minimization of functionals characterized by two terms in opposition
to each other. When the minimum is reached, the equilibrium between contrast and
dispersion is attained. To show the flexibility of the proposed framework, we
discuss several examples of such functionals in the field of color perception and
cognition which show adherence between theoretical predictions and empirical
results. With regard to social cognition theories, the simultaneous occurrence of
contrast and dispersion conflicts with sequential models, thus supporting the idea
of a concurrent presence of both effects in each judgment. The variational
framework can serve as a view from above on perceptual and cognitive phenomena that
may help in deriving new constraints for disambiguating alternative theories. (C)
2016 Elsevier Inc. All rights reserved.
The anterior cingulate cortex (ACC) is commonly associated with cognitive control
and decision making, but its specific function is highly debated. To explore a
recent theory that the ACC learns the reward values of task contexts (Holroyd &
McClure in Psychological Review, 122, 54-83, 2015; Holroyd & Yeung in Trends in
Cognitive Sciences, 16, 122-128, 2012), we recorded the event-related brain
potentials (ERPs) from participants as they played a novel gambling task. The
participants were first required to select from among three games in one "virtual
casino," and subsequently they were required to select from among three different
games in a different virtual casino; unbeknownst to them, the payoffs for the games
were higher in one casino than in the other. Analysis of the reward positivity, an
ERP component believed to reflect reward-related signals carried to the ACC by the
midbrain dopamine system, revealed that the ACC is sensitive to differences in the
reward values associated with both the casinos and the games inside the casinos,
indicating that participants learned the values of the contexts in which rewards
were delivered. These results highlight the importance of the ACC in learning the
reward values of task contexts in order to guide action selection.
This paper analyzes the effect of operational amplifier (OPAMP) input offset on
continuous-time (CT) delta-sigma (Delta Sigma) modulators with current-mode
feedback digital-to-analog converters (DAC). Our analysis shows that the input
offset leads to either increased harmonics or increased noise floor of the
modulator, depending on whether a DAC shuffling scheme, such as data-weighted
averaging (DWA), is applied or not. Analysis and mathematical derivation are given
and verified by transistor-level simulations. An input-offset cancellation scheme
is proposed and demonstrated by simulation results.
The current practice of discrete-time electricity pricing starts to fall short in
providing an accurate economic signal reflecting the continuous-time variations of
load and generation schedule in power systems. This paper introduces the
fundamental mathematical theory of continuous-time marginal electricity pricing. We
first formulate the continuous-time unit commitment problem as a constrained
variational problem, and subsequently define the continuous-time economic dispatch
(ED) problem where the binary commitment variables are fixed to their optimal
values. We then prove that the continuous-time marginal electricity price equals to
the Lagrange multiplier of the variational power balance constraint in the
continuous-time ED problem. The proposed continuous-time marginal price is not only
dependent to the incremental generation cost rate, but also to the incremental
ramping cost rate of the units, thus embedding the ramping costs in calculation of
the marginal electricity price. The numerical results demonstrate that the
continuous-time marginal price manifests the behavior of the constantly varying
load and generation schedule in power systems.
An approach to mass measurement for the electronic balance based on continuous-time
sigma-delta (CT Sigma-Delta) modulator is described in this paper. As an effect of
multifarious interfering noises, the accuracy of the electronic balance is
restricted. The general idea of this proposed approach is to apply an
electromagnetic-force-compensated load cell (EMCC), a related signal processing
circuit, and a composite filter. The circuit mainly consists of a proportional-
integral-differential controller and a pulsewidth modulator, which combine with the
EMCC to form a CT Sigma-Delta modulator. As the CT Sigma-Delta modulator possesses
inherent antialiasing filtering, oversampling, and noise-shaping characteristics,
the interfering noises can be effectively removed by the composite filter that is
composed of two sinc(N) filters. The simulations for both of the electronic balance
models adopting the proposed approach and working in conventional pulse current
mode are analyzed by adding the white Gaussian noise in Simulink. The simulation
results demonstrate the effectiveness of this proposed approach, the proposed
electronic balance in the field can improve its signal-to-noise ratio, and the
testing results meet the requirement for the weighing accuracy of the special-class
scale defined by Organisation Internationale De Metrologie Legale R76 nonautomatic
weighing instruments.
Precise knowledge of the plant time constant L/R is essential to perform a thorough
analysis and design of the current control loop in voltage source converters
(VSCs). From the perspective of the current controller dynamics in the low-
frequency range, such plant time constant is also suitable for most cases in which
an LCL filter is used. As the loop behavior can be significantly influenced by the
VSC working conditions, the effects associated to converter losses should be
included in the model, through an equivalent series resistance. In addition, the
plant inductance may also present important uncertainties with respect to the value
of the VSC L/LCL interface filter measured at rated conditions. Thus, in this
paper, a method is presented to estimate both parameters of the plant time
constant, i.e., the equivalent inductance and resistance in the plant model of
current-controlled VSCs. The proposed technique is based on the evaluation of the
closed-loop transient responses of both axes of the synchronous reference frame
when a proportional-integral current controller is implemented. The method gives a
set of resistance and inductance values that should be employed for a rigorous
design of the current controllers. Experimental results validate the approach.
Regression analysis using orthogonal polynomials in the time domain is used to
derive a digital filter with an infinite impulse response that satisfies maximally
flat design constraints near dc. The low-frequency phase, and high-frequency gain,
may be adjusted for lead or lag compensation of plant dynamics. Simulated design
examples are used to show how the compensating filter may be intuitively tuned for
the desired closed-loop response. It is shown that the second-order instantiation
of the compensating filter reduces to a proportional-differential plus filter
controller, with improved noise attenuation; closed-form expressions for the filter
coefficients, as a function of two design parameters, are provided.
In conventional relative gene expression analysis (Northern blotting, RT-PCR, and
in situ hybridization), housekeeping genes such as the glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) and beta-actin genes, whose expression levels are considered
stable, have been used as control genes for normalization of RNA quantitation.
However, it has been reported that the expression levels of these two control genes
are affected by ischemia. Therefore, we have been searching for novel control genes
whose expression levels are stable in a mouse model of transient forebrain
ischemia. Using the GeneChip Mu6500 array set, we monitored the expression levels
of approximately 6000 murine genes in the mouse hippocampus during 24 h of
ischemia-reperfusion. To select stable genes, we applied the restricted criterion
of a 1.5-fold change in expression level as the threshold. By adding statistical
analysis with this criterion, we identified 10 genes as candidates for control
genes from the GeneChip data. In this criterion, GAPDH and beta-actin genes were
not included in the 10 genes as candidates for control genes. The present findings
might be relevant to the use of control genes in quantitation of RNA, particularly
in the study of mouse transient forebrain ischemia.
The use of nuclear energy to generate electric power is crucial to meet the high
energy demand of a modern economy. In newly constructed nuclear power plants
(NPPs), the trend among control systems is to replace the obsolete analog hard-
wired systems with the contemporary digital and cyber-based systems. Therefore,
cyberphysical security as well as dependability are critical issues in safety
critical NPPs. In this paper, we present different levels/layers of protection to
manage cyber/physical security. We also discuss the interrelationship between cyber
and physical attacks. We adopt generalized stochastic Petri nets to quantitatively
evaluate the intrusion probability. We then propose a new cyberframework and show
that the proposed framework not only prevents cyberattacks but also conforms to
cybersecurity regulations. We also propose a physical framework to prevent
potential physical attacks. Finally, we discuss dependability through three
metrics, i.e., reliability, maintainability, and availability. A case study is
presented to demonstrate that the proposed cyberframework is highly dependable
through analyzing steady-state probabilities.
Home energy management system (HEMS) is essential for residential electricity
consumers to participate actively in demand response (DR) programs. Dynamic pricing
schemes are not sufficiently effective for end-users without utilizing a HEMS for
consumption management. In this paper, an intelligent HEMS algorithm is proposed to
schedule the consumption of controllable appliances in a smart household. Electric
vehicle (EV) and electric water heater (EWH) are incorporated in the HEMS. They are
controllable appliances with storage capability. EVs are flexible energy-intensive
loads, which can provide advantages of a dispatchable source. It is expected that
the penetration of EVs will grow considerably in future. This algorithm is designed
for a smart household with a rooftop photovoltaic (PV) system integrated with an
energy storage system (ESS). Simulation results are presented under different
pricing and DR programs to demonstrate the application of the HEMS and to verify
its' effectiveness. Case studies are conducted using real measurements. They
consider the household load, the rooftop PV generation forecast and the built-in
parameters of controllable appliances as inputs. The results exhibit that the daily
household energy cost reduces 29.5%-31.5% by using the proposed optimization-based
algorithm in the HEMS instead of a simple rule-based algorithm under different
pricing schemes. (C) 2017 Elsevier B.V. All rights reserved.
The development of a non-human primate (NHP) model of spinal cord injury (SCI)
based on mechanical and computational modeling is described. We scaled up from a
rodent model to a larger primate model using a highly controllable, friction-free,
electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries.
Graded contusion lesions with varying degrees of functional recovery, depending
upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-
operative magnetic resonance imaging (MRI) were used to optimize the predictability
of outcomes by matching impact protocols to the size of each animal's spinal canal,
cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement
and provided information on lesion volume and spread for comparison with
histological measures. We evaluated the relationships between impact parameters,
lesion measures, and behavioral outcomes, and confirmed that these relationships
were consistent with our previous studies in the rat. In addition to providing
multiple univariate outcome measures, we also developed an integrated outcome
metric describing the multivariate cervical SCI syndrome. Impacts at the higher
ranges of peak force produced highly lateralized and enduring deficits in multiple
measures of forelimb and hand function, while lower energy impacts produced early
weakness followed by substantial recovery but enduring deficits in fine digital
control (e.g., pincer grasp). This model provides a clinically relevant system in
which to evaluate the safety and, potentially, the efficacy of candidate
translational therapies.
A simple, convenient, easy-to-use, and low-cost platform for rapid molecular
detection of H1N1 virus is designed and implemented based on convective polymerase
chain reaction (CPCR) and dipstick assay at the point of care (POC) settings. A
fully disposable chemically-heated thermal processor is developed to heat the
capillary tube from the bottom at a fixed temperature for amplification without the
need for electrical power. Amplification is achieved when reagents in the capillary
tube are spontaneously and repeatedly transported through different temperature
zones, which significantly shortens the amplification time by eliminating the need
for controlled time-domain temperature cycling. A rapid one-step nucleic acid
dipstick assay is adopted to facilitate the detection of amplification products
with the eye instead of instrumentation. The utility of our POC diagnostic system
was demonstrated by detecting H1N1 virus with sensitivity of 1.0 TCID50/mL within
35 min. The developed system is particularly desired for resource poor settings,
for example, developing countries, outside centralized laboratories, doctor's
offices and homes, to relieve the requirements for laboratory facilities and
trained personnel. (C) 2016 Elsevier B.V. All rights reserved.
In this paper, a parallel structure fractional repetitive control (RC) scheme is
proposed to improve the performance of pulsewidth-modulation (PWM) inverters in
fractional cases where the sampling rate of the digital control system is not an
integral multiple of the fundamental frequency. By introducing a correction factor,
the new control scheme increases the control gains for all harmonics and locates
poles accurately at targeted harmonic frequencies. As a result, the proposed
control scheme achieves better tracking and rejection performance than conventional
RC. Moreover, the parallel structure fractional repetitive controller requires less
data memory. Dynamic response is also improved. The stability and convergence of
this method are proved. Experimental results on a single-phase PWM inverter
illustrate the advantages of this control scheme.
Entomopathogenic fungi play a pivotal role in the regulation of insect populations
in nature, and representative species have been developed as promising
environmentally friendly mycoinsecticides. Recent advances in the genome biology of
insect pathogenic fungi have revealed genomic features associated with fungal
adaptation to insect hosts and different host ranges, as well as the evolutionary
relationships between insect and noninsect pathogens. By using species in the
Beauveria and Metarhizium genera as models, molecular biology studies have revealed
the genes that function in fungus-insect interactions and thereby contribute to
fungal virulence. Taken together with efforts toward genetic improvement of fungal
virulence and stress resistance, knowledge of entomopathogenic fungi will
potentiate cost-effective applications of mycoinsecticides for pest control in the
field. Relative to our advanced insights into the mechanisms of fungal pathogenesis
in plants and humans, future studies will be necessary to unravel the gene-for-gene
relationships in fungus-insect interactive models.
The cement production process is energy intensive both in terms of the thermal
energy (firing the kiln, drying and De carbonation) and electrical energy for
driving the numerous drives within the process line. The average specific power
consumption of the case study plant was 111kWh/ton of cement with an average peak
demand of 9.7MW. The high cost of electric power at 0.14USD/kWh results in very
high cost of production that significantly lowers the company's profit margin and
limits its competitive advantage. The generation of electrical power from waste
heat recovery would reduce the electricity power bill through partially
substituting the power procured from the national grid. This research evaluated the
potential that the plant has for generating electrical power from the hot waste
gases vented into the atmosphere and it was found that the plant has the potential
to generate 3.4MWh of electrical power. This results to a net potential to generate
2.89MWh of electrical power after factoring in the auxiliary power consumption by
Waste heat recovery plant system at 15%. This ultimately gave a reduction of 33% in
the electricity power bill of the case study plant. The paper recommends the
installation of a steam rankine cycle for the power generating plant. In this work
the authors designed the steam boilers for the waste heat recovery plant for
conversion of thermal energy to electrical energy, selected a commercial steam
turbine and evaluated its economic feasibility and established that the designed
plant would have a simple payback period of 2.7years.
This paper presents the Local Vector Control ( LVC) algorithm that is applicable to
power electronic systems. This controller does not differentiate between linear or
non-linear systems and can operate, without change, in stationary or rotating
reference frames. The performance of this current controller with particular
emphasis on current clamp minimisation will be the paper's focus. A comparison
between the LVC, PI and predictive dead- beat current controllers ( PCC) is
presented.
This paper presents a digital Active Gate Drive (AGD) methodology for power
semiconductor devices. The inherent latency limitation of digital signal processing
systems is addressed by a sequential optimization procedure that uses voltage and
current signals recorded at the previous switching edge to develop an optimized
gate drive waveform for the next switching edge. Experimental results using a half-
bridge circuit operating at 180 V/100 A show that the proposed scheme is capable of
minimizing switching losses whilst constraining the overvoltage peaks occurring at
turn-on and turn-off to as low as 200 V and 300 V respectively.
Demand response (DR) is a recent effort to improve the efficiency of the
electricity market and the stability of the power system. A successful
implementation relies on both appropriate policy design and enabling technology.
This paper presents a multiagent system to evaluate optimal residential DR
implementation in a distribution network, in which the main stakeholders are
modeled by heterogeneous home agents (HAs) and a retailer agent (RA). The HA is
able to predict and control electricity load demand. A real-time price prediction
model is developed for the HA and the RA. The optimal control of electricity
consumption is formulated into a convex programming problem to minimize electricity
payment and waiting time under real-time pricing. Simulation results show that the
peak-to-average power ratio and electricity payments are significantly reduced
using the proposed algorithms. The HA, with the proposed optimal control
algorithms, can be embedded into a home energy management system to make
intelligent decisions on behalf of homeowners responding to DR policies. The
proposed agent system can be utilized to evaluate various strategies and emerging
technologies that enable the implementation of DR.
This study investigated interactive exchange in lovers and the associated
interpersonal brain synchronization (IBS) using functional near-infrared
spectroscopy (fNIRS)-based hyperscanning. Three types of female-male dyads, lovers,
friends, and strangers, performed a cooperation task during which brain activity
was recorded in right frontoparietal regions. We measured better cooperative
behavior in lover dyads compared with friend and stranger dyads. Lover dyads
demonstrated increased IBS in right superior frontal cortex, which also covaried
with their task performance. Granger causality analyses in lover dyads revealed
stronger directional synchronization from females to males than from males to
females, suggesting different roles for females and males during cooperation. Our
study refines the theoretical explanation of romantic interaction between lovers.
Hum Brain Mapp 38:831-841, 2017. (c) 2016 Wiley Periodicals, Inc.
Cooperative behavior is widespread among animals, yet the neural mechanisms have
not been studied in detail. We examined cooperative territory defense behavior and
associated neural activity in candidate forebrain regions in the cichlid fish,
Astatotilapia burtoni. We find that a territorial male neighbor will engage in
territory defense dependent on the perceived threat of the intruder. The resident
male, on the other hand, engages in defense based on the size and behavior of his
partner, the neighbor. In the neighbor, we find that an index of engagement
correlates with neural activity in the putative homolog of the mammalian
basolateral amygdala and in the preoptic area, as well as in preoptic dopaminergic
neurons. In the resident, neighbor behavior is correlated with neural activity in
the homolog of the mammalian hippocampus. Overall, we find distinct neural activity
patterns between the neighbor and the resident, suggesting that an individual
perceives and processes an intruder challenge differently during cooperative
territory defense depending on its own behavioral role. (C) 2017 Elsevier Inc. All
rights reserved.
Through a study of agricultural service cooperatives in Russia's Belgorod region,
this article addresses two gaps in the literature: first, the dearth of empirical
studies on cooperatives in post-socialist Russia; second, the lack of attention to
top-down cooperatives in the global literature, and the overly negative approach to
the topic in the few extant studies. Whereas state attempts to establish
agricultural cooperatives in Russia in a top-down fashion have largely failed, such
cooperatives have sprung up widely in Belgorod. The article investigates: (1) what
influence the (regional) state exerts on the cooperatives, and how that affects
their daily functioning and viability; and (2) to what extent such top-down
cooperatives might evolve into less state-led forms, such as classic member-driven
or business-like cooperatives.
Although it is well established that rhythmically coordinating with a social
partner can increase cooperation, it is as yet unclear when and why intentional
coordination has such effects. We distinguish three dimensions along which
explanations might vary. First, pro-social effects might require in-phase synchrony
or simply coordination. Second, the effects of rhythmic movements on cooperation
might be direct or mediated by an intervening variable. Third, the pro-social
effects might occur in proportion to the quality of the coordination, or occur once
some threshold amount of coordination has occurred. We report an experiment and two
follow-ups which sought to identify which classes of models are required to account
for the positive effects of coordinated rhythmic movement on cooperation. Across
the studies, we found evidence (1) that coordination, and not just synchrony, can
have pro-social consequences (so long as the social nature of the task is
perceived), (2) that the effects of intentional coordination are direct, not
mediated, and (3) that the degree of the coordination did not predict the degree of
cooperation. The fact of inter-personal coordination (moving together in time and
in a social context) is all that's required for pro-social effects. We suggest that
future research should use the kind of carefully controllable experimental task
used here to continue to develop explanations for when and why coordination affects
pro-social behaviors.
Background: Some COPD patients are more susceptible to exacerbations than others.
Mechanisms underlying these differences in susceptibility are not well understood.
We hypothesized that altered cell mediated immune responses may underlie a
propensity to suffer from frequent exacerbations in COPD. Methods: Peripheral blood
mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight
frequent exacerbators (>= 3 diary-card exacerbations/year) and 16 infrequent
exacerbators (< 3 diary-card exacerbations/year). Detailed multi-parameter flow
cytometry was used to study differences in innate and adaptive systemic immune
function between frequent and infrequently exacerbating COPD patients. Results: The
24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV1 1.43 (0.60) L,
53.3 (18.3)% predicted. PBMCs of frequent exacerbators (FE) contained lower
frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent
exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035). This observation was also
apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 x 10(Lambda)6/mL; IE =
0.25 x 10(Lambda)6/mL; p = 0.035). PBMCs of FE contained a lower frequency of CD8+
T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related)
compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007). Conclusion:
Differences in the adaptive systemic immune system might associate with
exacerbation susceptibility in the `frequent exacerbator' COPD phenotype. These
differences include fewer CD4+ T central memory cells and CD8+ T effector memory
cells.
Nutrients have been known to have a significant role in maintaining the health of
the skeleton, both bone and cartilage. The nutrients that have received the
majority of the attention are Vitamin D and calcium. However, limited attention has
been directed toward three trace elements that may have mechanistic impact upon the
skeletal tissues and could compromise skeletal health resulting from inadequate
intakes of copper, iron, and selenium. The role of copper and selenium has been
known, but the role of iron has only received recent attention. Copper deficiency
is thought to impact bone health by a decrease in lysyl oxidase, a copper-
containing enzyme, which facilitates collagen fibril crosslinking. Iron deficiency
impact upon bone has only recently been discovered but the exact mechanism on how
the deficient states enhance bone pathology is speculative. Selenium deficiency has
an impact on cartilage thereby having an indirect impact on bone. However, several
studies suggest that a mycotoxin when consumed by humans is the culprit in some
cartilage disorders and the presence of selenium could attenuate the pathology.
This review summarizes the current knowledge base with respect to skeletal
integrity when each of these three trace elements are inadequate in diets of both
animals and humans.
Aims: FIP-gsi, a fungal immunomodulatory protein found in Ganoderma sinense, has
antitumour, anti-allergy and immunomodulatory activities and is regulated by the
fip-gsi gene. In this study, we aimed to express the fip-gsi gene from G. sinense
in Coprinopsis cinerea to increase yield of FIPs-gsi. Methods and Results: A fungal
expression vector pBfip-gsi containing the gpd promoter from Agaricus bisporus and
the fip-gsi gene from the G. sinense was constructed and transformed into C.
cinerea. PCR and Southern blotting analysis verified the successful integration of
the exogenous gene fip-gsi into the genome of C. cinerea. RT-PCR and Northern
blotting analysis confirmed that the fip-gsi gene was transcribed in C. cinerea.
The yield of the FIP-gsi protein reached 314 mg kg-1 fresh mycelia. The molecular
weight of the FIP-gsi was 13 kDa, and the FIP-gsi was capable of hemagglutinating
mouse red blood cells, but no such activity was observed towards human red blood
cells in vitro. Conclusions: The fip-gsi from G. sinense has been successfully
translated in C. cinerea, and the yield of bioactive FIP-gsi protein was high.
Significance and Impact of the Study: This is the first report using the C. cinerea
for the heterologous expression of FIP-gsi protein and it might supply a basis for
large-scale production of the protein.
Effective and sensitive methods for the molecular detection of Echinococcus
multilocularis in faecal samples of final hosts are crucial for the prevention and
control of human alveolar echinococcosis and for studies on the epidemiology of the
parasite. Little is known about the suitability of commercial test kits for
isolating DNA of E. multilocularis from fox faeces and the performance of standard
Polymerase Chain Reaction (PCR) protocols in relation to the quality of DNA
extracted by these kits. We compared four different kits: ZR Faecal DNA MiniPrep
(TM) (Zymo Research), FastDNA (R) SPIN Kit for Soil (MP Biomedicals), QIAamp (R)
Fast DNA Stool Mini Kit (QIAGEN) and NucleoSpin (R) Soil Kit (Macherey-Nagel) for
the extraction of DNA from E. multilocularis eggs present in faeces of foxes.
Negative faecal samples were spiked with 600, 300, 150, 75, 37, 18, 9, 5 or 2 E.
multilocularis eggs, and each egg concentration was tested 10 times with each of
the DNA extraction kits. Each extracted DNA sample was amplified using three PCR
protocols: i. conventional PCR (cPCR, Platinum (R) Taq, Invitrogen), ii. qPCR with
the iQ (TM) Supermix (Bio-Rad) and iii. qPCR with the QuantiTect (R) Multiplex -
Master Mix (QIAGEN). The highest analytical sensitivities for molecular detection
of E. multilocularis eggs in spiked fox faeces were observed when combining either
the QIAamp (R) Fast DNA Stool Mini Kit or the ZR Faecal DNA MiniPrep (TM) kit with
the qPCR using the QuantiTect (R) Multiplex -Master Mix (Sensitivities 97% and 94%,
respectively). Combinations including the remaining test kits (NucleoSpin (R) Soil
Kit and FastDNA (R) SPIN Kit for Soil) showed a markedly lower analytical
sensitivity for PCR examinations. The results of the present study indicate that it
is of utmost importance to select suitable DNA extraction kits in combination with
robust PCR methods or reagents to achieve acceptable analytical sensitivity in the
molecular detection of E. multilocularis eggs in fox faecal samples. (C) 2017
Elsevier B.V. All rights reserved.
This paper examines the political activity of the Coptic diaspora in the United
States in support of the Coptic minority in Egypt. Analysing its strategy reveals
that for years it has focused on lobbying the United States and international
bodies, in order to raise international awareness of the Coptic minority status. By
using this strategy, it has framed the struggle for Copts' rights in a manner that
contradicts the Egyptian unity narrative, and the strategic choices of those they
are struggling for. This paper shows that understanding the limitations of this
strategy alongside a change in the structure of opportunities in Egypt has led to a
change in the pattern of activity of the diaspora activists. Alongside lobbying for
international involvement, they have developed additional strategies, including
strengthening their influence in the homeland and even direct action vis-a-vis the
Egyptian authorities. This paper, which emphasises the pattern of action of
diaspora activists that represent minorities, directs attention to the structure of
opportunities in the homeland, the variety of relationships between the diaspora
and the homeland, and their effect on the ability of the diaspora activists to
become a significant force in shaping the life of the minority.
Recently early diagnosis of squamous cell carcinoma antigen (SCCA) as a tumor maker
of various cancers has increasingly attracted a lot of attention with heightening
of incidence rate of cancer. The SCCA with low concentration in human serum should
be diluted before detecting. Thus, an immunoassay with high sensitivity is
significant for early detecting SCCA. Therefore, a nonenzymatic sandwich-type
electrochemical immunosensor herein was conducted to quantitative detection of
squamous cell carcinoma antigen (SCCA). The amino functionalized cobaltosic oxide @
ceric dioxide nanocubes with core-shell morphology were prepared to combine sea-
urchin like gold @ platinum nanoparticles (Co3O4@CeO2-Au@Pt), and used as labels to
conjugate with secondary antibodies for signal amplification. Due to the synergetic
effect, excellent electrochemical property and superior auxiliary catalytic
activity of Co3O4@CeO2-Au@Pt, high electrocatalytic current responses toward the
reduction of hydrogen peroxide (H2O2) were achieved. Besides, the electrodeposited
gold nanoparticles (D-Au NPs) which were modified on glassy carbon electrodes (GCE)
were used as antibodies carriers and sensing platforms. With the well cooperation
of Co3O4@CeO2-Au@Pt and D-Au NPs, a broad linear range from 100 fg/mL to 80 ng/mL
with a low detection limit of 33 fg/mL for detecting SCCA was achieved. In
addition, the immunosensor displayed with good reproducibility, high selectivity
and stability. The results are satisfactory when the proposed method has been
applied to analyze human serum samples, indicating that the potential application
is promising in clinical monitoring of tumor markers.
Rabbit cells and models are frequently used in pharmacological experiments and
toxicity tests and are particularly useful for corneal transplant experiments.
Here, we obtained a corneal endothelial cell line from normal rabbit corneal
endothelium that had acquired infinite proliferative potential without requiring
gene transfer. These infinitely proliferative rabbit corneal endothelial cells
(iRCECs) could be cultured for >250 generations and exhibited a greater ability to
proliferate than did normal rabbit corneal endothelial cells (RCECs) cultivated by
conventional methods. The results of reverse transcriptase-polymerase chain
reaction (RT-PCR) and immunostaining analyses revealed that the expression profiles
of corneal endothelial markers, such as collagen type VIII1 and Na+/K+-ATPase, were
similar to those of RCECs and in vivo corneal endothelium. Scanning electron
microscopy showed that many microvilli were present on the surface of the cells and
that the ultrastructure was maintained. In addition, we verified that the iRCECs
had similar levels of pump function as did RCECs using an Ussing chamber system.
The results of a soft agar colony-formation assay suggested that the iRCECs were
not tumourigenic. Taken together, our results demonstrated that the iRCECs
exhibited gene expression profiles and properties that were equivalent to those of
native rabbit corneal endothelium, making these cells useful for corneal
endothelial research studies. Copyright (c) 2015 John Wiley & Sons, Ltd.
Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in
the recent years as a candidate gene for hypertension, cardiovascular diseases and
type 2 diabetes. The aim of the present study was to investigate the association of
ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian
population. A total of 662 subjects (330 CAD patients and 332 healthy controls)
were examined for association of ACE gene (I/D) polymorphism and environmental risk
factors. The mean age of the CAD patients and control subjects was 60.53 +/- 8.6
years and 56.55 +/- 7.7 years, respectively (p = 0.000). Anthropometric and
demographic data showed BMI values significantly higher among CAD patients and
control subjects (26.98 +/- 4.9 vs 24.04 +/- 4.7, p = 0.000). We observed
pronounced central obesity in both CAD patients and controls, even at the lowest
BMI values (< 23 kg/m(2)). Dyslipidemia was highly prevalent in CAD patients
compared to control subjects. Genotypic data showed significantly higher frequency
of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No
significant difference was observed in the distribution of ID genotypes between CAD
patients and control subjects. Logistic regression analysis of data demonstrate
that DD genotype was associated with 1.8 fold increased risk of development of CAD
in Asian Indians (OR 1.8; 95 % CI 1.22-2.66; p = 0.003). The frequency of D allele
was significantly higher in CAD patients (p = 0.001). No significant difference was
observed in the clinical and biochemical characteristics of CAD patients and
controls when the data was stratified according to the genotypes of ACE gene. In
conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in
Asian Indian population.
Background: Electrocardiographic (ECG) monitored outpatient cardiac rehabilitation
(OP-CR) is routinely performed following a variety of cardiovascular procedures and
conditions. Objective: The aim of this study is to determine if diagnostic-quality
ECG monitoring in patients with coronary artery disease (CAD) during OP-CR is
useful in identifying asymptomatic myocardial ischemia, resulting in change(s) in
care or medical management. Methods: A retrospective analysis of ECG monitoring was
done on all OP-CR patients diagnosed with CAD (n = 1213) from January 2000 through
June 2013. Results: Nearly a quarter of the patients (24%; n = 288) displayed at
least 1 mm of asymptomatic ST-segment depression at 80 milliseconds after the J-
point during at least 1 session of OP-CR. Of these patients, 57% had medical
management change(s) compared with 24% for those who did not show ECG changes
suggesting ischemia (P < .0001). In patients with asymptomatic ischemia having
medical management change(s), 84% resulted directly from OP-CR staff detection.
Fewer patients diagnosed with myocardial infarction and coronary artery bypass
graft surgery demonstrated ECG signs of ischemia, whereas more patients diagnosed
with stable angina and percutaneous coronary interventions demonstrated ECG signs
of ischemia. Conclusion: This study demonstrates that most patients with CAD
showing asymptomatic ECG signs suggesting ischemia undergo medical management
change(s) as a result of the finding. Diagnostic-quality ECG monitoring during OP-
CR appears warranted in this population.
Previous research has found patients with the Fc gamma RIIIB NA1 variant having
increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease
(KD). Our previous studies revealed that elevated Fc gamma RIIA expression
correlated with the susceptibility of KD patients. We conducted this research to
determine whether and how Fc gamma receptors affect the susceptibility, IVIG
treatment response, and coronary artery lesions (CAL) of KD patients. The
activating Fc gamma RIIA and inhibitory Fc gamma RIIB methylation levels of seven
patients with KD and four control subjects were examined using HumanMethylation27
BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with
fevers. We performed real-time RT-PCR to determine the Fc.RIIA and Fc.RIIB
expression levels, as well as a luciferase assay of Fc gamma RIIA. We found a
considerable increase in methylation of both Fc gamma RIIA and Fc gamma RIIB in KD
patients undergoing IVIG treatment. Promoter methylation of Fc gamma RIIA inhibited
reporter activity in K562 cells using luciferase assay. The Fc gamma RIIB mRNA
expression levels were not found to increase susceptibility, CAL formation, or IVIG
resistance. Fc gamma RIIA mRNA expression levels were significantly higher in IVIG-
resistant patients than in those that responded to IVIG during the pre-treatment
period. Furthermore, the Fc gamma RIIA/ IIB mRNA expression ratio was considerably
higher in KD patients with CAL than in those without CAL. Fc gamma RIIA and Fc
gamma RIIB both demonstrated increased methylation levels in KD patients that
underwent IVIG treatment. Fc gamma RIIA expression influenced the IVIG treatment
response of KD patients. The Fc gamma RIIA/ IIB mRNA expression ratio was greater
in KD patients with CAL formation.
The significant contribution of microbial corrosion to material degradation in
industrial environments has been widely investigated, especially in recent years.
However, the process remains largely underestimated and, more than ever today, its
control is proved to be difficult. Indeed, some recent environmental issues and
regulatory led to the reduction of the biocides and anticorrosive treatments, often
without an appropriate revision of procedures and without a careful monitoring,
thus affecting the effectiveness of the treatments. A multitude of bacterial
species lives within the "corrosive" biofilm, where organisms interacts in
synergistically or competitive way adapting themselves to external agents, even in
extreme conditions. Combining modern electrochemical techniques and molecular
biology it is possible today to monitor the biocorrosion risk and to highlight the
complexity of the phenomenon. The relevant involvement of specific bacterial
strains, including the sulphate reducers and other bacteria of the sulfur cycle, as
well as the role of enzymes of the oxidative metabolism has been confirmed by these
techniques. These enzymes can be expressed by a vast number of microorganisms, both
aerobic and anaerobic, as function of environmental conditions.
The expression of cytochrome P-450 and cytochrome P-450 reductase (CPR) genes in
the conterminous biotransformation of corticosteroids and PAHs was studied in
Cunninghamella elegans 1785/21Gp. We had previously used this strain as a microbial
eucaryotic model for studying the relationship between mammalian steroid
hydroxylation and the metabolization of PAHs. We reported that cytochrome P-450
reductase is involved in the biotransformaton of cortexolone and phenanthrene. RT-
PCR and Northern blotting analyses indicated that the cytochrome P-450 and CPR
genes appear to be inducible by both steroids and PAHs. The expression of the
cytochrome P-450 gene was increased ninefold and the expression of the CPR gene
increased 6.4-fold in cultures with cortexolone and/or phenanthrene in comparison
with controls. We conclude that the increase in cytochrome P-450 gene expression
was accompanied by an increase in cytochrome P-450 enzymatic activity levels.
Background: Cognitive empathy is supported by the medial prefrontal cortex (mPFC),
inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS),
supplementary motor area (SMA), right temporo-parietal junction (TPJ), and
precuneus (PREC). In healthy controls, cortical thickness in these regions has been
linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we
examined whether reduced cortical thickness in these regions was associated with
poorer cognitive empathy in this population. Methods: 41 clinically-stable
community-dwelling individuals with schizophrenia and 46 healthy controls group-
matched on demographic variables completed self-report empathy questionnaires, a
cognitive empathy task, and structural magnetic resonance imaging. We examined
between-group differences in study variables using t-tests and analyses of
variance. Next, we used Pearson correlations to evaluate the relationship between
cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and
PREC in both groups. Results: Individuals with schizophrenia demonstrated cortical
thinning in the IFG, INS, SMA, TPJ, and PREC (all p < 0.05) and impaired cognitive
empathy across all measures (all p < 0.01) relative to controls. While cortical
thickness in the mPFC, IFC, aMCC, and INS (all p0.10). Conclusions: Individuals
with schizophrenia have reduced cortical thickness in empathy-related neural
regions and significant impairments in cognitive empathy. Interestingly, cortical
thickness was related to cognitive empathy in controls but not in the schizophrenia
group. We discuss other mechanisms that may account for cognitive empathy
impairment in schizophrenia. (C) 2016 Elsevier B.V. All rights reserved.
Epileptiform discharges on an isolated cortex are explored using neural field
theory. A neural field model of the isolated cortex is used that consists of three
neural populations, excitatory, inhibitory, and excitatory bursting. Mechanisms by
which an isolated cortex gives rise to seizure-like waveforms thought to underly
pathological EEG waveforms on the deafferented cortex are explored. It is shown
that the model reproduces similar time series and oscillatory frequencies for
paroxysmal discharges when compared with physiological recordings both during acute
and chronic deafferentation states. Furthermore, within our model ictal activity
arises from perturbations to steady-states very close to the dynamical system's
instability boundary; hence, these are distinct from corticothalamic seizures
observed in the model for the intact brain which involved limit-cycle dynamics. The
results are applied to experiments in deafferented cats.
Secreted phosphoprotein 1 (SPP1, also known as osteopontin) is expressed in large
pyramidal neurons in the primary motor cortex (M1) of certain primate species,
including macaque monkeys, but not of rodents. Based on this, we suggested that
SPP1 expression may reflect the functional or structural specialization of highly
developed corticospinal systems. In the present study, we further characterized
SPP1 in the human central nervous system by investigating its expression in the
primary somatosensory cortex (S1) and spinal cord, in addition to M1. Although a
small number of SPP1-positive pyramidal neurons were observed in S1, the number was
smaller than that in M1. In the cervical segment of the spinal cord, SPP1 was
principally expressed in choline acetyltransferase-positive motor neurons in lamina
IX. We also examined SPP1 expression in patients with amyotrophic lateral sclerosis
(ALS), a disease characterized by the degeneration of motor neurons. When SPP1
expression was compared in neurons of the same size range, expression in both M1
and the spinal cord of ALS patients was lower than that of subjects without ALS.
SPP1 expression was especially reduced in surviving large neurons in both M1 and
the spinal cord of ALS patients. The results further support the concept that SPP1
has a role in the specialization of motor projection neurons and suggest that its
reduced expression may be implicated in the neurodegeneration seen in ALS.
Virtually nothing is known about glucocorticoid receptor (GR) or mineralocorticoid
receptor (MR) gene expression in any avian species. Here we report the cloning of
partial cDNAs for chicken GR and MR. These partial cDNAs were used as probes to
characterize expression of GR and MR mRNA and to identify the full-length
transcripts within the chicken genome. Chicken GR and MR sequences predicted from
the genome sequence were compared with those of representatives of other vertebrate
classes. GR and MR genes are located on chicken chromosomes 13 and 4, respectively.
Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR)
results indicate that GR and MR are widely expressed in many tissues.
Characterization of mRNA levels in the anterior pituitary gland during chick
embryonic development by quantitative real time RT-PCR demonstrates decreased MR
and increased GR gene expression between embryonic days 12 and 17. Plasma levels of
corticosteroids increased during this same period. This is the first study of GR
and MR gene expression in any avian species and the first analysis of changes in
pituitary MR gene expression during embryonic development of any species. (C) 2006
Elsevier Inc. All rights reserved.
Background: Pregnant victims of childhood maltreatment are more likely to deliver
preterm. The mechanisms explaining this relationship are unclear. The goal of the
current pilot study was to investigate whether momentary stress and cortisol serve
as mechanisms linking maltreatment history to gestational length. Methods:
Seventeen women enrolled in the study (35% maltreated). Women completed two study
sessions at 27 and 34 weeks gestation. Following each session, at four times/day
over two days, women reported their momentary stress levels by text message and
provided corresponding salivary cortisol samples. Gestational length was determined
by medical chart review. Results: Higher reports of momentary stress were
associated with shortened gestational length. High stress predicted lower cortisol
concentrations for women with maltreatment histories but higher concentrations
among women without maltreatment. Conclusion: Results from this pilot study provide
preliminary evidence for understanding mechanisms explaining increased risk for
preterm birth among childhood maltreatment victims.
Chronic breathlessness is a common source of psychological and physical stress in
patients with advanced or progressive disease, suggesting that hypothalamic-
pituitary-adrenal (HPA) axis dysregulation may be prevalent. The aim of this study
was to measure the salivary diurnal cortisol profile in patients receiving
supportive and palliative care for a range of malignant and non-malignant
conditions and to compare the profile of those experiencing moderate-to-severe
disability due to breathlessness against that of patients with mild/no
breathlessness and that of healthy controls. Saliva samples were collected over two
consecutive weekdays at 3, 6, and 12 h after awakening in 49 patients with
moderate-to-severe breathlessness [Medical Research Council (MRC) dyspnoea grade >=
3], 11 patients with mild/no breathlessness (MRC dyspnoea grade <= 2), and 50
healthy controls. Measures of breathlessness, stress, anxiety, depression,
wellbeing and sleep were examined concomitantly. The diurnal cortisol slope (DCS)
was calculated for each participant by regressing log-transformed cortisol values
against collection time. Mean DCS was compared across groups using ANCOVA.
Individual slopes were categorised into one of four categories: consistent
declining, consistent flat, consistent ascending and inconsistent. Controlling for
age, gender and socioeconomic status, the mean DCS was significantly flatter in
patients with moderate-to-severe breathlessness compared to patients with mild/no
breathlessness and healthy controls [F (2,103) = 45.64, p<0.001]. Furthermore,
there was a higher prevalence of flat and ascending cortisol profiles in patients
with moderate-to-severe breathlessness (23.4%) compared to healthy controls (0%).
The only variable which correlated significantly with DCS was MRC dyspnoea grade
(rs=0.29, p<0.05). These findings suggest that patients with moderate-to-severe
breathlessness have evidence of HPA axis dysregulation and that this dysregulation
may be related to the functional disability imposed by breathlessness. (C) 2017
Elsevier Ltd. All rights reserved.
Two genes encoding methionine adenosyltransferase, SAM2 from Saccharomyces
cerevisiae and metK from Corynebacterium glutamicum, were individually cloned into
pDXW-8, the shuttle vector between Escherichia coli and C. glutamicum, and
overexpressed in E. coli DH5 and C. glutamicum ATCC13032. In DH5, both genes were
overexpressed and their protein products showed the activity of methionine
adenosyltransferase. In ATCC13032, metK was overexpressed, its product MetK showed
the enzyme activity and could convert l-methionine to S-adenosyl-l-methionine
(SAM). However, when SAM2 was overexpressed in ATCC13032, neither the enzyme
activity nor the conversion of SAM from l-methionine was observed. Reverse
transcription PCR analysis and SDS-PAGE showed that SAM2 was transcribed but not
translated in C. glutamicum. Therefore, SAM2-C, a mutant SAM2, was constructed by
codon optimization, and overexpressed in ATCC13032; it was well transcribed and
translated, and could convert l-methionine to SAM. Finally, SAM2-C and metK were
individually overexpressed in E. coli BL21(DE3), and their products SAM2-C and MetK
were purified and characterized. The optimum activity for both enzymes was found at
pH 8.5 and 35 degrees C; SAM2-C and MetK have similar K-m for ATP, but quite
different K-m for l-methionine. These results suggest that SAM2-C and MetK can be
useful for developing C. glutamicum to produce SAM. (C) 2015 International Union of
Biochemistry and Molecular Biology, Inc.
The SWIPE detector of the Ballon Borne Mission LSPE (see e.g. the contribution of
P. de Bernardis et al. in this conference) intends to measure the primordial 'B-
mode' polarization of the Cosmic Microwave Background (CMB). For this scope
microwave telescopes need sensitive cryogenic bolometers with an overall equivalent
noise temperature in the nK range. The detector is a spiderweb bolometer based on
transition edge sensor and followed by a SQUID to perform the signal readout. This
contribution will concentrate on the design, description and first tests on the
front-end electronics which processes the squid output (and controls it). The squid
output is first amplified by a very low noise preamplifier based on a discrete JFET
input differential architecture followed by a low noise CMOS operational amplifier.
Equivalent input noise density is 0.6 nV/Hz and bandwidth extends up to at least 2
MHz. Both devices (JFET and CMOS amplifier) have been tested at liquid nitrogen.
The second part of the contribution will discuss design and results of the control
electronics, both the flux locked loop for the squid and the slow control chain to
monitor and set up the system will be reviewed. The digital interface to the
control computer will be presented.
Predicting the evolution of phenotypic traits requires an understanding of natural
selection on them. Despite its indispensability in the fight against parasites,
selection on host immune defense has remained understudied. Theory predicts immune
traits to be under stabilizing selection due to associated trade-offs with other
fitness-related traits. Empirical studies, however, report mainly positive
directional selection. This discrepancy could be caused by low phenotypic variation
in the examined individuals and/or variation in host resource level that confounds
trade-offs in empirical studies. In a field experiment where we maintained Lymnaea
stagnalis snails individually in cages in a lake, we investigated phenotypic
selection on two immune defense traits, phenoloxidase (PO)-like activity and
antibacterial activity, in hemolymph. We used a diverse laboratory population and
manipulated snail resource level by limiting their food supply. For six weeks, we
followed immune activity, growth, and two fitness components, survival and
fecundity of snails. We found that PO-like activity and growth were under
stabilizing selection, while antibacterial activity was under positive directional
selection. Selection on immune traits was mainly driven by variation in survival.
The form of selection on immune defense apparently depends on the particular trait,
possibly due to its importance for countering the present parasite community.
Internal energy reserves of animals are limited, and the current investment in
reproduction often decreases survival or future reproductive success. Some studies
showed that copulatory activities impair the strength of immune function in
insects, while the recent evidence is contradictory. In this study we tested
whether copulatory activity affects the rate of encapsulation response in males of
Calopteryx splendens damselfly in allopatric populations, and in sympatric
populations where C. splendens stay together with their superior competitor C.
virgo. We also counted the number of eugregarines, which are common parasites of
damselflies. Copulation activity did not affect the immunity of C. splendens males
in allopatric populations. In sympatric populations C. splendens males had more gut
parasites, and we found a significant interaction between parasite number and
copulatory activity on the rate of encapsulation. Our results suggest that the
costs of reproduction are higher in infected males, which may affect reproductive
investment and sexual selection.
Households in the USA state of Oklahoma serviced by investor owned electric
utilities that have smart meters may select to be charged based on either a
traditional meter rate schedule, a smart meter schedule, or they may install a
household grid-tied wind turbine and be subject to a different rate schedule. The
objective of the research was to determine the economic consequences of installing
microgeneration grid-tied wind turbine systems (6 kW; 10 kW) given alternative
pricing structures for households at five unique locations with different wind
resources. Twenty years of hourly wind speed data, and hourly electricity use data
for representative households, were obtained for each location. The annual
household electricity cost among the five locations ranged from $894 to $1199 for
the smart meter rates and $870-$1191 for the traditional meter rates. The estimated
annual cost of $5389 for the least costly household grid-tied 6 kW wind turbine
system, is five times greater than the annual cost of purchasing from the grid. If
external consequences of electricity generation and distribution are ignored, given
current and proposed rate structures and prices, household wind turbine electricity
generation systems are not economically competitive in the region. (C) 2017
Elsevier Ltd. All rights reserved.
The absence of markers of inflammation in the cerebrospinal fluid (CSF) commonly
predicts the absence of herpes simplex virus (HSV) central nervous system (CNS)
infection. Consequently, multiple authors have proposed and validated criteria for
deferring HSV PCR testing of CSF in immunocompetent hosts with normal CSF white
blood cell and protein levels (<= 5 cells/mm(3) and= 2 years old and have not had
HIV or an organ transplant. Adoption of the criteria may erroneously exclude HSV-
infected persons from a necessary diagnostic test or, alternatively, reduce the
costs associated with HSV tests with minimal to no effect on patient care. Little
is known about the cost-effectiveness of this approach. A decision analysis model
was developed to evaluate the adoption of criteria for screening HSV tests of CSF.
Estimates of input parameter values combined available literature with a multiyear
multisite review at two of the largest health care systems in the United States.
Adoption of criteria to screen for HSV test need proved cost-effective when less
than 1 in 200 patients deferred from testing truly had an HSV CNS infection.
Similar to prior studies, none of the deferred cases had HSV encephalitis (n =
3120). Adoption of these criteria in the United States would save an estimated $127
million ($ 95 million to $158 million [+/- 25%]) annually. The model calculations
remained robust to variation in test cost, prevalence of HSV infection, and random
variation to study assumptions. The adoption of criteria to screen HSV PCR tests in
CSF represents a cost-effective approach.
Renewable energies have great potential to contribute to CO2 emissions reductions
by substituting for fossil fuels. This study examines whether renewable energies
with learning-by-doing technical change can compete with forest carbon
sequestration to cost-efficiently achieve the EU carbon target for 2050. Cost-
efficient abatement solutions are obtained using a dynamic optimisation model that
accounts for three kinds of mitigation options: renewable energies and abatement in
the forest and fossil fuel sectors. The results show a net present cost of reaching
the target of approximately 225 billion Euros and a carbon price of 306 Euro/ton
CO2 in 2050. Furthermore, the stock of renewables in 2050 can deliver almost twice
as much as the current electricity production from renewables, which implies a
contribution of 8.2% to meeting the emissions target. However, the average cost per
unit emissions reduction is more than twice as high for renewables as for forest
carbon sequestration. Hence, the results indicate that renewables are unable to
compete with forest carbon sequestration unless they receive continued government
support. (C) 2017 Elsevier Ltd. All rights reserved.
Salinity is one of the major environmental factors limiting plant growth and
productivity. An H+-PPase gene, TsVP from Thellungiella halophila, was transferred
into cotton (Gossypium hirsutum) in sense and antisense orientations under control
of the cauliflower mosaic virus (CaMV) 35S promoter. Southern and Northern blotting
analysis showed that the sense or antisense TsVP were integrated into the cotton
genome and expressed. Transgenic plants overexpressing the vacuolar H+-PPase were
much more resistant to 150 and 250 mM NaCl than the isogenic wild-type plants. In
contrast, the plants from the antisense line (L2), with lower H+-PPase activity,
were more sensitive to salinity than the wild-type plants. Overexpressing TsVP in
cotton improved shoot and root growth and photosynthetic performance. These
transgenic plants accumulated more Na+, K+, Ca2+, Cl- and soluble sugars in their
root and leaf tissues under salinity conditions compared with the wild-type plants.
The lower membrane ion leakage and malondialdehyde (MDA) level in these transgenic
plants suggest that overexpression of H+-PPase causes the accumulation of Na+ and
Cl- in vacuoles instead of in the cytoplasm, thus reducing their toxic effects. On
the other hand, the increased accumulation of ions and sugars decreases the solute
potential in cells, and facilitates water uptake under salinity, which is an
important mechanism for the increased salt tolerance in TsVP-overexpressing cotton.
An increasing number of microRNAs (miRNAs) have been shown to play crucial
regulatory roles in the process of plant development. Here, we used high-throughput
sequencing combined with computational analysis to characterize miRNAomes from the
ovules of wild-type upland cotton and a fiberless mutant during fiber initiation.
Comparative miRNAome analysis combined with northern blotting and RACE-PCR revealed
seven fiber initiation-related miRNAs expressed in cotton ovules and experimentally
validated targets of these miRNAs are involved in different cellular responses and
metabolic processes, including transcriptional regulation, auxin and gibberellin
signal transduction, actin bundles, and lignin biosynthesis. This paper describes a
complex regulatory network consisting of these miRNAs expressed in cotton ovules to
coordinate fiber initiation responses. In addition, 36 novel miRNAs and two
conserved miRNAs were newly identified, nearly doubling the number of known cotton
miRNA families to a total of 78. Furthermore, a chromatin remodeling complex
subunit and a pre-mRNA splicing factor are shown for the first time to be miRNA
targets. To our knowledge, this study is the first systematic investigation of
fiber initiation-related miRNAs and their targets in the developing cotton ovule,
deepening our understanding of the important regulatory functions of miRNAs in
cotton fiber initiation.
Arabinogalactan proteins (AGPs) are a large family of highly glycosylated of
hydroxyproline-rich glycoproteins that play important roles in plant growth,
development, and signal transduction. A cDNA encoding a putative classical AGP
named GhH6L was isolated from cotton fiber cDNA libraries, and the deduced protein
contains 17 copies of repetitive motif of X-Y-proline-proline-proline (where X is
serine or alanine and Y is threonine or serine). Northern blotting analysis and
quantitative RT-PCR results showed that it was preferentially expressed in 10 days
post-anthesis (dpa) fibers and was also developmentally regulated. A promoter
fragment was isolated from cotton (Gossypium hirsutum) by genome walking PCR.
Expression of beta-glucuronidase (GUS) gene under the GhH6L promoter was examined
in the transgenic Arabidopsis plants; only petiole and pedicel were stained, no
staining was detected in other tissues. Subcellular localization indicated that
GhH6L was localized to the plasma membrane and in the cytoplasm. These data further
our understanding of GhH6L as well as shed light on functional insight to GhH6L in
cotton.
Enzymatic treatments have gained recognition in textile industry because they are
stereo specific, nontoxic, environment friendly and energy conserving alternatives.
Enzymes are virtually applicable to all manufacturing steps of textile chemical
processing. Amylases for textile desizing; cellulases employed for bio-polishing &
denim washing; proteases for wool modifications are important to mention in this
category. However in spite of lot potentials, enzymes have limited industrial
acceptance due to extreme pH and temperature conditions employed in textile
processing leading to their reduced properties and action. Advances in enzymology
and molecular biology provide possibilities for new enzymes identification and
modifications in existing enzymes as well as in enzyme-based processes suitable/to
fit for environment friendly option. Enzyme immobilization is one such approach
which stabilizes enzymes, extends useful life and improves action in some cases
too. Additionally, recyclability & reuse of enzymes make process even more
economical. This review summarizes the potential research involved in the
development of enzymatic processing in textile chemical processing. The paper
highlights the significance and limitations of native enzymes as well as
immobilized enzymes applications in textile chemical industry. (C) 2017 Elsevier
Ltd. All rights reserved.
Cotton is a stubborn plant for genomic DNA isolation due to its high-level of
polyphenolics, polysaccharides and secondary metabolites. Genomics and molecular
biology studies require high quality and large quantity of DNA. We have
standardized an efficient miniprep protocol for cotton genomic DNA isolation, which
not only provides higher yield from 800 to 1400 lg of DNA from 200 to 300 mg of
fresh leaf tissue but also provide excellent purity. The DNA is amenable to all
elementary enzymatic preparations, PCR techniques, Southern blotting and to high
end genomic studies. The technique does not require liquid nitrogen, needs small
amount of sample, less time, fewer chemicals and one can process up to 100 samples
per day. The genomic DNA extracted was good for transgenic event characterization
and marker assisted selection.
Understanding pathogenic variation in plant pathogen populations is key for the
development and use of host resistance for managing verticillium wilt diseases. A
highly virulent defoliating (D) pathotype in Verticillium dahliae has previously
been shown to occur only in one clonal lineage (lineage 1A). By contrast, no clear
association has yet been shown for race 1 with clonal lineages. Race 1 carries the
effector gene Ave1 and is avirulent on hosts that carry resistance gene Ve1 or its
homologues. The hypothesis tested was that race 1 arose once in a single clonal
lineage, which might be expected if V. dahliae acquired Ave1 by horizontal gene
transfer from plants, as hypothesized previously. In a diverse sample of 195 V.
dahliae isolates from nine clonal lineages, all race 1 isolates were present only
in lineage 2A. Conversely, all lineage 2A isolates displayed the race 1 phenotype.
Moreover, 900-bp nucleotide sequences from Ave1 were identical among 27 lineage 2A
isolates and identical to sequences from other V. dahliae race 1 isolates in
GenBank. The finding of race 1 in a single clonal lineage, with identical Ave1
sequences, is consistent with the hypothesis that race 1 arose once in V. dahliae.
Molecular markers and virulence assays also confirmed the well-established finding
that the D pathotype is found only in lineage 1A. Pathogenicity assays indicated
that cotton and olive isolates of the D pathotype (lineage 1A) were highly virulent
on cotton and olive, but had low virulence on tomato.
Until the banking reform in 1936, banks and industrial companies in Italy were
strongly intertwined (both in terms of ownership and interlocking directorates).
Using Imita.db-a large dataset containing data on over 300,000 directors of Italian
joint-stock companies-this paper analyzes what would have happened to the Italian
corporate network in the years 1913, 1921, 1927 and 1936 if the German-type
universal banks and their directors would have not been there. Our test shows that
new centers of the system would have emerged (financial, electricity, and phone
companies), confirming the interconnected nature of the Italian capitalism. We also
analyze two industries (textiles and iron and steel) characterized by different
labor-to-capital intensities to check for sectoral differences. Contrary to
conventional wisdom, we find that local banks were important in funding both
industries.
This paper explores the proposal that there is a close link between counterfactual
thinking and lying. Both require the imagination of alternatives to reality and we
describe four studies which explore this link. In Study 1 we measured individual
differences in both abilities and found that individuals with a tendency to
generate counterfactual thoughts were also more likely to generate potential lies.
Studies 2 and 3 showed that counterfactual availability influences people's ability
to come up with lies and the extent to which they expect others to lie. Study 4
used a behaviotiral measure of deception to show that people tend to lie more in
situations also known to elicit counterfactual thoughts. Overall, the results show
that the imagination of alternatives to the past plays an important role in the
generation of lies. We discuss the implications for the fields of counterfactual
thinking and deception. (C) 2017 Elsevier B.V. All rights reserved.
Holographic algorithms, alternatively known as Pfaffian circuits, have received
much attention for giving polynomial-time algorithms to a subset of problems in #P.
Much work has been done determining the power of this machinery. One intriguing
aspect is that these circuits must be planar. We investigate relaxations of this
planarity condition. We show that an approach using orbit closures does not work,
but give a different technique that allows one SWAP gate to be used in a Pfaffian
circuit given suitable bases and restricted types of graphs. This is done by
exploiting the fact that Pfaffian gates lie in a hyperplane. (C) 2016 Elsevier Inc.
All rights reserved.
This article focuses on the design and investigation of a pair of unequally sized
wireless electricity (Witricity) devices that are equipped with integrated planar
coil strips. The proposed pair of devices consists of two different square-shaped
resonator sizes of 120 mm x 120 mm and 80 mm x 80 mm, acting as a transmitter and
receiver, respectively. The devices are designed, simulated and optimized using the
CST Microwave Studio software prior to being fabricated and verified using a vector
network analyzer (VNA). The surface current results of the coupled devices indicate
a good current density at 10 mm to 30 mm distance range. This good current density
demonstrates that the coupled devices' surface has more electric current per unit
area, which leads to a good performance up to 30 mm range. Hence, the results also
reveal good coupling efficiency between the coupled devices, which is approximately
54.5 % at up to a 30 mm distance, with both devices axially aligned. In addition, a
coupling efficiency of 50 % is achieved when a maximum lateral misalignment (LM) of
10 mm, and a varied angular misalignment (AM) from 0 degrees to 40 degrees are
implemented to the proposed device.
A battery-free, wireless neural probe system was developed for reading neural
signals in the brain by using a one-port surface acoustic wave (SAW) reflective
delay line, neural firing-dependent varicap diode, two antennas, and a network
analyzer as measurement unit. The one-port SAW reflective delay line replaces
existing complex wireless transceiver system composed of similar to 5000 electronic
components and makes battery-free, wireless measurements possible. The varicap
diode interconnected with sharp metal shank via operational amplifier (op-amp) was
electrically linked to the corresponding split-type reflectors on a one-port SAW
reflective delay line. A 4.3 nH inductor was also placed in between the split-type
reflector on one-port SAW reflective delay line and varicap diode to obtain a large
linearity and high sensitivity through impedance matching effect. As electrical
pulses imitating neural signals were applied to the sharp metal shanks, overall
impedance perturbations between the split-type reflector and external varicap diode
under reverse bias were observed, giving rise to amplitude changes in the
reflection peaks in the time domain depending on the magnitude of the electrical
pulses. Good linearity and sensitivity were observed at the amplitude variations in
terms of electrical pulses. Coupling-of-modes (COM) modeling and impedance matching
simulations were also performed to predict device performances and compare
experimental results. (C) 2014 Elsevier B.V. All rights reserved.
Integration of research experience into classroom is an important and vital
experience for all undergraduates. These course-based undergraduate research
experiences (CUREs) have grown from independent instructor lead projects to large
consortium driven experiences. The impact and importance of CUREs on students at
all levels in biochemistry was the focus of a National Science Foundation funded
think tank. The state of biochemistry CUREs and suggestions for moving biochemistry
forward as well as a practical guide (supplementary material) are reported here.
(c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):7-
12, 2017.
This article describes a court improvement initiative designed to promote
uniformity and improved court practice with the ultimate goal of the improvement of
outcomes for children and families. The article focuses on the results of
interviews and focus groups conducted as part of the evaluation of this initiative.
Twelve jurisdictions were purposively selected to exhibit a range of family court
and non-family court jurisdictions in rural and middle-sized locations. The
discussion of the qualitative results focuses on changes in court practice and the
impact of the initiative on case time. Key Points for the Family Court Community:
This initiative was undertaken to promote consistency of practice in family law
matters. We explain how the rules impact the following areas: divorce; property
distribution as a result of divorce; custody, visitation, and child support;
adoption; termination of parental rights; domestic violence, child abuse, and
neglect; and status offenses. We describe the impact of a state-wide court
improvement initiative. We identify areas of improvement within court operations
that may be modified in other jurisdictions.
Q fever is a worldwide zoonotic infection caused by the obligate intracellular
bacterium Coxiella burnetii that can course with acute or chronic disease. This
series describes 7 cases of acute Q fever admitted in a Portuguese University
Hospital between 2014 and 2015. All cases presented with hepatitis and had
epidemiological history. Diagnosis was done by PCR on majority (5) and by serology
and PCR in only 2. Serological tests can be negative in the initial period of the
disease. Molecular biology methods by polymerase chain-reaction are extremely
important in acute disease, allowing timely diagnosis and treatment. (C) 2016 The
Authors.
Increasingly, anthropogenic perturbations of the biosphere manifest in a broad
array of global phenomena, causing widespread contamination of most ecosystems,
with high dispersion rates of many contaminants throughout different environmental
compartments, including metals. Chromium (Cr) contamination in particular, is,
increasingly, posing a serious threat to the environment, emerging as a major
health hazard to the biota. However, although the molecular and physiological
mechanisms of plant responses to many heavy metals, especially lead (Pb) and
cadmium (Cd), have been focused upon in recent years, chromium has attracted
significantly less attention. In this context, this review discusses aspects of Cr
uptake and transport, some physiological and biochemical effects of Cr exposure in
plants, and molecular defense mechanisms against this metal. Recent advances in
determining these responses, in fields of knowledge such as genomics, proteomics
and metallomics, are discussed herein.
As a precursor of the major yolk protein vitellin (Vn), vitellogenin (Vg) has been
studied in crustacean for decades, mainly in shrimp. However, little is known about
the Vg molecule in crabs. In the present study, we report a cDNA encoding Vg in the
marine crab Portunus trituberculatus, an important commercial species in
aquaculture. The cDNA sequence is 7846 bp in length, containing a 7680 bp open
reading frame, that encodes 2560 amino acid residues. The deduced amino acid
sequence showed 32-75% identity with other known crustacean Vgs. Seven potential
cleavage sites (RXXR) were identified in the deduced Vg precursor. SDS-PAGE and
Westem blotting analysis demonstrated that Vns in the ovary of the mature crab
consisted of three major polypeptides (102, 100 and 85 kDa). Northern blotting
analysis revealed that Vg was mainly expressed in hepatopancreas in vitellogensis
females. A Vg transcript was also identified in the ovary of the crab by reverse
transcription-polymerase chain reaction analysis. (c) 2005 Elsevier Inc. All fights
reserved.
Culture-based pathogen identification in skull base osteomyelitis, particularly for
fungi, is often inaccurate. We report the case of patient with fungal skull base
osteomyelitis cured by sustained antifungal therapy after 16 months of debilitating
illness. Due to medical complications, a strong clinical rationale was needed to
justify long-term antifungal therapy. The offending fungus was identified by
experimental molecular technology (Ibis T5000 universal biosensor); invasive fungal
disease was corroborated by biochemical assays. Our discussion will help
familiarize the otolaryngologist with existing biochemical and molecular
diagnostics for invasive fungal disease. We encourage future investigators to study
their application in cases of skull base osteomyelitis.
The hypothalamic hormone oxytocin plays a major role in regulation of behavior and
body composition. Quality of survival is frequently impaired in childhood
craniopharyngioma patients due to sequelae such as behavioral deficits and severe
obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot
cross-sectional study, we analyzed emotion recognition abilities and oxytocin
concentrations in saliva and urine before and after single nasal administration of
24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented
with grade I lesions (limited to anterior hypothalamic areas) and 6
craniopharyngioma with grade II lesions (involving mammillary bodies and posterior
hypothalamic areas). Emotional tasks were assessed before and after administration
of oxytocin using the Geneva multimodal emotion portrayals corpus and the
Multidimensional Mood Questionnaire. All patients presented with detectable levels
of oxytocin before administration. Nasal administration of oxytocin was well-
tolerated and resulted in increased oxytocin concentrations in saliva and urine.
After oxytocin administration, craniopharyngioma patients with postsurgical lesions
limited to the anterior hypothalamus area showed improvements in emotional
identifications compared to craniopharyngioma patients with lesions of anterior and
posterior hypothalamic areas. Focusing on correct assignments to positive and
negative emotion categories, craniopharyngioma patients improved assignment to
negative emotions. Oxytocin might have positive effects on emotion perception in
craniopharyngioma patients with specific lesions of the anterior hypothalamic area.
Further studies on larger cohorts are warranted.
The eastern oyster Crassostrea virginica once supported one of the largest
fisheries in the eastern United States. Oyster populations and the reefs they form
have suffered chronic long-term decline throughout the species' range, including in
northwest Florida's Pensacola Bay estuary system (PBS). To guide efforts to rebuild
oyster populations in the PBS, connectivity patterns were evaluated among historic
and extant reef locations using an integrated biophysical numerical model. Water
quality parameters and oyster recruitment were monitored in May 2007 and then
monthly from July 2007 through July 2008. Resultant salinity data were used to
calibrate an Estuarine Coastal Ocean Model-based numerical circulation model of
Pensacola Bay, which was then coupled to an existing, individual-based, oyster
larvae routine to predict ontogenetic larval distribution. Three-dimensional
Lagrangian transport algorithms were used to simulate transport of modeled larvae
during four 20-day time periods during those summer and autumn months when oyster
recruitment was empirically recorded in the bay. Based on outcomes from
contemporaneous sampling of oyster larvae, the model was shown to represent the
salient features of oyster larval distribution in Pensacola Bay. There were,
however, instances of incongruity between modeled and sampled outcomes, indicating
that model outcomes not validated with field data must be interpreted with caution.
Larval supply was highly variable and spatially complex, but potentially limiting
to successful recruitment and reef replenishment. Larval transfer rates within and
among previously identified oyster reefs in Pensacola Bay were determined and were
used to predict optimal oyster reef restoration or rehabilitation sites. Finally,
larval exports from the bay were estimated and considered within the context of
larval exchange among north Florida estuaries and potential repercussions to the
long-term health of the Gulf of Mexico oyster metapopulation.
Background: Systemic inflammation has emerged as a promising marker and potential
mechanism underlying post-traumatic stress disorder (PTSD). The relationship
between posttraumatic stress pathology and systemic inflammation has not, however,
been consistently replicated and is potentially confounded by comorbid illness or
injury, common complications of trauma exposure. Methods: We analyzed a large
naturalistic cohort sharing a discrete physical and mental health trauma from the
destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641).
We evaluated the relationship between multiple physical and mental health related
indices collected through routine evaluations at the WTC Environmental Health
Center (WTC EHC), a treatment program for community members exposed to the
disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined
in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance,
negative cognitions/mood, arousal), depression and anxiety, while controlling for
WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential
risks or confounders. Results: CRP was positively associated with PTSD severity (p
< 0.001), trending toward association with depression (p = 0.06), but not with
anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001)
and avoidance (p < 0.05) symptom clusters, and trended toward associations with
negative cognitions/mood (p = 0.06) and arousal (p = 0.08). Conclusions: In this
large study of the relationship between CRP and posttraumatic stress pathology, we
demonstrated an association between systemic inflammation and stress pathology
(PTSD; trending with depression), which remained after adjusting for potentially
confounding variables. These results contribute to research findings suggesting a
salient relationship between inflammation and post traumatic stress pathology. (C)
2017 The Authors. Published by Elsevier Ltd.
The study aimed to generate a mouse line with green fluorescent protein (GFP)
specifically expressed in male germ cells to assess testicular toxicity. The mouse
line with GFP specifically expressed in male germ cells was generated by mating a
germ cell-specific transgenic Cre male mouse with a double-fluorescent reporter
female mouse using Cre/loxP. The mouse line was administered ethylene glycol
monomethyl ether (EGME) by oral gavage. Then, the green fluorescence intensity in
the testes was used as an indicator to examine the potential for testicular
toxicity testing by molecular biology, histopathology, and in vivo imaging
techniques. Specific testicular GFP expression was observed in mice. GFP was mainly
expressed in the germ cell lineage and concentrated in secondary
spermatocytes/spermatocytes and spermatozoa. After administration of EGME, at the
organ level, the green fluorescent intensity of the testes was decreased by 11 days
and had disappeared by 34 days. Frozen testicular sections stained with DAPI showed
significantly decreased green fluorescence in secondary spermatocytes and sperm
cells. These observations were consistent with the testis weight and results of
testicular histopathology. With the application of in vivo imaging becoming
popular, this mouse line with GFP specifically expressed in the male germ cells may
have some advantages for the study of reproductive toxicity.
Inadequate regulation of spatial development is at the origin of the current global
crisis and increases, in years of crisis, the unequal distribution of wealth. The
importance of the related risks for democracy draw attention to the systems of
spatial governance and planning, through which States regulate spatial development.
In Europe, the countries most affected by the unequal effects of the crisis have
spatial planning systems that are traditionally based on the preventive assignation
of rights for land use and development through a plan. The systems of other
countries had established beforehand that new rights for land use and for spatial
development are rather assigned only after the public control of development
projects and their distributional effects. Despite the evidence that some models
can operate better than others in ensuring public government of spatial
development, the improvement of spatial planning systems is, however, limited by
their complex nature of institutional technologies'. Especially in a context of
crisis, planners are responsible for the increase in public awareness concerning
the role of spatial governance in economic and social life.
Research on fungal pathogens with the aim to identify virulence determinants
strictly relies on the generation of defined, recombinant strains, a task that is
executed by means of a sophisticated molecular biology toolbox. Recent developments
in fungal genome engineering have opened a new frontier by implementing the CRISPR-
Cas9 technology, based on expression of the Cas9 endonuclease that is loaded by a
single guiding RNA (sgRNA) molecule to target a defined site in the recipient
genome. This novel approach has been adapted successfully to engineer fungal
genomes, among them the one of the human-pathogenic mould Aspergillus fumigatus.
Implementation of the required components was achieved by various means that differ
with respect to expression of the Cas9 enzyme and sgRNA delivery. Validation of
CRISPR-Cas9-mediated mutagenesis could be executed by targeting selected candidate
genes of A. fumigatus to provide a promising perspective for screening and
multiplexing approaches to scrutinize the virulome of this opportunistic fungal
pathogen in a comprehensive manner, such as by analyzing genetic polymorphisms or
the function of gene families.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has
emerged as a powerful technology for genome editing and is now widely used in basic
biomedical research to explore gene function. More recently, this technology has
been increasingly applied to the study or treatment of human diseases, including
Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, beta-
Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9) genome
editing has been used to correct disease-causing DNA mutations ranging from a
single base pair to large deletions in model systems ranging from cells in vitro to
animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also
been applied in immunology-focused applications such as the targeting of C-C
chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric
antigen receptors in T cells for purposes such as the treatment of the acquired
immune deficiency syndrome (AIDS) or promoting anti-tumor immunotherapy.
Furthermore, this technology has been applied to the genetic manipulation of
domesticated animals with the goal of producing biologic medical materials,
including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has
been teamed with induced pluripotent stem (iPS) cells to perform multiple tissue
engineering tasks including the creation of disease models or the preparation of
donor-specific tissues for transplantation. This review will explore the ways in
which the use of CRISPR/Cas9 is opening new doors to the treatment of human
diseases. Copyright (C) 2016, Chongqing Medical University. Production and hosting
by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
The emergence of proteomics has led to major technological advances in mass
spectrometry (MS). These advancements not only benefitted MS-based high-throughput
proteomics but also increased the impact of mass spectrometry on the field of
structural and molecular biology. Here, we review how state-of-the-art MS methods,
including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-
deuterium exchange-MS, nowadays enable the characterization of biomolecular
structures, functions, and interactions. In particular, we focus on the role of
mass spectrometry in integrated structural and molecular biology investigations of
biological macromolecular complexes and cellular machineries, highlighting work on
CRISPR-Cas systems and eukaryotic transcription complexes.
In this study, we used cytotoxicity assays, proteomic and gene expression analyses
to examine the difference in response of A549 cells to two silica particles that
differ in physical properties, namely cristobalite (CR) and -quartz (Min-U-Sil 5,
MI). Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2-
deoxyuridine incorporation and cellular ATP showed that both silica particles could
cause cell death, decreased cell proliferation and metabolism in the A549 human
lung epithelial cells. While cytotoxicity assays revealed little difference between
CR and MI exposures, proteomic and gene expression analyses unveiled both similar
and unique molecular changes in A549 cells. For instance, two-dimensional gel
electrophoresis data indicated that the expression of proteins in the cell death
(e.g., ALDH1A1, HTRA2 and PRDX6) and cell proliferation (e.g., FSCN1, HNRNPAB and
PGK1) pathways were significantly different between the two silica particles.
Reverse transcription-polymerase chain reaction data provided additional evidence
supporting the proteomic findings. Preliminary assessment of the physical
differences between CR and MI suggested that the extent of surface interaction
between particles and cells could explain some of the observed biological effects.
However, the differential dose-response curves for some other genes and proteins
suggest that other physical attributes of particulate matter can also contribute to
particulate matter-related cellular toxicity. Our results demonstrated that
toxicoproteomic and gene expression analyses are sensitive in distinguishing subtle
toxicity differences associated with silica particles of varying physical
properties compared to traditional cytotoxicity endpoints. Copyright (c) 2016 Her
Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by
John Wiley & Sons, Ltd.
The traditional critical conduction mode (CRM) flyback PFC converter with constant
on-time control strategy usually suffers low power factor (PF) and high total
harmonic distortion (THD) due to the nonsinusoidal input current waveform. In order
to solve this problem, an improved variable on-time control strategy for the CRM
flyback PFC converter is proposed in this letter. A simple analog divider circuit
consisting of an operational amplifier, two signal switches, and an RC filter is
proposed to modulate the turn-on time of the primary switch, and the PF and THD of
the CRM flyback PFC converter can be evidently improved. The theoretical analysis
is presented and the experiment results verify the advantages of the proposed
control scheme.
Actuated by spatial universal rotating magnetic vector through digital control, the
steering navigation of the spiral-type capsule robot in the gastrointestinal (GI)
tract becomes possible. However, as a potential risk, the fluid resistance torsion
moment generated by the rotating spiral-type capsule robot would distort the GI
tract with insufficient fluid. It is difficult to investigate the fluid distorting
effect on the GI tract, because online measurement of the fluid resistance torsion
moment still remains unsolved. In this paper, an innovative method employing
critical coupling magnetic moment for indirectly detecting the fluid resistance
torsion moment is proposed. To reduce fluid distorting effect, a petal-shaped
capsule robot, whose surface is composed of four petal-shaped tiles, is proposed,
and fluid resistance torsion moment-weaken effect of the petal-shaped capsule robot
is discovered and investigated, which happens to the fluid when it travels through
a convergent wedge-like gap between the surface of each of the four petal-shaped
tiles and the inner pipe wall. Simulations and experiments have demonstrated that
the twist impact on the GI tract by the petal-shaped capsule robot is reduced,
while the non-contact driving performance in the GI tract is improved greatly
isolated by fluid membrane with high dynamic pressure.
The purpose of this paper is to analyze the concept of transformative pedagogy'
(TP) in physical education and sport pedagogy (PESP) and research in order to
provide an alternative perspective on freedom, justice and the limits of
transformation. Although some of the limits of TP have already been pointed out in
the literature, such limits have been presented as though originating and having to
be resolved out there, in socio-cultural-political contexts. In an attempt to
redirect the attention from the social to the personal, this paper points out the
possibility of TP's limits being also within critical pedagogues and researchers
ourselves. After analyzing three barriers to (self-)consciousness/knowledge (SC/K),
two viable methods for developing SC/K and transformation are provided.
Introduction: As many inflammatory bowel disease (IBD) patients do not benefit from
long-term antitumour necrosis factor treatment, new anti-inflammatories are
urgently needed. After the discovery of the interleukin (IL) 23/17 axis being
pivotal in IBD pathogenesis, many different compounds were developed, targeting
different components within this pathway. Areas covered: A literature search to
March 2016 was performed to identify the most relevant reports on the role of the
IL-23/IL-17 axis in IBD and on the different molecules targeting this pathway.
First, the authors briefly summarize the immunology of the IL-23/IL-17 pathway to
elucidate the mode of action of all different agents. Second, they describe all
different molecules targeting this pathway. Besides discussing efficacy and safety
data, they also explore immunogenicity, exposure during pregnancy and
pharmacokinetics. Expert opinion: A new era in IBD treatment has recently been
initiated: besides immuno-modulators and TNF-antagonists, anti-adhesion molecules
and monoclonal antibodies targeting the IL-23/IL-17 pathway have been developed.
Biomarkers for personalized medicine are urgently needed. This therapeutic (r)
evolution will further improve disease-related and patient-reported outcome, though
a lot of questions should still be addressed in future years.
Effective disease management of crops is crucial to sustain food security and
safeguard potential losses in crop production that worth billions of dollars. The
key to success in plant disease management is having the ability to detect the
causal pathogen(s) early and accurately. Polymerase chain reaction (PCR) has been a
gold standard in nucleic acid-based diagnostics. Apart from PCR, within the last
decade, the development of a technique called "loop-mediated isothermal
amplification" or LAMP has facilitated the development of hundreds of simple assays
for plant disease diagnostics. There are now more than 200 LAMP publications per
year, of which 20% identify plant disease pathogens. Among them, LAMP assays are
available for pathogen detection of 50 plant viruses, 20 bacterial plant diseases,
7 fungal plant diseases and several phytoplasmas. Here, we provide a comprehensive
analysis of all LAMP assays available for detecting plant diseases, including
various detection chemistries used. We also discuss how to avoid pitfalls when
developing LAMP assays. Finally, we offer perspectives of the applications of LAMP
in plant disease management, addressing the questions as to which extent the assays
are helpful and whether they should be used outside the laboratory. This review
will be a "handbook" for researchers developing LAMP assays for plant disease
diagnostics.
We examined 261 5-, 7-, and 10-year-olds' (147 in Hong Kong, 114 in the USA)
evaluations of hypothetical scenarios where mothers sought to control personal
domain events by prohibiting, persuading, or shaming the child. The scenarios also
varied in their description of personal events as either essential or peripheral to
the self. Compliance was endorsed least (and emotions attributed to actors were
most positive) when mothers gently persuaded and endorsed most (with emotion
attributions most negative) when mothers prohibited personal choices. Evaluations
of compliance and associated emotions for shaming fell in-between. When mothers
were described as gently persuading, young children (and Chinese children) gave
priority to personal choices more when acts were described as essential rather than
peripheral to the self, based on personal reasons. When mothers were described as
shaming, noncompliance increased with age, along with pragmatic justifications for
choices, particularly when events were essentialized. Positive emotions in response
to shaming also increased with age, but differentially for Chinese and American
children.
Background: Crustaceans have been studied extensively as model systems for nervous
system function from single neuron properties to behavior. However, lack of
molecular sequence information and tools have slowed the adoption of these
physiological systems as molecular model systems. In this study, we sequenced and
performed de novo assembly for the nervous system transcriptomes of two decapod
crustaceans: the Jonah crab (Cancer borealis) and the American lobster (Homarus
americanus). Results: Forty-two thousand, seven hundred sixty-six and sixty
thousand, two hundred seventy-three contigs were assembled from C. borealis and H.
americanus respectively, representing 9,489 and 11,061 unique coding sequences.
From these transcripts, genes associated with neural function were identified and
manually curated to produce a characterization of multiple gene families important
for nervous system function. This included genes for 34 distinct ion channel types,
17 biogenic amine and 5 GABA receptors, 28 major transmitter receptor subtypes
including glutamate and acetylcholine receptors, and 6 gap junction proteins - the
Innexins. Conclusion: With this resource, crustacean model systems are better
poised for incorporation of modern genomic and molecular biology technologies to
further enhance the interrogation of fundamentals of nervous system function.
A new member of antimicrobial protein genes of the Crustin family was cloned from
haemocytes of the Chinese shrimp Fenneropenaeus chinensis by 3' and 5' RACE. The
full-length cDNA of Crustin-like gene contains a 390 bp open reading frame,
encoding 130 amino acids. The deduced peptide contains a putative signal peptide of
17 amino acids and mature peptide of 113 amino acids. The molecular mass of the
deduced mature peptide is 12.3 ku. It is highly cationic with a theoretical
isoelectric point of 8.5. The deduced amino acids sequence of this Crustin showed
high homology with those of Penaeus (Litopenaeas) setferus. Northern blotting
showed that the cloned Crustin gene was mainly expressed in haemocytes, gill,
intestine, and RNA in situ hybridization indicated that the Crustin gene was
constitutively expressed exclusively in haemocytes of these tissues. Capillary
electrophoresis RT-PCR analysis showed that Crustin was up-regulated dramatically
from 12 to 48 h after a brief decrease of mRNA during first 6 h in response to
microbe infection. The level of Crustin mRNA began to restore at 72 h post-
challenge. This indicated that Crustin gene might play an important role when
shrimps are infected by bacterial pathogen.
To realize a multipixel camera for astronomical observation, we developed cryogenic
multi-channel readout systems using gallium arsenide junction field-effect
transistor (GaAs JFET) integrated circuits (ICs). Based on our experience with
these cryogenic ICs, we designed, manufactured, and demonstrated operational
amplifiers requiring four power supplies and two voltage sources. The amplifiers
operate at 4.2 K with an open-loop gain of 2000. The gain-bandwidth product can
expect 400 kHz at a power dissipation of 6 mu W. In performance evaluations, the
input-referred voltage noise was 4 mu V-rms/Hz(0.5) at 1 Hz and 30 nV(rms)/Hz(0.5)
at 10 kHz, respectively. The noise power spectrum density was of type 1/f and
extended to 10 kHz. (C) 2015 Elsevier Ltd. All rights reserved.
This paper describes the main characteristics and the performance of a saturated
core type fault current limiter (FCL) rated 45MVA(33 kV-800 A) to be provided by
ASG Power Systems. The FCL, which has been submitted to preliminary laboratory
testing, will be installed at a 275/33 kV substation in the U.K. and will reduce
the fault current by 38%. The device is based on an open geometry of the magnetic
cores which allows reduced size and the weight. Magnetic saturation of the cores is
obtained by means of two magnesium diboride (MgB2) magnets. A numerical model of
the FCL has been developed and validated and the interaction of the device with the
power grid has been investigated. Details and results of the model are also
discussed in the paper.
Altered mental status in cryptococcal meningitis results in poorer survival, but
underlying causes of altered mentation are poorly understood. Within two clinical
trials, we assessed risk factors for altered mental status (GCS score<15)
considering baseline clinical characteristics, CSF cytokines/chemokines, and
antiretroviral therapy. Among 326 enrolled participants, 97 (30%) had GCS<15 and
these patients had lower median CSF cryptococcal antigen titers (P = .042) and CCL2
(P = .005) but higher opening pressures (320 vs. 269 mm H2O; P = .016), IL-10 (P
= .044), and CCL3 (P = .008) compared with persons with GCS = 15. Altered mental
status may be associated with host immune response rather than Cryptococcus burden.
Cryptosporidium and Giardia are important causes of diarrhoeal illness. Adequate
knowledge of the molecular diversity and geographical distribution of these
parasites and the environmental and climatic variables that influence their
prevalence is important for effective control of infection in at-risk populations,
yet relatively little is known about the epidemiology of these parasites in Africa.
Cryptosporidium is associated with moderate to severe diarrhoea and increased
mortality in African countries and both parasites negatively affect child growth
and development. Malnutrition and HIV status are also important contributors to the
prevalence of Cryptosporidium and Giardia in African countries. Molecular typing of
both parasites in humans, domestic animals and wildlife to date indicates a complex
picture of both anthroponotic, zoonotic and spill-back transmission cycles that
requires further investigation. For Cryptosporidium, the only available drug
(nitazoxanide) is ineffective in HIV and malnourished individuals and therefore
more effective drugs are a high priority. Several classes of drugs with good
efficacy exist for Giardia, but dosing regimens are suboptimal and emerging
resistance threatens clinical utility. Climate change and population growth are
also predicted to increase both malnutrition and the prevalence of these parasites
in water sources. Dedicated and co-ordinated commitments from African governments
involving "One Health" initiatives with multidisciplinary teams of veterinarians,
medical workers, relevant government authorities, and public health specialists
working together are essential to control and prevent the burden of disease caused
by these parasites.
Structural and molecular properties of antidepressants 1-(3-(dimethylamino)propyI)-
1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile were examined using
quantum mechanics of Density Functional Theory (DFT)/B3LYP and PBEPBE methods with
6-311 ++G(d,2p) and LanL2DZ basis sets to study the therapeutic properties of the
drug. For this, the structure of desired material was optimized by the computer
calculation method and with the use of powerful Gaussian 09 software. Then the
lowest energy value and the bond length, bond angle and dihedral angle between its
constituent atoms in the crystal structure of the desired material were measured
from the optimized values. Then the amount of positive and negative charges,
polarizability and dipole moment of its atoms using Mulliken charge and Natural
atomic charges, DFT/B3LYP and PBEPBE methods with 6311 ++ G(d,2p) and LanL2DZ basis
sets were determined and the results were compared with each other for individual
atoms and by mentioned methods. Also the type of stretching vibrations and bending
vibrations between the constituent atoms of the molecule were specified using
mentioned computational methods and FT IR vibrational spectra. The experimental
spectrum of this material was taken to determine the functional groups and the
computational and experimental values were compared to each other and Nuclear
Magnetic Resonance (NMR) was used to specify the isomer shift between the carbons
and protons in the presence of polar and non polar solvents. Also Natural Bond
Orbital (NBO) was used to determine the type of electron transfers in (sigma -
>sigma* and pi ->pi* and LP(1) ->sigma* and LP(2) sigma* and the amount of hardness
and softness in molecule was determined using the difference between ionization
energy and electron affinity energy in constituent atoms of that molecule in the
highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital
(LUMO) and in the presence of solvents H2O, CH3CN and C6H12. UV-Vis spectrum of the
drug was taken using DFT/B3LYP and PBEPBE methods with 6-311 ++ G(d,2p) and LanL2DZ
basis sets as well as solvents H2O, CH3CN and C6H12 and the associated
transmissions were examined. (C) 2017 Elsevier B.V. All rights reserved.
Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in
nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11
(nsp11) was shown to have NendoU activity and play essential roles in the viral
life cycle. Here, we report three crystal structures of porcine reproductive and
respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants.
The structures of arterivirus nsp11 contain two conserved compact domains: the N-
terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV
endoribonucleases are similar and conserved in the arterivirus, but they are
greatly different from that of severe acute respiratory syndrome (SARS) and Middle
East respiratory syndrome (MERS) coronaviruses (CoV), representing important human
pathogens in the Nidovirales order. The catalytic center of NendoU activity is
located in the CTD, where a positively charged groove is next to the key catalytic
residues conserved in nidoviruses. Although the NTD is nearly identical, the
catalytic region of the arterivirus nsp11 family proteins is remarkably flexible,
and the oligomerization may be concentration dependent. In summary, our structures
provide new insight into this key multifunctional NendoU family of proteins and lay
a foundation for better understanding of the molecular mechanism and antiviral drug
development. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV)
and equine arteritis virus are two major members of the arterivirus family. PRRSV,
a leading swine pathogen, causes reproductive failure in breeding stock and
respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or
effective drug treatment and the quick spread of these viruses, infected animals
either die quickly or must be culled. PRRSV costs the swine industry around $ 644
million annually in the United States and almost (sic)1.5 billion in Europe every
year. To find a way to combat these viruses, we focused on the essential viral
nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such
as RNA processing and suppression of the infected host innate immunity system. The
three structures solved in this study provide new insight into the molecular
mechanisms of this crucial protein family and will benefit the development of new
treatments against these deadly viruses.
Melanoma is a form of cancer that initiates in melanocytes. Melanoma has multiple
phenotypically distinct subpopulation of cells, some of them have embryonic like
plasticity which are involved in self-renewal, tumor initiation, metastasis and
progression and provide reservoir of therapeutically resistant cells. Cancer stem
cells (CSCs) can be identified and characterized based on various unique cell
surface and intracellular markers. CSCs exhibit different molecular pattern with
respect to non-CSCs. They maintain their stemness and chemoresistant features
through specific signaling cascades. CSCs are weak in immunogenicity and act as
immunosupressor in the host system. Melanoma treatment becomes difficult and
survival is greatly reduced when the patient develop metastasis. Standard
conventional oncology treatments such as chemotherapy, radiotherapy and surgical
resection are only responsible for shrinking the bulk of the tumor mass and tumor
tends to relapse. Thus, targeting CSCs and their microenvironment niche addresses
the alternative of traditional cancer therapy. Combined use of CSCs targeted and
traditional therapies may kill the bulk tumor and CSCs and offer a promising
therapeutic strategy for the management of melanoma.
Electricity generated using photovoltaic system can only be commercial if the
photovoltaic modules operate reliably for 20-25 years under field conditions.
Understanding the performance degradation of photovoltaic modules is critical for
optimizing its financial viability. Performance degradation of photovoltaic modules
is due to multiple factors such as installation site and module technologies. In
order to gain insight on performance degradation of crystalline silicon PV
technology in harsh environment, a degradation effects study of c-Si photovoltaic
modules in desert environment was carried. The main contribution of this paper is
focused on the evaluation of c-Si PV modules performance that operated in extreme
environmental conditions. This evaluation usually consists of I-V curve field
measurements and visual inspections. (C) 2017 Elsevier Ltd. All rights reserved.
Analysis of the genome of Chaetoceros salsugineum nuclear inclusion virus (CsNIV)
revealed the presence of six putative open reading frames (ORFs) in the genome. We
further characterized ORF3, which encodes a putative coat protein. Polymerase chain
reaction (PCR) using ORF3 gene-specific primers amplified a single DNA band nearly
1.2 kb. This amplified product was gel-purified, cloned, sequenced, and expressed
in Escherichia coli. Specific antiserum was raised against the recombinant protein
and used for Western blotting to test whether the ORF3 protein is the CsNIV coat
protein. One major CsNIV protein of approximately 46 kDa reacted positively with
the antiserum, suggesting that this antiserum is specific for the CsNIV coat
protein. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
analysis of the 46 kDa structural band revealed 14 peptide sequences that matched
the ORF3 regions of CsNIV. The expression of ORF3 in host cells was examined by
constructing a cDNA library of CsNIV-infected cells. Nucleotide sequences of the
cDNA clones were complementary to various regions of both CsNIV ORF3 and ORF4;
however, no clones containing only the ORF3 region were identified. Also, Northern
blotting revealed a single 2.5-kb transcript, indicating that ORF3 could be
transcribed together with ORF4. (C) 2009 Elsevier B.V. All rights reserved.
Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the
blood stream that are thought to have a key role in cancer metastasis.
Investigation of CTCs is an exciting area of research but remains in its infancy,
and the presence of CTCs has been associated with worse prognosis in several major
cancer types. Gastric cancer (GC) is a highly lethal malignancy and a serious
public health concern in East Asia especially in China. There is an urgent need for
identifying new, better prognostic markers to enhance diagnosis and prognosis,
facilitate drug development, and to improve the treatment of gastric cancer
patients. There are considerable interests in gastric CTCs given their potential
use as gastric cancer biomarkers. This review highlights recent advances in studies
of gastric CTCs, including the isolation and biological molecular characteristics
of gastric CTCs, and their clinical significance.
Introduction: Connective tissue growth factor (CTGF/CCN2) has been shown previously
to be aberrantly expressed in a high proportion of paediatric precursor B cell
acute lymphoblastic leukaemia (pre-B ALL), suggesting a potential oncogenic role in
this tumour type. We therefore assessed CTGF mRNA transcript diversity in B-lineage
ALL using primary patient specimens and cell lines. Methods: CTGF mRNA expression
was evaluated by quantitative real-time PCR and Northern blotting. We performed a
structural analysis of CTGF mRNA by nested reverse-transcriptase PCR and examined
CTGF protein diversity by immunoblotting. Results: Northern blot analysis of pre-B
ALL cell lines revealed short CTGF transcripts that were expressed in association
with the active phase of cellular growth. Structural analysis confirmed the
synthesis of several novel CTGF mRNA isoforms in B-lineage ALL cell lines that were
uniformly characterised by the retention of the coding sequence for the C-terminal
(CT) domain. One of these novel spliceforms was expressed in a majority (70%) of
primary pre-B ALL patient specimens positive for canonical CTGF mRNA. Evidence that
these alternative transcripts have coding potential was provided by cryptic CTGF
proteins of predicted size detected by immunoblotting. Conclusion: This study
identifies for the first time alternative splicing of the CTGF gene and shows that
a short CTGF splice variant associated with cell proliferation is expressed in most
cases of primary CTGF-positive pre-B ALL. This novel variant encoding only the CT
domain may play a role in pre-B ALL tumorigenesis and/or progression. (C) 2015
Elsevier Ltd. All rights reserved.
The past 20 years have heralded fascinating developments in the field of CTLA-4
biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and
its absence provokes severe lymphoproliferative disease. In a surprising twist, the
generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly
functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell
can modify the behaviour of another cell. This was followed by the demonstration
that CTLA-4 is highly expressed in regulatory T cells and can contribute to their
suppressive activity. In line with a cell-extrinsic function, increasing evidence
indicates that CTLA-4-positive cells can modify the phenotype of antigen presenting
cells (APC), thereby regulating the priming of naive T cells. Notably, CTLA-4 is
able to down regulate expression of costimulatory ligands on APC via a process of
trans-endocytosis. The identification of patients with mutations in the ctla4 gene
has provided an opportunity to study the contribution of CTLA-4 to Treg function
and immune regulation in the human immune system. Finally. it has become apparent
that CTLA-4 also plays a role in controlling humoral immunity, via the regulation
of CD28-driven follicular helper T cell differentiation. At the recent German
Society for Immunology congress, I discussed some of the contributions of my own
lab to the unfolding of the CTLA-4 story, in the context of the work of others in
the field. Despite the enormous clinical potential associated with modulation of
the CTLA-4 pathway, including the use of soluble CTLA-4 molecules in autoimmune
settings and blocking antibodies in cancer, it is clear there is still much to
learn about this important pathway. (C) 2017 European Federation of Immunological
Societies. Published by Elsevier B.V. All rights reserved.
Conclusions: The levels of expression of various C-type lectin receptors (CLRs)
messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas
than in normal skin, suggesting that these CLRs may be involved in the pathogenesis
of cholesteatoma. Objectives: Altered expression of pattern recognition receptors
may be associated with immune responses in patients with cholesteatoma. This study
assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma.
Methods: Cholesteatoma specimens were obtained from 38 patients with acquired
cholesteatoma. The levels of expression of various CLR mRNAs were assessed
quantitatively using real-time RT-PCR (Reverse transcription polymerase chain
reaction) and correlated with age, sex, the presence of bacteria, hearing level,
frequency of surgery, and degree of ossicle destruction. Results: The levels of
CD206 (cluster of differentiation 206), DEC-205 (Dendritic and epithelial cell-
205), MGL (monoacylglycerol lipase), CLEC5A (C-type lectin domain family 5 member
A), Dectin-2 (dendrite cell-associated C-type lectin-2), BDCA2 (Blood dendritic
cell antigen 2), Mincle, DCIR (dendritic cell immunoreceptor), Dectin-1, MICL
(Myeloid inhibitory C type-like lectin), and CLEC12B (C-type lectin domain family
12, member B) mRNAs were significantly higher in cholesteatoma than in control skin
samples (p= 2 than <= 1 destroyed ossicles (p<0.05), and the levels of MGL, Mincle,
Dectin-1, and CLEC12B mRNAs were significantly higher in recurrent than initial
cholesteatoma specimens (p<0.05). The level of CLEC5A mRNAs was significantly
higher in patients with severe than mild-to-moderate hearing loss (p<0.05). \
Lectin is regarded as a potential molecule involved in immune recognition and
phagocytosis through opsonization in crustacean. Knowledge on lectin at molecular
level would help us to understand its regulation mechanism in crustacean immune
system. A novel C-type lectin gene (Fclectin) was cloned from hemocytes of Chinese
shrimp Fenneropenaeus chinensis by 3' and 5' rapid amplification of cDNA ends
(RACE) PCR. The full-length cDNA consists of 1482 bp with an 861 bp open reading
frame, encoding 287 amino acids. The deduced amino acid sequence contains a
putative signal peptide of 19 amino acids. It also contains two carbohydrate
recognition domains/C-type lectin-like domains (CRD1 and CRD2), which share 78%
identity with each other. CRD1 and CRD2 showed 34% and 30% identity with that of
mannose-binding lectin from Japanese lamprey (Lethenteron japonicum), respectively.
Both CRD1 and CRD2 of Fclectin have I I amino acids residues, which are relatively
invariant in animals' C-type lectin CRDs. Five residues at Ca2+ binding site I are
conserved in Fclectin. The potential Ca2+/carbohydrate-binding (site 2) motif QPD,
E, NP (Gln-Pro-Asp, Glu, Asn-Pro) presented in the two CRDs of Fclectin may support
its ability to bind galactose-type sugars. It could be deduced that Fclectin is a
member of C-type lectin superfamily. Transcripts of Fclectin were found only in
hemocytes by Northern blotting and RNA in situ hybridization. The variation of mRNA
transcription level in hemocytes during artificial infection with bacteria and
white spot syndrome virus (WSSV) was quantitated by capillary electrophoresis after
RT-PCR. An exploration of mRNA expression variation after LPS stimulation was
carried out in primarily cultured hemocytes in vitro. Expression profiles of
Fclectin gene were greatly modified after bacteria, LPS or WSSV challenge. The
above-stated data can provide us clues to understand the probable role of C-type
lectin in innate immunity of shrimp and would be helpful to shrimp disease control.
(c) 2006 Elsevier Ltd. All rights reserved.
Former studies suggest that the core features of psychopathy, namely the callous-
unemotional (CU) traits are associated with emotional dysfunction characterized by
atypical processing of other people's distress. Using a dimensional approach to CU
traits, the current study aims to test neural activity during performance of a
facial expression recognition task in a community sample of young adults. Forty-one
participants (25 females, M age = 25.44, SD = 4.03) completed the Inventory of
Callous-Unemotional Traits. Functional magnetic resonance imaging data were
collected to measure neural responses to fearful, happy and sad faces as compared
with neutral facial expressions. Region-of-interest analyses revealed that during
exposure to fearful face expressions, blood oxygenation level-dependent responses
were negatively associated with CU traits in the right anterior cingulate gyms
(ACCg), but not in the amygdala. These findings support that CU traits are related
to a unique neural response to fearful faces in noncriminal population as well. It
also highlights the importance of taking into account other regions outside the
amygdala, in particular the ACC, when testing the relation between CU traits and
fear response. 2017 The Authors. Published by Elsevier Ltd. This is an open access
article under the CC BY-NC-ND license
A growing body of evidence indicates that lysozyme plays a significant role as an
indicator for many diseases and a drug for treatment of infections, ulcers and to
study the spatial conformation, enzyme kinetics, and molecular immunology.
Therefore, highly sensitive determination of lysozyme is necessary and vital in a
wide variety of fields. In this work, we put forward a simple but effective
strategy for colorimetric visualization of lysozyme based on iodide-responsive
Cu@Au nanoparticles (Cu@Au NPs) as well as the iodide-catalyzed H2O2-TMB (3,3,5,5-
tetramethylbenzidine) reaction system. Colorimetric detection is applied because of
its simplicity, fast response for analysis, high detection limit, low costs and
practicality. In our strategy, iodide is applied for the reason that it can induce
an obvious color change of the Cu@Au nanoparticles solution from gray to red, along
with the change of morphologies of the Cu@Au nanoparticles from irregular to
spherical. Consequently, this phenomenon results in colorimetric signal variation
of the iodide-catalytic H2O2-TMB system. What's more, by quite simple biomolecule
modification on the Cu@Au nanoparticles surface, an all-purpose colorimetric
platform is established for the accurate detection of lysozyme, which could lead to
the change of Cu@Au NP concentration through molecular recognition. The results
show that modified Cu-Au NPs successfully achieved a simple, selective, visualized,
and ultrasensitive detection of lysozyme with a linear range from 10(-7) to 10(-3)
M and a detection limit of 60 nM.
The 2b protein encoded by Cucumber mosaic virus (CMV) plays an important
pathogenicity role in many solanaceous hosts, but mechanism of inducing disease is
still unknown. In order to investigate virulence of the 2b protein on Nicotiana
glutinosa plants, in terms of chloroplast structure and photosynthesis, a mutant
Fny-CMV Delta 2bpro, which cannot express the 2b protein, was achieved by
introducing mutant sites in the 2b gene of Fny-CMV. N. glutinosa seedlings were
inoculated with wild-type Fny-CMV and the mutant Fny-CMV Delta 2bpro, and were
analyzed for symptom expression, chlorophyll content, photosynthetic rate, and
ultra-structural alteration of chloroplast. Up to 30 days post inoculation, wild-
type Fny-CMV caused symptoms of severe mosaic, leaf deformation, and stunting,
reduced photosynthetic rate and chlorophyll content, and altered the ultra-
structure and morphological characters of the chloroplasts. However, host seedlings
inoculated with the mutant Fny-CMV Delta 2bpro expressed only slight mosaic
symptom. Their photosynthetic rates and chlorophyll contents were not significantly
different from those of the mock-inoculated plants, and the ultra-structure and
morphological characters of their chloroplasts appeared to be normal. The observed
low photosynthetic rates and chlorophyll contents were related to the breakage of
the chloroplast morphology and ultra-structure. Results of Northern blotting showed
that the virulence of 2b protein was associated with high accumulation level of CMV
progeny RNAs in systemic leaves. Non-expression of the 2b protein reduced the
accumulation levels of its genomic RNAs I and 2. The level of subgenomic RNA4,
encoding CP protein, was found to be significantly decreased.
Full length cDNAs of Cucumber mosaic virus (CMV) CB7 strain, causing necrosis on
Nicotiana glutinosa, were obtained by RT-PCR, using viral genomic RNAs as
templates. cDNAs of CNW-CB7 genomic RNAs were cloned and sequenced and results
indicated that RNAI, 2 and 3 was 3 356 nt, 3 045 nt and 2 218 nt, respectively
(accordingly Accession Number EF216866, DQ785470 and EF216867). Infectious RNA
transcripts from cDNA clones of CMV-CB7 were inoculated onto N. glutinosa and the
seedlings of host plants displayed necrosis symptom, whist that of CMV-Fny induced
typical mosaic symptoms. Through pseudorecombination between CMV-CB7 and CNW-Fny
genomic RNAs, the genetic determinant of necrosis phenotype was mapped to RNA2.
Chimeric infectious clones consisting of partial sequences of RNA2 derived from
CNW-CB7 and CNW-Fny, respectively, were obtained by Overlapping PCR. Pathogenic
analysis with those chimeric RNA2 revealed that 2b gene or 3' UTR of CMV-CB7 RNA2
was responsible for the necrotic pathotype. Northern blotting analysis reflected
that both necrotic and non-necrotic viruses accumulated to similar levels of
genomic RNAs in host plants. Therefore, necrotic phenotype induced on N. glutinosa
was not related to the level of accumulation of CMV genomic RNAs.
Sex differentiation of flower buds is an important developmental process that
directly affects fruit yield of cucumber (Cucumis sativus L). Plant hormones, such
as gibberellins (GAs) and ethylene can promote development of male and female
flowers, respectively, however, the regulatory mechanisms of GA-induced male flower
formation and potential involvement of ethylene in this process still remain
unknown. In this study, to unravel the genes and gene networks involved in GA-
regulated cucumber sexual development, we performed high throughout RNA-Seq
analyses that compared the transcriptomes of shoot tips between GA(3) treated and
untreated gynoecious cucumber plants. Results showed that GA(3) application
markedly induced male flowers but decreased ethylene production in shoot tips.
Furthermore, the transcript levels of M (CsACS2) gene, ethylene receptor CsETR1 and
some ethylene-responsive transcription factors were dramatically changed after
GA(3) treatment, suggesting a potential involvement of ethylene in GA regulated sex
expression of cucumber. Interestingly, GA(3) down-regulated transcript of a C-class
floral homeotic gene, CAG2, indicating that GA may also influence cucumber sex
determination through an ethylene-independent process. These results suggest a
novel model for hormone-mediated sex differentiation and provide a theoretical
basis for further dissection of the regulatory mechanism of male flower formation
in cucumber. Statement: We reveal that GA can regulate sex expression of cucumber
via an ethylene dependent manner, and the M (CsACS2), CsETR1, and ERFs are probably
involved in this process. Moreover, CAG2, a C-class floral homeotic gene, may also
participate in GA-modulated cucumber sex determination, but this pathway is
ethylene-independent.
We exploited the potential of cucurbits for ectopic gene expression.
Agroinfiltration is a simple and commonly used method to obtain transient
expression of foreign genes in plants. In contrast to in vitro transformation
techniques, agroinfiltration can be used for genetic modification of mature plant
tissues. Although the cucurbits are commonly used as model plants for molecular
biology and biotechnology studies, to date there are no literature sources on the
possibility of transient gene expression in mature cucurbit tissues. Our research
has shown that mature leaves of Luffa cylindrica L. (luffa), in contrast to other
cucurbit species, can be successfully transiently transformed with Agrobacterium
tumefaciens. We efficiently transformed luffa leaves with a reporter gene encoding
beta-glucuronidase (GUS). The GUS activity in transiently transformed leaf tissues
was detected within 24 h after the infiltration with bacteria. Additionally, we
have shown that the activity of a transiently expressed the GUS gene can be
monitored directly in the EDTA-exudates collected from the cut petioles of the
agroinfiltrated leaves. The results suggest that luffa leaves can be useful as a
plant expression system for studies of physiological and biochemical processes in
cucurbits.
Background: Mosquitoes of the Culex pipiens complex, competent vectors for West
Nile virus (WNV) and Rift Valley fever virus (RVFV) are widely targeted by
insecticide treatments. The intensive application of chemical insecticides led to
the development of resistance in many insects including Culex pipiens mosquitoes.
The absence of data on resistance mechanisms in Morocco allow us to assess the
levels of lambda-cyhalothrin resistance and the frequency of the mutated gene
L1014F kdr in different forms of Cx. pipiens complex from three regions of Morocco.
Methods: Mosquito adults were reared from immature stages collected in three
different regions in Morocco (Tangier, Casablanca and Marrakech). Standard WHO
insecticide susceptibility tests were conducted on adults emerged from collected
larvae. Specimens were identified as belonging to the Culex pipiens complex using a
multiplex PCR assay with diagnostic primers designed from the flanking region of
microsatellite CQ11. Identified mosquitoes were then tested for the presence of the
L1014F kdr mutation using PCR assay. Results: Our results showed that 21% of the
tested population has a resistance to lambda-cyhalothrin. The molecular
identification of survivors shows that 43% belonged to the Cx. pipiens pipiens and
only 9.5% to the Cx. pipiens molestus form. On the other hand, 416 specimens were
screened for the L1014F kdr mutation. L1014F mutation was detected in different
forms of Cx. pipiens in different sites. The frequency of L1014F mutation was
similar between the Cx. pipiens pipiens form and hybrid form, while it was lower in
the Cx. pipiens molestus form. The presence of the L1014F kdr allele was
significantly associated with resistance to lambda-cyhalothrin in Cx. pipiens
pipiens (P < 0.0001) and hybrid form (P < 0.0001). Conclusion: Resistance to
lambda-cyhalothrin of Cx. pipiens populations appears to be largely due to the
L1014F kdr mutation. To our knowledge, the frequencies of L1014F kdr mutation are
examined for the first time in natural populations of the Culex pipiens complex in
Morocco. These findings will provide important information to propose more adapted
vector control measures towards this mosquito species, potential vector of
arboviruses.
The purpose of this paper, on the occasion of the 125(th) anniversary of The New
York Botanical Garden, is to provide an overview of NYBG's graduate studies program
along with updated information since the last major review of the program, 25 years
ago. Graduate student education has always been, and continues to be, a core
mission of The New York Botanical Garden. The program is affiliated six major
universities: the City University of New York, Columbia University, New York
University, Yale University, Cornell University, and Fordham University. In the 125
year history of the program, the Garden has produced more than 300 graduates,
including 216 Ph.D.s and 87 Master's degrees. Students have focused on floristics,
systematics, structural botany, and economic botany; the program has evolved to
keep up with the continuous changes in science, with students using the most modern
techniques to study plant diversity. Since 1996, the program has produced 93
graduates, including 81 Ph.D.s and 12 Master's degrees; the Garden's affiliation
with Yale's School of Forestry and Environmental Studies has produced a dozen
graduates; and the Garden's affiliation with Fordham University, which was
reinitiated in 2008, has produced its first graduates. With the growth of the
Cullman Program for Molecular Systematics and the Genomics Program in the mid-
1990s, student research projects began to incorporate molecular biology (primarily
based on DNA sequencing) and to address questions related to genome evolution and
evolutionary developmental biology. Technological advances have also changed
economic botany research. On the 125(th) anniversary of NYBG, the hallmark of the
graduate studies program is its excellence in teaching and training, with students
continuing to integrate data from modern and traditional sources to better
understand plant diversity.
The primary goal of the current study was to examine cultural differences in
Chinese and U.S. adolescents' and parents' perceptions and evaluations of
adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents (ages
11-19 years) and 255 parents participated in this study. Each participant generated
adolescent misconduct behaviors and rated each misconduct behavior as to the degree
of wrongness. The misconduct behaviors were coded into 10 categories across three
themes (moral offenses, drugs, and conventions). Results revealed significant
cultural differences in a number of adolescent misconduct behaviors. For example,
the United States generated more misconduct behaviors in weapon offenses and drug
use than did China. These cultural differences were further complicated by an
interaction between culture and generation. Chinese adolescents were more likely
than U.S. adolescents to use categories of school, home, and social conventional
violations, and considered these adolescent misconduct behaviors to be more wrong.
However, it was the U.S. parents who considered adolescent misconduct behaviors in
these categories to be more wrong than did Chinese parents.
Objective: There are limited data regarding Xpert performance to detect Group B
Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a
rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected
women.Methods: At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs
were collected for two GBS assays in a cohort of sequentially included HIV-infected
women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS
(Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity,
specificity, positive and negative-likelihood ratios were estimated.Results: From
June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman
was later excluded, due to failure to obtain a result in the index test; 336 were
included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and
specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85%
(95% CI: 91.55-96.91), respectively. Positive and negative predictive values were
79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22),
respectively.Conclusions: GeneXpert GBS is an acceptable test for the
identification of GBS colonization in HIV-infected pregnant women and represents a
reasonable option to detect GBS colonization in settings where culture is not
feasible.
The diversity and dynamics of the dominant bacterial communities arising during the
pickling process of bamboo shoots (Dendrocalamus latiflorus) were investigated by
nested polymerase chain reaction denaturing gradient gel electrophoresis combined
with quantitative real-time polymerase chain reaction. Results showed only several
kinds of halophilic bacteria during early sampling time (0-3days). After pickling
for 7days, Lactococcus lactis significantly increased (P<0.05, quantities were
6.39x10(5) copiesL(-1)) and became the first dominant bacterium. After pickling for
14days, Weissella sp. bands appeared and quickly became dominant on the 21st day
(4.07x10(6) copiesL(-1)). As maturation progressed, Lc.lactis decreased in
intensity whereas Weissella sp. increased in intensity. Finally, the quantities of
Weissella sp. (2.50x10(7) copiesL(-1)) became higher than those of Lc.lactis
(1.43x10(7) copiesL(-1)) after pickling for 56days. The pickling process was
initiated by Lc.lactis, followed by Lc.lactis and Weissella sp., and was finally
succeeded by Weissella sp.
Salt stress as a major limiting factor negatively affects many physiological
processes in plants. Salinity promotes the generation of reactive oxygen species
and subsequently oxidative damage of cellular components. Plant salt stress
tolerance requires activation of antioxidative pathways to prevent plant cell from
injurious effects. In this study real-time quantitative reverse transcription-
polymerase chain reaction was used to determine the protective role of two
antioxidant genes, i.e. iron-superoxide dismutase (Fe-SOD) and catalase (CAT) in
Cuminum cyminum L. after their treatment with 50, 100, 150 and 200 mM NaCl.
Enzymatic activities were assayed spectrophotometrically for three antioxidants.
Moreover, growth parameters, protein content and proline accumulation were
measured. In comparison with the control plants, those plants which were exposed to
50 and 100 mM NaCl concentration accumulated higher levels of proline. At 50, 100
and 150 mM of NaCl plants showed higher superoxide dismutase, ascorbate peroxidase
and catalase activities. The same condition also induced expression of the Fe-SOD
and CAT genes at mRNA level. Protein content of the treated plants was
significantly decreased at 50 mM NaCl and remained constant at other
concentrations. Whereas, the growth parameters, with one exception in case of shoot
length, did not change at plants receiving low and mild salt concentrations of up
to 150 mM NaCl, 200 mM of NaCl affected these parameters negatively. From these
details, it can be concluded that C. cyminum respond to salt stress by antioxidant
system efficiency and proline accumulation.
DNA methyltransferases (DNMTs) are promising epigenetic targets for the development
of novel drugs, especially for neurodegenerative disorders. In recent years, there
has been increased interest in small molecules that can cross the blood-brain
barrier for the treatment of neurodegenerative diseases. Therefore, comparing the
neuronal differentiative effects of a natural compound curcumin and a synthetic
small molecule RG108 was the aim of this study. The effects of curcumin and RG108
on neuronal differentiation and neurite outgrowth were investigated in the PC-12
Adh cell line. First, a nontoxic concentration was determined to be 100nM with WST-
1 assay. Subsequently, cells were treated with 100nM curcumin and RG108 alone or in
combination with 50nM nerve growth factor (NGF). Cell differentiations were
evaluated by a real-time cell analyzer system. Neurite outgrowth was determined and
morphologically shown by immunofluorescence staining with anti-beta III tubulin
antibody on PC-12 Adh cells. Also, growth-associated protein-43 (GAP-43) and b-
tubulin III mRNA expression levels, associated with neurite outgrowth promotion,
were determined with real-time polymerase chain reaction (RT-PCR). According to our
results, 100nM curcumin and RG108 significantly induced neurite outgrowth of PC-
12Adh cells with 50nM NGF. Curcumin + NGF combination further increased cell
differentiations and total neurite lengths more than curcumin alone and RG108 + NGF
combination groups. Strikingly, curcumin and NGF combination upregulated GAP43 and
b-tubulin mRNA expression levels excessively. In conclusion, curcumin was found to
be more effective than RG108 on neuronal differentiation and neurite outgrowth of
PC-12Adh cells in a combination with NGF. Therefore, natural DNMT1 inhibitors, such
as curcumin, can be a novel approach for the neurodegenerative disorders treatment.
Objectives: New evidence has proven the hepatoprotective activity of curcumin;
however, its underlying mechanisms remain to be elucidated. The aim of this study
was to investigate the protective effect of curcumin on hepatic damage by measuring
the antioxidant capacity and expression level of Rho-related C3 botulinum toxin
substrate (Rac1), Racl-Guanosine triphosphate (Racl-GTP), and NADPH oxidase 1(NOX1)
in biliary duct-ligated (BDL)-fibrotic rat model. Methods: Wistar rats weighing 200
to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group
(received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and
protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time
polymerase chain reaction and Western blotting, respectively. Results: Curcumin
treatment of BDL rats reduced liver injury, as verified by improvement of hepatic
cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the
increase in the expression of Racl, Racl-GTP, and NOX1 observed in BDL rats was
precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We
also observed an escalation of protein thiol groups, increased enzyme activity of
serum antioxidant markers (e.g., superoxide dismutase) and a decrease of
carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05).
Conclusions: Curcumin attenuated liver damage through the downregulation of Racl,
Racl-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver
tissue of BDL rats. (C) 2016 Elsevier Inc. All rights reserved.
This paper presents hybrid cascode compensation with current amplifiers (HCCCA) for
nano-scale area-efficient three-stage amplifiers driving ultra-large capacitive
loads. The total compensation capacitor is split and placed among two high-speed
feedback loops, each with a unique current amplifier. By using HCCCA, the load-
dependent non-dominant poles are pushed to much higher frequencies, thereby
achieving improved performance especially for heavy capacitive loads. The employed
current amplifiers make it possible to significantly reduce the physical size of
the compensation capacitors and to save more silicon area. The effectiveness of the
proposed technique has been verified in 90-nm CMOS process, where an HCCCA
amplifier prototype is designed to drive up to 10 nF load capacitor using a
compensation capacitor of only 0.5 pF. It achieves a 1.0 MHz gain-bandwidth product
and 0.19 V/A mu s slew-rate while consuming 80 A mu W power from a 1.2 V supply.
The achieved large-signal and small-signal performance metrics are superior to
those topologies reported in the literature.
Development of renewable power generation systems (RPGSs) is continually increasing
worldwide with Germany, China, Japan, Italy and the USA are the leaders
contributing to the largest, development in each region. Due to the increasing
number of RPGSs connected to the utility grid, power quality, safe operation, and
islanding protection of RPGSs are becoming important issues, among others. One of
the most important elements is the current control technique that must meet the
requirements for grid interconnection according to international standards and
practices. The RPGS itself must be safe and highly efficient for reliable and
secure grid interconnection operations. This paper presents a review of the state-
of-the-art of the current control techniques for three-phase grid-interconnection
of RPGSs. Several current control architectures, their operations including
advantages and disadvantages were discussed. Performance comparison and evaluation
of several controllers were also reviewed. (C) 2016 Elsevier Ltd. All rights
reserved.
In this paper, a serial-parallel hybrid (SPH) power system formed by a fuel cell
(FC), an auxiliary storage device (ASD), and the current-controlled dc-dc
converters responsible for the power management are realized by using the digital
signal controller (DSC) TMS32F28335. The main energy management goal is to transfer
energy from the sources (FC or ASD) to the load while ensuring dc bus voltage
regulation and high power conversion efficiency. In addition, a safe and reliable
operation of the system has to be achieved. The selected converter and its
controller features are noninverting voltage step up and step down, high
efficiency, regulation of input and output currents and low ripple values, and the
ability to change from input to output current regulation loop, suddenly and
smoothly, and vice versa. All these features allow it to be positioned in different
FC system localizations and simplify the design of the master control. Simulation
and experimental results have been validated on a 48-V 1200-W dc bus.
A digital dead-beat current controller for voltage source converters is presented
in this paper. The control structure is specified in a digital hardware description
language, synthesized, and deployed on a field-programmable gate array chip. By
updating, with negligible computation delay, the duty cycle twice in a switching
period, the reference current error is nulled in half a modulation period, so that
the controller's small-signal bandwidth is maximized. In addition, due to a simple
transient detection circuit, the large-signal response delay is reduced to a small
fraction of the modulation period, which is determined by the chosen current signal
oversampling rate. The controller can effectively support different voltage-source
inverter applications, such as active filters, uninterruptible power supplies,
microgrid distributed energy resource controllers, and dc-dc converter
applications, including interface converters for renewable energy sources,
laboratory battery chargers, and electronic welding machines.
This work presents a control system suitable for high-precision pulsed current
sources. The proposed control system is based on the detection of events so as to
define changes in the power converter state to produce the required current
waveform with a good dynamic response. Additionally, this control system is
designed to regulate the flat-top current with a well-defined precision. In order
to mitigate the effect of the measurement noise, an estimation algorithm for the
controlled current is incorporated. This algorithm generates a filtered version of
the controlled variable without affecting the control dynamics. The use of the
estimated current allows to improve the detection of the events and to avoid an
increase in the number of commutations due to possible erratic comparisons. Then,
the estimator gains are tuned by using genetic algorithm techniques to optimize the
root-mean-square value for a typical pulse. Furthermore, in order to independently
perform the required set of tasks, the proposed control system is implemented by
using a digital platform based on a field-programmable gate array. Additionally,
due to the demanding precision in these applications, different considerations
regarding its implementation, such as the digital wordlength, binary point
position, rounding method, and overflow behavior, have been taken into account.
Experimental results obtained from the application of the proposed control system
to a laboratory prototype are presented.
A fully digital, nonlinear, wide-bandwidth current controller for dc-ac and dc-dc
voltage source converters is presented in this paper. Exploiting over-sampling, the
controller mimics an analog hysteresis current controller, but it does not employ
analog comparators, digital-to-analog converters, or any other analog signal pre-
or postprocessing circuitry. Indeed, it fully virtualizes the hysteresis
controller's operation and, based only on a nonlinear, efficient current error
processing algorithm, drives the power converter at almost constant switching
frequency. Overall, it offers the same excellent dynamic performance of the analog
hysteresis controller and, at the same time, solves most of the related problems.
Because the current error sample processing algorithm is inherently parallel in
structure, the controller is suited for VHDL synthesis and field-programmable gate-
array implementation, which guarantees flexibility and low cost, together with
minimum computation and signal conversion delays. Its intended application areas
include active filters, uninterruptible power supplies, microgrid distributed
energy resource controllers, laboratory battery testers, and welding machines.
The current controller with fast transient response and satisfactory steady state
characteristics is required in PMSM Servo System. In this paper, the application of
active disturbance rejection control (ADRC) for current loop is proposed and the
design proceeding of a first-order ADRC controller in the current loop is
elaborated. Then, by taking use of the ADRC controller and the analysis of the
digital control delay effect, an improved method focusing on delay effects is
presented. By taking these measures, the current regulation can achieve high
performance. Simulation and experimental results verify the correctness and
feasibility of the proposed method.
This paper presents the analysis, design, and hardware implementation of a digital
polynomial Regulation, Steady-State Error and Tracking (RST) current controller-
based third-harmonic modulated boost-type power factor correction (PFC) rectifier.
The proposed rectifier is used at the front end of a vector controlled induction
motor drive (VCIMD) to eliminate harmonics at the input AC supply. The proposed PFC
rectifier modifies the input current to a sinusoid with unity power factor apart
from offering DC bus voltage regulation. In this paper, a digital proportional-
integral (PI) and RST current controllers are compared in terms of total harmonic
distortion (THD) and power factor (PF) at the point of common coupling for
different loading conditions. The RST current controller tracks the set-point
accurately with zero steady-state error and offers good disturbance rejection that
enables further reduction of supply current THD as compared to a conventional PI
current controller. The control algorithm for the PFC front end rectifier along
with vector control technique is implemented using a digital signal processor, and
the dynamic performance is analyzed for step changes in reference speed and load
torques, demonstrating significant improvement in the performance indices.
This paper presents new topologies for emulating floating immittance functions
using three to five passive elements and only two current-feedback operational-
amplifiers (CFOAs). The feasibility of using only two CFOAs and two passive
components is explored. The proposed topologies can emulate lossy positive and
negative inductances and capacitance-, inductance-, resistance-multipliers, and
frequency dependent negative and positive conductances. The functionality of the
proposed circuits was experimentally verified using the commercially available
AD844 CFOA. The experimental results are in excellent agreement with theoretical
calculations.
This paper presents a new topology for emulating floating lossless negative
inductance, positive frequency dependent resistance and resistance-controlled
resistance and capacitance multipliers. The circuit uses three current-feedback
operational-amplifiers (CFOAs), and three passive elements. The functionality of
the proposed circuit is verified using the Advanced Design System (ADS) software
and the AD844 CFOA. The simulation results are in excellent agreement with the
theoretical calculations.
It is shown that the recently-proposed modified current feedback operational
amplifier (MCFOA) is quite a versatile element in that given a realization for a
system function using MCFOAs, we can obtain three alternate realizations using the
same MCFOA but by appropriately connecting the y, x, w, and z terminals of the
MCFOA to the remaining part of the original realization. Using the results
concerning the transpose of a multi-terminal element, it is further shown that the
transpose of an MCFOA is another MCFOA. Thus, using the results of transposition,
given a voltage-mode circuit using MCFOAs, we can directly obtain four current-mode
circuits using the same MCFOAs or vice versa. Copyright (c) 2015 John Wiley & Sons,
Ltd.
New voltage-mode electronically tunable notch, bandpass, highpass and lowpass
shadow filters are presented. The filters are built around the current-feedback
operational-amplifier. In each case one or more of the parameters of the filter can
be electronically controlled by adjusting the gain of an external amplifier built
around the current-feedback operational-amplifier. Contrary to the current-mode
shadow filters where a summing junction must be used, no summing amplifiers are
used in these voltage-mode realizations. Experimental results obtained using the
AD844 current-feedback operational-amplifier are presented. The results obtained
confirm the functionality of the proposed circuits.
This paper presents the experimental results obtained from a memristor-based Wien-
bridge oscillator implemented using a new memristor emulator. The memristor
emulator can be implemented using off-the-shelf components. The experimental
results show that nonlinear chaotic as well as linear oscillations can be obtained
from the same circuit by careful adjustment of the value of a single resistor. The
proposed circuit can be easily presented in an undergraduate laboratory course to
demonstrate the use of memristors in generating chaotic oscillators.
Using a unified representation for the two current-feedback operational-amplifiers
(CFOAs) based sinusoidal oscillators, new structures and circuits of this type are
systematically discovered. Three catalogues for three different structures with
each structure realizing 17 oscillator circuits are presented. Some of the new
circuits are enjoying the attractive features of using grounded capacitors and/or
independent/orthogonal tuning for the frequency and condition of oscillation.
However, the classification of independent/orthogonal tuning may be misleading as
it is based on using the Barkhausen criterion. Therefore, it is shown that using
the roots of the characteristic equation of a specific oscillator circuit; while
not leading to accurate results, may avoid any misleading conclusion regarding the
orthogonal tuning of the frequency and condition of oscillation. Experimental
results using the AD844 CFOA are included.
This paper presents a low power, high slew rate, high gain, ultra wide band two
stage CMOS cascode operational amplifier for radio frequency application. Current
mirror based cascoding technique and pole zero cancelation technique is used to
ameliorate the gain and enhance the unity gain bandwidth respectively, which is the
novelty of the circuit. In cascading technique a common source transistor drive a
common gate transistor. The cascoding is used to enhance the output resistance and
hence improve the overall gain of the operational amplifier with less complexity
and less power dissipation. To bias the common gate transistor, a current mirror is
used in this paper. The proposed circuit is designed and simulated using Cadence
analog and digital system design tools of 45 nanometer CMOS technology. The
simulated results of the circuit show DC gain of 63.62 dB, unity gain bandwidth of
2.70 GHz, slew rate of 1816 V/mu s, phase margin of 59.5 degrees, power supply of
the proposed operational amplifier is 1.4 V ( rail- to- rail +/- 700 mV), and power
consumption is 0.71 mW. This circuit specification has encountered the requirements
of radio frequency application.
This paper presents a new current mode implementation of a balanced-output-signal
generator that utilizes an operational floating current conveyor (OFCC) as a basic
building block. The OFCC, as a current-mode device, shows flexible properties with
respect to other current or voltage-mode circuits. The advantages of the proposed
current mode balanced-output-signal generator (CMBG) are threefold. Firstly, it
offers an accurate phase and amplitude performance over a wide bandwidth without
requiring matched resistors. Secondly, it has a differential input and it can
provide either current or voltage outputs. Finally, the proposed CMBG circuit
offers a significant improvement in accuracy compared to other CMBGs based on the
current conveyor. The proposed CMBG has been analyzed, simulated and experimentally
tested. The experimental results verify that the proposed CMBG outperforms existing
CMBGs in terms of the number of basic building blocks used and accuracy.
In this paper, a single current sensor technique (SCST) is proposed for single-
phase full-bridge inverters. The proposed SCST measures the currents of multiple
branches at the same time, and reconstructs the average inductor, capacitor, and
load current in a single switching cycle. Since all of the branches' current in the
LC filter and the load are obtained using the SCST, both the inductor and the
capacitor current feedback schemes can be selectively applied while taking
advantages of each other. This paper also analyzes both of the current feedback
schemes from the view point of the closed-loop output impedance. The proposed SCST
and the analysis in this paper are verified through experiments on a 3kVA single-
phase uninterruptible power supply (UPS).
This paper presents a temperature-compensated CMOS current reference with low line
regulation current mirror. The circuit is based on a bandgap reference voltage that
achieves the temperature compensation of resistor by the negative temperature
coefficient (TC) of a high-resistance polysilicon (HR poly) resistor with the
positive TC of an n-well resistor. The low line regulation current mirror is
implemented by using a negative feedback connected operational amplifier.
Prototypes of 1 mu A current reference from 0.35 mu m CMOS process show a maximum
temperature coefficient of 139 ppm/A degrees C for a temperature range of 0-80 A
degrees C. The line regulation is reduced to 0.5 %/V for supply voltage of 3.5 to
5.5 V.
This paper presents a chopper amplifier for precision current sensing, capable of
handling common mode input voltages outside the supply rails. For high common mode
rejection ratio (CMRR) and DC gain, the amplifier employs a three-stage topology
with nested-Miller frequency compensation. By using the chopping technique, a
referred to input offset voltage of +/-90 mu V is obtained. To reduce the output
ripples caused by the chopping technique the amplifier employs a notch filter. A
CMRR of 123dB has been obtained, considering a supply voltage of 5V, for a common
mode input voltage range from 4V to 80V. The stability of the operational amplifier
(OA) is ensured for a minimum closed loop gain of 20V/V.
This paper presents a current sense amplifier (CSA) capable of performing
measurements at high input common mode (CM) voltages independent of the power
supply rail. The proposed circuit employs a fully low voltage amplifier cell, a
correction block for maintaining the linearity of the input stage over the entire
input CM and a protection circuit against high differential input voltages (DIFF).
Furthermore, a trimming procedure that enables the use of typical polysilicon gain
resistors without losing accuracy and precision is discussed. The proposed
architecture has been implemented in a standard 0.25 mu m BCD technology and its
performances have been confirmed by both simulations and measurements.
This paper presents a high accuracy and high bandwidth current sense circuit for
digitally controlled DC-DC buck converters. The circuit uses lossless inductor DCR
current sensing and a sigma delta modulator ADC to sense the average current in the
inductor to high accuracy. These accurate but low bandwidth measurements are
unsuitable for use in feedback control loops as their acquisition delay would limit
the achievable loop bandwidth. To solve this issue a Kalman Filter estimates the
inductor current at the switching frequency of the converter. The output of the
estimator is shown through experimental results to achieve 0.3A static current
accuracy when used in a buck converter switching at 1MHz and using a power
efficient inductor with a DCR of only 165 mu Ohms.
Current sensors are usually protected against electromagnetic interference (EMI) by
means of filters placed at the PCB level. The literature has plenty of solutions
aimed at keeping EMI filters' attenuation as high as possible in the widest
possible frequency range. However such filters are less effective than expected
because of the parasitic elements introduced by interconnects. As a consequence,
EMI can be propagated into ICs causing temporary or definitive operation failures.
This paper points out the causes of EMI-induced errors in high-side current sensors
based on low-offset chopper OTAs. Analyses presented in the paper are supported by
direct power injection measurements carried out on a test chip.
The design of a High Stability Voltage Controlled Current Source (VCCS) for
Cervical Cancer Detection (CCD) applying Electrical Bio-Impedance Spectroscopy
(EBS) is presented. The circuit was designed and simulated in TSMC 130 nm CMOS
technology at 1.3V power supply. The proposed Howland Current Source is based on
Self-Biased Complementary Folded Cascode (SB-CFC) Operational Amplifier (OA).
Complying with the requirements for medical electrical equipment of international
standard ABNT-NBR-IEC-60601-1 the sinusoidal current peak amplitude was settled at
10. A. In accordance with the requirements of the EBS for CCD, the specifications
for the SB-CFC-OA were calculated to meet the 100 Hz to 1 MHz frequency range for
the sinusoidal output current and the output impedance higher than 1 M Omega at 1
MHz frequency. Post-layout simulations were run and the main results were: 10 +/-
0.0335 mu A for the output current peak amplitude over the specified frequency
range and with 5 k Omega load impedance; values above 1.6 M Omega output impedance
@ 1 MHz; nominal current amplitude variations lower than 0.4% for load impedances
in the range of 10 Omega up to 5 k Omega. From these results, the performance of
the VCCS is adequate for EBS-CCD applications.
The design of a high stability voltage controlled current source (VCCS) for
cervical cancer detection (CCD) applying electrical bio-impedance spectroscopy
(EBS) is presented. The circuit was designed, simulated and fabricated in TSMC 130
nm CMOS technology at 1.3 V power supply. The proposed Howland current source is
based on self-biased complementary folded cascode (SB-CFC) operational amplifier
(OA). Complying with the requirements for medical electrical equipment of
international standard ABNT-NBR-IEC-60601-1 the sinusoidal current peak amplitude
was settled at 10 mu A. In accordance with the requirements of the EBS for CCD, the
specifications for the SB-CFC-OA were calculated to meet the 100 Hz-1 MHz frequency
range for the sinusoidal output current and the output impedance higher than 1
Ma"broken vertical bar at 1 MHz frequency. Post-layout simulations were run and the
main results were: 10 +/- 0.0335 mu A for the output current peak amplitude over
the specified frequency range and with 5 ka"broken vertical bar load impedance;
values above 1.6 Ma"broken vertical bar output impedance at 1 MHz; nominal current
amplitude variations lower than 0.4 % for load impedances in the range of 10
a"broken vertical bar up to 5 ka"broken vertical bar. And the experimental result
for maximum non-linearity was 2.19 % of full scale. From these results, the
performance of the VCCS is adequate for EBS-CCD applications.
This article presents a new topology for implementing an electronically tunable
bandpass filter using the current-feedback operational amplifier. The electronic
tuning of the center frequency of the proposed circuit is achieved using an
externally connected voltage amplifier in the feedback path without disturbing the
constituents of the filter itself, that is a shadow filter. The proposed circuit
can be used for developing an undergraduate experiment which illustrates the
operation of bandpass filter and the electronic control of its center frequency
using the concept of shadow filter. Experimental results obtained using the AD844
current-feedback operational amplifier are included.
This paper presents a new topology for emulating floating lossless negative
immittance functions. The proposed circuit uses three current-feedback operational-
amplifiers (CFOAs), and three passive elements. The functionality of the proposed
circuit is verified using the Advanced Design System (ADS) software and the AD844
CFOA. The simulation results obtained from a floating negative lossless inductance
emulator are in excellent agreement with the theoretical calculations.
This paper proposes a macromodel to emulate the nonlinear behavior of current-
feedback operational amplifiers (CFOAs) at low-frequency. The main difference
between this macromodel and those reported previously in the literature is that
herein, real physical active device performance parameters along with parasitic
elements associated to the input-output terminals of the amplifier are considered.
To validate the deduced behavioral model, a saturated nonlinear function series
(SNFS) based on CFOAs is built and numerical simulations are generated. In this
point, the modeling problem is cast in terms of an augmented set of equations but
that, unlike a piece-wise linear (PWL) approach, the dynamic behavior of each CFOA
is considered. Afterwards, the SNFS is experimentally tested by using commercially
available active devices, confirming good agreement among theoretical simulations
and experimental tests at two operating frequencies and showing a better accuracy
compared with a PWL approach and a linear model for CFOAs. Because the derived
nonlinear macromodel for CFOAs is used for generating the behavioral model of the
SNFS, one concludes that the latter is also both accurate and efficient with
respect to traditional techniques, such as PWL approaches. (C) 2015 Elsevier Ltd.
All rights reserved.
This paper presents a new topology for implementing a bandpass shadow filter using
the current-feedback operational amplifier (CFOA). The proposed circuit uses CFOAs,
and avoids the use of external summing circuit to implement a shadow bandpass
filter with controlled center frequency. Experimental results obtained using the
AD844 CFOA are included.
This paper presents a gray-box equivalent circuit model (ECM) in order to predict
the performance of direct methanol fuel cell (DMFC) unit. The ECM is composed of
electronic components ranging from operational amplifier resistors to diodes. The
current-voltage profiles and current-power profiles of this ECM are validated by
the simulation results of the COMSOL model. Afterward, the influences of methanol
concentration, operating temperature, and oxygen concentration on the performance
of the single passive DMFC are all validated experimentally. All validations show
that the ECM provides a good approximation of the behavior of the DMFC. In
addition, a simulated application of a circuit system employing the ECM is
explained. The simulated result is validated experimentally. This research makes it
possible to analyze the behavior of a DMFC in real applications.
This paper presents a reference modification model digitally controlled dc-dc
converter. The proposed method is able to obtain superior transient response
because it modifies a reference of conventional feedback loop against the change of
output voltage. The modifying process operates only in the transient state. During
the steady state, the feedforward control cancels a steady-state-error. Since the
feedforward control uses the load current value, this paper discusses two current-
sensing methods. One is the output current-sensing method using the sensing
resistor, and the reactor current-sensing method using the R-C filter is discussed
in order to reduce a performance loss by the sensing resistor. As a result, the
output current-sensing method is effective in case that high-transient-response
performance is required. On the other hand, it is better to use the reactor
current-sensing method when efficiency is important.
This work describes a 10-week laboratory project studying wild-type and mutant
bacterial alkaline phosphatase, in which students purify, quantitate, and perform
kinetic assays on wild-type and selected mutants of the enzyme. Students also
perform plasmid DNA purification, digestion, and gel analysis. In addition to
simply learning important techniques, students acquire novel biochemical data in
their kinetic analysis of mutant enzymes. The experiments are designed to build on
students' work from week to week in a way that requires them to apply quantitative
analysis and reasoning skills, reinforcing traditional textbook biochemical
concepts. Students are assessed through lab reports focused on journal style
writing, quantitative and conceptual question sheets, and traditional exams. (C)
2016 by The International Union of Biochemistry and Molecular Biology
Eucalyptus spp. and hybrids remain among the mostly widely-planted species in the
world, owed principally to its diverse genome, its site-adaptability, and
relatively fast growth rates. Numerous pure species, and yet more hybrid clones
have been globally deployed in plantations, as industry seeks to meet growing
demands for wood and their products. As a result, various propagation approaches
have been explored, from seeds to vegetative propagation by cuttings and trough in
vitro method, with a view to remaining cost-effective, yet efficient, and
sustainable. Vegetative propagation of eucalypts is preferred, as it conserves
valuable germplasm and offers predictability in commercial foplantations. The range
of eucalypt species and hybrids in commercial use, however, has resulted in an
array of propagation protocols, as researchers seek to optimise growth conditions
to enhance the quality and yields of rooted cuttings and in vitro propagules. The
exogenous supply of plant growth regulators (PGRs) is central to the objectives of
these protocols. The present review traces recent developments in Eucalyptus
propagation, and presents a selection of published protocols for a variety of
species, explants and PGR supply. With advancements in plant physiology, molecular
biology and biochemistry, a clearer picture of the vegetative physiological growth
requirements steadily develops, leading researchers to more accurately manipulate
and improve Eucalyptus propagation. Furthermore, the recent completion of the E.
grandis genome sequence will drive advancements in eucalypt genomics, metabolomics,
and proteomics. Collectively, these developments will present future opportunities
to accurately decipher, augment and significantly enhance sustainable growth,
yields, valuable traits and germplasm conservation of the eucalypts.
BACKGROUND: In 2014, the European Society for Immune Deficiencies (ESID) revised
the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new
clinical and biological markers. The new definition appeared more restrictive but
had not yet been evaluated in a large cohort of patients. OBJECTIVE: The objective
of this study was to evaluate the impact of this new definition in a large cohort
of patients with primary hypogammaglobulinemia. METHODS: Evaluation of 3 different
CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID
2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis
of primary hypogammaglobulinemia. RESULTS: Using the ESID/PAGID 1999 definition,
351 patients were classified as CVID. The new ESID 2014 definition excluded 62
(18%) patients. Most of them (n [56; 90%) had a less severe disease, whereas 6
(10%) presented with a severe disease with major T-cell defect. We propose
different criteria (occurrence of opportunistic infection or very low naive CD4D T-
cell count) to define this population with severe T-cell defect. Sixty-two patients
fulfilled these criteria, represented 20% of the initial CVID population but
accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95%
confidence interval, 51.0-79.6), and were considered as late onset combined
immunodeficiency (LOCID). CONCLUSIONS: The new ESID definition for CVID still fails
to exclude a large number of patients with severe T-cell defect. We propose a new
definition (DEFI 2015) that excluded more patients with a T-cell defect and
consider these patients as LOCID. This population has a poor outcome and should be
considered as a distinct group requiring specific care. (C) 2016 American Academy
of Allergy, Asthma & Immunology.
Leukocyte populations change profoundly in the human endometrium during the
menstrual cycle. However the predominant cell, the uterine natural killer (uNK)
cell does not contain steroid receptors. From gene array analysis we identified a
transcript encoding chemokine (C-X-C motif) ligand 14 (CXCL14) which is markedly
up-regulated in the secretory phase of the cycle. We confirm this data by northern
blotting and quantitative PCR. Using in situ hybridization we localized CXCL14 mRNA
to the glandular epithelial cells where it was detected only in the secretory phase
of the cycle. Candidate progesterone response elements were identified at positions
-2028/-2007 and -722/-697 (PRE1 and PRE2, respectively) relative to the translation
start site. These were functionally tested using luciferase reporter deletion
constructs, electrophoretic mobility shift assays and site-directed mutagenesis.
The deletion/mutation of these sites reduced progesterone induction by 40 and 20%,
respectively. Finally, we demonstrated that recombinant CXCL14 stimulated uNK cell
chemotaxis in vitro. We therefore conclude that CXCL14 is likely to be regulated by
progesterone in human endometrium and that it may exert a chemoattractive effect on
uNK cells and in part be responsible for their clustering around the epithelial
glands.
Background: Metastasis is a major cause of death in human colorectal cancer
patients. However, the contribution of chemokines in the tumor microenvironment to
tumor metastasis is not fully understood. Methods: Herein, we examinined several
chemokines in colorectal cancer patients using chemokine ELISA array.
Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer
patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5,
shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study.
Immunoblot, immunofluorescence and transwell assay were used to examine the
molecular biology and morphological changes in these cells. In addition, we used
nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. Results: We
found that CXCL5 was overexpressed in tumor tissues and associated with advanced
tumor stage as well as poor prognosis in colorectal cancer patients. We also
demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and
cell membranes, which may indicate that the CXCL5 was predominantly produced by
cancer epithelial cells instead of fibroblasts in the tumor mesenchyme.
Additionally, overexpression of CXCL5 enhanced the migration and invasion of
colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT)
through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3 beta/beta-
catenin pathway in a CXCR2-dependent manner. The silencing of Snail and beta-
catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The
elevated expression of CXCL5 can also potentiate the metastasis of colorectal
cancer cells to the liver in vivo in nude mice intrasplenic injection model.
Conclusion: In conclusion, our findings support CXCL5 as a promoter of colorectal
cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer
patients.
The accurately estimated state is of great importance for maintaining a stable
running condition of power systems. To maintain the accuracy of the estimated
state, bad data detection (BDD) is utilized by power systems to get rid of
erroneous measurements due to meter failures or outside attacks. However, false
data injection (FDI) attacks, as recently revealed, can circumvent BDD and insert
any bias into the value of the estimated state. Continuous works on constructing
and/or protecting power systems from such attacks have been done in recent years.
This survey comprehensively overviews three major aspects: constructing FDI
attacks; impacts of FDI attacks on electricity market; and defending against FDI
attacks. Specifically, we first explore the problem of constructing FDI attacks,
and further show their associated impacts on electricity market operations, from
the adversary's point of view. Then, from the perspective of the system operator,
we present countermeasures against FDI attacks. We also outline the future research
directions and potential challenges based on the above overview, in the context of
FDI attacks, impacts, and defense.
A frequency-domain approach to the design of digital feedback controls for SISO
systems is presented. The noise gain is minimized, subject to a phase margin
constraint. The controller is expressed as a repeated-pole expansion, which reduces
the optimization to a quadratic problem and a linear system of equations.
PID+filter controls are produced as a limiting case.
Researchers are concerned with identifying the risk and protective factors
associated with adolescents' involvement in cyberharassment. One such factor is
parental mediation of children's electronic technology use. Little attention has
been given to how different parental mediation strategies (i.e., instructive,
restrictive, co-viewing) relate to adolescents' cyberharassment (i.e.,
cyberbullying, cybertrolling) perpetration and victimization, and how gender might
impact these associations. To this end, the present study examined the moderating
effect of gender on the longitudinal association between parental mediation
strategies and adolescents' cyberharassment involvement. This focus was examined
using a sample of 568 (53% female) adolescents from the 8th grade in the United
States. The association between restrictive mediation and cybervictimization was
more positive for girls when compared to boys, while the relationship between
instructive mediation and cybervictimization was more negative for girls than for
boys. The findings underscore the importance of considering parents in adolescents'
cyberharassment involvement. (C) 2017 Elsevier Ltd. All rights reserved.
Type 4 cyclic nucleotide phosphodiesterases (PDE4) are major members of a
superfamily of enzymes (PDE) involved in modulation of intracellular signaling
mediated by cAMP. Broadly expressed in most human tissues and present in large
amounts in the liver, PDEs have in the last decade been key therapeutic targets for
several inflammatory diseases. Recently, a significant body of work has underscored
their involvement in different kinds of cancer, but with no attention paid to liver
cancer. The present study investigated the effects of two PDE4 inhibitors, rolipram
and DC-TA-46, on the growth of human hepatoma HepG2 cells. Treatment with these
inhibitors caused a marked increase of intracellular cAMP level and a dose- and
time-dependent effect on cell growth. The concentrations of inhibitors that halved
cell proliferation to about 50% were used for cell cycle experiments. Rolipram (10
mu M) and DC-TA-46 (0.5 mu M) produced a decrease of cyclin expression, in
particular of cyclin A, as well as an increase in p21, p27 and p53, as evaluated by
Western blot analysis. Changes in the intracellular localization of cyclin D1 were
also observed after treatments. In addition, both inhibitors caused apoptosis, as
demonstrated by an Annexin-V cytofluorimetric assay and analysis of caspase-3/7
activity. Results demonstrated that treatment with PDE4 inhibitors affected HepG2
cell cycle and survival, suggesting that they might be useful as potential
adjuvant, chemotherapeutic or chemopreventive agents in hepatocellular carcinoma.
(C) 2016 Wiley Periodicals, Inc.
The aim of the present study was to investigate the association between methylation
of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and telomerase
activity in children with acute lymphoblastic leukemia (ALL). A total of 72
children with ALL and 12 children with immune thrombocytopenia (ITP) were subjected
to bone marrow aspiration and methylation-specific polymerase chain reaction
analysis, and modified telomeric repeat amplification protocol assay analyses, to
evaluate CDKN2B methylation and telomerase activity, respectively. The results of
the present study demonstrated that, of these 72 children with ALL, 31 exhibited
CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited no CDKN2B methylation
(36.9%). However, no CDKN2B methylation was detected in the ITP controls.
Furthermore, the mean level of telomerase activity was 39.52 +/- 39.33 total
product generated (TPG) units in children with ALL, which was significantly
increased compared with 2.49 +/- 2.27 TPG units in the ITP controls (P=0.002). The
mean levels of telomerase were 49.09 +/- 44.43 and 29.99 +/- 32.43 TPG units in
children with ALL with and without CDKN2B methylation, respectively (P=0.041),
therefore children with ALL exhibited significantly increased levels of telomerase.
The increased telomerase activity was significantly associated with increased risk
of childhood ALL (P=0.023). A total of 22/31 children with ALL with methylated
CDKN2B (71.0%) and 17/41 children with ALL with unmethylated CDKN2B (41.46%)
exhibited increased telomerase activity (>15 TPG units). The results of the present
study suggest that hypermethylation of CDKN2B CpG islands and hyperactivity of
telomerase are common events in childhood ALL, and hypermethylation of CDKN2B CpG
islands was significantly associated with upregulated telomerase activity
(P=0.013).
Intestinal subepithelial myofibroblasts (SEMFs) is a specific population of cells
involved in intestinal inflammation and carcinogenesis via an elaborate network of
cytokines, chemokines and other inflammatory factors, including PGE2. Sphingosine-
1-phosphate (S1P) has been implicated as an important mediator of inflammation and
cancer and in certain cell types increases cyclooxygenase-2 (COX-2) expression. In
the present study, we aimed to assess involvement of S1P in COX-2 expression by
SEMFs. Primary SEMFs were obtained from C57BL/6J mouse and their identity was
verified by fluorescent staining of specific marker proteins. Expression of S1P
receptors 1, 2, 3 and sphingosine kinases 1 and 2 in SEMFs were determined by RT-
PCR analysis. COX-2 expression and PGE2 production were assayed by Western blotting
and ELISA, respectively. COX-2 mRNA stability was assayed by Northern blotting. S1P
produced dose-dependent increase in COX-2 expression, resulting in increased PGE2
release from SEMFs. Using specific inhibitors, we show that actions of p38, ERK,
IKK, and PKC were involved in S1P-induced COX-2 expression. On the other hand, p38
and PKC had lesser roles in IL-1 beta-induced COX-2 expression. Inhibition of
sphingosine kinase to block S1P production did not affect IL-1 beta-induced COX-2
expression, but S1P amplified IL-1 beta-induced p38 activation and COX-2
expression. PKC inhibition blocked S1P amplified COX-2 expression. S1P addition
increased COX-2 mRNA stability. In SEMFs, S1P amplifies IL-1 beta-induced COX-2
expression through increased mRNA stability. These observations point to
involvement of S1P in activation of SEMFs that may contribute to intestinal
inflammation and carcinogenesis.
Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival
of transformed cells. Transforming growth factor beta (TGF-beta) exerts anti-
proliferative effects on a broad range of epithelial cells. In the current study,
we investigated whether TGF-beta can regulate COX-2 expression in A549 human lung
adenocarcinoma cells, which are TGF-beta-responsive and overexpress COX-2.
Materials and Methods Western blotting, Northern blotting, and mRNA stability
assays were performed to demonstrate that COX-2 protein and mRNA expression were
suppressed by TGF-beta. We also evaluated the effects of tristetraprolin (UP) on
COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and
protein expression were both significantly suppressed by TGF-beta. An actinomycin D
chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the
presence of TGF-beta, suggesting that TGF-beta-induced inhibition of COX-2
expression is achieved via decreased mRNA stability. We also found that TGF-beta
rapidly and transiently induced the expression of UP, a well-known mRNA
destabilizing factor, before suppression of COX-2 mRNA expression was observed.
Using RNA interference, we confirmed that increased UP levels play a pivotal role
in the destabilization of COX-2 mRNA by TGF-beta. Furthermore, we showed that Smad3
is essential to UP-dependent down-regulation of COX-2 expression in response to
TGF-beta. Conclusion The results of this study show that TGF-beta down-regulated
COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin (PG)
biosynthesis, plays a key role in inflammation, tumorigenesis, development and
circulatory homeostasis. COX-2 expression is rapidly and sensitively regulated by
various stimuli, and also its regulation is distinct among cell types at
transcriptional and posttranscriptional levels. Therefore, it is important to
consider these features of COX-2 expression in the reporter assays we describe in
this chapter. Emphasis should be made with regard to two points. Firstly, COX-2
reporter assays should be evaluated by intrinsic COX-2 expression, such as RT-PCR,
northern blotting, western blotting, or by PGE(2) measurement. Secondly, one must
carefully choose several conditions in the reporter assays for experimental
purposes.
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other
chemotherapy drugs in the treatment of various types of cancer. It can be used not
only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10
expression and T regulatory cells (Tregs). Fibroblast activation protein alpha (FAP
alpha) is expressed in cancer-associated fibroblasts in the tumor microenvironment.
Immunotherapy based on FAP alpha, as a tumor stromal antigen, typically induces
specific immune response targeting the tumor microenvironment. This study evaluated
the efficacy of a previously unreported CY combination strategy to enhance the
limited anti-tumor effect of a DNA vaccine targeting FAP alpha. The results
suggested CY administration could promote the percentage of splenic CD8(+)T cells
and decrease the proportion of CD4(+)CD25(+)Foxp3(+)Tregs in spleen. In tumor
tissues, levels of immunosuppressive cytokines including IL-10 and CXCL-12 were
also reduced. Meanwhile, the CY combination did not impair the FAP alpha-specific
immunity induced by the DNA vaccine and further reduced tumor stromal factors. Most
importantly, FAP-vaccinated mice also treated with CY chemotherapy showed a marked
suppression of tumor growth (inhibition ratio =80%) and a prolongation of survival
time. Thus, the combination of FAP alpha immunotherapy and chemotherapy with CY
offers new insights into improving cancer therapies.
The retinoic acid metabolizing enzyme Cyp26a1 plays a pivotal role in vertebrate
embryo development. Cyp26a1 was characterized previously as a differentially
expressed gene in peri-implantation rat uteri via suppressive subtracted
hybridization analysis. However, the role of Cyp26a1 in rat embryo implantation
remained elusive. The expression of Cyp26a1 in the uteri of early pregnancy,
pseudopregnancy and artificial decidualization was detected by northern blotting,
real time-PCR, in situ hybridization, western blotting and immunofluorescent
staining. The effect of Cyp26a1 on apoptosis of endometrial stromal cells (ESCs)
isolated from rat uteri was determined by terminal deoxynucleotidyl transferase-
mediated dUTP nick-end labeling (TUNEL) and Hoechst staining. Apoptosis-related
proteins in ESCs were detected by western blotting. Cyp26a1 showed distinctive
expression patterns in embryos and uteri during the peri-implantation period, with
a remarkable increase (P < 0.01 versus Days 4-5) in mRNA and protein in the
implantation phase (Days 5.5-6.5 of pregnancy). CYP26A1 was specifically localized
in glandular epithelium, luminal epithelium and decidua basalis. The level of
CYP26A1 protein was significantly increased in uteri of artificial decidualization
(P < 0.01 versus control). Forced Cyp26a1 overexpression significantly reduced the
sensitivity of ESCs to etoposide-induced apoptosis, with reductions in p53 (P <
0.01) and Fas (P < 0.05) proteins versus control, while in contrast, FasL (P <
0.01) and proliferating cell nuclear antigen (P < 0.05) proteins increased. Cyp26a1
is spatiotemporally expressed in the uterus during embryo implantation and
decidualization. Overexpression of Cyp26a1 attenuates the process of uterine
stromal cell apoptosis, probably via down-regulating the expression of p53 and
FasL.
Introduction: Clopidogrel is an antiplatelet drug widely used in patients with
acute coronary syndromes or stroke. Despite adequate antiplatelet therapy, some
patients develop acute ischemic events. This is partly attributed to the fact that
they have poor inhibition of platelet reactivity, despite treatment. This study
aimed to assess the impact of clinical and demographic variables and of cytochrome
P450 2C19 (CYP2C19) loss-of-function polymorphisms on platelet response to
clopidogrel evaluated using impedance aggregometry in an East European population.
Methods: The study included 189 clopidogrel-treated patients with acute coronary
syndromes and noncardiogenic ischemic stroke. Platelet aggregation was evaluated by
impedance aggregometry. CYP2C19 loss-of-function polymorphisms were detected using
the polymerase chain reaction restriction fragment length polymorphism technique.
Various clinical and demographic data were also recorded. Results: In our data set,
81% of the patients were responders and 19% nonresponders to clopidogrel therapy.
The distribution of CYP2C19 polymorphisms was as follows: 61.1% of patients were
CYP2C19 wild-type homozygotes, 27.7% of patients were CYP2C19*2 heterozygotes, 1.1%
of patients were CYP2C19*3 heterozygotes, and 10% of patients were CYP2C19*2
homozygotes. The highest level of association with clopidogrel response status was
found for CYP2C19 polymorphisms, concomitant aspirin treatment, leukocyte and
platelet count, history of myocardial infarction, arterial hypertension, and ward
where patients were admitted. Conclusion: The prevalence of clopidogrel resistance
in our East European population was in line with that reported for Western
populations. Clopidogrel response was significantly influenced by the presence of
CYP2C19 polymorphisms. Interestingly, the concomitant use of aspirin had a
significant impact on platelet response to clopidogrel, indicating a synergic
interaction between these drugs.
Purpose: Asian populations have around 40-60% frequency of reduced function allele
CYP2D6*10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6
enzyme activities in subjects with the CYP2D6*10 variant is a big concern for
clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme
activity as a result of one CYP2D6*10 allele or two CYP2D6*10 alleles has not been
reported in large Asian populations. Methods: A total of 421 healthy Chinese
subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA
sequencing. A total of 235 subjects with CYP2D6*1/*1 (n = 22), CYP2D6*1/*10 (n =
93), CYP2D6*10/*10 (n = 85), and CYP2D6*5/*10 (n = 35) were phenotyped for CYP2D6
using dextromethorphan as the probe drug. Metabolic ratios (MR) were calculated as
the ratio of parent drug to metabolite in 0-3 h urine, 3 h plasma, and 3 h saliva
for each sample type. Results: The urinary, plasma, or salivary MRs increased
successively in subjects with CYP2D6*1/*1, *1/*10, *10/*10, and *5/* 10 (all P <
0.001). In the normal metabolizer group, homozygous CYP2D6*10/*10 decreased the
CYP2D6 enzyme activity further than heterozygous CYP2D6* 1/* 10. Urinary, plasma,
and salivary MRs were highly correlated. Conclusion: The normal metabolizer group
calls for a more detailed classification. The activity score system could more
accurately predict enzyme activity than by grouping a number of genotypes into a
single phenotype group. Single-point plasma samples and saliva samples could be
used as alternative phenotyping methods for clinical convenience.
Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in
detoxifying insecticides leading to resistance in insect populations. A polyphagous
pest, Spodoptera litura, has developed resistance to a wide range of insecticides.
In the present study, a novel P450 gene, CYP321B1, was cloned from S. litura. The
function of CYP321B1 was assessed using RNA interference (RNAi) and monitoring
resistance levels for three commonly used insecticides, including chlorpyrifos,
beta-cypermethrin and methomyl. The full-length complementary DNA sequence of
CYP321B1 is 1814 bp long with an open reading frame of 1488 bp encoding 495 amino
acid residues. Quantitative reverse-transcriptase polymerase chain reaction
analyses during larval and pupal development indicated that CYP321B1 expression was
highest in the midgut of fifth-instar larvae, followed by fat body and cuticle. The
expression of CYP321B1 in the midgut was up-regulated by chlorpyrifos, beta-
cypermethrin and methomyl with both lethal concentration at 15% (LC15) (50, 100 and
150 mu g/mL, respectively) and 50%(LC50) dosages (100, 200 and 300 mu g/mL,
respectively). Addition of piperonyl butoxide (PBO) significantly increased the
toxicity of chlorpyrifos, beta-cypermethrin and methomyl to S. litura, suggesting a
marked synergism of the three insecticides with PBO and P450-mediated
detoxification. RNAi-mediated silencing of CYP321B1 further increased mortality by
25.6% and 38.9% when the fifth-instar larvae were exposed to chlorpyrifos and beta-
cypermethrin, respectively, at the LC50 dose levels. The results demonstrate that
CYP321B1 might play an important role in chlorpyrifos and beta-cypermethrin
detoxification in S. litura.
Our previous studies have found that the levels of cytochrome P450 and oxidative
activities of cytochrome P450 monooxygenases were enhanced in a fenvalerate-
resistant strain (HDFR) of Helicoverpa armigera (Hubner) in China, comparing with
those of a susceptible strain (HDS). Here, we report the molecular cloning and gene
expression of a specific P450 CYP6B7 from HDFR and HDS strain of H. armigera.
Comparison of the deduced amino acid sequence showed that there were three
substitutions of amino acids in the coding region of CYP6B7 cDNA of HDFR strain,
comparing with that of HDS strain. Meanwhile, there were three mutative nucleotides
in the intron of CYP6B7 genomic DNA in HDFR strain. Northern blotting analysis
showed that the expression of CYP6B7 mRNA in HDFR strain of H. armigera was more
than 5-fold higher than that in HDS strain. Further studies indicated that the
expression of CYP6B7 mRNA increased as the larvae developed; however, it was rarely
detected in the pupae and adult stages. The results suggested that cytochrome P450
CYP6B7 plays an important role in the pyrethroid insecticide fenvalerate resistance
of HDFR strain of H. armigera; over-expression of CYP6B7 combined with relevant
substitution of amino acids might be responsible for fenvalerate-resistance in H.
armigera from China.
Although herpesviruses such as cyprinid herpesvirus 3 (CyHV-3) can establish
lifelong latent infections, little is known about latency conditions in farmed koi
populations in China. We used nested polymerase chain reaction targeting the TK
gene and an indirect antibody ELISA to screen asymptomatic fish obtained from
southern China for evidence of CyHV-3 infection. CyHV-3 DNA could be detected
either in peripheral blood leukocytes or from gills of asymptomatic koi. Most koi
sera did not contain anti-CyHV-3 antibodies; however, 5 samples were ELISA
positive, providing evidence of prior CyHV-3 infections. These findings suggest
that koi may survive CyHV-3 infections and become virus carriers.
Two genotypes showing differential immunity against Karnal bunt (Tilletia indica)
were used to investigate the role of three members of cystatin gene family in
growth stage dependent immunity in wheat (Triticum aestivum L.). Three members of
cystatin gene family (WC1, WC2, and WC4) were cloned and sequenced. Analysis of
sequenced data showed that there was 76-99% nucleotide and protein sequence
identity between different genes of the wheat cystatin. In silico amino acid
sequence analysis revealed the presence of a conserved signature pattern of
residues and also the functional domains were presumed to be actively involved in
imparting cysteine protease inhibition capability. The semi-quantitative and
quantitative levels of these members were measured by means of RT-PCR, northern
blotting, western blotting, and by ELISA techniques. The members of cystatin gene
family were expressed in both resistant (HD 29) and susceptible genotypes (WH 542);
however, the expression level was significantly (P0.05) in contrary to WC1 family
whose expression gradually increased from S-v to S-2 stage. According to the
intensity of the detected band in RT PCR, northern blot and western blot, WC1
family seems to be expressed more than the other gene families. The immunoassay
results further showed that WC1 protein was abundantly expressed in resistant
genotype and high expression was observed at the S2 stage as compared to
susceptible genotype (P < 0.001) suggesting that low level of expression of WC1 in
S2 stage is responsible for KB infection. The results of the present study clearly
indicate the role of cystatin gene family in differential and stage dependent
immunity against KB.
A cysteine protease inhibitor (CPI) with an apparent molecular mass of 11.5 kDa was
purified from larval hemolymph of the tobacco hornworm (Manduca sexta) by gel
filtration on Sephadex G-50 followed by hydrophobic and ion-exchange column
chromatographies. The purified cysteine proteinase inhibitor, denoted as MsCPI,
strongly inhibited the plant cysteine protease, papain, with a K-i value of 5.5 x
10(-9)M. Nucleotide sequence analysis of a partial cDNA encoding MsCPI indicated
that MsCPI consists of 105 amino acid residues in a sequence that is similar to
sarcocystatin A from Sarcophaga peregrina. However, northern blotting and PCR
analyses using the specific primers of MsCPI suggested that the mRNA encoding MsCPI
had a size of more than 12 kilobases, which included at least six tandemly repeated
MsCPI segments. MsCPI was expressed in Escherichia coli and the recombinant protein
effectively inhibited cysteine proteases from plants as well as from animals such
as cathepsins B (K-i, 6.8 nM), H (3.0 nM), and L (0.87 nM). There was no inhibition
exhibited toward trypsin, chymotrypsin, subtilisin, pepsin or themolysin. (c) 2007
Elsevier Ltd. All rights reserved.
The oomycete Phytophthora capsici is a plant pathogen responsible for important
losses to vegetable production worldwide. Its asexual reproduction plays an
important role in the rapid propagation and spread of the disease in the field. A
global proteomics study was conducted to compare two key asexual life stages of P.
capsici, i.e. the mycelium and cysts, to identify stage-specific biochemical
processes. A total of 1200 proteins was identified using qualitative and
quantitative proteomics. The transcript abundance of some of the enriched proteins
was also analysed by quantitative real-time polymerase chain reaction. Seventy-
three proteins exhibited different levels of abundance between the mycelium and
cysts. The proteins enriched in the mycelium are mainly associated with glycolysis,
the tricarboxylic acid (or citric acid) cycle and the pentose phosphate pathway,
providing the energy required for the biosynthesis of cellular building blocks and
hyphal growth. In contrast, the proteins that are predominant in cysts are
essentially involved in fatty acid degradation, suggesting that the early infection
stage of the pathogen relies primarily on fatty acid degradation for energy
production. The data provide a better understanding of P. capsici biology and
suggest potential metabolic targets at the two different developmental stages for
disease control.
Mice homozygous for a defect in the PTCD2 (pentatricopeptide repeat domain protein
2) gene were generated in order to study the role of this protein in mitochondrial
RNA metabolism. These mice displayed specific but variable reduction of ubiquinol-
cytochronic c reductase complex activity in mitochondria of heart, liver and
skeletal muscle due to a decrease in the expression of mitochondrial DNA-encoded
cytochrome b, the catalytic core of the complex. This reduction in mitochondrial
function has a profound effect on the myocardium, with replacement of ventricular
cardiomyocytes by fibro-fatty tissue. Northern blotting showed a reduction in the
mRNA for the mitochondrial DNA encoded proteins cytochrome b (cytb) and ND5 (NADH
dehydrogenase subunit 5) and an elevation in a combined pre-processed ND5-CYTB
transcript. This suggests that the PTCD2 protein is involved in processing RNA
transcripts involving cytochrome b derived from mitochondrial DNA. This defines the
site for PTCD2 action in mammalian mitochondria and suggests a possible role for
dysfunction of this protein in the actiology of heart failure.
Previous studies performed in our laboratory have measured the effect of atrazine
exposure on cytochrome P450-dependent monooxygenase activity and have found
increased activity in midge larvae (Chironomus tentans) as a result of atrazine
exposure (1-10 ppm). Here we report the cloning and expression of a specific C
tentans CYP4 gene that is responsive to atrazine induction with an open reading
frame of 1678 bp which encodes a putative protein of 559 amino acid residues.
Alignments of deduced amino acid sequences with other insect P450 genes and
phylogenetic analysis indicated a high degree of similarity to other insect CYP4
genes. Northern blotting analysis employing a fragment of 1200 bp from the CYP4
gene as a probe indicated that the CYP4 gene was expressed in all developmental
stages, but was expressed at highest levels in late instar larvae. Additionally,
over-expression of CYP4 in C. tentans exposed to atrazine (10 mg/l) confirms the
ability of atrazine to induce specific P450 genes and provides insight into
potential consequences of atrazine exposure in aquatic organisms. (C) 2007 Elsevier
Inc. All rights reserved.
A new cytochrome P450 gene, CYP4G25, was identified as a differentially expressed
gene between the diapausing and post-diapausing pharate first instar larvae of the
wild silkmoth Antheraea yamamai, using subtractive cDNA hybridization. The cDNA
sequence of CYP4G25 has an open reading frame of 1674 nucleotides encoding 557
amino acid residues. Sequence analysis of the putative CYP4G25 protein disclosed
the motif FXXGXRXCXG that is essential for heme binding in P450 cytochromes.
Hybridization in situ demonstrated predominant expression of CYP4G25 in the
integument of pharate first instar larvae. Northern blotting analysis showed an
intensive signal after the initiation of diapause and no or weak expression
throughout the periods of pre-diapause and post-diapause, including larval
development. These results indicate that CYP4G25 is strongly associated with
diapause in pharate first instar larvae. (c) 2008 Elsevier Ltd. All rights
reserved.
A novel cytochrome P450, CYP4x1, was identified in EST databases on the basis of
similarity to a conserved region in the C-helix of the CYP4A family. The human and
mouse CYP4x1 cDNAs were cloned and found to encode putative cytochrome P450
proteins. Molecular modelling of CYP4x1 predicted an unusual substrate binding
channel for the CYP4 family. Expression of human CYP4x1 was detected in brain by
EST analysis, and in aorta by northern blotting. The mouse cDNA was used to
demonstrate that the Cyp4x RNA was expressed principally in brain, and at much
lower levels in liver; hepatic levels of the Cyp4x1 RNA were not affected by
treatment with the inducing agents phenobarbital, dioxin, dexamethasone or
ciprofibrate, nor were the levels affected in PPAR alpha-/- mice. A specific
antibody for Cyp4x1 was developed, and shown to detect Cyp4x1 in brain;
quantitation of the Cyp4x1 protein in brain demonstrated approximate to 10 ng of
Cyp4x1 protein.mg(-1) microsomal protein, showing that Cyp4x1 is a major brain
P450. Immunohistochemical localization of the Cyp4x1 protein in brain showed
specific staining of neurons, choroids epithelial cells and vascular endothelial
cells. These data suggest an important role for Cyp4x1 in the brain.
CYP1B1 is a cytochrome P450 enzyme implicated in autosomal recessive primary
congenital glaucoma (PCG). The mechanism and function of CYP1B1 in the development
of the PCG phenotype is unknown. Previously, investigators have reported detection
of Cyp1b1 mRNA in the ciliary body and epithelium and neuroepithelium in the
developing mouse eye, employing in situ hybridization techniques. Similarly,
additional investigators have detected CYP1B1 mRNA in the iris, ciliary body, non-
pigmented ciliary epithelial line, cornea, retinal-pigment epithelium, and retina
in the human adult eye, using Northern blotting. This study was designed to
immunolocalize CYP1B1 protein in the various ocular structures of normal, human
fetal and adult eyes. Normal fetal and adult eyes were irrimunolabeled with a
polyclonal antibody against human CYP1B1 using indirect immunofluorescence, and
then compared with appropriate controls. The intensity of immunolabeling of the
various ocular structures was assessed by qualitative and semi-quantitative
techniques. In the anterior segment anti-CYP1B1 immunoreactivity (IR) was detected
early in fetal development in the primitive ciliary epithelium. As well, the most
intense CYP1B1 IR was in the non-pigmented ciliary epithelium. In addition, CYP1B1
IR was also present in the corneal epithelium and keratocytes, both layers of the
iris pigmented epithelium, and retina. However, CYP1B1 IR was absent in the
trabecular meshwork in all of the samples. In general, CYP1B1 immunolabeling in the
human fetal eyes was more intense when compared to adult eyes. CYP1B1 IR was
primarily immunolocalized to the non-pigmented ciliary epithelium and early in
fetal development. In addition, CYP1B1 IR was not detected in the trabecular
meshwork. These findings suggest that the abnormalities in the development of the
trabecular meshwork in PCG may result from diminished or absent metabolism of
important endogenous substrates in the ciliary epithelium due to non-functional
CYP1B1 enzyme. (C) 2005 Elsevier Ltd. All rights reserved.
Objectives: The expression patterns of cytokeratin (CK) filaments in human
epithelial neoplasms are complex and distinctive. The aims of this study were to
analyze CK expression and to evaluate the diagnostic application of CKs in human
non-small cell lung cancer (NSCLC). Methods: mRNA expression of CK5, CK6, CK14,
CK15, CK17, and CK19 was analyzed by Northern blotting. Protein expression of
CK5/6, CK7, CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue
microarrays. Results: Northern blotting showed that CKs were highly expressed in
human bronchial epithelial cells and/or small airway epithelial cells. In NSCLC
cell lines, the expression pattern of CKs was heterogeneous. Regarding protein
expression of CKs in 95 primary lung tumors, expression of CK5/6, CK14, and CK17
proteins was increased in squamous cell carcinomas compared to adenocarcinomas
(ADC; p = 0.001, p = 0.030, and p = 0.001, respectively), and higher expression was
significantly associated with lower grading (p = 0.006, p = 0.002, and p = 0.001,
respectively), while increased expression of CK7 and CK18 was observed in ADC (p =
0.001, respectively). Conclusions: Our data suggest that CK5/6, CK7, CK14, CK17,
and CK18 have diagnostic value in the subclassification of NSCLC. Copyright (C)
2011 S. Karger AG, Basel
Streptococcus mutans, the primary etiologic agent of dental caries, can gain access
to the bloodstream and has been associated with cardiovascular disease. However,
the roles of S.mutans in inflammation in cardiovascular disease remain unclear. The
aim of this study was to examine cytokine production induced by S.mutans in human
aortic endothelial cells (HAECs) and to evaluate the participation of toll-like
receptors (TLRs) and cytoplasmic nucleotide-binding oligomerization domain (NOD) -
like receptors in HAECs. Cytokine production by HAECs was determined using enzyme-
linked immunosorbent assays, and the expression of TLRs and NOD-like receptors was
evaluated by real-time polymerase chain reaction, flow cytometry and
immunocytochemistry. The involvement of TLR2 and NOD2 in cytokine production by
invaded HAECs was examined using RNA interference. The invasion efficiencies of
S.mutans strains were evaluated by means of antibiotic protection assays. Five of
six strains of S.mutans of various serotypes induced interleukin-6, interleukin-8
and monocyte chemoattractant protein-1 production by HAECs. All S.mutans strains
upregulated TLR2 and NOD2 mRNA levels in HAECs. Streptococcus mutans Xc upregulated
the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and
NOD2 genes in HAECs invaded by S.mutans Xc led to a reduction in interleukin-6,
interleukin-8 and monocyte chemoattractant protein-1 production. Cytokine
production induced by invasive S.mutans via intracellular TLR2 and NOD2 in HAECs
may be associated with inflammation in cardiovascular disease.
Background: TNF and its receptors TNF-Receptor 1 (TNFR1, CD120a) and TNF-Receptor 2
(TNFR2, CD120b) have been implicated in the rejection of transplanted cells and
organs. Although pig TNFR1 (pTNFR1) is known to mediate the effects of human TNF in
a xenogeneic setting, it is unclear whether pig TNFR2 (pTNFR2) could contribute to
xenograft rejection. Methods: We have cloned the cDNA of various pTNFR2 variants by
reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of
cDNA ends. We have characterized the predicted proteins with bioinformatic tools
and conducted expression, affinity, and functional studies to investigate their
roles. Results: We have identified four isoforms of pTNFR2: one comprising the four
cysteine-rich domains (CRD) conserved between species, a shorter variant (pTNFR2
Delta E7-10) encoding for a soluble isoform, another with only three CRD due to the
lack of exon 4 (pTNFR2 Delta E4), and a fourth variant containing both
modifications. Accordingly, multiple mRNA transcripts were observed by northern
blotting. Quantitative RT-PCR determined high pTNFR2 expression in lung and immune
cells and detected the two alternative splicings in all cells/tissues examined. The
full receptor was moderately expressed on the surface of pig cells such as porcine
aortic endothelial cells and PK-15 and was regulated by TNF. On the contrary, the
membrane-bound pTNFR2 Delta E4 was located only intracellularly. Plasmon resonance
studies showed that pTNFR2 binds pig and human TNF alpha with high affinity, but
pTNFR2 Delta E4 interacts poorly with pig TNF alpha and does not bind to the human
cytokine. Moreover, pull-down experiments with the two recombinant soluble isoforms
consistently demonstrated that the two bound together and soluble pTNFR2 Delta E4
was able to modulate the TNF inhibitory activity of pTNFR2-GST in a cell-based
assay. Conclusion: The pTNFR2 may participate in the process of xenograft rejection
and other related events, as well as be used in soluble form to block TNF in this
setting. In addition, we have discovered other pTNFR2 isoforms that may affect the
pig immune responses and have an impact on rejection of xenografts.
Objectives To determine the effects of dental implant surface chemistry and energy
on macrophage activation invitro. Materials and Methods Disks made from two
clinically used implant materials (titanium [Ti], titanium zirconium alloy [TiZr])
were produced with two different surface treatments (sandblast/acid-etch [SLA],
hydrophilic-SLA [modSLA]). Surface roughness, energy, and chemistry were
characterized. Primary murine macrophages were isolated from 6- to 8-week-old male
C57Bl/6 mice and cultured on test surfaces (Ti SLA, TiZr SLA, Ti modSLA, TiZr
modSLA) or control tissue culture polystyrene. mRNA was quantified by quantitative
polymerase chain reaction after 24h of culture. Pro- (IL-1, IL-6, and TNF-) and
anti-inflammatory (IL-4, IL-10) protein levels were measured by ELISA after 1 or
3days of culture. Results Quantitatively, microroughness was similar on all
surfaces. Qualitatively, nanostructures were present on modSLA surfaces that were
denser on Ti than on TiZr. modSLA surfaces were determined hydrophilic (high-energy
surface) while SLA surfaces were hydrophobic (low-energy surface). Cells on high-
energy surfaces had higher levels of mRNA from anti-inflammatory markers
characteristic of M2 activation compared to cells on low-energy surfaces. This
effect was enhanced on the TiZr surfaces when compared to cells on Ti SLA and Ti
modSLA. Macrophages cultured on TiZr SLA and modSLA surfaces released more anti-
inflammatory cytokines. Conclusions The combination of high-energy and altered
surface chemistry present on TiZr modSLA was able to influence macrophages to
produce the greatest anti-inflammatory microenvironment and reduce extended pro-
inflammatory factor release.
Background and ObjectiveOver the last 10 years, bioactive plant food compounds have
received considerable attention in regard to their beneficial effects against
periodontal disease. In this study, we investigated the effects of black tea
theaflavins (TFs) on the virulence properties of Porphyromonas gingivalis and
gingival keratinocyte tight junction integrity. In addition, the effects of black
tea TFs on the nuclear factor-B (NF-B) signaling pathway and proinflammatory
cytokine/matrix metalloproteinase (MMP) secretion by monocytes/macrophages were
assessed. Material and MethodsVirulence factor gene expression in P. gingivalis was
investigated by quantitative real-time PCR. A fluorescence assay was used to
determine P. gingivalis adherence to, and invasion of, a gingival keratinocyte
monolayer. Tight junction integrity of gingival keratinocytes was assessed by
determination of transepithelial electrical resistance. Proinflammatory cytokine
and MMP secretion by P. gingivalis-stimulated macrophages was quantified by ELISA.
The U937-3xB-LUC monocyte cell line transfected with a luciferase reporter gene was
used to monitor NF-B activation. Gelatin degradation was monitored using a
fluorogenic assay. ResultsBlack tea TFs dose-dependently inhibited the expression
of genes encoding the major virulence factors of P. gingivalis and attenuated its
adherence to gingival keratinocytes. A treatment of gingival keratinocytes with
black tea TFs significantly enhanced tight junction integrity and prevented P.
gingivalis-mediated tight junction damage as well as bacterial invasion. Black tea
TFs reduced the secretion of interleukin (IL)-1, tumor necrosis factor-, IL-6,
chemokine (C-X-C) ligand 8, MMP-3, MMP-8 and MMP-9 by P. gingivalis-stimulated
macrophages and attenuated the P. gingivalis-mediated activation of the NF-B
signaling pathway. Lastly, black tea TFs inhibited gelatin degradation by MMP-9.
ConclusionThis study provides clear evidence that black tea TFs represent promising
multifunctional therapeutic agents for prevention and treatment of periodontal
disease.
Melanoma is the leading cause of death among all skin cancers and its incidence
continues to rise rapidly worldwide in the past decades. The available treatment
options for melanoma remain limited despite extensive clinical research. Melanoma
is an immunogenic tumor and great advances in immunology in recent decades allow
for the development of immunotherapeutic agents against melanoma. In recent years,
immunotherapy utilizing cytokines has been particularly successful in certain
cancers and holds promise for patients with advanced melanoma. In this review, an
overview of the current status and emerging perspectives on cytokine immunotherapy
for melanoma are discussed in details. Such a study will be helpful to unveil the
mysterious mask of cytokine-based immunotherapy for melanoma. (C) 2017 Elsevier
B.V. All rights reserved.
ObjectiveTo conduct a systematic review and meta-analysis of studies that measured
cytokine and chemokine levels in individuals with major depressive disorder (MDD)
compared to healthy controls (HCs). MethodThe PubMed/MEDLINE, EMBASE, and PsycINFO
databases were searched up until May 30, 2016. Effect sizes were estimated with
random-effects models. ResultEighty-two studies comprising 3212 participants with
MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6),
tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine
ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF
receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-
gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1, IL-
2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and
transforming growth factor-beta 1 were not significantly altered in individuals
with MDD compared to HCs. Heterogeneity was large (I-2: 51.6-97.7%), and sources of
heterogeneity were explored (e.g., age, smoking status, and body mass index).
ConclusionOur results further characterize a cytokine/chemokine profile associated
with MDD. Future studies are warranted to further elucidate sources of
heterogeneity, as well as biosignature cytokines secreted by other immune cells.
Objective: Interleukin-10 (IL-10) is a pleiotropic cytokine with either
immunosuppressive or immunostimulative activities. It has been reported that in
cancer, the promoter region polymorphism of IL-10 (-A592C) alters both the
expression and serum levels of this cytokine. In the present study, we have
addressed the question as to whether the single nucleotide polymorphisms (SNPs) at
positions -592 A/C in the IL-10 gene promoter, could predispose an individual to
oral squamous cell carcinoma (OSCC). Design: We analyzed the genotype of the IL-10
(-A592C) gene, in 250 histopathologically confirmed OSCC patients and similar
number of healthy volunteers taken as controls, in an Indian population by using
polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
method. Allele and genotype frequencies were analyzed by the Student's t-test and
the chi-squared test, and strength of associations by the odds ratio (OR) with 95%
confidence intervals. Results: The genotype and allele distribution of IL-10 (-
A592C) gene polymorphism was significantly different between OSCC cases and
controls (genotype AA vs AC: OR 2.87; 95 % CI 1.50-5.48; p = 0.0016 and AA vs CC:
OR 4.08; 95 % CI 1.98-8.41; p = 0.0002). The -592 C alleles were found to be
significantly different among OSCC cases and controls (OR: 1.44, 95% CI: 1.12-1.85,
p < 0.0051). Conclusions: The IL-10 gene promoter region (-592) A/C polymorphism is
significantly associated with reduced risk of OSCC. The OSCC group had a
significantly greater frequency of genotype AA as compared to control group. (C)
2017 Elsevier Ltd. All rights reserved.
Mesangial re-modeling and mesangial cell (MC) migration are features of several
glomerular diseases including mesangiocapillary glomerulonephritis. In vitro
investigations have recently identified ADAM-15, a multidomain adamalysin, as
central to the migration of MC. The current study used array technology to
investigate the expression of other genes in migrating cells and identified
pleiotrophin (PTN), platelet-derived growth factor alpha polypeptide chain, colony
stimulating factor, and four members of the tumor necrosis factor-alpha superfamily
as major genes that were upregulated. Transcriptional induction of PTN was
confirmed by reverse transcription-polymerase chain reaction and Northern blotting
and induction of the protein by Western blotting and immunohistochemical
localization. PTN was observed associated with mesangial 'hillocks' in confluent MC
cultures. In contrast, in models of migration, migrating cells had the highest
expression of cell-associated PTN. PTN protein was less evident, however, in the
conditioned medium of MCs. Treatment of MC with heparanase removed PTN from the
cells suggesting that its localization was owing to an association with heparan
sulfates on the cell surface or in the extracellular matrix. This is the first
description of the expression of PTN by human MCs and the data suggest that it is
rapidly induced in cells that are triggered to migrate. The result of this
induction is currently under investigation.
The highly orchestrated transcriptional and metabolic reprogramming during
activation drastically transforms the main functions and physiology of human
macrophages across the polarization spectrum. Lipids, for example, can modify
protein function by acting remotely as signaling molecules but also locally by
altering the physical properties of cellular membranes. These changes play key
roles in the functions of highly plastic immune cells due to their involvement in
inflammation, immune responses, phagocytosis and wound healing processes. We report
an analysis of major membrane lipids of distinct phenotypes of resting (M0),
classically activated (M1), alternatively activated (M2a) and deactivated (M2c)
human monocyte derived macrophages from different donors. Samples were subjected to
supercritical fluid chromatography-ion mobility-mass spectrometry analysis, which
allowed separations based on lipid class, facilitating the profiling of their fatty
acid composition. Different levels of arachidonic acid mobilization as well as
other fatty acid changes were observed for different lipid classes in the distinct
polarization phenotypes, suggesting the activation of highly orchestrated and
specific enzymatic processes in the biosynthesis of lipid signaling molecules and
cell membrane remodeling. Thromboxane A2 production appeared to be a specific
marker of M1 polarization. These alterations to the global composition of lipid bi-
layer membranes in the cell provide a potential methodology for the definition and
determination of cellular and tissue activation states. (C) 2016 Elsevier Inc. All
rights reserved.
It is possible that during long lasting chronic infections such as tuberculosis
(TB) and leprosy individuals who generate a stronger immune response will produce a
chronic shift in the systemic levels of inflammatory proteins. Consequently, the
systemic immunological shift could affect inflammatory responses against other
persistent pathogens such as Porphyromonas gingivalis associated with periodontal
disease (PD). ObjectiveTo determine if in vitro exposure to Mycobacterium
tuberculosis or M. leprae lysates impacts subsequent immune responses to P.
gingivalis; and to propose a new dialogue between experimental immunology and
paleopathology. Material and methodsWe sequentially (2 days protocol) exposed
peripheral blood mononuclear cells (PBMCs) from healthy donors to bacterial lysates
either from M. tuberculosis, or M. leprae, or P. gingivalis. After collecting all
supernatants, we measured the expression of immune proteins TNF and IFN using an
enzyme-linked immunosorbent assay. ResultsEarly exposure (day 1) of PBMCs to M.
leprae or M. tuberculosis lysates induces an inflammatory shift detected by the
increase of TNF and IFN when the same cells are subsequently (day 2) exposed to
oral pathogen P. gingivalis. DiscussionBy extrapolating these results, we suggest
that chronic infections, such as TB and leprosy, could generate a systemic
immunological shift that can affect other inflammatory processes such the one
present in PD. We propose that the presence and severity of PD should be explored
as a proxy for inflammatory status or competence when reconstructing the health
profile in past populations.
Matrix metalloproteinases (MMPs) degrade collagen and mediate tissue remodeling.
The novel cytokine IL-17 is expressed during various inflammatory conditions and
modulates MMP expression. We investigated the effect of IL-17 on MMP-1 expression
in primary human cardiac fibroblasts (HCF) and delineated the signaling pathways
involved. HCF were treated with recombinant human IL-17. MMP-1 expression was
analyzed by Northern blotting, RT-quantitative PCR, Western blotting, and ELISA;
transcriptional induction and transcription factor binding by EMSA, ELISA, and
reporter assay; and p38 MAPK and ERK1/2 activation by protein kinase assays and
Western blotting. Signal transduction pathways were investigated using
pharmacological inhibitors, small interfering RNA (siRNA), and adenoviral dominant-
negative expression vectors. IL-17 stimulated MMP-1 gene transcription, net mRNA
levels, protein, and promoter-reporter activity in HCF. This response was blocked
by IL-17 receptor- Fc chimera and IL-17 receptor antibodies, but not by IL-6, TNF-
alpha, or IL-1 beta antibodies. IL-17-stimulated type I collagenase activity was
inhibited by the MMP inhibitor GM-6001 and by siRNA-mediated MMP-1 knockdown. IL-17
stimulated activator protein-1 [AP-1 (c-Fos, c-Jun, and Fra-1)], NF-kappa B (p50
and p65), and CCAAT enhancer-binding protein (C/EBP)-beta DNA binding and reporter
gene activities, effects attenuated by antisense oligonucleotides, siRNA-mediated
knockdown, or expression of dominant-negative signaling proteins. Inhibition of AP-
1, NF-kappa B, or C/EBP activation attenuated IL-17-stimulated MMP-1 expression.
IL-17 induced p38 MAPK and ERK1/2 activation, and inhibition by SB-203580 and PD-
98059 blunted IL-17-mediated transcription factor activation and MMP-1 expression.
Our data indicate that IL-17 induces MMP-1 in human cardiac fibroblasts directly
via p38 MAPK- and ERK-dependent AP-1, NF-kappa B, and C/EBP-beta activation and
suggest that IL-17 may play a critical role in myocardial remodeling.
We examined whether tumor necrosis factor-alpha (TNF-alpha) promotes postischemic
inflammation and myocardial injury via activation of nuclear factor kappa B (NF
kappa B) in an in vivo canine model. Isoflurane-anesthetized dogs underwent closed-
chest balloon occlusion of the anterior descending coronary artery for 90 minutes,
followed by reperfusion for 3 hours. Dogs randomly received a soluble TNF inhibitor
(etanercept, 0.5 mg/kg intravenously) or saline before occlusion. Collateral blood
flow and risk region size (RISK) were measured with radioactive microspheres,
infarct size (INF) was measured by triphenyltetrazolium chloride staining,
inflammation was measured by tissue mycloperoxidase (MPO) activity, intercellular
adhesion molecular-1 (ICAM-1) messenger ribonucleic acid (mRNA) was measured by
Northern blotting, and ICAM-1 protein expression was measured by Western blotting.
NF kappa B activation was measured in nuclear extracts by electrophoretlic mobility
shift assays. INF/RISK was significantly smaller in the etanercept group than in
the saline control group after adjusting for collateral flow (P < 0.009 by analysis
of covariance, mean reduction in INF/RISK = 40%, 0.32 +/- 0.09 versus 0.53 +/-
0.09). MPO activity, ICAM-1 mRNA and protein expression, and NF kappa B binding
activity were all significantly reduced in the etanercept group. Administration of
a soluble TNF-a inhibitor reduced NF kappa B activation, ICAM-1 upregulation, and
myocardial injury following ischemia-reperfusion. TNF-a appears to play a
significant role in vivo in the genesis of postischemic inflammation.
Purpose: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus
(CMV) anterior uveitis in a tertiary uveitis referral center in Brussels, Belgium.
Methods: A retrospective study of patients with a clinical diagnosis of CMV
anterior uveitis/endotheliitis demonstrated by a positive polymerase chain reaction
and/or Goldmann-Witmer coefficient (GWc). Results: We report a series of 15
patients presenting clinical characteristics of CMV anterior uveitis. Patients had
a pretreatment follow-up of 13.00 +/- 12.78 months and a posttreatment follow-up of
42.64 +/- 31.23 months. The 14 non-Asian patients (93.3%) had clinical
characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%)
had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation,
uveitis was unilateral in all patients, visual acuity (VA) was 0.91 +/- 0.25, and
all patients had an increased intraocular pressure (IOP), with a mean IOP of 41.40
+/- 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had glaucoma, 2
needed glaucoma surgery (13.3%). The mean final VA was 0.93 +/- 0.11; 13 patients
(86.5%) reached a final VA of 0.7 to 1. Patients had a significantly lower number
of recurrences/year posttreatment (0.76 +/- 0.57) than in the pretreatment period
(3.76 +/- 2.44) (P = 0.001). The mean time to recurrence increased from 4.03 months
before treatment to 12.58 months after treatment (P = 0.003). Conclusion: Our
results suggest that patients treated with 0.15% topical ganciclovir have a
decreased frequency of CMV anterior uveitis recurrences, most preserve a relatively
good central vision over time. However, glaucoma is a frequent and severe
complication.
Background. Systemic reactivations of herpesviruses may occur in intensive care
unit (ICU) patients, even in those without prior immune deficiency. However, the
clinical relevance of these events is uncertain. Methods. In this study we selected
patients admitted with septic shock and treated for more than 4 days from a
prospectively enrolled cohort of consecutive adults in the mixed ICUs of 2 tertiary
care hospitals in the Netherlands. We excluded patients who had received antiviral
treatment in the week before ICU admission and those with known immunodeficiency.
We studied viremia episodes with cytomegalovirus (CMV), Epstein-Barr virus (EBV),
human herpesvirus 6 (HHV-6), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2),
and varicella zoster virus (VZV) by weekly polymerase chain reaction in plasma.
Results. Among 329 patients, we observed 399 viremia episodes in 223 (68%)
patients. Viremia with CMV, EBV, HHV-6, HSV1, HSV-2, and VZV was detected in 60
(18%), 157 (48%), 80 (24%), 87 (26%), 13 (4%), and 2 (0.6%) patients, respectively;
112 (34%) patients had multiple concurrent viremia events. Crude mortality in the
ICU was 36% in this latter group compared to 19% in remaining patients (P < .01).
After adjustment for potential confounders, time-dependent bias, and competing
risks, only concurrent CMV and EBV reactivations remained independently associated
with increased mortality (adjusted subdistribution hazard ratio, 3.17; 95%
confidence interval, 1.41-7.13). Conclusions. Herpesvirus reactivations were
documented in 68% of septic shock patients without prior immunodeficiency and
frequently occurred simultaneously. Concurrent reactivations could be independently
associated with mortality.
Background: Viruses and atypical pathogens can cause significant respiratory
illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR)
has improved the diagnostic yield of pathogens, and it is easier to identify the
co-infections also. The present study was done to evaluate the performance of MPCR
on bronchoalveolar lavage (BAL) samples in immunocompromised patients. Methods: A
total of 177 BAL specimens collected over a 19 months period from immunocompromised
patients with respiratory illness were analyzed with the MPCR and aerobic culture.
Patients were divided into four according to the pathogens. Category V (only
viral), Category NV (nonviral, i. e., bacteria and atypical), Category M (mixed, i.
e., both viral and nonviral pathogen), and Category UK (unknown etiology). Results:
MPCR identified the causative pathogen in 59.3% of patients while culture could
identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella
pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii
(10%). Numbers of patients in each category were Category V (9.6%), Category NV
(43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly
higher in patients of Category M having mixed infections. Conclusion: MPCR is
highly sensitive and rapid tool which can be considered in the routine diagnostic
algorithm of respiratory illness in immunocompromised patients.
The transcriptional patterns of mitochondrial respiratory related genes were
investigated in cytoplasmic male-sterile and fertile maintainer lines of stem
mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of
NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel
open reading frame, hereafter named orfB gene, was located at the downstream of
mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with
YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana
tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis
thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220
gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified by
primers of nad2F and nad2R from CMS) were found in the CMS line following Southern
blotting digested with HindIII, but only a single copy in its maintainer line.
Meanwhile, two transcripts were shown in the CMS line following Northern blotting
while only one transcript was detected in the maintainer line, which were probed by
specific fragment (amplified by primers of nad2F and nad2R from CMS). Meanwhile,
the expression of nad2 gene was reduced in CMS bud compared to that in its
maintainer line. We thus suggested that nad2 gene may be co-transcripted with CMS-
associated orfB gene in the CMS. In addition, the specific fragment that was
amplified by primers of nad2F and nad2R just spanned partial sequences of nad2 gene
and orfB gene. Such alterations in the nad2 gene would impact the activity of NADH
dehydrogenase, and subsequently signaling, inducing the expression of nuclear genes
involved in male sterility in this type of cytoplasmic male sterility.
Purpose: To evaluate the effect of fractionated irradiation (FI) on tumor cells'
sensitivity to ionizing radiation (IR) and antineoplastic drugs, and examine the
potential of early growth response-1 (EGR-1) inhibition to sensitize tumor cells to
IR. Materials and methods: PC3 and HepG2 cells were subjected 10 times to gamma-
rays at 2 Gy. The surviving cells were named PC3/R and HepG2/R, respectively. The
cells' sensitivity to irradiation and chemotherapeutic drugs, including cisplatin
(PT), doxorubicin (DOX), mitomycin C (MMC) and 5-fluorouracil (5-FU), were
identified by colony formation assay and MMT method, respectively. Quantitative
real-time polymerase chain reaction (RT-qPCR) analysis was utilized to compare the
difference of gene expression between radioresistant cells and parental cells. The
small interfering RNA system was implemented to inhibit endogenous EGR-1 expression
in radiation-resistant cells. Western blot was employed to identify the possible
mechanism by which EGR-1 regulates cells' radiosensitivity. Results: FI induced
cross-resistant to IR and MMC in tumor cells. Along with the reduction of ovarian
cancer-2/disabled homolog 2 (DOC-2/DAB2) interactive protein (DAB2IP) expression,
EGR-1 gene was upregulated in FI-treated cells. On the other hand, downregulation
of EGR-1 gene expression sensitized radioresistant cells to IR accompanied by
DAB2IP overexpression and STAT3 inactivation. In addition, NF-kappa B inhibitor,
BAY11-7082 enhanced resistant cells' radiosensitivity and chemosensitivity.
Conclusions: Conventionally FI has a higher risk of forming acquired
radioresistance (ARR) in vitro. EGR-1 gene-targeted drug design could be an
effective strategy to overcome DAB2IP-dysregulation-induced ARR in tumor patients.
Tomato spotted wilt virus (TSWV) causes significant losses in the production of the
ornamental plant Dahlia variabilis in Japan. The purpose of this study was to
examine the distribution of TSWV in dahlia plants and identify plant parts that can
be used in the selection of TSWV-free plants. The distribution of TSWV was
investigated using reverse transcriptional polymerase chain reaction (RT-PCR) and
tissue blot immunoassay. The detection rate of TSWV in latent infected compound
leaves was the highest in the petiole, and it decreased from the veins and rachis
to the lamina. The tissue blot immunoassays of the leaflets showed an uneven
distribution of TSWV, especially along the edge of the leaf blade. In stems, the
detection rate of TSWV was high partway up the stem compared to that in the upper
and the lower parts of the stem during the vegetative growth stage. A highly uneven
distribution was observed in the bulb. Our results indicated that middle parts of
the stem as well as the petioles, rachis, and veins of compound leaves are suitable
for detection of TSWV in dahlias. This study is the first to report uneven
distribution of TSWV in dahlia plants.
Metabolic imbalance impairs fertility, because changes in concentrations of
metabolites and hormones in the blood and follicular fluid create an unfavourable
environment for early embryonic development. Insulin is a key metabolic hormone
known for its effects on fertility: insulin concentrations are increased during
energy balance disturbances in diabetes or metabolic syndrome. Still, insulin is
frequently used at supraphysiological concentrations for embryo in vitro culture
with unknown consequences for the developmental potential of the offspring. In the
present study we investigated the effects of insulin exposure during in vitro
bovine oocyte maturation on developmental rates, embryo quality and gene
expression. Supplementation of the maturation media with insulin at 10 or 0.1 mu
gmL(-1) decreased blastocyst rates compared with an insulin-free control (19.8 +/-
1.3% and 20.4 +/- 1.3% vs 23.8 +/- 1.3%, respectively; P<0.05) and led to increased
cell numbers (nearly 10% more cells on Day 8 compared with control; P<0.05).
Transcriptome analysis revealed significant upregulation of genes involved in lipid
metabolism, nuclear factor (erythroid-derived 2)-like 2 (NRF2) stress response and
cell differentiation, validated by quantitative polymerase chain reaction. To
conclude, the results of the present study demonstrate that insulin exposure during
in vitro oocyte maturation has a lasting effect on the embryo until the blastocyst
stage, with a potential negative effect in the form of specific gene expression
perturbations.
Background: A combined supplement of vitamins B9 and B12 was reported to increase
milk and milk component yields of dairy cows without effect on feed intake. The
present study was undertaken to verify whether this supplementation positively
modifies the pathways involved in milk and milk component synthesis. Thus, by
studying the transcriptome activity in these tissues, the effect of supplements of
both vitamins on the metabolism of both liver and mammary gland, was investigated.
For this study, 24 multiparous Holstein dairy cows were assigned to 6 blocks of 4
animals each according to previous 305-day milk production. Within each block, cows
were randomly assigned to weekly intramuscular injections of 5 mL of either saline
0.9 % NaCl, 320 mg of vitamin B9, 10 mg of vitamin B12 or a combination of both
vitamins (B9 + B12). The experimental period began 3 weeks before the expected
calving date and lasted 9 weeks of lactation. Liver and mammary biopsies were
performed on lactating dairy cows 64 +/- 3 days after calving. Samples from both
tissues were analyzed by microarray and qPCR to identify genes differentially
expressed in hepatic and mammary tissues. Results: Microarray analysis identified
47 genes in hepatic tissue and 16 genes in the mammary gland whose expression was
modified by the vitamin supplements. Gene ontology (GO) categorizes genes in non-
overlapping domains of molecular biology. Panther is one of the online GO resources
used for gene function classification. It classifies the 63 genes according to
Molecular Function, Biological Process and Protein Class. Most of the biological
processes modulated by the vitamin supplements were associated to developmental
process, protein metabolic process, transport and response to inflammation. In the
liver, most of the genes modulated by the vitamin treatments involved protein
metabolic process while developmental process appeared to be more affected by the
treatments in mammary gland. Out of 25 genes analysed by qPCR, 7 were validated.
Conclusion: The results indicate that several metabolic processes were modulated by
the supplementation of vitamins in early-lactating dairy cows. In addition, the
results suggest that the vitamin supplements promoted liver regeneration and
reduced catabolism of lipids in early lactation.
In this study, we evaluated whether quantitative PCR (qPCR) and reverse
transcription-qPCR (RT-qPCR) results could be affected by extracellular (free) DNA
or RNA, respectively, obtained either from isolated bacteria or from fermented
dairy foods manufactured with these microorganisms. These experimental set-ups
involved two starter lactic acid bacteria (SLAB), Streptococcus thermophilus and
Lactococcus lactis, as models across their most common technological environments:
yoghurt, milk and cheese. The presence of free DNA modified qPCR results in levels
sufficient to bias SLAB determinations, indicating that DNA may be a poor measure
of cellular integrity. Furthermore, we showed for the first time that an order of
magnitude more of free RNA than of DNA had to be used to modify RT-qPCR results.
Importantly, the interference produced by free DNA and RNA was maintained across
all the dairy matrices evaluated, independently of the SLAB and of the source of
nucleic acids used, in both negative and positive samples. This study suggests
that, contrary to DNA molecules, mRNA from dead microorganisms or from other
extracellular sources may not be a determinant factor in skewing molecular
quantifications. Therefore, our results support the potential use of mRNA as a
molecular signature of cell integrity in dairy matrices. (C) 2017 Elsevier Ltd. All
rights reserved.
Environmental managers in the United States and elsewhere are increasingly
perceiving dam removal as a critical tool for river restoration and enhancing
watershed resilience. In New England, over 125 dams have been dismantled for
ecological and economic rationales. A surprising number of these removals,
including many that are ongoing, have generated heated conflicts between
restoration proponents and local communities who value their dammed landscapes.
Using a comparative case study approach, we examine the environmental conflict
around efforts to remove six dams in New England. Each of these removal efforts
followed quite different paths and resultant outcomes: successful removal, stalled
removal, and failure despite seemingly favorable institutional conditions. Lengthy
conflicts often transpired in instances where removals occurred, but these were
successfully arbitrated by paying attention to local historical-geographical
conditions conducive to removal and by brokering effective compromises between dam
owners and the various local actors and stakeholders involved in the removal
process. Yet our results across all cases suggest that these are necessary, but not
sufficient conditions for restoration through dam removal since a similar set of
conditions typified cases where removals are continuously stalled or completely
halted. Scholars examining the intersection between ecological restoration and
environmental politics should remain vigilant in seeking patterns and generalities
across cases of environmental conflict in order to promote important biophysical
goals, but must also remain open to the ways in which those goals are thwarted and
shaped by conflicts that are deeply contingent on historical-geographical
conditions and broader institutional networks of power and influence.
DAMPE (DArk Matter Particle Explorer) is a scientific satellite which is mainly
aimed at indirectly searching for dark matter in space. One critical sub-detector
of the DAMPE payload is the BGO (bismuth germanium oxide) calorimeter, which
contains 1848 PMT (photomultiplier tube) dynodes and 16 FEE (Front-End Electronics)
boards. VA160 and VATA160, two 32-channel low power ASICs (Application Specific
Integrated Circuits), are adopted as the key components on the FEEs to perform
charge measurement for the PMT signals. In order to monitor the parameter drift
which may be caused by temperature variation, aging, or other environmental
factors, an onboard calibration circuit is designed for the VA160 and VATA160
ASICs. It is mainly composed of a 12-bit DAC (Digital to Analog Converter), an
operational amplifier and an analog switch. Test results showed that a dynamic
range of 0-30 pC with a precision of 5 fC (Root Meam Square, RMS) was achieved,
which covers the VA160's input range. It can be used to compensate for the
temperature drift and test the trigger function of the FEEs. The calibration
circuit has been implemented for the front-end electronics of the BGO Calorimeter
and verified by all the environmental tests for both Qualification Model and Flight
Model of DAMPE. The DAMPE satellite was launched at the end of 2015 and the
calibration circuit will operate periodically in space.
We investigated the effects of embryonic temperature (ET) treatments (22, 26 and 31
degrees C) on the life-time recruitment of fast myotomal muscle fibres in zebrafish
Danio rerio L. reared at 26/27 degrees C from hatching. Fast muscle fibres were
produced until 25 mm total length (TL) at 22 degrees C ET, 28 mm TL at 26 degrees C
ET and 23 mm TL at 31 degrees C ET. The final fibre number (FFN) showed an optimum
at 26 degrees C ET (3600) and was 19% and 14% higher than for the 22 degrees C ET
(3000) and 31 C ET (3100) treatments, respectively. Further growth to the maximum
TL of similar to 48mm only involved fibre hypertrophy. Microarray experiments were
used to determine global changes in microRNA (miRNA) and mRNA expression associated
with the transition from the hyperplasic myotube-producing phenotype (M(+), 10-12
mm TL) to the hypertrophic growth phenotype (M(-), 28-31 mm TL) in fish reared at
26-27 degrees C over the whole life-cycle. The expression of miRNAs and mRNAs
obtained from microarray experiments was validated by northern blotting and real-
time qPCR in independent samples of fish with the M(+) and M(-) phenotype. Fourteen
down-regulated and 15 up-regulated miRNAs were identified in the M- phenotype
together with 34 down-regulated and 30 up-regulated mRNAs (>2-fold; P<0.05). The
two most abundant categories of down-regulated genes in the M- phenotype encoded
contractile proteins (23.5%) and sarcomeric structural/cytoskeletal proteins
(14.7%). In contrast, the most highly represented up-regulated transcripts in the
M(-) phenotype were energy metabolism (26.7%) and immune-related (20.0%) genes. The
latter were mostly involved in cell-cell interactions and cytokine pathways and
included beta-2-microglobulin precursor (b2m), an orthologue of complement
component 4, invariant chain-like protein 1 (iclp), CD9 antigen-like (cd9l), and
tyrosine kinase, non-receptor (tnk2). Five myosin heavy chain genes that were down-
regulated in the M- phenotype formed part of a tandem repeat on chromosome 5 and
were shown by in situ hybridisation to be specifically expressed in nascent
myofibres. Seven up-regulated miRNAs in the M- phenotype showed reciprocal
expression with seven mRNA targets identified in miRBase Targets version 5
(http://microrna.sanger.ac.uk/targets/v5/), including asporin (aspn) which was the
target for four miRNAs. Eleven down-regulated miRNAs in the M- phenotype had
predicted targets for seven up-regulated genes, including dre-miR-181c which had
five predicted mRNA targets. These results provide evidence that miRNAs play a role
in regulating the transition from the M(+) to the M- phenotype and identify some of
the genes and regulatory interactions involved.
1. Finding and developing inhibitors of catechol-O-methyltransferase (COMT) from
natural products is highly recommended. Daphnetin, a naturally occurring catechol
from the family thymelaeaceae, has a chemical structure similar to several potent
COMT inhibitors reported previously. Here the potential of daphnetin and its Phase
II metabolites as inhibitors of COMT was investigated with human liver cytosol
(HLC). 2. Daphnetin and its methylated metabolite (8-O-methyldaphnetin) were found
to inhibit COMT-mediated dopamine O-methylation in a dose-dependent manner. The
IC50 values for daphnetin (0.51 similar to 0.53 mu M) and 8-O-methyldaphnetin (22.5
similar to 24.3 mu M) were little affected by changes in HLC concentrations.
Further kinetic analysis showed the differences in inhibition type and parameters
(K-i) between daphnetin (competitive, 0.37 mu M) and 8-O-methyldaphnetin
(noncompetitive, 25.7 mu M). Other metabolites, including glucuronidated and
sulfated species, showed negligible inhibition against COMT. By using in vitro-in
vivo extrapolation (IV-IVE), a 24.3-fold increase in the exposure of the COMT
substrates was predicted when they are co-administrated with daphnetin. 3. With
high COMT-inhibiting activity, daphnetin could serve as a lead compound for the
design and development of new COMT inhibitors. Also, much attention should be paid
to the clinical impact of combination of daphnetin and herbal preparations
containing daphnetin with the drugs primarily cleared by COMT.
The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf
(AKV) has been noted for decades and the relationship between the 2 entities
remains controversial. Although, it has been shown that both diseases are
associated with mutations in ATPA2 gene, it is yet to be determined if they are the
same disease, or separate but allelic, or interlinked in some other fashion.
Herein, the authors report the case of a 13-year-old girl presenting with shiny
flat-topped verruca plana-like papules, on the dorsal hands and feet and red-brown
crusted papules on her forehead and along the sides of her neck. Histological
evaluation of a wart-like lesion shows features of AKV, a verruca plana-like
histopathology and focal acantholytic dyskeratosis. Forehead biopsy also
demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD.
Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a
human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression
of the L1 capsid expression was seen in areas of hypergranulosis. The presence of
productive betaPV infection in the setting of DD and AKV suggests a susceptibility
to HPV infection.
There are significant differences between the DGIs and LGTs. Additionally, most of
the characteristics indicate that the DGIs are more similar to recovered tissue and
can resist viral attacks. Dark green islands (DGIs) surrounded by light green
tissues (LGTs) are common leaf symptoms of plants that are systemically infected by
various mosaic viruses. We performed cytological, physiological and molecular
biological analyses of the DGIs and LGTs in cucumber mosaic virus-infected
Nicotiana tabacum leaves. Our results indicated that the DGIs contained less virus
than did the LGTs. Compared to the LGTs, the DGIs contained higher levels of the
metabolites involved in plant defence. The contents of reduced glutathione and
ascorbic acid were increased in the DGIs to reach levels that were even higher than
those of control plants. Moreover, hormone measurements and quantitative real-time
PCR analysis revealed that the endogenous salicylic acid, ethylene and defence
genes mediated these elevations by playing positive roles in the regulation of the
DGIs responses to viral infection. The accumulation of cytokinin was also much
greater in the DGIs than in the LGTs. Finally, northern blotting analysis indicated
that the accumulation of viral small interfering RNAs was decreased in the DGIs
compared to the LGTs. Taken together, these results suggest that DGIs might
represent leaf areas that have recovered from viral infection due to locally
enhanced defence responses.
In this paper a new CMOS operational amplifier using a Darlington pair based gain
boosted technique has been enunciated. The proposed Opamp shows high gain as well
as high UGB using capacitor compensation technique and proper biasing circuit. It
is operated on rail to rail power supply of +/- 900mV. This amplifier is highly
useful for wireless communications due to low power consumption, high bandwidth,
high gain and high noise immunity. The designed operational amplifier gain is 89dB,
bandwidth is 4.40 GHz and phase margin is 67(O), and slew rate is 991.6V/mu S. This
circuit is designed using Cadence analog & digital system design tools of gpdk45nm
technology.
Diversity in major histocompatibility complex (MHC) genes can be correlated with
the level of immunological fitness of an individual or group of individuals. This
study tested published primer sets designed to amplify fragments of the MHC Class
II DAB and DBB genes to amplify the equivalent gene fragments in red-tailed
phascogales (Phascogale calura). Seventeen genomic DNA samples extracted from
phascogale muscle tissue were used to amplify the initial DAB and DBB fragments;
however, only DAB PCR proved successful. The fragments were 172 bp in length
between the primers and had a high level of identity to other known marsupial MHC
Class II DAB gene sequences (89-98%), including those of the koala (Phascolarctos
cinereus), Tasmanian devil (Sarcophilus harrisii), commonbrushtail possum
(Trichosurus vulpecula) and several wallaby species. Multiple sequence alignment
revealed limited variability of MHC Class II genes between the individuals, but
eight individual sequences in total. Genomic DNA was subsequently extracted from
three fresh red-tailed phascogale scat samples and DAB fragments successfully
amplified. The technique will allow for red-tailed phascogales to be sampled non-
invasively in the wild and to determine the level of MHC diversity among
individuals in the population.
In current industrial practice, thousands of industrial alarms generating millions
of alarm events, are built into digital control systems typically found in power
generation facilities, power grid and communication networks, oil refineries,
petrochemical plants, and other manufacturing plants. Given the increasing
complexity of such systems, an effective approach to managing alarms and the stream
of data they generate becomes imperative. Hitherto, much of alarm management
techniques are mostly rule-based with intensive engineering domain expertise
requiring an understanding of the underlying physical processes and special skills
on the part of the plant operator. This paper describes a novel graph-based data
mining approach that can be used to analyze industrial alarm data. Our method
leverages the availability of large timestamped historical alarm events datasets.
Using these historical datasets, we developed a graph analytics model that
identifies redundant alarms and the series of alarms associated with or leading to
critical events. Our experiments using real-world (a power generation station and
an oil refinery) industrial alarm datasets demonstrate that our proposed method is
both scalable and efficient.
Neuroscience and molecular biology have been generating large datasets over the
past years that are reshaping how research is being conducted. In their wake, open
data sharing has been singled out as a major challenge for the future of research.
We conducted a comparative study of citations of data publications in both fields,
showing that the average publication tagged with a data-related term by the NCBI
MeSH (Medical Subject Headings) curators achieves a significantly larger citation
impact than the average in either field. We introduce a new metric, the data
article citation index (DAC-index), to identify the most prolific authors among
those data-related publications. The study is fully reproducible from an executable
Rmd (R Markdown) script together with all the citation datasets. We hope these
results can encourage authors to more openly publish their data.
This brief conceives a learning system for implementing self-optimization-based
dynamic server resource provisioning (DSRP) of data centers under deregulated
electricity markets. We formulate the DSRP problem as a constrained Markov decision
process to minimize the electricity cost subject to a constraint on the queue
delay. Instead of applying conventional Q-learning to solve this problem, a
postdecision state learning-based DSRP algorithm having fast convergence is
proposed by estimating and exploiting the workload arrival distribution. We further
discuss the offline optimization of the DSRP problem, which is used as the
performance benchmark of the proposed method. Finally, we evaluate the performance
of the proposed scheme by using real workloads and electricity prices.
In this paper, the sensitivity of look-ahead economic dispatch in real-time power
markets with respect to data perturbation is studied. In the look-ahead dispatch
optimization problem, a small change in the data that are used for setting the
interspatial and temporal equality/inequality constraints and the objective
function may negatively affect normal operations, such as the calculation of real-
time wholesale electricity prices and operating costs. This could lead to more
distorted prices and larger operating costs with the look-ahead dispatch than with
a static dispatch that use data for a single future time. We perturb Karush-Kuhn-
Tucker conditions of the look-ahead dispatch optimization formulation and then,
using them, derive a linear sensitivity matrix that assesses the impact of data
corruption on look-ahead dispatch. This matrix illustrates the changing optimal
solution of look-ahead dispatch subject to potential corruption in various types of
spatial and temporal data-generator's bidding cost coefficients, capacity limits
for generators and transmission lines, ramp rates and the estimate of initial
generation output with ramp constraints, and multiple-time series of the forecast
load for the look-ahead horizon. The results of the simulation are illustrated with
numerical examples in the IEEE 14-bus system.
Achieving sustainable energy systems involves complex decision-making processes.
This article addresses the combination of life-cycle (LC) approaches and Data
Envelopment Analysis (DEA) for the sustainability assessment of energy systems.
Through a literature survey of Multi-Criteria Decision Analysis (MCDA) tools for
sustainability assessment of energy systems, the most commonly used criteria, data
sources and tools are identified. Moreover, a review of the LC + DEA approaches
available to date is performed in order to check their convenience to assess energy
systems in terms of sustainability. In this sense, the central focus of the article
is to explore and elucidate potentials of these combined approaches within
sustainability-oriented MCDA in the field of energy. These potentials are mainly
associated with the usefulness of sustainability benchmarks for decision-makers and
the wide availability of DEA models and life-cycle approaches. Given the growing
role of MCDA tools in energy scenario analysis and the innovative trends found in
LC + DEA, a novel methodological framework is proposed: enriched energy systems
modelling through (i) endogenous integration of life-cycle indicators and (ii)
ranking and benchmarking of energy scenarios according to sustainability criteria
using dynamic DEA. The LC + DEA concept emerges as a promising methodology to
evaluate and rank prospective scenarios in energy planning, thus facilitating
decision-making processes towards a sustainable energy future. (C) 2017 Elsevier
Ltd. All rights reserved.
This paper explores the link between the presence of unions in the workplace, the
adoption of decentralized labor agreements and technical efficiency, using a large
sample of Italian manufacturing firms. We apply the Data Envelopment Analysis, and
its robust version based on bootstrap theory, to get reliable estimates of
technical efficiency at the firm level in a standard first stage. We devote
particular attention to the specific technology adopted, by distinguishing 20
different sector frontiers, as well as to the presence of outliers. The obtained
efficiency scores are analyzed in a second stage applying a truncated regression
model estimated via Maximum Likelihood, following the Simar and Wilson (2007, 2011)
methodology. Our results highlight that the presence of workplace unionization
decreases the level of technical efficiency, while aspects limiting the unions'
power such as a strong exposure to international markets, high debt levels or the
prevalence of flexible assets partially reduce the negative effect. However, when
firms adopt decentralized labor contracts agreements, the effect on efficiency is
positive and partially compensates the negative unions' effect. (C) 2017 Elsevier
B.V. All rights reserved.
AimThe primary aim of this study was to evaluate 23 pathogens associated with peri-
implantitis at inner part of implant connections, in peri-implant and periodontal
pockets between patients suffering peri-implantitis and participants with healthy
peri-implant tissues; the secondary aim was to estimate the predictive value of
microbiological profile in patients wearing dental implants using data mining
methods. Material and MethodsFifty participants included in the present casecontrol
study were scheduled for collection of plaque samples from the peri-implant
pockets, internal connection, and periodontal pocket. Real-time polymerase chain
reaction was performed to quantify 23 pathogens. Three predictive models were
developed using C4.5 decision trees to estimate the predictive value of
microbiological profile between three experimental sites. ResultsThe final sample
included 47 patients (22 healthy controls and 25 diseased cases), 90 implants (43
with healthy peri-implant tissues and 47 affected by peri-implantitis). Total and
mean pathogen counts at inner portions of the implant connection, in peri-implant
and periodontal pockets were generally increased in peri-implantitis patients when
compared to healthy controls. The inner portion of the implant connection, the
periodontal pocket and peri-implant pocket, respectively, presented a predictive
value of microbiologic profile of 82.78%, 94.31%, and 97.5% of accuracy.
ConclusionThis study showed that microbiological profile at all three experimental
sites is differently characterized between patients suffering peri-implantitis and
healthy controls. Data mining analysis identified Parvimonas micra as a highly
accurate predictor of peri-implantitis when present in peri-implant pocket while
this method generally seems to be promising for diagnosis of such complex
infections.
In recent years, electricity crisis still becomes noticeable in some countries due
to a widening gap between demand and supply. Consequently, the future demand plays
a significant role in efficient management and utilization of electricity.
Pertaining to efficient supply handling to increase the power system reliability,
an electricity demand forecasting is one of the most crucial tools. The forecasting
technique is used by decision makers all over the world to predict the future
demand as key information for a proper policy. In this research, the hybrid model
consists of maximal overlap discrete wavelet transform (MODWT), support vector
machine (SVM), and differential evolution (DE) optimization emphasizing on
simplifying the complex structure in data pre-processing is proposed to forecast
the thirty-two annual electricity consumptions and is compared with traditional
forecasting models, hybrid model of MODWT and SVM, and combined model of SVM and DE
optimization based on mean absolute error (MAE), mean absolute percentage error
(MAPE) and symmetric mean absolute percentage error (sMAPE) measures as well as
Friedman test and post hoc test. The empirical results indicate that the proposed
model outperforms other forecasting models and provides more accurate forecasts
than other candidate models at 0.05 significance levels and the nearly highest
precision. Consequently, the proposed model is able to reduce the limitations of
individual models regarding annual electricity consumptions and can be used as a
promising tool in order to forecast annual electricity consumptions as well. (C)
2017 Elsevier B.V. All rights reserved.
It is shown that the problem of evaluation of states both object and controller
arises at digital control. In multi-circuit embedded systems time intervals of
residence of system in any state depends on both time complexity of control
algorithm and dispatching discipline. Two simplest disciplines, of most common use
are investigated: the cyclic dispatching and foreground (quasi-stochastic) one.
With use the semi-Markov process as fundamental theory, models of functioning of
control programs under investigated dispatching disciplines are worked out.
Mathematical relationships for time of return to any state of semi-Markov process
and time between switches are obtained. The parameters obtained are essential for
working out of efficient regimes of data processing in embedded systems.
In a conventional electricity market, trading is conducted based on power forecasts
in the day-ahead market, while the power imbalance is regulated in the real-time
market, which is a separate trading scheme. With large-scale wind power connected
into the power grid, power forecast errors increase in the day-ahead market which
lowers the economic efficiency of the separate trading scheme. This paper proposes
a robust unified trading model that includes the forecasts of real-time prices and
imbalance power into the day-ahead trading scheme. The model is developed based on
robust optimization in view of the undefined probability distribution of clearing
prices of the real-time market. For the model to be used efficiently, an improved
quantum-behaved particle swarm algorithm (IQPSO) is presented in the paper based on
an in-depth analysis of the limitations of the static character of quantum-behaved
particle swarm algorithm (QPSO). Finally, the impacts of associated parameters on
the separate trading and unified trading model are analyzed to verify the
superiority of the proposed model and algorithm.
Existing methods of measuring loop gain of digitally controlled DC/DC converters
mainly fall into two categories, namely the analog signal disturbance method (ASDM)
and the digital signal disturbance method (DSDM). However, the loop gains obtained
from these methods do not totally agree with each other. Through rigorous
theoretical analysis, this paper has derived the expressions of open-loop gains
obtained from these two methods, whose accuracy has been verified by simulation.
Also, this paper has put forward that the difference in signal that enters into the
sampler results in the variation of the transfer function of the sampler, and
further induces the difference between the open-loop gains obtained from the ASDM
and the DSDM.
Spread spectrum is a technique introduced for mitigating electromagnetic
interference (EMI) problems in many class of circuits. In this paper, with
particular emphasis on switching DC/DC converters, we consider the most common and
most efficient known spreading techniques, looking for spreading parameters that
ensure the highest EMI reduction and the lowest performance reduction in the
circuit where the spreading is applied. The result is an interesting tradeoff not
only between EMI reduction and performance drop, but also on the EMI reduction
itself when considering different EMI victim models. The proposed analysis is
supported by measurements on two switching DC/DC converters: 1) based on pulse
width modulation and 2) based on the resonant converter class.
This paper presents theoretical and practical results about dynamic analysis,
frequency response, and control of a LLC resonant dc/dc converter operating under
wide input voltage and load variations. A nonlinear model for the LLC resonant
converter was developed using the extended describing function method; then, based
on the derived model, a nonlinear observer-based controller was designed and
implemented with a digital signal processor. Transient responses obtained under
input voltage and output load variations show that the proposed controller is
capable to stabilize the output effectively. Experimental results prove the
superiority of the proposed observer-based controller over a conventional PID
controller.
This paper presents finite-control-set modelpredictive control (FCS-MPC) for a
three-phase quasi-Zsource (qZS) four-leg inverter under unbalanced load condition.
The key novelty of the proposed control approach is eliminating the double-line
frequency ripple in the inductor current with a simple and effective approach. The
proposed four-leg qZS inverter with an output LC filter can handle buck/boost and
dc/ac conversion features in a single stage. Furthermore, the FCS-MPC-based control
algorithm helps in maintaining balanced point of common coupling voltages for
stand-alone unbalanced loads. The behavior of the predictive controller has been
investigated under different operating conditions, and its robustness with the qZS
network and the LC filter parameter variations are also studied. Furthermore, the
effect of double-line frequency ripple and its relation with the inductor current
constraint have been tackled comprehensively. To verify the performance of the
proposed approach, simulation and experimental studies were performed for balanced
and unbalanced loads.
This paper introduces a high-frequency soft-switching pulse-width modulation DC-DC
power converter with secondary active rectifier tested as a DC current source for
arc welding applications. The soft-switching DC-DC converter consists of a high-
frequency full-bridge inverter, high-frequency power transformer, and a controlled
output rectifier with new secondary energy recovery turn-off snubber. Circulating
currents in the converter are reduced by using active rectifier, and RMS values of
the currents in primary and secondary switches are decreased by utilizing a novel
control algorithm. The experimental results of a 4.5kW DC-DC converter working at
switching frequency of 100kHz are presented.
A weighted controller structure for DC-DC converters is proposed to deal with
large-signal operations. For wide range variations of input voltage and load
conditions of DC-DC converters, we firstly divide the pre-defined global operation
space into local subspaces where each local linear compensator is designed for the
corresponding subspace, and then all the local linear compensators are weighted
into single controller structure. By doing so, the weighted controller can
automatically decide which local linear compensator regulates the dynamics of DC-DC
converter according to the operation conditions, and thus has the capability of
self-adaptation to wide range of operating point variations. Furthermore, the
prominent feature underlying the weighted control scheme is also that the
nonlinearities of DC-DC converters is easily to be handled by linear compensation
approaches that can be easily implemented with analog or digital control
circuitries. To demonstrate the effectiveness of this controller structure, a
stand-alone DC-DC converter and a cascaded DC-DC converter system are taken as
examples by simulation and experimental results.
The dc power feeding system has been attracted attention in recent years. Since the
load is dynamically changed in this system, the stability of dc-dc converter is
important. This paper presents the stability analysis and the transient response of
digital integral gain changeable control dc-dc converter using small output
capacitance. The proposed method changes the integral gain with a single logarithm
function according to the load current. It is verified the proposed method can
obtain a good transient response with high stability even when the output
capacitance is small.
Stability of power converters has become more and more important in hybrid green
energy systems because of its difficulties to maintain a stable dc-bus. This paper
presents dynamic characteristics of a digital integral gain changeable control dc-
dc converter to realize high stability with suppression of the output capacitance.
The integral gain changeable control method uses a variable integral gain, which is
changed by the value of load current. The stability analysis is conducted by Bode
diagrams. It is shown that the transient response and stability of the integral
gain changeable method are better than the conventional fixed integral gain control
method even if the output capacitance is smaller than the conventional method.
Simulation and experimental results show the effectiveness of our concept.
This paper presents a digital motion controller of an electric wheelchair by using
a low-cost real-time microcontroller unit (MCU) and an own developed power
electronic drive. The speed control of the wheels is implemented through a digital
pulse-width modulation technique which is varying with the reference generated by a
low-cost joystick. Voltage regulators and power converters are implemented to
supply correct voltage levels to control cards and to the DC motors from batteries.
Experimental results which have been obtained by using the MCU, the mechanical
structure of a used electric wheelchair and the developed electronic drive
demonstrate that the proposed digital controller meets the user requirements in
terms of reliability, good driving and fair economic cost.
The aim of this paper is to propose a neural network based reference modified PID
control which has a simple duration design method for transient characteristics
improvement of digitally controlled dc-dc converters. In renewable energy network
systems, various types of dc-dc converters are widely used for power conversion and
such converters require a superior control method for a stable operation.
Especially, transient characteristics should be improved since they heavily affect
the stability of the system. For such purposes, designing of conventional control
methods becomes a difficult task since the optimization of control parameters needs
complicated analysis and it is affected from variations of circuit components of
converters. Therefore, simple and easy design of control is widely required for a
stable operation of power converters. The neural network can provide a suitable
control methodology for such situation since it treats the plant as a black box and
it can realize a non-linear control based on training of the input-output relation
without complicated modelling and analysis. On the other hand, the neural network
based method has a disadvantage caused from the fact that the neural network is
trained with data obtained in advance and an overcompensation phenomenon occurs in
the transient response. In this paper, the neural network control is adopted to
control the dc-dc converter in coordination with a conventional PID control. The
neural network predicts the output voltage of the converter and the reference value
in the PID control is modified with the predictions to reduce the error of the
output voltage. To avoid overcompensation, a simple duration design for the neural
network control is also provided to improve the transient response effectively.
From prototype testing in simulation and experiment, it is revealed that the
proposed method contributes to obtain a superior transient performance compared
with the conventional PID control.
The purpose of this paper is to analyze the dynamic characteristics of proposed
digital peak current mode dc-dc converter. The waveforms of the output voltage and
the reactor current are derived by the small signal analysis. They are compared
with simulation results assuming an actual large amplitude operation. It is
confirmed that the tendency of the transient response is indicated based on the
analysis results. The experimental result of the proposed method shows the validity
of the proposed method and a gradual response is obtained by an improvement of the
stability of dc-dc converter. Consequently, the proposed method can be a solution
of implementing the peak current mode control in digital.
In this paper, second-order sliding-mode (SOSM) control approach is applied to
synchronous buck dc-dc converters. The proposed SOSM controller can stabilize
synchronous buck dc-dc converters using a simple digital state-machine structure,
without requiring current sensing or an integral term in the control loop. The SOSM
controller results in fast step-load and start-up transient responses, and is
robust against parameter uncertainties. Fast transients and current limitation
during start up can be accomplished by adjusting one controller parameter.
Furthermore, a hysteresis method is introduced to control the switching frequency.
The proposed approach is verified by experimental results on a 1.25-V 10-A
prototype.
We have proposed the sensorless model control based on the static model equation of
the dc-dc converter that is able to change the bias value corresponding to changes
of the load current, the input voltage and output voltage. The sensorless model
control can regulate the output voltage. On the other hand, the transient response
of output voltage is not improved. Therefore, an improvement of the transient
response is carried out by adding the transient improvement function which changes
a bias value drastically for a short time at the start of the transient state. The
purpose of this paper is to indicate the parameter setting of the transient
improvement function that improves the transient response by the simulation
analysis under changing the circuit condition.
A fully integrated low-dropout-regulated step-down multiphase-switched-capacitor
DC-DC converter (a.k.a. charge pump, CP) with a fast-response adaptive-phase (Fast-
RAP) digital controller is designed using a 65-nm CMOS process. Different from
conventional designs, a low-dropout regulator (LDO) with an NMOS power stage is
used without the need for an additional step-up CP for driving. A clock tripler and
a pulse divider are proposed to enable the Fast-RAP control. As the Fast-RAP
digital controller is designed to be able to respond faster than the cascaded
linear regulator, transient response will not be affected by the adaptive scheme.
Thus, light-load efficiency is improved without sacrificing the response time. When
the CP operates at 90 MHz with 80.3% CP efficiency, only small ripples would appear
on the CP output with the 18-phase interleaving scheme, and be further attenuated
at VOUT by the 50-mV dropout regulator with only 4.1% efficiency overhead and 6.5%
area overhead. The output ripple is less than 2 mV for a load current of 20 mA.
This paper presents a novel control method based on predictions of a neural network
in coordination with a conventional PID control to improve transient
characteristics of digitally controlled switching dc-dc converters. Power supplies
in communication systems require to achieve a superior operation for electronic
equipment installed to them. Especially, it is important to improve transient
characteristics in any required conditions since they affect to the operation of
power supplies. Therefore, dc-dc converters in power supplies need a superior
control method which can suppress transient undershoot and overshoot of output
voltage. In the presented method, the neural network is trained to predict the
output voltage and is adopted to modify the reference value in the PID control to
reduce the difference between the output voltage and its desired one in the
transient state. The transient characteristics are gradually improved as the
training procedure of the neural network is proceeded repetitively. Furthermore,
the timing and duration of neural network control are also investigated and devised
since the time delay, which is one of the main issue in digital control methods,
affects to the improvement of transient characteristics. The repetitive training
and duration adjustment of the neural network are performed simultaneously to
obtain more improvement of the transient characteristics. From simulated and
experimental results, it is confirmed that the presented method realizes superior
transient characteristics compared to the conventional PID control.
The aim of this paper is to present an overcurrent limitation for the digital peak
current mode dc-dc converter. The proposed method can detect the overcurrent in
real time and it also maintains arbitrary current in the overcurrent limitation
mode. It is expected to provide an effective function to protect the renewable
energy system. The effectiveness of proposed method is confirmed from both
simulated and experimental results.
The purpose of this paper is to propose a flexible load-dependent digital soft-
start control method for dc-dc converters in a 380 Vdc system. The soft-start
operation is needed to prevent negative effects such as large inrush current and
output overshoot to a power supply in the start-up process of dc-dc converters. In
the conventional soft-start operation, a dc-dc converter has a very slow start-up
to deal with the light load condition. Therefore, it always takes a long time in
any load condition to start up a power supply and obtain the desired output. In the
proposed soft-start control method, the speed of the start-up process is flexibly
controlled depending on the load condition. To obtain the optimal speed for any
load condition, the speed of the soft-start is determined from a approximated
function of load current, which is estimated from experiment results in advance.
The proposed soft-start control method is evaluated both in simulations and
experiments. From results, it is confirmed that the proposed method has superior
soft-start characteristics compared to the conventional one.
This paper describes a modular architecture based on the dual-active bridge (DAB)
converter in input-series-output-parallel (ISOP) connection. This work is focused
on the input voltage sharing to ensure a proper operation of each module by means
of an active control of input and output voltages. A small-signal model of the
modular architecture is proposed and a decoupled control loops' scheme is used to
implement the control strategy. An experimental setup has been built in order to
validate the model of the DAB converter in ISOP connection and the proposed control
strategy, taking different operating conditions and constructive parameter values
into account.
Dc-dc converters often exhibit undesirable oscillations due to their nonlinear
dynamics. Digitally controlled converters have further degrees of nonlinearity in
terms of quantization in the analog to digital converter and the digital pulse
width modulator, giving rise to the well known phenomenon of limit cycle
oscillations. In this study, a different and hitherto unreported class of
oscillations in digitally controlled converters has been reported, and its origin
has been traced to asymmetric saturation in the duty cycle. The study attempts to
provide physical insights behind this phenomenon of saturation generated
oscillation (SGO), and to identify the converter-system components responsible for
it. The challenges in the traditional stability analysis of such a system are
highlighted, followed by a simplified analysis leading to the calculation of the
oscillation-free operating-zone, and some of the effects of system parameters on
the SGO. The results have been used to show some potential ways in which the
oscillation can be avoided by using SGO-immune designs. Simulation and experimental
results have been provided to illustrate the points and substantiate the claims.
This study proposes a novel method to eliminate the limit cycle caused by low
resolution analogue-to-digital converter (ADC) in digitally controlled DC-DC
converter. The reduced state Kalman filter is proposed to get the optimum estimate
of the output voltage from the noisy measurement provided by the low resolution
ADC. The proposed scheme is simulated with 6 bit resolution of ADC and the
validation is performed with different resolutions using a prototype model which is
implemented in16 bit digital signal processor. The results show that the proposed
scheme eliminates limit cycle oscillation completely and is computationally more
efficient.
The loop-handover (LHO) technique is proposed to overcome the problem of close-loop
performance in digitally controlled single-inductor multiple-output dc-dc boost
converters during start-up. The presented technique utilises an existing clock
source and requires only a small number of blocks. It also occupies a smaller
silicon area, thus consuming low power and increasing efficiency. The presented
technique is validated with proposed on-chip digital controller with multiple-
output boost converter architecture using segmented delay line digital pulse width
modulation. Experimental results show a successful close loop with reduced
transients by using the simpler LHO technique.
This study presents an approach to system identification and adaptive control of a
non-inverting buck-boost converter in the presence of large signal changes,
uncertainty of converter components and effects of imperfect modelling. Feedback
loops of DC-DC converters are typically designed conservatively so that the closed-
loop regulation and stability margins are maintained over a pre-determined range of
operating conditions. The proposed approach is able to keep a high-performance
response without the instability issue of dynamic change of the converter. In the
presence of uncertainty on the parameters of a DC-DC converter, a digital adaptive
controller based on system identification and minimum degree pole placement is
proposed. To verify the validity of the proposed digital controller, an
experimental setup is constructed for a non-inverting buck-boost converter and the
fully digital adaptive control is implemented by a micro controller. The
experimental results show the capability of an adaptive controller during different
operating points.
Centralised electricity systems are being integrated by a multitude of small
distributed generation clusters, called nanogrids, capable of ensuring full
utilisation of renewable energy sources, high flexibility, efficiency and improved
reliability of the power grid due to redudancy. In this study, small photovoltaic
plants combined with energy storage systems represent a promising solution for full
exploitation of renewable energies and for effective development of
electromobility. The purpose of this study is two-fold: first it deals with a DC
nanogrid suitable for small energetic clusters such as residential or office
buildings and consisting of photovoltaic arrays, fuel cells, electric vehicle
charger stations, loads, then proposes a multifunctional full-bridge DC/DC LLC
resonant converter building block. The latter, while accepting large input/output
ranges is suitable for photovoltaic and fuel cells energy conversion, electric
vehicle recharging stations and other DC applications available in the nanogrid.
Proposed power system can be interconnected with conventional AC grid through
voltage source converter. After description of proposed nanogrid, some analyses are
performed on its core element, i.e. the DC converter building block.
This paper presents the stability analysis of dc distributed power systems with
multiple converter-controlled loads. The load converters are tightly controlled,
behaving as constant power loads with low-damped LC filters. The dynamic behavior
of the system in high frequency range is often not studied with the classical tools
based on conventional averaging techniques. However, dc power systems with the
reduced size filter, and consequently, the high resonant frequency, are widely used
in transportation applications. In this paper, the stability analysis of the system
is established based on a discrete-time model of the system, taking into account
the switching frequency and intrinsic nonlinearities of the system model. The
impacts of the filter parameters and interactions among the constant power loads
are investigated with the proposed discrete-time method. Moreover, an active
stabilizer is developed and included in the dynamic model of the system, in order
to extend the stability margin. The theoretical observations are then validated
experimentally on a laboratory hardware prototype.
Deficits in social interaction are hallmarks of neurological and psychiatric
disorders. However, its underlying mechanism is still unclear. Here, we show that
the loss of dendritic cell factor I (Dcf1) in the nervous system of mice induces
social interaction deficiency, autism-like behaviour, and influences social
interaction via the dopamine system. Dopamine receptor D1 agonist rescues this
social cognition phenotype, and improves short-term plasticity. Together, this
study presents a new genetic mechanism that affects social interaction and may
provide a new way to improve positive social interaction and treat autism spectrum
disorders.(C) 2017 Elsevier B.V. All rights reserved.
Soil salinity is a major environmental stress limiting plant growth and
productivity. We have reported previously the isolation of an Apocynum yenetum
DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here,
we report that the overexpression of AvDH1 driven by a constitutive cauliflower
mosaic virus 35S promoter in cotton plants confers salinity tolerance. Southern and
Northern blotting analyses showed that the AvDH1 gene was integrated into the
cotton genome and expressed. In this study, the growth of transgenic cotton
expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a
saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant
to salt than the wild-type plants when grown in a growth chamber. The lower
membrane ion leakage, along with increased activity of superoxide dismutase, in
AvDH1 transgenic lines suggested that these characteristics may prevent membrane
damage, which increases plant survival rates. In a saline field, the transgenic
cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed
cotton yields compared with wild-type plants, especially at high soil salinity
levels. This study indicates that transgenic cotton expressing AvDH1 is a promising
option for increasing crop productivity in saline fields.
This paper proposes a new method of dead-time effect compensation. The proposed
solution is based on additional phase current measurements realized by analog-to-
digital converters. These measurements are carried out at the time instants
specified by a pulsewidth-modulation (PWM) strategy. This makes it possible to
estimate inverter currents at the commutation instants and, finally, to estimate
the voltage error caused by dead time. This voltage error is compensated during the
next switching period by modification of a reference voltage. The proposed solution
can be used to compensate the voltage error in multilevel multiphase voltage source
inverters. The experimental research studies were carried out on three-phase two-
level and three-level neutral-point-clamped inverters supplying 55- and 160-kW
motors, respectively. The results of the experimental investigations are presented
in this paper.
By guiding our attention to the emotional responses of a little girl and her darkly
lit surroundings, Jude's film explores human existence in the face of death.
Informed by existential philosophy in the vein of Heidegger, this article
investigates the difference between fear of death and fear of the dead.
The nature and quality of social work decision making have been highlighted in
recent years by a number of high-profile child deaths. Recognising and assessing
child abuse is beset with uncertainties and complexities that profoundly shape
practice yet are often overlooked by more official and distanced accounts. This
paper draws on ethnographic data from a study of social workers' decision making to
uncover some of the issues they faced in gathering and assessing information.
Workers faced problems with inaccurate or incomplete information, poorly defined
situations, time pressures and heavy workloads. The paper draws attention to the
ways in which the team organised itself to manage these issues which could provide
a better understanding of how everyday decision making can be supported and
improved.
The primate prefrontal cortex represents both past and future goals. To investigate
its role in representing the goals of other agents, we designed a nonmatch-to-goal
task that involved a human-monkey (H-M) interaction. During each trial, 2 of 4
potential goal objects were presented randomly to the left or right part of a
display screen, and the monkey's (or human's) task was to choose the one that did
not match the object goal previously chosen. Human and monkey trials were
intermixed, and each agent, when acting as observer, was required to monitor the
other actor's choice to switch the object goal choice in case it became the actor
on the subsequent trial. We found neurons encoding the actor, either the monkey
itself or the human, neurons encoding the agent future goal position and neurons
encoding the agent previous goal position. In the category of neurons encoding the
human future goal, we differentiated between those encoding the future goal of both
agents and those encoding only the human agent future goal. While the first one
might represent a covert mental simulation in the human trials, the other one could
represent a prediction signal of the other's agent choice.
Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and
nonmotor symptoms. Nonmotor symptoms include cognitive deficits and impairment in
emotions recognition ability associated with loss of dopaminergic neurons in the
substantia nigra and with alteration in frontostriatal circuits. In this review, we
analyzed the studies on social cognition ability in patients with PD. We searched
on PubMed and Web of Science databases and screening references of included studied
and review articles for additional citations. From initial 260 articles, only 18
met search criteria. A total of 496 patients were compared with 514 health
controls, through 16 different tests that assessed some subcomponents of social
cognition, such as theory of mind, decision-making, and emotional face recognition.
Studies on cognitive function in patients with PD have focused on executive
function. Patients with PD showed impairment in social cognition from the earliest
stages of disease. This ability seems to not be significantly associated with other
cognitive functions.
A monolithic integrated low-voltage deep brain stimulator with wireless power and
data transmission is presented. Data and power are transmitted to the stimulator by
mutual inductance coupling, while the in-vitro controller encodes the stimulation
parameters. The stimulator integrates the digital control module and can generate
the bipolar current with equal amplitude in four channels. In order to reduce power
consumption, a novel controlled threshold voltage cancellation rectifier is
proposed in this paper to provide the supply voltage of the stimulator. The
monolithic stimulator was fabricated in a SMIC 0.18 mu m 1-poly 6-metal mixed-
signal CMOS process, occupying 0.23 mm(2), and consumes 180 mu W on average.
Compared with previously published stimulators, this design has advantages of large
stimulated current (0-0.8 mA) with the double low-voltage supply (1.8 and 3.3 V),
and high-level integration.
Literature studies showed the ability to treat neuropsychiatric disorders using H1
coil, developed for the deep Transcranial Magnetic Stimulation (dTMS). Despite the
positive results of the clinical studies, the electric field (E) distributions
inside the brain induced by this coil when it is positioned on the scalp according
to the clinical studies themselves are not yet precisely estimated. This study aims
to characterize the E distributions due to the H1 coil in the brain of two
realistic human models by computational electromagnetic techniques and to compare
them with the ones due to the figure-of-8 coil, traditionally used in TMS and
positioned as such to simulate the clinical experiments. Despite inter-individual
differences, our results show that the dorsolateral prefrontal cortex is the region
preferentially stimulated by both H1 and figure-of-8 coil when they are placed in
the position on the scalp according to the clinical studies, with a more broad and
non-focal distribution in the case of H1 coil. Moreover, the H1 coil spreads more
than the figure-of-8 coil both in the prefrontal cortex and medial prefrontal
cortex and towards some deeper brain structures and it is characterized by a higher
penetration depth in the frontal lobe. This work highlights the importance of the
knowledge of the electric field distribution in the brain tissues to interpret the
outcomes of the experimental studies and to optimize the treatments. (C) 2017 IPEM.
Published by Elsevier Ltd. All rights reserved.
Narratives are an important component of culture and play a central role in
transmitting social values. Little is known, however, about how the brain of a
listener/reader processes narratives. A receiver's response to narration is
influenced by the narrator's framing and appeal to values. Narratives that appeal
to "protected values," including core personal, national, or religious values, may
be particularly effective at influencing receivers. Protected values resist
compromise and are tied with identity, affective value, moral decision-making, and
other aspects of social cognition. Here, we investigated the neural mechanisms
underlying reactions to protected values in narratives. During fMRI scanning, we
presented 78 American, Chinese, and Iranian participants with real-life stories
distilled from a corpus of over 20 million weblogs. Reading these stories engaged
the posterior medial, medial prefrontal, and temporo-parietal cortices. When
participants believed that the protagonist was appealing to a protected value,
signal in these regions was increased compared with when no protected value was
perceived, possibly reflecting the intensive and iterative search required to
process this material. The effect strength also varied across groups, potentially
reflecting cultural differences in the degree of concern for protected values.
Communication between cortical regions is necessary for optimal cognitive
processing. Functional relationships between cortical regions can be inferred
through measurements of temporal synchrony in spontaneous activity patterns. These
relationships can be further elaborated by surveying effects of cortical lesions
upon inter-regional connectivity. Lesions to cortical hubs and heteromodal
association regions are expected to induce distributed connectivity changes and
higher-order cognitive deficits, yet their functional consequences remain
relatively unexplored. Here, we used resting-state fMRI to investigate intrinsic
functional connectivity (FC) and graph theoretical metrics in 12 patients with
circumscribed lesions of the medial prefrontal cortex (mPFC) portion of the Default
Network (DN), and compared these metrics with those observed in healthy matched
comparison participants and a sample of 1139 healthy individuals. Despite
significant mPFC destruction, patients did not demonstrate weakened intrinsic FC
among undamaged DN nodes. Instead, network-specific changes were manifested as
weaker negative correlations between the DN and attentional and somatomotor
networks. These findings conflict with the DN being a homogenous system
functionally anchored at mPFC. Rather, they implicate a role for mPFC in mediating
cross-network functional interactions. More broadly, our data suggest that lesions
to association cortical hubs might induce clinical deficits by disrupting
communication between interacting large-scale systems.
The symbiotic interaction between legume plants and rhizobia results in the
formation of root nodules, in which symbiotic plant cells host and harbor thousands
of nitrogen-fixing rhizobia. Here, a Medicago truncatula nodules with activated
defense 1 (nad1) mutant was identified using reverse genetics methods. The mutant
phenotype was characterized using cell and molecular biology approaches. An RNA-
sequencing technique was used to analyze the transcriptomic reprogramming of nad1
mutant nodules. In the nad1 mutant plants, rhizobial infection and propagation in
infection threads are normal, whereas rhizobia and their symbiotic plant cells
become necrotic immediately after rhizobia are released from infection threads into
symbiotic cells of nodules. Defense-associated responses were detected in nad1
nodules. NAD1 is specifically present in root nodule symbiosis plants with the
exception of Morus notabilis, and the transcript is highly induced in nodules. NAD1
encodes a small uncharacterized protein with two predicted transmembrane helices
and is localized at the endoplasmic reticulum. Our data demonstrate a positive role
for NAD1 in the maintenance of rhizobial endosymbiosis during nodulation.
BackgroundThere is increasing popularity of high-power lasers for surgical
debridement and antimicrobial therapy in the management of peri-implantitis and
periodontal therapy. Removal of the noxious foci would naturally promote tissue
healing directly. However, there are also anecdotal reports of better healing
around routine high-power laser procedures. The precise mechanisms mediating these
effects remain to be fully elucidated. This work examines these low-dose laser
bystander effects on oral human epithelial and fibroblasts, particularly focusing
on the role of human -defensin 2 (HBD-2 or DEFB4A), a potent factor capable of
antimicrobial effects and promoting wound healing. Material and MethodsLaser
treatments were performed using a near-infrared laser (810 nm diode) at low doses.
Normal human oral keratinocytes and fibroblast cells were used and HBD-2 mRNA and
protein expression was assessed with real time polymerase chain reaction, western
blotting and immunostaining. Role of transforming growth factor (TGF)-1 signaling
in this process was dissected using pathway-specific small molecule inhibitors.
ResultsWe observed laser treatments robustly induced HBD-2 expression in an oral
fibroblast cell line compared to a keratinocyte cell line. Low-dose laser
treatments results in activation of the TGF-1 pathway that mediated HBD-2
expression. The two arms of TGF-1 signaling, Smad and non-Smad are involved in
laser-mediated HBD-2 expression. ConclusionsLaser-activated TGF-1 signaling and
induced expression of HBD-2, both of which are individually capable of promoting
healing in tissues adjacent to high-power surgical laser applications. Moreover,
the use of low-dose laser therapy itself can provide additional therapeutic
benefits for effective clinical management of periodontal or peri-implant disease.
Specific defensive behaviors of rodents are shaped by features of the eliciting
threat stimuli and situation. Threat scenarios confirmed these relationships in
people, with results substantially replicated in 4 additional scenario studies.
Subsequent human studies involve computer games measuring fear as flight from
threat stimuli and anxiety as alternation between two threats. Stabilometric
studies have shown reduction in sway (freezing) to inescapable (e.g. with gun
pointed at subject) threatening photographs; but enhanced lateral sway (flight
attempts) to escapable threats; (gun pointed away from subject). Relationships
between threat ambiguity, risk assessment, and anxiety have been validated by
identification of videos of facial expressions to ambiguous threats, as anxiety;
and systematic biases toward threat stimuli by anxious individuals. Enhanced
rumination, interpretable as unsuccessful risk assessment, is a dynamic component
of both anxiety and depression, particularly in women. While there is less
experimental work on defensive threat/attack, a transdiagnostic "Fear of Harm"
phenotype of aggression associated with fear suggests that this is a component of
pathological as well as normal human defensive behavior. (C) 2016 Published by
Elsevier Ltd.
Background: The aim of the present study was to investigate the effects of the iron
chelator deferiprone in diabetic nephropathy (DN) rats and the mechanisms involved.
Methods: Thirty-two male Wistar rats (180-220 g, 6 weeks old) were randomly divided
into a control group, a DN group and two DN groups treated with either 50 or 100
mg/kg per day deferiprone. The DN group was established by feeding of a high-
carbohydrate-fat diet and injection of 35 mg/kg streptozotocin into the vena
caudalis. The duration of deferiprone treatment was 20 weeks. Histopathological
changes were detected by hematoxylin-eosin and Masson staining, as well as
transmission electron microscopy. Levels of nuclear factor (NF)-kappa B, monocyte
chemotactic protein (MCP)-1, matrix metalloproteinase (MMP)-9, tissue-specific
inhibitor of metalloproteinase (TIMP)-1, cyclo-oxygenase (COX)-2, and nitrotyrosine
were determined in kidney tissues using reverse transcription-polymerase chain
reaction (RT-PCR), western blotting, and immunohistochemistry. Results:
Histopathological observations showed that deferiprone treatment alleviated
inflammation infiltrates and collagenous fibrosis in DN rats. Results from RT-PCR
and western blotting indicated that deferiprone inhibited the expression of NF-
kappa B, MCP-1, COX-2, and nitrotyrosine, which were overexpressed in DN rats.
Immunohistochemistry showed that the mechanism of deferiprone action may involve
regulation of MMP-9 and TIMP-1. Decreased MMP-9 expression and increased TIMP-1
expression in DN rats were significantly promoted and inhibited by deferiprone,
respectively. Conclusion: Iron chelation by oral deferiprone has a renoprotective
effect in DN rats by relieving oxidative stress, inflammation, and fibrosis, which
is related to the cytokines NF-kappa B, MCP-1, MMP-9, TIMP-1, COX-2, and
nitrotyrosine.
Undocumented immigrant young adults growing up in the United States face
significant challenges. For those qualified, the Deferred Action for Childhood
Arrivals (DACA) program's protections may alleviate stressors, with implications
for their mental health and wellbeing (MHWB). We conducted nine focus groups with
61 DACA-eligible Latinos (ages 18-31) in California to investigate their health
needs. Participants reported MHWB as their greatest health concern and viewed DACA
as beneficial through increasing access to opportunities and promoting belonging
and peer support. Participants found that DACA also introduced unanticipated
challenges, including greater adult responsibilities and a new precarious identity.
Thus, immigration policies such as DACA may influence undocumented young adults'
MHWB in expected and unexpected ways. Research into the impacts of policy changes
on young immigrants' MHWB can guide stakeholders to better address this
population's health needs. MHWB implications include the need to reduce fear of
deportation and increase access to services.
Overpopulation and economic industrialization are two common explanations for
deforestation. Political ecology, however, highlights that good governance and
effective land management at the local level can offset the impact of population
growth and development on environmental degradation. In this paper, we provide an
innovative argument derived from political ecology to explain deforestation, but
rather than pursing a "bottom up" approach to governance, we take a "top down"
approach. We argue that the state can ease deforestation rates by weaning rural
populations off of the consumption of biomass for their energy needs by expanding
rural electrification access. Using a panel analysis of 158 countries for the years
1990, 2000, and 2010, we find that not only does rural electrification cause
deforestation rates to decrease, but also that it is more robust in explaining
deforestation than population growth or development. Our study provides two
innovations to political ecology: it highlights that the state can help, rather
than hinder, local populations with managing their local environments in a more
sustainable way by providing them with (public goods-based) energy alternatives,
and; it supplements political ecology's qualitative focus on environmental
degradation with a generalized quantitative analysis of state-based initiatives on
deforestation. Our results suggest that current global initiatives addressing
deforestation specifically the Reduction of Emissions from Deforestation and Forest
Degradation (REDD+) agenda of the United Nations' Framework Convention on Climate
Change should not only assist local land managers, but also work with the state to
ensure universal access to electricity. (C) 2017 Elsevier Ltd. All rights reserved.
Wiener processes have received considerable attention in degradation modeling over
the last two decades. In this paper, we propose a generalized Wiener process
degradation model that takes unit-to-unit variation, time-correlated structure and
measurement error into considerations simultaneously. The constructed methodology
subsumes a series of models studied in the literature as limiting cases. A simple
method is given to determine the transformed time scale forms of the Wiener process
degradation model. Then model parameters can be estimated based on a maximum
likelihood estimation (MLE) method. The cumulative distribution function (CDF) and
the probability distribution function (PDF) of the Wiener process with measurement
errors are given based on the concept of the first hitting time (FHT). The
percentiles of performance degradation (PD) and failure time distribution (FTD) are
also obtained. Finally, a comprehensive simulation study is accomplished to
demonstrate the necessity of incorporating measurement errors in the degradation
model and the efficiency of the proposed model. Two illustrative real applications
involving the degradation of carbon-film resistors and the wear of sliding metal
are given. The comparative results show that the constructed approach can derive a
reasonable result and an enhanced inference precision. (C) 2017 Elsevier Ltd. All
rights reserved.
Advanced extraction and purification techniques were found to be essential tools
for obtaining sufficient DNA from bones. However, in case of short tandem repeats
(STRs) typing failure especially with old skeletal remains, mitochondrial DNA
(mtDNA) analysis is the ultimate solution for individual and species
identification. Thirty six bone samples were collected from human remains. DNA was
extracted using the organic method after special sample preparations and quantified
using a Real-time polymerase chain reaction (RT-PCR). Polymerase chain reaction
(PCR) was done using Identifier Plus PCR Amplification Kit and amplified products
were typed using a Genetic Analyzer for autosomal STR typing. Samples with DNA
concentration above 0.04 ng were efficient in obtaining their complete STR
profiles. MtDNA control region was also amplified and sequenced. MtDNA was more
efficient than autosomal STR profiling in discriminating among human bone samples
especially those which have low and/or degraded DNA content.
Dehydrins, a large family of abiotic stress proteins, are defined by the presence
of a mostly conserved motif known as the K-segment, and may also contain two other
conserved motifs known as the Y-segment and S-segment. Using the dehydrin
literature, we developed a sequence motif definition of the K-segment, which we
used to create a large dataset of dehydrin sequences by searching the Pfam00257
dehydrin dataset and the Phytozome 10 sequences of vascular plants. A comprehensive
analysis of these sequences reveals that lysine residues are highly conserved in
the K-segment, while the amino acid type is often conserved at other positions.
Despite the Y-segment name, the central tyrosine is somewhat conserved, but can be
substituted with two other small aromatic amino acids (phenylalanine or histidine).
The S-segment contains a series of serine residues, but in some proteins is also
preceded by a conserved LHR sequence. In many dehydrins containing all three of
these motifs the S-segment is linked to the K-segment by a GXGGRRKK motif (where X
can be any amino acid), suggesting a functional linkage between these two motifs.
An analysis of the sequences shows that the dehydrin architecture and several
biochemical properties (isoelectric point, molecular mass, and hydrophobicity
score) are dependent on each other, and that some dehydrin architectures are
overexpressed during certain abiotic stress, suggesting that they may be optimized
for a specific abiotic stress while others are involved in all forms of dehydration
stress (drought, cold, and salinity).
The thyroid gland has an exceptionally high selenium content, even during selenium
deficiency. At least 11 selenoproteins are expressed, which may be involved in the
protection of the gland against the high amounts of H2O2 produced during thyroid
hormone biosynthesis. As determined here by in situ hybridization and Northern
blotting experiments, glutathione peroxidases (GPx) 1 and 4 and selenoprotein P
were moderately expressed, occurring selectively in the follicular cells and in
leukocytes of germinal follicles of thyroids affected by Hashimoto's thyroiditis.
Selenoprotein 15 was only marginally expressed and distributed over all cell types.
GPx3 mRNA was exclusively localized to the thyrocytes, showed the highest
expression levels and was down-regulated in 5 of 6 thyroid cancer samples as
compared to matched normal controls. GPx3 could be extracted from thyroidal colloid
by incubation with 0.5% sodium dodecyl sulfate indicating that this enzyme is (i)
secreted into the follicular lumen and (ii) loosely attached to the colloidal
thyroglobulin. These findings are consistent with a role of selenoproteins in the
protection of the thyroid from possible damage by H2O2. Particularly, GPx3 might
use excess H2O2 and catalyze the polymerization of thyroglobulin to the highly
cross-linked storage form present in the colloid.
Airway exposure of lipopolysaccharide (LPS) is shown to regulate type I and type II
helper T cell induced asthma. While high doses of LPS derive Th1- or Th17-immune
responses, low LPS levels lead to Th2 responses. In this paper, we analyze a
mathematical model of Thl/Th2/Th17 asthma regulation suggested by Lee et al. (S.
Lee, H.T. Hwang, and Y. Kim, Modeling the role of TGF-8 in regulation of the Th17
phenotype in the LPS-driven immune system, Bull Math Biol., 76 (5), 1045-1080,
2014) and show that the system can undergo a Hopf bifurcation at a steady state of
the Th17 phenotype for high LPS levels in the presence of time delays in inhibition
pathways of two key regulators: IL-4/Th2 activities (H) and TCF-beta levels (G).
The time delays affect the phenotypic switches among the Thl, Th2, and Th17
phenotypes in response to time-dependent LPS doses via nonlinear crosstalk between
H and G. An extended reaction-diffusion model also predicts coexistence of these
phenotypes under various biochemical and bio-mechanical conditions in the
heterogeneous microenvironment.
Background. Deficiencies in lysosomal a-mannosidase (LAM) activity in animals,
caused either by mutations or by consuming toxic alkaloids, lead to severe
phenotypic and behavioural consequences. Yet, epialleles adversely affecting LAM
expression exist in the honey bee population suggesting that they might be
beneficial in certain contexts and cannot be eliminated by natural selection.
Methods. We have used a combination of enzymology, molecular biology and
metabolomics to characterise the catalytic properties of honey bee LAM (AmLAM) and
then used an indolizidine alkaloid swainsonine to inhibit its activity in vitro and
in vtvo. Results. We show that AmLAM is inhibited in vitro by swainsonine albeit at
slightly higher concentrations than in other animals. Dietary exposure of growing
larvae to swainsonine leads to pronounced metabolic changes affecting not only
saccharides, but also amino acids, polyols and polyamines. Interestingly, the
abundance of two fatty acids implicated in epigenetic regulation is significantly
reduced in treated individuals. Additionally, swainsonie causes loco-like symptoms,
increased mortality and a subtle decrease in the rate of larval growth resulting in
a subsequent developmental delay in pupal metamorphosis. Discussion. We consider
our findings in the context of cellular LAM function, larval development,
environmental toxicity and colony-level impacts. The observed developmental
heterochrony in swainsonine-treated larvae with lower LAM activity offer a
plausible explanation for the existence of epialleles with impaired LAM expression.
Individuals carrying such epialleles provide an additional level of epigenetic
diversity that could be beneficial for the functioning of a colony whereby more
flexibility in timing of adult emergence might be useful for task allocation.
Porcine-transmissible gastroenteritis virus (TGEV) is a pathogenic coronavirus
responsible for high diarrhoea-associated morbidity and mortality in suckling
piglets. We analysed the TGEV ORF3 gene using nested polymerase chain reaction and
identified an ORF3a deletion in three field strains of TGEV collected from piglets
in China in 2015. Eight TGEV ORF3 sequences were obtained in this study.
Phylogenetic tree analysis of ORF3 showed that the eight TGEV ORF3 genes all
belonged to the Miller cluster. CH-LNCT and CH-MZL were closely correlated with
Miller M6, while CH-SH was correlated with Miller M60. These results thus indicate
that the existence of Miller, as well as the Purdue cluster, in Chinese field
strains of TGEV. Furthermore, we found the first evidence for a large deletion in
ORF3 resulting in the loss of ORF3a, previously reported in porcine respiratory
coronavirus, in three field strains (CH-LNCT, CH-MZL, and CH-SH) of TGEV. The
results of the present study thus provide important information regarding the
underlying evolution mechanisms of coronaviruses.
Modification of p53 expression levels and its principle apoptosis and cell cycle
regulatory partners, mouse double minute 2 homolog (MDM-2) and p21, has been
previously reported in various types of cancer. In the current study, the
expression of Delta 133p53 isoforms was investigated in lung carcinomas with
respect to the expression of the aforementioned genes. The expression of p53 full-
length transcript and Delta 133p53 isoforms alpha, beta and gamma transcripts, MDM-
2 and p21 transcripts were determined by reverse transcription-quantitative
polymerase chain reaction, in total RNA isolated from 17 lung carcinoma specimens
and 17 corresponding adjacent non-cancerous tissues. RNA expression analysis was
performed according to the Pfaffl equation and Rest tool using beta-actin as a
reference gene. Detection of the above proteins was additionally performed by
western blotting. Significant overexpression of the Delta 133p53 mRNAs was observed
in cancerous as compared with adjacent non-cancerous tissues (3.94-fold), whereas
full-length p53 and MDM-2 expression exhibited a smaller, however significant,
increase. The expression of the p21 transcript was significantly reduced in
cancerous specimens. Delta 133p53 and p21 expression levels varied in parallel,
however were not significantly correlated. p53 full-length protein expression
observed by western blot analysis strongly varied from the Delta 133p53 isoforms,
however MDM-2 protein isoforms were not detectable and p21 protein was more
abundant in non-cancerous tissues. In conclusion, Delta 133p53 mRNA levels is
suggested as a potentially useful marker of malignancy in lung cancer. The absence
of Delta 133p53 protein in lung carcinomas, which overexpress Delta 133p53
transcripts, may indicate the role of the latter in post-transcriptional regulation
through RNA interference in the cell cycle and apoptosis.
We propose an architecture that reduces the power consumption and active area of
such a modulator through a reduction in the number of active components and a
simplification of the topology. The proposed architecture reduces the power
consumption and active area by reducing the number of active components and
simplifying the modulator topology. A novel second-order loop filter that uses a
single operational amplifier resonator reduces the number of active elements and
enhances the controllability of the transfer function. A trapezoidal-shape half-
delayed return-to-zero feedback DAC eliminates the loop-delay compensation
circuitry and improves pulse-delay sensitivity. These simple features of the
modulator allow higher frequency operation and more design flexibility. Implemented
in a 130 nm CMOS technology, the prototype modulator occupies an active area of
0.098 mm(2) and consumes 5.23 mW power from a 1.2 V supply. It achieves a dynamic
range of 62 dB and a peak SNDR of 60.95 dB over a 15 MHz signal bandwidth with a
sampling frequency of 780 MHz. The figure-of-merit of the modulator is 191
fJ/conversion-step.
This paper discusses the use of a low gain amplifier and a passive switched-
capacitor (SC) network to enable the SC integrator function. The method is applied
to a delta-sigma modulator to achieve high resolution as proved by the 65-nm CMOS
technology test vehicle. Compared with the conventional operational amplifier (op-
amp)-based SC integrator, this solution utilizes a low-gain open-loop amplifier to
drive a passive SC integrator with positive feedback. Since the open-loop amplifier
requires a low dc gain and implements an embedded current adder, the power
consumption is very low. Power reduction for single bit is obtained by using
passive feed-forward with built-in adder to assist the first amplifier. The low
swing obtained at the output of the active blocks relaxes the slew rate requirement
and enhances the linearity. Implemented in 65-nm digital CMOS technology with an
active area of 0.1 mm(2), the test chip achieves a dynamic range of 91 dB, peak
signal-to-noise ratio of 88.4 dB, peak signal-to-noise-plus-distortion ratio of
88.2 dB, and a spurious free dynamic range of 106 dB while consuming 73.6 mu W in a
25-kHz signal bandwidth at 1 V supply, yielding a FoM(Walden) of 70 fJ/conv-step
and FoM(Schreier) of 176 dB.
This paper presents a low voltage continuous-time delta-sigma modulator (DSM)
intended for the receiver of an ultra-low-power radio. The DSM features a 2nd-order
loop filter implemented with a single operational amplifier to reduce the power
consumption. Furthermore, a 4-bit quantizer is used to achieve high resolution
while keeping the sampling frequency low. The quantizer is realized using the
successive approximation register architecture with asynchronous control which is
more power efficient than the commonly used flash architecture. The DSM has been
implemented in a 65 nm CMOS process. Simulation results show a peak SNDR of 65 dB
over a 500 kHz signal bandwidth. The DSM consumes 69 W from a 800 mV power supply.
China is quickly installing advanced metering infrastructure (AMI), which could
provide tremendous opportunities in developing and utilizing demand response
resources. Demand response may potentially create a profitable industry and
contribute to efficiency improvement, cost reduction, and pollution mitigation of
the entire electricity sector. However, China lags behind the developed world in
utilizing demand response. Institutional barriers, including the lack of
competitive electricity market and the resistance by the state grid corporations,
are preventing the commercialization of demand response. In order to fully realize
the potential of smart grid, China needs to push forward the reforms toward
establishing an open access electricity market so the pollution-free demand
response resources may compete with power generators on leveled field. (C) 2015
Elsevier B.V. All rights reserved.
Understanding the contribution a resource can make to the power system could
indicate where its value lies. This paper estimates the capacity value of a load-
shifting resource which is capable of providing multiple services. The capacity
value represents the contribution of a resource to generation adequacy and an
understanding of this contribution is important to compare how different power
system resources can assist power system operators and planners. Additionally,
policy-makers and market operators need an appreciation of the capacity value of
different resources in order to design capacity remuneration mechanisms. A building
energy model coupled with a power system model, co-optimizing the supplyside and
the demand-side, is employed in this paper to estimate the capacity value of a
specific load shifting resource. The resource examined is electric thermal storage
heating devices for space and water heating. Ireland is used as a test case. It was
found that these load-shifting devices can provide an adequacy contribution to the
power system and thus have a capacity value. The capacity value, for the Irish
case, can be up to 26% for the DR resource in question for the given year but the
values are typically much lower due to operational constraints (reserve provision)
and due to occupancy profile impacts. The results highlight the need for holistic
modeling of demand response resources, as well as the need for additional work for
different load-shifting resources and more data. (C) 2017 Elsevier Ltd. All rights
reserved.
We present an economic assessment of the impacts of Demand Response (DR) and
pricing schemes on the conditions for distributed solar photovoltaics, with the
focus on individual households. An optimization model has been developed that
minimizes the electricity cost for individual households with the option of
dispatching DR loads. DR of appliances and hydronic heating (electrical water
heating for both space heating and hot water) are investigated, as well as the
effects of applying a monthly, hourly or net metering pricing scheme for selling
excess generated electricity and a tax reduction scheme for electricity sold to the
grid. We show that for Swedish conditions a monthly net metering pricing scheme
would result in the largest PV installations per household (median rated capacity
of 4.21 Wpihousehold). The use of the tax reduction scheme reduces the installation
per household (2.1 kWp/household), but with an installation being profitable for a
larger fraction of the households. Furthermore, the tax reduction scheme retains an
incentive for engaging in DR. The use of hydronic DR can support the same
installations sizes as the tax reduction scheme, whilst Appliance DR is shown to
have only a low impact on the profitability of a PV installation. (C) 2017 Elsevier
Ltd. All rights reserved.
Power system reliability faces serious challenges when supply shortage occurs
because of unexpected generation or transmission line outages especially during
extreme weather conditions. Alternative to conventional approaches that solicit
aids from the generation side, operators can now leverage the demand-side resources
through a variety of electricity market mechanisms to balance the active power and
enhance system reliability. The benefits of the demand response (DR) have long been
recognized in many works and empirical cases. Systematic analyses, however, have
never been addressed to assess the values of the market-based DR for supporting
system reliability. In this paper, a case study on the performance of DR in PJM
Interconnections during the 2014 North American Polar Vortex is provided to
highlight the significant contributions to improving system reliability and
maintaining grid stability from DR programs. The unique merits in technical,
economic and environmental aspects exhibited by DR during this extreme event verse
conventional system-reliability-improving approaches are also demonstrated
accordingly. Furthermore, we reveal the difference of DR programs driven by various
existing market mechanisms after describing the fundamental DR functions. Values of
various DR programs are also highlighted. At last, challenges and opportunities
facing China on the design and implementation of DR programs during the transform
from the monopoly scheme to an open electricity market during the power industry
restructuring in recent years are also discussed. (C) 2017 Elsevier Ltd. All rights
reserved.
Demand response, defined as the shifting of electricity demand, is generally
believed to have value both for the grid and for the market: by matching demand
more closely to supply, consumers could profit from lower prices, while in a smart
grid environment, more renewable electricity can be used and less grid capacity may
be needed. However, the introduction of residential demand response programmes to
support the development of smart grids that includes renewable generation is
hampered by a number of barriers. This paper reviews these barriers and categorises
them for different demand programmes and market players. The case study for the
Netherlands shows that barriers can be country specific. Two types of demand
response programmes have been identified as being the most promising options for
households in smart grids: price-based demand response and direct load control,
while they may not be beneficial for market players or distribution system
operators. (C) 2016 The Authors. International Journal of Energy Research Published
by John Wiley & Sons Ltd.
This paper presents a novel approach to demand side management (DSM), using an
"individualized" price policy, where each end user receives a separate electricity
pricing scheme designed to incentivize demand management in order to optimally
manage flexible demands. These pricing schemes have the objective of reducing the
peaks in overall system demand in such a way that the average electricity price
each individual user receives is non-discriminatory. It is shown in this paper that
this approach has a number of advantages and benefits compared to traditional DSM
approaches. The "demand aware price policy" approach outlined in this paper
exploits the knowledge, or demand-awareness, obtained from advanced metering
infrastructure. The presented analysis includes a detailed case study of an
existing European distribution network where DSM trial data was available from the
residential end-users.
Objective: To examine the effects of using cognitive reappraisal to find positive
gains on caregivers' depressive symptoms, burden, and psychological well-being.
Method: Ninety-six caregivers of persons with Alzheimer's disease were randomly
assigned to receive a benefit-finding intervention or 1 of 2 treatment-as-usual
conditions, namely, simplified psychoeducation (lectures only; SIM-PE) or standard
psychoeducation (STD-PE). Each participant received 4 biweekly interventions of 3
hr each, over a 2-month period, at home. Results: Results showed that benefit-
finding participants reported lower depressive symptoms after treatment, when
compared with either SIM-PE (d = -0.46) or STD-PE (d = -0.50) participants. They
also reported less role overload when compared with STD-PE participants (d = -
0.46). Self-efficacy in controlling upsetting thoughts was a mediator for some of
the treatment effects. Conclusion: Finding positive gains is an effective
intervention to reduce depressive symptoms among Alzheimer caregivers.
Background: Cortical and subcortical cognitive impairments have been found in
dementia with Lewy bodies (DLB). Roughly, they comprise visuoconstructive and
executive dysfunction, whereas memory would remain relatively spared. However, the
cognitive profile of patients with prodromal DLB remains poorly illustrated to
date. Methods: We included 37 patients with prodromal DLB (age 67.2 +/- 8.6 years,
18 men, Mini Mental State Examination [MMSE] score 27.4 +/- 2) and 29 healthy
control subjects (HCs; age 68.8 +/- 7.9 years, 15 men, MMSE score 29.0 +/- 0.9).
They were presented with an extensive neuropsychological test battery to assess
memory; speed of processing; executive function; visuoperceptual, visuospatial and
visuoconstructive abilities; language; and social cognition. Results: Compared with
HCs, patients had lower scores on a visual recognition memory test (Delayed
Matching to Sample-48 items; p <= 0.021) and lower free recall (all p <= 0.035),
but not total recall, performance on a verbal episodic memory test (Free and Cued
Selective Reminding Test). Short-term memory (p = 0.042) and working memory (p =
0.002) scores were also lower in patients. Assessment of executive function showed
no slowing but overall lower performance in patients than in HCs (all p <= 0.049),
whereas assessment of instrumental function yielded mixed results. Indeed, patients
had lower scores on language tests (p <= 0.022), apraxia for pantomime of tool use
(p = 0.002) and imitation of meaningless gesture (p = 0.005), as well as weakened
visuospatial abilities (p = 0.047). Visuoconstruction was also impaired in
patients. However, visuoperceptual abilities did not differ between groups.
Finally, theory of mind abilities were lower in patients than in HCs (p < 0.05),
but their emotion recognition abilities were similar. Conclusions: This study
presents the cognitive profile in patients with prodromal DLB. In line with the
literature on DLB with dementia, our results show lower performance on tests of
executive function and visuoconstruction. However, we found, from a prodromal stage
of DLB, memory (free recall and visual recognition) and social cognition deficits,
as well as weakened visuospatial and praxic abilities.
We herein report the case of a 75-year-old male who had shown many psychiatric
symptoms, but whose autopsy disclosed the presence of dementia with Lewy bodies
(DLB). When he was 70 years old, the patient had presented with stereotyped
behavior, dietary changes, and a decline in social interpersonal conduct in
clinical settings, and it was thought that these symptoms were consistent with a
behavioral variant of frontotemporal dementia (bvFTD), and he lacked the core
features of DLB. Nevertheless, this case was pathologically defined as the limbic
type of DLB after he died at the age of 75 years. Looking retrospectively at the
clinical course, it was considered that the following features were suggestive or
supportive of DLB: neuroleptic sensitivity, autonomic symptoms, and psychiatric
symptoms. It can be presumed that the bvFTD-like behavioral disturbances were
caused by the severe Lewy pathology of the locus ceruleus (LC) and left anterior
temporal region. The clinical symptoms of DLB might be more multifarious than has
conventionally been thought, because the symptoms can be modified by the
pathological spread of DLB within the brain. It is important to be aware of these
possible symptoms of DLB so as not to overlook the diagnosis in the clinical
setting.
Dementia is an ever-expanding problem facing an ageing society. Currently, there is
a sharp paucity of treatment strategies. It has long been known that sex hormones,
namely 17 beta-estradiol and testosterone, possess neuroprotective- and cognitive-
enhancing qualities. However, certain lacunae in the knowledge underlying their
molecular mechanisms have delayed their use as treatment strategies in dementia.
With recent advancements in pharmacology and molecular biology, especially in the
development of safer selective oestrogen receptor modulators and the recent
discovery of the small-molecule brain-derived neurotrophic factor receptor agonist,
7,8-dihydroxyflavone, the exploitation of these signalling pathways for clinical
use has become possible. This review aims to adumbrate the evidence and hurdles
underscoring the use of sex hormones in the treatment of dementia as well as
discussing some direction that is required to advance the translation of evidence
into practise.
This cross-sectional study aimed to investigate the relationship between caregivers
and care receivers, defined as home-dwelling family members with dementia. We used
a self-rating questionnaire, the Felt Expressed Emotion Rating Scale (FEERS; 6
simple questions), to measure caregiver perceptions of the care receiver's
criticisms (CCs) and emotional overinvolvement (EOI) toward the caregiver. We
performed factor analyses to rank single items on the FEERS pertaining to CC and
EOI. We included 208 caregiver/care receiver pairs. Logistic regression analyses
tested associations between FEERS items and caregiver and care receiver variables.
The main contributors to caregiver perceptions of CC were the caregiver's own
distress and the amount of time spent with the care receiver. Socially distressed
caregivers perceived the care receiver as emotionally overinvolved. When offering a
psychosocial intervention, a tailored program should target the caregiver's
perceived relationship with the family member and the caregiver's distress. The
program should also endeavor to give the caretaker more opportunities for leisure
time.
The objectives of the nuclear fusion power plant DEMO, to be built after the ITER
experimental reactor, are usually understood to lie somewhere between those of ITER
and a 'first of a kind' commercial plant. Hence, in DEMO the issues related to
efficiency and RAMI (reliability, availability, maintainability and inspectability)
are among the most important drivers for the design, as the cost of the electricity
produced by this power plant will strongly depend on these aspects. In the
framework of the EUROfusion Work Package Heating and Current Drive within the Power
Plant Physics and Development activities, a conceptual design of the neutral beam
injector (NBI) for the DEMO fusion reactor has been developed by Consorzio RFX in
collaboration with other European research institutes. In order to improve
efficiency and RAMI aspects, several innovative solutions have been introduced in
comparison to the ITER NBI, mainly regarding the beam source, neutralizer and
vacuum pumping systems.
This paper presents a demodulation algorithm based on the synchronous integrator
circuit for the MEMS tuning fork gyroscope utilizing the digital processing
technology. The synchronous integral demodulator (SID) is adopted to demodulate the
drive-detection signal and sense-axis output signal separately. Combining with
automatic gain control and phase-locked loop technology, the closed-loop control of
drive mode has been implemented, and high precision output of the gyroscope has
been achieved. The simulation results have verified the effectiveness of the
synchronous integrator circuit, which is in good agreement with the theoretical
analysis. Compared with other demodulation algorithms, the SID has the advantages
of the lower noise level, a better ability to attenuate the harmonics, and the best
hardware efficiency. The frequency characteristic of the synchronous integrator is
also analyzed, which is vital to the bandwidth of gyroscope. The print circuit
board based on field-programmable gate array digital circuit is manufactured and
the corresponding experiment is carried out. The experimental results show that the
SID algorithm of digital control system for the gyroscope developed in our
laboratory has achieved a good performance. The bias instability of tested
gyroscope is measured to be 0.2 degrees l/h with the angle random walk of 0.14
degrees/root h and the nonlinearity of the scale factor is < 60 ppm with the
measurement range of +/- 100 degrees/s.
Though present in low numbers, dendritic cells (DCs) are recognized as major
players in the control of cancer by adaptive immunity. The roles of cytotoxic
CD8(+) T-cells and Th1 helper CD4(+) T-cells are well-documented in murine models
of cancer and associated with a profound prognostic impact when infiltrating human
tumors, but less information is known about how these T-cells gain access to the
tumor or how they are primed to become tumor-specific. Here, we highlight recent
findings that demonstrate a vital role of CD103(+) DCs, which have been shown to be
experts in cross-priming and the induction of anti-tumor immunity. We also focus on
two different mediators that impair the function of tumor-associated DCs:
prostaglandin E-2 and beta-catenin. Both of these mediators seem to be important
for the exclusion of T-cells in the tumor microenvironment and may represent key
pathways to target in optimized treatment regimens against cancer.
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to
CD8(+) T-cells, promoting their differentiation into cytotoxicT-lymphocytes (CTLs),
which play a pivotal role in anti-tumor immunity. Emerging evidence points to
dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied
how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-
deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-
tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs
potentiated antigen cross-presentation and CTLs activation. Our findings suggest
that D3R in DCs constitutes a new therapeutic target to strengthen anti-tumor
immunity. (C) 2016 Elsevier B.V. All rights reserved.
We introduce a versatile carrier system for in vitro and in vivo immune stimulation
based on soft matter DNA nanoparticles (NPs). The incorporation of lipid-modified
nucleotides into DNA strands enables the formation of micelles of uniform size. In
a single self-assembly step, the micelles can be equipped with immune adjuvant
(CpG) motifs and fluorescent probes. The immunological effects of CpG confined at
the NP surface were studied in a comprehensive manner in animal experiments. Dose-
dependent activation of spleen dendritic cells (DCs) by CpG-conjugated NP was
observed, which was accompanied by the pronounced up-regulation of co-stimulatory
molecule and cytokine production. (C) 2016 Elsevier Ltd. All rights reserved.
Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-
polarizing differentiation signals have paved the way for the development of DC-
based cancer vaccines. Critical parameters for assessment of the optimal functional
state of DCs and prediction of the vaccine potency of activated DCs have in the
past been based on measurements of differentiation surface markers like HLA-DR,
CD80, CID83, CD86, and CCR7 and the level of secreted cytokines like interleukin-
12p70. However, the level of these markers does not provide a complete Picture of
the DC phenotype and may be insufficient for prediction of clinical outcome for DC-
based therapy. We therefore looked for additional biomarkers by investigating the
differential expression of microRNAs (miRNAs) in mature DCs relative to immature
DCs. A microarray-based screening revealed that 12 miRNAs were differentially
expressed in the two DC phenotypes. Of these, four miRNAs, hsa-miR-155, hsa-miR-
146a, hsa-miR-125a-5p, and hsa-miR-29a, were validated by real-time polymerase
chain reaction and northern blotting. The matured DCs from 12 individual donors
were divided into two groups of highly and less differentiated DCs, respectively. A
pronounced difference at the level of miRNA induction between these two groups was
observed, suggesting that quantitative evaluation of selected miRNAs potentially
can predict the immunogenicity of DC vaccines. (C) 2010 American Society for
Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights
reserved.
Objective: To evaluate the trends in usage of dengue virus diagnostics in Pakistan.
Methods: This retrospective study was conducted at the Aga Khan University
Hospital, Karachi, and comprised data for specimens tested for dengue virus from
January 2012 to December 2015. Test for dengue virus ribonucleic acid by reverse
transcription polymerase chain reaction, dengue virus antigen by immunochromatic
assay and for human immunoglobulin M against dengue virus by enzyme-linked
immunosorbent assay were reviewed. SPSS 17 was used for data analysis. Results:
Overall, 33,577 specimens tested for dengue virus. Of them, 11,995 (35.7%) were
positive. among them, 1,039(8.66%) were reported in 2012; 5,791(48.28%) in 2013;
1,027(8.56%) in 2014; and 4,138(34.49%) in 2015. In 2012, 966(93%) of the positive
samples were diagnosed by immunoglobulin M-based method and 73(7%) by nonstructural
protein-1 antigen. In 2013, 4,401(76%) samples were tested positive by
immunoglobulinM, 1,332(23%) by antigen and 58(1%) by polymerase chain reaction. The
trend continued in 2014, but in 2015, 2,111(51%) of all dengue positive tests were
determined by antigen testing, 1,969(47.6%) by immunoglobulin M and 58(1.4%) by
polymerase chain reaction. Conclusion: There was a shift in usage of direct virus
identification for rapid diagnosis of dengue virus compared with host
immunoglobulin M testing.
An upsurge of fever cases of unknown origin, but resembling dengue and
leptospirosis was reported in Havelock, Andaman & Nicobar Islands, an important
tourism spot, during May 2014. Investigations were carried out to determine the
aetiology, and to describe the epidemiology of the outbreak. The data on fever
cases attending Primary Health Centre (PHC), Havelock showed that the average
number of cases reporting per week over the last 2 years was 461 (95% confidence
interval 194-729). A total of 27 (435%) patients out of the 62 suspected cases were
diagnosed as having DENV infection based on a positive enzyme immunoassay or
reverse transcriptase-polymerase chain reaction. The overall attack rate was 94
cases/1000 population and it ranged between 28 and 188/1000 in different villages.
The nucleotide sequencing showed that the virus responsible was DENV-3. DENV-3 was
first detected in the Andaman & Nicobar Islands in 2013 among wharf workers in Port
Blair and within a year it has spread to Havelock Island which is separated from
South Andaman by 36 nautical miles.
BACKGROUND Despite the current global trend of reduction in the morbidity and
mortality of neglected diseases, dengue's incidence has increased and occurrence
areas have expanded. Dengue also persists as a scientific and technological
challenge since there is no effective treatment, vaccine, vector control or public
health intervention. Combining bibliometrics and social network analysis methods
can support the mapping of dengue research and development (R&D) activities
worldwide. OBJECTIVES The aim of this paper is to map the scientific scenario
related to dengue research worldwide. METHODS We use scientific publication data
from Web of Science Core Collection - articles indexed in Science Citation Index
Expanded (SCI-EXPANDED) - and combine bibliometrics and social network analysis
techniques to identify the most relevant journals, scientific references, research
areas, countries and research organisations in the dengue scientific landscape.
FINDINGS Our results show a significant increase of dengue publications over time;
tropical medicine and virology as the most frequent research areas and biochemistry
and molecular biology as the most central area in the network; USA and Brazil as
the most productive countries; and Mahidol University and Fundacao Oswaldo Cruz as
the main research organisations and the Centres for Disease Control and Prevention
as the most central organisation in the collaboration network. MAIN CONCLUSIONS Our
findings can be used to strengthen a global knowledge platform guiding policy,
planning and funding decisions as well as to providing directions to researchers
and institutions. So that, by offering to the scientific community, policy makers
and public health practitioners a mapping of the dengue scientific landscape, this
paper has aimed to contribute to upcoming debates, decision-making and planning on
dengue R& D and public health strategies worldwide.
Background: Densoviruses (DVs) are highly pathogenic to their hosts. However, we
previously reported a mutualistic DV (HaDV2). Very little was known about the
characteristics of this virus, so herein we undertook a series of experiments to
explore the molecular biology of HaDV2 further. Results: Phylogenetic analysis
showed that HaDV2 was similar to members of the genus Iteradensovirus. However,
compared to current members of the genus Iteradensovirus, the sequence identity of
HaDV2 is less than 44% at the nucleotide-level, and lower than 36, 28 and 19% at
the amino-acid-level of VP, NS1 and NS2 proteins, respectively. Moreover, NS1 and
NS2 proteins from HaDV2 were smaller than those from other iteradensoviruses due to
their shorter N-terminal sequences. Two transcripts of about 2.2 kb coding for the
NS proteins and the VP proteins were identified by Northern Blot and RACE analysis.
Using specific anti-NS1 and anti-NS2 antibodies, Western Blot analysis revealed a
78 kDa and a 48 kDa protein, respectively. Finally, the localization of both NS1
and NS2 proteins within the cell nucleus was determined by using Green Fluorescent
Protein (GFP) labelling. Conclusion: The genome organization, terminal hairpin
structure, transcription and expression strategies as well as the mutualistic
relationship with its host, suggested that HaDV2 was a novel member of the genus
Iteradensovirus within the subfamily Densovirinae.
Dental teams have been involved with child protection for over 40years. This brief
review summarises their involvement in the detection of various types of child
abuse and goes on to discuss the gap between the proportions of dental
professionals who suspect child abuse or neglect in their paediatric patients and
those who refer such cases on. Potential reasons for this discrepancy are
discussed, and a glimpse of the future is given as to where further research may be
necessary to tackle this existing gap.
According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone
transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical
technique itself has a respectable number of reports regarding its clinical
efficacy, as measured by long-term survival of dental implants in grafted areas.
Uncertainty remains, however, as to whether fresh frozen grafts from human bone
donors remain immunologically innocuous in the body of the host. Six male with no
previous medical history of note, including systemic diseases, surgery or blood
transfusion were selected. These patients underwent reconstructive procedures
(sinus lifting) using fresh frozen human bone from a tissue bank. All patients had
venous blood samples collected prior to surgery and 6 months after the procedure.
Anti-HLA analysis for the detection of HLA(human leukocyte antigen) antibodies was
performed using methods such as the LAB Screen PRA Class I and Class II, LAB Screen
Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the
screening tests (LAB Screen PRA) were further investigated to determine the
specificity of the antibodies detected (LAB Screen Single Antigen) with a cutoff
value of median fluorescence intensity >= 500. As a result, it was observed that
two patients (33%) were positive in screening tests, one presenting with anti-HLA
Class I and II sensitization and the other with anti-HLA class II. The specificity
analysis showed that the patients sensitized to HLA class II presented 4
specificities, 3 of which immunologically relevant. In the second individual, 23
specificities were identified, 6 of which immunologically important for HLA class I
and 4 specificities for HLA class II, 3 of these were immunologically important.
All specificities detected had average fluorescence. These findings are suggestive
that sinus-lifting procedures with allogeneic bone can induce immunological
sensitization.
Objective: Pulp and periodontal tissues are well-known sources of mesenchymal stem
cells (MSCs) that provide a promising place in tissue engineering and regenerative
medicine. The molecular mechanisms underlying commitment and differentiation of
dental stem cells that originate from different dental tissues are not fully
understood. In this study, we have compared the expression levels of pluripotency
factors along with immunological and developmentally-related markers in the culture
of human dental pulp stem cells (hDPSCs), human dental follicle stem cells
(hDFSCs), and human embryonic stem cells (hESCs). Materials and Methods: In this
experimental study, isolated human dental stem cells were investigated using
quantitative polymerase chain reaction (qPCR), immunostaining, and fluorescence-
activated cell sorting (FACS). Additionally, we conducted gene ontology (GO)
analysis of differentially expressed genes and compared them between dental stem
cells and pluripotent stem cells. Results: The results demonstrated that
pluripotency (OCT4 and SOX2) and immunological (IL-6 and TLR4) factors had higher
expressions in hDFSCs, with the exception of the JAG-GED-1/NOTCH1 ratio, c-MYC and
NESTIN which expressed more in hDPSCs. Immunostaining of OCT4, SOX2 and c-MYC
showed cytoplasmic and nucleus localization in both groups at similar passages. GO
analysis showed that the majority of hDFSCs and hDPSCs populations were in the
synthesis (S) and mitosis (M) phases of the cell cycle, respectively. Conclusion:
This study showed different status of heterogeneous hDPSCs and hDFSCs in terms of
stemness, differentiation fate, and cell cycle phases. Therefore, the different
behaviors of dental stem cells should be considered based on clinical treatment
variations.
Fusarium Head Blight is a major disease of wheat and an important contributor to
the reduced cultivation of wheat in South Africa, where the crop often is grown
under irrigation. We collected Fusarium isolates from 860 Fusarium Head Blight-
infected wheat heads in seven irrigated wheat-growing areas of South Africa. Six
Fusarium species, i.e., F. chlamydosporum, F. crookwellense, F. culmorum, F.
equiseti, F. graminearum and F. semitectum were recovered, three of which, i.e., F.
chlamydosporum, F. equiseti and F. semitectum, were not previously associated with
Fusarium Head Blight in South Africa. Fusarium graminearum occurred at high
frequencies at all seven locations. Based on polymerase chain reaction (PCR) assays
of diagnostic sequences, more isolates were predicted to produce deoxynivalenol
than nivalenol. Fusarium graminearum (sensu lato) appears to be the primary causal
agent of Fusarium Head Blight in irrigated wheat in South Africa, which may not be
the case for wheat cultivated under rain-fed conditions. Rotations of irrigated
wheat with other graminaceous crops and maize could increase fungal inoculum and
disease pressure. The establishment of Fusarium Head Blight in the irrigated wheat
region of the country means that resistant lines and alternative agronomic
practices are needed to limit disease severity, yield losses and mycotoxin
contamination.
Since the invention of polymerase chain reaction (PCR) in 1985, PCR has played a
significant role in molecular diagnostics for genetic diseases, pathogens,
oncogenes and forensic identification. In the past three decades, PCR has evolved
from end-point PCR, through real-time PCR, to its current version, which is the
absolute quantitive digital PCR (dPCR). In this review, we first discuss the
principles of all key steps of dPCR, i.e., sample dispersion, amplification, and
quantification, covering commercialized apparatuses and other devices still under
lab development. We highlight the advantages and disadvantages of different
technologies based on these steps, and discuss the emerging biomedical applications
of dPCR. Finally, we provide a glimpse of the existing challenges and future
perspectives for dPCR.
Deoxyribonucleic acid (DNA) plays an extremely important role in storing genetic
messages that are used for cellular functions in living organisms. However, the
process of replicating these messages is not free from errors as internal and
external factors can contribute to the damages of DNA strands. These damages known
as lesions are problematic since they can lead to mutagenesis and carcinogenesis
after accumulation for a certain period of time. Thankfully, cells are able to
synthesize various DNA glycosylases to target different lesions, repairing and
restoring damaged DNA to its original state. This review article aims to explore
the variety of assays used to evaluate the efficiency of these glycosylases, mainly
focusing on uracil DNA glycosylase, thymine DNA glycosylase, and 8-oxoguanine DNA
glycosylase since they are deployed to the sites of damages much more often than
other repair enzymes. The progress in the development of DNA glycosylase assays is
reviewed with an emphasis on the configuration and operating mechanism of the
assays and with some discussion on challenges and prospects. It is hoped that this
article will provide an introductory overview and the current standing of DNA
glycosylase assays, opening up new perspectives towards the development DNA
glycosylase assays for uses in molecular biology and at point-of-care. (C) 2016
Elsevier B.V. All rights reserved.
In a digital control system, the dependency model between the actions of operators
differs from that in a conventional control room because information sharing and
the main control room (MCR) operations are team operations. Dependencies between
the actions of operators are more common in a digital control system compared with
a conventional control room because operators share the same information and MCR
operations are directed by team decisions. Therefore, assessing the dependencies
between operators is an important aspect of human reliability analysis. In this
study, we use a fuzzy logic-based approach to evaluate the dependencies among the
actions of operators in the present study. First, the factors that influence the
dependency levels among the actions of operators are identified by analyzing the
characteristic human factors in a digital control system and an analytical model of
the dependencies is then constructed. Second, a method for analyzing the
dependencies between the actions of operators is established based on a fuzzy logic
approach. This method can simulate vague and uncertain knowledge, but it also
provides a clear explanation of the origins of results and their reasoning process
by tracing the steps in reasoning. Therefore, traceability and repeatability are
characteristics of the proposed method. Third, we present a case study to
demonstrate the proposed approach. Finally, we demonstrate that the results
obtained are reasonable and that the established model is stable based on
validations that involve data comparisons and a sensitivity analysis of the model.
(C) 2015 Elsevier B.V. All rights reserved.
BackgroundAdolescence is a period of increased risk for the development of
depression. Epidemiological and clinical studies suggest that the phenomenology of
depression may differ during childhood and adolescence. However, participants in
these studies may not reflect depressed young people referred to routine clinical
services. The aim of this paper was to describe referrals for depression to a UK
routine public healthcare service for children and adolescents with mental health
difficulties. MethodThis paper describes a consecutive series of adolescents
(N=100, aged 12-17years), referred for depression to a routine public healthcare
child and adolescent mental health service, in the south of England. Young people
and their caregivers completed a structured diagnostic interview and self-report
measures of anxiety and depression. ResultsFewer than half of young people referred
for depression met diagnostic criteria for a depressive disorder. The key symptoms
reported by those with depression were low mood or irritability, cognitive
disturbances, sleep disturbances and negative self-perceptions. Suicidal ideation
was common and was considerably higher than reported in other studies. Caregiver
and young person's accounts of adolescent symptoms of depression and anxiety were
uncorrelated. Caregivers also reported fewer symptoms of depression in their child
than adolescents themselves. ConclusionsThese data have direct relevance to the
design and delivery of public mental health services for children and adolescents.
However, we do not know how representative this sample is of other clinical
populations in the UK or in other countries. There is a need to collect routine
data from other services to assess the needs of this group of high-risk
adolescents.
Objective: Adjunctive antipsychotic therapy can be prescribed to patients with
depression who have inadequate response to antidepressants. This study aimed to
describe the use of adjunctive antipsychotics over a time period that includes the
authorization in 2010 of prolonged-release quetiapine as the first adjunct
antipsychotic to be used in major depressive disorder in the UK.Research design and
methods: Adults with an episode of depression between January 1, 2005 and July 31,
2013 were identified from antidepressant prescriptions and depression diagnoses in
the UK Clinical Practice Research Datalink. Patients with prior records of bipolar
disorder, schizophrenia, or antipsychotic prescriptions were excluded.Main outcome
measures: Rates of adjunct antipsychotic initiation and characteristics and
management of patients with adjunct antipsychotics.Results: Of 224,353 adults with
depression, 5,807 (2.6%) initiated adjunct antipsychotic therapy. Overall incidence
of antipsychotic initiation was 7.4 per 1,000 patient-years (95% CI=7.2-7.6).
Between 2005-2013, the overall rate did not change, although initiation of typical
antipsychotic prescribing decreased (57.7% to 29.1%), while atypical
antipsychotics, especially quetiapine (14.1% to 49.7%), increased. Of those who
initiated antipsychotics, 59.4% were women (typical antipsychotics=62.8%, atypical
antipsychotics=56.1%) and median age was 46 years (typicals=49 years, atypicals=44
years).Conclusions: Antipsychotics were rarely used to treat depression between
2005-2013 in UK primary care. The choice of adjunctive antipsychotic therapy
changed over this time, with atypical antipsychotics now representing the preferred
treatment choice. However, information on patients strictly cared for in other
settings, such as by psychiatrists or in hospitals, potentially more severe
patients, was unavailable and may differ. Nonetheless, the high off-label use in
primary care, even after the authorization of quetiapine, suggests that there is a
need for more licensed treatment options for adjunctive antipsychotic therapy in
major depressive disorder.
Depression is a major health problem in which oxidative stress and inflammation are
inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important
anti-oxidant compound with anti-inflammatory and neuro-protective properties. This
study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and
anti-inflammatory potentials can alleviate depressive- like behavior by restoring
the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin
pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1).
Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS)
protocol including food or water deprivation, cage tilting, reversed light cycle
etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS
and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on
different behavioral and biochemical tests were analyzed. CoQ10 showed significant
antidepressant efficacy, as evidenced by significantly decreased stress induced
changes to forced swimming challenge and open field test, as well as attenuating
raised corticosterone level and adrenal glands weight. The anti-oxidant effect of
CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated
malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and
catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines
levels including interleukin (IL)-1 beta, IL-2, IL-6 and tumor necrosis factor-
alpha. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and
enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical
analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and
elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10
exhibited antidepressant-like effects on rats exposed to CUMS. This could be
attributed to its ability to reduce IDO-1 leading to shift the balance of the
Kynurenine/ serotonin toward the serotonin pathway.
Background: Collaborative Care is an evidence-based approach to the management of
depression within primary care services recommended within NICE Guidance. However,
uptake within the UK has been limited. This review aims to investigate the barriers
and facilitators to implementing Collaborative Care. Methods: A systematic review
of the literature was undertaken to uncover what barriers and facilitators have
been reported by previous research into Collaborative Care for depression in
primary care. Results: The review identified barriers and facilitators to
successful implementation of Collaborative Care for depression in 18 studies across
a range of settings. A framework analysis was applied using the Collaborative Care
definition. The most commonly reported barriers related to the multi-professional
approach, such as staff and organisational attitudes to integration, and poor
inter-professional communication. Facilitators to successful implementation
particularly focussed on improving inter-professional communication through
standardised care pathways and case managers with clear role boundaries and key
underpinning personal qualities. Limitations: Not all papers were independent title
and abstract screened by multiple reviewers thus limiting the reliability of the
selected studies. There are many different frameworks for assessing the quality of
qualitative research and little consensus as to which is most appropriate in what
circumstances. The use of a quality threshold led to the exclusion of six papers
that could have included further information on barriers and facilitators.
Conclusions: Although the evidence base for Collaborative Care is strong, and the
population within primary care with depression is large, the preferred way to
implement the approach has not been identified.
Objective: Depression screening should be increased when prevailing knowledge
underscoring medication associated mental health risk is highest. Depression
screening in primary care practices when medications with mental health risk were
prescribed was estimated while considering the absence and presence of clinical
decision support systems. Materials and methods: A cross-sectional, descriptive
study using the National Ambulatory Medical Care Survey (NAMCS) data from 2008 to
2010 was conducted. Primary care physician visits were classified based on whether
a medication prescribed had a contraindication, severe warning, moderate warning,
adverse event only, or no documented mental health risk. Adjusted odds of
depression screening for each risk warning level were estimated while controlling
for important sociodemographic factors and presence of computerized systems for
medication warnings and guideline recommendations. Results: Depression screening at
primary care practice visits when medications were prescribed was 2.1% and
increased to 2.8% or higher when medications had a moderate or severe mental health
risk warning or medication-disease contraindication. Depression screening was
increased at visits when at least one medication was prescribed that had a
contraindication (AOR = 6.31, P < 0.001), severe warning (AOR = 2.04, P = 0.003),
or moderate warning (AOR = 2.50, P = 0.012) for mental health risk, but not for
mental health adverse event only warnings alone (AOR = 1.54, P = 0.074).
Discussion: Depression screening is increased when medications were prescribed with
a documented mental health risk. Presence of clinical decision support systems may
help discern between minor and major medication-associated mental health risks.
Conclusions: Appropriately, positioned warning systems with targeted content,
workflow redesign, and health information exchange may improve depression screening
in at-risk patients. (C) 2016 Elsevier Inc. All rights reserved.
ObjectiveTo test the association between recall for socially rewarding (positive)
and/or socially critical (negative) information and depressive symptoms.
MethodCohort study of people who had visited UK primary care in the past year
reporting depressive symptoms (N=558, 69% female). Positive and negative recall was
assessed at three time-points, 2weeks apart, using a computerised task. Depressive
symptoms were assessed at four time-points using the Beck Depression Inventory
(BDI). Analyses were conducted using multilevel models. ResultsConcurrently we
found evidence that, for every increase in two positive words recalled, depressive
symptoms reduced by 0.6 (95% CI -1.0 to -0.2) BDI points. This association was not
affected by adjustment for confounders. There was no evidence of an association
between negative recall and depressive symptoms (-0.1, 95% CI -0.5 to 0.3).
Longitudinally, we found more evidence that positive recall was associated with
reduced depressive symptoms than vice versa. ConclusionPeople with more severe
depressive symptoms recall less positive information, even if their recall of
negative information is unaltered. Clinicians could put more emphasis on
encouraging patients to recall positive, socially rewarding information, rather
than trying to change negative interpretations of events that have already
occurred.
Aim: To evaluate the prevalence of recurrent falls and their risk factors among
older men living in the Veterans Homes in Taiwan. Methods: This cross-sectional
study enrolled 871 residents and all participants received the comprehensive
geriatric assessment, including Barthel Index, Mini-Mental Status Examination
(MMSE), Geriatric Depression Scale-5 questions (GDS-5), Mini-Nutrition Assessment
Short Form (MNA-SF), the status of urinary incontinence, stool incontinence,
polypharmacy, past history of falls, multimorbidity, and medication history.
Results: Overall, 871 subjects (mean age: 85.5 +/- 5.2 years, all males)
participated in this study, whereas 222(25.5%) of them had experienced falls in the
past year, and 91 were recurrent fallers. Comparisons between non-fallers, single
fallers and recurrent fallers disclosed that they were significantly different in
the following characteristics: diabetes mellitus, chronic kidney disease, coronary
artery disease, Charlson Comorbidity Index (CCI), Barthel Index, GDS-5, MNA-SF,
polypharmacy, use of hypnotics, urinary incontinence, and stool incontinence (P for
trend all <0.05). Multiple regression analysis identified that GDS-5 was
significantly associated with single falls and recurrent falls (OR 1.256, 95% CI
1.094-1.441, P = 0.001 for single fallers; OR 1.480, 95% CI 1.269-1.727, P < 0.001
for recurrent fallers). Besides, urinary incontinence was the independently
associated with recurrent fallers only (OR 2.369, 95% CI 1.449-3.817, P < 0.001),
but not single fallers. Conclusion: Urinary incontinence and depressive symptoms
were independent associated factors for falls among older men living in the
retirement communities. However, urinary incontinence was associated with recurrent
falls, but not single falls. Intervention study is needed to reduce recurrent falls
through management of urinary incontinence. (C) 2017 Elsevier B.V. All rights
reserved.
Sleep problems are common in patients with systemic lupus erythematosus (SLE). This
study aimed to examine the following: (1) predictors of sleep quality and (2)
fluctuations in sleep quality in patients with SLE. Patients with SLE were
recruited from three rheumatology centers in Japan. We collected demographic and
clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality
Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient
Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by
administering the PSQI a second time after a 2-week interval. We used multiple
linear regression analysis to predict sleep quality. Of 205 patients who completed
the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep
quality was for "waking in the middle of the night or early morning." "LupusPRO
pain/vitality" was a major predictor of poor sleep. The other significant
predictors were mostly LupusPRO subscales and clinical variables and SF-12
subscales were mostly non-predictive. The majority of the participants had poor
sleep quality. A lupus-specific QoL scale is important for understanding poor sleep
quality in SLE patients. Symptom management appeared to play a key role in
improving sleep quality.
A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is
an endocrine system responsible for coping with stress and it is likely to be
involved in depression. The dynamics of the system is studied and existence,
uniqueness and positivity of the solution and the existence of an attracting
trapping region are proved. The model is calibrated and compared to data for
healthy and depressed subjects. A sensitivity analysis resulting in a set of
identifiable physiological parameters is provided. A subset is selected for
parameter estimation and a reduced version of the model is stated and an
approximated version is discussed. The model is physiologically based, thus
parameters are representative for gland functions or elimination processes. Hence
the model may be used for pointing out pathologies by parameter estimation and
hypothesis testing whereby it may be used as an objective and refined method for
diagnosing depression and suggesting individual treatment protocols. Finally, the
method may inspire pharmaceutical companies to develop target specific
psychopharmaca for more effective and individual treatment. (C) 2016 Elsevier Inc.
All rights reserved.
There is some evidence that lowered tryptophan and an activated tryptophan
catabolite (TRYCAT) pathway play a role in depression, somatoform disorder, and
postpartum blues. The aim of this study is to delineate the associations between
the TRYCAT pathway and premenstrual syndrome (PMS) and perinatal depressive and
physio-somatic symptoms. We examine the associations between end of term serum IgM
and IgA responses to tryptophan and 9 TRYCATs in relation to zinc, C-reactive
protein (CRP), and haptoglobin and prenatal physio-somatic (previously known as
psychosomatic) symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation)
and prenatal and postnatal depression and anxiety symptoms as measured using the
Edinburgh Postnatal Depression Scale (EPDS), Hamilton Depression Rating Scale
(HAMD), and Spielberger's State Anxiety Inventory (STAI). We included pregnant
females with (n = 24) and without depression (n = 25) and 24 non-pregnant females.
There were no significant associations between the IgA/IgM responses to tryptophan
and TRYCATs and prenatal and postnatal depression/anxiety symptoms, except for
lowered IgA responses to anthranilic acid in prenatal depression. A large part of
the variance in IgA responses to most TRYCATs was explained by PMS and haptoglobin
(positively) and CRP (inversely) levels. The IgA responses to TRYCATs were
significantly increased in PMS, in particular picolinic, anthranilic, xanthurenic
and kynurenic acid, and 3OH-kynurenine. Variance (62.5%) in physio-somatic symptoms
at the end of term was explained by PMS, previous depressions, zinc (inversely),
CRP and haptoglobin (both positively), and the IgM responses to quinolinic acid
(positively), anthranilic acid, and tryptophan (both negatively). The results
suggest that mucosa-derived TRYCAT pathway activation is significantly associated
with PMS, but not with perinatal depression/anxiety symptoms. Physio-somatic
symptoms in pregnancy have an immune-inflammatory pathophysiology. Induction of the
TRYCAT pathway appears to be more related to physio-somatic than to depression
symptoms.
Major depressive disorder (MDD) is associated with disrupted relationships with
partners, family, and peers. These problems can precipitate the onset of clinical
illness, influence severity and the prospects for recovery. Here, we investigated
whether individuals who have recovered from depression use interpersonal signals to
form favourable appraisals of others as social partners. Twenty recovered-depressed
adults (with >1 adult episode of MDD but euthymic and medication-free for six
months) and 23 healthy, never-depressed adults completed a task in which the gaze
direction of some faces reliably cued the location a target (valid faces), whereas
other faces cued the opposite location (invalid faces). No participants reported
awareness of this contingency, and both groups were significantly faster to
categorise targets following valid compared with invalid gaze cueing faces.
Following this task, participants judged the trustworthiness of the faces. Whereas
the healthy never-depressed participants judged the valid faces to be significantly
more trustworthy than the invalid faces; this implicit social appraisal was absent
in the recovered-depressed participants. Individuals who have recovered from MDD
are able to respond appropriately to joint attention with other people but appear
to not use joint attention to form implicit trust appraisals of others as potential
social partners.
BACKGROUND: Depression among patients with acute myocardial infarction (AMI) is
prevalent and associated with an adverse quality of life and prognosis. Despite
recommendations from some national organizations to screen for depression, it is
unclear whether treatment of depression in patients with AMI is associated with
better outcomes. We aimed to determine whether the prognosis of patients with
treated versus untreated depression differs. METHODS: The TRIUMPH study
(Translational Research Investigating Underlying Disparities in Acute Myocardial
Infarction Patients' Health Status) is an observational multicenter cohort study
that enrolled 4062 patients aged >= 18 years with AMI between April 11, 2005, and
December 31, 2008, from 24 US hospitals. Research coordinators administered the
Patient Health Questionnaire-9 (PHQ-9) during the index AMI admission. Depression
was defined by a PHQ-9 score of >= 10. Depression was categorized as treated if
there was documentation of a discharge diagnosis, medication prescribed for
depression, or referral for counseling, and as untreated if none of these 3
criteria was documented in the medical records despite a PHQ score >= 10. One-year
mortality was compared between patients with AMI having: (1) no depression (PHQ-
9<10; reference); (2) treated depression; and (3) untreated depression adjusting
for demographics, AMI severity, and clinical factors. RESULTS: Overall, 759 (18.7%)
patients met PHQ-9 criteria for depression and 231 (30.4%) were treated. In
comparison with 3303 patients without depression, the 231 patients with treated
depression had 1-year mortality rates that were not different (6.1% versus 6.7%;
adjusted hazard ratio, 1.12; 95% confidence interval, 0.63-1.99). In contrast, the
528 patients with untreated depression had higher 1-year mortality in comparison
with patients without depression (10.8% versus 6.1%; adjusted hazard ratio, 1.91;
95% confidence interval, 1.39-2.62). CONCLUSIONS: Although depression in patients
with AMI is associated with increased long-term mortality, this association may be
confined to patients with untreated depression.
Simultaneous relief of the pain from body and brain remains an ongoing challenge.
The aim of the present study was to clarify whether plant-derived isoflavone
puerarin could ameliorate comorbid depression and pain. We investigated the effects
of puerarin on depressive-like behaviors and neuropathic pain in C57BL/6 N mice
with spared nerve injury (SNI). After SNI surgery, mice were allowed to recover
spontaneously for 7 days and subsequently treated with puerarin, anti-depressant
citalopram, and analgesic ibuprofen, alone or in combination, for 8 or 14 days.
Forced swim test and tail suspension test were used to assess depressive-like
behaviors, whereas von Frey filament test was used to estimate the sensitivity to
the mechanical stimulation. Our results suggested that puerarin effectively
ameliorated depression and pain in SNI mice although citalopram exhibited anti-
depressant activity. In contrast, ibuprofen showed lesser activities against SNI-
induced depression and pain. Further mechanistic studies revealed the uniqueness of
puerarin as follows: (1) puerarin did not recover SNI-induced depletion of reduced
glutathione and loss of superoxide dismutase (SOD), whereas citalopram and
ibuprofen showed somewhat antioxidant activities; (2) puerarin markedly promoted
the activation of CREB pathway although puerarin and citalopram activated ERK
pathway to the same extent; (3) puerarin rapidly and persistently induced brain-
derived neurotrophic factor (BDNF) expression whereas citalopram only induced BDNF
expression after a prolonged stimulation. Collectively, these results suggest that
puerarin may ameliorate the SNI-induced depression and pain via activating ERK,
CREB, and BDNF pathways. Puerarin may serve as new lead compound for the
development of novel therapeutics for depression and pain comorbidity.
Aims: To assess the association between chronic tension-type headache coexistent
with chronic temporomandibular disorder (TMD) pain and severe limitations in
physical and emotional functioning. Methods: Sample size estimation was used to
determine that this case-control study should include 126 subjects. Subjects
suffering from chronic TMD who were aged between 18 and 68 were recruited in
routine clinical practice. Of the 126 included subjects, 63 had TMD pain associated
with chronic tension-type headache (cases) and 63 had TMD pain without a history of
tension-type headache (controls). Clinical diagnosis of TMD was made according to
the Research Diagnostic Criteria for TMD (RDC/TMD) Axis I criteria, and clinical
diagnosis of headache was made according to the International Classification of
Headache (ICHD-II). RDC/TMD Axis II criteria were applied to record the scores from
the Graded Chronic Pain Scale (GCPS) and the Symptoms Checklist-90-Revised
Depression (SCL-DEP) and Somatization (SCL-SOM) scales. A logistic regression
analysis was used to assess the relationship between TMD pain with chronic tension-
type headache and high levels of depression and somatization severity as scored on
the SCL-DEP and SCL-SOM scales, respectively, and high pain-related disability
(GCPS grade III or IV). Data were adjusted to take into account age, gender, time
since TMD pain onset, chronic TMD pain intensity, and characteristic pain
intensity. Results: The presence of chronic tension-type headache was significantly
associated with severe SCL-DEP (odds ratio [OR] = 7.2; P <.001), severe SCL-SOM (OR
= 13.8; P <.001), and high pain-related disability (OR = 9.7; P <.001). Conclusion:
This study provides evidence of associations between the clinical diagnosis of
chronic tension-type headache coexistent with chronic TMD pain and key aspects of
physical and emotional functioning reflected in severe depression, severe
somatization, and high pain-related disability.
Over the past decade, rates of depression and of suicide in adolescents have been
increasing (Collishaw, Journal of Child Psychology and Psychiatry, 56, 2015, 370;
Bor etal., The Australian and New Zealand Journal of Psychiatry, 48, 2014, 606). At
the same time, there is some evidence that rates of diagnosis and, in the US at
least, referral for depression in adolescents has been declining (Libby etal.,
Archives of General Psychiatry, 66, 2009, 633; John etal., Psychological Medicine,
46, 2016, 3315). These worrying statistics highlight the importance of
disseminating accurate information about the risks and benefits of treatments for
adolescent depression, in order to combat therapeutic nihilism. Extant controversy
about the best ways to treat adolescent depression, and in particular with regards
to the use of antidepressants, may have contributed to these trends. More
specifically, we believe that some recent, high profile publications have
incorrectly interpreted the benefit to risk ratio for the use of antidepressants in
adolescent depression as unfavourable (e.g. Cipriani etal., The Lancet, 388, 2016,
881). In this editorial, we review clinical trial and pharmaco-epidemiological data
that supports the retention of the use of antidepressants in the management of
depressed adolescents.
Decades of research have shown that positive life events contribute to the
remission and recovery of depression; however, it is unclear how positive life
events are generated. In this study, we sought to understand if personality
strengths could predict positive life events that aid in the alleviation of
depression. We tested a longitudinal mediation model where gratitude and meaning in
life lead to increased positive life events and, in turn, decreased depression. The
sample consisted of 797 adult participants from 43 different countries who
completed online surveys at five timepoints. Higher levels of gratitude and meaning
in life each predicted decreases in depression over 3 and 6 months time. Increases
in positive life events mediated the effects of these personality strengths on
depression over 3 months; however, not over 6 months. Goal pursuit and positive
emotions are theorized to be the driving forces behind gratitude and meaning in
life's effects on positive life events. We used the hedonic treadmill to interpret
the short-term impact of positive life events on depression. Our findings suggest
the potential for gratitude and meaning in life interventions to facilitate
depression remission.
Objective: Our objective was to determine whether a score of >11 on the Edinburgh
postnatal depression scale (EPDS) at the initial prenatal visit was associated with
an increased use of acute medical visits when compared to pregnant women with an
initial EPDS score of 11.Methods: This was a retrospective cohort study comparing
the utilization of acute medical care during pregnancy and the first eight weeks
after delivery amongst 200 women with an EPDS score >11 at their initial prenatal
visit compared with 200 women with an EPDS score 11. Super-utilization was defined
as 4 acute or unscheduled medical visits during pregnancy and the first eight weeks
after delivery (90th percentile). Logistic regression was used to control for
confounders.Results: Women with an initial EPDS score >11 were significantly more
likely to engage in super-utilization of acute medical care compared with those
women scoring 11 (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI],
1.53-3.90).Conclusions: Pregnant women scoring >11 on the EPDS at their initial
prenatal visit are more likely to super-utilize acute medical care in the perinatal
period. This subset of patients at-risk for increased utilization can be identified
early during prenatal care. Interventions to better meet the medical and
psychosocial needs of these women warrant future research.
Background: The postpartum period represents a major transition in the lives of
many women, a time when women are at increased risk for the emergence of
psychopathology including depression and PTSD. The current study aimed to better
understand the unique contributions of clinically significant postpartum
depression. PTSD, and comorbid PTSD/depression on mother infant bonding and
observed maternal parenting behavior (i.e., behavioral sensitivity, negative
affect, positive affect) at 6 months postpartum. Methods: Mothers (n=164;
oversampled for history of childhood maltreatment given parent study's focus on
perinatal mental health in women with trauma histories) and infants participated in
6-month home visit during which dyads engaged in interactional tasks varying in
level of difficulties. Mothers also reported on their childhood abuse histories,
current depression/PTSD symptoms, and bonding with the infant using standardized
and validated instruments. Results: Mothers with clinically significant depression
had the most parenting impairment (self-report ant observed). Mothers with
clinically significant PTSD alone (due to interpersonal trauma that occurred
predominately in childhood) showed similar interactive behaviors to those who were
healthy controls or trauma-exposed but resilient (i.e., no postpartum
psychopathology). Childhood maltreatment in the absence of postpartum
psychopathology did not infer parenting risk. Limitations: Findings are limited by
(1) small cell sizes per clinical group, limiting power, (2) sample size and sample
demographics prohibited examination of third variables that might also impact
parenting (e.g., income. education), (3) self-report of symptoms rather than use of
psychiatric interviews. Conclusions: Findings show that in the context of child
abuse history and/or current PTSD, clinically significant maternal depression was
the most salient factor during infancy that was associated with parenting
impairment at this level of analysis.
Background: Universal screening of pregnant women for postpartum depression has
recently been recommended; however, optimal application of depression screening
tools in stratifying risk has not been defined. The current study examines new
approaches to improve the ability of the Edinburgh Postnatal Depression Scale
(EPDS) to stratify risk for postpartum depression, including alternate cut points,
use of a continuous measure, and incorporation of other putative risk factors.
Methods: An observational cohort study of 4939 women screened both antepartum and
postpartum with a negative EPDS screen antepartum(i.e. EPDS < 10). The primary
outcome was a probable postpartum major depressive episode(EPDS cut-off 10). Area
under the receiver operating characteristics curve(AUC), sensitivity, specificity,
and predictive values were calculated. Results: 287 women(5.8%) screened positive
for postpartum depression. An antepartum EPDS cut-off95%) at all antepartum EPDS
cut-off values from 4 to 8. Discrimination was improved(AUC ranging from 0.70 to
0.73) when the antepartum EPDS was combined with a prior history of major
depressive disorder before pregnancy. Limitations: An inability to assess EPDS
subscales and a relatively low prevalence of depression in this cohort.
Conclusions: Though an antepartum EPDS cut-off score < 5 yielded the greatest
discrimination identifying women at low risk for postpartum depression, the
negative predictive value was insufficient to substitute for postpartum screening.
This study evaluated the efficacy of an interactive media based, computer-delivered
depression treatment program (imbPST) compared to a no-treatment control condition
(NTC) in a parallel-group, randomized, controlled trial conducted in an outpatient
psychiatric research clinic. 45 adult participants with major depressive disorder
or dysthymia were randomized to receive either 6 weekly sessions of imbPST or no
treatment (No Treatment Control; NTC). The primary outcome measure was the Beck
Depression Inventory II (BDI-II). There was a significant Group x Time interaction
effect [F (1.73, 43)= 58.78; p <.001; eta 2 =.58, Cohens d = 1.94], such that the
patients receiving imbPST had a significantly greater reduction in depressive
symptoms compared to the patients in the NTC condition. Participants in the imbPST
group improved their depression symptoms significantly from moderate (BDI-II = 21.9
+/- 4.20) to mild levels of depression (BDI-II = 17.9 +/- 4.0) after receiving 3
weekly sessions of imbPST (p <0.001), and progressed to still milder levels of
depression after six weekly sessions (BDI-II = 14.5 +/- 3.7, p <0.001). NTC
participants showed no significant reduction in BDI-II scores (BDI-II =21.8 +/- 4.2
pre, = 21.5 +/- 5.2 post, N.S.). Additionally, 40% of the imbPST group showed a
clinically significant and reliable change in depression levels while none of the
NTC group met this criterion. imbPST participants rated the program highly usable
on the system usability scale (SUS) after the first session (SUS Session 1 = 74.6
+/- 7.2) and usability scores increased significantly by the last session (SUS
Session 6 = 85.4 +/- 5.6). We conclude that imbPST is an effective, engaging, and
easily used depression treatment program that warrants further evaluation with
heterogeneous depressed populations in a stand-alone, self-administered fashion.
The aim of this cross-sectional study was to analyse quality of life, socio-
demographic characteristics, family support, satisfaction with health services, and
effect of integrative community therapy among non-institutionalised elderly adults
with and without symptoms of depression in the state of Rio Grande do Norte,
Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive
symptoms were compared. The instruments used were the Mini-Mental State
Examination, the short version of the Geriatric Depression Scale, a clinical socio-
demographic questionnaire, the abbreviated version of the World Health Organisation
Quality of Life questionnaire, the Family Assessment Device, and the Patient
Satisfaction with Mental Health Services Rating Scale. Elderly adults with
depressive symptoms had lower quality of life in the social relations domain than
did those without depressive symptoms (p = 0.003). In addition, compared with those
without depression, fewer elderly adults with depressive symptoms attended
integrative community therapy (p = 0.04); they also reported a low degree of family
involvement in problem solving (p = 0.04) and showed apathy regarding their
satisfaction with health services (p = 0.007). These results have important
implications in the decision-making process with regard to strategies for improving
the health status of elderly adults with depressive symptoms.
BackgroundSleep disturbance is frequently comorbid with depression and sleep
complaints are the most common residual symptoms after treatment among adolescents
with depression. The present analyses investigated the effect of sleep disturbance
in depressed adolescents treated with interpersonal psychotherapy for adolescents
(IPT-A) versus treatment as usual (TAU) in school-based mental health clinics.
MethodSixty-three adolescents participated in a randomized clinical trial of IPT-A
versus TAU for adolescent depression. Participants were diagnosed with a DSM-IV
depressive disorder and assessed for symptoms of depression, interpersonal
functioning, and sleep disturbance. Measures were assessed at baseline, session 4
and 8 of treatment, and session 12 for postacute treatment follow-up. Hierarchical
linear modeling was used to model change in depression, interpersonal functioning,
and sleep disturbance. ResultsOngoing sleep disturbance was significantly
associated with worse depression scores as rated by clinician (=1.04, SE=.22,
p<.001) and self-report (=1.63, SE=.29, p<.001), as well as worse interpersonal
functioning across the course of treatment (=0.09, SE=.02, p<.001). Treatment
condition did not predict change in sleep disturbance (=-0.13, SE=.14, p=ns).
ConclusionsFor all patients in the study, sleep disturbance was a predictor of
depression and interpersonal functioning for depressed adolescents. Sleep
disturbance predicted more depression and interpersonal stress across treatments
and led to a slower improvement in depression and interpersonal functioning. These
data suggest that sleep disturbance should be a target for future treatment
development research among depressed adolescents.
Major depressive disorder is characterized by emotional dysfunction, but mood
states in daily life are not well understood. This study examined complex
explanatory models of daily stress and coping mechanisms that trigger and maintain
daily negative affect and (lower) positive affect in depression. Sixty-three
depressed patients completed perfectionism measures, and then completed daily
questionnaires of stress appraisals, coping, and affect for 7 consecutive days.
Multilevel structural equation modeling (MSEM) demonstrated that, across many
stressors, when the typical individual with depression perceives more criticism
than usual, he/she uses more avoidant coping and experiences higher event stress
than usual, and this is connected to daily increases in negative affect as well as
decreases in positive affect. In parallel, results showed that perceived control,
less avoidant coping, and problem-focused coping commonly operate together when
daily positive affect increases. MSEM also showed that avoidant coping tendencies
and ongoing stress, in combination, explain why people with depression and higher
self-critical perfectionism maintain daily negative affect and lower positive
affect. These findings advance a richer and more detailed understanding of specific
stress and coping patterns to target in order to more effectively accomplish the
two predominant therapy goals of decreasing patients' distress and strengthening
resilience.
Importance: Treatment augmentation is an important clinical decision in the
pharmacotherapy for depression, yet few studies have examined the rates of
treatment augmentation by medication class. Objective: The aim of this study was to
examine which initial pharmacotherapies for depression are more likely than others
to result in subsequent treatment augmentation. Methods: This study is a
retrospective cohort analysis of administrative data of 214,705 privately insured
US adults between the age of 18 and 64 years who were diagnosed with a new episode
of depression in 2009. Propensity score-adjusted logistic regression and Cox
regression were used to model the effect of the class of initial monotherapy on
treatment augmentation. Risk adjustors included depression severity, comorbidities,
provider type, insurance, and demographic characteristics. Exposure: The class of
initial monotherapy and the health care provider type were the main independent
variables of interest. Main Outcome: The outcome was the augmentation of
monotherapy. Results: Thirty-four percent of individuals received treatment
augmentation. Compared with selective serotonin reuptake inhibitor monotherapy,
second-generation antipsychotics as the initial treatment were associated with
significant increase in the likelihood of augmentation compared with the other
classes (hazards ratio, 2.59; 95% confidence interval [CI], 2.51-2.68). This result
was corroborated after propensity score adjustment (odds ratio, 2.85; 95% CI, 2.70-
3.00) when comparing second-generation antipsychotics to the other classes of
pharmacotherapy. The other significant predictor of treatment augmentation was the
provider type. Mental health specialists were 27% more likely to augment a
treatment compared with generalists (hazards ratio, 1.27; 95% CI, 1.25-1.30).
Conclusions: The type of initial antidepressant therapy is associated with the
chances of treatment augmentation. Second-generation antipsychotics progressed to
augmentation more rapidly than the other classes.
Depressive symptomatology in IBD patients is known to predict disease activity,
which, in turn, can increase depressive symptoms in perpetuating a cycle between
depression and IBD symptomatology. The mechanisms that contribute to the
relationship between disease activity and depressive symptoms are not clearly
investigated yet. Since emotion regulation has been considered particularly
relevant to define the impact of adverse experiences on different outcomes, the
current study aimed to examine the longitudinal influence of two maladaptive
emotion regulation processes, cognitive fusion and brooding, on the association
between disease activity and depressed mood. This study was conducted over an 18-
month period, using a sample of 116 IBD patients that completed self-report
validated measures in three different waves. Correlation analyses and cross-lagged
panel models were performed. The main result from this study discovered that the
experience of IBD symptomatology at baseline, although positively linked to the
manifestation of depressed mood 18 months later (r = 0.25; p < 0.01), does not
directly predict depressive symptoms. This relationship is rather indirect, as it
is explained by the engagement in cognitive fusion (p = 0.028) and brooding (p =
0.017). These maladaptive emotion regulation processes, that were revealed to be
consistent over time, link IBD symptoms with subsequent depressed mood. These
findings indicate that clinicians should be aware of the emotion regulation
processes patients tend to use to handle difficult experiences. The inclusion of
psychological assessments and interventions in the healthcare of IBD patients
should be seriously considered. Further implications are discussed.
The association between salivary flow rate (SFR) and depressive symptoms have been
inconclusive. The present study aimed to investigate the association between SFR
and depressive symptoms with and without adjustment for genetic and family
environmental factors. We conducted a cross-sectional study using twins and
measured SFR and depressive symptoms as the outcome and explanatory variables,
respectively. We also performed three-step regression analyses by first analysing
the association between SFR and depressive symptoms without adjustment for genetic
and family environmental factors (individual-level analyses). We then performed
between-within analyses using monozygotic (MZ) and same-sex dizygotic (DZ) twin
pairs, and finally using only MZ twin pairs. These between-within analyses
estimated the coefficients adjusted for genetic and family environmental factors.
Furthermore, differences in the associations between individual-level and between-
within suggest confounding by genetic and family environmental factors. We
conducted 448 twins aged ae20 years. In individual-level analyses in males and
between-within analyses using MZ and same-sex DZ male twin pairs, SFR associated
with depressive symptoms. In between-within analyses using only MZ male twin pairs,
SFR did not associate with depressive symptoms. In females, SFR did not associate
with depressive symptoms in both individual-level and between-within analyses. The
present study revealed that the association between SFR and depressive symptoms was
affected by common genetic factors in males. Understanding this association between
SFR and depressive symptoms with adjustment for genetic and family environmental
factors could lead to an important consideration for the prevention and treatment
of hyposalivation.
Objective: In adolescents and young adults, depressive symptoms are highly
prevalent and dynamic. For clinicians, it is difficult to determine whether a young
person reporting depressive symptoms is at risk of developing ongoing mood
difficulties or whether symptoms form part of a transient maturational process.
Trajectory analyses of longitudinally assessed symptoms in large cohorts have the
potential to untangle clinical heterogeneity by determining subgroups or classes of
symptom course and their risk factors, by interrogating the impact of known or
suspected risk factors on trajectory slope and intercept and by tracing the
interrelation between depressive symptoms and other clinical outcomes over time.
Method: We conducted a systematic review of trajectory studies conducted in cohorts
including people aged between 15 and 25years. Results: We retrieved 47 relevant
articles. These studies suggest that young people fall into common mood trajectory
classes and that class membership and symptom course are mediated by biological and
environmental risk factors. Furthermore, studies provide evidence that high and
persistent depressive symptoms are associated with a range of concurrent health and
behavioral outcomes. Conclusion: Findings could assist in the formulation of novel
concepts of depressive disorders in young people and inform preventive strategies
and predictive models for clinical practice.
The gut microbiota has recently emerged as an important regulator of brain
physiology and behaviour in animals, and ingestion of certain bacteria (probiotics)
therefore appear to be a potential treatment for major depressive disorder (MDD).
However, some conceptual and mechanistical aspects need further elucidation. We
therefore aimed at investigating whether the habitual diet may interact with the
effect of probiotics on depression-related behaviour and further examined some
potentially involved mechanisms underlying the microbe-mediated behavioural
effects. Forty male Sprague-Dawley rats were fed a control (CON) or high-fat diet
(HFD) for ten weeks and treated with either a multi-species probiotic formulation
or vehicle for, the last five weeks. Independently of diet, probiotic treatment
markedly reduced depressive-like behaviour in the forced swim test by 34% (95% CI:
22-44%). Furthermore, probiotic treatment skewed the cytokine production by
stimulated blood mononuclear cells towards IFN gamma, IL2 and IL4 at the expense of
TNF alpha and IL6. In addition, probiotics lowered hippocampal transcript levels of
factors involved in HPA axis regulation (Crh-r1, Crhr-2 and Mr), whereas HFD
increased these levels. A non-targeted plasma metabolomics analysis revealed that
probiotics raised the level of indole-3-propionic acid, a potential neuroprotective
agent. Our findings clearly support probiotics as a potential treatment strategy in
MDD. Importantly, the efficacy was not attenuated by intake of a "Western pattern"
diet associated with MDD. Mechanistically, the HPA axis, immune system and
microbial tryptophan metabolism could be important in this context. Importantly,
our study lend inspiration to clinical trials on probiotics in depressed patients.
(C) 2017 Elsevier Ltd. All rights reserved.
Nuclear power uprates are investments in generation capacity that enable reactors
to operate beyond their original power limit. We find that owners of deregulated
reactors are more likely to make investment in power uprates. Moreover, after
deregulation owners of boiling water reactors are more likely to choose Extended
Power Uprates (EPUs) that could add up to 20 percent of the original power, but
owners of pressurized water reactors, another type of reactors for which EPUs are
more technically challenging, tend to select other types of uprates that add less
of reactor power. Deregulation incentivizes reactor owners to pursue profitable
investments and propels them to make careful investment decisions more consistent
with the technological nature of their plants.
High-performance phase-locked loops (PLLs) are critical for power control in grid-
connected systems. This paper presents a new method of designing a PLL for single-
phase systems based on derivative elements (DEs). The quadrature signal generator
(QSG) is constructed by two DEs with the same parameters. The PLL itself is
realized by using the DE-based QSG. It avoids errors due to the overlap and
accumulation that are present in PLLs based on integral elements, such as a PLL
based on a second-order generalized integrator. Additionally, frequency feedback is
not needed which allows the proposed PLL to achieve high performance when the grid
frequency changes rapidly. This paper presents the model of the PLL and a
theoretical performance analysis with respect to both the frequency-domain and
time-domain behavior. The error arising from the discretization process is also
compensated, ensuring this PLL method is suitable for implementation in a digital
control system. Simulation and experimental results show that the proposed PLL
achieves good performance in both harmonic rejection and dynamic response.
Identification of fungi in dermatological samples using PCR is reliable and
provides significantly improved results in comparison with cultures. It is possible
to identify the infectious agent when negative results are obtained from cultures.
In addition, identification of the infectious agent can be obtained in 1 day.
Conventional and real-time PCR methods used for direct fungus identification in
collected samples vary by DNA extraction methods, targeted DNA and primers, and the
way of analysing the PCR products. The choice of a unique method in a laboratory is
complicated because the results expected from skin and hair sample analysis are
different from those expected in cases of onychomycosis. In skin and hair samples,
one dermatophyte among about a dozen possible species has to be identified. In
onychomycosis, the infectious agents are mainly Trichophyton rubrum and, to a
lesser extent, Trichophyton interdigitale, but also moulds insensitive to oral
treatments used for dermatophytes, which renders fungal identification mandatory.
The benefits obtained with the use of PCR methods for routine analysis of
dermatological samples have to be put in balance with the relative importance of
getting a result in a short time, the price of molecular biology reagents and
equipment, and especially the time spent conducting laboratory manipulations.
Neoscytalidium dimidiatum is an emerging fungus that causes a skin infection
similar to dermatophytosis; it affects both immunocompetent and immunosuppressed
individuals, and it may invade deeper tissues and organs and cause systemic
disease. Little is known about the etiopathogenesis of the infection caused by this
fungus, and no standard effective treatment is available. The aim of the present
experimental study was to develop an animal model of skin infection with N.
dimidiatum. BALB/c mice were inoculated with two fungal strains, and different
routes of infection were tested. When challenged intradermally, N. dimidiatum
strain HUPE164165 caused skin infection in 67% of the animals whereas strain
HUPE115669 did it in 49%. Neoscytalidium dimidiatum was isolated from the skin of
25% of the animals inoculated via epidermal scarification and from 100% of the
animals challenged via subcutaneous injection. Mice inoculated intradermally were
followed-up during four weeks, and clinical samples were collected on days 3, 8,
15, and 29 after inoculation, corresponding to different stages of infection. The
cutaneous infection rate, as measured by the recovery of N. dimidiatum strain
HUPE164165 from skin biopsies of animals inoculated intradermally, revealed the
presence of infection in 90% of the animals sacrificed at 3 days post-inoculation,
71% at 8, 85% at 15, and 33% at 29. Conidia and hyphae were observed in PAS-stained
sections as well as a mild to moderate inflammatory infiltrate in haematoxylin-
eosin, although it did not differ from animals inoculated either with T.
quinckeanum or PBS. The intradermal route of inoculation was considered to be
suitable for the study of skin infection with N. dimidiatum. The animal model
developed in this preliminary study is the first to allow the study of cutaneous
infection with N. dimidiatum and may contribute to further investigations of the
aetiology, immunology, pathogenesis and treatment targeting this emerging mycosis.
Dermatophyte species, isolation and identification in clinical samples are still
difficult and take a long time. The identification and molecular epidemiology of
dermatophytes commonly isolated in a clinical laboratory in Turkey by repetitive
sequence-based PCR (rep-PCR) were assessed by comparing the results with those of
reference identification. A total of 44 dermatophytes isolated from various
clinical specimens of 20 patients with superficial mycoses in Kayseri and 24
patients in Hatay were studied. The identification of dermatophyte isolates was
based on the reference identification and rep-PCR using the DiversiLab System
(BioMerieux). The genotyping of dermatophyte isolates from different patients was
determined by rep-PCR. In the identification of dermatophyte isolates, agreement
between rep-PCR and conventional methods was 87.8 % ( 36 of 41). The dermatophyte
strains belonged to four clones (A -D) which were determined by the use of rep-PCR.
The dermatophyte strains in Clone B, D showed identical patterns with respect to
the region. In conclusion, rep-PCR appears to be useful for evaluation of the
identification and clonal relationships between Trichophyton rubrum species complex
and Trichophyton mentagrophytes species complex isolates. The similarity and
diversity of these isolates may be assessed according to different regions by rep-
PCR.
We report here the isolation, molecular cloning and initial characterization of the
Trichophyton rubrum pacC gene, which encodes a putative protein that is homologous
to the PacC/Rim101p family of pH signaling transcription regulators. The promoter
region of the T. rubrum pacC gene contains four recognition sites 5'-GCCAAG-3' for
the PacC protein, suggesting that the transcription of this gene itself could be
induced under alkaline growth conditions. The enhanced expression profile of the T.
rubrum pacC gene in an alkaline environment was confirmed by Northern blotting
analysis. We also report that the disruption of pacC gene decreased both the
secretion of keratinolytic proteases and the ability of the mutant pacC-1 to grow
on human nail fragments as the sole source of nutrition, i.e., growth of the
dermatophyte T. rubrum appear to be related to molecular events which depend on the
action of protein PacC.
Despite their superficial localization in the skin, pathogenic dermatophytes can
induce a complex but still misunderstood immune response in their hosts. The cell-
mediated immunity (CMI) is correlated with both clinical recovery and protection
against reinfection, and CD4+ T lymphocytes have been recognized as a crucial
component of the immune defense against dermatophytes. Before the discovery of the
Th17 pathway, CMI was considered to be only dependent of Th1 cells, and thus most
studies on the immunology of dermatophytosis have focused on the Th1 pathway.
Nevertheless, the fine comparative analysis of available scientific data on
immunology of dermatophytosis in one hand and on the Th17 pathway mechanisms
involved in opportunistic mucosal fungal infections in the other hand reveals that
some key elements of the Th17 pathway can be activated by dermatophytes.
Stimulation of the Th17 pathway could occur through the activation of some C-type
lectin-like receptors and inflammasome in antigen-presenting cells. The Th17 cells
could go back to the affected skin and by the production of signature cytokines
could induce the effector mechanisms like the recruitment of polymorphonuclear
neutrophils and the synthesis of antimicrobial peptides. In conclusion, besides the
Th1 pathway, which is important to the immune response against dermatophytes, there
are also growing evidences for the involvement of the Th17 pathway.
Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell
sarcoma that typically occurs intra-abdominally in adolescents and young adults,
and is characterized by a recurrent t(11;22)(p13;q12) translocation leading to
generation of the EWSR1-WT1 fusion gene, which codes for a chimeric protein with
transcriptional regulatory activity. DSRCT has a characteristic histologic
appearance of nests of uniform small cells within prominent fibroblastic stroma and
immunohistochemically it shows multidirectional differentiation, with expression of
epithelial, neural, and muscle markers. We illustrate a case of DSRCT that
presented as a large intra-abdominal mass, which harbored EWSR1 rearrangement by
fluorescence in situ hybridization and EWSR1-WT1 fusion transcripts by reverse
transcription-polymerase chain reaction (RT-PCR), and which histologically had an
entirely solid morphology, lacking evidence of desmoplastic stroma. This purely
solid variant emphasizes that even when occurring at a typical location, DSRCT may
be difficult to recognize when lacking nonclassical morphology. This is of clinical
relevance, as DSRCT with this pattern could be misdiagnosed as Ewing sarcoma if RT-
PCR is not performed, with resulting prognostic and therapeutic implications.
While attracting new tourists is an important issue in destination marketing, it is
also imperative to manage tourists' experience post-trip, particularly in cases of
unsatisfying experiences. Yet, the questions of how to rectify unsatisfying tourism
experiences received little attention in tourism scholarship. In the present
research, we investigated the effectiveness of different forms of marketing
messages and the role of counterfactual thinking in the ability of a marketing
message to improve tourists' attitudes towards the destination and intentions to
recommend, when a tourism experience was not up to tourists' satisfaction. A
scenario-based experiment was conducted with 480 respondents. The results showed
that user-generated messages and the messages employing emotional appeal were more
impactful than destination-generated or rational messages. Respondents who engaged
in downward counterfactual thinking, that is imagining the situation in which their
experience could have been worse, was shown to have a greater positive effect on
unsatisfied tourists. (C) 2016 Elsevier Ltd. All rights reserved.
Bunch charge variations in Free Electron Lasers such as the Free Electron Laser in
Hamburg (FLASH) or the European X-Ray Free Electron Laser (E-XFEL) impacts the
longitudinal phase space distribution of the electrons resulting in different bunch
peak currents, pulse duration and pulse shapes. The electron bunches are generated
by short ultraviolet laser pulses impinging onto a photocathode inside a radio
frequency (RF) accelerating cavity. At FLASH, bursts of bunches up to 800 pulses
with an intra train repetition rate of 1 MHz are used and even higher repetition
rates for the E-XFEL (up to 4.5 Mhz) are planned. Charge variations along these
bunch-trains can be caused by variations of the laser pulse energies, instabilities
of the accelerating fields in the RF cavity and time dependent effects in the
photoemission process. To improve the intra bunch-train charge flatness and to
compensate train-to-train fluctuations a dedicated digital control system, based on
the Micro Telecommunication Computing Architecture (MicroTCA.4) standard, was
designed, implemented and successfully tested at the FLASH. The system consists of
a bunch charge detection module which analyzes data from toroid system and provides
the input signal for the controller which drives a fast UV-Pockels Cell installed
in the optical path of the photo-cathode laser. The Pockels cell alters the laser
polarization and thus the transmission through a polarizer. The modulation of UV
laser pulse energy with an iterative learning feed-forward minimizing the
repetitive errors from bunch-train to bunch-train and a fast feedback algorithm
implemented in a Field Programmable Gate Array (FPGA) allows for fast tuning of
bunch charge inside the bunch-train. In this paper a detailed description of the
system and first measurement results are presented.
Objective: To analyze the usefulness of rapid HIV testing in pregnant patients in
the delivery room. Methods: This prospective study compared a rapid test and a
fourth-generation enzyme-linked immunoassay (ELISA) for HIV screening among
pregnant patients admitted in labor with an unknown HIV status at a university
hospital in Mexico between July 2015 and February 2016. Pearson correlation
analysis was performed, and the diagnostic accuracy of the two tests was assessed
with HIV RNA polymerase chain reaction (PCR) as the reference method. Results:
Overall, 534 patients were included. With a signal-to-cutoff (S/CO) value of 1.0 or
more as a diagnostic criterion, 6 (1.1%) patients had a positive ELISA result.
Three had a negative rapid test and three had a positive test (r=0.705). With an
S/CO value of 2.0 or more as cutoff, 4 (0.7%) patients had a positive ELISA result.
Three had a positive rapid test and one had a negative test (r=0.865). Only three
of six patients with an S/CO of 1.0 or more were confirmed to have HIV by RNA PCR.
Conclusion: The rapid test showed a strong correlation with the fourth-generation
ELISA. Therefore, rapid testing is a useful tool in the delivery room for patients
with unknown HIV status.
The purpose of this study was to determine the efficacy of a nucleic acid sequence-
based amplification (NASBA) method of detecting noroviruses in artificially and
naturally contaminated shellfish. We used 58 fecal samples that tested positive for
noroviruses with electron microscopy (EM) to develop an NASBA assay for these
viruses. Oligonucleotide primers targeting the polymerase coding region were used
to amplify the viral RNA in an isothermal process that resulted in the accumulation
of RNA amplicons. These amplicons were detected by hybridization with digoxigenin-
labeled oligonucleotide probes that were highly specific for genogroup I (GI) and
genogroup II (GII) of noroviruses. The expected band of 327 bp appeared in
denaturing agarose gel without any nonspecific band. The specific signal for each
amplicon was obtained through Northern blotting in many repeats. All fecal samples
of which 46 (79.3%) belonged to GII and 12 (20.6%) belonged to GI were positive for
noroviruses by EM and by NASBA. Target RNA concentrations as low as 5 pg/ml were
detected in fecal specimens using NASBA. When the assay was applied to artificially
contaminated shellfish, the sensitivity to nucleic acid was 100 pg/1.5 g shellfish
tissue. The potential use of this assay was also confirmed in naturally
contaminated shellfish collected from different ponds in Guangzhou city of China,
of which 24 (18.76%) out of 128 samples were positive for noroviruses; of these, 19
(79.6 %) belonged to GII and 5 (20.4%) belonged to GI. The NASBA assay provided a
more rapid and efficient way of detecting noroviruses in fecal samples and
demonstrated its potential for detecting noroviruses in food and environmental
samples with high specificity and sensitivity.
As direct-drive actuators, permanent-magnet linear synchronous motors (PMLSMs) are
widely used in high velocity and high precision applications. The detent force,
however, can deteriorate the performance and even excite the mechanical resonance.
This paper focuses on a novel detent force compensation scheme for PMLSM systems
through a combination of structural design and control method. First, due to the
bandwidth constraint of the control system, eliminating high frequency ripples is
unfeasible; skewed permanent magnets (PMs) considering an optimal skewing length
are designed to suppress high order harmonic components. Second, based on the model
of PMLSM with skewed PMs, a linearization observer is derived and applied
independently to the velocity controller for further diminishing low-order harmonic
components. To facilitate implementation in the digital control system, a
discretization method taking account of estimated errors is designed. Through the
online calculation, the estimated detent force is injected to the control system in
a feedforward way. To tune the proposed scheme properly, the convergence of the
algorithm is analyzed by utilizing Lyapunov stability theory. Simulation studies
are performed to prove the effectiveness of the proposed method, and experiments
are provided to confirm the theoretical analysis and simulation results.
This study examined the risk of deterioration/relapse in pregnant women who
discontinued their antidepressant medications based on the discretion of the
psychiatric specialists compared with those who performed self-interruption. We
reviewed the obstetric records of all singleton deliveries beyond 22 weeks of
gestation at Japanese Red Cross Katsushika Maternity Hospital from January 2009
through December 2015. Compared with the women continuing antidepressant
medications throughout pregnancy, the incidence of deterioration/relapse was higher
in the women who discontinued their antidepressant medications regardless of who
made the decision (interruption based on the discretion of the psychiatric
specialists: 61%, odds ratio (OR), 8.05; 95% confidence interval (CI), 2.4-27;
p<0.01; self-interruption: 63%, odds ratio (OR), 8.79; 95% confidence interval
(CI), 2.6-29; p<0.01 versus 16%). The continuation of medications and careful
observation are required for pregnant women complicated by depressive disorders.
Compatibilism is the view that determinism is compatible with acting freely and
being morally responsible. Incompatibilism is the opposite view. It is often
claimed that compatibilism or incompatibilism is a natural part of ordinary social
cognition. That is, it is often claimed that patterns in our everyday social
judgments reveal an implicit commitment to either compatibilism or incompatibilism.
This paper reports five experiments designed to identify such patterns. The results
support a nuanced hybrid account: The central tendencies in ordinary social
cognition are compatibilism about moral responsibility, compatibilism about
positive moral accountability (i.e., about deserving credit for good outcomes),
neither compatibilism nor incompatibilism about negative moral accountability
(i.e., about deserving blame for bad outcomes), compatibilism about choice for
actions with positive outcomes, and incompatibilism about choice for actions with
negative or neutral outcomes.
This paper is devoted to the comparison of the numerically simulated Chua's circuit
and the real circuit. The aim of the research was to figure out the factors
affecting the computer simulation accuracy, and to find the ways to improve it. It
was discovered that the most influence is exerted by an inaccuracy of the nonlinear
Chua's diode characteristic measurement, a numerical integration method used for
simulation and the operational amplifier properties. A possibility of an analog
circuit application as a source of an accurate signal in order to find the most
appropriate numerical method for the chaotic systems simulation is shown.
Multiple mutation combinations in the IgG Fc have been characterized to tailor
immune effector function or IgG serum persistence to fit desired biological
outcomes for monoclonal antibody therapeutics. An unintended consequence of
introducing mutations in the Fc (particularly the C(H)2 domain) can be a reduction
in biophysical stability which can correlate with increased aggregation propensity,
poor manufacturability, and lower solubility. Herein, we characterize the changes
in IgG conformational and colloidal stability when 2 sets of C(H)2 mutations "TM"
(L234F/L235E/P331S) and "YTE" (M252Y/S254T/ T256E) are combined to generate an
antibody format lacking immune receptor binding and exhibiting extended half-life.
In addition to significantly lowered thermostability, we observe greater
conformational flexibility for TM-YTE in C(H)2, increased self-association, and
poorer solubility and aggregation profiles. To improve these properties, we
dissected the contributions of individual mutations within TM-YTE on
thermostability and substituted destabilizing mutations with new mutations that
raise thermostability. One novel combination, FQQ-YTE
(L234F/L235Q/K322Q/M252Y/S254T/T256E), had significantly improved conformational
and colloidal stability, and was found to retain the same biological activities as
TM-YTE (extended half-life and lack of antibody-dependent cell-mediated
cytotoxicity and complement-dependent cytotoxicity activity). Our engineering
approach offers a way to improve the developability of antibodies containing Fc
mutations while retaining tailored biological activity. (C) 2017 American
Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Background: An extremely high percentage of children worldwide are exposed to
stress from the first months of life. The aim of this review is to bring together
the experimental results related to chronic early-life stress in both human and
experimental models. Methods: We aimed to achieve our objective via a thorough
review of the literature. Results: Early-life stress is a challenge for the
developing organism and leads to negative effects in the medium and long term. The
emotional, cognitive, and behavioral domains are compromised due to alterations
produced in the nervous system, with some of the most important being related to
the main neurotransmission systems. Conclusions: By using experimental models, it
is possible to address the study of the structural and functional changes resulting
from early-life stress and, thus, plan intervention and prevention alternatives.
Developmental Dyslexia (DD) is a neurodevelopmental disorder affecting reading
acquisition. DD cannot be diagnosed before starting the primary school; thereby,
one of the main challenges is to obtain an early DD identification even during
preschool years. Achieving this goal could help children at risk for DD to limit
the impact of this disorder. To this aim, we have created a digital system composed
of various serious games designed for predicting the risk of DD in preschoolers and
potentially training specific skills impaired in this learning disability. Our set
of serious games are designed to be accessible from any device, a computer with
mouse and keyboard, but also a tablet with touch interface for younger children.
Lentinula edodes (Shiitake mushroom) is a common edible mushroom that has high
nutritional and medical value. Although a number of genes involved in the fruit of
the species have been identified, little is known about the process of
differentiation from dikaryotic mycelium to primordium. In this study, serial
analysis of gene expression (SAGE) was applied to determine the gene expression
profiles of the dikaryotic mycelium and primordium of L. edodes in an effort to
advance our understanding of the molecular basis of fruit body development. A total
of 6363 tags were extracted (3278 from the dikaryotic mycelium and 3085 from the
primordium), 164 unique tags matched the in-house expressed sequence tag (EST)
database. The difference between the expression profiles of the dikaryotic mycelium
and primordium suggests that a specific set of genes is required for fruit body
development. In the transition from the mycelium to the primordium, different
hydrophobins were expressed abundantly, fewer structural genes were expressed,
transcription and translation became active, different genes became involved in
intracellular trafficking, and stress responses were expressed. These findings
advance our understanding of fruit body development. We used cDNA microarray
hybridization and Northern blotting to verify the SAGE results, and found SAGE to
be highly efficient in the performance of transcriptome analysis. To our knowledge,
this is the first SAGE study of a mushroom. (c) 2008 The British Mycological
Society. Published by Elsevier Ltd. All rights reserved.
Although glucocorticoids are known to elicit functional maturation of the
gastrointestinal tract, the molecular mechanisms of glucocorticoid action on the
developing intestine have not been fully elucidated. Our previous microarray
studies identified 66 transcripts as being rapidly induced in the jejunum following
dexamethasone (Dex) administration to suckling mice. Now we report the specific
cellular location of a subset of these transcripts. Mouse pups at P8 received Dex
or vehicle and intestinal segments were collected 3-4 h later. Robotic-based in
situ hybridization (ISH) was performed with digoxygenin-labeled riboprobes.
Transcripts studied included Ndrg1, Sgk1, Fos, and two unknown genes (Gene 9 and
Gene 36). As predicted, ISH revealed marked diversity of cellular expression. In
small intestinal segments, Sgk1 mRNA was in all epithelial cells; Fos mRNA was
confined to epithelial cells at the villus tip; and Ndrg1 and Gene 36 mRNAs were
localized to epithelial cells of the upper crypt and villus base. The remaining
transcript (Gene 9) was induced modestly in villus stroma and strongly in the
muscle layers. In the colon, Ndrg1, Sgk1, and Gene 36 were induced in all
epithelial cells; Gene 9 was in muscle layers only; and Fos was not detectable. For
jejunal segments, quantitation of ISH signals in tissue from Dex-treated and
vehicle-treated mice demonstrated mRNA increases very similar to those measured by
Northern blotting. We conclude that glucocorticoid action in the intestine reflects
diverse molecular mechanisms operating in different cell types and that
quantitative ISH is a valuable tool for studying hormone action in this tissue.
Study objective: Administration of intranasal dexmedetomidine for sedation is
comfortable and effective in children who are afraid of needles, and it offers
efficient sedation similar to that of intravenous administration. We performed a
systematic review and meta-analysis to evaluate the clinical effects of the pre-
procedural administration of intranasal dexmedetomidine. Design: We identified
randomized controlled trials (RCTs) that compared intranasal dexmedetomidine
administration to other administration methods of various sedatives or placebo from
MEDLINE, EMBASE, Cochrane, KoreaMed and hand searches of trial registries. Setting:
Pediatrics who underwent interventional procedures and surgeries. Patients:
Children under the age of 18. Interventions: Studies were included if they were
compatible with the criteria that dexmedetomidine was administered intranasally.
Measurements: We pooled data on the sedation status as the primary outcome and
considered the behavioral score, blood pressure, heart rate and side effects to be
secondary outcomes. Risk ratio (RR) and the standardized mean difference (SMD) with
95% confidence intervals (CIs) were calculated for dichotomous and continuous
outcomes, respectively. Main results: This meta-analysis included 11 RCTs. The SMD
for the sedative effects of intranasal dexmedetomidine was 2.45 (random, 95% CI; -
3.33, -1.58) for continuous outcomes and RR of unsatisfactory patient outcome was
0.42 (M-H, random 95% CI; 026, 0.68 I-2 = 45%) for dichotomous outcomes compared to
that of intranasal saline. The SMD for the sedative effects of intranasal
dexmedetomidine was -0.41 (random, 95% CI; -1.09, 0.27 I-2 = 69%) for continuous
outcomes and RR was 0.43 (M-H, random 95% CI; 0.32, 0.58 I-2 = 0%) for dichotomous
outcomes compared to that of per os benzodiazepines. Conclusions: This review
suggests that intranasal dexmedetomidine is associated with better sedative effects
than oral benzodiazepines without producing respiratory depression, but it had a
significantly delayed onset of effects. (C) 2017 Elsevier Inc. All rights reserved.
Dexmedetomidine is a highly selective 2-adrenoceptor agonist with sedation,
anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This
study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons
correlated to histone acetylation via extracellular signal-regulated protein kinase
1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and
treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6),
dexmedetomidine 1 mg/kg (n = 6), 10 mg/kg (n = 6), and 100 mg/kg (n = 6).
Acetylation histone protein levels and ERK protein levels in rats dopamine neuron
from striatum were determined by Western blotting after various doses of
dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression
related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in
striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR)
analysis. Dexmedetomidine administration increased expression of ERK1/2
phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2,
almost completely blocked dexmedetomidine-induced histones H3 acetylation. In
addition, bioinformatics analysis in combination with qRT-PCR demonstrated that
dexmedetomidine could regulate the genes that are related to signal transduction
coupled to 5-HTR via 2-adrenoceptor. Our results define dexmedetomidine as a
modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine
neuron from striatum, which may provide clues for the mechanism underlying the
neuroprotective effects of dexmedetomidine.
Advances in prenatal diagnosis, perioperative management, and postoperative care
have dramatically increased the population of survivors of neonatal and infant
heart surgery. The high survival rate of these patients into adulthood has exposed
the alarming prevalence of long-term neuropsychological and psychiatric
morbidities. Dextro-transposition of the great arteries (D-TGA) is one of the most
extensively studied cyanotic congenital heart defect (CHD) with regard to
neurodevelopmental outcomes. Landmark studies have described a common
neurodevelopmental and behavioral phenotype associated with D-TGA. Children with D-
TGA display impairments in key neurocognitive areas, including visual-spatial and
fine motor abilities, executive functioning, processing speed, and social
cognition. As they grow older, they may face additional challenges with a worsening
of deficits in higher order cognitive skills, problems in psychosocial adjustment
and a higher-than-expected rate of psychiatric disorders, such as attention-deficit
hyperactivity disorder, depression, and anxiety. The aim of this review is to
summarize the available recent data on neuropsychological and psychiatric outcomes
in individuals with D-TGA after the arterial switch operation. We present findings
within a life-span perspective, with a particular emphasis on the emerging
literature on adolescent and young adult outcomes. Finally, we propose avenues for
future research in the CHD adult neuropsychology field. Among these avenues, we
explore the potential mechanisms by which pediatric neurodevelopmental impairments
may have lifelong adverse effects as well as alternative interventions that could
optimize outcomes.
The impedance-based model of doubly fed induction generator (DFIG) systems,
including the rotor part (rotor side converter (RSC) and induction machine), and
the grid part (grid side converter (GSC) and its output filter), has been developed
for analysis and mitigation of the subsynchronous resonance (SSR). However, the
high-frequency resonance (HFR) of DFIG systems due to the impedance interaction
between the DFIG system and parallel compensated weak network is often overlooked.
This paper, thus, investigates the impedance characteristics of DFIG systems for
the analysis of HFR. The influences of the rotor speed variation, the machine
mutual inductance and the digital control delay are evaluated. Two resonances
phenomena are revealed, i.e., 1) the series HFR between the DFIG system and weak
power grid; 2) the parallel HFR between the rotor part and the grid part of DFIG
system. The impedance modeling of DFIG system and weak grid network, as well as the
series HFR between DFIG system and parallel compensated weak network has been
validated by experimental results.
Background/aim: An in-depth understanding of the early phase of type 1 diabetes
(TID) pathogenesis is important for targeting primary prevention. We examined if 14
preselected mediators of immune responses differed in neonates that later developed
TID compared to control neonates. Methods: The study is a case-control study with a
1:2 matching. The individuals were born between 1981 through 2002. Cases were
validated using the National Patient Register and the Danish Childhood Diabetes
Register. Interleukin(1)-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, interferon
gamma, tumor necrosis factor alpha, transforming growth factor beta I (active
form), leptin, adiponectin, c-reactive protein, mannose-binding lectin and soluble
triggering receptor expressed on myeloid cells-1 were measured by using a
flowmetric Luminex xMAP (R) technology. We tested two models both including a
number of possible confounders. In the first model (model 1) we also adjusted for
HLA-DQ beta 1) genotype. A total of 1930 groups of assay-matched cases and controls
(4746 individuals) were included in the statistical analyses. Results: Adiponectin
was negatively associated with later risk of TID in both models (relative change
(RC), model 1: 0.95, P = 0.046 and model 2: 0.95, P = 0.006). IL-10 and IL-12 were
both positively associated with T1D risk in the model 2 (RC, 1.19, P = 0.006 and
1.07, P = 0.02, respectively) these results were borderline significant in model 1,
but showed the same direction as the results from model 2. Conclusions: Our results
indicate that specific immunological signatures are already present at time of
birth in children developing T1D before the age of 18 years. (C) 2016 Elsevier Inc.
All rights reserved.
Background and ObjectiveNo previous study has directly compared the levels of
matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs)
between smokers and individuals with diabetes mellitus (DM) with periodontitis.
Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-
2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of
smokers and individuals with type 2 DM. Material and MethodsGingival biopsies were
harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP
group); non-diabetic smokers ( 10 cigarettes per day for at least the past 5 years)
with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes
(glycated hemoglobin levels 7.5%) and ChP (n = 18) (DMChP group). The tissue levels
of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by
quantitative real-time polymerase chain reaction. ResultsThe MMP-8 expression was
the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA
levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1
expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1,
MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP
and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1
than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP
group (p < 0.05). ConclusionUncontrolled type 2 DM upregulates the ratio of
MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater
extracellular matrix degradation and periodontal breakdown in DM-related
periodontitis.
Background: Recent studies suggest that immunotherapy using T regulatory cells
(Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that
possibly affect the efficacy of this treatment. Methods: The metabolic and immune
background of 12 children with recently diagnosed T1DM, as well as that of
untreated subjects, during a 2-year follow-up is presented. Patients were treated
with up to 30 x 10(6)/kg b.w. of autologous expanded
CD3(+)CD4(+)CD25(high)CD127(-)Tregs. Results: The disease progressed and all
patients were insulin-dependent 2 years after inclusion. The beta-cell function
measured by c-peptide levels and the use of insulin were the best preserved in
patients treated with two doses of Tregs (3/6 in remission), less so after one dose
(1/6 in remission) and the worst in untreated controls (no remissions). Increased
levels of Tregs could be seen in peripheral blood after their adoptive transfer
together with the shift from naive CD62L(+)CD45RA(+) to memory
CD62L(+)CD45RA(-)Tregs. Increasing serum levels of proinflammatory cytokines were
found: IL6 increased in all subjects, while IL1 and TNF alpha increased only in
untreated group. Therapeutic Tregs were dependent on IL2, and their survival could
be improved by other lymphocytes. Conclusions: The disease progression was
associated with changing proportions of naive and memory Tregs and slowly
increasing proinflammatory activity, which was only partially controlled by the
administered Tregs. The therapeutic cells were highly dependent on IL2. We conclude
that the therapy should be administered at the earliest to protect the highest
possible mass of islets and also to utilize the preserved content of Tregs in the
earlier phases of T1DM.
Sleep problems are common in chronic disorders like diabetes and are the result of
poor diet and unhealthy lifestyles. Comprehensive management of diabetes entails
lifestyle management and restoration of good habits. Sleep hygiene maintenance
helps persons living with diabetes enjoy a better quality of life by restoring
normal sleep patterns and thereby improving glycaemic control.
Background: Calcium (Ca2+) handling proteins are known to play a pivotal role in
the pathophysiology of cardiomyopathy. However little is known about early changes
in the diabetic heart and the impact of insulin treatment (Ins). Methods: Zucker
Diabetic Fatty rats treated with or without insulin (ZDF +/- Ins, n = 13) and lean
littermates (controls, n = 7) were sacrificed at the age of 19 weeks. ZDF + Ins (n
= 6) were treated with insulin for the last 6 weeks of life. Gene expression of
Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a, further abbreviated
as SERCA) and phospholamban (PLB) were determined by northern blotting. Ca2+
transport of the sarcoplasmatic reticulum (SR) was assessed by oxalate-facilitated
45Ca-uptake in left ventricular homogenates. In addition, isolated neonatal
cardiomyocytes were stimulated in cell culture with insulin, glucose or
triiodthyronine (T3, positive control). mRNA expression of SERCA and PLB were
measured by Taqman PCR. Furthermore, effects of insulin treatment on force of
contraction and relaxation were evaluated by cardiomyocytes grown in a three-
dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5 days by
insulin. By western blot phosphorylations status of Akt was determed and the
influence of wortmannin. Results: SERCA levels increased in both ZDF and ZDF + Ins
compared to control (control 100 +/- 6.2 vs. ZDF 152 +/- 26.6* vs. ZDF + Ins 212
+/- 18.5*# % of control, *p < 0.05 vs. control, #p < 0.05 vs. ZDF) whereas PLB was
significantly decreased in ZDF and ZDF + Ins (control 100 +/- 2.8 vs. ZDF 76.3 +/-
13.5* vs. ZDF + Ins 79.4 +/- 12.9* % of control, *p < 0.05 vs control). The
increase in the SERCA/PLB ratio in ZDF and ZDF +/- Ins was accompanied by enhanced
Ca2+ uptake to the SR (control 1.58 +/- 0.1 vs. ZDF 1.85 +/- 0.06* vs. ZDF + Ins
2.03 +/- 0.1* mu g/mg/min, *p < 0.05 vs. control). Interestingly, there was a
significant correlation between Ca2+ uptake and SERCA2a expression. As shown by in-
vitro experiments, the effect of insulin on SERCA2a mRNA expression seemed to have
a direct effect on cardiomyocytes. Furthermore, long-term treatment of engineered
heart tissue with insulin increased the SERCA/PLB ratio and accelerated relaxation
time. Akt was significantly phosphorylated by insulin. This effect could be
abolished by wortmannin. Conclusion: The current data demonstrate that early type 2
diabetes is associated with an increase in the SERCA/PLB ratio and that insulin
directly stimulates SERCA expression and relaxation velocity. These results
underline the important role of insulin and calcium handling proteins in the
cardiac adaptation process of type 2 diabetes mellitus contributing to cardiac
remodeling and show the important role of PI3-kinase-Akt-SERCA2a signaling cascade.
Introduction: At present, treatment of diabetic kidney disease (DKD) is still
mainly based on drugs acting on glycemic and blood pressure control, as there is no
validated therapy able to halt the progression of renal failure. Because of the
high incidence of DKD, due to the increase of diabetes mellitus in general
population, new therapeutic strategies are needed.Areas covered: We analysed
ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed,
dealing with new therapies for DKD.Expert opinion: Among the drugs currently being
explored, the most promising molecules are those that interfere with glucose-
dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs
metabolic pathways, and impaired renal vascular regulation. One of the recent goals
achieved by molecular biology is the development of monoclonal antibodies able to
interfere with extracellular matrix accumulation and fibrosis. Other interesting
therapies are under investigation and further studies with a greater number of
patients will establish a better approach for diabetic nephropathy.
Wu D, Peng F, Zhang B, Ingram AJ, Kelly DJ, Gilbert RE, Gao B, Kumar S, Krepinsky
JC. EGFR-PLC gamma 1 signaling mediates high glucose-induced PKC beta 1-Akt
activation and collagen I upregulation in mesangial cells. Am J Physiol Renal
Physiol 297: F822-F834, 2009. First published July 15, 2009;
doi:10.1152/ajprenal.00054.2009.-Glomerular matrix accumulation is a hallmark of
diabetic nephropathy. We have recently shown that epidermal growth factor receptor
(EGFR) transactivation mediates high glucose (HG)-induced collagen I upregulation
through PI3K-PKC beta 1-Akt signaling in mesangial cells (MC). Phospholipase C
gamma 1 (PLC gamma 1) interacts with activated growth factor receptors and
activates classic PKC isoforms. We thus studied its role in HG-induced collagen I
upregulation in MC. Primary rat MC were treated with HG (30 mM) or mannitol as
osmotic control. Protein kinase activation was assessed by Western blotting and
collagen I upregulation by Northern blotting. Diabetes was induced in rats by
streptozotocin. HG treatment for 1 h led to PLC gamma 1 membrane translocation and
Y783 phosphorylation, both indicative of its activation. Mannitol was without
effect. PLC gamma 1 Y783 phosphorylation was also seen in cortex and glomeruli of
diabetic rats. HG induced a physical association between EGFR and PLC gamma 1 as
identified by coimmuno-precipitation. PLC gamma 1 activation required EGFR kinase
activity since it was prevented by the EGFR inhibitor AG1478 or overexpression of
kinase-inactive EGFR (K721A). Phosphoinositide-3-OH kinase inhibition also
prevented PLC gamma 1 activation. HG-induced Akt S473 phosphorylation, effected by
PKC beta 1, was inhibited by the PLC gamma inhibitor U73122. PLC gamma 1 inhibition
or downregulation by small interference RNA also prevented HG-induced collagen I
upregulation. Our results indicate that EGFR-PLC gamma 1 signaling mediates HG-
induced PKC beta 1-Akt activation and subsequent collagen I upregulation in MC.
Inhibition of EGFR or PLC gamma 1 may provide attractive therapeutic targets for
the treatment of diabetic nephropathy.
BackgroundPrevious studies found that metformin provided some renoprotection for
diabetic renal damage. In the present study, we evaluated the effects of different
doses of metformin on the expression of renal tissue nephrin in type 2 diabetes
mellitus (T2DM) model rats and the possible mechanism underlying its protective
effect in kidney podocytes. MethodsA high-fat diet combined with a low dose of
streptozotocin was used to induce T2DM model rats. Diabetic rats were treated with
150, 300, or 500mg/kg metformin for 8weeks. At the end of the study, urine and
blood samples were collected for measurement of different indices. Light microscopy
and transmission electron microscopy were used to identify morphological changes.
Renal expression of nephrin protein was assayed by immunohistochemical staining,
whereas real-time polymerase chain reaction was used to detect renal nephrin
(Nphs1) mRNA expression. ResultsMetformin treatment of T2DM rats produced dose-
dependent significant reductions in urinary albumin and nephrin concentrations,
glomerular basement membrane thickness (GBMT), and the foot process fusion rate
(FPFR) compared with control T2DM model rats, whereas renal expression of nephrin
protein and Nphs1 mRNA was dose-dependently increased by metformin treatment.
ConclusionMetformin protects kidney podocytes in T2DM model rats by dose-
dependently adjusting renal nephrin expression.
AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in
screening retinal endothelial injury and early diagnosis of proliferative diabetic
retinopathy. METHODS: The study included 184 serum samples, 59 samples from healthy
individuals, 44 samples from diabetes mellitus (DM) patients without diabetic
retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR) patients
and 39 samples from proliferative diabetic retinopathy (PDR) patients. The
expression of miR-126 was evaluated using a real-time quantitative polymerase chain
reaction. RESULTS: The serum content of miR-126 declined as the damage degree in
the retina. There was significant difference between the two retinopathy groups
(P0.05). Receiver operating characteristic curve (ROC) analyses indicated that
serum miR-126 had significant diagnostic value for PDR. It yielded an area under
the curve (AUC) of ROC of 0.976 with 81.21% sensitivity and 90.34% specificity in
discriminating PDR from healthy controls, and an AUC of ROC of 0.919 with 84.75%
sensitivity and 94.41% specificity in discriminating NDR and NPDR from healthy
controls. When the diagnostic threshold was greater than or equal to 8.43, there
was an increase in the possibility of NPDR. When the content of miR-126 was less
than or equal to 5.02, the possibility of the occurrence of PDR increased.
CONCLUSION: Serum miR-126 can serve as a non-invasive biomarker for screening
retinal endothelial injury and early diagnosis PDR.
PURPOSE. Diabetic retinopathy is a leading cause of vision loss. Previous studies
have shown signaling pathways mediated by Stat3 (signal transducer and activator of
transcription 3) play a primary role in diabetic retinopathy progression. This
study tested CLT-005, a small molecule inhibitor of Stat3, for its dose-dependent
therapeutic effects on vision loss in a rat model of diabetic retinopathy. METHODS.
Brown Norway rats were administered streptozotocin (STZ) to induce diabetes. CLT-
005 was administered daily by oral gavage for 16 weeks at concentrations of 125,
250, or 500 mg/kg, respectively, beginning 4 days post streptozotocin
administration. Systemic and ocular drug concentration was quantified with mass
spectrometry. Visual function was monitored at 2-week intervals from 6 to 16 weeks
using optokinetic tracking to measure visual acuity and contrast sensitivity. The
presence and severity of cataracts was visually monitored and correlated to visual
acuity. The transcription and translation of multiple angiogenic factors and
inflammatory cytokines were measured by real-time polymerase chain reaction and
Multiplex immunoassay. RESULTS. Streptozotocin-diabetic rats sustain progressive
vision loss over 16 weeks, and this loss in visual function is rescued in a dose-
dependent manner by CLT-005. This positive therapeutic effect correlates to the
positive effects of CLT-005 on vascular leakage and the presence of inflammatory
cytokines in the retina. CONCLUSIONS. The present study indicates that Stat3
inhibition has strong therapeutic potential for the treatment of vision loss in
diabetic retinopathy.
IgE-associated allergic diseases belong to the most common inflammatory conditions.
Their clinical manifestation ranges from mild symptoms to life-threatening
episodes. Often patients experience a reduction in physical and psychologic well-
being and suffer from a decreased quality of life due to disease activity. The
continuously rising number of people that are affected by an allergic condition
indicates an urgent need for better diagnostics and more efficient treatment
options. Recent progress in the understanding of pathophysiologic mechanisms
underlying IgE-associated allergic disorders has led to the identification of novel
therapeutic targets and the development of drug candidates that are currently under
evaluation. In this review, we highlight studies and clinical trials, which have
helped to gain further insight in the etiology of IgE-associated allergic
conditions as well as advances in the development of diagnostic tools and
therapeutic approaches recently published in Allergy (European Journal of Allergy
and Clinical Immunology).
Trichinellosis is a cosmopolitan zoonotic disease produced mainly by the
consumption of poorly cooked swine meat. Several studies have probed the efficiency
of immunotherapy as a method for the treatment of trichinellosis. In this work, a
45 kDa immunodominant antigen was characterized, and the presence of IgA, IgM and
IgG anti-Trichinella spiralis antibodies was evaluated during the course of the
infection. In addition, the differences between sublingual and parenteral
administration of the 45 kDa T. spiralis antigen were determined. Long Evans rats
were used both to purify the 45 kDa antigen and to evaluate the immune response
produced in six different groups: healthy and infected controls; two groups of
immunized murines (sublingually and parenterally) with four doses of the 45 kDa T.
spiralis immunogen administered at days 0, 7, 14 and 21 and challenged with 500 T.
spiralis infective larvae (IL) 7 days after the last immunization; and finally, two
groups of murines infected with 500 IL of T. spiralis, immunized at week 4 post
infection by the same two routes. The humoral response was evaluated by indirect
immunofluorescence by confocal microscopyin order to determine the presence of IgA,
IgM and IgG antibodies.
The detection of porcine reproductive and respiratory syndrome virus (PRRSV) in
oral fluids (OF) by quantitative real-time polymerase chain reaction (qRT-PCR) is
gaining increasing popularity. However, the different steps leading to a result
have not been extensively evaluated. The aim of the present study was to examine
the effect on the performance of qRT-PCR with different sampling materials,
conditions of storage of the OF, the need for centrifuging OF, as well as to
compare RNA extraction methods and PCR mixes. For the assays, pen-based oral fluids
were used, which were pooled and spiked in a serial dilution (up to genotype
10(circle) TCID50/mL) of type 1 PRRSV isolate 3267. Centrifugation at 15,000g for
15 min resulted in an increase in sensitivity (1-2 PCR cycles) that was significant
(P<0.05) at the lowest dilution tested. The TRIzol and MagMAX RNA extraction
methods gave the maximum sensitivity, lowest threshold cycle (Ct), at equivalent
virus concentrations. The AgPath-ID One-Step RT-PCR Kit PCR mix reagents were more
sensitive for the detection of PRRSV using a purified plasmid as standard, but LSI
VetMAX PRRSV EU/NA PRRSV reagents resulted in a slightly better sensitivity with OF
(p <0.05). The present results may be useful to standardize protocols for
optimizing detection of type I PRRSV in OF by qRT-PCR. (C) 2017 Elsevier B.V. All
rights reserved.
Equine herpesvirus type 1 (EHV-1) is a double -stranded DNA virus occurring in all
breeds of horses. It belongs to the Varicellovirus genus, Herpesviridae family and
Alphaherpesvirinae subfamily. EHV-1 may cause epidemic respiratory disorders,
abortions in pregnant mares, neonatal foal death, chorioretinopathy and also
neurological disease, termed equine herpesvirus myeloencephalopathy (EHM). The
infection spreads by inhalation of the aerosolised infectious virus or close
contact with aborted fetuses, fetal membranes and fomites. Lifelong latency has
been demonstrated especially in trigeminal ganglion, lymphatic tissues draining the
respiratory tract and in peripheral blood leukocytes, from where the virus can be
periodically reactivated. Both traditional serologic and virus isolation tests have
been available for a long time, however, these assays have disadvantages,
interfering with fast and reliable detection of EHV-1. Advances in molecular
biology and the use of quantitative PCR system allow for more sensitive detection
in a single genome copy range, higher analytical specificity and calculation of
EHV-1 viral loads.
One of the main factors limiting molluscs production is the presence of pathogens
and diseases. Disease agent transfer via transfers of live molluscs has been a
major cause of disease outbreaks and epizootics. Because of that, the European
Union has adopted several decisions and directives, the last in 2006 (2006/88/EC)
to control movements of marine organisms over the European countries. Once the
disease is established in a determined area its eradication is a complicated task
because life cycle of pathogens are not completely known and only a good and early
diagnosis of the disease could be the most appropriate way to deal with it.
Besides, molluscs do not have an adaptive immune response and vaccination
strategies are not possible. Molluscs listed diseases under EU legislation are
mainly protozoan parasites, that's why histological techniques are recognized for
their diagnosis. However, molecular techniques are being increasingly used
primarily as confirmatory techniques of the presence of the pathogens but also in
disease monitoring programs. Research perspectives are mainly focussed in the
optimization, of the already described techniques to gain in sensitivity and
sensibility and in the development of new molecular biology techniques
(quantitative real time PCRs), that are faster and easier to apply and that allow a
positive diagnosis even in early stages of infection. However, molecular tools
detect DNA sequences of the pathogen which does not imply that pathogen is viable
in the cell host and the infection is established. Consequently, it needs to be
validated against other techniques, such as histology or in situ hybridization, so
that its reliability can be determined.
Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers
since tumor-specific molecules can be found in exosomes isolated from biological
fluids. We have previously analyzed the proteome of urinary exosomes by mass
spectrometry, and identified proteins differentially expressed in prostate cancer
patients compared to healthy males. Since mass spectrometry is so far not commonly
used in clinical laboratories, we have here investigated whether antibody-based
methods such as Western blot or ELISA can be used to validate the use of the
identified proteins as prostate cancer biomarkers. Western blot experiments
designed to detect flotillin 2, TMEM256, Rab3B and LAMTORI showed that the level of
these proteins was higher in urinary exosomes from prostate cancer patients
compared to healthy males. Furthermore, a receiver operating characteristic curve
of flotillin 2 in samples from 16 controls and 16 patients showed an area under the
curve of 0.91, and 88% sensitivity at a threshold set to give 94% specificity. In
addition, ELISA-based detection of flotillin 2 and PARK7 showed that the
combination of these proteins was able to distinguish prostate cancer patients and
healthy controls with 68% sensitivity and 93% specificity. Several promising
biomarkers identified by mass spectrometry could not be evaluated by Western blot
or ELISA due to their low exosomal amount and/or lack of good antibodies. In
conclusion, our results show that several urinary exosomal proteins identified as,
prostate cancer biomarkers by mass spectrometry have a high diagnostic value also
when analyzed by immunology-based methods, thus bringing these biomarkers closer to
a potential clinical use. (C) 2016 Elsevier B.V. All rights reserved.
Purpose of review The purpose of this review is to give an overview of viral
meningitis and then focus in on some of the areas of uncertainty in diagnostics,
treatment and outcome. Recent findings Bacterial meningitis has been declining in
incidence over recent years. Over a similar time period molecular diagnostics have
increasingly been used. Because of both of these developments viral meningitis is
becoming relatively more important. However, there are still many unanswered
questions. Despite improvements in diagnostics many laboratories do not use
molecular methods and even when they are used many cases still remain without a
proven viral aetiology identified. There are also no established treatments for
viral meningitis and the one potential treatment, aciclovir, which is effective in
vitro for herpes simplex virus, has never been subjected to a clinical trial.
Summary Viruses are in increasingly important cause of meningitis in the era of
declining bacterial disease. The exact viral aetiology varies according to age and
country. Molecular diagnostics can not only improve the rate of pathogen detection
but also reduce unnecessary antibiotics use and length of hospitalization. Further
research is required into treatments for viral meningitis and the impact in terms
of longer term sequelae.
Background: Norovirus (NV) infection has been reported as a cause of severe chronic
diarrhea in transplant recipients, but this entity remains under-recognized in
clinical practice, leading to diagnostic delays. Transplant clinicians should
become familiar with this syndrome in order to facilitate early detection and
management. Methods: Demographic, clinical, and outcomes variables were summarized
from a series of transplant recipients with positive stool NV reverse transcription
polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors
associated with longer duration of symptoms were compared using random forest
analysis. Results: Thirty-one of 193 (16%) transplant recipients who were tested
for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%),
nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury
occurred in 23%, and persisted in 21% after 6months. Median duration of diarrheal
symptoms was 4months (range, <1-20) and 11/31 (35.4%) patients had relapses after
improvement. Wasting, incompatible kidney transplant status, and plasmapheresis
were associated with longer diarrhea durations. Treatments included nitazoxanide
(in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin
(32%). Six patients died, but no deaths were attributed to NV. Conclusions: It is
important for clinicians to recognize that NV can cause severe chronic diarrhea in
transplant recipients. In this series, receipt of a human leukocyte antigen- and/or
blood type-incompatible kidney transplant, and plasmapheresis were associated with
longer symptom duration.
Background: There are multiple etiologies responsible for infectious
gastroenteritis causing acute diarrhea which are often under diagnosed. Also acute
diarrhea is one of the major causes of morbidity and mortality among children less
than 5 years of age. Methods: In our study, fecal samples (n = 130) were collected
from children (< 5 years) presenting with symptoms of acute diarrhea. Samples were
screened for viral, bacterial, and parasitic etiologies. Rotavirus and Adenovirus
were screened by immunochromatographic tests. Diarrheagenic Escherichia coli (EPEC,
EHEC, STEC, EAEC, O157, O111), Shigella spp., Salmonella spp., Vibrio cholera,
Cryptosporidium spp., and Giardia spp. were detected by gene-specific polymerase
chain reaction. Results: Escherichia coli was detected to be the major etiological
agent (30.07%) followed by Rotavirus (26.15%), Shigella (23.84%), Adenovirus
(4.61%), Cryptosporidium (3.07%), and Giardia (0.77%). Concurrent infections with
two or more pathogens were observed in 44 of 130 (33.84%) cases with a predominant
incidence particularly in < 2-year-old children (65.90%) compared to children of 2-
5 years age group (34.09%). An overall result showed significantly higher detection
rates among children with diarrhea in both combinations of two as well as three
infections concurrently (p = 0.004915 and 0.03917, respectively). Conclusion:
Suspecting possible multiple infectious etiologies and diagnosis of the right
causative agent(s) can aid in a better pharmacological management of acute
childhood diarrhea. It is hypothesized that in cases with concurrent infections the
etiological agents might be complementing each other's strategies of pathogenesis
resulting in severe diarrhea that could be studied better in experimental
infections.
We have characterized the expression of microRNAs and selected microRNA precursors
within several synaptic fractions of adult mouse forebrain, including
synaptoneurosomes, synaptosomes and isolated post-synaptic densities (PSDs), using
methods of microRNA microarray, real time qRT-PCR, Northern blotting and
immunopurification using anti-PSD95 antibody. The majority of brain microRNAs
(especially microRNAs known to be expressed in pyramidal neurons) are detectably
expressed in synaptic fractions, and a subset of microRNAs is significantly
enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA
precursors are also detectable in synaptic fractions at levels that are comparable
to whole tissue. Whereas mature microRNAs are predominantly associated with soluble
components of the synaptic fractions, microRNA precursors are predominantly
associated with PSDs. For seven microRNAs examined, there was a significant
correlation between the relative synaptic enrichment of the precursor and the
relative synaptic enrichment of the corresponding mature microRNA. These findings
support the proposal that microRNAs are formed, at least in part, via processing of
microRNA precursors locally within dendritic spines. Dicer is expressed in PSDs but
is enzymatically inactive until conditions that activate calpain cause its
liberation; thus, we propose that synaptic stimulation may lead to local processing
of microRNA precursors in proximity to the synapse.
The present study aimed to investigate the effect of Dickkopf-related protein 3
(DKK3) on osteogenic differentiation of rat dental follicle cells (DECs). A PCR
array analysis of Wnt pathway activation in DECs identified genes dysregulated by
mineral induction. Among them, DKK3expression levels were decreased, and further
experiments were conducted to investigate its role in DEC osteogenesis. By
comparing DECs grown in normal growth and mineral-induction media for 4 weeks, the
present study confirmed that DKK3 was a potential target gene of osteogenesis
through reverse transcliption-quantitative polymerase chain reaction (RT-gPCR) and
western blotting (WB). A short hairpin RNA (shRNA) was introduced into DECs using a
lentiviral vector to inhibit DKK3 expression. An alkaline phosphatase (ALP)
activity assay and Alizarin Red staining were performed to observe the DKK3-shRNA
DECs. In addition, the osteogenic differentiation of DKK3-shRNA DECs was analyzed
by RT-gPCR and WB. In vivo, DKK3-shRNA DECs seeded on hydroxyapatiteiP-tricalcium
phosphate (HA/TCP) scaffolds were transplanted into the subcutaneous tissue of mice
with severe combined immunodeficiency, followed by hematoxylin-eosin and Masson
staining. The results confirmed that DKK3 expression was downregulated during
mineral induction in rat DECs. Lentivirus-mediated expression of DKK3 shRNA in DECs
promoted calcified-nodule formation, ALP activity and the expression of P-catenin,
runt-related transcription factor 2 and osteocalcin, compared with control cells.
In vivo, the implanted section presented the majority of newly formed osteoid
matrices and collagen, with limited space between the HA/TCP scaffolds and
matrices. In conclusion, DKK3 expression negatively regulates the osteogenic
differentiation of DECs and, conversely, downregulation of DKK3 may enhance DEC
osteogenesis.
The bewildering complexity of the relationship between genotype and phenotype in
human mitochondrial diseases has delayed an understanding of the related
cytopathological mechanisms. To explore the relationship between mitochondrial
dysfunction in Dictyostelium discoideum and the related cytopathologies, we
determined whether the phenotypic outcomes were similar regardless of which D.
discoideum mitochondrial gene was targeted for disruption. The disruption of the
mitochondrial genes resulted in a similar pattern of phenotypes to those caused by
other mitochondrial defects. These include impairment of phototaxis, multicellular
development and growth on plates and in liquid medium. As the reduced growth rates
could have been due to defective phagocytic or macropinocytic nutrient uptake,
these processes were tested but found to be unaffected. Since mitochondria have
been associated with Legionella pathogenesis of human macrophages, it was also
determined if mitochondrially diseased Dictyostelium strains were better or worse
than healthy cells at supporting the growth of Legionella pneumophila. The results
revealed that the mitochondrially diseased strains supported greater L pneumophila
growth than the wild type Dictyostelium strain (AX2). Quantitative Northern
blotting showed a significant reduction in the level of expression of the entire
mitochondrial genome, regardless of which mitochondrial gene was targeted for
disruption, suggesting a generalized deficiency in mitochondrial gene expression
and function. The phenotypic outcomes were the same as those shown previously to
result from chronic hyperactivity of the energy-sensing protein kinase, AMPK, after
knockdown of mitochondrial chaperonin 60. (C) 2011 Elsevier Inc. All rights
reserved.
Dielectric actuators are utilized to convert electrical power into mechanical
strain with considerable potential in microrobotic applications. However, critical
challenges that need to be addressed include high-voltage interface with high
conversion ratio, light weight, small size, and high power density. This study
proposes a high piezoelectric transformer-based high conversion ratio interface
that is integrated with a direct current/direct current high conversion ratio boost
stage and a direct current/alternating current high-voltage driving stage. A
piezoelectric transformer-based class-E zero voltage switching direct
current/direct current interface is controlled by a hybrid pulse frequency
modulation and pulse width modulation control strategies to obtain the desired high
step-up ratio in the direct current/direct current stage. A half-bridge converter
with special digital control algorithm in the direct current/alternating current
stage is designed to convert high direct current voltage into arbitrary unipolar
signal driving dielectric actuators. A prototype 23.3 g and 4W interface has been
fabricated for experimental validation to verify its ability to drive a 1 kV input
dielectric actuator at 5 Hz in microrobotic applications.
A poly(vinylidene fluoride) (PVDF) nanocom-posite incorporated with polydopamine-
coated reduced graphene oxide (rGO@PDOPA) nanosheets has been developed with high
dielectric permittivity and low loss for electricity storage applications.
Structural analysis indicates that PDOPA was successfully anchored onto rGOs
through non-covalent linkage under mild conditions. The presence of PDOPA layer
between rGO and PVDF can not only prevent the agglomeration and direct contact of
original rGOs but also enhance the interaction between PVDF and rGO and
microcapacitor formation. Compared to rGO/PVDF composites, higher dielectric
permittivity and lower loss factor were achieved simultaneously in rGO@PDOPA/PVDF
nanocomposites at low and moderate frequencies. The PDOPA interface layers are
effective in modifying the dielectric characteristics of the composites to increase
the dielectric permittivity without the introduction of loss mechanisms. This study
demonstrates that PDOPA is an ideal interface layer for the development of new
percolative dielectric composites with high dielectric permittivity and low loss.
This work describes an electrical interferometer for contactless permittivity
measurements working at 120 GHz. It was fabricated in a 130 nm SiGe process
featuring an ft and fmax of 240 and 330 GHz. The on-chip system contains a 120 GHz
VCO with a tuning range of 7 GHz featuring a divide-by- 64 circuit to enable
external PLL operation. The subsequent buffer provides 7 dBm of output power at 120
GHz. Additionally, the IC contains high-precision and high-resolution phase
shifters based on a slow-wave transmission line approach with digital control for
direct readout ability. A 120 GHz LNA with 17 dB gain and a power detector to
provide DC output signals were realized on chip. It enables sample emulation
capability by phase shift inducement in the measurement as well as a reference
transmission line. In terms of phase detection, the system shows a sensitivity of
907.36 MHz/degrees.
Diencephalic defects underlie an array of neurological diseases. Previous studies
have suggested that retinoic acid (RA) signaling is involved in diencephalic
development at late stages of embryonic development, but its roles and mechanisms
of action during early neural development are still unclear. Here we demonstrate
that mice lacking enzymatic activity of the acetyltransferase GCN5
((Gcn5(hat/hat))), which were previously characterized with respect to their
exencephalic phenotype, exhibit significant diencephalic expansion, decreased
diencephalic RA signaling, and increased diencephalic WNT and SHH signaling. Using
a variety of molecular biology techniques in both cultured neuroepithelial cells
treated with a GCN5 inhibitor and forebrain tissue from (Gcn5(hat/hat)) embryos, we
demonstrate that GCN5, RAR alpha/gamma, and the poorly characterized protein TACC1
form a complex in the nucleus that binds specific retinoic acid response elements
in the absence of RA. Furthermore, RA triggers GCN5-mediated acetylation of TACC1,
which results in dissociation of TACC1 from retinoic acid response elements and
leads to transcriptional activation of RA target genes. Intriguingly, RA signaling
defects caused by in vitro inhibition of GCN5 can be rescued through RA-dependent
mechanisms that require RAR beta. Last, we demonstrate that the diencephalic
expansion and transcriptional defects seen in (Gcn5(hat/hat)) mutants can be
rescued with gestational RA supplementation, supporting a direct link between GCN5,
TACC1, and RA signaling in the developing diencephalon. Together, our studies
identify a novel, nonhistone substrate for GCN5 whose modification regulates a
previously undescribed, tissue-specific mechanism of RA signaling that is required
to restrict diencephalic size during early forebrain development.
Pectinolytic bacteria from the genus Dickeya (former Erwinia chrysanthemi),
belonging to Dickeya dianthicola and Dickeya solani species, are causative agents
of blackleg and soft rot diseases in Europe. Recently, D. solani have been isolated
most frequently from potato plants with the symptoms of blackleg and soft rot. D.
solani strains were shown to cause more severe disease symptoms on potato plants
than D. dianthicola especially at the higher temperature. They are also able to
develop blackleg disease from lower inoculum levels. In the presented study we not
only compared phenotypic features of fifteen D. solani strains isolated in
countries having different climatic conditions, Poland, Finland and Israel, but
also we examined three D. dianthicola strains. The comparison was performed to
determine the influence of the strain origin and the temperature of incubation on
the ability of the strains to macerate potato tissue and on their major virulence
factors such as: pectinolytic, cellulolytic and proteolytic activities, siderophore
production and motility. Polish D. solani strains showed higher activities of cell
wall degrading enzymes than the Finnish and Israeli strains at all the tested
temperatures: 18, 27, 37 A degrees C. This observation is correlated with the
higher ability of Polish D. solani strains to cause soft rot. In addition, D.
solani strains exhibited higher activity of the above mentioned enzymes and caused
more severe potato tuber maceration in laboratory tests than the tested D.
dianthicola strains. The collected results indicate that although D. solani strains
from different climatic conditions have identical Pulse Field Gel Electrophoresis
(PFGE) profiles in addition to the same fingerprint profiles obtained by the
repetitive sequence-based polymerase chain reaction (REP, ERIC and BOX repetitive
sequences), they differ in the examined phenotypic features, especially in the
activities of pectinolytic, cellulolytic and proteolytic enzymes and their capacity
to macerate potato tuber tissue.
This paper introduces a nonlinear control scheme based on the differential flatness
approach for controlling the speed/torque of a permanent magnet synchronous motor
(PMSM) drive. The differential flatness estimation is a model based approach. Then,
two state-observers are proposed to estimate a load torque disturbance and a stator
resistance (represent losses in an inverter and PMSM) by means of its voltage drop.
It can help to improve the PMSM drive system and the efficiency. Using the flatness
property, we propose simple solutions to dynamics and stabilization problems. The
design controller parameters are autonomous of the operating point; moreover, high
dynamics in disturbance rejection is achieved. To validate the proposed method, a
hardware system is realized in a laboratory, and digital estimation is accomplished
with a dSPACE controller DSll04 platform. Simulation and experimental results with
a small-scale PMSM of 1000 W, 3000 rpm in a laboratory corroborate the excellent
control scheme during a motor-drive cycles.
Exposure of watermelon fruit to ethylene leads to acute placental-tissue softening
and watersoaking. mRNA differential display strategy was utilized to isolate and
characterize genes associated with development of the disorder. Watermelon fruit
were harvested at the full-ripe stage and exposed to 50 mu LL-1 ethylene for 12 h,
and 1, 3, and 6 d at 20 degrees C. DNA-free total RNA (0.2 mu g) isolated from
fruit treated with air or ethylene for 12 h was reverse transcribed using three
different one-base-anchored oligo dT primers. High stringency PCR was performed
using eight different 13-mer arbitrary primers in combination with the fluorescent-
labeled one-base-anchored oligo dT primers. The PCR fluorescent-labeled products
were separated-on a 6% polyacrylamide sequencing gel and differentially expressed
bands were isolated. Confirmation of true positive bands was performed by reverse
northern blotting. Comparison of mRNA profiles of ethylene- and air-treated fruit
revealed that 78 genes were differentially expressed, of which 15 partial cDNAs
were isolated and characterized. BLAST search results revealed significant
homologies to ethylene biosynthesis and signal transduction pathway genes, lipid-
metabolizing enzymes, proteins involved in plant defense responses, radical
scavenging enzymes, exonucleases, and expansins. Northern blot analysis of RNA
isolated from air- and ethylene-treated fruit stored for 1, 3, and 6d revealed an
ethylene-dependent expression pattern of all corresponding genes. The data indicate
that ethylene treatment of watermelon fruit results in a rapid up-regulation of
oxidative and hydrolytic enzymes. (C) 2007 Elsevier B.V. All rights reserved.
Early metastasis and a poor five-year survival make lung cancer the leading cause
of cancer related deaths worldwide. The clinical profile of lung cancer patients in
India differs from the West as they present earlier, with squamous cell carcinoma
being the commonest histological type. We compared gene expression profiles in
primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in
Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA
libraries containing differentially expressed genes in the tumors were constructed.
Differential expression was confirmed by reverse Northern blot analysis. DNA of
confirmed clones was sequenced and subjected to GenBank Blast searches. RNA
expression levels were then analyzed by Northern blotting and validated by
semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed
gene cDNA fragments of LSCC were analyzed. The differentially expressed genes
included those associated with cellular metabolism, cell-cycle, -structure, -
adhesion, transcription, proliferation, apoptosis and signal transduction. The
study provided first evidence that KLAA0767, a Death Inducing Protein, a novel p53
independent target of EM, and Geminin, an inhibitor of DNA replication are
differentially expressed in LSCC. Identification of the differentially expressed
genes in lung cancer in this study may serve as better molecular markers for early
diagnosis and identifying novel intervention sites for anticancer therapy. (c) 2008
Elsevier Inc. All rights reserved.
Overselective stimulus control refers to discriminative control in which the number
of controlling stimuli is too limited for effective behavior. Experiment 1 included
22 special-education students who exhibited overselective stimulus control on a
two-sample delayed matching task. An intervention added a compound identity
matching opportunity within the sample observation period of the matching trials.
The compound matching functioned as a differential observing response (DOR) in that
high accuracy verified observation and discrimination of both sample stimuli.
Nineteen participants learned to perform the DOR and two-sample delayed matching
accuracy increased substantially for 16 of them. When the DOR was completely
withdrawn after 10 sessions, accuracy declined. In Experiment 2, a more gradual
withdrawal of DOR requirements showed that highly accurate performance could be
maintained with the DOR on only a proportion of trials for most participants. The
results show that DOR training may lead to a general improvement in observing
behavior.
This paper describes a distributed maximum power point tracking control scheme for
photovoltaic (PV) systems at the submodule level. The system employs isolated
differential power processing (DPP) converters that require no perturb and observe
synchronization and little communication among power converters themselves. Design
and benefits of this architecture with respect to control, communication, and
converter efficiency are analyzed. Isolated dc-dc converter prototypes are
constructed and employed within a string of series-connected PV submodules to
experimentally validate the proposed control method. An experimental extraction
efficiency of 99.12% is achieved for a three submodule connection with similar to
30% mismatch-a 10.19% improvement from the conventional, non-DPP architecture.
Differential response (DR) is a system reform that allows child protective services
(CPS) agencies to divert low to-moderate risk families from an investigative track
to an alternate track that does not require a maltreatment disposition or
identification of an alleged perpetrator. Knowledge of how DR alters the flow of
cases through CPS systems has been restricted by methodological limitations in
prior research. This study uses cross-sectional and longitudinal data from the
National Child Abuse and Neglect Data System (NCANDS) child file to examine the
extent to which DR implementation affects the number and demographic composition of
cases investigated for neglect. Results from multivariate, multilevel cross-
sectional analysis of 2010 data indicated that investigations were 2.4 times more
likely to be substantiated in DR counties than in non-DR counties. Children with a
previous substantiated report were also more likely to have a current report
substantiated and this difference was significantly greater in DR counties than in
non-DR counties. Child race and ethnicity did not predict substantiation decisions.
Results from a mixed-effect longitudinal analysis of 997,512 cases from 269
counties between 2001 and 2010 suggest that the rate of investigations fell sharply
nationwide within three years of DR implementation. However, substantiation rates
did not change as a result of DR implementation. Instead, analysis indicated
differences between DR and non-DR counties emerged before the launch of DR. The
findings highlight the benefit of using "big data" and longitudinal analysis to
assess large-scale policy changes. (C) 2016 Elsevier Ltd. All rights reserved.
Using a simplified high-frequency small-signal equivalent circuit model for BSIM3
MOSFET, the fully differential two-stage folded-cascode CMOS operational amplifier
is analyzed to obtain its small-signal voltage transfer function. As a result, the
expressions for dc gain, five zero frequencies, five pole frequencies, unity-gain
frequency, and phase margin are derived for op amp design using design equations.
Then the analysis result is verified through the comparison with Spice simulations
of both a high speed op amp and a low power op amp designed for the 0.13 mu m CMOS
process.
Trifoliate orange (Poncirus trifoliata (L) Raf.) is extremely cold hardy when fully
acclimated, but knowledge relevant to the molecular events underlying the
acclimation is still limited so far. In this study, forward (4 degrees C over 25
degrees C) and reverse (25 degrees C over 4 degrees C) suppression subtractive
hybridization (SSH) libraries were constructed in order to identify the genes
involved in cold acclimation in trifoliate orange. After reverse northern blotting
analysis and sequencing, a total of 105 and 117 non-redundant differentially
expressed sequence tags (ESTs) were obtained from the forward and reverse
libraries, respectively. Blast2go analysis revealed that 91 ESTs, 31 from the
forward library and 60 from the reverse library, displayed significant sequence
homology to the genes with known or putative functions. They were categorized into
various functional groups, including catalytic activity, binding protein,
structural molecule, enzyme regulator, molecular transducer, electron carrier, and
transport activity/transcription regulation. Expression analysis of the selected
ESTs by reverse transcriptase polymerase chain reaction was consistent with the
results of differential screening. In addition, time-course expression patterns of
the genes further confirmed that they were responsive to low temperature treatment.
Among the genes of known functions, many are related to maintenance of cell wall
integrity, adjustment of osmotic potential and maintenance of reactive oxygen
species homeostasis, implying that these physiological processes might be of
paramount significance in rendering protective mechanisms against the low
temperature stress. The data presented here gain an insight into the molecular
changes underlying the cold acclimation of trifoliate orange, and the results can
be of reference for unraveling candidate genes that hold great potential for
genetic engineering in an effort to create novel germplasms with enhanced cold
stress tolerance. (C) 2011 Elsevier B.V. All rights reserved.
Work on standardising methods in the field of animal species differentiation has
been intensified in Germany in recent years, not least due to the horsemeat scandal
in 2013. Even though there are now hardly ever any positive findings any more in
examinations to detect horse elements in foods such as lasagne, animal species
differentiation altogether ranks high in detecting adulteration of foods. This
article therefore summarises the current status of analysis techniques in Germany
with a focus on standardisation. It has been established by the working group
"Biochemical and Molecular Biological Analytics" of the Lebensmittelchemische
Gesellschaft (Food Chemistry Society within the German Chemical Society) with
support of experts in the working group "Molecular biology techniques for
differentiating plant and animal species" [ 64 of the German Food and Feed Code -
LFGBI and the "Immunology and molecular biology" task force of the Food hygiene and
food of animal origin working group (ALTS), both from Germany.
Background: Major depressive disorder (MDD) and anxiety disorders are highly co-
morbid. Research has shown conflicting evidence for white matter alteration and
amygdala volume reduction in mood and anxiety disorders. To date, no studies have
examined differences in structural connectivity between anxious depressed and non-
anxious depressed individuals. This study compared fractional anisotropy (FA) and
density of selected white matter tracts and amygdala volume between anxious
depressed and non-anxious depressed individuals. Methods: 64- direction DTI and T1
scans were collected from 110 unmedicated subjects with MDD, 39 of whom had a co-
morbid anxiety disorder diagnosis. Region of interest (ROI) and tractography
methods were performed to calculate amygdala volume and FA in the uncinate
fasciculus, respectively. Diffusion connectometry was performed to identify whole
brain group differences in white matter health. Correlations were computed between
biological and clinical measures. Results: Tractography and ROI analyses showed no
significant differences between bilateral FA values or bilateral amygdala volumes
when comparing the anxious depressed and non-anxious depressed groups. The
diffusion connectometry analysis showed no significant differences in anisotropy
between the groups. Furthermore, there were no significant relationships between
MRI-based and clinical measures. Conclusion: The lack of group differences could
indicate that structural connectivity and amygdalae volumes of those with anxious-
depression are not significantly altered by a co-morbid anxiety disorder. Improving
understanding of anxiety co-morbid with MDD would facilitate development of
treatments that more accurately target the underlying networks. (C) 2017 Elsevier
Ltd. All rights reserved.
Whereas a number of studies have examined relationships among brain activity,
social cognitive skills, and autistic traits, fewer studies have evaluated whether
structural connections among brain regions relate to these traits and skills.
Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are white
matter tracts that may underpin the behavioral expression of these skills because
they connect regions within or provide sensory information to brain areas
implicated in social cognition, and structural differences in these tracts have
been associated with autistic traits. We examined relationships among self-reported
autistic traits, mentalizing, and water diffusivity in UF and ILF in a nonclinical
sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years; 15 women). We
measured autistic traits using the Autism-Spectrum Quotient, and we measured
mentalizing using the Dynamic Interactive Shapes Clips task. We used Tract-Based
Spatial Statistics and randomize to examine relationships among fractional
anisotropy (FA) values in bilateral ILF and UF, age, cognitive abilities, autistic
traits, and mentalizing. Autistic traits were positively related to FA values in
left ILF. No other relationships between FA values and other variables were
significant. Results suggest that left ILF may be involved in the expression of
autistic traits in individuals without clinical diagnoses.
The paper aims at explaining why large-scale energy-intensive industries-here the
German iron and steel industry-had a period of slow uptake of major energy-
efficient technologies from the mid 1990s to mid 2000s (Arens and Worrell, 2014)
and why from the mid 2000s onwards these technologies are increasingly implemented
again. We analyze the underlying factors and investment/innovation behavior of
individual firms in the German iron and steel industry to better understand
barriers and drivers for technological change. The paper gives insights on the
decision-making process on energy efficiency in firms and helps to understand how
policy affects decision-making. We use a mixed method approach. First, we analyze
the diffusion of three energy-efficient technologies (EET) for primary steelmaking
from their introduction until today (top-pressure recovery turbine (TRT), basic
oxygen furnace gas recovery (BOFGR), and pulverized coal injection (PCI)). We
derive the uptake of these technologies both at the national level and at the level
of the individual firm. Second, we analyze the impact of drivers and barriers on
the decision-making process of individual firms whether or not they want to
implement these technologies. Economics and access to capital are the foremost
barriers to the uptake of an EET. If the expected payback period exceeds a certain
value or if the company lacks capital, investments in EET seem not to happen. But
even if an EET is economically viable and the company has access to capital,
investments in EET might not be realized. Policy-induced prices might have
strengthened the recent diffusion of TRT. We found indications that in a limited
number of cases, policy intervention was a driving factor. Technical risks and
imperfect information are only marginal factors in our cases. Site-specific factors
seem to be important, as site-specific factors shape the economics of the selected
EET.
A digitally controlled operational amplifier (op-amp) with level-crossing-based
approximation is proposed. A high gain is effectively obtained by means of a
damping control without a stability problem occurring in the multiple gain stages.
Compared to the previous version of the zero-crossing-based algorithmic
approximation, the proposed scheme further improves the settling time with the
class AB operation obtained by switching of multiple driving paths. For
verification, the designed op-amp is applied to a 10-bit pipeline ADC and
implemented in a 0.18 mu m CMOS technology. Measured results show that the designed
op-amp successfully operates at 10-bit resolution, 10 MSample/s pipeline ADC and
achieves an effective gain of more than 60 dB.
Inspiring by the advantages of digital peak voltage (DPV) control and digital
average current (DAC) control, the digital average voltage (DAV) control for
switching DC-DC converter is proposed and investigated. Taking buck converter as an
example, DAV control algorithm is analyzed in detail. In order to explore the
stability of system, the z-domain transfer function is deduced, by which the
critical equivalent series resistance (ESR) of output capacitor is obtained.
Finally, DAV controlled, DPV controlled and DAC controlled buck converter are
compared by time-domain simulation. Results indicate that DAV control possesses
better steady accuracy as well as DAC control. In addition, DAV controlled buck
converter is in stable state during the whole duty ratio. Moreover, DAV control and
DPV control have similar load transient performance but DAV control behaves lower
overshoot voltage with load variation.
Brain-inspired circuits can provide an alternative solution to implement computing
architectures taking advantage of fault tolerance and generalization ability of
logic gates. In this brief, we advance over the memristive threshold circuit
configuration consisting of memristive averaging circuit in combination with
operational amplifier and/or CMOS inverters in application to realizing complex
computing circuits. The developed memristive threshold logic gates are used for
designing fast Fourier transform and multiplication circuits useful for modern
microprocessors. Overall, the proposed threshold logic outperforms previous
memristive-CMOS logic cells on every aspect, however, they indicate a lower chip
area, lower total harmonic distortion, and controllable leakage power, but a higher
power dissipation with respect to CMOS logic.
Loudspeakers line arrays are very common reproduction sound systems used in real
environments (e.g., theaters, stadiums, cinemas, and conference halls) for
synthesizing the directivity characteristics of a linear source. The sound field
emitted by a vertical line array can be pointed in a particular direction by using
digital signal processing techniques and avoiding any mechanical movements. The
approach proposed in this paper to obtain the desired directivity behavior takes
advantage of the reproduction of a virtual source with frequency-independent
directivity characteristics using wave field synthesis theory and introducing a
computational complexity reduction. A full investigation on the performance of the
technique has been carried out making comparisons with other approaches proposed in
the literature thus providing an overview of the results achievable with digital
steering of line arrays. (C) 2015 Elsevier Ltd. All rights reserved.
This study demonstrates a new method for rapid and precise maximum power point
tracking in photovoltaic (PV) applications using dithered PWM control. Constraints
imposed by efficiency, cost, and component size limit the available PWM resolution
of a power converter, and may in turn limit the MPP tracking efficiency of the PV
system. In these scenarios, PWM dithering can be used to improve average PWM
resolution. In this study, we present a control technique that uses ripple
correlation control (RCC) on the dithering ripple, thereby achieving simultaneous
fast tracking speed and high tracking accuracy. Moreover, the proposed method
solves some of the practical challenges that have to date limited the effectiveness
of RCC in solar PV applications. We present a theoretical derivation of the
principles behind dithering digital ripple correlation control, as well as
experimental results that show excellent tracking speed and accuracy with basic
hardware requirements.
A rapid prototyping methodology for digital controllers is presented in this paper.
Its main application is in the development, debugging, and test of microgrid
inverter controllers. To fulfill the application requirements, these systems are
characterized by complex multilayer architectures, extending from pulse width
modulation (PWM) and current control loops up to global optimization and high level
communication functions. The complexity and the wide variability of the different
layer implementations make digital control mandatory. However, developing so
complex digital controllers on conventional hardware platforms, like digital signal
processors (DSPs) or even FPGAs, is not the most practical choice. This paper shows
how multiplatform control devices, where software configurable DSP functions and
programmable logic circuits are efficiently combined, represent the optimal
solution for this field of application. Furthermore, this paper proposes hardware-
in-the-loop real-time simulation as an effective means of developing and debugging
complex hardware and software codesigned controllers. A case study is presented and
used to illustrate the different design and test phases, from initial concept and
numerical simulation to final experimental verification.
The article describes some of the features of the servo amplifier, developed in the
NRU "MPEI" for use in multi-axis high-precision materials processing. Simplified
structure of servo amplifier and some of the key components of servo drive digital
control system are presented. Two ways of multi-axes control are compared: using
the RS-232 interface and digital inputs/outputs, and using the CANopen standard
based digital CAN protocol. The benefits of multi-axis control with the CANopen
protocol are high-speed exchanges, reliability of data transmission,
standardization and simple communication topology.
There are many industrial applications where precise delivery of fluid required
such as ratio blending, delivery system, etc. One of such application is petroleum
product delivery system. As the price of these petroleum products is increasing day
by day, it is important to deliver the exact demanded quantity of product to the
customer. For such delivery systems the digital control valve is used. This paper
deals with the simulation of the digital control valve. The motivation behind this
is, if we know the behavior of the digital control valve then we can develop
different control strategies so that the fluid delivery can be done with accuracy
and precision.
Purpose - The model for digitally controlled three-phase pulse width modulation
(PWM) boost rectifiers is a sampled data model, which is different from the
continuous time domain models presented in previous studies. The controller, which
is tuned according to the model in continuous time domain and discretized by
approximation methods, may exhibit some unpredictable performances and even result
in unstable systems under some extreme situations. Consequently, a small-signal
discrete-time model of digitally controlled three-phase PWM boost rectifier is
required. The purpose of this paper is to provide a simple but accurate small-
signal discrete-time model of digital controlled three-phase PWM boost rectifier,
which explains the effect of the sampling period, modulator and time delays on
system dynamic and improves the control performance. Design/methodology/approach -
Based on the Laplace domain analysis and the waveforms of up-down-count modulator,
the small signal model of digital pulse width modulation (DPWM) in the Laplace
domain is presented. With a combination of state-space average and a discrete-time
modeling technique, a simplified large signal discrete time model is developed.
With rotation transformation and feed-forward decoupling, the large-signal model is
decoupled into a single input single output system with rotation transformation.
Then, an integrated small signal model in the Laplace domain is constructed that
included the time delay and modulation effect. Implementing the modified z-
transform, a small-signal discrete-time model is derived from the integrated small
signal model. Findings - In a digital control system, besides the circuit
parameters, the location of pole of open-loop transfer function is also related to
system sampling time, affecting the system stability, and the time delay determines
the location of the zero of open-loop transfer function, affecting the system
dynamic. In addition to the circuit parameters discussed in previous literature,
the right half plane (RHP) zero is also determined by the sampling period and the
time delay. Furthermore, the corner frequency of the RHP zero is mainly determined
by the sampling period. Originality/value - The model developed in this paper,
accounting for the effect of the sampling period, modulator and time delays on the
system dynamic, give a sufficient insight into the behavior of the digitally
controlled three-phase PWM rectifier. It can also explain the effect of sampling
period and control delay time on system dynamic, accurately predict the system
stability boundary and determine the oscillation frequency of the current loop in
critical stable. The experimental results verify that the model is a simple and
accurate control-oriented small-signal discrete-time model for the digitally
controlled three-phase PWM boost rectifier.
A simple method to aid in the design of digital compensators for DC-DC power
switching converter is presented. From simple equations, feasible designs are
determined, depending on the characteristics of the converter, sampling frequency
and time delay restrictions. It allows to carry out sensitivity analysis of
different parameters, obtaining an insightful assessment of their influence on the
system performance
Recently, there has been an increase in the use of finite control set model
predictive control (FCS-MPC) for power converters. Model predictive control (MPC)
uses the discrete-time model of the system to predict future values of control
variables for all possible control actions and computes a cost function related to
control objectives. This control technique can provide fast dynamic response.
However, MPC method implementation imposes a very high computational burden and
causes significant hardware requirements for real-time implementation. In this
paper, a fully field-programmable gate array (FPGA)-based real-time implementation
of MPC is proposed for direct matrix converter (DMC). In the proposed method, all
control calculations and the safe commutation scheme for DMC are fully implemented
in the FPGA and the need for another digital control platform, such as digital
signal processors (DSP) or dSPACE, is eliminated. The proposed scheme takes full
advantages of the parallel computation capability of FPGAs.
A fundamental challenge in digital control arises when the controlled plant is
subjected to a fast disturbance dynamics but is only equipped with a relatively
slow sensor. Such intrinsic difficulties are, however, commonly encountered in many
novel applications such as laser- and electron-beam-based additive manufacturing,
human-machine interaction, etc. This paper provides a discrete-time regulation
scheme for exact sampled-data rejection of disturbances beyond Nyquist frequency.
By introducing a model-based multirate predictor and a forward-model disturbance
observer, we show that the inter sample disturbances can be fully attenuated
despite the limitations in sampling and sensing. The proposed control scheme offers
several advantages in stability assurance and lucid design intuitions. Verification
of the algorithm is conducted on a motion control platform that shares the general
characteristics in several advanced manufacturing systems. (C) 2016 Elsevier B.V.
All rights reserved.
In this paper, a new control structure is presented to extract maximum power from a
wind regime. In this novel approach, a discrete-time higher order sliding-mode
controller is designed as an observer to construct the reference value for the
extractable power based on the condition that it operates. This is possible by
tracking the optimal tip speed ratio with manipulating the voltages of the rotor in
the doubly fed induction generator (DFIG) configuration. The presented structure
improves the performance under abrupt changes in the wind speed and can be used for
any type of optimum active power tracking algorithms. The simulations show the
significant improvement in performance of the nonlinear discrete-time backstepping
controller utilizing this technique.
A digital predictive peak current control (PPCC) employing the adaptive slope
compensation is proposed in this paper. The PPCC precisely predicts the peak
current reference with the adaptive slope compensation according to operation
regions and load conditions. Thereby, the PPCC can control the peak inductor
current, and it significantly reduces the total harmonic distortion compared to
that of the conventional digital average current control with duty ratio feed-
forward which is widely used. In addition, parts of the PPCC are implemented by
utilizing the internal high-resolution ramp generator and comparator of a digital
signal processor without external components. The principle and analysis of the
PPCC are presented, and the performance and feasibility are verified by
experimental results with universal input (90 V-rms similar to 260 V-rms) and 750 W
- 400 V output laboratory prototype.
In order to make the dynamic voltage restorer (DVR) concurrently compensate for
low-order harmonics and voltage sag, and eliminate the influence of digital control
on system performance, we propose a novel double closed-loop digital control
strategy, consisting of the fundamental proportional resonant (PR) control in a
voltage loop and selective harmonic PR control in an inductance current loop. Then,
we mainly analyse the discretization effects of the virtual LC method and the step
response method, and further present a straightforward digital design method. Next,
with this method, we design the parameters of the fundamental and selective
harmonic PR controllers in the discrete domain, which inhibit the influence of
sampling, calculation delay etc. on the steady-state error and the dynamic response
performance. Finally, an 11-kVA DVR prototype is developed and tested. The
experimental results indicate that the proposed control strategy satisfies the
requirement of voltage quality for sensitive loads and achieves a good dynamic
response performance.
Very-high-frequency (VHF) converters with the conventional driving scheme suffer
from serious efficiency drop over entire input voltage range due to gate drive
timing mismatch of the eGaN control and synchronous rectification (SR) HEMTs. A
digital adaptive driving scheme is proposed to adjust the control and SR gate drive
signals efficiently over input voltage range. A state-space model is derived to
predict drive timing precisely according to different input voltage and adjust the
gate drive signals correspondingly. A high time resolution circuit to improve time
resolution by selecting cascaded high-speed buffers is proposed. With the proposed
driving scheme, high-frequency switching loss and reverse conduction time of eGaN
HEMTs are reduced significantly to maintain high efficiency over entire input
voltage range. A 30-MHz VHF SR flyback with the printed circuit board (PCB)
fabrication air-core transformer was built. With 18-V input and 5V/10-W output, the
measured efficiency realizes 80.0%. With 24-V input and 5-V/10-W output, the
proposed solution improves the efficiency from 72.9% using the conventional driver
to 75.1% (an improvement of 2.2%).
This paper introduces a highly flexible multichannel output stage for battery-
powered portable electric stimulators (ESs), based on novel power converter
architecture. Compared with other solutions, the presented output stage for
transcutaneous (surface) stimulations increases the number of applicable therapies,
improves the battery operating time through reduced power consumption, and
potentially results in more comfortable and shorter healing therapies. The new
hybrid switch-mode power converter is a combination of flyback and switched-
capacitor (SC) topologies. The flyback steps up the battery voltage and provides
galvanic isolation. The following power-efficient SC stage replaces lossy linear
current sources (CSs) of conventional solutions and produces pulses with a much
higher slew rate, reducing the pulse energy needed to cause the stimulus. The SC
also inherently produces pulses with zero-net charge, eliminating bulky blocking
capacitors and/or dedicated discharging circuits. The regulation of the amplitudes
of the pulses is performed with a new digital voltage-programmed current mode
controller, forcing the output of the SC stage to behave as a CS. The flexible
digital controller allows for creation of various types of pulses and also features
several levels of patient protection. An experimental prototype of the output stage
has undergone proof of principle tests with able-bodied individuals. The results
show that the new output stage produces pulses with a 1-mA/ns slew rate, about two
orders of magnitude higher than the other known solutions. The trials show that the
faster slew rate pulses generate the same muscle contraction with 34% lower
amplitudes, reducing energy consumption by 55%, allowing longer battery life of
portable ES applications.
In order to meet the needs of modern intelligent agricultural detection, this paper
designs and develops a novel energy-saving intelligent wireless agricultural
detecting system combined with technologies green power supply, wireless
transmission and digital control. This system can be powered by green energy
resources such as solar energy or wind power and combined with digital control and
wireless communication technologies it can achieve collection of a large amount of
parameters in terms of modern agricultural cultivation, which will meet the needs
of different application scenarios. Results of repeated experiments have shown that
it has such advantages as being green and environmentfriendly, flexible and
reliable.
The advantages of minimum-phase (MP) systems for control applications are well
known. Prior research has shown that a non-MP (NMP) system can be discretized to an
MP system using either a zero-order hold (ZOH) or a square-pulse sample-and-hold
input (SHI). This paper investigates the MP characteristics of the discrete-time
(DT) system obtained by discretizing a continuous-time single-input single-output
NMP system using different SHIs. Two new SHIs (forward and backward triangular) are
studied in addition to the square pulse. Numerical simulations were adopted for
studying the MP property of the resulting DT system as a function of sample-and-
hold parameters. The simulation results show that it is possible to find a smaller
sampling period that results in an MP DT system using the proposed SHIs compared
with the ZOH. The q-Markov cover system identification with pseudorandom binary
signal was then used for a hardware-in-the-loop (HIL) simulation study. A resistor-
capacitor filter was used to represent the implementation error of the SHI due to
unmodeled actuator dynamics. The HIL simulation results show that the proposed SHI
scheme is robust to actuator modeling error. The MP properties of the DT systems
with three SHIs are compared. The results show that the forward triangle SHI has
the best performance due to its robustness to unmodeled actuator dynamics and the
capability of retaining the MP property of the discretized system at small sampling
periods.
This paper presents a cycle efficient software frequency response analyzer (SFRA),
which is integrated into the firmware of the digitally controller power converter
to measure the frequency response of the plant and the open-loop gain of the
closed-loop system. The algorithm uses the readily available measurements taken for
the power stage control and does not require additional hardware. This enables
periodic measurement of the frequency response which can be used to monitor changes
in the power converter. The proposed technique can run on a conventional
microcontroller without any host intervention, and adds no cost to the system,
which is important for the cost-sensitive power converters. Both floating point and
fixed point implementation are compared enabling widespread applicability of the
technique. In order to validate the efficacy of the analyzer, a synchronous buck
power converter is designed and its control transfer function is compared with the
measured online frequency response. An algorithm is outlined to fit the measured
SFRA data to a pole-zero format through intelligent cost function estimation. The
correlation of zeros and poles identified using this method with the modeled plant
transfer function is analyzed. A dual core approach is discussed to run SFRA on a
high-switching-frequency converter, thus showing applicability of the technique in
high-switching-frequency converters.
LCL filters have been widely used for grid-connected inverters. However, the
problem that how time delay affects the stability of digitally controlled grid-
connected inverters with LCL filters has not been fully studied. In this paper, a
systematic study is carried out on the relationship between the time delay and
stability of single-loop controlled grid-connected inverters that employ inverter
current feedback (ICF) or grid current feedback (GCF). The ranges of time delay for
system stability are analyzed and deduced in the continuous s-domain and discrete
z-domain. It is shown that in the optimal range, the existence of time delay
weakens the stability of the ICF loop, whereas a proper time delay is required for
the GCF loop. The present work explains, for the first time, why different
conclusions on the stability of ICF loop and GCF loop have been drawn in previous
studies. To improve system stability, a linear predictor-based time delay reduction
method is proposed for ICF, while a time delay addition method is used for GCF. A
controller design method is then presented that guarantees adequate stability
margins. The delay-dependent stability study is verified by simulation and
experiment.
The "noise" induced by quantization in digitally controlled systems can be modelled
as small amplitude chaotic behaviour described by a simple piecewise linear map,
the micro-chaos map. The chaotic nature of certain micro-chaos maps was proved
rigorously in the last 20 years. It was also pointed out that several disconnected
strange attractors or repellers may coexist far from the desired state of the
system. The control error is influenced by the number of these strange sets and the
local behaviour of trajectories in their neighbourhoods. In the present paper we
focus on the exploration of the possible attractor/repeller structures in the phase
space of a PD-controlled system and estimate the expected control error by several
methods.
Digital stabilization of unstable equilibria of linear systems may lead to small
amplitude stochastic-like oscillations. We show that these vibrations can be
related to a deterministic chaotic dynamics induced by sampling and quantization. A
detailed analytical proof of chaos is presented for the case of a PD controlled
oscillator: it is shown that there exists a finite attracting domain in the phase-
space, the largest Lyapunov exponent is positive and the existence of a Smale
horseshoe is also pointed out. The corresponding two-dimensional micro-chaos map is
a multi-baker map, i.e. it consists of a finite series of baker's maps.
A new, small and efficient voltage regulator, realized using a resonant switched-
capacitor converter technology, is introduced. Voltage regulation is implemented by
means of simple digital pulse density modulation. It displays an ideal transient
response with a zero-order nature to all disturbance types. The newly developed
topology acts as a gyrator with awide range of voltage conversion ratios (below as
well as above unity) with constant efficiency characteristics for the entire
operation range. The operation of the voltage regulator is verified on a 20 W
experimental prototype, demonstrating ideal transient recovery without
over/undershoots in response to load and line transients. Simple design guidelines
for the voltage regulation system are provided and verified by experiments.
In this paper, two discrete-time control schemes are presented for induction motors
(IMs) based on the discrete-time sliding-mode technique. The first controller is
designed using the equivalent control method. The second controller is based on a
discrete-time equivalent of the super-twisting algorithm, in which the sliding-mode
dynamics is robustified by adding an integral action. The non-measurable rotor
fluxes are estimated by two observers. The first observer design is based on a
simple copy of the rotor flux dynamics, whereas the second observer design is based
on the sliding-mode technique. A simulation study was carried out for the
evaluation of the closed-loop performance of the IM at different sampling periods
and to compare results with other discrete-time control techniques. Moreover, the
robust performance of the closed-loop IM is investigated under external and
internal perturbations. The simulation study predicts that the IM, when in closed-
loop with one of the proposed controllers, still performs well at a sampling time
of 1250 mu s, whereas other control strategies start to lose accuracy. Real-time
experiments were finally carried out, where the good performance of the proposed
strategy is verified.
In this paper an adaptive rotor flux observer is developed. This observer performs
a real-time correction of the mutual inductance and rotor resistance of the motor
using data from the DC-link voltage sensor, the inverter state and the phase
current and position sensors. The observer compares the behavior of two independent
observers (sensorless and sensored observers) in order to correct the parameters of
the sensored observer. The adaptation algorithm corrects the mutual inductance,
which can vary due to change of the magnetization current, and the rotor
resistance, which can change due to variation of the rotor temperature. Computer
simulation results are presented to validate the proposed method.
This paper proposes an LED driving circuit with a digital controller, power factor
correct (PFC) function, and low light flicker. The key topology of the proposed
circuit is a conventional Flyback combined with a pre-stage. As a result, there
will be less light flicker than with other one-stage PFC circuits. A digital
controller, implemented using a low-cost microcontroller, dsPIC30F2020, will meet
PFC and low light flicker. The experimental results validate the functionality of
the proposed circuit.
A digital pulse-frequency-modulated controller is designed by discretizing an
analog integral controller for an LLC resonant DC-DC converter using the so called
IA-PIM digital redesign method. It regulates the output voltage by adjusting the
frequency of the input switching, which in turn changes the gain of the LLC
converter. Its performances to sudden changes in the load are evaluated though
extensive simulations. These results show that the digital controller can realize
the performance of an analog controller at a sampling frequency that can be much
lower than those currently prevail, which may be advantageous in terms of reduced
computational requirements and power consumption.
This paper presents a new algorithm for controlling the magnetic induction waveform
in a specific measurement system for the magnetic characterization and modeling of
silicon steel sheets. Experimental results show that, with this new control
algorithm, the measurement system is able to characterize silicon steel sheets
under sinusoidal or nonsinusoidal waveforms in wide frequency and amplitude range.
In order to get a thorough understanding of the total digital silicon micro-
gyroscope, a novel system-level model with details of both the sense and circuit is
presented in this paper. Unlike the traditional structures of the digital part of
the digital gyroscope, a structure with programmable delay units (PDUs) instead of
DPLLs gives a brief and robust character of the whole system. And the PDUs
coordinating with the FIR filter could lead to a removal of the IF filters of the
sigma delta DAC for feedback, which saves a lot of consumption. Two MASH sigma
delta ADCs are designed to convert the output of the charge voltage converters to
digital signals, which also bring a better stability. The ADCs achieve an SNR of
102.5 dB with a 10 kHz bandwidth. The stabilization of the closed drive mode has
also been analyzed including how the noise caused by the quantization of the
digital circuit is affecting the stabilization of both the amplitude and frequency
of the driving signals. In the end, a final result of simulation of the gyroscope
shows the correctness and accuracy of the whole model of the gyroscope.
In boost converters and other indirect energy transfer topologies, the fastest
transient response usually does not coincide with the minimum possible output
voltage deviation. This paper introduces a practical mixed-signal current
programmed mode (CPM) controller that, compared to time-optimal solutions, provides
a smaller deviation, lower current stress, and simpler controller implementation.
To recover from transients, the controller passes through two phases. In the first
phase, the inductor current is set in the proximity of its steady-state value, so
that the initial transient-caused capacitor charging/discharging process is
reversed. In the second phase, the voltage is gradually recovered. The controller
implements a simple algorithm for setting up the inductor current and the output
voltage peak/valley values during transients, based on the output current estimate,
which is obtained through a self-tuning procedure. The operation of the controller
is verified both through simulations and experimentally, with a boost-based 12 to
48 V, 100-W prototype, operating at 100-kHz switching frequency. A comparison with
a time-optimal controller shows that the introduced programmable-deviation system
results in up to 1.9 times smaller voltage deviation while limiting component
stress.
A design of a new hybrid-type digital pulsewidth modulator (DPWM) with a wide
frequency range of 1000 : 1, from 10 kHz to 10 MHz, is presented. The proposed DPWM
has the maximum duty-cycle resolution of 11 bits and consumes the power of 17.5 mu
W at 10 kHz and 2.36 mW at 10 MHz, respectively. The proposed DPWM realizes the
upper 5-bit resolution using a programmable digital counter and the lower 6-bit
resolution using a current-integrating-type phase interpolator, employing an M2M-
ladder current-steering digital-to-analog converter for low power consumption. The
operating clock is generated in on-chip using a relaxation oscillator. The
prototype integrated circuit fabricated in a 0.25-mu m high-voltage complementary
metal-oxide-semiconductor demonstrates that the proposed DPWM maintains a good
linearity across the entire operating range.
The nonideal effects of the comparator and dead time in a synchronous controlled
dc-dc converter adversely affect the stability of a four-switch noninverting-buck-
boost (NIBB) converter. The pulse-skipping phenomenon occurs in the mode-transition
region near the boundary between the step-down and step-up regions, and this
phenomenon leads to an unstable output voltage and an unpredictable output voltage
ripple. However, these two results may damage the entire power system and
application system. This brief proposes an enhanced duty-cycle-overlap control
technique for a digitally controlled NIBB converter. The proposed technique offers
two duty cycle limitations for various conditions in the mode-transition region and
ensures the stability of the digital controller and output voltage. Moreover, this
technique involves combining the duty cycles of both step-down and step-upmodes for
deriving an accurate value of the output voltage. The experimental results derived
from a digital controller implemented through a field-programmable-gate-array-based
platform revealed that the output voltage of the NIBB converter was stable
throughout the transition region. The observed input voltage of the converter,
provided by a Li-ion battery, was 2.5-4.5 V, and the output voltage was typically
3.3 V, which is suitable for communication systems, audio systems, and I/O pad
power supplies. The switching frequency was 1 MHz, and the maximum load current was
500 mA.
In this technical note, we first present an adaptive distributed observer for a
discrete-time leader system. This adaptive distributed observer will provide, to
each follower, not only the estimation of the leader's signal, but also the
estimation of the leader's system matrix. Then, based on the estimation of the
matrix S, we devise a discrete adaptive algorithm to calculate the solution to the
regulator equations associated with each follower, and obtain an estimated
feedforward control gain. Finally, we solve the cooperative output regulation
problem for discrete-time linear multi-agent systems by both state feedback and
output feedback adaptive distributed control laws utilizing the adaptive
distributed observer.
The aim of this paper is to present a superior transient response of a digital peak
current mode dc-dc converter in order to address input voltage fluctuation. In the
dc power feeding system, a quick response is important for not only load
fluctuation but also input voltage fluctuation. Since the proposed peak current
mode control method can detect the peak current in real time, the transient
response can improve compared with the conventional digital voltage mode PID
control. As a result, the convergence time and undershoot of output voltage is
suppressed by more than 50%.
Phase-shift modulation (PSM) is a commonly used technique for controlling the
active power flow in resonant dc-ac and dc-dc converters. Although traditionally
developed as an analog modulation scheme, PSM is being increasingly implemented
digitally in conjunction with advanced multivariable digital controllers and online
efficiency optimization algorithms. While analog PSM is known not to introduce
additional dynamics from a small-signal standpoint, the analysis disclosed in this
study indicates that discrete-time, or uniformly sampled, PSM introduces a
transport delay of small-signal nature. Furthermore, and in close analogy with the
theory of uniformly sampled pulse width modulators, such delay depends on the
modulator carrier type as well as on the converter operating point. This paper
first clarifies the modeling procedure for describing the small-signal dynamics of
uniformly sampled phase-shift modulators. Second, it provides an extension of the
traditional phasor modeling to digital phase-controlled converters, allowing to
account for the additional modulator dynamics in the design of the closed-loop
compensation. Theoretical findings are validated via simulation and experimental
results.
This paper explores the performance of a DC-DC converter based with current mode
controller photovoltaic (PV) simulator which emulates the output characteristics of
a real PV module. A portable PV simulator prototype of 85 W is examined in terms of
its steady state IV curve matching capacity and the convergence time corresponding
to step change in current source load, voltage source load, and insolation levels.
The current voltage (IV) characteristics of the PV module are implemented as a
look-up-table (LUT) which determines the reference output current from measured
output voltage. A Thevenin Equivalent Method approach to PV arrays analysis is also
included in order to model the small-signal linearized characteristics. Extensive
simulation results obtained in MAT LAB are included to show that the PV simulator
can work in most situations as a real PV module. Preliminary experimental results
verify performance with current-source and voltage-source loads
How to control and monitor devices when I'm not at home? It is a question that
until the last century did not have an overwhelming answer from the engineering
field. The technological development of recent years has allowed us to perform this
task by using software and hardware tools: monitoring different devices from our
smart phone comes down to simply downloading an app or entering a website. This
article presents an application that can be example of how to answer the
aforementioned question.
This paper proposes a new approach of Field Programmable Gate Array (FPGA)
controlled digital implementation of shunt active power filter (SAPF) under steady
state and dynamic operations. Typical implementations of SAPF uses microprocessor
and digital signal processor (DSP) but it limited for complex algorithm structure,
absence of feedback loop delays and their cost can be exceed the benefit they
bring. In this paper, the hardware resources of an FPGA are configured and
implemented in order to overcome conventional microcontroller or digital signal
processor implementations. This proposed FPGA digital implementation scheme has
very less execution time and boosts the overall performance of the system. The FPGA
controller integrates the entire control algorithm of an SAPF, including
synchronous reference frame transformation, phase locked loop, low pass filter and
inverter current controller etc. All these required algorithms are implemented with
a single all-on chip FPGA module which provides freedom to reconfigure for any
other applications. The entire algorithm is coded, processed and simulated using
Xilinx 12.1 ISE suite to estimate the advantages of the proposed system. The coded
algorithm is also defused on a single all-on-chip Xilinx Spartan 3A DSP-XC3SD1800
laboratory prototype and experimental results thus obtained match with simulated
counterparts under the dynamic state and steady state operating conditions.
This paper describes the implementation of a second order sliding mode (SOSM)
controller for a practical point-of-load (POL) power supply with realistic values
of output capacitor equivalent series resistance (ESR) and equivalent series
inductance (ESL). The SOSM control presented in this paper results in fast
transient responses, has a current limiting feature, supports light load operation,
and achieves constant frequency steady state operation. Experimental results are
given for a 2.5 V - 5.5 V input, 0.6 V - 1.5 V output, 3 A prototype.
A new generator control unit (GCU) must be designed to work in a wide frequency
range in order to obtain better control performance in variable frequency AC power
system. Control algorithms make improvements in terms of determining the control
parameters and analyze the influence of the controller parameters on system
stability, and compensate for the loss of signals generated in the conditioning
process. This paper compares the pros and cons of different RMS algorithms and
determine the final RMS calculation scheme. Test results show a considerable
performance improvement for the proposed design in dynamic performance and
adjustment precision.
This paper discusses a discrete-time loop shaping algorithm for servo enhancement
at multiple wide frequency bands. Such design considerations are motivated by a
large class of practical control problems such as vibration rejection, active noise
control, and periodical reference tracking; as well as recent novel challenges that
demand new design in the servo technologies. A pseudo Youla-Kucera parameterization
scheme is proposed using the inverse system model to bring enhanced control at
selected local frequency regions. Design methodologies are created to control the
waterbed amplifications that come from the fundamental limitations of feedback
control. Finally, simulation and experimental verification are conducted in
precision control and semiconductor manufacturing. (C) 2015 Elsevier Ltd. All
rights reserved.
This paper presents the design and implementation of a digital control system for
modular multilevel converters, based on digital signal processors. To achieve
higher system control reliability and multi-functionality, the proposed
architecture has been built with an effective split of the control tasks involved
between a master controller and six slave controllers, one for each of the six arms
of the converter. The master controller handles energy flow within the converter
and user communication using Ethernet and universal serial bus. Each slave
controller handles capacitors voltages balancing within the arm. Intercommunication
between the different boards is achieved mainly through optical fiber and inter
integrated circuit bus. Experiments have been carried out to verify the
effectiveness of this architecture.
Digital micro-controllers/processors enable the costeffective control of grid-
connected power converter systems in terms of system monitoring, signal processing
(e.g., grid synchronization), control (e.g., grid current and voltage control),
etc. Normally, the control is implemented in a micro-controller/processor with a
fixed sampling rate considering the cost and complexity, where the number of unit
delays that have been adopted should be an integer. For instance, in conventional
digital control systems, a single-phase T/4 Delay Phase-Locked Loop (PLL) system
takes 50 unit delays (i.e., in a 50-Hz system with a sampling frequency of 10-kHz)
to create a 90 degrees-lagging voltage in order to achieve the grid synchronization
with the orthogonal voltage system. However, in practice, the grid frequency is a
time-variant parameter due to various eventualities, and thus rounding the number
of the unit delays for the T/4 Delay PLL system should be done in its
implementation. This process will result in performance degradation in the digital
control system, as the exactly required number of delays is not realized. Hence, in
this paper, a Virtual Unit Delay (VUD) has been proposed to address such challenges
to the digital T/4 Delay PLL system. The proposed VUD adopts linear interpolation
polynomial to approximate the fractional delay induced by the varying grid
frequency in such a way that the control performance is enhanced. The proposed VUD
has been demonstrated on a digitally controlled T/4 Delay PLL system. Experimental
results have confirmed the effectiveness of the proposal.
Our planet is gradually moving towards an urbanized world. Modern urban
agglomerations tend to turn nowadays into advanced information hubs supporting a
smart management of dynamic urban systems. The currently popular notion of 'smart
cities' aims to provide a new perspective for sustainable and high-performance
strategies of city stakeholders in our 'urban century'. In this context, digital
information technology provides a new tool for efficient and effective management
and planning of urban space, inter alia in the field of transportation,
environment, public facilities or advanced service provision to citizens. This
paper aims to offer, first, a concise overview of the emerging opportunities of
information and communication technology (ICT) for smart urban policy; digital
technology in particular, appears to provide novel pathways for modern planning
strategies in smart cities. Against this background, the paper sketches out the
complex force field of global urbanisation phenomena and highlights the data and
information needs for strategic planning of cities (using inter alia as a framework
the so-called 'urban piazza' strategy framework). Secondly, various new decision
support tools that are currently emerging and that offer a new promising scope for
handling complex urban management issues (for instance, on accessibility,
congestion, safety or sustainability) are briefly presented. And finally, the
potential of such digital data systems for urban management and policy is concisely
illustrated by means of some recent applications in the area of smartphone data
systems. The paper concludes with a discussion of the challenges ahead for urban
policy, inter alia by paying attention to institutional and governance aspects of
'big digital data' management in urban systems. (C) 2016 Elsevier Ltd. All rights
reserved.
Various versions of a typical control panels are experimentally analyzed both from
the effectiveness and efficiency point of view. The stimuli differed in objects'
locations within a panel, and the type of the expected response to the presented
stimuli. The results of users' performance are investigated using classical
analyses of variance. Moreover, visual activity of all examined persons gathered by
means of eye tracking system were presented and formally analyzed.
Quantitative PCR(qPCR) is an important tool in pathogen detection. However, the use
of different qPCR components, calibration materials and DNA extraction methods
reduces comparability between laboratories, which can result in false diagnosis and
discrepancies in patient care. The wider establishment of a metrological framework
for nucleic acid tests could improve the degree of standardisation of pathogen
detection and the quantification methods applied in the clinical context. To
achieve this, accurate methods need to be developed and implemented as reference
measurement procedures, and to facilitate characterisation of suitable certified
reference materials. Digital PCR(dPCR) has already been used for pathogen
quantification by analysing nucleic acids. Although dPCR has the potential to
provide robust and accurate quantification of nucleic acids, further assessment of
its actual performance characteristics is needed before it can be implemented in a
metrological framework, and to allow adequate estimation of measurement
uncertainties. Here, four laboratories demonstrated reproducibility(expanded
measurement uncertainties below 15%) of dPCR for quantification of DNA from human
cytomegalovirus, with no calibration to a common reference material. Using whole-
virus material and extracted DNA, an intermediate precision(coefficients of
variation below 25%) between three consecutive experiments was noted. Furthermore,
discrepancies in estimated mean DNA copy number concentrations between laboratories
were less than twofold, with DNA extraction as the main source of variability.
These data demonstrate that dPCR offers a repeatable and reproducible method for
quantification of viral DNA, and due to its satisfactory performance should be
considered as candidate for reference methods for implementation in a metrological
framework.
Digital PCR (dPCR) is a powerful method for the absolute quantification and rare
mutation detection of nucleic acids. However, the available dPCR platforms require
either expensive instruments or complicated operation, which limit their extensive
application. This paper describes a robust self-partition chip to perform dPCR in a
very simple and inexpensive format. The chip is constructed by sandwiching a
micromolded surfactant-doped PDMS layer between two glass slides, containing 10,000
reaction compartments (0.785 nL each). The two simple strategies, "glass-PDMS-
glass" sandwich configuration and surfactant-doped surface modification, are used
to enhance PCR compatibility and enable efficient amplification in the chip by
minimizing water loss and nonspecific adsorption of protein. Furthermore, powered
by pre-degassing of its PDMS substrate and an attached PDMS slab, the chip
autonomously loads and partitions sample into a high-density array of microwells
for performing dPCR analysis. We evaluated the quantitative capabilities of the
dPCR chip by measuring a ten-fold serial dilution of genomic DNA from lung cancer
cell line H1975. Finally, we also demonstrate its feasibility in the accurate
measurement of small copy number variations, which exhibited better accuracy than
real-time quantitative PCR (qPCR). Such simple and low-cost platform promises to
accelerate the widespread use of dPCR. (C) 2017 Elsevier B.V. All rights reserved.
A wide-swing optical modulator driver is implemented in 0.13-mu m SiGe-BiCMOS using
a three-stage distributed amplifier with a digital input line. Measurements
demonstrate 6-Vp-p differential output, symmetric 6-ps (min) rise/fall times, 333-
fs (rms) additive jitter, and better than 20-dB output return loss (S-11) below 58
GHz. Full output swing with adjustable (6-12 ps) rise/fall times is realized after
a three-step calibration sequence facilitated by an on-chip energy detector and
digital control. The circuit supports 28-48-Gb/s external data sources, or 2(11) -1
PRBS and 1-0 internal data generators for calibration and characterization
respectively. The 3-mm(2) driver IC (1.8-mm(2) active area) consumes 1.92 W from +
5/-2.5-V supplies.
Proportional Integral Differentiator (PID) is widely used in industrial control
applications; Digital PID is complicated and consists of many stages. This paper
introduces the design of an analog PID controller by using single active element
and implemented in 0.18 mu m CMOS technology. PID is tested by using three
structures: Two stage Operational Amplifier with common source buffer stage; Folded
cascade Operational Transconductance Amplifier and with a second generation Current
Conveyer CCII+. The results taken from the three methods are compared by using both
the frequency response and the transient response parameters.
A novel digital envelope modulator for envelope tracking radio frequency power
amplifier is presented in this paper. The proposed modulator consists of a parallel
combination of linear class AB and switching class D power amplifiers that are
controlled digitally. In the previous analog architectures, the requirements needed
for the AB operational amplifier such as high-current driving capability, high
bandwidth and large output swing is usually obtainable at high overall static power
dissipation. The digitally controlled power opamp presented here not only provides
the aforementioned requirements but also reduces power dissipation compared with
previous work. Furthermore, the digital control of the modulator makes it adaptive
to the input signal variations in comparison with conventional analog parallel
hybrid envelope modulators. The digital processor of the modulator is evaluated
with a 45-nm complementary metal oxide semiconductor technology. The overall power
consumption of the digital processor is around 142mW at 1.5-GHz clock frequency. As
an application, the designed digital class AB is incorporated in a complete
envelope modulator architecture. The overall efficiency of the modulator, including
the digital processor power consumption, is around 82% at an average 32dBm output
power for a 5-MHz input signal. Copyright (c) 2015 John Wiley & Sons, Ltd.
With the development of science and technology and the formation of a comprehensive
multidisciplinary technology. The emergence of new permanent magnetic actuator and
electronic operation of synchronous technology in the field of pressure to achieve
a hardware basis. In order to meet the high reliability of the vacuum circuit
breaker operation, our country is in-depth study, and gradually promote and
electronic control systems match the permanent mechanism. In this article, we have
the key technology of digital signal processing theory research motor and motor
control. Experimental results show the effectiveness of the method, to better
reflect the characteristics of the digital control system for digitizing motion
brushless DC motor control engineering applications useful to explore and try.
This paper presents a novel control circuit that eliminates signal overshoot
inherent to digital step attenuators (DSA) during state transitions. With the
addition of digital delay elements, transitions from attenuation state to insertion
loss state is delayed with respect to the transition from the insertion loss state
to the attenuation state. This prevents unintended signal leakage to the output,
eliminating possible signal overshoot. Since this novel technique achieves signal
overshoot suppression with a simple addition to the digital control circuit, it is
area efficient, and can be applied to any digital attenuator without degrading its
RF performance. To present its effectiveness, the proposed technique is employed in
a 6-bit DSA. The resulting reduced-overshoot DSA is manufactured in a commercial
0.18 mu m Silicon-On-Insulator (SOI) process. Measurement results show that this
technique successfully suppresses the signal overshoot to less than 0.2 dB.
With the development of power electronic technology, the control technology of
power electronic device is becoming more and more complicated. The switching power
supply is a indispensable component in modern power electronic equipment. Its
quality and size have a direct impact on the whole performance of electronic
equipment. Digital control technology and the applications of FPGA have become a
new research hotspot in the field of power electronics. Digital control can reduce
the aging of the device and the impact of temperature drift on the accuracy of the
convenient. This paper studies the digital switching power supply based on FPGA and
points out the system structure of the system.
A novel integrated fault diagnosis method of 8 bit Digital to Analog Converter
(DAC) circuit is presented in our paper. The circuit is based on the one presented
in the IEEE 1997 International Test Conference (ITC'97). The gain waveforms of
faulty and faults free (Golden) circuits as well as internal node voltages of two
stage CMOS Operational Amplifier is used to detect the faults. An assembled fault
detection procedure is introduced along with its localization and percentage of
detectable faults estimation using HSPICE and MATLAB. This type of test is defined
minutely accurate and effectiveness of it in detecting faulty circuit is evaluated.
For any wine estate, there is a need to demarcate homogeneous within-vineyard zones
('terroirs') so as to manage grape production, which depends on vine biological
condition. Until now, the studies performing digital zoning of terroirs have relied
on recent spatial data and scant attention has been paid to ancient geoinformation
likely to retrace past biological condition of vines and especially occurrence of
vine mortality. Is vine mortality characterized by recurrent and specific patterns
and if so, are these patterns related to terroir units and/or past landuse? This
study aimed at performing a historical and spatial tracing of vine mortality
patterns using a long time-series of aerial survey images (1947-2010), in
combination with recent data: soil apparent electrical conductivity EM38
measurements, very high resolution Pleiades satellite images, and a detailed field
survey. Within a 6 ha-estate in the Southern Rhone Valley, landuse and planting
history were retraced and the map of missing vines frequency was constructed from
the whole time series including a 2015-Pleiades panchromatic band. Within-field
terroir units were obtained from a support vector machine classifier computed on
the spectral bands and NDVI of Pleiades images, EM38 data and morphometric data.
Repeated spatial patterns of missing vines were highlighted throughout several
plantings, uprootings, and vine replacements, and appeared to match some within-
field terroir units, being explained by their specific soil characteristics,
vine/soil management choices and the past landuse of the 1940s. Missing vines
frequency was spatially correlated with topsoil CaCO3 content, and negatively
correlated with topsoil iron, clay, total N, organic C contents and NDVI. A
retrospective spatio-temporal assessment of terroir therefore brings a renewed
focus on some key parameters for maintaining a sustainable grape production. (C)
2017 The Author(s). Published by Elsevier B.V. This is an open access article under
the CC BY license.
This paper presents an innovative variable regulated high voltage power supply
(VRHVPS). It has an output voltage ranging from 0V to 500V, for a maximum current
of 0.25A. It consists of a switched mode power supply (SMPS) followed by a linear
regulator with a power supply rejection ratio (PSSR) of 58dB. The digital control
module consists of an 8bit microcontroller, a small digital display, an isolated
inter-integrated-circuit ((IC)-C-2) interface with an isolated hall sensor as a
current sensor and 12-bit analog to digital converters (ADC) to read the output
voltage and current, also a 12bit digital to analog converter (DAC) which controls
the linear regulator's output voltage.
Theorists of post capitalism have recently argued for a more or less inevitable end
to capitalism. They assume that private accumulation is systematically blocked by
the inability of capitalist corporations to create revenues by setting prices as
they lose control over the reproduction of their commodities and that in this
process, capitalist labour will eventually disappear. Drawing on a case study of
Amazon and thoughts on the policies of other leading digital corporations, we
challenge these assumptions. Key corporate players of digitization are trying to
become powerful monopolies and have partly succeeded in doing so, using the network
effects and scaling opportunities of digital goods and building socio-technical
ecosystems. These strategies have led to the development of in part isomorphic
structures, hence creating a situation of oligopolistic market competition. We draw
on basic assumptions of monopoly capital theory to argue that in this situation
labour process rationalization becomes key to the corporation's competitive
strategies. We see the expansion of digital control and the organizational
structures applied by key corporate players of the digital economy as evidence for
the expansion of capitalist labour, not its reduction.
Digitally controlled oscillators are the main cores in all-digital phase-locked
loops (ADPLL), which are important for determining the range of frequency and power
consumption in ADPLLs. In the conventional digitally controlled oscillator (DCO)
designs, one single band of operation is assigned to the DCO. The following paper
presents a new approach in the design of DCOs, which works in dual-band and wide-
band modes with a control unit. In dual-band mode, the DCO works in two different
ranges of frequencies simultaneously via digital control bits. The wide-band DCO
(WBDCO) works in one wider range of frequencies consecutively. It seems that in the
wide-band DCO, the gap width for the dual-band DCO (DBDCO) is zero. The previously
mentioned designs allow the designer to have standard frequencies with the help of
direct or multiplied frequencies. So, we can have a trade-off between power and
performance. This means that we can have low power consumption in low-frequency
applications and vice versa. The proposed designs are based on using digitally
controlled capacitors, current starving gates and Schmitt triggers in critical
points of the DCO loop, while preserving coarse and fine tunings. The non-delay
linearity factors are clearly investigated and resolved with the use of a new
combined control unit. The simulations of the proposed designs are performed in
Hspice with a voltage of v in 180 nm CMOS technology for 64- and 128-bit input
coarse codes. Our simulation and evaluation results showed that in the dual-band
DCO, a 14.8 ps jitter was calculated at 134 MHz with 1.2131 mW power consumption,
while in the wide band with overlap mode, a 68.7 ps jitter was measured at 184.61
MHz with 1.604 mW power consumption. Our designs are proper for reconfigurable and
multi-standard ADPLL designs.
Background: Dignity therapy is psychotherapy to relieve psychological and
existential distress in patients at the end of life. Little is known about its
effect. Aim: To analyse the outcomes of dignity therapy in patients with advanced
life-threatening diseases. Design: Systematic review was conducted. Three authors
extracted data of the articles and evaluated quality using Critical Appraisal
Skills Programme. Data were synthesized, considering study objectives. Data
sources: PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were
2002 (year of dignity therapy development) to January 2016. Dignity therapy' was
used as search term. Studies with patients with advanced life-threatening diseases
were included. Results: Of 121 studies, 28 were included. Quality of studies is
high. Results were grouped into effectiveness, satisfaction, suitability and
feasibility, and adaptability to different diseases and cultures. Two of five
randomized control trials applied dignity therapy to patients with high levels of
baseline psychological distress. One showed statistically significant decrease on
patients' anxiety and depression scores over time. The other showed statistical
decrease on anxiety scores pre-post dignity therapy, not on depression.
Nonrandomized studies suggested statistically significant improvements in
existential and psychosocial measurements. Patients, relatives and professionals
perceived it improved end-of-life experience. Conclusion: Evidence suggests that
dignity therapy is beneficial. One randomized controlled trial with patients with
high levels of psychological distress shows DT efficacy in anxiety and depression
scores. Other design studies report beneficial outcomes in terms of end-of-life
experience. Further research should understand how dignity therapy functions to
establish a means for measuring its impact and assessing whether high level of
distress patients can benefit most from this therapy.
Background. After long-term treatment with continuous ambulatory peritoneal
dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal
mesothelial cells (PMCs) participate in the inflammatory reactions in the
peritoneal cavity, and transforming growth factor-beta 1 (TGF-beta 1) and
interleukin-1 beta (IL-1 beta) are involved in peritoneal fibrosis. Diltiazem is
used frequently in patients with CAPD to treat hypertension. The objectives of this
study were to examine the effects of diltiazem on collagen- and IL-1 beta-induced
TGF-beta 1 production on human PMCs and the signalling pathway of diltiazem in this
induction. Methods. Human PMCs were cultured from the enzymatic disaggregation of
human omentum. Collagen synthesis was measured by [H-3]proline incorporation into
pepsin-resistant, salt-precipitated collagen. The expression of collagen I and III,
and TGF-beta 1 mRNA was evaluated by northern blotting. The production of TGF-beta
1 by human PMCs was measured by immunoassay. The changes of intracellular calcium
level after adding Fura-2-AM were measured by fluorescence spectrophotometry.
Western blotting was used to assess mitogen-activated protein kinase (MAPK)
signalling proteins. Results. We found that diltiazem (< 0.2 mM) inhibited collagen
I and III mRNA expression and collagen syntheses on a dose-dependent basis.
Diltiazem (0.2 mM) suppressed IL-1 beta- (5 ng/ml) induced TGF-beta 1 production on
human PMCs at both the protein and mRNA levels. Diltiazem (0.2 mM) also inhibited
IL-1 beta- (5 ng/ml) induced collagen I and III mRNA expression. Intracellular
calcium levels did not change after the treatment with diltiazem, IL-1 beta or
both. The IL-1 beta-treated human PMCs increased phospho-JNK (stress-activated c-
Jun N-terminal kinase) and phospho-p38 MAPK expression, while diltiazem could
suppress this phenomenon. Conclusions. Diltiazem suppressed collagen synthesis of
human PMCs and inhibited IL-1 beta-induced TGF-beta 1 production on human PMCs.
This signalling transduction may be through p38 MAPK and JNK pathways instead of
intracellular calcium. These results suggest diltiazem to be a potential
therapeutic regimen in preventing peritoneal fibrosis and support further in vivo
studies.
Recently, graph-based dimensionality reduction methods have attracted much
attention due to their widely applications in many practical tasks such as image
classification and data clustering. However, an inappropriate graph which cannot
accurately reflect the underlying structure and distribution of input data will
dramatically deteriorate the performances of these methods. In this paper, we
propose a novel algorithm termed Locality Constrained Graph Optimization
Dimensionality Reduction (LC-GODR) to address the limitations of existing graph-
based dimensionality reduction methods. Firstly, unlike most graph-based
dimensionality reduction methods in which the graphs are constructed in advance and
kept unchanged during dimensionality reduction, our LC-GODR combines the graph
optimization and projection matrix learning into a joint framework. Therefore, the
graph in the proposed algorithm can be adaptively updated during the procedure of
dimensionality reduction. Secondly, through introducing the locality constraints
into our LC-GODR, the local information of high-dimensional input data can be
discovered and well preserved, which makes the proposed algorithm distinct from
other graph optimization based dimensionality reduction methods. Moreover, an
effective updating scheme is also provided to solve the proposed LC-GODR. Extensive
experiments on two UCI and five image databases are conducted to demonstrate the
effectiveness of our algorithm. The experimental results indicate that the proposed
LC-GODR outperforms other related methods. (C) 2017 Elsevier B.V. All rights
reserved.
Dimethyl sulfoxide (DMSO) is an anti-inflammatory, antibacterial, analgesic drug
widely used to treat several diseases as reported in the literature. It has a
detractive effect on collagen deposition in the abnormal tissue. This study aimed
to investigate the possible therapeutic effects of DMSO on hypertrophic scar
formation in rabbits. Twenty-four New Zealand male albino rabbits were randomly
divided into four groups: control, sham, DMSO, and TRA (triamcinolone acetonide).
Except the control group, punch biopsy defects were created on each animal's right
ear. Following the hypertrophic scar formation on day 28, intralesional DMSO and
triamcinolone acetonide were administered once a week for 4 weeks into these scars
of the DMSO and TRA groups, respectively. No therapeutic agent was administered to
the control and sham groups. One week after the last injection, ear samples were
collected for histopathological, immunohistochemical, and real-time polymerase
chain reaction gene expression analyses. Histopathological examination revealed
that the epithelium in the DMSO group was thicker than that in the control and TRA
groups, but thinner than that in the sham group. Connective tissue thickness and
vascularity level of the sham group were higher than those of the control, DMSO,
and TRA groups. The collagen type I immunoreactivity level of the sham and TRA
groups was higher than those of the control and DMSO groups. The collagen type III
immunoreactivity level was higher in the sham group than in all other groups.
Collagen type I/type III immunoreactivity ratios were lower in the DMSO group. The
alignment of collagen fibers was normal in the DMSO group, but was irregular in the
sham and TRA groups. The collagen type I gene expression levels of the DMSO and TRA
groups were lower than that of the sham group. Collagen type III and IFN-gamma mRNA
expression levels were almost similar among the groups. TGF-1 beta mRNA expression
levels were higher in the DMSO and TRA groups than in the control and sham groups.
On the basis of the results, it can be concluded that intralesional administration
of DMSO decreases hypertrophic scar formation easily and safely. (C) 2017 British
Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by
Elsevier Ltd. All rights reserved.
Differential gene expression profile was studied in Dimocarpus longan Lour. in
response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH
5.6) using differential display reverse transcription polymerase chain reaction
(DDRT-PCR). Results showed that mRNA differential display conditions were optimized
to find an expressed sequence tag (EST) related with acid rain stress. The
potential encoding products had 80% similarity with a transcription initiation
factor IIF of Gossypium raimondii and 81% similarity with a protein product of
Theobroma cacao. This fragment is the transcription factor activated by second
messenger substances in longan leaves after signal perception of acid rain.
Fresh fruit of longan (Dimocarpus longan Lour.) are susceptible to pericarp
browning and aril breakdown. Aril breakdown in longan fruit is regarded as one of
the most important factors reducing quality and shortening storage life of the
fruit. To better understand the molecular mechanism of aril breakdown, the
expression patterns of three expansin (EXP) and three xyloglucan
endotransglucosylase (XET) genes in relation to the aril breakdown of longan fruit
stored at room temperature (25 degrees C) or low temperature (4 degrees C) were
investigated. The results showed that aril breakdown index increased progressively
during storage at 25 and at 4 degrees C. Northern blotting analysis revealed that
the accumulations of three EXP and three XET genes exhibited differential
characteristics with the occurrence of aril breakdown. During storage at 25 degrees
C, the accumulations of Dl-XET3 increased after 1 day, suggesting that Dl-XET3
correlated well with the early aril breakdown, while Dl-EXP3 together with Dl-XET1
and Dl-XET2 was involved in later aril breakdown. However, expression of Dl-XET1
and Dl-XET2 could be mainly involved in aril breakdown of longan fruit stored at 4
degrees C. In addition, Dl-EXP2, whose accumulation increased sharply when longan
fruit were transferred from low temperature to room temperature within 12 hours,
was related to the aril breakdown in this storage period. These data indicated that
Dl-EXPs and Dl-XETs were closely related to aril breakdown in longan fruit.
A biofilm-forming strain of Pichia fermentans was found to be a very strong
antagonist against brown rot and grey mold in artificially wounded apple fruit when
co-inoculated with either Monilinia fructicola or Botrytis cinerea, respectively.
The same strain of yeast, however, was an aggressive pathogen when inoculated on
peach fruit, causing rot of fruit tissues, even in the absence of other pathogens.
Optical and scanning electron microscopy showed that P. fermentans produces only
yeast-like shaped cells during colonization of apple tissue, while exhibiting
pseudohyphal growth on peach tissue. A rapid subtractive hybridization approach
(RaSH) was used to identify differentially expressed genes in the pathogenic form
of P. fermentans by comparing the cDNA of P. fermentans sampled after 24 hours
growth on apple with the cDNA of the same strain grown 24 hours on peach fruit. A
total of 450 clones were analysed by a reverse Northern Blotting technique,
yielding some fragments which were significantly expressed on peach but less on
apple tissue. These sequences were compared to the available genome sequences of
another dimorphic yeast, Candida albicans, and homologous genes were identified.
The relationship between these genes, dimorphism, and pathogenicity will be
discussed.
During the domestication of canids, humans have selected for particular traits and
selected against others. Wild canids and phylogenetically primitive breeds might
then be expected to show less 'desirable' traits than more recently derived
European breeds of dog. In order to examine this, we divided domestic dog breeds
according to their apparent genetic relatedness to the wolf, and compared them to a
wild canid, the dingo, using a validated behavioural assessment tool (C-BARQ). Our
sample included 49 dingoes, 6935 modern dogs, and 673 ancient dogs. Overall, a
number of differences were discovered between the breed groups, after accounting
for demographic effects and variability between breeds. Dingoes were significantly
less trainable than both ancient and modern dogs, and displayed greater stranger-
directed fear and non-social fear than modern dogs. Dingoes were also more prone to
escaping/roaming and urinating against objects than modern dogs, and tended to
exhibit compulsive 'staring' and rolling in animal droppings more than both ancient
and modern dogs. Using a multivariate test, we found that dingoes represented a
significant outlier from the range of typical between-breed variation of
domesticated dogs. Taken together, these results provide some evidence that (1)
selective processes during domestication are reflected in the behaviour of dog
breeds, and (2) primitive breed behaviour tends to reflect earlier and different
selection pressures (natural rather that artificial selection). (C) 2016 Elsevier
B.V. All rights reserved.
Karenia brevis is the Florida red tide dinoflagellate responsible for detrimental
effects on human and environmental health through the production of brevetoxins.
Brevetoxins are thought to be synthesized by a polyketide synthase ( PKS) complex,
but the gene cluster for this PKS has yet to be identified. Here, eight PKS
transcripts were identified in K. brevis by high throughput cDNA library screening.
Full length sequences were obtained through 30 and 50 RACE, which demonstrated the
presence of polyadenylation, 30-UTRs, and an identical dinoflagellate-specific
spliced leader sequence at the 50 end of PKS transcripts. Six transcripts encoded
for individual ketosynthase (KS) domains, one ketoreductase (KR), and one
transcript encoded both acyl carrier protein (ACP) and KS domains. Transcript
lengths ranged from 1875 to 3397 nucleotides, based on sequence analysis, and were
confirmed by northern blotting. Baysian phylogenetic analysis of the K. brevis KS
domains placed them well within the protist type I PKS clade. Thus although most
similar to type I modular PKSs, the presence of individual catalytic domains on
separate transcripts suggests a protein structure more similar to type II PKSs, in
which each catalytic domain resides on an individual protein. These results
identify an unprecedented PKS structure in a toxic dinoflagellate. Published by
Elsevier GmbH.
Dinoflagellates are key species in marine environments, but they remain poorly
understood in part because of their large, complex genomes, unique molecular
biology, and unresolved in-group relationships. We created a taxonomically
representative dataset of dinoflagellate transcriptomes and used this to infer a
strongly supported phylogeny to map major morphological and molecular transitions
in dinoflagellate evolution. Our results show an early-branching position of
Noctiluca, monophyly of thecate (plate-bearing) dinoflagellates, and paraphyly of
athecate ones. This represents unambiguous phylogenetic evidence for a single
origin of the group's cellulosic theca, which we show coincided with a radiation of
cellulases implicated in cell division. By integrating dinoflagellate molecular,
fossil, and biogeochemical evidence, we propose a revised model for the evolution
of thecal tabulations and suggest that the late acquisition of dinosterol in the
group is inconsistent with dinoflagellates being the source of this biomarker in
pre-Mesozoic strata. Three distantly related, fundamentally nonphotosynthetic
dinoflagellates, Noctiluca, Oxyrrhis, and Dinophysis, contain cryptic plastidial
metabolisms and lack alternative cytosolic pathways, suggesting that all free-
living dinoflagellates are metabolically dependent on plastids. This finding led us
to propose general mechanisms of dependency on plastid organelles in eukaryotes
that have lost photosynthesis; it also suggests that the evolutionary origin of
bioluminescence in nonphotosynthetic dinoflagellates may be linked to plastidic
tetrapyrrole biosynthesis. Finally, we use our phylogenetic framework to show that
dinoflagellate nuclei have recruited DNA-binding proteins in three distinct
evolutionary waves, which included two independent acquisitions of bacterial
histone-like proteins.
Two Keggin-type polyoxometalates (POMs) containing glycine, (HGly)(3)PW12O40 and
(HGly)(4)SiW12O40, were synthesized and evaluated as mushroom tyrosinase
inhibitors. The spectrophotometric method results showed that both (HGly)(3)PW12O40
and (HGly)(4)SiW12O40 could strongly inhibit the diphenolase activity of the
tyrosinase and that their inhibition mechanisms were reversible. Their half-
inhibition concentration values were estimated to be 1.55 and 1.39mmol/L,
respectively. The inhibition kinetics analysis by Lineweaver-Burk plots indicated
that (HGly)(3)PW12O40 was an uncompetitive inhibitor with K-IS=0.046mmol/L, whereas
(HGly)(4)SiW12O40 was a noncompetitive inhibitor with K-I=K-IS=2.17mmol/L. This
study may help to extend the application of POMs in the fields of medicine and food
preservation. (C) 2015 International Union of Biochemistry and Molecular Biology,
Inc.
Both cDNA and a genomic DNA fragment encoding a new potato proteinase inhibitor II
were isolated from a diploid potato IVP101 (Solanum phurejia L.) and named PINII-
2x. Nucleotide sequencing confirmed that the DNA fragment of PINII-2xwas 580 bp,
including a 115-bp intron and two exons. The deduced PINII-2x protein contained an
intact signal peptide and two active sites. The PINII-2x gene and its deduced
PINII-2x protein had 88% and 93% homology with another tetraploid potato proteinase
inhibitor II, respectively. Northern blotting analysis indicated that the mRNA of
PINII-2x gene was wound induced in potato leaves. Binary vector pNAR301 and pNAR302
were constructed for rice transformation, in which the PINII-2x cDNA was driven,
respectively, by rice actin I promoter (ActI) and maize ubiquitin promoter (UbiI).
Via an Agrobacterium-mediated method, these two constructs were transferred into
japonica rice cv. Xiushui 63. PCR and Southern blotting analysis for transgenic
rice revealed the integration of the PINII-2x gene. Northern blotting analysis also
confirmed transcripts of the PINII-2x gene in transgenic rice plants. Insect
bioassays using stripe stem borer (Chilo suppressalis Walker) demonstrated that the
average weight and body length of larvae in transgenic plants were only nearly 50%
and 61% of those of larvae in control plants, respectively. These results indicate
that the PINII-2x gene should be an effective insect-resistance gene and could be
valuable for application in crop breeding for insect resistance.
While much research focuses on the causes and consequences of direct democracy and
regime legitimacy, little attention has been paid to the potential relationship
between them. In an attempt to fill this void, this paper focuses on the legal
provisions for direct democracy and its use. The key argument is that possibilities
for the public's direct involvement reflect high importance given to citizens,
openness of the regime towards different modes of decision-making, and ways to
avoid unpopular institutions. Consequently, citizens are likely to accept and
support the regime, improving or maintaining its legitimacy. The cross-national
analysis includes 38 European countries ranging from transition countries to
established democracies. It uses bivariate statistical analysis and country-level
data collected from legislation, secondary sources, and aggregate surveys.
Direct gaze is a salient social cue that affords rapid detection. A body of
research suggests that direct gaze enhances performance on memory tasks (e.g.,
Hood, Macrae, Cole-Davies, & Dias, Developmental Science, 1, 67-71, 2003).
Nonetheless, other studies highlight the disruptive effect direct gaze has on
concurrent cognitive processes (e.g., Conty, Gimmig, Belletier, George, & Huguet,
Cognition, 115(1), 133-139, 2010). This discrepancy raises questions about the
effects direct gaze may have on concurrent memory tasks. We addressed this topic by
employing a change detection paradigm, where participants retained information
about the color of small sets of agents. Experiment 1 revealed that, despite the
irrelevance of the agents' eye gaze to the memory task at hand, participants were
worse at detecting changes when the agents looked directly at them compared to when
the agents looked away. Experiment 2 showed that the disruptive effect was
relatively short-lived. Prolonged presentation of direct gaze led to recovery from
the initial disruption, rather than a sustained disruption on change detection
performance. The present study provides the first evidence that direct gaze impairs
visual working memory with a rapidly-developing yet short-lived effect even when
there is no need to attend to agents' gaze.
Natural Gas Direct Injection (NGDI) engines have attracted attention of engine
manufacturers because of low pollutant emissions and high efficiency. The jet
structure and injector properties are control parameters for optimal mixture
formation and stable combustion. Here, the jet characteristics are investigated
experimentally. The natural gas jet, injected through a multi-hole injector, is
visualized using Schlieren photography. The effects of injection and chamber
pressures on macroscopic jet characteristics are examined. New correlations for tip
speed and tip penetration are presented. Results show that reducing chamber
pressure is more effective than injection pressure for increasing the jet axial
penetration. Moreover, the linear relation between non-dimensional tip penetration
and time is dependent on the chamber-toinjected gas density ratio. (C) 2017
Elsevier Ltd. All rights reserved.
The debate about direct perception encompasses different topics, one of which
concerns the richness of the contents of perceptual experiences. Can we directly
perceive only low-level properties, like edges, colors etc. (the sparse-content
view), or can we perceive high-level properties and entities as well (the liberal-
content view)? The aim of the paper is to defend the claim that the content of our
perceptual experience can include emotions and also person impressions. Using these
examples, an argument is developed to defend a liberal-content view for core
examples of social cognition. This view is developed and contrasted with accounts
which claim that in the case of registering another person's emotion while seeing
them, we have to describe the relevant content not as the content of a perceptual
experience, but of a perceptual belief. The paper defends the view that perceptual
experiences can have a rich content yet remain separable from beliefs formed on the
basis of the experience. How liberal and enriched the content of a perceptual
experience is will depend upon the expertise a person has developed in the field.
This is supported by the argument that perceptual experiences can be systematically
enriched by perceiving affordances of objects, by pattern recognition or by top-
down processes, as analyzed by processes of cognitive penetration or predictive
coding.
Models of reciprocity imply that cheater detection is an important prerequisite for
successful social exchange. Considering the fundamental role of memory in
reciprocal exchange, these theories lead to the prediction that memory for cheaters
should be preferentially enhanced. Here, we examine whether information of a
partner's previous behaviour in an interaction is automatically retrieved when
encountering the face of a partner who previously cheated or cooperated. In two
studies, participants played a sequential prisoner's dilemma game with cheaters and
cooperative partners. Alternating with the game blocks, participants were asked to
classify the smiling or angry facial expressions of cooperators and cheaters. Both
experiments revealed congruence effects, reflecting faster identification of the
smiles of cooperators (Experiments 1 and 2) and faster identification of the angry
facial expressions of cheaters (Experiment 2). Our study provides evidence for the
automatic retrieval of the partner's behaviour in the game, regardless of whether
partners cheated or cooperated, and thus provides further evidence against the
cheater detection hypothesis.
The Low-level Radio Frequency (LLRF) control system for linear accelerator at
Legnaro National Laboratories (LNL) of INFN is being upgraded by a new digital
Radio Frequency (RF) controller. This controller is critical to keep phase,
amplitude and frequency stability of the RF field in QuarterWave Resonator (QWR)
cavities of the linear accelerator. These cavities work in superconducting
condition. The resonance frequency of low beta cavities is 80 MHz, while medium and
high beta cavities resonate at 160 MHz. Each RF controller can control at the same
time eight different cavities. The RF signals picked-up from the cavities are
sampled by RF ADCs. The digitized signals are fed into a field programmable gate
array (FPGA) which implements the control loop. The signals processed by the FPGA
are in-phase/quadrature modulated and sent to power amplifiers and hence to the
cavities. The main feature of the new control system is an all-digital control loop
that originates from direct sampling of the antenna RF signal. In-phase and
quadrature components are obtained by a suitable choice of the undersampling
frequency, while control of the field and phase in the cavity is based on a digital
Complex Phase Modulator (CPM). This paper presents the FPGA firmware, the
acquisition techniques and the performances of the new RF controller.
The problem of direction of arrival (DOA) estimation of non-circular (NC) signal
for non-uniform linear array is investigated. A generalised-ESPRIT (GESPRIT)
algorithm can be treated as an improvement of ESPRIT algorithm and the inter-
elements spacing of the array geometry can be uniform or non-uniform within a half
wavelength. The authors combine the GESPRIT algorithm and the NC property, and
propose an NC-GESPRIT algorithm to obtain the DOAs of NC signals, which requires
spectrum peak searching. Moreover, a computationally efficient search-free root NC-
GESPRIT algorithm, which is based on polynomial rooting, is also proposed to
depress the computational cost. The proposed NC-GESPRIT algorithms have much better
estimation performance than the conventional GESPRIT algorithm and it can detect
2M-1 sources with only M sensors due to the NC property. Furthermore, the proposed
algorithms can work well without estimating NC phase. The effectiveness and
improvement of the proposed algorithms will be proved in the following simulation
results.
Canine dirofilarioses are mosquito-borne zoonotic diseases with a continuous
expansion of their geographical distribution, as a consequence of different
climatic and ecological factors. Dirofilaria immitis, the aetiological agent of
heartworm disease, has gained a major veterinary interest, mainly due to its severe
clinical implication. In the last decades, D. repens, despite of being regarded as
a less pathogenic species, regained attention due to its recognized zoonotic
potential. Romania has been traditionally regarded as a non-endemic country, but
recent epidemiological surveys are highlighting the presence of both D. repens and
D. immitis. The present case report describes the clinical and pathological
features of a natural co-infection with D. repens and D. immitis in 5 year old male
Boxer from north-western Romania. Based on clinical and laboratory investigations,
a diagnosis of kidney failure and chronical cystitis was established. The parasites
were identified by morphology and confirmed by PCR and sequencing. To the best of
our knowledge this is the first worldwide report of the ectopic presence of D.
repens adults in the pelvic cavity and mesentery by natural infection and first
report of the ocular localization of this parasite for Romania. The clinical and
paraclinical findings suggest the implication of D. repens microfilariae in the
aetiology of histopathological lesions. Further investigations are needed in order
to establish the actual pathogenic potential of D. repens, a frequently neglected
parasite. (C) 2017 Elsevier B.V. All rights reserved.
In the UK, child sexual exploitation (CSE) has received considerable attention in
the last few years, with evidence pointing to an increased risk for young people
with learning disabilities. However, no study has specifically focused on this and
little is known about how best to protect, identify or support this group. This
paper is based on a UK study which examined the identification of, and support for
sexual exploited young people with learning disabilities. Data collection included
surveys of all local authorities in the UK and of a sample of services supporting
vulnerable or disabled children, in-depth interviews with 34 professional
stakeholders and with 27 young people with-learning disabilities who were at risk
of, or who had experienced CSE. This paper provides an overview of the study and
identifies areas for improvement in policy and practice including the need for
education, training and awareness raising amongst young people, their families and
professionals; tackling social isolation, disempowerment and invisibility of young
people with learning disabilities, and the need for full implementation of
government guidance with a spotlight on this group of young people. (C) 2016
Elsevier Ltd. All rights reserved.
Children make many decisions about whether and how to disclose their performance to
peers, teachers, parents and others. Previous research has found that children's
disclosure declines with age and that older children and teenagers preferentially
choose a peer audience for performance disclosure based on similar achievement.
This research examines younger children's choice of a disclosure audience: whether
young children predict that people will distinguish between peers at different
achievement levels, and whether or not younger children expect preferential
selections between those peers for their performance disclosure. One hundred and
thirty-nine children, aged 3 to 6years, were asked about a character's disclosure
of classroom performance information. At least until the age of 6years, children
predicted significantly greater disclosure of failure to a high achieving peer who
had been successful. When asked to predict the disclosure of success, however,
children in all age groups did not discriminate between disclosing to the high-
achieving or low-achieving peer. This evidence suggests that very young children
may not show the same valence-matching preferences as older children and that early
school ages are a critical time when children begin to adopt social norms around
disclosure that impinge on possible help-seeking. Copyright (c) 2016 John Wiley &
Sons, Ltd.
A discretization method is proposed for a rather general class of nonlinear
continuous-time systems, which can have a piecewise-constant input, such as one
under digital control via a zero-order-hold device. The resulting discrete-time
model is expressed as a product of the integration-gain and the system function
that governs the dynamics of the original continuous-time system. This is made
possible with the use of the delta or Euler operator and makes comparisons of
discrete and continuous time systems quite simple, since the difference between the
two forms is concentrated into the integration-gain. This gain is determined in the
paper by using the Riccati approximation of a certain gain condition that is
imposed on the discretized system to be an exact model. The method is shown to
produce a smaller error norm than one uses the linear approximation. Simulations
are carried out for a Lotka-Volterra and an averaged van der Pol nonlinear systems
to show the superior performance of the proposed model to ones known to be online
computable, such as the forward-difference, Kahan's, and Mickens' methods. Insights
obtained should be useful for developing digital control laws for nonlinear
continuous-time systems, which is currently limited to the simplest forward-
difference model.
In many wild animal populations, hosts are at risk of parasites and malnutrition
and resource costs of defence may be difficult to afford. We postulate that
proteins, important in homeostasis and immunity, play a complex but central role in
condition dependence and resource costs of mammalian immune defence. To test this,
we measured plasma concentrations of albumin, total proteins. Self-reactive
antibodies and parasite-specific IgG in female Soay sheep. Using a principal
component analysis, we found a new metric of condition reflecting individual
variation in acquisition, assimilation and/or recycling of plasma proteins that
predicted overwinter survival. Controlling for this metric, an age-dependent trade-
off between antibody titres and protein reserves emerged, indicating costs of
mounting an antibody response: younger individuals survived best when prioritising
immunity while older individuals fared better when maintaining high-protein
nutritional plane. These findings suggest fascinating roles for protein acquisition
and allocation in influencing survival in wild animal populations.
Background: The efficacy of disease management programs in improving the outcome of
heart failure patients remains uncertain and may vary across health systems. This
study explores whether a countrywide disease management program is superior to
usual care in reducing adverse health outcomes and improving well-being among
community-dwelling adult patients with moderate-to-severe chronic heart failure who
have universal access to advanced health-care services and technologies. Methods:
In this multicenter open-label trial, 1,360 patients recruited after
hospitalization for heart failure exacerbation (38%) or from the community (62%)
were randomly assigned to either disease management or usual care. Disease
management, delivered by multi-disciplinary teams, included coordination of care,
patient education, monitoring disease symptoms and patient adherence to medication
regimen, titration of drug therapy, and home tele-monitoring of body weight, blood
pressure and heart rate. Patients assigned to usual care were treated by primary
care practitioners and consultant cardiologists. The primary composite endpoint was
the time elapsed till first hospital admission for heart failure exacerbation or
death from any cause. Secondary endpoints included the number of all hospital
admissions, health-related quality of life and depression during follow-up.
Intention-to-treat comparisons between treatments were adjusted for baseline
patient data and study center. Results: During the follow-up, 388 (56.9%) patients
assigned to disease management and 387 (57.1%) assigned to usual care had a primary
endpoint event. The median (range) time elapsed until the primary endpoint event or
end of study was 2.0 (0-5.0) years among patients assigned to disease management,
and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio,
0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly
(70%) unrelated to heart failure. Patients assigned to disease management had a
better health-related quality of life and a lower depression score during follow-
up. Conclusions: This comprehensive disease management intervention was not
superior to usual care with respect to the primary composite endpoint, but it
improved health-related quality of life and depression. A disease-centered approach
may not suffice to make a significant impact on hospital admissions and mortality
in patients with chronic heart failure who have universal access to health care.
Wall-associated protein kinases (WAKs) are a new group of receptor-like kinases
(RLK) recently identified in Arabidopsis. A cDNA encoding a novel WAK was isolated
from rice and was named OsWAK1 (Oryza sativa WAK). The deduced amino acid sequence
of OsWAK1 showed 27.6% identity to WAK2 from Arabidopsis. OsWAK1 not only has the
ability of autophosphorylation but also can phosphorylate OsRFP1, a putative
transcription regulator recently identified in rice. OsRFP1 strongly interacts with
the kinase domain of OsWAK1. This demonstrated that OsWAK1 is a functional protein
kinase. A fusion protein of OsWAK1 with GFP was found to be localized on the cell
surface. Plasmolysis experiments further revealed OsWAK1 is associated with the
cell wall. Northern blotting analysis showed that infection of the rice blast
fungus, Magnaporthe oryzae significantly induced the OsWAK1 transcripts, and the
accumulation of OsWAK1 mRNA occurred earlier and was more abundant in rice leaves
infected with an incompatible race than with a compatible race of the blast fungus.
OsWAK1 was also induced after treatment by mechanical wounding, SA and MeJA, but
not by ABA. These results imply that OsWAK1 is a novel gene involved in plant
defense. Furthermore, six transgenic rice lines with constitutive expression of
OsWAK1 became resistant to the compatible race. However, OsWAK1 expression was
undetectable in leaves, stems and flowers but very weak in roots under normal
growth conditions. This provides functional evidence that induction of OsWAK1 as a
novel RLK plays important roles in plant disease resistance.
Every cognitive process, including the conceptualization of some perceived facts,
such as human disease states, entails both an emotional as an evaluative aspect.
Regarding this, cross-cultural research has shown that there are common human value
contents. Therefore, in a human phylogenetic context, it is plausible to argue
that, along with the development of our language, both the hetero-perception and
self-perception of some specific human states have been termed descriptively to
communicate their adaptive significance. This is the case of those human states
whose properties have been conceptualized, with the corresponding evaluative
emotional component, as "disease". Since names are the symbols of a language that
designate any type of object, either perceptual or conceptual, reviewing the
etymology of terms related to "disease" could be a contribution to its elucidation.
In consequence, some equivalent terms to the Spanish word enfermedad were reviewed
in various Indo-European and non-Indo-European languages. From the analyzed
denominations we can conclude that the different words have described the
perception of human conditions as weak, evil, suffering states, etc. Therefore,
there is a denotative concordance with the diseased human states in the revised
cultures.
Viral vaccines have had remarkable positive impacts on human health as well as the
health of domestic animal populations. Despite impressive vaccine successes,
however, many infectious diseases cannot yet be efficiently controlled or
eradicated through vaccination, often because it is impossible to vaccinate a
sufficient proportion of the population. Recent advances in molecular biology
suggest that the centuries-old method of individual-based vaccine delivery may be
on the cusp of a major revolution. Specifically, genetic engineering brings to life
the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly
transmissible vaccine poses substantial evolutionary risks, including reversion to
high virulence as has been documented for the oral polio vaccine. An alternative,
and far safer approach, is to rely on genetically engineered and weakly
transmissible vaccines that have reduced scope for evolutionary reversion. Here, we
use mathematical models to evaluate the potential efficacy of such weakly
transmissible vaccines. Our results demonstrate that vaccines with even a modest
ability to transmit can significantly lower the incidence of infectious disease and
facilitate eradication efforts. Consequently, weakly transmissible vaccines could
provide an important tool for controlling infectious disease in wild and domestic
animal populations and for reducing the risks of emerging infectious disease in
humans.
Lymphocyte-to-monocyte ratio (LMR) was associated with survival benefit in some
types of cancer. The relationship between LMR and rectal cancer has not been
investigated. We conducted a retrospective cohort study to assess the prognostic
significance of LMR in patients with nonmetastatic rectal cancer. Patients with
rectal cancer who underwent potentially curative resection between January 2009 and
December 2013 were enrolled. The LMR was calculated from preoperative blood test by
dividing the absolute lymphocyte counts by the absolute monocyte counts. The
optimal cut-off value for LMR was calculated as the median value. On the basis of
the cut-off value, patients were divided into 2 groups: low group and high group. A
total of 543 patients with rectal cancer were eligible for this study. The median
follow-up time for all patients was 55 months (range 6-85 months). The cut-off
value of LMR was 5.13 and patients were divided into 2 groups: low group (LMR=
5.13). In the univariate and multivariate analysis, the LMR was not significantly
associated with overall survival (OS) [hazard ratio (HR): 1.034, 95% confidence
intervals (CIs): 0.682-1.566, P=0.876]. When disease-free survival (DFS) was
compared, univariate and multivariate analysis also indicated that the LMR was not
significantly associated with DFS (HR: 0.988, 95% CI: 0.671-1.453, P=0.950). In
addition, in the subgroup analysis by tumor-node-metastasis stage, there existed no
significance between LMR and OS and DFS. Although as an easy access and highly
efficient laboratorial inflammatory marker, LMR cannot predict the prognosis of
nonmetastatic rectal cancer patients.
The output stability of the displacement sensors is an important issue for safe
operations in magnetic bearing supported high-speed rotor system. This paper
proposes an effective postprocessing solution to the problems of temperature drift
and synchronous measuring error for the axial displacement sensor in a 10-kW
magnetically suspended motor. The proposed configuration of the axial displacement
sensor consists of three probes: one pair is used to eliminate the synchronous
measuring error, and the third probe is employed for the consideration of
temperature drift. First, the generating mechanism of the synchronous measuring
error caused by the improper assemble is presented, and an operational amplifier is
proposed to obtain an accurate position of the axial center by adjusting the
weights of sensing signals from one pair of probes. Then the scheme of temperature
compensation using an auxiliary probe is presented. In order to obtain accurately
the characteristics of temperature drift at the operating point, the detailed
procedure is given to determine the temperature-drift ratio. Finally, the terms
related to temperature drift and synchronous error in the final output of the
displacement sensor are both eliminated. Experimental results on a magnetically
suspended motor test rig show the effectiveness of the proposed solution.
1. Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein
translation inhibitor approved by the US Food and Drug Administration for adult
patients with chronic myeloid leukemia with resistance and/or intolerance to two or
more tyrosine kinase inhibitors. 2. The objective was to investigate the metabolite
profile of omacetaxine in plasma, urine and faeces samples collected up to 72h
after a single 1.25-mg/m(2) subcutaneous dose of C-14-omacetaxine in cancer
patients. 3. High-performance liquid chromatography mass spectrometry (MS) (high
resolution) in combination with off-line radioactivity detection was used for
metabolite identification. 4. In total, six metabolites of omacetaxine were
detected. The reactions represented were mepesuccinate ester hydrolysis, methyl
ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged
omacetaxine was the most prominent omacetaxine-related compound in plasma. In
urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces
very little unchanged omacetaxine was found and the pyrocatechol metabolite of
omacetaxine, M534 and 4'-desmethyl homoharringtonine (4'-DMHHT) was the most
abundant metabolites. 5. Omacetaxine was extensively metabolized, with subsequent
renal and hepatic elimination of the metabolites. The low levels of the metabolites
found in plasma indicate that the metabolites are unlikely to contribute materially
to the efficacy and/or toxicity of omacetaxine.
Objective: This paper builds upon the analyses presented in three companion papers
using data from the 2003 and 2008 cycles of the Canadian Incidence Study of
Reported Child Abuse and Neglect (CIS-2003 and CIS 2008) and the Ontario Child
Abuse and Neglect Data System (OCANDS) to examine disproportionality and disparity
of child welfare involvement for Asian-Canadian children involved in the child
welfare system. Methods: This study used CIS-2008 data adjusted by Census child
population data to examine rates per 1000 and three disparity indexes (population-
based disparity index [PDI], decision-based disparity index [DDI], and
maltreatment-based disparity index [MDI]) to determine the representation of child
maltreatment investigations for Asian-Canadian versus White-Canadian children
involved in the child welfare system. Logistic regression analyses were conducted
to determine the odds of case closure for substantiated child maltreatment
investigations, and whether Asian ethnicity remained significant while controlling
for child demographics and household composition, case characteristics, and
clinical concerns. Results: This study found that Asian-Canadian children were
underrepresented in the child welfare system compared to White-Canadian children
(13.9 per 1000 Asian children in the Canadian population vs. 36.1 per 1000 White
children in the Canadian population). Child welfare involvement for Asian-Canadian
children are almost 2 times more likely to close after an investigation than White-
Canadian children. The three disparity indexes (PDI, DDI, MDI) showed substantially
different results with respect to the representation of child maltreatment
investigations involving Asian-Canadian versus White-Canadian children for physical
abuse, sexual abuse, neglect, emotional maltreatment, and exposure to domestic
violence. Conclusions: Disproportionality and disparity are complex phenomena. The
variation in results derived from different methods of calculating representation
suggests the need for greater clarity and consistency in the definitions and
methodology in examining racial disparity in child welfare research. Some
methodological considerations for future child welfare research with Asian-Canadian
populations were discussed. (C) 2016 Elsevier Ltd. All rights reserved
The modification of an energy-based approach called the dissipating energy flow
(DEF) method is proposed, which uses data from phasor measurement units (PMUs) to
trace the source of poorly damped natural and forced oscillations in power systems.
The original energy-based approach (Chen et al., 2013) assumes the ability to
determine steady-state values of variables measured by PMU during the transient
process and that prevents the reliable use of the original method with actual PMU
data. PMU data processing, proposed in the DEF method, is a key step in converting
the energy-based method into a robust and automated tool for use with actual PMU
data. The effectiveness of the proposed DEF method is demonstrated by testing
multiple simulated cases of sustained oscillations, including both poorly damped
natural and forced oscillations and more than 30 actual events in ISO New England
(ISO-NE) and two events in Western Electricity Coordination Council (WECC) systems.
The study also demonstrates the potential for using the DEF method to estimate the
contribution of any generator to the damping of a specific oscillation mode. (C)
2016 Elsevier Ltd. All rights reserved.
Plunging water jets are used for oxygenation purposes due to their inherent
advantages such as simplicity, energy efficiency, and low operational cost.
Specifically, these provide an efficient gas-liquid interfacial area for dissolving
oxygen in water. Oxygen transfer by plunging jets into stagnant water has received
considerable attention; however, the oxygenation capacity of plunging water jets
discharging into turbulent cross-flow has received limited attention. The flow
characteristics such as volumetric oxygen transfer coefficient and standard oxygen
transfer efficiency are evaluated considering water jet to cross-flow velocity
ratio, jet fall height, cross-flow depth, and jet impact angle. Two equations are
proposed for estimating the oxygen transfer rate for a single plunging jet in a
turbulent cross-flow. Moreover, the dynamic behavior of the resulting two-phase
air-water flow is investigated with the aid of flow visualization. (C) 2017
American Society of Civil Engineers.
Recently, wireless charging via magnetic resonance coupling has gained attention
because it has the potential of efficient midrange wireless charging. Here,
functions such as sensing at the transmitter and wireless communication from the
target are the essential elements to realize a standard wireless charging system.
Currently, the sensing and communication protocol of the hardware (i.e., the high-
frequency power source and antenna configuration) compatible with wireless charging
is gaining attention in terms of its cost and space reduction due to the use of
common components for multiple functions. However, this protocol has the problem of
narrow effective areas due to the fact that the sensing range depends on the fixed
Q factor of the antenna. To overcome this problem, the concept of wide-area sensing
based on a Q controllable antenna is proposed, and the effectiveness is verified
through a theoretical analysis and an experiment. As a result, it is clarified that
the effective area can be expanded up to a ratio of the distance g between the
transmitting and receiving antennas to the inner diameter d of the antenna g/d =
5.0. (C) 2017 Wiley Periodicals, Inc.
Chongming's current energy system is highly import-dependent and the distributed
energy system with high renewable energy penetration should be taken into
consideration. In this paper, a simulation model based on EnergyPLAN software with
2014 as the reference year is developed to represent Chongming's present energy
structure. Four future scenarios which propose different further energy
constructions have been observed. Results show that reductions in primary energy
consumption, electricity import, annual operating costs as well as CO2 emissions
are realizable when switching to an energy system with a high share of renewable
sources combining natural gas CHP (Combined Heating and Power). After preliminary
discussions, the feasibility of different renewable sources penetration are
analyzed through calculating the excess electricity production (CEEP). The
estimated optimal combination is generated when the PV fraction is 20% while wind
energy fraction is 80%. Moreover, the analyses have taken into account that several
flexible techniques are needed in order to balance supply and demand and to ensure
the grid voltage and frequency stabilities. As a result, through the recommended
three techniques, the excess production can be avoided as far as a renewable energy
input of up to nearly 60%. (C) 2016 Elsevier Ltd. All rights reserved.
Recent years, installation of photovoltaic (PV) system is active by the
environmental problem and feed in tariff system. Due to PV's output fluctuation,
the static var compensator (SVC) made by power electronics technology is planning
to install in distribution system. The SVC is expected for maintain the voltage.
But SVC differs in a theory of operation of the existing voltage controller load
ratio control transformer (LRT) and step voltage regulator (SVR). Because the SVC
operation makes the system impedance changes, the existing voltage controller may
not operate effectively. In this study, the intelligent-control method which used
the radial basis function (RBF) network is proposed. This method can reduce the
effects of the SVC operation by including the performance characteristics of SVC in
the conventional method. An advantage of unnecessary arrangement attention of the
SVC setup node and easy cooperation with the existing equipment is obtained by
applying this method.
This study examined mostly lower-middle-income Latino (37%) and African American
(33%) adolescents'(N = 90, M-age = 15.90) conceptions of how U. S. wealth is and
ought to be distributed, and whether these judgments are related to
adolescents'views about societal and legal fairness and their immediate academic
plans. Individually administered multipart interviews assessed conceptions
regarding (a) actual and ideal U. S. wealth distribution and related
"Rawlsian"judgments, (b) social system and legal fairness, and (c)
adolescents'near-term life goals. Overall, adolescents underestimated actual levels
of U. S. wealth inequality while also preferring a more egalitarian distribution
than was believed to exist. Adolescents'wealth-related reasoning was mostly
unrelated to other societal or personal judgments, whereas societal and legal
fairness judgments were related to personal academic plans. Although adolescents
had generally negative views of societal and legal fairness, having more positive
fairness conceptions was related to a greater emphasis on academic plans. Compared
with their younger peers, older adolescents preferred somewhat more wealth
inequality for motivational and economic reasons and preferred living in a society
with some inequality.
In this paper, a hypothetical district representing the typical urban districts in
Hong Kong was considered and a district cooling system model was designed for this
district. Mathematical models were tailor-designed for all the major district
cooling system equipment to simulate the effects of changing the pumping station's
configuration on the energy performance of the district cooling system. The
measures included the use of multiple pumping stations and an unequal number of
pumps in each station. In view of the vast number of pumping station combinations
possible for analysis, a hydraulic gradient evaluation method was adopted to assist
a quick assessment and exploration of those combinations that would be technically
feasible. Furthermore, the energy performance of all these technically feasible
combinations was evaluated to identify an optimum design that would lead to the
lowest electricity consumption. Practical application: In a district cooling system
where there is only one main pumping station for distributing chilled water to all
the buildings in the district, the chilled water flow rate and pressure head are
very high. Adding booster pumping stations can help to reduce pressure head, pump
size and hence power demand of the main pumping station. In this paper, the effects
of different pumping station configurations on the energy performance of a district
cooling system were investigated. The configuration that could mitigate the impacts
of a low delta-T on the energy performance of the district cooling system was also
identified.
Pilots for the seasonal thermal energy storage of solar energy on a local basis are
few in Finland, even if international demonstrations show that the utilization
level of solar energy can exceed 50% of the annual local heat requirement in
similar climate zones. This study presents options for heat and electricity
generation based on local energy systems and utilizing seasonal thermal energy
storages. Energy needs and production on Vartiosaari district in Helsinki in
Finland were explored as a case area. The project studied the impacts of
introducing solar thermal energy on local energy self-sufficiency and emissions
from heating energy supply, if excess solar heat in the summer is stored using
borehole thermal energy storage or tank storage for use in the winter. Around 60%
self-sufficiency in heat production would have been achieved in the scenarios
studied. In addition, carbon dioxide emissions could be reduced by around 50%, and
sulphur dioxide and particulate emissions by up to 70% compared to the business-as-
usual situation. (C) 2017 Elsevier Ltd. All rights reserved.
Ensemble weather predictions are introduced in the operation of district heating
systems to create a heat load forecast with dynamic uncertainties. These provide a
new and valuable tool for time-dependent risk assessment related to e.g. security
of supply and the energy markets. As such, it is useful in both the production
planning and the online operation of a modern district heating system, in
particular in light of the low-temperature operation, integration of renewable
energy and close interaction with the electricity markets. In this paper, a simple
autoregressive forecast model with weather prediction input is used to showcase the
new concept. On the study period, its performance is comparable to more complex
forecast models. The total uncertainty of the heat load forecast is divided into a
constant model uncertainty plus a time-dependent weather-based uncertainty. The
latter varies by as much as a factor of 18 depending on the ensemble spread. As a
consequence, the total forecast uncertainty varies significantly. The forecast
model is applied to the operation of three heat exchanger stations. Applying an
optimized temperature control can significantly lower supply temperatures compared
to current operation. Improving the temperature control with dynamic time-dependent
weather-based uncertainties can lower the supply temperature further and reduce
heat losses to the ground. The potential benefit of using dynamic uncertainties is
larger for systems with relatively smaller pumping capacities. (C) 2017 Elsevier
Ltd. All rights reserved.
Wide bandgap semiconductors have been increasingly adopted to enhance the
efficiency and reduce the volume of power converters, as these devices are able to
switch at dozens of megahertz or even 100 megahertz with lower power losses.
However, such a high frequency operation may impose a challenge to the digital
control system, and the required clock frequency should be up to 100 gigahertz in
high precision applications, which is difficult to realize in low-cost
microprocessors such as field-programmable gate array (FPGA). Instead of using
hardware-dependent high frequency clocks, an alternative solution is to utilize
digital pulse-width-modulated (DPWM) dither techniques to enhance the DPWM
resolution. Unfortunately, this is achieved at the expense of introducing low
frequency harmonics, which may complicate the output filter and system controller
design. In this paper, an optimal dither technique is proposed to enhance the
resolution of DPWM power converters. The concepts of positive dither and negative
dither are first proposed in this paper. Furthermore, vector diagram-based analysis
indicates that with the combination of positive dithers, negative dithers and a
carefully selected dither sequence, the lowest order harmonics can be completely
eliminated when the dither period is multiples of six switching periods. In other
cases, the proposed optimal dither technique can produce minimized lowest order
harmonics. Finally, experimental results obtained from a synchronous buck converter
validate the feasibility of the proposed technique.
Sleep problems during pregnancy impair maternal health and increase the risk for
adverse pregnancy outcome. The circadian preference toward eveningness has been
associated with sleep problems in previous studies. Here, we studied whether
evening-type women had more sleep problems during their pregnancy, as compared with
other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish
CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the
morningness-eveningness questionnaire. Pregnant evening-type women reported more
sleep problems, including troubles of falling asleep ( OR = 3.4, p < 0.0001), poor
sleep quality ( OR = 2.9, p < 0.01) and daily tiredness ( OR = 3.2, p < 0.0001)
than the morning-type women, even after controlling for sleep duration and sleep
deprivation. They had higher scores on Epworth Sleepiness Scale ( p < 0.05), Basic
Nordic Sleep Questionnaire ( p < 0.0001) and Global Seasonality Score ( p < 0.01)
and were also more often smokers, also during pregnancy ( p < 0.001) and reported
poorer general health ( p < 0.001) than the morning-type women. They also reported
having had more sleep problems during their childhood ( OR = 1.5, p < 0.05) and
adolescence ( OR = 2.0, p < 0.001) than the morning-type women. Our results
indicate that eveningness is associated with more sleep problems and unhealthy life
habits during pregnancy.
The chief characteristic of Japan's postwar employment system, built around the
needs of large corporations, is (a) a higher rate of lifetime employment and (b)
'deferred compensation', which is reflected in Japan's steeper age-wage profile,
and relatively late-stage promotions and late-career tracking relative to
comparable nations. However, a key attribute of regular employment in Japan-its
'indefinite' or 'unrestricted' nature'-has received less attention than it
deserves. Companies make no guarantees regarding regular employees' duties, job
locations, and working hours at the time of hiring. All are left indeterminate. The
indefinite nature of regular employment is linked to the causes of many employment
problems. The diversification of regular employment needs to progress to the point
where 'job-specific' regular employment, in which employees' job contents are
clearly defined, becomes the new 'norm'. This article presents some of the policies
that must be put in place in order for this shift to occur.
Division-summation (D-Sigma) digital control has been successfully applied to the
single-phase bidirectional inverter with an LC filter, which can coverwide
inductance variation and achieve precise inverter current tracking. However, high
frequency ripple current injection to the grid cannot be avoided, and an LCL filter
is therefore required. Since there typically exist grid voltage harmonics, the
injected grid current will contain harmonic components due to the effect of the
LCL-filter capacitor. This paper presents an extended application of the D-Sigma
digital control associated with a filter-capacitor-current compensation to reduce
the injected grid-current harmonics. The control laws of the inverter with the D-
Sigma digital control and compensation approach are derived in detail, and the
reduction of grid-current harmonics is analyzed. With the proposed approaches, the
phase margin between the output impedance of the inverter and grid impedance can be
higher than 80 degrees from low to high frequencies, and the inverter can achieve
high harmonic voltage rejection ratio up to 39th harmonic, which is relatively
suitable for weak grid connection. Experimental results measured from a 5-kW
single-phase bidirectional inverter have verified the feasible application of the
D-Sigma digital control and proposed compensation.
The present study was aimed to evaluate the neuroprotective effects of NBP in the
mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the
assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was
employed to induce TBI. ICR mice were randomly assigned to four experimental
groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via
an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP
significantly ameliorated the effects of the brain injury, including neurological
deficits, brain water content, and cortical neuronal apoptosis. Furthermore, the
level of malondialdehyde and the activity of superoxide dismutase (SOD) paired with
glutathione peroxidase (GPx) were restored in the NBP treatment group. NBP promoted
the translocation of Nrf2 protein from the cytoplasm to the nucleus markedly,
increased the expressions of Nrf2-ARE pathway-related downstream factors, including
hemeoxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and prevented
the decline of antioxidant enzyme activities, including SOD and GPx. NBP enhanced
the translocation of Nrf2 to the nucleus from the cytoplasm,verified by a western
blot, immunofluorescence. Additionally, it upregulated the expression of the Nrf2
downstream factors such as HO-1 and NQO1 were also confirmed via a western blot and
real-time quantitative polymerase chain reaction. In conclusion, NBP administration
may increase the activities of antioxidant enzymes and attenuate brain injury in a
TBI model, potentially via the mediation of the Nrf2-ARE pathway.
The present study was designed to compare the expression pattern of Dlx3 in four
different mineralized tissues because of: 1-its role in skeleton patterning, 2-its
expression in dental epithelium and mesenchyme during morphogenesis, 3-the
membranous and endochondral bone and tooth phenotype of tricho-dento-osseous
syndrome related to Dlx3 gene mutation and 4-recently emerging knowledge on Dlx
family members in the bone field. Ameloblasts, odontoblasts, osteoblasts and
chondrocytes were analyzed ill vitro and in vivo. Dlx3 transcripts were detected by
RT-PCR in established model systems (microdissected dental epithelium and
mesenchyme; primary cultures of rat chondrocytes), as recently performed in
osteoblasts in vitro. A human 414-bp Dlx3 probe was generated. A 4.5-kb human Dlx3
sense RNA was identified in maxillo-facial samples by Northern blotting.
Immunolabeling and in situ hybridization were performed in mice from Theiler stage
E 14.5 until birth. In teeth, although Dlx3 was still expressed in differentiated
ameloblasts, it was down regulated during odontoblast polarization. During
endochondral bone formation, Dlx3 protein was detected in chondrocytes and was most
strongly expressed in the prehypertrophic cartilage zone and in differentiating and
differentiated osteoblasts of inetaphyseal periosteum. In vitro, real-time PCR
studies supported this upregulation in prehypertrophic chondrocytes, closely
Correlated with Ihh variations. In membranous bone, Dlx3 was present in
preosteoblasts, osteoblasts and osteoid-osteocytes. The present data on Dlx3 and
recently published functional studies show that this transcription factor may be
instrumental during growth in the control of matrix deposition and
biomineralization in the entire skeleton. (c) 2005 Elsevier Inc. All rights
reserved.
Objectives: The purpose of this study was to investigate the role of a novel mutant
DLX3 on the odontogenic differentiation of human dental pulp cells (hDPCs) in
tricho-dento-osseous (TDO) syndrome. Design: hDPCs were obtained from the healthy
premolars, stably-expressing wild-type DLX3 (WT), novel mutant DLX3 (Mu) and
control vector (NC) cells were generated using recombinant lentiviruses. The
proliferation rates of WT-hDPCs and Mu-hDPCs were measured by CCK8 assay. Odonto-
differentiation of hDPCs was assessed by alkaline phosphatase (ALP) activity assay,
and mineralization ability was assessed by Alizarin red staining. Odontogenic
markers, including DMP-1, DSPP, Nes, ALP, and DLX5, were analyzed using real-time
polymerase chain reaction (qPCR). DMP-1 and DSPP expressions were further confirmed
by Western blotting. Results: CCK8 results showed that the novel mutant DLX3
decreased the proliferation rate of hDPCs compared with wild-type DLX3. qPCR showed
that the novel mutant DLX3 weakened odontogenic differentiation by downregulating
the expression of odontogenic genes. These results were further confirmed by
Western blotting and ALP activity assay. Additionally, Alizarin red staining showed
that the novel mutant DLX3 decreased the mineralization of hDPCs compared with
wild-type DLX3. Conclusions: Novel de novo mutation of DLX3 significantly decreases
the proliferation rate and inhibits the odontogenic differentiation and
mineralization of hDPCs, suggesting that this novel mutation of DLX3 can influence
the dentinogenesis in TDO syndrome. (C) 2017 Elsevier Ltd. All rights reserved.
The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play a
role in tumorigenesis and pathogen defense. It encodes a protein with multiple
scavenger receptor cysteine-rich (SRCR) domains, which are involved in recognition
and binding of a broad spectrum of bacterial pathogens. The SRCR domains are
encoded by highly homologous repetitive exons, whose number in humans may vary from
8 to 13 due to genetic polymorphism. Here, we characterized the porcine DMBTI gene
on the mRNA and genomic level. We assembled a 4.5 kb porcine DMBT1 cDNA sequence
from RT-PCR amplified seminal vesicle RNA. The porcine DMBT1 cDNA contains an open
reading frame of 4050 nt. The transcript gives rise to a putative polypeptide of
1349 amino acids with a calculated mass of 147.9 kDa. Compared to human DMBT1, it
contains only four N-terminal SRCR domains. Northern blotting revealed transcripts
of similar to 4.7 kb in size in the tissues analyzed. Analysis of ESTs suggested
the existence of secreted and transmembrane variants. The porcine DMBT1 gene spans
about 54 kb on chromosome 14q28-q29. In contrast to the characterized cDNA, the
genomic BAC clone only contained 3 exons coding for N-terminal SRCR domains. In
different mammalian DMBT1 orthologs large interspecific differences in the number
of SRCR exons and utilization of the transmembrane exon exist. Our data suggest
that the porcine DMBT1 gene may share with the human DMBT1 gene additional
intraspecific variations in the number of SRCR-coding exons. (c) 2006 Elsevier B.V.
All rights reserved.
Penaeid shrimps represent the most economically important decapod group in the
Egyptian capture fisheries. Up till now, the absence of proper morphological and
genetic tools for species identification is negatively affecting the proper
management of fisheries, especially when associated with the scarcity of data about
fisheries of such species that have high economic value or the ones suffering from
overfishing. In the present study, we sampled three penaeid species that prevail
the Egyptian capture fisheries of the Mediterranean; Penaeus semisukatus,
Metapenaeus monoceros and Trachypenaeus curvirostris. Morphological clues for the
identification of these species were thoroughly recorded. Furthermore, the DNA was
extracted from these species and partial fragments of the cytochrome oxidase
subunit 1 (C01) and 16S rRNA genes were amplified using polymerase chain reaction
(PCR) and sequenced. New barcodes of these species were added to the GenBank
database as confirmed by the thorough morphological identification. Some
discrepancies were detected between our samples and those in the Genbank database
(whenever available). Hence, phylogenetic analyses ensued for proper placement of
our samples with their closest relatives that were previously submitted to GenBank.
Moreover, morphometric studies were conducted to provide the fundamental parameters
which are important for fisheries management of the currently studied shrimp
species. Through these parameters tested, the study provided a tool to select the
appropriate stocks for successful hatcheries, and added more value to the growing
sector of shrimp aquaculture in Egypt. This study is the first of its kind in Egypt
as it provides both morphological and genetic clues for identifying such species,
and also in assessing their fisheries in the Mediterranean supreme fishery in
Egypt. (C) 2016 Elsevier B.V. All rights reserved.
Gold nanoparticles have proven to be promising for decentralized nucleic acid
testing by virtue of their simple visual readout and absorbance-based
quantification. A major challenge toward their practical application is to achieve
ultrasensitive detection without compromising simplicity. The conventional strategy
of thermocycling amplification is unfavorable (because of both instrumentation and
preparation of thermostable oligonucleotide-modified gold nanoparticle probes).
Herein, on the basis of a previously unreported co-precipitation phenomenon between
thiolated poly(ethylene glycol)/11-mercaptoundecanoic acid co-modified gold
nanoparticles and magnesium pyrophosphate crystals (an isothermal DNA amplification
reaction byproduct), a new ultrasensitive and simple DNA assay platform is
developed. The binding mechanism underlying the co-precipitation phenomenon is
found to be caused by the complexation of carboxyl and pyrophosphate with free
magnesium ions. Remarkably, poly(ethylene glycol) does not hinder the binding and
effectively stabilizes gold nanoparticles against magnesium ion-induced aggregation
(without pyrophosphate). In fact, a similar phenomenon is observed in other
poly(ethylene glycol)- and carboxyl-containing nanomaterials. When the gold
nanoparticle probe is incorporated into a loop-mediated isothermal amplification
reaction, it remains as a red dispersion for a negative sample (in the absence of a
target DNA sequence) but appears as a red precipitate for a positive sample (in the
presence of a target). This results in a first-of-its-kind gold nanoparticle-based
DNA assay platform with isothermal amplification and real-time monitoring
capabilities.
Six different commercial methods were compared to evaluate their efficiency in
recovering high quantity/quality PCR compatible microbial DNA from an agricultural
biogas plant. Within the last two decades, biogas plants have been developed to
produce energy from organic wastes and from devoted biomass. The complex
biotransformations are performed by a diverse consortium of microorganisms that is
an important reserve of genes and enzymatic activities with a huge range of
applications in various commercial fields. In this respect, the ability to isolate
DNA from a complex matrix is of high importance. Important parameters of the
recovered DNA are good yield, purity, and quality. The methods examined showed
considerable differences about quantity and quality of the recovered DNA and,
usually, it was observed that a higher amount was accompanied by more degradation.
DNA purity was determined by its PCR amplificability. Only two methods were able to
provide DNA pure enough to be directly amplified. For the rest of the methods, a
few intermediate steps such as dilution and/or the addition of polyvinylpyrrolidone
were necessary to remove the inhibitors present and to amplify the DNA. Real-time
PCR analysis evidenced that, as expected, prokaryotic DNA was much more abundant
than eukaryotic DNA, but some methods were more suited to recovering prokaryotic or
eukaryotic DNA. The digestion analysis of ribosomal DNA amplicons confirmed the
influence of the methods on the final output, allowing the recovery of only a
fraction of the present species as determined by sequencing a small prokaryotic and
eukaryotic ribosomal library.
We present a label-free biosensor for the detection of nucleic acids from PCR
amplicons based on the surface plasmon resonance (SPR) with novel DNA
intercalators. These intercalators can specifically bind to double-stranded DNA
(ds-DNA), allowing ds-DNA to be quantitatively monitored by angle shifts of SPR
following mass changes on the SPR sensor surface. Pyrenyl intercalator compounds
that were synthesized consisted of pyrenyl groups as intercalating moieties,
ethylene glycol hexamer linkers that resist non-specific binding events and thiol
groups that formed self-assembled monolayers (SAMs) on a gold substrate. Also,
hydroxyl group terminated compound instead of pyrenyl group was synthesized to
ensure adequate separation between adjacent pyrene groups. The molar concentration
ratio of mixed SAMs on SPR sensor surface was selected for maximum mass sensitivity
on the basis of experimental results from various mixed ratios. Finally, we
investigated the sensor responses due to intercalations on various concentrations
of applied pure ds-DNA and demonstrated the capability for the analysis of PCR
amplicons in the reaction product mixtures without any purification process. These
results show that the proposed label-free biosensor devised based on strong binding
interactions between DNA intercalators and base pairs of any ds-DNA can
quantitatively analyze ds-DNA in accordance. (C) 2016 Elsevier B.V. All rights
reserved.
Stress plays an important role in major depressive disorder (MDD) and is one of the
state dependent factors in suicidal behavior. A dysfunctional hypothalamic-
pituitary-adrenal axis is a common feature in this disorder. The involvement of
environmental factors has added additional complexity to understanding depression
or suicidal behavior. In this regard, epigenetic regulation has been considered a
mechanistic interface between environmental stress stimuli and altered functioning
of underlying gene network that may increase susceptibility to depression or
suicidal behavior. The present study examined whether epigenetic modifications of
stress related genes are associated with MDD and whether there are differences in
these epigenetic marks between depressed individuals with and without serious
suicidal ideation. Using MeDIP analysis in genomic DNA isolated from peripheral
blood mononuclear cells (PBMC) of healthy controls (n = 20), MDD patients with (n =
14) or without serious suicidal ideation (n = 10), we studied methylation of the
stress-associated genes, Brain Derived Neurotrophic Factor (BDNF), Nuclear Receptor
Subfamily 3 Group C Member 1 (NR3C1), FK506 Binding Protein 5 (FKBP5),
Corticotropin Releasing Hormone Binding Protein (CRHBP), and Corticotropin
Releasing Hormone Receptor 1 (CRHR1). In addition, we determined their transcript
levels in RNAs isolated from the same PBMC. We found that BDNF, FKBP5, CRHBP, and
NR3C1 gene promoters were significantly hypermethylated in MDD patients with and
without suicidal ideation. We also found concomitant reductions in expression of
BDNF, FKBP5 transcript variants (1, 2 and 3), and NR3C1 genes in these patients,
suggesting that promoter hypermethylation in these genes may functionally be
associated with their observed downregulation in MDD patients. In a secondary
analysis, methylation of these genes was compared between MDD patients with or
without serious suicidal ideation and controls. The MDD with serious suicidal
ideation were significantly different from controls while the MDD without were not,
although MDD with or without suicidal ideation were not different from each other,
likely owning to a relatively small sample size. Thus, our findings underline the
importance of epigenetic modifications of stress-associated genes in depression
and, possibly, suicidal behavior, which, in future, needs to be confirmed in a
larger patient population. (C) 2017 Elsevier Ltd. All rights reserved.
Childhood maltreatment is a key risk factor for poor mental and physical health.
Recently, variation in epigenetic processes, such as DNA methylation, has emerged
as a potential pathway mediating this association; yet, the extent to which
different forms of maltreatment may be characterized by unique vs shared epigenetic
signatures is currently unknown. In this study, we quantified DNA methylation
across the genome in buccal epithelial cell samples from a high-risk sample of
inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported
experiencing at least one form of maltreatment while growing up. Our analyses aimed
to identify methylomic variation associated with exposure to five major types of
childhood maltreatment. We found that: (i) maltreatment types differ in the extent
to which they associate with methylomic variation, with physical exposures showing
the strongest associations; (ii) many of the identified loci are annotated to genes
previously implicated in stress-related outcomes, including psychiatric and
physical disorders (e.g. GABBR1, GRIN2D, CACNA2D4, PSEN2); and (iii) based on gene
ontology analyses, maltreatment types not only show unique methylation patterns
enriched for specific biological processes (e.g. physical abuse and cardiovascular
function), but also share a 'common' epigenetic signature enriched for biological
processes related to neural development and organismal growth. A stringent set of
sensitivity analyses were also run to identify high-confidence associations.
Together, findings lend novel insights into epigenetic signatures of childhood
abuse and neglect, point to novel potential biomarkers for future investigation and
support a molecular link between maltreatment and poor health outcomes.
Nevertheless, it will be important in future to replicate findings, as the use of
cross-sectional data and high rates of polyvictimization in our study make it
difficult to fully disentangle the shared vs unique epigenetic signatures of
maltreatment types. Furthermore, studies will be needed to test the role of
potential moderators in the identified associations, including age of onset and
chronicity of maltreatment exposure. (C) 2016 Elsevier Ltd. All rights reserved.
DNA methylation is a fundamental means of epigenetic gene regulation that occurs in
virtually all cell types. In many higher organisms, including humans, it plays
vital roles in cell differentiation and homeostatic maintenance of cell phenotype.
The control of DNA methylation has traditionally been attributed to a highly
coordinated, linear process, whose dysregulation has been associated with numerous
pathologies including cancer, where it occurs early in, and even prior to, the
development of neoplastic tissues. Recent experimental evidence has demonstrated
that, contrary to prevailing paradigms, methylation patterns are actually
maintained through inexact, dynamic processes. These processes normally result in
minor stochastic differences between cells that accumulate with age. However,
various factors, including cancer itself, can lead to substantial differences in
intercellular methylation patterns, viz. methylation heterogeneity. Advancements in
molecular biology techniques are just now beginning to allow insight into how this
heterogeneity contributes to clonal evolution and overall cancer heterogeneity. In
the current review, we begin by presenting a didactic overview of how the basal
bimodal methylome is established and maintained. We then provide a synopsis of some
of the factors that lead to the accrual of heterogeneous methylation and how this
heterogeneity may lead to gene silencing and impact the development of cancerous
phenotypes. Lastly, we highlight currently available methylation assessment
techniques and discuss their suitability to the study of heterogeneous methylation.
(C) 2016 Published by Elsevier Ltd.
Astrocytomas are the most common primary brain tumors. They are very resistant to
therapies and usually progress rapidly to high-grade lesions. Here, we investigated
the potential role of DNA repair genes in astrocytoma progression and resistance.
To this aim, we performed a polymerase chain reaction array-based analysis focused
on DNA repair genes and searched for correlations between expression patters and
survival prognoses. We found 19 genes significantly altered. Combining these genes
in all possible arrangements, we found 421 expression signatures strongly
associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2,
and BRIP1) were independently correlated with worse prognoses, revealing single-
gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed,
promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also
highly overexpressed, caused an increment in DNA damage and cell death after
irradiation of glioblastoma cells. These results disclose the importance of DNA
repair pathways for the maintenance of genomic stability of high-grade astrocytomas
and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-
strand break repair and resistance to reactive oxygen species, respectively.
Thereby, we highlight these two genes as potentially related with tumor
aggressiveness and promising candidates as novel therapeutic targets.
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-
1 (mTORC1) function may be involved in controlling the aging process. Our previous
studies have shown diminished mTORC1 activity in tissues of three long-lived mutant
mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in
this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The
ways in which lower mTOR signals slow aging and age-related diseases are, however,
not well characterized. Here, we show that Snell, GHKRO, and PAPPA-KO mice express
high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA
methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1).
Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein
expression via post-transcriptional mechanisms. We show that the CCR4-NOT complex,
a post-transcriptional regulator of gene expression, is downstream of the mTORC1
pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three
varieties of long-lived mice. Our data thus suggest a novel link between DNA repair
and mTOR signaling via post-transcriptional regulation involving specific
alteration in the CCR4-NOT complex, whose modulation could control multiple aspects
of the aging process.
Cellular sensing of virus-derived nucleic acids is essential for early defenses
against virus infections. In recent years, the discovery of DNA sensing proteins,
including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein
(IFI16), has led to understanding of how cells evoke strong innate immune responses
against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA
sensors depends on the adaptor protein STING (stimulator of interferon genes), to
enable expression of antiviral proteins, including type I interferon. To facilitate
efficient infections, viruses have evolved a wide range of evasion strategies,
targeting host DNA sensors, adaptor proteins and transcription factors. In this
review, the current literature on virus-induced activation of the STING pathway is
presented and we discuss recently identified viral evasion mechanisms targeting
different steps in this antiviral pathway.
With the intensification of human activities, fresh water resources are
increasingly being exposed to contamination from effluent disposal to land. Thus,
there is a greater need to identify the sources and pathways of water contamination
to enable the development of better mitigation strategies. To track discharges of
domestic effluent into soil and groundwater, 10 synthetic double-stranded DNA
(dsDNA) 3 tracers were developed in this study. Laboratory column experiment and
field groundwater and soil lysimeter studies were carried out spiking DNA with
oxidation-pond domestic effluent. The selected DNA tracers were compared with a
non-reactive bromide (Br) tracer with respect to their relative mass recoveries,
speeds of travel and dispersions using the method of temporal moments. In intact
stony soil and gravel aquifer media, the dsDNA tracers typically showed earlier
breakthrough and less dispersion than the Br tracer, and underwent mass reduction.
This suggests that the dsDNA tracers were predominantly transported through the
network of larger pores or preferential flow paths. Effluent tracking experiments
in soil and groundwater demonstrated that the dsDNA tracerswere readily detectable
in effluent-contaminated soil and groundwater using quantitative polymerase chain
reaction. DNA tracer spiked in the effluent at quantities of 36 mu g was detected
in groundwater 37 mdown-gradient at a concentration 3-orders of magnitude above the
detection limit. It is anticipated it could be detected at far greater distances.
Our findings suggest that synthetic dsDNA tracers are promising for tracking
effluent discharges in soils and groundwater but further studies are needed to
investigate DNA-effluent interaction and the impact of subsurface environmental
conditions onDNA attenuation. With further validation, synthetic dsDNA tracers,
especially when multiple DNA tracers are used concurrently, can be an effective new
tool to track effluent discharge in soils and groundwater, providing spatial
estimation on the presence or absence of contamination sources and pathways. (C)
2017 Elsevier B.V. All rights reserved.
Introduction: Unlike other molecular biology studies, the analysis of ancient DNA
(aDNA) requires special infrastructure and methodological conditions to guarantee
the quality of the results. One of the main authenticity criteria is DNA
quantification, where quantitative real-time PCR is often used given its
sensitivity and specificity. Nevertheless, the implementation of these conditions
and methodologies to fulfill authenticity criteria imply higher costs. Objective:
To develop a simple and less costly method for mitochondrial DNA quantification
suitable for highly degraded samples. Materials and methods: The proposed method is
based on the use of mini-primers for the specific amplification of short fragments
of mitochondrial DNA. The subsequent purification of these amplified fragments
allows a standard curve to be constructed with concentrations in accordance to the
state of degradation of the samples. Results: The proposed method successfully
detected DNA from ancient samples including bone remains and mummified tissue. DNA
inhibitory substances were also detected. Conclusion: The proposed method
represents a simpler and cost-effective way to detect low amounts of aDNA, and a
tool to differentiate DNA-free samples from samples with inhibitory substances.
DNA analysis of processed foods is performed widely to detect various targets, such
as genetically modified organisms (GMOs). Food processing often causes DNA
fragmentation, which consequently affects the results of PCR analysis. In order to
assess the effects of DNA fragmentation on the reliability of PCR analysis, we
investigated a novel methodology to quantify the degree of DNA fragmentation. We
designed four real-time PCR assays that amplified 18S ribosomal RNA gene sequences
common to various plants at lengths of approximately 100, 200, 400, and 800 base
pairs (bp). Then, we created an indicator value, "DNA fragmentation index (DFI)",
which is calculated from the Cq values derived from the real-time PCR assays.
Finally, we demonstrated the efficacy of this method for the quality control of GMO
detection in processed foods by evaluating the relationship between the DFI and the
limit of detection. (C) 2017 Elsevier Ltd. All rights reserved.
Considering that mislabeled milk products have been widely reported throughout the
world and that the authentication of food components is one of the key issues in
food safety and quality, the aim of this study was to use DNA-based methods to
investigate the prevalence of mislabeling among goat-milk products and,
consequently, how far the ingredients matched the labels. The study reveals a high
degree of species mislabeling in milk products (80%), underlining the need to
enhance dairy traceability practices, so as to guarantee product authenticity, and
provide reliable information to consumers. (C) 2017 Elsevier Ltd. All rights
reserved.
The aim of this study was to develop an ultra-fast molecular detection method for
meat identification using convection Palm polymerase chain reaction (PCR). The
mitochondrial cytochrome b (Cyt b) gene was used as a target gene. Amplicon size
was designed to be different for beef, lamb, and pork. When these primer sets were
used, each species-specific set specifically detected the target meat species in
singleplex and multiplex modes in a 24 min PCR run. The detection limit was 1 pg of
DNA for each meat species. The convection PCR method could detect as low as 1% of
meat adulteration. The stability of the assay was confirmed using thermal processed
meats. We also showed that direct PCR can be successfully performed with mixed
meats and food samples. These results suggest that the developed assay may be
useful in the authentication of meats and meat products in laboratory and rapid on-
site applications. (C) 2017 Elsevier Ltd. All rights reserved.
AIM: To investigate whether DNA-dependent activator of interferon-regulatory
factors (DAI) inhibits hepatitis B virus. (HBV) replication and what the mechanism
is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and
HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen)
secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was
analyzed by real-time polymerase chain reaction and Northern blotting, and viral
DNA replicative intermediates were examined by Southern blotting. Interferon
regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed
via Western blotting and immunofluorescence staining respectively. Nuclear factor-
kappa B (NF-kappa B) activity induced by DAI was detected by immunofluorescence
staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment
was performed in order to investigate whether the antiviral effects of DAI were
dependent on the secreted cytokines. RESULTS: Viral protein secretion was
significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced
by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically
down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling
pathways revealed that activation of NF-kappa B signaling was essential for DAI to
elicit antiviral response in Huh7 cells. When the NF-kappa B signaling pathway was
blocked by a NF-kappa B signaling suppressor (I kappa B alpha-SR), the anti-HBV
activity of DAI was remarkably abrogated. The inhibitory effect of DAI was
independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study
demonstrates that DAI can inhibit HBV replication and the inhibitory effect is
associated with activation of NF-kappa B but independent of IRF3 and secreted
cytokines. (C) 2012 Baishideng. All rights reserved.
To make the direct readout of loop-mediated isothermal amplification (LAMP) simpler
and more reliable and to enhance the visual sensitivy of LAMP detection, we
developed a facile cascade signal-on colorimetric DNAzyme LAMP (dLAMP) sensor that
integrates the amplification power of LAMP and the inherent catalytic activity of
the DNAzyme for the simple and ultrasensitive analysis of targets. First, a signal
inner primer with a 17-nt DNAzyme complementary sequence (a signal precursor) in
its middle insertable region was asymmetrically designed for the next amplification
and colorimetric reaction. In the presence of target DNA, the target specifically
initiated LAMP, and the signal precursor was amplified to a larger number of
DNAzyme sequences during the target DNA amplification. With the addition of hemin,
free DNAzyme fragments, which were released by ultrasonication and pPNA, formed G-
quadruplex-hemin conjugates that act as a signal readouts for the direct
colorimetric assay. Even less 0.5 pg genomic DNA were detected using the
established one-step cascade signal amplification strategy without the need for
gels or other apparatus. Moreover, the novel colorimetric strategy showed high
fidelity in DNA detection and visual sensitivity of LAMP. This method may pave the
way for the point-of-care detection and other PCR-based colorimetric analyses. (C)
2016 Elsevier B.V. All rights reserved.
Objectives: To investigate the expression, DNA methylation status and its
regulatory mechanism of tissue factor pathway inhibitor 2 (TFPI-2) in human
placenta tissues of preeclampsia (PE). Material and methods: We studied the mRNA
and protein expression and the promoter methylation levels of TFPI-2 in the PE
placentas compared with those in the normal pregnant (NP) women. Quantitative real-
time polymerase chain reaction, immunohistochemistry, western blot, and Sequenom
Mass ARRAY were used for placenta tissue detection. Results: The expressions of
TFPI-2 mRNA and protein were significantly elevated in the PE placentas when
compared with those in the NP ones (P<0.05). Hypomethylation of the TFPI-2 promoter
was detected both in PE patients and NP women, with a significant decrease in PE
placentas (P = 0.005). The methylation level was significantly decreased at CpG_6
(-168 to -167), CpG_15 (-98 to -97) and CpG_18.19 (-68 to -65) in PE patients than
that in normal placentas (P0.05). Conclusion: Over-expression of TFPI-2 and
aberrant promoter mythylation status presented in the PE placentas, suggesting that
epigenetic mechanism might contribute to the pathogenesis of PE. (C) 2017 Elsevier
Ltd. All rights reserved.
Background: Cellular stressors and apoptosis-inducing agents have been shown to
induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA
degradation in vivo was observed in patients with locally advanced breast cancer,
where mid-treatment tumor RNA degradation was associated with complete tumor
destruction and enhanced patient survival. However, it is not clear how widespread
chemotherapy induced "RNA disruption" is, the extent to which it is associated with
drug response or what the underlying mechanisms are. Methods: Ovarian (A2780,
CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated
with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also
prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells
following drug exposure. Disruption of RNA was analyzed by capillary
electrophoresis. Northern blotting was performed using probes complementary to the
28S and 18S rRNA to determine the origins of degradation bands. Apoptosis
activation was assessed by flow cytometric monitoring of annexin-V and propidium
iodide (PI) binding to cells and by measuring caspase-3 activation. The link
between apoptosis and RNA degradation (disruption) was investigated using a
caspase-3 inhibitor. Results: All chemotherapy drugs tested were capable of
inducing similar RNA disruption patterns. Docetaxel treatment of the resistant
A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in
RNA disruption. Northern blotting indicated that two RNA disruption bands were
derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel
treated cells, along with assessment of caspase-3 activation, showed concurrent
initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity
significantly reduced RNA disruption. Conclusions: Supporting the in vivo evidence,
our results demonstrate that RNA disruption is induced by multiple chemotherapy
agents in cell lines from different tissues and is associated with drug response.
Although present, the link between apoptosis and RNA disruption is not completely
understood. Evaluation of RNA disruption is thus proposed as a novel and effective
biomarker to assess response to chemotherapy drugs in vitro and in vivo.
We explored the social shaping of science at the microlevel reality of face-to-face
interaction in one of the traditional places for scientific activities-the
scientific lab. We specifically examined how doctoral students ' perception of
their: (i) interaction with doctoral mentors (MMI) and (ii) lab social environment
(LSE) influenced productivity. Construed as the production of peer-reviewed
articles, we measured productivity using total number of articles (TOTAL), number
of articles with impact factor greater than or equal to 4.00 (IFGE4), and number of
first-authored articles (NFA). Via face-to-face interviews, we obtained data from
n=210 molecular biology Ph. D. students in selected universities in Japan,
Singapore, and Taiwan. Additional productivity data (NFA) were obtained from online
bibliometric databases. To summarize the original 13 MMI and 13 LSE semantic-
differential items which we used to measure students ' perceptions, principal
component (PC) analyses were performed. The results were smaller sets of 4 MMI PCs
and 4 LSE PCs. To identify which PCs influenced publication counts, we performed
Poisson regression analyses. Although perceived MMI was not linked to productivity,
perceived LSE was linked: Students who perceived their LSE as intellectually
stimulating reported high levels of productivity in both TOTAL and IFGE4, but not
in NFA. Our findings not only highlight how students ' perception of their training
environment factors in the production of scientific output, our findings also carry
important implications for improving mentoring programs in science. (C) 2016 by The
International Union of Biochemistry and Molecular Biology, 45(2): 130-144, 2017.
The strongest and best-documented risk factor for drug hypersensitivity (DH) is the
history of a previous reaction. Accidental exposures to drugs may lead to severe or
even fatal reactions in sensitized patients. Preventable prescription errors are
common. They are often due to inadequate medical history or poor risk assessment of
recurrence of drug reaction. Proper documentation is essential information for the
doctor to make sound therapeutic decision. The European Network on Drug Allergy and
Drug Allergy Interest Group of the European Academy of Allergy and Clinical
Immunology have formed a task force and developed a drug allergy passport as well
as general guidelines of drug allergy documentation. A drug allergy passport, a
drug allergy alert card, a certificate, and a discharge letter after medical
evaluation are adequate means to document DH in a patient. They are to be handed to
the patient who is advised to carry the documentation at all times especially when
away from home. A drug allergy passport should at least contain information on the
culprit drug(s) including international nonproprietary name, clinical
manifestations including severity, diagnostic measures, potential cross-reactivity,
alternative drugs to prescribe, and where more detailed information can be obtained
from the issuer. It should be given to patients only after full allergy workup. In
the future, electronic prescription systems with alert functions will become more
common and should include the same information as in paper-based documentation.
The hormone oxytocin plays an important role in attachment formation and bonding
between humans and domestic dogs. Recent research has led to increased interest in
potential applications for intranasal oxytocin to aid with the treatment of
psychological disorders in humans. While a few studies have explored the effects of
intranasally administered oxytocin on social cognition and social bonding in dogs,
alternative applications have not yet been explored for the treatment of
behavioural problems in this species. One potentially important application for
intranasal oxytocin in dogs could be the treatment of separation anxiety, a common
attachment disorder in dogs. Here we provide an overview of what is known about the
role of oxytocin in the human-dog bond and canine separation anxiety, and discuss
considerations for future research looking to integrate oxytocin into behavioural
treatment based on recent findings from both the human and dog literature.
Reasoning about physical properties of objects such as heaviness by observing
others' actions toward them is important and useful for adapting to the
environment. In this study, we asked whether domestic dogs (Canis familiaris) can
use a human's action to infer a physical property of target objects. In Experiment
1, dogs watched an experimenter opening two differently loaded swinging doors with
different corresponding degrees of effort, and then were allowed to open one of the
doors. Dogs chose randomly between the two doors. In Experiment 2, we gave new dogs
the same test as in Experiment 1, but only after giving them experience of opening
the doors by themselves, so that they already knew that the doors could be either
light or heavy. In this test the dogs reliably chose the light door. These results
indicate that dogs are able to infer physical characteristics of objects from the
latters' movement caused by human action, but that this inferential reasoning
requires direct own experience of the objects. (C) 2017 Published by Elsevier B.V.
Babesiosis is a protozoal disease caused by Babesia spp. in mammals and humans
worldwide. It is one of the most important tick-borne diseases, which affects
livestock productions, reproductions, and accordingly failing economy. In this,
systematic review and meta-analysis, study, the prevalence of babesiosis among
domestic herbivores in Iran, between 1998 and 2015, was methodically reviewed. Nine
databases including five English and four Persian databases were explored. A total
of 49 articles, as regards the examination of 13,547 sheep, 1920 goats, 7167
cattle, and 940 horses, corresponding to prevalence of babesiosis from different
regions of Iran were gathered for our qualifying criteria. The overall prevalence
of babesiosis was expected to be 14% (95% CI 12%, 16%) in domestic herbivores. Our
results showed the highest prevalence in Khorasan Razavi (18.6%) and West
Azarbaijan (15.2%) and the lowest in Mazandaran (8.8%) and Isfahan provinces
(9.6%), respectively. The high prevalence of Babesia infection in herbivores
(mostly sheep and goats) confirms the established enzootic situation of babesiosis
in Iran, particularly in western and northeastern regions of the country. Our data
offered important and updated information on the epidemiology of babesiosis, for
the first time, in domestic herbivores in Iran, and will likely be contributing to
the expansion of the screening and control strategies to reduce health and economic
impacts among farm animals.
Study Objective: To describe the clinical characteristics of patients referred for
domestic minor sex trafficking (DMST) to improve identification and intervention.
Design: Retrospective cohort study. Setting: The Lawrence A. Aubin, Sr Child
Protection Center at Hasbro Children's Hospital where patients are evaluated by
child abuse pediatricians in outpatient, emergency department, and inpatient
settings. Participants: A total of 41 patients younger than the age of 18 years
referred for the evaluation of DMST involvement between August 1, 2013 and March
30, 2015. Interventions and Main Outcome Measures: We collected demographic,
social-environmental, medical, and psychiatric variables from the medical records
of patients referred for evaluation who have self-disclosed, been reported with
evidence, and/or have histories that place them at high risk for DMST involvement.
Results: Children had frequent contact with medical providers, with 81% seen in the
year before referral for DMST. Childhood maltreatment and family dysfunction were
identified (sexual abuse, 21/37 or 57%; parental substance abuse, 22/37 or 60%) in
the 41 patients. Children had medical problems (eg, sexually transmitted infection,
13/41 or 32%), psychiatric needs (eg, acute suicidality, 8/41 or 20%; at least 1
previous psychiatric admission, 19/41 or 46%), and substance use (36/41 or 88%).
Although 26/41 (63%) had runaway and 17/41 (42%) lived in a group home placement,
28/41 (68%) currently lived at home and 29/41 (71%) presented with a
parent/guardian or relative. Conclusion: Children referred for DMST present
frequently to physicians and have complex medical and psychiatric needs. Medical
providers' increased awareness of this health issue would inform victim
identification and intervention.
This study aimed to identify and analyze the prevalence of physical and
psychological family violence in a sample of children and adolescents with
different categories of disabilities in a hospital in Rio de Janeiro, Brazil. This
was a cross-sectional observational study based on application of the Parent-Child
Conflict Tactics Scale in a sample of 270 parents or guardians. Prevalence was
83.7% for psychological aggression and 84.4% for physical maltreatment, while 96.5%
of the children and adolescents with disabilities that suffered physical punishment
were also victims of psychological aggression ( p < 0.01) and 100% of those who
suffered severe physical maltreatment also suffered psychological aggression ( p =
0.01). Children and adolescents with disabilities showed increased risk of
suffering family violence compared to those without disabilities. In conclusion,
there is a need for greater awareness-raising and training of health teams for
detection and notification of child abuse, and efforts should be made to support
these families.
Victims of violence need special treatment in the emergency room, including exact
documentation that can stand up in court. It may happen that the documentation must
be made by the clinician if no forensic pathologist is on site The aim of this
review is to provide clinicians a guide for documenting information from victims of
violence and to identify potential victims of violence. Presentation of selected
and typical cases, discussion of basic literature and expert opinions. Victims of
violence can present a variety of injury patterns which the attending physician
must recognize as being the result of violence. If urgent care is needed or no
forensic pathologist is available, the documentation must be made by the clinician.
Particular importance is attached to the exact photo documentation and description
of injuries. Commonly physicians and nurses are not adequately trained in dealing
with medicolegal situations. Continuing education in the field of wound
documentation in words and pictures is necessary in order to provide proper
documentation. Cooperation between clinicians and forensic medicine specialists
should be intensified.
This research examined Children and Family Court Advisory and Support Service
(Cafcass) reports prepared for private family court proceedings in domestic
violence cases in England. The research found that in cases where children's
accounts identified them as victims of violence, these disclosures regularly
disappeared from report recommendations. Particular discourses regarding 'child
welfare' and 'contact' were identified, which routinely impacted on the ways in
which children's voices were taken into account. Whilst culturally there has
undoubtedly been an influential move towards including children's perspectives in
decision-making that affects them, how these views are interpreted and represented
is subject to adult 'gate-keeping' and powerful cultural and professional
ideologies regarding 'child welfare' and 'post-separation family relationships'.
This research found that the unrelenting influence of deeply embedded beliefs
regarding the preservation or promotion of relationships with fathers continues to
have the effect of marginalising issues of safeguarding, including children's
voiced experiences of violence, in all but the most exceptional of cases. Rather,
safeguarding concerns in respect of domestic violence and child abuse were
persistently overshadowed by a dominant presumption of the overall benefits of
contact with fathers. Crown Copyright (C) 2017 Published by Elsevier Ltd. All
rights reserved.
Exposure of children to domestic violence and abuse (DVA) is a form of child
maltreatment with short-and long-term behavioural and mental health impact. Health
care professionals are generally uncertain about how to respond to domestic
violence and are particularly unclear about best practice with regards to
children's exposure and their role in a multiagency response. In this systematic
review, we report educational and structural or whole-system interventions that aim
to improve professionals' understanding of, and response to, DVA survivors and
their children. We searched 22 bibliographic databases and contacted topic experts
for studies reporting quantitative outcomes for any type of intervention aiming to
improve professional responses to disclosure of DVA with child involvement. We
included interventions for physicians, nurses, socialworkers and teachers. Twenty-
one studiesmet the inclusion criteria: three randomised controlled trials (RCTs),
18 pre-post intervention surveys. There were 18 training and three system-level
interventions. Training interventions generally had positive effects on
participants' knowledge, attitudes towards DVA and clinical competence. The results
from the RCTs were consistent with the before-after surveys. Results from system-
level interventions aimed to change organisational practice and inter-
organisational collaboration demonstrates the benefit of coordinating system change
in child welfare agencies with primary health care and other organisations.
Implications for policy and research are discussed. (C) 2015 The Authors. Child
Abuse Review published by John Wiley & Sons Ltd.
The present study investigated the predictive utility of self-reported domestic
violence perpetrators' exposure to violence in their family of origin and patterns
related to this exposure through the use of longitudinal analyses on a sample of
228 men on probation in Lake County, Illinois. Differences in typology, recidivism,
recidivism frequency, and violent behavior survival patterns in men with a history
of domestic violence perpetration and with varying levels of family of origin
violence exposure were examined. Findings suggest that those who witnessed
interparental violence (either alone, or in combination with experiencing violence)
were most likely to be classified as Generally Violent offenders (e.g.,
perpetrators who direct violence toward their family and others), compared to those
who did not report experiencing or witnessing violence. In addition, results also
indicate that men who experienced both witnessing interparental violence and
receiving physical abuse in childhood were more likely to recidivate more
frequently compared to those who did not report experiencing or witnessing
violence. No significant findings for typology and recidivism were noted. Clinical
and policy/practice implications are discussed. (C) 2016 Elsevier Ltd. All rights
reserved.
Aim: The dengue virus is responsible for a high worldwide incidence of infections,
aggravated by late diagnosis, and often confused with other tropical diseases.
Results/methodology: Oligonucleotide aptamers binding to the 5'-UTR from dengue
virus selected after eight rounds by systematic evolution of ligands by exponential
enrichment technology were analyzed by dot-blot assay and in silico prediction of
secondary structures, demonstrating the presence of stem-loops that may have the
potential for interaction with the viral genome, which can lead to loss of their
original conformation. Conclusion: This is the first description of RNA aptamers
against functional RNA elements of the dengue virus genome with implications for
disease control, which may have potential as tools in the future of antiviral
therapies and for diagnostics.
Based on the orthogonal superposition theorem of three alternating magnetic
components, a universal uniform magnetic spin vector is superimposed using tri-
axial Helmholtz coils, achieving successive digital control of the orientation, the
rotational speed, and the magnetic flux density of the universal magnetic spin
vector. For increasing the magnitude and orientation accuracy of the magnetic spin
vector, this paper presents a mathematical model associated with the magnitude
error and orientation error of the universal magnetic spin vector, along with a
double error compensation method for the magnitude and orientation of the universal
magnetic spin vector superimposed by three alternating magnetic components. The
double error compensation method includes the current magnitude compensation by
three different structural coefficients of tri-axial Helmholtz coils and the
current phase compensation by two relative phase differences under linear
polarization. The results have shown that the double compensation method can
increase the magnitude and orientation accuracy of the rotating magnetic vector
effectively, which would achieve an accurate posture adjustment and steering
control on the capsule robots in curving environment.
Replacement of beef by buffalo and vice versa is frequent in global markets, but
their authentication is challenging in processed foods due to the fragmentation of
most biomarkers including DNA. The shortening of target sequences through use of
two target sites might ameliorate assay reliability because it is highly unlikely
that both targets will be lost during food processing. For the first time, we
report a tetraplex polymerase chain reaction (PCR) assay targeting two different
DNA regions in beef (106 and 120-bp) and buffalo (90 and 138-bp) mitochondrial
genes to discriminate beef and buffalo in processed foods. All targets were stable
under boiling, autoclaving and microwave cooking conditions. A survey in Malaysian
markets revealed 71% beef curries contained buffalo but there was no buffalo in
beef burgers. The assay detected down to 0.01 ng DNA and 1% meat in admixed and
burger products. (C) 2016 Elsevier Ltd. All rights reserved.
Background: The double-blind, placebo-controlled food challenge (DBPCFC) is
considered the definitive diagnostic test for food allergy. Nevertheless, validated
recipes for masking the foods are scarce, have not been standardized, and differ
between centers. Sensory evaluation techniques such as the triangle test are
necessary to validate the recipes used for DBPCFC. Methods: We developed 3 recipes
for use in DBPCFC with milk, egg white, and hazelnut and used the triangle test to
validate them in a 2-phase study in which 197 volunteers participated. In each
phase, participants tried 3 samples (2 active-1 placebo or 2 placebo-1 active) and
had to identify the odd one. In phase 1, the 3 samples were given simultaneously,
whereas in phase-2, the 3 samples of foods that failed validation in phase 1 were
given sequentially. A visual analog scale (VAS) ranging from 1 to 10 was used to
evaluate how much participants liked the recipes. Results: In phase 1, the egg
white recipe was validated (n=89 volunteers, 38.9% found the odd sample, P=.16).
Milk and hazelnut recipes were validated in phase 2 (for both foods, n=30
participants, 36.7% found the odd sample, P=.36). Median VAS scores for the 3
recipes ranged from 6.6 to 9.7. Conclusions: We used sensory testing to validate
milk, egg white, and hazelnut recipes for use in DBPCFC. The validated recipes are
easy to prepare in a clinical setting, provide the equivalent of 1 serving dose,
and were liked by most participants.
This paper is concerned with the design of a self-scheduled current controller for
doubly fed induction machines. The design is based on the framework of linear
parameter-varying systems where the mechanical angular speed is considered to be a
measurable time-varying parameter. The objective is to obtain robust dynamic
performance for all variations of the mechanical rotor speed in a specified
operating range. Employing the benefits of digital control, a continuous-to-
discrete time transformation is utilized to replace the continuous-time current
controller by an approximating discrete-time controller. Experimental results are
provided to demonstrate the performance and robustness of the controlled system
with respect to changes of the mechanical rotor speed and against stator voltage
dips.
Some children with Down syndrome may experience difficulties in recognizing facial
emotions, particularly fear, but it is not clear why, nor how such skills can best
be facilitated. Using a photo-matching task, emotion recognition was tested in
children with Down syndrome, children with nonspecific intellectual disability and
cognitively matched, typically developing children (all groups N = 21) under four
conditions: veridical vs. exaggerated emotions and emotion-labelling vs. generic
task instructions. In all groups, exaggerating emotions facilitated recognition
accuracy and speed, with emotion labelling facilitating recognition accuracy.
Overall accuracy and speed did not differ in the children with Down syndrome,
although recognition of fear was poorer than in the typically developing children
and unrelated to emotion label use. Implications for interventions are considered.
Solar energy has an enormous potential to solve society energy needs in a
sustainable way. Notably, photovoltaic systems (PV) permit to obtain electricity
based on solar energy. However, some issues must be addressed to establish PV as a
reliable source of electrical power, for example, its low energy density. One of
the approaches to improve the performance of PV systems is to utilize the solar
spectrum in solar cells efficiently. Downconversion (DC) is a process where a high
energy photon is converted into two or more photons with lower energy. Trough
downconversion is possible to use a wider portion of the solar spectrum raising the
efficiency in different kinds of solar cells. The present paper reviews the state
of the art of materials and methods used to take advantage of downconversion
processes in solar cells. Here we discuss some of the pros and cons of different
designs in solar cells as well as the main characteristics of the materials
utilized.
Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool
for cancer diagnosis and therapy. In the present study MCS nanogels were prepared
by Myristate: Chitosan at 1: 9 ratio and were characterized by several techniques.
A selected ssDNA aptamer (Apt) capable of detecting LNCaP cells was linked to
Myristilated Chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded with
Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate cancer
cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the binding
efficiency was estimated by flow cytometry. The binding affinity of the selected
aptamers was above 70% compared to the initial library. The loading capacity of the
nanogel was as high as 97% and up to 40% of DOX were released from MCS within 15
days. Cytotoxicity of nanodrug on LNCaP cells was determined by MTT assay. Apt-MCS-
DOX was specifically binded to LNCaP cells whereas it didn't show any specificity
to PC-3 cells as a negative control. Both MCS-DOX and Apt-MCS-DOX showed a lethal
effect on LNCaP cells. Our results can lead to an aptamer based simple and
applicable technique for early diagnosis and treatment of cancerous cells.
Cancer is currently treated by a combination of therapies, including chemotherapy
which is believed to suppress the immune system. Combination of immunotherapy and
chemotherapy correlates with improved survival but needs careful planning in order
to achieve a synergistic effect. In this study, we have demonstrated that
doxorubicin treatment of B cells resulted in increased expression of CD86 and
concordantly increased CD4(+) T cell activation in the presence of superantigen, an
effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore,
doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-
10 and TNF-alpha. Finally, B cells from urinary bladder cancer patients, treated
with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-
expression. We conclude that doxorubicin induces CD86 expression on B cells and
hence enhances their antigen-presenting ability in vitro, a finding verified in
patients. Development of tailored time and dose schedules may increase the
effectiveness of combining chemotherapy and immunotherapy. (C) 2016 Published by
Elsevier Inc.
Facile probing organic solvents is attracting intense attention due to the growing
environmental issues. Herein, for the first time, we report a novel D-pi-A
structured methanol responsive fluorescence molecule (TTO), synthesized by coupling
triphenylamine (electron-donor) and p-toluenesulfonyl (electron-acceptor) via Cu
(I) catalytic 1,3-dipolar cycloaddition (click chemistry) forming a triazole
bridge. Density functional theory (DFT) calculations and X-ray single crystal
structure reveal that TTO has a highly twisted conformation and unique D-pi-A
structure which render it exceptional optical properties. TTO exhibits strong
fluorescence in methanol (QE>0.67) but weak fluorescence in other organic solvents
(QE<0.1) including various alcohols and can be used as a highly selective
fluorescence probe for methanol identification. Notably, TTO is able to excellently
probe methanol from its homologue ethanol in water with a detection limit of below
0.7% (volume concentration), which demonstrates the promise potential of TTO for
practical applications. (C) 2017 Elsevier B.V. All rights reserved.
In this study, a specific and sensitive method for simultaneous detection of human
astrovirus, human rotavirus, norovirus, sapovirus and enteric adenovirus associated
with acute enteritis was developed, based on the specific dual priming
oligonucleotide (DPO) system and the sensitive high-performance liquid
chromatography (HPLC) analysis. The DPO system-based multiplex reverse
transcription-polymerase chain reaction (RT-PCR) combined with HPLC assay was more
sensitive than agarose gel electrophoresis analysis and real-time SYBR Green PCR
assay, and showed a specificity of 100% and sensitivity of 96%-100%. The high
sensitivity and specificity of the assay indicates its great potential to be a
useful tool for the accurate diagnosis of enteric virus infections. (C) 2017
Elsevier B.V. All rights reserved.
Surface characteristics play a special role for the biological performance of
implants and several strategies are available to this end. The OGI (Osteo Growth
Induction) titanium surface is a surface, obtained by applying a strong acid onto
the blasted surface. The aim of this in-vitro study is to evaluate in vitro the
osteoproperties of OGI surfaces on Mesenchymal Stem cells derived from dental pulp.
Our results confirm that this treatment exert a positive effect on mitochondrial
homeostasis, as shown by a decrease in ROS production related to environmental
stress on the mitochondria. Morphological and molecular biology analyses confirmed
more over that the DPSC cultured on the OGI surfaces appeared more spread in
comparison to those grown on control titanium surface and real time PCR and
biochemical data clearly demonstrated the increase of osteoconductive properties of
the OGI treatment. In conclusion, our results suggest that mesenchymal stem cells
sensitively respond to surface properties related to OGI treatment enhancing their
osteogenic activities. (C) 2016 Elsevier B.V. All rights reserved.
Duck plaque virus (DPV) belongs to the family Herpesviridae. The live attenuated
vaccine is the only way to protect the ducks from DPV infection. The
ineffectiveness of vaccine is one of the major causes of DPV outbreaks in the field
condition. DPV is not well characterized for its pathogenicity and molecular
biology in poultry. In the present study, we discuss briefly about the biology of
DPV and its proteins under different conditions of temperature and pH in order to
evaluate its infectivity under adverse physical conditions. Our results indicate
that the DPV is non-infective above 42 degrees C and unstable above 65 degrees C.
In addition, change in pH or salt concentrations significantly decreases the
stability of the DPV. The study will be useful in estimating an optimum storage
condition for DPV vaccines without causing any deterioration in its viability and
effectiveness. (C) 2016 International Alliance for Biological Standardization.
Published by Elsevier Ltd. All rights reserved.
While digital control has achieved success in various power electronic
applications, data conversion remains a primary challenge and limitation compared
to conventional analog methods. In particular, tradeoffs among resolution,
switching frequency, and power consumption of digital pulse-width modulation (DPWM)
blocks limit performance, particularly in high conversion-ratio applications.
Analog-digital conversion is also challenging when line-voltage feedforward
techniques are applied as it requires high speed, accuracy, and in some cases
exposure to voltages exceeding the rating of deep-submicron CMOS technologies. This
work explores tradeoffs in power consumption of counter/delay-line DPWM circuits,
implemented in CMOS, and derives an optimization method to segment the bit
allocation among the counter and delay line components. A method for line-voltage
feedforward is also presented that can instrument and quantize transients on the
supply voltage without direct exposure of low voltage devices to the supply. An
automotive 48V:7V application is considered.
Development of effective monitoring systems of power exchange fluctuations and
proportional alignment of loading on gas-diesel-generator units requires carrying
out detailed researches both their own fluctuations, and exchange fluctuations in
case of parallel work of several units. Carrying out such researches on real
objects is limited to their considerable cost and can be given only at the final
stage. Therefore it is very important for developers to have adequate models of the
studied objects. The researches of output voltage frequency fluctuations for real
objects executed by authors showed that in general they have casual character, and
these fluctuations in all range of loadings represent non-stationary casual process
with the changing population mean and dispersion. Authors developed mathematical
model of the regulator stabilizing exchange fluctuations of power in the studied
system. But there was a question of its hardware realization because it requires
solving the problem of identification of the structure of this system and on-line
monitoring of changes in its parameters and signals. The authors have proposed a
candidate solution for such a problem through the example of identification and
synthesis of the system of measuring system performance indicators required to
appraise the electric power quality in this system and, as consequence, performance
quality.
Biofilm detachment caused by flushing can result in secondary contamination in
drinking water distribution systems (DWDSs). To evaluate the impact of flushing on
biofilm detachment, actual water supply pipes including ductile cast iron pipes
(DCIPs), gray cast iron pipes (GCIPs), and stainless steel compound pipes (SSCPs)
were used in this study. Real-time quantitative polymerase chain reaction and 454
pyrosequencing were used to quantify bacteria and analyse microbial community
composition, respectively. The results showed that the pipe material greatly
influences the resistance of a biofilm to flushing. Biofilms attached to DCIPs were
able to resist quite strong flushing, while those attached to GCIPs and SSCPs were
sensitive to flushing. Both flush-resistant and flush-sensitive bacteria were
present in all the biofilms, but their frequency differed among the different metal
pipes. Thus, the resistance to flushing of bacteria is related not only to the
nature of the bacteria, but also to the pipe material. Although flushing can remove
some of the biofilm and may be a good way to clean the DWDS, the shear stress
needed to remove the biofilm differs among different pipe types. The results of
this study provide technical support for the management and operation of DWDS.
Vehicle driveability describes the complex interactions between the driver and the
vehicle, mainly related to longitudinal vibrations. Today, a relevant part of the
driveability process optimisation is realised by means of track tests, which
require a considerable effort due to the number of parameters (such as stiffness
and damping components) affecting this behaviour. The drawback of this approach is
that it is carried on at a stage when a design iteration becomes very expensive in
terms of time and cost. The objective of this work is to propose a light and
accurate tool to represent the relevant quantities involved in the driveability
analysis, and to understand which are the main vehicle parameters that influence
the torsional vibrations transmitted to the driver. Particular attention is devoted
to the role of the tyre, the engine mount, the dual mass flywheel and their
possible interactions. The presented nonlinear dynamic model has been validated in
time and frequency domain and, through linearisation of its nonlinear components,
allows to exploit modal and energy analysis. Objective indexes regarding the
driving comfort are additionally considered in order to evaluate possible
driveability improvements related to the sensitivity of powertrain parameters.
With the development of economic globalization, the cultivation of minority
secretary major should follow the principle of compound talents training mode and
improve the overall quality of the talent of minority secretary major. Secretary
major training plan has shortage of teaching content and lacks cross-cultural
communication training program. Its teaching mission objectives is not new and
secretary professional competence of teachers are not enough and the teaching
method is too traditional and curriculum is unreasonable. Based on this situation,
the paper does the digitization DRM solutions using the DRM digital control program
based on multivariate intelligent teaching reform program of talent training. This
paper establishes and develops the ODRL talent model and achieves the segmentation
description and dynamic segmentation authorization of tasks and contents of
minority secretary major secretary courses. It also achieves the secondary
development of DRM under the ODRL control model and verifies the feasibility and
reliability of the training mode using the teaching effect evaluation method of
OpenAPI, which provides a reliable theoretical basis for the reform of minority
secretary major training model.
Background: In many parts of the Old World, domesticated camels (genus - Camelus)
are an essential resource, providing food, labor, commodities, and sport to
millions of people Of the three extent species, two have been domesticated (single-
humped dromedarius, Camelus dromedarius, and two humped Bactrian camels Camelus
bactrianus) and one remains wild (two-humped wild Bactrian camels Camelus ferus).
All three species possess a variety adaptations to harsh desert conditions,
including mechanisms to tolerate of extreme temperatures, dehydration, and sandy
terrain. People residing in harsh climate zones of the world are being benefitted
by raising camels in terms of draft, milk, meat, hides and wool from centuries.
There are different breeds of dromedary camels distributed in various parts of
Pakistan; however there have been scarcity of research work on camels in Pakistan.
Identification of novel link between Camel breeders with fatal neurodegenerative
disorders is presence or not can be detect by a Prion gene and it was not carried
out in Pakistan soil to date. Prion diseases which are a group of fatal
neurodegenerative disorders affect both animals and humans. It is believed that the
prions are infectious agents responsible for transmissible spongiform
encephalopathies. In this study we report the first study on Prion protein gene in
dromedary camels of Pakistan. Material, Methods & Results: Genes are the blueprint
of life and determine the functional aspects of cellular mechanisms. Genomic DNA of
the enrolled blood samples was extracted using the Nucleospin((R)) DNA extraction
kit. Genomic DNA was run on Agarose gel electrophoresis, checked the Genomic DNA
quality and amplified using prion region specific primer pair. Prion protein gene
was amplified (770 bp) in 35 individuals of seven dromedary camel breeds from the
province Balochistan and Punjab of Pakistan. Samples having required fragment size
were selected and sent for sequencing through Sanger Sequencing. All the sequences
were aligned through multiple sequence alignment and edited using Codon Code
aligner and explored for phylogenetic analysis. A portion of 667 bp was finally
selected for phylogenetic analysis of dromedary camels from Pakistan with 61
different mammalian species (drawn from GenBank) that revealed five different
clades. We found 99.9% nucleotide sequence similarities among Dromedary camels
(Germany), Dromedary camels (Iran), and Dromedary camels (Pakistan). We observed
deletion in dromedary camels in codon region 66-69 except wild Bactrian camels that
might be the causative factor for Prion protein gene resistance in camels. The
Neighbor-Joining method with bootstrap analysis of 1000 replicates was used to draw
phylogenetic tree. Discussion: This study documents the presence of 14 PrP
polymorphisms and shows the relationship between different camel breeds. The
deletion had not previously been examined PrP allelic variation, and was found to
segregate in these breeds. However, additional data are necessary to demonstrate
PrP and genetic approach will be ideal for the future studies and, more
investigations are necessary to demonstrate PrP genetic resistance in camels. The
utility of these techniques in identifying Prion genes and selecting superior
animals and culling the weak animals and making them parents of the next generation
that will lead to producing more meat and milk with fewer animals are well
discussed and by slaughtering of high Prion incidence will eliminate human animal
fatal neurodegenerative disorders.
Three novel small noncoding RNAs were identified from the conserved intronic
regions of D. melanogaster by using comparative genomics method and molecular
biology approach. One is a novel snoRNA in a combinated way, which displays
structural features typical of C/D box snoRNA family and possesses a 10-nt-long
rRNA antisense element for guiding the 2'-O-methylation of the D. melanogaster 28S
rRNA at C2673. The other two are miRNAs whose predicted precursors adopt a stem-
loop structure characteristic of known miRNA. The two miRNAs genes appear to have
ubiquitous expression profiles with similar to 23-nt RNA transcripts detected by
Northern blotting. Our study revealed 396 multi-species intronic conserved
sequences (MCIS) that nested in the introns with a length from 100 to 500 bp. In
addition to small RNA coding, the MCIS might function as cis-acting elements
involved in gene transcription or post-transcriptional processing.
An H+-PPase gene, TsVP from Thellungiella halophila, was transferred into two
cotton (Gossypium hirsutum) varieties (Lumianyan19 and Lumianyan 21) and southern
and northern blotting analysis showed the foreign gene was integrated into the
cotton genome and expressed. The measurement of isolated vacuolar membrane vesicles
demonstrated that the transgenic plants had higher V-H+-PPase activity compared
with wild-type plants (WT). Overexpressing TsVP in cotton improved shoot and root
growth, and transgenic plants were much more resistant to osmotic/drought stress
than the WT. Under drought stress conditions, transgenic plants had higher
chlorophyll content, improved photosynthesis, higher relative water content of
leaves and less cell membrane damage than WT. We ascribe these properties to
improved root development and the lower solute potential resulting from higher
solute content such as soluble sugars and free amino acids in the transgenic
plants. In this study, the average seed cotton yields of transgenic plants from
Lumianyan 19 and Lumianyan 21 were significantly increased compared with those of
WT after exposing to drought stress for 21 days at flowering stage. The average
seed cotton yields were 51 and 40% higher than in their WT counterparts,
respectively. This study benefits efforts to improve cotton yields in arid and
semiarid regions.
Drug courts were implemented nationwide during the 1990s to expand alternatives to
incarceration for individuals with substance use disorders that were charged with
nonviolent felonies or misdemeanors. Although these courts were publicized as a
facilitator of treatment and alternative to incarceration, researchers and
advocates have suggested that this approach may have unintentionally intensified
law enforcement focus on casual drug users and individuals with minor substance
dependency. The primary objective of this study was to determine whether there is
evidence that drug courts systemically increased the arrest and punishment of
misdemeanor drug use and possession by conducting a series of panel data analyses
among more than 8,000 city and county jurisdictions while controlling for economic,
demographic, and nationwide law enforcement trends. Analyses in this study provide
evidence that local police increased their attention toward minor drug offenses in
jurisdictions where drug courts were implemented across the nation.
Exosomes are naturally occurring extracellular vesicles released by most mammalian
cells in all body fluids. Exosomes are known as key mediators in cell-cell
communication and facilitate the transfer of genetic and biochemical information
between distant cells. Structurally, exosomes are composed of lipids, proteins, and
also several types of RNAs which enable these vesicles to serve as important
disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery
tools owing to their multiple advantages over conventional delivery systems.
Recently, increasing attention has been focused on exosomes for the delivery of
drugs, including therapeutic recombinant proteins, to various target tissues.
Exosomes are also promising vehicles for the delivery of microRNAs and small
interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as
well as inefficient tissue specificity of currently available delivery strategies.
This review highlights the most recent accomplishments and trends in the use of
exosomes for the delivery of drugs and therapeutic RNA molecules.
Background: Theory of mind concerns the sociocognitive ability to infer others'
thoughts. It has been theorized to be impaired in substance use and abuse, as its
alterations might explain negative social and interpersonal outcomes noted in the
course of disorders. In addition, the brain structures involved in Theory of Mind
(ToM) have been found to be disrupted in drug use conditions. Objective: We
undertook a systematic review of ToM functioning in drug use conditions. Methods:
Four electronic databases (MEDLINE, Web of Science, PsycINFO, and Embase) were
searched to find studies that have addressed ToM and conditions related to actual
or previous drug use. Results: The search found 147 papers, of which 14 fulfilled
our review eligibility criteria. Different methods were used, but overall, results
indicated that drugs are related to ToM deficits, particularly related to alcohol
and amphetamines use. These impairments correlate with other clinical and cognitive
functions. Conclusion: Despite the lack of studies and the methodological
limitations of the existing ones Theory of Mind seems to play a role in drug use
conditions, which requires further investigation.
Purpose of reviewTo highlight recent advances in the understanding of nutritional
immunology and in the development of novel therapeutics for inflammatory bowel
disease (IBD).Recent findingsWe highlight the variety of factors that contribute to
the interaction of the immune system and nutrition including the microbiome and the
nervous system stimulation of the gut. We describe the potential for therapeutic
development in IBD. Further, we review the cellular metabolic effects on immune
activation and promising therapeutic targets. Finally, we show how the progression
of understanding the role of lanthionine synthetase C-like 2 has encompassed both
nutritional and therapeutic advances and led to the development of novel oral small
molecule therapeutics for IBD.SummaryNutritional immunology and drug development
research centered around immunoregulatory pathways can provide safer and more
effective drugs while accelerating the path to cures.
Protein-protein interactions are fundamental for virtually all functions of the
cell. A large fraction of these interactions involve short peptide motifs, and
there has been increased interest in targeting them using peptide-based
therapeutics. Peptides benefit from being specific, relatively safe, and easy to
produce. They are also easy to modify using chemical synthesis and molecular
biology techniques. However, significant challenges remain regarding the use of
peptides as therapeutic agents. Identification of peptide motifs is difficult, and
peptides typically display low cell permeability and sensitivity to enzymatic
degradation. In this review, we outline the principal highthroughput methodologies
for motif discovery and describe current methods for overcoming pharmacokinetic and
bioavailability limitations.
Pancreatic cancer represents one of the most aggressive types of malignancy due to
its high resistance toward most clinically available treatments. The presence of
pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically
high resistance and highly metastatic potential of this disease. Here, we
identified and isolated pancreatic CSCs using the side population (SP) method from
human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-
1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced
self-renewal ability, increased metastatic potential, and resistance toward
gemcitabine treatment. These cancer stem-like phenotypes were supported by their
enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived
antioxidant, garcinol, has been implicated for its anticancer properties. Here, we
found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-
like properties of PANC-1 SP cells and metastatic potential by downregulating the
expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol
treatment led to the upregulation of several tumor suppressor microRNAs, and miR-
200c increased by garcinol treatment was found to target and downregulate Notch1.
Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic
CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs. (C)
2015 International Union of Biochemistry and Molecular Biology, Inc.
Purpose of review Endometrial cancer incidence is increasing in North America and
is a major cause of morbidity and mortality in women. We review recent literature
published on treatment of endometrial cancer and highlight areas of active
interest. Recent findings There has been movement toward minimal invasive surgery
at diagnosis; lymph node staging remains controversial and continues to be
investigated. Progress has been made to establish consensus on endometrial cancer
risk classification to promote consistency for future trial design. Molecular
characterization of endometrial cancer and its integration into clinicopathological
profiling to develop predictive biomarkers for treatment selection are active areas
of research. Optimal adjuvant treatment strategy in high-risk endometrial cancer
remains to be defined with recognition of treatment-related toxicity. Despite
encouraging results in drug development for treatment of advanced/recurrent
endometrial cancer, no targeted therapies beyond hormonal therapy are approved.
There is an urgent need for scientifically validated therapy with predictive
biomarkers. Summary Our understanding of endometrial cancer has evolved through
improvements in molecular biology, allowing improved definition of target-specific
therapies. The precise role and sequence of conventional and targeted therapies,
including immunotherapy, will require careful attention to the design of clinical
trials with translational emphasis to allow the discovery, validation, and
implementation of predictive biomarkers into clinical care.
PurposeTo investigate tear film stability and secretion according to serum 25-
hydroxyvitamin D3 [25(OH)D] levels in dry eye patients. MethodsIn this
retrospective observational study, the medical charts of 92 patients who visited
the Department of Ophthalmology at Hallym University Kangnam Sacred Heart Hospital
from April to August 2015 were reviewed. Serum 25(OH)D levels were measured.
Subjects were divided into three groups according to serum 25(OH)D levels:
sufficient, inadequate or deficient group. Eye discomfort was measured by ocular
surface disease index (OSDI). Tear break-up time (TBUT), fluorescein staining score
and Schirmer's tear secretion test were measured. ResultsThe mean age was
53.3813.69years. Mean serum 25(OH)D level was 14.41 +/- 5.98ng/ml. Tear break-up
time (TBUT) and tear secretion were positively correlated with serum 25(OH)D levels
(r=0.389, p=0.001; and r=0.428, p<0.001, Pearson correlation test). Tear break-up
time (TBUT) and tear secretion were shorter in the vitamin D-deficient group
compared to the sufficient group (p=0.022 and p=0.004). Fluorescein staining scores
and OSDI scores were not different between the three groups. ConclusionTear break-
up time (TBUT) and secretion were correlated with serum vitamin D levels. Vitamin D
status may be an important factor for dry eye syndrome.
The division-summation (D-Sigma) current control and one-cycle voltage regulation
(OCVR) of a 5-kW surface-mounted permanent-magnet synchronous generator (SPMSG)
drive is developed. With the advancement of motor manufacturing, motor design,
digital control units and power electronics converters, the permanent-magnet
synchronous generator (PMSG) is broadly applied to electric vehicles, hybrid
electric vehicles, flywheel energy storage system and wind power generators.
Satisfactory current control scheme of a PMSG is significant to achieve desired
generating performance. The D-Sigma current control is proposed and derived from
the conventional space-vector modulation and two-phase modulation. A simplification
of the complex self-and mutual inductances in a PMSG is demonstrated. The proposed
current control can achieve the current waveform tracking through the
simplification of winding inductances without parameter designing procedure of the
feedback controller. The computation time of the microcontroller is reduced via the
proposed current control scheme. The processing times of the conventional control
and the D-Sigma control are compared. Moreover, the dc-link voltage can be well
regulated by the proposed OCVR. This method can reduce the complexity of the
voltage controller design. The merits of these two methods are easy to implement
and the parameter designing procedure of the feedback controller is unnecessary. In
addition, the system stability and the parameter sensitivity are analyzed and
evaluated. Some measured waveforms verify the current tracking, torque ripple,
dynamic performance and voltage regulation of the SPMSG drive. The reduction of the
switching losses is verified by the calculation results.
This paper presents a three-phase transformerless uninterruptible power supply
(UPS) with sinusoidal pulse width modulation (SPWM) based division-summation (D-
Sigma) digital control. A transformerless UPS controls the power flow between dc
link and utility grid, as well as tracks the ac reference voltage. The proposed
control law derived with D-Sigma digital approach takes into account the effects of
dc-link voltage fluctuation, grid-voltage distortion and inductance variation due
to different current levels. Thus, distortion of input current and filter inductor
core size can be reduced significantly. However, circulating current may flow
through the common ground between the input power factor corrector (PFC) and the
output three-phase four-wire inverter. The derived control law based on SPWM can
suppress this circulating current and regulate output voltages tightly.
Experimental results measured from a three-phase transformerless UPS have confirmed
the analysis and discussion of the proposed control approach.
A division-summation (D-Sigma) digital control for three-phase inverters to achieve
active and reactive power injection has been presented. It can overcome the
limitation of abc to dq frame transformation. However, the D-Sigma control requires
four sets of control laws to cover four quadrant operations, namely, grid
connection (power factor (PF) 1 similar to +/- 0.866), rectification with PF
correction, PF leading (0 similar to 0.866), and PF lagging (0 similar to-0.866).
Moreover, the switching sequences for the four modes are also different from each
other, increasing complexity of firmware programming. In this paper, improvement of
the control law derivation and region selection for the D-Sigma digital control is
presented. By selecting the zero-crossing points of phase voltages as region
transitions, the control laws and the related parameter tables for the four modes
can be unified to a general form. The switching sequences of the four modes are
also unified to the switching pattern of the grid-connectionmode. Additionally, a
D-Sigma transformation matrix is identified to simplify the derivation procedure of
the division (D) and summation (Sigma), which can obtain the control law directly.
Measured results from a 10-kVA 3 phi bidirectional inverter have been presented to
confirm the improvement.
This paper presents a division-summation (D-Sigma) digital control based modular
multilevel converter. Modular multilevel converters (MMC) have been applied to
static synchronous compensators (STATCOM), high-voltage direct-current transmission
(HVDCT), back-to-back power transfer systems, wind/solar power generation and
battery storage systems. The D-Sigma digital control is adopted to track current
reference, balance dc-bus capacitor voltage and regulate cell module capacitor
voltage. The adopted D-Sigma digital control can accommodate wide filter inductance
variation and take care of source voltage harmonics to achieve fast tracking
response and low-distortion output current for the applications of active and
reactive power injection and rectification with power factor correction. Based on
power-balance principle, the combination of dc offset current and the ac current of
each arm can be determined. According to charge-balance principle and with the D-
Sigma digital control, dc-bus capacitor voltage balancing and cell voltage
regulation can be achieved. To ensure the output current with low harmonics, a
limitation factor for cell voltage regulation is discussed. In the paper, the MMC
configuration is introduced first, and then the control laws for current tracking
and voltage regulation are derived in detail. Simulated and experimental results
obtained from a 54 kW MMC have verified the analysis and discussion.
Previous findings on the diagnostic validity and reliability of generalized anxiety
disorder (GAD)-associated symptom criteria suggest need for further evaluation. The
current study examined convergent validity and specificity of GAD-associated
symptoms in a representative Singapore community sample. The Singapore of Mental
Health Study a cross-sectional epidemiological survey conducted among 6166
Singapore residents aged 18 and older. The Composite International Diagnostic
Interview version 3.0 was used to diagnose mental disorders. Associated symptoms in
the GAD criteria and autonomic hyperactivity symptoms showed convergent validity
with a GAD diagnosis. However, associated symptoms of GAD were also linked to major
depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder,
suggesting lack of adequate specificity. The inability of the diagnostic criteria
to differentiate GAD from symptoms of other conditions highlights the need to
better define its associated symptoms criteria. The relationship of overlapping
symptoms between GAD and MDD is also discussed.
The control of UPS inverters has a special importance in applications where a high
quality output voltage is needed. Several control schemes have been proposed for
the control of three-phase inverter. This paper presents a simple and powerful
control scheme using model predictive control (MPC). It uses a discrete-time model
of the system to predict the behaviour of the output voltage for all possible
switching states generated by the inverter. Then, a cost function is used for
selecting the optimal switching state that will be applied at the next sampling
instant. The simulation results under linear and nonlinear loads are presented,
using MATLAB/Simulink tools, verifying the feasibility and good performance of the
proposed control scheme. Finally, experimental results are presented, using HIL
simulation, to verify the feasibility and good performance of the proposed MPC
under realistic conditions.
Design and implementation of a current controlled single stage single phase
integrated AC/DC isolated Power Factor Correction (PFC) converter is -presented in
this paper. With the integrated topology reduces the number control switches. The
proposed converter has the advantage of low bulk capacitor voltage and only single
control switch hence reduce in complexity in control and cost. Sub-harmonic
oscillations which are produced in conventional current controller. By adding an
external compensating signal effect of oscillations are reduced and performance of
the converter is improved. The proposed scheme is implemented in real time by
TMS320F2812 digital signal processor (DSP) board. The performance of converter is
verified both experimentally and by simulation at different load and line
conditions. The proposed converter is designed for 90-230 V, 50 Hz AC input, 48 V
DC output and operating at 100 kHz switching frequency. The Experimental results
shows that the DSP-based fuzzy controlled single phase single switch integrated PFC
converter achieve high power factor and satisfies IEC-61000-3-2 and other European
input current harmonic limits for Class-C & Class-D applications.
Viruses with segmented RNA genomes must package the correct number of segments for
synthesis of infectious virus particles. Recent studies suggest that the members of
the Reoviridae family with segmented double-stranded RNA genomes achieve this
challenging task by forming RNA networks of segments prior to their recruitment
into the assembling capsid albeit direct evidence is still lacking. Here, we
investigated the capability of virus recovery by preformed complexes of ten RNA
segments of Epizootic Haemorrhagic Disease Virus ( EHDV), a Reoviridae member, by
transcribing exact T7 cDNA copies of genomic RNA segments in a single in vitro
reaction followed by transfection of mammalian cells. The data obtained was further
confirmed by RNA complexes generated from Bluetongue virus, another family member.
Formation of RNA complexes was demonstrated by sucrose gradient
ultracentrifugation, and RNA-RNA interactions inherent to the formation of the RNA
complexes were demonstrated by electrophoretic mobility shift assay. Further, we
showed that disruption of RNA complex formation inhibits virus recovery, confirming
that recruitment of complete RNA networks is essential for packaging and
consequently, virus recovery. This efficient reverse genetics system will allow
further understanding of evolutionary relationships of Reoviridae members and may
also contribute to development of antiviral molecules.
Rice false smut caused by Ustilaginoidea virens is a destructive disease in many
rice-growing areas. Mycoviruses have been described in many fungal species, but
there is little information regarding mycoviruses in U. virens. In this study,
double-stranded (ds) RNA banding patterns were assessed in 198 wild-type isolates
of U. virens obtained from different geographical regions in China. The presence of
viral infections was unusually common in U. virens: 188 of the 198 isolates
contained dsRNA elements with viral characteristics, and the presence of mixed
infections with two or more related or unrelated mycoviruses was commonly detected.
The GX-1 isolate contained four dsRNA mycoviruses: Ustilaginoidea virens RNA virus
1 (UvRV1) belonging to Totiviridae, Ustilaginoidea virens RNA virus 4 (UvRV4)
belonging to an unclassified family which includes the Curvularia thermal tolerance
virus, and the last two probably belonging to Partitiviridae. Biological
comparisons of virus-free and infected fungal isolates revealed that UvRV1 strain
GX-1 and UvRV4 were likely cryptic, since the infected strains did not show
apparent symptoms or debilitation. Northern blotting experiments revealed that
UvRV1 strain GX-1 and UvRV4 were frequently found in U. virens, irrespective of the
place of origin, and similarly sized dsRNA bands were not always of similar
sequence. Thus, our findings suggest that mycoviruses infecting U. virens in China
are widespread and highly diverse. (C) 2014 Elsevier B.V. All rights reserved.
The dual active bridge (DAB) converter has been widely used in the distributed
power systems and the energy storage devices. However, the inherent nonlinearity of
the DAB converter can cause serious stability problem. In this paper, the dynamics
of a digital controlled DAB converter with output voltage closed loop control is
studied. Firstly, to accurately study the nonlinear dynamics and stability in a DAB
converter, a full discrete-time model for the DAB converter is established. The
model considers the ESR of the output capacitor and also considers the digital
control delay and sample-and-hold process. Using this model, the stability of the
DAB converter versus the parameter of the proportional controller is analyzed and
the stability boundary is accurately predicted. Further, this paper also points out
that the ESR of the output capacitor can bring a great effect to the stability of
the system. Finally, simulation and experimental results verify the theoretical
analysis.
The concepts expressed by social role terms such as artist and scientist are unique
in that they seem to allow two independent criteria for categorization, one of
which is inherently normative (Knobe, Prasada, & Newman, 2013). This study presents
and tests an account of the content and structure of the normative dimension of
these dual character concepts. Experiment 1 suggests that the normative dimension
of a social role concept represents the commitment to fulfill the idealized basic
function associated with the role. Background information can affect which basic
function is associated with each social role. However, Experiment 2 indicates that
the normative dimension always represents the relevant commitment as an end in
itself. We argue that social role concepts represent the commitments to basic
functions because that information is crucial to predict the future social roles
and role-dependent behavior of others.
Neuroscience investigations of emotional influences on social cognition have been
dominated by the somatic marker hypothesis and dual-process theories. Taken
together, these lines of inquiry have not provided strong evidence that emotional
influences on social cognition rely on neural systems which code for bodily signals
of arousal nor distinguish emotional reasoning from other modes of reasoning.
Recent findings raise the possibility that emotionally influenced social cognition
relies on two stages of neural changes: once when emotion is elicited and a
different set of changes at the time of social cognitive judgment. These findings
suggest that affect infusion models may be a fruitful framework for bridging
neuroscience and psychological understanding of the role of emotion in social
cognition.
Since the decision of non-price feature such as product quality draws a little
attention in the literature of dual-channel supply chains, this paper investigates
price and quality decisions in dual-channel supply chains, in which a single
product is delivered through a retail channel, a direct channel, or a dual channel
with both retail and direct channels. Considering the supply chains can be
centralized or decentralized, we demonstrate that quality improvement can be
realized when a new channel is introduced. Moreover, we employ two themes in terms
of channel-adding Pareto zone to characterize the impacts of channel structures on
supply-chain performance, including the whole system's profit (for the centralized
system), each player's profit (for the decentralized system), and consumer surplus.
When price and quality decisions are considered, we find the supply chain
performance could be improved due to a new channel augmented. Moreover, we show the
effects of the quality sensitivity parameters of different channels on price and
product quality, as well as profits and consumer surplus. (C) 2016 Elsevier B.V.
All rights reserved.
Hepatitis A virus is one of five types of hepatotropic viruses that cause human
liver disease. A similar liver disease is also identified in ducks caused by Duck
Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be
detected in urine. However, how those viruses enter into the urine is largely
unexplored. To elucidate the potential mechanism, we used the avian hepatotropic
virus to investigate replication strategies and immune responses in kidney until
280 days after infection. Immunohistochemistry and qPCR were used to detect viral
distribution and copies in the kidney. Double staining of CD4+ or CD8+ T cells and
virus and qPCR were used to investigate T cell immune responses and expression
levels of cytokines. Histopathology was detected by standard HE staining. In this
study, viruses were persistently located at scattered renal tubules. No CD4+ or
CD8+ T cells were recruited to the kidney, which was only accompanied by transient
cytokine storms. In conclusion, the extremely scattered infection was the viral
strategy to escape host immunity and may persistently shed virus into urine. The
deletion of Th or Tc cell responses and transient cytokine storms indeed provide an
advantageous renal environment for their persistent survival.
Purpose of review The review intends to describe recent studies on the development
of pancreatic cancer from a genetic, molecular, and microenvironment perspective.
Recent findings Pancreatic cancer has been discovered to have distinct molecular
subtypes based on transcriptome analyses that may have implications for treatment.
Recent studies are also mapping the complex molecular biology of this cancer as it
relates to the core signaling abnormalities inherent to this disease. There have
been discoveries of novel modes of regulation of pancreatic cancer development,
including alterations in key transcription factors, epigenetic modifiers, and
metabolic pathways. Studies of the tumor-associated microenvironment continue to
reveal its complex role in tumor development. Summary Pancreatic cancer development
appears to depend on a multifaceted network of signals that are dynamic, involve
multiple cell types, and are linked to spatiotemporal factors in tumor evolution.
Understanding the development of pancreatic cancer in this context is key to
identifying novel and effective targets for treatment.
Theileria spp. and Anaplasma spp., which are important tick-borne pathogens (TBP5),
impact the health of humans and animals in tropical and subtropical areas.
Theileria and Anaplasma co-infections are common in sheep and goats. Following
alignment of the relevant DNA sequences, two primer sets were designed to
specifically target the Theileria spp. 18S rRNA and Anaplasma spp. 16S rRNA gene
sequences. Genomic DNA from the two genera was serially diluted tenfold for testing
the sensitivities of detection of the primer sets. The specificities of the primer
sets were confirmed when DNA from Anaplasma and Theileria (positive controls),
other related hematoparasites (negative controls) and ddH2O were used as templates.
Fifty field samples were also used to evaluate the utility of single PCR and duplex
PCR assays, and the detection results were compared with those of the PCR methods
previously published. An optimized duplex PCR assay was established from the two
primer sets based on the relevant genes from the two TBPs, and this assay generated
products of 298-bp (Theileria spp.) and 139-bp (Anaplasma spp.). The detection
limit of the assay was 29.4 x 10(-3) ng per I, and there was no cross-reaction with
the DNA from other hematoparasites. The results showed that the newly developed
duplex PCR assay had an efficiency of detection (P >0.05) similar to other
published PCR methods. In this study, a duplex PCR assay was developed that can
simultaneously identify Theileria spp. and Anaplasma spp. in sheep and goats. This
duplex PCR is a potentially valuable assay for epidemiological studies of TBP5 in
that it can detect cases of mixed infections of the pathogens. (C) 2017 Elsevier
Inc. All rights reserved.
The temporal pole (TP) has been associated with diverse functions of social
cognition and emotion processing. Although the underlying mechanism remains
elusive, one possibility is that TP acts as domain-general hub integrating
socioemotional information. To test this, 26 participants were presented with 60
empathy-evoking film clips during fMRI scanning. The film clips were preceded by a
linguistic sad or neutral context and half of the clips were accompanied by sad
music. In line with its hypothesized role, TP was involved in the processing of sad
context and furthermore tracked participants' empathic concern. To examine the
neuromodulatory impact of TP, we applied nonlinear dynamic causal modeling to a
multisensory integration network from previous work consisting of superior temporal
gyrus (STG), fusiform gyrus (FG), and amygdala, which was extended by an additional
node in the TP. Bayesian model comparison revealed a gating of STG and TP on
fusiform-amygdalar coupling and an increase of TP to FG connectivity during the
integration of contextual information. Moreover, these backward projections were
strengthened by emotional music. The findings indicate that during social
cognition, TP integrates information from different modalities and top-down
modulates lower-level perceptual areas in the ventral visual stream as a function
of integration demands.
Time-domain simulations are heavily used in today's planning and operation
practices to assess power system transient stability, posttransient
voltage/frequency profiles as well as oscillatory behavior following severe
contingencies to comply with industry standards. Because of the increased modeling
complexity, it is many times slower than real time for state-of-the-art commercial
software packages to complete a dynamic simulation for a large-scale model. With
the growing stochastic behavior introduced by emerging technologies, power industry
has seen a growing need for performing security assessment in real time. This paper
presents an innovative parallel implementation framework to speed up a single
dynamic simulation by leveraging the existing stability model library in commercial
tools through their application programming interfaces (APIs). Several high
performance computing (HPC) techniques are explored and implemented such as
parallelizing the calculation of generator current injection, identifying fast
linear solvers for network solution, and parallelizing data outputs when
interacting with APIs in the commercial package, TSAT. The proposed method has been
tested on a Western Electricity Coordinating Council (WECC) planning base case with
detailed synchronous generator models and it exhibits outstanding scalable
performance with sufficient accuracy.
Conventional Organic Rankine Cycles (ORCs) using ambient air as their coolant
cannot fully utilize the greater temperature differential available to them during
the colder months. However, changing the working fluid composition so its boiling
temperature matches the ambient temperature as it changes has been shown to have
potential to increase year-round electricity generation. Previous research has
assumed that the cycle pressure ratio is able to vary without a major loss in the
isentropic efficiency of the turbine. This paper investigates if small scale ORC
systems that normally use positive-displacement expanders with fixed expansion
ratios could also benefit from this new concept. A numerical model was firstly
established, based on which a comprehensive analysis was then conducted. The
results showed that it can be applied to systems with positive-displacement
expanders and improve their year-round electricity generation. However, such an
improvement is less than that of the systems using turbine expanders with variable
expansion ratios. Furthermore, such an improvement relies on heat recovery via the
recuperator. This is because expanders with a fixed expansion ratio have a
relatively constant pressure ratio between their inlet and outlet. The increase of
pressure ratio between the evaporator and condenser by tuning the condensing
temperature to match colder ambient condition in winter cannot be utilised by such
expanders. However, with the recuperator in place, the higher discharging
temperature of the expander could increase the heat recovery and consequently
reduce the heat input at the evaporator, increasing the thermal efficiency and the
specific power. The higher the amount of heat energy transferred in the
recuperator, the higher the efficiency improvement.
Dysfibrinogenemia is characterized by blood coagulation dysfunction induced by an
abnormal molecular structure of fibrinogen. Here, we describe a new case. A 32-
year-old female was suspected of having dysfibrino-genemia during routine
laboratory screening, based on her decreased functional fibrinogen level, normal
fibrinogen antigen level, and prolonged thrombin time. We extracted DNA and
performed polymerase chain reaction and DNA sequencing to identify genetic
mutation. Fibrin polymerization, the kinetics of the fibrinopeptide release,
scanning electron microscopy, mass spectrometric analysis, fibrin cross-linking,
sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot were
conducted. DNA sequencing identified a heterozygous point mutation, Gly13Arg in A
alpha chain. Fibrin polymerization was markedly impaired (prolonged lag phase and
decreased final turbidity). The rate and extent of fibrinopeptide A release from
the patient were abnormal and reduced. The mass spectrometry analysis revealed the
presence of mutant fibrinogen chains in the patient's circulation. Electron micro-
graphs revealed abnormal fibrin clots. Fibrin cross-linking was normal. Sodium
dodecyl sulfate polyacrylamide gel electrophoresis and western blot showed no
difference. We report a new case with a mutation in the fibrinopeptide A region, A
alpha Gly13Arg. These results indicated that the functional abnormalities were
related to delayed and defective fibrinopeptide A cleavage and likely impaired
thrombin binding.
Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential
Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major
nociceptive integrators. They are also present on the rat endometrium in an
oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian
endometriosis patients, but there is no information about TRPA1 and their
pathophysiological significances. In this study, patients undergoing laparoscopic
surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep
infiltrating endometriosis (n=15), uterine fibroid-induced moderate dysmenorrhoea
(n=7) and tubal infertility with no pain (n=6). TRPA1 and TRPV1 mRNA and protein
expressions were determined by quantitative polymerase chain reaction and semi-
quantitative immunohistochemistry from the endometrium samples taken by curettage.
Results were correlated with the clinical characteristics including pain intensity.
TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA
and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1
immunopositivities were found in the stroma and epithelial layers. We detected
upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene
expression was also elevated in autocontrol endometrium of deep infiltrating
endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1
difference between deep infiltrating endometriosis stroma and epithelium, and in
deep infiltrating endometriosis epithelium compared to control samples. Besides, we
measured elevated stromal TRPV1 immunopositivity in deep infiltrating
endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with
dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and
macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity
also positively correlated with dyschezia severity. We provide the first evidence
for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium
and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid
deep infiltrating endometriosis lesions and correlations with pain intensity
suggest potential roles in pathophysiological mechanisms of the disease.
Dystonia musculorum (dt) is an inherited autosomal recessive neuropathy in mice.
Homozygous animals display primarily sensory neuro degeneration resulting in a
severe loss of coordination. Several dt strains exist, including spontaneous
mutants dt-Alb (Albany), dt-J (Jackson Labs), and dt-Frk (Frankel), and a transgene
insertion mutant, Tg4. They contain mutations in the gene encoding Bullous
Pemphigoid Antigen 1 (BPAG1), or dystonin. BPAG1 is a member of the plakin family
of cytolinker proteins. BPAG1 is alternatively spliced to produce several isoforms,
including the major brain-specific isoform, BPAG1a. The neurological phenotype
observed in dt-Alb mice is thought to result from the absence of BPAG1a protein in
the developing nervous system. The goal of this study was to determine the precise
molecular nature of the dt-Alb mutation and examine residual BPAG1 expression in
homozygous dt-Alb mice. A combination of molecular biological strategies revealed
that the dt-Alb lesion is a deletion-insertion eliminating a large part of the
coding region of BPAG1a. The molecular lesion in the dt-Alb BPAG1 allele is
expected to render it completely non-functional. Although transcripts corresponding
to BPAG1 segments still remaining in homozygous dt-Alb mice could be detected by
RT-PCR, there was no positive signal for BPAG1 in the brain of dt-Alb mice by
Northern blotting. Western blotting with polyclonal anti-BPAG1 antibodies confirmed
the absence of functional BPAG1 protein (full-length or truncated) in the dt-Alb
brain. our identification of the 5' junction of the dt-Alb insertion makes it
possible to genotype dt-Alb animals by standard PCR. (c) 2006 Elsevier B.V. All
rights reserved.
Genetic findings of the past years have provided ample evidence for a substantial
etiologic heterogeneity of dystonic syndromes. While an increasing number of genes
are being identified for Mendelian forms of isolated and combined dystonias using
classical genetic mapping and whole-exome sequencing techniques, their precise role
in the molecular pathogenesis is still largely unknown. Also, the role of genetic
risk factors in the etiology of sporadic dystonias is still enigmatic. Only the
systematic ascertainment and precise clinical characterization of very large
cohorts with dystonia, combined with systematic genetic studies, will be able to
unravel the complex network of factors that determine disease risk and phenotypic
expression.
ATR in EHEC 0157:H7 and the cross-protection effects thus induced lead to the
uncertainty of food safety. This study aimed to identify factors that are
associated with the ATR in EHEC 0157:H7 under stomach acidity using RNA-seq. In
total, 223 DEGs in E. coil 0157:H7 and 110 DEG5 in E. coli after acid treatment
were identified, including 118 upregulated and 105 downregulated in EHEC 0157:H7,
and 89 upregulated and 21 downregulated in E. coil ATCC 25922. According to our
results, when facing the ATR environment, protein Asr regulated the whole add
resistance process. In E. coli ATCC 25922, cadA and cadB mediate the lysine
decarboxylation consumed the extra protons inside and keep the neutral pH value in
cytoplasm to protect the E. coli from death. In contrast, oxidation-reduction
mediated by ahpC, which was activated by the depression of oxyR, and hydrogenation
mediated by mhpA consumed the protons inside keeping the neutral pH value to
protect the EHEC 0157:H7 from harm induced by a low pH environment. In addition,
EHEC 0157:H7 expressed more anti-oxidation enzymes to repair damage caused by acid
stress, which enhanced its resistance to acid compared to E. coli ATCC 25922. (c)
2017 Elsevier Ltd. All rights reserved.
Escherichia coli O157 related foodborne illnesses continue to be one of the most
important global public health problems in the world. This study aims to determine
E. coli O157 prevalence in 375 chicken meat parts and giblets. The samples were
collected randomly from several supermarkets and butchers in Diyarbakir, a city in
southeast Turkey. They were analyzed and confirmed using the immunomagnetic
separation (IMS), Vitek (R) 2 microbial identification system and polymerase chain
reaction (PCR) method. This study also aims to detect the presence of fliC(H7),
eaeA, stx(1), stx(2) and hlyA genes by using PCR. The overall E. coli O157
prevalence in chicken meat parts and giblets was 1.3%. All of the E. coli O157
isolates carried rfbE(O157) and eaeA genes; but not any fliC(H7) and hlyA genes.
The E. coli O157 isolates obtained from drumstick and breast meat carried either
stx(1) or stx(2) genes, which were related to important virulence factors of the
disease.
Phosphorylation and ubiquitination are pervasive post-translational modifications
that impact all processes inside eukaryotic cells. The role of each modification
has been studied for decades, and functional interplay between the two has long
been demonstrated and even more widely postulated. However, our understanding of
the molecular features that allow phosphorylation to control protein ubiquitination
and ubiquitin to control phosphorylation has only recently begun to build. Here, we
review examples of regulation between ubiquitination and phosphorylation, aiming to
describe mechanisms at the molecular level. In general, these examples illustrate
phosphorylation as a versatile switch throughout ubiquitination pathways, and
ubiquitination primarily impacting kinase signalling in a more emphatic manner
through scaffolding or degradation. Examples of regulation between these two
processes are likely to grow even further as advances in molecular biology,
proteomics, and computation allow a system-level understanding of signalling. Many
new cases could involve similar principles to those described here, but the
extensive co-regulation of these two systems leaves no doubt that they still have
many surprises in store. (C) 2017 Elsevier Ltd. All rights reserved.
The European Academy of Allergy and Clinical Immunology (EAACI) Junior Members (JM)
comprise the largest EAACI section with around 4000 clinicians and scientists under
35 years of age working in the field of allergy and clinical immunology. The Junior
Member collaboration with Clinical and Translational Allergy Journal is a mutually
beneficial relationship providing Junior Members of EAACI with excellent
opportunities to publish their work in the Journal, enhance their visibility in
their respective field, and get involved with Journal-related activities and
processes. In the future, this collaboration will grow, not only by the
consolidation of these activities, but also by the implementation of new
initiatives, such as a platform for discussing and/or publishing Junior Members'
dissertations in the Journal. From the CTA perspective, the collaboration presents
an opportunity to promote a new generation of allergists with experience of
conducting and presenting research, with improved skills in critical review.
Objective: Insulin-like growth factor (IGF)-axis is involved in human oncogenesis
and metastasis development for various solid tumors including breast cancer. Aim of
this study was to assess the association between IGF-1, IGFbinding protein-3
(IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the
peripheral blood of women diagnosed with early breast cancer (EBC), before and
after adjuvant chemotherapy. Design: 171 patients with early-stage breast
adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays
were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in
blood samples collected after surgical treatment and before initiation of adjuvant
chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-
19) mRNA transcripts using quantitative real timereverse transcription polymerase
chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CFCs'
presence before and after adjuvant chemotherapy as well as with tumor
characteristics including tumor size, axillary lymph node status, oestrogen
(ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2)
receptor status. Log-rank test was applied to investigate possible association
between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall
survival (OS). Results: Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum
levels were moderately associated (Spearman's rho = 0361, p < 0.001) with each
other, while presenting significant differences across age groups (all p values <
0.05). IGF-1 serum levels did not correlate with the presence of CTCs before
initiation (p = 0.558) or after completion (p = 0.474) of adjuvant chemotherapy.
Similarly, IGFBP-3 serum levels did not show significant association with
detectable CTCs either before (p = 0.487) or after (p = 0.134) completion of
adjuvant chemotherapy. There was no statistically significant association between
the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p = 0.499; OS:
p = 0.220) or IGFBP-3 (DFI: p = 0.900; OS: p = 0.406) serum levels. Conclusions:
IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not
indicative of CTCs' presence in the blood and do not correlate with clinical
outcome of women with early-stage breast cancer. (C) 2017 Elsevier Ltd. All rights
reserved.
Home visitation programs are designed to provide comprehensive services that
promote parent's abilities to create stable, nurturing care environments for their
children. In order for program goals to be met, parents must participate actively
and be engaged with the programs' mission. However, promoting engagement and
participation are complex processes that have been understudied in research on home
visitation. The current qualitative study examined how a national, federally funded
home visitation program, Early Head Start (EHS), engaged and retained families so
that potentially helpful preventative interventions could be delivered. The study
also identified barriers to active engagement. Semistructured interviews were
conducted with 10 parents of children enrolled in EHS. Findings suggest that
engagement increased when EHS reduced social isolation by forming connections among
parents and when the program focused on involving parents in fostering their
children's meeting of important developmental milestones. Barriers to engagement
identified included logistical and organizational challenges, as well as parental
biases and differences in values and attitudes. Practice and policy recommendations
for improving EHS and other programs that serve similar populations to increase
engagement are discussed.
Background: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability
factor that predates depression; however, in healthy people, who experience early
life stress but do not become depressed, it may represent a resilience mechanism.
We aimed to test these hypothesis examining whether increased amygdala activity in
association with a history of early life stress (ELS) was negatively or positively
associated with depressive symptoms and impact of negative life event stress in
never-depressed adults. Methods: Twenty-four healthy participants completed an
individually tailored negative mood induction task during functional magnetic
resonance imaging (fMRI) assessment along with evaluation of ELS. Results: Mood
change and amygdala reactivity were increased in never-depressed participants who
reported ELS compared to participants who reported no ELS. Yet, increased amygdala
reactivity lowered effects of ELS on depressive symptoms and negative life events
stress. Amygdala reactivity also had positive functional connectivity with the
bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory
recall. Conclusions: Increased amygdala activity in those with ELS was associated
with decreased symptoms and increased neural features, consistent with emotion
regulation, suggesting that preservation of robust amygdala reactions may reflect a
stress buffering or resilience enhancing factor against depression and negative
stressful events.
Background: A number of mosquito vectors bite and rest outdoors, which contributes
to sustained residual malaria transmission in endemic areas. Spatial repellents are
thought to create a protective "bubble" within which mosquito bites are reduced and
may be ideal for outdoor use. This study builds on previous studies that proved
efficacy of transfluthrin-treated hessian strips against outdoor biting mosquitoes.
The goal of this study was to modify strips into practical, attractive and
acceptable transfluthrin treated sisal and hessian emanators that confer protection
against potential infectious bites before people use bed nets especially in the
early evening and outdoors. This study was conducted in Kilombero Valley, Ulanga
District, south-eastern Tanzania. Results: The protective efficacy of hand-crafted
transfluthrin-treated sisal decorative baskets and hessian wall decorations against
early evening outdoor biting malaria vectors was measured by human landing catches
(HLC) in outdoor bars during peak outdoor mosquito biting activity (19: 00 to 23:
00 h). Treated baskets and wall decorations reduced bites of Anopheles arabiensis
mosquitoes by 89% (Relative Rate, RR = 0.11, 95% confidence interval, CI: 0.09-
0.15, P < 0.001) and 86% (RR = 0.14, 95% CI: 0.11-0.18, P < 0.001), respectively.
In addition, they significantly reduced exposure to outdoor bites of Culex spp. by
66% (RR = 0.34, 95% CI: 0.22-0.52, P < 0.001) and 56% (RR = 0.44, 95% CI: 0.29-
0.66, P < 0.001), respectively. Conclusion: Locally hand-crafted transfluthrin-
treated sisal decorative baskets and hessian wall decorations are readily
acceptable and confer protection against outdoor biting malaria vectors in the
early evening and outdoors: when people are resting on the verandas, porches or in
outdoor social places such as bars and restaurants. Additional research can help
support the use of such items as complementary interventions to expand protection
to communities currently experiencing outdoor transmission of mosquito-borne
pathogens.
Metacognition refers to a range of cognitive processes that allow one to form
complex ideas of self and others and to use this information to navigate
psychosocial challenges. Several studies in both early-phase and prolonged
schizophrenia have demonstrated not only that significant deficits in metacognitive
ability are present, but importantly that they are associated with significant
functional impairment and decreased quality of life. In spite of the importance of
metacognitive impairment in schizophrenia, relatively little is known about the
biological substrates that may contribute to this dysfunction. In this study, we
examined the relationship between resting state functional connectivity of the
medial prefrontal cortex (mPFC), a structure shown in prior voxel-based morphometry
studies to be associated with metacognition, with metacognitive function in an
early phase psychosis cohort (n=18). Analyses revealed a positive association of
resting state functional connectivity between the mPFC and precuneus and posterior
cingulate structures and metacognitive ability. These results provide evidence of
disrupted resting state connectivity in structures relevant to metacognitive
dysfunction in early-phase psychosis, which may have implications for
pathophysiological models of complex cognitive deficits in this illness.
The paper sets out to explore the possibility that citizen-led surveys provide a
better coverage of populations and specifically of hard-to-reach poorer areas than
the international standardized household surveys which are the basis for many of
the estimates used in assessing progress toward meeting the MDGs and will be for
the SDGs. This hypothesis is based on the argument that, the local volunteer
enumerators of citizen-led surveys are likely to be more sensitive to the
specificities of local population distribution and (recent) changes than those
centrally trained; and may be more effective at reaching hard-to reach groups such
as those nomadic groups and those in urban slums. To test the hypothesis, the
results of UWEZO (meaning "capability") surveys have been compared at a regional
level with those of contemporaneous DHS surveys in Kenya, Tanzania, and Uganda for
estimates of access to water and electricity. Overall, at national level, we find
that UWEZO estimates for access to clean water were lower at a statistically
significant level than those of DHS and these differences were statistically
significant at the 0.01% level; in particular, the DHS values were much higher in
regions where there are high concentrations of nomads and of urban slums, implying
that the UWEZO surveys "catch" more poverty. The suggestion therefore is that
citizen surveys such as UWEZO provide better, and more accurate, coverage of the
poorest of the poor. Using the lowest estimate of the percentage "missing" in urban
slums and extrapolating to all developing countries, there are an estimated 369
million missing from the sampling frames of standardized household surveys
worldwide. This has important implications for the "Leave no one behind" appeal of
the UN Secretary General and for the UN's "Data Revolution". Some suggestions are
made about how to progress improved population estimates. (C) 2017 Elsevier Ltd.
All rights reserved.
Anorexia nervosa (AN) is an illness that frequently begins during adolescence and
involves weight loss. Two groups of adolescent girls (AN-A, weight-recovered
following AN) and (HC-A, healthy comparison) completed a functional magnetic
resonance imaging task involving social evaluations, allowing comparison of neural
activations during self-evaluations, friend-evaluations, and perspective-taking
self evaluations. Although the two groups were not different in their whole-brain
activations, anxiety and body shape concerns were correlated with neural activity
in a priori regions of interest. A cluster in medial prefrontal cortex and the
dorsal anterior cingulate correlated with the body shape questionnaire; subjects
with more body shape concerns used this area less during self than friend
evaluations. A cluster in medial prefrontal cortex and the cingulate also
correlated with anxiety such that more anxiety was associated with engagement when
disagreeing rather than agreeing with social terms during self evaluations. This
data suggests that differences in the utilization of frontal brain regions during
social evaluations may contribute to both anxiety and body shape concerns in
adolescents with AN. Clinical follow-up was obtained, allowing exploration of
whether brain function early in course of disease relates to illness trajectory.
The adolescents successful in recovery used the posterior cingulate and precuneus
more for friend than self evaluations than the adolescents that remained ill,
suggesting that neural differences related to social evaluations may provide
clinical predictive value. Utilization of both MPFC and the precuneus during social
and self evaluations may be a key biological component for achieving sustained
weight-recovery in adolescents with AN. (C) 2016 Elsevier Ltd. All rights reserved.
Background: By the end of the 2013-2016 West African Ebola Virus Disease (EVD)
outbreaks, a total of 3814 cases (probable and confirmed) and 2544 deaths were
reported in Guinea. Clearly, surveillance activities aiming at stopping human-to-
human transmission have been the breakthrough of EVD outbreak management, but their
application has been at times easier said than done. This article presents five
confirmed or probable EVD cases that arose in Conakry towards the end of the Guinea
epidemic, which demonstrate flaws in surveillance and follow-up. Case presentation:
For case 1, safe burial requirements were not followed. For cases 1 and 2, negative
Polymerase Chain Reaction (PCR) results were interpreted as no infection. For the
first case, the sample may have not been taken properly while for the second the
disease was possibly at its early stage. Case 3 was stopped at a border health
checkpoint and despite her high temperature she was allowed to continue the bus
journey. For case 4, an oral swab sample was supposedly taken after death but could
not be found for retrospective testing. Despite characteristic symptomatology, case
5 was not identified as a suspect case for as long as 3 weeks. Conclusion: In
epidemic contexts, health systems must be able to track all samples of suspect
cases and deaths, regardless of their laboratory results. Social mobilization in
communities and training in health care facilities must be strengthened at the tail
of an outbreak, to avoid the natural slackening of disease surveillance, in
particular for long-lasting and deadly epidemics.
The tragic West African Ebola epidemic claimed many lives, but would have been
worse still if scientific insights from many disciplines had not been integrated to
create a strong technical response. Epidemiology and modelling triggered the
international response and guided where response efforts were directed; virology,
engineering and clinical science helped reduce deaths and transmission in and from
hospitals and treatment centres; social sciences were key to reducing deaths from
funerals and in the community; diagnostic and operational research made the
response more efficient; immunology and vaccine research contributed to the final
stages of the epidemic and will help prevent future epidemics. These varied
scientific contributions had to be integrated into a combined narrative,
communicated to policymakers to inform decisions, and used by courageous local and
international responders in the field in real time. Not every area of science was
optimal, and in particular, clinical trials of simple interventions such as fluid
management were slow to be adopted and sharing of data was initially poor. This
Ebola epidemic demonstrated how science can respond to a major emergency, but also
has lessons for better responses in future infectious emergencies. This article is
part of the themed issue 'The 2013-2016 West African Ebola epidemic: data,
decision-making and disease control'.
Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans
and nonhuman primates. The majority of ebolavirus species, most notably Zaire
ebolavirus, can cause Ebola virus disease (EVD), formerly known as Ebola
hemorrhagic fever, in humans. EVD is associated with case-fatality rates as high as
90%, and there is currently no specific treatment or licensed vaccine available
against EVD. Understanding the molecular biology and pathogenesis of ebolaviruses
is important for the development of antiviral therapeutics. Ebolavirus encodes
several forms of glycoproteins (GPs), which have some interesting characteristics,
including the transcriptional editing coding strategy and extensive O-glycosylation
modification, clustered in the mucin-like domain of GP1, full-length GP (GP(1,2)),
and shed GP. In addition to the canonical role of the spike protein, GP(1,2), in
viral entry, ebolavirus GPs appear to have multiple additional functions, likely
contributing to the complex pathogenesis of the virus. Here, we review the roles of
ebolavirus GPs in viral pathogenesis.
Infection with Epstein-Barr virus (EBV) usually leads to a latent state in B
lymphocytes. The virus can be reactivated through two viral transactivators. Zta
and Rta, leading to a cascade of gene expression. An EBV DNA array was generated to
analyze the pattern of transcription of the entire EBV genome under various
Conditions. Firstly, a complete set of temporal expression clusters of EBV genes
was displayed by analyzing the array data of anti-IgG-induced Akata cells. In
addition to assigning genes of unknown function to the various Clusters, increasing
expression of latent genes, including EBNA2, EBNA3A and EBNA 3C, was observed
during virus replication. Secondly, gene expression independent of viral DNA
replication was analyzed in PAA blocked Akata cells and in chemically induced Raji
cells. Several genes with presumed late functions were found to be expressed with
early kinetics and independent of vital DNA replication, suggesting possible novel
functions for these genes. Finally, the EBV array was used to identify Rta
responsive gene expression in Raji cells, and in the EBV-positive epithelial cells
NA, using a Zta siRNA strategy. The array data were confirmed by Northern blotting,
RT-PCR and reporter assays. All the information here thus provides a better
understanding of the control of EBV lytic gene expression. (c) 2005 Elsevier Inc.
All rights reserved.
Unaccustomed exercise is known to produce strength loss, soreness, and myocellular
disruption. With repeated application of exercise stimuli, the appearance of these
indexes of muscle damage is attenuated, the so-called " repeated bout effect." No
direct connection has been established between this repeated bout effect and
exercise-induced increases in protein turnover, but it appears that a degree of
tolerance is developed toward exercise for both. The present study sought to
investigate markers of protein degradation by determining the expression of
components related to the ubiquitin-proteasome system (UPS) with repeated exercise
bouts. Healthy men carried out 30 min of bench stepping, performing eccentric work
with one and concentric work with the other leg (n = 14), performing a duplicate
exercise bout 8 wk later. A nonexercising control group was included (n = 6). RNA
was extracted from muscle biopsies representing time points preexercise, + 3 h, +
24 h, and + 7 days, and selected mRNA species were quantified using Northern
blotting. The exercise model proved sufficient to produce a repeated bout effect in
terms of strength and soreness. For forkhead box O transcription factor 1 (FOXO1)
and muscle RING finger protein-1 (MURF1), strong upregulations were seen
exclusively with concentric loading (P < 0.001), while atrogin-1 displayed a strong
downregulation exclusively in response to eccentric exercise (P < 0.001). For MURF1
transcription, the first bout produced a downregulation that persisted until the
second bout (P < 0.01). In conclusion, the UPS is modulated differentially in
response to varying loading modalities and with different time frames in a way that
to some extent reflects changes in protein metabolism known to take place with
exercise.
Echinococcus Granulosus (EG) is the major cause of cystic echinococcosis in humans
and livestock in the world. In Chile is a zoonosis of great importance. The most
frequently affected geographic areas are the Regions of Aysen, Los Rios, Los Lagos,
Coquimbo and the Araucania. Hence, it was discovered that in endemic areas of
hydatidosis there could be several strains and genotypes of EG. In addition, there
is evidence that some strains and genotypes are more infectious for human beings
than others. This interesting phenomenon of the biology of EG has been studied
using molecular biology techniques based on polymerase chain reaction (PCR) and DNA
sequence analysis, which has made it possible to characterize the cestode species
complex called EG sensu lato (s l) as being comprised of EG sensu stricto (s. s.)
(Genotypes G1-G3), E. equinus (G4), E. ortleppi (G5) and E. canadensis (G6-G10),
which present an important phenotypic variation detectable in characteristics of
the biological cycle, specificity of the intermediate host, pattern of development,
pathogenicity, antigenicity, transmission dynamics and, consequently, in the
measures needed to control the disease. The aim of this manuscript is to describe
the different genotypes of EG described in humans and different livestock host
reported in the literature.
Multidirectional interactions among the immune, endocrine, and nervous systems have
been demonstrated in humans and non-human animal models for many decades by the
biomedical community, but ecological and evolutionary perspectives are lacking.
Neuroendocrine-immune interactions can be conceptualized using a series of feedback
loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can
exert profound influences on these phenotypes, which can in turn reciprocally
modulate behavior. For example, the behavioral aspects of reproduction, including
courtship, aggression, mate selection and parental behaviors can impinge upon
neuroendocrine-immune interactions. One classic example is the immunocompetence
handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators
of traits important for female choice while suppressing the immune system.
Reciprocally, neuroendocrine-immune pathways can promote the development of altered
behavioral states, such as sickness behavior. Understanding the energetic signals
that mediate neuroendocrine-immune crosstalk is an active area of research.
Although the field of psychoneuroimmunology (PNI) has begun to explore this
crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus
has been relatively underappreciated in comparative species. The field of
ecoimmunology, while traditionally emphasizing the study of non-model systems from
an ecological evolutionary perspective, often under natural conditions, has focused
less on the physiological mechanisms underlying behavioral responses. This review
summarizes neuroendocrine-immune interactions using a comparative framework to
understand the ecological and evolutionary forces that shape these complex
physiological interactions. (C) 2016 Elsevier Inc. All rights reserved.
Little research has been conducted specifically on the factors which have a bearing
on a special education teacher's decision to report sexual victimization. The aim
of this study is to determine what these factors are and the role they play amongst
special education teachers in Taiwan. Individual interviews were conducted with
eight female and four male special education teachers and thematic analysis was
used to interpret the data. The relevant factors are categorized in accordance with
the ecological system theory proposed by Bronfenbrenner. Microsystem factors
include consequences of reporting, severity of victimization, and characteristics
of students with disabilities. Mesosystem factors include relationship with
student's family and colleagues, and support from school administration. Exosystem
factors include paperwork load, rotation of social workers, and oppositional
positions between school and government. Macrosystem factors include emphasis on
maintaining harmonious relationships with colleagues and the student's family, and
doubts about the applicability of mandatory reporting in cases involving students
with disabilities. The results of this study indicate the need for clearer
reporting standards for students with disabilities, more support and resources from
school administration, and more comprehensive training on the mandatory reporting
policy.
Citrus canker, caused by Xanthomonas citri pv. citri, is a serious disease of
citrus plants worldwide. Earlier phylogenetic studies using housekeeping genes
revealed that X. citri pv. citri is related to many other pathovars, which can be
collectively referred as Xanthomonas citri pathovars (XCPs). From the present
study, we report the genome sequences of 18 XCPs and compared them with four XCPs
available in the public domain. In a tree based on phylogenomic marker genes, all
the XCPs form a monophyletic cluster, suggesting their origin from a common
ancestor. Phylogenomic analysis using the type strain further established that all
the XCPs belong to one species. Clonal analysis of the core genome revealed the
presence of two major lineages within this monophyletic cluster consisting of some
clonal variants. Incidentally, the majority of these XCPs were first noticed in
India, corroborating their clonal relationship and their common origin. Comparative
analysis revealed an open pan-genome and the role of interstrain genomic flux of
these XCPs since their diversification from a common ancestor. Even though there
are wide variations in type III gene effectomes, we identified three core effectors
which can be valuable in resistance-breeding programs. Overall, genomic examination
of ecological relatives allowed us to dissect the tremendous genomic potential of
X. citri species to rapidly evolve into specialized strains infecting diverse crop
plants. IMPORTANCE Host specialization is one of the characteristic features of
highly evolved pathogens such as the Xanthomonas group of phytopathogenic bacteria.
Since the hosts involve staple crops and economically important fruits such as
citrus, detailed understanding of the diversity and evolution of such strains
infecting diverse plants is important for quarantine purposes. In the present
study, we carried out genomic investigation of members of a phylogenetically and
ecologically defined group of Xanthomonas strains pathogenic to diverse plants,
including citrus. This group includes the oldest Xanthomonas pathovars and also
recently emerged pathovars in a particular country where they are endemic. Our
high-throughput genomic study has provided novel insights into the evolution of a
unique lineage consisting of serious pathogens and their ecological relatives,
suggesting the nature, scope, and pattern of rapid and recent diversification.
Further, from the level of species to that of clonal variants, the study revealed
interesting genomic patterns in diversification of a Xanthomonas lineage and
perhaps will inspire careful study of the host range of the included pathovars.
While maps of solar irradiance are readily available, they do not represent the
economic viability of a solar project in any particular location. This paper
provides a financial analysis with different electricity tariffs and then maps the
internal rate of return (IRR) of solar load displacement projects. We examine 25
locations in the southwestern USA and show that IRR maps differ substantially from
irradiance maps. Our analysis includes 27 scenarios derived from the following
combinations: three types of solar installations (concentrated photovoltaic (CPV),
south-facing PV and PV oriented so as to optimize IRR); three project start dates
(2016, 2018, 2020); and three price projections for grid-connected systems
(optimistic, central, pessimistic). The variation of irradiance across these 25
locatibns is much lower than the variation of IRR. Direct normal irradiance is
almost uncorrelated with the IRR from CPV projects, indicating that irradiance
alone is a poor predictor of IRR. Tariff differences among the 25 locations,
including time of use aspects, play a major role in determining economic viability
and IRR varies considerably even within a single city. Orienting PV modules so as
to optimize the IRR brings little benefit unless the optimized azimuth is greater
than 20 west of south. (C) 2017 Elsevier Ltd. All rights reserved.
The Pharmacogenomics and Personalized Medicine group belongs to the Laboratory of
Molecular Biology and Immunology, Department of Pharmacy and is active since 2009
mainly in the field of pharmacogenomics and personalized medicine. Herein, we
describe the research interests, collaborations and accomplishments of the
Pharmacogenomics and Personalized Medicine group together with the teaching
activities of the group that greatly enhance the pharmacogenomics knowledge of
graduate/postgraduate students and healthcare professionals.
This paper examines the current electrical generation expansion plan of Ghana and
compares it with proposed expansion pathways with higher penetration of Renewable
Energy Technologies. An adaptation of Schwartz's Scenario Methodology was used to
develop the scenarios which were then analysed using the Long-range Alternatives
Planning (LEAP) model. Each of the scenarios represents policy options for
generation expansion in Ghana up to 2040. Energy, economic and environmental
analysis of the three alternative scenarios compared to the base scenarios was
undertaken. Sensitivity results show that, if the country were to follow the
generation expansion path described in the renewable energy scenarios, it could
reap economic benefits of 0.5-13.23% depending on the developments in fuel prices
and renewable technology capital cost. The analysis further quantifies benefits to
be derived from a reduction in Greenhouse gases of the scenarios. Policy
implications for the generation system of Ghana based on the results are also
discussed.
The soil organic carbon (SOC) stock is an important indicator in ecosystem service
assessments. Even though a considerable fraction of the total stock is stored in
the subsoil, current assessments often consider the topsoil only. Furthermore,
mapping efforts are hampered by the limited spatial density of these topsoil
measurements. The aim of this study was to assess the SOC stock in the upper 100 cm
of soil in 30,556 ha of Low-Input High-Diversity systems, such as nature reserves,
in Flanders (Belgium) and compare this estimate with the stock found in the topsoil
(upper 15 cm). To this end, we combined depth extrapolation of 139 measurements
limited to the topsoil with four digital soil mapping techniques: multiple linear
regression, boosted regression trees, artificial neural networks and least-squares
support vector machines. Particular attention was given to vegetation
characteristics as predictors. For both the stock in the upper 15 cm and 100 cm, a
boosted regression trees approach was most informative as it resulted in the lowest
cross-validation errors and provided insights in the relative importance of
predictors. The predictors of the stock in the upper 100 cm were soil type,
groundwater level, clay fraction and community weighted mean (CWM) and variance
(CWV) of plant height. These predictors, together with the CWM of specific leaf
area, aboveground biomass production, CWV and CWM of rooting depth, terrain slope,
CWM of mycorrhizal associations and species diversity also explained the topsoil
stock. Our total stock estimates show that focusing on the topsoil (1.63 Tg OC)
only considers 36% of the stock in the upper 100 cm (4.53 Tg OC). Given the
magnitude of subsoil OC and its dependency on typical ecosystem characteristics, it
should not be neglected in regional ecosystem service assessments. (C) 2017
Elsevier B.V. All rights reserved.
Two-component signal transduction system (TCS) is a common mechanism of signal
transduction and exists in almost all bacterial species. The putative two-component
genes SCO6421 (ecrE(1)) and SCO6422 (ecrE(2)) in Streptomyces coelicolor, which
located in the vicinity of the red locus, could modulate the antibiotic
undecylprodigiosin (Red) biosynthesis. In this study, the mutants of M145E1
(ecrE(1) knock-out) and M145E2 (ecrE(2) knock-out) were constructed using
homologous recombination by double crossover. Red production of two mutants
decreased dramatically compared with that of the wild-type strain. However, the
production of actinorhodin (Act) of two mutants had not changed significantly. The
results suggested that ecrE(1)/ecrE(2) participated in regulating the antibiotic
Red synthesis. Northern blotting analysis indicated that ecrE(1)/ecrE(2) may
regulate the biosynthesis of Red through influencing the transcription of redD and
redZ during cell growth. Therefore, ecrE(1)/ecrE(2), as a specific pair of TCS,
most likely regulates the red gene cluster positively.
Thyroid cancer is very common, but skull ectopic thyroid cancer has not been
reported in 50 years of literatures in foreign countries. There are only four cases
of the skull ectopic thyroid cancer reported in more than 30 years of domestic
literature including the cases in this report. This paper aims to investigate the
clinical characteristics and possible molecular mechanisms of this rare disease.
Five keywords of "thyroid gland", "ectopic thyroid", "thyroid cancer", "ectopic
thyroid cancer" and "metastatic thyroid cancer" were included and 50 years of
literatures in the PubMed-MEDLINE and Wanfang database were reviewed. By combining
the test data of 2 cases of surgical patient tissue microarray specimens-molecular
immunology pathology, the possible molecular mechanisms were analyzed and molecular
regulation network diagram was drawn. The skull ectopic thyroid cancer has not been
reported in 50 years of literatures in foreign countries and there are only four
cases of the skull ectopic thyroid cancer reported in more than 30 years of
domestic literature including the cases in this report. The molecular expressions
of skull ectopic thyroid cancer, orthotopic thyroid cancer, and metastatic thyroid
cancer were not the same: (I) AKT (P=0.012, 0.002) and mTOR (P=0.002, 0.004) were
highly expressed in the skull ectopic thyroid cancer; (II) BRAF (P=0.029, 0.014)
and ERK (P=0.002, 0.001) were highly expressed in orthotopic thyroid cancer; (III)
MMP-9 (P=0.023, 0.016) was highly expressed in metastatic thyroid cancer. According
to the molecular information base, the PI3K is predicted to be a key crossing gene
of the above three signaling pathways, which showed no significant differences in
these three thyroid cancers (P=0.692, 0.388, 0.227), but PI3K has regulation roles
in the three signaling pathways of Akt/mTOR, MAPK, and NF-kappa B. PI3K gene is an
important starting gene of thyroid cancers. After the canceration starts, due to
the fact that the local microenvironments of thyroid cancers in different parts are
different, the thyroid cancers are regulated by different signaling pathways. The
ectopic thyroid cancer was correlated with Akt/mTOR pathway high expression;
orthotopic thyroid was related with MAPK/BRAF/ERK signaling pathway high
expression; and the metastatic thyroid cancer was related with NFkB/MMP9 high
expression.
In high-quality education, topics concerning the behavior and control of electrical
machines and power electronics have to be taught not only theoretically but also in
a practical manner. Hard-and software tools are necessary to fulfil this
obligation. Nevertheless, commercial systems partially lack of functionality or
full accessibility to implement custom solutions, which is obligatory in the
research and education domain. Therefore, a digital signal processing system is
presented, that allows full modification of every used device, both in hardware and
in software.
Undergraduate medical curricula typically include forensic and legal medicine
topics that are of a highly sensitive nature. Examples include suicide, child
abuse, domestic and sexual violence. It is likely that some students will have
direct or indirect experience of these issues which are prevalent in society. Those
students are vulnerable to vicarious harm from partaking in their medical
education. Even students with no direct or indirect experience of these issues may
be vulnerable to vicarious trauma, particularly students who are especially
empathetic to cases presented. Despite these risks, instruction relating to these
topics is necessary to ensure the competencies of graduating doctors to respond
appropriately to cases they encounter during their professional careers. However,
risk can be minimised by a well-designed and thoughtfully delivered educational
programme. We provide recommendations for the successful inclusion of sensitive
forensic and legal medicine topics in undergraduate medical curricula. (C) 2016
Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
The power of local borders to resist and prevent transnational mobilities in
education has received little attention in comparative education. In this article
we explore the motif of border immunology' with reference to new history, a mobile
paradigm of history teaching, and Greek-Cypriot and Turkish-Cypriot history
textbooks as types of local borders that have been impermeable to new history. The
overall argument we explore here is that ethnonational forms of collective
identities that are imagined to be constitutive of textbook borders account for
immunity to mobility and change.
The present research is aimed at analyzing the professional gestures of a museum
educator in a specific situation: the demonstration of the Foucault Pendulum in the
Arts et Metiers Museum in Paris. What professional gestures can give him the
ability to present this object to a mixed audience in a museum space open to
visitor circulation? How does he manage to capture the attention of his audience
and make scientific knowledge accessible? Does the educator work like a teacher?
Such are the questions that the research team had in mind and which allowed them to
conceive the scientific museum educator's action from the point of view of
professional gestures.
Background: Electroencephalography (EEG) is still a widely used imaging tool that
combines high temporal resolution with a relatively low cost. Ag/AgCl metal
electrodes have been the gold standard for non-invasively monitoring electrical
brain activity. Although reliable, these electrodes have multiple drawbacks: they
suffer from noise, such as offset potential drift, and usability issues, for
example, difficult skin preparation and cross-coupling of adjacent electrodes. New
method: In order to tackle these issues a prototype Electric Potential Sensor (EPS)
device based on an auto-zero operational amplifier was developed and evaluated. The
EPS is a novel active ultrahigh impedance capacitively coupled sensor. The absence
of 1/f noise makes the EPS ideal for use with signal frequencies of similar to 10
Hz or less. A comprehensive study was undertaken to compare neural signals recorded
by the EPS with a standard commercial EEG system. Results: Quantitatively, highly
similar signals were observed between the EPS and EEG sensors for both free running
and evoked brain activity with cross correlations of higher than 0.9 between the
EPS and a standard benchmark EEG system. Comparison with existing method(s): These
studies comprised measurements of both free running EEG and Event Related
Potentials (ERPs) from a commercial EEG system and EPS. Conclusions: The EPS
provides a promising alternative with many added benefits compared to standard EEG
sensors, including reduced setup time and elimination of sensor cross-coupling. In
the future the scalability of the EPS will allow the implementation of a whole head
ultra-dense EPS array. (C) 2015 Elsevier B.V. All rights reserved.
Egocentric vs. allocentric perspective during observation of hand movements has
been related to self-other differentiation such that movements observed from an
egocentric viewpoint have been considered as self-related while movements observed
from an allocentric viewpoint have been considered as belonging to someone else.
Correlational studies have generally found that egocentric perspective induces
greater neurophysiological responses and larger behavioral effects compared to an
allocentric perspective. However, recent studies question previous findings by
reporting greater (mu) suppression and greater transcranial magnetic
stimulation(TMS)-induced motor-evoked potentials (MEPs) during observation of
allocentric compared to egocentric movements. Furthermore, self-other
differentiation has been generally related to activity within the inferior parietal
lobe (IPL), but direct evidence for a causal and functional role of IPL in self-
other differentiation is lacking. The current study was therefore designed to
investigate the influence that IPL exerts on self-other differentiation. To this
aim, we measured the impact of individually adjusted alpha-tuned transcranial
alternating current stimulation (tACS) applied over IPL on it-suppression during
hands movement observation from an egocentric and allocentric perspective.
Electroencephalography (EEG) was recorded during movement observation before and
immediately after tACS. Results demonstrated that tACS decreased it-reactivity over
sensorimotor (but not visual) regions for egocentric (but not allocentric) movement
observation providing direct evidence for a causal involvement of IPL in the
observation of self- but not other-related hand movement. (C) 2016 IBRO. Published
by Elsevier Ltd. All rights reserved.
Increased attention on what works' in education has led to an emphasis on
developing policy from evidence based on comparing and combining a particular
statistical summary of intervention studies: the standardised effect size. It is
assumed that this statistical summary provides an estimate of the educational
impact of interventions and combining these through meta-analyses and meta-meta-
analyses results in more precise estimates of this impact which can then be ranked.
From these, it is claimed, educational policy decisions can be driven. This paper
will demonstrate that these assumptions are false: standardised effect size is open
to researcher manipulations which violate the assumptions required for legitimately
comparing and combining studies in all but the most restricted circumstances.
League tables of types of intervention, which governments point to as an evidence
base for effective practice may, instead, be hierarchies of openness to research
design manipulations. The paper concludes that public policy and resources are in
danger of being misdirected.
To foster the connection between biochemistry and the supporting prerequisite
concepts, a collection of activities that explicitly link general and organic
chemistry concepts to biochemistry ideas was written and either assigned as pre-
class work or as recitation activities. We assessed student learning gains after
using these activities alone, or in combination with regularly-integrated clicker
and discussion questions. Learning gains were determined from student performance
on pre-and post-tests covering key prerequisite concepts, biochemistry course
exams, and stu-dent self-evaluation. Long-term retention of the material was
assessed using a comprehensive exam given to a subset of the students. Our results
show that using the preclass exercises in combination with integrative questions
was effective at improving student performance in both the short and long term.
Similar results were obtained at both a large research institution with large class
enrollments and at a private liberal arts college with moderate enrollments. (C)
2016 by The International Union of Biochemistry and Molecular Biology, 45(2): 97-
104, 2017.
Understanding the rationale for the generation of a pool of highly differentiated
effector memory CD8(+) T cells displaying a weakened capacity to scrutinize for
peptides complexed with major histocompatibility class I molecules via their T cell
receptor, lacking the "signal 2" CD28 receptor, and yet expressing a highly diverse
array of innate receptors, from natural killer receptors, interleukin receptors,
and damage-associated molecular pattern receptors, among others, is one of the most
challenging issues in contemporary human immunology. The prevalence of these
differentiated CD8(+) T cells, also known as CD8(+)CD28(-), CD8(+)KIR(+), NK-like
CD8(+) T cells, or innate CD8(+) T cells, in non-lymphoid organs and tissues, in
peripheral blood of healthy elderly, namely centenarians, but also in stressful and
chronic inflammatory conditions suggests that they are not merely end-of-the-line
dysfunctional cells. These experienced CD8+ T cells are highly diverse and capable
of sensing a variety of TCR-independent signals, which enables them to respond and
fine-tune tissue homeostasis.
The trend toward a more fiercely competitive and strictly environmentally regulated
electricity market in several countries, including China has led to efforts by both
industry and government to develop advanced performance evaluation models that
adapt to new evaluation requirements. Traditional operational and environmental
efficiency measures do not fully consider the influence of market competition and
environmental regulations and, thus, are not sufficient for the thermal power
industry to evaluate its operational performance with respect to specific marketing
goals (operational effectiveness) and its environmental performance with respect to
specific emissions reduction targets (environmental effectiveness). As a complement
to an operational efficiency measure, an operational effectiveness measure not only
reflects the capacity of an electricity production system to increase its
electricity generation through the improvement of operational efficiency, but it
also reflects the system's capability to adjust its electricity generation
activities to match electricity demand. In addition, as a complement to an
environmental efficiency measure, an environmental effectiveness measure not only
reflects the capacity of an electricity production system to decrease its pollutant
emissions through the improvement of environmental efficiency, but it also reflects
the system's capability to adjust its emissions abatement activities to fulfill
environmental regulations. Furthermore, an environmental effectiveness measure
helps the government regulator to verify the rationality of its emissions reduction
targets assigned to the thermal power industry. Several newly developed
effectiveness measurements based on data envelopment analysis (DEA) were utilized
in this study to evaluate the operational and environmental performance of the
thermal power industry in China during 2006-2013. Both efficiency and effectiveness
were evaluated from the three perspectives of operational, environmental, and joint
adjustments to each electricity production system. The operational and
environmental performance changes over time were also captured through an
effectiveness measure based on the global Malmquist productivity index. Our
empirical results indicated that the performance of China's thermal power industry
experienced significant progress during the study period and that policies
regarding the development and regulation of the thermal power industry yielded the
expected effects. However, the emissions reduction targets assigned to China's
thermal power industry are loose and conservative. (C) 2017 Elsevier Ltd. All
rights reserved.
We describe a spectrum splitting solar module design approach using ensembles of 2-
20 subcells with bandgaps optimized for the AM1.5D spectrum. Device physics
calculations and experimental data determine radiative efficiency parameters for
III-V compound semiconductor subcells and enable modification of conventional
detailed balance calculations to predict module efficiency while retaining
computational speed for a wide search of the design space. Accounting for nonideal
absorption and recombination rates due to realistic material imperfections allows
us to identify the minimum subcell quantity, quality, electrical connection
configuration, and concentration required for 50% module efficiency with realistic
optical losses and modeled contact resistance losses. We predict a module
efficiency of 50% or greater will be possible with 7-10 electrically independent
subcells in a spectral splitting optic at 300-500 suns concentration, assuming a
90% optical efficiency and 98% electrical efficiency, provided the subcells can
achieve an average external radiative efficiency of 3-5% and a short circuit
current that is at least 90% of the ideal. In examining spectrum splitting solar
cells with both series-connected and electrically independent subcells, we identify
a new design trade-off independent of the challenges of fabricating optimal bandgap
combinations. Series-connected ensembles, having a single set of electrical
contacts, are less sensitive to lumped series resistance losses than ensembles
where each subcells are contacted independently. By contrast, ensembles with
electrically independent subcells can achieve lower radiative losses when the
subcells are designed for good optical confinement. Distributing electrically
independent subcells in a concentrating receiver module allows flexibility in
subcell selection and fabrication, and can achieve ultra-high efficiency with
conventional III-V cell technology.
Epigallocatechin-3-O-gallate (EGCG), derived from green tea, has been studied
extensively because of its diverse physiological and pharmacological properties.
This study evaluates the protective effect of EGCG on angiotensin II (Ang II)-
induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from
the thoracic aorta of adult Wistar rats were cultured and induced with Ang II.
Western blotting, Northern blotting, real-time PCR and promoter activity assay were
performed. Ang II increased endoglin expression significantly as compared with
control cells. The specific extracellular signal-regulated kinase inhibitor
SP600125 (JNK inhibitor), EGCG (100 M) and c-Jun N-terminal kinase (JNK) siRNA
attenuated endoglin proteins following Ang II induction. In addition, pre-treated
Ang II-induced endoglin with EGCG diminished the binding activity of AP-1 by
electrophoretic mobility shift assay. Moreover, the luciferase assay results
revealed that EGCG suppressed the endoglin promoter activity in Ang II-induced CFs
by AP-1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have
attenuated endoglin expression significantly in Ang II-induced CFs, as determined
through confocal microscopy. Following in vivo acute myocardial infarction (AMI)-
related myocardial fibrosis study, as well as immunohistochemical and confocal
analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of
myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular
end-diastolic and systolic dimensions, and friction shortening in hemodynamic
monitor. In conclusion, epigallocatechin-3-O-gallate (EGCG) attenuated the endoglin
expression and myocardial fibrosis by anti-inflammatory effect in vitro and in
vivo, the novel suppressive effect was mediated through JNK/AP-1 pathway.
A fish egg envelope is composed of several glycoproteins, called zona pellucida
(ZP) proteins, which are conserved among vertebrate species. Euteleost fishes
synthesize ZP proteins in the liver, while otocephalans synthesize them in the
growing oocyte. We investigated ZP proteins of the Japanese eel, Anguilla japonica,
belonging to Elopomorpha, which diverged earlier than Euteleostei and Otocephala.
Five major components of the egg envelope were purified and their partial amino
acid sequences were determined by sequencing. cDNA cloning revealed that the eel
egg envelope was composed of four ZPC homologues and one ZPB homologue. Four of the
five eel ZP (eZP) proteins possessed a transmembrane domain, which is not found in
the ZP proteins of Euteleostei and Otocephala that diverged later, but is found in
most other vertebrate ZP proteins. This result suggests that fish ZP proteins
originally possessed a transmembrane domain and lost it during evolution. Northern
blotting and RT-PCR revealed that all of the eZP transcripts were present in the
ovary, but not in the liver. Phylogenetic analyses of fish zp genes showed that
ezps formed a group with other fish zp genes that are expressed in the ovary, and
which are distinct from the group of genes expressed in the liver. Our results
support the hypothesis that fish ZP proteins were originally synthesized in the
ovary, and then the site of synthesis was switched to the liver during the
evolutionary pathway to Euteleostei.
MicroRNA (miRNA) is a highly conserved class of small noncoding RNA about 19-24
nucleotides in length that function in a specific manner to post-transcriptionally
regulate gene expression in organisms. Tissue miRNA expression studies have
discovered a myriad of functions for miRNAs in various aspects, but a role for
miRNAs in chicken ovarian tissue at 300 days of age has not hitherto been reported.
In this study, we performed the first miRNA analysis of ovarian tissues in chickens
with low and high rates of egg production using high-throughput sequencing. By
comparing low rate of egg production chickens with high rate of egg production
chickens, 17 significantly differentially expressed miRNAs were found (P < 0.05),
including 11 known and six novel miRNAs. We found that all 11 known miRNAs were
involved mainly in pathways of reproduction regulation, such as steroid hormone
biosynthesis and dopaminergic synapse. Additionally, expression profiling of six
randomly selected differentially regulated miRNAs were validated by quantitative
real-time polymerase chain reaction (RT-qPCR). Some miRNAs, such as gga-miR-34b,
gga-miR-34c and gga-miR-216b, were reported to regulate processes such as
proliferation, cell cycle, apoptosis and metastasis and were expressed
differentially in ovaries of chickens with high rates of egg production, suggesting
that these miRNAs have an important role in ovary development and reproductive
management of chicken. Furthermore, we uncovered that a significantly up-regulated
miRNA-gga-miR-200a-3p- is ubiquitous in reproductionregulation- related pathways.
This miRNA may play a special central role in the reproductive management of
chicken, and needs to be further studied for confirmation.
To further the understanding of climate change adaptation processes, more attention
needs to be paid to the various contextual factors that shape whether and how
climate-related knowledge and information is received and acted upon by actors
involved. This study sets out to examine the characteristics of forest owners' in
Sweden, the information and knowledge-sharing networks they draw upon for decision-
making, and their perceptions of climate risks, their forests' resilience, the need
for adaptation, and perceived adaptive capacity. By applying the concept of ego-
network analysis, the empirical data was generated by a quantitative survey
distributed to 3000 private forest owners' in Sweden in 2014 with a response rate
of 31%. The results show that there is a positive correlation, even though it is
generally weak, between forest owner climate perceptions and (i) network features,
i.e. network size and heterogeneity, and (ii) presence of certain alter groups
(i.e. network members or actors). Results indicate that forest owners' social
networks currently serve only a minimal function of sharing knowledge of climate
change and adaptation. Moreover, considering the fairly infrequent contact between
respondents and alter groups, the timing of knowledge sharing is important. In
conclusion we suggest those actors that forest owners' most frequently communicate
with, especially forestry experts providing advisory services (e.g. forest owner
associations, companies, and authorities) have a clear role to communicate both the
risks of climate change and opportunities for adaptation. Peers are valuable in
connecting information about climate risks and adaptation to the actual forest
property.
This research seeks to investigate the antecedents of e-Government adoption in a
small island developing state. An extended model comprising of the unified theory
of acceptance and use of technology 2 and the e-Government adoption model was
employed. Results from a cross-sectional survey of 247 citizens show that
performance expectancy, facilitating conditions, perceived value are positively
related to behavioural intention. Computer self-efficacy is shown to have a
significant negative relationship with behavioural intention and resistance to
change. Our results further demonstrate that trustworthiness is inversely related
to resistance to change. Small island developing states should engage in proper
awareness campaigns of e-Government services offered and focusing their efforts on
citizens aged 18-39 years old to obtain a critical mass of users. Website design
and information quality should be improved paying particular attention to security
and privacy, thereby increasing trust and reducing resistance to change. (C) 2017
Elsevier Ltd. All rights reserved.
E-government (E-Govt) services provide new opportunities to citizens by allowing
them to use government services (paying electricity bill, e-filing, e-ticketing,
get information about government policies & schemes etc.) anytime from anywhere
irrespective of geographical location and releases citizens bound by government
official hours. Experience plays an important role to change users' intention to
adopt, that impacts their behavior and attitude too. The aim of this study was to
investigate how citizens experience e-Gov services and how that experience
influences their behavior. The study also investigates how users value e-Gov
services. The study has used a qualitative approach involving 31 citizens of India,
where e-Gov services are still at an early stage. The findings highlight the extent
to which citizens are moving from traditional ways of using government services to
using it electronically. The study also takes into account the effect of these
technological innovations in government settings from a participant's perspective.
The implications for researchers and practitioners are then discussed, with
emphasis on government need to develop competent e-Gov services. (C) 2017 Elsevier
Ltd. All rights reserved.
Unresolved experimental Lyme arthritis in C3H (5-LOX)(-/-) mice is associated with
impaired macrophage phag-ocytosis of Borrelia burgdorferi. In the present study, we
further investigated the effects of the 5-LOX metabolite, (LT)B-4, on phagocytosis
of B. burgdorferi. Bone marrow-derived macrophages (BMDM) from 5-LOX-/- mice were
defective in the uptake and killing of B. burgdorferi from the earliest stages of
spirochete internali-zation. BMDM from mice deficient for the LTB4 high-affinity
receptor (BLT1(-/-)) were also unable to efficiently phagocytose B. burgdorferi.
Addition of exogenous LTB4 augmented the phagocytic capability of BMDM from both 5-
LOX-/- and BLT1(-/-) mice, suggesting the low-affinity LTB4 receptor, BLT2, might
be involved. Blocking BLT2 activity with the specific antagonist, LY255283,
inhibited phagocytosis in LTB4-stimulated BLT1(-/-) BMDM, demonstrating a role for
BLT2. However, the lack of a phagocytic defect in BLT2(-/-) BMDM suggested this was
a compensatory effect. In contrast, 12-HHT, a natural BLT2-specific high-affinity
ligand, and RvE1, a BLT1 agonist, were both unable to boost phagocytosis in BMDM
from either 5-LOX-/- or BLT1(-/-) mice, suggesting a specific role for LTB4 in
mediating phagocytosis in murine macrophages. This study demonstrates LTB4 promotes
macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfil this role in
the absence of BLT1.
Peripheral neuronal activation by inflammatory mediators is a multifaceted
physiological response that involves a multitude of regulated cellular functions.
One key pathway that has been shown to be involved in inflammatory pain isGq/GPCR,
whose activation by inflammatory mediators is followed by the regulated response of
the cation channel transient receptor potential vanilloid 1 (TRPV1). However, the
mechanism that underlies TRPV1 activation downstream of the Gq/GPCR pathway has yet
to be fully defined. In this study, we employ pharmacological and molecular biology
tools to dissect this activation mechanism via perforated-patch recordings and
calcium imaging of both neurons and a heterologous system. We showed that TRPV1
activity downstream of Gq/GPCR activation only produced a subdued current, which
was noticeably different from the robust current that is typical of TRPV1
activation by exogenous stimuli. Moreover, we specifically demonstrated that 2
pathways downstream of Gq/GPCR signaling, namely endovanilloid production by
lipoxygenases and channel phosphorylation by PKC, converge on TRPV1 to evoke a
tightly regulated response. Of importance, we show that only when both pathways are
acting on TRPV1 is the inflammatory-mediated response achieved. We propose that the
requirement of multiple signaling events allows subdued TRPV1 activation to evoke
regulated neuronal response during inflammation.- KumarR., Hazan, A., Geron, M.,
Steinberg, R., Livni, L., Matzner, H., Priel, A. Activation of transient receptor
potential vanilloid 1 by lipoxygenase metabolites depends on PKC phosphorylation.
This paper presents a harmonic instability analysis method using state-space
modeling and participation analysis in the inverter-fed ac power systems. A full-
order state-space model for the droop-controlled distributed generation (DG)
inverter is built first, including the time delay of the digital control system,
inner current and voltage control loops, and outer droop-based power control loop.
Based on the DG inverter model, an overall state-space model of a two-inverter-fed
system is established. The eigenvalue-based stability analysis is then presented to
assess the influence of controller parameters on the harmonic instability of the
power system. Moreover, the harmonic-frequency oscillation modes are identified,
where participation analysis is presented to evaluate the contributions of
different states to these modes and to further reveal how the system gives rise to
harmonic instability. Based on the participation analysis, a reduced-order model
for harmonic instability analysis is also proposed. The experimental results are
presented for validating the theoretical analyses.
We studied the metallothionein (NIT) response in cadmium-exposed worms (Eisenia
fetida) both at the protein level by Dot Immunobinding Assay (DIA) with a
polyclonal antibody raised against the most immunogenic part of this protein and at
the expression level by Northern blotting using a specific probe. NIT appeared as
two close isoforms. DIA results clearly demonstrated significant differences in MT
level of whole worm heat-treated supernatants between E. fetida exposed to Cd
concentrations as low as 8 mg Cd kg(-1) of dry soil compared to controls. Northern
blotting analysis performed on whole bodies of worms revealed that a single
exposure to 8 mg Cd kg-1 of dry soil for I day resulted in the production of NIT
mRNA. This response was maintained for exposure of at least I month. Clear
differences of NIT gene expression were also observed between worms exposed to
different Cd concentrations (8, 80 or 800 mg; Cd kg(-1) of dry soil).
Immunocytochemistry demonstrated that NIT was located in the chloragogenous tissue
surrounding the gut where metals are known to be accumulated. This work revealed
that E. fetida NIT is a sensitive and relevant biomarker of Cd exposure and
especially when considering gene expression response. Further experiments have now
to prove its usefulness in natural metal-contaminated soil toxicity assessments.
(c) 2006 Elsevier Inc. All rights reserved.
We studied metallothionein (NIT) response in the manure worm Eisenia fetida after
exposures to cadmium (Cd), zinc (Zn) or cadmium and zinc spiked media. NIT was
studied both at the protein level by Dot Immunobinding Assay, (DIA) and at the
expression level by Northern blotting. Cd was highly accumulated by worms whereas
Zn body concentration was regulated. In addition, Zn would limit Cd accumulation in
worms exposed to low Cd concentrations (1 and 8 mg Cd kg(-1) of dry soil). Exposure
to a mixture of Cd and Zn at high concentrations increased cytosolic NIT levels.
This increase would allow worms to regulate body Zn concentrations and also to
limit Cd toxicity. Cd exposures increased gene expression of Cd-binding MT isoform
(MT 2A) whereas Zn did not. However, when both metals were at high concentrations
in the exposure medium, this expression was further increased. Several hypotheses
are proposed to explain the results and the best approach to estimate metal
exposure of this earthworm species is given. Further experiments have now to be
performed to evaluate the usefulness of these NIT responses for field contaminated
soils toxicity assessment using this earthworm species. (C) 2007 Elsevier Inc. All
rights reserved.
Chronic organochlorine (OC) exposure has been shown to cause immune impairment in
numerous vertebrate species. To determine if elasmobranchs exhibited compromised
immunity due to high OC contamination along the coastal mainland of southern
California, innate immune function was compared in round stingrays (Urobatis
halleri) collected from the mainland and Santa Catalina Island. Proliferation and
phagocytosis of peripheral blood, splenic, and epigonal leukocytes were assessed.
Percent phagocytosis and mean fluorescence intensity (MFI) were evaluated by
quantifying % leukocytes positive for, and relative amounts of ingested fluorescent
E. coli BioParticles. Total cell proliferation differed between sites, with
mainland rays having a higher cell concentration in whole blood. Sigma PCB load
explained significantly higher % phagocytosis in blood of mainland rays, while
Sigma PCB and Sigma pesticide loads described increased splenic % phagocytosis and
MFI in the mainland population. Data provides evidence of strong OC-correlated
immunostimulation; however, other site-specific environmental variables may be
contributing to the observed effects. (C) 2016 Elsevier Ltd. All rights reserved.
Instead of analog electronic circuits and components, digital controllers that are
capable of active multi-resonant piezoelectric shunting are applied to elastic
metamaterials integrated with piezoelectric patches. Thanks to recently introduced
digital control techniques, shunting strategies are possible now with transfer
functions that can hardly be realized with analog circuits. As an example, the
`pole-zero' method is developed to design single-or multi-resonant bandgaps by
adjusting poles and zeros in the transfer function of piezoelectric shunting
directly. Large simultaneous attenuations in up to three frequency bands at deep
subwavelength scale (with normalized frequency as low as 0.077) are achieved. The
underlying physical mechanism is attributable to the negative group velocity of the
flexural wave within bandgaps. As digital controllers can be readily adapted via
wireless broadcasting, the bandgaps can be tuned easily unlike the electric
components in analog shunting circuits, which must be tuned one by one manually.
The theoretical results are verified experimentally with the measured vibration
transmission properties, where large insulations of up to 20 dB in low-frequency
ranges are observed.
Purpose: Emergency department assessment represents a critical but often missed
opportunity to identify elder abuse, which is common and has serious consequences.
Among emergency care providers, diagnostic radiologists are optimally positioned to
raise suspicion for mistreatment when reviewing imaging of geriatric injury
victims. However, little literature exists describing relevant injury patterns, and
most radiologists currently receive neither formal nor informal training in elder
abuse identification. Methods: We present 2 cases to begin characterisation of the
radiographic findings in elder abuse. Results: Findings from these cases
demonstrate similarities to suspicious findings in child abuse including high-
energy fractures that are inconsistent with reported mechanisms and the coexistence
of acute and chronic injuries. Specific injuries uncommon to accidental injury are
also noted, including a distal ulnar diaphyseal fracture. Conclusions: We hope to
raise awareness of elder abuse among diagnostic radiologists to encourage future
large-scale research, increased focus on chronic osseous findings, and the addition
of elder abuse to differential diagnoses.
Objectives: Physical activity may have positive effects on decreasing anxiety,
stress and depression, maintaining mental health and ensuring psychological
vitality. This study aimed to determine how a "Physical Activity Program" for
elderly people in nursing homes affected their depressive symptoms and quality of
life. Methods: We included 80 individuals aged >65 years (40 in the intervention
group, 40 controls) in this experimental, randomized, controlled pretest-posttest
study. Besides socio-demographic data, depressive symptoms and quality of life were
assessed by standardized procedures (Beck Depression Scale [BDI], SF 36 Quality of
Life Questionnaire) before and after a ten-weeks lasting "Physical Activity
Program", consisting of 10 min warm-up activities, 20 mintes rhythmic exercices, 10
min cool-down exercises and a 30 mintes free walking period on four days of the
week. Results: In contast to controls, individuals of the intervention group
presented with a significant decrease in the BDI after the "Physical Activity
Program". Likewise, eight-subscales and two sub-dimensions of the SF 36 Quality of
Life Questionnaire significantly improved only in the experimental group (p <
0.05). Conclusions: Our results suggest that a structured physical activity program
positively impacts depressive symptoms and quality of life in elderly individuals.
(C) 2017 Elsevier B.V. All rights reserved.
Whether total joint replacement (TJR) patients are susceptible to postoperative
cognitive dysfunction (POCD) remains unclear due to inconsistencies in research
methodologies. Moreover, cognitive reserve may moderate the development of POCD
after TJR, but has not been investigated in this context. The current study
investigated POCD after TJR, and its relationship with cognitive reserve, using a
more rigorous methodology than has previously been utilized. Fifty-three older
adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6months).
Forty-five healthy controls matched for age, gender, and premorbid IQ were re-
assessed after an equivalent interval. Cognition, cognitive reserve, and physical
and mental health were all measured. Standardized regression-based methods were
used to assess cognitive changes, while controlling for the confounding effect of
repeated cognitive testing. TJR patients only demonstrated a significant decline in
Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive
reserve only predicted change in TMT B scores among a subset of TJR patients.
Specifically, patients who showed the most improvement pre to post surgery had
significantly higher reserve than those who showed the greatest decline. The
current study provides limited evidence of POCD after TJR when examined using a
rigorous methodology, which controlled for practice effects. Cognitive reserve only
predicted performance within a subset of the TJR sample. However, the role of
reserve in more cognitively compromised patients remains to be determined.
Static VAR compensators (SVC) can improve some of the power quality (PQ) indices
such as voltage flicker, unbalances, and power factors in power systems if properly
controlled. Different nonlinear and time-varying loads generate these parameters.
One of the great nonlinear loads is the electric arc furnace (EAF), which causes
waveform distortions, voltage unbalances, and fluctuations. In this paper, a new
digital and prediction-based control for thyristor switched capacitors (TSCs) was
proposed to compensate an actual steel industrial plant. The digital control was
based on generating adequate synchronous pulses, calculating required suitable
susceptance, and measuring correct reactive power. The proposed TSC improved the PQ
by means of the feedback from voltage and power factor. A predictive method based
on time series and recursive least square with dynamic learning factor was then
applied to estimate EAF reactive power in the future so that the TSC performance
was enhanced by reducing the natural time delay. A band-pass harmonic filter was
designed to compensate the load current harmonics and to protect the capacitor
banks in the TSC. Finally, the suggested TSC was implemented in a steel industrial
plant as an actual power system with 2 EAFs. The modeling and experimental results
indicate the effectiveness of the proposed TSC.
This study presents control algorithms for a new unified power quality conditioner
(UPQC) without the series transformers that are frequently used to make the
insertion of the series converter of the UPQC between the power supply and the
load. The behaviour of the proposed UPQC is evaluated in presence of voltage
imbalances, as well as under non-sinusoidal voltage-and current conditions. The
presented algorithms derive from the concepts involving the active and non-active
currents, together with a phase-locked-loop circuit. Based on these real-time
algorithms, and considering the proposed hardware topology, the UPQC is able to
compensate the harmonic components of the voltages and currents, correct the power
factor, and keep the load voltages regulated, all of this in a dynamic way,
responding instantaneously to changes in the loads or in the electrical power
system. The control algorithms were distributed in a two-DSP digital control
architecture, without any communication between them. Consequently, can be
increased the sampling frequency of the acquired voltages and currents and improve
the UPQC performance. Furthermore, some constraints of the proposed UPQC are
evidenced, particularly when the main voltages are imbalanced. Simulation and
experimental results are presented to verify the UPQC performance under transient
and steady state conditions.
Second-order generalised integrator or resonant integrator (RI) has wide range of
applications. Forward and backward Euler's approximation based two integrator
realisation of RI is an easily implementable frequency adaptive method. However, it
suffers from resonant frequency deviation due to discretisation. The discretisation
methods that lead to accurate realisation of RI require online calculation or
lookup table of trigonometric functions to accommodate frequency variation. In this
study, multi-rate computation-based implementation of two integrator-based RI has
been proposed to minimise resonant frequency deviation. In this method, no
additional logic elements are consumed to achieve accurate resonant frequency
location. This along with down-sampling leads to lesser phase lag of RI. The effect
of quantisation on resonant frequency deviation has been analysed for proper choice
of calculation time. It is also shown that appropriate choice of down-sampling
instants give a range of phase response characteristics around the nominal
continuous time RI phase response. The accuracy of resonant frequency emulation has
been experimentally verified by implementing a proportional-resonant controller as
current controller.
This paper is a study on the real-time implementation of a position-control based
electric elevator drive. The information contained within this paper serves as a
framework to expand the usefulness of electric drives through the addition of
digital control systems and switching power supplies. The tangible example of an
elevator driven by a permanent-magnet DC motor with position control is used to
relate to the work and apply it to various mechanical systems. The tasks to be
accomplished to achieve an electric elevator drive with position control are as
follows: determining the parameters of the motor, designing a control system to
direct the motor as desired, and verifying the performance of the system through
the use of computer simulations and real-time Hardware-In-The-Loop (HIL)
experimental testing.
Electricity load demand estimation has a remarkable impact on the economic policies
of power industry and business cycles. Forecasting the movements of load demand
provides to know the tendency of the future and can lead to a clear decision in
strategic, planning or investments. Besides the ability to know the fluctuations of
the future values contributes to the management of daily/weekly and long term
operations. This study aims to predict the electricity load demand using a hybrid
method that incorporates Empirical Mode Decomposition (EMD) and Support Vector
Regression (SVR) algorithms. The proposed EMD-SVR method integrates the EMD method
to SVR algorithm by using EMD as a denoising step on the training data. Unlike the
previous studies, the proposed algorithm is not dependent to a specific Intrinsic
Mode Function (IMF) for denoising and model learning. Experimental results are
conducted on 3 electricity load datasets from different countries and the proposed
method is compared with SVR algorithm using different feature vectors as well. It
is shown that the proposed algorithm outperforms the SVR and non-feature used
denoised-SVR algorithm on electricity load forecasting. (C) 2017 Elsevier Ltd. All
rights reserved.
As environmental issues become more prominent, electric vehicles (EV) have
attracted an increasing amount of attention. However, the continuous cruising
distance of an EV is limited to approximately 160 km, which is insufficient for
everyday use. Battery capacity is the limiting factor in long-distance EV travel,
because the vehicles need to stop at EV recharging stations multiple times. In
Japan, there are more than 2,000 EV charge stations, but there are, at most, two
rapid chargers. When multiple users converge at the station, a queuing (or waiting)
condition is created, which may lead to a call-loss condition. In other words, an
appropriate number of chargers must be installed at each station when planning the
EV infrastructure. Therefore, the number of vehicles entering the station must be
estimated. In this study, a mathematical model based on the supporting
infrastructure for widespread EV use is proposed to estimate the number of vehicles
arriving at each charge station.
In order to attain emissions reduction targets to improve air quality and reduce
global warming, electric vehicles (EVs) arise as alternatives to conventional
vehicles fueled by fossil fuels. In this context, this work presents a comparative
study between an EV and its conventional version, a medium-duty, diesel engine
powered vehicle, from road tests following a standard cycle in urban driving
conditions. The performance parameters evaluated are EV electric energy consumption
and carbon dioxide (CO2) emissions from electricity generation and, for the
conventional vehicle, exhaust CO2 emissions and energy consumption calculated from
fuel consumption and heating value. Five scenarios were built to conduct an
economic viability study in terms of payback and net present value (NPV).
Considering the conditions applied, the results from the environmental analysis
showed that CO2 emissions from the EV was 4.6 times lower in comparison with the
diesel vehicle. On the other hand, the economic analysis revealed that the
viability of the EV is compromised, mainly due to the imported parts with
unfavorably high exchange rates. In the best scenario and not considering revenue
from commercial application, the calculated payback period of the EV is 13 years of
operation. (C) 2017 Elsevier Ltd. All rights reserved.
State-of-energy (SoE) is an important index for batteries in electric vehicles and
it provides the essential basis of energy application, load equilibrium and
security of electricity. To improve the estimation accuracy and reliability of SoE,
a novel multi-model fusion estimation approach is proposed against uncertain
dynamic load and different temperatures. The main contributions of this work can be
summarized as follows: (1) Through analyzing the impact on the estimation accuracy
of SoE due to the complexity of models, the necessity of redundant modeling is
elaborated. (2) Three equivalent circuit models are selected and their parameters
are identified by genetic algorithm offline. Linear matrix inequality (LMI) based
H-infinity state observer technique is applied to estimate SoEs on aforementioned
models. (3) The concept of fusion estimation is introduced. The estimation results
derived by different models are merged under certain weights which are determined
by Bayes theorem. (4) Batteries are tested with dynamic load cycles under different
temperatures to validate the effectiveness of this method. The results indicate the
estimation accuracy and reliability on SoE are elevated after fusion. (C) 2016
Elsevier Ltd. All rights reserved.
The increasing demand for electricity caused by a growing number of electric
vehicles (EV) might challenge future energy systems. For a smooth integration of
the electricity demand from EV, a comprehensive knowledge of its characteristics is
essential. The analysis of charging behavior patterns of EV and resulting load
profiles become important premises for this crucial task. Three electric mobility
studies in Germany's southwestern region (Get eReady, iZEUS, and CROME) deliver
comprehensive data of EV use for this purpose. In this paper we analyze and discuss
the mobility and charging characteristics of this data in detail. We derive
empirical EV load profiles and show how they are affected by charging management.
We present a model to simulate EV loads based on statistical characteristics of the
conducted studies. The resulting charging load profiles show similar patterns as
other EV studies. The developed simulation model and its results (see supplementary
data available online) allow a realistic representation of EV demand in analyses of
future energy systems. (C) 2017 Elsevier Ltd. All rights reserved.
This paper investigates the impact of plug-in electric vehicle (EV) integration on
the power systems scheduling and energy cost. An intermediary entity, the EV
aggregator, participates in the market on behalf of the EV owners by optimally
self-scheduling under the price-taking approach. Through detailed rolling
simulations for a year and different EVs' penetration scenarios at a large insular
power system, this work highlights the different impact of direct and smart
charging on power system scheduling and energy costs, the limitations of the price-
taking approach, which is widely used in self-scheduling models, and the difference
in system value and market value that smart charging adoption creates in
restructured markets under the marginal pricing rule.
In this paper, we use the electricity consumption model for electric vehicular flow
[H. Xiao, H. J. Huang and T. Q. Tang, Mod. Phys. Lett. B 30 (2016) 1650325] to
study the effects of road conditions on the electricity consumption of electric
vehicular flow during the evolutions of shock, rarefaction wave and small
perturbation. The numerical results indicate that road conditions have negative
influences on the electricity consumption during the evolutions of shock and
rarefaction wave (i.e. the electricity consumption increases when road conditions
become better) and positive impacts on the electricity consumption during the
evolution of small perturbation when the traffic flow is unstable (i.e. the
electricity consumption produces oscillation, but its amplitude decreases when road
conditions become better).
This paper examines students' achievements in solving problems and their
misunderstandings when using models. A mixed research methodology was applied.
Quantitative research investigated how the performance of students with various
levels of high school GPAs correlated with their rating of their lecturers'
teaching proficiency. Four lecturers and 336 mechanical and electronics engineering
students participated in the study. Achievement tests, consisting of problems to be
solved by using models of a diode and an ideal operational amplifier, were
implemented in introductory courses in electronics. Students taught by lecturers
whom they rated as having high levels of teaching expertise achieved significantly
higher grades on these tests than did students taught by lecturers receiving lower
ratings for their teaching expertise. The tests investigated performance on three
taxonomy levels, and the results were consistent on all three levels. The grades on
the knowledge taxonomy level were higher than the grades on the routine level, and
both were higher than the grades on the interpretation level, as expected.
Qualitative research, based on analysis of students' written explanations and on
face-to-face interviews, exposed three kinds of misunderstanding: 1) that the
purpose of engineering models is just to simplify calculations, not to yield
usable, reliable results; 2) that a nonlinear problem can be solved using linear
concepts; and 3) that the accuracy of a solution is indicated by the number of
decimal places in the result, rather than by its closeness to the actual value.
Electrical impedance spectroscopy usually requires a wide bandwidth current source
with high output impedance. Non-idealities of the operational amplifier (op-amp)
degrade its performance. This work presents a particle swarm algorithm for
extracting the main AC characteristics of the op-amp used to design a mirrored
modified Howland current source circuit which satisfies both the output current and
the impedance spectra required. User specifications were accommodated. Both
resistive and biological loads were used in the simulations. The results showed
that the algorithm can correctly identify the open-loop gain and the input and
output resistance of the op-amp which best fit the performance requirements of the
circuit. It was also shown that the higher the open-loop gain corner frequency the
higher the output impedance of the circuit. The algorithm could be a powerful tool
for developing a desirable current source for different bioimpedance medical and
clinical applications, such as cancer tissue characterisation and tissue cell
measurements.
In this paper, a low-power and precise electrical stimulator is introduced in which
no operational amplifier (OPAMP) is used. For electrical stimulations that have low
pulse width, an OPAMP with high slew rate is needed which is power consuming. In
this work, the OPAMP is substituted with a digital circuitry. A 100 KHz clock is
also used to update the current of the stimulator in the stimulation phases in
order to make the stimulator accurate enough. Producing such a clock needs only few
micro watts. This stimulator is simulated in a 0.18 mu m CMOS process, as well. The
simulation results shows that this stimulator has only 0.056% charge mismatch in 1
mA stimulation current with a pulse width of 32 mu s.
Gap junctions underlie electrical synaptic transmission between neurons. Generally
perceived as simple intercellular channels, electrical synapses have demonstrated
to be more functionally sophisticated and structurally complex than initially
anticipated. Electrical synapses represent an assembly of multiple molecules,
consisting of channels, adhesion complexes, scaffolds, regulatory machinery, and
trafficking proteins, all required for their proper function and plasticity.
Additionally, while electrical synapses are often viewed as strictly symmetric
structures, emerging evidence has shown that some components forming electrical
synapses can be differentially distributed at each side of the junction. We propose
that the molecular complexity and asymmetric distribution of proteins at the
electrical synapse provides rich potential for functional diversity. (c) 2016 Wiley
Periodicals, Inc.
Studies on the implications of population density on energy consumption in small
and medium-sized cities in low- and middle-income countries are limited. This paper
estimates and analyses energy consumption, using a diverse set of methods, to
compare two medium-sized cities in Thailand with similar urban forms and
socioeconomic characteristics but different population densities - namely, the less
dense city Chaiyaphum and denser city Roi Et. The results reveal that the annual
household electricity consumption per capita of these two cities is similar,
showing no implications of density. However, private transport energy consumption
per capita in Chaiyaphum is 22 per cent higher, supporting the hypothesis that a
less dense city will have higher transport energy consumption. The key factor
identified is the greater distance travelled by households located in the peri-
urban areas in the less dense city. This has important policy implications for
urban planning and urban development practices in Thailand.
Since the reforming and opening up in 1978, China has experienced a miraculous
development. To investigate the transformation and upgrading of China's economy,
this study focuses on the relationship between economic growth and electricity
consumption of the secondary and tertiary industry in China. This paper captures
the dynamic interdependencies among the related variables using a theoretical
framework based on a Vector Autoregressive (VAR)-Vector Error Correction (VEC)
model. Using the macroeconomic and electricity consumption data, the results show
that, for secondary industry, there is only a unidirectional Granger causality from
electricity consumption to Gross Domestic Product (GDP) from 1980 to 2000. However,
for the tertiary industry, it only occurs that GDP Granger causes electricity
consumption from 2001 to 2014. All these conclusions are verified by the impulse
response function and variance decomposition. This study has a great significance
to reveal the relationship between industrial electricity consumption and the
pattern of economic development. Meanwhile, it further suggests that, since China
joined the World Trade Organization (WTO) in 2001, the trend of the economic
transformation and upgrading has gradually appeared. (C) 2017 Elsevier B.V. All
rights reserved.
Recently, several articles (Cullmann, 2012; Agrell et al., 2014; Filippini and
Orea, 2014; Llorca et al., 2014) address the issue of benchmarking decision making
units with different technologies by using latent class models. This method groups
units that have similar technology for better comparison. Under this scheme, there
are two implicit assumptions: First, that each class reflects a unique technology
where its elements are not outliers. Second, classes are assumed to be stationary
and fixed. If this assumption is violated, the classification is transient and
time-dependent, inadequate for the regulatory use suggested in the seminal papers.
We apply latent class models to classify Swedish electricity distributors under
different specifications. In most of the models, we identify one large class with
approximately 78.4% of the DMU's and two small classes with 7.4% and 14.2%
respectively. Moreover, most of small classes elements switch between categories.
We contrast our parametric results with nonparametric outlier detector methods and
find a relationship between identified outliers and the elements of smaller
residual classes. We believe that our work is an important caveat to the adoption
of latent class modelling as an alternative or remedy for conventional models,
relying on a homogeneous reference set.
The increasing limitations on available energy require use of new environmentally
friendly resources and enhancement of utilization efficiency of available
resources. Energy storage systems (ESSs) are a promising technology to realize such
a goal; however, their application in networks requires an investment that must be
economically justified. This study examined the effect of ESS use on energy
generation costs in networks for a specific time period. This includes determining
the best location for installation of the ESS and the best possible operation
schedules for the ESS and power plants to achieve the greatest decrease in daily
energy generation costs. The influences of all the factors affecting the final
solution were studied under different scenarios. The effects of power plant cost
functions, transmission line capacity, and network upgrades were compared. All
scenarios were implemented in an IEEE standard 30-bus network. The best possible
specifications of ESS can reduce daily energy generation cost by 3% for selected
power plant cost functions. It was found that the use of ESS in a network uniformed
stress on the transmission line and, in such a case, it would be possible to defer
the network upgrade for 21 years.
Since 2009, Singapore has set about implementing mitigation and energy efficiency
measures in key sectors to achieve unilaterally pledged reductions in greenhouse
gas (GHG) emissions of 7-11% below business-as-usual (BAU) levels in 2020. Carbon
dioxide (CO2) emissions from fossil fuel-fired power plants are a major focus for
emissions abatement, with an expected reduction of 4 Mt CO2 from the electricity
generation sector in 2020. In this paper, we explore Singapore's various strategies
in the electricity generation sector to fulfil this target and use an EnergyPLAN
optimization model to assess the impact of these strategies on CO2 emissions from
Singapore's electricity generation sector through to 2020. A comparison of BAU
scenario in 2020 (BAU 2020), 2020 target emissions reduction trajectory, and three
emissions reduction alternative policy scenarios (denoted APS-I, APS-II, and APS-
III) is carried out. The EnergyPLAN simulation results indicate that all three APS
scenarios achieve the 2020 carbon emissions reduction target in Singapore's
electricity generation sector. The results furthermore suggest that the 2020
electricity generation associated emissions reduction target can be met through
measures that are already available. Vulnerabilities are identified in Singapore's
electricity generation fuel mix, and emission reduction strategies beyond 2020 are
outlined. (C) 2017 Elsevier Ltd. All rights reserved.
Currently, privatized state-owned Taiwan Power Company (Taipower) has a monopoly
over energy production and vertically integrates the electricity market in Taiwan.
Because of the geographical environments, economies of scales, social structures,
and diverse political ideologies in Taiwan, the electricity market exhibits unique
characteristics. To maximize the benefits of electricity liberalization, future
market operations must not only involve conventional considerations for economic
dispatch; overall social welfare should be included by incorporating the
perspectives of fairness, responsibility, and the environment, and key electrical
grid operations should be executed appropriately. We responded to the future market
liberalization planning by including factors, such as, environmental effects and
government policies, in addition to electrical line construction, and operation
cost factors involved in the entire operational model planning. On the basis of
responsibility sharing, this study used the simulated -responsibility three-phase
pricing method. The proposed pricing method is expected to help attain the
following policy goals: 1. Achieving reasonable power price allocations; 2.
Simultaneously ensuring fair and efficient electric grid operation; 3. Changing the
operation orientations of the power plants and electrical grid facilities; and 4.
Increasing the rate of renewable energy use.
Countries are implementing policies to develop greener energy markets worldwide. In
Europe, the "2030 Energy and Climate Package" asks for further reductions of green
house gases, renewable sources integration, and energy efficiency targets. But the
polluting intensity of electricity may be different in average than when
considering market inefficiencies, in particular losses, and therefore the
implemented policy must take those differences into account. Precisely, herein we
study the importance in terms of CO2 emissions the extra amount of energy necessary
to cover losses. With this purpose we use Spanish market and system data with
hourly frequency from 2011 to 2013. Our results show that indeed electricity losses
significantly explain CO2 emissions, with a higher CO2 emissions rate when covering
losses than the average rate of the system. Additionally, we find that the market
closing technologies used to cover losses have a positive and significant impact on
CO2 emissions: when polluting technologies (coal or combined cycle) close the
market, the impact of losses on CO2 emissions is high compared to the rest of
technologies (combined heat and power, renewables or hydropower). To the light of
these results we make some policy recommendations to reduce the impact of losses on
CO2 emissions.
This paper addresses electricity transmission planning under the new industry and
institutional structure of the Mexican electricity market, which has engaged in a
deep reform process after decades of a state-owned vertically -integrated-non-
competitive-closed industry. Under this new structure, characterized by a nodal
pricing system and an independent system operator (ISO), we analyze welfare-optimal
network expansion with two modeling strategies. In a first model, we propose the
use of an incentive price-cap mechanism to promote the expansion of Mexican
networks. In a second model, we study centrally-planned grid expansion in Mexico by
an ISO within a power-flow model. We carry out comparisons of these models which
provide us with hints to evaluate the actual transmission planning process proposed
by Mexican authorities (PRODESEN). We obtain that the PRODESEN plan appears to be a
convergent welfare-optimal planning process.
We study supply function competition among conventional power generators with
different levels of flexibility and the impact of intermittent renewable power
generation on the competition. Inflexible generators commit production before
uncertainties are realized, whereas flexible generators can adjust their production
after uncertainties are realized. Both types of generators compete in an
electricity market by submitting supply functions to a system operator, who solves
a two-stage stochastic program to determine the production level for each generator
and the corresponding market prices. We aim to gain an understanding of how
conventional generators' (in) flexibility and renewable energy's intermittency
affect the supply function competition and the market price. We find that the
classic supply function equilibrium model overestimates the intensity of the market
competition, and even more so when more intermittent generation is introduced into
the system. The policy of economically curtailing intermittent generation
intensifies the market competition, reduces price volatility, and improves the
system's overall efficiency. Furthermore, these benefits of economic curtailment
are most significant when the production-based subsidies for renewable energy are
absent.
We conduct a fractional integration and cointegration study of several Kenyan
electricity price series in order to determine whether signs of persistence or mean
reversion can eventually be discovered. Such features can be considered as relevant
when considering the possibilities of shocks affecting the energy market of Kenya,
which has recently been subjected to major debate. We conclude that electricity
prices in Kenya contain unit roots, implying permanent shocks lasting forever.
Among the factors affecting electricity prices, we find oil prices and interest
rates have significant positive effects on electricity, and based on the fact that
all the series are I(1), long run relationships are examined by means of fractional
cointegration. The recently introduced FCVAR model is implemented, with results
showing that the series under study are fractionally cointegrated, with oil price
shocks affecting electricity prices. (C) 2017 Elsevier Ltd. All rights reserved.
Electricity customers who install solar panels often are paid the prevailing retail
price for the electricity they generate. We demonstrate that this rate of
compensation typically is not optimal. A payment for distributed generation (w)
that is below the retail price of electricity (r) often will induce the welfare-
maximizing level of distributed generation (DG) when the fixed costs of centralized
electricity production and the network management costs of accommodating
intermittent solar DG are large, and when centralized generation and DG produce
similar (pollution) externalities. w can optimally exceed r under alternative
conditions. The optimal DG compensation policy varies considerably as industry
conditions change. Furthermore, a requirement to equate w and r can reduce
aggregate welfare substantially and can generate pronounced distributional effects.
Electricity security, generally referring to a system's capability to provide
electricity to its users, is a multi-faceted problem attracting mounting attention
from policy makers and scientists around the world. Electricity security
encompasses largely different properties based upon the time/geographical scales of
the factors affecting electricity delivery; it is challenged by threats surfacing
in spheres far beyond the physical one; it involves a myriad of stakeholders
spanning manifold disciplines and with considerably different expectations from the
electricity commodity or services; it can be studied as a complicated techno-
economic problem or as a complex socio-economic problem. All the above reasons, in
a framework of changing European Union (EU) and global energy scenarios, render
electricity security ever more challenging to assess and critical to safeguard.
Against this background, this work presents recommendations to bring science and
policy making closer towards evaluating and handling EU electricity security. More
in detail, this is done by: Characterising electricity security via features at the
cross-roads of policy and science. Reviewing the electricity security modelling and
assessment approaches across sectors. Proposing elements for a novel electricity
security decision-analytic framework for the EU. Contextualising the proposed
framework in EU's Energy Union grid design initiatives.
This paper accepts the widespread view that as electricity generation systems
transition towards a greater proportion of renewables provision, there will be an
increasing need for storage facilities. However, it differs from most such studies
in contrasting the private incentives of a storage operator with the public
desirability of bulk storage. A key factor in the context of a market such as
Britain, where renewable energy largely means wind generation, is the nature of
wind generation itself. The problem of wind's high variance and intermittent nature
is explored. It is argued that not only is there a missing money and a missing
market issue in providing secure energy supplies, there is also a missing
informational issue. A key opportunity for new storage is participation in a
capacity market, if the setting is right.
Liberalization policies, the challenges of integrating distributed generation
resources, and the recent flattening of electricity demand due to the economic
crisis and technological change have led to lower returns for European electricity
suppliers. Innovative and sustainable business models are needed to serve
electricity customers while reflecting the operational needs of the system and
maintaining supplier financial viability. This paper describes a novel model of
Integrated Energy Services that encompasses distributed generation (DG) and demand
response (DR) resources for industrial customers. We further reflect on some of the
market opportunities and regulatory drivers for the development of similar schemes
across Europe. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents an integrated model for risk management of electricity traders.
It integrates the Unit Commitment (UC) problem, which provides the power generation
units' dispatch and the electricity price forecasting of a power system, with
artificial neural network (ANN) models, which provide electricity price forecasting
of a neighbouring power system by incorporating a clustering algorithm. The
integrated model is further extended to estimate the traders' profitability and
risk, incorporating risk provisions. The integrated model is applied in bi-
directional trading between the Italian and Greek day-ahead electricity markets.
The UC and neural network models provide forecasts of the wholesale electricity
price in Greece and Italy respectively. The model attributes a confidence level of
the price forecasts, depending on the data clustering and the forecasting
performance of each model. The integrated model identifies periods with high price
margins for trading for each power flow, aligned with a forecasting confidence and
a risk level. The integrated model can provide price signals on the profitability
of traders and useful insights into the risk of traders. (C) 2017 Elsevier Ltd. All
rights reserved.
This paper introduces a panel threshold model to empirically estimate the main
drivers of electricity performance. The empirical analysis is based on a panel data
set including 30 OECD countries over the period 1975-2013. We argue that effective
regulatory reforms have positive interaction with the electricity generated leading
to a higher capacity utilization and an increase in the level of labor productivity
of the sector. The threshold analysis suggests that for already economically
liberalised countries the level of economic freedom does not affect electricity
generation and subsequently the level of electricity performance. Finally, the
results do not drastically change when the Renewable Energy Sources (RES) are taken
into account.
In the last decade, the share of renewable energy sources in the energy mix has
risen significantly in many countries, and the large-scale integration of these
intermittent energy sources constitutes a major challenge to the power grid. A
crucial building block of a successful transformation of today's energy systems is
the use of energy storage, either co-located with renewable energy sources or on a
grid-level. To this end, we present a model on the basis of a Markov Decision
Process for the short-term trading of intermittent energy production co-located
with energy storage. The model explicitly considers the time lag between trade and
delivery of energy, which is characteristic for energy markets. Our storage
representation includes asymmetrical conversion losses, asymmetrical power, and
self-discharge. Stochastic production and market prices are represented by ARIMA
processes, and the producer may also undertake price arbitrage by purchasing energy
on the market when prices are comparatively low. Regarding the solution of our
model, we develop several intuitive and easily interpretable decision rules that
can be readily applied in practice. An extensive numerical study, based on real-
world data, confirms the excellent performance of these rules in comparison to a
sophisticated Approximate Dynamic Programming algorithm adapted from literature.
(C) 2017 Elsevier Ltd. All rights reserved.
Resources scarcity and electricity demand have been dramatically increasing.
Wastewater is recognized as one of resources for water, energy and plant
fertilizing nutrients. Nevertheless, current wastewater treatment technologies have
limitations due principally to their energy- and cost-intensive for achieving the
conversion target of wastewater recovery. It is desired to develop a new technology
to generate alternatives to conventional energy sources in a sustainable manner. An
innovative technology based on the use of microbial fuel cells (MFCs) has been
proved as a critical pathway for bioconversion processes towards electricity
generation, then for addressing energy and environmental problems. Three special
features including energy saving, less sludge production and less energy production
make MFCs outstanding compared with the existing technologies. Multiform
wastewaters could be efficiently degraded through advancing MFCs alone or
integrating MFCs with other processing units. However, the low power density and
the high operating cost of MFCs have greatly limited their applications on large-
scale problems, and then result in some debates and doubts about their development
and applications. Therefore, this paper objectively discussed the problems and
applications of MFCs in wastewater treatment. Moreover, the integration of MFCs
with other treatment processes was presented to verify the practicality and
effectiveness of MFCs in contaminants removal. Furthermore, the primary challenges
and opportunities for scaling-up and future applications of MFCs in wastewater were
analyzed.
A digitally controlled sonar power amplifier for underwater transmitter is
explained in this paper. It proposes a method of generating unipolar Sine Pulse
Width Modulation (SPWM) signals for echo ranging sonar. This method can be
effectively used in all kinds of inverters including high frequency inverters. A
low cost digital signal controller was used to generate SPWM signals and used as
gating pulses for a Controlled Full Bridge Circuit (CFBC). The power required,
frequency, pulse-width and pulse repetition interval are given as the inputs to the
digital controller and gating pulses for the CFBC are generated as output from the
controller. A power transformer connected across CFBC boosts output voltage
followed by power filter which removes unwanted harmonics present in the output.
The output after the power filter is used to excite electro-acoustic transducer
elements underwater. The voltage and current of the load were given as feedback to
the same controller for voltage mode control loop implementation of the system. A
prototype of 1kW Switch Mode Power Amplifier (SMPA) for echo ranging sonar has been
designed and digital control has been implemented. Salient results are presented.
This paper introduces DNA-wrapped multi-walled carbon nanotube (MWCNT)-modified
genosensor for the detection of Escherichia coli (E. coli) from polymerase chain
reaction (PCR)-amplified real samples while Staphylococcus aureus (S. aureus) was
used to investigate the selectivity of the biosensor. The capture probe
specifically recognizing E. coli DNA and it was firstly interacted with MWCNTs for
wrapping of single-stranded DNA (ssDNA) onto the nanomaterial. DNA-wrapped MWCNTs
were then immobilised on the surface of disposable pencil graphite electrode (PGE)
for the detection of DNA hybridization. Electrochemical behaviors of the modified
PGEs were investigated using Raman spectroscopy and differential pulse voltammetry
(DPV). The sequence selective DNA hybridization was determined and evaluated by
changes in the intrinsic guanine oxidation signal at about 1.0 V by DPV. Numerous
factors affecting the hybridization were optimized such as target concentration,
hybridization time, etc. The designed DNA sensor can well detect E. coli DNA in 20
min detection time with 0.5 pmole of detection limit in 30 mu L of sample volume.
Electrochemical immunosensors have the potential to transform analytical procedures
within the food industry by providing highly specific, rapid, and inexpensive
determination of pathogens. In this paper, recent advances in this area are
outlined. In particular, attention is paid to new methods that have been developed
for the modification of working electrode surfaces. Many advances have been related
to the use of novel nanomaterials such as carbon nanotubes, graphene, and metallic
nanoparticles, often used in conjunction with each other or polymers. The use of
these materials has generally provided superior sensor sensitivity. The application
of immunosensors to the detection of a range of pathogens in real samples is then
investigated to establish whether they provide solutions in practical applications.
A platform for electrochemical transduction suitable for miniaturised point-of-care
diagnostic solutions with intuitive optical read-out was designed. Electrolytic
current from electrochemical cell was transduced into the glow of a light-emitting
diode. Its performance was optimised and several variants of transducing circuitry
were tested. The circuit comprising field-effect transistor (FET) exhibited the
sought abilities - absolute simplicity and high and tuneable sensitivity of the
transducing device. Limit-of-detection, i.e. a signal readable by naked-eye without
any additional instrumentation was as low as 4 mu M for direct assay of H2O2. The
whole transducing system employing FET consisted of 4 off-the-shelf components and
its price reached <0.3 (sic) even at small-scale experimental production. As our
system was rather suitable for the semiquantitative "YES/NO" applications due to
the steep response curve, an alternative circuitry for widening the linear range
was also probed. Finally, rather higher initial voltage that was required in the
electrochemical cell for FET-based transducer lead us to design a further
simplified and more variable circuit employing the operational amplifier. (C) 2016
Elsevier Ltd. All rights reserved.
Electrochemistry coupled to liquid chromatography and mass spectrometry was used
for simulating the biological and environmental fate of polycyclic aromatic
hydrocarbons (PAHs) as well as for studying the PAH degradation behavior during
electrochemical remediation. Pyrene and benzo[a]pyrene were selected as model
compounds and oxidized within an electrochemical thin-layer cell equipped with
boron-doped diamond electrode. Atpotentials of 1.2 and 1.6 V vs. Pd/H-2,H- quinones
were found to be the major oxidation products for both investigated PAHs. These
quinones belong to a large group of PAH derivatives referred to as oxygenated PAHs,
which have gained increasing attention in recent years due to their high abundance
in the environment and their significant toxicity. Separation of oxidation products
allowed the identification of two pyrene quinone and three benzo[a]pyrene quinone
isomers, all of which are known to be formed via photooxidation and during
mammalian metabolism. The good correlation between electrochemically generated PAH
quinones and those formed in natural processes was also confirmed by UV irradiation
experiments and microsomal incubations. At potentials higher than 2.0 V, further
degradation of the initial oxidation products was observed which highlights the
capability of electrochemistry to be used as remediation technique. (C) 2017
Elsevier Ltd. All rights reserved.
ObjectiveElectroconvulsive therapy (ECT) remains underutilized because of fears of
cognitive and medical risks, including the risk of death. In this study, we aimed
to assess the mortality rate of ECT by means of a systematic review and pooled
analysis. MethodThe study was conducted in adherence with the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related
mortality rate was calculated as the total number of ECT-related deaths reported in
the included studies divided by the total number of ECT treatments. ResultsFifteen
studies with data from 32 countries reporting on a total of 766 180 ECT treatments
met the inclusion criteria. Sixteen cases of ECT-related death were reported in the
included studies yielding an ECT-related mortality rate of 2.1 per 100 000
treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001
(covering 414 747 treatments), there was only one reported ECT-related death.
ConclusionThe ECT-related mortality rate was estimated at 2.1 per 100 000
treatments. In comparison, a recent analysis of the mortality of general anesthesia
in relation to surgical procedures reported a mortality rate of 3.4 per 100 000.
Our findings document that death caused by ECT is an extremely rare event.
A novel driving method implemented with high frequency electromagnetic isolation is
proposed in this paper. And the hardware designing schematic diagram and the
software configuration method are presented. Then the corresponding operating
principle is analyzed in detail based on digital control chip and analog circuits.
The proposed driving method can be applied to real-time varying pulse width of the
control signal and the duty-cycle ratio of this control pulse can be regulated in
the range of 0-100 %. This novel driving method can achieve not only the advantages
of high insulation and high common-mode suppression, but also the merits of low
cost and fast dynamic response speed, and it is suitable for the isolation and
amplification of high frequency switching control pulse signal. Finally, the
experimental results show that the proposed driving method in this paper is
effective.
Prior to 1950, the consensus was that biological transformations occurred in two-
electron steps, thereby avoiding the generation of free radicals. Dramatic advances
in spectroscopy, biochemistry, and molecular biology have led to the realization
that protein-based radicals participate in a vast array of vital biological
mechanisms. Redox processes involving high-potential intermediates formed in
reactions with O-2 are particularly susceptible to radical formation. Clusters of
tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O-2-reactive
enzymes, raising the possibility that they play an antioxidant protective role. In
blue copper proteins with plastocyanin-like domains, Tyr/Trp clusters are uncommon
in the low-potential single-domain electron-transfer proteins and in the two-domain
copper nitrite reductases. The two-domain muticopper oxidases, however, exhibit
clusters of Tyr and Trp residues near the trinuclear copper active site where O-2
is reduced. These clusters may play a protective role to ensure that reactive
oxygen species are not liberated during O-2 reduction.
In the neural network field, many application models have been proposed. Previous
analog neural network models were composed of the operational amplifier and fixed
resistance. It is difficult to change the connecting weight of a network. In this
study, we used analog electronic multiple and sample hold circuits. The connecting
weights describe the input voltage. It is easy to change the connection
coefficient. This model works only on analog electronic circuits. It can finish the
learning process in a very short time and this model will enable more flexible
learning. However, the structure of this model includes only one input and one
output network. We improved the number of unit and network layers. Moreover, we
suggest the possibility of the realization the hardware implementation of the deep
learning model. (C) 2015 The Authors. Published by Elsevier B.V.
In the neural network field, many application models have been proposed. Previous
analog neural network models were composed of the operational amplifier and fixed
resistance. It is difficult to change the connecting weight of network. In this
study, we used analog electronic multiple and sample hold circuits. The connecting
weights describe the input voltage. It is easy to change the connection
coefficient. This model works only on analog electronic circuits. It can finish the
learning process in a very short time and this model will enable more flexible
learning. However, the structure of this model is only one input and one output
network. We improved the number of unit and network layer. Moreover, we suggest the
possibility of realization about the hardware implementation of the deep learning
model.
The recommendation system is a useful tool that can be employed to identify
potential relationships between items and users in electronic commerce systems.
Consequently, it can remarkably improve the efficiency of a business. The topic of
how to enhance the accuracy of a recommendation has attracted much attention by
researchers over the past decade. As such, many methods to accomplish this task
have been introduced. However, more complex calculations are normally necessary to
achieve a higher accuracy, which is not suitable for a real-time system. Hence, in
this paper, we propose a weight-based item recommendation approach to provide a
balanced formula between the recommended accuracy and the computational complexity.
The proposed methods employ a newly defined distance to describe the relationship
between the users and the items, after which the recommendations and predictive
algorithms are developed. A data analysis based on the MovieLens datasets indicates
that the methods applied can obtain suitable prediction accuracy and maintain a
relatively low computational complexity.
The performance for fuse electronic components may have degradation after long-
term-storage. In order to as-certain the components which its performance has
degradation, two fuse electronic parts, which have been stored for 10 years, are
chosen as samples for an accelerated test. It shows that the white noise from the
resistance and the interfering noise between different resistances may lead the
performance degradation. The zero drift due to the brokenness of bonding wire may
magnify the noise voltage when under storage, and influence the reliability of the
operational amplifier. The result indicates that the resistances and operational
amplifiers should be concerned more when test fuse electronic device after a long
storage.
With growing Electronic Design Automation (EDA) industry, automated analog circuit
design is now a feasible solution for the demand to exploit a span of nonlinear
circuit behaviors from devices to circuits with the flexibility to optimize
numerous competing continuous-valued performance specifications. In order to meet
desired specifications, state-of art EDA tools are employed which depend upon more
efficient and effective optimization techniques to suffice the cost of designing
complex analog systems. In this paper, a hybrid metaheuristic based on PSO and SA
is presented to design one of the most prominent design specifications, i.e. gains
of a two-stage CMOS operational amplifier circuit and a simple operational
transconductance amplifier circuit subject to a variety of design conditions and
constraints. Here convergence of PSO is improved by advancing through local
solutions using SA to achieve quality global optimum solution. Experimental results
are compared with other standard optimization techniques to show performance of
proposed hybrid metaheuristic in terms of optimization quality and robustness.
As silicon process geometry is reduced in scale with growing Electronic Design
Automation (EDA) industry, the underlying circuitry on a chip has become more
complex. The cost of designing such complex systems drives towards the path of
employing automation in the field of analog circuit design. In this paper, a
heuristic based on river formation dynamics (RFD) is presented to design analog
circuits with user-defined specifications. Here search strategy of RFD scheme is
employed to advance through stringent design requirements to evaluate an optimum
solution for two-stage CMOS operational amplifier circuit. Experimental results
show competent performance of RFD scheme in terms of quality of solution when
compared with standard optimization techniques.
It is well known that electrostatic discharges can ignite mixtures of flammable
gases with air and suspensions of combustible dust in air. For this reason, the
prevention of electrostatic discharges is an essential part of measures to prevent
explosions and fires. Incendive electrostatic discharges occurred in five cases in
various chemical plants. The incidents involved were: 1. Spark type electrostatic
discharges from a leaking steam pipe. 2. Spark type electrostatic discharges inside
a charging chute for a solid. 3. A spark type electrostatic discharge whilst
transferring a solid powder from a bin, which led to ignition of the powder. 4. A
propagating brush discharge during pneumatic transfer of solid, which caused a
severe electric shock to a process operator. 5. A brush discharge inside an
electrostatic precipitator which caused ignition of an aerosol of hydrocarbon. To
avoid explosions and fires it is important to prevent incendive electrostatic
discharges from occurring in industrial facilities. To help managers of chemical
plants to do this, the incidents above are presented in the form of learning
lessons including: the mechanism of the generation and separation of electrical
charges, the mechanism of the electrostatic discharge, the root causes of the
incident, the safety measures which are necessary to avoid a repetition. (C) 2017
Published by Elsevier B.V.
Enzyme linked immunosorbent assay (ELISA) is one of the most popular and
indispensable tools in molecular biology. Despite numerous advances in ELISA
methods that markedly improve the sensitivity and throughput of detection, a
hallmark of all ELISA continues to be repeated pipetting of fluids that is not only
cumbersome but can easily introduce errors or contaminations. Robotics, despite
obvious advantages, remains expensive. Here, we designed and produced cheap "pillar
plates" using stereolithography-based 3D printing that can be readily inserted into
conventional 96- and 384- well plates and serve as the substrate for ELISA. We
demonstrate that ELISA using these "pillar plates" affords comparable specificity
and sensitivity of detection of serum antibodies to traditional sandwich ELISA,
while markedly reducing the time and efforts associated with fluid transfer. These
results underscore "pillar plates" as an attractive platform for rapid yet
robotics-free ELISA.
Recently, human leukocyte antigen-G (HLA-G) has been a focus in the field of
reproductive immunology, tumor progression and transplantation, because of its
inhibitory function as ligand to the inhibitory receptors leukocyte immunoglobulin-
like receptors (LILR) B1 and LILRB2. The HLA-G is expressed in distinct mRNA
isoforms, one of which encodes a soluble HLA-G (sHLA-G) protein, detectable by
sandwich ELISA. Therefore, sHLA-G ELISAs have been used as a noninvasive diagnosis
system. While a number of sHLA-G-specific ELISAs have been described, our prior
studies showed that data obtained by the conventional ELISA system detecting sHLA-G
in body fluids was not consistent with the data obtained from immunoprecipitation
(IP)/immunoblotting (IB). Therefore, we established an optimized ELISA system
described in this report, which yields results consistent with IP/IB analysis.
Using this system, we determined sHLA-G protein in amniotic fluids, and found that
sHLA-G levels at preterm (similar to 36 weeks) were clearly higher than those at
term (37-41weeks). These data and supporting experiments showed that the ELISA
system we established can be an useful tools for the detection of sHLA-G protein in
body fluids than the conventional ELISA system.
Elongation factor (EF) is a key regulation factor for translation in many
organisms, including plants, bacteria, fungi, animals and insects. To investigate
the nature and function of elongation factor 1 beta' from Spodoptera exigua (SeEF-1
beta'), its cDNA was cloned. This contained an open reading frame of 672
nucleotides encoding a protein of 223 amino acids with a predicted molecular weight
of 24.04 kDa and pI of 4.53. Northern blotting revealed that SeEF-1 beta' mRNA is
expressed in brain, epidermis, fat body, midgut, Malpighian tubules, ovary and
tracheae. RT-PCR revealed that SeEF-1 beta' mRNA is expressed at different levels
in fat body and whole body during different developmental stages. In RNAi
experiments, the survival rate of insects injected with SeEF-1 beta' dsRNA was
58.7% at 36 h after injection, which was significantly lower than three control
groups. Other elongation factors and transcription factors were also influenced
when EF-1 beta' was suppressed. The results demonstrate that SeEF-1 beta' is a key
gene in transcription in S. exigua.
Single-phase inverters are widely used to connect small-scale distributed renewable
energy sources to the grid. However, unlike a three-phase system, designing the
vector control for a single-phase inverter is more challenging. This paper presents
a neural network based vector control technique for a single-phase inverter, as
well as how to develop and design an embedded digital control system to implement
the neural network vector controller by using Texas Instruments TMS320F28335 chip.
The paper addresses circuit design for effective interface between the high power
inverter system and the embedded microcontroller as well as how to utilize built-in
interrupts to achieve efficient digital control implementation, with user specified
sampling time, and generation of high-quality pulse-width modulated driving pulses.
Moreover, an embedded software design was developed to implement the neural network
vector control for the single-phase inverter. A laboratory scale single-phase
inverter system was built to test and evaluate the embedded neural network
microcontroller. The hardware experiment assessment shows that the microcontroller
works well using the novel neural network vector control mechanism in challenging,
variable, and distorted hardware experiment conditions.
Psychological perspective-taking is a powerful social cognition that helps us to
understand other people. It creates feelings of closeness and sympathy, motivates
us to help others, and is important for positive social relationships. In contrast
to the impressive knowledge about its consequences, relatively little is known
about how exactly people achieve them. The present paper addresses this question
from a grounded cognition perspective, drawing on recent findings on the embodiment
of visuospatial perspective-taking. Visuospatial perspective-taking involves a
mental transformation of one's body schema into the physical location of another
person. We argue that when people psychologically "put themselves in another
person's shoes,"this simulation of physical proximity happens, too, and is one
source of perceived closeness. In five experiments (total N = 1067), participants
completed a visuospatial perspective-taking task. During half of the trials,
angular disparity between the target person and the participant was high and
participants had to adopt the target's visual perspective (which involves an
embodied simulation). During the remaining trials, angular disparity was low and
participants could solve the task egocentrically. Taking another's perspective led
participants to adopt the thoughts of the target person more strongly (Experiments
1-3) and increased the perceived similarity of that person to the self (Experiment
4) and participants' liking of that person (Experiment 5). These effects were
independent of task difficulty (Experiment 2), and only present during trials where
an embodied transformation happened (i.e., at high angular disparities; Experiment
3). Implications for psychological and visuospatial perspective-taking research and
related phenomena are discussed.
Mammalian embryonic implantation requires reciprocal interactions between
implantation-competent blastocysts and a receptive uterus. Some microRNAs might
play a key role during embryo implantation in the mouse, but the let-7a expression
profiles in the rat uterus during peri-implantation are unknown. In the study, the
expression of let-7a in the uterus during early pregnancy, pseudopregnancy,
artificial decidualization and activation of delayed implantation was detected by
Northern blotting and in situ hybridization. The effect of steroid hormones on let-
7a expression was also detected by Northern blotting and in situ hybridization.
Here, we found that the expression level of let-7a was higher on gestation day 6-7
(g.d. 6-7) in rats than oil g.d.4-5 and g.d.8-9. Let-7a was specifically localized
in glandular and luminal epithelia and decidua. The expression of let-7a was not
significantly different in the pseudopregnant uterus and increased significantly in
the uteri of rats subjected to artificial decidualization and activation of delayed
implantation. Treatment with estradiol-17 beta or progesterone significantly
increased let-7a expression. Thus, let-7a expression was significantly induced by
the process of embryo invasion, and this increased expression level was mainly
induced by active blastocysts and decidualization during the window of
implantation, implying that let-7a may participate in endometrial decidualization.
Steroid hormones, estradiol-17 beta or progesterone stimulated let-7a expression.
Somatic embryogenesis is an important biotechnological tool in breeding and
conservation programmes for woody species. It exists an increasing interest in the
improvement of somatic embryogenesis induction in commercial species such as Pinus
radiata. One approach to obtain markers of successful somatic embryogenesis can be
the study of protein profiling in a descriptive study. In order to accomplish this
objective, 2-D and MALDI-TOF/TOF-MS analysis were used in the identification and
quantification of proteins from Pinus radiata D. Don somatic embryos derived from 4
cell lines that were generated under different environmental conditions at
initiation stage. Based on the Swiss-Prot database, among the 139 proteins
detected, 25 of them appeared only in those cell lines with low initiation
percentage at the initial stage of somatic embryogenesis. Only two proteins were
detected differentially in cell lines with high initiation rates. Approximately 60%
of the proteins identified were related to carbohydrate metabolic process and
defence response. This study gives new insights about the proteomics in forest
trees, as well as provides clues on the underlying causes of the mechanisms
governing Pinus radiata somatic embryogenesis process, and can serve as a tool for
facing the improvement ofthe breeding programmes.
The embryology of the eyelid is a complex process that includes interactions
between the surface ectoderm and mesenchymal tissues. In the mouse and human, the
eyelids form and fuse before birth; they open prenatally in the human and
postnatally in the mouse. In the mouse, cell migration is stimulated by different
growth factors such as FGF10, TGF-, Activin B, and HB-EGF. These growth factors
modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several
mechanisms, such as the Wnt/-catenin signaling pathway, may inhibit and regulate
eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad
signaling system. Several human genetic disorders result from dysregulation of the
above molecular pathways.
Digital Active EMI Filtering (DAEF) technique is a new direction of conductive EMI
suppression technologies for switched-mode power converters. However, the
conventional DAEF topology only suppresses EMI to ground on the AC (or DC) ports.
It doesn't definitely aim to Common Mode (CM) or Differential Mode (DM) EMI. In
this paper, a novel DAEF topology is proposed. It can flexibly suppress CM and DM
EMI, and also effectively adjust EMI suppression ability as well as prevent
interconversion between CM and DM EMI. On the other hand, because of the parasitic
parameters of circuit and the time delay of controlling system, the traditional
model of DAEF cannot describe the system behavior accurately. This paper proposes a
precise model of DAEF system. The model not only considers the passive device
parasitic parameters of sense circuit, injection circuit and decoupling circuit,
but also considers the time delay of the digital control system. This model can
accurately describe filter performance of DAEF. Finally, simulation and
experimental results show that the proposed DAEF effectively suppress CM EMI.
Moreover, the precise model can predict the system filter performance accurately.
Objectives: Emotion recognition impairments have been demonstrated in schizophrenia
(Sz), but are less consistent and lesser in magnitude in bipolar disorder (BD).
This may be related to the extent to which different face processing strategies are
engaged during emotion recognition in each of these disorders. We recently showed
that Sz patients had impairments in the use of both featural and configural face
processing strategies, whereas BD patients were impaired only in the use of the
latter. Here we examine the influence that these impairments have on facial emotion
recognition in these cohorts. Methods: Twenty-eight individuals with Sz, 28
individuals with BD, and 28 healthy controls completed a facial emotion labeling
task with two conditions designed to separate the use of featural and configural
face processing strategies; part-based and whole-face emotion recognition. Results:
Sz patients performed worse than controls on both conditions, and worse than BD
patients on the whole-face condition. BD patients performed worse than controls on
the whole-face condition only. Conclusions: Configural processing deficits appear
to influence the recognition of facial emotions in BD, whereas both configural and
featural processing abnormalities impair emotion recognition in Sz. This may
explain discrepancies in the profiles of emotion recognition between the disorders.
Background and Objectives: Although humans have developed abundant strategies to
down regulate their own negative emotions, at times of distress they frequently
turn to significant others to seek comfort. In the present study we use a novel
performance-based paradigm to evaluate the effectiveness of this interaction.
Methods: Forty-seven couples in a long-term relationship volunteered to participate
in the study. In each couple the two partners were randomly assigned as either
target or regulator. The target viewed pictures with negative valance. In response
to each picture he/she was then instructed to choose and apply a regulatory
strategy (i.e., intrapersonal emotion regulation) or to apply a regulatory strategy
chosen by his/her partner, the regulator (i.e., interpersonal emotion regulation).
Results: We found that the outside perspective of the regulator helped reducing
distress more effectively than intrapersonal emotion regulation. Moreover, the
cognitive, but not the emotional, empathy of the regulator predicted the added
value of interpersonal emotion regulation. Specifically, regulators with a better
ability to understand their partners' point of view, selected regulatory strategies
that reduced levels of distress more effectively. Limitations: While the present
study examined possible effects of depression, anxiety and the ability to identify
and describe feelings, a larger sample is needed in order to optimally address
their potential moderating effect. Conclusions: The results illuminate the value of
non-professional interventions and the importance of cognitive empathy in reducing
distress. The study has significant clinical implications, providing a simple
behavioral tool that can be used to decrease and prevent psychopathology. (C) 2016
Elsevier Ltd. All rights reserved.
It was recently proposed that the neural substrate mediating smile production might
play a key role also in the recognition of others' smile. This hypothesis, however,
has been challenged by difficulties in eliciting ecological smiling in standard
laboratory settings. Here we report of a case where these difficulties were
overcome by combining electrical stimulation and intracranial electroencephalogram
recording in a patient with drug-resistant focal epilepsy. The stimulation of the
pregenual anterior cingulate cortex (pACC) elicited a smiling facial expression.
The same leads exploring pACC showed an increase of gamma band activity (50-100 Hz)
during the observation of video-clips depicting actors laughing, relative to video-
clips depicting actors crying or producing a neutral expression. These findings
indicate that both smile production and recognition are encoded in pACC and further
support the role of this region in social cognition.
The study examined third-party listeners' ability to detect the Hellos spoken to
prevalidated happy, neutral, and sad facial expressions. The average detection
accuracies from the happy and sad (HS), happy and neutral (HN), and sad and neutral
(SN) listening tests followed the average vocal pitch differences between the two
sets of Hellos in each of the tests; HS and HN detection accuracies were above
chance reflecting the significant pitch differences between the respective Hellos.
The SN detection accuracy was at chance reflecting the lack of pitch difference
between sad and neutral Hellos. As expected, the SN detection accuracy positively
correlated with theory of mind; participating in these tests has been likened to
the act of eavesdropping, which has been discussed from an evolutionary
perspective. An unexpected negative correlation between the HS detection accuracy
and the empathy quotient has been discussed with respect to autism research on
empathy and pitch discrimination.
Individuals with Autism Spectrum Disorder (ASD) are characterized by severe
deficits in social communication, whereby the nature of their impairments in
emotional prosody processing have yet to be specified. Here, we investigated
emotional prosody processing in individuals with ASD and controls with novel,
lifelike behavioral and neuroimaging paradigms. Compared to controls, individuals
with ASD showed reduced emotional prosody recognition accuracy on a behavioral
task. On the neural level, individuals with ASD displayed reduced activity of the
STS, insula and amygdala for complex vs basic emotions compared to controls.
Moreover, the coupling between the STS and amygdala for complex vs basic emotions
was reduced in the ASD group. Finally, groups differed with respect to the
relationship between brain activity and behavioral performance. Brain activity
during emotional prosody processing was more strongly related to prosody
recognition accuracy in ASD participants. In contrast, the coupling between STS and
anterior cingulate cortex (ACC) activity predicted behavioral task performance more
strongly in the control group. These results provide evidence for aberrant
emotional prosody processing of individuals with ASD. They suggest that the
differences in the relationship between the neural and behavioral level of
individuals with ASD may account for their observed deficits in social
communication.
Schadenfreude occurs when people feel pleasure at others' misfortunes. Previous
research suggested that individuals feel such a malicious pleasure when the
misfortune befalls social targets perceived as highly competent but lacking human
warmth. Two experiments explored whether the two components of warmth (i.e.,
sociability and morality) have distinct roles in driving schadenfreude. Study 1 (N
= 128) compared a competent but immoral individual to a competent but unsociable
person and found that people felt more schadenfreude when a misfortune befell an
individual lacking morality. Study 2 (N = 199) confirmed the primary role of
morality in driving schadenfreude by manipulating not only morality and
sociability, but also competence. Moreover, both experiments showed that social
targets lacking moral qualities elicited higher levels of schadenfreude because
their misfortunes were perceived as deserved. Overall, our findings suggest that
morality has a primary role over other basic dimensions of person perception (i.e.,
sociability and competence) in driving schadenfreude.
Background: Functional brain imaging research has already demonstrated that
patients with schizophrenia had difficulties with emotion processing, namely in
facial emotion perception and emotional prosody. However, the moderating effect of
social context and the boundary of perceptual categories of emotion attribution
remain unclear. This study investigated the neural bases of emotional sentence
attribution in schizophrenia. Methods: Twenty-one schizophrenia patients and 25
healthy subjects underwent an event-related functional magnetic resonance imaging
paradigm including two tasks: one to classify sentences according to their
emotional content, and the other to classify neutral sentences according to their
grammatical person. Results: First, patients showed longer response times as
compared to controls only during the emotion attribution task. Second, patients
with schizophrenia showed reduction of activation in bilateral auditory areas
irrespective of the presence of emotions. Lastly, during emotional sentences
attribution, patients displayed less activation than controls in the medial
prefrontal cortex (mPFC). Conclusions: We suggest that the functional abnormality
observed in the mPFC during the emotion attribution task could provide a biological
basis for social cognition deficits in patients with schizophrenia. (C) 2016
Elsevier B.V. All rights reserved.
Background. Previous studies suggest that adults with Tourette syndrome (TS) can
respond unconventionally on tasks involving social cognition. We therefore
hypothesized that these patients would exhibit different neural responses to
healthy controls in response to emotionally salient expressions of human eyes.
Method. Twenty-five adults with TS and 25 matched healthy controls were scanned
using fMRI during the standard version of the Reading the Mind in the Eyes Task
which requires mental state judgements, and a novel comparison version requiring
judgements about age. Results. During prompted mental state recognition, greater
activity was apparent in TS within left orbitofrontal cortex, posterior cingulate,
right amygdala and right temporo-parietal junction (TPJ), while reduced activity
was apparent in regions including left inferior parietal cortex. Age judgement
elicited greater activity in TS within precuneus, medial prefrontal and temporal
regions involved in mentalizing. The interaction between group and task revealed
differential activity in areas including right inferior frontal gyrus. Task-related
activity in the TPJ covaried with global ratings of the urge to tic. Conclusions.
While recognizing mental states, adults with TS exhibit greater activity than
controls in brain areas involved in the processing of negative emotion, in addition
to reduced activity in regions associated with the attribution of agency. In
addition, increased recruitment of areas involved in mental state reasoning is
apparent in these patients when mentalizing is not a task requirement. Our findings
highlight differential neural reactivity in response to emotive social cues in TS,
which may interact with tic expression.
It is known that children with mental and developmental problems are at risk of
abuse and neglect. Attention-deficit/hyperactivity disorder is one of the most
frequent neurodevelopmental disorders in children and adolescents. The purpose of
this study is to examine whether children diagnosed with ADHD are under more risk
in terms of child abuse and neglect compared to controls. In this case-control
study, 104 children, who applied to Child and Adolescent Psychiatry Unit of Bursa
Yuksek Ihtisas Training and Research Hospital between January and June 2015, were
diagnosed with ADHD, and had no other psychiatric comorbidity except for disruptive
behavior disorders, and 104 healthy children were compared. Abuse Assessment
Questionnaire was applied to children after approval of the families was received.
It was determined that the children diagnosed with ADHD were exposed to more
physical (96.2%) and emotional abuse (87.5%) in a statistically significant way
compared to controls (46.2%; 34.6%), they were exposed to physical and emotional
neglect (5.8%) at a lower rate compared to healthy children (24.0%), and there was
no difference between them and healthy children in terms of witnessing family
violence (56.7%; 47.1%) and being exposed to sexual abuse (5.8%; 1.9%). The
children diagnosed with ADHD were exposed to physical and emotional abuse at a
higher rate; further studies should emphasize the role of parents in this topic and
how parental education and treatment programs change the results. (C) 2016 Elsevier
Ltd. All rights reserved.
This research analyses the emotional competence difficulties (measured through
emotional intelligence and empathy) and social communication disorders of young
victims of abuse. These minors are in residential care centres with protective
measures after suffering maltreatment and/or neglect. The relation between their
emotional competence and social communication is analysed, as well as the
contribution of empathy and emotional intelligence in predicting their social
communication. The results indicate that a lack of emotional competence is related
to and can predict their difficulties in social communication. The study manifests
a scarcity of emotional intelligence, affecting attention, emotional repair and
clarity of feelings, as well as a deterioration in affective and cognitive empathy.
The minors' scarce ability to put themselves in the place of others, to understand
others' intentions and emotional states, limits their use of language in social
interactions. The research stresses the need to set up intervention programmes
aimed at training in interpersonal and intrapersonal emotional competences which
can encourage social communication.
The deleterious effects of school burnout (academic-related stress) on academic,
physiological, and cognitive outcomes have been previously established. However,
school burnout's relationship to emotional and relationship outcomes as well as
underlying factors contributing to their potential relationship are less
understood. Therefore, three studies were conducted to fill this gap by examining
the relationship between school burnout, self-control, emotional dysregulation, and
intimate partner violence. In emerging adult samples, results demonstrate that
school burnout is positively associated with emotional dysregulation, independent
of anxiety and depression (Study 1), and that self-control moderates this
relationship (Study 2) as well as the relationship between school burnout and
intimate partner violence perpetration and victimization (Study 3). Specifically,
the relationship between school burnout and emotional dysregulation (Study 2), as
well as with both victimization and perpetration (Study 3), are stronger under
lower levels of dispositional self-control. Findings from these studies identify
school burnout as an important phenomenon of inquiry in relation to psychosocial
outcomes among emerging adults. More importantly, findings suggest that self-
control may serve as a potential point of intervention for ameliorating school
burnout's damaging effects. Limitations and directions for future research are
discussed. (C) 2017 Elsevier Ltd. All rights reserved.
Emotional processing (EP) is a complex cognitive function necessary to successfully
adjust to social environments where we need to interpret and respond to cues that
convey threat or reward signals. Ex-combatants have consistently shown atypical EP
as well as poor social interactions. Available reintegration programs aim to
facilitate the re-adaptation of ex-combatants to their communities. However, they
do not incorporate actions to improve EP and to enhance cognitive-emotional
regulation. The present study was aimed at evaluating the usefulness of an
intervention focused on Social Cognitive Training (SCT), which was designed to
equip ex-combatants enrolled in the Social Reintegration Route with EP and social
cognition skills. A group of 31 ex-combatants (mean age of 37.2, 29 men) from
Colombian illegal armed groups were recruited into this study. Of these, 16 were
invited to take part in a SCT and the other continued with the conventional
reintegration intervention. Both groups underwent 12 training sessions in a period
12-14 weeks. They were assessed with a comprehensive protocol which included
Psychosocial, Behavioral, and Emotion Processing instruments. The scores on these
instruments prior to and after the intervention were compared within and between
groups. Both groups were matched at baseline. Ex-combatants receiving the SCT
experienced significant improvements in EP and a reduction in aggressive attitudes,
effects not observed in those continuing the conventional reintegration
intervention. This is the first study that achieves such outcomes in such a
population using SCT intervention. We discuss the implications of such results
toward better social reintegration strategies.
Recognition of facial affect has been studied extensively in adults with and
without traumatic brain injury (TBI), mostly by asking examinees to match basic
emotion words to isolated faces. This method may not capture affect labelling in
everyday life when faces are in context and choices are open-ended. To examine
effects of context and response format, we asked 148 undergraduate students to
label emotions shown on faces either in isolation or in natural visual scenes.
Responses were categorised as representing basic emotions, social emotions,
cognitive state terms, or appraisals. We used students' responses to create a
scoring system that was applied prospectively to five men with TBI. In both groups,
over 50% of responses were neither basic emotion words nor synonyms, and there was
no significant difference in response types between faces alone vs. in scenes.
Adults with TBI used labels not seen in students' responses, talked more overall,
and often gave multiple labels for one photo. Results suggest benefits of moving
beyond forced-choice tests of faces in isolation to fully characterise affect
recognition in adults with and without TBI.
Relative to the general population, individuals with psychotic disorders have a
higher risk of suicide. Suicide risk is also elevated in criminal offenders. Thus,
psychotic-disordered individuals with antisocial tendencies may form an especially
high-risk group. We built upon prior risk analyses by examining whether
neurobehavioral correlates of social cognition were associated with suicidal
behavior in criminal offenders with psychotic disorders. We assessed empathic
accuracy and brain structure in four groups: (i) incarcerated offenders with
psychotic disorders and past suicide attempts, (ii) incarcerated offenders with
psychotic disorders and no suicide attempts, (iii) incarcerated offenders without
psychotic disorders and (iv) community non-offenders without psychotic disorders.
Established suicide risk variables were examined along with empathic accuracy and
gray matter in brain regions implicated in social cognition. Relative to the other
groups, offenders with psychotic disorders and suicide attempts had lower empathic
accuracy and smaller temporal pole volumes. Empathic accuracy and temporal pole
volumes were significantly associated with suicide attempts independent of other
risk variables. The results indicate that brain and behavioral correlates of social
cognition may add incremental value to models of suicide risk.
We hypothesized that distinct acute right hemisphere lesions disrupt separate
components of valuation and emotional response to winning and losing money and of
emotional empathy in observing a partner win or lose money. We measured skin
conductance response (SCR) and ratings of emotions when acute right hemisphere
stroke patients or healthy controls won or lost money in roulette, or when they
watched a partner win or lose. Our results showed that percentage of damage after
stroke to right anterior insula and frontal operculum negatively correlated with
both SCR to winning and losing and difference between rating wins versus losses.
The concept of empathy has received much attention from philosophers and also from
both cognitive and social psychologists. It has, however, been given widely
conflicting definitions, with some taking it primarily as an epistemological notion
and others as a social one. Recently, empathy has been closely associated with the
simulationist approach to social cognition and, as such, it might be thought that
the concept's utility stands or falls with that of simulation itself. I suggest
that this is a mistake. Approaching the question of what empathy is via the
question of what it is for, I claim that empathy plays a distinctive
epistemological role: it alone allows us to know how others feel. This is
independent of the plausibility of simulationism more generally. With this in view
I propose an inclusive definition of empathy, one likely consequence of which is
that empathy is not a natural kind. It follows that, pace a number of empathy
researchers, certain experimental paradigms tell us not about the nature of empathy
but about certain ways in which empathy can be achieved. I end by briefly
speculating that empathy, so conceived, may also play a distinctive social role,
enabling what I term 'transparent fellow-feeling'.
Inferring beliefs and social emotions of others has different neural substrates and
possibly different roles in the pathophysiology of different clinical phases of
schizophrenia. The current study investigated the neural basis for inferring
others' beliefs and social emotions, as individual concepts, in 17 subjects at
ultra-high risk for psychosis (UHR), 16 patients with schizophrenia and 20 healthy
controls. Brain activity significantly differed from normal in both the left
superior temporal sulcus (STS) and the inferior frontal gyrus (IFG) in the
schizophrenia group while inferring others' beliefs, whereas those of UHR group
were in the middle of those in the schizophrenia and healthy-control groups. Brain
activity during inferring others' social emotions significantly differed in both
the left STS and right IFG among individuals at UHR; however, there was no
significant difference in the schizophrenia group. In contrast, brain activity
differed in the left IFG of those in both the schizophrenia and UHR groups while
inferring social emotion. Regarding the difference in direction of the abnormality,
both the UHR and schizophrenia groups were characterized by hyper-STS and hypo-IFG
activations when inferring others' beliefs and emotions. These findings might
reflect different aspects of the same pathophysiological process at different
clinical phases of psychosis.
Empathy for pain is often described as automatic. Here, we used implicit
measurement and multinomial modeling to formally quantify unintentional empathy for
pain: empathy that occurs despite intentions to the contrary. We developed the pain
identification task (PIT), a sequential priming task wherein participants judge the
painfulness of target experiences while trying to avoid the influence of prime
experiences. Using multinomial modeling, we distinguished 3 component processes
underlying PIT performance: empathy toward target stimuli (Intentional Empathy),
empathy toward prime stimuli (Unintentional Empathy), and bias to judge target
stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow)
response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing
imagine-self (vs. imagine-other) perspective-taking uniquely increased
Unintentional Empathy. In Experiment 3, Intentional and Unintentional Empathy were
stronger toward targets with typical (vs. atypical) pain outcomes, suggesting that
outcome information matters and that effects on the PIT are not reducible to
affective priming. Typicality of pain outcomes more weakly affected task
performance when target stimuli were merely categorized rather than judged for
painfulness, suggesting that effects on the latter are not reducible to semantic
priming. In Experiment 4, Unintentional Empathy was stronger for participants who
engaged in costly donation to cancer charities, but this parameter was also high
for those who donated to an objectively worse but socially more popular charity,
suggesting that overly high empathy may facilitate maladaptive altruism.
Theoretical and practical applications of our modeling approach for understanding
variation in empathy are discussed.
Recent research suggests that prosocial outcomes in sharing games arise from
prefrontal control of self-maximizing impulses. We used continuous theta burst
stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right
dorsolateral prefrontal cortex (DLPFC) and the dorsomedial prefrontal cortex
(DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested
subjects' prosocial inclinations with an unsupervised Dictator Game in which they
allocated real money anonymously between themselves and low and high socioeconomic
status (SES) players. cTBS over the two prefrontal sites made subjects more
generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to
high-SES players, while cTBS over DMPFC caused increased offers to low-SES players.
These data, the first to demonstrate an effect of disruptive neuromodulation on
costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial
inclinations during costly sharing, though they may do so in different ways. DLPFC
may implement contextual control, while DMPFC may implement a tonic form of
control. This study demonstrates that humans' prepotent inclination is toward
prosocial outcomes when cognitive control is reduced, even when prosocial decisions
carry no strategic benefit and concerns for reputation are minimized.
Introduction. Empathy is a sub-process of social cognition that is defined as the
capacity to understand and share another person's thoughts, wishes and feelings,
and is crucial in many forms of adaptive social interaction. It is a contextual,
flexible and multidimensional phenomenon that is related with different neuronal
networks and processes. Aims. To assess empathy in a sample of subjects diagnosed
with conditions belonging to the category of severe mental disorders who were under
treatment in a psychosocial rehabilitation programme. Subjects and methods. The
sample consisted of 22 persons with severe mental disorders receiving treatment
consisting in a psychosocial rehabilitation programme, and 22 healthy controls. A
battery of tests, including the empathy quotient, Reading the Mind in the Eyes Test
and the interpersonal reactivity index, was administered to each subject. Results.
In the Reading the Mind in the Eyes Test, the experimental group scored
significantly lower than the control group (t = 2.8; p < 0.05). No statistically
significant differences were found on the other variables. Conclusions. Persons
with a severe mental disorder do not display a generalised deficit of empathy. They
do, however, have difficulty when it comes to recognising emotional states by
looking, which suggests they process information about faces in a different way to
subjects in the normal population.
Load demand forecasting is a critical process in the planning of electric
utilities. An ensemble method composed of Empirical Mode Decomposition (EMD)
algorithm and deep learning approach is presented in this work. For this purpose,
the load demand series were first decomposed into several intrinsic mode functions
(IMFs). Then a Deep Belief Network (DBN) including two restricted Boltzmann
machines (RBMs) was used to model each of the extracted IMFs, so that the
tendencies of these IMFs can be accurately predicted. Finally, the prediction
results of all IMFs can be combined by either unbiased or weighted summation to
obtain an aggregated output for load demand. The electricity load demand data sets
from Australian Energy Market Operator (AEMO) are used to test the effectiveness of
the proposed EMD-based DBN approach. Simulation results demonstrated attractiveness
of the proposed method compared with nine forecasting methods. (C) 2017 Elsevier
B.V. All rights reserved.
One of the most important issues in strategic management is enhancing employees'
motivation to contribute in the implementation of strategies; because they usually
do not pay necessary attention to strategies. Accordingly, it is required to
consider and calculate their roles in implementing strategies. In terms of
employees' role in the organization, they have managerial (goal setter) and/or non-
managerial (non-goal setter) role. We are looking for a strategic performance
measurement method to involve both roles. Since there was not a pervasive method in
the literature to cover both roles properly, this research introduces a method that
measures and calculates the strategic performance of employees based on two main
parts: Project effectiveness (for managerial roles) and project efficiency (for
non-managerial roles). This method tested on a sample of employees in Hormozgan
Cement Company. Results show a significant difference between employees who
participated and those who did not participate in implementation of strategies in
their performance value. Achieved values are tangible and traceable; therefore,
employees can have a proper sense and reaction to outputs of this method.
Job assistance programs are commonly recommended for parents of children who have
been victimized by child maltreatment, particularly when illicit drugs are
indicated. However, the relationship between employment factors, substance abuse,
and risk of child maltreatment has received limited empirical attention. Therefore,
the current study examines employment factors in a sample of 72 mothers, who were
referred by child protective services for treatment of substance abuse and child
neglect. Child maltreatment potential was found to be negatively associated with
number of hours employed and self-reported happiness with employment. The
association between child abuse potential and personal income of participants
approached significance (p = .057), and the results were not influenced by social
desirability. Employment satisfaction significantly contributed to the prediction
of child maltreatment potential over and above other employment factors and control
variables. These findings suggest that when mothers are involved in child
protective services their risk of perpetrating child maltreatment may be reduced
when they are assisted in gainful employment that is personally satisfying.
Happiness with employment was the only employment factor correlated (inversely)
with substance use (biological testing, self-report of participants). Future
directions are discussed in light of the results, including the importance of
considering employment satisfaction when conducting vocational assistance programs
in this population.
This paper examines the long-run employment consequences of experiencing
homelessness in childhood rather than later in life. We use novel panel data that
link survey and administrative data for a sample of disadvantaged adults who are
homeless or at risk of homelessness. Our estimation approach pays particular
attention to the potential pathways linking childhood homelessness to adult
employment. We find that those experiencing homelessness for the first time as
children are less likely to be employed. For women, this relationship is largely
explained by the lower educational attainment and higher welfare receipt (both in
general and in the form of mental illness-related disability payments) of those
experiencing childhood homelessness. Higher rates of high school incompletion and
incarceration explain some of the link between childhood homelessness and men's
employment; however, childhood homelessness continues to have a substantial direct
effect on male employment rates.
The integration of multibarrel glass capillaries into a microfluidic co-flow
configuration is demonstrated for parallel production of nanoliter scale droplets.
The multibarrel system supports the generation of a continuous stream of single-
phase or dual-phase droplets with digital control over droplet content, enabling
the formation of dynamically-programmable and tunable emulsions. The multibarrel
capillary method allows simultaneous generation of multiple droplets from parallel
droplet generators, with controlled switching between selected dispersed phase or
continuous phase compositions. Individual phases emerging from each capillary
outlet may be selected to yield merged droplets combining continuous phase emitted
from one or more neighboring droplet generators. Because the capillary emitters are
configured in a two dimensional array, the multibarrel system provides greater
flexibility toward producing controlled interactions between multiple solutions and
phases than conventional planar microfluidic droplet generators. Using a 7-barrel
capillary configuration, the ability to regulate droplet composition and particle
size of individual as well as combined single and merged water-in-oil droplets is
explored, together with the use of two-dimensional spatial control within the
multibarrel array to generate higher order emulsions. (C) 2015 Elsevier B.V. All
rights reserved.
We previously reported expression of a protein by enamel organ (EO) cells in rat
incisors, originally isolated from the amyloid of Pindborg odontogenic tumors
called Apin. The aim of the present study was to further characterize the Apin,
gene and its protein in various species, assess tissue specificity, and clarify its
localization within the EO. Northern blotting and RT-PCR revealed that expression
of Apin was highest in the EO and gingiva, moderate in nasal and salivary glands,
and lowest in the epididymis. The protein sequences deduced from the cloned cDNA
for rat, mouse, pig, and human were aligned together with those obtained from four
other mammal genomes. Apin is highly conserved in mammals but is absent in fish,
birds, and amphibians. Comparative SIDS-PAGE analyses of the protein obtained from
bacteria, transfected cells, and extracted from EOs all indicated that Apin is
post-translationally modified, a finding consistent with the presence of predicted
sites for phosphorylation and O-linked glycosylation. In rodent incisors, Apin was
detected only in the ameloblast layer of the EO, starting at post-secretory
transition and extending throughout the maturation stage. Intense labeling was
visible over the Golgi region as well as on the apices of ameloblasts abutting the
enamel matrix. Apin was also immunodetected in epithelial cells of the gingiva
which bind it to the tooth surface (junctional epithelium). The presence of Apin at
cell-tooth interfaces suggests involvement in adhesive mechanisms active at these
sites, but its presence among other epithelial tissues indicates Apin likely
possesses broader physiological roles.
Background: The aetiological spectrum of acute encephalitis shows inter- and intra-
geographical variations. We aimed to identify the viruses that cause infectious
encephalitis in Sri Lanka, which represents a South Asian population. Methods: A
cross-sectional study was conducted among 99 patients with
encephalitis/meningoencephalitis admitted to two tertiary-care hospitals in
Colombo. Cerebrospinal fluid and serum were tested for conventional and emerging
encephalitogenic viruses. Specific nucleic acid amplification and antibody assays
were used to identify viruses. Plaque reduction neutralization test was done to
confirm the diagnosis of West Nile virus (WNV). Results: Patients' age ranged from
1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1.
A viral aetiology was identified in only 27.3%. These included dengue virus
(40.7%), Japanese encephalitis virus (25.9%), varicella zoster virus, WNV and
probable Epstein Barr virus (11.1% each). None were positive for herpes simplex
viruses or cytomegalovirus. Screening for bacterial aetiologies was negative for
all patients. There were no distinguishable clinical or laboratory findings between
the different viral aetiologies. The case fatality rate was 7%, which was higher
among patients with an identified viral aetiology. Conclusions: A viral aetiology
was identified in only about a quarter of patients with encephalitis. Dengue virus
accounted for the majority.
Glycan conversion of glycoprotein via the transglycosylation activity of endo-beta-
N-acetylglucosaminidase is a promising chemoenzymatic technology for the production
of glycoproteins including bio-medicines with a homogeneous glycoform. Although
Endo-M is a key enzyme in this process, its product undergoes rehydrolysis, which
leads to a lower yield, and limits the practical application of this enzyme. We
developed several Endo-M mutant enzymes including N175Q with glycosynthase-like
activity and/or transglycosidase-like activity. We found that the Endo-M N175H
mutant showed glycosynthase-like activity comparable to N175Q as well as
transglycosidase-like activity superior to N175Q. Using a natural
sialylglycopeptide as a donor substrate, N175H readily transferred the sialo-glycan
onto an N-acetylglucosamine residue attached to bovine ribonuclease B (RNase B),
yielding a nonnative sialoglycosylated RNase B. These results demonstrate that use
of Endo-M N175H is an alternative glycoengineering technique, which provides a
relatively high yield of transglycosylation product and avoids the laborious
synthesis of a sugar oxazoline as a donor substrate. (C) 2015 International Union
of Biochemistry and Molecular Biology, Inc. Volume 63, Number 6, Pages 812-819,
2016
Osteoclasts and chondroclasts are necessary, during endochondral ossification, for
the resorption of primary bone and calcified cartilage septa, respectively. The
bisphosphonates inhibit mineralized tissue resorption by various mechanisms
according to the different types of this drug, which can affect bone remodeling
during skeletal growth. The objective of the present study is to analyze the way
that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone
formation during endochondral ossification of the long bones of growing rats.
Newborn Wistar rats were treated daily with ETN, ALN, or sterile saline solution
(control) for 21 days. Their femur and tibiae epiphyses were radiographed and
analyzed by light, scanning and transmission electron microscopy. The expression of
genes related to osteogenesis and to osteoclast differentiation and activity were
analyzed by real-time quantitative polymerase chain reaction. The ETN group
presented reduced body weight, disorganized growth plate and an extended area of
cartilage in the ossification zone with little bone matrix; in the ALN group, this
area was not altered. The ALN presented latent TRAP-positive cells, whereas in the
ETN group, they were activated. The expression of NF kappa B1 and 2, OPG, Spp1 and
Runx2 in the ossification zone was reduced by both bisphosphonates. RANKL
expression was reduced by ETN, whereas ALN decreased the expression of RANK. The
results also indicated that, in addition to the anti-resorptive effect of the
drugs, disturbances in bone deposition occurred concomitantly with the reduced
expression of osteogenesis-related genes.
IntroductionWomen with polycystic ovary syndrome have a three-fold higher risk of
endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors
in the pathogenesis of both conditions. The aim of this study was to investigate
endometrial sterol regulatory element binding protein-1 gene expression in
polycystic ovary syndrome and endometrial cancer endometrium, and to correlate
endometrial sterol regulatory element binding protein-1 gene expression with serum
lipid profiles. Material and methodsA cross-sectional study was performed at
Nottingham University Hospital, UK. A total of 102 women (polycystic ovary
syndrome, endometrial cancer and controls; 34 participants in each group) were
recruited. Clinical and biochemical assessments were performed before endometrial
biopsies were obtained from all participants. Taqman real-time polymerase chain
reaction for endometrial sterol regulatory element binding protein-1 gene and its
systemic protein expression were analyzed. ResultsThe body mass indices of women
with polycystic ovary syndrome (29.282.91kg/m(2)) and controls (28.58 +/-
2.62kg/m(2)) were not significantly different. Women with endometrial cancer had a
higher mean body mass index (32.22 +/- 5.70kg/m(2)). Sterol regulatory element
binding protein-1 gene expression was significantly increased in polycystic ovary
syndrome and endometrial cancer endometrium compared with controls (p<0.0001).
Sterol regulatory element binding protein-1 gene expression was positively
correlated with body mass index (r=0.017, p=0.921) and waist-hip ratio (r=0.023,
p=0.544) in polycystic ovary syndrome, but this was not statistically significant.
Similarly, statistically insignificant positive correlations were found between
endometrial sterol regulatory element binding protein-1 gene expression and body
mass index in endometrial cancer (r=0.643, p=0.06) and waist-hip ratio (r=0.096,
p=0.073). Sterol regulatory element binding protein-1 gene expression was
significantly positively correlated with triglyceride in both polycystic ovary
syndrome and endometrial cancer (p=0.028 and p=0.027, respectively). Quantitative
serum sterol regulatory element binding protein-1 gene correlated with endometrial
gene expression (p<0.05). ConclusionsSterol regulatory element binding protein-1
gene expression is significantly increased in the endometrium of women with
polycystic ovary syndrome and women with endometrial cancer compared with controls
and positively correlates with serum triglyceride in both polycystic ovary syndrome
and endometrial cancer.
The endoparasitoid wasp, Meteorus pulchricornis (Wesmael), introduces virus-like
particles [M. pulchricornis VLP (MpVLP)] and venom into its lepidopteran host
larvae upon oviposition. These wasp-associated factors are considered to help
impair some host functions including immune defense. To obtain the major protein
repertoire of the MpVLP and venom that might support successful parasitism, we
constructed a conventional cDNA library of the venom gland filament that produces
both of them, and sequenced cDNA clones arbitrarily in the 5' regions. The 5'
expressed sequence tags obtained from 473 independent cDNA clones were grouped into
228 clusters. One hundred and five of these clusters were annotated with one or
more gene ontology (GO) terms by Blast2GO analyses. While the major repertoire of
the M. pulchricornis venom gland shared some constituents with those of the venom
glands of other parasitoid wasp species, it was distinct from those encoded by
polydnaviruses. Twenty clusters selected for further analyses were fully sequenced
and characterized again. Among them, 17 factors were subjected to quantitative
reverse transcription polymerase chain reaction analyses, and 12 factors were
suggested to be highly adult specific. Among these 17 factors, ten were tested as
RNA interference targets, and effective gene silencing was observed for five
factors. These five factors included two components of MpVLP. The MpVLP deficient
in the two factors prepared from the knockdown wasps was less effective than the
wild-type MpVLP in terms of the inhibitory activity against host hemocyte spreading
estimated in vitro.
Endophytes are microorganisms that inhabit plant tissues without causing disease.
Some endophytes help their hosts to combat pathogens. Here we explored the
hypothesis that the plant-derived foods consumed by humans and other animals host
endophytes that also antagonize foodborne pathogens or food-rotting agents. Our
laboratory previously cultured a library of bacterial endophytes from different
members of the maize/corn family (Zea) including wild relatives. Here, 190 of these
endophytes were screened for their ability to antagonize four foodborne pathogens
(Escherichia coli O157:H7, Listeria monocytogenes, Clostridium perfringens, and
Salmonella enterica Newport) and a food spoiling agent (Pseudomonas fluorescens)
using dual culture assays. Two Paenibacillus polymyxa endophytes (strains 3C6 and
3G11) were found to inhibit the growth of all five deleterious strains on agar.
Using conserved polymerase chain reaction primers and sequencing, both beneficial
endophytes were found to encode polymyxin genes, suggesting a potential
antibacterial mechanism of action. Polymyxin production by both strains was
confirmed using enzyme-linked immunosorbent assay. Strains 3C6 and 3G11 originated,
respectively, from the seeds of the wild Central American maize species Zea
diploperennis, and the wild ancestor of modern maize, Zea mays ssp parviglumis
(Parviglumis). As the latter is the direct ancestor of modern maize, we discuss the
role its endophyte(s) may have played in promoting crop domestication by
suppressing foodborne pathogens and/or food-spoilage agents.
Taxol or paclitaxel, an approved drug by the Food and Drug Administration, is being
used for the treatment of human cancers. This study aimed to isolate and determine
different species of native endophytic fungi from Iranian Taxus baccata (yew)
plants located in the northern forests of Iran. To do so, a novel molecular
screening approach was performed for 50 isolated endophytic fungi through
amplification of exon No. 1 of taxadine synthase as a key gene in taxol production
pathway. We used effective colony-polymerase chain reaction technique for rapid
screening of potent taxol-producing fungi instead of genomic DNA extraction.
Production of taxol was performed in batch culture by selected fungi individually
and produced taxol was assayed quantitatively by high-performance liquid
chromatography using standard taxanes. We found that only six fungi could produce
taxol and baccatin III. Interestingly, after 7 days of incubation, the highest
level of taxol was found to be 129 and that of baccatin 139.2 mg/kg dw for two
native isolated Cladosporium sp. named F1 and F3. The fungal taxols could decrease
cell viability in MTT assay same as commercial taxol. The fungal taxols semi-
quantitatively showed antimitotic effects on MCF-7 cells as human breast cancer
cell line. The expression of bcl-2 anti-apoptotic gene, in contrast to bax pro-
apoptotic gene, significantly decreased after treatment by standard and fungal
taxols. As fungal taxol was produced simpler than other methods and could
significantly affect viability and specific genes expression profile, it is
recommended that using of taxol-producing fungi from Iranian yew could be a safe
and confident procedure to overcome challenges of using other methods.
Since their discovery about 20 years ago, small RNAs have been shown to play a
critical role in a myriad of biological processes. The greater availability of
high-throughput sequencing has been invaluable to furthering our understanding of
small RNAs as regulatory molecules. In particular, these sequencing technologies
have been crucial in understanding the role of small RNAs in reproductive tissues,
where millions of individual sequences are generated. In this context, high-
throughput sequencing provides the requisite level of resolution that other
procedures, like northern blotting, would not be able to achieve. Here, we describe
a protocol for the preparation of small RNA libraries for sequencing using the
Solexa/Illumina technology.
Background: Improving islet graft revascularization has become a crucial task for
prolonging islet graft survival. Endothelial cells (ECs) are the basis of new
microvessels in an isolated islet, and EC coating has been demonstrated to improve
the vascularization and survival of an islet. However, the traditional method of EC
coating of islets has low efficiency in vitro. This study was conducted to evaluate
the effect of a polyglycolic acid (PGA) scaffold on the efficiency of islet coating
by ECs and the angiogenesis in the coated islet graft. Methods: A PGA fibrous
scaffold was used for EC coating of islet culture and was evaluated for its
efficiency of EC coating on islets and islet graft angiogenesis. Results: In in
vitro experiments, we found that apoptosis index of ECs-coating islet in PGA group
(27% +/- 8%) was significantly lower than that in control group (83% +/- 20%, P <
0.05) after 7 days culture. Stimulation index was significantly greater in the PGA
group than in the control group at day 7 after ECs-coating (2.07 +/- 0.31 vs. 1.80
+/- 0.23, P < 0.05). vascular endothelial growth factor (VEGF) level in the PGA
group was significantly higher than the coating in the control group after 7 days
culture (52.10 +/- 13.50 ng/ml vs. 16.30 +/- 8.10 ng/ml, P < 0.05). Because of a
tight, circumvallated, adhesive and three-dimensional growth microenvironment,
islet cultured in a PGA scaffold had higher coating efficiency showing stronger
staining intensity of enzyme than those in the control group after 14 days of
culture following ECs-coating. For in vivo study, PGA scaffold significantly
prolonged the average survival time of EC-coated islet graft after transplantation
compared with control group (15.30 +/- 5.60 days vs. 8.30 +/- 2.45 days, P < 0.05).
The angiogenesis and area of survived grafts were more in the PGA group compared
with the control group by measuring the mean microvessel density (8.60 +/-
1.21/mm(2) vs. 5.20 +/- 0.87/mm(2), P < 0.05). In addition, expression of VEGF and
tyrosin-protein kinase receptor (Tie-2) gene increased in PGA scaffold group than
that in control group by real-time reverse transcription-polymerase chain reaction
analysis. Conclusions: These results demonstrate that the efficiency of EC coating
of islets was successfully increased by culturing ECs on a PGA scaffold. This
method enhances the function, survival, and vascularization of isolated islets in
vitro and in vivo.
Aim: Existing evidence suggests that endothelial lipase (EL) plays an important
role in high-density-lipoprotein (HDL) metabolism. Because rabbits are a useful
animal model for the study of human lipid metabolism and atherosclerosis, we
characterized rabbit EL (rEL) expression and investigated its relationship with
plasma HDL levels in normal and hyperlipidemic rabbits. Methods: We cloned the rEL
cDNA and analyzed the EL tissue expression using Northern blotting, real-time RT-
PCR, Western blotting, and in situ hybridization. We evaluated the effects of rEL
antisense on plasma HDL levels. Results: We found that rEL mRNA was highly
expressed in cholesterol synthesis-related organs, including the liver, testis, and
adrenal along with its expression in the lung, kidney, bone marrow, and small
intestine. Interestingly, Watanabe heritable hyperlipidemic (WHHL) rabbits, a model
of human familial hypercholesterolemia, had lower plasma levels of HDLs than normal
rabbits. The plasma HDL levels in WHHL rabbits were inversely associated with high
levels of plasma rEL proteins and hepatic expression of rEL mRNA. Injection of rEL-
specific antisense oligonucleotides into rabbits resulted in the elevation of
plasma large HDLs. Furthermore, we demonstrated that rEL mRNA was expressed by both
endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL
rabbits. Conclusions: rEL is expressed in multiple tissues and may have many
physiological and pathophysiological functions, such as in the regulation of
cholesterol metabolism and atherosclerosis. Our results suggest that EL is an
important regulator of plasma HDL levels in rabbits.
In the present study, we have investigated the effect of (i) ET-I (endothelin-1)
and its precursor, big ET-1, on MMP (matrix metal loproteinase)-2 and MMP-9
synthesis and activity in osteosarcoma tissue, and (ii) ET-I receptor antagonists
on cell invasion. Using Western blotting, zymography, RT-PCR (reverse
transcription-PCR), immunohistochemistry, immunofluorescence and Northern blotting,
we have shown that ET-I and ET-I receptors (ETA and ETB) were expressed in these
cells. Additionally, we have demonstrated that ET-I markedly induced the synthesis
and activity of MMP-2, which was significantly increased when compared with MMP-9.
Furthermore, inhibition of NF-kappa B (nuclear factor kappa B) activation blocked
MMP-2 production and activity, indicating the involvement of NF-kappa B, a
ubiquitous transcription factor playing a central role in the differentiation,
proliferation and malignant transformation. Since ET-I acts as an autocrine
mediator through gelatinase induction and because inhibition of ETA receptor is
beneficial for reducing both basal and ET-I-induced osteosarcoma cell invasion,
targeting this receptor could be an attractive therapeutic alternative for the
successful treatment of osteosarcoma.
Leptin, one of the adipocyte-secreted peptides, is involved in the control of
appetite and body weight. Several studies have demonstrated that plasma leptin
levels are elevated in obese subjects and are positively correlated with body
weight. The arterial endothelin (ET) system plays an important role in the
regulation of vascular tone, and ET-1 overexpression may be involved in the
pathogenesis of the hypertension associated with insulin resistance. This study was
performed to explore the regulatory effects of leptin on ET receptor expression and
ET binding in A10 vascular smooth muscle cells (VSMCs) by use of Northern blotting,
immunoblotting, and a I-125-labeled ET-1 binding assay. The effect of leptin on ET
receptor-mediated cell proliferation was also tested. The results showed that
leptin caused a significant increase in [I-125]-ET-1 binding, which was time- and
dose-dependent. Immunoblotting showed that expression of the ET type A receptor
(ETAR) in leptin (10(-7) M)-treated cells was increased by up to 2.3-fold compared
with controls. Levels of ETAR mRNA measured by Northern blotting were also
increased by up to 2.2-fold in leptin (10(-7) M)-treated cells. Pretreatment with
an ERK inhibitor, PD-98059 (2.5 X 10(-5) M), blocked the leptin-induced increase in
I-125-ET-1 binding. Finally, ET-1 (10(-7) M)-stimulated cell proliferation was
enhanced by leptin (10(-7) M) pretreatment, with a maximal increase of twofold
compared with controls. In conclusion, leptin increases ETAR expression in VSMCs in
a time- and dose-dependent manner. This effect is ERK dependent and is associated
with increased ET-1-stimulated cell proliferation. These findings provide support
for roles for leptin and the ET system in the pathogenesis of obesity-associated
hypertension.
Endothelin-1 (ET-1) is involved in the development of cardiac hypertrophy and heart
failure. We investigated the effects of ET-1 on intracellular calcium transient and
its mechanisms. Neonatal rat cardiomyocytes were prepared and calcium transient was
measured using fura-2. Treatment with ET-1 for 48 h prolonged calcium transient
decay. In the presence of thapsigargin, ET-1 did not alter calcium transient decay.
On the other hand, the prolonged calcium transient decay was maintained even when
sodium was removed from the bath solution. These results indicate that ET-1-induced
prolongation of calcium transient decay is mainly due to the suppression of calcium
uptake by sarcoplasmic reticulum, but not inhibition of the sodium/calcium
exchanger. Northern blotting analysis revealed that sarcoplasmic reticulum ATPase
(SERCA2) mRNA was decreased in ET-1-treated cardiomyocytes, and that this decrease
was inhibited by BQ-123 but not by BQ-788. Moreover, pretreatment with
chelerythrine partially restored the ET-1-induced decrease in SERCA2 mRNA, whereas
phorbol 12-myristate 13-acetate markedly reduced SERCA2 gene expression. Real-time
RT-PCR analysis showed abundant ETA receptor gene expression in cardiomyocytes. ET-
1 reduces SERCA2 gene expression through the ETA receptor and PKC pathway, and
prolongs intracellular calcium transient decay. Specific inhibition of the ETA
receptor may be a possible therapeutic strategy for improving cardiac performance.
Leprosy triggers a complex relationship between the pathogen and host immune
response. Endothelium plays an important role in this immune response by directly
influencing cell migration to infected tissues. The objective of this work is to
investigate the possible role of endothelium in M. leprae infection, correlating
the characteristics of endothelial markers with the expression pattern of
cytokines. Thirty-six skin biopsy samples were cut into 5-mu m thick sections and
stained with hematoxylin-eosin and Ziehl-Neelsen for morphological analysis and
then submitted to immunohistochemical analysis using monoclonal antibodies against
ICAM-1, ICAM-2, VCAM-1, and VLA-4. Immunostaining for ICAM-1 showed a significantly
larger number of stained endothelial cells in the tuberculoid leprosy (9.92 +/-
1.11 cells/mm(2)) when compared to lepromatous samples (5.87 +/- 1.01 cells/mm(2))
and ICAM-2 revealed no significant difference in the number of endothelial cells
expressing this marker between the tuberculoid (13.21 +/- 1.27 cells/mm(2)) and
lepromatous leprosy (14.3 +/- 1.02 cells/mm(2)). VCAM-1-immunostained showed 18.28
1.46/mm(2) cells in tuberculoid leprosy and 10.67 +/- 1.25 cells/mm(2) in the
lepromatous leprosy. VLA-4 exhibited 22.46 +/- 1.38 cells/mm(2) in the tuberculoid
leprosy 16.04 +/- 1.56 cells/mm(2) in the lepromatous leprosy. Samples with
characteristics of the tuberculoid leprosy exhibited a larger number of cells
stained with ICAM-1, VCAM-1 and VLA-4, demonstrating the importance of these
molecules in the migration and selection of cells that reach the inflamed tissue.
(C)2017 Elsevier Ltd. All rights reserved.
This paper uses data on the life satisfaction of more than 100,000 individuals in
21 European countries from 2002 to 2011, to study the relationship between
subjective well-being and the affordability for households of electricity, heating
oil and natural gas. We find that energy prices have statistically and economically
significant effects on subjective well-being. The effect sizes are smaller than but
comparable to the effects of important personal factors of well-being. Effects
above average are found in individuals from the lowest income quartile. In
addition, effects are strongest at times when required energy expenditures can be
expected to be high. The empirical results are consistent with the prediction that
greater fuel poverty implies a greater effect of energy prices on well-being.
Energy saving is a hot topic due to the proliferation of climate changes and energy
challenges globally. However, people's perception about using smart technology for
energy saving is still in the concept stage. This means that people talk about
environmental awareness readily, yet in reality, they accept to pay the given
energy bill. Due to the availability of electricity and its integral role,
modulating consumers' attitudes towards energy savings can be a challenge. Notably,
the gap in today's smart technology design in smart homes is the understanding of
consumers' behaviour and the integration of this understanding into the smart
technology. As part of the Paris Climate change agreement (2015), it is paramount
for Singapore to introduce smart technologies targeted to reduce energy
consumption. This paper focused on the perception of Singapore households on smart
technology and its usage to save energy. Areas of current research include: (1)
energy consumption in Singapore households, (2) public programs and policies in
energy savings, (3) use of technology in energy savings, and (4) household
perception of energy savings in smart homes. Furthermore, three case studies are
reviewed in relation to smart homes and smart technology, while discussing the
maturity of existing solutions.
As part of EU incentives, the UK government have set ambitious environmental
targets relating to energy consumption including a reduction of carbon emissions of
80% by 2050. The use of various technologies can help meet these targets as well as
providing a secure energy source for the UK in the future. This research took the
UK as a case study and investigated where reduction measures are most suited to
reduce energy consumption. This paper presents a review on the current state-of-
the-art on the domestic technology available, in particular solar energy, heat
pumps, phase changing materials (PCMs) and micro combined heat and power (micro-
CHP) systems, aiming at identifying research and development opportunities for
energy saving in these fields. Furthermore, the financial as well as environmental
aspects are assessed as these are the two key considerations of typical household.
A typical UK house design, including the floor plan, is created through the use of
computer aided design (CAD) software. The house design gives a payback period
between 8.7 years at best and 11.6 years at worst.
Climatic conditions are commonly considered the primary determinant of consumers'
choices about energy use for heating. Besides, current regulations on the matter
focus on the physical characteristics of the buildings, relying on a strict
relationship between efficiency and savings. Nevertheless, the literature shows
that energy demand determinants are difficult to be estimated with the accuracy
required for predictive purposes, while the energy savings stemming from efficiency
gains are partly outweighed by the consumers' behavior. We deal with these issues
by analyzing spatial series data of natural gas consumptions for space heating and
hot water production in the residential sector. The regression analysis takes four
fields of covariates into account: climate, building characteristics, market
aspects, and technological development. The estimation process is based on the
following cornerstones: a spatially lagged dependent variable to deal with the
problem of spatial autocorrelation, linear and logarithmic functional forms, and a
two-stage interpolation strategy that is meant to provide unbiased estimates of
both the dispersion matrix and the t-statistics by combining Ordinary Least Squares
and Weighted Least Squares. The models turn out to be well specified, and their
explanatory power is high, so the results are suitable for demand forecasting.
Although the spatial autoregressive term does not appear among the significant
regressors, we show that space does matter in shaping the natural gas consumption
in different regions. Our analysis proves that heating gas demand is characterized
by a positive elasticity to income. We use these results to provide estimates of
the rebound effect. Nevertheless, the additional consumption directly attributable
to an income effect is of moderate magnitude when the gas price does not vary. (C)
2017 Elsevier Ltd. All rights reserved.
This paper investigates the impact of stock market developments on oil and
electricity demand of OECD member countries. We conduct different panel data
methodologies and use annual data ranging from 1996 to 2011. The overall findings
substantiate that income, real prices, size of the stock market and liquidity are
important determinants for both oil and electricity demand. We also compute long-
run elasticity coefficients by using a simple Partial Adjustment Model (PAM) and
find that the long run elasticity coefficients are larger than the short run
parameters. Moreover, our results show that the demand for oil and electricity is
inelastic with respect to both own real price and real income over the short-run
and the long-run. From a policy making perspective, the findings suggest that
potential policy tools to reduce energy consumption may not be useful as the demand
for energy is inelastic with respect to energy prices. Our results also manifest
that although stock market deepening variables do not have a large effect on energy
use as energy price and economic growth have, market size and liquidity
significantly affect energy consumption. Therefore, energy demand estimations based
on solely energy price and income may be inaccurate when some stock market
development indicators are excluded. The empirical findings of this paper provide
further insights for policy makers, energy companies and energy economists in terms
of demand management policies and pricing decisions.
The empirical literature on the energy efficiency gap concentrates on demand
inefficiencies in the energy-using durables markets and finds evidence that
consumers underestimate future energy costs when purchasing a new appliance. We
take a broader view and also consider the impact of imperfect competition. Using
data on the UK refrigerator market (2002-2007), we find that the average energy
consumption of appliances sold during this period was only 7.2% higher than what
would have been observed under a scenario with a perfectly competitive market and
non-myopic consumers. One reason for this small gap is that market power actually
reduces energy use. (C) 2017 Elsevier B.V. All rights reserved.
The program administrator and total cost of saved energy allow comparison of the
cost of efficiency across utilities, states, and program types, and can identify
potential performance improvements. Comparing program administrator cost with the
total cost of saved energy can indicate the degree to which programs leverage
investment by participants. Based on reported total costs and savings information
for U.S. utility efficiency programs from 2009 to 2013, we estimate the savings-
weighted average total cost of saved electricity across 20 states at $0.046 per
kilowatt-hour (kW h), comparing favorably with energy supply costs and retail
rates. Programs targeted on the residential market averaged $0.030 per kW h
compared to $0.053 per kW h for nonresidential programs. Lighting programs, with an
average total cost of $0.018 per kW h, drove lower savings costs in the residential
market. We provide estimates for the most common program types and find that
program administrators and participants on average are splitting the costs of
efficiency in half. More consistent, standardized and complete reporting on
efficiency programs is needed. Differing definitions and quantification of costs,
savings and savings lifetimes pose challenges for comparing program results.
Reducing these uncertainties could increase confidence in efficiency as a resource
among planners and policymakers.
This study presents an input-powered high-efficiency interface circuit for energy
harvesting systems, and introduces a zero standby power design to reduce power
consumption significantly while removing the external power supply. This interface
circuit is composed of two stages. The first stage voltage doubler uses a positive
feedback control loop to improve considerably the conversion speed and efficiency,
and boost the output voltage. The second stage active diode adopts a common-grid
operational amplifier (op-amp) to remove the influence of offset voltage in the
traditional comparator, which eliminates leakage current and broadens bandwidth
with low power consumption. The system supplies itself with the harvested energy,
which enables it to enter the zero standby mode near the zero crossing points of
the input current. Thereafter, high system efficiency and stability are achieved,
which saves power consumption. The validity and feasibility of this design is
verified by the simulation results based on the 65 nm CMOS process. The minimum
input voltage is down to 0.3 V, the maximum voltage efficiency is 99.6% with a DC
output current of 75.6 mu A, the maximum power efficiency is 98.2% with a DC output
current of 40.4 mu A, and the maximum output power is 60.48 mu W. The power loss of
the entire interface circuit is only 18.65 mu W, among which, the op-amp consumes
only 2.65 mu W.
Fuel cell electric vehicles convert chemical energy of hydrogen into electricity to
power their motor. Since cars are used for transport only during a small part of
the time, energy stored in the on-board hydrogen tanks of fuel cell vehicles can be
used to provide power when cars are parked. In this paper, we present a community
microgrid with photovoltaic systems, wind turbines, and fuel cell electric vehicles
that are used to provide vehicle-to-grid power when renewable power generation is
scarce. Excess renewable power generation is used to produce hydrogen, which is
stored in a refilling station. A central control system is designed to operate the
system in such a way that the operational costs are minimized. To this end, a
hybrid model for the system is derived, in which both the characteristics of the
fuel cell vehicles and their traveling schedules are considered. The operational
costs of the system are formulated considering the presence of uncertainty in the
prediction of the load and renewable energy generation. A robust min-max model
predictive control scheme is developed and finally, a case study illustrates the
performance of the designed system. (C) 2016 The Authors. Published by Elsevier
Ltd.
With the development of home area network, residents have the opportunity to
schedule their power usage at the home by themselves aiming at reducing electricity
expenses. Moreover, as renewable energy sources are deployed in home, an energy
management system needs to consider both energy consumption and generation
simultaneously to minimize the energy cost. In this paper, a smart home energy
management model has been presented that considers both energy consumption and
generation simultaneously. The proposed model arranges the household electrical and
thermal appliances for operation such that the monetary expense of a customer is
minimized based on the time-varying pricing model. In this model, the home gateway
receives the electricity price information as well as the resident desired options
in order to efficiently schedule the appliances and shave the peak as well. The
scheduling approach is tested on a typical home including variety of home
appliances, a small wind turbine, PV panel and a battery over a 24-h period. (C)
2017 Elsevier Ltd. All rights reserved.
In this work a photovoltaic energy station system is proposed. Power converters are
designed to transfer energy between source, storage and underwater autonomous
vehicle (AUV) load plus variable load station. Efficient regulation of the energy
is achieved by linear control PI to track DC bus voltage. Energy management has a
power configuration composed of DC-DC converters with digital-control using a
Matlab software in order to do calculations. The mathematical formulation of system
is analyzed to local stability and controlability. Gains of PI controllers are
choice through two methods: Siso-tool of Matlab and stability gain analysis based
on the transfer function. Stability proof analysis of converters is demonstrated by
Routh Hurwitz even variation load station. Simulation evidence results of the
performance improvement are shown.
Downhill conveyors are important potential energy sources within conveyor belt
systems (CBSs). Their energy can be captured using regenerative drives. This paper
presents a generic optimisation model for the energy management of CBSs that have
downhill conveyors. The optimisation model is able to optimally schedule three
configurations of a case-study CBS that is connected to the grid and operated under
a time-of-use tariff. The three suggested drive configurations showcase potential
energy savings/incomes that can be obtained from implementing: (a) variable speed
control, (b) internal use of downhill conveyor energy and (c) the export of energy
to the grid. The results show that a CBS with a daily energy consumption of 924 kWh
can be reconfigured and controlled to reduce consumption by 53 or 100 % or be made
to generate 1984 kWh, depending on the configuration. Analysis of the investment in
each of the three configurations is assessed using a life-cycle cost and payback
period (PBP). The daily operation simulation results show that the use of
regenerative drives and variable speed control is able to provide energy savings in
CBSs. The cost analysis shows that the configuration that enables sale of energy to
the grid is the most profitable arrangement, for the case study plant under
consideration. The sensitivity analysis indicates that the PBPs are more sensitive
to the annual electricity price increases than changes in the discount rate.
Combining regenerative drives and optimal operation of CBS generates energy savings
that give attractive PBPs of less than 5 years.
This paper presents the system integration and hierarchical control implementation
in an inverter-based Microgrid Research Laboratory (MGRL) at Aalborg University,
Denmark. MGRL aims to provide a flexible experimental platform for comprehensive
studies of microgrids. The structure of the laboratory, including the facilities,
configurations, and communication network, is first introduced. The complete
control system is based on a generic hierarchical control scheme including primary,
secondary, and tertiary control. Primary control loops are developed and
implemented in digital control platform, while system supervision, advanced
secondary, and tertiary management are realized in a microgrid central controller.
The software and hardware schemes are described. Several example case studies are
introduced and performed to achieve power quality regulation, energy management,
and flywheel energy storage system control. Experimental results are presented to
show the performance of the whole system.
The Pacific white shrimp Litopenaeusvannamei is a euryhaline species with optimal
salinity of 20-25 practical salinity unit (psu) for growth and survival, but has
been cultured in inland water with salinity <5psu worldwide. In the past decade,
much research progress has been made on the physiological and nutritional
requirements of white shrimp at low salinity. This study reviews the recent
findings in the aspects of growth, survival, energy metabolism, stress resistance
and immunity of white shrimp at low salinity and synthesizes recent research
outcomes in nutritional requirements in an attempt to improve the shrimp
performance in aquaculture at low salinity. The white shrimp at low salinity
usually show slow growth, low immunity, high susceptibility to pathogens and high
energy demand. The diet containing 30-36% protein, 15-20% carbohydrate and
supplementations of potassium, sodium, vitamin E and C, free amino acids (gly-cine,
alanine, proline and taurine), antioxidants and probiotics can improve shrimp
growth and immunity at low salinity. The white shrimp has demonstrated the ability
to synthesize DHA and EPA from LNA at low ambient salinity, but further studies are
needed to further confirm this finding. Future research should focus on the
understanding of physiological mechanism and adaptation associated with salinity
change and nutritional manipulation. The specific dietary requirements of essential
fatty acids, essential amino acids, vitamins and minerals and the nutrition-
mediated immune response also warrant further study on shrimp at low salinity.
When talking about energy conservation, "Rebound Effect" (RE) is always concerned,
which defined as the increasing energy consumption relative to the counterfactual
predicted by technological progress because of efficiency induced decrease in the
real price of energy services. In this paper, we try to find a way to figure out
the RE through calculating the substitution relations accord with the definition.
Based on the trans-log cost function and considering the asymmetric impact on
energy-cost share equation, the paper applies Allen-Uzawa substitution elasticity
to establish the price-oriented analysis diagram of fossil-energy consumption RE.
'Using time series data, applying the joint method of the dynamic OLS (DOLS) and
the seemingly unrelated regressions (SUR), the RE in China's electricity generation
sector is estimated. The results showed that the RE is 11.6% in China's electricity
generation sector if allowing for asymmetric price effects, which indicates that
China's power generation sector generally displays a feature of energy saving.
In this paper, we propose novel techniques to reduce total cost and peak load of
factories from a customer point of view. We control energy storage system (ESS) to
minimize the total electricity bill under the Korea commercial and industrial (KCI)
tariff, which both considers peak load and time of use (ToU). Under the KCI tariff,
the average peak load, which is the maximum among all average power consumptions
measured every 15 min for the past 12 months, determines the monthly base cost, and
thus peak load control is extremely critical. We aim to leverage ESS for both peak
load reduction based on load prediction as well as energy arbitrage exploiting ToU.
However, load prediction inevitably has uncertainty, which makes ESS operation
challenging with KCI tariff. To tackle it, we apply robust optimization to minimize
risk in a real environment. Our approach significantly reduces the peak load by
49.9% and the total cost by 10.8% compared to the case that does not consider load
uncertainty. In doing this we also consider battery degradation cost and validate
the practical use of the proposed techniques.
The economic and environmental benefits brought by electric vehicles (EVs) cannot
be fully delivered unless these vehicles are fully or partially charged by
renewable energy sources (RES) such as photovoltaic system (PVS). Nevertheless, the
EV charging management problem of a parking station integrated with RES is
challenging due to the uncertain nature of local RES generation. This paper aims to
address these difficulties by deploying an energy storage system (ESS) in parking
stations and exploiting the charging and discharging scheduling of EVs to achieve
better utilization of intermittent PVS for EV charging. A real-time charging
optimization scheme is also formulated, using mixed-integer linear programming
(MILP) to coordinate the charging or discharging power of EVs along with the power
dispatches of power grid and ESS based on the vehicles' charging or discharging
priorities and electricity price preferences. Extensive simulations show that the
proposed approach not only maximizes the satisfaction of EV owners in terms of
fulfilling all charging and discharging requests, but also minimizes the overall
operational cost of the parking station by prioritizing the utilization of energy
from PVS, ESS, and scheduling of every EV's charging and discharging.
Energy storage is unique in that it can provide multiple services. This feature
raises cost-recovery issues for storage, due to the combination of competitive
markets and ratebased cost recovery used in many power systems today. This hybrid
regulatory paradigm relies on classifying assets as providing competitively prices
or unpriced services and handling cost recovery based on that classification. Some
recent regulatory precedents suggest that storage developers must choose between
classifying their assets as providing competitively priced or unpriced services. In
the former case, storage costs must be recovered through the market. If an asset is
classified as providing only unpriced services, costs can be recovered through the
ratebase. This regulatory design can hamper cost recovery for storage and may lead
to inefficient storage investment and use. We propose an alternate solution whereby
storage-capacity rights are auctioned to third parties that use their rights for
priced or unpriced services. Storage-capacity rights disentangle storage cost
recovery from the regulatory treatment of its end use. We formulate the storage-
capacity auction model and demonstrate how to efficiently price storage-capacity
rights. We show that the revenues earned by the storage owner through the auction
equals the imputed marginal value of storage capacity, as revealed by the market
bids.
In the transition to renewable energy systems, fluctuating renewable energy, such
as wind and solar power, plays a large and important role. This creates a challenge
in terms of meeting demands, as the energy production fluctuates based on weather
patterns. To utilise high amounts of fluctuating renewable energy, the energy
system has to be more flexible in terms of decoupling demand and production. This
paper investigates two potential ways to increase flexibility. The first is the
interconnection between energy systems, for instance between two countries,
labelled as cross-border interconnection, and the second is cross-sector
interconnection, i.e., the integration between different parts of an energy system,
for instance heat and electricity. This paper seeks to compare the types of
interconnectivity and discuss to which extent they are mutually beneficial. To do
this, the study investigates two energy systems that represent Northern and
Southern Europe. Both systems go through three developmental steps that increase
the cross-sector interconnectivity. At each developmental step an increasing level
of transmission capacities is examined to identify the benefits of cross-border
interconnectivity. The results show that while both measures increase the system
utilisation of renewable energy and the system efficiency, the cross-sector
interconnection gives the best system performance. To analyse the possible
interaction between cross-sector and cross-border interconnectivity, two main
aspects have to be clarified. The first part defines the approach and the second is
the construction of the two archetypes. (C) 2017 Elsevier Ltd. All rights reserved.
To alleviate environmental pollution and improve the efficient use of energy,
energy systems integration (ESI)-covering electric power systems, heat systems and
natural gas systems-has become an important trend in energy utilization. The
traditional power flow calculation method, with the object as the power system,
will prove difficult in meeting the requirements of the coupled energy flow
analysis. This paper proposes a generalized energy flow (GEF) analysis method which
is suitable for an ESI containing electricity, heat and gas subsystems. First, the
models of electricity, heat, and natural gas networks in the ESI are established.
In view of the complexity of the conventional method to solve the gas network
including the compressor, an improved practical equivalent method was adopted based
on different control modes. On this basis, a hybrid method combining homotopy and
the Newton-Raphson algorithm was executed to compute the nonlinear equations of
GEF, and the Jacobi matrix reflecting the coupling relationship of multi-energy was
derived considering the grid connected mode and island modes of the power system in
the ESI. Finally, the validity of the proposed method in multi-energy flow
calculation and the analysis of interacting characteristics was verified using
practical cases.
The EU dependence on imported gas is increasing, rising to 67% in the year 2014
with 30% of total gas consumption used for electricity generation that year. With
such a dependence on imported gas, gas supply interruptions can have significant
impacts on the EU energy system and economy. This points to the need for integrated
electricity and gas modelling tools to fully explore the potential impacts of gas
supply interruptions. This paper builds and applies a detailed publically available
integrated electricity and gas model for the EU-28. We use this model to examine a
number of hypothetical scenarios where gas supply routes are interrupted for yearly
periods and the impacts on power system operation and gas flow in Europe observed.
Model results show that interruption of Russian gas supply to the EU could lead to
a rise in average gas prices of 28% and 12% in electricity prices. When supply from
North Africa was removed all Southern European states were affected heavily, Spain
in particular saw large increases of 30% in gas prices with a corresponding rise of
18% in electricity prices as a result. In addition to supply interruptions, all gas
storages were removed from the model to examine the importance of gas storage
infrastructure. This resulted in an average increase in power prices of 6% across
Europe. These additional insights offer an increased understanding of the interplay
between the gas and power systems and identify challenges which may arise when
seeking to understand energy systems as a whole. (C) 2017 Elsevier Ltd. All rights
reserved.
Drawing on basic physics, Kummel [24] and Beaudreau [4,5] attributed the
productivity slowdown to the OPEC price-hike-led decrease in the rate of growth of
energy consumption in the mid-1970s. The high post-WWII energy use growth rates
observed in most OECD countries fell drastically, decreasing productivity and GDP
growth. However since, considerable doubt has been cast on this view. For example,
why did the rate of growth of energy use in manufacturing, specifically electricity
use, fall when and where the price of electricity was either unaffected or
increased slightly afterwards? Second, why did it fall instantaneously that is,
without the usual lag? Third, why did energy consumption growth rates not return to
their pre-1973 level once real energy prices had returned to their pre-1973 levels.
Drawing from kinetics, this paper presents an alternative hypothesis, namely that
energy demand-related factors, notably the physical limits to energy-based speed-
ups, not energy supply-related factors, may have been behind this sudden decrease
in productivity growth and hence behind the productivity slowdown. Specifically, in
many industries and sectors, maximum machine speed/velocity may have been or was
near to being reached in the late 1960s/early 1970s, making further increases
physically impossible or not economically viable. (C) 2017 Elsevier Ltd. All rights
reserved.
The global and UK drive for a low-carbon dioxide environment, as well as a secure
and affordable energy supply, has encouraged nuclear power to play a core role in
the UK energy mix: the UK landscape today houses eight large nuclear plants (15
reactors) reported to generate about 21% of UK electricity. By 2030, two-thirds of
the UK's electricity generation capacity will have retired; it will need to be
replaced with low-carbon dioxide and reliable power for the future to improve the
UK's energy security and meet its commitments on carbon dioxide emissions targets.
With 50% cumulative growth in nuclear capacity forecast between 2014 and 2035 (in
comparison to coal at 10%, oil at 20% and gas at 44%) still leaving nuclear with
only a 5% share of global capacity in 2035, there is considerable scope for nuclear
in the long term.
Small modular reactors are a new generation of low-energy-output, low-hazard,
compact and modular nuclear reactors, with an output of <300 MWe per unit. With the
integration of inherent and passive safety measures, off-site construction and
higher fuel burn-up rates, they promise a safer, lower-waste and reduced-risk
venture, with earlier investment returns for investors compared with large-scale
nuclear power plants. Moreover, non-proliferation is enhanced through the use of
small quantities of non-weapons-grade nuclear fuel or the introduction of
alternative potential fuels, such as thorium or fuel waste and actinides. This
paper reviews the state of the art and discusses the economic feasibility of small
modular reactors, with a focus on levelised cost of electricity, economy of scale
and limitations for a country wishing to embark on nuclear energy through their
deployment. Concerns regarding the integration of small modular reactors into the
existing electrical grids of countries with various or no levels of nuclear-power
production capability are also discussed. Suggestions on alternatively calculating
the cost of small modular reactors and the legislation route are also provided,
along with the pros and cons of the economics and safety of small modular reactor
deployment in a country new to nuclear power.
More than two decades have passed since the start of the worldwide market-oriented
electricity sector reforms. The reforms have varied in terms of structure, market
mechanisms, and regulation. However, the passage of time calls for taking stock of
the performance of the reforms in developing countries. This paper surveys the
empirical literature on electricity sector reforms and draws some conclusions with
a view to the future. Overall, the reforms have tended to improve the technical
efficiency of the sector. The macroeconomic benefits of reforms are less clear and
remain difficult to identify. Also, the gains from the reforms have often not
trickled down to consumers because of institutional and regulatory weaknesses. In
order to achieve lasting benefits, reforms need to adopt measures that align their
pursuit of economic efficiency with those of equity and provision of access.
Reforms can deliver more economic benefits and alleviate poverty when the poor have
access to electricity. New technologies and institutional capacity building can
help improve the performance of reforms.
Cloud computing has recently emerged as a dominant Internet service computing model
due to its "payas-you-go" and "elastic service" features. Cloud computing systems
are usually composed of distributed datacenters, which leverage virtualization
technology to provide a scalable and reliable service. Optical networks are
recognized as promising next-generation core networks for connecting these
distributed datacenters due to their characteristics such as high bandwidth
provisioning, low latency, low bit error rate, etc. However, concern about the
ever-increasing energy consumption of cloud computing systems together with core
networks has been raised due to high electricity bills as well as environmental
pollution. In this paper, we study the Energy-aware Provisioning in Optical Cloud
Networks (EPOCN) problem for both dynamic and static cases. When traffic requests
arrive in an online fashion, we propose a polynomial-time energy-aware routing
algorithm to solve the dynamic EPOCN problem. Simulations show that our energy-
aware routing algorithm brings more energy savings in comparison to a shortest
path-based routing algorithm and a traffic grooming algorithm. On the other hand,
we show that the EPOCN problem in the static case (the traffic matrix is known in
advance) is NP-hard. We further divide this problem into (1) the Energy-Aware
Routing (EAR) problem in optical networks and (2) the Energy-efficient Server and
Switch Allocation (ESSA) problem in datacenter networks. Considering these two
(sub)problems are still NP-hard, we present an exact Integer Linear Program (ILP)
and a heuristic to solve each problem. We also conduct simulations to compare the
proposed ILPs and heuristics in terms of energy consumption and running time. (C)
2017 Elsevier B.V. All rights reserved.
In recent years, significant attention has been given to renewable energy
integration within the context of global climate change. In the meantime, the
energy-water nexus literature has recognized that the electricity & water
infrastructure that enables the production, distribution, and consumption of these
two precious commodities is intertwined. While these two issues may seem unrelated,
their resolution is potentially synergistic in that renewable energy technologies
not only present low CO2 emissions but also low water-intensities as well.
Therefore, renewable energy integration has the potential to address both
sustainability concerns. And yet, renewable energy integration studies have yet to
methodologically consider an integrated energy-water infrastructure. Many of these
works rely on a coupled unit commitment-economic dispatch simulation. Recently, a
simultaneous co-optimization method has been contributed for the economic dispatch
of networks that include water, power, and co-production facilities. This paper
builds upon this foundation with the development of the corresponding unit
commitment problem. It demonstrates the optimization on several case studies
inspired by Singapore & the Middle East. It concludes that renewable energy
simultaneously reduces CO2 emissions and water withdrawals. Furthermore, it shows
how water storage can help alleviate binding co-production constraints, flatten
production profiles and reduce production cost levels. (C) 2017 Elsevier Ltd. All
rights reserved.
A facile, controllable, inexpensive and green electrochemical synthesis of IrO2-
graphene nanohybrid thin films is developed to fabricate an easyto-use integrated
paper microfluidic electrochemical pH sensor for resource-limited settings. Taking
advantages from both pH meters and strips, the pH sensing platform is composed of
hydrophobic barrier-patterned paper micropad (mu PAD) using polydimethylsiloxane
(PDMS), screen-printed electrode (SPE) modified with IrO2-graphene films and molded
acrylonitrile butadiene styrene (ABS) plastic holder. Repetitive cathodic potential
cycling was employed for graphene oxide (GO) reduction which can completely remove
electrochemically unstable oxygenated groups and generate a 2D defect-free
homogeneous graphene thin film with excellent stability and electronic properties.
A uniform and smooth IrO2 film in nanoscale grain size is anodically
electrodeposited onto the graphene film, without any observable cracks. The
resulting IrO2-RGO electrode showed slightly super-Nernstian responses from pH 2-12
in Britton-Robinson (B-R) buffers with good linearity, small hysteresis, low
response time and reproducibility in different buffers, as well as low
sensitivities to different interfering ionic species and dissolved oxygen. A simple
portable digital pH meter is fabricated, whose signal is measured with a
multimeter, using high input-impedance operational amplifier and consumer
batteries. The pH values measured with the portable electrochemical paper-
microfluidic pH sensors were consistent with those measured using a commercial
laboratory pH meter with a glass electrode.
The construction of physical three-dimensional (3D) models of biomolecules can
uniquely contribute to the study of the structure-function relationship. 3D
structures are most often perceived using the two-dimensional and exclusively
visual medium of the computer screen. Converting digital 3D molecular data into
real objects enables information to be perceived through an expanded range of human
senses, including direct stereoscopic vision, touch, and interaction. Such tangible
models facilitate new insights, enable hypothesis testing, and serve as
psychological or sensory anchors for conceptual information about the functions of
biomolecules. Recent advances in consumer 3D printing technology enable, for the
first time, the cost-effective fabrication of high-quality and scientifically
accurate models of biomolecules in a variety of molecular representations. However,
the optimization of the virtual model and its printing parameters is difficult and
time consuming without detailed guidance. Here, we provide a guide on the digital
design and physical fabrication of biomolecule models for research and pedagogy
using open source or low-cost software and low-cost 3D printers that use fused
filament fabrication technology.
Background: Various insect species have been added to genomic databases over the
years. Thus, researchers can easily obtain online genomic information on
invertebrates and insects. However, many incorrectly annotated genes are included
in these databases, which can prevent the correct interpretation of subsequent
functional analyses. To address this problem, we used a combination of dry and wet
bench processes to select functional genes from public databases. Results: Enolase
is an important glycolytic enzyme in all organisms. We used a combination of dry
and wet bench processes to identify functional enolases in the silkworm Bombyx mori
(BmEno). First, we detected five annotated enolases from public databases using a
Hidden Markov Model (HMM) search, and then through cDNA cloning, Northern blotting,
and RNA-seq analysis, we revealed three functional enolases in B. mori: BmEno1,
BmEno2, and BmEnoC. BmEno1 contained a conserved key amino acid residue for metal
binding and substrate binding in other species. However, BmEno2 and BmEnoC showed a
change in this key amino acid. Phylogenetic analysis showed that BmEno2 and BmEnoC
were distinct from BmEno1 and other enolases, and were distributed only in
lepidopteran clusters. BmEno1 was expressed in all of the tissues used in our
study. In contrast, BmEno2 was mainly expressed in the testis with some expression
in the ovary and suboesophageal ganglion. BmEnoC was weakly expressed in the
testis. Quantitative RT-PCR showed that the mRNA expression of BmEno2 and BmEnoC
correlated with testis development; thus, BmEno2 and BmEnoC may be related to
lepidopteran-specific spermiogenesis. Conclusions: We identified and characterized
three functional enolases from public databases with a combination of dry and wet
bench processes in the silkworm B. mori. In addition, we determined that BmEno2 and
BmEnoC had species-specific functions. Our strategy could be helpful for the
detection of minor genes and functional genes in non-model organisms from public
databases.
Two bacterial strains isolated from root nodules of soybean were characterized
phylogenetically as members of a distinct group in the genus Ensifer based on 16S
rRNA gene comparisons. They were also verified as a separated group by the
concatenated sequence analyses of recA, atpD and glnII (with similarities <= 93.9%
to the type strains for defined species), and by the average nucleotide identities
(ANI) between the whole genome sequence of the representative strain CCBAU
251167(T) and those of the closely related strains in Ensifer glycinis and Ensifer
fredii (90.5% and 90.3%, respectively). Phylogeny of symbiotic genes (nodC and
nifH) grouped these two strains together with some soybean-nodulating strains of E.
fredii, E. glycinis and Ensifer sojae. Nodulation tests indicated that the
representative strain CCBAU 251167(T) could form root nodules with capability of
nitrogen fixing on its host plant and Glycine soja, Cajanus cajan, Vigna
unguiculata, Phaseolus vulgaris and Astragalus membranaceus, and it formed
ineffective nodules on Leucaena leucocephala. Strain CCBAU 251167(T) contained
fatty acids 18:1 omega 9c, 18:0 iso and 20:0, differing from other related strains.
Utilization of L-threonine and D-serine as carbon source, growth at pH 6.0 and
intolerance of 1% (w/v) NaCI distinguished strain CCBAU 251167(T) from other type
strains of the related species. The genome size of CCBAU 251167(T) was 6.2 Mbp,
comprising 7,581 predicted genes with DNA G+C content of 59.9 mol% and 970 unique
genes. Therefore, a novel species, Ensifer shofinae sp. nov., is proposed, with
CCBAU 251167(T) (=ACCC 19939(T) = LMG 29645(T)) as type strain. (C) 2017 Elsevier
GmbH. All rights reserved.
To investigate the microbial quality of retail pepper in Vietnam, the enumeration
and detection of Enterobacteriaceae and the screening of cefotaxime (CTX)-resistant
coliforms were performed by using 84 commercial samples. Although
Enterobacteriaceae were isolated from 78 samples, the number of Enterobacteriaceae
was lower than 1.0 log CFU/g in 46 samples. For the detection of Enterobacteriaceae
with the International Organization for Standardization methods, Salmonella spp.,
Escherichia coli, Klebsiella pneumoniae, Cronobacter sakazakii, and Enterobacter
cloacae complex were isolated from 5, 12, 36, 19, and 30 samples, respectively.
During screening of CTX-resistant coliforms, K. pneumoniae, C. sakazakii, and E.
cloacae complex were isolated from 8, 1, and 21 samples, respectively. Seven K.
pneumoniae and seven E. cloacae complex isolates obtained in the screening of CTX-
resistant coliforms were resistant to at least one of the three third-generation
cephalosporins (CTX, ceftazidime, and cefpodoxime). Moreover, one E. cloacae
complex cluster IV and all K. pneumoniae isolates were positive for extended-
spectrum beta-lactamase genes or plasmid-mediated AmpC P-lactamase genes or both.
Additionally, two extended-spectrum beta-lactamase-producing K. pneumoniae isolates
and one AmpC beta-lactamase-producing E. cloacae complex cluster IV isolate were
positive for the plasmid-mediated quinolone resistance determinants and also had
amino acid alterations in the quinolone resistance-determining regions of GyrA and
ParC. Furthermore, 10 E. cloacae complex isolates were positive for the plasmid-
mediated fosfomycin resistance gene fosA. As pepper is often consumed without a
heating process, the possible spread to humans of foodborne, opportunistic, and
nosocomial infection pathogens or resistance genes from foods prepared or seasoned
with pepper cannot be excluded. Therefore, it is necessary to handle pepper by
using hygienic conditions during the cultivation, harvesting and processing steps.
Most studies of opportunistic infections focus on immunocompromised patients.
However, there is a lack of information on microsporidiosis in healthy people
(immunocompetent) worldwide. This study aimed to detect and identify microsporidia
species in immunocompetent Orang Ash living in Pahang, Malaysia. Orang Ash is a
collective term for a group of indigenous people that usually reside in the
interior regions of Peninsular Malaysia. They comprise about 0.7% of the total
population in Malaysia and 76% of them lived below the poverty line i.e., poor
housing conditions with the lack of access to safe drinking water and adequate
sanitation, contaminated environment, high illiteracy rate and unhygienic practices
by these people. Stool samples were collected from 209 Orang Asli and analyzed for
detecting the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis
by polymerase chain reaction assay targeting small subunit ribosomal RNA gene. E.
bieneusi was detected in 8 individuals (3.83%). This infection was commonly found
in males than females (5.2% vs. 2.7%). All infected Orang Asli were adults, with a
mean age of 44 years. Diarrhea and other gastrointestinal symptoms were reported in
one case (12.5%) among individuals infected with this species. These findings
clearly show that exposure to E. bieneusi may actually be common than reported. The
accurate detection and identification of microsporidian species by molecular
technique will improve therapy, clinical manifestations and prognosis of this
infection, as no antiparasitic therapy has been approved for E. bieneusi. It is
hoped that these findings will allow the formulation of better health management
and disease prevention advisories, and improvement in the standards of health in
similar communities. (C) 2017 Elsevier Ireland Ltd. All rights reserved.
BackgroundHuman enteroviruses (EV) have been associated with severe acute
respiratory illness (SARI) in South Africa. ObjectivesWe aimed to describe the
molecular epidemiology of EV serotypes among patients hospitalized with SARI during
2009-2011. Patients/MethodsStudy samples from patients were tested for the presence
of enterovirus using a polymerase chain reaction assay. Results8.2% (842/10260) of
SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44%
(20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV
serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and
Echovirus 3 (11%; 5/45) were the most prevalent. ConclusionsEV-D68 should be
monitored in South Africa to assess the emergence of highly pathogenic strains.
Purpose of review Dermatologic findings may be the first signs of a neonatal viral
infection. This review provides an update of the diagnostic features and therapies
for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus,
enterovirus, and Zika virus] that present with cutaneous manifestations in the
neonate. Recent findings HSV DNA polymerase chain reaction of plasma and
cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have
expanded utility in assessing prognosis and acyclovir therapeutic efficacy.
Maternal antiviral suppressive therapy may alter the clinical appearance of
congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella
zoster immune globulin, is a US Food and Drug Administration approved form of
prophylaxis for varicella. The Centers for Disease Control and Prevention has
expanded the period of VariZIG eligibility for preterm infants, a group
particularly susceptible to severe varicella infection. For severe neonatal
enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled
trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an
effective therapy. Human Parechovirus type 3, a strain within a newly formed viral
genus, has a similar, and potentially underestimated, clinical presentation to
enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be
specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in
the neonate may present with a nonspecific macular and papular rash. As this rash
is not specific, obtaining a maternal travel history and, if appropriate,
requesting additional diagnostic testing are critical for early diagnosis. Summary
Neonatal rashes may be harmless and transient, whereas others may reflect the
presence of a severe systemic illness. Recognizing key cutaneous features of viral-
associated rashes may aid in the prompt and accurate diagnosis and treatment of
neonatal viral illnesses.
Enterovirus (EV) belongs to the picornavirus family and is common pathogen in
clinics. Early study regarding EV infection mainly utilized pathogen culture, but
retarding diagnosis and treatment. Recent progress of molecular biology has made
progress for pathogen diagnosis. This study thus investigated the expression of EV
in cerebrospinal fluid (CSF) of children with central nervous infection, in an
attempt to discuss the clinical significance of EV genotyping. 94 children with
aseptic encephalitis (or meningitis) were enrolled in parallel with 37 controls.
Fluorescent RT-PCR was used to screen EV from CSF, with positive results obtained
from those samples with CT values less than 30. After primary screening of EV,
amplification of VP1 and VP4 segment was then performed, followed by sequencing of
positive fragments and genotyping. No EV RNA was detected in 37 control patients,
while 69 out of 94 aseptic encephalitis patients had EV RNA expression. Among those
53 samples were positive for VP1 segment while 47 samples were VP4-positive.
Sequencing of those segments showed more than 96% homology with Gen Bank EV
standard viral strain. Fluorescent RT-PCR can detect EV RNA from CSF of central
nervous infection children with efficiency and accuracy. The combined genotyping of
VP4 sequence can further improve sensitivity of EV typing.
The entrepreneurial ecosystem (EE) literature has attracted much attention,
especially in policy circles. However, the concept suffers from a number of
shortcomings: (1) it lacks a clear analytical framework that makes explicit what is
cause and what is effect in an EE; (2) while being a systemic concept, the EE has
not yet fully exploited insights from network theory, and it is not always clear in
what way the proposed elements are connected in an EE; (3) it remains a challenge
what institutions (and at what spatial scale) impact on the structure and
performance of EE; (4) studies have often focused on the EE in single regions or
clusters, but lack a comparative and multi-scalar perspective and (5) the EE
literature tends to provide a static framework taking a snapshot of EE without
considering systematically their evolution over time. For each of these
shortcomings, we make a number of suggestions to take up in future research on EE.
We describe the development and potential use of various designs of recombinant
HIV-1 envelope glycoprotein trimers that mimic the structure of the virion-
associated spike, which is the target for neutralizing antibodies. The goal of
trimer development programs is to induce broadly neutralizing antibodies with the
potential to intervene against multiple circulating HIV-1 strains. Among the topics
we address are the designs of various constructs; how native-like trimers can be
produced and purified; the properties of such trimers in vitro and their
immunogenicity in various animals; and the immunization strategies that may lead to
the eventual elicitation of broadly neutralizing antibodies. In summary, native-
like trimers are a now a platform for structure- and immunology-based design
improvements that could eventually yield immunogens of practical value for solving
the long-standing HIV-1 vaccine problem.
Envelope tracking (ET) and envelope elimination and restoration (EER) are
techniques that have gained in importance in the last decade in order to obtain
highly efficient radio frequency power amplifier that transmits signals with high
peak-to-average power ratio. In this study, a multilevel multiphase buck converter
is presented as a solution for the envelope amplifier used in ET and EER. The
presented multiphase buck converter generates multilevel voltage using "node" duty
cycles and nonlinear control. In this way, the multilevel is implemented using only
one simple power stage. However, the complexity of the multilevel converter
implementation has been shifted from complicated power topologies to complicated
digital control. Detailed discussion regarding the influence of the design
parameters (switching frequency, output filter, and time resolution of the digital
control) on the performance of the proposed envelope amplifier is presented. The
design of the output filter is conducted fulfilling the constraints of the envelope
slew rate and minimum driver pulse that can be reproduced. In the cases when these
two constraints cannot be fulfilled, they may be relieved by the modified control
that is presented and experimentally validated. Finally, in order to validate the
concept, a prototype has been designed and integrated with a nonlinear class F
amplifier. Efficiency measurements showed that by employing EER, it is possible to
save up to 15% of power losses, comparing to the case when it is supplied by a
constant voltage. Additionally, adjacent channel power ratio has been measured. The
obtained results showed the value higher than 30 dB for signals up to 5 MHz of
bandwidth, without using a predistortion technique.
In this paper, a novel digital predistortion assisted supply modulator is
presented. The proposed modulator is suitable for envelope tracking power
amplifiers. In this topology, a digitally controlled linear power amplifier is used
to compensate the switching noise ripples of the switching modulator. The proposed
structure is evaluated with a 0.18 mu m CMOS process technology. The results show
up to 9% static efficiency improvement in comparison with previous one-phase and
two-phase architectures. It is shown that for a 5 MHz WiMAX signal with a 6.7 dB
PAPR at 26.8 dBm output power, a maximum average efficiency of 73.5% is achieved in
the proposed design. (C) 2015 Elsevier B.V. All rights reserved.
Purpose Knowledge regarding environmental impacts of agricultural systems is
required. Consideration of uncertainty in life cycle assessment (LCA) provides
additional scientific information for decision making. The aims of this study were
to compare the environmental impacts of different growing cherry tomato cultivation
scenarios under Mediterranean conditions and to assess the uncertainty associated
to the different agricultural production scenarios. Materials and methods The
burdens associated to cherry tomato production were calculated and evaluated by the
LCA methodology. The functional unit (FU) chosen for this study was the mass unit
of 1 t of commercial loose cherry tomatoes. This study included the quantitative
uncertainty analysis through Monte Carlo simulation. Three scenarios were
considered: greenhouse (GH), screenhouse (SH), and open field (OF). The flows and
processes of the product scenario were structured in several sections: structure,
auxiliary equipment, fertilizers, crop management, pesticides, and waste
management. Six midpoint impact categories were selected for their relevance:
climate change, terrestrial acidification, marine eutrophication, metal depletion,
and fossil depletion using the impact evaluation method Recipe Midpoint and
ecotoxicity using USEtox. Results and discussion The structure, auxiliary
equipment, and fertilizers produced the largest environmental impacts in cherry
tomato production. The greatest impact in these stages was found in the manufacture
and drawing of the steel structures, manufacture of perlite, the amount of HDPE
plastics used, and the electricity consumed by the irrigation system and the
manufacture and application of fertilizers. GH was the cropping scenario with the
largest environmental impact in most categories (varying from 18 and 37% higher
than SH and OF, respectively, in metal depletion, to 96% higher than SH and OF, in
eutrophication). OF showed the highest uncertainty in ecotoxicity, with a bandwidth
of 60 CTUe and a probability of 100 and 99.4% to be higher than GH and SH,
respectively. Conclusions The LCA was used to improve the identification and
evaluation of the environmental burdens for cherry tomato production in the
Mediterranean area. This study demonstrates the significance of conducting
uncertainty analyses for comparative LCAs used in comparative relative product
environmental impacts.
In Pisum sativum, the short-chain alcohol dehydrogenase-like protein (SAD) gene
family consists of at least three members (SAD-A, -B, and -C). Expression of two of
these genes (SAD-A and -C) in Escherichia coli or Pichia pastoris resulted in full-
length soluble proteins. Purified SAD-A was used as antigen for antibody production
in rabbits. With these antibodies the recombinant SAD-C protein (which was most
highly expressed of the two isoforms) was shown to be a tetramer consisting of a
dinner of dimers. The SAD genes are transiently expressed in plants by short
exposures to ultraviolet-B radiation (UV-B), as judged by northern blotting. In
turn, mRNA accumulation leads to formation of SAD protein in leaf and stem tissue
upon prolonged UV-B irradiation. (c) 2008 Elsevier Inc. All rights reserved.
Lignin has recently attracted much attention due to their renewable nature. Here we
focused on a simple self-assembly method for fabricating size and shape uniform
enzymatic hydrolysis lignin (EHL) nanospheres, without chemical modification of
lignin. EHL was dissolved in tetrahydrofuran at different initial concentrations
and subsequently self-assembly with adding water under magnetic stirring for
fabricating the nanospheres. The self-assembled structure, process parameters and
formation mechanism of the nanospheres Were investigated by transmission electron
microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering
(DLS), fourier transform infrared spectroscopy (FTIR), and UV-vis absorption
spectra. Results showed that the nanospheres were formed through a layer-by-layer
self-assembly approach from inside to outside based on pi-pi interactions, which
enabled the formation of nanospheres in the size range of 190-590 nm. Increasing
the pre -dropping EHL concentration resulted in an increase of the average diameter
and yield of the nanospheres. The nanospheres have good stability, and their
average diameters had no significant change after 30 days. The chemical structural
features of the nanospheres had not produced a significant change in the
preparation process. High preparation temperature brought about the formation of
the gaps at the surface of the nanospheres due to the effect of volatile speed of
solvent. Moreover, the average diameter of the nanospheres decreased with an
increase of stirring rate or the dropping speed of water. The proposed EHL
nanospheres are eco-friendly, cost-effective and therefore a promising candidate
for biomass based carrier. (C) 2017 Elsevier B.V. All rights reserved.
This study is the first comprehensive, report on the molecular cloning, structural
characterization, sequence comparison between wild and mutant types, copy number in
the genome, expression features and activities of a gene encoding 5-
enolpyruvylshikimate-3-phosphate synthase (EPSPS) in Korean lawn grass (Zoysia
japonica). The full length cDNA of the EPSPS from Korean lawn grass (zjEPSPS)
obtained from a 3' and 5' RACE method was 1540 bp, containing a 1176 bp ORF, a 144
bp leader sequence (5' UTR) and a 220 bp 3' UTR, which was eventually decoded 391
amino acid residues with a molecular mass of 41.74 kDa. The Southern blot detection
of the zjEPSPS showed that the gene exists as a single copy in the Korean lawn
grass genome. Sequence comparison of the zjEPSPS gene demonstrated that the
glyphosate-tolerant mutant (GT) having a Pro-53 to Ser substitution in the gene
seems to have a preferred binding activity of the enzyme to phosphoenol
pyruvate(PEP) over glyphosate, which allows the continuous synthesis of aromatic
amino acids in the shikimate pathway. From the Northern blotting analysis, the
zjEPSPS was found to be highly expressed, with continuous increase until 36 hours
after 0.5% glyphosate treatment in both wild and mutant samples, but 1.5-fold
higher EPSP synthase activity was observed in the tolerant mutant when exposed to
the glyphosate treatment. The molecular information of the zjEPSPS gene obtained
from this study needs to be further dissected to be more effectively applied to the
development of gene-specific DNA markers and zoysiagrass cultivars; nevertheless,
the glyphosate-tolerant mutant having the featured zjEPSPS gene can be provided to
turfgrass managers for weed problems with timely adoptable management options.
A kinesthetic classroom activity was designed to help students understand enzyme
activity and catalysis of reaction rate. Students served the role of enzymes by
manipulating Pop-It Beads as the catalytic event. This activity illuminates the
relationship between reaction rate and reaction progress by allowing students to
experience first-hand the effect of substrate depletion on catalyzed reaction rate.
Preliminary findings based on survey results and exam performance suggest the
activity could prove beneficial to students in the targeted learning outcomes.
Unique to previous kinesthetic approaches that model Michaelis-Menten kinetics,
this activity models the effects of substrate depletion on catalyzed reaction rate.
Therefore, it could prove beneficial for conveying the reasoning behind the initial
rate simplification used in Michaelis-Menten kinetics. (C) 2016 by The
International Union of Biochemistry and Molecular Biology, 45( 2): 179183, 2017.
Flat enzyme-based lactate biofuel cell (ELBC) integrated with power management
system (PMS) was developed as a potential power supply for wearable sensors.
Kinetic models of power output and chemical reagent concentration (lactate oxidase
LOx and lactate) were developed to determine the limiting factor of the ELBC
performance. Given the lactate concentration (0-40 mM) in human sweat, the optimum
LOx amount coated on the anode ranged from 6U to 54U based on the experimental
maximum power output. In the ELBC-PMS entity simulation test, power discharge
recharge frequency was calculated for self-sustained sensing and data transmission,
indicating that the ELBC could support wearable sensors (power requirement: 1-1350
mW; signal transfer frequency: 1-1320 times/h). The electrochemical activity of LOx
coated anode was validated using the cyclic voltammetry (CV). The coefficient of
variance and regression statistical analysis revealed the high stability and long
lifespan (2 weeks) of ELBC without the need of lactate refill. Published by
Elsevier Ltd.
BACKGROUND: Some patients with aspirin-exacerbated respiratory disease (AERD) and
eosinophilia report angina-type chest pain that occurs at rest and responds to
corticosteroid therapy. The frequency of eosinophilia-associated coronary artery
vasospasm in patients with AERD, a disease characterized by blood and respiratory
tissue eosinophilia, however, is unknown. OBJECTIVE: The objective of this study
was to understand the cause of the chest pain described above and determine the
most appropriate treatment for it. METHODS: A chart review of 153 patients with
AERD who are followed at Brigham and Women's Hospital was performed. Patients who
reported any type of chest pain were assessed for the presence of cardiac risk
factors, eosinophilia, and response of chest pain to a variety of treatments. Two
patients with AERD and eosinophilia who had recurrent chest pain due to suspected
vasospasm are described in detail, and 8 other cases are also summarized. RESULTS:
Of the 153 patients reviewed, 10 had a history of chest pain concerning for
ischemia. Of the 10 patients with chest pain, 8 had undergone aspirin
desensitization and initiated high-dose aspirin therapy; of these, 6 reported an
increase in the frequency or severity of chest pain while on high-dose aspirin with
improvement after aspirin discontinuation or dose reduction. Many patients had
traditional cardiac risk factors, but none had any evidence of coronary
atherosclerosis; almost all had significant eosinophilia. Their chest pain did not
improve with typical antianginal treatments but did respond to corticosteroid
therapy. CONCLUSIONS: Although uncommon, patients with AERD can develop
eosinophilia-associated coronary artery vasospasm, which is occasionally worsened
by high-dose aspirin. Patients with AERD who present with symptoms of ischemic
chest pain should be screened for eosinophilia, as early treatment with
corticosteroids can be life-saving. (C) 2016 American Academy of Allergy, Asthma &
Immunology
AIM To define clinical criteria to differentiate eosinophilic gastrointestinal
disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the
analyses of the clinical presentation of eosinophilic esophagitis (EoE),
subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis
(EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-
IgE), in combination with histological and polymerase chain reaction analyses on
esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed
longitudinal furrows and white plaques in all, and fixed rings in two. In one
patient with sEoE and four with EoEM, endoscopy showed luminal compression only.
Using manometry, failed peristalsis was observed in patients with EoE and sEoE with
some variation, while EoEM was associated with hypercontractile or hypertensive
peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per
high-power field values. EoE = 41.4 +/- 7.9 in the epithelium and 2.3 +/- 1.5 in
the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium
(conventional biopsy); EoEM = none in the epithelium, 10.7 +/- 11.7 in the
subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 +/-
16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of
dilated epithelial intercellular space and downward papillae elongation were
specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION
Based on clinical and histological data, we identified criteria, which
differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis
between these esophageal EoGDs.
Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016
classification, pathology is enriched by localization and molecular biology.
Whatever the age, total removal by one or several looks when required remains a
major prognostic factor. In children, focal radiation remains a standard, while the
role of chemotherapy is matter of randomized studies. In infants, front line
chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is
encouraged. In case of relapse, further surgery and radiation are advised, while
inclusion in innovative trials including re-irradiation, and phase I-II should be
encouraged. A better understanding of underlying mechanisms of ependymoma cell will
provide in the close future, the key to use targeted therapies at time of relapse,
and very soon as first line therapy for some subgroups of patients.
Glaucoma is the second leading cause of blindness worldwide and is usually
diagnosed in higher age groups. The goal was to survey how patient age influences
the development of glaucoma. A web-based search on aging of the visual system and
its influence on glaucoma was performed and the most important results are
summarized. The prevalence of glaucoma rises with age. Aging processes of the
trabecular meshwork and the uveoscleral outflow pathway lead to a rise in the
intraocular pressure. Chronically elevated intraocular pressure leads to
remodelling of the lamina cribrosa and narrowing of its pores through which
ganglion cell axons leave the eye. Age-dependent glia cell, mitochondria and immune
system alterations are discussed to influence glaucoma. Patient age and further
age-related nonophthalmological systemic diseases also influence adherence and
persistence to the prescribed therapy. Aging is an important risk factor for
developing glaucoma and is a main factor which influences therapy and course of the
disease. At this point in time it remains unclear to which extent additional
factors determine the development of glaucoma.
Cytomegalovirus (CMV) infection occurs frequently in young children, who, when
infected, are then a major source of transmission. Oral CMV shedding by 14 infants
with primary infection was comprehensively characterized using quantitative
polymerase chain reaction weekly for >= 9 months. Three phases of oral shedding
were identified: expansion, transition, and clearance. Viral expansion occurred
over a median of 7 weeks, with a median doubling time of 3 days. During the
transition phase, expansion slowed over a median of 6 weeks before peak viral load
was reached. Clearance was slow (22-day median half-life), and shedding did not
resolve during observation for any infant. Mathematical modeling demonstrated that
prolonged oral CMV expansion is explained by a low within-host reproduction number
(median, 1.63) and a delayed immune response that only decreases the infected cell
half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary
infection can be explained by slow viral expansion and inefficient immunologic
control.
Background: Germline mutations of the REarranged during Transfection (RET) proto-
oncogene cause multiple endocrine neoplasia 2 (MEN2). It is unclear whether the
distribution of RET mutations varies among populations. The first nationwide study
of the distribution of RET mutations was conducted, and the results were compared
to those of other populations. Methods: This retrospective cohort study included
1583 patients who underwent RET gene testing in one of three centers covering all
of Denmark between September 1994 and December 2014. Primary testing method was
Sanger sequencing, which included exons 8-11 and 13-16. Mutations were defined
according to the ARUP database July 1, 2016. Results: RET mutations were identified
in 163 patients from 36 apparently unrelated families. Among the 36 families 13
(36.1%) carried mutations in codon 611, four (11.1%) in codon 618, three (8.3%) in
codon 620, one (2.8%) in codon 631, six (16.7%) in codon 634, one (2.8%) in codon
790, one (2.8%) in codon 804, one (2.8%) in codon 852, one (2.8%) in codon 883, and
five (13.9%) in codon 918. Among the 13 families with codon 611 mutations, 12 had
the p. C611Y mutation. Conclusions: The distribution of RET mutations in Denmark
appears to differ from that of other populations. Mutations in codon 611 were the
most prevalent, followed by more frequently reported mutations. This might be due
to a possible founder effect for the p. C611Y mutation. However, further studies
are needed to find possible explanations for the skewed mutational spectrum in
Denmark.
Objectives Sleep problems and deprivation are common during pregnancy, particularly
in the third trimester. Previous studies are mostly descriptive or focused on
specific clinical groups and late pregnancy. We aimed to identify sleep duration
trajectories during the pregnancy period, their associated factors, and impact on
pregnancy and birth outcomes. Methods We studied 200 women from a mother-child
cohort recruited in 2009-2011 from the French general population. We used semi-
parametric models to analyze data collected through questionnaires. Results We
detected three sleep duration trajectories during pregnancy: short-decreasing
(8h/night, 31.6%) trajectories. Factors associated with the short-decreasing
trajectory relative to the medium-decreasing trajectory were older age (odds-
ratio/year = 1.13 [95%Confidence-Interval 1.00-1.29]) and working >28 weeks of
gestational age (odds-ratio = 0.30 [0.10-0.90]). Sleep duration during pregnancy in
this trajectory group was modified by insomniac symptoms (regression
coefficient/trimester = -0.74 [Standard-Error 0.12]) and naps (regression
coefficient/trimester = 0.58 [0.25]). Restless legs syndrome was the only factor
associated with the long-increasing trajectory and decreased sleep duration
(regression coefficient/trimester = -0.88 [0.25]). Assisted delivery (i.e. cesarean
section and/or instrumental delivery) and post-partum depression were more frequent
among women with the short-decreasing and long-increasing trajectories whereas
cesarean section alone was more prevalent among those with the short-decreasing
trajectory. Proportion of premature births was higher in the short-decreasing
trajectory group. Birth-weight-z-score was lower in the long-increasing trajectory
group. Conclusion We identified sleep trajectories among pregnant women with
specific risk factors that could affect both pregnancy and birth outcomes. Taking
these into consideration could improve both maternal and child health.
Environmental epigenetics is the study of how environmental signals affect gene
expression. Within this growing field of molecular biology, experiments on the
epigenetic effects of 'maternal care' on offspring health have received much
scientific and public attention and are often called upon to showcase how
environmental epigenetics will create a new understanding of life as inherently
'biosocial.' While, on the one hand, this research is exciting and offers possible
opportunities for collaboration between molecular biology and the social sciences,
it is also necessary to consider its political dimensions. In this paper, we show
how commonsense assumptions about sex, gender, sexuality, and class are present in
the design, interpretation, and dissemination of experiments on the epigenetic
effects of maternal care. As these experiments come to support claims about human
motherhood through a dense speculative cross-traffic between epigenetic studies in
rodents and psychological and epidemiological studies in humans, current research
trends work to illustrate rather than interrogate existing stereotypes about
maternal agency and responsibility. With this analysis, we offer a cautionary
perspective regarding the potentials and challenges for new forms of collaborative
biosocial knowledge practices emerging out of environmental epigenetics.
Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism
phenotype in people with epilepsy support shared mechanisms between epilepsy and
autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on
mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder
(ASD), we conducted meta-analyses to test whether impaired facial emotion
recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more
common in people with epilepsy (PWE) than controls. We contrasted these findings
with those of relatives of individuals with ASD (ASD-relatives) compared to
controls. Furthermore, we examined the relationship of demographic (age, IQ, sex)
and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and
origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449
individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295)
were identified by a systematic database search. Analyses revealed reduced FER and
ToM in PWE compared to controls (p < 0.001), but only reduced ToM in ASD-relatives
(p < 0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were
found between FER and ToM and epilepsy-related factors. These findings suggest
shared mechanisms between epilepsy and ASD, independent of intellectual disability.
(C) 2017 Elsevier Ltd. All rights reserved.
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe
seizures and prominent co-morbidities (e.g., physical, intellectual disabilities).
More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage
gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered
the market since 1990, these drugs often fail to adequately control seizures in DS
patients. Nonetheless, current clinical data shows significant seizure reduction in
DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug
fenfluramine (FA). Recent preclinical research confirmed the anti-epileptiform
activity of FA in homozygous scn1a mutant zebrafish larvae that mimic DS well. Here
we explored the anti-epileptiform mechanisms of FA by investigating whether
selective agonists/antagonists of specific receptor subtypes were able to
counteract the FA-induced inhibition of seizures and abnormal brain discharges
observed in the scn1a mutants. We show that antagonists of 5-HT1D and 5-HT2C
receptor subtypes were able to do so (LY 310762 and SB 242084, respectively), but
notably, a 5-HT2A-antagonist (ketanserin) was not. In addition, exploring further
the mechanism of action of FA beyond its serotonergic profile, we found that the
anti-epileptiform brain activity of FA was significantly abolished when it was
administered in combination with a sigma(1)-agonist (PRE 084). Our study therefore
provides the first evidence of an involvement of the sigma(1) receptor in the
mechanism of FA. We further show that the level of some neurotransmitters [i.e.,
dopamine and noradrenaline (NAD)] in head homogenates was altered after FA
treatment, whereas g-aminobutyric acid (GABA) and glutamate levels were not. Of
interest, NAD-decreasing drugs have been employed successfully in the treatment of
neurological diseases; including epilepsy and this effect could contribute to the
therapeutic effect of the compound. In summary, we hypothesize that the anti-
epileptiform activity of FA not only originates from its 5-HT1D and 5-HT2C-agonism,
but likely also from its ability to block sigma(1) receptors. These findings will
help in better understanding the pharmacological profile of compounds that is
critical for their applicability in the treatment of DS and possibly also other
drug-resistant epilepsies.
The red-spotted grouper, Epinephelus akaara, is a protogynous hermaphroditic fish
that shows the characteristic of natural sex change. In this study, 2-year-old
female groupers were successfully reversed to functional males by oral
administration of 17 alpha-methyltestosterone (MT) for 42 days. The protein
inhibitor of the neuronal nitric oxide synthase (PIN) gene was cloned from sex-
reversed male gonads using modern suppression subtractive hybridization (SSH), cDNA
synthesis and rapid amplification of cDNA ends-polymerase chain reaction (RACE-
PCR). The full-length cDNA of PIN is 499 bp containing a 270 bp open reading frame
(ORF) that encodes 89 amino acids. Virtual Northern blotting and reverse
transcription-PCR (RT-PCR) analysis revealed that PIN was specifically transcribed
in sex-reversed male gonads. Tissue-specific expression analysis showed that PIN
gene was expressed in the brain, heart, liver, spleen, and kidney but not in the
muscle tissue. Analyses of the expression pattern by RT-PCR and Western blotting
indicated that transcription and the level of expression of PIN in the gonads
increased gradually during the transformation from female to male. The results
showed that PIN is strongly expressed in the sex-reversed male gonad but scarcely
in the female gonad, and that its expression is upregulated as the change of sex
proceeds. Taken together, these findings demonstrate that PIN is associated with
the MT-induced sex transition of the red-spotted grouper, but the precise role of
the gene in this process remains to be further investigated. (C) 2009 Elsevier
Ireland Ltd. All rights reserved.
The default mode network (DMN) has been identified reliably during rest, as well as
during the performance of tasks such as episodic retrieval and future imagining. It
remains unclear why this network is engaged across these seemingly distinct
conditions, though many hypotheses have been proposed to account for these effects.
Prior to generating hypotheses explaining common DMN involvement, the degree of
commonality in the DMN across these conditions, within individuals, must be
statistically determined to test whether or not the DMN is truly a unitary network,
equally engaged across rest, retrieval and future imagining. To provide such a
test, we used comparable paradigms (self-directed, uninterrupted thought of equal
duration) across the three conditions (rest, retrieval, and future imagining) in a
within-participant design. We found lower than expected pattern similarity in DMN
functional connectivity across the three conditions. Similarity in connectivity
accounted for only 40-50% of the total variance. Partial Least Squares (PLS)
analyses revealed the medial temporal regions of the DMN were preferentially
coupled with one another during episodic retrieval and future imagining, whereas
the non-medial temporal regions of the DMN (e.g., medial prefrontal cortex, lateral
temporal cortex, and temporal pole) were preferentially coupled during rest. These
results suggest that DMN connectivity may be more flexible than previously
considered. Our findings are in line with emerging evidence that the DMN is not a
static network engaged commonly across distinct cognitive processes, but is instead
a dynamic system, topographically changing in relation to ongoing cognitive
demands. Hum Brain Mapp 38:1155-1171, 2017. (C) 2016 Wiley Periodicals, Inc.
Basement membranes maintain the epithelial phenotype and prevent invasion and
metastasis. We hypothesized that expression of basement membrane laminins might be
regulated by epithelial-mesenchymal transition (EMT), hallmark of cancer
progression. As EMT is mediated by transcription factor Snail, we used oral
squamous carcinoma cells obtained from a primary tumor (43A), from its EMT-
experienced recurrence (43B) and Snail-transfected 43A cells (43A-SNA) displaying
full EMT, as a model to study laminins and their receptors. Northern blotting,
immunofluorescence, and immunoprecipitation showed a gradual loss of laminin-511
and its receptor Lutheran from 43A to 43B and 43A-SNA cells. In contrast,
neoexpression of laminin alpha 4 mRNA was found congruent with synthesis of
laminin-411. Chromatin immunoprecipitation disclosed direct binding of Snail to
regions upstream of laminin alpha 5 and alpha 4 genes. Immunofluorescence and
immunoprecipitation showed a switch from hemidesmosomal integrin alpha(6)beta(4) to
alpha(6)beta(1) and neoexpression of alpha(1)beta(1) in 43A-SNA cells, and
upregulation of integrin-linked kinase in both 43B and 43A-SNA cells. The cells
adhered potently to laminin-511 and fibronectin, whereas adhesion to laminin-411
was minimal. In contrast, laminin-411 inhibited cell adhesion to other
extracellular matrix proteins. In conclusion, EMT induces a switch from laminin-511
to laminin-411 expression, which may be directly controlled by Snail. Concomitant
changes take place in laminin- and collagen-binding receptors. Laminin-411 reduces
adhesion to laminin-511 and fibronectin, suggesting that tumor cells could utilize
laminin-411 in their invasive behavior.
MicroRNAs (miRNAs) are involved in sequence-specific cleavage, translational
repression or deadenylation of specific target mRNAs resulting in post-
transcriptional gene silencing. Epstein-Barr Virus (EBV) infection induces cellular
non-coding (nc)RNAs e.g., the "vault" RNAs or miRNAs such as miR-21, miR-155 or
miR-146a. MiR-146a is upregulated in various tumours and plays a role in innate
immunity. We show that the EBV-encoded latent membrane protein 1 (LMP1) induces the
expression of miR-146a via NF kappa B. LMP1 activates the miR-146a promoter but not
a promoter with a mutation of the NF kappa B-response elements. Conversely, a LMP1-
mutant deficient in NF kappa B-activation failed to activate the promoter. The
"CAO"-LMP1 variant which has an increased potential to induce NF kappa B also
showed a higher ability to activate the miR-146a promoter as compared to standard
B95.8-LMP1. Northern blotting revealed high levels of miR-146a and miR-155 in the
Burkitt's lymphoma cell line Jiioye which expresses LMP1 while the LMP1-deficient
P3HR1 mutant derived from Jiioye expresses less miR-146a or miR-155. Likewise, EBV-
latency type I Burkitt's lymphoma cells with low LMP1 levels also contain low
levels of either miR-146a or miR-155 while their levels are increased in LMP1-
expressing EBV-latency type III BL cells. Expression of LMP1 in P3HR1 cells
upregulates miR-146a levels. Neither miR-146a nor miR-155 are detectable in BCBL-1
cells transformed by the Kaposi-Sarcoma Herpes virus (KSHV/HHV8). It is possible
that the induction of miR-146a plays a role in the induction or maintenance of EBV
latency by modulating innate immune responses to the virus infected host cell.
Increase in power demand has required providing infrastructure, such as huge power
plants and transmission lines. However, the recent trends in power system planning
and operation are being toward maximum utilization of existing electricity
infrastructure with tight operating margins because of new constraints placed by
economic, political, and environmental issues. This might cause serious stability
problems when a severe fault or a sudden outage of critical lines occurs.
Therefore, the special protection scheme (SPS) has been used by generator tripping
and successive load shedding to prevent a large-scale blackout by the cascading
effect. If the number of tripping generators in the SPS operation is reduced, the
enormous cost of power outage can be saved. This paper analyzes the enhancement of
SPS via the transient stability improvement by the static synchronous compensator
(STATCOM) applied to a generation side of Korea electric power system. First, its
characteristic related to the SPS is described. Then, the proper capacity of
STATCOM is determined with the equal area criterion to reduce the number of
tripping generators. Also, the new control method for STATCOM is proposed for its
full utilization. Finally, its effectiveness is verified by the case study with the
practical data of Korea electric power system.
Invasive trophoblast from Day 34 horse conceptuses survives in extrauterine sites
in allogeneic recipients that are immunologically naive to donor major
histocompatibility complex class I antigens. The ectopic trophoblast retains its in
utero characteristics, including similar lifespan, physiologic effect of its
secreted product (equine chorionic gonadotropin) upon the recipient's ovaries, and
induction of host immune responses. Immunologic memory has not been considered
previously in this experimental system. We hypothesized that primary exposure to
ectopic trophoblast would affect the recipient's immune status such that the
survival time of subsequent transplants would be altered. Secondary transplant
lifespans could be shortened by destructive memory responses, as has been observed
in ectopic trophoblast studies in rodents, or lengthened, as occurs when male skin
grafts follow multiple syngeneic pregnancies in mice. Eight mares received two
closely spaced trophoblast transplants. Both grafts for each recipient were
obtained from conceptuses sired by the same stallion to provide consistency in
histocompatibility antigen exposure. Donor stallions were major histocompatibility
complex class I homozygotes. Cytotoxic antibody production was tracked to monitor
recipients' immune responses to the transplants. Detection of serum equine
chorionic gonadotropin was used as a proxy for transplant lifespan. There was no
significant difference between the distributions of primary and secondary
transplant lifespans, despite evidence of immunologic memory. These data
demonstrate that secondary ectopic trophoblast transplants in horses do not
experience earlier destruction or prolonged survival following immune priming of
recipients. Mechanisms responsible for the eventual demise of the transplants
remain unperturbed by secondary immune responses or chronic antigenic exposure.
Although equine herpesvirus myeloencephalopathy (EHM) is a sporadic and relatively
uncommon manifestation of equine herpesvirus-1 (EHV-1), it has the potential for
causing devastating outbreaks in horses. Up till now, there were no reported EHM
outbreaks in donkeys and mules. This study describes the isolation and molecular
characterization of EHV-1 from clinically EHM-affected horses (n = 6), mules (n =
3) and donkeys (n = 82) in Ethiopia during outbreaks from May 2011 to December
2013. The incidence of EHM cases was higher from April to mid-June. EHM in donkeys
was more severe and death without clinical signs of paralysis, and recumbency was
frequently observed. The main age of affected equines ranged from 7 to 10 years (n
= 51; 56.0%), and females (n = 58; 63.7%) were more affected than males. The
incidence of neuropathogenic (D-752) and non-neuropathogenic (N-752) variants of
EHV-1 from EHM-affected equines in Ethiopia was assessed by sequencing the DNA
polymerase gene (ORF30) of the EHV-1 isolates. The results indicated that from the
total of 91 clinically affected equines, 90 (98.9%) of them had an ORF30 D-752
genotype. An ORF30 N-752 variant was only found in one donkey. Analysis of ORF68 as
grouping marker for geographical differences showed that the Ethiopian EHV-1
isolates belong to geographical group 4. Due to the fatal nature of EHV-1 in
donkeys, it would be interesting to examine the pathogenesis of EHM in this
species. At present, there is no vaccine available in Ethiopia, and therefore,
outbreaks of EHV-1 should be controlled by proper management adaptations. In
addition, it is important to test the efficacy of the commercial vaccines not only
in horses, but also in donkeys and mules.
Established tumors build a stressful and hostile microenvironment that blocks the
development of protective innate and adaptive immune responses. Different subsets
of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived
suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu
and represent a major impediment to the success of various forms of cancer
immunotherapy. Specific conditions and factors within tumor masses, including
hypoxia, nutrient starvation, low pH, and increased levels of free radicals,
provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and
infiltrating myeloid cells. In order to cope with ER stress, cancer cells and
tumor-associated myeloid cells activate an integrated signaling pathway known as
the Unfolded Protein Response (UPR), which promotes cell survival and adaptation
under adverse environmental conditions. However, the UPR can also induce cell death
under unresolved levels of ER stress. Three branches of the UPR have been
described, including the activation of the inositol-requiring enzyme 1 (IRE1), the
pancreatic ER kinase (PKR)-like ER kinase (PERK), and the activating transcription
factor 6 (ATF6). In this minireview, we briefly discuss the role of ER stress and
specific UPR mediators in tumor development, growth and metastasis. In addition, we
describe how sustained ER stress responses operate as key mediators of chronic
inflammation and immune suppression within tumors. Finally, we discuss multiple
pharmacological approaches that overcome the immunosuppressive effect of the UPR in
tumors, and that could potentially enhance the efficacy of cancer immunotherapies
by reprogramming the function of tumor-infiltrating myeloid cells.
Anti-ErbB2 antibodies are used as convenient tools in exploration of ErbB2
functional mechanisms and in treatment of ErbB2-overexpressing tumors. When we
employed the yeast Pichia pastoris to express an anti-ErbB2 single-chain antibody
(scFv) derived from the tumor-inhibitory monoclonal antibody A21, the yield did not
exceed 1-2 mg/L in shake flask cultures. As we considered that the poor codon usage
bias may be one limiting factor leading to the inefficient translation and scFv
production, we designed and synthesized the full-length scFv gene by choosing the
P. pastoris preferred codons while keeping the G + C content at relatively low
level. Codon optimization increased the scFv expression level 3- to 5-fold and up
to 6-10 mg/L. Northern blotting further confirmed that the increase of scFv
expression was mainly due to the enhancement of translation efficiency.
Investigation of culture conditions revealed that the maximal cell growth and scFv
expression were achieved at pH 6.5-7.0 with 2% casamino acids after 72 h methanol
induction. Secreted scFv was easily purified (>95% homogeneous product) from
culture supernatants in one step by using Ni2+ chelating affinity chromatography.
The yield was approximately 10-15 mg/L. Functional studies showed that the A21 scFv
could be internalized with high efficiency after binding to the ErbB2-
overexpressing cells, suggesting this regent may prove especially useful for ErbB2-
targeted immunotherapy. (c) 2005 Elsevier Inc. All rights reserved.
Background: Impaired function of endothelial nitric oxide synthase (eNOS) is
involved in the pathologic processes of erectile dysfunction (ED), and three
functional polymorphisms (G894T, T-786C, and a tandem repeat of 27 bp in intron 4)
in the NOS3 gene, which encodes eNOS, are associated with the clinical
characteristics of ED in several populations. Aim: To investigate the effect of
these variations of NOS3 on ED phenotypes and the response to sildenafil in a Han
Chinese population. Methods: This case-control study enrolled 112 patients with ED
and 156 age-matched healthy men. Their medical history and laboratory data were
collected. ED severity and response to sildenafil were assessed using the five-item
International Index of Erectile Function (IIEF-5) score. Routine polymerase chain
reaction and Sanger sequencing were used to genotype the three polymorphisms of
NOS3. Outcomes: The frequencies of alleles, genotypes, and haplotypes of the loci
in patients and controls; the IIEF-5 scores of patients carrying the risk and non-
risk genotype; and the frequencies of risk and non-risk genotypes in patients with
different ages at onset and responses to sildenafil were assessed. Results: The
frequencies of drinkers and diabetic and hyperlipidemic patients in the ED group
were higher than those in the age-matched control group (P<.05). The distributions
of alleles (G894T, P<.005; T-786C, P<.015), genotypes (G894T, P<0.015; T-786C,
P<.010), and haplotypes (G894T/T-786C, P<.015) of the NOS3 polymorphisms were
significantly different between patients with ED and controls. An increased risk
for earlier onset of ED was observed in the G894T risk genotype carriers (odds
ratio = 3.572; P<.020). Patients with the risk genotype of T-786C exhibited lower
IIEF-5 scores than patients with the non-risk genotype (8.2 +/- 4.5 vs 12.2 +/-
5.0; P<.015). The influence of the T-786C or G894T genotype on the response to
sildenafil was not observed. Clinical Translation: The detectable effect of NOS3
functional polymorphisms on ED suggests their application potential as a molecular
biomarker in predicting ED susceptibility and severity in the Han Chinese
population. Strengths & Limitations: This study provides strong evidence that NOS3
functional variation is an independent risk factor for ED in the Han Chinese
population, which should be confirmed in larger cohorts considering the limited
number of subjects in this study. Conclusion: These results are the first to
identify a clear association between NOS3 functional variation and ED
susceptibility, age at onset, and severity in the Han Chinese population.
The paper presents an application of Hidden Markov Models (HMM) to fixations'
sequences analysis. The examination concerns eye tracking data gathered during
performing simple comparison and decision tasks for four versions of plain control
panels. The panels displayed the target and current velocity either on a digital or
analog (clock-face) speedometers. Subjects were to decide whether increase or
decrease the current speed by pressing the appropriate button. The obtained results
suggest that females, generally exhibit different covert attention patterns than
men. Moreover, the article demonstrates the estimated four HMM with three hidden
states for every examined control panels variant and provides discussion of the
outcomes.
Infection of the freshwater Chinese mitten crab Eriocheir sinensis with
hepatopancreatic necrosis disease (HPND) has been a major problem in the crab-
cultivated Chinese Province of Jiangsu since 2015. To explore the etiology of HPND,
meta-transcriptomic libraries of the hepatopancreata from crabs with and without
HPND were constructed. Comparison analyses showed that there were no statistically
significant differences in viral and microsporidial communities in the
hepatopancreata of diseased and healthy crabs. Bacteroidetes, Proteobacteria, and
Firmicutes were the most dominant bacterial phyla in the hepatopancreata of healthy
crabs, with a combined prevalence of 93%. However, a decrease in bacterial
diversity and a striking shift in the microbial composition were found in the
hepatopancreata of crabs infected with HPND. Tenericutes was the most prevalent
bacterial phylum in diseased crabs (31.82%), whereas its prevalence was low in
healthy crabs (0.02%). By contrast, the prevalence of Bacteroidetes was
significantly lower in crabs with HPND (3.49%) than in crabs without HPND (41.04%).
We also found that the prevalence of Actinobacteria was higher in crabs with HPND
(16.70%) than in crabs without the disease (4.03%). The major bacterial family
within the Tenericutes phylum in crabs with HPND was detected by polymerase chain
reaction and determined to be Mycoplasmataceae. In conclusion, there were striking
changes in the microbiota of diseased and healthy crabs. Specifically, the
prevalence of bacteria belonging to Tenericutes and Actinobacteria phyla increased,
whereas the prevalence of bacteria belonging to the Bacteroidetes phylum decreased
in crabs with HPND, clearly pointing to an association with HPND.
Molt-inhibiting hormone (MIH), a member of the crustacean hyperglycemic hormone
(CHH) family, inhibits the synthesis of ecdysteroid in Y-organ (YO) and plays a
significant role in the regulation of molting and growth of crustaceans. A complete
cDNA sequence encoding MIH (Ers-MIH, GenBank Accession No.: DQ341280) was cloned
from eyestalk of Chinese mitten crab (Eriocheir sinensis) by 5' and 3' RACEs and
PCR cloning. The full-length cDNA consists of 1457 bp with a 330 bp open reading
frame, encoding 110 amino acids, containing a 75 amino acid mature peptide. The
deduced amino acid sequence contains a typical CHH domain. Transcripts of Ers-MIH
mRNA were detected in eyestalk by Northern blotting. The production of purified
recombinant Ers-MIH (rErs-MIH) expressed in Escherichia coli was 0.3 g/L. The LC-
ESI-MS analysis showed that two peptide fragments of the recombinant protein were
identical to the deduced amino acid sequence of Ers-MIH. By in vitro assay on E.
sinensis YOs, a cGMP mediated suppression of rErs-MIH on ecdysteroidogenesis could
be observed. Accumulation of cGMP in YOs showed a concentration-dependent manner
within 0.01-1 nmol/mL of rErs-MIH; ecdysteroid secretion was inhibited
significantly at the range of 0.01-100 nmol/mL rErs-MIH; furthermore, a significant
inhibition effect on ecdysteroid releasing was shown when cGMP analog (8-Br-cGMP)
concentration rose up to 100 nmol/mL. This study would facilitate to investigate
the roles of MIH in molt cycle regulation. (C) 2011 Elsevier Inc. All rights
reserved.
BACKGROUND. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lipid
mediators that bind to G-protein-coupled receptors. In this study, signaling
responses to 18:1 LPA and S1P were examined in parallel in three human prostate
cancer cell lines: PC-3, Du145, and LNCaP. METHODS. Receptor expression was
assessed by RT-PCR, Northern blotting, and immunoblotting. Cellular responses to
mediators were studied by proliferation assays, phosphoprotein immunoblotting, and
phospholipid metabolism assays. RESULTS. All cell lines express mRNA for both LPA
and S1P receptors. PC-3 and Du145, but not LNCaP, proliferate in response to LPA
and S1P. Epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), LPA,
and S1P induce activation of Erks in PC-3 and Du145; only EGF and PMA activate Erks
in LNCaP. In Du145 and PC-3, Akt is activated by EGF, LPA, and S1P. Akt is
constitutively active in LNCaP; EGF but not LPA or S1P stimulates further
phosphorylation. FAK is phosphorylated in response to both LPA and S1P in PC-3 and
Du145, but not in LNCaP. LPA and S1P stimulate phospholipase D (PLD) activity to
varying extents in the different cell lines. Notably, both lipid mediators activate
PLD in LNCaP. In Du145, LPA, but not S1P, activates PLD and enhances cellular
production of LPA. CONCLUSIONS. Although both LPA and S1P induce signal
transduction in all prostate cancer cell lines studied, a proliferation response is
observed only when the Erk, Akt, and FAK pathways are activated. Other responses to
the lipid mediators, such as PLD activation, likely contribute to other cellular
outcomes. Prostate 69: 1493-1506, 2009. (C) 2009 Wiley-Liss, Inc.
Bacteriorhodopsin is considered an important biomolecule for biochemical and
technology-oriented studies. The modeling and functionality of bacteriorhodopsin
sensors have been extensively studied, but the studies lack the analysis of the
errors present in the measurements. Further, the impacts of these errors on
photoelectric measurements are mostly unknown. In this paper, we discuss the errors
caused by a transimpedance amplifier in the photocurrent measurements on a dry
bacteriorhodopsin sensor. This information is especially useful when evaluating the
reliability of photocurrent measurements.
With the rapid developments of computer technology and information technology,
human-machine interfaces of aircrafts, ships, nuclear power plants, battlefield
command system, and other complex information systems have evolved from the
traditional control mode to digital control mode with visual information interface.
This paper studies error factors of information interface in human-computer
interaction based on visual cognition theory. A feasible error-cognition model is
established to solve some design problems which result in serious failures in
information recognition and analysis, and even in operation and execution
processes. Based on Rasmussen, Norman, Reason and other error types as well as the
HERA and CREAM failure identification models, we performed classification and
cognitive characterization for error factors according to information search,
information recognition, information identification, information selection and
judgment as well as the decision-making process and obtained the comprehensive
error-cognition model for complex information interface.
Erythema nodosum leprosum (ENL) is a painful inflammatory complication of leprosy
occurring in 50% of lepromatous leprosy patients and 5-10% of borderline
lepromatous patients. It is a significant cause of economic hardship, morbidity and
mortality in leprosy patients. Our understanding of the causes of ENL is limited.
We performed a systematic review of the published literature and critically
evaluated the evidence for the role of neutrophils, immune complexes (ICs), T-
cells, cytokines, and other immunological factors that could contribute to the
development of ENL. Searches of the literature were performed in PubMed. Studies,
independent of published date, using samples from patients with ENL were included.
The search revealed more than 20,000 articles of which 146 eligible studies were
included in this systematic review. The studies demonstrate that ENL may be
associated with a neutrophilic infiltrate, but it is not clear whether it is an IC-
mediated process or that the presence of ICs is an epiphenomenon. Increased levels
of tumor necrosis factor-a and other pro-inflammatory cytokines support the role of
this cytokine in the inflammatory phase of ENL but not necessarily the initiation.
T-cell subsets appear to be important in ENL since multiple studies report an
increased CD4(+)/CD8(+) ratio in both skin and peripheral blood of patients with
ENL. Microarray data have identified new molecules and whole pathophysiological
pathways associated with ENL and provides new insights into the pathogenesis of
ENL. Studies of ENL are often difficult to compare due to a lack of case
definitions, treatment status, and timing of sampling as well as the use of
different laboratory techniques. A standardized approach to some of these issues
would be useful. ENL appears to be a complex interaction of various aspects of the
immune system. Rigorous clinical descriptions of well-defined cohorts of patients
and a systems biology approach using available technologies such as genomics,
epigenomics, transcriptomics, and proteomics could yield greater understanding of
the condition.
Congenital causes of erythrocytosis are now more easily identified due to the
improvement of the molecular characterization of many of them. Among these causes,
hemoglobins with high oxygen affinity take a large place. The aim of this work was
to reevaluate the diagnostic approach of these disorders. To assess the current
practices, we sent a questionnaire to the expert laboratories in the diagnosis of
hemoglobinopathies in France and Belgium. In parallel, we gathered the methods used
for the diagnosis of the hemoglobins with high oxygen affinity indexed in the
international database HbVar. Even though they remain a rare cause of
erythrocytosis (1 to 5 positive diagnosis every year in each of the questioned
specialized laboratories), hemoglobins with high oxygen affinity are increasingly
suspected by clinicians. Phenotypic it enables the finding of 93% of them in the
questioned laboratories (28 of the 30 variants diagnosed during the last 5 years).
Among the 96 hemoglobin variants with high oxygen affinity indexed in the
international database, 87% could be diagnosed with phenotypic techniques. A direct
measure of the p50 with the Hemox-Analyzer is included in the diagnostic approach
of half of the laboratories only, because of the poor availability of this
apparatus. Comparatively, the estimation of p50 by blood gas analyzers on venous
blood is a much more convenient and attractive method but due to the lack of proof
as to its effectiveness in the diagnosis of hemoglobins with high oxygen affinity,
it requires further investigations. Beta- and alphaglobin genes analysis by
molecular biology techniques is essential as it either allows a quick and definite
identification of the variant or definitely excludes the diagnosis. It is thus
systematically performed as a first or second step method, according to the
laboratory practice.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and
multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-
18, in particular, has a significant positive correlation with RA. In this study,
we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which
is negatively regulated by IL-18, in an animal model of inflammatory arthritis,
collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant
(r) Erdr1 significantly suppressed the severity of arthritis, histologic features
of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1,
IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected
synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed
migration in contrast to the pro-migratory effect of IL-18, indicating the
therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast
migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling
pathway in migration of various cell types. Taken together, these data show that
rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast
migration, suggesting that rErdr1 treatment might be an effective therapeutic
approach for RA.
Testing for the presence of specific cell-surface receptors (such as EGFR or HER2)
on tumor cells is an integral part of cancer care in terms of treatment decisions
and prognosis. Understanding the strengths and limitations of these tests is
important because inaccurate results may occur if procedures designed to prevent
false-negative or false-positive outcomes are not employed. This review discusses
tests commonly used to identify and characterize cell-surface receptors, such as
the erythropoietin receptor (EpoR). First, a summary is provided on the biology of
the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors
and precursors in the bone marrow where it mediates red blood cell production in
response to Epo. Second, studies are described that investigated whether
erythropoiesis-stimulating agents could stimulate tumor progression in cancer
patients and whether EpoR is expressed and functional on tumor cells or on
endothelial cells. The methods used in these studies included immunohistochemistry,
Northern blotting, Western blotting, and binding assays. This review summarizes the
strengths and limitations of these methods. Critically analyzing data from tests
for cell-surface receptors such as EpoR requires understanding the techniques
utilized and demonstrating that results are consistent with current knowledge about
receptor biology.
The present study investigated the correlation and significance of HOX transcript
antisense RNA (HOTAIR) and epithelial-mesenchymal transition (EMT)-related factors
in the occurrence and metastasis of esophageal squamous cell cancer (ESCC)
progression. The mRNA and protein expression levels of HOTAIR and EMT-related
factors were detected in 96 ESCC and para-carcinoma tissues using reverse
transcription-quantitative polymerase chain reaction and western blot analysis. The
expression levels of these factors, and the correlation between these factors and
clinicopathological characteristics were subsequently analyzed. HOTAIR mRNA
expression levels were significantly higher in ESCC compared with in para-carcinoma
tissues, and HOTAIR mRNA expression levels were significantly higher in the groups
with lymph node involvement or organ metastasis compared with the group without.
Furthermore, HOTAIR expression levels demonstrated a significant increasing trend
from well-differentiated cancer to poorly differentiated cancer. The mRNA and
protein expression levels of zinc finger protein SNAI1 (Snail) and beta-catenin in
ESCC were significantly higher compared with para-carcinoma tissues, whereas E-
cadherin mRNA and protein expression levels were lower in ESCC tissues compared
with in para-carcinoma tissues. Snail mRNA and protein expression levels were also
significantly higher in groups with lymph node involvement or organ metastasis
compared with those without, and beta-catenin protein expression levels were
significantly higher in the groups with lymph node involvement or organ metastasis
compared with the group without. In the 96 ESCC tissues, HOTAIR mRNA expression
levels were positively correlated with Snail mRNA and protein expression levels,
and were negatively correlated with E-cadherin expression levels. HOTAIR mRNA
expression levels were also positively correlated with beta-catenin mRNA expression
levels. In conclusion, HOTAIR may be involved in carcinogenesis and metastasis, and
may induce the expression of EMT-related factors; detection of these factors may
assist in early diagnosis and prognostic prediction.
The Escherichia coli sequence type 648 complex (STc648) is an emerging lineage
within phylogroup F-formerly included within phylogroup D-that is associated with
multidrug resistance. Here, we designed and validated a novel multiplex PCR-based
assay for STc648 that took advantage of (i) four distinctive single-nucleotide
polymorphisms in icd allele 96 and gyrB allele 87, two of the multilocus sequence
typing alleles that define ST648; and (ii) the typical absence within STc648 of
uidA, an E. coli-specific gene encoding beta-glucuronidase. Within a diverse 212-
strain validation set that included 109 STs other than STc648, from phylogroups A,
B1, B2, C, D, E, and F, the assay exhibited 100% sensitivity (95% confidence
interval [CI], 82% to 100%) and specificity (95% CI, 98% to 100%). It functioned
similarly well in two distant laboratories that used boiled lysates or DNAzol-
purified DNA as the template DNA. Thus, this novel multiplex PCR-based assay should
enable any laboratory equipped for diagnostic PCR to rapidly, accurately, and
economically screen E. coli isolates for membership in STc648.
Escherichia coli is able to utilize d-ribose as its sole carbon source. The genes
for the transport and initial-step metabolism of d-ribose form a single rbsDACBK
operon. RbsABC forms the ABC-type high-affinity d-ribose transporter, while RbsD
and RbsK are involved in the conversion of d-ribose into d-ribose 5-phosphate. In
the absence of inducer d-ribose, the ribose operon is repressed by a LacI-type
transcription factor RbsR, which is encoded by a gene located downstream of this
ribose operon. At present, the rbs operon is believed to be the only target of
regulation by RbsR. After Genomic SELEX screening, however, we have identified that
RbsR binds not only to the rbs promoter but also to the promoters of a set of genes
involved in purine nucleotide metabolism. Northern blotting analysis indicated that
RbsR represses the purHD operon for de novo synthesis of purine nucleotide but
activates the add and udk genes involved in the salvage pathway of purine
nucleotide synthesis. Taken together, we propose that RbsR is a global regulator
for switch control between the de novo synthesis of purine nucleotides and its
salvage pathway.
OBJECTIVES: Matrix metalloproteinases (MMPs) regulated by ets transcription factors
facilitate carcinoma cell invasion. An ets family member, ESE-1, is expressed
specifically in epithelial tissues, but its association with MMPs is obscure. In
this study, we investigated whether ESE-1 regulates invasion of oral squamous cell
carcinoma (SCC) via transcriptional activity of MMP-9. METHODS: HSC-3 and KB were
used as human oral SCC lines. The expression of ESE-1 and MMP-9 was detected by in
situ hybridization and immunohistochemistry. Invasion assay, gelatin zymography and
Northern blotting were used to detect the invasion activity, the gelatinolytic
activity and the expression of MMP-9 in the ESE-1 transfectants. Luciferase assays
and mutation analysis were used for the transcriptional analysis of MMP-9 promoter
region by ESE-1. RESULTS: ESE-1 was expressed in the intermediate layer but not in
the invasive area, in which MMP-9 was expressed, in the oral SCC tissues. ESE-1
suppressed invasion activity and 92 kDa gelatinolytic activity in HSC-3 as a result
of transfection. ESE-1 regulates MMP-9 expression in a negative manner and the ets
binding site on the MMP-9 promoter contributed to suppression by ESE-1.
CONCLUSIONS: These findings indicate that ESE-1 negatively regulates the invasion
of oral SCC via transcriptional suppression of MMP-9.
Esophageal cancer (EC) is a highly malignant tumor, and the overall survival rate
remains very low. Traditional treatment is not sufficiently effective, and thus,
there is an urgent need for new and effective treatments. The advances in cancer
immunotherapy have changed this situation because this type of therapy has a
significant potential to eliminate tumors with little damage to normal tissue. This
treatment primarily aims to enhance the ability of the immune system to eliminate
tumors and prevent tumor immune escape, which is associated with immune
surveillance. This review summarizes current cancer therapeutic strategies and
immunotherapy studies to demonstrate the potential of immunotherapy for the
treatment of EC.
Radiotherapy is a common therapeutic strategy used to treat esophageal squamous
cell carcinoma (ESCC). However, tumor cells often develop radioresistance, thereby
reducing treatment efficacy. Here, we aimed to identify the mechanisms through
which ESCC cells develop radioresistance and identify associated biomarkers. Eca109
cells were exposed to repeated radiation at 2 Gy/fraction for a total dose of 60 Gy
(Eca109R60/2Gy cells). MTT and colony formation assays were performed to measure
cell proliferation and compare the radiation biology parameters of Eca109 and
Eca109R60/2Gy cells. Cell cycle distributions and apoptosis were assessed by flow
cytometry. Reverse transcription-quantitative polymerase chain reaction and western
blotting were employed to analyze the expression of HOX transcript antisense RNA
(HOTAIR), in addition to biomarkers of the epithelial-mesenchymal transition (EMT)
and cancer stem cells (CSCs). Eca109R60/2Gy cells exhibited increased cell
proliferation and clone formation, with significantly higher radiobiological
parameters compared with the parental Eca109 cells. The Eca109R60/2Gy cells also
exhibited significantly decreased accumulation in G(2) phase and increased
accumulation in S phase. Additionally, the apoptosis rate was significantly lower
in Eca109R60/2Gy cells than in parental Eca109 cells. Finally, HOTAIR expression
levels and SNAI1 and beta-catenin mRNA and protein expression levels were
significantly higher, whereas E-cadherin levels were significantly lower in
Eca109R60/2Gy cells than in Eca109 cells. Therefore, our findings demonstrated that
radioresistance was affected by the expression of HOTAIR and biomarkers of the EMT
and CSCs.
Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is an
important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a
long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently
revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether
serum HOTAIR is involved in the diagnosis of ESCC. Methods: In this study, we
detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor
resection and 8 without surgery) and 20 healthy volunteers to investigate the role
of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction
(qRT-PCR) method. Results: Clinical data indicated that serum HOTAIR were
correlated with TNM stage. The expression level of serum HOTAIR (0.189 +/- 0.010)
was significantly higher in ESCC patients compared with that of healthy controls
(0.055 +/- 0.008, P < 0.01). The ROC curve analysis yielded an area under the ROC
curve (AUC) value of 0.793 (95% CI: 0. 692 to 0.895, P < 0.01). Also, the serum
HOTAIR expression level decreased obviously in postoperative samples (one month
after the surgery) compared to preoperative specimens. Moreover, there was a
significant correlation between serum HOTAIR expression and the expression of
HOTAIR in ESCC tissue according to Pearson correlation analysis. Conclusions: Our
study, for the first time, demonstrated that serum HOTAIR might serve as a
potential biomarker for the diagnosis of ESCC.
The DNA mismatch repair (MMR) gene MutL homolog 1 (MLH1) is critical for the
maintenance of genomic integrity. Methylation of the MLH1 gene promoter was
identified as a prognostic marker for numerous types of cancer including
glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to
determine whether MLH1 promoter methylation was associated with survival in male
patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-
embedded ESCC tissues were collected from 87 male patients. MLH1 promoter
methylation was assessed using the methylation-specific polymerase chain reaction
approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the
association between MLH1 promoter methylation and overall survival (OS) in patients
with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard
ratios (HR), and 95% confidence intervals (CI). The present study revealed that
MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC.
Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was
significantly associated with poorer prognosis in patients with ESCC (P= 0.048).
Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an
independent predictor of poor OS in male patients with ESCC (HR= 1.716; 95% CI=
1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of
prognosis in male patients with ESCC.
The brown planthopper (BPH), Nilaparvata lugens (Stal), is one of the major pests
of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens
has resulted in the development of insecticide resistance leading to frequent
control failures in the field. The aim of the present study was to evaluate
resistance in the field populations of N. lugens from major rice growing states of
South India to various insecticides. We also determined the activity of detoxifying
enzymes (esterases [ESTs], glutathione S-transferases [GSTs], and mixed-function
oxidases [MFOs]). Moderate levels of resistance were detected in the field
populations to acephate, thiamethoxam and buprofezin (resistance factors 1.05-20.92
fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively) as compared with
susceptible strain while there were low levels of resistance to imidacloprid
(resistance factor 1.23-6.70 fold) and complete sensitivity to etofenoprox
(resistance factor 1.05-1.66 fold). EST activities in the field populations were
1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the
ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity
was found to be correlated to acephate resistance (r = 0.999, P 0.001). The high
selection pressure of organophosphate, neonicotinoid, and insect growth regulator
(IGR) in the field is likely to be contributing for resistance in BPH to multiple
insecticides, leading to control failures. The results obtained will be beneficial
to IPM recommendations for the use of effective insecticides against BPH.
This work describes the co-fermentation to the simultaneous production of
rhamnolipids and ethanol from exploded sugarcane bagasse (ESB) using Saccharomyces
cerevisiae, Pseudomonas aeruginosa and crude enzyme complexes (CECs). The CECs were
produced by Aspergillus niger in solid-state fermentation (SSF), using different
levels of ESB, rice bran (RB) and corn cob (CC) as substrates. The best results for
rhamnolipids (9.1 g/L, emulsification index of 84%, surface tension of 35 mN/m) and
ethanol (8.4 g/L) were obtained after 86 h of fermentation of ESB (250 g/L, 30
degrees C), using CEC from SSF of ESB (20% wt/wt), RB (30% wt/wt) and water (50%
wt/wt). It was also observed that the fermented bagasse had approximately the same
calorific value of a bagasse in nature and could be used as a potential source of
energy. These findings suggest that co-fermentation using P. aeruginosa, S.
cerevisiae and ESB can be used in the successful co-production of rhamnolipids and
ethanol, with the recovery of energy present in the fermented bagasse. (C) 2017
Elsevier Ltd. All rights reserved.
Responsible conduct in learning and research (RCLR) was progressively introduced
into the pharmacology curriculum for undergraduate science students at The
University of Western Australia. In the second year of this undergraduate
curriculum, a lecture introduces students to issues such as the use of animals in
teaching and responsible conduct of research. Third year student groups deliver
presentations on topics including scientific integrity and the use of human
subjects in research. Academic and research staff attending these presentations
provide feedback and participate in discussions. Students enrolled in an optional
capstone Honours year complete an online course on the responsible conduct of
research and participate in an interactive movie. Once RCLR became established in
the curriculum, a survey of Likert-scaled and open-ended questions examined student
and staff perceptions. Data were expressed as Approval (% of responses represented
by Strongly Agree and Agree). RCLR was found to be relevant to the study of
pharmacology (69-100% Approval), important for one's future career (62-100%
Approval), and stimulated further interest in this area (32-75% Approval). Free
entry comments demonstrated the value of RCLR and constructive suggestions for
improvement have now been incorporated. RCLR modules were found to be a valuable
addition to the pharmacology undergraduate curriculum. This approach may be used to
incorporate ethics into any science undergraduate curriculum, with the use of
discipline-specific topics. (c) 2016 by The International Union of Biochemistry and
Molecular Biology, 45(1):53-59, 2017.
Ross Cheit's The Witch-Hunt Narrative raises a number of complex moral issues.
Cheit's principal purpose is to challenge the belief that our society has
overreacted to claims about the sexual abuse of children. Both directly and
indirectly, Cheit's in-depth analysis broaches moral concerns pertaining to the
integrity of child abuse allegations, investigations, civil litigation, and
criminal prosecution, with an emphasis on the mixed motives of the parties involved
in key cases. This article provides an overview of ethical questions pertaining to
gathering information from very vulnerable individuals, informed consent,
institutional review, protection of research participants, the use of deception and
coercion, confidentiality and privacy, reporting research results, and conflicts of
interest. In addition, the author discusses the phenomenon of whistle-blowing as it
pertains to professionals' ethical judgments about disclosure of wrongdoing and
misconduct. The author outlines key ethics-related concepts, applies relevant moral
theory, and explores the implications of the moral issues raised by The Witch-Hunt
Narrative for child sexual abuse victims, perpetrators, child welfare and law
enforcement professionals, scholars and researchers, and the public at large.
Adding ethidium bromide (EtBr) at low concentrations to RNA samples before running
formaldehyde-agarose gels affords the advantages of checking RNA integrity and
evaluating the quality of size-separation at any time during electrophoresis or
immediately after either electrophoresis or blotted the separated RNA onto the
membrane without significantly compromising mobility, transfer, or hybridization.
In this study, we systematically examined the factors that affect the sensitivity
of RNA prestaining by heating RNA samples that include EtBr before electrophoresis
under different denaturation conditions. We also examined the efficiency of the
hybridization of EtBr-prestained RNA with heterologous DNA probes. The results
showed that the fluorescent intensity of EtBr-prestained RNA was affected not only
by the EtBr concentration as previously reported but also by the RNA amount,
denaturation time, and denaturation temperature. Prior staining of RNA with 40 mu
g/mL EtBr significantly decreased the efficiency of Northern blot hybridization
with heterologous DNA probes. We propose that to best combine staining sensitivity
and the efficiency of Northern blot hybridization with heterologous DNA probes, the
concentration of EtBr used to prestain RNA should not exceed 30 mu g/mL. The
efficiency of the hybridization of EtBr-prestained RNA was affected not only by
factors that affect staining sensitivity but also by the type of probe used.
Little population-based work has been published about the mental health of
adolescents with both sexual/gender (SG) and ethnic minority (i.e. double minority)
status. This study aimed to provide an overview on their mental health. Analysis of
data from a total of 17,607 high school students from New Zealand's 2007 and 2012
cross-sectional nationally representative Adolescent Health Surveys, including a
total of 1306 (7.4%) SG minority participants, of whom 581 (3.3%) were also an
ethnic minority. SG minority status, minority ethnicity, and female sex were
associated with higher mental distress and poorer well-being. Generally speaking,
double minority students reported poorer mental health than SG majority students of
the same ethnicity, but reported better mental health than SG minority New Zealand
European students. Explanations and future directions for research were suggested
to further explore how double minority students negotiate mental health in the
context of their communities/cultures in New Zealand.
This paper pursues an inquiry into the relationship between ethnicity and
development in the largest authoritarian country in the contemporary world, the
People's Republic of China. It engages the theoretical literature on ethnic
diversity and development in general, but also pays special attention to political
economy logics unique to authoritarian systems. Focusing on the western part of
China over a decade since the launch of China's Western Development Program (xibu
da kaifa) in 2000, this paper utilizes the data from two censuses (2000 and 2010)
together with nighttime streetlight imagery data to analyze the overall
relationship between ethnicity and development provision. It also analyzes changes
in such a relationship during this period. The paper finds that ethnic minority
concentration negatively correlates with economic development in both the years
2000 and 2010 across the western provinces. It also finds that counties in non-
autonomous provinces, which are historically more integrated with the rest of China
than autonomous provinces, have a positive and systematic correlation between
changes in ethnic minority concentration and changes in development during the 10-
year period. The counties in autonomous provinces, on the other hand, show the
opposite trend. Using three case studies of Tibet, Inner Mongolia, and Xinjiang,
the paper concludes that although there is in general a tendency for ethnic
minority concentrated areas to be less developed, ultimately which groups prosper
more or less depends upon specific economic development and which political control
logics the Chinese state implements. (C) 2017 The Authors. Published by Elsevier
Ltd.
Matrix metalloproteinase (MMP) is closely involved in the degradation of
extracellular matrix and confers invasive and metastatic potential to malignant
tumors. MMP-2 is a type-IV collagenase secreted as a proenzyme that is activated on
the surface of the tumor cell by membrane-type I MMP (MT1-MMP). MT1-MMP plays a
critical role during tumor progression and metastasis. We investigated the
expression levels of E1AF and MT1-MMP in malignant melanoma cell lines and
specimens from patients in order to clarify the mechanisms responsible for the
invasion and metastasis of malignant melanoma. High levels of E1AF and MT1-MMP mRNA
expression were observed in melanoma cells by Northern blotting and real-time PCR.
The expression level was highly correlated with an invasive potential determined by
an in vitro invasion assay. The down-regulation of MT1-MMP was identified when E1AF
was knocked down by RNA interference. These results suggest that E1AF plays a
crucial role in the invasion and metastasis of malignant melanoma through up-
regulating the MT1-MMP expression.
The chenopodiaceae Suaeda salsa L. is a leaf succulent euhalophyte. Shoots of the
S. salsa are larger and more succulent when grown in highly saline environments.
This increased growth and water uptake has been correlated with a large and
specific cellular accumulation of sodium. S. salsa does not have salt glands or
salt bladders on its leaves. Thus, this plant must compartmentalize the toxic Na+
in the vacuoles. The ability to compartmentalize sodium may result from a
stimulation of the proton pumps that provide the driving force for increased sodium
transport into the vacuole. In this work, we isolated the cDNA of the vacuolar
membrane proton-translocating inorganic pyrophosphatase (H+-PPase) from S. salsa.
The SsVP cDNA contains an uninterrupted open reading frame of 2292 bp, coding for a
polypeptide of 764 amino acids. Northern blotting analysis showed that SsVP was
induced in salinity treated leaves. The activities of both the V-ATPase and the V-
PPase in Arabidopsis overexpressing SsVP-2 is higher markedly than in wild-type
plant under 200 mM NaCl and drought stresses. The Overexpression of SsVP can
increase salt and drought tolerance of transgenic Arabidopsis.
Background: Jackals are medium-sized canids from the wolf-like clade, exhibiting a
unique combination of ancestral morphotypes, broad trophic niches, and close
phylogenetic relationships with the wolf and dog. Thus, they represent a potential
host of several pathogens with diverse transmission routes. Recently, populations
of the Eurasian golden jackal Canis aureus have expanded into the Western
Palaearctic, including most of Europe. The aim of our study was to examine Eurasian
golden jackals from Romania, Czech Republic and Austria for a wide spectrum of
vector-borne protists and to evaluate the role of this species as a reservoir of
disease for domestic dogs and/or humans. Results: Diagnostic polymerase chain
reaction (PCR) DNA amplifications revealed 70% of jackals to be positive for
Hepatozoon, 12.5% positive for piroplasms, and one individual positive for
Leishmania infantum. Phylogenetic analyses of partial 18S rDNA sequences invariably
placed sequenced isolates of Hepatozoon into the H. canis clade. For piroplasms,
both the 18S and cox1 sequences obtained confirmed the presence of Babesia canis
and "Theileria annae" in 5 and 2 individuals, respectively, providing the first
records of these two piroplasmids in Eurasian golden jackals. A single animal from
Dolj County (Romania) was PCR-positive for L. infantum, as confirmed also by
sequencing of ITS1-5.8S. Conclusions: Apparently, expanding populations of jackals
can play a significant role in spreading and maintaining new Babesia canis foci in
Central Europe. The role of jackals in the epidemiology of " Theileria annae" and
H. canis is probably similar to that of red foxes and should be taken into account
in further research on these parasites. Also the presence of L. infantum deserves
attention. Our study confirms that once established, the populations of Eurasian
golden jackals constitute natural reservoirs for many canine vector-borne diseases,
analogous to the role of the coyotes in North America.
This article reviews recent advances in the study of the European Court of Justice
(ECJ) and its political impact at the European and member state levels. New
quantitative as well as qualitative analyses show with great empirical precision
that member state preferences guide the Court. The article summarises these
findings, but argues that greater attention needs to be given to the
(over-)constitutionalisation of EU law in order to fully capture the political
impact of ECJ jurisprudence. Even if European judges are less activist than is
often assumed and individual decisions are more restrained in the face of member
state opposition, incrementally, case law evolves in a highly expansive fashion.
And, exercising caution regarding unrealistic expectations about quasi-
deterministic judicial law-making, it is found that the Court's constitutionalised
jurisprudence impacts heavily on European and member state policy-making.
Events are temporal "figures", which can be defined as identifiable segments in
time, bounded by beginnings and endings. But the functions and importance of these
two boundaries differ. We argue that beginnings loom larger than endings by
attracting more attention, being judged as more important and interesting,
warranting more explanation, and having more causal power. This difference follows
from a lay notion that additions (the introduction of something new) imply more
change and demand more effort than do subtractions (returning to a previous state
of affairs). This "beginning advantage" is demonstrated in eight studies of
people's representations of epochs and events on a historical timeline as well as
in cyclical change in the annual seasons. People think it is more important to know
when wars and reigns started than when they ended, and are more interested in
reading about beginnings than endings of historical movements. Transitional events
(such as elections and passages from one season to the next) claim more interest
and grow in importance when framed as beginnings of what follows than as
conclusions of what came before. As beginnings are often identified in retrospect,
the beginning advantage may distort and exaggerate their actual historical
importance. (C) 2017 Elsevier B.V. All rights reserved.
The conglomerate layer at the upper section of the 4th member of the Shahejie
formation(S-4(u)) of the Yongan district at the Donying depression is a well-
developed sedimentation of several periods. It lacks stable muddy layers and
sophisticated classification of the sedimentation periods and the proportion of
sedimentary layering in each period has long been a difficult task for geologists.
In addressing this problem, this paper attempts to introduce the theory of climatic
cycles driven by astronomical periods from astronomical stratigraphy on the basis
of the characteristics of the sedimentation under the turbidity current in the
region of study. Through studying the conditions for the formation of the
conglomerate layer and the factors of control, we pinpoint the formation of the
layer in chronology and differentiate the cycle interface and correlation in the
same formation period. Milankovitch analysis is conducted on the sedimentation of
the conglomerate layer in the region of study to determine if the stratigraphy
cycle of the region is primarily controlled by the eccentricity cycle and calculate
MSC1 and MSC2 thicknesses of 189.3 m and 78.05 m, respectively. Milankovitch theory
is the primary tool used in the analysis, in conjunction with petrographic
analysis. The stratum at the S-4(u) is classified into four IV-grade sequences and
11 V-grade sequences. The information on the dominant cycle frequency is used for
wave filtering of the well logs and to determine the significant Milankovitch wave
log. With the data from this curve, we may compare the stratigraphy cycle with the
characteristics of the standard cycle and classify and compare the sedimentation
periods of the conglomerate layers in further detail.
Hostile attribution bias (e.g., tendency to interpret the intention of others as
hostile in ambiguous social contexts) has been associated with impulsive aggression
in adults, but the results are mixed and the complete sequence of hostile
inferential processes leading to aggression has not been investigated yet. The goal
of this event-related brain potentials (ERPs) study was to track the neural
activity associated with the violation of expectations about hostile versus
nonhostile intentions in aggressive and nonaggressive individuals and examine how
this neural activity relates to self-reported hostile attributional bias and
impulsive aggression in real life. To this end, scenarios with a hostile versus
nonhostile social context followed by a character's ambiguous aversive behavior
were presented to readers, and ERPs to critical words that specified the hostile
versus nonhostile intent behind the behavior were analysed. Thirty-seven aggressive
and fifty nonaggressive individuals participated in the study. The presentation of
a critical word that violated hostile expectation caused an N400 response that was
significantly larger in aggressive than nonaggressive individuals. Results also
showed an enhanced late positive potential-like component in aggressive individuals
when hostile intention scenarios took place in a nonhostile context, which is
associated with impulsive aggression in real life even after having controlled for
the effect of self-reported hostile attributional bias. The Hostile Expectancy
Violation paradigm evaluated in this study represents a promising tool to
investigate the relationship between the online processing of hostile intent in
others and impulsive aggression. Aggr. Behav. 43:217-229, 2017. (c) 2016 Wiley
Periodicals, Inc.
When we hear an event description, our mental construal is not only based on
lexical items, but also on the message's syntactic structure. This has been well-
studied in the domains of causation, event participants, and object
conceptualization. Less studied are the construals of temporality and numerosity as
a function of syntax. We present a theory of how syntax affects the construal of
event similarity and duration in a way that is systematically predictable from the
interaction of mass/count syntax and verb semantics, and test these predictions in
six studies. Punctive events in count syntax (give a kiss) and durative events in
mass syntax (give advice) are construed as taking less time than in transitive
frame (kiss and advise). Durative verbs in count syntax (give a talk), however,
result in a semantic shift, orthogonal to duration estimates. These results
demonstrate how syntactic and semantic structure together systematically affect
event construal. (C) 2016 The Author(s). Published by Elsevier Inc.
Event-triggered control aims at reducing the resource utilization, especially the
communication over the feedback link, while guaranteeing a certain control
performance. Although setpoint tracking problems are common in practice, the
majority of the proposed approaches in literature focus on regulation problems.
Therefore, an event-triggered PI control design strategy with guaranteed
performance is proposed in this paper, where both the event-triggering condition
and the PI controller are implemented periodically. Based on a quadratic cost
function, the PI control design problem is introduced and formulated as an LMI
optimization problem. Comparisons with other approaches in the literature are made
by simulation and by experimental studies to demonstrate the effectiveness of the
proposed strategy.
An effective approach in early intervention for children and families, including
child maltreatment prevention, is home-based services. Although several evidence-
based programs exist, they are often grouped or delivered together, despite having
different foci and approaches. This article describes the development and pilot
phases of a trial evaluating the systematic braiding of 2 evidence-based home-based
models, SafeCare and Parents as Teachers. We describe the methodology for braiding
model implementation and curriculum, specifically focusing on how structured
qualitative feedback from pilot families and providers was used to create the
braided curriculum and implementation. Systematic braiding of 2 models at the
implementation and curriculum levels is a mechanism that has the potential to meet
the more comprehensive needs of families at risk for maltreatment.
Despite their differences, human language and the vocal communication of nonhuman
primates share many features. Both constitute forms of coordinated activity, rely
on many shared neural mechanisms, and involve discrete, combinatorial cognition
that includes rich pragmatic inference. These common features suggest that during
evolution the ancestors of all modern primates faced similar social problems and
responded with similar systems of communication and cognition. When language later
evolved from this common foundation, many of its distinctive features were already
present.
A complicated, almost conflicting situation exists in contemporary biology, i.e.,
there are two scientific concepts in existence that solve some phylogenetic
problems in a different way. These concepts are evolutionary morphology and
molecular biology. Modern biology urgently needs these contradictions to be
examined and removed.
This paper presents an efficient approach for the optimal designs of two analog
circuits, namely complementary metal oxide semiconductor) two-stage comparator with
p-channel metal oxide semiconductor input driver and n-channel input and folded-
cascode operational amplifier using a recently proposed meta-heuristic-based
optimization algorithm named as colliding bodies optimization (CBO). It is a multi-
agent algorithm that does not depend upon any internal control parameter, making
the algorithm extremely simple. The main objective of this paper is to optimize the
metal oxide semiconductor (MOS) transistors' sizes using CBO in order to reduce the
areas occupied by the circuits and to get better performance parameters of the
circuits. Simulation Program with Integrated Circuit Emphasis simulation has been
carried out by using the optimal values of MOS transistors' sizes and other design
parameters to validate that CBO-based design is satisfying the desired
specifications. Simulation results demonstrate that the design specifications are
closely met and the required functionalities are achieved. The simulation results
also confirm that the CBO-based approach is superior to the other algorithms in
terms of MOS area and performance parameters like gain, power dissipation, etc.,
for the examples considered. Copyright (c) 2016 John Wiley & Sons, Ltd.
Recurrent gene fusions involving EWSR1 with members of the cAMP response element
binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse
group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and
gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and
hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a
group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the
CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from
any of the previously described pathologic entities. Tumors occurred in children or
young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1
were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal.
Histologically, the tumors were well circumscribed, often lobulated, composed of
uniform ovoid to round cells, and arranged in cord-like or reticular structures in
a myxoid background. All except 1 displayed unique sunburst amianthoid fibers.
Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4
focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA
sequencing in the perirectal tumor, which was further confirmed by fluorescence in
situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-
PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and
FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence
of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a
distinct group of myxoid mesenchymal neoplasms occurring in children or young
adults with a predilection for intracranial locations. Although the immunoprofile
[epithelial membrane antigen (EMA), desmin] and the fusion type raise the
possibility of a myxoid AFH, none of the typical histologic findings of AFH were
present, suggesting a novel entity.
This paper presents a nonlinear power system stabilizer based on a pointwise min-
norm control law and a third order state space mathematical model of the
synchronous generator connected through transmission lines to the power system.
Commonly, the mathematical model includes transient electromotive force as a state
variable that cannot be measured. Therefore, the mathematical model is transformed
in a form containing all measurable variables. Furthermore, the control law for the
proposed stabilizer also considers voltage regulation. The proposed algorithm has
been implemented in a digital control system and its performance experimentally
verified on a 83 kVA synchronous generator connected to the power system.
Experimental results referring to the change in voltage and mechanical power
reference, for disconnection of the transmission line, three phase and two phase
short circuit, and forced oscillations are presented and compared to a PSS2A
stabilizer. The experimental results show better performance of the excitation
system with the proposed stabilizer compared to the system with a conventional PI
voltage controller and PSS2A stabilizer. Furthermore, the results show that the
proposed stabilizer is robust to system changes in the case of small and large
disturbances, as well as near the generator stability limit. (C) 2016 Elsevier B.V.
All rights reserved.
A novel, optimized numerical method of modeling of an exciton polariton superfluid
in a semiconductor microcavity was proposed. Exciton polaritons are spin-carrying
quasiparticles formed from photons strongly coupled to excitons. They possess
unique properties, interesting from the point of view of fundamental research as
well as numerous potential applications. However, their numerical modeling is
challenging due to the structure of nonlinear differential equations describing
their evolution. In this paper, we propose to solve the equations with a modified
Runge Kutta method of 4th order, further optimized for efficient computations. The
algorithms were implemented in form of C++ programs fitted for parallel
environments and utilizing vector instructions. The programs form the EPCGP suite
which has been used for theoretical investigation of exciton polaritons. Program
summary Program title: EPCGP Catalogue identifier: AFBQ_v1_0 Program summary URL:
http://cpc.cs.qub.ac.uk/summaries/AFBQ_v1_0.html Program obtainable from: CPC
Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: BSD-
3 No. of lines in distributed program, including test data, etc.: 2157 No. of bytes
in distributed program, including test data, etc.: 498994 Distribution format:
tar.gz Programming language: C++ with OpenMP extensions (main numerical program),
Python (helper scripts). Computer: Modern PC (tested on AMD and Intel processors),
HP BL2x220. Operating system: Unix/Linux and Windows. Has the code been vectorized
or parallelized?: Yes (OpenMP) RAM: 200 MB for single run Classification: 7, 7.7.
Nature of problem: An exciton polariton superfluid is a novel, interesting physical
system allowing investigation of high temperature Bose Einstein condensation of
exciton polaritons-quasiparticles carrying spin. They have brought a lot of
attention due to their unique properties and potential applications in polariton-
based optoelectronic integrated circuits. This is an out-of-equilibrium quantum
system confined within a semiconductor microcavity. It is described by a set of
nonlinear differential equations similar in spirit to the Gross Pitaevskii (GP)
equation, but their unique properties do not allow standard GP solving frameworks
to be utilized. Finding an accurate and efficient numerical algorithm as well as
development of optimized numerical software is necessary for effective theoretical
investigation of exciton-polaritons. Solution method: A Runge Kutta method of 4th
order was employed to solve the set of differential equations describing exciton-
polariton superfluids. The method was fitted for the exciton polariton equations
and further optimized. The C++ programs utilize OpenMP extensions and vector
operations in order to fully utilize the computer hardware. Running time: 6h for
100 ps evolution, depending on the values of parameters (C) 2017 Elsevier B.V. All
rights reserved.
Objective: Interest continues in neuropsychological measures as cross-disorder
intermediate phenotypes in understanding psychopathology. A central question
concerns their specificity versus generalizability to particular forms of
psychopathology, particularly for executive functioning (EF) and response speed.
Three conceptual models examining these relationships were tested to clarify this
picture at different levels in the diagnostic hierarchy. Method: Participants
(total n = 641, age 18-60) yielded complete structured diagnostic interviews and a
neuropsychological test battery comprising measures of executive function,
processing speed, and IQ. Repeated measures multivariate analysis of variance,
linear regression, and structural equation modeling (SEM) were used to test (a) a
specificity model, which proposes that individual disorders are associated with
component EF processes and speed; (b) a severity model, which proposes that the
total number of comorbid disorders explain poor EF and/or slow speed; and (c) a
higher-order dimensional model, which proposes that internalizing versus
externalizing disorders are differentially related to EF or speed. Results: EF
effects were best explained by a specificity model, with distinct aspects of EF
related to attention deficit hyperactivity disorder versus antisocial substance use
disorders. Speed, on the other hand, emerged as a general indicator of
externalizing psychopathology in the dimensional model, as well as overall severity
of psychopathology in the severity model. Conclusions: Granular approaches are
likely to be most productive for linking EF to psychopathology, whereas response
speed has underused potential as an endophenotype for psychopathology liability.
Results are discussed in terms of an integrated conceptualization of
neuropsychological processes and putative neural systems involved in general and
specific aspects of psychopathology.
The Bangor Gambling Task (BGT, Bowman & Turnbull, 2004) is a simple test of
emotion-based decision making, with contingencies varying across five blocks of 20
trials. This is the first study to characterise BGT performance in survivors of
traumatic brain injury (TBI) relative to healthy controls. The study also aimed to
explore sub-groups (cluster analysis), and identify predictors of task performance
(multiple regression). Thirty survivors of TBI and thirty-nine controls completed
the BGT and measures of processing speed, pre-morbid IQ, working memory, and
executive function. Results showed that survivors of TBI made more gamble choices
than controls (total BGT score), although the groups did not significantly differ
when using a cut-off score for 'impaired'performance. Unexpectedly, the groups did
not significantly differ in their performance across the blocks; however, the
cluster analysis revealed three subgroups (with survivors of TBI and controls
represented in each cluster). Findings also indicated that only age and group were
significant predictors of overall BGT performance. In conclusion, the study
findings are consistent with an individual difference account of emotion-based
decision making, and a number of issues need to be addressed prior to recommending
the clinical use of the BGT.
OBJECTIVE: To provide selectable microRNA for intervening diabetes mellitus
diseases, NOD mice's expression of microRNA in pancreas tissues and blood under the
exendin-4 intervention of was observed and the difference of microRNA target gene
was screened. MATERIALS AND METHODS: Forty clean NOD mice were randomly divided
into four groups (in each group, n = 10): One is blank control group D which is
intervened with normal saline, and the other three groups were divided into low-
dose group A, middle-dose group B, and high-dose group C according to the different
exendin- 4 dosage 2, 4, and 8 mu g/kg.d. After the 8-week intervention, these four
groups were killed, and the pancreatic tissue and blood were left to prepare
specimens for morphology and molecular biology analysis. The specimen with
differential expression microRNA in pancreas tissue and blood should be screened
out after detected with the locked nucleic acid array system (LNATM) microRNA
expression profile chip. The primers should be designed, and the ABI7500 real-time
fluorescent quantitative PCR should be applied to amplify, analyze, and verify
according to the screen results of the microRNA chip in order to screen out the
significant differentially expressed microRNA. RESULTS: Histological detection
showed that the pancreas of the mice in control group D was fibrosis gradually and
the islet frame was relatively disordered and significantly atrophied. Groups A, B,
and C have no islet hypertrophy or atrophy and the degree of fibrosis of the
pancreas has reduced. According to the gene chip detection, there are four
significantly differently expressed microRNAs in pancreas tissue and blood among
the group A, B, and C, among which miR-19a, miR-19b, and miR-22 were down-regulated
expressed while the miRNA-1 was upregulated expressed. Bioinformatics analysis
showed that the target genes of 4 differentially regulated microRNA genes were
related to cell proliferation, apoptosis, glucose metabolism, and angiogenesis. The
expression of microRNA in pancreatic tissue and blood of NOD rats was highly
consistent. CONCLUSIONS: MicroRNA expression file of pancreatic tissue and blood
can be changed during the intervention of the NOD rat model with exendin-4.
MicroRNA that indicates the differential expression may take part in the recovering
process of the NOD pancreatic trauma. At the same time, the administration of
exendin- 4 can protect NOD mice, reduce its pancreatic tissue fibrosis, and
regulate molecular markers of pancreatic cells in size and pancreatic mast cells.
This may be one of the main mechanisms of pancreatic injury in diabetes prevention.
Exercise immunology research has traditionally focussed on aerobic-exercise,
however it has become apparent in more recent years that resistance-exercise can
also considerably affect host immunobiology. To date however, no systematic process
has been used to establish a dose-response relationship between resistance-exercise
and the immune system. The present systematic review was thus conducted to
determine the dose-response effects of a bout of resistance-exercise on acute
leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature
search was conducted in the electronic databases, PubMed, Web of Science, and
Google Scholar, over the date range of 1989-2016. Following the PICO elements,
eligibility criteria included: i) participants: healthy humans aged 18-40; ii)
intervention: a single bout of resistance-exercise; iii) comparator: at least one
comparator group; iv) outcome: acute measures of circulating leukocyte counts.
Specific exclusion criteria were also applied. Risk of bias and quality of evidence
was assessed using the PEDro scale. Due to the individual designs of the admitted
studies, a qualitative analysis (systematic narrative synthesis) was employed in
the present review. The results of the present review demonstrate that a single
bout of resistance-exercise induces an acute monocytosis, neutrophilia, and
lymphocytosis. It became apparent that the reviewed literature either does not
consistently specify, or does not describe with sufficient detail, the time-course
between the onset of exercise and the collection of blood. We recommend that
researchers consider addressing this in future studies, and also collect blood
measures during exercise to aid with comparison of temporal effects. Regarding the
determination of a dose-response relationship, an acute neutrophilia, monocytosis
and lymphocytosis appears to occur more rapidly and to a greater magnitude
following a single bout of high-dose vs low-dose resistance-exercise.
Mechanistically, exercise-induced cell trafficking changes are associated with
mechanical, metabolic and endocrine factors. Physical aptitude of the host may also
affect resistance-exercise-induced lymphocyte trafficking responses. (C) 2016
European Federation of Immunological Societies. Published by Elsevier B.V. All
rights reserved.
Background: Exercise immunology has become a growing field in the past 20 years,
with an emphasis on understanding how different forms of exercise affect immune
function. Mechanistic studies are beginning to shed light on how exercise may
impair the development of cancer or be used to augment cancer treatment. The
beneficial effects of exercise on the immune system may be exploited to improve
patient responses to cancer immunotherapy. Methods: We investigated the effects of
acute exercise on the composition of peripheral blood leukocytes over time in a
male population of varying fitness. Subjects performed a brief maximal intensity
cycling regimen and a longer less intense cycling regimen at separate visits.
Leukocytes were measured by multi-parameter flow cytometry of more than 50
immunophenotypes for each collection sample. Results: We found a differential
induction of leukocytosis dependent on exercise intensity and duration. Cytotoxic
natural killer cells demonstrated the greatest increase (average of 5.6 fold)
immediately post-maximal exercise whereas CD15(+) granulocytes demonstrated the
largest increase at 3 h post-maximal exercise (1.6 fold). The longer, less intense
endurance exercise resulted in an attenuated leukocytosis. Induction of
leukocytosis did not differ in our limited study of active (n = 10) and sedentary
(n = 5) subjects to exercise although we found that in baseline samples, sedentary
individuals had elevated percentages of CD45RO(+) memory CD4(+) T cells and
elevated proportions of CD4(+) T cells expressing the negative immune regulator
programmed death-1 (PD-1). Finally, we identified several leukocytes whose presence
correlated with obesity related fitness parameters. Conclusions: Our data suggests
that leukocytes subsets are differentially mobilized into the peripheral blood and
dependent on the intensity and duration of exercise. Pre-existing compositional
differences of leukocytes were associated with various fitness parameters.
Purpose: The study aimed to investigate the effects of chronic moderate exercise on
regulation of intracellular calcium signaling as an important link to proliferation
capacity in murine splenic T lymphocytes. Methods: Male CD1 Swiss mice were
randomly assigned either to a control group (CG) or an exercise training group
(EG). EG mice performed voluntary exercise for 3 months. Lymphocytes were isolated
from murine spleens and intracellular calcium was determined by using Fura-2(AM)
and fluorescence spectrometry. The combination of flow cytometry and carboxy-
fluorescein succinimidyl ester labeling technique was used for determination of
cell proliferation. The expression levels of Ca2+-regulating genes were determined
by quantitative polymerase chain reaction (qPCR) analysis. Results: Basal [Ca2+](i)
was significantly higher in mice from the EG compared with mice of the CG (P <
0.001, n = 6). Similarly, [Ca2+](i) transients after stimulation with
phytohemagglutinin, concanavalin A, and the anti-CD3 antibody induced were
significantly increased in mice from the EG (P < 0.05, n = 5). However, no
differences were found after stimulation with thapsigargin (P < 0.05, n = 5). CD3+
T cells from EG showed higher mitogen-induced proliferation levels than from CG (P
< 0.05/0.01, n = 5). The mRNA expression of cellular Ca2+-regulating genes, such as
STIM1, Cav2.3, TRPV4, IP3R2, ORAI1, MCU, TRPM5, and TRPC1, were significantly
downregulated (P < 0.05/0.01, n = 5). Conclusion: This study suggests that chronic
moderate exercise improves intracellular Ca2+ signaling in murine splenic
lymphocytes. The enhanced availability of the second messenger Ca2+ is followed by
an improved cellular function such as cell proliferation. The downregulation of
Ca2+ homeostasis-related factor expression might be considered as a self-protective
mechanism against elevated intracellular Ca2+ signals.
In this paper, a geothermal based multi-generation energy system, including organic
Rankine cycle, domestic water heater, absorption refrigeration cycle and proton
exchange membrane electrolyzer, is developed to generate electricity, heating,
cooling and hydrogen. For this purpose, energetic, exergetic and exergoeconomic
analysis are undertaken upon proposed system. Also, the effects of some important
variables, i.e. geothermal water temperature, turbine inlet temperature and
pressure, generator temperature, geothermal water mass flow rate and electrolyzer
current density on the several parameters such as energy and exergy efficiencies of
the proposed system, heating and cooling load, net electrical output power,
hydrogen production, unit cost of each system products and total unit cost of the
products are investigated. For specified conditions, the results show that energy
and exergy efficiencies of the proposed multigeneration system are calculated about
34.98% and 49.17%, respectively. The highest and lowest total unit cost of the
products estimated approximately 23.18 and 22.73 $/GJ, respectively, by considering
that geothermal water temperature increases from 185 degrees C to 215 degrees C.
(C) 2017 Published by Elsevier Ltd.
Exergy Life Cycle Assessment (ELCA) is proposed by literature to account for the
exergy embodied in products of energy systems. In order to make results of ELCA
comparable, supply chains that support the life cycle of the system should be
analyzed through a unified model: this is one of the main concerns related to Life
Cycle Assessment and Industrial Ecology disciplines. In this paper, Hybrid Input-
Output analysis is proposed as the computational structure of ELCA: according to
this method, national supply chains are modeled through the Monetary Input Output
Tables (MIOTs) of national economies, a constantly updated and freely available
data source. Then, the adopted national MIOT is expanded to include the detailed
model of the considered energy system, hence defining a Hybrid Input-Output model.
The (non-renewable) exergy embodied in electricity production and the Exergy Return
on Investment (ExROI) are defined as the appropriate performance indicators based
on ELCA. The introduced model is here adopted for the analysis of a Waste-to-Energy
(WtE) power plant currently operating in the Italian context. It is found that the
primary non-renewable exergy embodied in electricity produced by the analyzed WtE
is non-negligible for both the construction (127.1 toe) and the operation phases
(11.6 toe/y). Nonetheless, the plant is able to produce a net amount of electricity
that pays back such primary non-renewable resources requirements about a hundred
times. Finally, the joint application of Exergy Analysis and ELCA lead to improve
the overall thermodynamic performances of the WtE system, increasing its exergy
efficiency by 1%, and reducing the non-renewable exergy embodied in electricity
production by 7938 toe. (C) 2016 Elsevier Ltd. All rights reserved.
Exfoliation syndrome (XFS) is a common age-related disorder that leads to
deposition of extracellular fibrillar material throughout the body. The most
recognized disease manifestation is exfoliation glaucoma (XFG), which is a common
cause of blindness worldwide. Recent developments in XFS genetics, cell biology and
epidemiology have greatly improved our understanding of the etiology of this
complex inherited disease. This review summarizes current knowledge of XFS
pathogenesis, identifies gaps in knowledge, and discusses areas for future
research. (C) 2016 Published by Elsevier Ltd.
Exosomes secreted from the cell to the extracellular environment play an important
role in intercellular communication. Next-generation sequencing technology, which
has achieved great development recently, allows us to detect more complete data and
gain even deeper analyses of RNA transcriptomes. In our research, we extracted
exosomes from different gastric cancer cell lines and immortalized normal gastric
mucosal epithelial cell line and examined the amounts of exosomal proteins and
RNAs. Our data showed that the secreted amount of cancer cell-derived exosomes,
which contain proteins and RNAs, was much higher than that of normal cell-derived
exosomes. Moreover, next-generation sequencing technology confirmed the presence of
small non-coding RNAs in exosomes. Based on publicly available databases, we
classified small non-coding RNAs. According to the microRNA profiles of exosomes,
hsa-miR-21-5p and hsa-miR-30a-5p were two of the most abundant sequences among all
libraries. The expression levels of the two microRNAs, miR-100 and miR-148a, in
exosomes were validated through reverse transcription polymerase chain reaction.
The reverse transcription polymerase chain reaction result, consistent with the
trend of sequencing result, indicated a significant difference in exosomes between
gastric cancer and gastric mucosal epithelial cell lines. We also predicted novel
microRNA candidates but they need to be validated. This research provided an atlas
of small noncoding RNA in exosomes and may make a little contribution to the
understanding of exosomal RNA composition and finding parts of differential
expression of RNAs in exosomes.
BACKGROUNDStereotactic body radiation therapy (SBRT) for localized prostate cancer
involves high-dose-per-fraction radiation treatments. Its use is increasing, but
concerns remain about treatment-related toxicity. The authors assessed the
incidence and predictors of a global decline in health-related quality of life
(HRQOL) after prostate SBRT. METHODSFrom 2008 to 2014, 713 consecutive men with
localized prostate cancer received treatment with SBRT according to a prospective
institutional protocol. Expanded Prostate Cancer Index Composite (EPIC-26) HRQOL
data were collected at baseline and longitudinally for 5 years. EPIC-26 is
comprised of 5 domains. The primary endpoint was defined as a decline exceeding the
clinically detectable threshold in 4 EPIC-26 domains, termed multidomain decline.
RESULTSThe median age was 69 years, 46% of patients had unfavorable intermediate-
risk or high-risk disease, and 20% received androgen-deprivation therapy. During 1
to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had
multidomain declines, respectively. On multivariable analysis, lower baseline bowel
HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) and baseline
depression (odds ratio, 5.7; 95% confidence interval, 1.3-24.3; P = .02)
independently predicted for multidomain decline. Only 3% to 4% of patients had
long-term multidomain declines exceeding twice the clinical threshold, and 30% of
such declines appeared to be related to prostate cancer treatment or progression of
disease. CONCLUSIONSProstate SBRT has minimal long-term impact on multidomain
decline, and the majority of more significant multidomain declines appear to be
unrelated to treatment. This emphasizes the importance of focusing not only on the
side effects of prostate cancer treatment but also on other comorbid illnesses that
contribute to overall HRQOL. Cancer 2017;123:1635-1642. (c) 2017 American Cancer
Society. In a cohort of over 700 patients with prospective health-related quality-
of-life information, prostate stereotactic body radiation therapy has minimal long-
term impact on clinically detectable declines in global quality of life. Baseline
poor bowel function and clinical depression are associated with an increased rate
of multidomain decline.
An alpha-expansin (RiEXPA1) gene was cloned and sequenced from raspberry.
Expression of RiEXPA1 in different ripening stages of raspberry fruits has been
detected. Northern blotting showed that the level of RiEXPA1 transcript
accumulation increased with fruit ripening and the highest level of expression
appeared at the later stages of ripening. This indicates that expression of RiEXPA1
is closely correlated with the ripening and softening of raspberry fruits. In order
to determine whether expression of the RiEXPA1 was regulated by ethylene, we cloned
and sequenced a 1-aminocyclo-propane-1-carboxylic acid synthase cDNA (RiACS1) that
encodes the rate-limiting enzyme for ethylene production. Transcript accumulation
of RiACS1 was detected at a low level only in the later stage of fruit ripening.
This reveals that ethylene is not a regulatory factor of RiEXPA1 expression in
raspberry fruit. The results of this investigation suggest that the expression of
RiACS1 gene during ripening resembles that of non-climacteric fruits. (C) 2010
Elsevier Ireland Ltd. All rights reserved.
People who are high in victim-sensitivity a personality trait characterized by a
strong fear of being exploited by others are more likely to attend to social cues
associated with untrustworthiness rather than to cues associated with
trustworthiness compared with people who are low in victim-sensitivity. But how do
these people react when an initial expectation regarding a target's trustworthiness
turns out to be false? Results from two studies show that victim-sensitive compared
with victim-insensitive individuals show enhanced source memory and greater change
in person perception for negatively labeled targets that violated rather than
confirmed negative expectations (the "trustworthy trickster"). These findings are
in line with recent theorizing on schema inconsistency and expectancy violation
effects in social cognition and with research on the different facets of justice
sensitivity in personality psychology.
Distinct explicit and implicit memory processes support weight predictions used
when lifting objects and making perceptual judgments about weight, respectively.
The first time that an object is encountered weight is predicted on the basis of
learned associations, or priors, linking size and material to weight. A fundamental
question is whether the brain maintains a single, global representation of priors,
or multiple representations that can be updated in a context specific way. A second
key question is whether the updating of priors, or the ability to scale lifting
forces when repeatedly lifting unusually weighted objects requires focused
attention. To investigate these questions we compared the adaptability of weight
predictions used when lifting objects and judging their weights in different groups
of participants who experienced size-weight inverted objects passively (with the
objects placed on the hands) or actively (where participants lift the objects)
under full or divided attention. To assess weight judgments we measured the size-
weight illusion after every 20 trials of experience with the inverted objects both
passively and actively. The attenuation of the illusion that arises when lifting
inverted object was found to be context-specific such that the attenuation was
larger when the mode of interaction with the inverted objects matched the method of
assessment of the illusion. Dividing attention during interaction with the inverted
objects had no effect on attenuation of the illusion, but did slow the rate at
which lifting forces were scaled to the weight inverted objects. These findings
suggest that the brain stores multiple representations of priors that are context
specific, and that focused attention is important for scaling lifting forces, but
not for updating weight predictions used when judging object weight. (C) 2017
Elsevier B.V. All rights reserved.
In applications involving digital control, the set of admissible control actions is
finite/quantized. Coupled with state constraints and fast dynamics, explicit model
predictive control (EMPC) provides an attractive control formalism. However, the
design of data-driven EMPCs with finite admissible control sets is a challenging
and relatively unexplored problem. In this paper, a systematic data-driven method
is proposed for the design of quantized EMPCs (Q-EMPCs) for time-varying output
tracking in nonlinear systems. The design involves: 1) sampling the admissible
state space using low-discrepancy sequences to provide scalability to higher
dimensional nonlinear systems; 2) at each sampled data point, solving for optimal
quantized model predictive control actions and determining feasibility of the
intrinsic mixed-integer nonlinear programming problem; and 3) constructing the Q-
EMPC control surface using multiclass support vector machines (MC-SVMs). In
particular, four widely used MC-SVM algorithms are employed to construct the
proposed data-driven Q-EMPC. Extensive testing and comparison among the different
MC-SVM algorithms is performed on 2-D and 5-D benchmark examples to demonstrate the
effectiveness and scalability of the proposed methodology.
Background: The concept of well-being is multi-faceted by encompassing both
positive and negative emotions and satisfaction with life. Measuring both positive
and negative thoughts and emotions is highly relevant in maternity care that aims
to optimise a woman's experience of pregnancy and childbirth, focussing on positive
aspects of health and well-being, not just the prevention of ill health. Yet our
understanding of well-being in pregnancy and childbirth is limited as research to
date has focussed on negative aspects such as stress, anxiety or depression. The
primary aim of this study is to describe the psychometric properties of a newly
developed Well-being in Pregnancy (WiP) questionnaire.Methods: A cohort study of
318 women attending hospital antenatal clinics in Belfast completed a questionnaire
including three general well-being measures (not pregnancy specific) and the newly
developed WiP questionnaire. The psychometric properties of the questionnaire were
analysed using correlations to explore the relationship between the WiP
questionnaire with the generic well-being measures administered at the same time
and exploratory factor analysis was conducted.Results: The overall Cronbach's alpha
of the WiP was 0.73. Principal factor analysis was run on the WiP items and two
factors were identified, one reflecting positive affect and satisfaction
(Cronbach's alpha=0.718) and the other concerns (Cronbach's alpha=0.702). Both the
overall WiP score and WiP sub-scale scores displayed significant correlations with
the other well-being scales (r=0.235-0.527).Conclusions: Measuring well-being in
pregnancy is an important step in understanding the potential physical,
psychological and social benefits of pregnancy and in understanding how well-being
can be enhanced for women and their families at this important life stage. The
initial psychometric data presented for the WiP questionnaire are encouraging. Most
importantly, the measure provides an opportunity for women to express positive and
negative emotions and thoughts about their pregnancy thus reflecting the whole
spectrum of well-being.
In screening for potent antimicrobial proteins (AMPs) from plant seeds, we had
purified a heat-stable AMP, LJAMP2, from the seeds of a medicine herb, motherwort
(Leonurus japonicus Houtt). In an in vitro assay, the protein can inhibit the
growth of both fungi and bacteria. Then a cDNA encoding LJAMP2 was cloned by the
rapid amplification of cDNA ends based on the N-terminal amino acid sequence
determined. The deduced amino acid sequences of this cDNA show similarity to plant
non-specific lipid transfer proteins. Northern blotting assay revealed that this
nsLTP-like gene, designated LJAMP2, was expressed in seeds. Overexpression of
LJAMP2 in tobacco enhanced resistance to the fungal pathogen Alternaria alternata
and the bacterial pathogen Ralstonia solanacearum, significantly, while no visible
alteration in plant growth and development. Our data confirm the antifungal and
antibacterial function of LJAMP2 from motherwort seeds and suggest the potential of
LJAMP2 in improving disease resistance in plants.
In mammals, 10 isoforms of fatty acid-binding protein (FABP) are expressed in
various tissues. To understand the role of multiple FABP isoforms, we have
quantitatively examined the transcript levels of individual FABP isoforms in each
of various tissues by Northern blotting using synthesized RNAs corresponding to the
mRNA of each isoform as external standards. As a result, absolute transcript levels
of individual FABP isoforms expressed in each tissue were successfully determined.
The 10 FABP isoforms were classified into three categories: (1) isoforms FABP7 and
12 were not markedly expressed in any tissue examined; (2) isoforms showing certain
transcript levels in multiple tissues; and (3) isoforms FABP6, 8, and 9, expressed
at certain levels in one particular tissue. Based on the expression profiles of the
isoforms, individual tissues were also classified into three groups: (1) tissues in
which high-level expression of FABP isoforms was not observed, (2) tissues in which
multiple FABP isoforms were expressed at certain levels, and (3) tissues in which a
single FABP isoform was dominantly expressed at a certain level. These results give
a better understanding of the meaning of the presence of multiple FABP isoforms in
mammals.
Superoxide dismutases (SODs) constitute the first line of cellular defense against
oxidative stress in plants. SODs generally occur in three different forms with
Cu/Zn, Fe, or Mn as prosthetic metals. We cloned the full-length cDNA of the
Thellungiella halophila Cu/Zn-SOD gene ThCSD using degenerate RT-PCR and rapid
amplification of cDNA ends (RACE). Sequence analysis indicated that the ThCSD gene
(GenBank accession number EF405867) had an open reading frame of 456 bp. The
deduced 152-amino acid polypeptide had a predicted molecular weight of 15.1 kDa, an
estimated pI of 5.4, and a putative Cu/Zn-binding site. Recombinant ThCSD protein
was expressed in Escherichia coli and assayed for SOD enzymatic activity in a
native polyacrylamide gel. The SOD activity of ThCSD was inactivated by potassium
cyanide and hydrogen peroxide but not by sodium azide, confirming that ThCSD is a
Cu/Zn-SOD. Northern blotting demonstrated that ThCSD is expressed in roots, stems,
and leaves. ThCSD mRNA levels increased by about 30-fold when plants were treated
with sodium chloride (NaCl), abscisic acid (ABA), and indole-acetic acid (IAA) and
by about 50-fold when treated with UVB light. These results indicate that ThCSD is
involved in physiological pathways activated by a variety of environmental
conditions.
The melanocortin 1 receptor (MCIR) gene is a candidate functional gene that
controls the pigment production in melanocytes. The aim of this study was to
identify polymorphisms and investigate the effect of the MCIR gene on plumage
coloration in duck breeds, including Korean native ducks. Initially, 34 individuals
from seven duck breeds were sequenced, obtaining 12 polymorphisms. Five single
nucleotide polymorphisms (SNPs) in the coding region were non-synonymous, with
mutations corresponding to amino acid changes. Among these, four SNPs were geno-
typed using polymerase chain reaction-restriction fragment length polymorphism
method in 264 individuals from same seven duck breeds. Fisher's exact test was
conducted to identify possible relationships between the MCIR gene polymorphisms
and plumage color variations. Four non-synonymous SNPs, c.52A>G (p.Lys18Glu), and
c.376 A>G (p.Ile126Val), c.409G>A (p.Ala137Thr) and c.649C>T (p.Arg217Cys), were
associated with the two deduced genotypes (i.e., E/E and e+ /e+) based on plumage
color phenotypes. In addition, we reconstructed MCIR gene haplotypes, where the
haplotype AAGC showed its highest frequency in Nageswari duck breed, which presents
an extended black phenotype. Our results indicate that the identified polymorphisms
by this study can be used to explore associations with plumage color variations in
Asian duck breeds.
Background: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are
resistant to several types of antibiotics excluding carbapenems. A transmissibility
of ESBL-producing Enterobacteriaceae would be depending on each bacterial property,
however, that has not been elucidated in clinical setting. In this study, we
attempted to identify the source of an outbreak of ESBL-producing bacteria in a
medical oncology and immunology care unit. Methods: An ESBL-producing
Enterobacteriaceae (ESBL-E) outbreak observed between July 2012 and August 2012 in
Kagawa University Hospital was surveyed using various molecular microbiology
techniques. We used Pulsed-field gel electrophoresis (PFGE), PCR-based ESBL gene
typing, and direct sequence of ESBL gene as molecular microbiology typing method to
distinguish each strain. Results: The typical prevalence of ESBL-E isolation in the
unit was 7.0 per month (1.7 per week). The prevalence of ESBL-E isolation during
the target research period was 20.0 per month (5.0 per week). In total, 19 isolates
(11 K. pneumoniae and 8 E. coli) were obtained from clinical samples, including
four control strains (two each of both bacteria), that were physically different
from those obtained from other inpatient units in our hospital. Pulsed-field gel
electrophoresis (PFGE) for K. pneumoniae (digested by XbaI) produced similar
patterns excluding one control strain. PCR classification of the ESBL gene for K.
pneumoniae revealed that all strains other than the control strain carried SHV and
CTX-M-9. This result was reconfirmed by direct DNA sequencing. Although the
outbreak of K. pneumoniae was considered to be "clonal," PFGE and PCR
classification of the ESBL genes for E. coli uncovered at least six different "non-
clonal" strains possessing individual ESBL gene patterns. According to the result
of an antibiogram, the pattern of antimicrobial susceptibility was more variable
for K. pneumoniae than for E. coli. Conclusions: Typing by PFGE and ESBL gene PCR
analysis is practical for discriminating various organisms. In our cohort, two
outbreaks were concomitantly spread with different transmission strategies, namely
clonal and non-clonal, in the same unit. This might represent clinical evidence
that transmissibility differs according to the type of strain. We speculated that
patient-to-patient transmission of ESBL-E occurred according to the properties of
each individual strain.
Despite a substantial body of research examining the relationship between child
maltreatment and externalizing, antisocial, and criminal behavior problems, theory
is rarely applied in the current empirical research literature. The lack of
theoretical application limits opportunities to understand the mechanisms
explaining why maltreatment is associated with behavior problems, and the best
strategies for intervening to interrupt this association. The purpose of this paper
is to analyze relevant theoretical perspectives and develop a conceptual model
explaining the relationship between maltreatment and behavior problems, and the
intervening role of child welfare services. Six theoretical perspectives were
selected for analysis: the ecological model, the transactional model, attachment
theory, the life course perspective, the social learning perspective, and social-
biological models. After applying these theories to understanding the maltreatment-
behavior problem association and the role of child welfare services in intervening,
insights from these theories were synthesized into a conceptual model. The policy
and practice implications of this model are discussed, with a focus on the
implications for child welfare workers, administrators, and policymakers. (C) 2016
Elsevier Ltd. All rights reserved.
ADAMTS-like 2 (ADAMTSL2), is a secreted protein resembling the ancillary domains of
the ADAMTS proteases, but with distinct structural features. It has 7
thrombospondin type-1 repeats (TSRs), but an unusually long spacer module, which in
both humans and mice, contains a novel insertion bearing six N-glycosylation sites.
The ADAMTSL2 protein expressed in HEK293F and COS-I cells, is a cell-surface and
extracellular matrix binding glycoprotein, with N-linked carbohydrate constituting
similar to 20% by mass. The 4.0 kb Adamtsl2 mRNA is found most abundantly in adult
mouse liver, lung and spleen by northern blotting. During mouse embryogenesis,
Adamtsl2 was expressed most strongly in the third week of gestation. Adamtsl2 mRNA
was detected by in situ hybridization in developing skeletal muscle, liver,
bronchial and arterial smooth muscle, skin, intervertebral disc, perichondrium,
pancreas and spinal cord. Immunohistochemical localization of ADAMTSL2 protein was
similar to mRNA expression. Detection of Adamtsl2 mRNA and protein in developing
skeletal myotubes, but not undifferentiated myogenic precursors led us to
investigate its regulation during in vitro myogenic differentiation. In C2C12 and
23A2 myogenic cells, but not in 23A2 cells rendered non-myogenic by expression of
G12V:H-Ras (9A2 cells), differentiation induced by serum starvation triggered
expression of Adamtsl2 mRNA, coordinately with Myog, a marker of muscle
differentiation. Furthermore, activation of the key myogenic determinant MyoD in
10T1/2 fibroblasts also triggered expression of Adamtsl2 mRNA. Collectively, the
data suggest that induction of Adamtsl2 mRNA is an integral feature of myogenesis.
(c) 2007 Elsevier B.V./International Society of Matrix Biology. All rights
reserved.
The detection of exogenous plant microRNAs in human/animal plasma/sera lies at the
foundation of exploring their cross-kingdom regulatory functions. It is necessary
to establish a standard operation procedure to promote study in this nascent field.
In this study, 18 plant miRNAs were assessed in watermelon juice and mixed fruits
by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). C-T
values, no-template controls and standard curves for each miRNA were used to
evaluate the specificity and sensitivity of qRT-PCR and to obtain concentrations.
Sixteen miRNAs were selected and measured in human plasma from volunteers after
drinking juice. The CT values of 6 plant miRNAs in human plasma fell outside the
linear ranges of their standard curves. The remaining 10 miRNAs were present at
high basal levels, and 6 of them showed a dynamic physiological pattern in plasma
(absorption rates of 0.04% to 1.31%). Northern blotting was used to confirm the
qRT-PCR results. Critical issues such as RNA extraction and internal controls were
also addressed. (C) 2015 The Authors. Published by Elsevier Inc. This is an open
access article under the CC BY-NC-ND license.
Evolution of melanoma from a primary tumor to widespread metastasis is crucially
dependent on lymphatic spread. The mechanisms regulating the initial step in
metastatic dissemination via regional lymph nodes remain largely unknown; however,
evidence supporting the establishment of a pre-metastatic niche is evolving. We
have previously described a dysfunctional immune profile including reduced
expression of dendritic cell (DC) maturation markers in the first node draining
from the primary tumor, the sentinel lymph node (SLN). Importantly, this phenotype
is present prior to evidence of nodal metastasis. Herein, we evaluate melanoma-
derived extracellular vesicles (EVs) as potential mediators of the premetastatic
niche through cargo-specific polarization of DCs. DCs matured in vitro in the
presence of melanoma EVs demonstrated significantly impaired expression of CD83 and
CD86 as well as decreased expression of Th1 polarizing chemokines FIt3L and IL15
and migration chemokines MIP-l alpha and MIP-1 beta compared to liposome-treated
DCs. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures
including S100A8 and S100A9 protein cargo, which in vitro compromised DC maturation
similar to melanoma EVs. Early evidence demonstrates that similar EVs can be
isolated from human afferent lymphatic fluid ex vivo. Taken together, here, we
propose melanoma EV cargo as a mechanism by which DC maturation is compromised
warranting further study to consider this as a potential mechanism enabled by the
primary tumor to establish the premetastatic niche in tumor-draining SLNs of
patients.
Extracellular vesicles (EVs), including exosomes, play a key role in inter and
intracellular communication, promoting the proliferation and invasion of recipient
cells to support tumor growth and metastasis. Metastasis comprises multiple steps
that first include the detachment of tumor cells through epithelial to mesenchymal
transition (EMT), allowing the physical dissemination to distant organs.
Thereafter, cancer-derived exosomes are still critical components for preparing the
tumor microenvironment by (i) enabling tumor cells to escape from the immunological
surveillance and (ii) arranging the pre-metastatic site for the engraftment of
detached cancer cells. In this review, we discuss the multifaceted role of EVs in
the multiple steps of metastasis. Future research directions draw attention to EVs
as biological targets for cancer diagnosis, prognosis and therapy. However, due to
their significant role in cell communication, they may become a valuable drug
delivery system.
Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated
soft tissue sarcoma with a high propensity for metastases. Using a clinical
sequencing approach, we genomically profiled patients with metastatic EMC to
elucidate the molecular biology and identify potentially actionable mutations. We
also evaluated potential predictive factors of benefit to sunitinib, a multi-
targeted tyrosine kinase inhibitor with reported activity in a subset of EMC
patients. Between January 31, 2012 and April 15, 2016, six patients with EMC
participated in the clinical sequencing research study. High quality DNA and RNA
was isolated and matched normal samples underwent comprehensive next generation
sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and
capture transcriptome). The expression levels of sunitinib targeted-kinases were
measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4.
The previously reported EWSR1-NR4A3 translocation was identified in all patient
tumors; however, other recurring genomic abnormalities were not detected. RET
expression was significantly greater in patients with EMC relative to other types
of sarcomas except for liposarcoma (p<0.0002). The folate receptor was
overexpressed in two patients. Our study demonstrated that similar to other
translocation-associated sarcomas, the mutational profile of metastatic EMC is
limited beyond the pathognomonic translocation. The clinical significance of RET
expression in EMC should be explored. Additional pre-clinical investigations of EMC
may help elucidate molecular mechanisms contributing to EMC tumorigenesis that
could be translated to the clinical setting.
Traditional cognitive assessment in neurological conditions involving physical
disability is often prevented by the presence of verbal-motor impairment; to date,
an extensive motor-verbal-free neuropsychological battery is not available for such
purposes. We adapted a set of neuropsychological tests, assessing language,
attentional abilities, executive functions and social cognition, for eye-tracking
(ET) control, and explored its feasibility in a sample of healthy participants.
Thirty healthy subjects performed a neuropsychological assessment, using an ET-
based neuropsychological battery, together with standard "paper and pencil"
cognitive measures for frontal (Frontal Assessment Battery-FAB) and working memory
abilities (Digit Sequencing Task) and for global cognitive efficiency (Montreal
Cognitive Assessment-MoCA). Psychological measures of anxiety (State-Trait Anxiety
Inventory-Y-STAI-Y) and depression (Beck Depression Inventory-BDI) were also
collected, and a usability questionnaire was administered. Significant correlations
were observed between the "paper and pencil" screening of working memory abilities
and the ET-based neuropsychological measures. The ET-based battery also correlated
with the MoCA, while poor correlations were observed with the FAB. Usability
aspects were found to be influenced by both working memory abilities and
psychological components. The ET-based neuropsychological battery developed could
provide an extensive assessment of cognitive functions, allowing participants to
perform tasks independently from the integrity of motor or verbal channels. Further
studies will be aimed at investigating validity and usability components in
neurological populations with motor-verbal impairments.
Background: STAT3 signaling plays the pivotal role in tumorigenesis through EZH2
epigenetic modification, which enhanced STAT3 activity by increased tyrosine
phosphorylation of STAT3. Here, another possible feedback mechanism and clinical
significance of EZH2 and STAT3 were investigated in gastric cancer (GC). Methods:
STAT3, p-STAT3 (Tyr 705) and EZH2 expression were examined in 63 GC specimens with
matched normal tissues by IHC staining. EZH2 and STAT3 were also identified in five
GC cell lines using RT-PCR and western blot analyses. p-STAT3 protein was detected
by western blotting. In order to investigate whether EZH2 expression was directly
regulated by STAT3, EZH2 expression was further detected using siRNA for STAT3 or
IL-6 stimulation, with dual luciferase reporter analyses, electrophoretic mobility
shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. The clinical
significance of STAT3, p-STAT3 and EZH2 expression was evaluated by multi-factor
COX regression and Kaplan-Meier analyses. Results: Hyper-activation of STAT3, p-
STAT3 and EZH2 expression were observed in GC cells and tissues. STAT3 signaling
was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was
consistent with our data showing that STAT3 as the transcriptional factor enhanced
EZH2 transcriptional activity by binding the relative promoter region (-214 similar
to-206). STAT3 was an independent signature for poor survival (P = 0.002). Patients
with STAT3(+)/EZH2(+) or p-STAT3(+)/EZH2(+) had a worse outcome than others (P <
0.001); Besides, high levels of STAT3 and EZH2 was associated with advanced TNM
staging (P = 0.017). Moreover, treatment with a combination of siSTAT3 and EZH2-
specific inhibitor, 3-deazaneplanocin A (DZNEP), increased the apoptotic ratio of
cells. It is benefit for targeting STAT3-EZH2 interplay in GC treatment.
Conclusions: Our results indicate that STAT3 status mediated EZH2 upregulation,
associated with advanced TNM stage and poor prognosis, suggesting that combination
with knockdown of STAT3 and EZH2 inhibitor might be a novel therapy in GC
treatment. Collectively, STAT3, p-STAT3 and EZH2 expression were provided for the
precision medicine in GC patients.
The 1994 structure of a transition-state analogue with AlF4- and GDP complexed to
G1 alpha, a small G protein, heralded a new field of research into the structure
and mechanism of enzymes that manipulate the transfer of phosphoryl (PO3-) groups.
The number of enzyme structures in the PDB containing metal fluorides (MFx) as
ligands that imitate either a phosphoryl or a phosphate group was 357 at the end of
2016. They fall into three distinct geometrical classes: 1) Tetrahedral complexes
based on BeF3- that mimic ground-state phosphates; 2) octahedral complexes,
primarily based on AlF4-, which mimic "in-line" anionic transition states for
phosphoryl transfer; and 3) trigonal bipyramidal complexes, represented by MgF3-
and putative AlF30 moieties, which mimic the geometry of the transition state. The
interpretation of these structures provides a deeper mechanistic understanding into
the behavior and manipulation of phosphate monoesters in molecular biology. This
Review provides a comprehensive overview of these structures, their uses, and their
computational development.
A cDNA clone encoding an amphioxus fatty acid binding protein-like (AmphiFABPL)
protein was isolated from a gut cDNA library of Branchiostoma belcheri. It
contained a 423 bp open reading frame corresponding to a deduced protein of 140
amino acids with a predicted molecular mass of approximately 15.9 kDa. Phylogenetic
analysis showed that AmphiFABPL fell outside the vertebrate clade of fatty acid
binding proteins (FABPs), being positioned at the base of the chordate lineage, and
was almost equally homologous to various vertebrate FABPs, suggesting that it may
be the archetype of vertebrate FABPs. Both northern blotting and in situ
hybridization analyses demonstrated that AmphiFABPL was expressed in the hepatic
caecum and hind-gut, and although at a much lower level, it was also present in the
endostyle, ovary and testis. In addition, whole-mount in situ hybridization
revealed that AmphiFABPL was initially expressed in the posterior two thirds of the
primitive gut, including the mid-gut where the hepatic caecum will form later, in
2-day larvae. The expression pattern is closely similar to that of the L-FABP and
I-FABP genes in vertebrates, supporting the hypothesis that the hepatic caecum in
the amphioxus is homologous to the vertebrate liver.
The confounded signal hypothesis maintains that facial expressions of anger and
happiness, in order to more efficiently communicate threat or nurturance, evolved
forms that take advantage of older gender recognition systems, which were already
attuned to similar affordances. Two unexplored consequences of this hypothesis are
(1) facial gender should automatically interfere with discriminations of anger and
happiness, and (2) controlled attentional processes (like working memory) may be
able to override the interference of these particular expressions on gender
discrimination. These issues were explored by administering a Garner interference
task along with a working memory task as an index of controlled attention. Results
show that those with good attentional control were able to eliminate interference
of expression on gender decisions but not the interference of gender on expression
decisions. Trials in which the stimulus attributes were systematically correlated
also revealed strategic facilitation for participants high in attentional control.
Individuals with moderate to severe traumatic brain injury (TBI) have been shown to
experience significant problems in facial affect recognition (FAR). However, it is
not known how these impairments relate to overall functioning and quality of life
(QoL) following TBI. The aim of the current study was to test the hypothesis that
worse performance on an FAR task would be associated with reduced QoL (related to
social and emotional functioning), worse mood, and increased fatigue. Forty-seven
individuals with TBI and 27 healthy controls (HCs) completed the facial emotion
identification task (FEIT), as well as questionnaires assessing social and
emotional QoL, mood, and fatigue. The TBI group performed significantly worse than
HCs on the FEIT. A significant relationship between FAR and fatigue and QoL related
to social and emotional functioning was documented, but in an unexpected direction:
individuals who performed better on the FEIT reported poorer QoL and greater
fatigue. Individuals who have better FAR may require increased effort to perform
this task, and thus experience greater fatigue and poorer social and emotional QoL.
Schizophrenia patients have impaired performance and abnormal brain activation
during facial emotion recognition, which may represent a marker of genetic
liability to schizophrenia. However, it remains unclear whether the impairment is
specific to recognizing emotion from faces or is instead attributable to more
generalized dysfunction. The current study aimed to distinguish between specific
and generalized neural dysfunction underlying impaired facial emotion recognition
in schizophrenia and examine associations with genetic liability. Twenty-eight
schizophrenia patients, 27 nonpsychotic first-degree relatives, and 27 community
controls underwent functional magnetic resonance imaging while making judgments
about either the emotion or age of emotional faces. Patients had performance
deficits during the emotion and age discrimination conditions compared to relatives
and controls, while relatives had intact performance. Patients had hypoactivation
compared to controls across conditions, mainly in medial prefrontal cortex. Unlike
controls, patients demonstrated a failure to recruit the dorsomedial prefrontal
cortex, a region involved in social cognition and decision-making, and relatives
had a pattern of recruitment intermediate between patients and controls. Compared
to controls, relatives had greater deactivation of regions associated with the
default mode network, and patients had similar findings during age discrimination.
The common patterns of performance deficits and activation abnormalities during
emotion and age discrimination in schizophrenia suggest that generalized cognitive
impairment, notably in social cognition and decision-making, contributes to
impaired facial emotion recognition. Similar functional activation patterns in
relatives, despite intact performance, suggest that brain activation may represent
a more sensitive marker of genetic liability than behaviour. Hyperdeactivation of
default mode network regions in relatives may represent cognitive inefficiency, or
compensatory mechanisms that help maintain intact performance.
Human adults automatically mimic others' emotional expressions, which is believed
to contribute to sharing emotions with others. Although this behaviour appears
fundamental to social reciprocity, little is known about its developmental process.
Therefore, we examined whether infants show automatic facial mimicry in response to
others' emotional expressions. Facial electromyographic activity over the
corrugator supercilii (brow) and zygomaticus major (cheek) of four-to five-month-
old infants was measured while they viewed dynamic clips presenting audiovisual,
visual and auditory emotions. The audiovisual bimodal emotion stimuli were a
display of a laughing/crying facial expression with an emotionally congruent
vocalization, whereas the visual/auditory unimodal emotion stimuli displayed those
emotional faces/vocalizations paired with a neutral vocalization/face,
respectively. Increased activation of the corrugator supercilii muscle in response
to audiovisual cries and the zygomaticus major in response to audiovisual laughter
were observed between 500 and 1000 ms after stimulus onset, which clearly suggests
rapid facial mimicry. By contrast, both visual and auditory unimodal emotion
stimuli did not activate the infants' corresponding muscles. These results revealed
that automatic facial mimicry is present as early as five months of age, when
multimodal emotional information is present.
Globally, coastal waters have emerged into a pool of antibiotic resistance genes
and multiple antibiotic resistant microorganisms, and pathogenicity of these
resistant microorganisms in terms of serotypes and virulence genes has made the
environment vulnerable. The current study underscores the presence of multiple
antibiotic resistant pathogenic serotypes and pathotypes of Escherichia coli, the
predominant faecal indicator bacteria (FIB), in surface water and sediment samples
of famous recreational beaches (Juhu, Versova, Mahim, Dadar, and Girgaon) of
Mumbai. Out of 65 faecal coliforms (FC) randomly selected, 38 isolates were
biochemically characterized, serotyped (for 'O' antigen), antibiogram-phenotyped
(for 22 antimicrobial agents), and genotyped by polymerase chain reaction (for
virulence factors). These isolates belonged to 16 different serotypes (UT, O141,
O2, O119, O120, O9, O35, O126, O91, O128, O87, O86, R, O101, O118, and O15) out of
which UT (18.4%), O141 (15.7%), and O2 (13.1%) were predominant, indicating its
remarkable diversity. Furthermore, the generated antibiogram profile revealed that
95% of these isolates were multiple antibiotic resistant. More than 60% of
aminoglycoside-sensitive E. coli isolates exhibited resistance to penicillin,
extended penicillin, quinolone, and cephalosporin classes of antibiotic while
resistance to other antibiotics was comparatively less. Antibiotic resistance (AR)
indexing indicated that these isolates may have rooted from a high-risk source of
contamination. Preliminary findings revealed the presence of enterotoxin-encoding
genes (stx1 and stx2 specific for enterohaemorrhagic E. coli and Shiga toxin-
producing E. coli, heat-stable toxin enterotoxin specific for enterotoxigenic E.
coli) in pathogenic serotypes. Thus, government authorities and environmental
planners should create public awareness and adopt effective measures for coastal
management to prevent serious health risks associated with these contaminated
coastal waters.
A type III polyketide synthase (PKS) cDNA and the corresponding gene (FmPKS) were
isolated from the rhizomes of Fallopia multiflora (Thunb.) (Polygonaceae). The
full-length FmPKS cDNA was 1,228 bp, containing an open reading frame of 1,137 bp
encoding a 378 amino acid residues long protein. The coding sequence of the gene
was interrupted by three introns, a different gene structure from most of the type
III PKS genes studied so far containing only one intron at a conserved site, except
for the recently cloned gene PcPKS2 from Polygonum cuspidatum. Phylogenetic
analysis revealed that it shares a close relationship with Rheum tataricum stilbene
synthase and formes a group with functionally diverse chalcone synthase-like
enzymes. Southern blotting showed that there are three to four copies of the FmPKS
gene in the genome. The expression pattern of the FmPKS transcript was determined
by Northern blotting and high expression levels were detected in rhizomes and old
stems, while the lowest levels were found in old leaves, a pattern that strongly
correlates with the accumulation of the major bioactive principles called 2,3,5,4'-
tetra-hydroxy-stilbene-2-O-beta-D-glucoside, suggesting that FmPKS might play an
important role in its biosynthesis.
Achieving false belief understanding is an important cognitive milestone that
allows children to understand that thoughts and reality can differ. Researchers
have found that low-income children score significantly lower than middle-income
children on false belief understanding but have not examined why this difference
exists. We hypothesized that children's language and parent discipline mediate the
income-false belief relation. Participants were 174 3- to 6-year-olds. False belief
understanding was significantly correlated with family income, children's
vocabulary, parents' self reported discussion of children's behavior, discussion of
emotions, and power assertion. Family income had a significant indirect effect on
false belief understanding through children's vocabulary and parent discipline when
examined independently, but only through children's vocabulary when using parallel
multiple mediation. This study contributes to our knowledge of individual
differences in false belief understanding. (C) 2017 Elsevier Inc. All rights
reserved.
Recent studies suggest that by the second year of life, infants can attribute false
beliefs to agents. However, prior studies have largely focused on infants' ability
to predict a mistaken agent's physical actions on objects. The present research
investigated whether 20-month-old infants could also reason about belief-based
emotional displays. In Experiments 1 and 2, infants viewed an agent who shook two
objects: one rattled and the other was silent. Infants expected the agent to
express surprise at the silent object if she had a false belief that both objects
rattled, but not if she was merely ignorant about the objects' properties.
Experiment 3 replicated and extended these findings: if an agent falsely believed
that two containers held toy bears (when only one did so), infants expected the
agent to express surprise at the empty, but not the full, container. Together,
these results provide the first evidence that infants in the second year of life
understand the causal relationship between beliefs and emotional displays. These
findings thus provide new evidence for false-belief understanding in infancy and
suggest that infants, like older children, possess a robust understanding of belief
that applies to a broad range of belief-based responses. (C) 2016 Elsevier B.V. All
rights reserved.
Familial adenomatous polyposis (FAP; Mendelian of Inherintance in Man ID, 175100)
is a rare autosomal dominant disorder characterized by the development of numerous
adenomatous polyps throughout the colon and rectum associated with an increased
risk of colorectal cancer. FAP is at time accompanied with certain extraintestinal
manifestations such as congenital hypertrophy of the retinal pigment epithelium,
dental disorders and desmoid tumors. It is caused by mutations in the adenomatous
polyposis coli (APC) gene. The present study reported on a Chinese family with FAP.
Polymerase chain reaction and direct sequencing of the full coding sequence of the
APC gene were performed to identify the mutation in this family. A nonsense
mutation of the APC gene was identified in this pedigree. It is a heterozygous G>T
substitution at position 2,971 in exon 15 of the APC gene, which formed a premature
stop codon at amino acid residue 991 (p.Glu991*). The resulting truncated protein
lacked 1,853 amino acids. The present study expanded the database on APC gene
mutations in FAP and enriched the spectrum of known germline mutations of the APC
gene. Prophylactic proctocolectomy may be considered as a possible treatment for
carriers of the mutation.
Lung cancer, which has a low survival rate, is a leading cause of cancer-associated
mortality worldwide. Smoking and air pollution are the major causes of lung cancer;
however, numerous studies have demonstrated that genetic factors also contribute to
the development of lung cancer. A family history of lung cancer increases the risk
for the disease in both smokers and never-smokers. This review focuses on familial
lung cancer, in particular on the familial aggregation of lung cancer. The
development of familial lung cancer involves shared environmental and genetic
factors among family members. Familial lung cancer represents a good model for
investigating the association between environmental and genetic factors, as well as
for identifying susceptibility genes for lung cancer. In addition, studies on
familial lung cancer may help to elucidate the etiology and mechanism of lung
cancer, and may identify novel biomarkers for early detection and diagnosis,
targeted therapy and improved prevention strategies. This review presents the
aetiology and molecular biology of lung cancer and then systematically introduces
and discusses several aspects of familial lung cancer, including the
characteristics of familial lung cancer, population-based studies on familial lung
cancer and the genetics of familial lung cancer.
Background: This research was conducted to investigate the effects of a nursing
supportive program on anxiety and stress levels in the family members of patients
admitted to the intensivee care unit (ICU) after cardiac surgery. Methods: This
research was a quasi-experimental study. A control group and an intervention group
(each = 35), both comprised of the family members of post-cardiac surgery patients
admitted to the ICU, were studied. The intervention group received a nursing
supportive program initially 2 hours after their patients entered the ICU (1st day)
and thereafter on the 2nd and 3rd days. The control group received only the routine
information. Demographic variables and an adjusted Depression Anxiety Stress Scales
(DASS-21) were used to assess the anxiety and stress levels of the family members
of the patients. Results: Demographic variables and the DASS scores had no
statistically significant differences in stress levels between the 2 groups before
the intervention. However, after the intervention, the mean score of the stress
level in the intervention group dropped significantly in comparison with the
control group (P = 0.0001). Anxiety levels in both groups were reduced after the
intervention. However, although a statistically significant difference was observed
between the 2 groups 2 hours after ICU admission and on the 2nd ICU day (P =
0.0001), there was no significant difference on the 3rd ICU day (P = 0.993).
Conclusions: In light of the findings of the present study, our nursing supportive
program, which was aimed at providing information, emotional and mental support,
and reassurances to the family members of post-cardiac surgery patients
hospitalized in the ICU, was able to decrease their stress levels and to some
extent their anxiety levels.
Hegemonic masculinities (i.e., sets of socially accepted masculine behaviors and
beliefs within a given time and culture) may affect the well-being of sexual
minority men, yet quantitative relationships between these masculinities and well-
being remain largely unexplored. Using data from a national cross-sectional survey
of young sexual minority men (N = 1,484; ages 18-24 years), the current study
examined the relationship between parental gender policing during childhood and
adolescence and subsequent substance use and psychological distress. Over one third
of the sample (37.8%) reported their parent(s) or the person(s) who raised them had
policed their gender, including the use of disciplinary actions. Using
multivariable regression, this study examined the relationship between parental
gender policing and psychological well-being and substance use, after adjusting for
age, race/ethnicity, educational attainment, and current student status. Gender
policing during childhood and adolescence was associated with recent substance use
behaviors and psychological distress in multivariable models. A linear association
between substance use behaviors and psychological distress and the number of
disciplinary actions experienced during childhood and adolescence was also
observed. Parents' attempts to police their sons' gender expression were associated
with markers of distress among young sexual minority men. The relationship between
parental gender policing during childhood and adolescence and distress among young
sexual minority men are discussed.
Clause 13 of the United Nations Convention on the Rights of the Child states that
children have the right 'to seek, receive or impart information and ideas of all
kinds, regardless of frontiers, either orally, in writing or in print, in art or in
any other media of the child's voice'. However, there is one area in which this
directive is constrained in various countries by domestic regulations curtailing
children's access to information. That area is human sexuality. The arguments for
and against children's access to sex education are well rehearsed. In this article,
the author pursues a different angle, looking instead at the increasing
restrictions placed upon young people's ability to imagine and communicate with
each other about sexual issues, particularly in online settings. The advent of the
internet and a range of social networking sites have not only enabled young people
to access previously quarantined information about sexuality, but also to actively
engage in forms of 'intimate citizenship' online. In this article, the author
focuses on young people's online fan communities which use characters from popular
culture such as Harry Potter or a range of Japanese manga and animation to imagine
and explore sexual issues. 'Child abuse publications legislation' in Australia and
elsewhere now criminalizes the representation of even imaginary characters who are
or may only 'appear to be' under the age of 18 in sexual scenarios. Hence these
children and young people are in danger of being charged with the offence of
manufacturing and disseminating child pornography. Despite research into these
fandoms that indicates that they are of positive benefit to young people in
developing 'sexual literacies', there is increasingly diminishing space for young
people under the age of 18 to imagine or communicate about sexuality, even in the
context of purely fictional scenarios.
Introduction: There is limited evaluation of clinical and theoretical claims that
sexual thoughts of children and coercing others facilitate sexual offending. The
nature of these thoughts (what they contain) also is unknown. Aim: To examine the
relation between child or coercive sexual thoughts and sexual offending and to
determine the nature of these thoughts and any differences among sexual offending
(SO), non-sexual offending (NSO), and non-offending (NO) men. Methods: In a cross-
sectional computerized survey, anonymous qualitative and quantitative self-reported
sexual thought and experience data were collected from 279 adult volunteers
composing equal numbers of SO, NSO, and NO men recruited from a medium-security UK
prison and a community sample of 6,081 men. Main Outcome Measures: Computerized
Interview for Sexual Thoughts and Computerized Inventory of Sexual Experiences.
Results: Three analytical approaches found child sexual thoughts were related to
sexual offending; sexual thoughts with coercive themes were not. Latent class
analyses identified three types of child sexual thought (primarily differentiated
by interpersonal context: the reporting of own emotions, emotions of others, or
both) and four types of sexual thoughts of coercing others (chiefly discriminated
by the other person's response: no emotional states reported, consent, non-consent,
or mixed). Type of child sexual thought and participant group were not
significantly related. Type of coercive sexual thought and group were marginally
related; the consensual type was more common for the NO group and the non-
consensual type was more common for the SO group than expected statistically.
Conclusion: Child sexual thoughts are a risk factor for sexual offending and should
be assessed by clinicians. In general, sexual thoughts with coercive themes are not
a risk factor, although thought type could be important (ie, thoughts in which the
other person expresses an enduring lack of consent). Exploring the dynamic risk
factors associated with each type of child and coercive thought could lead to more
targeted treatment. Copyright (C) 2016, International Society for Sexual Medicine.
Published by Elsevier Inc. All rights reserved.
Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of
epilepsy phenotypes. Recent technological advances in molecular biology have also
rapidly expanded the genotype of EOEE. Genes involved in diverse molecular
pathways, including ion channels, synaptic structure, transcription regulation, and
cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA
synthetase, which plays a key role in mitochondrial protein synthesis by attaching
20 different amino acids to the tRNA tail, has been recently linked with the
epilepsy phenotype. Here, we report a novel homozygous c.925G >A (G309S) missense
mutation in the gene that encodes the human mitochondrial phenylalanyl-tRNA
synthetase (FARS2) in four patients from two nonconsanguineous Korean families. All
four patients suffered from intractable seizures that started at the age of 3 and 4
months. Seizure types were variable, including infantile spasms and myoclonic
seizures, and often prolonged. Although their initial development seemed to be
normal, relentless regression after seizure onset occurred in all patients. An
etiologic investigation, including brain imaging and metabolic studies, did not
reveal a specific etiology. We reviewed the epilepsy phenotypes of six additional
FARS2 mutation-positive patients and suggest that FARS2 can be considered one of
the genetic causes of EOEE. (C) 2016 Elsevier B.V. All rights reserved.
Background: Representatives of the trematode family Fasciolidae are responsible for
major socio-economic losses worldwide. Fascioloides magna is an important
pathogenic liver fluke of wild and domestic ungulates. To date, only a limited
number of studies concerning the molecular biology of F. magna exist. Therefore,
the objective of the present study was to determine the complete mitochondrial (mt)
genome sequence of F. magna, and assess the phylogenetic relationships of this
fluke with other trematodes based on the mtDNA dataset. Findings: The complete F.
magna mt genome sequence is 14,047 bp. The gene content and arrangement of the F.
magna mt genome is similar to those of Fasciola spp., except that trnE is located
between trnG and the only non-coding region in F. magna mt genome. Phylogenetic
relationships of F. magna with selected trematodes using Bayesian inference (BI)
was reconstructed based on the concatenated amino acid sequences for 12 protein-
coding genes, which confirmed that the genus Fascioloides is closely related to the
genus Fasciola; the intergeneric differences of amino acid composition between the
genera Fascioloides and Fasciola ranged 17.97-18.24 %. Conclusions: The
determination of F. magna mt genome sequence provides a valuable resource for
further investigations of the phylogeny of the family Fasciolidae and other
trematodes, and represents a useful platform for designing appropriate molecular
markers.
Background: Fasciolosis remains a significant food-borne trematode disease causing
high morbidity around the world and affecting grazing animals and humans. A deeper
understanding concerning the molecular mechanisms by which Fasciola hepatica
infection occurs, as well as the molecular basis involved in acquiring protection
is extremely important when designing and selecting new vaccine candidates. The
present study provides a first report of microarray-based technology for describing
changes in the splenic gene expression profile for mice immunised with a highly
effective, protection-inducing, multi-epitope, subunit-based, chemically-
synthesised vaccine candidate against F. hepatica. Methods: The mice were immunised
with synthetic peptides containing B-and T-cell epitopes, which are derived from F.
hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against
F. hepatica formulated in an adjuvant adaptation vaccination system; they were
experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice
immunised with the highest protection-inducing synthetic peptides was isolated,
amplified and labelled using Affymetrix standardised protocols. Data was then
background corrected, normalised and the expression signal was calculated. The
Ingenuity Pathway Analysis tool was then used for analysing differentially
expressed gene identifiers for annotating bio-functions and constructing and
visualising molecular interaction networks. Results: Mice immunised with a
combination of three peptides containing T-cell epitopes induced high protection
against experimental challenge according to survival rates and hepatic damage
scores. It also induced differential expression of 820 genes, 168 genes being up-
regulated and 652 genes being down-regulated, p value <0.05, fold change ranging
from -2.944 to 7.632. A functional study of these genes revealed changes in the
pathways related to nitric oxide and reactive oxygen species production,
Interleukin-12 signalling and production in macrophages and Interleukin-8
signalling with up-regulation of S100 calcium-binding protein A8, Matrix
metallopeptidase 9 and CXC chemokine receptor 2 genes. Conclusion: The data
obtained in the present study provided us with a more comprehensive overview
concerning the possible molecular pathways implied in inducing protection against
F. hepatica in a murine model, which could be useful for evaluating future vaccine
candidates.
Activated B-cells increase T-cell behaviour during autoimmune disease and other
infections by means of cytokine production and antigen-presentation. Functional
studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell
deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We
hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA
expression using real-time PCR from healthy community controls, individuals with
other lung diseases and newly diagnosed untreated pulmonary TB patients at three
different time points (diagnosis, month 2 and 6 of treatment). We show that FASLG,
IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to
healthy controls. The changes in expression levels of CD38 may be due to a reduced
activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there
was a significant increase in the expression of APRIL and IL5RA in TB cases.
Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were
upregulated in B-cells from TB cases. The increase in the expression of APRIL and
CD19 suggests that there may be restored activation of B-cells following anti-TB
treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing
regulatory genes may play an important role in the protective immunity against M.
tb infection. Our results show that increased activation of B-cells is present
following successful TB treatment, and that the expression of FASLG and IL5RA could
potentially be utilised as a signature to monitor treatment response.
The concepts of protein purification are often taught in undergraduate biology and
biochemistry lectures and reinforced during laboratory exercises; however, very few
reported activities allow students to directly gain experience using modern protein
purification instruments, such as Fast Protein Liquid Chromatography (FPLC). This
laboratory exercise uses size exclusion chromatography (SEC) and ion exchange (IEX)
chromatography to separate a mixture of four different proteins. Students use an
SEC chromatogram and corresponding SDS-PAGE gel to understand how protein
conformations change under different conditions (i.e. native and non-native).
Students explore strategies to separate co-eluting proteins by IEX chromatography.
Using either cation or anion exchange, one protein is bound to the column while the
other is collected in the flow-through. In this exercise, undergraduate students
gain hands-on experience with experimental design, buffer and sample preparation,
and implementation of instrumentation that is commonly used by experienced
researchers while learning and applying the fundamental concepts of protein
structure, protein purification, and SDS-PAGE. (c) 2016 by The International Union
of Biochemistry and Molecular Biology, 45(1):60-68, 2017.
this paper presents triple mode to optimize settling, current consumption and noise
of a crystal oscillator (XTAL). The proposed XTAL driver has three mode. Fast
settling mode is used to reduce settling time. To reduce the start-up time of a
XTAL driver, internal noise booster (INB) and negative resistance booster (NRB) are
proposed. The simulated start-up time of a 4.19403MHz XTAL Driver in 0.18um CMOS is
reduced by 80% from 4ms to 800us. Retention mode is only operated in stand-by to
reduce total power consumption. A Peak and Low detection (PLD) is proposed. The
stand-by of the XTAL driver does not effect to load. Therefore, the PLD blocks
input supply voltage until HVT signal goes to down. It reduces power consumption up
to 60%. EMI reduction mode is proposed to reduce output spur noise. To reduce
output spur noise, pseudorandom-number generator (PRNG) is used makes 4bits random
signal to spread frequency up to -10dB. All mode is controlled by Digital Control
block. An inverter amplifier driver is optimized to reduce power consumption to
30uA and gets +/- 100 ppm operation in changing temperature from -40 degrees C to
60 degrees C.
A novel folded-cascode operational amplifier (opamp) employing the nested gain-
boosted technique is presented. The gain-booster in the signal path consists of
two-level recursive folded-cascode amplifier to achieve high gain and high speed.
The opamp is designed and simulated in 0.13 mu m CMOS technology, bode-plot results
that an open-loop gain over 90dB and a unity-gain frequency up to 4.75G for loads
of 1.6pF have been obtained. Settling measurements shows that the opamp has a
settling time less than 2.5ns. So the proposed opamp can be employed in high speed
and high resolution Analog-to-Digital converters (ADCs) such as pipelined ADC.
Background:Infants who are not breast-fed benefit from formula with both
docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of
ARA needed to support immune function is unknown. Infants who carry specific fatty
acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain
adequate ARA status.Objective:The aim of the study was to determine whether ARA
intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood
cells in term infants fed infant formula.Methods:Infants (N=89) were enrolled in
this prospective, double-blind controlled study. Infants were randomized to consume
formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for
10 weeks. Fatty acid composition of plasma phosphatidylcholine and
phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells,
activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were
determined.Results:Lymphocyte ARA was higher in the 25-ARA formula group than in
the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of
phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and
18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of
FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA
consumed. B-cell activation marker CD54 was elevated in infants who consumed
formula containing no ARA.Conclusions:ARA level in plasma is reduced by low ARA
consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory
role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of
phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell
ARA level in infants across genotypes.
Biotechnological production of fatty alcohols, important raw materials in the
chemical industry, has been receiving considerable attention in recent years. Fatty
alcohols are formed by the reduction of fatty acyl-CoAs or fatty acyl-ACPs
catalyzed by a fatty acyl reductase (FAR). In this study, we introduced genes
encoding FARs from Arabidopsis thaliana (AtFAR5) and Simmondsia chinensis (ScFAR)
into Crambe abyssinica hairy roots via Agrobacterium rhizogenes-mediated
transformation. The efficiency of the transformation ranged between 30 and 45%. The
fatty alcohols were only detected in the transgenic hairy root lines expressing
ScFAR gene. In all tested lines stearyl alcohol (18:0-OH), arachidyl alcohol (20:0-
OH), and behenyl alcohol (22:0-OH) were produced. The content of 18:0-OH varied
from 1 to 3% of total fatty acids and fatty alcohols, while the amount of either
20:0-OH and 22:0-OH did not exceed 2%. The transgenic hairy root lines produced
from 0.98 to 2.59nmol of fatty alcohols per mg of dry weight. Very low activity of
ScFAR was detected in the microsomal fractions isolated from the selected hairy
root lines. To our knowledge, this is the first report on the fatty alcohol
production in the hairy root cultures. Biotechnol. Bioeng. 2017;114: 1275-1282. (c)
2016 Wiley Periodicals, Inc.
In response to overfeeding, geese develop fatty liver. To understand the fattening
mechanism, mRNA differential display reverse transcription PCR was used to study
the gene expression differences between French Landes grey geese and Xupu white
geese in conditions of overfeeding and normal feeding. One gene was found to be up-
regulated in the fatty liver in both breeds, and it has a 1797 bp cDNA with 83%
identity to chicken SELENBP1. The sequence analysis revealed that its open reading
frame of 1413 bp encodes a protein of 471 amino acids, which contains a putative
conserved domain of 56 kDa selenium binding protein with high homology to its
homologues of chicken (95%), rat (86%), mouse (84%), human (86%), monkey (86%), dog
(86%), and cattle (86%). The function of this protein has been briefly reviewed
based on published information. In tissue expression analysis, the expression of
geese SELENBP1 mRNA was found to be higher in liver or kidney than in other tested
tissues. The results showed that overfeeding could increase the mRNA expression
level of geese SELENBP1.
In a medium-voltage power system, fault currents are subjected to uncertainties in
lines and distributed generations. Uncertainties in fault currents in a power grid
can introduce system protection problems. Superconducting cablewith fault current
limiting capability can be used as means to meet the increasing electricity demand
while resolving the issues involving system protection. In order to integrate the
fault current limiting superconducting cable into a power grid, its impedance
selection under fault conditions needs to consider the impact of power system
uncertainties on system protection. In this paper, an expected regret-based method
is proposed for determining the impedance of the fault current limiting
superconducting cable incorporating the uncertainties in fault currents. The
results of numerical simulations are presented to show the effectiveness of the
proposed expected regret-based impedance selection method.
A novel observer-based fault accommodation technique for linear multi-input multi-
output sampled-data systems affected by a general class of actuator faults in the
presence of quantization errors is addressed in the paper. Only the output signal
has been assumed to be available for direct measurement. A simulation study on a
three-tank system supports theoretical developments. Copyright (c) 2014 John Wiley
& Sons, Ltd.
This paper proposes a novel DC-side discrete-time voltage controller for grid-
connected voltage-sourced converters during asymmetrical faults. The main objective
is to eliminate the second-order voltage oscillation on the VSC's DC-side, as well
as the positive sequence third-order harmonic current injection into the grid
during asymmetrical faults. The compensator is designed based on the comprehensive
discrete-time model of the DC-side dynamics. It is shown that DC-side average
voltage can be controlled by the positive sequence direct axis current, while the
oscillating component can be fully controlled by negative sequence dq-axes
currents. The negative sequence current references are obtained using a discrete
resonant controller plus a lead filter in order to achieve zero steady state error
and asymptotically stability, without injecting harmonics currents into the grid.
Simulation results showed the effectiveness of the proposed strategy under severe
fault conditions. (C) 2016 Elsevier Ltd. All rights reserved.
Background and Objective: Primary progressive aphasia (PPA) is a clinical syndrome
due to different neurodegenerative conditions in which an accurate early diagnosis
needs to be supported by a reliable diagnostic tool at the individual level. In
this study, we investigated in PPA the FDG-PET brain metabolic patterns at the
single-subject level, in order to assess the case-to-case variability and its
relationship with clinical-neuropsychological findings. Material and Methods: 55
patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17
logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-
PPA) were included. Clinical-neuropsychological information and FDG-PET data were
acquired at baseline. A follow-up of 27.4 +/- 12.55 months evaluated the clinical
progression. Brain metabolism was analyzed using an optimized and validated voxel-
based SPM method at the single-subject level. Results: FDG-PET voxel-wise metabolic
assessment revealed specific metabolic signatures characterizing each PPA variant
at the individual level, reflecting the underlying neurodegeneration in language
networks. Notably, additional dysfunctional patterns predicted clinical progression
to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern
characterized by involvement of parietal, subcortical and brainstem structures
predicted progression to a corticobasal degeneration syndrome or to progressive
supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease
and frontotemporal dementia at the follow-up presented with extended bilateral
patterns at baseline. Discussion: Our results indicate that FDG-PET voxel-wise
imaging is a valid biomarker for the early differential diagnosis of PPAs and for
the prediction of progression to specific dementia condition. This study supports
the use of FDG-PET imaging quantitative assessment in clinical settings for a
better characterization of PPA individuals and prognostic definition of possible
endo-phenotypes.
Recalling positive autobiographical memories is a powerful strategy to repair
affect. Positive memory recall operates as a reparative strategy by enhancing
positive affect, which facilitates the down-regulation of negative affect. There
are individual differences, however, in the ability to use positive material to
repair mood. Participants with elevated depression scores, for example, are less
likely to profit from this strategy. Depression has been associated with elevated
fear of positive emotion and the current study examined whether elevated fear of
positive emotion is associated with depression-related difficulties in mood repair.
Ninety-four participants first underwent a mood repair task in which a sad mood
induction was followed by a cue to recall positive autobiographical memories.
Subjective measures of state happiness and sadness were collected across the mood
induction and positive memory recall procedures. Results revealed that greater fear
of positive emotion was linked to less ability to enhance positive affect and down-
regulate negative affect using positive memories. Results also provided preliminary
support for a mediation model in which greater depressive symptoms predicted
elevated fear of positive emotion, which in turn predicted less ability to repair
positive affect. These findings highlight fear of positive emotion as a potential
target for interventions aimed at improving affect regulation.
Integrated heat and electricity dispatch is crucial to exploit synergistic benefits
from integrated energy systems. However, this requires information from both
electricity systems and district heating systems (DHSs), which are managed by an
electricity control center (ECC) and district heating control centers (DHCCs),
respectively. For reasons pertaining to privacy, communication, dimension, and
compatibility, it is not practical for DHCCs to send detailed models to the ECC.
Therefore, a new feasible region method is proposed for formulation of new DHS
models, which exploit the flexibility of DHSs with consideration of building
thermal inertia. A greedy method is developed to solve the new modified feasible
region models by calculating a series of linear programming problems efficiently.
Then the new models are sent to the ECC to be used in central dispatch considering
DHS operation constraints, i.e. integrated heat and electricity dispatch. The
modified models are similar to conventional power plants and storages, and are thus
compatible with current dispatch programs. Case studies verify the effectiveness of
the method. Although some conservativeness exists, the total cost and wind energy
curtailment are both decreased compared to conventional decoupled dispatch. (C)
2016 Elsevier Ltd. All rights reserved.
Biotreatment of feather wastes and utilization of the degraded products in feed and
foodstuffs has been a challenge. In the present study, we have demonstrated the
degradation of feather waste by Bacillus cereus DCUW strain isolated during a
functional screening based microbial diversity study on East Calcutta Wetland Area.
A high molecular weight keratinolytic protease from feather degrading DCUW strain
was purified and characterized. Moreover, utilization of degraded products during
feather hydrolysis was developed and demonstrated. The purified keratinolytic
protease was found to show pH and temperature optima of 8.5 and 50 degrees C,
respectively. PMSF was found to inhibit the enzyme completely. The purified enzyme
showed molecular weight of 80 kDa (from SDS-PAGE). The protease was found to have
broad range substrate specificities that include keratin, casein, collagen, fibrin,
BAPNA and gelatin. The protease was identified as minor extracellular protease
(Vpr) by RT-PCR and northern blotting techniques. This is the first report
describing the characterization of minor extracellular protease (Vpr) and its
involvement in feather degradation in B. cereus group of organisms.
Real numbermodeling of analog circuits in hardware description languages (HDLs) has
become more common as a part of mixed-signal SoC validation. We propose two methods
that both improve the fidelity and simulation speed, and make the event-driven,
piecewise linear (PWL) analog functional models easier to write. First we use the
accuracy set by users to dynamically determine when a new output segment should be
emitted, which is computed without any iteration. This capability allows designers
to trade accuracy for simulation speed of analog models without any time-consuming
model calibration/error estimation, and creates models which generate events only
when needed to maintain output accuracy. We next extend this method to eliminate
limit-cycle oscillations that occur when simulating circuits with continuous-time
feedback in a discrete-time event simulator. Handling this feedback efficiently
allows the user to create the system model from simpler component models. The
performance of this modeling approach is demonstrated on various analog filter
models, an operational amplifier, and a high-speed, wireline transceiver system,
and is 3.1x faster than an optimally-chosen, fixed-time step simulation for the
transceiver.
In grid-connected converter control, grid voltage feedforward is usually introduced
to suppress the influence of grid voltage distortion on the converter's grid-side
AC current. However, owing to the time-delay in control systems, the suppression
effect of the grid voltage distortion is seriously affected. In this paper, the
positive effects of the grid voltage feedforward control are analyzed in detail,
and the time-delay caused by the low-pass filter (LPF) in the voltage filtering
circuits and digital control are summarized. In order to reduce the time-delay
effect on the performance of the feedforward control, a voltage feedforward control
strategy with time-delay compensation is proposed, in which, a leading correction
of the feedforward voltage is used. The optimal leading step used in this strategy
is derived from analyzing the phase-frequency characteristics of a LPF and the
implementation of digital control. By using the optimal leading step, the delay in
the feedforward path can be further counteracted so that the performance of the
feedforward control in terms of suppressing the influence of grid voltage
distortion on the converter output current can be improved. The validity of the
proposed method is verified through simulation and experiment results.
Incentivizing development and deployment of renewable energy sources (RES), but
also other low carbon technologies (LCT), has been a successful way of promoting
new technologies by creating a feasible investment case and making them competitive
with traditional energy sources. Although different incentive mechanisms exist,
feed-in tariffs have shown to be the best model for accelerating LCT development
guaranteeing producers preferential prices for the produced electricity over a
period of time and enabling them access to the power network to sell/inject
produced electricity. Due to these benefits, feed-in tariff models are the most
common model for stimulating RES integration in southeast Europe. The paper reviews
the current state of preferential tariffs for RES in countries of southeast Europe.
While some countries already have significant installed RES capacity, others are
still in the planning stage. The review shows that the amount of installed capacity
of a specific technology has a strong impact on the support for the future projects
for same technology. This comprehensive review of legislative development
supporting RES, as well as technologies preferred in different countries of the
region, is supported with feasibility assessment of investing in RES using the
example of two different technology projects, wind and photovoltaic, analysing the
impact of the current tariffs on the return on investment for each country of the
region.
The present study evaluated the Response Bias scale (RBS), a symptom validity test
embedded within the Minnesota Multiphasic Personality Inventory (MMPI)-2
Restructured Form (MMPI-2-RF) that assesses for feigned neurocognitive complaints,
in a sample of pretrial incompetent to stand trial (IST) criminal defendants.
Additionally, we examined the Improbable Failure (IF) scale, a performance validity
test embedded within the Structured Interview of Reported Symptoms, Second Edition
(SIRS-2), which similarly assesses for feigned cognitive impairment (FCI). Results
indicated that both the RBS (area under the curve [AUC] = .76) and IF scale (AUC
= .72) achieved moderate classification accuracy using the Test of Memory
Malingering (TOMM) as the criterion. Further, the RBS and IF scale appeared to be
most useful for screening out those defendants who presented as genuine
(specificity = 99% and 88%, respectively), and less effective at classifying those
defendants suspected of feigning according to the TOMM (sensitivity = 29% and 46%,
respectively). In order to identify a significant proportion of IST defendants who
may be feigning impairment, considerably lower cutoff scores than those recommended
in each measure's manual were evaluated. An RBS T score of 63 (sensitivity = 86%;
specificity = 37%), and IF scale raw score of 2 (sensitivity = 80%; specificity =
43%), was required to achieve >= 80% sensitivity; these alternate cutoff scores may
therefore be useful when screening inpatient forensic psychiatric IST defendants.
Further, the 2 scales effectively predicted TOMM classification in combination,
although only the RBS significantly contributed to the model. Implications for the
assessment of FCI in forensic psychiatric settings are discussed.
We describe the rationale and methods of a study designed to compare vaginal and
urinary microbiomes in women with mixed urinary incontinence (MUI) and similarly
aged, asymptomatic controls. This paper delineates the methodology of a
supplementary microbiome study nested in an ongoing randomized controlled trial
comparing a standardized perioperative behavioral/pelvic floor exercise
intervention plus midurethral sling versus midurethral sling alone for MUI. Women
in the parent study had at least "moderate bother" from urgency and stress urinary
incontinence symptoms (SUI) on validated questionnaire and confirmed MUI on bladder
diary. Controls had no incontinence symptoms. All participants underwent vaginal
and urine collection for DNA analysis and conventional urine culture. Standardized
protocols were designed, and a central lab received samples for subsequent
polymerase chain reaction (PCR) amplification and sequencing of the bacterial16S
ribosomal RNA (rRNA) gene. The composition of bacterial communities will be
determined by dual amplicon sequencing of variable regions 1-3 and 4-6 from vaginal
and urine specimens to compare the microbiome of patients with controls. Sample-
size estimates determined that 126 MUI and 84 control participants were sufficient
to detect a 20 % difference in predominant urinary genera, with 80 % power and 0.05
significance level. Specimen collection commenced January 2015 and finished April
2016. DNA was extracted and stored for subsequent evaluation. Methods papers
sharing information regarding development of genitourinary microbiome studies,
particularly with control populations, are few. We describe the rigorous
methodology developed for a novel urogenital microbiome study in women with MUI.
Low-temperature NH3-SCR is an environmentally important reaction for the abatement
of NOx from stationary sources. In recent years FeMnOx has attracted significant
attention as a potential catalyst for this process, however its catalytic activity
and SO2 resistance require further improvement. In this contribution FeMnOx has
been modified to examine the effect of ceria on catalytic activity and SO2
resistance in the low temperature region. Preparation of catalysts via the citric
acid method generate modified materials that exhibit enhanced NO turnover compared
to FeMnOx. A reduction in NH3 adsorption (NH3-TPD) and a suitable ratio between NO
sites (NO-TPD) and chemisorbed surface oxygen (XPS) are beneficial for the
promotion of fast-SCR. A comparative SO2 resistance study of FeMnOx and Ce(12.5)
showed that the latter exhibited improved stability in the presence of SO2, as
indicated by the retention of pore volume (N-2 adsorption) and surface composition
(XPS). In-situ DRIFTS demonstrated that chemisorbed N-containing species on
Ce(12.5) were much more stable in the presence of SO2 compared to FeMnOx, which
resulted in the formation of significantly less metal sulphates and NH4HSO4. Crown
Copyright (C) 2017 Published by Elsevier B.V.All rights reserved.
Background: Ovarian tissue cryopreservation (OTC) is the only option available to
preserve fertility in prepubertal females with neuroblastoma (NB), a childhood
solid tumor that can spread to the ovaries, with a risk of reintroducingmalignant
cells after an ovarian graft. Procedure: We set out to determine whether the
analysis of TH (tyrosine hydroxylase), PHOX2B (paired-like homeobox 2b), and DCX
(doublecortin) transcripts using quantitative reverse transcriptase polymerase
chain reaction (RT-qPCR) could be used to detect NB contamination in ovarian
tissue. Analyses were performed on benign ovarian tissue from 20 healthy women
between November 2014 and September 2015 at the University Hospital of Clermont-
Ferrand. Pericystic benign ovarian tissues were collected and contaminated with
increasing numbers of human NB cells (cell lines IMR-32 and SK-N-SH) before
detection using RT-qPCR. Results: TH and DCX transcripts were detected in
uncontaminated ovarian tissue from all the donors, hampering the detection of small
numbers of tumor cells. By contrast, PHOX2B was not detected in any uncontaminated
ovarian fragment. PHOX2B levels were significantly increased from 10 NB cells. Our
study is the first to evaluate minimal residual disease detection using NB mRNAs in
human ovarian tissue. Only PHOX2B was a reliable marker of NB cells contaminating
ovarian tissue. Conclusions: These results are encouraging and offer hope in the
near future for grafting ovarian tissue in women who survive cancer, whose
fertility has been jeopardized by treatment, and who could benefit fromOTC without
oncological risk.
Objective: To determine the role of Dkkl1 in mouse development, viability, and
fertility. Design: Prospective experimental study. Setting: Government research
institution. Animal(s): Mice of C57BL/6. B6D2F1/J, and 129X1/SvJ strains, as well
as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the
studies. Intervention(s): Expression of the Dkkl1 gene was characterized during
early mouse development, and the effects of Dkkl1 ablation on reproduction and
fertility were characterized in vitro and in vivo. Main Outcome Measure(s): Dkkl1
RNA expression was determined by Northern blotting hybridization as well as
quantitative reverse transcriptase-polymerase chain reaction assays. In vitro
fertilization assays were used to assess fertility of sperm from male mice lacking
functional Dkkl1. Result(s): Dkkl1 is a gene unique to mammals that is expressed
primarily in developing spermatocytes and its product localized in the acrosome of
mature sperm. Here we show that Dkkl1 also is expressed in the
trophectoderm/placental lineage. Surprisingly, embryos lacking DKKL1 protein
developed into viable, fertile adults. Nevertheless, the ability of sperm that
lacked DKKL1 protein to fertilize wild-type eggs was severely compromised in vitro.
Because this defect could be overcome either by removal of the zona pellucida or by
the presence of wild-type sperm. Dkkl1, either directly or indirectly, facilitates
the ability of sperm to penetrate the zona pellucida. Penetration of the zona
pellucida by Dkkl1 sperm was delayed in vivo as well as in vitro, but the delay in
vivo was compensated by other factors during preimplantation development.
Accordingly, Dkkl1 I males offer an in vitro fertilization model for identifying
factors that may contribute to infertility. Conclusion(s): DKKL1 is a mammalian-
specific, acrosomal protein that strongly affects in vitro fertilization, although
the effect is attenuated in vivo. (Fertil Steril (R) 2010;93:1533-7. (C)2010 by
American Society for Reproductive Medicine.)
Conditionally transformed human myocardial cell lines would be a valuable resource
for studying human cardiac cell biology. We generated clonal human fetal cardiocyte
cell lines by transfection of fetal ventricular cardiac cell clones with a plasmid
containing a replication-defective mutant of the temperature-sensitive SV40 strain
tsA58. Multiple resulting cell lines showed similar features, namely: (1) T antigen
(TAg) expression at both permissive (34 degrees C) and restrictive (40.5 degrees C)
temperatures; (2) extended growth capacity in comparison with parental wild type,
when grown at the permissive temperature; (3) both temperature-dependent and serum-
responsive growth, and; (4) an incompletely differentiated fetal phenotype which
was similar at both permissive and restrictive temperatures and in the presence and
absence of serum. The transformed myocyte phenotype was demonstrated using
immunocytochemistry, Western and Northern blotting, and reverse transcription-
polymerase chain reaction (RT-PCR). Cell lines expressed skeletal alpha-actin,
atrial natriuretic peptide (ANP), and keratins, but no sarcomeric myosin heavy
chain or desmin. Immunoreactive sarcomeric actin was expressed predominantly as a
truncated protein of approximately 38 kD. The phenotype of the transformed cells
differs from that of the wild-type parental cells as well as from those reported by
others who have used TAg to immortalize rodent or human ventricular myocytes. Our
cell lines should provide a useful tool for study of the molecular mechanisms
regulating growth and differentiation in human cardiac muscle cells.
Fibroblast growth factor 2 (FGF2) plays an important role in cortical development.
However, the genes downstream of FGF2 that mediate its effect are largely unknown.
We have performed a microarray screening of genes regulated by FGF2 using primary
cortical neuron culture derived from embryonic day 14.5 (E14.5) mouse forebrains.
In this study, we have analysed a previously uncharacterised gene encoding a 180-
amino acid protein, hereby named 'coiled-coil protein 1 (ccp1)', that showed a
modest up-regulation upon FGF2 stimulation. Northern blots and RT-PCR showed
specific expression of ccp1 in multiple tissues including adult and embryonic
brains. In situ hybridizations revealed that ccpl was expressed in the cortical
plate between Reelin and Tbr1-positive layers in the dorsal cortex at E15.5.
Furthermore, the expression pattern of ccp1 at E13.5-E14.5 reflected some of the
aspects of tangential migration of cortical progenitors during the early phase. We
observed that the expressed ccpl protein was localised to endo/lysosomal
compartment in the cell body as well as to vesicles present in the processes of
primary cortical neurons and oligodendrocyte cell line. (C) 2005 Elsevier B.V. All
rights reserved.
FH98 digital scheduling system can realize the functions of centralized monitoring,
remote maintenance, fault diagnosis, and environmental monitoring, etc. so that the
remote equipment can be attended. In this way, railway scheduling, station and
station communication can adapt to the future development of railway communication.
This paper describes the common faults and processing methods of application of
FH98 digital dispatching system.
The use of hybrid short fibers in a suitable combination as reinforcement for
cement based materials has attracted widespread attention because of their benefits
compared to mono fiber reinforcement in recent years. This paper provides a review
of recent developments on the area of the cement-based composites reinforced by
hybrid short fibers. The aim of paper is to represent the effects of hybridization
by elaborating upon the chemical, physical and mechanical properties of fibers on
the performance of fiber reinforced concretes (FRC). This provides a summary of the
existing knowledge about the successful use of different hybrid forms such as
combination of steel, polymer and natural fibers in cementitious composites.
Different types of hybrid system depending on fiber type are classified and
reviewed. Furthermore, the physical and mechanical properties of resultant
composites are also presented. Generally, inclusion of fibers in concrete as hybrid
forms, improves many of its engineering properties such as toughness, ductility,
energy absorption capacity and durability performance in comparison with mono fiber
reinforcement. (C) 2017 Elsevier Ltd. All rights reserved.
Objective: The molecular mechanisms underlying fibrillation potentials are still
unclear. We hypothesised that expression of the cardiac-type voltage-gated sodium
channel isoform Nav1.5 in denervated rat skeletal muscle is associated with the
generation of such potentials. Methods: Muscle samples were extracted and analysed
biologically from surgically denervated rat extensor digitorum longus muscle after
concentric needle electromyographic recording at various time points after
denervation (4 h to 6 days). Results: Both nav1.5 messenger RNA (mRNA) signal on
northern blotting and Nav1.5 protein expression on immunohistochemistry appeared on
the second day after denervation, exactly when fibrillation potentials appeared.
Administration of lidocaine, which has much stronger affinity for sodium channels
in cardiac muscle than for those in skeletal muscle, dramatically decreased
fibrillation potentials, but had no effect on contralateral compound muscle action
potentials. Conclusions: Expression of Nav1.5 participates in the generation of
fibrillation potentials in denervated rat skeletal muscle. Significance: We
proposed an altered expression of voltage-gated sodium channel isoforms as a novel
mechanism to explain the occurrence of fibrillation potentials following skeletal
muscle denervation. (C) 2012 International Federation of Clinical Neurophysiology.
Published by Elsevier Ireland Ltd. All rights reserved.
Research into regenerative dentistry has contributed momentum to the field of
molecular biology. Periapical surgery aims at removing periapical pathology to
achieve complete wound healing and regeneration of bone and periodontal tissue.
Regenerative endodontic procedures are widely being added to the current
armamentarium of pulp therapy procedures. The regenerative potential of platelets
has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue-engineering
product and has recently gained much popularity due its promising results in wound
healing bone induction. The features of this product are an attribute of platelets
which, after cellular interactions, release growth factors and have shown
application in diverse disciplines of dentistry. This paper is intended to shed
light onto the various prospects of PRF and to provide clinical insight into
regenerative endodontic therapy.
Background: Aloe vera (A. v) have been used traditionally for topical treatment of
wounds and burns in different countries for centuries, but the mechanism of this
effect is not well understood. Various growth factors are implicated in the process
of wound healing. Among the different growth factors involved in the process, TGF
beta 1 and bFGF are the most importantly expressed in fibroblast cells. The aim of
this study was to evaluate the effect of A. v on the expression of angiogenesis
growth factors in mouse embryonic fibroblast cells. Methods: We exposed mouse
embryonic fibroblast cells to different concentrations of A. v (50, 100 and 150 mu
g/ml) at two different time of 12 and 24 h. Fibroblast cell without A. v treatment
serves as the control. The expression of TGF beta 1 and bFGF was measured by real
time-polymerase chain reaction (real-time-PCR) and enzyme-linked immunosorbent
assay (ELISA) at the level of gene and protein. Results: We observed that A.v gel
at first up-regulated the expression of TGF beta 1 and bFGF, but, these genes were
later repressed after a particular time. Conclusion: Our results demonstrated that
A. v was dose-dependent and time-dependent on the expression of bFGF and TGFb1 in
fibroblast cell in vitro. This mechanism can be employed in the prospective
treatment of physical lesion. (C) 2017 Elsevier Masson SAS. All rights reserved.
Background: Human skin shows various morphological characteristics, depending on
the body site. As these distinct phenotypes have been explained on the basis of the
variance in epidermal keratinocytes and the presence of skin appendages, the
spatial distinction of the dermal components has not been fully elucidated.
Objectives: To identify and characterize the profiles of mRNAs that are abundantly
or specifically expressed by fibroblasts derived from trunk skin, but not from
palmoplantar skin or oral mucosa. Methods: In order to identify the distinct mRNA
expression by trunk skin fibroblasts, a subtraction cDNA screening was performed
first, followed by Northern blotting, Western blotting and immunohistochemistry for
cultured human and rat dermal fibroblasts and those skin tissues. Finally, whole
mount in situ hybridization (WISH) was performed to examine the differences in the
expression of the corresponding gene during the developmental stage of mouse
embryos. Results: We identified three cDNA clones encoding fibronectin (FN),
pregnancy-specific beta 1-glycoprotein 5 and beta-actin, respectively, whose mRNAs
were abundantly or specifically expressed by trunk skin fibroblasts. FN and some
integrins were further confirmed to be expressed more selectively in human and rat
trunk skin fibroblasts, both in terms of the RNA and the protein levels, compared
with the fibroblasts derived from plamoplantar skin and oral mucosa. WISH
demonstrated that FN was localized around the hair follicles of mouse embryos.
Conclusion: FN, one of most potent extracellular matrix molecules, was demonstrated
to be spatially transcribed depending on the body sites. The distinct expression of
FN was suggestive of the essential commitment in the process of cutaneous
development and morphogenesis of appendages originated from hair germ. The paucity
of FN in palmoplantar skin and oral mucosa might explain the characteristics of
these skin phenotypes.
This descriptive study evaluates how dance movement psychotherapy (DMP) works in
patients with fibromyalgia, analysing the psychotherapeutic process. As a second
objective, we considered the effects of DMP on pain, stiffness, fatigue, anxiety,
depression and lifestyle changes. The study includes 16 patients with a diagnosis
of primitive fibromyalgia who were referred to individual DMP for psychological
distress related to pain. Self-assessment questionnaires were administered before
and after the intervention, and the data were analysed using a simple regression
model and Student's test. Despite limitations, the study highlights changes in many
areas of the relationship with Self and with Others. Some of the symptoms of
fibromyalgia seem to have decreased, but the results were not statistically
significant. The patients used the movement as a means of expression despite pain
or other disabling symptoms. A low drop-out rate suggests that this approach could
be useful when it is difficult to develop a therapeutic alliance.
This study explored the role of fibulin-4 in osteosarcoma progression and the
possible signaling pathway involved. Fibulin-4 mRNA and protein expression in
normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines, the
normal osteoblastic cell line hFOB, and different invasive subclones were evaluated
by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real-time reverse
transcriptase-polymerase chain reaction (real-time qRT-PCR). Using in vitro
functional assays, we analyzed the invasive and proliferative abilities of
different osteosarcoma cell lines and subclones with differing invasive potential.
To assess the role of fibulin-4 in the invasion and metastasis of osteosarcoma
cells, lentiviral vectors with fibulin-4 small hairpin RNA (shRNA) and pLVX-
fibulin-4 were constructed and used to infect the highly invasive and low invasive
subclones and osteosarcoma cell lines. The effects of fibulin-4 knockdown and
upregulation on the biological behavior of osteosarcoma cells were investigated by
functional in vitro and in vivo assays. The results revealed that fibulin-4
expression was upregulated in osteosarcoma, and was positively correlated with low
differentiation, lymph node metastasis, and poor prognosis. Fibulin-4 was also
found to be over-expressed in highly invasive cell lines and in the highly invasive
subclones. Fibulin-4 could promote osteosarcoma cell invasion and metastasis by
inducing EMT via the PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate
that fibulin-4 is a promoter of osteosarcoma development and progression, and
suggest a novel therapeutic target for future studies.
Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk
human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC)
is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and
multifactorial process involving genetic and epigenetic events. The majority of
HNSCC patients present with locoregional advanced stage disease and are treated
with combined modality strategies that can markedly impair quality of life and
elicit unpredictable results. A large fraction of those who undergo locoregional
treatment and achieve a complete response later develop locoregional recurrences or
second field tumors. Biomarkers that are thus able to stratify risk and enable
clinicians to tailor treatment plans and to personalize post-therapeutic
surveillance strategies are highly desirable. To date, only HPV status is
considered a reliable independent predictor of treatment response and survival in
patients with HNSCC arising from the oropharyngeal site. Recent studies suggest
that telomere attrition, which may be an early event in human carcinogenesis, and
telomerase activation, which is detected in up to 90 % of malignancies, could be
potential markers of cancer risk and disease outcome. This review examines the
current state of knowledge on and discusses the implications linked to telomere
dysfunction and telomerase activation in the development and clinical outcome of
HNSCC.
A 5-bit digital controlled switch-type passive phase shifter realised in a 40 nm
digital CMOS technology without ultra-thick metals for the 60 GHz Industrial,
Scientific and Medical (ISM) band is presented. A patterned shielding with
electromagnetic bandgap structure and a stacked metals method to increase the on-
chip inductor quality factor are proposed. To reduce the insertion loss from the
transistors, the transistor switches are implemented with a body-source connection.
For all 32 states, the minimum phase error is 1.5 degrees, and the maximum phase
error is 6.8 degrees. The measured insertion loss is -20.9 +/- 1 dB including pad
loss at 60 GHz and the return loss is >10 dB over 57-64 GHz. The total chip size is
0.24 mm(2) with 0 mW DC power consumption.
Newtonian fluid dynamics simulations were performed using the Navier-Stokes-Fourier
formulations to elucidate the short time-scale (mu s and longer) evolution of the
density and temperature distributions in an argon-gas-filled attenuator for an X-
ray free-electron laser under high-repetition-rate operation. Both hydrodynamic
motions of the gas molecules and thermal conductions were included in a finite-
volume calculation. It was found that the hydrodynamic wave motions play the
primary role in creating a density depression (also known as a filament) by
advectively transporting gas particles away from the X-ray laser-gas interaction
region, where large pressure and temperature gradients have been built upon the
initial energy deposition via X-ray photoelectric absorption and subsequent
thermalization. Concurrent outward heat conduction tends to reduce the pressure in
the filament core region, generating a counter gas flow to backfill the filament,
but on an initially slower time scale. If the inter-pulse separation is
sufficiently short so the filament cannot recover, the depth of the filament
progressively increases as the trailing pulses remove additional gas particles.
Since the rate of hydrodynamic removal decreases while the rate of heat conduction
back flow increases as time elapses, the two competing mechanisms ultimately reach
a dynamic balance, establishing a repeating pattern for each pulse cycle. By
performing simulations at higher repetition rates but lower per pulse energies
while maintaining a constant time-averaged power, the amplitude of the hydrodynamic
motion per pulse becomes smaller, and the evolution of the temperature and density
distributions approach asymptotically towards, as expected, those calculated for a
continuous-wave input of the equivalent power.
Background: The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia
malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati
& Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi
(Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans
in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis &
Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia,
Southeast Asia, Sri Lanka and India. However, the origin and evolution of the
species in the Wuchereria-Brugia clade remain unclear. While investigating the
diversity of filarial parasites in Malaysia, we discovered an undescribed species
in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia).
Methods: We examined 81 common treeshrews from 14 areas in nine states and the
Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae
that were found had been isolated, we examined their morphological characteristics
and determined the partial sequences of their mitochondrial cytochrome c oxidase
subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of
the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T
vector, and the recombinant plasmids were used as templates for sequencing.
Results: Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described
based on the morphological characteristics of adults and microfilariae found in
common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter
distance between the cox1 gene sequences of the new species and W. bancrofti was
11.8%. Based on the three gene sequences, the new species forms a monophyletic
clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues
surrounding the lymph nodes of the neck of common treeshrews. Conclusions: The
newly described species appears most closely related to Wuchereria spp. and Brugia
spp., but differs from these in several morphological characteristics. Molecular
analyses based on the cox1 and 12S rRNA genes and the ITS1 region indicated that
this species differs from both W. bancrofti and Brugia spp. at the genus level. We
thus propose a new genus, Malayfilaria, along with the new species M. sofiani.
In this paper inlcjet-shaped barium-titanate thin films were examined by SEM, AFM
and optical microscopy, along with XRD and Raman spectroscopy in order to study
effects of drying chemical additives, ink concentration and printing parameters on
microstructure and phase composition. Inkjet printing is a very attractive way of
shaping functional materials. Simple setup, low-cost, digital control and the
possibility of obtaining complex forms without post-processing make this technique
highly competitive for application in microelectronics. The most common way of
preparing inks via powder dispersion involves high-temperature treatment (900
degrees C and above) in order to achieve dense and uniform structure. Thus, we
utilized an energy efficient sol gel approach where the final phase composition is
achieved in situ on the substrate. (C) 2015 Elsevier Ltd and Techna Group S.r.l.
All rights reserved.
This paper deals with the application of the simulated inductor in the continuous-
time allpass filters and group delay sensitivity analysis of the realized filter.
The realization of filter pair based on the LCR resonator circuits employs a single
generalized grounded impedance converter, which can be implemented with only one
operational amplifier. A group delay sensitivity measure can be useful for
comparison of the second order allpass filter cells, used for continuous-time
filter pair design. It can be related to the well known pole Q factor- and pole
frequency-sensitivities by a simple analytic expression. A design procedure is
developed in which tuning can be achieved by trimming only resistors.
Little work has focused on the underlying mechanisms that may link financial strain
and smoking processes. The current study tested the hypothesis that financial
strain would exert an indirect effect on cognitive-based smoking processes via
depressive symptoms. Three clinically significant dependent variables linked to the
maintenance of smoking were evaluated: negative affect reduction motives, negative
mood abstinence expectancies, and perceived barriers for quitting. Participants
included 102 adult daily smokers (M-age = 33.0 years, SD = 13.60; 353% female)
recruited from the community to participate in a self-guided (unaided; no
psychological or pharmacological intervention) smoking cessation study. Results
indicated that depressive symptoms explain, in part, the relation between financial
strain and smoking motives for negative affect reduction, negative mood abstinence
expectancies, and perceived barriers for quitting. Results indicate that smoking
interventions for individuals with high levels of financial strain may potentially
benefit from the addition of therapeutic tactics aimed at reducing depression. (C)
2017 Elsevier Ltd. All rights reserved.
Sparked by the conjunction of food, fuel, and financial crises, there has been an
increasing awareness in recent years of the scarce and finite character of natural
resources. Productive resources such as agricultural land have been touted by
financial actors-such as merchant banks, pension funds, and investment companies-as
providing the basis for a range of new "alternative" financial asset classes and
products. While the drivers, motives, and rationales behind the increasing interest
of turning farmland into a financial asset class have been traced by a number of
scholars, the interpretations of, and interactions with, financial actors at the
community level have received less attention. Based on qualitative research in
rural Australia, this paper reveals the grounds on which finance-backed investments
have been accepted and accommodated by communities in rural Australia and
delineates the reasons that have led to feelings of unease or refusal. The paper
thereby demonstrates that the financialization of farmland is neither abstract nor
one-sided but rather a multidimensional process that not only includes financial
actors but also the impacted rural populations in various ways. Positioning the
activities of financial actors in Australia within the emerging research on the
financialization of farmland, the paper endorses context-sensitive analyses to
better interpret these recent transformations of the agri-food system.
This paper demonstrates a 0.8-V rail-to-rail operational amplifier (op-amp) for
ultra-low-power Internet-of-Things (IoT) sensor nodes. To suppress the leakage
current in the logic part, a FinFET technology with 0.4-V threshold voltage (V-t),
is chosen. To realize the rail-to-rail operation in the small common-mode (CM)
voltage headroom, V-DD - V-t, a 4-stage chopper-stabilized topology with high-pass
filters, multi-path hybrid-nested Miller compensation, and a push-pull output stage
are introduced. A near-V-t amplifier is also introduced to the second stage to
boost the gain. The fabricated op-amp shows 1-MHz Gain-Bandwidth in whole of the CM
voltage range.
In communication and computing devices, the growing demand for high performance,
battery-operated portable equipments have transferred the concentration from staid
constraints (such as area, performance and reliability) to power consumption. In
the present scenario there is a cardinal requirement to diminish power consumption
for non-portable systems where power dissipation and leakage current are censorious
concerns. In VLSI circuits and systems, power dissipation is still censorious
because the leakage occurs when device is in inactive mode. To reduce the leakage
power and leakage current in FinFET based operational amplifier, a new circuit
technique called low power state technique is adduced in this paper. This approach
reduces significant amount of power during active mode and also has an endowment of
conserving the state in state retention mode 1. The op-amp electrical
characteristics are obtained by employing Cadence Virtuoso tool for circuit
simulation at 0.7 V input supply voltage. The simulated DC gain thus obtained is
65.4 dB in the active mode. The proposed FinFET based operational amplifier
performance traits are studied and compared with the existing CMOS technology at 45
nm scale. Here, the effect of temperature variation on electrical characteristics
of op-amp at 45 nm technology regime has been reconnoitered. FUrthermore, by
employing low power approach, the enhancement in slew rate has been significantly
attained. The simulation results are given and concluded.
The operating voltages of low-voltage control circuits in power plants and
substations have decreased with the installation of digital control equipment. This
increases the susceptibility of control equipment to abnormal surges, which arise
mainly from lightning. To protect control equipment from lightning, it is necessary
to predict lightning surges invading power plants and substations and design
effective lightning protection methodologies. Compared with conventional simulation
techniques based on circuit theory, full-wave numerical approaches are advantageous
in handling three-dimensional structures such as transmission line towers,
grounding structures, nonhorizontal wires, such as incoming power lines to power
plants and substations, and lightning-induced effects. In this study, to apply the
finite-difference time-domain (FDTD) method to the lightning surge analysis of an
air-insulated substation, we first propose techniques for simulating the nonlinear
breakdown characteristics of short-air-gap arcing horns and transmission line surge
arresters installed in 77 kV transmission lines for FDTD-based surge simulations,
and compare the breakdown characteristics calculated using the proposed techniques
with measured results for validation. Second, as an example of the application of
the proposed techniques to practical surge analysis, it is confirmed that we can
reproduce the measured results of lightning surges invading a 77 kV air-insulated
substation in the case of a direct lightning strike to its nearby transmission line
tower by taking into account lightning-induced voltages arising from the lightning
current flowing through the lightning channel and transmission line tower, which
are commonly ignored in conventional circuit-theory-based simulations, multiphase
back-flashover phenomena, and the effect of applied AC voltages.
Empirical analysis of the price fluctuations of financial markets has received
extensive attention because a substantial amount of financial market data has been
collected and because of advances in data-mining techniques. Price fluctuation
trends can help investors to make informed trading decisions, but such decisions
may also be affected by a psychological factors the anchoring effect. This study
explores the intraday price time series of Taiwan futures, and applies diffusion
model and quantitative methods to analyze the relationship between the anchoring
effect and price fluctuations during first passage process. Our results indicate
that power-law scaling and anomalous diffusion for stock price fluctuations are
related to the anchoring effect. Moreover, microscopic price fluctuations before
switching point in first passage process correspond with long-term price
fluctuations of Taiwan's stock market. We find that microscopic trends could
provide useful information for understanding macroscopic trends in stock markets.
(C) 2017 Elsevier B.V. All rights reserved.
Aim: Most studies on the determinants of psychosocial functioning in first-episode
psychosis used few predictors. This study examines the effects of multiple
cognitive domains and multiple symptoms on psychosocial functioning. Methods: A
total of 162 patients with a first-episode psychosis were assessed within 3 months
after referral to an early psychosis treatment department. Four psychopathological
subdomains (positive and negative symptoms, depression and anxiety) and five
subdomains of psychosocial functioning (work/study, relationships, self-care,
disturbing behaviour and general psychosocial functioning) were measured.
Neurocognitive and social cognitive factors were identified through principal
component analyses (PCA) of a 15-measure cognitive battery. Stepwise backward
regression models were computed to identify the determinants of psychosocial
functioning. Results: The three neurocognitive and four social cognitive factors
identified through PCA were largely independent of psychopathology. The strongest
associations were between cognitive factors and anxiety. Higher levels of negative
symptoms, poor general neurocognition and poor general social cognition showed
strongest associations with impaired psychosocial functioning, followed by low
verbal processing speed and low emotion processing speed. Together, these factors
accounted for 39.4% of the variance in psychosocial functioning. Conclusions: The
results suggest that negative symptoms, impaired neurocognition and poor social
cognition are related to psychosocial problems in patients with first-episode
psychosis. None of the affective or positive symptoms had a marked impact on
psychosocial functioning.
To achieve higher engineering efficiency in solar cells, group-DT compound
semiconductors, such as silicon (Si) or germanium (Ge), in the form of thin films
containing carbon (C) and/or tin (Sn) atoms, are gaining attention as alternatives
to poly-silicon crystals. Atomic configurations of C and Sn atoms near the (001)
surface of a Si thin film were analyzed by first-principles calculation based on
density functional theory (DFT). The results of the analysis are threefold. First,
C and Sn atoms are most stable at the first atomic layer of the Si thin film, and
the surface does not affect the stability of C or Sn atoms deeper than the fifth
layer. Second, C and Sn atoms deeper than the fifth layer do not affect the
stability of newly arrived C and Sn atoms at the surface during film growth. The
effects of the (001) surface and interacting C and/or Sn atoms on the thermal-
equilibrium concentrations of C and Sn in each layer of the Si thin film were
evaluated in consideration of the degeneracy of the atomic configurations. Third,
in the case of mono-doping, formation energy of C (Sn) at the (001) surface
increases with increasing concentration of surface C (Sn). In the case of co-doping
at C/Sn concentration ratio of 1:1, the formation energies of C and Sn decrease
with increasing surface concentrations of C and Sn. It is concluded from these
results that co-doping enhances the incorporation of C and Sn atoms in the Si thin
film.
Laboratory sessions are designed to develop the experimental skills and the
acquaintance with instruments that may contribute to a successful career in
Biochemistry and associated fields. This study is a report on improving a
traditional Biochemistry course by devising the laboratory sessions as an inquiry-
based environment to develop the students' autonomy to plan, perform, and interpret
experiments. We reformulated our Biochemistry laboratory to have three activities
that sequentially increase regarding autonomy. We used an autonomy support
structure consisting of varying levels of engagement by the student in such aspects
as Organizational, Procedural, and Cognitive, gradually transferring to students
the responsibility for their decisions within the laboratory. Our results show that
students performed better on the less instructed worksheet activities,
characterized by a more complex autonomy support, as compared to the activities
tightly controlled by worksheet directions. A review of the group lab reports
suggests that students showed skills required to work with different levels of
autonomy. Thus, this approach has positively supported the students' autonomy, not
only mapping their progress through the activities proposed but also encouraging
them to make decisions during their experiments and stimulating their ability to
think and to plan experiments themselves.
Diaz Encarnacion MM, Warner GM, Cheng J, Gray CE, Nath KA, Grande JP. n-3 Fatty
acids block TNF-alpha-stimulated MCP-1 expression in rat mesangial cells. Am J
Physiol Renal Physiol 300: F1142-F1151, 2011. First published March 2, 2011;
doi:10.1152/ajprenal.00064.2011.-Monocyte chemoattractant protein 1 (MCP-1) is a CC
cytokine that fundamentally contributes to the pathogenesis of inflammatory renal
disease. MCP-1 is highly expressed in cytokine-stimulated mesangial cells in vitro
and following glomerular injury in vivo. Interventions to limit MCP-1 expression
are commonly effective in assorted experimental models. Fish oil, an abundant
source of n-3 fatty acids, has anti-inflammatory properties, the basis of which
remains incompletely defined. We examined potential mechanisms whereby fish oil
reduces MCP-1 expression and thereby suppresses inflammatory responses to tissue
injury. Cultured mesangial cells were treated with TNF-alpha in the presence of the
n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA);
equimolar concentrations of the n-6 fatty acids LA and OA served as controls. MCP-1
mRNA expression was assessed by Northern blotting, and transcriptional activity of
the MCP-1 promoter was assessed by transient transfection. The involvement of the
ERK and NF-kappa B pathways was evaluated through transfection analysis and the use
of the MEK inhibitor U0126. DHA and EPA decreased TNF-alpha-stimulated MCP-1 mRNA
expression by decreasing transcription of the MCP-1 gene. DHA and EPA decreased p-
ERK expression and nuclear translocation of NF-kappa B, both of which are necessary
for TNF-alpha-stimulated MCP-1 expression. Both NF-kappa B and AP-1 sites were
involved in transcriptional regulation of the MCP-1 gene by DHA and EPA. We
conclude that DHA and EPA inhibit TNF-alpha-stimulated transcription of the MCP-1
gene through interaction of signaling pathways involving ERK and NF-kappa B. We
speculate that such effects may contribute to the salutary effect of fish oil in
renal and vascular disease.
The Shi-Hang Belt is a Mesozoic tectonic zone and has always been regarded as the
boundary between the Yangtze and Cathaysia blocks. It occupies a key tectonic
location and attracts considerable attention due to its dynamic formation
mechanism. However, its Cenozoic dynamic process is poorly constrained. The
Cenozoic activation of the Shi-Hang Belt, as well as its cooling and exhumation,
aids in dating the onset time of the formation of the mountain ranges and reveals
the deformation process of the South China Block. To uncover the history of its
Cenozoic cooling and denudation, apatite fission-track (AFT) thermochronology was
applied to batholiths and strata spread across the Shi-Hang Belt in the Hunan
Province. Twenty-three samples are dated with ages ranging from 23.6 +/- 1.5 to
45.8 +/- 3.0Ma. Except for two older ages (42.1 +/- 2.6 and 45.8 +/- 3.0Ma), the
other ages range from 23 to 36Ma with less variation on both sides of the Chenzhou-
Linwu fault. The thermochronological modelling of 15 measured samples demonstrates
that rocks rapidly passed through the AFT partial annealing zone to the near
surface at different onset times from 36 to 23Ma. The regional AFT cooling pattern
is unrelated to the internal structures of the Shi-Hang Belt characterized by a
Mesozoic fold-thrust feature. We attribute the Cenozoic exhumation of the Shi-Hang
Belt to the dynamic topography of the South China Block, which is related to mantle
downwellings and upwellings due to several episodes of quick subduction of the
Pacific Plate underneath Eurasia during the Late Cretaceous-early Cenozoic and the
Oligocene-early Miocene. The far-field effect of the India-Tibet collision may have
contributed to the exhumation of the Shi-Hang Belt.
This paper presents a novel method for the design of analog integrated circuit,
making use of fixator-norator pairs for the performance design and biasing design.
Fixators are the distinctive tools for setting a critical design parameter at a
desired value whereas the pairing norator renders these critical parameters into
adequate supporting components, mainly resistors. For analog ICs, active loads and
current mirrors serve as supporting components. Hence, the use of fixator-norator
pairs may abbreviate as defining the dynamic and static resistance of active loads
and current mirrors that should be affirmative with a given design. The proposed
methodology is illustrated by the use of a common emitter amplifier, a BJT
differential amplifier, a MOS operational amplifier and a three-stage CMOS
operational amplifier.
FK506 binding protein (FBBP) 14 belongs to the family of FKBPs. Altered expression
of FKBPs are observed in several malignancies. The present study aimed to explore
the expression and biological function of FKBP14 in gastric cancer. FKBP14
expression levels in 40 gastric cancer samples and matched control samples were
evaluated using quantitative polymerase chain reaction. Cell proliferation was
evaluated using Cell Counting kit-8 assay. A cell adhesion and a Transwell assay
were performed to detect cell adhesion and invasion. Protein expression was
determined using western blot analysis. It was found that FKBP14 expression in
gastric cancer tissues was elevated compared with normal tissues. Silencing of
FKBP14 expression in the gastric cancer MKN-45 and AGS cell lines, which have a
higher expression level of FKBP14 compared with four other gastric cancer cell
lines, significantly inhibited cellular proliferation, adhesion and invasion. In
addition, the protein levels of proliferating cell nuclear antigen, matrix
metalloproteinase 2 and the epithelial-mesenchymal-transition (EMT) markers beta-
catenin, Snail1 and Twist were repressed in gastric cancer cells with FKBP14
silenced. In conclusion, FKBP14 may act as an oncogene by suppressing cellular
proliferation, adhesion and invasion and EMT in gastric carcinogenesis. FKBP14 may
be a diagnosis marker and potential therapeutic target in gastric cancer.
We carried out molecular analyses of the novel flaky skin mutation, Ttc7(fsn-Jic)
(a synonym for fsn(Jic)), which we found in a previous study. It was revealed that
this mutation involved a genomic in-frame deletion including exons 9 and 10 of the
Ttc7 gene, and that the genomic deletion in Ttc7(fsn-Jic) may disrupt the
tetratricopeptide repeat-2B domain of the TTC7 protein. Based on a comparison of
three Ttc7 mutations, including Ttc7(fsn-J) (a synonym for fsn) and Ttc7(fsn-hea)
(a synonym for hea), it was suggested that either exon 9 or exon 10 or both may
play a more important role than the other exons of the Ttc7 gene. Ttc7 gene
expression analyses using Northern blotting revealed that Ttc7 mRNA is expressed in
11 tissues, except muscle. In conclusion, we confirmed that the Ttc7(fsn-Jic)
mutation, as well as the Ttc7(fsn-J) and Ttc7(fsn-hea) mutations, is responsible
for abnormal phenotypes observed in various tissues of mice with the flaky skin
mutation.
A new microbent in-line microfiber interferometer (MI-MI) is proposed and
demonstrated as a compact temperature and current sensor. The MI-MI is capable of
generating interference fringes with a high extinction ratio of about 12.0 dB and a
free spectral range of 1.9 nm at a wavelength of 1545 nm. When employed as a
temperature sensor, a copper wire carrying a direct current is placed against the
MI-MI sensor, and the interference fringes of the MI-MI sensor shifts toward the
longer wavelength as the heat generated by the copper wire increases. As the
temperature increase corresponds linearly to the current, thus the measurement of
the current can be extrapolated as well. The sensor has a temperature responsivity
of 33.0 pm/degrees C with a linearity of more than 0.97 as well as a current
responsitivity of 1.46 degrees C/A(2), and has significant potential for
application as a health and warning sensor for electricity generation and
distribution grids.
Careful characterization and standardization of the composition of plant-derived
food supplements is essential to establish a cause-effect relationship between the
intake of that product and its health effect. In this review we follow a specific
grape seed extract containing monomeric and oligomeric flavan-3-ols from its
creation by Jack Masquelier in 1947 towards a botanical remedy and nutraceutical
with proven health benefits. The preparation's research history parallels the
advancing insights in the fields of molecular biology, medicine, plant and
nutritional sciences during the last 70 years. Analysis of the extract's flavanol
composition emerged from unspecific colorimetric assays to precise high performance
liquid chromatography - mass spectrometry and proton nuclear magnetic resonance
fingerprinting techniques. The early recognition of the preparation's auspicious
effects on the permeability of vascular capillaries directed research to unravel
the underlying cellular and molecular mechanisms. Recent clinical data revealed a
multitude of favorable alterations in the vasculature upon an 8 weeks
supplementation which summed up in a health benefit of the extract in healthy
humans. Changes in gene expression of inflammatory pathways in the volunteers'
leukocytes were suggested to be involved in this benefit. The historically grown
scientific evidence for the preparation's health effects paves the way to further
elucidate its metabolic fate and molecular action in humans.
Flavivirus genome encodes seven non-structural proteins (NSPs) and these NSPs are
believed to be involved in their genomic RNA replication, of which the mechanism is
unclear. We find that West Nile virus (WNV) NSPs were capable of self-assembling
membranous vesicles in cells, which are composed of the host endoplasmic reticulum
membrane integrated with viral NS1 and NS4A, and possibly NS2A. The vesicles can
further organize into replication complex (RC)-associated vesicles which combine
both the vesicle and predicted RC components. The authentic RC -associated vesicles
were observed in cells transfected with infectious WNV cDNA as well as WNV
replicon. Further mutational analysis showed that WNV/DENY heterologous NS
polyproteins derived from lethal chimeric recombinants produced abnormal vesicles.
Site-directed mutation of either NS2A or NS4A, which resulted in failure of viral
RNA replication, caused immature vesicles too. These findings reveal molecular
composition and assembly of the virus-specific nanomachine and confirm that these
structures are used for the viral RNA replication.
Zika virus (ZIKV; family Flaviviridae, genus Flavivirus) is a rapidly expanding
global pathogen that has been associated with severe clinical manifestations,
including devastating neurological disease in infants. There are currently no
molecular clones of a New World ZIKV available that lack significant attenuation,
hindering progress toward understanding determinants of transmission and
pathogenesis. Here we report the development and characterization of a novel ZIKV
reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We
generated a two-plasmid infectious clone system from which infectious virus was
rescued that replicates in human and mosquito cells with growth kinetics
representative of wildtype ZIKV. Infectious clone-derived virus initiated infection
and transmission rates in Aedes aegypti mosquitoes comparable to those of the
primary isolate and displayed similar pathogenesis in AG129 mice. This infectious
clone system provides a valuable resource to the research community to explore ZIKV
molecular biology, vaccine development, antiviral development, diagnostics, vector
competence, and disease pathogenesis. IMPORTANCE ZIKV is a rapidly spreading
mosquito-borne pathogen that has been linked to Guillain-Barre syndrome in adults
and congenital microcephaly in developing fetuses and infants. ZIKV can also be
sexually transmitted. The viral molecular determinants of any of these phenotypes
are not well understood. There is no reverse genetics system available for the
current epidemic virus that will allow researchers to study ZIKV immunity, develop
novel vaccines, or develop antiviral drugs. Here we provide a novel infectious
clone system generated from a recent ZIKV isolated from a patient infected in
Puerto Rico. This infectious clone produces virus with in vitro and in vivo
characteristics similar to those of the primary isolate, providing a critical tool
to study ZIKV infection and disease.
Geometric and electrostatic modeling is an essential component in computational
biophysics and molecular biology. Commonly used geometric representations admit
geometric singularities such as cusps, tips and self-intersecting facets that lead
to computational instabilities in the molecular modeling. The present work explores
the use of flexibility and rigidity index (FRI), which has a proved superiority in
protein B-factor prediction, for biomolecular geometric representation and
associated electrostatic analysis. FRI rigidity surfaces are free of geometric
singularities. We proposed a rigidity based Poisson -Boltzmann equation for
biomolecular electrostatic analysis. Our approaches to surface and electrostatic
modeling are validated by a set of 21 proteins. Our results are compared with those
of established methods. Finally, being smooth and analytically differentiable, FRI
rigidity functions offer excellent curvature analysis, which characterizes concave
and convex regions on protein surfaces. Polarized curvatures constructed by using
the product of minimum curvature and electrostatic potential is shown to predict
potential protein-ligand binding sites. (C) 2016 Elsevier B.V. All rights reserved.
This paper presents a flexible and low-power Read-Out Circuit (ROC) with tunable
sensitivity, designed to interface a wide range of commercial resistive pressure
sensors for robotic applications. The ROC provides contact detection, monitoring
small capacitance variations at low pressure (<100 mbar), and encodes pressure
measurement on 8 bit, evaluating resistive variations. Two all-digital circuits
implement the conversion of the input resistance and capacitance-to-frequency,
exploiting an on-chip ring oscillator as timing reference. A 130 nm RFCMOS
prototype (with an active area of 428 x 159 mu m(2)) has a power consumption of
27.2 mu W, for VDD 1 V. Using digital control inputs, the ROC allows a wide range
tuning of measurement sensitivity (6.7-46.4 mbar/LSB) and adjustable acquisition
time (226.6-461.7 mu s and 648-890 mu s, for contact detection and pressure
evaluation, respectively). The read-out time of similar to 1 ms is compatible with
human response after touch.
Flexible Hybrid Electronics combine the best characteristics of printed electronics
and silicon ICs to create high performance, ultra-thin, physically flexible
systems. New static and dynamic tests are being developed to evaluate the
performance of these systems. Dynamic radius of curvature and torsional test
results are presented for a flexible hybrid electronics system with a FleX Silicon-
on-Polymer operational amplifier manufactured in an 180nm CMOS process with 4-
levels of metal interconnect mounted on a PET substrate.
In this paper, a new methodology for design of folded cascode (FC) and recycling
folded cascode (RFC) OTAs based on 1/f noise reduction is presented. With a new
formulation for input referred flicker noise based on Gm/Id characteristic in all
operation regions significantly enhance of the noise performance is achieved. Also,
this technique leads to the larger DC gain and gain-bandwidth, and phase margin
degeneration. The amplifiers were simulated in the 0.18 mu m CMOS technology and
the simulation results confirm the theoretical analyses. Proposed design
methodology exhibits 50 % reduction of input voltage noise @ 1 Hz for RFC compared
to the FC amplifier, without increasing the power consumption and silicon area.
This paper concerns automatic welding system with digital control and is directed
to the improvement of certain drive and guide means for a relatively freely carried
welding of wheel rim and wheel spider for continuous welding of a part resting on a
freely rotatable table. The drive and guide means are carried on the welding head
and impart drive to the part while maintaining the welding head properly positioned
relative to the part. The system presented is a slightly simplified version of a
real automobile wheel-welding system. Although system operation is explained in
terms of wheel welding, the design of the system has much in common with other
welding operations utilizing the basic industrial automatic welding sequence of
Squeeze, Weld, Hold, Release, and Standby with digital control.
This work describes the practical implementation of a Floating-Interleaving Boost
Converter (FIBC) for fuel cell applications. The paper aims to validate the concept
of digitally-controlled from four-phases-FIBC for fuel cell applications. FIBC
exhibits interesting performance in terms of magnetics, input, and output current
ripple, part count and distributed power losses. A potential field of application
is indeed medium and higher power fuel cell front-end converters, where minimizing
input current ripple is significant but also redundancy and reliability are
crucial. Actually, this approach covers all these aspects since provide module and
device redundancy with real-time and flexible digital control reconfiguration.
Relevant aspects related to design; modeling, simulation and experimental
verification of 100W, Arduino-controlled, 4-phases-FIBC are treated in this paper.
Recent technological developments in high-dimensional flow cytometry and mass
cytometry (CyTOF) have made it possible to detect expression levels of dozens of
protein markers in thousands of cells per second, allowing cell populations to be
characterized in unprecedented detail. Traditional data analysis by "manual gating"
can be inefficient and unreliable in these high-dimensional settings, which has led
to the development of a large number of automated analysis methods. Methods
designed for unsupervised analysis use specialized clustering algorithms to detect
and define cell populations for further downstream analysis. Here, we have
performed an up-to-date, extensible performance comparison of clustering methods
for high-dimensional flow and mass cytometry data. We evaluated methods using
several publicly available data sets from experiments in immunology, containing
both major and rare cell populations, with cell population identities from expert
manual gating as the reference standard. Several methods performed well, including
FlowSOM, X-shift, PhenoGraph, Rclusterpp, and flowMeans. Among these, FlowSOM had
extremely fast runtimes, making this method well-suited for interactive,
exploratory analysis of large, high-dimensional data sets on a standard laptop or
desktop computer. These results extend previously published comparisons by focusing
on high-dimensional data and including new methods developed for CyTOF data. R
scripts to reproduce all analyses are available from GitHub
(https://github.com/lmweber/cytometry-clustering-comparison), and pre-processed
data files are available from Flow Repository (FR-FCM-ZZPH), allowing our
comparisons to be extended to include new clustering methods and reference data
sets. (C) 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc.
on behalf of ISAC.
Purpose of reviewThis review gives an overview of the systems-immunology single-
cell proteomic and transcriptomic approaches that can be applied to study primary
immunodeficiency. It also introduces recent advances in multiparameter tissue
imaging, which allows extensive immune phenotyping in disease-affected
tissue.Recent findingsMass cytometry is a variation of flow cytometry that uses
rare earth metal isotopes instead of fluorophores as tags bound to antibodies,
allowing simultaneous measurement of over 40 parameters per single-cell. Mass
cytomety enables comprehensive single-cell immunophenotyping and functional
assessments, capturing the complexity of the immune system, and the molecularly
heterogeneous consequences of primary immunodeficiency defects. Protein epitopes
and transcripts can be simultaneously detected allowing immunophenotype and gene
expression evaluation in mixed cell populations. Multiplexed epitope imaging has
the potential to provide extensive phenotypic characterization at the subcellular
level, in the context of 3D tissue microenvironment.SummaryMass cytometry and
multiplexed epitope imaging can complement genetic methods in diagnosis and study
of the pathogenesis of primary immunodeficiencies. The ability to understand the
effect of a specific defect across multiple immune cell types and pathways, and in
affected tissues, may provide new insight into tissue-specific disease pathogenesis
and evaluate effects of therapeutic interventions.
Angiosperms and gymnosperms are two major groups of extant seed plants. It has been
suggested that gymnosperms lack FLOWERING LOCUS T (FT), a key integrator at the
core of flowering pathways in angiosperms. Taking advantage of newly released
gymnosperm genomes, we revisited the evolutionary history of the plant
phosphatidylethanolamine-binding protein (PEBP) gene family through phylogenetic
reconstruction. Expression patterns in three gymnosperm taxa and heterologous
expression in Arabidopsis were studied to investigate the functions of gymnosperm
FT-like and TERMINAL FLOWER 1 (TFL1)-like genes. Phylogenetic reconstruction
suggests that an ancient gene duplication predating the divergence of seed plants
gave rise to the FT and TFL1 genes. Expression patterns indicate that gymnosperm
TFL1-like genes play a role in the reproductive development process, while GymFT1
and GymFT2, the FT-like genes resulting from a duplication event in the common
ancestor of gymnosperms, function in both growth rhythm and sexual development
pathways. When expressed in Arabidopsis, both spruce FT-like and TFL1-like genes
repressed flowering. Our study demonstrates that gymnosperms do have FT-like and
TFL1-like genes. Frequent gene and genome duplications contributed significantly to
the expansion of the plant PEBP gene family. The expression patterns of gymnosperm
PEBP genes provide novel insight into the functional evolution of this gene family.
Site specific recombinases are invaluable tools in molecular biology, and are
emerging as powerful recorders of cellular events in synthetic biology. We have
developed a stringently controlled FLP recombinase system in Escherichia coli using
an arabinose inducible promoter combined with a weak ribosome binding site. (C)
2016 Elsevier B.V. All rights reserved.
Near-field thermophotovoltaic (NFTPV) devices have received much attention lately
as an alternative energy harvesting system, whereby a heated emitter exchanges
super-Planckian thermal radiation with a photovoltaic (PV) cell to generate
electricity. This work describes the use of a grating structure to enhance the
power throughput of NFTPV devices, while increasing the energy conversion
efficiency by ensuring that a large portion of the radiation entering the PV cell
is above the band gap. The device contains a high-temperature tungsten grating that
radiates photons to a room-temperature In0.18Ga0.82Sb PV cell through a vacuum gap
of several tens of nanometers. Scattering theory is used along with the rigorous
coupled-wave analysis (RCWA) to calculate the radiation energy exchange between the
grating emitter and the TPV cell. A parametric study is performed by varying the
grating depth, period, and ridge width in the range that can be fabricated using
available fabrication technologies. It is found that the power output can be
increased by 40% while improving the efficiency from 29.9% to 32.0% with a selected
grating emitter as compared to the case of a flat tungsten emitter. Reasons for the
enhancement are found to be due to the enhanced energy transmission coefficient
close to the band gap. This work shows a possible way of improving NFTPV and sheds
light on how grating structures interact with thermal radiation at the nanoscale.
The reservoir diagenetic process and the petroleum charge histories of the
Cretaceous Bashijiqike Formation (K(1)bs) in the Kuqa Depression, Tarim Basin were
studied using an integrated petrographic, fluid inclusion, reservoir diagenesis and
basin modeling approach. A suite of techniques were used in the investigation
including optical microscopy, scanning, electron microscope (SEM), X-ray
diffraction (XRD), fluorescence spectroscopy, microthermometry, and Laser Raman
microspectroscopy. The workflow comprises petrographic characterization of the
reservoir sandstone, identification of fluid inclusion assemblages, and
construction of the diagenetic history of the reservoir sandstone with reference to
the hydrocarbon charge and emplacement. Key diagenetic events identified include
quartz overgrowths, early calcite cementation, dolomite cementation, alteration of
kaolinite, bitumen emplacement, micro quartz and ankerite cementation. The first
diagenetic event was characterized by quartz overgrowths and followed by calcite
and dolomite cementation. Kaolinite and ankerite cementation were the last
diagenetic events, coincided with hydrocarbon charge and emplacement. Three
episodes of hydrocarbon charge and emplacement have been recorded by the diagenetic
products and fluid inclusions in the K1bs Formations: (1) the first episode of oil
charge was recorded in the early calcite cement, and were trapped around at 18 Ma;
(2) the second and third episodes of hydrocarbon charge were recorded in the telo-
diagenetic ankerite, and were trapped around at 4-6 Ma. The timing of oil
emplacement determined from fluid inclusion homogenization temperature and basin
modeling is consistent with the formation order of the diagenetic minerals. This
study has thus demonstrated that integrated analysis of fluid inclusion and
reservoir diagenesis can be an effective tool for determining hydrocarbon charge
and emplacement history. (C) 2017 Elsevier B.V. All rights reserved.
The quantitative grain fluorescence and quantitative grain fluorescence on extract
have become effective approaches in the analysis of hydrocarbon evolution in
clastic reservoirs recently. The cutoff threshold for differentiating
current/paleo-oil and water zones is crucial to reconstruct accurately hydrocarbon
accumulation history. However, the absence of theoretical study on the cutoff
threshold in the carbonate reservoir has precluded their application and
development. In this paper, we attempted to investigate the cutoff threshold by
analyzing the quantitative grain fluorescence and quantitative grain fluorescence
on extract parameters and spectra of the cores and natural carbonate outcrop
samples in known current/paleo-oil and water zones revealed by the frequency of oil
inclusions, formation test, logging analysis, etc. Based on this, the hydrocarbon
charging history of the Suqiao Buried-hill Zone, Bohai Bay Basin, eastern China was
reconstructed using the gotten threshold. Results show that the carbonate minerals
fluorescing will lead to a higher cutoff threshold of quantitative grain
fluorescence index value in the carbonate reservoir, while the threshold of
quantitative grain fluorescence on extract intensity value is coincident with the
corresponding value in the clastic reservoir. The quantitative grain fluorescence
and quantitative grain fluorescence on extract data have unraveled a complicated
hydrocarbon accumulation history in Suqiao Buried-hill Zone including oil charging
before gas and paleo-oil loss due to the tectonism. The ascertained cutoff
threshold in this study is of great significance for reconstructing accurately and
effectively the complicated hydrocarbon charging history in the carbonate
reservoir, which provides significant models for future petroleum exploration.
The design of tailor-made gelators has attracted tremendous level of attention for
the fabrication of novel nanogels with responsive characteristics. Exploiting the
gel properties of nanocellulose (NC) because of its abundance, sustainability and
renewability, we reported the fabrication of a fluorescent hydrogel based on S,N-
codoped Graphene Quantum Dots (S,N-GQDs) acting as luminophore and sensitizer. The
incorporation of the GQDs into the hydrogel resulted in a significant fluorescence
intensity enhancement if compared to GQ.D solutions. In conjunction with recent
efforts in the applicability of optical responsive gels, a simple method based on
the selectively sensing ability of the GQD/NC hydrogel towards 2,4,5-
trichlorophenol (TCP) through the fluorescence enhancement is disclosed. The
validity of this strategy is demonstrated with the analysis of TCP in red wine and
environmental water samples. (C) 2017 Elsevier B.V. All rights reserved.
A digital control method combining primary-side sensing, observer and model-
predictive-control techniques is proposed. A conventional isolated Flyback
converter is chosen for demonstrating the method. The only measured signal is the
drain-source voltage over the switch. Following a procedure of signal processing,
state estimation and constraint problem formulation, the controller determines the
optimal duty cycle ratio. The advantages of the proposed method include minimal
overshoot and fast stabilization, converter state restriction, and measurement
network simplification.
The expression of antigens in transgenic plants has increasingly been used as an
alternative to the classical methodologies for the development of experimental
vaccines, and it remains one of the real challenges in this field to use transgenic
plant-based vaccines effectively as feedstuff additives. We report herein the
development of a new oral immunization system for foot and mouth disease with the
structural protein VP1 of the foot and mouth disease virus (FMDV) produced in
transgenic Stylosanthes guianensis cv. Reyan II. The transgenic plantlets were
identified by polymerase chain reaction (PCR), Southern blotting, and northern
blotting; and the production of VP1 protein in transgenic plants was confirmed and
quantified by western blotting and enzyme-linked immunosorbent assays (ELISA). Six
transformed lines were obtained, and the level of the expressed protein was 0.1-
0.5% total soluble protein (TSP). Mice that were orally immunized using studded
feedstuff mixed with desiccated powder of the transgenic plants developed a virus-
specific immune response to the structural VP1 and intact FMDV particles. To our
knowledge, this is the first report of transgenic plants expressing the antigen
protein of FMDV as feedstuff additives that has demonstrated the induction of a
protective systemic antibody response in animals. These results support the
feasibility of producing edible vaccines from transgenic forage plants, and provide
proof of the possibility of using plant-based vaccines as feedstuff additives.
Previous research has provided qualitative evidence for overlap in a number of
brain regions across the subjective value network (SVN) and the default mode
network (DMN). In order to quantitatively assess this overlap, we conducted a
series of coordinate-based meta-analyses (CBMA) of results from 466 functional
magnetic resonance imaging experiments on task-negative or subjective value-related
activations in the human brain. In these analyses, we first identified significant
overlaps and dissociations across activation foci related to SVN and DMN. Second,
we investigated whether these overlapping subregions also showed similar patterns
of functional connectivity, suggesting a shared functional subnetwork. We find
considerable overlap between SVN and DMN in subregions of central ventromedial
prefrontal cortex (cVMPFC) and dorsal posterior cingulate cortex (dPCC). Further,
our findings show that similar patterns of bidirectional functional connectivity
between cVMPFC and dPCC are present in both networks. We discuss ways in which our
understanding of how subjective value (SV) is computed and represented in the brain
can be synthesized with what we know about the DMN, mind-wandering, and self-
referential processing in light of our findings.
In small, selected samples, an approach combining resting-state functional
connectivity MRI and multivariate pattern analysis has been able to successfully
classify patients diagnosed with unipolar depression. Purposes of this
investigation were to assess the generalizability of this approach to a large
clinically more realistic sample and secondarily to assess the replicability of
previously reported methodological feasibility in a more homogeneous subgroup with
pronounced depressive symptoms. Two independent subsets were drawn from the
depression and control cohorts of the BiDirect study, each with 180 patients with
and 180 controls without depression. Functional connectivity either among regions
covering the gray matter or selected regions with known alterations in depression
was assessed by resting-state fMRI. Support vector machines with and without
automated feature selection were used to train classifiers differentiating between
individual patients and controls in the entire first subset as well as in the
subgroup. Model parameters were explored systematically. The second independent
subset was used for validation of successful models. Classification accuracies in
the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In
the subgroup with higher depression severity, three out of 90 models performed
significantly above chance (60.8-61.7% at independent validation). In conclusion,
common classification methods previously successful in small homogenous depression
samples do not immediately translate to a more realistic population. Future
research to develop diagnostic classification approaches in depression should focus
on more specific clinical questions and consider heterogeneity, including symptom
severity as an important factor.
The present study used functional near-infrared spectroscopy (fNIRS) to measure 5-
to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to
visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-
month-old infants watched video clips of Peek-a-Boo (social signal) performed by an
anime character (AC) or a human, and hand movements without social signal performed
by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while
behaviors including looking time were recorded simultaneously. NIRS data showed
that infants hemodynamic responses in the PFC generally decreased due to these
stimuli, and the decrease was most prominent in the frontopolar (FP), covering
medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC.
Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when
infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly,
behavioral data revealed significantly longer looking times when Peek-a-Boo was
performed by an AC than by a human. No significant difference between Peek-a-Boo
and non-Peek-a-Boo conditions was observed in either measure. These findings
indicate that infants at this age may prefer stimuli with more salient features,
which may be more effective in attracting their attentions. In conjunction with our
previous findings on responses to self-name calling in infants of similar age, we
hypothesize that the dynamic function of the MPFC and its vicinity (as part of
default mode network (DMN): enhanced by self-focused stimuli, attenuated by
externally focused stimuli), which is consistently observed in adults, may have
already emerged in 5- to 6-month-old infants.
Background: Foamy viruses (FVs) of the Spumaretrovirinae subfamily are distinct
retroviruses, with many features of their molecular biology and replication
strategy clearly different from those of the Orthoretroviruses, such as human
immunodeficiency, murine leukemia, and human T cell lymphotropic viruses. The FV
Gag N-terminal region is responsible for capsid formation and particle budding via
interaction with Env. However, the critical residues or motifs in this region and
their functional interaction are currently ill-defined, especially in non-primate
FVs. Results: Mutagenesis of N-terminal Gag residues of feline FV (FFV) reveals key
residues essential for either capsid assembly and/or viral budding via interaction
with the FFV Env leader protein (Elp). In an in vitro Gag-Elp interaction screen,
Gag mutations abolishing particle assembly also interfered with Elp binding,
indicating that Gag assembly is a prerequisite for this highly specific
interaction. Gradient sedimentation analyses of cytosolic proteins indicate that
wild-type Gag is mostly assembled into virus capsids. Moreover, proteolytic
processing of Gag correlates with capsid assembly and is mostly, if not completely,
independent from particle budding. In addition, Gag processing correlates with the
presence of packaging-competent FFV genomic RNA suggesting that Pol encapsidation
via genomic RNA is a prerequisite for Gag processing. Though an appended
heterogeneous myristoylation signal rescues Gag particle budding of mutants unable
to form capsids or defective in interacting with Elp, it fails to generate
infectious particles that co-package Pol, as evidenced by a lack of Gag processing.
Conclusions: Changes in proteolytic Gag processing, intracellular capsid assembly,
particle budding and infectivity of defined N-terminal Gag mutants highlight their
essential, distinct and only partially overlapping roles during viral assembly and
budding. Discussion of these findings will be based on a recent model developed for
Gag-Elp interactions in prototype FV.
Mobile technologies are increasingly adopted by information intensive organizations
such as public police corporations to support the tasks of its employees, for
information management and innovation. However, because police organizations are
government organizations, technology decisions are largely made by managers and
politicians with budget being a key factor. Therefore, whether the technologies
adopted are suitable for police tasks, and if they enhance performance, is
generally not assessed. The aim of this research is to establish if mobile
technologies support police tasks, and if Tablet PCs especially are suitable for
specialist police tasks of the Criminal Investigators and Sexual Offence and Child
Abuse Units. Guided by an interpretive paradigm and the theory of task technology
fit, this research explores the use of Tablet PCs by the two police units for
improved performance. Because information is critical for police tasks, data
collected via focus groups establishes the impact of these technologies on case
investigations, information management, and the performance of these units with the
use of Tablet PCs. The contribution this study makes to mobile information systems
is that if technology dimensions are suitable for information based tasks, the
outcome is virtualization of processes through which improved performance is
achieved due to reduced costs, transparency, teamwork, and quick and informed
decisions. The findings of this research can be used by police organizations, as
well as by other organizations, for effective implementation of mobile
technologies.
Fiber optical gyro (FOG) is a kind of solid-state optical gyroscope with good
environmental adaptability, which has been widely used in national defense,
aviation, aerospace and other civilian areas. In some applications, FOG will
experience environmental conditions such as vacuum, radiation, vibration and so on,
and the scale-factor performance is concerned as an important accuracy indicator.
However, the scale-factor performance of FOG under these environmental conditions
is difficult to test using conventional methods, as the turntable can't work under
these environmental conditions. According to the phenomenon that the physical
effects of FOG produced by the sawtooth voltage signal under static conditions is
consistent with the physical effects of FOG produced by a turntable in uniform
rotation, a new method for the scale-factor performance test of FOG without
turntable is proposed in this paper. In this method, the test system of the scale-
factor performance is constituted by an external operational amplifier circuit and
a FOG which the modulation signal and Y waveguied are disconnected. The external
operational amplifier circuit is used to superimpose the externally generated
sawtooth voltage signal and the modulation signal of FOG, and to exert the
superimposed signal on the Y waveguide of the FOG. The test system can produce
different equivalent angular velocities by changing the cycle of the sawtooth
signal in the scale-factor performance test. In this paper, the system model of FOG
superimposed with an externally generated sawtooth is analyzed, and a conclusion
that the effect of the equivalent input angular velocity produced by the sawtooth
voltage signal is consistent with the effect of input angular velocity produced by
the turntable is obtained. The relationship between the equivalent angular velocity
and the parameters such as sawtooth cycle and so on is presented, and the
correction method for the equivalent angular velocity is also presented by
analyzing the influence of each parameter error on the equivalent angular velocity.
A comparative experiment of the method proposed in this paper and the method of
turntable calibration was conducted, and the scale-factor performance test results
of the same FOG using the two methods were consistent. Using the method proposed in
this paper to test the scale-factor performance of FOG, the input angular velocity
is the equivalent effect produced by a sawtooth voltage signal, and there is no
need to use a turntable to produce mechanical rotation, so this method can be used
to test the performance of FOG at the ambient conditions which turntable can not
work.
This paper presents a novel CMOS folded cascode operational amplifier that leads to
high PSRR and provides gain nearly equal to that of a two stage op-amp. The
proposed design is implemented in GPDK 0.18 m CMOS technology. This op amp uses a
folded cascode structure in the output stage combined with the differential
amplifier having PMOS input transistors to achieve good input common mode range and
lower flicker noise. It has an important feature that it allows the input common
mode level close to supply voltage. The proposed topology improves the PSRR of op-
amp which can be used for LDO applications. Simulations using Cadence under 1.8 V
show a DC gain of 72.0404 dB and a phase margin of 62.4636 degree at a unity gain
bandwidth of 13.33 MHz with the power consumption smaller than 0.13 mW along with a
PSRR of 72.0966 dB. The layout of the design shows that the area acquired on the
chip is approximately equal to 8897.27 mu m(2).
An amplifier and capacitor sharing technique with applications in a multiplying
digital-to-analog converter (MDAC) of CMOS pipelined ACDC is presented. The
amplifier used in this implementation is a recycling amplifier based on the folded
cascode operational amplifier with gain improved using positive feedback. The
operational amplifier designed in 0.35um CMOS process show a simulated gain of 75
dB, frequency bandwidth of 95 MHz, phase margin of 75 degree and power consumption
of 0.75 mW on a 1.8V power supply. The simulation results in MDAC of 1.5 bits show
that this configuration can be used in a implementation of a 10 bits 10 MSample/s
CMOS pipelined ADC with 2.8 mW power consumption (analog part) on a 1.8V supply.
We screened the gene that encodes tetratricopeptide repeat domain 29 (Ttc29) in the
maturing rat testis. Gene expression was determined by Northern blotting of 7-week-
old rat testes, and a strong signal was detected close to the 18S rRNA band in
addition to two weak high-molecular-weight signals. In situ hybridization revealed
that Ttc29 was expressed primarily in the spermatocytes. We evaluated the effect of
gonadotropin on Ttc29 expression using hypophysectomized rats. The pituitary was
removed from 3-week-old rats, gonadotropin was injected at 5 weeks, and Ttc29
expression was determined at 7 weeks. Although testicular development and
hyperplasia of interstitial cells were observed following chorionic gonadotropin
treatment after hypophysectomy, Ttc29 expression was upregulated by treatment with
follicle-stimulating hormone. Ttc29 encodes axonemal dynein, a component of sperm
flagella. Taken together, these data indicate that axonemal dynein expression
starts in the spermatocytes and is regulated by follicle-stimulating hormone.
Recent food safety scandals in Taiwan have caused panic among the Taiwanese public
and have become a primary concern because foods were discovered containing a
dangerous amount of illegal additives. The theory of planned behavior (TPB) model
is extremely useful for predicting people's food choices and consumption habits.
This study included an examination of the public attention to and perceived
credibility of mass media food safety information and the perceived risk as
background factors in the extended TPB model to predict public intention to take
precautions to avoid consuming foods with additives. The empirical results of
structural equation modeling analysis with 487 useful samples revealed that the
extended TPB model has an increased explanatory power relative to the original
model regarding the intention of the public in Taiwan to take precautions to avoid
consuming foods that contain additives. In addition to attitudes toward and
perceived behavioral control of the consumption of food with additives, the impact
of risk perceptions plays an important role in determining an individual's
intention to take precautions to avoid consuming foods that contain additives. The
attention of an individual to food additive scandal news and their perceived risk
determine their attitude toward consuming food with additives. An individual's
perceived risk of consuming food with additives was determined through the
attention paid to food additive scandal news and the perceived credibility of such
news. (C) 2017 Elsevier Ltd. All rights reserved.
The diagnosis of food allergy is challenging due to different immunologic
mechanisms and diversity of symptoms. An open or double-blinded oral food challenge
(OFC) was performed on 391 children (aged 0.2-16.9 years) with suspected cow's milk
(n = 266) or wheat allergy (n = 125) to characterize immediate, delayed, and
transient symptoms, and to evaluate the role of earlier food-related symptoms and
immunoglobulin E (IgE)-[pmediated sensitization for the OFC outcome. The OFC
resulted in an immediate positive reaction in 38% (n = 148) and a delayed positive
reaction in 21% (n = 81) of the 391 children. Transient reactions, the majority of
which were localized skin reactions, were seen in almost third (n = 50) of the
patients with a negative OFC result (n = 162/391). Immediate localized skin
reactions were more common during the milk challenge (p = 0.010), whereas immediate
lower respiratory tract symptoms (p = 0.001) were more common during the wheat
challenge. Although 14% (n = 21) of those with an immediate reaction received i.m.
adrenalin as a treatment of the reaction, there were no life-threatening events.
Multivariate analyses revealed that independent risk factors for the immediate OFC
outcome were earlier moderate-to-severe immediate food-related reactions, marked
IgE-mediated sensitization to the suspected food, and in case of wheat, age <12
months. The accuracy of OFCs can be enhanced without increasing the risk of serious
allergic reactions by taking into account earlier food-related symptoms and the
level of IgE-mediated sensitization, by refining our knowledge of transient
nonspecific reactions, and by applying standardized OFC protocols with over-one-day
challenges.
This study examines the time to re-report following the close of a maltreatment
investigation for cases involving food neglect. Data on families of children 0 to
17 involved in Child Protective Services (CPS) investigations from a merger of the
2010 cohort of the National Survey of Child and Adolescent Well-Being (NSCAW II)
and the National Child Abuse and Neglect Data System (NCANDS) were used (n = 3580).
More than half of the families had a history of CPS involvement, a third received
CPS services, and one-in-ten families had their child place in out of-home care
following an investigation. After controlling for other types of maltreatment
allegations and multiple covariates, families investigated for food neglect had a
greater chance of being re-reported for a subsequent CPS investigations in a
shorter length of time than families without an allegation of food neglect. While
only a small percentage of families had a food neglect allegation, problems
adequately feeding a child - whether due to severe poverty, inattentiveness, or
abusive negligence - placed a family at a higher risk of a future CPS
investigation. (C) 2016 Elsevier Ltd. All rights reserved.
Food protein-induced enterocolitis (FPIES) is a non-IgE cell-mediated food allergy
that can be severe and lead to shock. Despite the potential seriousness of
reactions, awareness of FPIES is low; high-quality studies providing insight into
the pathophysiology, diagnosis, and management are lacking; and clinical outcomes
are poorly established. This consensus document is the result of work done by an
international workgroup convened through the Adverse Reactions to Foods Committee
of the American Academy of Allergy, Asthma & Immunology and the International FPIES
Association advocacy group. These are the first international evidence-based
guidelines to improve the diagnosis and management of patients with FPIES. Research
on prevalence, pathophysiology, diagnostic markers, and future treatments is
necessary to improve the care of patients with FPIES. These guidelines will be
updated periodically as more evidence becomes available.
Recent attention to communities "localizing" food systems has increased the need to
understand the perspectives of people working to foster collaboration and the
eventual transformation of the food system. University Cooperative Extension
Educators (EEs) increasingly play a critical role in communities' food systems
across the United States, providing various resources to address local needs. A
better understanding of EEs' perspectives on food systems is therefore important.
Inspired by the work of Stevenson, Ruhf, Lezberg, and Clancy on the social food
movement, we conducted national virtual focus groups to examine EEs' attitudes
about how food system change should happen, for what reasons, and who has the
resources, power, and influence to effect change. The institutions within which EEs
are embedded shape their perceptions of available resources in the community,
including authority and power (and who holds them). These resources, in turn,
structure EEs' goals and strategies for food system change. We find that EEs
envision working within the current food system: building market-centric
alternatives that address inequity for vulnerable consumers and producers. EEs
bring many resources to the table but do not believe they can influence those who
have the authority to change policy. While these findings could suggest EEs'
limited ability to be transformative change agents, EEs can potentially connect
their efforts with new partners that share perceptions of food system problems and
solutions. As EEs increasingly engage in food system work and with increasingly
diverse stakeholders, they can access alternative, transformational frames within
which to set goals and organize their work.
Background: Food allergy is an important public health problem because it affects
children and adults, can be severe and even life-threatening, and may be increasing
in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious
Diseases, working with other organizations and advocacy groups, led the development
of the first clinical guidelines for the diagnosis and management of food allergy.
A recent landmark clinical trial and other emerging data suggest that peanut
allergy can be prevented through introduction of peanut-containing foods beginning
in infancy. Objectives: Prompted by these findings, along with 25 professional
organizations, federal agencies, and patient advocacy groups, the National
Institute of Allergy and Infectious Diseases facilitated development of addendum
guidelines to specifically address the prevention of peanut allergy. Results: The
addendum provides 3 separate guidelines for infants at various risk levels for the
development of peanut allergy and is intended for use by a wide variety of health
care providers. Topics addressed include the definition of risk categories,
appropriate use of testing (specific IgE measurement, skin prick tests, and oral
food challenges), and the timing and approaches for introduction of peanut-
containing foods in the health care provider's office or at home. The addendum
guidelines provide the background, rationale, and strength of evidence for each
recommendation. Conclusions: Guidelines have been developed for early introduction
of peanut-containing foods into the diets of infants at various risk levels for
peanut allergy. Published by Elsevier Inc on behalf of the American College of
Allergy, Asthma & Immunology.
State statutes regarding the best interests of the child (BIC) in deciding disputed
custody were reviewed and independently coded with respect to three issues (i) the
child's preference and any limits (ii) parental alienation and (iii) psychological
maltreatment. Results revealed that many states allowed for the child's preferences
to be considered and none qualified that preference when undue influence has
occurred; parental alienation as a term was not found in any state statutes but 70%
of the states included at least one BIC factor relevant to its core construct of
the parent supporting the child's relationship to the other parent; and many states
included a history of domestic violence or child abuse but only three states
explicitly mentioned psychological maltreatment. These findings highlight yet
another way in which the BICS factors lack specificity in ways that could
negatively impact children caught in their parents' conflict.
This review was prepared for the American Society of Mechanical Engineers Lissner
Medal. It specifically discusses research performed in the Orthopaedic Biomechanics
Laboratories on pediatric cranial bone mechanics and patterns of fracture in
collaboration with the Forensic Anthropology Laboratory at Michigan State
University. Cranial fractures are often an important element seen by forensic
anthropologists during the investigation of pediatric trauma cases litigated in
courts. While forensic anthropologists and forensic biomechanists are often called
on to testify in these cases, there is little basic science developed in support of
their testimony. The following is a review of studies conducted in the above
laboratories and supported by the National Institute of Justice to begin an
understanding of the mechanics and patterns of pediatric cranial bone fracture.
With the lack of human pediatric specimens, the studies utilize an immature porcine
model. Because much case evidence involves cranial bone fracture, the studies
described below focus on determining input loading based on the resultant bone
fracture pattern. The studies involve impact to the parietal bone, the most often
fractured cranial bone, and begin with experiments on entrapped heads, progressing
to those involving free-falling heads. The studies involve head drops onto
different types and shapes of interfaces with variations of impact energy. The
studies show linear fractures initiating from sutural boundaries, away from the
impact site, for flat surface impacts, in contrast to depressed fractures for more
focal impacts. The results have been incorporated into a "Fracture Printing
Interface (FPI)," using machine learning and pattern recognition algorithms. The
interface has been used to help interpret mechanisms of injury in pediatric death
cases collected from medical examiner offices. The ultimate aim of this program of
study is to develop a " Human Fracture Printing Interface" that can be used by
forensic investigators in determining mechanisms of pediatric cranial bone
fracture.
Rapid and progressive advances in molecular biology techniques and the advent of
Next Generation Sequencing (NGS) have opened new possibilities for analyses also in
the identification of entomological matrixes. Insects and other arthropods are
widespread in nature and those found at a crime scene can provide a useful
contribution to forensic investigations. Entomological evidence is used by experts
to define the postmortem interval (PMI), which is essentially based on
morphological recognition of the insect and an estimation of its insect life cycle
stage. However, molecular genotyping methods can also provide an important support
for forensic entomological investigations when the identification of species or
human genetic material is required. This case study concerns a collection of
insects found in the house of a woman who died from unknown causes. Initially the
insects were identified morphologically as belonging to the Pediculidae family, and
then, human DNA was extracted and analyzed from their gastrointestinal tract. The
application of the latest generation forensic DNA assays, such as the Quantifiler
(R) Trio DNA Quantification Kit and the HID-Ion AmpliSeq (TM) Identity Panel
(Applied Biosystems (R)), individuated the presence of human DNA in the samples and
determined the genetic profile. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
For more than two decades, conventional wisdom about the high-profile day care
cases of the 1980s and early 1990s suggests all were modern-day witch hunts, based
on false allegations made by highly suggestible children during an era when society
was gripped by a "believe the children" hysteria. Author Ross Cheit refutes
conventional wisdom by conducting an exhaustive examination of original data from
dozens of cases bearing the witch hunt label. He concludes there was no witch-hunt
epidemic, finding substantial evidence of sexual abuse in nearly every case he
reviewed, contradicting the assertions made about those cases by what he calls the
witch-hunt narrative. Cheit examines the legacy of the witch-hunt narrative and
contends its exaggerated claims about the suggestibility of children have had a
negative effect on the credibility of children today who allege being sexually
abused. This writer examines Cheit's conclusions in light of her own experience as
a career prosecutor of crimes against children as well as her involvement in a
high-profile day care case encompassed by the witch-hunt narrative. Setting the
record straight about these cases is important not only for the sake of historical
accuracy and intellectual honesty but also because the witch-hunt narrative's
unwarranted assertions about the suggestibility of children have had a negative
effect on society's perception of their credibility. Bringing public attention to
the fallacies of the witch-hunt narrative and shining a light on questionable
tactics used by some in academia to support their contention that all children are
highly suggestible will ultimately serve to strengthen society's ability to believe
a child who discloses sexual abuse.
We comment on The Witch-Hunt Narrative (TWHN) by Cheit. As its first hypothesis,
TWHN argues that most of the famous ritual child abuse cases of the 1980s and 1990s
were not really witch-hunts at all. In response, we criticize the TWHN definition
of a witch-hunt as overly narrow and idiosyncratic. Based on the scholarly
literature, we propose 10 criteria for identifying a witch-hunt. We rate four well-
known ritual child abuse cases with these criteria and show they were classic
witch-hunts. As its second hypothesis, TWHN argues that most defendants in child
ritual abuse cases were guilty or probably guilty. In response, we point out many
instances in which TWHN has omitted or mischaracterized important facts or ignored
relevant scientific information running contrary to its hypotheses. We conclude
that TWHN is often factually inaccurate and tends to make strong assertions without
integrating relevant scholarly and scientific information. Scholars should approach
the book with caution.
Clinical forensic medicine (CFM), as a single discipline, encompasses a number of
areas of medico-legal practice including injury interpretation, management of
sexual and physical assault cases (both adult and child; alleged victim and
offender), mental health issues, traffic medicine, custodial medicine and
toxicology. The cases are usually alive but in some jurisdictions the forensic
practitioner also engages in death investigation with some undertaking autopsies.
During the last 20-30 years, the discipline has fragmented with areas being hived
off to other medical specialist disciplines and, importantly, to nurses. Any user
of forensic services wants the best value for money particularly when under
financial pressure. To this end, governments have sought savings through
privitisation of services and/or the utilisation of less qualified personnel to
undertake some or all of the tasks. This places CFM at a crossroads. To ensure
survival, the discipline needs to reconsider its direction and performance,
convince stakeholders of its relevance and importance, and lift its profile within
the legal, academic and medical world. It will need to think outside the square,
place greater emphasis on the 'clinical' and relinquish those activities that are
better undertaken by less expensive and qualified personnel. The establishment of
meaningful research and academic centres are essential. The loss of and/or failure
to grow CFM will result in the loss of a skills base and the subsequent potential
for the miscarriages of justice. (C) 2017 Elsevier Ltd and Faculty of Forensic and
Legal Medicine. All rights reserved.
Retinal hemosiderin deposition is a histologic indicator of sustained hemorrhage
but cannot be used to precisely estimate the elapsed time since an episode of
trauma. A 5-month-old male infant was admitted to hospital after acute
deterioration. Examination revealed encephalopathy, subdural hematomas, and retinal
hemorrhages consistent with abusive head trauma (AHT). At the age of 3, he was
readmitted to hospital with spontaneous osteopenic fracture of the right femur. The
patient deteriorated and died after unsuccessful resuscitation.
Ophthalmopathological investigation showed atrophy of the retina and optic nerve
and hemosiderin deposition in both eyes. Retinal hemosiderin deposition is
currently generally assumed to disappear within 6-8 weeks after the occurrence of
hemorrhage in AHT. This case report describes an infant with bilateral retinal
hemosiderin depositions due to hemorrhages sustained from AHT occurring 32 months
prior to death. Implications of this finding for the interpretation of retinal
hemosiderin depositions in AHT are discussed.
Case files from the Cook County Medical Examiner's Office from 2007 to 2012 were
reviewed to analyze homicides due to physical child abuse in children <3 years old.
Fatal cases mostly involved younger subjects. Intracranial injuries were the
leading cause of death, while death due to extracranial injuries was uncommon. Eyes
were involved in most of the cases. Spinal cord was involved in about 1/3 of the
cases, mostly in the thoracic area. In some cases, previous injuries were present.
There were significant differences in the pattern of injuries between age groups.
Subjects showing signs of impact to the head and subjects with no evidence of an
impact showed no significant difference in internal injuries. The association of
multiple injuries is highly suggestive of child abuse. In suspected child abuse, a
postmortem examination including neuropathological, ophthalmological, and
radiological information should be always evaluated, together with investigative
reports and the medical history.
Since its introduction, colonoscopy has played an important role as a diagnostic,
therapeutic, and screening tool. In general, colonoscopy is regarded as a safe
procedure, but complications may occur. The most dreaded of these complications is
colonic perforation. Bacteremia postprocedure may occur, and although it is not
uncommon, it rarely results in clinically significant complications. Patients with
IBD (inflammatory bowel disease) are a high-risk population for bacteremia, which
may leads to bowel wall overstepping by the bacteria. With regard to that, we
report a fatal case of gas gangrene complicating colonoscopy polypectomy without
bowel perforation in a healthy adult. To the best of our knowledge, only two other
cases of retroperitoneal gas gangrene associated with colonoscopy polypectomy
without bowel perforation have been described in international literature, but none
of which was completed by a molecular biology analysis.
Skull fracture characteristics are associated with loading conditions (such as the
impact point and impact velocity) and could provide indication of abuse or
accident-induced head injuries. However, correlations between fracture
characteristics and loading conditions in infant and toddler are ill-understood. A
simplified computational model representing an infant head was built to simulate
skull responses to blunt impacts. The fractures were decided through a first
principal strain-based element elimination strategy. Simulation results were
qualitatively compared with test data from porcine heads. This simplified model
well captured the fracture pattern, initial fracture position, and direction of
fracture propagation. The model also very well described fracture characteristics
found in studies with human infant cadaveric specimens. A series of parametric
studies was conducted, and results indicated that the parameters studied had
substantial effects on fracture patterns. Additionally, the jagged shapes of
sutures were associated with strain concentrations in the skull.
The international prevalence of legal high drugs necessitates the development of a
method for their detection and identification. Herein, we describe the development
and validation of a tetraplex multiplex real-time polymerase chain reaction (PCR)
assay used to simultaneously identify morning glory, jimson weed, Hawaiian
woodrose, and marijuana detected by high-resolution melt using LCGreen Plus((R)).
The PCR assay was evaluated based on the following: (i) specificity and
selectivityprimers were tested on DNA extracted from 30 species and simulated
forensic samples, (ii) sensitivityserial dilutions of the target DNA were prepared,
and (iii) reproducibility and reliabilitysample replicates were tested and remelted
on different days. The assay is ideal for cases in which inexpensive assays are
needed to quickly detect and identify trace biological material present on drug
paraphernalia that is too compromised for botanical microscopic identification and
for which analysts are unfamiliar with the morphology of the emerging legal high
species.
A verification methodology is described and evaluated to formally determine
uncertain linear systems stability in digital controllers with considerations to
the implementation aspects. In particular, this methodology is combined with the
digital-system verifier (DSVerifier), which is a verification tool that employs
Bounded Model Checking based on Satisfiability Modulo Theories to check the
stability of digital control systems with uncertainty. DSVerifier determines the
control system stability, considering all the plant interval variation set,
together with the Finite Word-length (FWL) effects in the digital controller
implementation; DSVerifier checks the robust non-fragile stability of a given
closed-loop system. The proposed methodology and respective tool are evaluated
considering non-fragile control examples from literature. Experimental results show
that the approach used in this study is able to foresee fragility problems in
robust controllers, which could be overlooked by other existing approaches due to
underestimating of FWL effects.
This work outlines an equation-based formulation of a digital control program and
transducer interacting with a continuous physical process, and an approach using
the Coq theorem prover for verifying the performance of the combined hybrid system.
Considering thermal dynamics with linear dissipation for simplicity, we focus on a
generalizable, physically consistent description of the interaction of the real-
valued temperature and the digital program acting as a thermostat. Of interest in
this work is the discovery and formal proof of bounds on the temperature, the
degree of variation, and other performance characteristics. Our approach explicitly
addresses the need to mathematically represent the decision problem inherent in an
analog-to-digital converter, which for rare values can take an arbitrarily long
time to produce a digital answer (the so-called Buridan's Principle); this
constraint ineluctably manifests itself in the verification of thermostat
performance. Furthermore, the temporal causality constraints in the thermal physics
must be made explicit to obtain a consistent model for analysis. We discuss the
significance of these findings toward the verification of digital control for more
complex physical variables and fields.
Catalytic oxidation at ambient temperature has drawn wide attention as a new
promising method of air cleaning, converting hazardous materials into non-hazardous
ones. However, limited information is available regarding catalytic filter
performance/characteristics under real operating conditions, especially on service
efficiency and byproducts. Also, no practical scale-up method/evidence for filter
performance evaluation is currently available to scale-up laboratory results to
real application conditions. These limitations and knowledge gaps prevent building
owners/designers from adopting this new promising technique in their
commercial/industrial applications. The present study conducted experiments from
small-scale to full-scale chamber tests which challenged a developed catalytic
filter under realistic conditions. Formaldehyde was selected for approach
demonstration due to its indoor ubiquitousness and criticality for human health
even at low-levels. Results showed that the competition level for reaction sites in
filter media had a crucial role in the performance for formaldehyde abatement, a
high initial (77%; under no competing pollutants) to a typical stable level (23-
32%), depending on the coexistence of other pollutants and moisture in the air,
that the employment of this type of filter might generate byproducts (opposite to
previous literature reports), and that small-scale column tests represented a good
indication for large-scale filter performance as a practical screening method. (C)
2017 Elsevier B.V. All rights reserved.
AIM: To study the expression of collagen I and transcription factor specificity
protein 1 (Sp1), a transforming growth factor-beta 1 (TGF-beta 1) downstream
target, and reveal the impact of the TGF-beta 1-Sp1 signaling pathway on collagen
remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were
randomly divided into normal control, form deprivation myopia (FDM), and self-
control groups. FDM was induced for different times using coverage with translucent
latex balloons and FDM recovery was performed for 1wk after 4wk treatment; then,
changes in refractive power and axial length were measured. Immunohistochemistry
and reverse transcription-polymerase chain reaction were used to evaluate dynamic
changes in collagen I and Sp1 expression in the sclera of guinea pigs with
emmetropia and experimental myopia, and the relationship between collagen I and Sp1
levels was analyzed. RESULTS: In the FDM group, the refractive power was gradually
changed (from 2.09 +/- 0.30 D at week 0 to -1.23 +/- 0.69 D, -4.17 +/- 0.59 D, -
7.07 +/- 0.56 D, and -4.30 +/- 0.58 D at weeks 2, 4, 6, and 1wk after 4wk,
respectively; P<0.05), indicating deepening of myopia. The axial length was
increased (from 5.92 +/- 0.39 mm at week 0 to 6.62 +/- 0.36 mm, 7.30 +/- 0.34 mm,
7.99 +/- 0.32 mm, and 7.41 +/- 0.36 mm at weeks 2, 4, 6, and 1wk after 4wk;
P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of the
FDM group was lower than that of the control groups (P<0.05), and the reduction was
eye-coverage time-dependent. Furthermore, correlation between Sp1 and collagen I
down-regulation in the myopic sclera was observed. CONCLUSION: Our data indicate
that transcription factor Sp1 may be involved in the regulation of type I collagen
synthesis/degradation during myopic sclera remodeling, suggesting that TGF-beta 1
signaling plays a role in the development and progression of myopia.
Trinidad and Tobago is an oil exporting small island developing state (SIDS) with a
0.12% contribution to global emissions and with important socio-economic
challenges. It has producer, electricity and transport fuel subsidies. It is at an
interesting juncture in subsidy reform: the government faces the embeddedness of
distributive justice norms that are contested by fiscal prudence and environmental
stewardship norms. The value of the paper is twofold. First it develops a subsidy
intractability framework to explain reform global narratives that highlights: the
power of agents, the nature of contested economic, justice and environmental norms
and the availability of mechanisms for reform. Second, this framework is used to
explain reform narratives and trajectories in Trinidad and Tobago using data from
public documents and from a unique elite survey of former and present heads of
state, politicians, policy makers and stakeholders. Even in conditions of falling
oil prices and national revenue and pressures to reduce emissions, where
redistributive justice arguments are heavily embedded in public discourses, those
aspects of the subsidy that have developmental or distributive justice goals are
more intractable. The results of the study have implications for carbon emission
reduction strategies in developing states with fossil fuel reserves.
The control system of moving mirror scanning is an important part of the Fourier
transform spectrometer, and its dynamic and static performance determines the
interference effect and the spectral resolution of the spectrometer. To meet the
requirement of the uniform velocity of moving mirror scanning, a completely digital
control scheme is proposed with FPGA as the key hardware, and this scheme is
applied to the moving mirror movement in the spectrometer. According to the need of
the current detection and the velocity detection, a dual closed loop control
composed of current loop and velocity loop is realized, with current loop and
velocity loop using PI control and fuzzy PID control respectively. The experiment
results show that the current curve is smooth in the uniform scan phase of moving
mirror, and that the peak current is 0.5 A in acceleration and deceleration period.
Additionally, when the angular velocity of moving mirror is 30/s in the uniform
section, the maximum relative error is less than 4%. From research results, it can
be drawn that the digital control strategy can significantly improve the velocity
stability of moving mirror, and meet the performance requirements of the control
system. (C) 2016 Elsevier GmbH. All rights reserved.
The mechanism and characteristic of current oscillation of four-quadrant converter
with predictive current controller caused by nonlinear characteristic of the system
is analyzed in the paper. With the discrete model considering the digital control
delay of the single-phase four-quadrant converter, the stability condition is
derived. Using the describing function of saturation characteristic, the frequency
and amplitude of the nonlinear oscillation is obtained. The simulation and
experiment results verify the analyses.
This paper presents the flexibility of technology FPGA in the implementation of
automatic control systems. A digital structure at level hardware of a regulator of
PI action was designed and built by the VHDL standard. Also, a Java graphical
interface was developed for monitoring and control. Experiments were performed on a
mechanism for position control consisting of DC motors with encoder, checking an
agile response to different reference values and graphing the results from the
embedded Java application in real time.
A current fed push pull converters cascaded with a buck pre-regulator is proposed.
Voltage stress of the push pull switches is reduced by buck pre regulation. Pulse
width modulation is done only to the switch in buck stage. Output voltage and the
buck inductor current is controlled using average current mode control. The closed
loop simulation of a 20W, 100V, 0.2A cascaded buck push pull converter with analog
control circuit is done using PSIM. Closed loop simulation using digital control
circuit is done by using a SIMCOUPLER module which couples power electronic circuit
in PSIM and digital control circuit in MATLAB. Further, hardware implementation of
digital controllers on two platforms is explained. Switching pulses are generated
using digital circuit are fed to the converter switches and the converter is tested
for the open loop operation.
Chemokines are a family of small cytokines that share a typical key structure that
is stabilized by disulfide bonds between the cysteine residues at the NH2-terminal
of the protein, and they are secreted by a great variety of cells in several
different conditions. Their function is directly dependent on their interactions
with their receptors. Chemokines are involved in cell maturation and
differentiation, infection, autoimmunity, cancer, and, in general, in any situation
where immune components are involved. However, their role in postfracture
inflammation and fracture healing is not yet well established. In this article, we
will discuss the response of chemokines to bone fracture and their potential roles
in postfracture inflammation and healing based on data from our studies and from
other previously published studies.
Strawberry is an ideal model for studying the molecular biology of the development
and ripening of non-climacteric fruits. Hormonal regulation of gene expression
along all these processes in strawberries is still to be fully elucidated. Although
auxins and ABA have been pointed out as the major regulatory hormones, few high-
throughput analyses have been carried out to date. The role for ethylene and
gibberellins as regulatory hormones during the development and ripening of the
strawberry fruit remain still elusive. By using a custom-made and high-quality
oligo microarray platform done with over 32,000 probes including all of the genes
actually described in the strawberry genome, we have analysed the expression of
genes during the development and ripening in the receptacles of these fruits. We
classify these genes into two major groups depending upon their temporal and
developmental expression. First group are genes induced during the initial
development stages. The second group encompasses genes induced during the final
maturation and ripening processes. Each of these two groups has been also divided
into four sub-groups according their pattern of hormonal regulation. By analyzing
gene expression, we clearly show that auxins and ABA are the main and key hormones
that combined or independently are responsible of the development and ripening
process. Auxins are responsible for the receptacle fruit development and, at the
same timeA prevent ripening by repressing crucial genes. ABA regulates the
expression of the vast majority of genes involved in the ripening. The main genes
expressed under the control of these hormones are presented and their physiological
rule discussed. We also conclude that ethylene and gibberellins do not seem to play
a prominent role during these processes.
CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been
associated with promoter methylation, consequent silencing of gene expression and
fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid
autism. Unmethylated premutation (55-199 repeats) and FM alleles have been
associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset
neurodegenerative disorder. Here we present a 33-year-old male with FXS, with white
matter changes and progressive deterioration in gait with cerebellar signs
consistent with probable FXTAS; there was no evidence of any other cerebellar
pathology. We show that he has tissue mosaicism in blood, saliva, and buccal
samples for the size and methylation of his expanded alleles and a de novo,
unmethylated microdeletion. This microdeletion involves a similar to 80 bp sequence
in the FMR1 promoter as well as complete loss of the CGG repeat in a proportion of
cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation
and CGG sizing results are consistent with the diagnosis of concurrent FXS and
probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain
the manifestation of milder than expected cognitive and behavioral impairments and
early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who
manifest symptoms of FXTAS, may benefit from more detailed laboratory testing. (C)
2016 Wiley Periodicals, Inc.
Since the devastating 2011 tornado season, there has been renewed interest in
understanding tornado wind loads and developing methodologies to reduce the risk of
tornado damage. This study focuses on the assessment of the system-level
performance of five different residential light-frame wood building archetypes
subjected to tornado winds. The system-level performance considered three critical
components along the vertical load path within each building, namely, the roof
sheathing, roof-to-wall connection, and wall-to-foundation anchorage. Although
there has been significant work on each of these components independently, combined
uplift and lateral forces have received less attention. Therefore, a laboratory
testing program for wood shear walls, reported herein, was performed to determine
the wall-failure mechanisms and capacities when subjected to combined shear and
uplift forces. Each building archetype was designed at varying locations across the
United States based on the current residential building code and/or observed
practice. Fragilities were developed, based on the assumption that failure of any
component along the vertical load path results in failure of the system. Because
the forces in each connection along the vertical load path arise from the same
tornado wind load, the connection failures are not statistically independent, and
Monte Carlo simulation was applied to perform the system reliability analysis. (C)
2017 American Society of Civil Engineers.
The antibody crystallizable fragment (Fc) is recognized by effector proteins as
part of the immune system. Pathogens produce proteins that bind Fc in order to
subvert or evade the immune response. The structural characterization of the
determinants of Fc-protein association is essential to improve our understanding of
the immune system at the molecular level and to develop new therapeutic agents.
Furthermore, Fc-binding peptides and proteins are frequently used to purify
therapeutic antibodies. Although several structures of Fc-protein complexes are
available, numerous others have not yet been determined. Protein-protein docking
could be used to investigate Fc-protein complexes; however, improved approaches are
necessary to efficiently model such cases. In this study, a docking-based
structural bioinformatics approach is developed for predicting the structures of
Fc-protein complexes. Based on the available set of X-ray structures of Fc-protein
complexes, three regions of the Fc, loosely corresponding to three turns within the
structure, were defined as containing the essential features for protein
recognition and used as restraints to filter the initial docking search. Rescoring
the filtered poses with an optimal scoring strategy provided a success rate of
approximately 80% of the test cases examined within the top ranked 20 poses,
compared to approximately 20% by the initial unrestrained docking. The developed
docking protocol provides a significant improvement over the initial unrestrained
docking and will be valuable for predicting the structures of currently
undetermined Fc-protein complexes, as well as in the design of peptides and
proteins that target Fc.
Objective This study aimed to evaluate the efficacy of the Functional Independence
Measure to assess preoperative frailty for elderly patients undergoing surgical
aortic valve replacement. Methods Eighty-five patients >65 years who survived
elective isolated aortic valve replacement from January 2008 to October 2015 were
included. The mean age at the operation was 78 +/- 6 years old (n = 28 males, n =
57 females). The patients were divided into two groups according to their status at
discharge: impossible to discharge home or hospitalization for >30 days
(compromised group, n = 8), or unaffected (unaffected group, n = 77). Preoperative
frailty was evaluated with the Functional Independence Measure, which comprises 18
items divided into six domains: self-care, sphincter control, mobility, locomotion,
communication, and social cognition. Results The preoperative total Functional
Independence Measure score was significantly lower in the compromised group (79 +/-
32) than in the unaffected group (120 +/- 9, p < 0.01). The preoperative motor
Functional Independence Measure score was significantly lower in the compromised
group (45 +/- 24) than in the unaffected group (85 +/- 9, p = < 0.01). The duration
of postoperative intubation, intensive care unit stay, and postoperative
hospitalization were significantly longer in the compromised group than in the
unaffected group (48 +/- 67 vs 16 +/- 12 h, p < 0.01; 6.7 +/- 5.3 vs 3.4 +/- 2.0
days, p < 0.01; 34 +/- 27 vs 23 +/- 11 days, p = 0.02, respectively). Conclusions
The preoperative Functional Independence Measure is effective for assessing
preoperative frailty in elderly patients undergoing aortic valve replacement in
terms of predicting operative morbidity.
Vaccine development against extracellular bacteria has been important for the
sustainability of the aquaculture industry. In contrast, infections with
intracellular pathogens remain largely an unresolved problem. Francisella
noatunensis subsp. orientalis is a Gram-negative, facultative intracellular
bacterium that causes the disease francisellosis in fish. Francisellosis is
commonly characterized as a chronic granulomatous disease with high morbidity and
can result in high mortality depending on the host. In this study, we explored the
potential of bacterial membrane vesicles (MVs) as a vaccine agent against F.
noatunensis subsp. orientalis. Bacterial MVs are spherical structures naturally
released from the membrane of bacteria and are often enriched with selected
bacterial components such as toxins and signaling molecules. MVs were isolated from
broth-cultured F. noatunensis subsp. orientalis in the present work, and proteomic
analysis by mass spectrometry revealed that MVs contained a variety of immunogenic
factors, including the intracellular growth proteins lgIC and lgIB, known to be
part of a Francisella pathogenicity island (FPI), as well as outer membrane protein
OmpA, chaperonin GroEL, and chaperone ClpB. By using flow cytometry and electron
microscopy, we observed that F. noatunensis subsp. orientalis mainly infects
myelomonocytic cells, both in vivo and in vitro. Immunization with MVs isolated
from F. noatunensis subsp. orientalis protects zebrafish from subsequent challenge
with a lethal dose of F. noatunensis subsp. orientalis. To determine if MVs induce
a typical acute inflammatory response, mRNA expression levels were assessed by
quantitative real-time PCR. Expression of tnfa, il1b, and ifng, as well as mhcii,
mpeg1.1, and ighm, was upregulated, thus confirming the immunogenic properties of
F. noatunensis subsp. orientalis-derived MVs.
To measure the nonlinear impedance of interdigital electrode-solution system, a
novel method based on free damped oscillation is proposed. A high valued active
inductance with adjustable negative resistance is constructed by an operational
amplifier. A second order oscillation system for measurement is then set up by
connecting the active inductance with the device under test. The active inductance
is designed to be around 470H to meet the measurement requirements of low
frequency. The negative resistor is utilized to adjust damping coefficient of the
oscillation system in order to obtain enough number of ring-down oscillation cycles
for parameter estimation. The free damped oscillation signal of the oscillation
system is obtained under square wave voltage excitation. After processed by Hilbert
transform, the instantaneous capacitance and resistance can be calculated
simultaneously to implement nonlinear impedance measurement. The operational
availability of the proposed method is verified by experimental results of
commercial available resistors and capacitors. The impedance nonlinearity of a gold
interdigital electrode immersed in KCl solutions of different concentration is
tested and compared with that obtained by sweep-amplitude sinusoidal excitation
methods. The results indicate that the proposed method can successfully obtain
impedance nonlinearity in half of the square wave period.
Inferring the intentions and beliefs of another is an ability that is fundamental
for social and affiliative interactions. A substantial amount of empirical evidence
suggests that making sense of another's intentional and belief states (i.e. theory
of mind) relies on exteroceptive (e.g. visual and auditory) and proprioceptive
(i.e. motor) signals. Yet, despite its pivotal role in the guidance of behaviour,
the role of the observer's interoceptive (visceral) processing in understanding
another's internal states remains unexplored. Predicting and keeping track of
interoceptive bodily states - which inform intentions and beliefs that guide
behaviour - is one of the fundamental purposes of the human brain. In this paper,
we will focus on the role of interoceptive predictions, prescribed by the free
energy principle, in making sense of internal states that cause another's
behaviour. We will discuss how multimodal expectations induced at deep (high)
hierarchical levels - that necessarily entail interoceptive predictions -
contribute to inference about others that is at the heart of theory of mind. (C)
2015 The Authors. Published by Elsevier Inc.
The light emitting diode (LED) based visible light communication (VLC) system can
provide lighting and communication simultaneously. It has attracted much
attenuation recently. As the photovoltaic cell (also known as solar cell) is
physically flexible, low cost, and easily available, it could be a good choice for
the VLC receiver (Rx). Furthermore, besides acting as the VLC Rx, the solar cell
can convert VLC signal into electricity for charging up the Rx devices. Hence, it
could be a promising candidate for the future internet-of-thing (IoT) networks.
However, using solar cell as VLC Rx is challenging, since the response of the solar
cell is highly limited and it will limit the VLC data rate. In this work, we
propose and demonstrate for the first time using pre-distortion Manchester coding
(MC) signal to enhance the signal performance of solar cell Rx based VLC. The
proposed scheme can significantly mitigate the slow response, as well as the
direct-current (DC) wandering effect of the solar cell; hence 50 times increase in
data rate can be experimentally achieved.
Freedom is one of the central values in political and moral philosophy. A number of
theorists hold that freedom (or, relatedly, opportunity) should either be the only
or at least one of the central distribuenda in our theories of distributive
justice. Moreover, many follow Mill and hold that a concern for personal freedom
should guide, and limit, how paternalist public policy can be. For the most part,
theorists have focussed on a person's freedom at one specific point in time but
have failed to give proper attention to freedom across time. Given that we care
about personal freedom now, we have reason to care about future freedom too. But
what kind of distribution of freedom across a person's lifetime should we promote
as a matter of legislation and public policy? I argue that none of the candidate
principles for the distribution of freedom across time is plausible. Neither a
starting gate view, nor a maximisation nor a sufficientarian view is satisfactory,
because none adequately reflects our various reasons to value freedom. I show that
this result presents a tough challenge for theories of distributive justice and
paternalism that set great store by personal freedom.
A grid-connected inverter is indispensable for photovoltaic power generation and
smart grid systems, and it must be designed for stable operation. The impedance
method based on the Nyquist criterion is often utilized to analyze the stability of
grid-connected inverter systems. The impedance method is based on the eigenvalues
of the product of the inverter output admittance and the line impedance matrices in
the frequency domain. However, the frequency characteristics have so far been
derived only for inverters with analog control systems. A new frequency analysis
method for inverters with digital control systems is proposed in this paper. First,
a stability analysis example for a three-phase LCL-type inverter controlled
digitally is shown and the results are compared and validated with those by
simulation using a Saber simulator. Finally, they are also compared and validated
with experimental results digitally controlled by a DSP-based system. (C) 2017
Wiley Periodicals, Inc.
Background and ObjectivesVariant RHD genes associated with the weak D phenotype can
result in complete or partial D-epitope expression on the red cell. This study
examines the genetic classification in Australian blood donors with a weak D
phenotype and correlates RHD variants associated with the weak D phenotype against
D-epitope profile. Materials and MethodsFollowing automated and manual serology,
blood samples from donors reported as weak D' (n = 100) were RHD genotyped by a
commercial SNP-typing platform and Sanger sequencing. Two commercial anti-D
antibody kits were used for extended serological testing for D-epitope profiles.
ResultsThree samples had wild-type RHD exonic sequences, and 97 samples had RHD
variants. RHD*weak D type 1, RHD*weak D type 2 or RHD*weak D type 3 was detected in
75 donors. The remaining 22 samples exhibited 17 different RHD variants. One donor
exhibited a novel RHD*c.939+3A>C lacking one D-epitope. Weak D types 11, 5, 15, 17
and 90 showed a partial D-epitope profile. ConclusionThe array of RHD variants
detected in this study indicated diversity in the Australian donor population that
needs to be accommodated for in future genotyping strategies.
Aims: This study explored the sex-specific associations between friendship trust
and the psychological well-being of young Swedes from late adolescence to early
adulthood. Methods: A random sample of native Swedes born in 1990 was surveyed at
age 19 years and again at age 23 years regarding their own well-being and their
relationships with a maximum of five self-named peers. The response rate was 31.3%,
resulting in 782 cases to be analysed. We used sex-stratified structural equation
models to explore the associations between trust and well-being. Psychological
well-being was constructed as the latent variable in the measurement part. The
structural part accounted for the autocorrelation of trust with respect to well-
being over time and incorporated the cross-lagged effects between late adolescence
and early adulthood. Results: It was found that trust increased while well-being
decreased for young men and remained stable for young women from 19 to 23 years of
age. The young women reported lower well-being at both time points, whereas no sex
difference was found for trust. Based on model fit comparisons, a simple model
without forward or reward causation was accepted for young men, whereas reversed
causation from well-being to trust was suggested for young women. Subsequent
analysis based on these assumptions confirmed the reversed effect for young women.
Conclusions: The findings suggest that young people do not benefit from trustful
social relations to the same extent as adult populations. Young women who express
impaired well-being run a greater risk of being members of networks characterized
by low friendship trust over time.
Background Friendships between people with and without intellectual disability
remain elusive. Little is known about factors that support the development of such
friendships and what services can do to promote the likelihood that contact will
develop into friendship.Method A case study approach was used to explore the
qualities and development of a long-term friendship between 2 women, 1 of whom has
severe intellectual disability. Qualitative methods of data collection and analysis
were used including interviews and field notes from participant
observation.Findings The relationship progressed through 3 stages of introduction,
consolidation, and autonomy supported by the working practices and culture of the
disability support organisation. Individualised activity, the role of a connector,
and a culture of positive expectations underpinned the growth of the
friendship.Conclusions Friendships do not happen by chance but require thought,
attention, dedicated resources, and commitment to long-term outcomes to be
achieved.
Wood frogs (Rana sylvatica) are highly susceptible to infection with Frog virus 3
(FV3, Ranavirus, Iridoviridae), a cause of mass mortality in wild populations. To
elucidate the pathogenesis of FV3 infection in wood frogs, 40 wild-caught adults
were acclimated to captivity, inoculated orally with a fatal dose of 10(4.43)
pfu/frog, and euthanized at 0.25, 0.5, 1, 2, 4, 9, and 14 days postinfection (dpi).
Mild lesions occurred sporadically in the skin (petechiae) and bone marrow
(necrosis) during the first 2 dpi. Severe lesions occurred 1 to 2 weeks
postinfection and consisted of necrosis of medullary and extramedullary
hematopoietic tissue, lymphoid tissue in spleen and throughout the body, and
epithelium of skin, mucosae, and renal tubules. Viral DNA was first detected
(polymerase chain reaction) in liver at 4 dpi; by dpi 9 and 14, all viscera tested
(liver, kidney, and spleen), skin, and feces were positive. Immunohistochemistry
(IHC) first detected viral antigen in small areas devoid of histologic lesions in
the oral mucosa, lung, and colon at 4 dpi; by 9 and 14 dpi, IHC labeling of viral
antigen associated with necrosis was found in multiple tissues. Based on IHC
staining intensity and lesion severity, the skin, oral, and gastrointestinal
epithelium and renal tubular epithelium were important sites of viral replication
and shedding, suggesting that direct contact (skin) and fecal-oral contamination
are effective routes of transmission and that skin tissue, oral, and cloacal swabs
may be appropriate antemortem diagnostic samples in late stages of disease (>1 week
postinfection) but poor samples to detect infection in clinically healthy frogs.
Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a
hemideletion in chromosome 7, which manifests a distinct behavioral phenotype
characterized by a hyperaffiliative social drive, in striking contrast to the
social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI
studies have observed structural and functional abnormalities in WS cortex,
including the prefrontal cortex (PFC), a region implicated in social cognition.
This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique
resource that comprises the largest WS postmortem brain collection in existence,
and is the first to quantitatively examine WS PFC cytoarchitecture. We measured
neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10
and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in
six matched pairs of WS and typically developing (TD) controls. Neuron density in
PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest
decrease in density, reaching statistical significance in BA 10. In contrast, BA 3
and BA 18 demonstrated a higher density in WS compared to TD, although this
difference was not statistically significant. Neuron density in BA 4 was similar in
WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared
to be most affected. Neuron density is also altered in the PFC of individuals with
ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental
disorders associated with sociobehavioral alterations. Autism Res2017, 10: 99-112.
(c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Background: Anterior encephalocele (AE) is a rare congenital anomaly of the central
nervous system which is thought to be associated with genetic defects in folate
metabolism. Methods: This case-control study investigated the interactions of
methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-1958G>A (rs2236225) and the
methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133) and 1298A>C
(rs1801131) polymorphisms with the risk of AE in the Northeast Indian population. A
total of 40 AE cases and 80 controls were investigated using polymerase chain
reaction-restriction fragment length polymorphism technique. Results: MTHFR 1298CC
was significantly associated with AE risk (odds ratio [OR] 4.21; p = 0.01). The
MTHFR haplotypes 677C-1298C/677T-1298A (OR, 2.50) and 677T-1298C (OR, 2.86)
conferred risk in a progressive manner ((2) = 9.82; pA was not associated with
disease susceptibility. Children with the rs2236225 GA and the rs1801131 CC
genotypes were at an increased risk as compared to the reference genotype of
rs2236225 GG and rs1801131 AA (OR, 14.4; p = 0.02). Children with the rs2236225 GG
and rs1801133 CT genotypes were also at an elevated risk (OR, 4.76; p = 0.01). The
MTHFD1 polymorphism together with the MTHFR haplotypes elevated risk in a
progressive manner (chi(2) = 6.29; p = 0.01). Conclusion: The data support our
hypothesis of gene-gene interaction between MTHFD1 and MTHFR and the risk of AE.
Together with the MTHFR haplotypes, MTHFD1 elevates risk in a progressive manner.
The minor allelic frequencies of the MTHFD1 1958G>A and MTHFR 1298A>C in our
populations were similar to those reported from Southeast Asian population,
suggesting a possible explanation for the prevalence of this malformation in these
regions. (C) 2017 Wiley Periodicals, Inc.
Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly
prevalent and may complicate clinical management of these patients. Purpose of the
present article is to present and discuss available data about the pharmacological
treatment of psychiatric symptoms in patients with FTD. A research in the main
database sources has been conducted to obtain an overview of the pharmacological
management of psychiatric symptoms in patients with FTD. The search strategy
included the following termsFTD and psychiatry, FTD and behavioural disturbances,
and FTD and treatment. Pathophysiology of psychiatric symptoms in FTD is different
from other types of dementia. Although drugs for Alzheimer disease appear to be
ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence
supports a possible usefulness of serotonergic antidepressants for these patients.
Data are too scanty to draw definitive conclusions, but antidepressant treatment,
particularly with serotonergic compounds, may improve psychiatric symptoms in
patients with FTD. Large observational studies are needed to confirm this
preliminary evidence, and a lot of effort and collaboration between neurologists
and psychiatrists will be definitely crucial for future research of effective
treatments for FTD.
Frontotemporal dementia is a neurodegenerative disease affecting cognition and
behavior in multiple devastating ways. This article highlights diagnostic features
helpful in differentiating frontotemporal dementia from other dementias, most
commonly Alzheimer disease.
Using structural MRI, we investigated the brain substrates of both affective and
cognitive theory of mind (ToM) in 19 patients with semantic dementia. We also ran
intrinsic connectivity analyses to identify the networks to which the substrates
belong and whether they are functionally disturbed in semantic dementia. In line
with previous studies, we observed a ToM impairment in patients with semantic
dementia even when semantic memory was regressed out. Our results also highlighted
different neural bases according to the nature (affective or cognitive) of the
representations being inferred. The affective ToM deficit was associated with
atrophy in the amygdala, suggesting the involvement of emotion-processing deficits
in this impairment. By contrast, cognitive ToM performances were correlated with
the volume of medial prefrontal and parietal regions, as well as the right frontal
operculum. Intrinsic connectivity analyses revealed decreased functional
connectivity, mainly between midline cortical regions and temporal regions. They
also showed that left medial temporal regions were functionally isolated, a further
possible hindrance to normal social cognitive functioning in semantic dementia.
Overall, this study addressed for the first time the neuroanatomical substrates of
both cognitive and affective ToM disruption in semantic dementia, highlighting
disturbed connectivity within the networks that sustain these abilities.
An experimental study was conducted to investigate the influence of FRP confinement
on the buckling behavior of longitudinal steel reinforcing bars (rebars) in RC
columns subjected to monotonic and cyclic axial compression. Test results of 12
FRP-confined RC columns and 12 FRP-confined plain concrete columns (control
specimens) are presented with particular attention to the evolution of strains in
the longitudinal steel rebars and the FRP jacket as the load increases. For an FRP-
confined RC column subjected to monotonic axial compression, the contribution of
longitudinal steel rebars to the overall axial load carried by the column was
deduced by subtracting the contribution of the FRP-confined plain concrete from the
total axial load. The test results showed that the compressive stress-strain
response of longitudinal steel rebars in FRP-confined RC columns follows that from
tensile testing before the axial stress reduces gradually due to the onset of
buckling deformation. Significant interactions were found to exist between FRP
confinement and the buckling of longitudinal steel rebars. This interaction should
be carefully considered when formulating constitutive laws for both the
longitudinal steel rebars and the FRP-confined concrete for use in theoretical
modeling. (C) 2017 Elsevier Ltd. All rights reserved.
The present study examines the moderating role of unconditional self acceptance and
self esteem in relation to frustration intolerance beliefs and psychological
distress. Participants were one hundred and fifty student (aged 18-25) studying at
three universities (COMSATS Institute of Information Technology, University of
Management Sciences, and University of Central Punjab) of Lahore, Pakistan. They
completed a demographic information sheet, the Frustration Discomfort Scale
(Harrington in Clin Psychol Psychother 12:374-387, 2005a), the Rosenberg Self-
Esteem Scale (Rosenberg in Society and the adolescent self image. Princeton
University Press, Princeton, 1965), the Unconditional Self Acceptance Questionnaire
(Chamberlain and Haaga in J Ration Emotive Cogn Behav Ther 19:163-176, 2001a), and
the General Health Questionnaire (Goldberg in Manual of the General Health
Questionnaire. NFERNelson, Great Britain, 1972). The results demonstrated the
moderating effects of unconditional self acceptance and self esteem in the
relationship between frustration intolerance beliefs (entitlement, achievement,
emotional intolerance, and discomfort intolerance) and psychological distress . The
present findings highlight the importance unconditional self acceptance that
reduces the emotional problems of students hindering their educational and personal
growth.
Fucoidan, a sulfated marine polysaccharide, has many potential biological
functions, including anticancer activity. Recently, fucoidan has been reported to
target P-selectin expressed on metastatic cancer cells. Increasing research
attention has been devoted to the developments of fucoidan-based nanomedicine.
However, the application of traditional chitosan/fucoidan nanoparticles in
anticancer drug delivery may be limited due to the deprotonation of chitosan at a
pH greater than 6.5. In this study, a mutlistimuli-responsive nanoparticle self-
assembled by fucoidan and a cationic polypeptide (protamine) was developed, and
their pH-/enzyme-responsive properties were characterized by circular dichroism
(CD) spectroscopy, dynamic light scattering (DLS), and zeta potential analysis.
Enzymatic digestion and acidic intracellular microenvironment (pH 4.5-5.5) in
cancer cells triggered the release of an anticancer drug (doxorubicin) from the
nanoparticles. The protamine/fucoidan complex nanoparticles with P-selectin
mediated endocytosis, charge conversion and stimuli-tunable release properties
showed an improved inhibitory effect against a metastatic breast cancer cell line
(MDA-MB-231). (C) 2017 Elsevier Ltd. All rights reserved.
Recent advances in thermoelectric technology have made exhaust-based thermoelectric
generators (TEGs) promising for recovery of waste heat. Utilization of exhaust-
based TEGs in heavy-duty vehicles was studied in this work. Given that the
generated power is limited, the alternator is still indispensable. To improve the
fuel economy, the generated electricity must be integrated into the automotive
electrical system and consumed by electrical loads. Therefore, two feasible ways of
integrating the generated electricity into the automotive electrical system are
discussed: one in which the original alternator works only under certain
conditions, i.e., the "thermostat" strategy, and another in which a smaller
alternator is adopted and works together with the TEG, i.e., the "cooperative work"
strategy. The overall performance and efficiency are obtained through simulation
analysis. The simulation results show that both methods can improve the fuel
economy, but the former provides better results. Moreover, if the electrical loads
can be properly modified, the fuel economy is further improved. These simulation
results lay a solid foundation for application of TEGs in vehicles in the future.
The ultrarapid underpass (URUP) tunneling method, in which a shield machine is
launched and received at the ground surface level, has been developed for tunneling
in congested areas. This paper reports monitoring results of a full-scale test
conducted for the first URUP tunneling project in China. In the investigation,
special attention was paid to tunneling phases in which the shield machine was
buried super-shallowly or partially above the ground surface. The paper focuses on
the tunneling-induced soil movements and on the grouting process. Measurement
results indicated that surface settlements can be represented by the commonly used
Gaussian function regardless of the cover depth, and that the load-factor approach
provides a fair prediction of the volume loss. A contracting transverse soil-
displacement field was identified as the dominating pattern, although an expanding
displacement field was observed at several locations. Pressure measurements were
used to identify a time-dependent response of the grouting process.
In this paper a novel high-frequency fully differential pure current mode current
operational amplifier (COA) is proposed that is, to the authors' knowledge, the
first pure MOSFET Current Mode Logic (MCML) COA in the world, so far. Doing fully
current mode signal processing and avoiding high impedance nodes in the signal path
grant the proposed COA such outstanding properties as high current gain, broad
bandwidth, and low voltage and low-power consumption. The principle operation of
the block is discussed and its outstanding properties are verified by HSPICE
simulations using TSMC CMOS technology parameters. Pre-layout and Post-layout both
plus Monte Carlo simulations are performed under supply voltages of to investigate
its robust performance at the presence of fabrication non-idealities. The pre-
layout plus Monte Carlo results are as; 93 dB current gain, phase margin, 137 dB
CMRR, 13 input impedance, output impedance and 1.37 mW consumed power. Also post-
layout plus Monte Carlo simulation results (that are generally believed to be as
reliable and practical as are measuring ones) are extracted that favorably show(in
abovementioned order of pre-layout) 88 dB current gain, phase margin and 96 dB
CMRR, input impedance, output impedance and only 1.43 mW consumed power. These
results altogether prove both excellent quality and well resistance of the proposed
COA against technology and fabrication non-idealities.
This paper presents a dual band Digitally-Controlled-Oscillator (DCO) based on
Ring-Oscillators (RO) topology with differential input/output at 1.45 GHz is
proposed. The circuit has two frequency band which switches by a digital mode bit.
Switching between two bands of DCO, will change delay path and power consumption
during the run time. A new Source-Coupled-Logic (SCL) based reconfigurable delay
element with Schmitt-Trigger (ST) characteristic is used in each stage and 6 bits
digital code control their current tails. Power consumption profile with frequency
in each band has a steady regime. The proposed designs are fully differential,
which is appropriate for low jitter high performance applications. The proposed DCO
is simulated by spice with CMOS standard 0.18 mu m @ 1.8 v supply. The frequency,
power consumption and jitter in lower band are 455.2 MHz to 505.1 MHz, 1.98 mW (at
455 MHz), 6.04 ps (at 505.1 MHz) and for upper band are from 1.39 MHz to 1.45 MHz,
9.7 mW (at 1.39 GHz) and 3.48 ps (at 1.45 MHz), sequentially. In this paper also
circuit analysis of proposed DCO, delay calculation and comparison and analytical
equation for frequency bands are obtained. Also, Monte Carlo and PVT test shows
acceptable frequency tolerance.
When interpreting results of a functional analysis, a clinician may conclude an
automatic function either because problem behavior is elevated in the alone/ignore
condition relative to other conditions or because problem behavior is elevated and
undifferentiated across multiple conditions. In the latter, it is difficult to
determine if problem behavior is maintained by automatic reinforcement alone or is
multiply maintained. The current study tested for multiply-maintained self-
injurious behavior exhibited by two participants by implementing functional
analysis contingencies while controlling for automatic reinforcement through
sensory extinction. Results suggest that self-injury was maintained by automatic
reinforcement alone for one participant and both automatic reinforcement and
physical attention for another participant. These results were then used to create
function-based treatments for self-injury that were successfully generalized across
settings and caregivers.
Multiferroic materials have attracted the attention of scientific community all
over the world due to smart functionality and attractive applications such as in
magnetoelectric memory and magnetoelectric sensors. In this paper, we report on the
ferroelectric, magnetic and magnetoelectric properties of microwave sintered BiFeO3
(BFO) and Bi0.90La0.10Fe0.95Mn0.05O3 (BLFMO) ceramics. The ferromagnetic and
paramagnetic components have been deconvoluted using standard magnetization
equation. The ferromagnetic saturation and paramagnetic susceptibility for BFO are
found to be 0.046 emu/g and 1.17 x 10(-5) emu/g.Oe respectively. The magnetization
in BLFMO increases enormously as compared to BFO due to suppression of cycloid
spin. The magnetoelectric voltage coefficient for BFO is 3.37 mV/cm.Oe, while for
BLFMO it is 10.11 mV/cm.Oe. As compared to BFO, BLFMO exhibits improved
ferroelectric, magnetic and magnetoelectric properties. (C) 2017 Elsevier B.V. All
rights reserved.
Similarity search and related issues are current topic in databases. Over the last
ten years more then 6500 papers dealing with similarity in databases were published
according to Web of Science. The rising in the number of articles in the recent
years shows that the research in this direction is still in its early stage. From
the wide range of topics related with similarities in databases, one received a
considerable attention already, namely functional dependencies which take
similarities into account. Our main concern in this paper is to review and
critically examine the existing work on this topic. (C) 2016 Elsevier B.V. All
rights reserved.
Functional electrical stimulation has been widely used for the restoration of
bladder functions after spinal cord injury or other neurological disorders.
However, most of the neuroprostheses for bladder control are still imperfect due to
lack of the feedback information about the state of the controlled bladder. The
purpose of this study is to develop an implantable system which allows us to
stimulate the nerves and record the nerve signals related to the condition of the
bladder. The proposed stimulator consists of three parts: a digital-to-analog
converter (DAC), a current driver, and a switch network. Using the same current
source with a switch network eliminates the need for separate current sources for
anodic and cathodic sections and reduce the need for interconnect lines of control
signals which is an area-saved and power-efficient configuration. A symmetrical
regulated cascode current driver is used to implement a high voltage compliance and
a high output impedance which improves its ability with load. The amplitude,
frequency and the pulse width of the stimulating current are adjusted by encoding
the DAC and switch sequences, respectively. In addition, we also present two-stage
fully differential capacitively-coupled amplifiers for neural recording. The neural
amplifier's parameters are carefully chosen according to the characteristics of
neural signal; meanwhile, we analyzed theoretically the main noise sources,
especially the pseudo-resistor in the feedback path which gives little attention by
previous studies. The integrated neural stimulating and recording frontend for
bladder control prosthesis has been designed and simulated, using a TSMC's 0.18-mu
m CMOS process. The proposed stimulator can provide a symmetrical cathodic-first
biphasic current pulse with interphasic gap, a low headroom voltage of 0.168 V
corresponding to 2.48 mA full-scale current, an adjustable pulse width of 100-500
mu s and frequency of 1-40 Hz. The recording amplifier with a low input-referred
noise of 3.62 mu V, an NEF of 3.88 and a low power dissipation of 7.2 mu W has a
gain of 61.6 dB and a frequency bandwidth from 300 Hz to 5.3 kHz. Both circuit
analysis and simulations are presented to examine the performance of the proposed
designs.
The transcript pool of a plant part, under any given condition, is a collection of
mRNAs that will pave the way for a biochemical reaction of the plant to stimuli.
Over the past decades, transcriptome study has advanced from Northern blotting to
RNA sequencing (RNA-seq), through other techniques, of which real-time quantitative
polymerase chain reaction (PCR) and microarray are the most significant ones. The
questions being addressed by such studies have also matured from a solitary process
to expression atlas and marker-assisted genetic enhancement. Not only genes and
their networks involved in various developmental processes of plant parts have been
elucidated, but also stress tolerant genes have been highlighted. The transcriptome
of a plant with altered expression of a target gene has given information about the
downstream genes. Marker information has been used for breeding improved varieties.
Fortunately, the data generated by transcriptome analysis has been made freely
available for ample utilization and comparison. The review discusses this wide
variety of transcriptome data being generated in plants, which includes
developmental stages, abiotic and biotic stress, effect of altered gene expression,
as well as comparative transcriptomics, with a special emphasis on microarray and
RNA-seq. Such data can be used to determine the regulatory gene networks, which can
subsequently be utilized for generating improved plant varieties.
Psychopathological symptoms and cognitive impairment are related to psychosocial
functioning. However, the nature of the association of cognitive impairment with
psychosocial functioning still remains under scrutiny. We aimed to examine the
relationships of premorbid adjustment, lifetime psychopathological dimensions, and
cognitive performance with the typical level of psychosocial functioning during the
previous year. We assessed ninety patients with schizophrenia spectrum disorders
and affective disorders with psychotic symptoms to collect data on premorbid
adjustment, lifetime psychopathological dimensions, cognitive performance and
psychosocial functioning. Sixty-five healthy volunteers were included as controls.
Pearson's correlations and hierarchical regression analyses were performed to
ascertain to what extent the aforementioned variables predicted psychosocial
functioning. Functional domains were significantly correlated with most of the
premorbid features, lifetime psychopathological dimensions and cognitive domains.
However, lifetime negative symptoms were the best predictors of psychosocial
functioning in the hierarchical regression analyses (explaining between 47 and 64%
of the variance). For psychosocial outcome in patients with psychoses, lifetime
negative symptoms showed a stronger predictive validity than cognitive impairment
or premorbid adjustment. (C) 2016 Elsevier B.V. All rights reserved.
The Cognitive Assessment Interview (CAI) is an interview-based instrument to assess
cognition considering the impact of cognitive impairment on daily activities. We
aimed to explore the associations of the Spanish version of the CAI (CAI-Sp) with a
neuropsychological battery and a measure of psychosocial functioning in psychosis.
The sample consisted of fifty-six first episode psychosis (FEP) patients and 66
non-FEP patients, who were assessed with a neuropsychological battery, the CAI-Sp
and the Short Disability Schedule (DAS-S). Patients also underwent clinical
assessment. Additionally, 37 controls were assessed with the neuropsychological
battery and CAI-Sp, for normalization purposes. The results showed that CAI-Sp
scores were overall correlated with the neuropsychological battery in non-FEP
patients. In FEP patients, we found fewer significant correlations. Most
associations were maintained after controlling for clinical symptoms. CAI-Sp rater
scores contributed to the variance in the DAS-S scores in both groups, as did
negative and disorganized symptoms. The CAI-Sp may be a good instrument to assess
cognition in non-FEP patients. In FEP patients, it was less effective in capturing
cognitive impairments and their functional consequences, probably because cognitive
deficits have yet to become evident, due to the recency of illness onset, and no
functional disturbances were observed due to these cognitive impairments. (C) 2016
Elsevier B.V. All rights reserved.
This paper pays attention to predicting the nonlinear bending behaviors of
functionally graded materials (FGM) infinite cylindrical shallow shells with a two-
parameter elastic foundation by using a two-step perturbation method. The shells
are subjected to uniform temperature rise and temperature dependency of the
constituents is also taken into account. Two ends of the shells are assumed to be
clamped or pinned and in-plane boundary conditions are immovable. The governing
equations are derived based on physical neutral surface concept and high order
shear deformation theory. The explicit expressions between the transverse load and
the deflection are obtained by perturbation method. In numerical examples, some
comparisons are shown to verify the correctness of the present research and
solution method. It can be concluded that FGM cylindrical shallow shells subjected
to uniform bending loadings will bring about snap-through buckling and jump
changes, and the foundation can enhance the stability of the shells. (C) 2017
Elsevier Ltd. All rights reserved.
Objective: Social and role functioning are compromised for the majority of
individuals at ultra-high risk of psychosis, and it is important to identify
factors that contribute to this functional decline. This study aimed to investigate
social cognitive abilities, which have previously been linked to functioning in
schizophrenia, as potential factors that impact social, role and global functioning
in ultra-high risk patients. Method: A total of 30 ultra-high risk patients were
recruited from an established at-risk clinical service in Melbourne, Australia, and
completed a battery of social cognitive, neurocognitive, clinical and functioning
measures. We examined the relationships between all four core domains of social
cognition (emotion recognition, theory of mind, social perception and attributional
style), neurocognitive, clinical and demographic variables with three measures of
functioning (the Global Functioning Social and Role scales and the Social and
Occupational Functioning Assessment Scale) using correlational and multiple
regression analyses. Results: Performance on a visual theory of mind task (visual
jokes task) was significantly correlated with both concurrent role (r=0.425,
p=0.019) and global functioning (r=0.540, p=0.002). In multivariate analyses, it
also accounted for unique variance in global, but not role functioning after
adjusting for negative symptoms and stress. Social functioning was not associated
with performance on any of the social cognition tasks. Conclusion: Among specific
social cognitive abilities, only a test of theory of mind was associated with
functioning in our ultra-high risk sample. Further longitudinal research is needed
to examine the impact of social cognitive deficits on long-term functional outcome
in the ultra-high risk group. Identifying social cognitive abilities that
significantly impact functioning is important to inform the development of targeted
intervention programmes for ultra-high risk individuals.
The purpose of this study was to ascertain whether uses of music partially mediate
the link between personality and music preference. Undergraduate students (N = 122)
completed the following scales: The Brief Big Five Inventory, The Uses of Music
Inventory, The Short Test of Music Preference, The Life Orientation Test Revised,
The Beck Depression Inventory, and the Perceived Stress Scale. Openness to
experience positively predicted preferences for reflective-complex (RC; e.g.,
jazz/blues) and intense-rebellious (IR; e.g., rock/metal) music and was inversely
related to upbeat-conventional (UC; e.g., country/pop) music, whereas extraversion
was positively related to preferences for energetic-rhythmic (ER; e.g., rap/soul)
and UC genres. A link between trait optimism and ER music preference was fully
mediated by the more prominent extraversion trait. The relationship between
openness to experience and RC music preference was partially mediated by cognitive
uses of music, with a marginally significant analysis indicating partial mediation
of emotional uses of music for openness to experience and IR music preference.
Trait neuroticism, perceived stress, and depression scores all correlated
positively with emotional uses of music. The current findings support studying
personality contextually alongside uses of music when investigating music
preference and shed light on how negative affect may inform emotional uses of
music.
Perturbations to the colonization process of the human gastrointestinal tract have
been suggested to result in adverse health effects later in life. Although much
research has been performed on bacterial colonization and succession, much less is
known about the other two domains of life, archaea, and eukaryotes. Here we
describe colonization and succession by bacteria, archaea and microeukaryotes
during the first year of life (samples collected around days 1, 3, 5, 28, 150, and
365) within the gastrointestinal tract of infants delivered either vaginally or by
cesarean section and using a combination of quantitative real-time PCR as well as
16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to
all three domains of life were detectable in all of the collected meconium samples.
The microeukaryotic community composition fluctuated strongly over time and early
diversification was delayed in infants receiving formula milk. Cesarean section-
delivered (CSD) infants experienced a delay in colonization and succession, which
was observed for all three domains of life. Shifts in prokaryotic succession in CSD
infants compared to vaginally delivered (VD) infants were apparent as early as days
3 and 5, which were characterized by increased relative abundances of the genera
Streptococcus and Staphylococcus, and a decrease in relative abundance for the
genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was
detected as early as day 5 postpartum in CSD infants, causing a significantly
increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD
infants. Although the delivery mode appeared to have the strongest influence on
differences between the infants, other factors such as a younger gestational age or
maternal antibiotics intake likely contributed to the observed patterns as well.
Our findings complement previous observations of a delay in colonization and
succession of CSD infants, which affects not only bacteria but also archaea and
microeukaryotes. This further highlights the need for resolving bacterial,
archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial
colonization and succession within the neonatal gastrointestinal tract.
P>Sucrose exuded by plants into the rhizosphere is a crucial component for the
symbiotic association between the beneficial fungus Trichoderma and plant roots. In
this article we sought to identify and characterize the molecular basis of sucrose
uptake into the fungal cells. Several bioinformatics tools enabled us to identify a
plant-like sucrose transporter in the genome of Trichoderma virens Gv29-8 (TvSut).
Gene expression profiles in the fungal cells were analyzed by Northern blotting and
quantitative real-time PCR (qRT-PCR). Biochemical and physiological studies were
conducted on Gv29-8 and fungal strains impaired in the expression of TvSut. TvSut
exhibits biochemical properties similar to those described for sucrose symporters
from plants. The null expression of tvsut caused a detrimental effect on fungal
growth when sucrose was the sole source of carbon in the medium, and also affected
the expression of genes involved in the symbiotic association. Similar to plants,
T. virens contains a highly specific sucrose/H+ symporter that is induced in the
early stages of root colonization. Our results suggest an active sucrose
transference from the plant to the fungal cells during the beneficial associations.
In addition, our expression experiments suggest the existence of a sucrose-
dependent network in the fungal cells that regulates the symbiotic association.
Pathogenic isolates of Fusarium oxysporum applied on a non-host plant species, as
soil-borne nonpathogenic isolates, are able to protect this plant against
pathogenic strains inducing wilts. Several modes of action contribute to the
biocontrol activity of these protective strains; however the genetic basis of the
biocontrol mechanisms is far from being understood. The aim of this study was to
identify genes involved in biocontrol activity of F. oxysporum using an original
model made of Fom24, a strain protective on tomato and its mutant rev157 which has
lost its protective capacity. A Rapid Subtractive Hybridization (RaSH) approach was
chosen to identify genes up-regulated in the protective or in the non-protective
interaction when germinated conidia of either Fom24 or rev157 are confronted to
tomato cell cultures. A total of 86 up-regulated sequences were generated, 42 and
44 from the protective and the non-protective interaction respectively. Homology
searches led to identification of both plant and fungal genes that were grouped
according to their putative functions. Among plant genes, those involved in plant
response to stresses were the most abundant. Expression profiles of genes homolog
to a basic endochitinase, a ferredoxine-NADP(H) reductase (FNR), an ATP synthase
and the RPM1-interacting protein 4 (RIN4) were confirmed by Northern blotting. A
large proportion of fungal sequences were encoding genes of unknown function; among
other, those involved in response to oxidative stress and a gene putatively
encoding an enolase are the most promising to further study their potential role in
the protective interaction between F. oxysporum and tomato. (C) 2011 Elsevier Ltd.
All rights reserved.
Fusarium head blight (FHB), mainly caused by Fusarium graminearum species complex
(FGSC) and also by other species of this genus, is one of the most destructive
cereal diseases with high yield losses and mycotoxin contamination worldwide. The
aim of this study was to identify Fusarium species, characterize their virulence
factors such as trichothecene genotypes and cell wall degrading enzymes (CWDEs),
and also investigate virulence of the isolates obtained from wheat plants with FHB
symptoms in Golestan province of Iran. Among 41 isolates tested, 24 were F.
graminearum sensu stricto (s.s.), six were F. proliferatum, four were F. culmorum,
three isolates belonged to each of F. subglutinans and F. meridionale species and
one isolate of F. asiaticum was identified. Among Fusarium isolates, the nivalenol
(NIV) genotype could be found more frequently, followed by 3-acetyl deoxynivalenol
(3-ADON) and 15-acetyl deoxynivalenol (15-ADON) genotypes. Production of
trichothecenes in autoclaved rice cultures was analyzed by gas chromatography (GC)
and confirmed by GC-MS. The mean levels of NIV, 3-ADON and 15-ADON produced by
Fusarium spp. were 824, 665 and 622 mu g kg(-1), respectively. All Fusarium
isolates were capable of producing CWDEs, mainly cellulase and xylanase. Lipase and
pectinase activities appeared later and at less quantities. In overall, the
isolates FH1 of F. graminearum and FH8 of F. proliferatum showed the maximum
activity of CWDEs, which was correlated with high level of their virulence and
aggressiveness on wheat. On the other hand, correlation was observed between the
level and type of trichothecene produced by each isolate and its virulence on
wheat. Virulence of trichothecene producing isolates was higher than that of non-
trichothecene producing isolates. Our results suggested that CWDEs and
trichothecenes, as virulence factors, have considerable roles on virulence and
aggressiveness of the pathogen. This is the first report on the effect of
trichothecenes and CWDEs on virulence and aggressiveness of Fusarium spp.
associated with FHB disease in wheat growing regions of Iran.
Fusarium wilts of strawberry, caused by Fusarium oxysporum f. sp. fragariae, is a
serious soil-borne disease. Fusarium wilt causes dramatic yield losses in
commercial strawberry production and it is a very stubborn disease to control.
Reliable chemical control of strawberry Fusarium wilt disease is not yet available.
Moreover, other well-known F. oxysporum have different genetic information from F.
oxysporum F.. sp. fragariae. This analysis investigates the genetic diversity of
strawberry Fusairum wilt pathogen. In total, 110 pathogens were isolated from three
major strawberry production regions, namely Sukok, Hadong, Sancheong in Gyeongnam
province in South Korea. The isolates were confirmed using F. oxysporum f. sp.
fragariae species-specific primer sets. Polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) analyses were executed using the internal
transcribed spacer, intergenic spacer, translation elongation factorl-alpha, and
beta-tubulin genes of the pathogens and four restriction enzymes: AluI, HhaI and
Hpy1I. Regarding results, there were diverse patterns in the three gene regions
except for the beta-tubulin gene region. Correlation analysis of strawberry
cultivation region, cultivation method, variety, and phenotype of isolated
pathogen, confirmed that genetic diversity depended on the classification of the
cultivated region.
IntroductionDetection of recurrent genetic abnormalities is of great significance
for a refined diagnosis and assessment of prognosis in leukemia. Conventional
nested reverse transcription PCR is labor intensive and time-consuming. MethodsWe
have developed a novel dual-color TaqMan probe-based real-time PCR method for the
simultaneous screening of 45 fusion transcripts in 12 parallel reactions. The
method was tested and validated with cell lines carrying known fusion transcripts
and patient samples. ResultsA multiplex real-time PCR method was successfully
developed for rapid detection of 45 fusion genes and validated for 15 of the more
commonly detected fusion genes. Intra-assay reproducibility assessed for the most
frequent rearrangements ranged from 0.41% to 0.74% for the coefficient of variation
(CV) of cycle threshold (Ct) and the interassay reproducibility ranged from 1.62%
to 2.83% in five separate experiments. The lowest detection limit for the
translocations tested ranged between 1 : 16 000 and 1 : 32 000. Validation of the
method with 213 patient samples showed 100% specificity and excellent consistence
with conventional nested RT-PCR. ConclusionOverall, we believe that this method is
easily applicable, cost-effective, and clinically useful for a rapid screening of
fusion genes in the initial diagnostic phase of leukemia. Its use can also be
extended to the monitoring of minimal residual disease.
The gene Par -4 (Prostate Apoptosis Response 4) was originally identified in
prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer
specific proapoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4)
selectively kills cancer cells leaving normal cells unaffected. The therapeutic
significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its
large scale production is still a matter of concern. Here we report the production
of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5'
AM\/) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun
NN plants under the control of a unique recombinant promoter M24. Transgene
integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-
time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA
confirmed expression of recombinant SACPar-4-GFP protein and it was as high as
0.15% of total soluble protein. In addition, we found that targeting of plant
recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was
essential for the stability of plant recombinant protein in comparison to the
bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted
SAC-Par-4-GFP-SEKDEL undergoes 0-linked glycosylation unlike apoplast-targeted SAC-
Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation
assay (MU), apoptosis induction assays, and NF-KB suppression suggested the
cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple
prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer
cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a
syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made
SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer
in the new era.
BACKGROUNDNovel fusion transcripts (FTs) caused by chromosomal rearrangement are
common factors in the development of cancers. In the current study, the authors
used massively parallel RNA sequencing to identify new FTs in colon cancers.
METHODSRNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in
colon cancers. The authors then investigated whether the novel FT nuclear receptor
subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT)
was transcribed from a genomic chromosomal rearrangement. Next, the expression of
NR5A2-KLHL29FT was measured by quantitative real-time polymerase chain reaction in
colon cancers and matched corresponding normal epithelia. RESULTSThe authors
identified the FT NR5A2-KLHL29FT in normal and cancerous epithelia. While
investigating this transcript, it was unexpectedly found that it was due to an
uncharacterized polymorphic germline insertion of the NR5A2 sequence from
chromosome 1 into the KLHL29 locus at chromosome 2, rather than a chromosomal
rearrangement. This germline insertion, which occurred at a population frequency of
0.40, appeared to bear no relationship to cancer development. Moreover, expression
of NR5A2-KLHL29FT was validated in RNA specimens from samples with insertions of
NR5A2 at the KLHL29 gene locus, but not from samples without this insertion. It is
interesting to note that NR5A2-KLH29FT expression levels were significantly lower
in colon cancers than in matched normal colonic epithelia (P =.029), suggesting the
potential participation of NR5A2-KLHL29FT in the origin or progression of this
tumor type. CONCLUSIONSNR5A2-KLHL29FT was generated from a polymorphism insertion
of the NR5A2 sequence into the KLHL29 locus. NR5A2-KLHL29FT may influence the
origin or progression of colon cancer. Moreover, researchers should be aware that
similar FTs may occur due to transchromosomal insertions that are not correctly
annotated in genome databases, especially with current assembly algorithms. Cancer
2017;123:1507-1515. (c) 2017 American Cancer Society. A novel fusion transcript
identified by RNA sequencing, nuclear receptor subfamily 5, group A, member 2
(NR5A2)-Kelch-like family member 29 fusion transcript (KLHL29FT), was generated
from a polymorphism insertion at the KLHL29 locus instead of a chromosome
rearrangement. The expression of NR5A2-KLHL29FT appears to be lower in colon
cancers than in matched normal tissues, suggesting potential participation of
NR5A2-KLHL29FT in the origin or progression of colon cancer.
Mushroom production is one of the biggest solid state fermentation industries in
the world. The success in mushroom planting depends on how the control temperature,
humidity and CO2 parameters. This paper presents a novel method for modeling an
environment of mushrooms growth to comparing the performance of two controlling
methods (fuzzy logic and digital (ON/OFF) control) for controlling mentioned
parameters on production rate. The Controllers and other equipment were developed
to data collection and analysis of these parameters was performed by using Simulink
part of MATLAB software. Precise control of the parameters involved in the growth
of mushrooms caused to improve product quality and reduced energy consumption. The
results of tests and mean value obtained on two different methods showed that the
fuzzy controlling with having least standard deviation, variance and error, is
better than digital controlling. Fuzzy controlling system had the lowest
fluctuation and lowest band pass. According to gradient of graph, maximum and
minimum of results, can conclude that the fuzzy controlling has shown better
response in controlling the process. Based on the number of actuators mode changing
on both systems, it can be understood that in digital control system, downtime, and
depreciation and energy consumption would be higher than the fuzzy control system.
(C) 2016 Elsevier Ltd. All rights reserved.
This paper focuses on dynamic modeling, simulation and control of Advanced
Automatic Pumping Station with Canal Level Remote Control System using ABB PLC
(Programmable Logical Controller) based Fuzzy Logic Controller. The system is
designed for the agricultural land where the water level (i.e. canals or rivers) is
low and traditional system of irrigation is not working well. System is automated
through two different controllers, first controller automate the water reservoir
gate according to the upper and lower limits of reservoir level and second
controller dealt with speed of two pumps with respect to the set point of water
level in canal. For controlling, monitoring and real time visualization of a
system, HMI (Humane Interface Machine -CP 405) is connected. The applied control
method is based on Fuzzy Logic System, designed in MATLAB Simulink, which can
communicate with PLC through OPC server by using gateway. Through GPRS based system
communication is done between PLC and canal water level meter. A digital control
unit PLC (AC500 PM556-ETH) gets data from the system, take the require actions and
make decision to operate the pumping station. Simulation results show that system
can effectively operate in both, automatic as well as manual conditions depending
on selection switch.
In this paper, we illustrate a proposed method for control that combines the
outputs of several individual controllers to improve global control of complex
nonlinear plants. In the first part of this paper, we illustrate the proposed
method that consists of two levels, where in the top level a fuzzy system
represents a superior control that is designed for adjusting the behavior of the
individual fuzzy controllers at the lower level. To test the approach, we consider
the problem of flight control because it requires several individual controllers.
Also a comparison is performed, where the hierarchical control strategy is compared
with a simple control approach using the t student test. In this paper, we show
that the proposed method outperforms the conventional fuzzy control approach. In
the optimal design of the proposed control architecture a genetic algorithm was
also applied to tune the parameters of the fuzzy systems in an optimal fashion. (C)
2015 Elsevier B.V. All rights reserved.
Galactose metabolism in the yeast Saccharomyces cerevisiae is carried out by a
specialized GAL pathway consisting of structural and regulatory proteins. It is
known that cells with unbalanced Gal proteins accumulate toxic metabolic
intermediates and exhibit severe growth defects. Recently, we found that the
molecular chaperone Hsp90 controls the abundance of multiple Gal proteins, possibly
to prevent these defects. Hsp90 regulates various cellular processes including cell
morphology in response to environmental cues. Yeast cells are known to resort to
filamentous growth upon exposure to galactose or other environmental stresses. Our
previous and current findings support the "Hsp90 titration model" of Hsp90
buffering, which links the cell morphology and galactose pathways. Our results
suggest that, when a large proportion of Hsp90 molecules are used to help Gal
proteins, the Hsp90 client proteins in cell morphology pathways are left
unattended, leading to filamentous growth. It remains unclear whether this
phenomenon serves any biological function or simply reflects a cellular constraint.
Nonetheless, it provides an alternative explanation why the GAL pathway is
degenerated in some yeast species.
Galactosemia, an inborn error of galactose metabolism, was first described in the
1900s by von Ruess. The subsequent 100 years has seen considerable progress in
understanding the underlying genetics and biochemistry of this condition. Initial
studies concentrated on increasing the understanding of the clinical manifestations
of the disease. However, Leloir's discovery of the pathway of galactose catabolism
in the 1940s and 1950s enabled other scientists, notably Kalckar, to link the
disease to a specific enzymatic step in the pathway. Kalckar's work established
that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible
for the majority of cases of galactosemia. However, over the next three decades it
became clear that there were two other forms of galactosemia: type II resulting
from deficiencies in galactokinase (GALK1) and type III where the affected enzyme
is UDP-galactose 4'-epimerase (GALE). From the 1970s, molecular biology approaches
were applied to galactosemia. The chromosomal locations and DNA sequences of the
three genes were determined. These studies enabled modern biochemical studies.
Structures of the proteins have been determined and biochemical studies have shown
that enzymatic impairment often results from misfolding and consequent protein
instability. Cellular and model organism studies have demonstrated that reduced
GALT or GALE activity results in increased oxidative stress. Thus, after a century
of progress, it is possible to conceive of improved therapies including drugs to
manipulate the pathway to reduce potentially toxic intermediates, antioxidants to
reduce the oxidative stress of cells or use of "pharmacological chaperones" to
stabilise the affected proteins. (C) 2015 Elsevier B.V. All rights reserved.
Aims: Understanding the metabolism of lactose and galactose and their regulation in
Lactobacillus rhamnosus. Methods and Results: A gene cluster containing nine open
reading frames (ORFs) involved in the metabolism of lactose and galactose in Lact.
rhamnosus TCELL-1 was sequenced and characterized. The order of the ORFs was
lacTEGF and galKETRM. Northern blotting experiments revealed that the gene cluster
could be transcribed as one lacTEGF-galKETRM mRNA though three major transcripts
(lacTEGF, galKETRM and galETRM) were detected for the gene cluster. The
transcription of the lac or gal operon was independently induced in the presence of
lactose or galactose. Northern blotting and primer extension experiments found the
presence of four putative promoters upstream from the ORFs lacT (lacTp), galK
(galKp1 and galKp2) and galE (galEp). The measurements of enzymatic activities of
GalK, GalE and GalT suggested that the expression of the gal operon was subjected
to a galactose activation and glucose repression mechanism. Conclusions: In Lact.
rhamnosus TCELL-1, the galactose moiety of lactose could be metabolized by two
alternative pathways (the Leloir and the tagatose 6-phosphate pathways) whereas
galactose metabolism could be mediated by the Leloir pathway. Significance and
Impact of the Study: This work provides important information about sugar
metabolism in Lact. rhamnosus.
We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on
thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein
carbonyl content, on the activities of the antioxidant enzymes catalase (CAT),
superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on
acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and
hippocampus of rats. We also investigated the influence of the antioxidants (each
at 1 mM), alpha-tocopherol, ascorbic acid and glutathione, on the effects elicited
by galactose on the parameters tested. Results showed that galactose, at a
concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex
and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0
and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased
CAT activity and decreased AChE activity. In the cerebellum, galactose at
concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In
the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS
and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the
pathologically high concentration (greater than 5.0 mM), galactose induces lipid
peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum,
and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione
addition prevented the majority of alterations in oxidative stress parameters and
the decrease in AChE activity that were caused by galactose. Our findings lend
support to a potential therapeutic strategy for this condition, which may include
the use of appropriate antioxidants for ameliorating the damage caused by
galactose.
We study the role of environment in the evolution of central and satellite galaxies
with the Sloan Digital Sky Survey. We begin by studying the size-mass relation,
replicating previous studies, which showed no difference between the sizes of
centrals and satellites at fixed stellar mass, before turning our attention to the
size-core velocity dispersion (sigma(0)) and mass-sigma(0) relations. By comparing
the median size and mass of the galaxies at fixed velocity dispersion, we find that
the central galaxies are consistently larger and more massive than their satellite
counterparts in the quiescent population. In the star-forming population, we find
there is no difference in size and only a small difference in mass. To analyse why
this difference may be present, we investigate the radial mass profiles and stellar
metallicity of the galaxies. We find that in the cores of the galaxies there is no
difference in mass surface density between centrals and satellites, but there is a
large difference at larger radii. We also find almost no difference between the
stellar metallicity of centrals and satellites when they are separated into star-
forming and quiescent groups. Under the assumption that sigma(0) is invariant to
environmental processes, our results imply that central galaxies are likely being
increased in mass and size by processes such as minor mergers, particularly at high
sigma(0), while satellites are being slightly reduced in mass and size by tidal
stripping and harassment, particularly at low sigma(0), all of which pre-dominantly
affect the outer regions of the galaxies.
Background: Functionalized nanoparticles (NPs) are one promising tool for detecting
specific molecular targets and combine molecular biology and nanotechnology aiming
at modern imaging. We aimed at ligand-directed delivery with a suitable target-
biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising
targets are galectins (Gal), due to their strong expression in and on PDAC-cells
and occurrence at early stages in cancer precursor lesions, but not in adjacent
normal tissues. Results: Molecular probes (10-29 AA long peptides) derived from
human tissue plasminogen activator (t-PA) were selected as binding partners to
galectins. Affinity constants between the synthesized t-PA peptides and Gal were
determined by microscale thermophoresis. The 29 AA-long t-PA-peptide-1 with a
lactose-functionalized serine revealed the strongest binding properties to Gal-1
which was 25-fold higher in comparison with the native t-PA protein and showed
additional strong binding to Gal-3 and Gal-4, both also over-expressed in PDAC. t-
PA-peptide-1 was selected as vector moiety and linked covalently onto the surface
of biodegradable iron oxide nanoparticles (NPs). In particular, CAN-doped maghemite
NPs (CAN-Mag), promising as contrast agent for magnetic resonance imaging (MRI),
were selected as magnetic core and coated with different biocompatible polymers,
such as chitosan (CAN-Mag-Chitosan NPs) or polylactic co glycolic acid (PLGA)
obtaining polymeric nanoparticles (CAN-Mag@PNPs), already approved for drug
delivery applications. The binding efficacy of t-PA-vectorized NPs determined by
exposure to different pancreatic cell lines was up to 90%, as assessed by flow
cytometry. The in vivo targeting and imaging efficacy of the vectorized NPs were
evaluated by applying murine pancreatic tumor models and assessed by 1.5 T magnetic
resonance imaging (MRI). The t-PA-vectorized NPs as well as the protease-activated
NPs with outer shell decoration (CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac) showed
clearly detectable drop of subcutaneous and orthotopic tumor staining-intensity
indicating a considerable uptake of the injected NPs. Post mortem NP deposition in
tumors and organs was confirmed by Fe staining of histopathology tissue sections.
Conclusions: The targeted NPs indicate a fast and enhanced deposition of NPs in the
murine tumor models. The CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac interlocking steps
strategy of NPs delivery and deposition in pancreatic tumor is promising.
An analogue-digital circuit for thermal control of the resonance frequency of
optical ring resonators is suggested. This approach is characterised by a low power
dissipation of 209 mu W and needs only 2800 mu m(2) of chip area in 0.16 mu m CMOS
technology. Therefore, it is well appropriate to be used to control each of the
cells of large optical switch matrices. Compared with a purely analogue heater
control approach the power dissipation is reduced to 7%.
During recent years, the practice of adding game design to non-game services has
gained a relatively large amount of attention. Popular discussion connects
gamification to increased user engagement, service profitability, goal commitment
and the overall betterment of various behavioral outcomes. However, there is still
an absence of a coherent and ample body of empirical evidence that would confirm
such expectations. To this end, this paper reports the results of a 2 year (1 + 1
year - between- group) field experiment in gamifying a service by implementing a
game mechanic called 'badges'. During the experiment a pre-implementation group (N
= 1410) was monitored for 1 year. After the implementation, the post-implementation
(the gamified condition) group (N = 1579) was monitored for another full year.
Results show that users in the gamified condition were significantly more likely to
post trade proposals, carry out transactions, comment on proposals and generally
use the service in a more active way. (C) 2015 Elsevier Ltd. All rights reserved.
Gamification has become a focus of attention in an increasing number of fields
including business, education, and health care. Through a wide range of
applications and support functions, its potential for the tourism industry is
significant. Gamification of tourism can contribute to a more rewarding
interactions and higher level of satisfaction, as well as increase brand awareness
and loyalty to the destination. As one of the first attempts to conceptualize
gamification of tourism, this paper examines gaming in general terms and the
application of it in specific tourism fields. It identifies game design elements
that can contribute to a meaningful gamification. A few cases of best practices are
presented to show how this innovative concept can benefit tourism marketing.
Implications for tourism marketing and management are discussed as well as future
research recommendations. (C) 2016 Elsevier Ltd. All rights reserved.
Human gamma delta T cells comprise a first line of defense through T-cell receptor
(TCR) recognition of stressed cells. However, the molecular determinants and stress
pathways involved in this recognition are largely unknown. Here we show that
exposure of tumor cells to various stress situations led to tumor cell recognition
by a V.8Vd3 TCR. Using a strategy that we previously developed to identify
antigenic ligands of gamma delta TCRs, annexin A2 was identified as the direct
ligand of V.8Vd3 TCR, and was found to be expressed on tumor cells upon the stress
situations tested in a reactive oxygen species-dependent manner. Moreover, purified
annexin A2 was able to stimulate the proliferation of a Vd2neg gamma delta T-cell
subset within peripheral blood mononuclear cells and other annexin A2-specific
Vd2neg gamma delta T-cell clones could be derived from peripheral blood mononuclear
cells. We thus propose membrane exposure of annexin A2 as an oxidative stress
signal for some Vd2neg gamma delta T cells that could be involved in an adaptive
stress surveillance.
This paper presents an improved phase leg power loop design for enhance mode
lateral structure Gallium Nitride (GaN) transistors. Static characterization
results of a 650V/30A GaN transistor are presented to determine the design
parameters of the gate driver circuits. The control of Common Mode (CM) noise
current propagation is considered during the gate driver design by optimizing the
power distribution and grounding structure of the gate driver and digital control
circuits. By differentiating the propagation path impedance of digital control
circuits and their power supply circuits, conductive CM noise can propagate through
power supply path to protect the digital control circuits. In order to reduce
current commutation loop inductance within the GaN phase leg, an improved power
loop design with vertical structure is proposed for lateral structure GaN
transistors which can significantly reduce power loop inductance compared with
conventional lateral power loop design. The design is verified through experiments
on a phase leg prototype which prove the performance of the proposed phase leg on
the overvoltage reduction during current transition along with less cross-coupling
between power loop and gate loop compared with conventional lateral power loop
design. A full bridge voltage source inverter is implemented with the designed
phase leg and tested with EMI noise measurement that verifies the effectiveness of
the CM propagation path control.
This paper presents the first multi vector energy analysis for the interconnected
energy systems of Great Britain (GB) and Ireland. Both systems share a common high
penetratioh of wind power, but significantly different security of supply outlooks.
Ireland is heavily dependent on gas imports from GB, giving significance to the
interconnected aspect of the methodology in addition to the gas and power
interactions analysed. A fully realistic unit commitment and economic dispatch
Model coupled to an energy flow model of the gas supply network is developed.
Extreme weather events driving increased domestic gas demand and low wind power
output were utilised to increase gas supply network stress. Decreased wind profiles
had a larger impact on system security than high domestic gas demand. However, the
GB energy system was resilient during high demand periods but gas network stress
limited the ramping capability of localised generating units. Additionally, gas
system entry node congestion in the Irish system was shown to deliver a 40%
increase in short run costs for generators. Gds storage was shown to reduce the
impact of high demand driven congestion delivering a reduction in total generation
costs of 14% in the period studied and reducing electricity imports from GB,
significantly contributing to security of supply. (C) 2016 The Authors. Published
by Elsevier Ltd.
The objective of this study is to analyze and optimize a solar assisted gas turbine
system. Parabolic trough collectors are used in order to supply a part of the
demanded heat input, reducing the natural gas consumption and leading to an
environmental friendly system. Emphasis is given in the pressure losses in the
collector field loop which reduce the pressure level in the turbine inlet, leading
to lower electricity production. In the first part of this study, the gas turbine
and the collector field are investigated separately and in the second part, the
solar assisted gas turbine is investigated parametrically and it is optimized. In
the optimization part, a multi-objective optimization is performed by setting as
goals the minimization of the collector area, of the fuel consumption and of the
inversed electricity production. The final results proved that 1050 collector
modules lead to 0.3389 kg/s natural gas consumption and to electricity production
equal to 14.81 MWel. This optimum solution leads to 64% fuel savings with a 2.8%
penalty on the produced electricity. The system is analyzed in steady state
conditions with the Engineering Equator Solver (EES). (C) 2017 Elsevier Ltd.
A comparative analysis of electricity and gas demand in the industrial sector over
a long period of time appears to be absent in the literature. In fact, unlike
electricity demand, natural gas demand in the industrial sector has not been well
researched. Our paper aims to cover this gap. It analyses electricity and gas
consumption patterns by the Spanish manufacturing sector, between 1995 and 2010. A
novel and innovative quantitative approach based on, both, homogenous and
heterogeneous estimators was used for this purpose. The results of the no-spurious
estimations (the Augmented Mean Group Estimator) show that the price elasticity of
gas demand is significantly negative and within the -0.44 to -0.48 range. In
contrast, the price elasticity of electricity demand is not statistically
significant. The income elasticities show the opposite pattern: those of natural
gas are not statistically significant, whereas the income elasticities for
electricity are statistically significant and within the 0.22 to 0.29 range.
Compared to previous findings, our preferred estimation shows some variation
regarding price elasticities of natural gas demand. (C) 2017 Elsevier Ltd. All
rights reserved.
Small-scale thermal treatment of municipal solid waste (MSW) was investigated using
mass and energy balances based on the assumption of thermodynamic equilibrium. A
typical average MSW composition from the literature was used as basis for modelling
of a one ton per day waste gasification facility (plant). Syngas production by
pyrolysis, stoichiometric O-2 addition and auto-thermal (gasification with oxygen
and/or air where no external heat input is required) combustion were considered.
These cases were evaluated for production of electricity only, and steam. From
purely thermodynamic considerations, it was observed that auto-thermal oxygen
gasification produces the most electricity (47.00 kWe) and oxygen plasma
gasification produces a positive net amount (4.07 kWe) on a 1 ton per day scale.
Although auto-thermal air gasification also produces a net positive amount, the
calorific value of the syngas is too low to fuel an internal combustion engine. As
expected, the amount of steam generated by the different scenarios is high due to
higher process efficiencies. The close-coupled auto-thermal oxygen process proved
to be the most efficient. The cost of additional oxygen generation was however not
taken into account, and may change the picture significantly.
Gasification is a promising alternative for polymeric waste valorization when
mechanical recycling is unfeasible on account of its heterogeneity or partial
contamination, or simply when it yields a product of lower quality than what the
market requires. Apart from its application for electricity generation, the waste-
derived syngas shows a great potential for chemical waste recycling for the
synthesis of hydrogen, methane, natural gas or methanol. In spite of the effort
devoted so far to the experimental demonstration of these processes to enable this
technology to access commercial stage, it is still necessary to develop detailed
models of the process that allow a precise prediction of the resulting syngas
composition, as well as tar formation and global efficiency of the process. This
research work presents the development of a polyolefin gasification model for
fluidized bed reactors. The model details the behaviour of primary pyrolysis and
homogeneous reactions of oxidation, steam reforming, aromatization and thermal
cracking. To accomplish this, it adopts new modelling strategies for the definition
of primary tar species in order to reflect their twofold nature (aliphatic and
aromatic), as well as to describe kinetics and stoichiometry involved in thermal
cracking processes of tar species. The model is able to successfully predict the
generation, volume composition and heating value of the syngas, final tar
generation and global efficiency of the process. (C) 2017 Elsevier Ltd. All rights
reserved.
Background: Emerging evidences have verified that long non-coding RNAs (lncRNAs)
play important regulatory roles in the pathogenesis and progression of cancers.
lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been
found to be up-regulated in some human cancers. The main objective of this study
was to investigate the expression level and biological function of MALAT1 in
gastric cancer (GC). Methods: Quantificational real-time polymerase chain reaction
(qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric
carcinoma tissues and adjacent normal tissues, and the associations of MALAT1
expression with the clinicopathological features were analyzed, and the prognosis
of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions
were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was
used to determine miR-1297 was a target of MALAT1. Results: In this study, we
demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal
tissues and higher MALAT1 expression was correlated with local invasion, lymph node
metastasis and TNM stage. Patients with higher MALAT1 expression predicted a
shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted
cells proliferation and invasion in GC. Mechanistically, our results demonstrated
that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular
sponging miR-1297, antagonizing its ability to suppress HMGB2 expression.
Conclusions: Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2
axis acted as critical regulator pathway in GC tumorigenesis and progression, which
provided a novel therapeutic target for gastric cancer.
Despite advances in molecular biology, imaging, and treatment, gastric neoplasms
remain a significant cause of morbidity and mortality; gastric adenocarcinoma is
the fifth most common malignancy and third most common cause of death worldwide
(Brenner et al., Methods Mol Biol 472:467-477, 2009; Howson et al. Epidemiol Rev
8:1-27, 1986; Roder, Gastric Cancer 5(Suppl 1):5-11, 2002; Ferlay et al., GLOBOCAN
2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11
[Internet]. International Agency for Research on Cancer, 2013). Because of both the
frequency at which malignant gastric tumors occur as well as the worldwide impact,
gastric neoplasms remain important lesions to identify and characterize on all
imaging modalities. Despite the varied histologies and behaviors of these
neoplasms, many have similar imaging features. Nonetheless, the treatment,
management, and prognosis of gastric neoplasms vary by pathology, so it is
essential for the radiologist to make every effort to differentiate between these
lesions and raise the less common entities as differential diagnostic
considerations when appropriate.
Circular RNAs are a special class of endogenous RNAs characterized by jointing 3'
and 5' ends together via exon or intron circularization. Recent studies found that
circular RNAs are involved in the development of some human diseases. However,
little is known about their roles in human gastric cancer. In this study, we chose
hsa_circ_0001895 as a targeted circRNA to investigate its clinical significances in
gastric cancer patients. Hsa_circ_0001895 expression levels in five gastric cancer
cell lines and 257 specimens of tissues were measured by real-time quantitative
reverse transcription polymerase chain reaction. Then, the potential relationship
between hsa_circ_0001895 expression levels and patients' clinicopathological
factors was investigated. A receiver operating characteristic curve was constructed
for evaluating the diagnostic value of hsa_circ_0001895. Hsa_circ_0001895
expression levels in five detected gastric cancer cell lines (AGS, BGC-823, HGC-27,
MGC-803, and SGC-7901) were all significantly downregulated than those in normal
gastric epithelial GES-1 cells. Besides, compared with healthy control tissues, it
was downregulated not only in 69.8% (67/96) gastric cancer tissues but also in
gastric precancerous lesions. Moreover, hsa_circ_0001895 expression levels were
significantly correlated with cell differentiation, Borrmann type, and tissue
carcino-embryonic antigen expression. Our results suggested that hsa_circ_0001895
may play crucial roles during gastric cancerogenesis and is a potential biomarker
for clinical prognosis prediction.
Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-
Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and
clinical features. In this study, we aimed to determine the potential utility of
circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of
therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC).
The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC
tumors and plasma samples were determined by quantitative real-time polymerase
chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed
by the conventional method. Circulating cell-free EBV DNA was detected in 14
patients with GC: the sensitivity and specificity of detection were 71.4% (10/14)
and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated
with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in
EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better
prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis.
In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a
decrease and increase in plasma EBV DNA after treatment and during tumor
progression/recurrence, respectively. These results suggest the potential utility
of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC
subtype and/or for real-time monitoring of tumor progression as well as treatment
response in patients with EBVaGC.
O-GlcNAcylation is a monosaccharide modification by a residue of N-
acetylglucosamine (GlcNAc) attached to serine or threonine moieties on nuclear and
cytoplasmic proteins. O-GlcNAcylation is dynamically regulated by O-GlcNAc
transferase (OGT) and O-GlcNAcase (OGA). Increasing evidence suggests that O-
GlcNAcylation is involved in a variety of human cancers. However, the exact role of
O-GlcNAcylation in tumor progression remains unclear. Here, we show that O-
GlcNAcylation accelerates oncogenic phenotypes of gastric cancer. First, cell
models with increased or decreased O-GlcNAcylation were constructed by OGT
overexpression, downregulation of OGA activity with specific inhibitor Thiamet-G,
or silence of OGT. MTT assays indicated that O-GlcNAcylation increased
proliferation of gastric cancer cells. Soft agar assay and Transwell assays showed
that O-GlcNAcylation significantly enhanced cellular colony formation, migration,
and invasion in vitro. Akt1 activity was stimulated by upregulation of
phosphorylation at Ser473 mediated by elevated O-GlcNAcylation. The enhanced cell
invasion by Thiamet-G treatment was suppressed by PI3K inhibitor LY294002. Although
the cell invasion induced by Thiamet-G was reduced by Akt1 shRNA, it was still
higher in comparison with that to the control (cells with Akt1 shRNA alone). And
Akt1 overexpression promoted Thiamet-G-induced cell invasion. These results
suggested that O-GlcNAcylation enhanced oncogenic phenotypes possibly partially
involving PI3K/Akt signaling pathway. (C) 2015 International Union of Biochemistry
and Molecular Biology, Inc. Volume 63, Number 6, Pages 841-851, 2016
Background: Suitable diagnostic markers for cancers are urgently required in
clinical practice. Long non-coding RNAs, which have been reported in many cancer
types, are a potential new class of biomarkers for tumor diagnosis. Results: Five
lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were
validated to be increased in gastric cancer tissues. Furthermore, we found that
plasma level of these five lncRNAs were significantly higher in gastric cancer
patients compared with normal controls. By receiver operating characteristic
analysis, we found that the combination of plasma lncRNAs with the area under the
curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is a
better indicator of gastric cancer than their individual levels or other lncRNA
combinations. Simultaneously, we found that the expression levels of a series of
MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of
them higher than that in healthy control plasma samples. Materials and Methods:
LncRNA gene expression profiles were analyzed in two pairs of human gastric cancer
and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer-
associated lncRNAs were selected and assessed by quantitative real-time polymerase
chain reaction in gastric tissues, and 5 of them were further analyzed in gastric
cancer patients' plasma. Conclusions: Our results demonstrate that certain lncRNAs,
such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are enriched in human
gastric cancer tissues and significantly elevated in the plasma of patients with
gastric cancer. These findings indicate that the combination of these four lncRNAs
might be used as diagnostic or prognostic markers for gastric cancer patients.
AIM To investigate the role of Delta 133p53 isoform in nuclear factor-kappa B (NF-
kappa B) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of
MKN45 gastric cancer cells. METHODS The growth rate of MKN45 cells after treatment
with different concentrations of only PDTC or PTDC in combination with cisplatin
was detected by the CCK-8 assay. mRNA expression levels of Delta 133p53, p53 beta,
and the NF-kappa B p65 subunit and p65 protein levels were detected by reverse
transcription-polymerase chain reaction (RT-PCR) and immunofluorescence,
respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a
dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was
remarkably enhanced in a dose- dependent manner by co-treatment with PDTC (P <
0.01). RESULTS RT-PCR analysis revealed that mRNA expression of p65 was curbed
significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01),
and this suppressive effect was further enhanced when co-treated with cisplatin (P
< 0.01). With respect to the other p53 isoforms, mRNA level of Delta 133p53 was
significantly reduced in a dose-dependent manner by treatment with only PDTC or
PTDC in combination with cisplatin (P0.05). A similar tendency of change in p65
protein expression, as observed for the corresponding mRNA, was detected by
immunofluorescence analysis (P0.01). CONCLUSION Delta 133p53 isoform (not p53 beta)
is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating
that disturbance in the cross-talk between p53 and NF-kappa B pathways is a
promising target in pharmaceutical research for the development of treatment
strategies for gastric cancer.
The protocadherin 7 is a member of the protocadherin family that expressed
aberrantly in many types of human cancers. However, its expression, function, and
underlying mechanisms are little known in gastric cancer. In this study, we
detected protocadherin 7 expression in gastric cancer tissues and non-tumorous
gastric mucosa tissues by realtime quantitative polymerase chain reaction and
immunohistochemistry. The association of protocadherin 7 expression with the
clinicopathological characteristics and the prognosis was subsequently analyzed.
MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-
tetrazolium))and transwell assays were performed to assess the effect of
protocadherin 7 on proliferation, migration, and invasion in gastric cancer cell
lines. Moreover, real-time quantitative polymerase chain reaction and western blot
were used to detect the expression of epithelial-mesenchymal transition markers.
Protocadherin 7 expression was decreased gradiently from normal tissue to gastric
cancer, especially in gastric cancer tissue with lymph node metastasis. Low
expression of protocadherin 7 was significantly associated with Lauren's
classification (p = 0.0005), lymph node metastases (p = 0.0002), and tumor node
metastasis stage (p = 0.0221), as well as poor prognosis (p < 0.05). Furthermore,
down-regulation of protocadherin 7 in gastric cancer cell lines significantly
increased their migration and invasion abilities (both p0.05). Additionally, our
results demonstrated that E-cadherin expression was down-regulated in gastric
cancer cells with protocadherin 7 depletion. Our data indicated that protocadherin
7 may play important roles in the invasion and metastasis of gastric cancer, and
protocadherin 7 could suppress cell migration and invasion through E-cadherin
inhibition. Protocadherin 7 can serve as a novel biomarker for diagnostic and
prognosis in patients with gastric cancer.
Neuroendocrine (NE) gastroenteropancreatic tumors are a heterogeneous group of
neoplasias arising from neuroendocrine cells of the embryological gut. Their
incidence have increased significantly over the past 3 decades probably due to the
improvements in imaging and diagnosis. The recent advances in molecular biology
have translated into an expansion of therapeutic approaches to these patients.
Somatostatin analogs, which initially were approved for control of hormonal
syndromes, have recently been proven to inhibit tumor growth. Several new drugs
such as antiangiogenics and others targeting mammalian target of rapamycin pathways
have been approved to treat progressive pancreatic neuroendocrine tumors (NETs)
although their role in nonpancreatic is still controversial. The treatment of NETs
requires a coordinated multidisciplinary approach. The management of localized NETs
primarily involves surgical resection followed by surveillance. However, the
treatment of unresectable and/or metastatic disease may involve a combination of
surgical resection, systemic therapy, and liver-directed therapies with the goal of
alleviating symptoms of peptide release and controlling tumor growth. This article
will review the current therapeutic strategies for metastatic
gastroenteropancreatic NETs and will take a glimpse into the future approaches.
Gastroesophageal (GE) malignancies make up a significant and growing segment of
newly diagnosed cancers. Approximately 80% of patients who have GE cancers die
within 5 years of diagnosis, which means that effective treatments for these
malignancies need to be found. Currently, targeted therapies have a minimal role in
this disease group. Intensive study of the molecular biology of GE cancers is a
relatively new and ongoing venture, but it has already led to a significant
increase in our understanding of these malignancies. This understanding, although
still limited, has the potential to enhance our ability to develop targeted
therapies in conjunction with the ability to identify actionable gene mutations and
perform genomic profiling to predict drug resistance. Several cell surface growth
factor receptors have been found to play a prominent role in GE cancer cell
signaling. This discovery has led to the approval of 2 agents within the last few
years: trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2)
monoclonal antibody used in the first-line treatment of HER2-positive GE cancers,
and ramucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2)
monoclonal antibody that is currently used in later lines of therapy. This review
discusses the current state of molecular testing in GE cancers, along with the
known molecular biology and current and investigational treatments. The development
of trastuzumab and ramucirumab represents a significant advance in our ability to
make use of GE tumor molecular profiles. As our understanding of the impact of
molecular aberrations on drug effectiveness and disease outcomes increases, we
anticipate improved therapy for patients with GE cancers.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A
group of experts from the Spanish Society of Pathology and the Spanish Society of
Oncology met to discuss a brief update on GISTs and agree on aspects relating to
the pathological and molecular diagnosis of these tumors. GISTs are generally
solitary, well-circumscribed lesions of variable size (< 10 mm-35 cm) that may
present with intra- or extra-luminal parietal growth or a mixed-type (hourglass)
growth pattern. Histologically, they are unencapsulated neoplasms displaying
expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity
(10%). Mitotic activity is generally moderate or low and should be evaluated only
in areas with high cellularity or higher mitotic frequency. The great majority of
GISTs harbour mutually exclusive activating mutations in genes coding for the type
III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been
reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex
genes. The method most widely used to detect KIT and PDGFRA mutations is
amplification of the exons involved by polymerase chain reaction followed by direct
sequencing (Sanger method) of these amplification products. Molecular analyses
should always specify the type of analysis performed, the region or mutations
evaluated, and the sensitivity of the detection method employed.
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by
driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These
mutations have been linked to the response to imatinib, a multikinase inhibitor,
and have independent prognostic impact. Here, we describe the prospective study of
the molecular characteristics of 104 GISTs from French adult patients analyzed
routinely through the National Hospital Program of Molecular Cancer Diagnosis. All
patients with GISTs diagnosed at the University Hospital of Besancon between August
2005 and October 2014 were prospectively included in the present study. KIT, PDGFRA
and KRAS-codons 12 and 13 as well as BRAF codon 600 mutations were analyzed by
Sanger sequencing or SNaPshot. KIT and PDGFRA mutations were detected in 71.2 and
19.2% of the cases, respectively. A total of 43 different mutations were detected
of which 13 had never been described. As expected, KIT exon 9 and PDGFRA exon 18
mutations were associated with small bowel and gastric localizations respectively.
No mutation was found in KRAS and BRAF. Molecular studies are critical to improve
the management of GISTs. Our study enhances the current knowledge by describing 13
new mutations in KIT. A common molecular pattern in all KIT exon 11 substitutions
is also described for the first time in this study but its significance remains
unknown since genetic and environmental risk factors favoring the development of
GISTs such as DNA repair defects and exposure to carcinogens are not currently
known.
This study tested whether including objects perceived as highly interesting by
children with autism during a gaze following task would result in increased first
fixation durations on the target objects. It has previously been found that
autistic children differentiate less between an object another person attends to
and unattended objects in terms of this measure. Less differentiation between
attended and unattended objects in ASD as compared to control children was found in
a baseline condition, but not in the high interest condition. However, typically
developing children differentiated less between attended and unattended objects in
the high interest condition than in the baseline condition, possibly reflecting
reduced influence of gaze cues on object processing when objects themselves are
highly interesting.
Biological functions of globo-series glycosphingolipids are not well understood. In
this study, murine cDNAs of two glycosyltransferases responsible for the synthesis
of globo-series glycolipids and mRNA expression of those genes were analyzed.
Distribution of their products was also analyzed. Murine cDNAs for Gb3/CD77
synthase and Gb4 synthase predicted that both of them are type II membrane proteins
with 348 and 331 amino acids, respectively. In northern blotting, Gb3/CD77 synthase
gene was mainly expressed in kidney and lung but also detected in many other
tissues. Gb4 synthase was expressed in brain, heart, kidney, liver, skin, and
testis. In the immunohistological analysis, Gb3/CD77 was mainly expressed in the
proximal tubules as revealed with coincidental expression with angiotensin-
converting enzyme (ACE). In spleen, it was detected in pre-B cells in the
peripheral region of the white pulp, as suggested with coincidental expression with
CD10. It was also expressed on the endothelia of the alveolar capillaries in lung
and on the sebaceous ducts aside of the hair follicles. Gb4 was also detected
mainly on the proximal tubules in kidney and on the endothelia of the alveolar
capillaries in lung as Gb3/CD77. But it was also detected on the epithelium of the
bronchus, seminiferous tubules and tails of spermatozoa in testis, blood vessels of
choroids plexus and endothelial cells in brain, and central and hepatoportal veins
in liver. The expression patterns of two genes and their products almost
corresponded with some exception. The results would provide essential information
for the functional studies of globo-series glycolipids.
In this paper a high gain low noise Op-Amp has been designed. In designing of a
high gain Op-Amp, for large values of coupling capacitor, gain will decrease. Since
our requirement was to increase the gain, so we have designed a three stage Op-Amp.
Our designed circuit provides gain of 78.4 dB, which is very much larger than two
stage Op-Amp. There is a trade-off between various parameters like Phase margin,
gain, slew rate etc. For example, to achieve larger values of GBW, PM will
decrease. We have compared the results for two values of input common mode range.
Improvement in the designed circuit is done to achieve the desired GBW by
recalculating the transistor's W/L ratios and then simulating the results. Gain
Bandwidth product of 176.9 MHz and Phase Margin greater than 60 degrees is achieved
but at the cost of power dissipation and area. The Op-Amp is designed in gpdk 180
nm CMOS technology.
Microarrays can quantitatively measure the expression of thousands of genes
simultaneously but they are also powerful tools to examine the expression of
specific genes in different tissues and cell types. They complement other methods
used to detect gene expression at the transcript level, including Northern blotting
and RT-PCR. This study uses oligonucleotide microarray expression profiling to
compare maize beta-tubulin (tub) gene expression at the transcript level in
different tissues and during various stages of development and adds to what is
known about maize beta-tubulin expression. In maize, at least nine beta-tubulin
genes are expressed. The presence of multiple tub genes suggests that some could
have evolved to provide fine control of expression or even have distinct biological
or physiological properties in the plant. This is supported by the differential
expression at the transcript level of the maize beta-tubulins in different tissues
during development. The following work has added evidence of maize beta-tubulin
gene differential expression and regulation. Based oil microarray data, some beta-
tubulins exhibit statistically significant differences in transcript abundance in
11-day old seedling shoots, immature ears, 19-DAP embryos, 13-DAP endosperm and 19-
DAP endosperm. There are also different expression patterns for many of the tubulin
genes within the tissues Studied. As the plant develops it may use beta-tubulins in
different amounts in specific tissues, and these tubulins may even interact
differently with other proteins present at these developmental stages. In immature
ears, tub1 and tub2 have higher transcript abundances. Comparisons of expression
patterns indicate that tub3 and tub4 have very similar expression patterns, which
may be a result of similar transcriptional regulation. The highest transcript
abundance of these two genes occurs in developing seedling shoots. tub3 and tub4
transcripts have also been detected for the first time in maize endosperm. This
chapter describes a variety of methods for array analysis of tubulin gene
expression as well as important considerations before taking oil this type of work.
In the seminiferous epithelium of the testis, Sertoli cells are key niche cells
directing proliferation and differentiation of spermatogonial stem cells (SSCs)
into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor
(GDNF), which is essential for SSC self-renewal and progenitor expansion. While the
role of GDNF in the testis stem cell niche is established, little is known about
how this factor is regulated. Our previous studies on NOTCH activity in Sertoli
cells demonstrated a role of this pathway in limiting stem/progenitor cell numbers,
thus ultimately downregulating sperm cell output. In this study we demonstrate
through a double-mutant mouse model that NOTCH signaling in Sertoli cells functions
solely through the canonical pathway. Further, we demonstrate through Dual
luciferase assay and chromatin immunoprecipitation quantitative polymerase chain
reaction (ChIP-qPCR) analysis that the NOTCH targets HES1 and HEY1, which are
transcriptional repressors, directly downregulate GDNF expression by binding to the
Gdnf promoter, thus antagonizing the effects of FSH/ cAMP. Finally, we demonstrate
that testicular stem/progenitors cells are activating NOTCH signaling in Sertoli
cells in vivo and in vitro through the NOTCH ligand JAG1 at their surface,
indicating that these cells may ensure their own homeostasis through negative
feedback regulation.
The beta-keratins constitute the hard epidermis and adhesive setae of gecko
lizards. Nucleotide and amino acid sequences of beta-keratins in epidermis of gecko
lizards were cloned from mRNAs. Specific oligonucleotides were used to amplify by
3'- and 5'-rapid amplification of cDNA ends analyses five specific gecko beta-
keratin cDNA sequences. The cDNA coding sequences encoded putative glycine-proline-
serine-rich proteins of 16.8-18 kDa containing 169-191 amino acids, especially
17.8-23% glycine, 8.4-14.8% proline, 14.2-18.1% serine. Glycine-rich repeats are
localized toward the initial and end regions of the protein, while a central
region, rich in proline, has a strand conformation (beta-pleated fold) likely
responsible for the formation of beta-keratin filaments. It shows high homology
with a core region of other lizard keratins, avian scale, and feather keratins.
Northern blotting and reverse transcriptase-polymerase chain reaction (RTPCR)
analysis show a higher beta-keratin gene expression in regenerating epidermis
compared with normal epidermis. In situ hybridization confirms that mRNAs for these
proteins are expressed in cells of the differentiating oberhautchen cells and beta-
cells. Expression in adhesive setae of climbing lamellae was shown by RT-PCR.
Southern blotting analysis revealed that the proteins are encoded by a multigene
family. PCR analysis showed that the genes are presumably located in tandem along
the DNA and are transcribed from the same DNA strand like in avian beta-keratins.
The enolase2 gene is usually expressed in mature neurons and also named neuron
specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA
sequence by using the RACE method based on the expressed sequence tag (EST)
fragment from the cDNA library of Gekko japonicus and identified one transcript of
about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The
open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We
further investigated the multi-tissue expression pattern of NSE by RT-PCR and found
that the expression of NSE mRNA was very high in brain, spinal cord and low in
heart, while it was not detectable in other tissues. The real-time quantitative PCR
was used to investigate the time-dependent change in the expression of the NSE mRNA
level after gecko spinal cord transection and found it significantly increased at
one day, reaching its highest level three days post-injury and then decreasing at
the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was
constructed and induced to express His fused NSE protein. The purified NSE protein
was used to immunize rabbits to generate polyclonal antisera. The titer of the
antiserum was more than 1:65536 determined by ELISA. Western blotting showed that
the prepared antibody could specifically recognize the recombinant and endogenous
NSE protein. The result of immunohistochemistry revealed that positive signals were
present in neurons of the brain and the spinal cord. This study provided the tools
of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus.
Introduction: Tuberculous Meningitis (TBM) is the most severe form of Central
Nervous System Tuberculosis (CNS- TB) and constitutes about 6% of all
Extrapulmonary TB (EPTB) cases. Most guidelines for the diagnosis and management of
TBM agree on the use of simple Cerebrospinal Fluid (CSF) analysis using molecular
tools like Polymerase Chain Reaction (PCR). However, the sensitivity of PCR varies
while using a CSF sample. In the present study, we have compared the diagnostic
utility of PCR assay in both peripheral blood and CSF sample collected from TBM
cases. Aim: To evaluate the application of the peripheral blood PCR assay as an
alternate tool for TBM diagnosis compared to conventional CSF-PCR based system
Materials and Methods: A total of 50 TBM patients were prospectively recruited from
in patient department wards of Central India Institute of Medical Sciences (CIIMS)
between January 2014 - Feburary 2015. Mycobacterium tuberculosis (MTB) specific
IS6110 PCR and BactT liquid culture were performed in 20 of recruited cases
classified as Stage 1, 2 and 3 based on British Medical Research Council (BMRC)
contemporary clinical criteria for the severity of TBM. Clinical characteristics
were summarised in terms of percentages for categorical variables, i.e., age
groups, gender, signs and symptoms. All statistical analysis was carried out using
MedCalc software version 11.6. Results: Overall IS6110 PCR positivity in CSF was
around 80% (16/20), which was higher than culture (29.3%) and peripheral blood
(39%). Out of 8 positive cases, stage wise positivity of peripheral blood PCR assay
in three TBM stages was 0% (stage1) 50% (stage 2) and 67% (Stage 3) respectively.
Positivity of peripheral blood PCR was significantly more (86%) in patients with
CSF culture/IS6110 PCR positive for MTB infection with sensitivity and specificity
of 50 and 100% respectively. Increased positivity rates of peripheral blood PCR was
observed with decreased CSF/Blood sugar ratio in stage 3 cases, suggesting enhanced
probability of mycobacterial blood dissemination in cases of TBM severity.
Conclusion: Our results suggest that although the molecular diagnosis of TBM
infection in CSF remains the method of choice, peripheral blood based PCR can be
used as a good alternative to CSF in case of TBM severity where the repeated CSF
collection may be needed. However, study demands further validation in large
cohorts to justify the present hypothesis.
Northern blotting analysis is a classical method for analysis of the size and
steady-state level of a specific RNA in a complex sample. In short, the RNA is
size-fractionated by gel electrophoresis and transferred by blotting onto a
membrane to which the RNA is covalently bound. Then, the membrane is analysed by
hybridization to one or more specific probes that are labelled for subsequent
detection. Northern blotting is relatively simple to perform, inexpensive, and not
plagued by artefacts. Recent developments of hybridization membranes and buffers
have resulted in increased sensitivity closing the gap to the more laborious
nuclease protection experiments.
Several studies have demonstrated that women show a greater interest for social
information and empathic attitude than men. This article reviews studies on sex
differences in the brain, with particular reference to how males and females
process faces and facial expressions, social interactions, pain of others, infant
faces, faces in things (pareidolia phenomenon), opposite-sex faces, humans vs.
landscapes, incongruent behavior, motor actions, biological motion, erotic
pictures, and emotional information. Sex differences in oxytocin-based attachment
response and emotional memory are also mentioned. In addition, we investigated how
400 different human faces were evaluated for arousal and valence dimensions by a
group of healthy male and female University students. Stimuli were carefully
balanced for sensory and perceptual characteristics, age, facial expression, and
sex. As a whole, women judged all human faces as more positive and more arousing
than men. Furthermore, they showed a preference for the faces of children and the
elderly in the arousal evaluation. Regardless of face aesthetics, age, or facial
expression, women rated human faces higher than men. The preference for opposite-
vs. same-sex faces strongly interacted with facial age. Overall, both women and men
exhibited differences in facial processing that could be interpreted in the light
of evolutionary psychobiology. (C) 2016 Wiley Periodicals, Inc.
ObjectiveThere is evidence that some transgender people find aspects of the
Standards ofCare (SOC) for theHealth ofTranssexual,Transgender,
andGenderNonconformingPeople, and/or their implementation by health professionals,
problematic and counterproductive to transitioning. This study evaluated the
significance of this dissatisfaction to the transitioning and mental health of
transgender people. Method161 self-identified transgender people responded to an
online survey that assessed satisfaction with health services provided in
accordance with SOC guidelines, satisfaction with health professionals assisting
with their transition, personal hardiness, gender congruence, steps to transition,
and depression, anxiety, and stress. ResultsAlthough results revealed
dissatisfaction with the Standards of Care and with health professionals
(particularly psychiatrists), subsequent path analyses conducted via structural
equation modelling failed to reveal associations between this dissatisfaction and
factors relevant to transitioning or mental health. However, personal hardiness was
found to be associated with greater progress in transitioning and, by way of this,
improved gender congruence, self-esteem, and mental health. ConclusionWhile the
results reveal dissatisfaction with the Australian health system and its
professionals, this does not appear to translate into poor mental health outcomes.
Rather personal hardiness during transition is the important predictor of
transitioning and mental health. This argues for greater emphasis to be placed on
building and supporting personal resilience in transgender people.
The rapid advances in the field of computational genomics and bioinformatics have
motivated the development of innovative engineering methods for data acquisition,
interpretation, and analysis. With the help of the later methods, many processes in
molecular biology can be modeled and further analyzed. Identification and discovery
of the coding regions in the genomic structure using computational algorithms is a
clear example of such processes. This work proposes a novel application of well-
known principles and concepts from communications theory and digital signal
processing for the detection of protein coding regions in prokaryotic genomes. The
proposed algorithm employs a polyphase complex mapping scheme to provide a
numerical representation of the genomic sequences involved in the analysis. It then
utilizes concepts in communications theory such as correlation, the maximal ratio
combining (MRC) algorithm, and filtering to generate a signal whose peaks and
troughs signify coding and noncoding regions, respectively. The proposed algorithm
is applied to several prokaryotic genome sequences. Two Bayesian classifiers are
designed to evaluate the performance of the proposed algorithm. The obtained
simulation results show that the algorithm is able to efficiently and accurately
identify protein coding regions with sensitivity and specificity values comparable
to well-known gene detection methods in prokaryotes such as GLIMMER and GeneMark.
This further proves the relevance of using communications theory concepts for
genomic sequence analysis. (C) 2016 Elsevier Ltd. All rights reserved.
The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR-associated
protein (Cas) pathway is revolutionizing biological research. Modifications to this
primitive prokaryotic immune system now enable scientists to efficiently edit DNA
or modulate gene expression in living eukaryotic cells and organisms. Thus, many
laboratories can now perform important experiments that previously were considered
scientifically risky or too costly. Here, we describe the components of the
CRISPR/Cas system that have been engineered for use in eukaryotes. We also explain
how this system can be used to genetically modify cell lines and model organisms,
or regulate gene expression in order to search for new participants in biological
pathways. (c) 2017 American Society for Bone and Mineral Research.
Objective: Normalization of mRNA data, i.e., the calculation of mRNA expression
values comparable in between different experiments, is a major issue in biomedical
and orthopaedic/rheumatology research, both for single-gene technologies [Northern
blotting, conventional and quantitative polymerase chain reaction (qPCR)] and
large-scale gene expression experiments. In this study, we tested several
established normalization methods for their effects on gene expression
measurements. Method. Five standard normalization strategies were applied on a
previously published data set comparing peripheral and central late stage
osteoarthritic cartilage samples. Results: The different normalization procedures
had profound effects on the distribution as well as the significance values of the
gene expression levels. All applied normalization procedures, except the median
absolute deviation scaling, showed a bias towards up- or down-regulation of genes
as visualized in volcano plots. Of interest, the P-values were much more depending
on the normalization procedure than the fold changes. Ten commonly used
housekeeping genes showed a significant variability in between the different
specimens investigated. The gene expression analysis by cDNA arrays was confirmed
for these genes by qPCR. Conclusion: This study documents how much normalization
strategies influence the outcome of gene expression profiling analysis (i.e., the
detection of regulated genes). Different normalization approaches can significantly
change the P-values and fold changes of a large number of genes. Thus, it is of
vital importance to check every individual step of gene expression data analysis
for its appropriateness. The use of global robustness and quality measures for
analyzing individual outcomes can help in estimating the reliability of final
microarray study results. (c) 2007 Osteoarthritis Research Society International.
Published by Elsevier Ltd. All rights reserved.
This study presents the isolation and characterization of a novel nonsymbiotic Hb
gene from sessile oak (Quercus petraea) seedlings, herein designated QpHb1. The
cellular and tissue expression of QpHb1 was analysed by Northern blotting and in
situ hybridization. The encoded protein was predicted to consist of 161 amino acid
residues, and shares 71 and 51% amino acid sequence identity with the Arabidopsis
class 1 and 2 nonsymbiotic Hb, respectively. Northern blot analysis revealed that
QpHb1 was strongly expressed in roots. Spatial expression analysis of QpHb1 in the
root apical region of sessile oak by in situ hybridization indicated that
transcripts were mostly abundant in protoxylem cell initials, some cortical cells
and the protoderm. In addition, when comparing the expression profile of QpHb1 in
sessile and pedunculate oak (Quercus robur), two species with contrasted hypoxia
tolerance, the transcript level of QpHb1 rose early in the most flood-tolerant
species, pedunculate oak, during root submergence. The spatial-temporal expression
of QpHb1 suggests that this gene could participate in perception and signalling
during hypoxia.
Much effort has been devoted to the metabolic engineering of Klebsiella pneumoniae;
however, our knowledge of the actual expression level of promoters used in
K.pneumoniae is limited. In this study, the expression levels of three promoters
were compared systematically by using the lacZ reporter gene with different carbon
sources in K.pneumoniae. The results showed that, although promoters PT5 and Ptac
designed for Escherichia coli were functional, PT5 appeared more efficient and the
induction/repression ratio of Ptac was decreased extremely in K.pneumoniae. The
basal level of Ptac for lacZ expression reached 396.5U/mg, which was 9.5-fold
higher compared with PT5 in LB medium, indicating Ptac can be used as an efficient
constitutive promoter as well as an efficient induced promoter in K.pneumoniae. In
different carbon sources medium, a newly constructed endogenous constitutive Pbud
proved to be a stable and weak promoter. On the basis of our data, a set of Pbud
and Ptac promoters could meet the broad range (about 1,000 orders of magnitude) of
gene expression needed for engineered K.pneumoniae in glycerol-based medium. (C)
2015 International Union of Biochemistry and Molecular Biology, Inc.
Lung cancer is the deadliest among all cancers in the US for both men and women.
Early detection of premalignant lesions or tumors appears to be a promising
approach to reducing the morbidity and mortality from lung cancer because the
survival of early stage lung cancer patients is better than that of patients with
advanced cancers. We approached the identification of early biomarkers of human
lung carcinogenesis, by combining the use of cDNA array and an in vitro human lung
carcinogenesis model that consists of normal (NHBE), immortalized (BEAS-2B and
1799), transformed ( 1198) and tumorigenic (1170-I) human bronchial epithelial
(HBE) cells. We hypothesized that certain genes that are expressed differentially
among these cells can serve as both biomarkers for early detection and targets for
intervention. Nineteen genes were downregulated and six were upregulated in
tumorigenic 1170-I HBE cells compared to normal HBE cells ( NHBE) using cDNA array.
Downregulated genes encode cell-to-cell and cell-to-matrix adhesion-related
proteins, calcium-binding proteins and some enzymes or growth factor-related
proteins. The functions of upregulated gene were more variable. Similar expression
of selected genes was found in different nonsmall cell lung cancer cell lines
analyzed by Northern blotting. Furthermore, the differential expression of some
genes was also observed by in silico analysis of database of human lung tumors. The
differentially expressed genes encode calcium-binding proteins and cell-cell and
cell-matrix adhesion proteins. Furthermore, Northern blotting analysis of RNA from
different cell lines comprising an in vitro carcinogenesis model including normal,
immortalized, transformed, and tumorigenic cells indicated that the expression of
subsets of the identified genes changed at different stages of carcinogenesis.
These data show that the in vitro carcinogenesis cell system could be useful for
discovering potential biomarkers of early and late stages of lung carcinogenesis
and targets for chemoprevention.
Zymoseptoria tritici, the causal agent of septoria tritici blotch, a serious foliar
disease of wheat, is a necrotrophic pathogen that undergoes a long latent period.
Emergence of insensitivity to fungicides, and pesticide reduction policies, mean
there is a pressing need to understand septoria and control it through greater
varietal resistance. Stb6 and Stb15, the most common qualitative resistance genes
in modern wheat cultivars, determine specific resistance to avirulent fungal
genotypes following a gene-for-gene relationship. This study investigated
compatible and incompatible interactions of wheat with Z. tritici using eight
combinations of cultivars and isolates, with the aim of identifying molecular
responses that could be used as markers for disease resistance during the early,
symptomless phase of colonization. The accumulation of TaMPK3 was estimated using
western blotting, and the expression of genes implicated in gene-for-gene
interactions of plants with a wide range of other pathogens was measured by qRT-PCR
during the presymptomatic stages of infection. Production of TaMPK3 and expression
of most of the genes responded to inoculation with Z. tritici but varied
considerably between experimental replicates. However, there was no significant
difference between compatible and incompatible interactions in any of the responses
tested. These results demonstrate that the molecular biology of the gene-for-gene
interaction between wheat and Zymoseptoria is unlike that in many other plant
diseases, indicate that environmental conditions may strongly influence early
responses of wheat to infection by Z. tritici, and emphasize the importance of
including both compatible and incompatible interactions when investigating the
biology of this complex pathosystem.
Microarray analysis was initially performed to screen for differentially expressed
genes between nitrate-and ammonium-fed rice (Oryza sativa L.) leaves. In total, 198
genes were shown to have a unique expression response to each treatment and most of
the genes for which function is known were involved in signal transduction, plant
stress resistance, transcriptional regulation, and basic metabolism. Northern
blotting analysis confirmed that expression of the MT and PCS genes was highly
upregulated in ammonium-fed leaves compared with expression in nitrate-fed leaves
and it was further revealed that ammonium-fed leaves accumulated more cysteine and
glutathione. The upregulated expressions of the MT and PCS genes and the higher
levels of cysteine and glutathione in ammonium-fed leaves indicate that ammonium
may be able to accelerate sulfur assimilation metabolism in rice leaves.
Unexpectedly, Northern blotting analysis showed that the expression of the two key
enzymes in the sulfur assimilation pathway, namely adenosine 5'-phosphosulfate
reductase and O-acetylserine(thiol)lyase, was not upregulated by ammonium
treatment. It was found that the total content of free amino acids was much higher
in ammonium-fed leaves compared with nitrate-fed leaves, mainly resulting from an
increase in several amino acids such as serine, asparagine, glutamine, and
arginine. The increased amino acids, in particular serine (as a central substrate
for the synthesis of the thiol metabolites), may have promoted sulfur assimilation
metabolism under conditions of ammonium nutrition.
Increasing evidence indicates an association between the concentration of systemic
progesterone during the early luteal phase of the oestrous cycle and embryo
survival rate in cattle. We examined the relationship between the concentration of
systemic progesterone on Days 4 to 8 post-ovulation and expression of progesterone
receptor (PGR), oestrogen receptor a (ESR1) and retinol-binding protein (RBP) mRNA
in the bovine endometrium. Heifers were blood sampled from the day of ovulation
(Day 0) to Day 8 post-ovulation. On Day 4, animals were divided into low
progesterone control (LC) and high progesterone control (HC) groups based on their
plasma progesterone concentrations. Half of each group was supplemented with
exogenous progesterone resulting in two further groups, low progesterone
supplemented (LS) and high progesterone supplemented (HS). Endometrial tissues were
recovered from all groups on Day 6 or Day 8 and gene expression was analysed
following Northern blotting. Increasing progesterone concentrations were associated
with decreased PGR and ESR1 expression. Duration-dependent effects of progesterone
supplementation on ESR1 were evident and there was an effect of systemic
progesterone concentrations between Day 0 and Day 4 on the expression of RBP at
Days 6 and 8. Such progesterone-responsive changes in uterine gene expression are
likely to affect embryo development.
An important issue for molecular biology is to establish whether transcript levels
of a given gene can be used as proxies for the corresponding protein levels. Here,
we have developed a targeted proteomics approach for a set of human non-secreted
proteins based on parallel reaction monitoring to measure, at steady-state
conditions, absolute protein copy numbers across human tissues and cell lines and
compared these levels with the corresponding mRNA levels using transcriptomics. The
study shows that the transcript and protein levels do not correlate well unless a
gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type
is introduced, thus significantly enhancing the predictability of protein copy
numbers from RNA levels. The results show that the RTP ratio varies significantly
with a few hundred copies per mRNA molecule for some genes to several hundred
thousands of protein copies per mRNA molecule for others. In conclusion, our data
suggest that transcriptome analysis can be used as a tool to predict the protein
copy numbers per cell, thus forming an attractive link between the field of
genomics and proteomics.
Quantitative real-time reverse transcription PCR (RT-qPCR) has been widely used in
the detection and quantification of gene expression levels because of its high
accuracy, sensitivity, and reproducibility as well as its large dynamic range.
However, the reliability and accuracy of RT-qPCR depends on accurate transcript
normalization using stably expressed reference genes. Amorphophallus is a perennial
plant with a high content of konjac glucomannan (KGM) in its corm. This crop has
been used as a food source and as a traditional medicine for thousands of years.
Without adequate knowledge of gene expression profiles, there has been no report of
validated reference genes in Amorphophallus. In this study, nine genes that are
usually used as reference genes in other crops were selected as candidate reference
genes. These putative sequences of these genes Amorphophallus were cloned by the
use of degenerate prirners. The expression stability of each gene was assessed in
different tissues and under two abiotic stresses (heat and waterlogging) in A.
albus and A. konjac. Three distinct algorithms were used to evaluate the expression
stability of the candidate reference genes. The results demonstrated that EF1-a,
EIF4A, H3 and UBQ were the best reference genes under heat stress in
Amorphophallus. Furthermore, EF1-a, EIF4A, TUB, and RP were the best reference
genes in waterlogged conditions. By comparing different tissues from all samples,
we determined that EF1-a, EIF4A, and CYP were stable in these sets. In addition,
the suitability of these reference genes was confirmed by validating the expression
of a gene encoding the small heat shock protein SHSP, which is related to heat
stress in Amorphophallus. In sum, EF1-a and EIF4A were the two best reference genes
for normalizing mRNA levels in different tissues and under various stress
treatments, and we suggest using one of these genes in combination with 1 or 2
reference genes associated with different biological processes to normalize gene
expression. Our results will provide researchers with appropriate reference genes
for further gene expression quantification using RT-qPCR in Amorphophallus.
Background/Aims: Liver injury results in the activation of hepatic stellate cells
(HSCs), which in turn produce matrix metalloproteinase (MMP) in response to pro-
inflammatory cytokines for tissue remodelling. This study explored the
transcriptional induction of the MMP-1 gene by tumour necrosis factor-alpha (TNF-
alpha) in HSCs. Methods: The LI90 human HSC line was used in the present study.
Gelatin zymography, enzyme-linked immunosorbent assay, Northern blotting and gene
promoter-reporter assays were used to analyse the induction of MMP-1 protein, mRNA
expression and gene transcription respectively. Deletional or site-directed
mutations were introduced into the promoter region and transiently transfected into
LI90 cells to determine the cis-acting elements necessary for TNF-alpha
inducibility. Gel shift mobility assays were used to determine the transcriptional
factors involved in the TNF-alpha responsiveness. Results: TNF-alpha upregulated
MMP-1 protein and mRNA expression in a dose-dependent manner. A time-course
experiment revealed a rapid induction of MMP-1 mRNA expression after TNF-alpha
treatment. Mutation in a putative nuclear factor (NF)-kappa B-binding site at -2541
bp almost completely abolished the TNF-alpha response to MMP-1 gene-promoter
activity, suggesting transcriptional regulation of MMP-1 expression by TNF-alpha
via this site. Electrophoretic mobility shift assay and supershift assays indicated
that this transcriptional regulation was regulated via the p50/p50 homodimer of NF-
kappa B. Conclusions: MMP-1 gene expression might be induced by TNF-alpha via the
p50/p50 homodimer of NF-kappa B in activated human HSCs.
At the end of June, over 120 microbiologists from 18 countries gathered in Dundee,
Scotland for the fourth edition of the Young Microbiologists Symposium on 'Microbe
Signalling, Organisation and Pathogenesis'. The aim of the symposium was to give
early career microbiologists the opportunity to present their work in a convivial
environment and to interact with senior world-renowned scientists in exciting
fields of microbiology research. The meeting was supported by the Microbiology
Society, the Society of Applied Microbiology and the American Society for
Microbiology with further sponsorship from the European Molecular Biology
Organisation and the Royal Society of Edinburgh. In this report, we highlight some
themes that emerged from the many interesting talks and poster presentations, as
well as some of the other activities that were on offer at this energetic meeting.
Harnessing the immune system to fight cancer is an exciting advancement in lung
cancer therapy. Antitumor immunity can be augmented by checkpoint blockade therapy,
which removes the inhibition/brakes imposed on the immune system by the tumor.
Checkpoint blockade therapy with anti-programmed cell death protein 1
(anti-PD-1)/anti-programmed death ligand 1 (anti-PDL-1) antibodies causes tumor
regression in about 25% of patients with lung cancer. In another approach, the
immune system is forced or accelerated to attack the tumor through augmentation of
the antitumor response against mutations carried by each lung tumor. This latter
approach has become feasible since the advent of next-generation sequencing
technology, which allows identification of the specific mutations that each
individual lung tumor bears. Indeed lung cancers are now known to have high
mutation rates, making them logical targets for mutation-directed immune therapies.
We review how sequencing of lung cancer mutations leads to better understanding of
how the immune system recognizes tumors, providing improved opportunities to track
antitumor immunity and ultimately leading to the development of personalized
vaccine strategies aimed at unleashing the host immune system to attack mutations
in the tumor.
Recent studies in our laboratories have shown that Protein Kinase C delta (PKC
delta) is essential for insulin-induced glucose transport in skeletal muscle, and
that insulin rapidly stimulates PKC delta activity skeletal muscle. The purpose of
this study was to examine mechanisms of regulation of PKC delta protein
availability. Studies were done on several models of mammalian skeletal muscle and
utilized whole cell lysates of differentiated myotubes. PKC delta protein levels
were determined by Western blotting techniques, and PKC delta RNA levels were
determined by Northern blotting, RT-PCR and Real-Time RT-PCR. Insulin stimulation
increased PKC delta protein levels in whole cell lysates. This effect was not due
to an inhibition by insulin of the rate of PKC delta protein degradation. Insulin
also increased 35 S-methionine incorporation into PKC delta within 5-15 min.
Pretreatment of cells with transcription or translation inhibitors abrogated the
insulin-induced increase in PKC delta protein levels. We also found that insulin
rapidly increased the level of PKC delta RNA, an effect abolished by inhibitors of
transcription. The insulin-induced increase in PKC delta expression was not reduced
by inhibition of either P13 Kinase or MAP kinase, indicating that these signaling
mechanisms are not involved, consistent with insulin activation of PKC delta.
Studies on cells transfected with the PKC delta promoter demonstrate that insulin
activated the promoter within 5 min. This study indicates that the expression of
PKC delta may be regulated in a rapid manner during the course of insulin action in
skeletal muscle and raise the possibility that PKC delta may be an immediate early
response gene activated by insulin. (c) 2005 Elsevier Inc. All rights reserved.
Gene trapping is a powerful method for identifying novel genes and for analyzing
their functions. It is, however, difficult to select trapped genes on the basis of
their function. To identify genes regulated by transcription factors that are
important in the mesodermal formation, we selected trapped ES clones by infection
of adenoviral vectors expressing Pax1, Brachyury, and Foxa2. Among 366 trapped
genes, seven seemed to be controlled by these transcription factors in the first
screening. The trapped genes were identified by 5' RACE, and a Northern blotting
revealed that expressions of three trapped genes were regulated by these
transcription factors. Expression patterns of Cx43 and HPI gamma implicated their
functional relationships to Foxa2 in the formation of the notochord and the neural
tube. Furthermore, Wtap mutant mice derived from the trapped clone showed defects
in the mesendoderm formation. Our results indicate that trapped ES clones could be
selected effectively using transcription factors. (c) 2007 Elsevier Inc. All rights
reserved.
Few studies have addressed likely gene x gene (ie, epistatic) interactions in
mediating risk for schizophrenia. Using a preclinical genetic approach, we
investigated whether simultaneous disruption of the risk factors Neuregulin-1
(NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant
phenotypic profile different from that observed following disruption to either gene
alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse
inhibition, both reversed by antipsychotic treatment, and accompanied by reduced
striatal dopamine D2 receptor protein expression, impaired social cognition, and
altered glutamatergic synaptic protein expression in selected brain areas. Single
gene DISC1 mutants demonstrated a disruption in social cognition and nest-building,
altered brain 5-hydroxytryptamine levels and hippocampal ErbB4 expression, and
decreased cortical expression of the schizophrenia-associated microRNA miR-29b. Co-
disruption of DISC1 and NRG1, indicative of epistasis, evoked an impairment in
sociability and enhanced self-grooming, accompanied by changes in hypothalamic
oxytocin/ vasopressin gene expression. The findings indicate specific behavioral
correlates and underlying cellular pathways downstream of main effects of DNA
variation in the schizophrenia-associated genes NRG1 and DISC1.
Differential display (DD) experiments were performed on drought-tolerant rice
(Oryza sativa L.) genotype N22 to identify both upregulated and down-regulated
partial cDNAs with respect to moisture stress. DNA polymorphism was detected
between drought-stressed and control leaf tissues on the DD gels. A partial cDNA
showing differential expression, with respect to moisture stress was isolated from
the gel. Northern blotting analysis was performed using this, cDNA as a probe and
it was observed that mRNA corresponding to this transcript was accumulated to high
level in rice leaves under water deficit stress. At the DNA sequence level, the
partial cDNA showed homology with psb A gene encoding for D1 protein.
Objective To test the phenotypic plasticity framework using a polygenic approach in
a prospective depression cohort of primary care attendees with and without
histories of severe childhood abuse. Methods Depressive symptoms were assessed at
baseline and annually for 5 years post-baseline using the Primary Care Evaluation
of Mental Disorders Patient Health Questionnaire-9 (PHQ-9) among 288 adult primary
care attendees. Twelve polymorphisms in nine genes were genotyped and polygenic
phenotypic plasticity allelic load (PAL) calculated. Linear mixed models assessed
differences in depressive symptom severity over the 5-year follow-up period by PAL
and history of severe childhood abuse. Results A higher PAL conferred greater
depressive symptom severity among those with a history of severe childhood abuse
but conferred significantly lower symptom severity among those without this
history. Importantly, this interaction withstood adjustments for important
covariates (e.g., antidepressant use, comorbid anxiety) and was stable over the 5
years of observation. Conclusions Aligned with the phenotypic plasticity framework,
depressive symptom severity was dependent on the interaction between PAL and
history of severe childhood abuse in a for better and for worse manner. Measures of
polygenic phenotypic plasticity, such as ours, may serve as a trait marker of
sensitivity to negative and potentially positive environmental influences.
Although intelligence should theoretically evolve to help animals solve specific
types of problems posed by the environment, it is unclear which environmental
challenges favour enhanced cognition, or how general intelligence evolves along
with domain-specific cognitive abilities. The social intelligence hypothesis posits
that big brains and great intelligence have evolved to cope with the labile
behaviour of group mates. We have exploited the remarkable convergence in social
complexity between cercopithecine primates and spotted hyaenas to test predictions
of the social intelligence hypothesis in regard to both cognition and brain size.
Behavioural data indicate that there has been considerable convergence between
primates and hyaenas with respect to their social cognitive abilities. Moreover,
compared with other hyaena species, spotted hyaenas have larger brains and expanded
frontal cortex, as predicted by the social intelligence hypothesis. However,
broader comparative study suggests that domain-general intelligence in carnivores
probably did not evolve in response to selection pressures imposed specifically in
the social domain. The cognitive buffer hypothesis, which suggests that general
intelligence evolves to help animals cope with novel or changing environments,
appears to offer a more robust explanation for general intelligence in carnivores
than any hypothesis invoking selection pressures imposed strictly by sociality or
foraging demands.
Generalized additive mixed models are introduced as an extension of the generalized
linear mixed model which makes it possible to deal with temporal autocorrelational
structure in experimental data. This autocorrelational structure is likely to be a
consequence of learning, fatigue, or the ebb and flow of attention within an
experiment (the 'human factor'). Unlike molecules or plots of barley, subjects in
psycholinguistic experiments are intelligent beings that depend for their survival
on constant adaptation to their environment, including the environment of an
experiment. Three data sets illustrate that the human factor may interact with
predictors of interest, both factorial and metric. We also show that, especially
within the framework of the generalized additive model, in the nonlinear world,
fitting maximally complex models that take every possible contingency into account
is illadvised as a modeling strategy. Alternative modeling strategies are discussed
for both confirmatory and exploratory data analysis. (C) 2016 Elsevier Inc. All
rights reserved.
Some areas in China are facing pressing air pollution problems. Measures from the
power sector can be taken to cope with air pollution issues, including reducing
emission levels of thermal units and integrating wind and solar power. Social
welfare, emission, and renewable integration are three major concerns in modern
power system operations. This paper describes three stochastic scheduling models
aiming at maximizing social welfare (SW), minimizing emission (EM) and maximizing
renewable production (RE). A multi-objective scheduling model (MT) is also proposed
that properly balances the above objectives. Wind power uncertainty and
dispatchable loads are considered in the model. The outcomes of the three models
are compared through an illustrative example and a 57-node case study. Results show
that model EM results in 36% of the social welfare of model SW, 27% of its
emissions, and 43% of its wind spillage, while model RE results in 55% of the
social welfare of model SW, 56% of its emissions and 28% of its wind spillage.
Additionally, we analyze how the optimal generation scheduling is affected by the
weights in model MT. This work provides insight to policy makers on how to balance
social welfare, emissions and renewable production. (C) 2017 Elsevier Ltd. All
rights reserved.
High-temperature superconducting (HTS) generators for large-scale wind power
generation systems attract much research attention. Excitation systems in HTS
generators, particularly brushless HTS exciters, are a new challenge. To verify the
possibility of a brushless HTS exciter in a large-scale wind power generator, we
designed and fabricated HTS coils for a laboratory-scale wind power generator
employing a brushless exciter. In order to supply dc current into the HTS coils, a
brushless exciter was considered in the generator. All of the field coils were
wound with an HTS coated conductor made of 2G GdBCO wire. The conduction cooling
test was executed in a cryogenic test chamber to check the performances at 30 K.
The detailed results of the operating performance of the HTS coils were discussed
in detail.
A complete model of a thermionic generator has been developed in order to optimise
the technology for application in the solar thermal generation of electricity.
Steady state current densities predicted by the model have been shown to agree with
published experimental thermionic data. Two separate genetic algorithm
optimisations have been carried out for both power density and efficiency, in which
electrode temperatures and work functions, external circuit resistance and
electrode separation were varied. The result of these optimisations were two
configurations separately exhibiting a maximum power density of 1.66 W/cm(2), and a
Maximum efficiency of 7.69% for parameter ranges applicable to concentrating solar
thermal power. Examination of the optimum simulation parameters indicated that
future developments in lowering collector work functions, increasing emitter
service temperature and decreasing attainable electrode separations will all
positively impact device performance. (C) 2017 Elsevier Ltd. All rights reserved.
Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details
have been uncovered in several model organisms, and most of its essential features
have received various and often contradictory evolutionary interpretations. In this
perspective, we present an overview of these often 'weird' features. We discuss the
origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis),
its secondary modifications (in polyploids or asexuals, inverted meiosis), its
importance in punctuating life cycles (meiotic arrests, epigenetic resetting,
meiotic asymmetry, meiotic fairness) and features associated with recombination
(disjunction constraints, heterochiasmy, crossover interference and hotspots). We
present the various evolutionary scenarios and selective pressures that have been
proposed to account for these features, and we highlight that their evolutionary
significance often remains largely mysterious. Resolving these mysteries will
likely provide decisive steps towards understanding why sex and recombination are
found in the majority of eukaryotes. This article is part of the themed issue
'Weird sex: the underappreciated diversity of sexual reproduction'.
Modern biotechnology is one of the most important scientific and technological
revolutions in the 21st century, with an increasing and measurable impact on
society. Development of biotechnology curriculum has become important to high
school bioscience classrooms. This study has monitored high school students in
Taiwan on their knowledge of and attitudes towards biotechnology for nearly two
decades. Not surprisingly, knowledge of biotechnology of current students has
increased significantly (p<0.001) and most students have learned some definitions
and examples of biotechnology. There was a positive correlation between
biotechnology knowledge and attitudes toward biotechnology for current students who
study Advanced Biology (AB). However, for current students who did not study AB,
there was a negative correlation. The attitude results showed that students today
expressed less favorable opinions toward agricultural biotechnology (p < 0.001)
despite studying AB or not. However, there is no significant difference between
students today and 18 years ago in opinions towards medical biotechnology. In
addition, current students showed a greater concern involving environmental risks
than former students. Interestingly, the high school curriculum did affect
students' attitudes toward genetically engineered (GE) plants but not GE animals.
Our current study also found that the students' attitude towards GE animals was
influenced more by their limited knowledge than by their moral belief. On the basis
of findings from this study, we suggest that more materials of emerging animal
biotechnology should be included in high school curriculum and recommend that high
school teachers and university faculty establish a collaborative framework in the
near future. (C) 2016 by The International Union of Biochemistry and Molecular
Biology
Aim of study - to estimate leptin gene (Arg223Gln) genotypes polymorphism in
patients with coronary heart disease and obesity. Materials and Methods. 222
patients with the coronary heart disease (CHD) and obesity have been
comprehensively examined. All patients were on treatment in cardiologic unit of KUZ
of the Kharkiv city hospital. 27, which is the basic clinic of Department of
Internal Medicine. 2 and Clinical Immunology and Allergology of the Kharkiv
National Medical University of MH of Ukraine. The comparison group consisted of 115
ischemic heart disease patients with normal body weight. 35 practically healthy
persons formed the control group. Groups were comparable in age and sex. The study
didn't include the patients with the serious accompanying pathology of respiratory
organs, digestion, kidneys and persons with oncological diseases. Results. In the
control group there was the following distribution of leptin gene (Arg223Gln)
alleles and genotypes polymorphism frequency: 15 people were allele A that made
42.86 %, allele G -20 people (57.14 %); genotypes G/G, A/A and G/G had 15 (42.86
%), 7 (20 %) and 13 (37.14 %) persons respectively. 42 patients with CHD were
allele A, which made 36.52 %, allele G -73 patients (63.48 %). Genotypes G/G, A/A
and G/G had 47 (40.87 %), 20 (17.39 %) and 48 (41.74%) patients with CHD
respectively. In group of patients with combination of CHD and obesity 71 patients
(31.98 %) were allele A, allele G -151 people (68.02 %); genotypes G/G, A/A and G/G
-81 (36.49 %), 33 (14.87 %) and 108 (48.64 %) respectively. Comparison of leptin
gene (Arg223Gln) alleles and genotypes polymorphism frequency of detection between
groups showed the reliable differences of alleles A, G and a genotype G/G. In
patients with CHD and obesity allele G was 10.88 % more and genotype G/G was 11.5 %
more, than in the control group. Allele A was 10.88 % more in the control group,
than in patients with CHD and obesity (p < 0.05). Reliable differences between
group of CHD patients and the control group in distribution of detected alleles and
genotypes frequency of leptin gene (Arg223Gln) polymorphism were not found (p <
0.05). Conclusions. By results of the study allele G and a genotype G/G of leptin
gene (Arg223Gln) polymorphism in patients with CHD has been associated with
obesity.
India is rich in genetic diversity of major pulse crops, but the productivity and
the production of pulse crops remains low compared to the world and hence, there is
a need to enhance the utilization for increasing the production. Major pulse
species for which genetic diversity is occurring in India include Vigna, Cajanus,
Cicer, Pisum, Lens, Phaseolus and few minor pulses such as Macrotyloma, Canavalia,
Lathyrus, Vicia, Mucuna, Moghania and Rhynchosia etc. National Bureau of PInt
Genetic Resources (NBPGR) is the nodal institute for the "management of plant
genetic resources in India. It has assembled-70,000 accessions of different pulse
crops majoring Cajanus cajan, Cicer arietinum, Phaseolus vulgaris, Pisum sativum,
Vigna mungo, Vigna radiata, Vigna umbellata, Vigna unguiculata, Viceasp. and Lens
sp. through collection and introduction from India and from >70 other countries of
the world. Several pests of quarantine significance have been identified and
salvaged from the exotic germplasm. The ex situ base collection at NBPGR conserve
64,744 accessions of 20 genera and 61 species of pulses. This germplasm has been
characterized for agro-morphological, quality and biochemical traits, biotic and
abiotic stresses for identifying trait-specific reference sets and 28 catalogues
describing about 45,000 accessions of 14 pulse crops. A total of 121 accessions of
various pulse crops have been registered as unique/potential donors. Core and mini
cores have been developed in chickpea, pigeonpea, common bean, mungbean, adzuki
bean, cowpea, lentil, moth bean and pea both nationally and internationally. Wild
species of pulse crops have been utilized for transferring desirable traits into
cultivated species. Application of modern tools and technologies of molecular
biology will accelrate the process of gene transfer for improvement of pulse crops.
Background: A comprehensive evaluation of associations between the susceptibility
to norovirus infections and histo-blood group antigens is not available in the
Taiwanese population, in which the nonsecretor phenotype is absent. Methods: A 1: 1
matched case-control study was conducted in northern Taiwan from February 2013 to
December 2014 when an epidemic of norovirus infection occurred. Cases were children
<18 years old who were hospitalized because of diarrhea and were found to have
laboratory-confirmed norovirus infections. Controls were healthy children matched
to the cases by age and gender. The norovirus genotype was determined by polymerase
chain reaction sequencing of the VP1 gene. The secretor status, Lewis antigen and
ABO type were determined by characterization of genetic polymorphisms in the FUT2,
FUT3 and ABO genes, respectively. Results: A total of 147 case-control pairs were
included. GII. 4 Sydney strain was the major genotype and identified in 78.3% of
the cases. The weak-secretor and Lewis-positive genotypes were less commonly
identified in cases than in controls (5.4% vs. 23.1% and 79.6% vs. 89.8%,
respectively). Multivariate analysis revealed that the secretor and Lewis-negative
genotypes were both independent factors associated with increased risk of norovirus
infections [matched odds ratio: 6.766, 95% confidence interval (CI): 2.649-17.285,
P0.05). Conclusion: The weak-secretor genotype and the Lewis antigen-positive
genotype were both protective factors against severe norovirus gastroenteritis
during the GII. 4 Sydney strain epidemic in Taiwan.
The aim of the current study was to use gene therapy to attenuate or reverse the
degenerative process within the intervertabral disc. The effect of survivin gene
therapy via lentiviral vector transfection on the course of intervertebral disc
degeneration was investigated in the current study in an in vivo rabbit model. A
total of 15 skeletally mature female New Zealand White rabbits were randomly
divided into three groups: Punctured blank control group (group A, n=5), punctured
empty vector control group (group B, n=5) and the treatment group (group C, n=5).
Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in
accordance with a previously validated rabbit annulotomy model for intervertebral
disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was
injected into the nucleus pulposus. The results demonstrated that through magnetic
resonance imaging, histology, gene expression, protein content and apoptosis
analyses, group A and B were observed to exhibit disc degeneration, which increased
over time, and no significant difference was observed between the two groups
(P>0.05). However, there was reduced disc degeneration in group C compared with the
punctured control groups, and the difference was statistically significant
(P<0.05). Overall, the results of the present study demonstrated that injection of
the LV carrying survivin into punctured rabbit intervertebral discs acted to delay
changes associated with the degeneration of the discs. Although data from animal
models should be extrapolated to the human condition with caution, the present
study suggests potential for the use of gene therapy to decelerate disc
degeneration.
Gene editing is a relatively recent concept in the molecular biology field.
Traditional genetic modifications in animals relied on a classical toolbox that,
aside from some technical improvements and additions, remained unchanged for many
years. Classical methods involved direct delivery of DNA sequences into embryos or
the use of embryonic stem cells for those few species (mice and rats) where it was
possible to establish them. For livestock, the advent of somatic cell nuclear
transfer platforms provided alternative, but technically challenging, approaches
for the genetic alteration of loci at will. However, the entire landscape changed
with the appearance of different classes of genome editors, from initial zinc
finger nucleases, to transcription activator-like effector nucleases and, most
recently, with the development of clustered regularly interspaced short palindromic
repeats (CRISPR) and CRISPR-associated proteins (Cas). Gene editing is currently
achieved by CRISPR-Cas-mediated methods, and this technological advancement has
boosted our capacity to generate almost any genetically altered animal that can be
envisaged.
Genetically modified organisms are increasingly used in the production of feed and
food, which has met with opposition from consumers. The aim of the study was the
use of molecular biology methods with particular emphasis on techniques of real-
time PCR in the research in the detection and identification of genetically
modified feed. The research materials were samples of feed taken from feed produced
and used in animal nutrition in Poland in the years 20042015. The applied research
methods included PCR and real-time PCR techniques, and consisted in the detection
and determination of the DNA content of genetically modified plants. Cascade
methods used in this study included the screening method of detection of GMOs, the
method of identifying the type of GMO, and methods of quantitative analysis of GMO
content. As part of the research task in the years 20042015 a total of 1435 samples
of feed towards GMOs were examined. A positive result was found in 559 cases (39%).
Most frequently the positive samples were found the presence of genetically
modified soybeans (531, 37%). Moreover, within the years 20142015 an increase in
the number of positive GM rape samples was observed (56, 4%). GM maize contained
the least positive samples (38, 2.6%). GMO content above the legislative threshold
0.9% was found in the vast majority of samples containing GM soy, while for maize
and rapeseed the number of samples containing more than 0.9% GMO was respectively
12 and 8. Analysis of the feed market in Poland indicates that the soybean plant is
the most common genetically modified crop. Analysis of the origin of sources of GM
rapeseed showed that the reasons for this should be sought in batches of rapeseed
imported from third countries. It has been observed with regard to the situation of
GM maize for the feed market in Poland that from 2013 the situation changed
radically as a result of the Decree of the Ministry of Agriculture issued
prohibiting the cultivation of MON810 maize on Polish fields. The result of our
study showed that the proportion of genetically modified feed on the feed market in
Poland is very similar to other EU countries. The source of GMOs in feed on the
Polish market is feed materials imported into Poland as a source of feed protein.
One novel standard reference plasmid, namely pUC-RICE5, was constructed as a
positive control and calibrator for event-specific qualitative and quantitative
detection of genetically modified (GM) rice (Bt63, Kemingdaol, Kefeng6, Kefeng8,
and LLRice62). pUC-RICE5 contained fragments of a rice-specific endogenous
reference gene (sucrose phosphate synthase) as well as the five GM rice events. An
existing qualitative PCR assay approach was modified using pUC-RICE5 to create a
quantitative method with limits of detection correlating to approximately 1-10
copies of rice haploid genomes. In this quantitative PCR assay, the square
regression coefficients ranged from 0.993 to 1.000. The standard deviation and
relative standard deviation values for repeatability ranged from 0.02 to 0.22 and
0.10% to 0.67%, respectively. The Ministry of Food and Drug Safety (Korea)
validated the method and the results suggest it could be used routinely to identify
five GM rice events. (C) 2017 Elsevier Ltd. All rights reserved.
Purpose of Review The ebb and flow of genetic influence relative to the
understanding of craniofacial and dental disorders has evolved into a tacit
acceptance of the current genetic paradigm. This review explores the science behind
craniofacial and dental disorders through the lens of recent past and current
findings and using tooth agenesis as a model of advances in craniofacial genetics.
Recent Findings Contemporary studies of craniofacial biology takes advantage of the
technological resources stemming from the genomic and post-genomic eras. Emerging
data highlights the role of key genes and the epigenetic landscape controlling
these genes, in causing dentofacial abnormalities. We also report here a novel
Glu78FS MSX1 mutation in one family segregating an autosomal dominant form of
severe tooth agenesis as an illustration of an evolving theme, i.e., different
mutations in the same gene can result in a spectrum of dentofacial phenotypic
severity. Summary The future of clinical therapeutics will benefit from advances in
genetics and molecular biology that refine the genotype-phenotype correlation.
Indeed, the past century suggests a continued convergence of genetic science in the
practice of clinical dentistry.
The overarching theme of the 2016 Society of Toxicology Pathology's Annual
Symposium was "The Basis and Relevance of Variation in Toxicologic Responses.''
Session 4 focused on genetic variation as a potential source for variability in
toxicologic responses within nonclinical toxicity studies and further explored how
knowledge of genetic traits might enable targeted prospective and retrospective
studies in drug development and human health risk assessment. In this session, the
influence of both genetic sequence variation and epigenetic modifications on
toxicologic responses and their implications for understanding risk were explored.
In this overview, the presentations in this session will be summarized, with a goal
of exploring the ramifications of genetic and epigenetic variability within and
across species for toxicity studies and disseminating information regarding novel
tools to harness this variability to advance understanding of toxicologic responses
across populations.
Introduction: Tumour necrosis factor-alpha (TNF alpha) gene -308G/A polymorphism
(rs1800629) are associated with psoriasis in several populations worldwide.
Presently, there is no literature on the status of this polymorphism in the South
Indian population. Aim: To determine the profile of TNF alpha -308G/A polymorphism
among psoriatic patients. Materials and Methods: This case-control study involved
74 patients with Psoriasis Vulgaris (PsV) and 74 age and gender matched healthy
individuals. Patients were recruited from the Department of Dermatology of R. L.
Jalappa Hospital and Research Center, Tamaka, Kolar, Karnataka, India, from March
2014 to March 2016. TNF alpha -308G/A polymorphism was genotyped by Polymerase
Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results:
The frequency of TNF alpha -308A allele 7.4% among psoriatic and 8.8% among non-
psoriatic individuals. The difference was not statistically significant (p=0.82).
Conclusion: Our results indicate that TNF alpha gene -308G/A polymorphism is not a
significant marker for the risk of developing PsV among South Indian (Karnataka)
psoriatic patients.
The aim of this study was to analyze the influence of nucleotide transition (G/A)
in position -2518 of the MCP-1 gene related to the susceptibility of developing RA.
Two hundred twenty-three consecutive RA patients according to 2010 ACR/EULAR
criteria were included; 120 healthy subjects were used as controls. MCP-1 -2518 A/G
polymorphism (AG + GG) was present in 162 (72.6 %) RA patients and in 63 (52.5 %)
healthy subjects [OR 2.44 (IC95% 1.53-3.88, p = 0.0002)]; associations for
heterozygotes and homozygotes were OR 1.92 (IC95% 1.19-3.15, p = 0.001) and OR 5.19
(IC95% 2.34-11.51, p = 0.001), respectively. In Argentine patients, MCP-1 gene
polymorphism confers susceptibility for developing RA.
Background: Several lines of evidence suggest that the dietary isoflavone genistein
(Gen) has beneficial effects with regard to cardiovascular disease and in
particular on aspects related to blood pressure and angiogenesis. The biological
action of Gen may be, at Least in part, attributed to its ability to affect cell
signalling and response. However, so far, most of the molecular mechanisms
underlying the activity of Gen in the endothelium are unknown. Methods and results:
To examine the transcriptional response to 2.5 mu M Gen on primary human
endothelial cells (HUVEC), we applied cDNA array technology both under baseline
condition and after treatment with the pro-atherogenic stimulus, copper-oxidized
LDL. The alteration of the expression patterns of individual transcripts was
substantiated using either RT-PCR or Northern blotting. Gen significantly affected
the expression of genes encoding for proteins centrally involved in the vascular
tone such as endothelin-converting enzyme-1, endothetin-2, estrogen related
receptor a and atria[ natriuretic peptide receptor A precursor. Furthermore, Gen
countered the effect of oxLDL on mRNA levels encoding for vascular endothelial
growth factor receptor 165, types 1 and 2. Conclusions: Our data indicate that
physiologically achievable levels of Gen change the expression of mRNA encoding for
proteins involved in the control of blood pressure under baseline conditions and
reduce the angiogenic response to oxLDL in the endothelium. (c) 2005 Elsevier B.V.
All rights reserved.
Background. The mechanisms by which DNA sequences are expressed is the central
preoccupation of molecular genetics. Recently, ourselves and others reported that
in the diplomonad protist Giardia lamblia, the coding regions of several mRNAs are
produced by ligation of independent RNA species expressed from distinct gnomic
loci- Such trans splicing of introns was found to affect nearly as many genes in
this organism as does classical cis-splicing of introns. These findings raised
questions about the incidence of intron trans-splicing both across the G. lamblia
transcriptome and across diplomonad diversity in general, however a dearth of
transcriptomic data at the time prohibited systematic study of these questions.
Methods. I leverage newly available transcriptornic data from G. lamblia and the
related diplomonad Spironucleus salmonicida to search for trans-spliced introns. My
computational pipeline recovers all four previously reported trans spliced introns
in G. lamblia, suggesting good sensitivity. Results. Scrutiny of thousands of
potential cases revealed only a single additional trans-spliced intron in G.
lamblia, in the p68 helicase gene, and no cases in S. salmorticida. The p68 intron
differs from the previously reported trans-spliced introns in its high degree of
streamlining: the core features of G. lamblia trans-spliced introns are closely
packed together, revealing striking economy in the implementation of a seemingly
inherently uneconomical molecular mechanism. Discussion. These results serve to
circumscribe the role of trails splicing in diplomonads both in terms of the number
of genes effected and taxonomically. Future work should focus on the molecular
mechanisms, evolutionary origins and phenotypic implications of this intriguing
phenomenon.
The clustered, regularly interspaced, short palindromic repeat (CRISPR) and CRISPR
associated protein 9 (Cas9) system discovered as an adaptive immunity mechanism in
prokaryotes has emerged as the most popular tool for the precise alterations of the
genomes of diverse species. CRISPR/Cas9 system has taken the world of genome
editing by storm in recent years. Its popularity as a tool for altering genomes is
due to the ability of Cas9 protein to cause double-stranded breaks in DNA after
binding with short guide RNA molecules, which can be produced with dramatically
less effort and expense than required for production of transcription-activator
like effector nucleases (TALEN) and zinc-finger nucleases (ZFN). This system has
been exploited in many species from prokaryotes to higher animals including human
cells as evidenced by the literature showing increasing sophistication and ease of
CRISPR/Cas9 as well as increasing species variety where it is applicable. This
technology is poised to solve several complex molecular biology problems faced in
life science research including cancer research. In this review, we highlight the
recent advancements in CRISPR/Cas9 system in editing genomes of prokaryotes, fungi,
plants and animals and provide details on software tools available for convenient
design of CRISPR/Cas9 targeting plasmids. We also discuss the future prospects of
this advanced molecular technology. Crown Copyright (C) 2016 Published by Elsevier
B.V. All rights reserved.
Volvariella volvacea is difficult to store fresh because of the lack of low-
temperature resistance. Many traditional mutagenic strategies have been applied in
order to select out strains resistant to low temperature, but few commercially
efficient strains have been produced. In order to break through the bottleneck of
traditional breeding and significantly improve low-temperature resistance of the
edible fungus V. volvacea, strains resistant to low temperature were constructed by
genome shuffling. The optimum conditions of V. volvacea strain mutation, protoplast
regeneration, and fusion were determined. After protoplasts were treated with 1%
(v/v) ethylmethylsulfonate (EMS), 40Sec of ultraviolet (UV) irradiation, 600 Gy
electron beam implantation, and 750 Gy(60)Co- irradiation, separately, the
lethality was within 70%-80%, which favored generating protoplasts being used in
following forward mutation. Under these conditions, 16 strains of V. volvacea
mutated by EMS, electron beam, UV irradiation, and Co-60- irradiation were
obtained. The 16 mutated protoplasts were selected to serve as the shuffling pool
based on their excellent low-temperature resistance. After four rounds of genome
shuffling and low-temperature resistance testing, three strains (VF1, VF2, and VF3)
with high genetic stability were screened. VF1, VF2, and VF3 significantly enhanced
fruit body shelf life to 20, 28, and 28H at 10 degrees C, respectively, which
exceeded 25%, 75%, and 75%, respectively, compared with the storage time of V23,
the most low-temperature-resistant strain. Genome shuffling greatly improved the
low-temperature resistance of V. volvacea, and shortened the course of screening
required to generate desirable strains. To our knowledge, this is the first paper
to apply genome shuffling to breeding new varieties of mushroom, and offers a new
approach for breeding edible fungi with optimized phenotype. (C) 2015 International
Union of Biochemistry and Molecular Biology, Inc.
Genome sequences nowadays play a central role in molecular biology and
bioinformatics. These sequences are shared with the scientific community through
sequence databases. The sequence repositories of the International Nucleotide
Sequence Database Collaboration (INSDC, comprising GenBank, ENA and DDBJ) are the
largest in the world. Preparing an annotated sequence in such a way that it will be
accepted by the database is challenging because many validation criteria apply. In
our opinion, it is an undesirable situation that researchers who want to submit
their sequence need either a lot of experience or help from partners to get the job
done. To save valuable time and money, we list a number of recommendations for
people who want to submit an annotated genome to a sequence database, as well as
for tool developers, who could help to ease the process.
A current goal of molecular biology is to identify transcriptional networks that
regulate cell differentiation. However, identifying functional gene regulatory
elements has been challenging in the context of developing tissues where material
is limited and cell types are mixed. To identify regulatory sites during sex
determination, we subjected Sertoli cells from mouse fetal testes to DNaseI-seq and
ChIP-seq for H3K27ac. DNaseI-seq identified putative regulatory sites around genes
enriched in Sertoli and pregranulosa cells; however, active enhancers marked by
H3K27ac were enriched proximal to only Sertoli-enriched genes. Sequence analysis
identified putative binding sites of known and novel transcription factors likely
controlling Sertoli cell differentiation. As a validation of this approach, we
identified a novel Sertoli cell enhancer upstream of Wt1, and used it to drive
expression of a transgenic reporter in Sertoli cells. This work furthers our
understanding of the complex genetic network that underlies sex determination and
identifies regions that potentially harbor non-coding mutations underlying
disorders of sexual development.
Genomic DNA of good quality is a prerequisite in molecular biology studies involved
in deciphering the information contained in the molecules that are chosen for
studying the evolutionary interrelationships among taxa. Genomic DNA should be free
of contaminants which may otherwise interfere while performing PCR. This is
particularly essential while isolating genomic DNA from gastropods due to the
presence of large amounts of mucopolysaccharides in their tissues. In the present
study, we have developed a new method for obtaining high quality genomic DNA from a
pulmonate snail Achatina fulica, which secretes a large amount of mucus. In this
method, we have obtained good quality genomic DNA, compatible for downstream
molecular biology applications like PCR and sequencing of 16S rDNA. The yield of
the genomic DNA was 2790 mu g/ml. This method may be extended for isolating high
quality genomic DNA from different gastropods native to Indian sub-continent, which
serves as a starting point for studying their phylogenetic affinities.
Single nucleotide polymorphisms (SNPs) in DNA can result in phenotypes where the
biochemical basis may not be clear due to the lack of protein structures. With the
growing number of modeling and simulation software available on the internet,
students can now participate in determining how small changes in genetic
information impact cellular protein structure and function. We have developed a
modular series of activities to engage lab or lecture students in examining the
basis for common phenotypes. The activities range from basic phenotype
testing/observation to DNA sequencing and simulation of protein structure and
dynamics. We provide as an example study of the bitterness receptor TAS2R38 and PTC
tasting, however these activities are applicable to other SNPs or genomic variants
with a direct connection to an observable phenotype. These activities are modular
and can be mixed to meet the student capabilities and infrastructure availability.
The complete sequence of activities will demonstrate the direct connection between
gene structure, protein structure and organism function. (C) 2016 by The
International Union of Biochemistry and Molecular Biology
DNA microarrays are one of the new tools of genomics that have become quite
commonplace in plant science research within the past decade. Essentially, DNA
microarrays are an extension of the more traditional molecular biology technique of
northern blotting. Unlike northern blotting, however, in which the expression of a
single gene is monitored, DNA microarrays allow for the simultaneous monitoring of
thousands of genes-or, in fact, potentially all of an organism's genes-in a single
experiment. Most of the currently available plant microarrays are designed for
crops species or the model plant, Arabidopsis; however, a microarray for at least
one major weed species is currently available. Furthermore, CDNA-based microarrays
prepared for one species can be used to investigate gene expression in related
species. As the technology is maturing it is becoming much more accessible, and now
is the time to begin utilizing microarrays in weed science research. Questions
related to herbicide activity are particularly well suited for a microarray
approach. Additionally, gene-expression profiling via microarrays can be used to
address questions relating to weed biology, weed-crop competition, allelopathy,
parasitic weeds, and biological control of weeds.
In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we
utilized a multi-dimensional approach to test the hypothesis that mutations in
myelin proteins lead to immune activation and central nervous system autoimmunity
in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions
revealed seven unique mutations of PLP1; a key myelin protein that is known to be
destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the
genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA.
Quantification of wild type and mutant PLP RNA levels by qPCR further validated the
presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations
in abundant myelin proteins and immune-mediated destruction of myelin, specific
immune response against mutant PLP1 in MS patients was examined. Thus, we have
designed paired, wild type and mutant peptide microarrays, and examined antibody
response to multiple mutated PLP1 in sera from MS patients. Consistent with the
idea of different patients exhibiting unique mutation profiles, we found that 13
out of 20 MS patients showed antibody responses against specific but not against
all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody
response against specific mutant peptides in the sera of pre-MS controls. The
results from integrative proteomic, genomic, and immune analyses reveal a possible
mechanism of mutation-driven pathogenesis in human MS. The study also highlights
the need for integrative genomic and proteomic analyses for uncovering pathogenic
mechanisms of human diseases.
High-grade osteosarcomas are the most common primary malignant tumors of bone. With
complete surgical resection and multi-agent chemotherapy up to 70% of patients with
high-grade osteosarcomas and localized extremity tumors can become long-term
survivors. The prognosis, however, is poor for patients with nonresectable, primary
metastatic or relapsed disease. Outcome is essentially unchanged for three decades.
Herein, we describe selected novel insights into the genomics, biology and
immunology of the disease and discuss selected strategies, which hold promise to
overcome the current stagnation in the therapeutic success in childhood
osteosarcoma.
Characterizing the immune response to pneumococcal proteins is critical in
understanding this bacterium's epidemiology and vaccinology. Probing a custom-
designed proteome microarray with sera from 35 healthy US adults revealed a
continuous distribution of IgG affinities for 2,190 potential antigens from the
species-wide pangenome. Reproducibly elevated IgG binding was elicited by 208
"antibody binding targets" (ABTs), which included 109 variants of the diverse
pneumococcal surface proteins A and C (PspA and PspC) and zinc metalloprotease A
and B (ZmpA and ZmpB) proteins. Functional analysis found ABTs were enriched
inmotifs for secretion and cell surface association, with extensive representation
of cell wall synthesis machinery, adhesins, transporter solute-binding proteins,
and degradative enzymes. ABTs were associated with stronger evidence for evolving
under positive selection, although this varied between functional categories, as
did rates of diversification through recombination. Particularly rapid variation
was observed at some immunogenic accessory loci, including a phage protein and a
phase-variable glycosyltransferase ubiquitous among the diverse set of genomic
islands encoding the serine-rich PsrP glycoprotein. Nevertheless, many antigens
were conserved in the core genome, and strains' antigenic profiles were generally
stable. No strong evidence was found for any epistasis between antigens driving
population dynamics, or redundancy between functionally similar accessory ABTs, or
age stratification of antigen profiles. These results highlight the paradox of why
substantial variation is observed in only a subset of epitopes. This result may
indicate only some interactions between immunoglobulins and ABTs clear pneumococcal
colonization or that acquired immunity to pneumococci is an accumulation of
individually weak responses to ABTs evolving under different levels of functional
constraint.
MicroRNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in both
plants and animals. A large number of miRNAs has been identified from various
animals and model plant species such as Arabidopsis thaliana and rice (Oryza
sativa); however, characteristics of wheat (Triticum aestivum) miRNAs are poorly
understood. Here, computational identification of miRNAs from wheat EST sequences
was preformed by using the in-house program GenomicSVM, a prediction model for
miRNAs. This study resulted in the discovery of 79 miRNA candidates. Nine out of 22
miRNA representatives randomly selected from the 79 candidates were experimentally
validated with Northern blotting, indicating that prediction accuracy is about 40%.
For the 9 validated miRNAs, 59 wheat ESTs were predicted as their putative targets.
Between July 2009 and June 2014, a total of 1,546 fecal specimens were collected
from children <5 years of age with acute gastroenteritis admitted to Kiambu County
Hospital, Central Kenya. The specimens were screened for group A rotavirus (RVA)
using ELISA, and RVA-positive specimens were subjected to semi-nested RT-PCR to
determine the G and P genotypes. RVA was detected in 429/1,546 (27.5%) fecal
specimens. RVA infections occurred in all age groups <59 months, with an early peak
at 6-17 months. The infections persisted year-round with distinct seasonal peaks
depending on the year. G1P[8] (28%) was the most predominant genotype, followed by
G9P[8] (12%), G8P[4] (7%), G1P[4] (5%), G9P[4] (4%), and G12P[6] (3%). In the
yearly change of G and P genotypes, a major shift from G9P[8] to G1P[8] was found
in 2012. Phylogenetic analysis of the nucleotide sequences of the VP7 and VP4 genes
of seven strains with unusual G8 or P[6] showed that the VP7 nucleotide sequences
of G8 were clustered in lineage 6 in which African strains are included, and that
there are at least two distinct VP4 nucleotide sequences of P[6] strains. These
results represent basic data on RVA strains circulating in this region before
vaccine introduction. (C) 2016 Wiley Periodicals, Inc.
Microtremor survey is a kind of passive-source methods which uses ambient ground
tremors for geological investigation. Compared with traditional geophysical
methods, it is more flexible, cost-efficient, and environmentally friendly. Most
currently used geophones are expensive and bulky, and therefore inconvenient to
large-scale deployment. In this study, a no-cable low-cost geophone was optimized
to suit for large-scale microtremor survey. The method of optimization is based on
the following four points: First, it selects a sensor through the analysis of the
self-noise of to meet the needs of microtremor survey. Second, it chooses the right
operational amplifier and AD conversion module. Third, it integrates design of the
entire system without using external module. And fourth, it makes a low-cost design
of the geophone system, including selection of low-cost hardware components and
reducing the amount of software code. Finally, the optimized geophone was used in
three areas with different geological conditions in order to verify the rationality
of the improvement and the possibilities for large-scale microtremor survey. The
purpose of optimization has been achieved in this research. The no-cable geophone
wrights only 600 g, and the maximum average power cost does not exceed 0. 1 mW. The
entire system costs less than 2000 RMB. The most important thing is the optimized
geophone can record the microtremor signal from O. 5 to 20 Hz effectively.
Experiments show that in different geological conditions the geophone can be setup
quickly and work smoothly and reliably. The results of microtremor survey
experiments are consistent with the existing geological data. Because the new
geophone is much cheaper than the existing microtremor survey equipment, it is
possible to use it in low-cost large-scale survey. The optimized geophone has a
very small volume and light weight, and can be rapidly emplacedinto a variety of
detector arrays. After the emplacement of large number of geophones, it can easily
and quickly conduct survey to two-dimensional or three-dimensional velocity
structure of the area. Such microtremor survey with environment-friendly and low-
cost advantages has broad application prospects.
PurposeAlthough much has been written about Medicare Part D enrollment, much less
is known about beneficiaries' personal experiences with choosing a Part D plan,
especially among rural residents. This study sought to address this gap by
examining geographic differences in Part D enrollees' perceptions of the plan
decision-making process, including their confidence in their choice, their
knowledge about the program, and their satisfaction with available information.
MethodsWe used data from the 2012 Medicare Current Beneficiary Survey and included
adults ages 65 and older who were enrolled in Part D at the time of the survey (n =
3,706). We used ordered logistic regression to model 4 outcomes based on
beneficiaries' perceptions of the Part D decision-making and enrollment process,
first accounting only for differences by rurality, then adjusting for
sociodemographic, health, and coverage characteristics. FindingsOverall, half of
all beneficiaries were not very confident in their Part D knowledge. Rural
beneficiaries had lower odds of being confident in the plan they chose and in being
satisfied with the amount of information available to them during the decision-
making process. After adjusting for all covariates, micropolitan residents
continued to have lower odds of being confident in the plan that they chose.
ConclusionsPolicy-makers should pay particular attention to making information
about Part D easily accessible for all beneficiaries and to addressing unique
barriers that rural residents have in accessing information while making decisions,
such as reduced Internet availability. Furthermore, confidence in the decision-
making process may be improved by simplifying the Part D program.
Osmoprimed seeds increased the abundance of pGlcT proteins. Osmopriming together
with heat shock increased the abundance of RBR proteins. NAD-ME increased when
osmoprimed and heat-shocked seeds were imbibed at low temperature. The purpose of
seed priming is to accelerate and synchronize germination and to increase stress
tolerance through the activation of genes that function when seeds are exposed to
unfavorable conditions. The objectives of this study were: (1) to evaluate the
effects of osmopriming and heat-shock treatment on the germination of Eucalyptus
urophylla seeds at different temperatures and (2) to analyze the seed proteome to
elucidate the mechanisms of tolerance to thermal stress in primed and unprimed
seeds. Untreated (control) seeds, osmoprimed (polyethylene glycol for 3 days) and
redried seeds, and osmoprimed/heat-shocked (45 A degrees C for 1 h) and redried
seeds were germinated for 14 days under constant light (2 x 40 W fluorescent
daylight tubes) at 9, 16, 22, 24, or 31 A degrees C. Osmopriming, with or without
heat-shock, led to a significant increase in the germination percentage at 9 A
degrees C and induced the highest germination speed index at 31 A degrees C.
According to proteomic analysis, osmoprimed seeds exhibited an increased abundance
of several proteins, including sugar transport proteins, and this may have
influenced the metabolic rate during germination. Osmopriming together with heat-
shock treatment increased the abundance of proteins associated with regulation of
the cell cycle suggesting that such proteins may be involved in protection against
thermal stress. The Krebs cycle enzyme was increased when osmoprimed and heat-
shocked seeds were imbibed at low temperature, possibly signifying increased
synthesis of adenosine triphosphate. The results reported herein serve to explain
some of the benefits of osmopriming/heat-shock treatment.
This study used Gestalt theory to examine the effects of colour similarity on
blurring the boundary between banner advertising and web page content, as well as
how colour similarity can elicit unconscious scanning behaviour and improve
attitudes towards brands advertised using banner advertising at the pre-attention
stage. An eye tracking device was used to record and analyse participants' eye
movement, and a psychological scale was used to measure the participants' brand
attitudes. The results suggested that using banner advertisements with background
colours similar to those of the web page content increases the fixation time and
fixation count. In addition, the results revealed that a longer fixation time and a
higher fixation count increase positive attitudes towards a brand advertised in a
banner advertisement. The results clarify the relationship between unconscious
exposure and brand attitudes and provide physiological information relevant to e-
commerce.
Viewing and manipulating three-dimensional (3D) structures in molecular graphics
software are essential tasks for researchers and students to understand the
functions of molecules. Currently, the way to manipulate a 3D molecular object is
mainly based on mouse-and-keyboard control that is usually difficult and tedious to
learn. While gesture-based and touch-based interactions are increasingly popular in
interactive software systems, their suitability in handling molecular graphics has
not yet been sufficiently explored. Here, we designed the gesture-based and touch-
based interaction methods to manipulate virtual objects in PyMOL utilizing the
motion and touch sensors in a mobile device. Three fundamental viewing controls-
zooming, translation and rotation-and frequently used functions were implemented.
Results from a pilot user study reveal that task performances on viewing controls
using a mobile device are slightly reduced as compared to mouse-and-keyboard
method. However, it is considered to be more suitable for oral presentations and
equally suitable for education scenarios such as school classes. Overall, PyMOL
mControl provides an alternative way to manipulate objects in molecular graphic
software with new user experiences. The software is freely available at . (c) 2016
by The International Union of Biochemistry and Molecular Biology, 45(1):76-83,
2017.
According to the World Health Organization, mental distress and related illnesses
are becoming leading causes of morbidity and mortality in developing countries.
Despite the influence of food insecurity on mental health, empirical understanding
of this relationship in sub-Saharan Africa, where incidence of food insecurity is
relatively high, is almost non-existent. This study contributes to the literature
by examining the association between food insecurity and mental health in the Upper
West Region of Ghana. We used Ordinary Least Square (OLS) to analyze cross-
sectional data collected on household heads (n = 1438) in 2014 using the Household
Food Insecurity Access Scale and the DUKE Health Profile. The results show that
heads of severely food insecure (beta= 0.934, p <= 0.001) and moderately food
secure households (beta = 0.759, p <= 0.001) were more likely to report elevated
mental distress compared to those from food secure households. We also found that
female household heads were more likely to report elevated mental distress (beta=
0.164, p <= 0.05) compared to their male counterparts. Our findings suggest the
need to improve food security as a strategy targeted at improving overall mental
health in the Ghanaian context. (C) 2017 Elsevier Ltd. All rights reserved.
Flow cytometry has contributed to virology but has faced many drawbacks concerning
detection limits, due to the small size of viral particles. Nonetheless, giant
viruses changed many concepts in the world of viruses, as a result of their size
and hence opened up the possibility of using flow cytometry to study them.
Recently, we developed a high throughput isolation of viruses using flow cytometry
and protozoa co-culture. Consequently, isolating a viral mixture in the same sample
became more common. Nevertheless, when one virus multiplies faster than others in
the mixture, it is impossible to obtain a pure culture of the minority population.
Here, we describe a robust sorting system, which can separate viable giant virus
mixtures from supernatants. We tested three flow cytometry sorters by sorting
artificial mixtures. Purity control was assessed by electron microscopy and
molecular biology. As proof of concept, we applied the sorting system to a co-
culture supernatant taken from a sample containing a viral mixture that we couldn't
separate using end point dilution. In addition to isolating the quick-growing
Mimivirus, we sorted and re-cultured a new, slow-growing virus, which we named
Cedratvirus. The sorting assay presented in this paper is a powerful and versatile
tool for separating viral populations from amoeba co-cultures and adding value to
the new field of flow virometry.
Ginger (Zingiber officinale Rosc.) is prone to photoinhibition under intense
sunlight. Excessive light can be dissipated by the xanthophyll cycle, where
violaxanthin de-epoxidase (VDE) plays a critical role in protecting the
photosynthesis apparatus from the damage of excessive light. We isolated similar to
2.0 kb of ginger VDE (GVDE) gene promoter, which contained the circadian box, I-
box, G-box and GT-1 motif. Histochemical staining of Arabidopsis indicated the GVDE
promoter was active in almost all organs, especially green tissues. beta-
glucuronidase (GUS) activity driven by GVDE promoter was repressed rather than
activated by high light. GUS activity was altered by hormones, growth regulators
and abiotic stresses, which increased with 2,4-dichlorophenoxyacetic acid and
decreased with abscisic acid, salicylic acid, zeatin, salt (sodium chloride) and
polyethylene glycol. Interestingly, GUS activities with gibberellin or indole-3-
acetic acid increased in the short-term (24 h) and decreased in the long-term (48
and 72 h). Analysis of 5' flank deletion found two crucial functional regions
residing in -679 to -833 and -63 to -210. Northern blotting analysis found
transcription to be regulated by the endogenous circadian clock. Finally, we found
a region necessary for regulating the circadian rhythm and another for the basic
promoter activity. Key message A novel promoter, named GVDE promoter, was first
isolated and analyzed in this study. We have determined one region crucial for
promoter activity and another responsible for keeping circadian rhythms.
ObjectivesTo investigate the gene expression profile of human gingiva following
surgical wounding. MethodsTen volunteers had one side of the palate wounded. Five
days later, biopsies were harvested from both wounded (healing gingiva) and contra-
lateral site (normal gingiva). Tissue samples were processed for gene expression
(RNA-Seq, real-time PCR) and immunohistochemistry. Gene set enrichment/pathway
analysis was also performed. ResultsSeven hundred genes were significantly
differentially expressed in healing gingiva. Among genes with >twofold change (FC)
in expression, 399 genes were up-regulated and 88 down-regulated, several not
previously reported expressed in gingiva. Most increased in expression (30-FC) were
MMP1, CCL18, SPP1, MUC21, CTHRC1, MMP10, and SERPINE1; most decreased (7-FC) were
COCH, SIAH3, MT4, IGFL3, KY, and SYT16. Real-time PCR confirmed significantly
changed mRNA levels for selective genes tested. Gene set enrichment analysis
revealed several significantly enriched biological pathways. Immunohistochemistry
confirmed protein expression of MUC21, CTHRC1, CTGF, and SYT16 in normal and
healing gingiva. ConclusionsThis first comprehensive analysis of the human gingival
transcriptome during surgical wound healing offers novel insights into the
participating molecular and biological mechanisms. The present results could serve
as basis for future investigations into gingival wound healing following surgical,
traumatic, or other type of injury.
The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key
factor of resistance to oncolytic therapy. Here, we identify FAM96A as a
ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate
its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal
tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating
factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by
deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and
immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis
sensitivity were examined in cancer cells and zebrafish embryos. Expression of
FAM96A in GISTs and histogenetically related cells including interstitial cells of
Cajal (ICCs), fibroblast-like cells (FLCs) and ICC stem cells (ICC-SCs) was
investigated by Northern blotting, reverse transcriptionpolymerase chain reaction,
immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and
transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by
xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1
and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was
dramatically reduced or lost in 106 of 108 GIST samples representing three
independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal
counterparts of GIST, were found to robustly express FAM96A protein and mRNA,
FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A
in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and
diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor
suppressor that is lost during GIST tumorigenesis. What's new? The emergence of
drug resistance is a major problem in gastrointestinal stromal tumors (GISTs),
where tumor cell escape appears in many instances to be associated with acquired
resistance to apoptosis. Here, a protein known as FAM96A was found to bind to
apoptotic peptidase activating factor 1 (APAF1) and to be profoundly reduced in
most GISTs. When FAM96A expression was re-established in cells, tumor sensitivity
to apoptosis increased. In xenograft and allograft murine models, tumor growth
slowed with FAM96A re-expression. Hence, FAM96A may have a tumor-suppressive role
in GISTs. Knowledge of its function could aid the development of novel GIST
therapies.
Treatment of diseases with gene therapy is advancing rapidly. The use of gene
therapy has expanded from the original concept of replacing the mutated gene
causing the disease to the use of genes to control nonphysiological levels of
expression or to modify pathways known to affect the disease. Genes offer numerous
advantages over conventional drugs. They have longer duration of action and are
more specific. Genes can be delivered to the target site by naked DNA, cells,
nonviral, and viral vectors. The enormous progress of the past decade in molecular
biology and delivery systems has provided ways for targeting genes to the intended
cell/ tissue and safe, long-term vectors. The eye is an ideal organ for gene
therapy. It is easily accessible and it is an immune-privileged site. Currently,
there are clinical trials for diseases affecting practically every tissue of the
eye, including those to restore vision in patients with Leber congenital amaurosis.
However, the number of eye trials compared with those for systemic diseases is
quite low (1.8%). Nevertheless, judging by the vast amount of ongoing preclinical
studies, it is expected that such number will increase considerably in the near
future. One area of great need for eye gene therapy is glaucoma, where a long-term
gene drug would eliminate daily applications and compliance issues. Here, we review
the current state of gene therapy for glaucoma and the possibilities for treating
the trabecular meshwork to lower intraocular pressure and the retinal ganglion
cells to protect them from neurodegeneration.
Glioblastoma is the most common type of primary brain tumor in adults, and is
usually fatal in a short duration. Acquiring a better understanding of the
pathogenic mechanisms of glioblastoma is essential to the design of effective
therapeutic strategies. Grb2-associated binding protein 2 (GAB2) is a member of the
daughter of sevenless/Gab family of scaffolding adapters, and has been reported to
be important in the development and progression of human cancer. Previously, it has
been reported that GAB2 is expressed at high levels in glioma, and may serve as a
useful prognostic marker for glioma and a novel therapeutic target for glioma
invasion intervention. Elucidating why GAB2 is overexpressed in glioma, and
investigating how to downregulate it will assist in further understanding the
pathogenesis and progression of the disease, and to offer novel targets for
therapy. The present study used in situ hybridization to detect microRNA (miR)-197
expression levels and Targetscan to predict that the 3'-UTR of GAB2 was targeted by
miR-197. Northern blotting and reverse transcription-quantitative polymerase chain
reaction were also conducted in the current study. miR-197 is downregulated in
glioblastoma tissues, compared with adjacent normal tissues, however it involvement
continues to be detected in the disease. The results of the present study
demonstrated that miR-197, as a tumor suppressor gene, inhibited proliferation by
regulating GAB2 in glioblastoma cells. Furthermore, GAB2 was not only upregulated
in glioma, but its expression levels were also associated with the grades of glioma
severity. In addition, overexpression of GAB2 suppressed the expression of miR-197
in glioblastoma cells. Therefore, restoration of miR-197 and targeting GAB2 may be
used, in conjunction with other therapies, to prevent the progression of
glioblastoma.
Activation of the AKT (serine-threonine kinase) pathway is a common feature in
glioblastoma cells. Downstream factors of the AKT pathway are involved in cell
proliferation, apoptosis, cellular migration and angiogenesis. Micro-RNAs (miRNAs)
are highly conserved small non-coding RNAs that block targeted mRNA expression at
the post-transcriptional level. The aim of this study was to investigate the role
of the AKT pathway in regulating miRNA. The changes of miRNA expression profile in
human glioblastome U251 cells after AKT small interfering RNA transfection were
examined by a microarray, and confirmed by Northern blotting. Down-regulation of
AKT expression by siRNA decreased the activity of AKT pathway in U251 cells.
Interruption of AKT pathway suppressed the expression of NF-kappa B and c-Myc,
furthermore, the expression of a set of miRNAs was also changed after AKT siRNA
transfection. There are putative binding sites of NF-kappa B and c-Myc in the
promoters of several up-regulated miRNAs, indicating these transcription factors
may also be involved in the regulation of miRNA expression, thus affecting the
activity of AKT pathway in tumorigenesis. We provide new components of the
regulatory function of AKT pathway to better understand the regulatory network
mediated by downstream transcription factors. The understanding of the regulatory
function of AKT pathway is crucial in tailored therapy of gliomas.
Aberrant expression of microRNAs correlates with the development and progression of
human cancers by targeting downstream proteins. MiR-1202 is downregulated in
ovarian cancer and clear cell papillary renal cell carcinoma; however, its role in
glioma remains unknown. The purpose of this study was to determine the expression
and the role of miR-1202 and to elucidate its regulatory mechanism in glioma. We
used quantitative real-time polymerase chain reaction to measure miR-1202
expression in both glioma tissues and cell lines. The findings showed that the miR-
1202 expression decreased dramatically in clinical glioma tissues and cell lines,
and miR-1202 expression was inversely correlated with the expression of Rab1A.
Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel
and direct target of miR-1202. In vitro, overexpression of miR-1202 inhibited
glioma cell proliferation and induced endoplasmic reticulum stress and apoptosis
through targeting Rab1A, whereas suppression of miR-1202 promoted cell
proliferation and inhibited endoplasmic reticulum stress and apoptosis. Similarly,
silencing Rab1A with small interfering RNA also suppressed glioma cell growth and
induced endoplasmic reticulum stress and apoptosis. Taken together, our data
indicate that miR-1202 suppresses proliferation and induces endoplasmic reticulum
stress and apoptosis through targeting and inhibiting Rab1A in glioma cells. These
results suggest miR-1202 as a potential therapeutic target for the treatment of
glioma patients.
Prolonged translation arrest correlates with delayed neuronal death of hippocampal
CA1 neurons following global cerebral ischemia and reperfusion. Many previous
studies investigated ribosome molecular biology, but mRNA regulatory mechanisms
after brain ischemia have been less studied. Here we investigated the embryonic
lethal abnormal vision/Hu isoforms HuR, HuB, HuC, and HuD, as well as expression of
mRNAs containing adenine and rich uridine elements following global ischemia in rat
brain. Proteomics of embryonic lethal abnormal vision immunoprecipitations or
polysomes isolated from rat hippocampal CA1 and CA3 from controls or following
10min ischemia plus 8h of reperfusion showed distinct sets of mRNA-binding
proteins, suggesting differential mRNA regulation in each condition. Notably, HuB,
HuC, and HuD were undetectable in NIC CA1. At 8h reperfusion, polysome-associated
mRNAs contained 46.1% of ischemia-upregulated mRNAs containing adenine and rich
uridine elements in CA3, but only 18.7% in CA1. Since mRNAs containing adenine and
rich uridine elements regulation are important to several cellular stress
responses, our results suggest CA1 is disadvantaged compared to CA3 in coping with
ischemic stress, and this is expected to be an important contributing factor to CA1
selective vulnerability. (Data are available via ProteomeXchange identifier
PXD004078 and GEO Series accession number GSE82146).
Purpose of Review Globally, the majority of those who need mental health care
worldwide lack access to high-quality mental health services. Stigma, human
resource shortages, fragmented service delivery models, and lack of research
capacity for implementation and policy change contribute to the current mental
health treatment gap. In this review, we describe how health systems in low-and
middle-income countries (LMICs) are addressing the mental health gap and further
identify challenges and priority areas for future research. Recent Findings Common
mental disorders are responsible for the largest proportion of the global burden of
disease; yet, there is sound evidence that these disorders, as well as severe
mental disorders, can be successfully treated using evidence-based interventions
delivered by trained lay health workers in low-resource community or primary care
settings. Stigma is a barrier to service uptake. Prevention, though necessary to
address the mental health gap, has not solidified as a research or programmatic
focus. Research-to-practice implementation studies are required to inform policies
and scale-up services. Summary Four priority areas are identified for focused
attention to diminish the mental health treatment gap and to improve access to
high-quality mental health services globally: diminishing pervasive stigma,
building mental health system treatment and research capacity, implementing
prevention programs to decrease the incidence of mental disorders, and establishing
sustainable scale up of public health systems to improve access to mental health
treatment using evidence-based interventions.
Riboswitches are cis-acting mRNA elements that regulate gene expression in response
to ligand binding. Recently, a class of riboswitches was proposed to respond to the
molybdenum cofactor (Moco), which serves as a redox center for metabolic enzymes.
The 5' leader of the Escherichia coli moaABCDE transcript exemplifies this
candidate riboswitch class. This mRNA encodes enzymes for Moco biosynthesis, and
moaA expression is feedback inhibited by Moco. Previous RNA-seq analyses showed
that moaA mRNA copurified with the RNA binding protein CsrA (carbon storage
regulator), suggesting that CsrA binds to this RNA in vivo. Among its global
regulatory roles, CsrA represses stationary phase metabolism and activates central
carbon metabolism. Here, we used gel mobility shift analysis to determine that CsrA
binds specifically and with high affinity to the moaA 5' mRNA leader. Northern
blotting and studies with a series of chromosomal lacZ reporter fusions showed that
CsrA posttranscriptionally activates moaA expression without altering moaA mRNA
levels, indicative of translation control. Deletion analyses, nucleotide
replacement studies and footprinting with CsrA-FeBABE identified two sites for CsrA
binding. Toeprinting assays suggested that CsrA binding causes changes in moaA RNA
structure. We propose that the moaA mRNA leader forms an aptamer, which serves as a
target of posttranscriptional regulation by at least two different factors, Moco
and the protein CsrA. While we are not aware of similar dual posttranscriptional
regulatory mechanisms, additional examples are likely to emerge. (c) 2012 Elsevier
Ltd. All rights reserved.
Background: In vitro experiments have revealed that toll-like receptor 4 (TLR4)
pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by
induction of proinflammatory cytokines. Evidence showed that, in other disease
models, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have
been shown to exert anti-inflammatory effects through suppression of the expression
and activity of TLR4. However, the interaction between PPAR-gamma and TLR4 in IgAN
has not been fully studied both in vitro and in vivo. In this study, we explored
whether TLR4 pathway attributed to the progression of IgAN in experimental rats.
Methods: Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis
rats were randomly divided into six groups: Control(TAK242), IgAN(TAK242), toll-
like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4
inhibitor, TAK242) and Control(Pio), IgAN(Pio), Pio groups (rats were administrated
with PPAR-y agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR),
serum creatinine, and blood urea nitrogen were detected by automatic biochemical
analyzer. Renal histopathological changes were observed after hematoxylin-eosin
staining, and the IgA deposition in glomeruli was measured by immunofluorescence
staining. Real-time polymerase chain reaction and Western blotting were used to
detect TLR4 and interleukin-1 beta (IL-1 beta) message ribonucleic acid (mRNA) and
protein expression in renal tissues. Results were presented as mean +/- standard
deviation. Differences between groups were analyzed by one-way analysis of
variance. Results: Compared to normal rats, experimental rats showed higher ACR
(4.45 +/- 1.33 mg/mmol vs. 2.89 +/- 0.96 mg/mmol, P < 0.05), obvious IgA deposition
with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by
increased serum IL-1 beta (48.28 +/- 13.49 pg/ml vs. 35.56 +/- 7.4 lpg/ml, P <
0.05), and renal expression of IL-1 beta and TLR4. The biochemical parameters and
renal pathological injury were relieved in both TAK242 group and Pio group. The
expressions of renal tissue TLR4, IL-1 beta, and serum IL-113 were decreased in
rats treated with TAK242, and the expression of TLR4 mRNA and protein was
significantly reduced in Pio group compared to IgAN(Pio) group (1.22 +/- 0.28 vs.
1.72 +/- 0.45, P < 0.01, and 0.12 +/- 0.03 vs. 0.21 +/- 0.05, P< 0.01).
Conclusions: Our study proves that inflammation mediated by TLR4 signaling pathway
is involved in the progression of IgAN in rat models. Moreover, pioglitazone can
inhibit the expression of TLR4 in IgAN.
Background: Stem cell factor (SCF) has been implicated in many disease processes
characterized by tissue remodelling and fibrosis. The growth factor (SCF) was
evaluated in a rat model of nephrotoxic serum nephritis (NTN), characterized by
early inflammation followed by later tissue fibrosis. Methods: NTN was induced in
male Wistar Kyoto rats using rabbit anti-rat glomerular basement membrane
antibodies. Animals were sacrificed at days 7, 15, 30 and 45 (n = 4-10 per group).
Rats' kidneys were immunostained for ED1 as marker of inflammation, CD34, SCF, c-
kit, mast cell tryptase and markers of fibrosis; collagens III and IV and alpha-
SMA. Changes in SCF protein and mRNA content were evaluated by Western blotting and
Northern blotting, respectively. Results: In the NTN kidney, levels of
immunoreactive SCF and SCF receptor (c-kit) were significantly higher in
glomerular, tubular and interstitial compartments. Mast cells were barely
detectable in NTN and control rat sections. Double immunostaining showed the co-
localization of SCF with alpha-SMA and of the SCF receptor with CD34 and ED1
positive cells. Immunostainable SCF protein in each of the 3 compartments,
glomerular, tubular and interstitial, showed a positive linear correlation with
serum creatinine, proteinuria, glomerulosclerosis score and interstitial fibrosis
scores. Using multivariate analysis, immunostainable tubular SCF was a predictor of
glomerular sclerosis and immunostainable glomerular SCF predicted tubular atrophy.
Increased SCF immunostain was not a consequence of altered transcription as there
was a fall in SCF mRNA determined by Northern blotting. Western blotting of NTN
kidney homogenates revealed two bands for SCF, a 43-kDa band which decreased, and a
19-kDa band which increased throughout the study. Conclusion: These results
highlight the potential role of SCF and its receptor in the remodelling process of
the NTN kidney. Upregulation of SCF may involve a translational mechanism, with the
soluble SCF protein KL-S1 (19 kDa) being derived from the transmembrane SCF protein
KL-S1 (43 kD) by proteolytic cleavage. The immunohistochemical staining of few
CD34+ cells in NTN kidneys warrants further evaluation of the nature of these cells
in the context of the inflammatory as well as the fibrotic processes. Copyright (c)
2007 S. Karger AG, Basel.
Background and Objectives The mechanism of glucocorticoid -induced apoptosis is not
fully understood and early predictive assays based on apoptotic markers for
clinical outcome in acute lymphoblastic leukemia (ALL) are scarce. The aim of this
study was to characterize the involvement of Bcl-2 family members and caspase
activation in dexamethasone(Dex)induced apoptosis in ALL. Design and Methods
Primary childhood ALL samples, the pre-B ALL cell line RS(4;11), and the T-ALL cell
line CCRF-CEM were used. The involvement of Bcl-2 family members was evaluated by
flow cytometry, immunocytochemistry, and western and northern blotting. Apoptosis
was analyzed by annexin V and TMRE staining. Caspase activity was evaluated by a
fluorometric assay. Results Dex induced significant down-regulation of the anti-
apoptotic Bcl-2 family members Bcl-2 and Bcl-xL, differential activation of the
pro-apoptotic Bak and Bax, loss of Delta psi m and cytochrome c release. Dex-
induced apoptosis also involved early activation of caspases 2 and -3. Inhibition
of caspase activity did not, however, protect against Dex-induced Bak/Bax
activation, loss of Delta psi m or cell death. In 12 primary ALL samples Dex-
induced apoptosis was associated with activation of Bax (p=0.045) and clown-
regulation of Bcl-2 (p=0.016) and/or Bcl-xL (p=0.004). Furthermore, ex vivo Dex-
sensitivity was associated with an early treatment response to polychemotherapy
(p=0.026). Interpretation and Conclusions The differential regulation of pro- and
anti-apoptotic Bcl-2 family members appears to be a key event in the execution of
Dex-induced apoptosis in ALL cell lines, and also indicates a role for these
proteins in primary ALL cells.
Experimental and epidemiological evidence suggests that consumption of hydrolyzable
carbohydrate, hCHO (grain), by horses is an important risk factor for colic, a
common cause of equine mortality. It is unknown whether the small intestinal
capacity to digest hCHO and/or to absorb monosaccharides is limiting, or even if
horses can adapt to increased carbohydrate load. We investigated changes in the
brush-border membrane carbohydrate digestive enzymes and glucose absorptive
capacity of horse small intestine in response to increased hCHO. Expression of the
Na+/glucose co-transporter, SGLT1, was assessed by Western blotting,
immunohistochemistry, Northern blotting, QPCR, and Na+-dependent d-glucose
transport. Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-
fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses
maintained on a hCHO-enriched diet compared to pasture forage. Activity of the
disaccharidases was unaltered by diet. In a well-controlled study, we determined
SGLT1 expression in the duodenal and ileal biopsies of horses switched, gradually
over a 2-month period, from low (< 1.0 g/kg bwt/day) to high hCHO (6.0 g/kg
bwt/day) diets of known composition. We show that SGLT1 expression is enhanced,
with time, 2-fold in the duodenum and 3.3-fold in the ileum. The study has
important implications for dietary management of the horse.
Reciprocal signalling and gene expression play a cardinal role during pathogen-host
molecular interactions and are prerequisite to the maintenance of balanced
homeostasis. Gene expression repertoire changes during rickettsial infection and
glutathione-S-transferases (GSTs) were among the genes found up-regulated in
Rickettsia-infected Dermacentor variabilis. GSTs are well known to play an
important part in cellular stress responses in the host. We have cloned two full-
length GSTs from D. variabilis (DvGST1 and DvGST2). Comparison of these two DvGST
molecules with those of other species indicate that DvGST1 is related to the
mammalian class theta and insect class delta GSTs, while DvGST2 does not seem to
fall in the same family. Northern blotting analyses revealed differential
expression patterns, where DvGST1 and DvGST2 transcripts are found in the tick gut,
with DvGST2 transcripts also present in the ovaries. Both DvGST transcripts are up-
regulated upon tick feeding. Challenge of fed adult ticks with Escherichia coli
injection showed decreased transcript amounts compared with ticks injected with
phosphate-buffered saline (sham) and naive ticks.
The addition of soybean protein materials to meat products is a common practice in
the food industry, being a potential hidden allergenic commodity. This study aimed
at proposing a novel specific and highly sensitive real-time PCR system for the
detection/quantification of soybean as an allergenic ingredient in processed meat
products. The method achieved a limit of detection of 9.8 pg of soybean DNA (8.6
copies), with adequate real-time PCR performance parameters, regardless of the
soybean material (concentrate or isolate) and after thermal treatments. A
normalised approach was also proposed in the range of 0.001-10% (w/w) of soybean
material in pork meat, which was successfully validated and applied to processed
meat products. Soybean was identified in more than 40% of tested samples of cooked
ham and mortadella in the range of 0.1-4% (w/w), 3 samples not complying with
labelling regulations as a result of undeclared soybean. (C) 2016 Elsevier Ltd. All
rights reserved.
Glycogen and trehalose are important energy source and key regulation factors in
the development of many organisms pass through energy metabolism, including
bacteria, fungi, and insects. To study glycogen metabolism pathway in Spodoptera
exigua, first cDNAs for glycogen synthase (SpoexGS) and glycogen phosphorylase
(SpoexGP) were cloned from S. exigua. SpoexGS cDNA contains an open reading frame
of 2,010 nucleotides encoding a protein of 669 amino acids with a predicted
molecular mass of 76.19 kDa and a pI of 5.84. SpoexGP contains an open reading
frame of 2,946 nucleotides, which encodes a protein of 841 amino acids with a
predicted molecular mass of approximately 96.63 kDa and a pI of 6.03. Second,
Northern blotting revealed that SpoexGS and SpoexGP mRNAs were expressed in brain,
fat body, mid-gut, Malpighian tubules, spermary, and tracheae of S. exigua.
Expression patterns for SpoexGS and SpoexGP mRNAs were similar in fat body, but
differed in whole body at different developmental stages. The last, under
starvation conditions, SpoexGS and SpoexGP transcript expression rapidly decreased
with increasing starvation time. When the starvation stress was removed, SpoexGS
and SpoexGP mRNA levels were lower in the groups starved for 6 and 12 h than in the
24-h starvation and control groups. Treatment with excessive sugar intake led to
higher levels of SpoexGS and SpoexGP transcripts after 12 h compared to the control
group. These findings provide new data on the tissue distribution, expression
patterns, and potential function of glycogen synthase and glycogen phosphorylase
proteins. (c) 2012 Wiley Periodicals, Inc.
The spermatogenic cell-specific variant of glyceraldehyde 3-phosphate dehydrogenase
(GAPDS) has been cloned from a rat testis cDNA library and its pattern of
expression determined. A 1,417 nucleotide cDNA has been found to encode an enzyme
with substantial homology to mouse GAPDS (94% identity) and human GAPD2 (83%
identity) isozymes. Northern blotting of rat tissue RNAs detected the 1.5 kb Gapds
transcript in the testis and not in RNA from liver, spleen, epididymis, heart,
skeletal muscle, brain, seminal vesicle, and kidney. The rat Gapds mRNA was first
detected at day 29 of postnatal testis development, an age which coincides with the
initial post-meiotic differentiation of round spermatids. When isolated rat
spermatogenic cell RNA was probed for Gapds expression, transcripts were detected
only in round spermatids and condensing spermatids, but not in pachytene
spermatocytes, demonstrating haploid expression of the Gapds gene. However,
immunohistochemical staining of rat testis sections with anti-GAPDS antisera did
not detect GAPDS in round spermatids, but localized the protein only to stage XIII
and later condensing spermatids as well as testicular spermatozoa, indicating that
Gapds expression is translationally regulated. The current results are similar to
those previously obtained for mouse GAPDS and human GAPD2, suggesting that reliable
comparisons can be made between these species in toxicant screening and
contraceptive development.
The gene encoding a cellobiohydrolase 7B (CBH7B) of the thermophilic fungus
Thielavia terrestris was identified, subcloned, and expressed in Pichia pastoris.
CBH7B encoded 455 amino acid residues with a molecular mass of 51.8 kDa. Domain
analysis indicated that CBH7B contains a family 7 glycosyl hydrolase catalytic core
but lacks a carbohydrate-binding module. Purified CBH7B exhibited optimum catalytic
activity at pH 5.0 and 55 degrees C with 4-methylumbelliferryl-cellobioside as the
substrate and retained 85% of its activity following 24 H incubation at 50 degrees
C. Despite the lack of activity toward microcrystalline substrates, this enzyme
worked synergistically with the commercial enzyme cocktail Cellic((R)) CTec2 to
enhance saccharification by 39% when added to a reaction mixture containing 0.25%
alkaline pretreated oil palm empty fruit bunch (OPEFB). Attenuated total
reflectance Fourier transform infrared spectroscopy suggested a reduction of lignin
and crystalline cellulose in OPEFB samples supplemented with CBH7B. Scanning
electron microscopy revealed greater destruction extent of OPEFB strands in samples
supplemented with CBH7B as compared with the nonsupplemented control. Therefore,
CBH7B has the potential to complement commercial enzymes in hydrolyzing
lignocellulosic biomass. (C) 2015 International Union of Biochemistry and Molecular
Biology, Inc.
Interleukin-13 (IL-13) is a pleiotropic regulatory cytokine with the potential for
treating several human diseases, including type-1 diabetes. Thus far, conventional
expression systems for recombinant IL-13 production have proven difficult and are
limited by efficiency. In this study, transgenic plants were used as a novel
expression platform for the production of human IL-13 (hIL-13). DNA constructs
containing hIL-13 cDNA were introduced into tobacco plants. Transcriptional
expression of the hIL-13 gene in transgenic plants was confirmed by reverse
transcriptase-polymerase chain reaction and Northern blotting. Western blot
analysis showed that the hIL-13 protein was efficiently accumulated in transgenic
plants and present in multiple molecular forms, with an expression level as high as
0.15% of total soluble protein in leaves. The multiple forms of plant-derived
recombinant hIL-13 (rhIL-13) are a result of differential N-linked glycosylation,
as revealed by enzymatic and chemical deglycosylation, but not of disulphide-linked
oligomerization. In vitro trypsin digestion indicated that plant rhIL-13 was more
resistant than unglycosylated control rhIL-13 to proteolysis. The stability of
plant rhIL-13 to digestion was further supported with simulated gastric and
intestinal fluid digestion. In vitro bioassays using a factor-dependent human
erythroleukaemic cell line (TF-1 cells) showed that plant rhIL-13 retained the
biological functions of the authentic hIL-13 protein. These results demonstrate
that transgenic plants are superior to conventional cell-based expression systems
for the production of rhIL-13. Moreover, transgenic plants synthesizing high levels
of rhIL-13 may prove to be an attractive delivery system for direct oral
administration of IL-13 in the treatment of clinical diseases such as type-1
diabetes.
Gnathostomiasis is a foodborne zoonotic parasitosis caused by Gnathostoma
nematodes. It has caused significant public problems worldwide, but its molecular
biology is limited. The purpose of this study was to decode the complete
mitochondrial (mt) genomes of Gnathostoma nipponicum and Gnathostoma sp., and
compare their mt sequences with other Gnathostoma species. The complete mt genome
sequences were amplified by long-range PCR and determined by subsequent primer
walking. The complete mt genomes of G. nipponicum and Gnathostoma sp. were 14,093
bp and 14,391 bp, respectively. Both of the two mt genomes contain 12 protein-
coding genes (PCGs), 2 ribosomal RNA genes and 22 transfer RNA genes. The gene
order and transcription direction are the same as G. spinigerum and G. doloresi.
The sequence difference across the entire mt genomes varied from 14.4% to 18.2%
between G. nipponicum, Gnathostoma sp., G. spinigerum and G. doloresi of Japan and
China isolates. Phylogenetic analyses by Bayesian inference (BI) using concatenated
amino acid sequences of 12 PCGs showed that G. nipponicum and Gnathostoma sp. are
two distinctive species of Gnathostoma, and G. nipponicum are more closely related
to Gnathostoma sp. than to G. spinigerum. The mtDNA datasets provide abundant
resources of novel markers, which can be used for the studies of molecular
epidemiology and diagnosis of Gnathostoma spp. (C) 2016 Elsevier B.V. All rights
reserved.
Caseins are widely used for species identification of dairy products. Isoelectric
focusing (IEF) of para-kappa-casein peptide is used as the official German method
for the differentiation between caprine (isoform A) and ovine (isoform B) dairy
products, based on their different isoelectric points. The discrimination between
Greek goat and ewe dairy products using IEF has, however, been shown to he
problematic because of the existence of the ewe isoform in milk from Greek
indigenous dairy goats. This could be due to nucleotide polymorphisms within the
goat kappa-casein gene of Greek indigenous breeds, which alter the isoelectric
point of the para-kappa-casein peptide and lead to false positive results. Previous
DNA analysis of the goat kappa-casein gene has shown high levels of polymorphism;
however, no such information is available for Greek indigenous dairy goats.
Therefore, 87 indigenous dairy goats were sequenced at exon IV of kappa-casein
genie. In total, 9 polymorphic sites were detected. Three nonsynonymous point
mutations were identified, which change the isoelectric point of the goat para-
kappa-casein peptide so that it appears identical to that of the ewe peptide. Ten
composite genotypes were reconstructed and 6 of them included the problematic point
mutations. For the verification of genetic results, IEF was carried out. Both goat
and ewe patterns appeared in the problematic genotypes. The frequency of these
genotypes could be characterized as moderate (0.23) to high (0.60) within Greek
indigenous breeds. However, this is not an issue restricted to Greece, as such
genotypes have been detected in various non-Greek goat breeds. In conclusion, IEF
based on the official German method is certainly inappropriate for ovine and
caprine discrimination concerning Greek dairy goat products, and consequently a new
method should be established.
Classical contagious caprine pleuropneumonia is one of the most fatal contagious
disease of goats listed by World Organization for Animal Health that leads to major
economic losses. It is caused by infection with Mycoplasma capricolum subspecies
capripneumoniae. In order to isolate the causative agents of CCPP for the first
time in the Kingdom of Saudi Arabia, fifteen flocks from Eastern region (Al Ahsa,
Dammam and Hafr Albaten) and ten flocks from Riyadh and Al-Kharj regions were
selected for this study. A total of 700 samples (400 nasal swabs, 300 pleural fluid
samples and lung samples (from necropsied animals)) were collected from goats
showing typical signs of CCPP. The clinical signs of diseased cases revealed serous
to mucoid nasal discharge, coughing, dyspnea, frothy salivation, and fever (40-42
degrees C). Necropsied animals showed fibrinous pleuropneumonia and increased
pleural fluid. Of 400 nasal swabs, 190 pleural fluid, and 110 lung samples, 26
(6.5%), 31 (16.3%) and 19 (17.3%) Mycoplasma isolates were recovered, respectively.
Biochemically, all isolates were sensitive to digitonin and fermented glucose.
Sixty seven of Mycoplasma isolates were belonged to Mycoplasma mycoides cluster
based on detection of 16S rRNA. Polymerase chain reaction screening of Mycoplasma
isolates using specific primer for M. capricolum subsp. capripneumoniae confirmed
55 isolates to be M. capricolum subsp. capripneumoniae. (C) 2017 Elsevier B.V. All
rights reserved.
In view of the high biotoxicity and trace concentration of mercury (Hg) in
environmental water, developing simple, ultra-sensitive and highly selective method
capable of simultaneous determination of various Hg species has attracted wide
attention. Here, we present a novel catalysis-reduction strategy for sensing
inorganic and organic mercury in aqueous solution through the cooperative effect of
AuNP-catalyzed properties and the formation of gold amalgam. For the first time, a
new AuNP-catalyzed-organic reaction has been discovered and directly used for
sensing Hg2+, Hg-2(2+) and CH3Hg+ according to the change of the amount of the
catalytic product induced by the deposition of Hg atoms on the surface of AuNPs.
The detection limit of Hg species is 5.0 pM (1 ppt), which is 3 orders of magnitude
lower than the U.S. Environmental Protection Agency (EPA) limit value of Hg for
drinking water (2 ppb). The high selectivity can be exceptionally achieved by the
specific formation of gold amalgam. Moreover, the application for detecting tap
water samples further demonstrates that this AuNP-based assay can be an excellent
method used for sensing mercury at very low content in the environment.
Nanocarrier design combined with pulmonary drug delivery holds great promise for
the treatment of respiratory tract disorders. In particular, targeting of dendritic
cells that are key immune cells to enhance or suppress an immune response in the
lung is a promising approach for the treatment of allergic diseases. Fluorescently
encoded poly(vinyl alcohol) (PVA)-coated gold nanoparticles, functionalized with
either negative (-COO-) or positive (-NH3+) surface charges, were functionalized
with a DC-SIGN antibody on the particle surface, enabling binding to a dendritic
cell surface receptor. A 3D coculture model consisting of epithelial and immune
cells (macrophages and dendritic cells) mimicking the human lung epithelial tissue
barrier was employed to assess the effects of aerosolized AuNPs. PVA-NH2 AuNPs
showed higher uptake compared to that of their COOH counterparts, with the highest
uptake recorded in macrophages, as shown by flow cytometry. None of the AuNPs
induced cytotoxicity or necrosis or increased cytokine secretion, whereas only PVA-
NH2 AuNPs induced higher apoptosis levels. DC-SIGN AuNPs showed significantly
increased uptake by monocyte-derived dendritic cells (MDDCs) with subsequent
activation compared to non-antibody-conjugated control AuNPs, independent of
surface charge. Our results show that DC-SIGN conjugation to the AuNPs enhanced
MDDC targeting and activation in a complex 3D lung cell model. These findings
highlight the potential of immunoengineering approaches to the targeting and
activation of immune cells in the lung by nanocarriers.
Gorham-Stout disease (GSD) is a rare condition of osteolysis with excessive
lymphangiogenesis within bone tissue. The etiology of this condition remains
unknown but seems to affect mainly children and young adults of both genders all
over the world. Unfortunately, there is no standardized method for diagnosis;
however, histopathology remains as the gold standard. This condition is often
misdiagnosed due to its varying clinical presentations from case-to-case. Here, we
report the case of an 8-year-old girl who presented with chronic mandibular pain
during mastication and received multiple antibiotic treatment due to infectious
origin suspicion. After integrating information from clinical manifestations,
radiographic, laboratory, and histopathology information, she was diagnosed with
GSD. Additionally, due to the lack of literature with respect to insights into
biological mechanisms and standardized treatment for this condition, we underwent a
literature revision to provide information related to activation of cells from the
immune system, such as macrophages, T-cells, and dendritic cells, and their
contribution to the lymphangiogenesis, angiogenesis, and osteoclastogenic process
in GSD. It is important to consider these mechanisms in patients with GSD,
especially since new studies performed in earlier stages are required to confirm
their use as novel diagnostic tools and find new possibilities for treatment.
microRNAs (miRNAs) are 20-24 nucleotide non-coding small RNAs that play important
roles in plant development. The stages of cotton fiber development include
initiation, elongation, secondary wall thickening (SWT) and maturation. We
constructed seven fiber RNA libraries representing the initiation, elongation and
SWT stages. In total, 47 conserved miRNA families and seven candidate miRNAs were
profiled using small RNA sequencing. Northern blotting and real-time polymerase
chain reaction (PCR) analyses revealed the dynamic expression of miRNAs during
fiber development. In addition, 140 targets of 30 conserved miRNAs and 38 targets
of five candidate miRNAs were identified through degradome sequencing. Analysis of
correlated expression between miRNAs and their targets demonstrated that specific
miRNAs suppressed the expression of transcription factors, SBP and MYB, a leucine-
rich receptor-like protein kinase, a pectate lyase, a-tubulin, a UDP-glucuronic
acid decarboxylase and cytochrome C oxidase subunit 1 to affect fiber development.
Histochemical analyses detected the biological activity of miRNA156/157 in ovule
and fiber development. Suppressing miRNA156/157 function resulted in the reduction
of mature fiber length, illustrating that miRNA156/157 plays an essential role in
fiber elongation.
Kisspeptins and G protein coupled receptor (GPR54) play significant roles in
regulating reproductive activity among seasonally reproductive animals; however,
the mechanisms of KiSS-1 and GPR54 gene affecting the seasonal reproduction in
striped hamster are still unknown. In this study, real-time quantitative polymerase
chain reaction was employed to examine the expression profiles of KiSS-1 and GPR54
in the hypothalamus, ovaries, testes, uterus and epididymis of striped hamsters
across 4 different seasons. Our results showed that, across different seasons, the
KiSS-1 expression mode of male striped hamsters and the GPR54 expression mode of
female striped hamsters were consistent with the seasonal photoperiod in the
hypothalamus. Meanwhile, across different seasons, the expression profile of KiSS-1
in the testes and the GPR54 expression profile of male striped hamsters in the
hypothalamus were consistent with the intensity of their seasonal reproductive
activity. Among different tissues, the expression trend for GPR54 is consistent
across 4 seasons, while that for KiSS-1 is tissue-dependent. The expression trend
for GPR54 across 4 seasons is the same regardless of gender, while that for KiSS-1
is dramatically different and sex-dependent across different seasons. These results
suggest that the expressions of KiSS-1 and GPR54 in the striped hamsters were
regulated by complicated mechanisms, and the regulatory mechanisms in the striped
hamsters are seasonal-dependent and sex-dependent. This research will provide a
theoretical basis for studying how KiSS-1 and GPR54 affect seasonal reproduction
and the mechanisms behind their influence.
AIM: To generate a Gpr128 gene knockout mouse model and to investigate its
phenotypes and the biological function of the Gpr128 gene. METHODS: Bacterial
artificial chromosome-retrieval methods were used for constructing the targeting
vector. Using homologous recombination and microinjection technology, a Gpr128
knockout mouse model on a mixed 129/BL6 background was generated. The mice were
genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a
standard laboratory chow diet. Animals of both sexes were used, and the phenotypes
were assessed by histological, biochemical, molecular and physiological analyses.
Semi-quantitative reverse transcription-PCR and Northern blotting were used to
determine the tissue distribution of Gpr128 mRNA. Beginning at the age of 4 wk,
body weights were recorded every 4 wk. Food, feces, blood and organ samples were
collected to analyze food consumption, fecal quantity, organ weight and
constituents of the blood and plasma. A Trendelenburg preparation was utilized to
examine intestinal motility in wild-type (WT) and Gpr128(-/-) mice at the age of 8
and 32 wk. RESULTS: Gpr128 mRNA was highly and exclusively detected in the
intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in reduced
body weight gain, and mutant mice exhibited an increased frequency of peristaltic
contraction and slow wave potential of the small intestine. The Gpr128(+/+) mice
gained more weight on average than the Gpr128(-/-) mice since 24 wk, being 30.81
+/- 2.84 g and 25.74 +/- 4.50 g, respectively (n = 10, P < 0.01). The frequency of
small intestinal peristaltic contraction was increased in Gpr128(-/-) mice. At the
age of 8 wk, the frequency of peristalsis with an intraluminal pressure of 3 cmH2O
was 6.6 +/- 2.3 peristalsis/15 min in Gpr128(-/-) intestine (n = 5) vs 2.6 +/- 1.7
peristalsis/15 min in WT intestine (n = 5, P < 0.05). At the age of 32 wk, the
frequency of peristaltic contraction with an intraluminal pressure of 2 and 3
cmH(2)O was 4.6 +/- 2.3 and 3.1 +/- 0.8 peristalsis/15 min in WT mice (n = 8),
whereas in Gpr128(-/-) mice (n = 8) the frequency of contraction was 8.3 +/- 3.0
and 7.4 +/- 3.1 peristalsis/15 min, respectively (2 cmH(2)O: P < 0.05 vs WT; 3
cmH2O: P < 0.01 vs WT). The frequency of slow wave potential in Gpr128(-/-)
intestine (35.8 +/- 4.3, 36.4 +/- 4.2 and 37.1 +/- 4.8/min with an intraluminal
pressure of 1, 2 and 3 cmH(2)O, n = 8) was also higher than in WT intestine (30.6
+/- 4.2, 31.4 +/- 3.9 and 31.9 +/- 4.5/min, n = 8, P < 0.05). CONCLUSION: We have
generated a mouse model with a targeted deletion of Gpr128 and found reduced body
weight and increased intestinal contraction frequency in this animal model. (C)
2014 Baishideng Publishing Group Co., Limited. All rights reserved.
In 2008, we established the Integrated Graduate Program in Physical and Engineering
Biology (IGPPEB) at Yale University. Our goal was to create a comprehensive
graduate program to train a new generation of scientists who possess a
sophisticated understanding of biology and who are capable of applying physical and
quantitative methodologies to solve biological problems. Here we describe the
framework of the training program, report on its effectiveness, and also share the
insights we gained during its development and implementation. The program features
co-teaching by faculty with complementary specializations, student peer learning,
and novel hands-on courses that facilitate the seamless blending of
interdisciplinary research and teaching. It also incorporates enrichment activities
to improve communication skills, engage students in science outreach, and foster a
cohesive program cohort, all of which promote the development of transferable
skills applicable in a variety of careers. The curriculum of the graduate program
is integrated with the curricular requirements of several Ph.D.-granting home
programs in the physical, engineering, and biological sciences. Moreover, the wide-
ranging recruiting activities of the IGPPEB serve to enhance the quality and
diversity of students entering graduate school at Yale. We also discuss some of the
challenges we encountered in establishing and optimizing the program, and describe
the institution-level changes that were catalyzed by the introduction of the new
graduate program. The goal of this article is to serve as both an inspiration and
as a practical "how to" manual for those who seek to establish similar programs at
their own institutions. (C) 2016 The Authors Biochemistry and Molecular Biology
Education published by Wiley Periodicals, Inc. on behalf of International Union of
Biochemistry and Molecular Biology
The efficacy of rabbit antithymocyte globulin (ATG) for the prevention of graft-
versus-host disease (GVHD) has been evaluated in several randomized control trials,
but the results show some discrepancies. Therefore, we performed a systematic
review and meta-analysis covering the latest RCTs including six trials (total 845
patients). The incidence of acute and chronic GVHD was significantly lower in the
ATG arms (risk ratio, 0.75 and 0.54, respectively). No significant differences were
found regarding overall survival, the incidence of relapse, and non-relapse
mortality; however, the incidence of cytomegalovirus and Epstein-Barr virus
reactivation increased (risk ratio, 1.25 and 1.33), and neutrophil engraftment was
significantly delayed (median, 2.66 days). In conclusion, rabbit ATG should be
beneficial as a GVHD prophylaxis in addition to conventional regimens, with close
monitoring of virus reactivation and enough attention to delayed engraftment.
Studies comparing the timing and dosage of ATG are essential to determine the
suitable prophylactic regimens.
Graft-versus-host disease (GVHD) is the major complication of hematopoietic stem
cell transplantation and is associated with high mortality in severe cases. The
skin is one of the major organs affected in both acute and chronic GVHD. This
review aims to elucidate the basic characteristics of GVHD, and the role and
contribution of dermatologists in the care of patients with this condition.
The aim of this study was to investigate the prevalence of fosfomycin resistance
gene fosA3 and characterize plasmids harboring fosA3 among CTX-M-producing
Escherichia coli from chickens in China. A total of 234 CTX-M-producing E. coli
isolates collected from chickens from 2014 to 2016 were screened for the presence
of plasmid-mediated fosfomycin resistance genes (fosA, fosA3, and fosC2). Clonal
relatedness of fosA3-positive isolates was determined by pulsed-field gel
electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic
environment of fosA3 was analyzed by polymerase chain reaction (PCR) mapping.
Plasmids were studied by using conjugation experiments, PCR-based replicon typing
and plasmid MLST. Sixty-four (27.4%) fosA3-positive E. coli isolates were
identified in this study. The gene bla(CTX-M-55) (31/64) was predominant among
these strains, followed by bla(CTX-M-14) (18/64) and bla(CTX-M-65) (14/64). Various
PFGE patterns and sequence types (STs) indicated that these isolates were clonally
unrelated. Seven different genetic environments of fosA3 were identified and two
new combinations (ISEcp1-bla(CTX-M-65)-IS903D-IS26-fosA3-orf1-orf2-orf3-IS26 and
IS26-ISEcp1-bla(CTX-M-3)-orf477-bla(TEM-1)-IS26-fosA3-orf1-orf2-orf3-IS26) were
discovered for the first time. Conjugation experiments were successful for 47
isolates and 33 transconjugants harbored a single plasmid. Plasmids carrying fosA3
belonged to incompatibility group IncFII (17/33), IncI1 (2/33), IncHI2 (3/33), and
IncB/O (1/33). F33:A-:B- plasmids carrying bla(CTX-M-55), IncHI2/ST3 plasmids
carrying bla(CTX-M-65), and F2:A-:B-plasmids carrying bla(CTX-M-55) were found in
E. coli isolates from different provinces. Our results revealed a considerable
prevalence of fosA3 gene among CTX-M-producing E. coli with clonal diversity from
chickens in China. The transmission of different kinds of plasmids is responsible
for the dissemination of fosA3 in chicken farms in China.
Plasminogen is a major plasma protein and the zymogen of the broad spectrum
protease plasmin. Plasmin activity leads to tissue degradation, direct and through
activation of metalloproteinases. Infected tooth root canals, as a consequence of
the inflammatory response and eventual necrosis, contain tissue fluid and blood
components. These will coat the root canal walls and act as conditioning films that
allow bacterial biofilms to grow and be a potential source of hematogenously
spreading bacteria. We investigated the effect of in vitro surface conditioning
with human plasminogen on the initial adhesion of bacteria. Four bacterial species,
L. salivarius, E. faecalis, A. naeslundii, and S. gordonii, isolated from dental
root canals, and three other oral streptococci, S. oralis, S. anginosus, and S.
sanguinis, were grown in albumin- or plasminogen-coated flow chambers and studied
by confocal laser scanning microscopy using the cell viability staining LIVE/DEAD
and 16S rRNA fluorescence in situ hybridization (FISH). A. naeslundii, L salivarius
and in particular S. gordonii showed a higher initial adhesion to the plasminogen-
coated surfaces. E. faecalis did not show any preference for plasminogen. Four-
species biofilms cultured for 96 h showed that streptococci increased their
proportion with time. Further experiments aimed at studying different streptococcal
strains. All these adhered more to plasminogen-coated surfaces than to albumin-
coated control surfaces. The specificity of the binding to plasminogen was verified
by blocking lysine-binding sites with epsilon-aminocaproic acid. Plasminogen is
thus an important plasma component for the initial adhesion of oral bacteria, in
particular streptococci. This binding may contribute to their spread locally as
well as to distant organs or tissues. (C) 2016 Elsevier Ltd. All rights reserved.
Low-velocity impact cratering experiments are conducted in sloped granular targets
to study the effect of the slope angle theta on the crater shape and its scales. We
use two types of granular matter, sand and glass beads, former of which has a
larger friction coefficient mu(s) = tan theta(r), where theta(r) is the angle of
repose. Experiments show that as theta increases, the crater becomes shallower and
elongated in the direction of the slope. Furthermore the crater floor steepens in
the upslope side and a thick rim forms in the downslope side, thus forming an
asymmetric profile. High-speed images show that these features are results of
ejecta being dispersed farther towards the downslope side and the subsequent
avalanche which buries much of the crater floor. Such asymmetric ejecta dispersal
can be explained by combining the Z-model and a ballistic model. Using the
topographic maps of the craters, we classify crater shape regimes I-III, which
transition with increasing theta : a full-rim crater (I), a broken-rim crater (II),
and a depression (III). The critical theta for the regime transitions are larger
for sand compared to glass beads, but collapse to close values when we use a
normalized slope (theta) over cap = tan theta / tan theta(r). Similarly we derive
(theta) over cap -dependences of the scaled crater depth, length, width and their
ratios which collapse the results for different targets and impact energies. We
compare the crater profiles formed in our experiments with deep craters on asteroid
Vesta and find that some of the scaled profiles nearly overlap and many have
similar depth / length ratios. This suggests that these Vestan craters may also
have formed in the gravity regime and that the formation process can be
approximated by a granular flow with a similar effective friction coefficient. (C)
2017 Elsevier Inc. All rights reserved.
BackgroundThe incidence of cutaneous nontuberculous mycobacterial (NTM) infection
has increased in recent decades because of widespread use of immunosuppressive
therapy and better detection methods. The histopathology of cutaneous NTM infection
is not pathognomic and the organisms are slow and difficult to culture, making
diagnosis challenging. MethodsWe reviewed the clinical and histopathological
features of 13 cases of cutaneous NTM infection, and performed panmycobacterial
polymerase chain reaction (PCR) on the paraffin blocks. ResultsThe immunocompetent
patients presented with localized lesions on the extremities, whereas the
immunocompromised patients presented with disseminated cutaneous lesions. The
histopathology in immunocompetent patients was characterized by
pseudoepitheliomatous epidermal hyperplasia, intraepithelial abscesses,
transepidermal elimination and dermal granulomatous inflammation accompanied by
necrosis and suppuration. The immunocompromised patients showed suppurative
inflammation with little granuloma formation and numerous acid-fast bacilli.
Paraffin block PCR was positive in 4 of 13 cases (31%), whereas culture was
positive in 11 of 13 cases (85%). ConclusionThe aforementioned histological
features should help in diagnosing cutaneous NTM infection when combined with
clinical and microbiological correlation. In our study, we did not find paraffin
block PCR to be superior to conventional culture in detecting cutaneous NTM
infection.
Purpose There is no information available about the IL-18 receptor in ovarian
follicles, so the present study attempts to demonstrate the expression of IL-18 and
its receptor in human granulosa cells (GCs). Methods To evaluate the concentration
of IL-18 in serum and follicular fluid (FF), we collected serum and FF from 102
women undergoing oocyte retrieval. Also, to detect expression of IL-18 and its
receptor by luteinized GCs, these cells were pooled six times from a total of
twenty individual patients with 5-16 follicles each. The IL-18 concentration was
determined by ELISA and the expression of IL-18 and its receptor by
immunocytochemistry and reverse transcription polymerase chain reaction. Results
Our results showed that the median IL-18 concentration in serum, 159.27 pg/ml (IQR
121.41-210.1), was significantly higher than in FF, 142.1 pg/ml (IQR 95.7176.5), p
< 0.001. Moreover, we found that IL-18 and its receptor are expressed by GCs.
Conclusion The presence of IL-18 in FF and the expression of IL-18 and its receptor
by GCs suggest an important role for this cytokine in ovarian function.
Proanthocyanidins have been suggested as an effective antibiotic alternative,
however their mechanisms are still unknown. The present study investigated the
effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier using
a weaned piglet model in comparison with colistin. Piglets weaned at 28 day were
randomly assigned to four groups treated with a control ration, or supplemented
with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg
proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut chyme
and tissue samples were collected to test intestinal microbiota and barrier
function, respectively. Proanthocyanidins treated piglets had better growth
performance and reduced diarrhea incidence (P < 0.05), accompanied with decreased
intestinal permeability and improved mucosal morphology. Gene sequencing analysis
of 16S rRNA revealed that dietary proanthocyanidins improved the microbial
diversity in ileal and colonic digesta, and the most abundant OTUs belong to
Firmicutes and Bacteroidetes spp.. Proanthocyanidins treatment decreased the
abundance of Lactobacillaceae, and increased the abundance of Clostridiaceae in
both ileal and colonic lumen, which suggests that proanthocyanidins treatment
changed the bacterial composition and distribution. Administration of
proanthocyanidins increased the concentration of propionic acid and butyric acid in
the ileum and colon, which may activate the expression of GPR41. In addition,
dietary proanthocyanidins improved the antioxidant indices in serum and intestinal
mucosa, accompanied with increasing expression of barrier occludin. Our findings
indicated that proanthocyanidins with half-dose colistin was equivalent to the
antibiotic treatment and assisted weaned animals in resisting intestinal oxidative
stress by increasing diversity and improving balance of gut microbes.
Isolation of high quality RNA from plant tissues is one of the most critical steps
for the successful application of diagnostic tests such as reverse transcription
polymerase chain reaction (RT-PCR), northern blotting, microarray hybridization.
The presence of inhibitors such as secondary metabolites, phenolic compounds and
RNAses can cause inaccurate and undesirable results. Grapevine is rich in a wide
range of metabolites which interfere with RNA isolation. From this point of view,
we researched six different total RNA extraction methods on leaves of Vitisvinifera
L. to find the best one that contribute the purity and high quality. The methods
tested are silica-capture, modified silica-capture, commercial kit, the new
combined, lithium chloride and citric buffer. RNA quality was
analyzedspectrophotometrically by nanodrop, agarose gel electrophoresis and RT-PCR.
As a result of all, it is clear that the most suitable TNA isolation protocol is
the new combined method which experienced and named firstly by us, in terms of RNA
purity, concentration, less time consuming of isolation step and achievement on
detection of GYSVd-1.
Recent studies showed that a large amount of graphene oxide accumulated in kidney
and liver when it injected intravenously. Evaluation of lethal and apoptosis gene
expression in these tissues, which are under stress is very important. In this
paper the in vivo dose-dependent effects of graphene oxide and reduced graphene
oxide nanoplatelets on kidney and liver of mice were studied. Balb/C mice were
treated by 20 mg/kg body weight of nanoplatelets. Molecular biology analysis showed
that graphene nanoplatelets injected intravenously lead to overexpression of BAX
gene in both kidney and liver tissues (P >= 0.01). In addition these nanoparticles
significantly increase BCL2 gene expression in both kidney and liver tissues (P >=
0.05). Graphene significantly increase level of SGPT in groups 1 (220.64 +/- 13), 2
(164.44 +/- 9.3) in comparison to control group (P <= 0.05). Also in comparison
with control group (148.11 +/- 10.4), (P <= 0.05), the level of SGOT in groups
1(182,01 +/- 12.6) and 2 (1782 +/- 22) significantly increased. (C) 2016 Published
by Elsevier B.V.
Triboelectric generators, which can directly transform energy from our living
environment into electricity, are self-powered component for wearable devices.
Flexible and transparent triboelectric generators (FTTGs) with high output power
densities are urgently needed for wearable electronics. By introducing graphene (G)
and indium tin oxide (ITO) as transparent electrodes and optimizing the electrode
structure, a FTTG with polyimide (PI) and polyethylene terephthalate (PET) as
friction layers and graphene (ITO) as top (bottom) electrode was obtained and it
has a large output power density of 10.1Wcm(-2), which is over four times larger
than previously reported FTTGs ca. 2Wcm(-2). Moreover, the output voltage of the
graphene-based FTTG is as large as 56V, and it exhibits excellent cycling behavior.
The effects of electrode structure on the performance of FTTG have been analyzed
and corresponding mechanism has been discussed. Light-emitting diodes (LED) can be
easily powered by the FTTG, suggesting its potential application in harvesting
electrical energy from human activities by using flexible and transparent devices.
How to preserve the structure integrity of graphene while enhance its dispersion
and compatibility in matrix attracts the attention of researchers in
graphene/polymer nanocomposite field. In this paper, methacryloxyethyltrimethyl
ammonium chloride (DMC), a kind of ionic liquids, was first used to non-covalently
functionalize graphene in the process of graphene oxide (GO) reduction. The as-
modified graphene (DMC-rGO) was further incorporated into poly(vinyl alcohol) (PVA)
matrix by solution casting technique to fabricate DMC-rGO/PVA composites. The
structure and properties of the obtained DMC-rGO were investigated by X-ray
diffraction analysis (XRD), X-ray Photoelectron Spectroscopy (XPS), Transmission
Electron Microscope (TEM), Atomic force microscopy (AFM), and Raman test. The
results showed that graphene could be successfully modified by DMC through ionic-
interaction and the structure integrity of the graphene could be reserved by this
non-covalently approach. Furthermore, after co-reduction process, some hydroxyl
groups were introduced into DMC-rGO. In virtue of these intrinsic properties of
DMC-rGO, the fabricated DMC-rGO/PVA composites exhibit considerable enhancements in
mechanical properties and remarkable improvements in thermal stability, as well as
the enhancement in electrical conductivity at low DMC-rGO loading. This simple
modification approach gives a new opportunity to improve the performances of
graphene/polymer composites. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci.
2017, 134, 45006.
We propose a multi-resolution scanning approach to identifying two-sample
differences. Windows of multiple scales are constructed through nested dyadic
partitioning on the sample space and a hypothesis regarding the two-sample
difference is defined on each window. Instead of testing the hypotheses on
different windows independently, we adopt a joint graphical model, namely a Markov
tree, on the null or alternative states of these hypotheses to incorporate spatial
correlation across windows. The induced dependence allows borrowing strength across
nearby and nested windows, which we show is critical for detecting high resolution
local differences. We evaluate the performance of the method through simulation and
show that it substantially outperforms other state of the art two-sample tests when
the two-sample difference is local, involving only a small subset of the data. We
then apply it to a flow cytometry data set from immunology, in which it
successfully identifies highly local differences. In addition, we show how to
control properly for multiple testing in a decision theoretic approach as well as
how to summarize and report the inferred two-sample difference. We also construct
hierarchical extensions of the framework to incorporate adaptivity into the
construction of the scanning windows to improve inference further.
Chemical fertilizers, especially nitrogen (N) and phosphorus (P), are used in
grasslands to maximize plant biomass production for livestock. Despite a
substantial body of work on how fertilization affects aboveground plant and
belowground microbial communities, the short-term response of soil ammonia
oxidizing microbial communities, which play the central role in nitrification, to
fertilization is not well understood. The responses of ammonia-oxidizing microbial
communities to short-term (3 years) N and/or P additions were investigated in an
alpine grassland of the Qinghai-Tibetan Plateau. Quantitative polymerase chain
reaction (qPCR) analysis of the amoA genes showed that ammonia-oxidizing archaea
(AOA) dominated over ammonia-oxidizing bacteria (AOB) in non-amended soil. Short-
term urea addition significantly increased the abundance of AOB, whereas AOA
abundance remained unchanged, resulting in a shift from AOA to AOB dominance, which
suggests that AOB are likely to be more important in the first step of the
nitrification following urea amendment. Pyrosequencing demonstrated a significant
shift in AOB but not AOA community composition within short-term N fertilizer
plots, indicating that AOB community composition was more sensitive than AOA in
response to urea amendment. This study demonstrated that the abundance and
composition of AOA and AOB communities responded differently to 3 years of urea
addition, suggesting that N fertilizer may be an important controller of ammonia
oxidizing microbial communities in managed alpine grasslands, such as those of the
Qinghai-Tibet Plateau.
The Great East Japan Earthquake (GEJE) and subsequent tsunamis that occurred in
2011 caused extensive and severe structural damage and interrupted numerous
research activities; however, the majority of such activities have been revived,
and further public health researches and activities have started to follow the
population affected by the disaster. In this mini-review, we overview our recent
activities regarding epidemiologic studies in Miyagi Prefecture, the region most
affected by the GEJE. Through our study processes, we were able to identify the
particular characteristics of vulnerable populations, and provide ideas that may
help save lives and reduce the amount of damage caused by a future disaster. Long-
term follow-up and care of survivors is essential in affected areas, and health
professionals should pay particular attention to various diseases, e.g.,
cardiovascular complications and mental disorders. Furthermore, building up
resilience and social relationships in the community is beneficial to survivors.
Ongoing cohort studies conducted before disasters can help minimize biases
regarding the survivors' pre-disaster information, and emerging cohort studies
after disasters can find potential helpful novel indices. To identify
characteristics of vulnerable populations, save lives, and reduce the amount of
damage caused by a future disaster, constant research that is consistently improved
by new data needs to be performed.
OBJECTIVES: The objectives of this study were to identify interrelations between
matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients
with aortic root/ascending aortic aneurysms and to describe comorbidities as
possible biasing factors in the widely discussed correlation of serum MMP levels
and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32
consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at
the Heart Center University of Freiburg from May 2013 to January 2014. The
influence of comorbidities and medication on serum MMP2 and MMP9 levels was
studied. We took into account ascending aortic diameter (aAD), aortic valve
configuration, hypertension, age and hyperlipidaemia as factors possibly altering
serum MMP levels. The relation between serum MMP levels and aAD was examined by a
correlation test based on ranks. RESULTS: Serum MMP2 levels and aAD correlated
positively. Correlation was increased in patients without hyperlipidaemia
(Spearman's rho = 0.62, P = 0.008 in patients without hyperlipidaemia;rho = 0.409,
P = 0.020 in all patients). Serum MMP9 levels did not correlate with aAD and showed
greater variation. Serum MMP9 levels were significantly associated with
hyperlipidaemia (P = 0.037). CONCLUSIONS: The distinct correlation patterns in
patients with and without hyperlipidaemia have to be considered when defining the
potential of MMP2 as a biomarker in future studies. The relation between MMP9 and
hyperlipidaemia has to be further investigated.
Rhodanese-domain proteins (RDPs) are widespread in plants and other organisms, but
their biological roles are mostly unknown. Here we report on a novel RDP from
Chlamydomonas that has a single rhodanese domain, and a predicted chloroplast
transit peptide. The protein was produced in Escherichia coli with a His-tag, but
lacking most of the N-terminal transit peptide, and after purification was found to
have rhodanese activity in vitro. It was also used to elicit antibodies for western
blot analysis, which showed that the native Chlamydomonas protein migrated slower
on SDS gels (apparent M-r = 34 kDa) than its predicted size (27 kDa), and co-
fractionated with chloroplasts. To assess function in vivo, the tandem-RNAi
approach was used to generate Chlamydomonas strains that had reductions of 30-70 %
for the mRNA and similar to 20-40 % for the 34-kDa protein. These strains showed
reduced growth under all trophic conditions, and were sensitive to even moderate
light; properties reminiscent of chloroplast translation mutants. Pulse-labeling in
the presence of cycloheximide indicated that chloroplast protein synthesis was
broadly reduced in the RNAi strains, and transcript analysis (by RT-PCR and
northern blotting) indicated the effect was mainly translational. These results
identify a novel rhodanese-like protein that we have named CRLT, because it is
required to maintain chloroplast translation.
Green planning is critically important during the design phases of construction
projects but continually gets less attention during construction. Project owners
and planners need to understand how communication influences green implementation.
To address a gap in the extant research, this paper presents the evaluation results
on how sustainability awareness of field supervision personnel impacts the
successful completion of school projects by proving that communicating
sustainability goals with them is vital for decision-making during the construction
stage of the project. This paper uses data collected from 162 new school
construction projects to compare sustainability design goals with their successful
incorporation into completed projects. Seventy-one project managers and inspectors
were surveyed to assess their awareness of key high-performance sustainability
requirements that were built into the designs. The responses from these two groups
were compared to examine the positive or negative impacts. The analysis results
show that early and continuous communication of sustainability design goals with
field supervision personnel has a significant impact on whether those goals are
realized when the project is turned over to the owner for occupancy. Successful
implementation of sustainability goals not only provides economic benefits from
fully exploiting life-cycle costs, but also holds the promise of providing a
healthier working environment.
Several studies on sustainable technologies for the built environment (e.g., green
roofs, green walls, etc.) have been carried out. Many of these focus on the
technical performance of such technologies. Nonetheless, it also becomes necessary
to examine how the public perceives such technologies. This understanding is
clearly important to support their widespread use. More specifically, such
perception can be incorporated into product design to increase people's acceptance.
The contribution of this paper is twofold. First, it presents results of a survey
examining the perception of people from a small city in the Southern region of
Brazil (Feliz, RS) regarding three sustainable technologies: green roofs, green
walls, and composting (or dry) toilets. Second, it proposes a set of preliminary
design guidelines to improve acceptance of more sustainable technologies based on
people's perception: (1) make the technology look good; (2) make visible the
benefits provided by the technology; and (3) design the technology to avoid
misunderstandings and concerns. (C) 2016 American Society of Civil Engineers.
Previous research focusing on rodent cells and animal models has demonstrated that
gremlin-1 antagonizes bone morphogenetic proteins (BMPs) in order to suppress
osteogenesis. However, the impact of gremlin-1 on osteogenesis in human bone
marrow-derived mesenchymal stem cells (MSCs) remains unknown. The aim of the
present study was to test the effects of gremlin-1 on viability and invitro BMP-2-
induced osteogenic differentiation of human bone marrow-derived mesenchymal stem
cells (MSCs). Gremlin-1-specific small interfering RNA (siRNA) inhibited gremlin-1
mRNA and protein expression in human MSCs. The mRNA expression levels of
osteoblastic genes were analyzed using reverse transcription-quantitative
polymerase chain reaction, and calcification and enzymatic alkaline phosphatase
(ALP) activity assessed the BMP-2-induced osteogenic differentiation of human MSCs.
The results indicated that gremlin-1 suppression significantly increased human MSC
metabolism and DNA content. The expression levels of osteoblastic genes were also
significantly increased by gremlin-1 inhibition. In the gremlin-1-inhibited group,
enzymatic ALP activity was significantly increased. In addition, due to BMP-2-
inducing osteoblasts, gremlin-1 inhibition increased calcium deposits. The present
study indicated that gremlin-1 inhibited the cell viability and osteogenic
differentiation of human MSCs and that the suppression of gremlin-1 expression
suppressed can increase the cell viability and osteogenic differentiation of human
MSCs induced by BMP-2.
Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank
illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial
functioning. This study used voxel-based morphometry to investigate if baseline
grey and white matter brain densities at identification as UHR were associated with
functional outcome at medium-to long-term follow-up. Participants were help-seeking
UHR individuals (n = 109, 54M: 55F) who underwent magnetic resonance imaging at
baseline; functional outcome was assessed an average of 9.2 years later. Primary
analysis showed that lower baseline grey matter density, but not white matter
density, in bilateral frontal and limbic areas, and left cerebellar declive were
associated with poorer functional outcome (Social and Occupational Functioning
Assessment Scale [SOFAS]). These findings were independent of transition to
psychosis or persistence of the at-risk mental state. Similar regions were
significantly associated with lower self-reported levels of social functioning and
increased negative symptoms at follow-up. Exploratory analyses showed that lower
baseline grey matter densities in middle and inferior frontal gyri were
significantly associated with decline in Global Assessment of Functioning (GAF)
score over follow- up. There was no association between baseline grey matter
density and IQ or positive symptoms at followup. The current findings provide novel
evidence that those with the poorest functional outcomes have the lowest grey
matter densities at identification as UHR, regardless of transition status or
persistence of the at-risk mental state. Replication and validation of these
findings may allow for early identification of poor functional outcome and targeted
interventions.
Background Blood parameters such as haematocrit or leucocyte counts are indicators
of immune status and health, which can be affected, in a complex way, by exogenous
as well as endogenous factors. Additionally, social context is known to be among
the most potent stressors in group living individuals, therefore potentially
influencing haematological parameters. However, with few exceptions, this potential
causal relationship received only moderate scientific attention. Methods In a free-
living and individually marked population of the highly social and long-lived
Greylag goose, Anser anser, we relate variation in haematocrit (HCT), heterophils
to lymphocytes ratio (H/L) and blood leucocyte counts to the following factors:
intrinsic (sex, age, raising condition, i.e. goose- or hand-raised), social (pair-
bond status, pair-bond duration and parental experience) and environmental
(biologically relevant periods, ambient temperature) factors. Blood samples were
collected repeatedly from a total of 105 focal birds during three biologically
relevant seasons (winter flock, mating season, summer). Results We found
significant relationships between haematological parameters and social as well as
environmental factors. During the mating season, unpaired individuals had higher
HCT compared to paired and family individuals and this pattern reversed in fall.
Similarly, H/L ratio was positively related to pair-bond status in a seasonally
dependent way, with highest values during mating and successful pairs had higher
H/L ratio than unsuccessful ones. Also, absolute number of leucocytes tended to
vary depending on raising condition in a seasonally dependent way. Discussion
Haematology bears a great potential in ecological and behavioural studies on wild
vertebrates. In sum, we found that HTC, H/L ratio and absolute number of leucocytes
are modulated by social factors and conclude that they may be considered valid
indicators of individual stress load.
Declining costs for solar photovoltaics (PV) and excitement about new technologies
have led to speculation that self-sufficient PV/battery storage systems will soon
become competitive with traditional electricity service. We compare a grid-tied
residential solar system with an off-grid solar-plus-battery system at 1020 US
locations, and calculate three effects of "grid defection" for each: the private
net costs to the homeowner, the change in system generation costs, and change in
system emissions. For the average US location, an off-grid solar system is almost
double the price of grid-connected solar, is associated with higher system
generation costs, and has no emissions benefit. (C) 2017 Elsevier Ltd. All rights
reserved.
Power grid interconnection has gained attention in Northeast Asia (NEA) as a means
to effectively utilize the abundant renewable resources in Mongolia. This paper
quantifies the potential economic and environmental benefits of deploying massive
wind turbines and solar PV in Mongolia for power exports. The author uses an NEA-
wide multi-region power system model formulated as a linear programming problem.
The analysis considers power systems characteristics, such as the seasonal and
daily electric load curves of the NEA regions. The simulation results show that the
large-scale Mongolian renewables contribute to significant CO2 reductions in NEA.
China, in particular, benefits from a significant reduction in coal-fired
generation. However, huge investments would be required for the massive renewables
and cross-boundary transmission facilities, pushing up electricity supply cost. The
relevant planning organizations need to carefully consider these environmental
opportunities and economic barriers before implementation. This paper also
investigates the economic impacts of transmission route circuity due to avoiding
transmission through the Democratic People's Republic of Korea (DPRK). Our results
imply modest effects of the circuity on the total system cost; availability of
routes through the DPRK would not significantly increase the benefits to the NEA
system of integrating massive renewables in Mongolia. (C) 2017 The Author(s).
Published by Elsevier Ltd.
A systematic design method for 3-D grid multiscroll chaotic attractors by using
staircase nonlinear functions (SNFs) is proposed in this paper. Equations of
parameters for 3-D grid multiscroll chaotic attractors are derived in the
consideration of the dynamic range for the active device and the number of
multiscroll chaotic attractors. 5 x 4 and 4 x 3 of 3-D grid multiscroll chaotic
attractors are generated by this method. A chaotic circuit is designed only using
current feedback operational amplifiers (CFOAs). The circuit consists of three
integrators and two nonlinear circuits. The parameters of the circuit are
calculated by the parameters of 3-D grid multiscroll chaotic attractors. The
circuit can generate 3-D grid multiscroll chaotic attractors. The central frequency
of the circuit is higher with fewer active devices and simpler circuit construction
for the good frequency characteristic and port characteristic of the CFOA.
Numerical simulation results and the circuit simulation results show that the
method is feasible and the designed circuit is correct.
In this paper, a method is proposed to realize the grid multi-scroll chaotic system
with the current feedback operational amplifier (CFOA). Firstly, nonlinear circuit
is designed based on the CFOA. Then the grid multi-scroll chaotic circuit is
designed and relevant circuit parameters are calculated. Finally circuit simulation
is conducted, and the results show that the circuit has a higher central frequency,
needs less components, and possesses simpler circuit structure, good frequency
characteristic and port characteristic of the CFOA.
A power distribution grid exhibits the characteristics of a weak grid owing to the
existence of scattered high-power distributed power-generation devices. The grid
impedance affects the robust stability of grid-connected inverters, leading to
harmonic resonance, or even instability in the system. Therefore, a study of the
stability of grid-connected inverters with high grid impedance based on impedance
analysis is presented in this paper. The output impedance modeling of an LCL-type
single-phase grid-connected inverter is derived, where the effects of the PLL loop
and the digital control delays on the output impedance characteristics have been
taken into account. To enhance the stability of grid-connected inverters with
different grid impedance, a novel impedance-phased compensation control strategy is
proposed by increasing the phase margin of the grid-connected inverters.
Specifically, a detailed implementation and parameter design of the impedance-
phased compensation control method is depicted. Finally, an impedance-phased
dynamic control scheme combined with online grid impedance measurement is
introduced and also verified by the experiment results.
In a distributed generation system, the stability of grid-connected inverters is
directly related to the reliable operation of the grid-connected system. The
impedance-based analysis method can be employed to effectively study the
interaction stability between grid-connected inverters and grid, which means that
it is necessary to obtain the impedance modeling of grid-connected inverters for
the analysis of impedance stability. Based on the three-phase LCL-type grid-
connected inverter, the harmonic linearization method was adopted in this paper to
analyze the frequency characteristic of Phase-Locked Loop (PLL), and a design
approach of PLL regulator parameters was proposed. Meanwhile, the impacts of the
factors that include PLL and digital control delay on the impedance characteristic
were considered, and the positive-sequence and negative-sequence impedance model of
the gridconnected inverter was built by combining the harmonic linearization and
symmetrical component methods. Then, the frequency characteristic of PLL was
verified by the simulation results and the output impedance model of the grid-
connected inverter was verified by the experimental results, which effectively
proved the correctness of the theoretical analysis. Finally, based on the output
impedance model of the grid-connected inverter, the impedance-based analysis method
was adopted to make a theoretical analysis and experiment validation of the
interaction stability of the grid-connected system.
Direct Model Predictive Power Control (DMPPC) has emerged as a viable alternative
for grid-tied Active Front End (AFE) power converters. However, its one-switching-
vectorper-sampling-interval character leads to big ripples in its control
variables. This work proposes a Performance-Enhanced Direct Multiple-Vector Model
Predictive Power Control (DMV-MPPC) solution for grid-tied AFEs directly
implementable on an FPGA. The proposed control scheme is compared with the
classical DMPPC. The presented experimental results illustrate that the control
performance can be significantly improved by the proposed DMV-MPPC scheme.
One of the recent developments in personality psychology is the emergence of a new
construct, Grit. Its emergence led to a proliferation of studies advancing Grit as
a significant predictor of various positive outcomes. So far, little attention has
been paid to testing its relevance for various work-related outcomes. The present
paper unraveled Grit's validity in predicting a series of work-relevant outcomes,
namely, organizational citizenship behavior, in-role performance, counter-
productive work behaviors and job satisfaction over the Five-Factor Model (FFM) of
personality. These constructs were assessed on a sample including 170 worldng
adults. Grit had limited predictive validity over the FFM dimensions in predicting
the focal outcomes. Consequently, its relevance in the workplace should be treated
with caution. More research should be conducted before using Grit as a basis for
personnel selection or for interventions focusing on various aspects of performance
or job satisfaction. (C) 2017 Elsevier Ltd. All rights reserved.
The Gromov-Hausdorff distance of two compact metric spaces is a measure for how far
the spaces are from being isometric and has been extensively studied in the field
of metric geometry. In recent years, a lot of attention has been devoted to
computational aspects of the Gromov-Hausdorff distance. One of the most prominent
applications is the problem of shape matching, where the goal is to decide whether
two shapes given as polygonal meshes are equivalent under certain invariances.
Therefore, many methods have been proposed which heuristically estimate the Gromov-
Hausdorff distance of metric spaces induced by the shapes. However, the
computational complexity of computing the Gromov-Hausdorff distance has not yet
been thoroughly investigated. We show that-under standard complexity theoretic
assumptions-determining the Gromov-Hausdorff distance of two finite metric spaces
cannot be approximated within any reasonable bound in polynomial time. Furthermore,
we discover attributes of metric spaces which have a major impact on the complexity
of an instance. This enables us to develop an approximation algorithm which is
fixed parameter tractable with respect to corresponding parameters.
Transcriptional enhancers are DNA regulatory elements that are bound by
transcription factors and act to positively regulate the expression of nearby or
distally located target genes. Enhancers have many features that have been
discovered using genomic analyses. Recent studies have shown that active enhancers
recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs
(eRNAs). GRO-seq, a method for identifying the location and orientation of all
actively transcribing RNA polymerases across the genome, is a powerful approach for
monitoring nascent enhancer transcription. Furthermore, the unique pattern of
enhancer transcription can be used to identify enhancers in the absence of any
information about the underlying transcription factors. Here, we describe the
computational approaches required to identify and analyze active enhancers using
GRO-seq data, including data pre-processing, alignment, and transcript calling. In
addition, we describe protocols and computational pipelines for mining GRO-seq data
to identify active enhancers, as well as known transcription factor binding sites
that are transcribed. Furthermore, we discuss approaches for integrating GRO-seq-
based enhancer data with other genomic data, including target gene expression and
function. Finally, we describe molecular biology assays that can be used to confirm
and explore further the function of enhancers that have been identified using
genomic assays. Together, these approaches should allow the user to identify and
explore the features and biological functions of new cell type-specific enhancers.
In this paper, two lossy grounded inductor simulators (GISs) and one lossless GIS
including an inverting type current feedback operational amplifier (CFOA), two
resistors and a capacitor are proposed. All the proposed GISs can be easily
obtained with commercial available active devices such as AD844s. Also, they do not
need any critical passive component matching conditions. Both of the proposed lossy
GISs employ a grounded capacitor, whereas the lossless one has a floating
capacitor. In order to show performance of the proposed GISs, a number of
simulation and experimental test results are given.
In this paper a novel lossless grounded negative inductance simulator is proposed
using only one operational transresistance amplifier (OTRA) as an active element
and one capacitor and three or four resistors as passive elements. All the
properties of the proposed negative inductance simulator are verified using both
CMOS and current feedback operational amplifier (CFOA) based OTRA realization is
PSPICE. The proposed circuit is also tested experimentally to verify the
theoretical results. As an application, the cancellation of unwanted inductance is
tested using the proposed inductance simulator.
Groundwater vulnerability assessment delineating areas that are susceptible to
contamination from future scenarios has aroused worldwide attention. In this study,
the authors (1)estimate future groundwater vulnerability in Hunan province, China,
under urban-related land-use change and climate change scenarios; and (2)analyze
the importance of related parameters to future groundwater vulnerability. The
DRASTIC model [including seven parameters: depth to water table (D), net recharge
(R), aquifer type (A), soil type (S), topography (T), impact of vadose zone (I) and
conductivity (C)] together with an extra parameter, land-use patterns, was used to
generate the map of groundwater vulnerability in future scenarios. The results
indicated that vulnerability classes had an increasing trend from low to high
vulnerability in the future scenarios. Hunan province may face high groundwater
pollution risk in the future. The sensitivity analysis indicated that the depth-to-
water table may be the dominant factor, and the land-use pattern was the most
sensitive parameter on the predicted future groundwater vulnerability in Hunan
province. Decision makers should identify the potential future groundwater
vulnerability and take early steps to protect groundwater resources.
Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription
factor retinoid-related orphan receptor gamma t, play key roles in the regulation
of inflammation and immunity in the gastrointestinal tract and associated lymphoid
tissues. ILC3 consist largely of two major subsets, NCR+ ILC3 and LTi-like ILC3,
but also demonstrate significant plasticity and heterogeneity. Recent advances have
begun to dissect the relationship between ILC3 subsets and to define distinct
functional states within the intestinal tissue microenvironment. In this review we
discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis,
infection and inflammation - with a focus on comparing and contrasting the relative
contributions of ILC3 subsets.
This Reflection investigates some of the questions that arise when one attempts to
write lives together'. What are the intellectual and theoretical implications of
this mode of biographical writing? What might be its seductions? What are its
creative possibilities? It considers the place of invisible figures in group
biography, and argues that the genre enables the recovery of these figures in
particularly productive ways. It does so because its focus rests not on individuals
but on the interstices between them. Two women receive particular attention. The
first is Elizabeth Kent, the sister-in-law of the radical Romantic journalist Leigh
Hunt. The second is Virginia Edgar, a friend and correspondent of Mary Anne
Disraeli. The Reflection explores what happens to the versions of the past we
construct when such figures disappear from dominant cultural narratives, how group
biography enables their recovery, and the theoretical pitfalls inherent in
returning them to the foreground. Through a sustained focus on creative experience
it suggests a way of deploying the possibilities of group biography in an act of
resistance towards posthumous and anachronistic constructions of significance, and
argues that such resistance has the potential to be creatively liberating.
Social groups aid human beings in several ways, ranging from the fulfillment of
complex social and personal needs to the promotion of survival. Despite the
importance of group affiliation to humans, there remains considerable variation in
group preferences across development. In the current study, children and
adolescents completed an explicit evaluation task of ingroup and out-group members
during functional neuroimaging. We found that participants displayed age-related
increases in bilateral amygdala, fusiformgyrus and orbitofrontal cortex (OFC)
activation when viewing in-group relative to out-group faces. Moreover, we found an
indirect effect of age on in-group favoritism via brain activation in the amygdala,
fusiform and OFC. Finally, with age, youth showed greater functional coupling
between the amygdala and several neural regions when viewing in-group relative to
out-group peers, suggesting a role of the amygdala in directing attention to
motivationally relevant cues. Our findings suggest that the motivational
significance and processing of group membership undergoes important changes across
development.
The operation of blood banks aims at the cost-efficient supply of uncontaminated
human blood. Each unit of donated blood goes through multiple testing for the
presence of various pathogens which are able to cause transfusion-transmitted
diseases. The blood screening process is comprised of two phases. At the first
phase, blood units are screened together in pooled groups of a certain size by the
ELISA (Enzyme Linked Immuno-Sorbent Assay) test to detect various virus-specific
antibodies. The second phase of the screening process is conducted by PCR
(Polymerase Chain Reaction) testing of the individual blood units of the groups
found clean by the initial ELISA phase. Thousands of units of donated blood arrive
daily at the central blood bank for screening. Each screening scheme has associated
testing costs and testing times. In addition, each blood unit arrives with an
expiration date. As a result, the shorter the testing time, the longer the residual
lifetime that is left for the blood unit for future use. The controller faces a
natural and well-motivated operations management problem. He will attempt to
shorten the testing period and reduce the testing costs without compromising too
much on the reliability. To achieve these goals, we propose a new testing procedure
that we term Recycled Incomplete Identification Procedure (RIIP). In RIIP, groups
of pooled blood units which are found contaminated in the ELISA test are divided
into smaller subgroups and again group-tested by ELISA, and so forth, until
eventually the PCR test is conducted for those subgroups which are found clean. We
analyze and optimize the performance of RIIP by deriving explicit formulas for the
cost components of interest and maximize the profit associated with the procedure.
Our numerical results suggest that it can indeed be profitable to do several cycles
at ELISA. (C) 2016 Elsevier B.V. All rights reserved.
Purpose: The aim of this study was to provide the first formal evaluation of a
unique 12-session group therapy programme developed by the UK-based National
Association for People Abused as Children (NAPAC). Method: The therapy outcomes of
this programme were assessed using the CORE-OM tool. Clients comprised 26
individuals (7 males and 19 females), with an age range of 19-67 (mean = 41; SD =
12.76). Clients were survivors of sexual, physical, emotional or neglectful
childhood abuse, or a combination of these, and were from four different locations:
London (n = 9), Bury (n = 4), Belfast (n = 8) and prison (n = 5). Findings: Across
all CORE domains, improvements were shown from pre-to post-therapy. No gender or
age differences were revealed, and improvements were shown across both community
members and prison inmates. Implications: A person-centred approach to group
therapy is beneficial to a wide range of adult clients within the community and
prison settings that require therapy after historical sexual, physical, emotional
or neglectful childhood abuse.
Group-focused moral foundations (GMFs) - moral values that help protect the group's
welfare sharply divide conservatives from liberals and religiously devout from non-
believers. However, there is little evidence about what drives this divide. Moral
foundations theory and the model of motivated social cognition both associate
group-focused moral foundations with differences in conflict detection and
resolution capacity, but in opposing directions. Individual differences in conflict
detection and resolution implicate specific neuroanatomical differences. Examining
neuroanatomy thus affords an objective and non-biased opportunity to contrast these
influential theories. Here, we report that increased adherence to group-focused
moral foundations was strongly associated (whole-brain corrected) with reduced gray
matter volume in key regions of the conflict detection and resolution system
(anterior cingulate cortex and lateral prefrontal cortex). Because reduced gray
matter is reliably associated with reduced neural and cognitive capacity, these
findings support the idea outlined in the model of motivated social cognition that
belief in group-focused moral values is associated with reduced conflict detection
and resolution capacity. (C) 2017 Elsevier B.V. All rights reserved.
Embryo implantation involves a complex sequence of events, and a large amount of
molecules have been postulated to be involved in the interaction of embryo and
endometrium. This study evaluated the endometrial expression of -inhibin and -
glycan in the mid-secretory phase of women scheduled to in vitro fertilization
(IVF) and tested whether these markers are associated with implantation failure. We
performed a nested case-control study including 52 women submitted to IVF and
embryo transfer, divided into 2 groups: cases with implantation failure (n = 33)
and controls with confirmed clinical pregnancy (n = 19). Endometrial -inhibin and -
glycan gene expression was evaluated in the mid-secretory phase of the natural
menstrual cycle immediately before IVF, using real-time polymerase chain reaction.
We found a higher gene expression of -inhibin (fold increase = 2.14 +/- 0.32, P
< .05) and -glycan (fold increase = 1.44 +/- 0.16, P < .05) in implantation failure
patients compared to confirmed clinical pregnancy patients. The areas under the
receiver operating characteristics curves for prediction of implantation failure in
this context were 0.692 and 0.678 for -inhibin and -glycan, respectively. The
present results suggest that high expression levels of -inhibin and -glycan
transcripts in secretory phase endometrium are associated with a lower chance of
achieving pregnancy with IVF.
The aim of this study was to investigate effects of two dietary medicinal herbs,
Rose hip (Rosa canina) and Safflower (Carthamus tinctorius) supplementation on
growth performance, haematological, biochemical parameters and innate immune
response of in juvenile beluga, Huso huso. Fish (263 +/- 0.4 g) were allocated into
15 tanks (20 fish per tank) and triplicate groups were fed a control diet or diets
containing 1% and 2% of medicinal herbs, respectively. Feed conversion ratio (FCR),
specific growth rate (SGR) and condition factor (CF) did not show significant
differences (P >0.05) in fish given herbal diets. Significant differences were
observed in number of white blood cells (WBC) and haemoglobin (Hb) values among the
dietary treatments. The serum alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) levels were significantly lower in supplemented diet groups
compared with the control. Innate immune responses (lysozyme activity and ACH(50))
were significantly higher in 2% Safflower-fed fish compared with other groups (P <
0.05). These results indicate that medicinal herbs in diets can be considered as a
beneficial dietary supplement for improving the physiological parameters and
enhance the immune response of Persian sturgeon. (C) 2016 Elsevier Ltd. All rights
reserved.
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine
kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there
are certain differences in biology between CML and Philadelphia-positive acute
lymphoblastic leukemia (Ph+ ALL). Little is known about the role and mechanism of
hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co-cultured hBMSCs
with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected
using a Cell Counting Kit-8. Additionally, quantitative polymerase chain reaction
and flow cytometry were used to detect the expression of the associated genes and
proteins. The present study explores the role and mechanism of hBMSCs on the growth
of TKI-resistant Ph+ ALL. The current study showed that hBMSCs promoted the
proliferation of TKI-resistant Ph+ ALL. This was shown by the increase in cells in
the S+ G2-M phase of the cell cycle. It was also found that the expression of
cyclins A, C, D1 and E was increased. Apoptosis was inhibited through upregulation
of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2) and BCL-extra large] and
downregulation of apoptotic genes (BCL-XS, BCL-2-associated X protein, and caspases
3, 7 and 9). Expression of the breakpoint cluster region (BCR)-Abelson murine
leukemia viral oncogene homolog 1 (ABL) gene, Wnt5a, and Wnt signaling pathway-
associated genes (glycogen synthase kinase-3 beta, beta-catenin, E-cadherin and
phosphoinositide 3-kinase) and transcription factors (c-myc, ephrin type-B2,
fibroblast growth factor 20 and matrix metalloproteinase 7) was also increased.
Furthermore, the expression of drug resistance genes (low-density lipoprotein
receptor, multidrug resistanceasso-ciated protein and multi-drug resistance gene)
was increased and the expression of anti-oncogenes (death-associated protein kinase
and interferon regulatory factor-1) was decreased. It was concluded that hBMSCs
promote the growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms.
Therefore, targeting hBMSCs may be a promising approach for preventing the growth
of TKI-resistant Ph+ ALL.
In the 21st century, systems biology is a holistic approach to understand life by
the cross-talk study between the genome, Rnome and proteome of a cell. We describe
a column-based rapid method for the simultaneous extraction of DNA, RNA, miRNA
(microRNA) and proteins from the same experimental sample without prior
fractionation, which allows a direct correlation between genomic, epigenomic,
transcriptomic and proteomic data. This method provides a simple and effective way
to analyse each of these biomolecules without affecting yield and quality. We also
show that isolated biomolecules are of the highest purity and compatible for all
the respective downstream applications, such as PCR amplification, RT-PCR (reverse
transcription-PCR), real-time PCR, reverse Northern blotting, SDS/PAGE and Western
blot analysis. The buffers and reagents used in this method are optimized
extensively to achieve the cost effective and reliable procedure to separate the
functional biomolecules of the cell.
Gamma-interferon-inducible lysosomal thiol reductase (GILT) is a key enzyme in the
antigen processing and presentation pathway whereby it reduces disulfide bonds at
an acidic pH. In this study, a homolog of GILT from guinea pigs (designated gpGILT)
was identified and characterized using bioinformatic methods and bioactivity
assays. The open reading frame of gpGILT is 705 bp in length and encodes 234 amino
acids, with a putative molecular weight of about 25.85 kDa. The structure of gpGILT
is similar to those of humans and zebrafish, containing six introns and seven
exons. The deduced primary structure of the gpGILT protein includes all of the
typical features of other known GILT proteins, including an active-site motif,
CXXC, a GILT signature sequence, CQHGX(2)ECX(2)NX(4)C, three potential Asn-linked
glycosylation sites, and six other conserved cysteines. The predicted tertiary
structures of gpGILT, human GILT, and mouse GILT are quite similar in shape and
positional arrangement of the key motifs modeled on the same template. Amino acid
sequence-based alignment and phylogenetic analysis showed that gpGILT is most
closely related to that from the rat, with an identity of 68.40%. Additionally, the
constitutive expression and immune response to lipopolysaccharide (LPS) challenge
of gpGILT were tested using real-time quantitative polymerase chain reaction. A
tissue-specific expression pattern in selected tissues and remarkable up-regulation
of gpGILT mRNA in spleen and blood within 12 h of LPS stimulation were observed,
suggesting that GILT functions as an immunological surveillance-related factor in
both innate and adaptive immunity. Soluble recombinant gpGILT produced in E. coli
could reduce the interchain disulfide bonds of IgG in an acidic reaction system in
vitro, suggesting thiol reductase activity in antigen processing. The results of
this study provide a better understanding of the molecular characteristics of
gpGILT and are a useful reference for further investigation of its involvement in
antigen processing and immunological surveillance using the laboratory guinea pig.
(C) 2016 Elsevier Ltd. All rights reserved.
Objectives:The aim of the study was to assess the effect of nutritional
supplementation with lipid-based nutrient supplements (LNS) and corn-soy blend
flour on Bifidobacterium and Staphylococcus aureus gut microbiota composition in
Malawian infants. In addition, the microbiota changes over time were characterized
in the study infants. Methods:Healthy 6-month-old Malawian infants were randomly
assigned to 1 of 4 intervention schemes for a 6-month period. Infants in the
control group were not provided with any supplementary food. Infants in other 3
groups received either micronutrient-fortified corn-soy blend, micronutrient-
fortified LNS with milk protein base, or micronutrient-fortified LNS with soy
protein base between 6 and 12 months of age. Fecal bifidobacteria and S aureus gut
microbiota at 6 and 12 months of age were analyzed by quantitative real-time
polymerase chain reaction method. Results:There was no difference in change in
bacterial prevalence or counts between the intervention groups during the 6-month
study period. When looking at the total study population, higher counts of total
bacteria (P=0.028), Bifidobacterium genus (P=0.027), B catenulatum (P=0.031), and
lower counts of B infantis (P<0.001), B lactis (P<0.001), B longum (P<0.001), and S
aureus (P<0.001) were detected in the children's stools at 12 months rather than at
6 months of age. Conclusions:The dietary supplementation did not have an effect on
the Bifidobacterium and S aureus microbiota composition of the study infants. The
fecal bifidobacterial diversity of the infants, however, changed toward a more
adult-like microbiota profile within the observed time.
Background: Up-regulation of P-gp is an adaptive survival mechanism of cancer cells
from chemotherapy. Three new phytochemicals including two benzophenones,
guttiferone K (GK) and oblongifolin C (OC), and a xanthone, isojacaruebin (ISO),
are potential anti-cancer agents. However, the capability of these compounds to
increase multidrug-resistance (MDR) through P-gp up-regulation in cancer cells has
not been reported. Purpose: This study was to investigate the effects of GK, OC and
ISO on P-gp up-regulation in colorectal adenocarcinoma cells (Caco-2 cells). In
addition, the mechanisms underlying their inductive effect were also determined.
Methods: The inductive effect of GK, OC and ISO on P-gp expression at transcription
level was measured by real-time reverse transcription polymerase chain reaction.
The reactive oxygen species production was determined by 2', 7'-dichlorofluorescin
diacetate assay. The protein content of P-gp and involvement of mitogen-activated
protein kinases (MAPK) pathway was evaluated by western blot analysis. Results: GK,
OC and ISO (50 mu M, 24 h) were able to increase the amount of MDR1 mRNA and
protein in Caco-2 cells. The presence of N-acetyl-l -cysteine significantly
prevented the inductive effect of GK, OC and ISO on MDR1 mRNA level. Moreover, MAPK
inhibitors including U0126 (an ERK1/2/MAPK inhibitor) and SB202190 (p38/MAPK
inhibitor) suppressed an increase of MDR1 mRNA levels in the cells treated with
benzophenones (GK, OC) and xanthone ISO, respectively. These findings were in
agreement with the increase of phosphorylated form of either ERK1/2 (p-ERK1/2) or
p38 (p-p38) upon treatment of the cells with these three compounds. In addition, OC
and ISO, but not GK, increased mRNA of c-Jun level. Conclusion: The benzophenones
GK, OC and xanthone ISO are likely MDR inducers through up-regulation of P-gp
expression at transcription level. Their molecular mechanisms involve oxidative
stress-mediated activation of MAPK signaling pathway. (C) 2017 Elsevier GmbH. All
rights reserved.
The paper investigates the behavior of unidirectional two-port equivalent circuit
composed of an electronic gyrator with Antoniou operational amplifier and a
reciprocal two-port built by a transversal resistance (RT). From the analysis of
two-port equations standpoint, by correct choice of circuit conductance, the two-
port can operate as an ideal or a lossy gyrator. Due to the interest in practical
aspects of energy transfer from one terminal to other, an analysis of the two-port
parameters for the unidirectional circuit diagram is performed. The validity of the
tested circuit results obtained analytically and through numerical simulation
PSpice has been verified experimentally, in two cases, with equal and different
transfer conductance.
In this study, we describe the complete mitochondrial genomes of Gyrodactylus
brachymystacis and Gyrodactylus parvae infecting rainbow trout (Oncorhynchus
mykiss) and the invasive topmouth gudgeon (Pseudorasbora parva), respectively. The
two circular genomes have a common genome organization found in other Gyrodactylus
species. Comparative analyses of mitochondrial genomes from six Gyrodactylus
species were carried out to determine base composition, codon usage, transfer RNA
and ribosomal RNA genes, major non-coding regions, and nucleotide diversity within
the genus. We also provide the first universal models of the secondary structures
of rrnS and rrnL for this group thereby promoting utilization of these genetic
markers. Universal primers provided herein can be used to obtain more mitochondrial
information for pathogen identification and may reveal different levels of
molecular phylogenetic inferences for this lineage.
A 24 kDa protein is one of the important components in Haemonchus contortus (barber
pole worm) excretory/secretory products (HcESPs), which was shown to have important
antigenic function. However, little is known about the immunomodulatory effects of
this protein on host cell. In the present study gene encoding 24kDa
excretory/secretory protein (HcES-24) was cloned. The recombinant protein of HcES-
24 (rHcES-24) was expressed in a histidine-tagged fusion protein soluble form in
Escherichia coli. Binding activity of rHcES-24 to goat PBMCs was confirmed by
immunofluorescence assay (IFA) and its immunomudulatory effect on cytokine
secretion, cell proliferation, cell migration and nitric oxide production were
observed by co-incubation of rHcES-24. IFA results revealed that rHcES-24 could
bind to the PBMCs. The interaction of rHcES-24 increased the production of IL4,
IL10, IL17 and cell migration in dose dependent manner. However, rHcES-24 treatment
significantly suppressed the production of IFN gamma, proliferation of the PBMC and
Nitric oxide (NO) production. Our findings showed that the rHcES-24 played
important regulatory effects on the goat PBMCs.
Degradation of RNA as an intermediate message between genes and corresponding
proteins is important for rapid attenuation of gene expression and maintenance of
cellular homeostasis. This process is controlled by ribonucleases that have
different target specificities. In the bacterial pathogen Helicobacter pylori, an
exo- and endoribonuclease RNase J is essential for growth. To explore the role of
RNase J in H. pylori, we identified its putative targets at a global scale using
next generation RNA sequencing. We found that strong depletion for RNase J led to a
massive increase in the steady-state levels of non-rRNAs. mRNAs and RNAs antisense
to open reading frames were most affected with over 80% increased more than 2-fold.
Non-coding RNAs expressed in the intergenic regions were much less affected by
RNase J depletion. Northern blotting of selected messenger and non-coding RNAs
validated these results. Globally, our data suggest that RNase J of H. pylori is a
major RNase involved in degradation of most cellular RNAs.
As biodiversity declines with anthropogenic land-use change, it is increasingly
important to understand how changing biodiversity affects infectious disease risk.
The dilution effect hypothesis, which points to decreases in biodiversity as
critical to an increase in infection risk, has received considerable attention due
to the allure of a win-win scenario for conservation and human well-being. Yet some
empirical data suggest that the dilution effect is not a generalizable phenomenon.
We explore the response of pathogen transmission dynamics to changes in
biodiversity that are driven by habitat loss using an allometrically scaled multi-
host model. With this model, we show that declining habitat, and thus declining
biodiversity, can lead to either increasing or decreasing infectious-disease risk,
measured as endemic prevalence. Whether larger habitats, and thus greater
biodiversity, lead to a decrease (dilution effect) or increase (amplification
effect) in infection prevalence depends upon the pathogen transmission mode and how
host competence scales with body size. Dilution effects were detected for most
frequency-transmitted pathogens and amplification effects were detected for
density-dependent pathogens. Amplification effects were also observed over a
particular range of habitat loss in frequency-dependent pathogens when we assumed
that host competence was greatest in large-bodied species. By contrast, only
amplification effects were observed for density-dependent pathogens; host
competency only affected the magnitude of the effect. These models can be used to
guide future empirical studies of biodiversity-disease relationships across
gradients of habitat loss. The type of transmission, the relationship between host
competence and community assembly, the identity of hosts contributing to
transmission, and how transmission scales with area are essential factors to
consider when elucidating the mechanisms driving disease risk in shrinking habitat.
This article is part of the themed issue 'Conservation, biodiversity and infectious
disease: scientific evidence and policy implications'.
Background: Exercise is beneficial for depression, but less is known about its
impact on post-intervention physical activity and sedentary behavior. The aim of
this paper was to determine the extent to which participation in light-, moderate-
and vigorous-intensity exercise intervention influenced habitual physical activity
and sedentary behavior patterns in depressed adults. Methods: Accelerometer data
was collected pre- and post-intervention from depressed participants randomized to
one of three 12-week intervention groups: light (n = 21), moderate (n = 25) and
vigorous (n = 22) exercise. Mixed models examined changes in time spent sedentary
and in light and moderate to-vigorous physical activity (MVPA); time accumulated in
sedentary and MVPA bouts; and, number of MVPA bouts and interruptions in sedentary
time. Results: Overall sedentary time decreased while light activity time increased
across all intervention groups but not significantly so. The light exercise
intervention group reduced MVPA minutes (-8.22, 95% CI: -16.44, -0.01), time in
MVPA bouts (-8.44, 95% CI: -14.27, -2.62), and number of activity bouts (-0.43, 95%
CI: -0.77, -0.09). The moderate exercise intervention group reduced time in MVPA
bouts (-6.27, 95% CI: -11.71, -0.82) and number of sedentary interruptions (-6.07,
95% CI: -9.30, -2.84). No changes were observed for the vigorous exercise
intervention group. Conclusions: The exercise intervention led to an increase in
overall light physical activity and decrease in sedentary time, though neither
change was statistically significant. Participation in the light and moderate
exercise intervention groups was associated with reductions of time in MVPA bouts,
but this was not evident for the vigorous exercise intervention group. (C) 2017 The
Authors. Published by Elsevier Ltd.
Ticks are blood-sucking ectoparasites of great medical and veterinary significance
that can transmit bacteria, protozoa, fungi and viruses, causing a variety of human
and animal diseases worldwide. In the present study, the intestinal bacterial flora
associated with Haemaphysalis flava ticks in different developmental stages were
analyzed using polymerase chain reaction (PCR) and denaturing gradient gel
electrophoresis (DGGE). Eleven distinct DGGE bands were found using PCR-DGGE
method. Sequences analyses indicated that they belonged to Bacillus cereus,
Candidatus rickettsia, Erwinia sp., Klebsiella pneumoniae, Pectobacterium
carotovorum, Pseudomonas aeruginosa, Rickettsia peacockii, Rickettsia helvetica,
Rickettsia slovaca, Staphylococcus simulans and Uncultured bacterium clone. Our
find that the K. pneumoniae and P. aeruginosa isolates were presented in all H.
flava ticks in different developmental stages. The present results indicated that
zoonotic pathogens are present in H. flava ticks in Henan province, China. To our
knowledge, this is the first report on intestinal bacterial flora associated with
H. flava ticks in China.
Objective The effect of polyomavirus infection in HSCT recipients is poorly
understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by
nested qualitative polymerase chain reaction (PCR) assays of urine. The risk
factors for BK virus and JC virus were analysed. The kidney and liver functions of
infected and uninfected patients were compared. Results BK virus, JC virus, and
simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients respectively.
HCMV infection was found to be an independent risk factor for JC virus infection
(odds ratio (OR): 8.528), while transplants with mismatched HLA are more
susceptible to BK virus infection (OR: 12.000). Liver function of JC virus-infected
subjects was worse than that of uninfected subjects. Conclusion We must be vigilant
for opportunistic polyomavirus infections in HSCT recipients, especially those with
HCMV co-infection or a mismatched HLA transplant. When unexplained liver function
deterioration is observed, JC virus infection should be considered.
We investigated the presence of ectoparasites and hemoparasites in side-blotched
lizards (Uta stansburiana) across a large part of their range and measured how
parasitic infection related to several key physiological indicators of health.
Blood samples were collected from 132 lizards from central Arizona, southern Utah,
and eastern Oregon. Hemoparasites were found in 22 individuals (3.2% prevalence in
Arizona, 19.1% in Utah, and 6.3% in Oregon), and ectoparasites were found on 51
individuals (56.3% prevalence in Arizona, 56.1% in Utah, and 6.7% in Oregon), with
11 individuals infected with both. Hemoparasites and ectoparasites were found in
all three states. Immunocompetence was higher in individuals infected with both
hemoparasites and ectoparasites. Body condition, glucocorticoid levels, and
reproductive investment were not related to infection status. Our study provides
evidence that parasitic infection is associated with an active immune system in
wild reptiles but may not impose other costs usually associated with parasites.
Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which
fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies.
HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We
recently found N-linked glycosylation of anti-D to be skewed towards low
fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb,
which correlated with HDFN disease severity. Here, we analysed 230 pregnant women
with anti-c, -E or -K alloantibodies from a prospective screening cohort and
investigated the type of Fc-tail glycosylation of these antibodies in relation to
the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show -
independent of the event that had led to immunisation - a different kind of Fc-
glycosylation compared to that of the total IgG fraction, but with less pronounced
differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c
correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated
with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped
depending on the antigen. These features influence their clinical potency and may
therefore be used to predict severity and identify those needing treatment.
Semecarpus anacardium L. is a tree species which produces secondary metabolites of
medicinal importance. Roots of the plant have been traditionally used in folk
medicines. Different strains of Agrobacterium rhizogenes (A4, ATCC15834 and LBA
9402) were used for induction of hairy roots in in vitro grown tissues of the
plant. Hairy root initiation was observed after 25-30 days of infection. Optimum
transformation frequency of 61% was achieved on leaf explants with ATCC15834
strain. Infection time of 30 min resulted in greater transformation frequency
compared to 10 and 20 min, respectively. The hairy roots cultured in growth
regulator-free semi-solid woody plant medium differentiated into callus. Whole
shoots infected with ATCC 15834 were found to produce more transformants upon co-
cultivation for 4 (65%) and 5 (67%) days. Induction of hairy roots in stem explants
infected with ATCC 15834 was lower (52%) compared to leaves (62%) after 4 days of
co-cultivation. In A4 and LBA9402 strains transformation efficiency was 49 +/- 2.8%
and 36 +/- 5.7% in shoots after 4 days of co-cultivation. Transformation frequency
was higher in ATCC15834 strain, irrespective of explants. The hairy roots of S.
anacardium elongated slowly upon transfer to half-strength liquid medium. After 3-4
passages in liquid medium slender hairy roots started differentiating which were
separated from the original explants. Visible growth of the roots was observed in
hormone-free liquid medium after 2-3 months of culturing. Polymerase chain reaction
with gene-specific primers from rol A, B and C genes confirms the positive
transformation events.
This paper presents the design and multivariable feedback control of a compact
precision positioner. The moving stage that has a total mass of 1.52 kg can
generate all 6-axis motions with a single frame. Aerostatic bearings levitate the
positioner and three 3-phase synchronous permanent-magnet planar motors (SPMPMs)
generate electromagnetic forces over the concentrated-field permanent-magnet
matrix. Three Hall-effect sensors measure the magnetic flux to calculate the planar
position and three laser-distance sensors detect the vertical displacement. Real
Time Application Interface (RTAI) with Comedi on a Linux personal computer is used
for real-time control. Single-input single-output (SISO) digital lead-lag
controllers for each axis are designed, and a multi-input multi output (MIMO) model
is developed for the positioner. Reduced-order linear-quadratic-Gaussian (LQG)
controllers are applied in horizontal positioning. Several experimental results
demonstrate the dynamic performance of the positioner.
The discrete-time robust disturbance attenuation problem for the n-degrees of
freedom (dof) mechanical systems with uncertain energy function is considered in
this paper. First, it is shown in the continuous time-setting that the robust
control problem of n-dof mechanical systems can be reduced to a disturbance
attenuation problem when a specific type of control rule is used. Afterwards, the
robust disturbance attenuation problem is formulised as a special disturbance
attenuation problem. Then, the discrete-time counterpart of this problem
characterised by means of L-2 gain is given. Finally, a solution of the problem via
direct-discrete-time design is presented as a sufficient condition. The proposed
discrete-time design utilizes discrete gradient of the energy function of
considered system. Therefore, a new method is also proposed using the quadratic
approximation lemma to construct discrete gradients for general energy functions.
The proposed direct-discrete-time design method is used to solve the robust
disturbance attenuation problem for the double pendulum system. Simulation results
are given for the discrete gradient obtained with the method presented in this
paper. Note that the solution presented here for the robust disturbance attenuation
problem give an explicit algebraic condition on the design parameter, whereas
solution of the same problem requires solving a Hamilton-Jacobi-Isaacs partial
differential inequality in general nonlinear systems.
The field of vascularized composite allotransplantation combining advances in
reconstructive surgery, transplantation, and immunology offers great promise for
patients with heretofore unsolvable problems. In the last 30 years, hand
transplantation has progressed through the phases of being a research subject, a
controversial clinical procedure, a more widely accepted and expanding field, and
now a promising endeavor undergoing refined indications. Although many lessons have
been learned, few procedures in the author's experience have been as life-
transformative in restoring the body image, motor and sensory functions, activities
of daily living, and personal autonomy as successful hand transplantation.
Copyright (C) 2017 by the American Society for Surgery of the Hand. All rights
reserved.)
A high-order curvature-compensated bandgap reference (BGR) with low temperature
coefficient (TC) is proposed in this paper. The curvature compensation is
maintained through the use of Pplus poly resistor and Nplus poly resistor to
achieve temperature-dependent resistor ratios. A T-resistor structure is adopted
which enables the BGR to work under low supply voltage or high MOSFET threshold
voltage and to reduce the mismatches in transistors and resistors. The design is
implemented in 65-nm CMOS technology with a 1.8-V supply. The output reference
voltage is 550 mV and shows a TC of 0.22 ppm/degrees C in a temperature range from
-20 degrees C to 80 degrees C. A high gain operational amplifier is used that
enhances the power supply rejection ratio to -117.8 dB at DC and -75 dB at 1 kHz.
The effect of mismatch is 4.3%. The proposed BGR achieves a line regulation of 0.8
mV/V and total power consumption of 20.8 mu W.
The MHC is a highly polymorphic genomic region that encodes the transplantation and
immune regulatory molecules. It receives special attention for genetic
investigation because of its important role in the regulation of innate and
adaptive immune responses and its strong association with numerous infectious
and/or autoimmune diseases. The MHC locus was first discovered in the mouse and for
the past 50 years it has been studied most intensively in both mice and humans.
However, in recent years the macaque species have emerged as some of the more
important and advanced experimental animal models for biomedical research into MHC
with important human immunodeficiency virus/simian immunodeficiency virus and
transplantation studies undertaken in association with precise MHC genotyping and
haplotyping methods using Sanger sequencing and next-generation sequencing. Here,
in this special issue on 'Macaque Immunology' we provide a short review of the
genomic similarities and differences among the human, macaque and mouse MHC class I
and class II regions, with an emphasis on the association of the macaque class I
region with MHC polymorphism, haplotype structure and function.
The alignment of many short sequences of DNA, called reads, to a long reference
genome is a common task in molecular biology. When the problem is expanded to
handle typical workloads of billions of reads, execution time becomes critical. In
this paper we present a novel reconfigurable architecture for minimal perfect
sequencing (RAMPS). While existing solutions attempt to align a high percentage of
the reads using a small memory footprint, RAMPS focuses on performing fast exact
matching. Using the human genome as a reference, RAMPS aligns short reads hundreds
of thousands of times faster than current software implementations such as SOAP2 or
Bowtie, and about a thousand times faster than GPU implementations such as SOAP3.
Whereas other aligners require hours to preprocess reference genomes, RAMPS can
preprocess the reference human genome in a few minutes, opening the possibility of
using new reference sources that are more genetically similar to the newly
sequenced data.
The optimal management of chronic hepatitis B virus (HBV) infections is known to be
related with the genotype of HBV in order to prescribe the most appropriate
treatment. In this study, including 19 chronic HBV patients from St. Parascheva
Clinical Infectious Disease Hospital, Ia degrees i, we attempted to double test
their samples for DNA/HBV detection and genotyping. DNA/HBV evidenced from19
patients known as being chronic infected by HBV were tested by two molecular
techniques: Real Time PCR (Polymerase Chain Reaction) and genotyping by
hybridization on strips. We obtained identical results from both methods. The most
frequent genotype was D (47.4%), followed by genotype A (10,5%); 9 samples were
negative, probably because of virus suppressed replication under treatment. The
double testing is accurate, time and cost efficient, and for these reasons we
propose this double testing like a possible algorithm for routine diagnostic, being
time-efficient and accurate for HBV chronic infected patients' management cases.
Recently the performance of dual fuel strategy on multi-cylinder engines over the
whole engine map has received increasing attention. This research focuses on the
potential of Homogeneous Charge Induced Ignition (HCII) combustion fueled with
gasoline and diesel meeting Euro V emission standard through the whole operating
range using a simple after-treatment system. This combustion mode utilizes a port
injection of high-volatile fuel (gasoline) to form a homogeneous charge and a
direct injection of high ignitable fuel (diesel) near the Top Dead Center (TDC) to
trigger combustion. In this paper, an experimental and numerical investigation of
the combustion characteristics and emission formation of HCII on a multi-cylinder
heavy-duty engine is conducted. The effects of gasoline ratio (R-g), one of the
most important parameters in dual-fuel mode, are explored and analyzed in detail. A
R-g of 70-80% is recommended for better combustion and emission performance at the
operating condition in this paper. HCII also turns out to be an effective strategy
to reduce NOx and soot emissions at the same time. Furthermore, the high THC and CO
emissions of HCII combustion can be eliminated using Diesel Oxidation Catalyst
(DOC). Then the HCII strategy was optimized through the whole operating range
showing a great potential of meeting Euro V limitations only with DOC as an after-
treatment device. The fuel consumption also reduced with dual fuel strategy. (C)
2017 Elsevier Ltd. All rights reserved.
Background: Human Cytomegalovirus (HCMV) infections can be found throughout the
body, especially in epithelial tissue. Animal model was established by inoculation
of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into the
ligated sacculus rotundus and vermiform appendix in living rabbits. The specimens
were collected from animals sacrificed 1 and a half hours after infection. Results:
The virus was found to be capable of reproducing in these specimens through RT-PCR
and Western-blot. Severe inflammation damage was found in HCMV-infected tissue. The
viral protein could be detected in high amounts in the mucosal epithelium and
lamina propria by immunohistochemistry and immunofluorescense. Moreover, there are
strong positive signals in lymphocytes, macrophages, and lymphoid follicles.
Quantitative statistics indicate that lymphocytes among epithlium cells increased
significantly in viral infection groups. Conclusions: The results showed that HCMV
or HEV + HCMV can efficiently infect in rabbits by vivo ligated intestine loop
inoculation. The present study successfully developed an infective model in vivo
rabbit ligated intestinal Loop for HCMV pathogenesis study. This rabbit model can
be helpful for understanding modulation of the gut immune system with HCMV
infection.
The rapid advances in research on antisense transcripts are gradually changing our
understanding of the expression of the Herpesviridae genome. In this study, the
transcripts of the human cytomegalovirus (HCMV) UL83 antisense strand were
investigated in three clinical isolates. Three cDNA clones containing sequences
with an antisense orientation to the UL83 gene were identified in a late HCMV cDNA
library. The UL83 antisense transcripts (UL83asts) were then shown to be
transcribed only in the late infection phase of the three clinical HCMV strains,
using rapid amplification of cDNA ends (RACE) and northern blotting. These UL83asts
were identical at their 3 termini but different at 5 ends. Two open reading frames
were predicted in the UL83asts. J. Med. Virol. 86:2033-2041, 2014. (c) 2014 Wiley
Periodicals, Inc.
Background Hepatitis C virus (HCV) core protein, in addition to its structural role
to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by
interfering in several cellular processes, including microRNA and mRNA homeostasis.
The C-terminal truncated HCV core protein (C124) is intrinsically unstructured in
solution and is able to interact with unspecific nucleic acids, in the micromolar
range, and to assemble into nucleocapsid-like particles (NLPs) in vitro. The
specificity and propensity of C124 to the assembly and its implications on HCV
pathogenesis are not well understood. Methods Spectroscopic techniques,
transmission electron microscopy and calorimetry were used to better understand the
propensity of C124 to fold or to multimerize into NLPs when subjected to different
conditions or in the presence of unspecific nucleic acids of equivalent size to
cellular microRNAs. Results The structural analysis indicated that C124 has low
propensity to self-folding. On the other hand, for the first time, we show that
C124, in the absence of nucleic acids, multimerizes into empty NLPs when subjected
to a pH close to its isoelectric point (pH ? 12), indicating that assembly is
mainly driven by charge neutralization. Isothermal calorimetry data showed that the
assembly of NLPs promoted by nucleic acids is enthalpy driven. Additionally, data
obtained from fluorescence correlation spectroscopy show that C124, in nanomolar
range, was able to interact and to sequester a large number of short unspecific
nucleic acids into NLPs. Discussion Together, our data showed that the charge
neutralization is the major factor for the nucleocapsid-like particles assembly
from C-terminal truncated HCV core protein. This finding suggests that HCV core
protein may physically interact with unspecific cellular polyanions, which may
correspond to microRNAs and mRNAs in a host cell infected by HCV, triggering their
confinement into infectious particles.
Histone deacetylation, reciprocally mediated by histone deacetylases (HDAC) and
acetyltransferases, represents one major form of post-translational modification.
Previous research indicates that HDACs play an essential regulatory role in the
development of various immune cells. However, the specific function of individual
HDACs remains largely unexplored. HDAC4, a member of class II HDACs, profoundly
investigated in the nervous system, while the expression profile and function of
HDAC4 in T cells are barely known. For the first time, we report here that HDAC4 is
expressed in the multiple T cell lineages. Using T-cell-specific HDAC4-deficient
mice, we discovered that lack of HDAC4 did not alter the frequencies of
conventional T cells, invariant NKT (iNKT) cells or regulatory T cells within both
the thymus and secondary lymphoid organs. Moreover, conventional T cells and iNKT
cells from wild-type and HDAC4-deficient mice displayed no significant difference
in cytokine production. In conclusion, our results imply that under steady stage,
HDAC4 is not required for the development and function of multiple T cell lineages,
including conventional T cells and iNKT cells.
DNA damage response failure may influence the efficacy of DNA-damaging treatments.
We determined the expression of 16 genes involved in distinct DNA damage response
pathways, in association with the response to standard therapy. Twenty patients
with locoregionally advanced, squamous cell head and neck carcinoma were enrolled.
The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and
5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy
(RT) alone. The volumetric metabolic therapeutic response was determined by
[18F]FDG-PET/CT. In the tumor and matched normal tissues collected before
treatment, the gene expressions were examined via the quantitative real-time
polymerase chain reaction (qRT-PCR). The down-regulation of TP53 was apparently
associated with a poor response to iChT, its up-regulation with complete regression
in 2 cases. 7 cases with down-regulated REV1 expression showed complete regression
after ChRT/RT, while 1 case with REV1 overexpression was resistant to RT. The
overexpression of WRN was an independent predictor of tumor relapse. Our results
suggest that an altered expression of REV1 predicts sensitivity to RT, while WRN
overexpression is an unfavorable prognostic factor.
Background: HPV-16 modifies the overall survival (OS) of patients with
oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC,
but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated
HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients.
Methods: HPV-16 infection was confirmed by amplification of E6 and E7 viral
oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between
HPV-16 status and clinicopathological parameters were performed using Fisher's
exact test and x(2). Survival analysis was completed using Kaplan-Meier estimator
and multivariate Cox regression analysis. Results: OS of HPV-16 positive patients
was longer compared to HPV-16 negative patients (P = 0.002). HPV-16 positive tumors
of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16
negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a
better survival. Conclusions: HPV-16 status has a positive prognostic value in
HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment
in prognosis and guide treatment for HNSCC patients.
Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal
SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites.
Human papillomavirus (HPV) is now recognized as a significant risk factor of the
carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively
young, less exposed to tobacco and alcohol, and have a relatively high
socioeconomic status and education level, which is distinct from HPV-unrelated
classical OPSCC. The neck metastases tend to be aggressive and cystic. The better
response to treatment resulting in improved prognosis of HPV-related OPSCC led to
reconsidering the clinical staging and treatment approaches. Clinical trials of
treatment deintensification to reduce the acute and late toxicity without
compromising efficacy have been conducted. This review of HPV-related OPSCC focuses
on current and generally accepted facts regarding the biology, epidemiology, and
therapeutic strategy of this new disease entity.
Context: Pediatric abusive head trauma (AHT) can be defined as an injury to the
skull or intracranial contents of a child under the age of 5 due to inflicted blunt
impact or violent shaking. Evidence Acquisition: AHTis the most commoncause of
traumatic death in children younger than 1 year, and it is the leading cause of
death due to child abuse. Clinical presentation observed in children with AHT
depends on the type of AHT and accompanying injuries. History and physical
examination are important for diagnosing AHT and for distinguishing it from other
conditions that can mimic shaken baby syndrome, such as accidental trauma, cancer,
metabolic diseases, and others. Results: Progress in research on the medical
diagnosis of AHT has been remarkable, while the development of treatment strategies
has been limited. For these reasons, there is an urgent need to develop effective
treatment strategies for AHT able to improve the outcomes. Conclusions: The
construction of a nationwide database that supports clinical studies is required in
the future.
Purpose Headache is a common presenting feature of patients with pituitary adenomas
and other tumors of the sellar region. However, at present, it still is unclear
whether the headache is actually caused by the tumor. To explore whether there is a
relation, we examined in detail the headache types, their relationship to the
underlying pathology, and if the headache responded to neurosurgery in a
prospective study design. Methods One hundred twelve patients with tumors of the
sellar region scheduled for neurosurgery in a single center were analyzed for
presence and quality of headache before surgery and at least 3 months after
surgery. Patients received headache and depression self-rating inventories,
presented on a handheld computer (PainDetect(A (R))). Clinical variables thought to
impact on headache were analyzed in conjunction with the inventories. Results
Fifty-nine (53%) patients reported headache in the 3 months prior to neurosurgery,
49 (44%) had headache at the time of filling in the questionnaires. The four
patients with pituitary apoplexy described thunderclap headache. In the other
patients diverse headache types were encountered, most frequently migraine.
Untreated gonadotroph deficiency was significantly associated with absence of
headache, while none of the other clinical and morphological variables related to
headache. Presence of headache and disability due to headache were not
significantly reduced after surgery. Conclusion Apart from pituitary apoplexy we
detected no specific headache type in our patient group and no significant
improvement of headache after neurosurgery. Headache alone constitutes neither a
valid diagnostic marker for the presence of tumors of the sellar region nor a
sufficient indication for tumor removal.
This paper describes a provider-patient communication process, which although not
new to health care in general, is new to the pharmacy profession. Health coaching
is a technique that empowers patients to make lasting health behavior changes that
improve overall well-being. It provides patients with health care implementation
options that better suit their lifestyle and abilities. Health coaching programs
have the potential to foster better health outcomes, especially with patients who
are chronically ill or represent an at risk population for medication non-adherence
(e.g. elderly, patients on psychotropic medications). Other health professions
(e.g. nursing and medicine) have had success with the implementation of health
coaching models. For example, nurse coaching is recognized by the American Nurse
Association and recent statistics show 3.1 million nurses in the U.S.A are also
trained in nurse coaching. The pharmacy profession has yet to tap the patient-
related benefits of health coaching. This commentary will discuss (i) The
theoretical foundations of health coaching (ii) Distinctions between health
coaching, motivational interviewing and traditional medication therapy counseling
(iii) Training necessary for health coaching; and (iv) How pharmacists can use
health coaching in practice. (C) 2016 Elsevier Inc. All rights reserved.
Background Health care providers fill a central role in the prevention of both
child abuse and neglect (CA/N) and unintentional childhood injury. Health
communication interventions hold promise for promoting attitudes and behaviours
among parents that increase positive parenting practices, which may be linked to
decreased rates of intentional and unintentional childhood injuries. This
manuscript describes the development of `RISE Up', an ambulatory clinic-based
childhood injury prevention programme that provides tailored, injury prevention
print materials to parents of children ages 0-5. Methods Fifteen semi-structured
key informant interviews were conducted with clinic healthcare providers and staff
to develop communication strategies and materials for caregivers. Cognitive
response testing was then conducted with 20 caregivers of the priority population
to assess all materials. Interviews were recorded, transcribed and analyzed using
thematic coding methods. Results Formative research revealed that health care
providers and caregivers were very responsive to messages and materials. Health
care providers reported that abuse and neglect were particularly relevant to their
patients and noted several benefits to implementing the RISE Up programme in a
health care setting. Caregivers generally found messages on reducing the risks of
injuries, as well as the graphics displayed in the RISE Up programme to be helpful.
Conclusions Addressing the common determinants of both intentional and
unintentional childhood injury through customized print materials may be a useful
component of comprehensive prevention efforts to address childhood injury risk with
greater impact. Providers and parents responded favourably to this communication
strategy.
Background Low engagement in prenatal home visiting may limit programme
effectiveness to improve birth outcomes. Multiple factors may influence engagement.
Methods A retrospective cohort study of first-time mothers enrolled in home
visiting prenatally in southwest Ohio from 2007 to 2010. The primary outcome was
enrolment by 20weeks' gestation; a secondary outcome included home visit frequency.
Two multilevel assessments were conducted using random intercept multilevel
modelling; maternal covariates were nested first within the home visiting agency
and then within the ZIP code. In the first model, variations attributable to
individual agency and agency volume were assessed. In the second model nested
within the ZIP code, violence rates by ZIP code and interaction terms between
violence rates and maternal factors were evaluated. Results Of 837 women, 25.3%
enrolled 20weeks and 7.4% enrolled early and received 75% of expected visits. The
first model demonstrated a significant variation in early enrolment based on
clustering by agency (p<0.001), however, agency volume was not a significant
predictor. In the second model, violence rate was not associated with early
enrolment (AOR 0.92, p=0.08), but an interaction term with maternal race was
significant (p=0.02). The effect of increasing community violence
disproportionately affected early enrolment among white women (AOR 0.80, p=0.005)
compared with black women (AOR 0.95, p=0.30). In both the random intercept
multilevel models, teenagers demonstrated a decreased likelihood of enrolling early
(AOR 0.58, p=0.046 and AOR 0.49, p=0.004). Conclusions Prenatal home visiting
engagement is related to maternal, agency and community factors, presenting
multiple opportunities to optimise programme implementation.
There is wide variation in reported impact of caring on caregiver wellbeing, and
often a negative appraisal of caregiving. Researchers are beginning to question the
robustness of the evidence base on which negative appraisals are based. The present
study aimed to draw on data from a population-representative sample to describe the
health, quality of life and impact of caring of informal caregivers of people with
an intellectual disability. Informal carers of people with intellectual disability
(N = 260) were identified among 2199 carers in the English Survey of Carers in
Households 2009/10. Generalised estimating equations explored the association
between socio-demographic and caring profile with quality of life, physical health
status, and impact on psychological health and personal life. Compared to other
caregivers, providing care to a person with intellectual disability was not
associated with reduced quality of life. There was an 82% increased risk of
reporting poorer health status, even though poorer health was not likely to be
attributed to caregiving. A higher risk of negative impact on personal life was
seen in comparison with the wider group of caregivers, but not in comparison with
more similar-sized caregiver groups (mental health or dementia). Carers of people
with intellectual disability were more likely to be struggling financially and have
a high caring load. These factors were systematically related to lower well-being.
A uniformly negative appraisal of caring for people with intellectual disability
was not supported by these English population-representative data. Poverty and long
caregiving hours may make caregivers more susceptible to negative wellbeing.
Support for caregivers of people with intellectual disability should focus on
alleviating those two factors.
The health and well-being consequences of social isolation and loneliness in old
age are increasingly being recognised. The purpose of this scoping review was to
take stock of the available evidence and to highlight gaps and areas for future
research. We searched nine databases for empirical papers investigating the impact
of social isolation and/or loneliness on a range of health outcomes in old age. Our
search, conducted between July and September 2013 yielded 11,736 articles, of which
128 items from 15 countries were included in the scoping review. Papers were
reviewed, with a focus on the definitions and measurements of the two concepts,
associations and causal mechanisms, differences across population groups and
interventions. The evidence is largely US-focused, and loneliness is more
researched than social isolation. A recent trend is the investigation of the
comparative effects of social isolation and loneliness. Depression and
cardiovascular health are the most often researched outcomes, followed by well-
being. Almost all (but two) studies found a detrimental effect of isolation or
loneliness on health. However, causal links and mechanisms are difficult to
demonstrate, and further investigation is warranted. We found a paucity of research
focusing on at-risk sub-groups and in the area of interventions. Future research
should aim to better link the evidence on the risk factors for loneliness and
social isolation and the evidence on their impact on health.
Objectives: This study aims to describe the dietary status of Turkish adults using
two different versions of the Healthy Eating Index (HEI). Methods: In this cross
sectional study, 494 healthy participants (311 females) with randomly selected and
living in Ankara were included between September 2013 and March 2014. A
questionnaire was completed and anthropometric measurements (weight and height)
were performed. The 24-h dietary recall of individuals was collected. Diet quality
was measured through HEI-2005 and HEI-2010 scores. Results: The mean age, body mass
index (BMI), HEI-2005 and HEI-2010 scores of individuals were 32.9 +/- 10.8 years;
25.0 +/- 4.8 kg/m(2); 56.1 +/- 13.9 and 41.5 +/- 13.7 points, respectively.
Significant differences were found between mean HEI-2005 and HEI-2010 scores (p <
0.05). The individual's whose diet quality needs to be improved according to mean
HEI-2005 score, had poorer diet based on mean HEI-2010 scores. The highest mean
HEI-2005 and HEI-2010 scores were stated in female, in subjects had low education
levels, aged 51 years or older and in overweight groups (p < 0.05). Both versions
of healthy eating indices were correlated positively with BMI and age Conclusion:
Diet qualities of the individuals are associated with age, gender, education and
BMI. Although the components and scores in HEI-2010 version were changed from the
version of HEI-2005, the changes may encourage healthy choices of some food group.
HEI-2010 gives more attention to food quality than HEI-2005. Thus, in the present
study it was concluded that HEI-2010 provided more precise results about diet
quality.
Background: Increased spiritual well-being is related to quality of life (QOL) in
patients with heart failure (HF). However, consistent and deliberate integration of
spirituality into HF patient care has received limited attention. Objective: The
aim of this study was to evaluate the feasibility, acceptability, and preliminary
evidence regarding the efficacy of a resource-sparing psychospiritual intervention
to improve QOL in HF patients. Methods: A 12-week mail-based intervention
addressing spirituality, stress, coping, and adjusting to illness was developed and
tested using a mixed-methods, 1-group pretest-posttest pilot study design. A
convenience sample of patients with HF completed prestudy and poststudy
questionnaires, including the Kansas City Cardiomyopathy Questionnaire, Patient
Health Questionnaire, Meaning in Life Questionnaire, and Functional Assessment of
Chronic Illness Therapy-Spiritual. Research staff conducted semistructured
interviews with program completers. Interviews were coded and analyzed using
conventional content analysis. Results: Participants (N = 33; 82% male; mean age,
61 years) completed 87% of baseline data collection, an average of 9 intervention
modules, and 55% of poststudy questionnaires. Participants rated all the modules as
at least moderately helpful, and qualitative themes suggested that patients found
the intervention acceptable and beneficial. Most participants believed spirituality
should continue to be included, although they disagreed on the extent to which
religion should remain. Participants who completed the intervention reported
evidence suggesting increased QOL (Kansas City Cardiomyopathy Questionnaire; effect
size [ES], 0.53), decreased depressive symptoms (Patient Health Questionnaire-9;
ES, 0.62), and less searching for meaning (Meaning in Life Questionnaire; ES,
0.52). Conclusions: Results indicate that a module-based program integrating
spirituality and psychosocial coping strategies was feasible and acceptable and may
improve QOL. This preliminary study suggests that clinicians be open to issues of
spirituality as they may relate to QOL in patients with HF. Future research will
test a revised intervention.
Air pollution represented by haze in China has attracted great global attention in
recent years. China has recently introduced a series of action plans to improve air
quality and prevent air pollution. Remediation on small coal-fired boilers and the
development of heat and power cogeneration (HPC) and centralized heat supply (CHS)
are important measures for preventing air pollution. This paper introduces the
above mentioned policies, An industrial park in Guangdong Province, China, is taken
as an example to analyze the contributions of HPC-based industrial CHS to energy
saving and environmental protection. The benefits to the heat supplier and user are
also analyzed. Furthermore, this paper presents the difficulties and challenges in
developing industrial CHS, including mismatching in the early phase, price dispute,
measure dispute, and negative inter-effects. The reasons for these problems are
analyzed and possible solutions are provided. (C) 2016 Elsevier By. All rights
reserved.
To gain insight into the comparative function in stress response of HSPs in
insects, three HSP cDNAs were cloned from the fat body of the beet armyworm
Spodoptera exigua (Lepidoptera, Noctuidae). SexHSP70, SexHSP74 and SexHSP83 cDNAs
encoding the protein of 667, 685 and 717 amino acids, with the pI of 5.52, 5.75 and
5.02, respectively. Northern blotting revealed that all three SexHSP mRNAs are
expressed in the fat body, mid-gut, spermary and tracheae. SexHSP70, SexHSP74and
SexHSP83 mRNAs were expressed in the fat body and whole body at different levels
during different developmental stages. The three SexHSP transcripts were highly
expressed in the fat body on the first day of fifth instar larvae, on the fourth
and seventh days of the pupa stage, and in the whole body on the initial stages of
larvae. Under heat and cold shock conditions, SexHSP70 and SexHSP83 mainly
functioned during heat shock and cooling and SexHSP83 also had a function in the
recovery stage. SexHSP74 had important functions in short-term heat shock and
recovery, as well as long-term cooling. The results revealed that long-term
shocking can affect SexHSP74 and SexHSP83 expression and long-term cooling can
influence SexHSP83 expression during the recovery stage. Published by Elsevier Inc.
Heat shock transcription factor I (HSF1) regulates heat shock proteins (HSPs),
which assist in protein folding and inhibit protein denaturation following stress.
HSFI was firstly cloned from orange-spotted grouper and exists as two isoforms, one
with (osgHSF1a) and one without (osgHSF1b) exon 11. Heat exposure increased the
expression of osgHSFlb while cold exposure increased that of osgHSFla. Both
isoforms were mainly expressed in the brains, eyes, and fins. Expression of
osgHSF1b was higher than osgHSFla during development. Poly I:C and LPS could also
induce osgHSF1 isoforms expression differentially. Exposure to nervous necrosis
virus (NNV) increased the level of both osgHSF1 isoforms at 12 h. GF-1 cells with
overexpression of osgHSF1 isoforms enhanced viral loads within 24 h, whereas both
pharmacological inhibition and RNA interference of HSF1 reduced virus infection.
This study shows that osgHSF1 can support the early stage of virus infection and
provides a new insight into the molecular regulation of osgHSF1 between the
influence of temperatures and immunity. (C) 2016 Elsevier Ltd. All rights reserved.
The common existence of heat transfer phenomena in energy utilization systems
highlights the importance of appropriate design and optimization methods of heat
transfer systems to an unprecedented level. In this contribution, we defined an
alternative thermal resistance for heat exchangers based on the inlet temperature
difference of hot and cold fluids, which was influenced by such two aspects as the
finite heat capacity rates of hot and cold fluids and the entransy dissipation-
based thermal resistance of heat exchangers. Meanwhile, the corresponding energy
flow models are proposed to analyze the heat transfer performance of both
individual heat exchangers and three basic heat exchanger networks, i.e. series,
parallel and multi-loop by the thermo-electrical analogy method, which offer the
solution for constructing the energy flow models of any heat transfer system. For
validation, we constructed the energy flow model of a double-loop thermal
management system. On this basis, the heat transfer characteristic was described on
the system level and the overall system constraints were obtained by the Kirchhoffs
Law without introducing any intermediate variables. With these system constraints,
the optimization equations for the system were derived theoretically by applying
the Lagrange multiplier method. Simultaneously solving these equations gave the
optimal thermal conductances of each heat exchanger and the best allocations of
heat capacity rate directly, which benefited energy conservation. That is, the
energy flow model is reliable and convenient for the analysis and optimization of
heat transfer systems. (C) 2016 Elsevier Ltd. All rights reserved.
In this study, we develop a novel system to recover the waste heat from the exhaust
of a passenger car. A heat exchanger is therefore placed after the exhaust manifold
of the vehicle. Thermoelectric generators (TEG) are installed on all pipes of the
heat exchanger to generate electricity by the temperature difference between hot
and cold sides of the TEG. The heat transfer of the TEG is analyzed numerically.
Two configurations of TEG units are investigated for various exhaust flow rates and
temperatures. The overall heat transfer rates from the exhaust gas to the TEG, the
power capacity of the system and the overall heat transfer coefficients of the
system are calculated. It is observed that the power capacity of the system is
directly related to the inlet temperature and mass flow rate of the exhaust gas
entering the system. The power generated by the system can be improved by 90% with
an increase of the mass flow rate and temperature of the exhaust gas. Increasing
the size of the TEG system by 66.7% rises the overall heat transfer rate of the
system by 33.8%. (C) 2017 Elsevier Ltd. All rights reserved.
Physical treatments have gained great interest in recent years to control many
postharvest diseases in fruits and vegetables because the total absence of residues
in the treated product and minimal environmental impact. The present review shows
the extensive research work conducted during many years and increased in the last
10 years, developing physical means for consistent disease control. The review
include the use of cold storage as the main physical method for delaying or
reducing biotic and abiotic diseases. Physical treatments, like heat, including hot
water and hot air treatments, radio frequency and microwave, hypobaric and
hyperbaric pressure and far ultraviolet radiation (UV-C light), are treated as
promising control means, and controlled and modified atmospheres as complementary
physical tools essential to reduce or delay the development of postharvest
pathogens. A particular emphasis is given to the mode of action, which involve
direct effect to the pathogen (lethal or sub-lethal) of spore germination and
mycelial growth of fungi and the resistance induction in the host which is not well
known but nowadays, with the new tools available in molecular biology will be easy
to highlight other physiological and biochemical pathways on which the phenomenon
are based. Besides benefits of treatment in different commodities, also limitations
of use, including low persistence, risk of adverse effects and technological
problems for commercial application are discussed. (C) 2016 Elsevier B.V. All
rights reserved.
Microbially induced corrosion (MIC) has been identified as the main cause of the
rupture of a key heat exchanger shell at a local refinery. The failure occurred at
the 6 o'clock position, close to the girth weld, halfway along the length of the
carbon steel shell. An ultrasonic survey revealed up to 90% wall thinning in the
ruptured zone. Despite extensive crystallization at the external cooling seawater
inlet of the cooling system tubing, there was no evidence of internal leakage of
seawater into the shell compartment. The total dissolved solids in the condensate
dropout sample were found to be 262 mg/L. The investigation also confirmed that the
girth weld had been satisfactorily conducted, including post heat treatment, and
that the failure occurred outside the heat affected zone (HAZ). Quantitative
polymerase chain reaction (qPCR) analysis of the dry surface film from a crack in
the ruptured area confirmed the suitability of the operating environment for
prokaryotic growth and the presence of both groups of highly corrosive acid
producing bacteria (APB) and denitrifying bacteria (DNB) in moderate numbers (1.92
x 10(3) APB/g and 1.81 x 10(5) DNB/g respectively). The colonization of different
groups of corrosion-causing bacteria of a sour system resulted in the localized
generation of highly aggressive metabolic by-products causing substantial loss of
wall thickness of the heat exchanger shell. The localized wall thinning by over 90%
of its original thickness led to the loss of pressure retention capacity of the
shell and the rupture of the wall. (C) 2016 Elsevier Ltd. All rights reserved.
Transformation of DNA into microbial cells via heat-shock approach has been well
established in the field of molecular biology for decades. Herein we described an
unexpected finding that heat-shock may not play an essential role in the
transformation process. This observation was verified via UV-Vis and fluorescence
spectroscopies, and confocal microscopy images for various DNAs and bacterial
cells. The non-heat-shock approach proposed in this study can be a convenient and
beneficial modification for DNA transformation, especially for those laboratories
lacking ice machine and heat-shock equipment.
Sunflower leaf spot caused by the necrotrophic pathogen Alternaria helianthi is one
of the most important biotic constraints in sunflower production. The biochemical
basis of resistance to infection by A. helianthi in sunflower is poorly elucidated.
Differential activation of early defense responses like increased peroxidase
activity predisposes the host plant resistance. In the present study, the active
role of peroxidase in resistant and susceptible interactions of sunflower with the
leaf spot pathogen was demonstrated using native PAGE analysis and Northern
blotting. Differential time-dependent induction of peroxidase isoforms was evident
in resistant and susceptible genotypes after pathogen inoculation. In the resistant
interaction, three peroxidase (PO) isoforms (PO1, PO2, and PO3) were found to be
expressed at 2 and 12 h after inoculation, but in susceptible interaction, PO2 was
present at 24 and 48 h and PO3 was found only at 24 h after inoculation. However,
in the susceptible genotype, expression intensity was lower than in the resistant
interaction at all the time intervals. Molecular expression profiling by Northern
blotting using heterologous cDNA probes showed rapid up-regulation of peroxidase at
2 and 12 h in resistant interaction. These results demonstrate that peroxidase
isoforms are involved in defense against A. helianthi, and genetic regulation in
the form of transcript accumulation is important for expression of disease
resistance.
The main problem of Helicobacter pylori (H. pylori) infection management is linked
to antibiotic resistances. This phenomenon has grown in the last decade, inducing a
dramatic decline in conventional regimen effectiveness. The causes of resistance
are point mutations in bacterial DNA, which interfere with antibiotic mechanism of
action, especially clarithromycin and levofloxacin. Therefore, international
guidelines have recently discouraged their use in areas with a relevant resistance
percentage, suggesting first-line schedules with expected high eradication rates,
i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require
the daily assumption of a large number of tablets. Consequently, a complete
adherence is expected only in subjects who may be motivated by the presence of
major disorders. However, an incomplete adherence to antibiotic therapies may lead
to resistance onset, since sub-inhibitory concentrations could stimulate the
selection of resistant mutants. Of note, a recent meta-analysis suggests that
susceptibility tests may be more useful for the choice of first than second-line or
rescue treatment. Additionally, susceptibility guided therapy has been demonstrated
to be highly effective and superior to empiric treatments by both meta-analyses and
recent clinical studies. Conventional susceptibility test is represented by culture
and antibiogram. However, the method is not available everywhere mainly for
methodology-related factors and fails to detect hetero-resistances. Polymerase
chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are
accurate in finding even minimal traces of genotypic resistant strains and hetero-
resistant status by the identification of specific point mutations. The need for an
invasive endoscopic procedure has been the most important limit to their spread. A
further step has, moreover, been the detection of point mutations in bacterial DNA
fecal samples. Few studies on clarithromycin susceptibility have shown an overall
high sensitivity and specificity when compared with culture or PCR on gastric
biopsies. On these bases, two commercial tests are now available although they have
shown some controversial findings. A novel PCR method showed a full concordance
between tissue and stool results in a preliminary experience. In conclusion,
despite poor validation, there is increasing evidence of a potential availability
of noninvasive investigations able to detect H. pylori resistances to antibiotics.
These kinds of analysis are currently at a very early phase of development and
caution should be paid about their clinical application. Only further studies aimed
to evaluate their sensitivity and specificity will afford novel data for solid
considerations. Nevertheless, noninvasive molecular tests may improve patient
compliance, time/cost of infection management and therapeutic outcome. Moreover,
the potential risk of a future increase of resistance to quadruple regimens as a
consequence of their use on large scale and incomplete patient adherence could be
avoided.
The management of Helicobacter pylori (H. pylori) infection treatment differs from
the common treatment protocol for other infectious diseases. Because culture-or
molecular-guided approaches face several practical issues, such as the invasive
procedures required to obtain gastric biopsy specimens and the lack of availability
of routine laboratory testing in some places, H. pylori treatment includes the
administration of two or three empirically selected antibiotics combined with a
proton pump inhibitor rather than evidence-based eradication treatment. The
efficacy of empirical therapy is decreasing, mostly due to increasing multiple
resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole,
which are commonly used in empirical treatments, appears to have increased in many
countries. Mutations play a primary role in the antimicrobial resistance of H.
pylori, but many different mechanisms can be involved in the development of
antibiotic resistance. Determining and understanding these possible mechanisms
might allow the development of new methods for the detection of H. pylori and the
determination of antimicrobial resistance. A treatment based on the detection of
antimicrobial resistance is usually more effective than empirical treatment.
Nevertheless, such an approach before treatment is still not recommended in the
Maastricht guidelines due to the difficulty associated with the routine application
of available culture-or molecular-based susceptibility tests, which are usually
administered in cases of treatment failure. The management of first and rescue
treatments requires further research due to the steadily increase in antimicrobial
resistance.
Acyl-CoA-binding protein (ACBP), also known as the diazepam-binding inhibitor
(DBI), has been identified in diverse species and is evolutionarily conserved in
plants and animals. In a recent study, an ACBP cDNA (HaACBP) encoding 85 amino
acids was isolated from the cotton bollworm Helicoverpa armigera. The isolated
protein is highly homologous to the ACBP present in the Bombyx mori midgut, where
it is highly expressed. Northern and Western blot analyses revealed that HACBP is
expressed predominantly in the midgut. Moreover, Northern blotting revealed that
HaACBP was probably stimulated by a high juvenile hormone titer at ecdysis and
increased along with feeding at 12 h post-ecdysis. Immunohistochemistry of the
midgut revealed that HaACBP is localized in columnar cells. Data from the Northern
blotting and immunohistochemistry suggested that HaACBP was expressed during the
larval period and is probably responsible for nutrition absorption. However,
Western blot analysis of the midgut at different developmental stages indicated
that HaACBP was upregulated during larval molting and metamorphosis, which
suggested that HaACBP expression was posttranscriptionally regulated.
Helminthic therapy of immune-mediated diseases has gained attention in recent
years, but we know little of how helminths modulate human immunity. In this study,
we investigated how self-infection with Trichuris (T.) trichiura in an adult man
without intestinal disease affected mucosal and systemic immunity. Colonic mucosal
biopsies were obtained at baseline, during T. trichiura infection, and after its
clearance following mebendazole treatment. Unexpectedly, the volunteer experienced
a Campylobacter colitis following T. trichiura clearance, and this served as a
positive infectious control. Trichuris trichiura colonization induced equally
increased expressions of T-helper (h) 1-, Th2-, Th17- and Treg-associated cytokines
and transcription factors, measured by quantitative polymerase chain reaction. We
observed several indicators of modulation of systemic immunity during the T.
trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly
during the inoculation phase, and a shift towards a Th2-dominated T cell response
at the expense of the Th1-response was observed in circulating T cells. Taken
together, our findings corroborate that helminths modulate regional and systemic
human immunity.
This study examined the services provided by one statewide warmline established to
assist parents and caregivers of children from birth through adolescence. Warmlines
offer telephone-based, non-crisis support for individuals experiencing diverse
issues that include parenting questions and concerns. The University of Alabama
Child Development Resources collaborated with the Alabama State Department of Child
Abuse and Neglect Prevention to institute the Parenting Assistance Line to provide
information and support to parents and caregivers of children, age birth through
adolescence. Overall, the staff of the Parenting Assistance Line responded to 9487
calls during the 6 years of data reported here. Through a secondary data analysis
of calls to the Parenting Assistance Line from June 2007 to July 2013, this study
describes the concerns of callers in relation to the ages of the children about
whom they are calling and also evaluates the perceptions of the helpfulness of the
information and support provided by the warmline. We found that frequently calls
involved parent support and parental stress for parents and caregivers of children
from infancy through adolescence. The findings suggest that telephone assistance
lines offer a viable choice for parents and caregivers seeking affordable and
accessible resources when stressed by the responsibilities of caring for children
and adolescents and/or seeking information related to parenting issues. The study
identified the limitations of research involving secondary data collected for
purposes other than research that program administrators and evaluators should
consider when planning and implementing services of this nature.
A feeding trial was conducted to investigate the effects of different levels of
dietary Lactobacillus plantarum on hemato-immunological parameters and resistance
against Streptococcus iniae infection in juvenile Siberian sturgeon Acipenser
baerii. Fish (14.6 +/- 2.3 g) were fed three experimental diets prepared by
supplementing a basal diet with L. plantarum at different concentrations [1 x
10(7), 1 x 10(8) and 1 x 10(9) colony-forming units (cfu) g(-1)] and a control
(non-supplemented basal) diet for 8 weeks. Innate immune responses (immunoglobulin
(Ig), alternative complement activity (ACH50) and lysozyme activity) were
significantly higher in fish fed the 1 x 10(8) and 1 x 10(9) cfu g(-1) L. plantarum
diet compared to the other groups (P < 0.05). Furthermore, fish fed on various
levels of L. plantarum significantly showed higher red blood cell (RBC), hemoglobin
(Hb), white blood cell (WBC) and monocyte compared to those of the control group (P
< 0.05). At the end of the feeding experiment, some fish were challenged with S.
iniae to quantify the level of disease resistance. The mortality after S. iniae
challenge was decreased in fish fed a probiotic. These results indicated that
dietary supplementation of L. plantarum improved immune response and disease
resistance of Siberian sturgeon juvenile.
Hematopoietic cells are continuously generated throughout life from hematopoietic
stem cells, thus making hematopoiesis a favorable system to study developmental
cell lineage commitment. The main factors incorporating environmental signals to
developing hematopoietic cells are cytokines, which regulate commitment of
hematopoietic progenitors to the different blood lineages by acting either in an
instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL)
and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as
manifested by the severely compromised B-cell development in their absence.
However, their precise role in regulating B-cell commitment has been the subject of
debate. In the present study we assessed the rescue of B-cell commitment in mice
lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate
that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting
in significant Ebf1 and Pax5 expression in Ly6D(+) CD135(+)CD127(+)CD19(-)
precursors and subsequent generation of normal numbers of CD19(+) B-cell
progenitors, therefore indicating that IL-7 can be dispensable for commitment to
the B-cell lineage. Further analysis of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors
in IL-7-or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic
mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive
manner: FL by inducing proliferation of Ly6D(+)CD135(+)CD127(+)CD19(-) progenitors
and IL-7 by providing survival signals to these progenitors.
Aging is associated with significant changes in hematopoiesis, including clonal
dominance, anemia, myeloid malignancies, and reduced activation of signal
transducer and activator of transcription 5 (Stat5). In previous studies, Stat5
deletion surprisingly amplified FLT3/ITD+ myeloid expansion or Myc-driven lymphoid
expansion. Here we show that Stat5 deficiency has a strong impact upon
transcriptional heterogeneity in single sorted c-Kit(+) Lin-Sca-1(+) (KLS) cells or
CD150(+) CD48-KLS long-term repopulating hematopoietic stem cells (LT-HSC). Single
cell polymerase chain reaction (PCR) was performed on selected regulators of multi-
lineage hematopoiesis. At least two dominant sub-populations were identified by
increased expression of cell cycle regulatory and leukemia-associated genes.
Furthermore, in the top expressing quartile of cells, the majority of genes were
proportionally overrepresented. In wildtype KLS cells, Stat5 mRNA levels were also
strongly correlated with several genes. Since heterogeneity decreases with age or
inflammatory or oncogenic stress, these results provide a potential mechanistic
linkage to Stat5 expression.
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation
(HSCT) has become an established curative treatment for an increasing number of
patients with life-threatening hematological, oncological, hereditary, and
immunological diseases. This has become possible due to worldwide efforts of
preclinical and clinical research focusing on issues of transplant immunology,
reduction of transplant-associated morbidity, and mortality and efficient malignant
disease eradication. The latter has been accomplished by potent graft-versus-
leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights
into the genetics of the human leukocyte antigen (HLA) system allowed improved
donor selection, including HLA-identical related and unrelated donors. Besides bone
marrow, other stem cell sources like granulocyte-colony stimulating-mobilized
peripheral blood stem cells and cord blood stem cells have been established in
clinical routine. Use of reduced-intensity or non-myeloablative conditioning
regimens has been associated with a marked reduction of non-hematological
toxicities and eventually, non-relapse mortality allowing older patients and
individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL
or antitumor effects. Whereas in the early years, malignant disease eradication by
high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic
HSCT has been recognized as cellular immunotherapy relying prominently on immune
mechanisms and to a lesser extent on non-specific direct cellular toxicity. This
chapter will summarize the key milestones of HSCT and introduce current
developments.
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2(-/-) mice
develop severe anomalies in HSC maintenance leading to defective hematopoiesis.
Whereas, lack of IL-2 signaling was detrimental for lympho-and erythropoiesis,
myelopoiesis was enhanced in Il2(-/-) mice. Investigation of the underlying
mechanisms of dysregulated hematopoiesis in Il2(-/-) mice shows that the IL-2-Treg
cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of
Treg activity resulted in increased IFN-gamma production by activated T cells and
an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population
successfully rescued HSC maintenance in Il2(-/-) mice, preventing IFN-gamma
activity could do the same even in the absence of Treg cells. Our study suggests
that equilibrium in IL-2 and IFN-gamma activity is critical for steady state
hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-gamma
treatment might help to restore hematopoiesis.
The diagnosis of hemophagocytic lymphohistiocytosis ( HLH) can be a difficult one,
and the distinction between primary versus secondary HLH can be particularly
challenging during the early stages of diagnosis. This distinction is important to
make as primary HLH requires allogeneic hematopoietic cell transplantation for a
definitive cure. Flow cytometric screening tests for many of the genetic forms of
HLH are available. However, not all patients with primary HLH are captured by these
screening tests, due to the fact that no screening test is 100% sensitive, and
additionally, some patients with "primary" forms of HLH may have mutations in genes
which are yet to be discovered. In this issue of the European Journal of
Immunology, Ammann et al. [Eur. J. Immunol. 2017. 47: 364-373] compare T-cell
phenotype patterns among patients with primary and secondary HLH, and find that
assessment of T-cell activation and differentiation may assist with the diagnosis
of HLH. Furthermore, this phenotypic analysis has the potential to help make the
important distinction between primary and secondary HLH.
Heparin-induced thrombocytopenia (HIT) is a serious drug reaction that leads to a
decrease in platelet count and a high risk of thrombosis. HIT patients produce
pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet
factor-4 (PF4) and heparin. HIT immune complexes crosslink Fc-receptors resulting
in platelet and monocyte activation. These events lead to the release of
procoagulant chemokines and tissue factor, which together create an intensely
prothrombotic state. HIT represents an atypical immune response because it has
features of both T cell-dependent and T cell-independent mechanisms. The disorder
is characterized by newly formed anti-PF4/heparin IgG antibodies, which are
characteristic of a T cell-dependent mechanism; however, re-exposure to heparin,
months after HIT, does not lead to a memory response, which is consistent with a T
cell-independent mechanism. In this review, we discuss the immunobiological events
that can explain these features, including the role for T cell-dependent and T
cell-independent mechanisms in HIT antibody generation, the immunogenic
characteristics of the PF4/heparin antigen, and the concept of a temporary loss in
immune regulation contributing to the onset of HIT. We also present a novel
immunobiological model to explain the atypical immune response that is
characteristic of HIT.
Tumor metastasis is a multistep process involving a number of genetic alterations
so that the genetic diagnosis is got increasingly attentions today. The aim of this
study was to use RNA-seq to screen the effective differential expression genes in
the peripheral blood mononuclear cells for the hepatic carcinoma with metastasis.
The results showed that hepatic carcinoma samples gathered according to different
metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in inflammation
mediated by chemokine and cytokine signaling pathway (P00031) in the hepatic
carcinoma samples with metastasis, and subsequently confirmed by quantitative real-
time polymerase chain reaction. In conclusions, CCL3, CCL3L1, JUN, IL8, and IL1B
have the potential to be considered as candidates for future molecular diagnosis of
the hepatic carcinoma with metastasis. This work may provide us with new visions
into the metastasis process and potential efficient clinical diagnosis in the
future.
Background: The sodium taurocholate co-transporting polypeptide, encoded by
SLC10A1, was identified as a functional receptor for hepatitis B virus (HBV). The
objective of this study was to determine if there was an association of the
Ser267Phe variant (rs2296651) with HBV infection status in Moroccan patients.
Methods: Using a TaqMan 5' allelic discrimination assay, the Ser267Phe variant was
genotyped in 286 chronic hepatitis B patients, 135 individuals with spontaneous
clearance from HBV infection and 109 healthy controls negative for hepatitis B
serological markers. Results: In this cohort, we detected only wild-type genotype
(S267S) in all groups. This polymorphism was not associated with the HBV infection
status in Moroccan patients. Conclusions: The S267F variant is absent among
Moroccans regardless of chronic HBV infection status.
The aim of this study was to compare the data obtained using the new LIAISON (R) XL
chemiluminescence system to search for HBsAg, antiHCV, and anti-HIV1-2/p24 Ag with
those obtained using the VITROS system currently adopted by the Microbiology Unit
of the Hospital of Legnano. Routine samples of patients who were referred by
practitioners for the determination of HBsAg (1,000 samples) and/or anti-HCV (1,002
samples) and/or anti-HIV1-2 (995 samples) were simultaneously analyzed using both
systems. The concordant positive and discordant samples were re-examined for
confirmation by means of an HBsAg neutralization assay, anti-HCV immunoblot, or
anti-HIV1-2 Western blot; HBV-DNA, or HCV-RNA or HIV-RNA was also sought in the
discordant samples. Samples of patients known to be positive were tested (100 HBsAg
positive, 100 anti-HCV positive, and 100 HIV 1-2 positive) as well throughout
treatment, with viremia levels becoming undetectable after treatment. The HBsAg,
anti-HCV, and anti-HIV1-2 concordance between the two systems in routine series was
respectively 99.8%, 98.5% and 99.7%, and 100% for all markers in samples known
positive. The various molecular biology and confirmatory tests of the discordant
samples were all negative (except for one anti-HCV positive sample). Measure of
Cohen's kappa coefficient for HBsAg, anti-HCV, and anti-HIV gave K values of
respectively 0.992, 0.946, and 0.980. In conclusion, the performance of the LIAISON
(R) XL system in the routine laboratory determination for all three markers was
comparable with that of the VITROS system. (C) 2016 Wiley Periodicals, Inc.
Hepatitis B virus (HBV) infection is one of the major risk factors leading to the
development of hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg)
plays a pivotal role in HBV-related HCC pathogenesis, and Toll-like receptor (TLR)
2 is also considered to mediate tumor progression. However, the interaction between
HBsAg and TLR2 in HCC progression remains unclear. Thus, the aim of the study was
to explore the effect of HBsAg-TLR2 pathway on growth and invasion of HBV-related
HCC cells and examine the potential mechanisms been involved. The expression of
TLR2 was measured in two different HCC cell lines (HepG2 and HepG2.2.15) with or
without recombinant HBsAg by real-time reverse polymerase chain reaction and
Western blot. Cellular proliferation, invasion, cytokine productions, and
downstream signaling pathways were also measured in TLR2-silencing HepG2.2.15 cells
in response to HBsAg stimulation. The mRNA and protein levels of TLR2 were
significantly elevated in HepG2.2.15 cells than those in HepG2 cells. HBsAg
simulation increased proinflammatory cytokine production and invasion of HepG2.2.15
cells, while this process was inhibited by TLR2 silence. However, TLR2 siRNA
transfection alone did not affect the bioactivities of tumor cells. Moreover, HBsAg
increased expression of MyD88 and phosphorylation of NF-kappa B p50 and p38MAPK.
Downregulation of TLR2 inhibited HBsAg-induced MyD88 and p-NF-kappa B, but not p-
p38MAPK in HepG2.2.15 cells. In conclusion, HBsAg stimulation promotes the invasion
of HBV-related HCC cells. TLR2/MyD88/NF-kappa B signaling pathway may be involved
in this procession by upregulation of cytokine production. The interaction between
TLR2 and HBsAg may contribute to the poor prognosis of HBV-related HCC.
Longan County is considered a highly endemic area for hepatitis B virus (HBV). The
plasma-derived vaccine has been used in newborns in this area since 1987. A cross-
sectional survey was conducted to evaluate the long-term effectiveness of this
vaccine. In total, 1634 participants born during 1987-1993 and who had received a
series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled.
Serological HBV markers were detected and compared with previous survey data.
Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants
was 3.79%; 3.47% of subjects who had received the first dose within 24 h were HBsAg
positive, and 8.41% of subjects who had received a delayed first dose were also
HBsAg positive. There were 1527 subjects identified who had received the first dose
within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after
immunization, while the anti-HBspositive rate and vaccine effectiveness declined.
The geometric mean concentration of antibody in the anti-HB-positive participants
was 55.13 mIU/ml and this declined after immunization. Fewer than 2.0% of
participants had anti-HB levels 51000 mIU/ml. The data show that the protective
efficacy of the plasma-derived vaccinations declined and administration of HB
vaccine within 24 h of birth was very important. To reduce the risk of HBV
infection in this highly endemic area, a booster dose might be necessary if anti-
HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the
immune memory induced by plasma-derived HB vaccine are needed.
Background MicroRNAs (miRNAs) are highly conserved small non-coding RNAs of 18-25
nucleotides (nt) that mediate post-transcriptional gene regulation. Hepatitis B
virus (HBV) can cause either acute or chronic hepatitis B, and is a high risk
factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses
have been shown to modulate the expression of host cellular miRNAs. However,
interactions between the HBV and the host cellular miRNAs are largely unknown.
Methods miRNA microarray and Northern blotting analysis were used to compare the
expression profile of cellular miRNAs of a stable HBV-expressing cell line
HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda
program were used to predict the miRNA targets. A flow cytometric assay was further
used to investigate the expression of human leukocyte antigen (HLA)-A. Results
Eighteen miRNAs were differentially expressed between the two cell lines. Among
them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells.
Northern blotting analysis confirmed that the expression of miR-181a, miR-181b,
miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-
regulated, which was in consistent with the results of the microarray analysis.
Furthermore, some putative miRNA targets were predicted and verified to be linked
with mRNA expression. The 3'-UTR of HLA-A gene had one partially complementary site
for miR-181a and miR-181a might down-regulate the expression of HLA-A. Conclusion
HBV replication modulates the expression of host cellular miRNAs, which may play a
role in the pathogenesis of HBV-related liver diseases.
Hepatitis B virus (HBV) infection is a major global health challenge. HBV can cause
significant morbidity and mortality by establishing acute and chronic hepatitis.
Approximately 250 million people worldwide are chronically infected, and more than
2 billion people have been exposed to HBV. Since the discovery of HBV, the advances
in our understanding of HBV virology and immunology have translated into effective
vaccines and therapies for HBV infection. Although current therapies successfully
suppress viral replication but rarely succeed in viral eradication, recent
discoveries in HBV virology and immunology provide exciting rationales for novel
treatment strategies aiming at HBV cure.
Aim: To investigate the action of isothiafludine (NZ-4), a derivative of bis-
heterocycle tandem pairs from the natural product leucamide A, on the replication
cycle of hepatitis B virus (HBV) in vitro and in vivo. Methods: HBV replication
cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and
Northern blotting. HBV protein expression and capsid assembly were detected using
Western blotting and native agarose gel electrophoresis analysis. The interaction
of pregenomic RNA (pgRNA) and the core protein was investigated by RNA
immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected
ducks were orally administered NZ-4 (25, 50 or 100 mg.kg(-1).d(-1)) for 15 d.
Results: NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an
IC50 value of 1.33 mu mol/L, whereas the compound inhibited the cell viability with
an IC50 value of 50.4 mu mol/L. Furthermore, NZ-4 was active against the
replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant
and ADV-resistant HBV mutants. NZ-4 (5, 10, and 20 mu mol/L) concentration-
dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of
replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4
dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks.
Conclusion: NZ-4 inhibits HBV replication by interfering with the interaction
between pgRNA and HBcAg in the capsid assembly process, thus increasing the
replication-deficient HBV capsids. Such mechanism of action might provide a new
therapeutic strategy to combat HBV infection.
Vasculitis is a remarkable presentation of the extrahepatic manifestations of HCV.
According to the presence or absence of cryoglobulins it is subdivided into two
main types: cryoglobulinemic vasculitis and non cryoglobulinemic vasculitis based
on the attribution of vasculitis to serum cryoglobulins as a pathogenic factor. The
attribution of cryoglobulinemia to HCV represents a success story in the history of
immunology, microbiology, and clinical medicine. HCV can bind to and invade
lymphocytes, consequently triggering an immune response through different
mechanisms. The epidemiology of the disease is well described and the clinical
picture describes cutaneous, pulmonary, musculoskeletal, neurological, renal,
endocrine, gastrointestinal, hepatic and cardiovascular manifestations. It may also
be associated with sicca symptoms, an increased risk of lymphoma and serious
catastrophic events. The pathology is well characterized. A classification criteria
of the syndrome that was validated in 2014 is discussed. Management of CV is
decided according to the presence and severity of its clinical presentation. It is
divided into asymptomatic, mild, moderate, severe and life threatening disease.
Recently introduced direct antiviral agents are proving safe and effective in the
management of cryoglobulinemic vasculitis, and it is advocated that the two types
of vasculitis be given prioritization in the Egyptian mass campaign to eradicate
HCV. (C) 2016 Production and hosting by Elsevier B.V. on behalf of Cairo
University.
Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral
route. In humans, HEV mainly causes acute hepatitis and is responsible for large
outbreaks of hepatitis across the world. The case fatality rate of HEV-induced
hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant
women. HEV strains infecting humans are classified into four genotypes. HEV strains
from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no
known animal reservoirs. Recently, notable progress has been accomplished for
better understanding of HEV biology and infection, such as chronic HEV infection,
in vitro cell culture system, quasi enveloped HEV virions, functions of the HEV
proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and
vaccine development. However, further investigation on the cross-species HEV
infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is
still needed. This review mainly focuses on molecular biology and infection of HEV
and offers perspective new insight of this enigmatic virus.
Although rat hepatitis E virus (HEV) has been identified in wild rats, no cell
culture systems for this virus have been established. A recent report suggesting
the presence of antibodies against rat HEV in human sera encouraged us to cultivate
rat HEV in human cells. When liver homogenates obtained from wild rats (Rattus
rattus) in Indonesia were inoculated onto human hepatocarcinoma cells, the rat HEV
replicated efficiently in PLC/PRF/5, HuH-7 and HepG2 cells, irrespective of its
genetic group (G1-G3). The rat HEV particles released from cultured cells harbored
lipid-associated membranes on their surface that were depleted by treatment with
detergent and protease, with the buoyant density in sucrose shifting from 1.15-1.16
g/ml to 1.27-1.28 g/ml. A Northern blotting analysis revealed genomic RNA of 7.0 kb
and subgenomic RNA of 2.0 kb in the infected cells. The subgenomic RNA of G1-G3
each possessed the extreme 5'-end sequence of GUAGC (nt 4933-4937), downstream of
the highly conserved sequence of GAAUAACA (nt 4916-4923). The establishment of
culture systems for rat HEV would allow for extended studies of the mechanisms of
viral replication and functional roles of HEV proteins. Further investigation is
required to clarify the zoonotic potential of rat HEV. (C) 2014 Elsevier B.V. All
rights reserved.
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis
infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th) 1
inflammatory cells, characterized by interferon (IFN)-gamma and interleukin (IL)-2
secretion, predominate in the liver during chronic HCV infection, and chemokines
attracting these cells are particularly important in disease progression. Among C-
X-C chemokines, the non-ELR group [as IFN-gamma-induced protein 10 (IP-10),
monokine induced by IFN-gamma (MIG) and IFN-inducible T-cell-alpha chemoattractant
(I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3). IP-
10 has uniquely been shown to have prognostic utility as a marker of treatment
outcome. IFN-gamma-induced chemokines, as MIG and IP-10, may promote lymphocyte
recruitment to HCC playing important roles in cancer immunology. The production of
CXC chemokines by HCC cell lines has been shown. It has been identified immune-gene
signature that predicts patient survival including the chemokine gene IP-10.
Inflammatory cytokines (tumour necrosis factor-alpha, IFN-gamma) and Toll-like
receptor 3 ligands stimulate intratumoral production of these chemokines which
drive T and Natural Killer cells tumor infiltration, leading to enhanced cancer
cell death. Furthermore selective recruitment of CXCR3(+) B-cells that bridges
proinflammatory IL-17 response and protumorigenic macrophage polarization in HCC
has been shown, suggesting that blocking CXCR3(+) B-cell migration or function may
help defeat HCC. It has been also shown that the overexpression of IP-10, which
induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER
stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential
adjuvant therapy to sensitize HCC-cisplatin treatment.
Hepatocellular carcinoma is an aggressive neoplasm and is one of the most common
human cancers. Recently, long non-coding RNAs have been demonstrated to participate
in pathogenesis of many diseases including the progression in several cancers. In
this study, we found that the long non-coding RNA colon cancer-associated
transcript 1 was upregulated in hepatocellular carcinoma tissues (p < 0.05), and
high colon cancer-associated transcript 1 expression level was positively
associated with tumor volume (p < 0.05) and American Joint Committee on Cancer
stage (p < 0.05) in hepatocellular carcinoma patients. Luciferase reporter assays
and RNA-pulldown assays showed that colon cancer-associated transcript 1 is a
target of miR-490-3p. Real-time quantitative polymerase chain reaction and Western
blot analysis indicated that colon cancer-associated transcript 1 regulated cyclin-
dependent kinase 1 expression as a competing endogenous RNA by sponging miR-490-3p
in hepatocellular carcinoma cells. Furthermore, colon cancer-associated transcript
1 silencing decreased hepatocellular carcinoma cells proliferation and invasion and
overexpression promoted cell proliferation and invasion in vitro. These data
demonstrated that the colon cancer-associated transcript 1/miR-490-3p/cyclin-
dependent kinase 1 regulatory pathway promotes the progression of hepatocellular
carcinoma. Inhibition of colon cancer-associated transcript 1 expression may be a
novel therapeutic strategy for hepatocellular carcinoma.
Limited efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC)
was observed in clinical trials, thus prompting investigation into combination
therapy. Interleukin-6 (IL-6) has important roles in modeling immune responses in
cancers. Here, we hypothesized that IL-6 blockade would enhance antitumor immunity
of HCC and synergize with anti-programmed death-1-ligand 1 (PD-L1) checkpoint
inhibitor in treating HCC. The sources and immune modulating effects of IL-6 were
investigated in HCC models. Combination of anti-IL-6 and anti-PD-Ll was tested in
HCC bearing mice. We found that IL-6 is mainly secreted by cancer associated
fibroblast (CAFs), but not tumor cells in HCC. High IL-6 expression CAFs could
induce strong immunosuppression in HCC microenvironment by recruiting
immunosuppressive cells, such as myeloid derived suppressive cells. In addition,
high IL-6 expression CAFs also impaired tumor infiltrating T-cell function via
upregulating inhibitory immune checkpoints. Using IL-6 blockade could reverse anti-
PD-LI resistance in HCC tumor model. In conclusion, our study indicates that
targeted inhibition of IL-6 may enhance the efficacy of anti-PD-Ll in HCC,
providing a potential strategy to overcoming anti-PD-Ll resistance in HCC.(C) 2017
Published by Elsevier Inc.
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies
worldwide, and tumor recurrence and metastasis are major factors that contribute to
the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to
regulate different tumorigenic processes, and a growing body of evidence indicates
that Hippo kinase signaling is inactivated in many cancers. However, the upstream
lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. Methods:
Using a lncRNA microarray, we identified a novel lncRNA, uc.134, whose expression
was significantly decreased in the highly aggressive HCC cell line HCCLM3 compared
with MHCC97L cells. Furthermore, we evaluated uc.134 expression in clinical samples
using in situ hybridization (ISH) and quantitative real-time polymerase chain
reaction (qRT-PCR) analysis. The full-length transcript of uc.134 was confirmed
using rapid amplification of cDNA ends (RACE) analyses. To investigate the
biological function of uc.134, we performed gain-of-function and loss-of-function
studies both in vitro and in vivo. The underlying mechanisms of uc.134 in HCC were
investigated using RNA pulldown, RNA immunoprecipitation, ubiquitination assays,
Western blotting, mRNA microarray analyses, and qRT-PCR analyses. Results: The ISH
assay revealed that uc.134 expression was significantly decreased in 170 paraffin-
embedded samples from patients with HCC compared with adjacent tissues and uc.134
expression directly correlated with patient prognosis. Furthermore, we defined a
1867-bp full-length transcript of uc.134 using 5'-and 3'-RACE analysis. The
overexpression of uc.134 inhibited HCC cell proliferation, invasion, and metastasis
in vitro and in vivo, whereas the knockdown of uc.134 produced the opposite
results. Furthermore, we confirmed that uc.134 (1408-1867 nt) binds to CUL4A (592-
759 aa region) and inhibits its nuclear export. Moreover, we demonstrated that
uc.134 inhibits the CUL4A-mediated ubiquitination of LATS1 and increases YAPS127
phosphorylation to silence the target genes of YAP. Finally, a positive correlation
between uc.134, LATS1, and pYAP(S127) was confirmed in 90 paraffin-embedded samples
by ISH and immunohistochemical staining. Conclusions: Our study identifies that a
novel lncRNA, uc.134, represses hepatocellular carcinoma progression by inhibiting
the CUL4A-mediated ubiquitination of LATS1 and increasing YAPS127 phosphorylation.
The use of this lncRNA may offer a promising treatment approach by inhibiting YAP
and activating Hippo kinase signaling.
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the
third leading cause of cancer-related death. The high rate of diagnosis in non-
curable stages and the lack of novel active treatments make it necessary to review
all the possible sources of misleading results in this scenario. The incidence of
HCC shows clear geographical variation with higher annual incidence in Asia and
Africa than in Western countries; we aimed to review the literature to find if
there are different trends in the main activated molecular pathways.
Hyperactivation of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signalling and epithelial to
mesenchymal transition (EMT) process are more prevalent in the Western population;
however, fibroblast growth factor (FGF), transforming growth factor beta (TGF beta)
and Notch pathways seems to be more relevant in Asian population. Whether these
variations just reflect the distinct distribution of known causes of HCC or proper
ethnical differences remain to be elucidated. Nevertheless, these clearly different
patterns are relevant to regional or worldwide clinical trial design. If this
information is neglected by sponsors and researchers the rate of failure in HCC
trials will not improve. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Octamer 4 (Oct4), a member of the Pit-Oct-Unc transcription factor family required
to maintain self-renewal and pluripotency of embryonic stem cells, has been
previously identified to be associated with tumorigenesis and malignant
transformation of numerous types of cancer including hepatocellular carcinoma
(HCC). The present data shows that Oct4 enhances cancer stem cell properties and
increases invasion ability in the Huh7 cell line. To increase understanding of the
role of Oct4 in HCC, the present study used a functional genomics approach and
analyzed the resulting transcriptional profiles to identify Oct4-dependent genes in
Huh7. Affymetrix GeneChip Human genome U133 Plus 2.0 Arrays were used to determine
differential gene expression profiles and then validated by quantitative polymerase
chain reaction. The present study found that altered expression of 673 genes (fold-
change >= 2) affected multiple signaling pathways linked with self-renew and
metastasis. Among these differentially expressed genes, the present study noticed
that the key component of the WNT signaling pathway lymphoid enhancer binding
factor 1 (LEF1) and Twist Family BHLH transcription factor 1 were upregulated by
Oct4, whilst cadherin 2 was downregulated. Additional studies found that the
nuclear beta-catenin aggregation was increased in Oct4 overexpressed HCC cell
lines. These results suggest that Oct4 regulates LEF1 to active LEF1/beta-catenin
dependent WNT signaling pathway and promote epithelial-mesenchymal transition. The
present findings provide novel mechanistic insight into an important role of Oct4
in HCC.
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2)
are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics
involving an increase in glycolysis is a characteristic of HCC. This study examined
whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human
HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3,
STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of
mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression
and cell glycolysis were determined. STAT3 and HK2 expressions were evaluated by
real-time polymerase chain reaction and Western blotting. The level of glycolysis
metabolism was assessed by the determination of glucose consumption and lactate
production. The results showed that transfection of HepG2 and Hep3B cells with
pcDNA3.1(+)-EGFP-STAT3 significantly increased STAT3 mRNA and protein expression,
glucose consumption and lactate production, and HK2 mRNA and protein expression.
However, transfection of HepG2 and Hep3B cells with STAT3 siRNA significantly
decreased glucose consumption and lactate production and HK2 mRNA and protein
expression. Transfection of HepG2 and Hep3B cells with HK2 siRNA significantly
decreased glucose consumption and lactate production. Treatment of HepG2 and Hep3B
cells with rapamycin significantly reduced HK2 mRNA and protein expression and
glucose consumption and lactate production. These results suggest that mTOR-STAT3-
HK2 pathway is involved in the glycolysis of HCC cells and STAT3 may regulate HCC
glycolysis through HK2 pathway, providing potential multiple therapeutic targets
through intervention of glycolysis for the treatment of HCC.
Sphingosine kinase 1 (Sphk1) is an oncogenic kinase that is responsible for the
phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). Mounting evidence
suggests that Sphk1 serves a crucial role in the proliferation and development of a
variety of human cancer cells. However, the role of Sphk1 in hepatocellular
carcinoma (HCC) has not been fully elucidated. Therefore, the expression of Sphk1
was examined in 127 formalin-fixed, paraffin-embedded HCC tissues using
immunohistochemistry, and its clinical implications and prognostic significance
were analyzed. As a result, the expression of Sphk1 in HCC tissue was revealed to
be significantly higher than in normal tissue (P<0.01). In addition, Sphk1
expression was significantly associated with tumor size, tumor stage and
histological differentiation (all P<0.05). The patients with low Sphk1 expression
had higher overall survival and recurrence-free survival rates compared with
patients with high Sphk1 expression. Furthermore, Sphk1-specific shRNA was used to
downregulate the expression of Sphk1 in HCC cell lines, including hepatoblastoma G2
and HCC-9724. The CRISPR/Cas9 based transcription activation system was used to
upregulate Sphk1 expression in the normal live cell, L02. Cell proliferation, mRNA
expression and protein expression were measured using Cell Counting Kit-8, reverse
transcription polymerase chain reaction and western blot analysis in the
transfected cells. To the best of our knowledge, the present study provides the
first evidence that Sphk1 promotes HCC cell proliferation and is involved in tumor
progression. Notably, the data presented suggest that Sphk1 may be a potential
independent prognosis biomarker for the treatment of HCC.
To date, the American Joint Committee on Cancer (AJCC) and the Union for
International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification
represents the standard system for evaluation of prognosis in solid tumors.
However, the clinical outcome can be significantly different in patients with the
same TNM stage. Therefore, many efforts have been made aiming to define new
prognostic parameters. Indeed, analyses conducted in large cohorts of colorectal
cancer patients emphasized the prognostic value of tumor-infiltrating lymphocytes,
leading to the development of a prognostic score referred to as "Immunoscore". In
this commentary, we recapitulate the study by Gabrielson and colleagues, recently
published in Cancer Immunology Research, addressing the role of intratumoral CD3(+)
and CD8(+) T cells as well as as prognostic markers for hepatocellular carcinoma.
The authors demonstrate that Immunoscore represents a valuable prognostic marker in
patients with hepatocellular carcinoma who have undergone primary tumor resection,
supporting its application in a tumor setting other than colorectal cancer.
The present study investigated ubiquitin specific peptidase 39 (USP39) gene
knockdown on SMMC-7721 cells in vitro and in vivo, and the role of USP39 in
regulating the growth of hepatocellular carcinoma (HCC). Two small interfering RNAs
(siRNA) were constructed, which targeted the USP39 gene and control sequences were
synthesized and inserted into a pGCSIL-GFP lentiviral vector. The full length of
USP39 cDNA was amplified by polymerase chain reaction (PCR) and cloned into pEGFP-
N2, and the recombinant plasmids were transfected into cells. Knockdown efficiency
and upregulation of USP39 was determined by reverse transcription-quantitative PCR
and western blotting. The impact of USP39 on the growth of SMMC-7721 cells in vitro
was examined using an MTT assay, colony formation, flow cytometry (FCM) and
immunohistochemical staining. The impact of USP39 on the growth of SMMC-7721 cells
in vivo was examined by assessing tumorigenicity in nude mice. Western blotting was
performed to examine the mechanism of USP39 regulation on SMMC-7721 cell growth.
Recombinant vectors containing specific and scrambled USP39 siRNA sequences were
constructed and transfected into SMMC-7721 cells. USP39 knockdown inhibited cell
proliferation and colony formation in SMMC-7721 cells, while upregulation of USP39
promoted the growth of tumor cells. FCM indicated that USP39 knockdown led to G2/M
arrest and induced apoptosis in SMMC-7721 cells. USP39 knockdown inhibited
xenograft tumor growth in nude mice and led to the downregulation of the
transcription factor Forkhead Box M1 (FoxM1). Gene expression of FoxM1 targets,
including polo-like kinase 1, cyclin B1 and centromere protein A also decreased
following USP39 knockdown. The results suggest that knockdown of USP39 inhibits the
growth of HCC in vitro and in vivo, potentially through the induction of G2/M
arrest by regulating the pre-mRNA splicing of FoxM1.
Background: Hepatocyte growth factor (HGF) was initially discovered as a mitogen
for hepatocytes, but it is also known to be related to carcinogenesis in many other
organs. However, the role of HGF in lung carcinogenesis is not fully-understood. In
this study, we investigated the role of HGF in lung carcinogenesis using HGF
transgenic mice. Materials and Methods: To elucidate the role of HGF in lung
carcino genesis, 5 mu g/g body weight diethylnitrosamine (DEN) were administered
intraperitoneally to HGF transgenic (TG) mice and wild-type (WT) mice at 15 days of
age. The incidence and number of lung tumors, the expression of HGF and of its
receptor (c-Met) were compared between HGF TG and WT mice. Results: HGF
overexpression accelerated DEN-induced lung carcinogenesis. Seventy-six percent of
TG mice (versus 50% of WT mice) developed malignant lung tumors by 48 weeks. The
incidence of lung tumors was significantly higher in the TG mice in comparison with
WT mice (p<0.05). Furthermore, the mean diameter and number of tumors in each mouse
were significantly higher in the TG mice compared to the WT mice (p<0.01). The
northern blotting analyses revealed that there was overexpression of the HGF trans
gene in the lung tumors of TG mice in comparison with the surrounding non-tumorous
lesions. The western blotting analyses of the tumor lesions revealed increased
phosphorylation of c-Met. Conclusion: Our results suggest that HGF promotes lung
carcino genesis through the autocrine activation of the HGF/c-Met signaling
pathway. The HGF/c-Met signaling pathway appears to have vital roles in lung
carcinogenesis.
Changes in the expression of hepatocyte membrane transporters in advanced fibrosis
decrease the hepatic transport function of organic anions. The aim of our study was
to assess if these changes can be evaluated with pharmacokinetic analysis of the
hepatobiliary transport of the MR contrast agent gadoxetate. Dynamic gadoxetate-
enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats.
After deconvolution, hepatocyte three-compartmental analysis was performed to
calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The
expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was
assessed with reverse transcription polymerase chain reaction. In the rats with
advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the
backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively).
Significant correlations were found between influx and Oatp1a1 expression (r =
0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal
backflux and Mrp3 (r = 0.61, p = 0.002). These results show that changes in the
bidirectional organic anion hepatocyte transport function in rats with advanced
liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced
MRI. aEuro cent Expression of hepatocyte transporters is modified in rats with
advanced liver fibrosis. aEuro cent Kinetic parameters at gadoxetate-enhanced MRI
are correlated with hepatocyte transporter expression. aEuro cent Hepatocyte
transport function can be assessed with compartmental analysis of gadoxetate-
enhanced MRI. aEuro cent Compartmental analysis of gadoxetate-enhanced MRI might
provide biomarkers in advanced liver fibrosis.
BACKGROUND: The anti-proliferative gene, PC3 (pheochromocytoma cell 3)/BTG2 (B-cell
translocation gene 2), is one of the early growth response genes and belongs to the
BTG/Tob protein family. This study aimed to assess the effects of recombinant human
hepatopoietin (HPO) and partial hepatectomy on rapidly induced expression of
immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in
hepatocellular carcinoma (HCC) at different stages of progression. METHODS: After a
rat model of partial hepatectomy was established, we investigated gene expression
within I hour after 2/3 partial hepatectomy by representational difference analysis
and in a primary cultured hepatocyte system. The expression levels of PC3/BTG2 from
liver tissues of the rat model were assessed by RT-PCR and Northern blotting.
Meanwhile, the expression of BTG2 mRNA in a tissue microarray of HCC was determined
by in situ hybridization. RESULTS: The PC3/BTG2 gene was rapidly induced after 2/3
partial hepatectomy and its expression peaked within 1-2 hours after operation. HPO
rapidly induced the expression of the genes c-fos, LRF-1, and PC3 in primary
cultured rat hepatocytes, which might be one of the molecular mechanisms by which
HPO stimulates hepatocyte proliferation. Positive BTG2 mRNA expression was detected
in 71.19% (42/59) of the HCC samples and in 75% (3/4) of the normal liver tissue
samples obtained from the region around the HCC tissues. PC3/BTG2 mRNA was located
mainly in the cytoplasm of HCC cells and its expression was related to the degree
of differentiation. CONCLUSIONS: Recombinant human HPO and partial hepatectomy
rapidly induce the expression of the PC3/BTG2 gene. PC3/BTG2 mRNA is highly
expressed in HCC cells and its expression is related to the degree of cell
differentiation. The abnormal expression of PC3/BTG2 is closely related to the
genesis and development of HCC, so PC3/BTG2 may play an important role in these
processes. (Hepatobilimy Pancreat Dis Int 2009; 8: 288-293)
Background/Aims: Hepcidin is a liver-produced hormone that regulates systemic iron
homeostasis. Hepcidin expression is stimulated upon iron overload or inflammation
while iron deficiency, anemia and tissue hypoxia are negative regulators. We
investigated the involvement of 2-oxoglutarate-dependent oxygenases, HIF-1 and
other transcription factors in the hypoxic suppression of hepcidin. Methods:
Northern blotting analysis and real time PCR were used to determine hepcidin mRNA
levels in hepatoma cells and hepcidin promoter activity was measured using Huh7
cells transfected with suitable reporter constructs under various conditions.
Results: Treatment of human cultured hepatoma cells with hypoxia or known
inhibitors of 2-oxoglutarate-dependent oxygenases, such as the iron chelator
desferrioxamine, cobalt or the 2-oxoglutarate analogue dimethyl-oxalylglycine
significantly reduced hepcidin mRNA levels and down-regulated its gene promoter
activity. This effect was not dependent on the HREs or other known putative
response elements in the hepcidin promoter and was observed even under interleukin-
6 treatment. Conclusions: 2-Oxoglutarate-dependent oxygenases are important to
maintain high hepcidin mRNA expression in a HIF-1-independent manner. We suggest
that modulation of oxygenase activity may be of therapeutic value in iron-related
disorders. (C) 2008 European Association for the Study of the Liver. Published by
Elsevier B.V. All rights reserved.
The anti-HER2 antibody trastuzumab (Herceptin (R)) has been used to treat patients
with breast cancers that overexpress HER2. We have demonstrated that p27(Kip1)
upregulation is one of the key events that cause G(1) arrest upon trastuzumab
treatment. Here, we have examined the effect of trastuzumab on expression of CDK2,
Rb, E2F, NPAT and histone H4 in breast cancer cells that overexpress HER2.
Trastuzumab treatment dramatically inhibited the kinase activity and expression of
CDK2, whereas the kinase activity and expression of CDK4 were not affected. Unlike
the p27(Kip1) upregulation that occurs primarily through post-translational
mechanisms, CDK2 was downregulated primarily at a transcriptional level as shown by
Northern blotting and real-time RT-PCR analyses. With a decrease in CDK2 activity,
trastuzumab decreased the kinase activity of cyclin E but had little effect on
cyclin E protein level. Overexpression of wild-type cyclin E or its lower molecular
weight forms did not influence the response to trastuzumab. Levels and activities
of CDK6, cyclin A, and cyclin D1 were all suppressed by trastuzumab. As a result,
trastuzumab inhibited Rb phosphorylation that associates with CDK2, cyclin E, CDK6,
cyclin A, or cyclin D1. As predicted from these changes, trastuzumab decreased the
DNA-binding activity of E2F, decreased the level of NPAT protein, and decreased the
level of histone H4 mRNA. Blockade of the PI3K pathway with LY294002 produced
similar effects to trastuzumab treatment on expression of each of these genes.
Taken together, treatment of breast cancer cells that overexpress HER2 with the
anti-HER2 antibody trastuzumab inhibits CDK2, Rb phosphorylation, E2F activity,
NPAT, and histone H4 via PI3K signaling that are needed for both DNA and histone
synthesis during progression from G1 phase to S phase of the cell cycle.
BACKGROUND. Men with biochemical recurrence of prostate cancer following local
therapies often use natural supplements in an attempt to delay metastases and/or
avoid the need for more aggressive treatments with undesirable side-effects. While
there is a growing body of research into phytotherapeutic agents in this cohort,
with some promising results, as yet no definitive recommendations can be made. This
pilot study was undertaken to assess the feasibility of a fully-powered study to
examine the effects of this phytotherapeutic intervention (containing turmeric,
resveratrol, green tea and broccoli sprouts) on PSA doubling time in men with
biochemical recurrence with a moderate PSA rise rate. METHODS. A double blind,
randomized, placebo-controlled parallel trial was conducted with 22 men with
biochemically recurrent prostate cancer and a moderate rise rate (PSA doubling time
of 4-15 months and no evidence of metastases from conventional imaging methods).
Patients were randomized to either the active treatment arm or placebo for 12
weeks. The primary endpoints were feasibility of study recruitment and procedures,
and measurement of proposed secondary endpoints (prostate symptoms, quality of
life, anxiety, and depression as measured on the EORTC QLQ-C30 and PR-25, the IPSS
and HADS). Data were collected to estimate PSA-log slopes and PSA-doubling times,
using a mixed model, for both the pre-intervention and post-intervention periods.
RESULTS. Adherence to study protocol was excellent, and the phytotherapeutic
intervention was well-tolerated, with similar numbers of mild-to-moderate adverse
events in the active and placebo arms. Both the intervention and data collection
methods were acceptable to participants. No statistical difference between groups
on clinical outcomes was expected in this pilot study. There was between-subject
variation in the PSA post treatment, but on average the active treatment group
experienced a non-significant increase in the log-slope of PSA (pre-treatment
doubling time = 10.2 months, post-treatment doubling time = 5.5 months), and the
placebo group experienced no change in the log-slope of PSA (pre-treatment doubling
time = 10.8 months, post-treatment doubling time = 10.9 months). CONCLUSION. The
findings suggest that a fully powered study of this combination is feasible in men
with biochemically recurrent prostate cancer and a moderate PSA rise rate. (C) 2017
Wiley Periodicals, Inc.
Hereditary fever syndromes (HFS) include a group of disorders characterized by
recurrent self-limited episodes of fever accompanied by inflammatory manifestations
occurring in the absence of infection or autoimmune reaction. Advances in the
genetics of HFS have led to the identification of new gene families and pathways
involved in the regulation of inflammation and innate immunity. The key role of
several cytokine networks in the pathogenesis of HFS has been underlined by several
groups, and supported by the rapid response of patients to targeted cytokine
blocking therapies. This can be due to the direct effect of cytokine overproduction
or to an absence of receptor antagonist resulting in dysbalance of downstream pro-
and anti-inflammatory cytokine networks. The aim of this study was to present an
overview and to discuss the major concepts regarding the cellular and molecular
immunology of HFS, with a particular focus on their specific cytokine signatures
and physiopathological implications. Based on their molecular and cellular
mechanisms, HFS have been classified into intrinsic and extrinsic IL-1 beta
activation disorders or inflammasomopathies, and protein misfolding disorders. This
review integrates all recent data in an updated classification of HFS. (C) 2016
Elsevier Ltd. All rights reserved.
The virion host shutoff protein (vhs), encoded by the gene UL41, has RNase activity
and is the key regulator of the early host shutoff response induced by type 1
herpes simplex virus. Despite low amino acid similarity, the vhs protein of the
swine herpesvirus, pseudorabies virus (PrV), also exhibits RNase activity. However,
the mechanism underlying the action of vhs remains undefined. Here, we report that
the RNA degradation profile of PrV vhs is similar, but not identical, to that of
type 1 herpes simplex virus vhs. Notably, the presence of a cap structure enhances
both the degradation rate and the preferential targeting of the vhs protein towards
the 3-end of the encephalomyocarditis virus internal ribosome entry site (IRES).
Furthermore, type 1 herpes simplex virus vhs produces a simple degradation pattern,
but PrV vhs gives rise to multiple intermediates. The results of northern blotting
using probes recognizing various regions of the RNA substrate found that PrV vhs
also cleaves downstream of the IRES region and this vhs protein overall shows 5 to
3 RNase activity. Moreover, addition of the translation initiation factors eIF4H
and eIF4B significantly increased the RNase activity of recombinant PrV vhs against
capped RNA. Nonetheless, these proteins did not fully reconstitute the IRES-
directed targeting pattern observed for vhs translated in a rabbit reticular lysate
system. The interaction between PrV vhs and eIF4H/eIF4B implies that the
translation initiation machinery within the cell is able to stimulate the nuclease
activity of PrV vhs. However, this process remains inefficient in terms of the
IRES-targeting pattern.
Within Solanaceae, Nolana L. f. and Sclerophylax Miers are two genera that have
deserved special attention because of their rare anatomical characteristics.
However, they are poorly known from the cytogenetic perspective. In order to
discuss their chromosome features in an evolutionary context, classical staining,
chromomycin A(3)/4-6-diamidino-2-phenylindole (CMA/DAPI) fluorescent banding and in
situ hybridisation (FISH) with probes for the 18-5.8-26S and the 5S rDNA loci were
applied to root tips of germinating seeds. All the species presented the chromosome
number 2n=24. Karyotypes were highly symmetric, with most chromosomes being
metacentric and with a maximum of three submetacentric pairs in N. divaricata. The
CMA/DAPI banding technique, assayed for the first time in Sclerophylax, showed
CMA(+)/DAPI(-) bands associated with nucleolar organiser regions (NORs) in the
first metacentric chromosome pair in each species. The FISH technique (applied to
four species of Sclerophylax and, for the first time, in one species of Nolana)
showed that the 18-5.8-26S loci coincide with CMA(+)/DAPI(-) bands. Three
Sclerophylax species presented two pairs of 5S signals, whereas S. adnatifolia
showed three. The rDNA loci resulted as asyntenic in Sclerophylax, but were
localised in the same chromosome in N. divaricata. Despite the morphological
peculiarities of Nolana and Sclerophylax, the chromosome number and karyotype
features are consistent with the position of the two genera within the x=12 clade',
while the number and position of rDNA loci established the chromosome
rearrangements, suggesting different evolutionary pathways with respect to their
closest relatives, Lycium and Jaborosa.
Novel hybrid nanostructures or nanocomposites are receiving increasing attention
due to their newly evolved properties. In this work, alpha-Fe2O3 anchored to
graphene oxide (GO) nanosheet (alpha-Fe2O3@GO) was synthesized through a facile
hydrolysis process and its photo-catalytic performances and dtlrability in
heterogeneous Fenton system were fully evaluated. The decolorization rates of
methylene blue in alpha-Fe2O3@GO + H2O2 + UV system within a wide pH range were
approximately 2.9-fold that of classical Degussa P25 TiO2 +UV and 2.4-fold that of
alpha-Fe2O3 + H2O2 + UV. This enhanced decolorization of methylene blue (MB) in
alpha-Fe2O3@GO + H2O2 + UV system were attributed to the unique incorporation of GO
into the catalyst which not only mediated the morphology of active sites alpha-
Fe2O3 nanoparticles but also offered high electron conductivity and electrostatic
attraction between negatively charged GO with positively charged MB. High
efficiencies of degradation were achieved on various surface charged organic
pollutants (around 96-100%), such as cationic compounds of MB and rhodamine B
(RhB), anionic compound Orange II (OII) and Orange G (OG), neutral compounds of
phenol, 2-nitrophenol (2 -NP) and endocrine disrupting compound 17 beta-estradiol
(E2). The dominant reactive oxygen species (ROS) responsible for decolorization,
such as hydroxyl radicals ((OH)-O-circle) and superoxide anion radicals (O-
2(circle-)) generated by activation of H2O2 on the surface of alpha-Fe2O3@GO were
detected and quantified by free radical quenching methods. The possible degradation
mechanism of MB involved the rupture of phenothiazine ring by desulfurization and
the rupture of phenyl ring due to the attack of ROS, which was analyzed by
LC/MS/MS. The reduction of MB and its intermediates was consistent with the
decreasing trend of the acute toxicity towards luminous bacteria with the
increasing irradiation time. The results lay a foundation for highly effective and
durable photo-Fenton technologies for organic wastewater within wider pH ranges
than the conventional photo-Fenton reaction.(C) 2017 Elsevier B.V. All rights
reserved.
The present study aimed to detect early changes in the concentration of matrix
metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and tissue
inhibitor of metalloproteinase-1 (TIMP-1) in a rat model of brain injury combined
with traumatic heterotopic ossification (HO). A total of 132male Sprague-Dawley
rats were used to establish the experimental and control groups. Anatomy and sample
collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin
and eosin and immunohistochemical staining were performed for local tissues. MMP-9,
MMP-2 and TIMP-1 levels and gene expression level were measured by ELISA and
reverse transcription-quantitative polymerase chain reaction. Radiological
investigation of the rat lower limbs was conducted at weeks 5 and 10 following
modeling to observe the occurrence of HO. The incidence of HO for rats in the
experimental group was higher compared with the control group. The serum MMP-9
levels of the experimental group were notably higher on postoperative days 5-7
compared with the control group. The MMP-9 gene expression of the experimental
group was higher on postoperative days 3-7 compared with the control group. The
TIMP-1 gene expression levels were markedly higher compared with the control group
at each time point. Thus, an increase in inflammatory response is closely
associated with brain injury, in addition to an increase in the number of
inflammatory cells with the incidence of HO. The pathological elevation of MMP-9
and the altered dynamic equilibrium between MMP-9 and TIMP-1 contributed to the
degradation, remodeling and calcification of the extracellular matrix, resulting in
the induction of osteoblast precursor cells in HO. MMP-9 is a predictive marker of
HO.
Human foamy virus (HFV) is a complex and unique retrovirus with the longest genomes
among retroviruses that are used as vectors for gene therapy. Long non-coding RNAs
(lncRNAs) are regarded as key regulators that are involved in diverse biological
processes during viral infection. However, the role of lncRNAs in HFV infection
remains unknown. In this study, we utilized next-generation sequencing to first
characterize lncRNAs in 293T cells after HFV infection, evaluating length
distribution, exon number distribution, volcano picture, and lncRNA class
distribution. We identified 11,336 lncRNAs (4,729 upregulated lncRNAs and 6,588
down-regulated lncRNAs) and 61,367 mRNAs (30,133 upregulated mRNAs and 31,220
downregulated mRNAs), which were differentially expressed in the HFV-infected 293T
cells. Subsequently, six differentially expressed lncRNAs characterized using RNA-
seq were confirmed by quantitative real-time polymerase chain reaction assays.
Interestingly, Gene Ontology (GO)/Gene Ontology Tree Machine (GOTM) and Kyoto
Encyclopedia of Gene and Genomes (KEGG) pathway analyses indicated that positive
regulation of interleukin 8 (IL8) production and cytokine-cytokine receptor
interaction might be involved in the functional enrichment of lncRNAs. Moreover,
cis-acting and trans-acting regulatory networks show that NR_028036 may target the
fas gene in a cis-acting manner and that ENST00000354838 may target the IL18 gene
in a trans-acting manner. Overall, these results not only provide novel insights
into the relationship between HFV and lncRNAs in the host response to infection but
also have implications for the future wider application of HFV as a vector.
A hydrokinetic smart grid (KSG) concept powered by modules of hydrokinetic
microturbines arranged in rows is proposed in this work. A complete description of
each module: mechanical design, hydropower characteristics, power electronics and
control strategies have been included. A complete dynamic simulation of an example
of a KSG has been performed. It considers microturbine modules, power loads, energy
storage modules and a grid tie inverter that interface with the mains using a
single connection. Additionally, the control and power stages of a hydrokinetic
microturbine has been validated. The satisfactory technical results obtained in
addition with the acceptable results of an investment analysis, encourage future
implementations of KSGs.
This paper presents a computational platform for dynamic security assessment (DSA)
of large electricity grids, developed as part of the iTesla project. It leverages
high performance computing to analyze large power systems, with many scenarios and
possible contingencies, thus paving the way for pan-European operational stability
analysis. The results of the DSA are summarized by decision trees of 11 stability
indicators. The platform's workflow and parallel implementation architecture is
described in detail, including the way commercial tools are integrated into a plug-
in architecture. A case study of the French grid is presented, with over 8000
scenarios and 1980 contingencies. Performance data of the case study (using 10 000
parallel cores) is analyzed, including task timings and data flows. Finally, the
generated decision trees are compared with test data to quantify the functional
performance of the DSA platform.
The invention of the microscope has been fundamental for the understanding of
tissue architecture and subcellular structures. With the advancement of higher
magnification microscopes came the development of various molecular biology tools
such as Forster resonance energy transfer (FRET) and in situ proximity ligation
assay (in situ PLA) to monitor protein interactions. Microscopy has become a
commonly used method for the investigation of molecular events within the cell, for
the identification of key players in signaling networks, and the activation of
these pathways. Multiple approaches are available for functional analyses in single
cells. They provide information not only on the localization of proteins at a given
time point, but also on their expression levels and activity states, allowing us to
pinpoint hallmarks of different cellular identities within tissues in health and
disease. Clever solutions to increase the sensitivity of molecular tools, the
possibilities for multiplexing, as well as image resolution have recently been
introduced; however, these methods have their pros and cons. Therefore, one needs
to carefully consider the biological question of interest along with the nature of
the sample before choosing the most suitable method or combination of methods.
Herein, we review a few of the most exciting microscopy-based molecular techniques
for proteomic analysis and cover the benefits as well as the disadvantages of their
use.
This study focuses on characterizing the effect of a high salt diet (HSD) on
intestinal immunity and the risk of inflammatory bowel diseases (IBD). We found
that mice on a HSD had an increased frequency of IL-17A producing cells in the
intestinal lamina propria (LP) compared to mice on a normal diet (ND). Furthermore,
most intestinal IL-17A producing cells were CD4(+)TCR beta(+) cells. A HSD
increased the LP T helper 17 (Th17) responses in both the small and large
intestines but did not increase the Th17 response of other gut-associated lymphoid
organ. Although, HSD did not change the percentage of regulatory T (Treg) cells,
HSD significantly inhibit secretion of IL-10 and the suppressive function of Treg
cells. Moreover, we found that HSD exacerbates trinitrobenzenesulfonic acid (TNBS)
induced colitis, and Th17 response was significantly increased in the colonic LP of
HSD TNBS-treated mice compared with the ND TNBS-treated mice. This study
demonstrates that HSD stimulates the intestinal Th17 response but inhibits the
function of Treg cells. Moreover, HSD exacerbates TNBS induced mice colitis,
suggesting that HSD disrupts the intestinal immunity and increases the risk of IBD.
The digital control of high speed Permanent Magnet Synchronous Motor (PMSM) is
carried out as part of mass reduction for embedded systems. This paper focuses on
improving the stability of high speed PMSM digital control. A study of the
stability of the closed-loop system shows the importance of taking into account the
constraints of digital control (delay and discrete characteristics) in the
calculation of decoupling terms and inverse Park transformation. The proposed
decoupling is done using the discrete model of the system and a prediction of the
evolution of the currents during the delay. The voltage, calculated by vector
control, is applied to the machine by a three-phase voltage-source Power Width
Modulation PWM converter. This voltage is modified because the rotor reference d-q
frame turns during the delay and the switching period. The voltage error caused by
this rotation can be significant at high speeds and more generally when the ratio
of the switching frequency over the electrical output frequency becomes too high.
To stabilize the system, we suggest predicting the average electric angle that the
motor will have during the application of the voltage vector. The efficiency is
shown through a time simulation.
In sensor-node applications, the auxiliary power is drawn from the ac mains to
supply the mixed-signal sensor components. There is therefore a need for low-cost,
sub-1W, miniature non-isolated ac-dc down-converters. In this work, a new two-chip
architecture is proposed to implement a high-voltage quasi-resonant buck converter
with peak current-mode control. The current and voltage control loops are
implemented in the high-side (HS) and low-side (LS) IC, respectively. Each IC
includes a 700V power transistor, sensing and control circuits. The LS IC transmits
the digital peak current command, along with mode selection information, to the HS
IC using a low-power 20 MHz isolated communication interface. The architecture
achieves a peak simulated efficiency of 85.6% when converting from 339 V to 12 V
and allows the size of the input filter to be greatly reduced due to the current-
mode operation. State-of-the- art UHV BCD technologies offer a unique opportunity
to increase the level of integration and reduce the system cost in the targeted
sensor node applications, despite the relatively poor figure-of-merit of the HV
devices compared to discrete Silicon super-junction or GaN alternatives.
This paper describes the implementation of a load voltage observer into the control
algorithms of a Rapid Capacitor Charger controlled by a digital signal controller
(DSC) with a fast DSP core. A hybrid peak current mode control algorithm with
digital control of the PWM signal and high speed analog current sensing is used to
control the inverter of the charger. The DSC controller keeps the current loop
stable using adaptive slope compensation. In addition to providing fast adaptive
digital control of the current loop, the DSC can perform additional functions such
as estimation of the voltage level of the load capacitor. This avoids the cost,
bandwidth limitations and insulation challenges of a conventional HV-sensor. To
evaluate the performance of the load voltage observer, we measured the output
voltage with a laboratory grade HV probe to establish a reference to test the
results of the digital algorithm.
This work presents a high-voltage (HV) operational amplifier (OPA). OPAs are widely
used in signal conditioning circuits for industrial applications and integrated
circuits (ICs). Particularly, in HV applications like BMS (battery management
system), the signal conditioning circuits are always used to transfer voltage
signal between HV domain and low voltage (LV) domain. Notably, the voltage from the
HV domain could be as high as tens of volts, which might cause damages to regular
silicon-based transistors. Nevertheless, since the resolution of the signal
conditioning circuits depends on the output range and the operation range is
determined by the input range, the input and output ranges of the signal
conditioning circuits have been a key issue in the HV applications. We propose a
rail-to-rail HV OPA to resolve these issues. The proposed design is implemented
using 0.25 mu m 1-poly 3-metal 60 V BCD process. The core area is 0.809 x 0.303
mm(2). DC gain and unit-gain bandwidth of the proposed railto-rail HV OPA are
measured to be 41 dB and 0.3 MHz, respectively. Finally, the proposed rail-to-rail
HV OPA is proven on silicon to receive any signals between 0 and 30 V and transmit
a signal in the range of [0.4, 29.6] V. (C) 2015 Elsevier Ltd. All rights reserved.
The multivariate location problem is addressed. The most familiar method to address
the problem is the Hotelling test. When the hypothesis of normal distributions
holds, the Hotelling test is optimal. Unfortunately, in practice the distributions
underlying the samples are generally unknown and without assuming normality the
finite sample unbiasedness of the Hotelling test is not guaranteed. Moreover, high-
dimensional data are increasingly encountered when analyzing medical and biological
problems, and in these situations the Hotelling test performs poorly or cannot be
computed. A test that is unbiased for non-normal data, for small sample sizes as
well as for two-sided alternatives and that can be computed for high-dimensional
data has been recently proposed and is based on the ranks of the interpoint
Euclidean distances between observations. Five modifications of this test are
proposed and compared to the original test and the Hotelling test. Unbiasedness and
consistency of the tests are proven and the problem of power computation is
addressed. It is shown that two of the modified interpoint distance-based tests are
always more powerful than the original test. Particularly, the modified test based
on the Tippett criterium is suggested when the assumption of normality is not
tenable and/or in case of high-dimensional data with complex dependence structure
which are typical in molecular biology and medical imaging. A practical application
to a case-control study where functional magnetic resonance imaging is used is
discussed.
Higher education is understood as essential to enabling social mobility. Research
and policy have centred on access to university, but recently attention has turned
to the journey of social mobility itself - and its costs. Long-distance or extreme'
social mobility journeys particularly require analysis. This paper examines
journeys of first-in-family university students in the especially high-status
degree of medicine, through interviews with 21 students at an Australian medical
school. Three themes are discussed: (1) the roots of participants' social mobility
journeys; (2) how sociocultural difference is experienced and negotiated within
medical school; and (3) how participants think about their professional identities
and futures. Students described getting to medical school the hard way', and
emphasised the different backgrounds and attitudes of themselves and their
wealthier peers. Many felt like imposters', using self-deprecating language to
highlight their lack of fit' in the privileged world of medicine. However, such
language also reflected resistance to middle-class norms and served to create
solidarity with community of origin, and, importantly, patients. Rather than
narratives of loss, students' stories reflect a tactical refinement of self and
incorporation of certain middle-class attributes, alongside an appreciation of the
worth their difference' brings to their new destination, the medical profession.
In this paper, a unified averaged modeling method is proposed to investigate the
fast-scale period-doubling bifurcation of a full-bridge integrated buck-boost
inverter with peak current control. In order to increase the resolution of the
conventional classic averaged model to half the switching frequency, sample-and-
hold effect of inductor current is absorbed into the averaged model, i.e. the
proposed unified averaged model can capture the high-frequency dynamical
characteristics of the buck-boost inverter, which is both an extension and a
modification of conventional averaged model. Based on the unified mode, fast-scale
bifurcation is identified, and the corresponding bifurcation point is predicted
with the help of the locus movement of all the poles, and their underlying
mechanisms are revealed. Detailed analysis shows that the occurrence of high-
frequency oscillation means fast-scale bifurcation, while the occurrence of low-
frequency oscillation leads to slow-scale bifurcation. Finally, it is demonstrated
that the unified averaged model can provide not only a general method to
investigate both the slow-and fast-scale bifurcations in a unified framework but
also a quite straightforward design-oriented method which can be directly
applicable.
ObjectivesMicroRNA-155 (miR-155) regulates T-cell differentiation and activation.
It has also been associated with HIV infection. However, it remains unclear whether
miR-155 is related to the T-cell response in HIV-infected individuals (e.g. T-cell
activation and exhaustion). MethodsWe performed a cross-sectional study involving
121 HIV-1-infected patients on highly active antiretroviral therapy (HAART) and 43
HAART-naive patients. MiR-155 levels in the peripheral blood were determined by
quantitative reverse transcription-polymerase chain reaction (PCR). T-cell immune
activation, exhaustion, and homeostasis were measured by determining the expression
of CD38, programmed death 1 (PD-1) and CD127 via flow cytometry. ResultsThe levels
of miR-155 in total peripheral blood mononuclear cells, CD4 T cells and CD8 T cells
from HIV-1-infected patients were increased (P < 0.01). Nonresponders and HAART-
naive patients also exhibited a higher percentage of CD8(+)CD38(+) T cells and a
lower percentage of CD4(+)CD127(+) and CD8(+)CD127(+) T cells (P < 0.05). We also
found higher levels of PD-1 expression on the CD4(+) and CD8(+) T cells of HIV-1-
infected patients (P < 0.05). ConclusionsOur findings suggest that miR-155 levels
in the peripheral blood of HIV-1-infected patients are increased and associated
with T-cell activation. Therefore, miR-155 is a potential biomarker of the immune
response following HIV-1 infection.
A highly linear PGA with level shifter and class AB output stage for BLE receiver
is reported in this paper. Both merits of degenerated PGA and operational amplifier
based PGA are synthesized in proposed PGA. It is implemented in 0.18 mu m CMOS
process and draws 290pA current from a supply of 1.8V when driving a capacitor load
of 2p at the IF of 1MHz, while high SR up to 2.2 x 10(7) V/s is obtained. OIP3 of
40dBm is achieved under all gain modes due to the constant loop bandwidth. Proposed
PGA has a gain range from 0dB to 14dB at the step of 2dB. The THD reaches 72.7dB at
the frequency of 1MHz when proposed PGA outputs a 1.3Vpp differential voltage
signal.
Conventional time series forecast models can hardly develop the inherent rules of
complex non-linear dynamic systems because the strict assumptions they need cannot
always be met in reality, whereas fuzzy time series (FTS) techniques can be used
even the records of times series have uncertainty and instability since they do not
need strict assumptions. In previous study of FTS, the process of aggregating the
past observations and assigning proper weights of fuzzy logical relationship groups
are ignored, which may lead to poor forecasting accuracy since they are important
aspects in time series prediction and analysis where determination of future trends
depends only on past observations. In this paper, a novel high-order FTS model is
constructed to make time series forecasting. Specifically, by applying the harmony
search intelligence algorithm, the optimal lengths of intervals are tuned.
Moreover, regularly increasing monotonic quantifiers are employed on fuzzy sets to
obtain the weights of ordered weighted aggregation. Simultaneously, the weights of
right-hand side of fuzzy logical relationship groups are explored to compensate the
presence of bias in the prediction. In the part of empirical analysis, the
developed model was applied to predict three well-known time series: numbers of
enrollment of Alabama University, TAIEX and electricity load demand of New South
Wales and the results obtained were compared with several counterparts, including
some old and recently developed models. Experimental results demonstrate that the
developed model cannot only achieve higher accuracy of prediction, but also capture
the fuzzy features and characters. (C) 2017 Elsevier B.V. All rights reserved.
Time-delays (dead time) are found in many processes in industrial practice. Time-
delays are mainly caused by the time required to transport mass, energy and
information. In many cases time-delay is caused by the effect produced by the
accumulation of a large number of low-order systems. One of possibilities of
control of such processes is their approximation by lower-order model with time-
delay. The contribution is focused on the design of an algorithm for digital
control of high order process that is approximated by a second-order model with
time-delay. The controller algorithms use the digital modification of the linear
quadratic (LQ) Smith predictor (SP). The LQ criterion was combined with pole
assignment principle. These algorithms were applied to the control of a set of
equal liquid cylinder atmospheric tanks.
Introduction: Emotion recognition, a social cognition domain, is impaired in people
with schizophrenia and contributes to social dysfunction. Whether impaired emotion
recognition emerges as a manifestation of illness or predates symptoms is unclear.
Findings from studies of emotion recognition impairments in first-degree relatives
of people with schizophrenia are mixed and, to our knowledge, no studies have
investigated the link between emotion recognition and social functioning in that
population.Methods: This study examined facial affect recognition and social skills
in 16 offspring of parents with schizophrenia (familial high-risk/FHR) compared to
34 age- and sex-matched healthy controls (HC), ages 7-19.Results: As hypothesised,
FHR children exhibited impaired overall accuracy, accuracy in identifying fearful
faces, and overall recognition speed relative to controls. Age-adjusted facial
affect recognition accuracy scores predicted parent's overall rating of their
child's social skills for both groups.Conclusions: This study supports the presence
of facial affect recognition deficits in FHR children. Importantly, as the first
known study to suggest the presence of these deficits in young, asymptomatic FHR
children, it extends findings to a developmental stage predating symptoms. Further,
findings point to a relationship between early emotion recognition and social
skills. Improved characterisation of deficits in FHR children could inform early
intervention.
miRNAs have emerged as key regulators of gene expression in both plants and
animals. These small (generally 21-22 nt) RNA molecules, originated from primary
"hairpin" transcripts, can induce translational suppression or direct mRNA
cleavage. Similar to regular mRNAs, the expression of miRNAs is highly regulated.
Their expression pattern could provide critical clues to understanding miRNA
functions. However, man), previously identified miRNA families have multiple
paralogous loci. Within each family, different members are often closely related
and sometimes give rise to identical miRNAs. This poses critical challenges in the
analysis of individual miRNA genes. This chapter describes several methods that are
commonly used for miRNA expression analysis, including high-throughput sequencing,
microarrays, and briefly discusses qRT-PCR, northern blotting, and other approaches
used for data validation.
The purposes of this study were to determine: (i) the extent of an acute session of
high-intensity intermittent exercise (HIIE) followed by a concurrent strength
session (Conc) on the increase of systemic inflammatory cytokines and chemokines,
and (ii) whether eight weeks of high intensity interval training plus concurrent
strength training alters the acute inflammatory response and immune status. Ten
recreationally active males (aged 26.9 +/- 4.3 years) performed two experimental
exercise sessions interspersed by eight weeks of HILT plus concurrent strength
training. The experimental exercise session was composed of a 5-km run on a
treadmill (1:1 at 100% of maximal aerobic speed (MAS)), and after 10 min of passive
recovery, back squat exercises were performed (80% 1RM, four sets until
exhaustion). Serum samples were collected after fasting, pre-HIIE, post-HIIE, Pre-
Conc, Post-Conc, and 30 and 60 min postexercise session. The comparison between
both concurrent exercise sessions was performed using repeated measure ANOVA, with
the Bonferroni Post-hoc when necessary. Interleukin-6 (IL-6) presented a moment
effect (F = 6.72; p < 0.05), with Post-Conc significantly higher than pre-HIIE,
Post-HIIE, and 60 min, only a tendency was found between pre-HIIE and post-HIIE
(difference =-5.99; p = 0.09). MCP-1 and IL-Ira did not present effects for
condition, moment, or interaction. Interleuldn-10 (IL-10) presented both moment and
interaction effects (F = 5.31 and 2.50; p = 0.005 and 0.036). Pre-Conc and Post-
Conc were significantly higher than Pre-HIIE. The interaction between before and
after eight weeks of concurrent training probably occurred at Post-Conc (11.42 +/-
3.09 pg mL(-1) and 8.88 +/- 1.29 pg mL(-1)). In addition, maintenance of immune
function was observed. Therefore, HIIE and concurrent strength exercise lead to an
increase in cytokines response, but eight weeks of training program promoted
antiinflammatory response after an acute session of concurrent exercise. (C) 2016
Elsevier Ltd. All rights reserved.
Between the 24th of June and the 6th of July 2005, nine men came to Fort-deFrance
emergency department (Martinique, French West Indies) with more or less pronounced
pulmonary symptoms associated in two cases with skin lesions. Three weeks before
these nine men performed work in a deserted house. The diagnosis of histoplasmosis
was based on pulmonary sample mycological analysis (direct examination and
culture), molecular biology and serological tests. Interrogatory and environmental
investigations on the presumed place of exposition to H. capsulatum var. capsulatum
spores allowed confirming how and where contamination took place. (C) 2016 Elsevier
Masson SAS. All rights reserved.
Background: The planorbid snail Indoplanorbis exustus is the sole intermediate host
for the Schistosoma indicum species group, trematode parasites responsible for
cattle schistosomiasis and human cercarial dermatitis. This freshwater snail is
widely distributed in Southern Asia, ranging from Iran to China eastwards including
India and from the southeastern Himalayas to Southeast Asia southwards. The
veterinary and medical importance of this snail explains the interest in
understanding its geographical distribution patterns and evolutionary history. In
this study, we used a large and comprehensive sampling throughout Indo-Malaya,
including specimens from South India and Indonesia, areas that have been formerly
less studied. Results: The phylogenetic inference revealed five highly divergent
clades (genetic distances among clades: 4.4-13.9%) that are morphologically
indistinguishable, supporting the assumption that this presumed nominal species may
represent a cryptic species complex. The species group may have originated in the
humid subtropical plains of Nepal or in southern adjacent regions in the Early
Miocene. The major cladogenetic events leading to the fives clades occurred
successively from the Early Miocene to the Early Pleistocene, coinciding with major
periods of monsoonal intensification associated with major regional paleogeographic
events in the Miocene and repeated climate changes due to the Plio-Pleistocene
climatic oscillations. Our coverage of the Indo-Australian Archipelago (IAA)
highlights the presence of a single clade there. Contrary to expectations, an AMOVA
did not reveal any population genetic structure among islands or along a widely
recognised zoogeographical regional barrier, suggesting a recent colonisation
independent of natural biogeographical constraints. Neutrality tests and mismatch
distributions suggested a sudden demographic and spatial population expansion that
could have occurred naturally in the Pleistocene or may possibly result of a modern
colonisation triggered by anthropogenic activities. Conclusions: Even though
Indoplanorbis is the main focus of this study, our findings may also have important
implications for fully understanding its role in hosting digenetic trematodes. The
existence of a cryptic species complex, the historical phylogeographical patterns
and the recent range expansion in the IAA provide meaningful insights to the
understanding and monitoring of the parasites potential spread. It brings a
substantial contribution to veterinary and public health issues.
OBJECTIVE: To describe the evolution of serological markers among HIV and hepatitis
B coinfected patients, with emphasis on evaluating the reactivation or
seroreversion of these markers. METHODS: The study population consisted of patients
met in an AIDS Outpatient Clinic in Sao Paulo State, Brazil. We included in the
analysis all HIV-infected and who underwent at least two positive hepatitis B
surface antigen serological testing during clinical follow up, with tests taken six
months apart. Patients were tested with commercial kits available for hepatitis B
serological markers by microparticle enzyme immunoassay. Clinical variables were
collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase
level, exposure to antiretroviral drugs including lamivudine and/or tenofovir.
RESULTS: Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with
chronic hepatitis B. Follow up time for these patients varied from six months to
20.5 years. All patients underwent antiretroviral therapy during follow-up. Among
patients with chronic hepatitis B, 58% were hepatitis B "e" antigen positive at the
first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105)
of patients with chronic hepatitis B, and 50% (8/16) of these patients presented
subsequent reactivation or seroreversion of hepatitis B surface antigen. Among
hepatitis B "e" antigen positive patients, 57% (35/61) presented clearance of this
serologic marker. During clinical follow up, 28.5% (10/35) of those who initially
cleared hepatitis B "e" antigen presented seroreversion or reactivation of this
marker. CONCLUSIONS: Among HIV coinfected patients under antiretroviral therapy,
changes of HBV serological markers were frequently observed. These results suggest
that frequent monitoring of these serum markers should be recommended.
The prevalence and associated factors of erectile dysfunction (ED) in Human
Immunodeficiency Virus (HIV)-infected men remain controversial. The authors
evaluated ED, clinical, and emotional variables in a group of 501 HIV-infected men
in a cross-sectional 4-month observational study. ED was assessed using the
International Index of Erectile Function-5 and emotional status using the Hospital
Anxiety and Depression (HAD) questionnaire. Median age (interquartile range) was 42
(35, 48) years. Time since HIV diagnosis was 6.3 (2.6, 17.1) years, 92% were taking
antiretroviral treatment and 81.8% had an HIV-RNA viral load <50 copies. The
prevalence of ED was 58.5%. ED was mild in 30.1%, mild to moderate in 19.5%,
moderate in 6.1%, and severe in 2.5%. ED medications were used by 19% of men. In
the univariate analysis, the variables associated with all degrees of ED were older
age, longer time since HIV diagnosis, higher scores in HAD, not taking efavirenz,
taking etravirine, taking ritonavir, HIV/Hepatitis C Virus coinfection, and taking
a protease inhibitor-containing regimen. For mild to moderate, moderate, and severe
ED, the same variables were significant, as were lower nadir CD4 cell count, lower
social support, taking atazanavir, concomitant conditions, and concomitant
treatments. The variables that remained significant in the multivariate analyses,
considering all degrees of ED or excluding mild ED were the following: older age
and higher scores in HAD total. In summary, ED affected more than half of this
cohort of well controlled HIV-infected men. Age and emotional status seemed to play
a fundamental role in its presence.
Unlike in most of the world, HIV incidence in the former Soviet Union continues to
rise. While international labor migration has been identified as a potentially
important contributor to this trend, most attention has been focused on risks of
male migrants themselves. This study uses recent household survey data to examine
HIV-related perceptions and actions of migrants' left-behind wives in Armenia.
Multivariate logistic regression analyses show that migrants' wives are
significantly more likely to suspect their husbands of extramarital sex than are
non-migrants' wives. The analyses detect greater worries about HIV infection and a
higher likelihood of spousal communication on HIV matters among migrants' wives,
compared to non-migrants' wives, but these differences are largely explained by the
suspicion of husband's extramarital sex. Finally, no difference between the two
categories of women in the probability of consistent condom use with husbands is
found. These findings are interpreted within the context of patriarchal culture and
unequal gender relations in Armenian society as they are further reinforced by male
migration. Implications of these findings for policies to increase women's
awareness of HIV risks associated with migration and their ability to reduce those
risks are discussed.
This study investigated how HIV-related shame is associated with health-related
quality of life (HRQoL) in older people living with HIV (PLHIV). Structural
equation modeling tested whether HIV-related shame was associated with three
dimensions of HRQoL (physical, emotional, and social well-being) and whether there
were significant indirect associations of HIV-related shame with the three HRQoL
dimensions via depression and loneliness in a sample of 299 PLHIV >= 50 years old.
Results showed that depression and loneliness were key mechanisms, with depression
at least partially accounting for the association between HIV-related shame and
both emotional and physical well-being, respectively, and loneliness accounting for
the association between HIV-related shame and social well-being. HIV-related shame
appears to be an important correlate of HRQoL in older PLHIV and may provide a
promising leveraging point by which to improve HRQoL in older PLHIV.
Background: Few studies have evaluated the impact of pre-treatment drug resistance
(PDR) on response to combination antiretroviral treatment (cART) in children. The
objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the
prevalence of PDR mutations and their association with virological outcome in the
first year of cART in children. Methods: HIV-infected children500 copies/mL after 6
months cART and was assessed by Cox proportional hazards models. All models were
adjusted for baseline demographic, clinical, immunology and virology
characteristics and calendar period of cART start and initial cART regimen.
Results: Of 476 children, 88 % were vertically infected. At cART initiation, median
(interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm(3)
(98-639), and HIV-RNA 5.2 log(10)copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 %
confidence interval (CI), 5.5-10.6) harboring a virus with >= 1 PDR mutations, 30
children had a virus resistant to >= 1 of the prescribed drugs. Overall, the
cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 % CI, 16.4-
23.9). Cumulative risk for VF tended to be higher among children harboring a virus
with PDR and resistant to = 1 drug prescribed than among those receiving fully
active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In
multivariable analysis, age was associated with a higher risk of VF with a 12 %
reduced risk per additional year (HR 0.88; 95 % CI, 0.82-0.95; P < 0.001).
Conclusions: PDR was not significantly associated with a higher risk of VF in
children in the first year of cART. The risk of VF decreased by 12 % per additional
year at treatment initiation which may be due to fading of PDR mutations over time.
Lack of appropriate formulations, in particular for the younger age group, may be
an important determinant of virological failure.
Mutations in the connection and RNase H C-terminal reverse transcriptase (RT)
domains of HIV-1 have been shown to impact drug resistance to RT inhibitors.
However, their impact in the context of non-B subtypes has been poorly assessed.
This study aimed to characterize resistance-related mutations in the C-terminal
portions of RT in treatment-failing patients from southern Brazil, a region with
endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed
from 280 infected subjects, and genomic regions were analyzed by polymerase chain
reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and
E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients.
In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and
CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal
RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel
mutations that display subtype-specific predominance or occurrence.
Prior studies indicate a substantial link between maternal depression and early
child health but give limited consideration to the direction of this relationship
or the context in which it occurs. We sought to create a contextually informed
conceptual framework of this relationship through semi-structured interviews with
women that had lived experience of caring for an HIV-infected child while coping
with depression and anxiety symptoms. Caregivers explained their role in raising
healthy children as complex and complicated by poverty, stigma, and isolation.
Caregivers discussed the effects of their own mental health on child well-being as
primarily emotional and behavioral, and explained how looking after a child could
bring distress, particularly when unable to provide desired care for sick children.
Our findings suggest the need for investigation of the reciprocal effects of child
sickness on caregiver wellness and for integrated programs that holistically
address the needs of HIV-affected families.
Forkhead box O (FOXO)1, FOXO3, interferon regulatory factor (IRF)4, X-linked
inhibitor of apoptosis protein (xIAP), and E74-like factor (ELF)4 have been
described as important regulators of T cell functions and differentiation. However,
whether these molecules are associated with HIV-1 disease progression is still
unknown. In this study, we showed that the levels of FOXO3, IRF4, and xIAP mRNA in
rapid progressors (RPs) were significantly higher than in HIV-negative healthy
controls (HCs). Moreover, FOXO3 expression was positively correlated with HIV-1
viral load and CD4(+) T cell activation. Remarkably, increased CD4(+) and CD8(+) T
cell activation was apparent in RPs compared with typical progressors and HCs. In
addition, a profile of higher apoptosis, more CD8(+) T-EM cells, and fewer CD4(+)
and CD8(+) Naive T cells were observed in early HIV infection patients with low
CD4(+) T cell counts. Furthermore, in vitro, IRF4 and xIAP expression was enhanced
in peripheral blood mononuclear cells from healthy people following T cell receptor
stimulation. T cell activation was decreased by treatment with siRNA inhibiting
FOXO3, IRF4, and xIAP. Our results show that significantly increased levels of
FOXO3, IRF4, and xIAP mRNA in Chinese HIV-1-infected patients were related to T
cell immune activation, implicating them as potential targets for developing new
therapeutic avenues to slow down HIV-1 disease progression.
Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-
based trajectory modeling followed by multinomial logistic regression was used to
identify distinct trajectories and their association with baseline characteristics
among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three
trajectories were identified: (1) 72% never/sporadic opioid use (referent group),
(2) 11% episodic use (associated with female sex, depression, drug-related
diagnoses, antiretroviral therapy use, and undetectable HIV RNA), and (3) 16%
chronic use (associated with older age, female sex, and mental health diagnoses).
Overall, opioid prescription decreased substantially with longer time in HIV care
among both episodic and chronic users.
CXCR4-using HIV-1 was previously shown to replicate more efficiently in a healthy
donor-derived CD4(+) CD38(+) than in a CD4+ CD38(-) T-cell subset after stimulation
with interleukin(IL)-4. Here, we identified 3 cellular genes, which were expressed
to a higher level in an IL-4-stimulated CD38(-) subset. One of the 3 genes,
RNF125/TRAC-1, was involved in the down-regulation of HIV-1 replication not only in
cell lines, but also in peripheral blood mononuclear cells. RNFI25/TRAC-1 bears the
RING finger domain, important for E3 ubiquitin protein ligase. Mutations in this
domain of RNFl25/TRAC-1 led to the loss of HIV-1 down-modulatory activity,
suggesting that E3 ligase activity is necessary. In addition, the results of
Northern blotting and reporter gene analysis indicated that RNFl25/TRAC-1 function
occurs at the viral transcription step. These results suggest that RNFI25/TRAC-1
could function to recruit host factor(s) controlling HIV-1 transcription to the
ubiquitin-proteasome pathway. (C) 2007 Elsevier Inc. All rights reserved.
HLA-B*13:83 differs from HLA-B*13:01:01 by 2 nucleotide substitutions at positions
103 and 106.
HLA-B*52:01:27 differs from HLA-B*52:01:01 by a single nucleotide substitution at
position 681 C>T.
HLA-C*01:109N differs from HLA-C*01:02:01 by a single nucleotide substitution at
position 683 G >A.
Objective:The monitoring of septic shock induced immunosuppression has been
proposed to identify patients who could benefit from specific immunoadjuvant
therapies. Among potential biomarkers to monitor immunological status, functional
testing remains the gold standard because it directly measures the capacity of a
cell population to respond to an immune challenge. We investigated a new approach
in intracellular staining for flow cytometry to measure tumor necrosis factor
(iTNF) produced in vitro by monocytes in response to lipopolysaccharide.Design,
Setting, Subjects, and Interventions:Observational study in intensive care unit and
immunology laboratory of a university medical center. Sixteen septic shock patients
and eight control subjects were included.Main Results:Monocyte iTNF was determined
by flow cytometry in whole blood and completed in 2.5h according to a no-wash, no
centrifuge procedure. Lipopolysaccharide challenge induced a tremendous expression
of iTNF that was statistically more pronounced in controls than in patients. This
was observed when results were expressed as medians of fluorescence intensity
(median: 16.1 [IQR: 14.5-19.1] vs. 5 [4.0-8.0], P=0.0001) or as percentages of
positive cells (99.7 [99.6-99.8] vs. 85 [74-97], P=0.0001). iTNF expression was
correlated to monocyte HLA-DR expression in patients and controls.Conclusions:These
preliminary results illustrate the feasibility of immune functional testing on a
routine manner in septic shock patients. They now deserve to be widely assessed and
validated in various intensive care unit conditions. This could be a major step to
characterize the rapidly changing immune response overtime and thus permit
personalized medicine.
Human leukocyte antigens (HLA) have been extensively studied as being antigen
presenting receptors, but many aspects of their function remain elusive, especially
their association with various autoimmune diseases. Here we discuss an illustrative
case of the reciprocal relationship between certain HLA-DRB1 alleles and two
diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly
associated with HLA-DRB1 alleles that encode a five amino acid sequence motif in
the 70-74 region of the DR beta chain, called the shared epitope (SE), while PV is
associated with the HLA-DRB1*04:02 allele that encodes a different sequence motif
in the same region. Interestingly, while HLA-DRB1*04: 02 confers susceptibility to
PV, this and other alleles that encode the same sequence motif in the 70-74 region
of the DR beta chain are protective against RA. Currently, no convincing
explanation for this antagonistic effect is present. Here we briefly review the
immunology and immunogenetics of both diseases, identify remaining gaps in our
understanding of their association with HLA, and propose the possibility that the
70-74 DR beta epitope may contribute to disease risk by mechanisms other than
antigen presentation.
Establishing and maintaining maternal-fetal tolerance is essential for a successful
pregnancy; failure of immunological adaptation to pregnancy leads to severe
complications such as abortion or preterm delivery. Myeloid-derived suppressor
cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during
pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen
G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-
modulatory properties, which is expressed during pregnancy. Here, we investigated
the impact of HLA-G on MDSCs accumulation and activation in pregnant women. We
demonstrate that granulocytic MDSCs (GR-MDSCs) express receptors for HLA-G, namely
immunoglobulin-like transcript (ILT) 2 and 4, and that ILT4-expression by GR-MDSCs
is regulated during pregnancy. Stimulation with soluble HLA-G (sHLA-G) increased
suppressive activity of GR-MDSCs, induced MDSCs from peripheral blood mononuclear
cells (PBMCs) and led to phosphorylation of the signal transducer and activator of
transcription 3 (STAT3) and induction of indoleamine-2,3-dioxygenase (IDO) in
myeloid cells. Effects of sHLA-G on MDSC accumulation were mediated through ILT4.
These results suggest an interaction between MDSCs and HLA-G in humans as a
potential mechanism for maintaining maternal-fetal tolerance. Modulating MDSC
function during pregnancy via HLA-G might provide new opportunities for a
therapeutic manipulation of immunological pregnancy complications.
Background: Gastric cancer is the second most common cause of global cancer-related
mortality. Although dedifferentiation predicts poor prognosis in gastric cancer,
the molecular mechanism underlying dedifferentiation, which could provide
fundamental insights into tumor development and progression, has yet to be
elucidated. Furthermore, the molecular mechanism underlying the effects of
hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer,
requires investigation and there are no reported studies concerning the effect of
HMBA on gastric cancer. Methods: Based on the results of FACS analysis, the levels
of proteins involved in the cell cycle or apoptosis were determined using western
blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-
3 beta and proton pump were investigated by western blotting after up-regulating
Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein
localization and the activities of GSK-3 beta, CDK2 and CDK4, kinase assays,
immunoprecipitation and western blotting were performed. In addition, northern
blotting and RNase protection assays were carried out to determine the functional
concentration of HMBA. Results: HMBA increased p27(Kip1) expression and induced
cell cycle arrest associated with gastric epithelial cell differentiation. In
addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-
regulation of the proton pump, a marker of gastric cancer differentiation.
Moreover, treatment with HMBA increased the expression and activity of GSK-3 beta
in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced
p27Kip1 expression, which could be rescued by inhibition of GSK-3 beta.
Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-
3 beta inhibition. Conclusions: The results presented herein suggest that GSK-3
beta functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical
role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell
differentiation.
Vitamin B-1 ( thiamine) is an essential cofactor for several key enzymes of
carbohydrate metabolism. Mammals have to salvage this crucial nutrient from their
diet to complement their deficiency of de novo synthesis. In contrast, bacteria,
fungi, plants and, as reported here, Plasmodium falciparum, possess a vitamin B-1
biosynthesis pathway. The plasmodial pathway identified consists of the three
vitamin B-1 biosynthetic enzymes 5-(2-hydroxy-ethyl)-4-methylthiazole (THZ) kinase
(ThiM), 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP)/HMP-P kinase ( ThiD) and
thiamine phosphate synthase (ThiE). Recombinant PfThiM and PfThiD proteins were
biochemically characterised, revealing K-m(app) values of 68 mu M for THZ and 12 mu
M for HMP. Furthermore, the ability of PfThiE for generating vitamin B1 was
analysed by a complementation assay with thiE-negative E. coli mutants. All three
enzymes are expressed throughout the developmental blood stages, as shown by
Northern blotting, which indicates the presence of the vitamin B-1 biosynthesis
enzymes. However, cultivation of the parasite in minimal medium showed a dependency
on the provision of HMP or thiamine. These results demonstrate that the human
malaria parasite P. falciparum possesses active vitamin B-1 biosynthesis, which
depends on external provision of thiamine precursors.
The concept of functional neutrophil subsets is new and their clinical significance
in malignancies is unknown. Our study investigated the role of CD16(dim)
CD62L(high), CD16(high) CD62L(high) and CD16(high) CD62L(dim) neutrophil subsets in
head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets
may play different roles in immune-related activity in cancer, based on their
profile, activation state and migration ability within a tumor site, which may be
important in predicting cancer prognoses. Tumor biopsies and blood were obtained
from newly diagnosed untreated HNSCC patients and healthy controls. Neutrophil
subsets and their phenotype were characterized using flow cytometry. Isolated
granulocytes were assessed for anti-tumor immune functions. Compared to controls
HNSCC patients exhibited increased CD16(high) CD62L(dim) neutrophils in blood; this
subset displayed a distinct phenotypes with high expression of CD11b and CD18. This
subset was prone to migrate into the tumor facilitated by tumor-derived IL-8.
Furthermore, IL-8 was also found to activate neutrophils and thereby promoting
subset transition. Various assays demonstrated that activated CD16(high) CD62L(dim)
neutrophils inhibited migration, proliferation and induced apoptosis of FaDu cancer
cells. Neutrophil elastase detected in activated CD16(high) CD62L(dim) neutrophils
and tumor biopsies suggested that CD16(high) CD62L(dim) neutrophils impart anti-
tumoral activity via neutrophil extracellular traps. Furthermore, increased
fraction of CD16(high) CD62L(dim) neutrophils was shown to correlate with an
increased survival rate. Our study demonstrates the clinical relevance of the
CD16(high) CD62L(dim) neutrophil subset, providing evidence for its increased
migration capacity, its anti-tumor activity including increased NET formation and
finally its correlation with increased survival in HNSCC patients. What's new?
Evidence is growing for distinct neutrophil subsets with diverse roles in cancer
immunology, but a clinical link remains to be established. Our study demonstrates
the clinical relevance of the CD16(high) CD62L(dim) neutrophil subset in head and
neck squamous cell carcinoma (HNSCC). Patients harbored an increased fraction of
anti-tumorigenic CD16(high) CD62L(dim) neutrophils in the circulation compared to
healthy controls. The subset had an enhanced capacity to elicit neutrophil
extracellular traps (NETs) extrusion, and an increased fraction of CD16(high)
CD62L(dim) neutrophils in the circulation correlated with increased survival. The
findings demonstrate an anti-tumoral role of the CD16(high) CD62L(dim) neutrophil
subset in HNSCC.
Home health care workers interventions have been implemented in western countries
to improve health status of patients with respiratory diseases especially asthma
and allergic illnesses. Twenty-six controlled studies dealing with prevention and
control of these diseases through home environmental interventions were reviewed.
After a comprehensive description of the characteristics of these studies, the
effectiveness of each intervention was then evaluated in terms of participants'
compliance with the intervention program, improvement of quality of the indoor
environment, and finally improvement of health outcomes, in detailed tables.
Limitations and biases of the studies are also discussed. Overall, this review aims
at giving a toolbox for home health care workers to target the most appropriate
measures to improve health status of the patient depending on his and/or her
environment and disease. Only a case-by-case approach with achievable measures will
warrant the efficacy of home interventions. This review will also provide to the
research community a tool to better identify targets to focus in future evaluation
studies of home health care workers action. (C) 2016 American Academy of Allergy,
Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:66-79)
Substance use and depression are prevalent among mothers enrolled in home visiting
programs and are significant risk factors for child maltreatment, yet most home
visiting programs are staffed by workers who lack the training and clinical skills
to address these risks. Emanating from one state network's interest in advancing
its practice in this area, the current study surveyed 159 home visitors on their
current practices, training, knowledge, and perceived self-efficacy, and perceived
system- and client-level barriers regarding client substance use and depression.
Home visitors reported managing maternal depression more extensively than substance
use, though overall management of both risk areas was low. More training was
associated with more extensive management of both risk domains, as was greater home
visitor knowledge and self-efficacy. Implications for the development of strategies
to improve home visitor management of client behavioral health risks, including
enhanced skills-based training and supervision, are discussed.
This study examined the relationship between different areas of family need and the
utilization of home-based, post-investigation services (HBPS) following a child
protective services (CPS) investigation. The sample consisted of 2598 families with
children who remained at home after an initial CPS investigation between July 2006
and April 2011. Family need was measured in three areas (concrete, clinical, and
educational) using the Family Assessment Form (FAF), and families received one or
more of the following HBPS: case management, concrete, educational, and clinical
services. Pearson chi-square analyses were utilized to identify significant areas
of needs to be included in a final multivariate logistic regression for each HBPS
while controlling for demographic characteristics. Numerous areas of family need
were associated with receipt of services intended to address those needs.
Specifically, concrete need related to financial conditions was met with concrete
services, educational need related to child development (an indicator of parenting
need) was met with educational services, and clinical need related to interactions
between caregivers (a potential indicator of domestic violence) was met with
clinical services. In contrast, caregivers with concrete need related to living
conditions were less likely to receive both educational and clinical services.
Findings from the study highlight that matching concrete needs to related services
is relatively straightforward but that the match between educational and clinical
needs to respective services is more complex. We discuss the complexities of
matching different areas of need and HBPS following a CPS investigation and the
importance of "bridging services" to engage families at risk of maltreatment in
additional prevention services. Published by Elsevier Ltd.
The aim of this review was to describe HIV prevalence in children and youth living
on the street and subject to commercial sexual exploitation, and the studies'
characteristics in terms of place, time, population, and sample design. This was a
systematic review, not a meta-analysis, based on an article search in 10 electronic
databases: Science Direct, MEDLINE, OVID, LILACS, Wiley InterScience, MD Consult,
Springer Link, Embase, Web of Science, and Ebsco. A complementary search was also
performed in the libraries of schools of public health and webpages of U.N.
agencies, besides the reference lists from the selected articles. We selected
observational studies focused on children and youth living on the street and
subject to commercial sexual exploitation, ranging in age from 10 to 20 years, with
the results for HIV prevalence rates. A total of 9,829 references were retrieved,
of which 15 met the inclusion criteria and comprise this descriptive summary. Of
these 15 articles, 12 were conducted in children and youth living on the street and
three in children subject to commercial sexual exploitation. All 15 were cross-
sectional studies. HIV prevalence in children and youth living on the street ranged
from 0% in Dallas, USA and Cochabamba, Bolivia to 37.4% in St. Petersburg, Russia.
In children and youth living subject to commercial sexual exploitation, prevalence
ranged from 2% in Toronto, Canada to 20% in Kolkata, India. In conclusion, HIV
infection is present in children and youth living on the street and subject to
commercial sexual exploitation. Measures are needed for prevention, diagnosis, and
treatment as a public health priority and an ethical responsibility on the part of
governments and society.
The causes of homelessness are complex and poorly understood. This paper describes
the homeless population in Santa Clara County, California in terms of Adverse
Childhood Events, Traumatic Brain Injuries (TBIs), and family breakdown.
Respondents reported severely traumatic childhoods; 78.7% grew up in a household
with a person with drug or alcohol dependence and 64.6% endured psychological abuse
as a child. Seventy-six percent of subjects recalled at least one TBI, 58.4% with
loss of consciousness. Nineteen percent were in foster care as children and 40.2%
reported having someone other than a parent as a primary caregiver. Fifty-three
percent felt they had moved too much as children, and 37.5% had experienced
homelessness as children. Santa Clara County has both the highest median income and
the highest rate of unsheltered homelessness in the nation. Leaders and community
members should work together to improve the lives of the homeless and to prevent
another generation of homeless people.
The gender of the offender has been proved to be an important factor in judicial
sentencing. In this study, we analyze the judgments of College students regarding
perpetrators of familial homicides to evaluate the presence of these gender norms
and biases in the larger society. The sample included 303 college students (54.8%
female) enrolled in several social sciences and engineering courses. Participants
were asked to read 12 vignettes based on real crimes taken from Portuguese
newspapers. Half were related to infanticide, and half were related to intimate
partner homicide. The sex of the offender was orthogonally manipulated to the type
of crime. The results show that gender had an important impact on sentences, with
males being more harshly penalized by reasons of perversity and women less
penalized by reason of mental disorders. In addition, filicide was more heavily
penalized than was intimate partner homicide. The results also revealed a tendency
toward a retributive conception of punishment. We discuss how gender norms in
justice seem to be embedded in society as well as the need for intervention against
the punitive tendency of this population.
Glomerulonephritis (GN) is still the most common cause of end-stage renal disease.
Accumulation of glomerular macrophages, proliferation of mesangial cells, and
deposition of extracellular matrix proteins are pathobiological hallmarks of GN.
Pharmacological interventions that can inhibit these insults may be beneficial in
the retardation of the progression of GN. Honokiol originally isolated from
Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative
activities in a variety of inflammation models. In this study, we first
investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1
nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies
intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5mg/kg,
twice a day) or vehicle and were killed at various time points. Glomerular
histology and immunohistopathology and urine protein excretion were studied.
Western blotting was conducted for markers of proliferation. Adhesion molecules,
chemokine, and extracellular matrix gene expression were evaluated by Northern
blotting. Honokiol-treated nephritic rats excreted less urinary protein and had
lower glomerular cellularity and sclerosis. The increased intraglomerular
proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could
be abolished by the treatment of honokiol. Honokiol also alleviated glomerular
monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar
to type I (alpha 1) collagen and fibronectin mRNA levels of nephritic rats. These
results indicate that honokiol may have therapeutic potential in mesangial
proliferative GN.
BSMV (barley stripe mosaic virus) particles were obtained in a pure state from
infected host plant tissues of Hordeum vulgare. The three genomic parities (alpha,
beta and gamma) were amplified by PCR using specific primers for each particle;
each was cloned. Partial sequence of the alpha, beta and gamma segments was
determined for the Egyptian isolate of barley stripe mosaic virus (BSMV AE1).
Alignment of nucleotide sequences with that of other known strains of the virus,
BSMV type strains (CV17, ND18 and China), and the generation of phylogenetic trees
was performed. A low level of homology was detected comparing 467 bp of the alpha
and 643 bp of the segments to that of the other strains, and thus BSMV alpha and
beta segments were in separate clusters. However, 1154 bp of the gamma segments of
BSMV AE1 showed a high level of homology especially to strain BSMV ND18, as they
both formed a distinct cluster. Northern blotting of pure BSMV AE1 virus and H.
vulgare-infected tissue were compared using an alpha ND18 specific probe. Western
blotting using antibodies specific for the coat protein (CP) and the triple gene
block 1. (TGB1) protein, which are both encoded by the beta ND18 segment, still
indicated a high level of similarity between proteins produced by BSMV ND18 and AEL
We suggest that the BSMV AE1 isolate is a distinct strain of BSMV which reflects
the genetic evolutionary divergence among BSMV strains and members of the
Hordeivirus group.
Horizontal gene transfer (HGT) is pervasive in viruses and thought to be a key
mechanism in their evolution. On the other hand, strong selective constraints
against increasing genome size are an impediment for HGT, rapidly purging
horizontally transferred sequences and thereby potentially hindering evolutionary
innovation. Here, we explore experimentally the evolutionary fate of viruses with
simulated HGT events, using the plant RNA virus Tobacco etch virus (TEV), by
separately introducing two functional, exogenous sequences to its genome. One of
the events simulates the acquisition of a new function though HGT of a conserved
AlkB domain, responsible for the repair of alkylation or methylation damage in many
organisms. The other event simulates the acquisition of a sequence that duplicates
an existing function, through HGT of the 2b RNA silencing suppressor from Cucumber
mosaic virus. We then evolved these two viruses, tracked the maintenance of the
horizontally transferred sequences over time, and for the final virus populations,
sequenced their genome and measured viral fitness. We found that the AlkB domain
was rapidly purged from the TEV genome, restoring fitness to wild-type levels.
Conversely, the 2b gene was stably maintained and did not have a major impact on
viral fitness. Moreover, we found that 2b is functional in TEV, as it provides a
replicative advantage when the RNA silencing suppression domain of HC-Pro is
mutated. These observations suggest a potentially interesting role for HGT of short
functional sequences in ameliorating evolutionary constraints on viruses, through
the duplication of functions.
Current evidence is mixed on the role of progesterone and its metabolites in
perinatal mood and anxiety disorders. We measured second and third trimester (T2
and T3) progesterone (PROG) and allopregnanolone (ALLO) levels by ELISA and
postpartum depression (PPD) by clinician interview (DSM-IV criteria) in 60 pregnant
women with a prior diagnosis of a mood disorder. Methods included multivariate and
logistic regression with general linear mixed effect models. We found that, after
adjustment, every additional ng/mL of T2 ALLO resulted in a 63% (95% CI 13% to 84%,
p = 0.022) reduction in the risk of developing PPD. Our findings extend previous
work connecting ALLO and depression within pregnancy, and indicate that the
relationship between pregnancy ALLO and PPD is worth further exploration in a
larger sample. (C) 2017 Elsevier Ltd. All rights reserved.
Some domestic animals are thought to be skilled at social communication with humans
due to the process of domestication. Horses, being in close relationship with
humans, similar to dogs, might be skilled at communication with humans. Previous
studies have indicated that they are sensitive to bodily signals and the
attentional state of humans; however, there are few studies that investigate
communication with humans and responses to the knowledge state of humans. Our first
question was whether and how horses send signals to their potentially helpful but
ignorant caretakers in a problem-solving situation where a food item was hidden in
a bucket that was accessible only to the caretakers. We then examined whether
horses alter their behaviours on the basis of the caretakers' knowledge of where
the food was hidden. We found that horses communicated to their caretakers using
visual and tactile signals. The signalling behaviour of the horses significantly
increased in conditions where the caretakers had not seen the hiding of the food.
These results suggest that horses alter their communicative behaviour towards
humans in accordance with humans' knowledge state.
C-reactive protein (CRP) is present at sites of inflammation including amyloid
plaques, atherosclerotic lesions, and arthritic joints. CRP, in its native
pentameric structural conformation, binds to cells and molecules that have exposed
phosphocholine (PCh) groups. CRP, in its non-native pentameric structural
conformation, binds to a variety of deposited, denatured, and aggregated proteins,
in addition to binding to PCh-containing substances. In this study, we investigated
the effects of H2O2, a prototypical reactive oxygen species that is also present at
sites of inflammation, on the ligand recognition function of CRP. Controlled H2O2
treatment of native CRP did not monomerize CRP and did not affect the PCh binding
activity of CRP. In solid phase ELISA-based ligand binding assays, purified
pentameric H2O2-treated CRP bound to a number of immobilized proteins including
oxidized LDL, IgG, amyloid peptide 1-42, C4b-binding protein, and factor H, in a
CRP concentration- and ligand concentration-dependent manner. Using oxidized LDL as
a representative protein ligand for H2O2-treated CRP, we found that the binding
occurred in a Ca2+-independent manner and did not involve the PCh-binding site of
CRP. We conclude that H2O2 is a biological modifier of the structure and ligand
recognition function of CRP. Overall, the data suggest that the ligand recognition
function of CRP is dependent on the presence of an inflammatory microenvironment.
We hypothesize that one of the functions of CRP at sites of inflammation is to
sense the inflammatory microenvironment, change its own structure in response but
remain pentameric, and then bind to pathogenic proteins deposited at those sites.
Aggressive behavior is assumed to be associated with certain patterns of social
information processing. While some theories link aggression to a tendency to
interpret ambiguous stimuli as hostile (i.e., enhanced sensitivity to anger),
others assume an insufficient ability to perceive emotional expressions,
particularly fear. Despite compelling evidence to support both theories, no
previous study has directly investigated the predictions made by these two accounts
in aggressive populations. The aim of the current study was to test processing
patterns for angry and fearful facial expressions in violent offenders (VOs) and
healthy controls (CTLs) and their association with self-reported aggression and
psychopathy scores. In Experiment 1, we assessed perceptual sensitivity to neutral-
emotional (angry, fearful, happy) blends in a task which did not require
categorization, but an indication whether the stimulus is neutral or emotional. In
Experiment 2, we assessed categorization performance for ambiguous fearful-happy
and angry-happy blends. No group differences were revealed in Experiment 1, while
Experiment 2 indicated a deficit in the categorization of ambiguous fearful blends
in the VO group. Importantly, this deficit was associated with both self-reported
psychopathy and aggression in the VO, but not the CTL group. The current study
provides evidence for a deficient categorization of fearful expressions and its
association with self-reported aggression and psychopathy in VOs, but no support
for heightened sensitivity to anger. Furthermore, the current findings indicate
that the deficit is tied to categorization but not detection stages of social
information processing.
The study of child abuse effects in conjunction with witnessing domestic violence
has shown some influence of this dual exposure on the development of behavior
problems in children. Thus, this study goal was to analyze the likely influence of
dual exposure on adolescent drug use and antisocial behavior. The sample comprised
247 adolescents from juvenile offenders and foster care centers in the autonomous
community of Galicia (Spain). Results showed that adolescents who have witnessed
family violence had higher rates of aggressive and rule-breaking behaviors, theft
and substance abuse, as well as more frequent use of alcohol, cannabis and cocaine,
compared to: a) youths without history of family violence, b) adolescents
maltreated in childhood, and c) those with dual victimization.
Hosts can utilize different types of defense against the effects of parasitism,
including avoidance, resistance, and tolerance. Typically, there is tremendous
heterogeneity among hosts in these defense mechanisms that may be rooted in the
costs associated with defense and lead to trade-offs with other life-history
traits. Trade-offs may also exist between the defense mechanisms, but the
relationships between avoidance, resistance, and tolerance have rarely been
studied. Here, we assessed these three defense traits under common garden
conditions in a natural host-parasite system, the trematode eye-fluke Diplostomum
pseudospathaceum and its second intermediate fish host. We looked at host
individuals originating from four genetically distinct populations of two closely
related salmonid species (Atlantic salmon, Salmo salar and sea trout, Salmo trutta
trutta) to estimate the magnitude of variation in these defense traits and the
relationships among them. We show species-specific variation in resistance and
tolerance and population-specific variation in resistance. Further, we demonstrate
evidence for a trade-off between resistance and tolerance. Our results suggest that
the variation in host defense can at least partly result from a compromise between
different interacting defense traits, the relative importance of which is likely to
be shaped by environmental components. Overall, this study emphasizes the
importance of considering different components of the host defense system when
making predictions on the outcome of host-parasite interactions.
Background. Nasal colonization has gained attention as an effect modifier in
Staphylococcus aureus vaccine trials, suggesting interference of carriage with T-
cell immunity. Likewise, T-cell signals may be involved in regulating effectors of
epithelial innate defense. Methods. Whole blood from 43 persistent carriers and 49
noncarriers was stimulated with viable S. aureus. T-helper type 1 (Th1), Th2, and
Th17 cytokine expression was measured, compared between carrier groups, and linked
with data on human beta-defensin 3 (hBD-3) messenger RNA (mRNA) in skin while
adjusting for transcriptionally relevant promoter haplotypes. Results. Compared
with carriers, stimulated whole blood from noncarriers contained on average 60%
more interferon gamma mRNA (P = .031) and 19% less interleukin 17A (IL-17A) mRNA (P
= .11), resulting in, on average, a 90% higher IFN-gamma to IL-17A mRNA ratio (P
= .003). In a multivariable model, per duplication of the mRNA template, the risk
of being a carrier increased by 93% for IL-17A (odds ratio [OR], 1.93; 95%
confidence interval [CI], 1.10-3.41; P = .023) and decreased by 35% for IFN-gamma
(OR, 0.65; 95% CI, 0.47-0.91; P = .01). Independent of carriage and DEFB promotor
haplotype, a 1-unit increase in the IFN-gamma to IL-17A mRNA ratio (mean +/- SD,
5.93 +/- 1.60) led to a 24% increase in hBD-3 transcription in experimentally
wounded human skin (P = .003). Conclusions. A low Th1 to Th17 mRNA ratio increases
the propensity for persistent S. aureus nasal colonization, with down-regulated
hBD-3 transcription providing a potential link.
Protein-protein interaction is a vital process which drives many important
physiological processes in the cell and has also been implicated in several
diseases. Though the protein-protein interaction network is quite complex but
understanding its interacting partners using both in silico as well as molecular
biology techniques can provide better insights for targeting such interactions.
Targeting protein-protein interaction with small molecules is a challenging task
because of druggability issues. Nevertheless, several studies on the kinetics as
well as thermodynamic properties of protein-protein interactions have immensely
contributed toward better understanding of the affinity of these complexes. But,
more recent studies on hot spots and interface residues have opened up new avenues
in the drug discovery process. This approach has been used in the design of hot
spot based modulators targeting protein-protein interaction with the objective of
normalizing such interactions. (c) 2016 The Authors. Production and hosting by
Elsevier B. V. on behalf of King Saud University. This is an open access article
under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Housekeeping genes are widely used as internal controls for gene expression
normalization for western blotting, northern blotting, RT-PCR, etc. They are
generally thought to be expressed in all cells of the organism at similar levels
because it is assumed that these genes are required for the maintenance of basic
cellular function as constitutive genes. However, real-time RT-PCR experiments
revealed that their expression may vary depending on the developmental stage, type
of tissue examined, experimental condition, and so on. To date, no histological
data on their expression are available for embryonic development. In the present
study, we compared the histological expression profile of two commonly used
housekeeping genes, GAPDH and beta-actin, in the developing chicken embryo by using
section and whole mount in situ hybridization supplemented by RT-PCR. Our results
show that neither GAPDH mRNA nor beta-actin mRNA is expressed in all cell types or
tissues at high levels. Strikingly, expression levels are very low in some organs.
Moreover, the two genes show partially complementary expression patterns in the
liver, the vascular system and the digestive tract. For example, GAPDH is more
strongly expressed in the liver than beta-actin, but at lower levels in the
arteries. Vice versa, beta-actin is more strongly expressed in the gizzard than
GAPDH, but it is almost absent from cardiac muscle cells. Researchers should
consider these histological results when using GAPGD and beta-actin for gene
expression normalization in their experiments.
Background/Aims: Sexual differences in the transcript levels of various genes
including the hepatic isoforms of cytochrome P450 have been extensively studied.
Expression of these sexual dimorphic genes have been quantified by Northern
blotting, nuclear run on assays and reverse transcriptase-polymerase chain reaction
(RT-PCR) methods using numerous housekeeping genes to normalize results. Earlier
reports apparently assumed that these internal controls were sex-independent. We
have studied sex differences in the expression levels of seven different commonly
used housekeeping genes. Methods: We have used quantitative and semiquantitative
RT-PCR to monitor the levels of hepatic mRNAs in intact and hypophysectomized male
and female rats. Results: We have observed sex-dependent expression of the commonly
used housekeeping genes tubulin, cyclophilin, tyrosine aminotransferase, beta-
actin, glyceraldehyde-3-phosphate dehydrogenase, 18S and one unconventional
housekeeping gene, that is, hypoxia inducing factor-1 alpha, in the livers of
intact male and female rats. With the exception of glyceraldehyde-3-phosphate
dehydrogenase and 18S which were female-predominant (P < 0.01), the five other
genes were found to be expressed at significantly (P < 0.01) higher concentrations
in the livers of intact male rats. Similar to findings in which hypophysectomy
eliminates sexual dimorphisms in cytochromes P450 expression, of the five
housekeeping genes examined, cylophilin, tyrosine aminotransferase, glyceraldehyde-
3-phosphate dehydrogenase, beta-actin, and 18S, all lost their sex-dependent
expression following pituitary ablation. Conclusionds: Our data suggest that
expression levels of these commonly measured housekeeping genes (structural and
metabolic) are not constant, but rather are directly or indirectly regulated by
sex-dependent hormones, compromising their application as normalizing controls. (c)
2005 Blackwell Publishing Asia Pty Ltd.
Current sources with Howland topology made with operational amplifier are often
used for sensors that requires constant current polarization, for bioimpedance
measuring, actuators driving systems and so on. Theoretical determination of
overall performances for this circuits is generally known. This paper presents a
practical method for real output impedance determining of such current sources
based on performing two simple measurements. The results is according with the
measurements on the practical circuit. Using the TL084 circuit the frequency cut-
off was 250 KHz but using one other circuit as THS3201 the cut-off frequency was
20MHz.
MicroRNAs (miRNA), small noncoding RNAs, affect a broad range of biological
processes, including tumorigenesis, by targeting gene products that directly
regulate cell growth. Human polynucleotide phosphorylase (hPNPase(old-35)), a type
I IFN-inducible 3'-5' exoribonuclease, degrades specific mRNAs and small noncoding
RNAs. The present study examined the effect of this enzyme on miRNA expression in
human melanoma cells. miRNA microarray analysis of human melanoma cells infected
with empty adenovirus or with an adenovirus expressing hPNPase(old-35) identified
miRNAs differentially and specifically regulated by hPNPase(old-35). One of these,
miR-221, a regulator of the cyclin-dependent kinase inhibitor p27(kip1), displayed
robust down-regulation with ensuing up-regulation of p27(kip1)by expression of
hPNPase(old-35), which also occurred in multiple human melanoma cells upon IFN-beta
treatment. Using both in vivo immunoprecipitation followed by Northern blotting and
RNA degradation assays, we confirm that mature miR-221 is the target of
hPNPase(old-35). Inhibition of hPNPase(old-35) by shRNA or stable overexpression of
miR-221 protected melanoma cells from IFN-beta-mediated growth inhibition,
accentuating the importance of hPNPase(old-35) induction and miR-221 down-
regulation in mediating IFN-beta action. Moreover, we now uncover a mechanism of
miRNA regulation involving selective enzymatic degradation. Targeted overexpression
of hPNPase(old-35) might provide an effective therapeutic strategy for miR-221-
overexpressing and IFN-resistant tumors, such as melanoma.
Background: The highly pathogenic porcine reproductive and respiratory syndrome
virus (HP- PRRSV) continues to pose one of the greatest threats to the swine
industry. M protein is the most conserved and important structural protein of
PRRSV. However, information about the host cellular proteins that interact with M
protein remains limited. Methods: Host cellular proteins that interact with the M
protein of HP- PRRSV were immunoprecipitated from MARC145 cells infected with PRRSV
HuN4-F112 using the M monoclonal antibody (mAb). The differentially expressed
proteins were identified by LC-MS/MS. The screened proteins were used for
bioinformatics analysis including Gene Ontology, the interaction network, and the
enriched KEGG pathways. Some interested cellular proteins were validated to
interact with M protein by CO-IP. Results: The PRRSV HuN4-F112 infection group had
10 bands compared with the control group. The bands included 219 non-redundant
cellular proteins that interact with M protein, which were identified by LC-MS/MS
with high confidence. The gene ontology and Kyoto encyclopedia of genes and genomes
(KEGG) pathway bioinformatic analyses indicated that the identified proteins could
be assigned to several different subcellular locations and functional classes.
Functional analysis of the interactome profile highlighted cellular pathways
associated with protein translation, infectious disease, and signal transduction.
Two interested cellular proteins-nuclear factor of activated T cells 45 kDa (NF45)
and proliferating cell nuclear antigen (PCNA)-that could interact with M protein
were validated by Co-IP and confocal analyses. Conclusions: The interactome data
between PRRSV M protein and cellular proteins were identified and contribute to the
understanding of the roles of M protein in the replication and pathogenesis of
PRRSV. The interactome of M protein will aid studies of virus/host interactions and
provide means to decrease the threat of PRRSV to the swine industry in the future.
Dysregulated expression of oncogenic types of E6 and E7 is necessary for human
papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ hybridization
(ISH) assay covering 18 common high-risk types ("HR-RISH,"aka HR-HPV RNA18 ISH) has
not been extensively studied in the anogenital tract or validated on automated
technology. We herein compare HR-RISH to DNA polymerase chain reaction (PCR), p16
immunohistochemistry, and a previously available HPV DNA ISH assay in HPV-related
anogenital and head and neck (H&N) neoplasia. A total of 102 squamous
intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3, 9 VIN3)/invasive
squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well as 10 normal and 15
reactive cervix samples were collected. HRRISH, DNA ISH, and p16
immunohistochemistry were performed on whole formalin-fixed, paraffin-embedded
sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed. RNA and
DNA ISH assays used automated systems. HR-HPV PCR was performed on morphology-
directed formalin-fixed, paraffin-embedded punches. HR-RISH was Z97% sensitive for
PCR+and p16+neoplasia, as well as morphologically defined anogenital high grade
squamous intraepithelial lesion/invasive squamous cell carcinoma. HR-RISH was also
positive in 78% of anogenital low grade squamous intraepithelial lesion, including
81% of CIN1. Furthermore, a subset of PCR-negative/invalid and p16-negative lesions
was positive for HR-RISH. Only 1 problematic reactive cervix sample and no normal
cervix samples stained. These results demonstrate that HR-RISH is a robust method
for the detection of HR-HPVrelated neoplasia and provides insight into HPV
pathobiology.Performance meets or exceeds that of existing assays in anogenital and
H&N lesions and may play a role in resolving diagnostically challenging CIN1 versus
reactive cases.
Decentralized energy supply is a frequently discussed topic in German industry,
caused by continuously rising energy prices. This study assesses configurations of
hybrid renewable energy systems (HRES) with regard to their ability to decrease a
company's energy supply costs. We apply mixed-integer linear programming (MILP) to
optimize an electricity and heat supply system with the aim of minimizing annual
costs and perform energy system optimizations for a sample of three case studies
and 363 virtual companies. Our results show that systems consisting of grid supply,
combined heat and power plants (CHP), heat storage facilities and, in some cases,
photovoltaics can lower the sample companies' annual energy costs by an average of
8.3%, including annualized investments. For a time frame of 20 years, the average
internal return rate of the HRES investments is 29.8%. This work expands the body
of literature on HRES optimizations by shifting the research focus from household
to industrial supply. Our model can support corporate investment decisions on
decentralized supply facilities. (C) 2017 Published by Elsevier Ltd.
Heat shock factor 1 (HSF1) is the major heat shock transcription factor and plays
an essential role in mediating the cellular response to physiological and
environmental stress. We found that LPS-induced expression of the granulocyte-
colony stimulating factor (G-CSF) gene was upregulated in HSF1 knock-out
(HSF1(-/-)) mice using a gene array. In order to determine whether and how HSF1
regulates the induced expression of G-CSF, mRNA, and protein levels of G-CSF were
detected by Northern blotting and ELISA, the promoter of G-CSF was analyzed with an
online transcription element search system and the transcriptional activity of the
G-CSF promoter was analyzed by EMSA and a reporter gene assay. The results showed
that transcription and protein secretion of G-CSF induced by LPS are both inhibited
by HSF1. Three high affinity binding sites for NF-IL6/CCAAT enhancer binding
protein beta, but no heat shock element, were identified in the core promoter of G-
CSF. The DNA-binding capability of NF-IL6 to the G-CSF promoter was reinforced by
LPS but not influenced by heat shock or HSF1. However, HSF1 was observed to bind to
the binding sites of NF-IL6 in the G-CSF promoter. The transcriptional activity of
the G-CSF promoter was enhanced by LPS or NF-IL6 and inhibited by HSF1 in a dose
dependent manner. We conclude that HSF1 regulates expression of G-CSF through
binding to the NF-IL6-binding element.
The cDNA of Crassostrea gigas HSP70 was cloned and rapid amplification of cDNA
(RACE) techniques were used. The full length of HSP70 cDNA was 2045 bp, consisting
of a 5' terminal untranslated region (UTR) of 80 bp, a 3' terminal UTR 146 bp, and
an open reading frame (ORE) of 1829 bp encoding deduced 620 amino acids. The HSP70
cDNA contained HSP70 family signatures, ATP-GTP binding site motif, tetrapeptide
(GGMP) and conserved carboxyl terminal region (EEVD) at C-terminal of deduced amino
acid sequence. BLAST analysis revealed that the HSP70 gene has an extreme
similarity of 98.9% with C. gigas (AF144646). Northern blotting was used to examine
the expression of HSP70 mRNA in the gill tissue of the oyster obtained from
surface, middle and bottom layers. The HSP70 mRNA observed the samples taken from
middle and bottom layers in September and February, but samples from the surface
layer did not find a signal intensity of HSP70 mRNA transcript. Consequently, it
seems that the oyster occurring middle and bottom layer have been stressed during
the period of summer and winter, which is associated with the massive mortality in
Gamak bay.
Herpes simplex virus (HSV) infections of the central nervous system (CNS) are
associated with significant morbidity and mortality rates in children. This study
assessed the impact of a direct HSV (dHSV) PCR assay on the time to result
reporting and the duration of acyclovir therapy for children with signs and
symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR
results from cerebrospinal fluid (CSF) samples were included in this retrospective
analysis, divided into preimplementation and postimplementation groups. For the
preimplementation group, CSF testing was performed using a laboratory-developed
real-time PCR assay; for the postimplementation group, CSF samples were tested
using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over
60% of patients from both groups were prescribed acyclovir. The average HSV PCR
test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h
versus 9.1 h; P < 0.001). Furthermore, 79 patients (43.6%) in the
postimplementation group had dHSV PCR results reported < 4 h after specimen
collection. The mean time from specimen collection to acyclovir discontinuation was
17.1 h shorter in the postimplementation group (31.1 h versus 14 h; P < 0.001). The
median duration of acyclovir therapy was also significantly reduced in the
postimplementation group (29.2 h versus 14.3 h; P = 0.01). Our investigation
suggests that implementation of rapid HSV PCR testing can decrease turnaround times
and the duration of unnecessary acyclovir therapy.
AIM: To investigate the effect of HtrA1 on the proliferation, migration and
apoptosis of human retinal pigment epithelium (RPE) cells in the light injured
model, as well as the expression of the apoptosis related molecules. METHODS: The
human RPE cell line ARPE-19 was exposed to blue light to establish the light
injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1
expression. Subsequent expression of HtrA1 was determined by real-time polymerase
chain reaction (RTPCR) and Western blot, respectively. Changes in cell
proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-
8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA
and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was
highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1
expression inhibited the proliferation, migration and apoptosis of the blue-light-
irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were significantly
reduced both at mRNA and protein levels (P<0.05) after siRNA treatment. Bcl-2
expression significantly increased in blue-light irradiated ARPE-19 cells after
siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may inhibit the
proliferation, migration and apoptosis of ARPE-19 cells in light injured model.
Moreover, HtrA1 suppression in blue-light irradiated ARPE-19 cells may ameliorate
cell apoptosis through down-regulation of Bax and Caspase-3, and up regulation of
Bcl-2 expression.
Surface characteristics and cellular response to titanium surfaces that had been
implanted with calcium and magnesium ions using plasma immersion ion implantation
and deposition (PIIID) were evaluated. Three different titanium surfaces were
analyzed: a resorbable blast media (RBM) surface (blasted with hydroxyapatite
grit), a calcium ion-implanted surface, and a magnesium ion-implanted surface. The
surface characteristics were investigated by scanning electron microscopy (SEM),
surface roughness testing, X-ray diffraction (XRD), and Auger electron spectroscopy
(AES). Human bone marrow derived mesenchymal stem cells were cultured on the 3
different surfaces. Initial cell attachment was evaluated by SEM, and cell
proliferation was determined using MTT assay. Real-time polymerase chain reaction
(PCR) was used to quantify osteoblastic gene expression (i.e., genes encoding
RUNX2, type I collagen, alkaline phosphatase, and osteocalcin). Surface analysis
did not reveal any changes in surface topography after ion implantation. AES
revealed that magnesium ions were present in deeper layers than calcium ions. The
calcium ion- and magnesium ion-implanted surfaces showed greater initial cell
attachment. Investigation of cell proliferation revealed no significant difference
among the groups. After 6 days of cultivation, the expression of RUNX2 was higher
in the magnesium ion-implanted surface and the expression of osteocalcin was lower
in the calcium ion-implanted surface. In conclusion, ion implantation using the
PIIID technique changed the surface chemistry without changing the topography.
Calcium ion- and magnesium ion-implanted surfaces showed greater initial cellular
attachment.
Objective: To review contemporary knowledge of the hCG molecule, its isoforms and
the importance of glycosylation. Biologic variants and glycoforms of hCG have
different biological activities and functions related to the control of menstrual
cycle, conception, gestation as well as gynaecologic and non-gynaecologic
malignancies. Design: A review. Setting: Department of Obstetrics and Gynaecology,
University Hospital Olomouc. Methods: To present own experience and an overview of
recent literature in molecular biology, clinical biochemistry and clinical
practice. Conclusion: Recent knowledge of the role of hCG glycosylation in
physiologic and pathologic events in female organism will provide a better
understanding of regulation of processes like ovulation (co-operation of pituitary
hCG with LH), implantation and hemochorial placentation (invasivity of
hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important
for the prediction of certain pathologies of pregnancy, prenatal screening of
inborn errors (free beta hCG) as well as in the treatment of infertility.
Background. DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid
(CSF) by polymerase chain reaction (PCR) is a marker of central nervous system
(CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is
unknown. Methods. A multicenter, retrospective study was performed using the
Spanish Congenital Cytomegalovirus Infection Database (REDICCMV;
http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed
were included and classified according to their hCMV-PCR in CSF result
(positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma
viral load, and audiological and neurological outcomes of both groups were
compared. Results. A total of 136 neonates were included in the study: 21 (15.4%)
with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen
patients (81%) in the positive group were symptomatic at birth compared with 52.2%
of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval
[CI], 1.28-14.1; P=.01). Only 4 asymptomatic newborns (6.8%) had a positive CSF
hCMV-PCR. There were no differences between groups regarding the rate of
microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age,
or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated
with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P=.04), although
no association was found at 6 months of age. Conclusions. A positive hCMV-PCR
result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no
differences in neuroimaging studies, plasma viral load, or outcomes at 6 months
were found. These results suggest that hCMV-PCR in CSF may not be a useful
prognostic marker in cCMV.
Background: It has been predicted that the UL31 gene originates from the positive
strand of the human cytomegalovirus (HCMV) genome, whereas the UL30 and UL32 genes
originate from the complementary strand. Except for the UL32 gene, the
transcription of this gene region has not been investigated extensively. Methods:
Northern blotting, cDNA library screening, RACE-PCR, and RT-PCR were used. Results:
At least eight transcripts of the antisense orientation of UL31 were transcribed
from the UL30-UL32 region during the late phase of HCMV infection. The 3'
coterminus of these transcripts was located within the predicted UL30 gene. The
longest 6.0-kb transcript was initiated upstream of the predicted UL32 gene. Other
transcripts were derived from the predicted UL30 and UL31 gene region. Except for
the previously predicted UL32 open reading frame (ORF), three novel ORFs, named
UL31anti-1, UL31anti-2 and UL31anti-3, were located in the transcripts from the
UL31anti-UL32 transcription unit. No transcription was found in UL31. Conclusion: A
family of novel 3' coterminal transcripts was transcribed from the UL30-UL32 gene
region.
Objective: To study the mRNA expression of the two leucine-rich repeat-containing
G-protein-coupled receptors LGR-4 and LGR-5 and the mRNA and protein expression of
LGR-7, the relaxin receptor, in the human cyclic endometrium. Design: Retrospective
study. Setting: Department of Anatomy and Reproductive Biology, Rheinisch-
Westfalische Technische Hochschule Aachen, Aachen, Germany. Method(s): LGR-4, -5,
and -7 mRNA expression was assessed by semiquantitative and real time reverse
transcription-polymerase chain reaction in the endometrium of premenopausal women
(n = 26) and cultured primary endometrial epithelial cells and fibroblasts (n = 3).
Transcript size was determined by Northern blotting. LGR-7 protein expression was
assessed by immunohistochemistry. Result(S): The mRNA of LGR-4, LGR-5, and LGR-7
was expressed constitutively throughout the menstrual cycle in the endometrium, and
characterized by substantial differences in expression levels of individual women.
LGR-7 immunostaining was detected in the epithelium of the functional layer
throughout the cycle, with lowest staining in the midproliferative phase.
Furthermore, individual stromal cells of the functional layer and the stroma of the
basal layer showed LGR-7 immunostaining. Conclusion(S): Endometrial expression of
the mRNA of orphan receptors LGR-4 and LGR-5 implies that the endometrium is
potentially influenced by as yet unknown mediators, which are possibly involved in
fertility control. Furthermore, we confirmed constitutive endometrial mRNA
expression of LGR-7, the classical relaxin receptor, and demonstrated specific LGR-
7 immunostaining of different endometrial cell types, which suggests a
physiological role of relaxin in the human endometrium.
Background. Seasonal influenza is responsible for high annual morbidity and
mortality worldwide, especially in elderly patients. The aim of the study was to
analyse the epidemiological, clinical and prognostic features of influenza in
octogenarians and nonagenarians admitted to a general hospital, as well as risk
factors associated with mortality. Methods. Retrospective, cross-sectional,
descriptive study in patients admitted and diagnosed with influenza by molecular
biology in the General University Hospital of Alicante from 1 January to 31 April
2015. Results. A total of 219 patients were diagnosed with influenza in the study
period: 55 (25.1%) were= 90 years. Most flu episodes were caused by influenza A
(n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration
rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive
mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac
insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%,
p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis,
mortality was higher in those aged 80 or over (adjusted odds ratio [ORa] 9.2, 95%
confidence interval [CI] 1.65-51.1), those who had acquired the flu in a long-term
care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa
1.89, 95% CI 1.20-3.00). Conclusions. Seasonal influenza is a serious problem
leading to elevated mortality in octogenarian and nonagenarian patients admitted to
a general hospital.
Background: The human leukocyte antigen (HLA) system plays critical roles in
regulating immune responses to various vaccines. This study aimed to evaluate the
association of HLA class II gene polymorphisms and the long-term duration of anti-
HBs response in children vaccinated against hepatitis B during infancy. Methods:
Totally 297 children 5-7 years after the completion of primary vaccination against
hepatitis B in infancy, without booster immunization or natural resolved infection,
were enrolled. Of them, 86 children with anti-HBs= 10 mIU/ml were defined as long-
term responders. Ten alleles in HLA-DR and -DQ subregions were detected by
polymerase chain reaction with sequence-specific primers. Results: The frequency of
HLA-DQB1*0401 was 15.1% in the long-term non- or hypo-responder group, relatively
higher than 7.6% in the long-term responder group (OR = 2.17, 95% CI 1.01-4.73),
however, the difference had no statistical significance after Bonferroni correction
(P = 0.470). The frequencies of seven HLA-DRB1 alleles, including (*)01, (*)03,
(*)04, (*)07, (*)08, (*)11, and (*)1301/1302, and two HLA-DQB1 alleles, including
(*)0201 and (*)0501, were each similarly distributed in the long-term non- or hypo
responders and responders respectively. Conclusion: None of the ten HLA class II
gene alleles previously reported to be related with short-term antibody response to
hepatitis B vaccine is associated with the long-term antibody response after
vaccination during infantile. (C) 2017 Elsevier Ltd. All rights reserved.
A sensitive and rapid sandwich immunoassay (IA) was developed for human lipocalin-2
(LCN2) by functionalizing a KOH-treated polystyrene microtiter plate with
multiwalled carbon nanotubes (MWCNTs) dispersed in 3-aminoproyltriethoxysilane
(APTES). The significantly increased surface area due to the presence of MWCNTs led
to a high immobilization density of 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide
(EDC) activated anti-LCN2 capture antibodies (Ab). The anti-LCN2 Ab-bound MTPs were
stable for 6 weeks when stored in 0.1 M PBS, pH 7.4 at 4 degrees C. The IA detects
LCN2 from 0.6 to 5120 pg mL(-1) with a limit of detection (LOD) and limit of
quantification (LOQ) of 0.9 pg mL(-1) and 6 pg mL(-1), respectively. The assay
offered similar to 50-fold lower LOD and similar to 3-fold faster IA, compared to a
commercial sandwich enzyme-linked immunosorbent assay kit. (C) 2016 Elsevier B.V.
All rights reserved.
The profound influence of ATP-binding cassette (ABC) transporters on the
disposition of numerous drugs has led to increased interest in characterizing their
expression profiles in various epithelial and endothelial barriers. The present
work examined the presence and functional activity of five ABC efflux proteins,
i.e., MRP 1-5, in freshly isolated human nasal epithelial cells and two in vitro
models based on the human RPMI 2650 cell line. To evaluate the expression patterns
of MRP1, MRP2, MRP3, MRP4, and MRP5 at the mRNA and protein levels in the ex vivo
model and the differently cultured RPMI 2650 cells, reverse transcriptase
polymerase chain reaction (RT-PCR), Western blot analysis, and indirect
immunofluorescence staining were used. The functionality of the MRP transporters in
the three models was assessed using efflux experiments and accumulation assays with
the respective substrates and inhibitors. The mRNA and protein expression of all
selected ABC transporters was detected in excised human nasal mucosa as well as in
the corresponding cell culture models. Moreover, the functional expression of the
MRP transport proteins was demonstrated in the three models for the first time.
Therefore, the potential impact of multidrug resistance-associated proteins 1-5 on
drug disposition after intranasal administration may be taken into consideration
for future developments. The specimens of human nasal turbinate exhibited slightly
lower efflux capacities of MRP1, MRP3, and MRP5 in relation to the submerged and
ALI-cultured RPMI 2650 cells, but showed a promising comparability to both in vitro
models concerning the activity of MRP2 and MRP4. In this regard, the different RPMI
2650 cell culture models will be able to provide useful experimental data in the
preclinical phase to estimate the interaction of particular efflux transporters
with drug candidates for nasal application.
A novel approach for stem cell generation is the attempt to induce conversion of
the adult somatic cells into pluripotent stem cells so called induced pluripotent
stem cells (iPSCs) by introducing specific transcription factors. iPSCs have two
essential cell characteristics, they are pluripotent and posses long term cell-
renewal capacity. Additionally, iPSCs can be derived from patient-specific somatic
cells, thus bypassing ethical and immunological issues. The aim of our study was to
reprogram long-term cryopreserved human neonatal fibroblasts by new method using
lipid nano-particle technology (Lipofectamine 3000 reagent transfection system) in
combination with Epi 5 reprogramming vectors. Obtained iPSCs were characterized by
several sophisticated methods of molecular biology and microscopy. Distinct
colonies of iPSCs started to appear by day 20 after reprogramming. The presence of
iPSCs colonies was proved by alkaline phosphatase (AP) live staining. After manual
picking the colonies and their subsequent passaging, they did not lose ability to
form embryoid bodies, they were positive for AP, Tra-1-60, and SSEA-5. Moreover,
obtained iPSCs expressed pluripotency markers Oct4, Sox2 and Nanog, and the
expression levels of chondrogenic, osteogenic and adipogenic markers were
significantly higher in comparison to control (p < 0.05). In summary, we have
demonstrated that long-term cryopreserved human neonatal fibroblasts can be
reprogrammed into iPSCs and after further analysis concerns on their biological
safety they may be used as patient-specific cells in regenerative medicine.
Rapid methods for the detection and clinical treatment of human norovirus (HuNoV)
are needed to control foodborne disease outbreaks, but reliable techniques that are
fast and sensitive enough to detect small amounts of HuNoV in food and aquatic
environments are not yet available. We explore the interactions between HuNoV and
concanavalin A (Con A), which could facilitate the development of a sensitive
detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange
(HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the
metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine
alanine residues (mCon AM), the affinity for HuNoV (GII.4) diminishes,
demonstrating that this Ca2+ and Mn2+ coordinated region is responsible for the
observed virus-protein interaction. The mutated carbohydrate binding region of Con
A (mCon A(CBR)) does not affect binding affinity significantly, indicating that MCR
of Con A is a major region of interaction to HuNoV (GII.4). The results further
contribute to the development of a HuNoV concentration tool, Con A-immobilized
polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I
and II (GI and GII). This method offers many advantages over currently available
methods, including a short concentration time. HuNov (GI and GII) can be detected
in just 15 min with 90% recovery through Con A-PAB application. In addition, this
method can be used over a wide range of pH values (pH 3.0 - 10.0). Overall, this
rapid and sensitive detection of HuNoV (Cl and GII) will aid in the prevention of
virus transmission pathways, and the method developed here may have applicability
for other foodborne viral infections. (C) 2017 Elsevier Ltd. All rights 'reserved.
TEA domain transcription factor 4 (TEAD4), which has critical functions in the
process of embryonic development, is expressed in various cancers. However, the
important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain
unclear. Here we investigated the TEAD4 expression level and the functional
mechanism in OSCC using quantitative reverse transcriptase-polymerase chain
reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4
knockdown model was used to evaluate cellular proliferation, cell-cycle analysis,
and the interaction between TEAD4 and Yes-associated protein (YAP) which was
reported to be a transcription coactivator of cellular proliferation. In the
current study, we found that TEAD4 expression increased significantly in vitro and
in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC
cells showed decreased cellular proliferation resulting from cell-cycle arrest in
the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and
up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the
nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken
together, we concluded that TEAD4 might play an important role in tumoral growth
and have potential to be a therapeutic target in OSCCs. (C) 2017 Elsevier Inc. All
rights reserved.
Background: Human papillomavirus (HPV) infection is linked to cervical cancer. With
the technological development of molecular biology and epidemiology, detection and
treatment of HPV has become an important mean to prevent cervical cancer. Methods:
A simple, rapid, and sensitive colorimetric loop-mediated isothermal amplification
(LAMP) method was established herein to detect 23 HPV genotypes. The sequences of
the primers for the LAMP reaction were located in the L1 gene of the HPV genome. As
it is a fluorescent dye, calcein was added before the reaction. The reaction was
run under isothermal conditions at 65 degrees C for 40 minutes. A positive reaction
was indicated by a color change from yellow to fluorescent green. The fluorescence
curve diagram represents the monitoring of real time quantitative instrument. 450
cervical swab samples from patients with single infections of 23 different HPV
genotypes were examined to evaluate the specificity. Results: The results revealed
no cross-reaction with other HPV genotypes. A serial dilution of a cloned plasmid
containing 23 HPV L1 gene sequences was employed to evaluate the sensitivity.
Different HPV subtypes have different detection capability. The sensitivity of
different HPV subtypes tested by LAMP assay was in the range from 1.0 x10 to 4.0 x
10(3) copies per reaction. The LAMP assay and the RDB (reverse dot blot) were
compared for detecting and genotyping HPV among the 450 clinical samples. There
were 385 (85.6%) and 375 (83.3%) HPV positive specimens detected by LAMP and RDB,
respectively, as well as 306 (68.0%) and 296 (65.8%) for HR-HPV positive specimens.
The agreement between the LAMP and RDB assays was 93.3% (kappa = 0.75) for HPV
positivity and 94.7% (kappa = 0.88) for HR-HPV positivity. Conclusions: It was
concluded that this colorimetric LAMP assay had potential application for the rapid
screening of the HPV infection in resource-limited hospitals or rural clinics.
BackgroundHuman papillomavirus (HPV)-positive oropharyngeal cancer is generally
associated with excellent response to therapy, but some HPV-positive tumors
progress despite aggressive therapy. The purpose of this study was to evaluate
viral oncogene expression and viral integration sites in HPV16- and HPV18-positive
squamous cell carcinoma lines. MethodsE6/E7 alternate transcripts were assessed by
reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated
papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites
and affected host genes. Cellular gene expression was assessed across viral
integration sites. ResultsAll HPV-positive cell lines expressed alternate HPVE6/E7
splicing indicative of active viral oncogenesis. HPV integration occurred within
cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in
8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1
had only intergenic integration. ConclusionHPV integration into cancer-related
genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors
that progressed. HPV integration into cancer-related genes may be a secondary
carcinogenic driver in HPV-driven tumors. (c) 2017 Wiley Periodicals, Inc. Head
Neck 39: 840-852, 2017
Cervical cancer, which is the second most common female malignancy, is
characterized by the consistent presence of human papillomavirus. Inappropriate
activation of Notch signaling has been associated with various types of cancer;
however, the role of Notch in cervical cancer remains unclear. The present study
aimed to investigate the role of Notch in cervical cancer. The methods used
included the generation of plasmids, viability assays, polymerase chain reaction
and western blotting The present findings demonstrated that cervical cancer samples
also consistently exhibit abnormal activation of the Notch pathway. The data also
indicated that different Numb isoforms may have opposite effects on the
proliferation of cervical cancer cells. As a result, the activated Notch signaling
pathway regulates the alternative splicing of the Numb gene, which affects the
proliferation of the cervical cancer cells. These findings suggest that activated
Notch signaling may lead to the development of cervical cancer by regulating Numb
splicing. Thus, Numb splice variants may be a potential clinical marker for
indicating cervical cancer genesis and development.
Many epidemical and biological studies have proposed that human papillomavirus
(HPV), primarily high-risk HPV16/18, is an etiological factor for a subset of head
and neck (HN) cancers. On that premise, we systematically reviewed relevant
articles and improved the understanding of HPV-related cancers. This article
comprehensively described the characteristics of HPV-associated HN tumors according
to demography, histopathology, molecular biology, and prognosis. Meta-analyses were
conducted to combine the studies that reported the association between HPV status
and these variables using Rev Man 5.0. The pooled results showed that HPV-positive
tumors were not only poorly differentiated (OR = 2.77, 95% CI: 2.3-3.32) and
smaller (OR = 2.21, 95% CI: 1.75-2.8) but were also strongly associated with
oropharynx (OR = 5.8, 95% CI: 4.01-8.38) and node involvement (OR = 2.77, 95% CI:
2.3-3.32). HPV-related tumors showed significantly more p16 overexpression (OR =
34.55, 95% CI: 20.91-57.09) and less TP53 mutations (OR = 0.27, 95% CI: 0.18-0.41)
than HPV-negative tumors. The patients with HPV-positive cancers had different
clinical behaviors, such as a reduced risks of death (HR = 0.32, 95% CI: 0.29-
0.36). This study supported the view point that HPV is a favorable indicator of
prognosis and that HPV-related HN tumors are distinct from traditional tumors. This
etiological relationship could impact future strategies of diagnosis, prevention,
therapy, and prognosis for this subset of patients. (C) 2016 Wiley Periodicals,
Inc.
Objectives/HypothesisThe human papillomavirus (HPV) is known to infect the tissues
of the oropharynx as demonstrated in HPV-positive oropharyngeal squamous cell
carcinoma (OPSCC). HPV has also been shown to induce benign lymphoid hypertrophy.
We sought to investigate an association between obstructive sleep apnea (OSA) and
the presence of HPV in palatine and lingual tonsillar oropharyngeal tissue. Study
DesignCase series with chart review. MethodsThis retrospective laboratory-based
study of oropharyngeal tissue from patients with OSA included patients >18 years
old who underwent surgical treatment for OSA at a single institution between
January 2012 and May 2014. Surgical specimens of adequate size were analyzed for
HPV6, 11, and 16 using real-time quantitative polymerase chain reaction from DNA
extracted from formalin-fixed paraffin-embedded tissue blocks. Student t test,
Pearson (2) test, and linear logistic regression were used to assess comparisons of
body mass index (BMI), apnea-hypopnea index (AHI), age, and gender between HPV-
positive and HPV-negative groups. ResultsOf 99 cases included in the study, six
were positive for HPV: two with HPV16 and four with HPV6. BMI, AHI, age, and gender
showed no significant differences between the HPV-positive and HPV-negative groups.
Logistic regression to predict HPV positivity accounting for each variable and
multivariate analysis were not statistically significant. ConclusionsOur study did
not show HPV to have a statistically significant association with OSA. None of the
covariates analyzed (BMI, AHI, gender, age) predicted HPV positivity in surgically
resected oropharyngeal tissue from OSA patients. Level of Evidence4 Laryngoscope,
127:1231-1234, 2017
Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically
transmitted to the developing fetus. In addition, the anti-B19 antibodies induced
by B19 infection are believed to have a cytopathic role in B19 transmission;
however, knowledge regarding the effects of anti-B19 antibodies during pregnancy is
limited. To investigate the possible roles of anti-B19 antibodies during pregnancy,
the present study examined the effects of anti-B19-VP1 unique region (VP1u), anti-
B19-VP2 and anti-B19-nonstructural protein 1 (NS1) immunoglobulin G (IgG)
antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with
purified IgG against B19-VP1u, B19-VP2 and B19-NS1. Subsequently, the expression of
surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using
flow cytometry, ELISA and western blotting. The expression levels of human
leukocyte antigen (HLA)-G were significantly increased on BeWo trophoblasts treated
with rabbit anti-B19-VP1u IgG, and were unchanged in those treated with rabbit
anti-B19-NS1 and anti-B19-VP2 IgG, as compared with the control group. Furthermore,
the expression levels of globoside (P blood group antigen) and cluster of
differentiation (CD) 29 (beta 1 integrin) were significantly increased in BeWo
trophoblasts treated with rabbit anti-B19-NS1 and anti-B19-VP2 IgG, whereas only
CD29 was also significantly increased in cells treated with anti-B19-VP1u IgG. In
addition, the number of cells at sub-G(1) phase; caspase-3 activity; and the
expression of intrinsic and extrinsic apoptotic molecules, including Fas-associated
death domain protein, activated caspase-8, activated caspase-3, B-cell lymphoma 2-
associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and
activated caspase-9, were significantly increased in BeWo trophoblasts treated with
anti-B19-VP1u and anti-B19-NS1 IgG. In conclusion, the present study demonstrated
that antibodies against B19 may have a crucial role in pathological processes
during pregnancy. These findings may help to elucidate the mechanisms underlying
transmission of the B19 virus during pregnancy.
Objective: Potassium channels of the ATP-sensitive family (K-ATP channel) are
inhibited by increase in intracellular ATP. Electrophysiological studies have
demonstrated that the kinetics and pharmacological properties of KAT? channels vary
among different tissues, suggesting structurally and functionally distinct types.
There are studies showing human periodontal ligament (PDL) cells respond to
mechanical stress by increasing ATP release, which participates in bone resorption
or bone homeostasis. So, in this study we investigated the existence of KAT?
channel subunit and their single channel properties in human periodontal ligaments.
Materials & method: The human PDL cells were isolated from healthy erupted third
molar. For patch clamp experiments, human PDL fibroblasts were seeded on 3.5 cm
plastic dishes. The inside-out patch clamp recordings were performed under voltage
clamp mode. Reverse transcriptase polymerase chain reaction (RT-PCR) was conducted
to identify the channel subunits. All pair-wise comparisons were performed by
Paired t-test. A P value < 0.05 was considered significant. Results: We observed
mRNA transcripts for Kir6.1, Kir6.2 and Sur2B subuits in the human PDL cells. In
inside-out patch mode, the single channel conductance was 163 pS at symmetrical K+
concentration of 140 mM and inward rectification was seen in ATP-free bath
solution. The reversal potential of the currents was found to be 0 mV at
symmetrical concentration (140 mM) of K+ in bath solution. The single channel
currents were almost blocked by adding 5 mM ATP in the bath solution. However, the
currents were not blocked by 100 mu M glibenclamide, a subunit specific K-ATP
channel blocker. Conclusions: These results indicate that human PDL cells express
K-ATP channels subunit including Sur2B and Kir6.1 and Kir6.2 which are sensitive to
ATP but insensitive to glibenclamide. (C) 2017 Elsevier Ltd. All rights reserved.
Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to
all treatment modalities. Therefore, the investigation of global gene expression in
HRCC might help understand its biologic behavior and develop treatment strategies.
Using cDNA microarray analysis, we initially compared gene expression profiles
between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and
127 genes were down-regulated. Next, a subset of genes, twofold differentially
expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene
reported to be a tumor suppressor gene, was found to be up-regulated in HRCC
tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was
higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to
doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving
SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were
transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to
SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor
formation in subcapsule of kidney and lung metastasis. On the other hand, induction
of caveolin-1 gene affected the production of lung metastasis under anti-cancer
drug treatment: the incidence of pulmonary metastasis was significantly lower in
SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules
decreased significantly (p = 0.0004). The above results together suggest that
caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy
and surviving HRCC cells eventually might develop lung metastasis.
The necessity for schools to implement human resources management (HRM) is
increasingly acknowledged. Specifically, HRM holds the potential of increasing
student outcomes through the increased involvement, empowerment and motivation of
teachers. In educational literature, however, little empirical attention is paid to
the ways in which different HRM practices could be bundled into a comprehensive HRM
system (content) and how HRM could best be implemented to attain positive teacher
and student outcomes (process). Regarding the content, and following the AMO theory
of performance', it is argued that HRM systems should comprise (A) ability-, (M)
motivation- and (O) opportunity-enhancing HRM practices. Regarding the process, and
based on HRM system strength' literature, it is argued that when teachers perceive
HRM as distinctive and consistent, and if they perceive consensus, this will
enhance teachers' and schools' performance. By combining insights from educational
studies on single HRM practices with HRM theories, this paper builds a conceptual
framework which can be used to design HRM systems and to understand the way they
operate.
Background: The administration of cisplatin is limited due to its nephrotoxic side
effects, and prevention of this nephrotoxicity of cisplatin is difficult.
Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel
therapeutic approach for tissue injury. In this study, we demonstrated that the
pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent
the development of cisplatin-induced renal toxicity by activation of autophagy in
vitro and in vivo. Methods: In vitro, rat renal tubular epithelial (NRK-52E) cells
were pre-incubated with exosomes from hucMSC or HFL1 (human lung fibroblast cells;
as control) for 30 min, and 3-methyladenine (an autophagic inhibitor) and rapamycin
(an autophagic inducer) for 1 h before cisplatin treatment for 8 h, respectively.
Cells were harvested for apoptosis assay, enzyme-linked immunosorbent assay
(ELISA), Western blot, and quantitative real-time polymerase chain reaction (qRT-
PCR). In vivo, we constructed cisplatin-induced acute kidney injury rat models.
Prior to treatment with cisplatin for 0.5 h, hucMSC-Ex or HFL1-Ex were injected
into the kidneys via the renal capsule. 3-methyladenine and rapamycin were injected
under the kidney capsule before hucMSC-Ex. All animals were sacrificed at 3 days
after cisplatin injection. Renal function, Luminex assay, tubular apoptosis and
proliferation, and autophagy response were evaluated. Results: hucMSC-Ex inhibited
cisplatin-induced mitochondrial apoptosis and secretion of inflammatory cytokines
in renal tubular epithelial cells in vitro. hucMSC-Ex increased the expression of
the autophagic marker protein LC3B and the autophagy-related genes ATG5 and ATG7 in
NRK-52E cells. Rapamycin mimicked the effects of hucMSC-Ex in protecting against
cisplatin-induced renal injury, while the effects were abrogated by the autophagy
inhibitor 3-methyladenine in the animals. Conclusions: Our findings indicate that
the activation of autophagy induced by hucMSC-Ex can effectively relieve the
nephrotoxicity of cisplatin. Therefore, pre-treatment of hucMSC-Ex may be a new
method to improve the therapeutic effect of cisplatin.
Objective: Ulinastatin reduces the high permeability of vascular endothelial cells
induced by tumor necrosis factor alpha (INF-alpha). This study investigated the
molecular mechanism behind this effect, with the aim of understanding the action of
ulinastatin in sepsis therapy and exploring novel therapeutic strategies for sepsis
patients. Methods: A TNF-alpha treated human umbilical vein endothelial cell line
(EA.hy926) was employed as an inflammation model. Horseradish peroxidase
permeability assays and an epithelial voltmeter method were used to measure the
permeability of EA.hy926 cells. Immunocytochemistry was used to assay the
expression of p-MYPT1 and the distribution and morphology of F-actin; the
expression of the key molecules related to vascular endothelial permeability.
(RhoA, ROCK2, MYPT1, p-MYPT1 and VE-cadherin) was detected by immunocytochemistry
assays, western blotting and quantitative real-time polymerase chain reaction.
Results: After incubation with TNF-a or septic serum, the transendothelial
electrical resistance of EA.hy926 cells decreased and the permeability of the cells
increased significantly (all P < 0.05). The expression of p-MYPT1 was higher and
VE-cadherin was lower compared with the control group, and F-actin was
redistributed, with the formation of additional stress fibers in the cells.
Ulinastatin treatment moderated these phenomena. The immunocytochemistry assays and
western blots showed that the expression of RhoA and ROCK2 was significantly
upregulated in cells treated with TNF-alpha (P < 0.05); however, ulinastatin could
inhibit the high expression of these two proteins. Under treatment with TNF-alpha
and ulinastatin, compared with normal EA.hy926 cells, overexpression of RhoA
upregulated expression of RhoA, ROCK2 and p-MYPT1, downregulated expression of VE-
cadherin, and restored the hyperpermeability of vascular endothelial cells due to
TNF-alpha treatment (P < 0.05). Conclusions: Ulinastatin inhibited the
hyperpermeability of vascular endothelial cells induced by TNF-alpha. This
inhibitory effect of ulinastatin may be related to the RhoA/ROCK signaling pathway.
(C) 2017 Elsevier B.V. All rights reserved.
Helminths and their products can suppress the host immune response to escape host
defense mechanisms and establish chronic infections. Current studies indicate that
macrophages play a key role in the immune response to pathogen invasion. They can
be polarized into two distinct phenotypes: M1 and M2. The present paper examines
the impact of the adult Hymenolepis diminuta (HD) tapeworm and its
excretory/secretory products (ESP) on THP-1 macrophages. Monocytes were
differentiated into macrophages and cultured with a living parasite or its ESP. Our
findings indicate that HD and ESP have a considerable impact on human THP-1
macrophages. Macrophages treated with parasite ESP (with or without LPS)
demonstrated reduced expression of cytokines (i. e., IL-1 alpha, TNF alpha, TGF
beta, IL-10) and chemokines (i. e., IL-8, MIP-1 alpha, RANTES, and IL-1ra), while
s-ICAM and CxCL10 expression rose after ESP stimulation. In addition, inflammatory
factor expression rose significantly when macrophages were exposed to living
parasites. Regarding induced and repressed pathways, significant differences were
found between HD and ESP concerning their influence on the phosphorylation of
ERK1/2, STAT2, STAT3, AMPKa1, Akt 1/2/3 S473, Hsp60, and Hck. The superior
immunosuppressive properties of ESP compared to HD were demonstrated with lower
levels of IL-1 beta, TNF-alpha, IL-6, IL-23, and IL-12p70 following stimulation.
The presence of HD and its ESP were found to stimulate mixed M1/M2 macrophage
phenotypes. Our findings indicate new molecular mechanisms involved in the response
of human macrophages to tapeworm infection, this could be a valuable tool in
understanding the mechanisms underlying the processes of immune regulation during
cestodiasis.
The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete
human immune system, therefore providing a powerful tool to study human immunology
and immunotherapy. However, its application is greatly limited by the restricted
supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are
needed to generate these mice. The restriction is especially significant for the
study of human immune systems with special genetic traits, such as certain human
leukocyte antigen (HLA) haplotypes or monogene deficiencies. To circumvent this
critical limitation, we have developed a method to quickly propagate established
BLT mice. Through secondary transfer of bone marrow cells and human thymus implants
from BLT mice into NSG (NOD/SCID/IL-2R gamma(-/-)) recipient mice, we were able to
expand one primary BLT mouse into a colony of 4-5 proBLT (propagated BLT) mice in
6-8 weeks. These proBLT mice reconstituted human immune cells, including T cells,
at levels comparable to those of their primary BLT donor mouse. They also
faithfully inherited the human immune cell genetic traits from their donor BLT
mouse, such as the HLA-A2 haplotype that is of special interest for studying HLA-
A2-restricted human T cell immunotherapies. Moreover, an EGFP reporter gene
engineered into the human immune system was stably passed from BLT to proBLT mice,
making proBLT mice suitable for studying human immune cell gene therapy. This
method provides an opportunity to overcome a critical hurdle to utilizing the BLT
humanized mouse model and enables its more widespread use as a valuable preclinical
research tool.
Although Small Hydropower Projects (SHPs) are encouraged as sources of clean and
green energy, there is a paucity of research examining their socio-ecological
impacts. We assessed the perceived socio-ecological impacts of 4 SHPs within the
Western Ghats in India by conducting semi-structured interviews with local
respondents. Primary interview data were sequentially validated with secondary
data, and respondent perceptions were subsequently compared against the expected
baseline of assured impacts. We evaluated the level of awareness about SHPs, their
perceived socio-economic impacts, influence on resource access and impacts on
human-elephant interactions. The general level of awareness about SHPs was low, and
assurances of local electricity and employment generation remained largely
unfulfilled. Additionally most respondents faced numerous unanticipated adverse
impacts. We found a strong relationship between SHP construction and increasing
levels of human-elephant conflict. Based on the disparity between assured and
actual social impacts, we suggest that policies regarding SHPs be suitably revised.
Affective "Theory of Mind" (ToM) is the specific ability to represent own and
others' emotional states and feelings. Previous studies examined affective ToM
ability in patients with Huntingtons disease (HD), using the "Reading the Mind in
the Eyes test" (RMET). Results were consistent in showing difficulties in inferring
complex mental states from photographs of people even in the early stage of HD.
However, there has been no agreement as to whether or not cognitive impairments in
HD population might have contributed to poor performance on the RMET test. The aim
of the present study was to assess whether the affective ToM ability was impaired
in the mild to moderate stages of HD, and whether there was an association between
compromised ToM ability and the presence of cognitive impairment. We evaluated ToM
by means of RMET and global cognitive functioning by means of the MoCA
questionnaire in 15 HD patients and 15 healthy subjects (HS). Both groups were
matched for age and level of education. Our study showed that the ability to judge
a persons mental states from a picture of their eyes was impaired in HD patients
compared to normal population. Indeed, HD subjects gave the 34% of correct
responses on RMET, whereas healthy control subjects percentage of correct responses
was 71%. Furthermore, this impairment was not correlated with global cognitive
functioning except for the visuospatial task. These results show that RMET might
represent a valid instrument to assess affective ToM ability in HD patients in the
mild to moderate stages of the disease, independently from their cognitive status.
Since it is known that HD patients, in addition to motor symptoms, suffer from
cognitive deficits, including memory and executive impairments, it is important to
have an instrument, which is not influenced by cognitive abilities. It is possible
therefore to use RMET to assess important aspects of HD patients such as their
ability to recognize others emotions and feelings even when patients suffer from
cognitive decline.
Purinergic signaling maintains local tissue homeostasis in blood vessels via the
regulation of vascular tone, blood platelet aggregation, cell proliferation, and
differentiation as well as inflammatory responses. Extracellular purines are
important signaling molecules in the vasculature, and both purine-hydrolysing as
well as -phosphorylating enzymes are considered to selectively govern extracellular
nucleotide/nucleoside metabolism. Recent studies have provided some evidence for
the existence of these enzymes in a soluble form in human blood and their secretion
into the extracellular space under physiological and pathological conditions.
However, the comprehensive analysis of endothelium-derived enzymes involved in
purine metabolic pathways has received no attention so far. In the presented study,
in vitro cultured human umbilical vein endothelial cells (HUVEC) are shown to be an
abundant source of exo-nucleotidases comprising 5-nucleotidase (exo-5-NT), and
nucleoside triphosphate diphosphohydrolases (exo-NTPDase) as well as
phosphotransferases, represented by nucleoside diphosphate kinase (exo-NDPK) and
adenylate kinase (exo-AK). An attempt is also made to demonstrate that, in contrast
to the metabolic pattern determined on the endothelial cell surface, exo-
phosphorylating activities markedly predominate over exo-hydrolytic ones. We
present for the first time the expression profiles of genes encoding isoenzymes
belonging to distinct nucleotide kinase and nucleotidase families. The genes
encoding NDPK1, NDPK2, AK1, and AK2 phosphotransferases have been shown to be
expressed at the highest level in HUVEC cells. The data indicate the coexistence of
secreted and cell-associated factors of endothelial origin mediating ATP-consuming
and ATP-generating pathways with the predominance of exo-phosphotransferases
activity. The described enzymes contribute to the regulation of purinergic signal
duration and extent in the venous vasculature. J. Cell. Biochem. 118: 1341-1348,
2017. (C) 2016 Wiley Periodicals, Inc.
The paper postulates the feasibility and optimization of HVAC systems using
programmable controllers. HVAC (heating, ventilating and air conditioning) systems
are used for controlled maintenance of indoor ambient characteristics in optimal
manner; with regards to outdoor ambient characteristics. The paper includes a
simplified sequence of diagrams to represent the architecture of the system.
Further, it also comprises of the systems and software's used for the same. Also,
the paper gives an insight of the advantages of using programmable controllers, and
the challenges which are overcome by it. For the ease of understanding a case study
of a pharmaceutical company is given who is currently using the system. The main
purpose of this project was to create a regulated monitoring system, integration of
the utilities like electricity and water, creating a general report of the system
for the given or needed time span, also to create a graphical visualization of the
real time data and system.
this paper presents a column-level 14-bit two-stage analog-to-digital converter
(ADC) based on pseudo-differential operational amplifier, which is designed for the
readout circuit of X-ray sensor array. This low-power hybrid ADC employs an
incremental sigma-delta ADC and a cyclic ADC, achieving a good trade-off between
accuracy and conversion speed. The two stages share the same analog circuit to
reduce area and power consumption. A test chip is fabricated in 0.18 mu m CMOS
technology. The hybrid ADC in each column is performed in parallel with power
consumption of 218.813 mu W. The simulation result reveals the effective number of
bits (ENOB) is 13.775 bits.
this paper presents a low-power 14-bit hybrid incremental Sigma-Delta/cyclic
analog-to-digital converter (ADC) based on pseudo-differential operational
amplifier, which is designed for the readout circuit of infrared focal plane array
detector. This two-stage hybrid ADC employs an incremental sigma-delta ADC and a
cyclic ADC, achieving a good trade-off between accuracy and conversion speed. The
two stages share the same analog circuit to reduce area and power consumption. A
common-mood feedback module is used to suppress the influence of charge injection,
and the effectiveness is demonstrated by detailed theoretical analysis and
simulation result. A test chip is fabricated in 0.18 mu m CMOS technology. The
hybrid ADC in each column is performed in parallel with power consumption of
218.813 mu W. The simulation result reveals the effective number of bits (ENOB) is
13.775 bits.
This paper proposes a method for three-phase state estimation (SE) in power
distribution network including on-load tap changers (OLTC) for voltage control. The
OLTC tap positions are essentially discrete variables from the SE point of view.
Estimation of these variables in SE presents a formidable challenge. The proposed
methodology combines discrete and continuous state variables (voltage magnitudes,
angles, and tap positions). A hybrid particle swarm optimization (HPSO) is applied
to obtain the solution. The method is tested on standard IEEE 13-and 123-bus
unbalanced test system models. The proposed algorithm accurately estimates the
network bus voltage magnitudes and angles, and discrete tap values. The HPSO-based
tap estimation provides a more accurate estimation of losses in the network, which
helps in fair allocation of cost of losses in arriving at overall cost of
electricity.
The current increase in the deployment of new renewable electricity generation
systems is creating new challenges in balancing electric grids. Solutions including
energy storage at small and large scales are becoming of paramount importance to
guarantee and secure a stable supply of electricity. This paper presents a study
about a hybrid solution including a large scale energy storage system coupled with
power generation and fast responding energy storage systems. The hybrid plant is
able to deliver the energy previously stored by using an air liquefaction process
either with or without the contribution of additional energy from combustion. The
paper also highlights how such hybrid plants may offer the chance of providing the
grid with fast control services. An ideal energy storage technology should have a
high power rating, a large storage capacity, high efficiency, low costs and no
geographic constraints. The use of air as energy carrier has been studied since the
20th century with the first compressed air energy storage (CAES) systems. This
technology is still considered to have a potential but it is geographically
constrained, where suitable geological reservoirs are available, unless compressed
air is stored in pressurized tanks with significant costs. Liquid Air Energy
Storage (LAES) represents an interesting solution due to its relatively large
volumetric energy density and ease of storage. Different process schemes for hybrid
plants were modeled in this study with Aspen HYSYS (R) simulation software and the
results were compared in terms of equivalent round-trip and fuel efficiencies.
Equivalent round-trip efficiencies, higher than 80%, have been calculated showing
that the proposed configurations might play an important role for power systems
balancing in the near future. (C) 2016 Elsevier Ltd. All rights reserved.
Off-grid electricity generation using renewable energy technologies has become a
more reliable source to fulfill the needs of rural areas at limited level without
considering conventional resources. The main purpose of this study was to propose
an economical and optimized design for electricity generation using hybrid energy
source PV/Biomass for an agricultural farm and a residential community centered in
a small village of district Layyah in the Punjab province of Pakistan. The electric
load data was collected for the irrigation and residential needs. Hybrid
Optimization Model for Electric Renewable (HOMER) was used to design and perform
techno-economic analysis to meet the load requirements using PV/biomass hybrid
configuration. The solar irradiance data and the available biomass potential on the
farm was used in the HOMER software to perform the analysis. Total net present cost
(NPC) and cost of electricity (COE) were obtained as a solution by the HOMER
analysis and then these results were refined further by performing sensitivity
analysis. Sensitivity parameter such as biomass potential, biomass price, solar
irradiance and variations in loads were used in the sensitivity analysis. This
analysis compares the performance of the system and shows that system is techno-
economically viable based on the net present cost and cost of energy. (C) 2017
Elsevier Ltd. All rights reserved.
The paper presents a real-time open software simulation framework, dedicated to the
analysis of control systems deployed over distributed execution resources and
wireless links. It is able to consistently simulate in parallel the numerical
devices (real-time tasks and communication links) and the evolution of the
controlled continuous time plant. It is applied to foresee future enhancements of a
Functional Electrical Stimulation (FES) system used in therapy for rehabilitation
or substitution for disabled people. It is a distributed control system using
electrodes to interface a digital control system with livings. Hence the whole
system gathers continuous-time (muscles and nerves) and discrete-time (controllers
and wireless links) components. During the design process, realistic simulation
remains a precious tool ahead of real experiments to check without danger that the
implementation matches the functional and safety requirements. The simulation tool
is especially devoted to the joint design and analysis of control loops and real-
time features.
The assessment of off-grid electrification programs in developing countries largely
based on mini-grid and solar home system (SHS) has shown that they are faced with
low development imparts and sustainability challenges, which has resulted in
failure of many projects. This study provides solutions on how to surmount these
challenges, leaning on the experience of a hybrid solar-diesel mini-grid at Tsumkwe
village in Namibia. It provides analyses of a case study based on empirical
evidence from field studies, interviews of representatives of households, public
institutions and energy providers. In addition, it investigates the technical
challenges and economic impacts of the electrification program. HOMER (TM) and
MATLAB (TM) models were used in the analysis and investigations. The findings show
that despite the challenges, the system has been sustained because it keyed into an
existing structure with growth potentials. The progressive tariff system adopted by
the government helped to cushion costs and allow low income households in the
energy matrix. Adoption of strict maintenance measures, and implementation of
energy efficiency measures prior to the commissioning of the program, resulted in
the reduction of costs. The success elements identified in this study could be
extrapolated in other sub-Saharan African countries if the challenges are properly
addressed. (C) 2017 Elsevier Ltd. All rights reserved.
Recent advances in power generation from renewable resources necessitate conversion
of electricity to chemicals and fuels in an efficient manner. Electrocatalytic
water splitting is one of the most powerful and widespread technologies. The
development of highly efficient, inexpensive, flexible, and versatile water
electrolysis devices is desired. This review discusses the significance and impact
of the electrolyte on electrocatalytic performance. Depending on the circumstances
under which the water splitting reaction is conducted, the required solution
conditions, such as the identity and molarity of ions, may significantly differ.
Quantitative understanding of such electrolyte properties on electrolysis
performance is effective to facilitate the development of efficient
electrocatalytic systems. The electrolyte can directly participate in reaction
schemes (kinetics), affect electrode stability, and/or indirectly impact the
performance by influencing the concentration overpotential (mass transport). This
review aims to guide fine-tuning of the electrolyte properties, or electrolyte
engineering, for (photo)electrochemical water splitting reactions.
Background: Oxidative stress can induce cell injury in vascular endothelial cells,
which is the initial event in the development of atherosclerosis. Although
quantitative real-time polymerase chain reaction (qRT-PCR) has been widely used in
gene expression studies in oxidative stress injuries, using carefully validated
reference genes has not received sufficient attention in related studies. The
objective of this study, therefore, was to select a set of stably expressed
reference genes for use in qRT-PCR normalization in oxidative stress injuries in
human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide
(H2O2). Results: Using geNorm analysis, we found that five stably expressed
reference genes were sufficient for normalization in qRT-PCR analysis in HUVECs
treated with H2O2. Genes with the most stable expression according to geNorm were
U6, TFRC, RPLP0, GAPDH, and ACTB, and according to NormFinder were ALAS1, TFRC, U6,
GAPDH, and ACTB. Conclusion: Taken together, our study demonstrated that the
expression stability of reference genes may differ according to the statistical
program used. U6, TFRC, RPLP0, GAPDH, and ACTB was the optimal set of reference
genes for studies on gene expression performed by qRT-PCR assays in HUVECs under
oxidative stress study.
A 1 kW-class electrochemical reactor for hydrogen production was developed using
bipolar plates. To fabricate thick, large-area electrodes, a particle electrode
fabrication method was also introduced. Scanning electron microscopy with energy
dispersive X-ray spectroscopy and galvanostatic performance measurements were
performed to evaluate the particle electrodes. The results show that the particle
electrodes exhibit an excellent charge performance despite the electrode material
layer being relatively thick and highly porous. The electrochemical reactor
contained 20 single cells stacked together with 30 A h of nickel hydroxide and 15 A
h of metal hydride as the positive and negative electrodes, respectively. The
electrochemical tests showed that the stack exhibited a high hydrogen production
efficiency with a maximum current efficiency of 95.3% for hydrogen production and a
hydrogen evolution amount per unit input electrical energy of 259.1 mL/W h at 0.2
C. At high current densities (2.0 C), a rapid temperature increase was also
observed during the charging process, which led to a reduction of the hydrogen
production efficiency. Therefore, further design modifications are needed to
control heat generation during operation of the device. (C) 2016 Published by
Elsevier Ltd.
Recent environmental and economic considerations have made the focus of attention
new treatment processes of the residual (tail) gas of Claus plants, based on the
oxidative decomposition of H2S to Sulphur and Hydrogen, In this work, the thermal,
oxidative decomposition of H2S in an homogeneous phase has been studied by
developing a comprehensive chemical kinetic model for the oxidation of H2S in a low
oxygen atmosphere, by varying the O-2/H2S ratio (0.2-0.35), residence time (150-300
ms), and process temperatures (900-1100 C-omicron). The kinetic model has been
developed by combining existing models for the oxidation of H2S, with no tuning of
the parameters or kinetic constants and validated in relation to the experimental
data. The results show a very good agreement with the experimental values at higher
temperatures (1100 C-omicron). At 900 C-omicron, the H2S conversion is well
predicted by the model, whereas the H-2 yield and SO2 selectivity are consistently
higher than the experimental values. A sensitivity analysis for the complex kinetic
system has highlighted the importance of the reaction (O-2 + SO + SO) at lower
temperatures. (C) 2016 Elsevier Ltd. All rights reserved.
Flow Induced Motions (FIMs) of rigid circular cylinders, and particularly VIV
(Vortex Induced Vibrations) and galloping, are induced by alternating lift. The
VIVACE (VIV for Aquatic Clean Energy) Converter uses single or multiple cylinders,
in tandem, on elastic end-supports, in synergistic FIM, to convert MHK energy to
electricity. Selectively distributed surface roughness is applied to enhance FIM
and increase efficiency. In this paper, two cylinders are Used in tandem with
center-to-center spacing of 1.57, 2.0 and 2.57 diameters, harnessing damping ratio
0.004<zeta < 0.24, for Reynolds number 30,000 < Re < 120,000. The virtual spring-
damping system V-ck in the Marine Renewable Energy Laboratory (MRELab) enables
embedded computer-controlled change of viscous-damping and spring-stiffness for
fast and mathematically correct oscillator realization, without including the
hydrodyllamic force in the closed control loop. Experimental results for
oscillatory response, energy harvesting, and efficiency are presented and the
envelope of optimal power is derived. All the experiments were conducted in the Low
Turbulence Free Surface Water (LTFSW) Channel of the MRELab of the University of
Michigan. The main conclusions are: (1) For the tested cylinder spacing, two
cylinders harness power is between 2.56 and 13.49 times the power of a single
cylinder, the efficiency of two cylinders is between 2.0 and 6.68 of a single
cylinder. (2) The MHK power harnessed by the upstream cylinder is increased by up
to 100%, affected by the downstream cylinder. (3) The MHK power harnessed by the
downstream cylinder and its FIM are affected to a lesser extent by the interaction.
(4) VIVACE can harness energy from flows as slow as 0.4 m/s with no upper limit in
flow velocity. (5) Close spacing and high spring Stiffness yield highest harnessed
power. (6) The optimal harnessed power shifts to softer springs as spacing
increases. (C) 2017 Elsevier Ltd. All rights reserved.
Omeprazole is one of the world-wide most frequently prescribed and administered
pharmaceuticals in humans for the relief of gastro-intestinal disorders. Despite
its high worldwide consumption, omeprazole is rarely detected in urban wastewaters
and environmental waters. On the other hand, its human urinary metabolites and
transformation products formed through abiotic processes in the environment have
been recently documented. Despite these available data, however, there is still a
lack of information on the extent of environmental fate and occurrence, on
elimination mechanisms and efficiencies in waste water treatment plants. In this
study, the relevance of photodegradation processes on the environmental persistence
of omeprazole under simulated and solar irradiation was investigated.
Photodegradation experiments were performed in distilled water, lake, river and
seawater, and revealed that the different matrix in natural waters significantly
affect the photolytic behavior of the investigated compound. Overall, the results
highlight that photodegradation process by solar irradiation significantly
contributes to omeprazole degradation and elimination from the aquatic environment.
TPs formed through the process were identified and elucidated by using liquid
chromatography high resolution mass spectrometry. In total seven TPs were
identified, among of which four were also detected as hydrolysis TPs. The Microtox
bioassay showed that solar photolysis is efficient to detoxify omeprazole and its
TPs in aqueous solutions. Finally, a systematic investigation was conducted in
order to provide information on removal efficiency and occurrence of omeprazole and
its metabolites/TPs in 8 WWTPs in North West Greece by performing target and
suspect screening analysis. The findings revealed the presence of both parent
compound and metabolites/TPs in wastewaters. Given, however, the scarce detection
of omeprazole at fairly low concentration levels, from analytical and environmental
point of view, further attention should be given to metabolites/fPs instead of the
parent compound. (C) 2017 Elsevier B.V. All rights reserved.
An important and plausible impact of a changing global climate is altered power
generation from hydroelectric dams. Here we project 21st century global hydropower
production by forcing a coupled, global hydrological and dam model with three
General Circulation Model (GCM) projections run under two emissions scenarios. Dams
are simulated using a detailed model that accounts for plant specifications,
storage dynamics, reservoir bathymetry and realistic, optimized operations. We show
that the inclusion of these features can have a non-trivial effect on the simulated
response of hydropower production to changes in climate. Simulation results
highlight substantial uncertainty in the direction of change in globally aggregated
hydropower production (similar to-5 to +5% change in mean global production by the
2080s under a high emissions scenario, depending on GCM). Several clearly impacted
hotspots are identified, the most prominent of which encompasses the Mediterranean
countries in southern Europe, northern Africa and the Middle East. In this region,
hydropower production is projected to be reduced by approximately 40% on average by
the end of the century under a high emissions scenario. After accounting for each
country's dependence on hydropower for meeting its current electricity demands, the
Balkans countries emerge as the most vulnerable (similar to 5-20% loss in total
national electricity generation depending on country). On the flipside, a handful
of countries in Scandinavia and central Asia are projected to reap a significant
increase in total electrical production (similar to 5-15%) without investing in new
power generation facilities. (C) 2017 Elsevier B.V. All rights reserved.
The hydrothermal electrochemical deposition (HED) synthesis NiSe2 as counter
electrode(CE) of dyesensitized solar cells(DSSCs), which shows excellent catalytic
activity in reduction of triiodide. Hydrothermal and electro-deposition(ED) have
been widely used to synthetize NiSe2, herein, we fistly introduce the HED to
produce the NiSe2 material as the CE of DSSCs. In addition, cyclic voltammetry(CV)
curves, Tafel plots and electrochemical impedance spectroscopy(EIS) indicated that
HED-NiSe2 as CE shows better electrocatalytic activity for reduction of
iodine/iodide electrolyte than ED-NiSe2 and Pt. The DSSC fabricated by the HED-
NiSe2 CE displays a solar-to-electricity conversion efficiency of 8.24% comparing
with 7.68% the convention Pt as reference, and significant higher than that of
based on the ED-NiSe2(7.97%). Furthermore, we demonstrate that the HED method is a
promising way to design and synthesize advanced CE materials for utilizing solar
energy. (C) 2017 Elsevier B. V. All rights reserved.
Hydroidfest 2016 took place on September 23-25 at the UC Davis Bodega Marine
Laboratory in Bodega Bay, CA. The meeting brought together cnidarian researchers,
with an emphasis on those studying hydrozoans, from North America and other parts
of the world. The scientific topics discussed were diverse, including sessions
focused on development, regeneration, aging, immunology, symbiosis, and
neurobiology. Thanks to the application of modern biological technologies,
hydrozoans and other cnidarians are now fertile ground for research in numerous
disciplines. Moreover, their amenability to comparative approaches is a powerful
asset that was repeatedly showcased during the meeting. Here, we give a brief
account of the work that was presented and the opportunities that emerged from the
ensuing discussions.
Objectives. To describe (i) the clinical characteristics of workers, exposed to
hymenoptera stings, with an ascertained diagnosis of Hymenoptera Venom Allergy
(HVA), (ii) the specific role of occupational exposure, (iii) the effect of Venom
Immunotherapy (VIT) in reducing the severity of allergic episodes in workers
exposed to repeated stings of hymenoptera, and (iv) the management of the
occupational consequences caused by allergic reactions due to hymenoptera stings.
Methods. Between 2000 and 2013 an observational study, including patients referred
to the regional reference hospital of Liguria, Italy, with an ascertained diagnosis
of HVA and treated with VIT, was performed. A structured questionnaire was
administered to all patients to investigate the occupational features of allergic
reactions. These were graded according to standard systems in patients at the first
episode, and after re-stings, during VIT. Results. One-hundred and 8four out of the
202 patients referred had a complete data set. In 32 (17.4%) patients, the allergic
reaction occurred during work activities performed outdoor. Of these, 31.2%
previously stung by hymenoptera at work, and receiving VIT, were re-stung during
occupational activity. The grades of reaction developed under VIT treatment
resulted clinically less severe than of those occurred at the first sting (p-value
= 0.031). Conclusion. Our findings confirmed the clinical relevance of HVA, and
described its occupational features in outdoor workers with sensitization,
stressing the importance of an early identification and proper management of the
professional categories recognized at high risk of hymenoptera stings. The
Occupational Physician should be supported by other specialists to recommend
appropriate diagnostic procedures and the prescription of VIT, which resulted an
effective treatment for the prevention of episodes of severe reactions in workers
with a proven HVA.
The separation of aromatic/aliphatic mixtures is significant in chemical industry.
Pervaporation has attracted increasing attention due to its low energy consumption
and environmentally friendly process. However, the formation of membranes mostly
use toxic organic solvents, whereas in this study water was used instead to prepare
membrane in separating aromatic/aliphatic mixtures. W3000 were dispersed in water
to form micelles, which were then deposited onto the surface of the tubular porous
ceramic substrate through the negative pressure-driven assembly method. The
emulsion and composite membranes were characterized by TEM, SEM and FTIR. The
crosslinking density of W3000 was also tested using NMR XLD analyzing system. The
membranes were used for separating aromatic/aliphatic mixtures through
pervaporation. The results showed that compared with the membrane prepared by DMF,
the pervaporation separation index (PSI) of the composite membrane formed using
water as solvent was 3.3-fold increased for separating toluene/n-heptane mixtures.
The as-prepared composite membranes showed a better comprehensive pervaporation
performance. This facile strategy may have a potential in the application of
pervaporation for separating aromatic/aliphatic mixtures in industry. (C) 2017
Elsevier B.V. All rights reserved.
Broadband infrared response has attracted great attention due to its potential
applications in silicon based photodetectors. We have studied broadband infrared
response of sulfur hyperdoped silicon under femtosecond laser irradiation. The
fabricated PN photodiodes exhibit several photoresponse spectral peaks in near and
mid-infrared region of electromagnetic spectrum. The onset energies corresponding
to the distinct sub-band gap photoresponse features are consistent with the active
energy levels of known sulfur within the silicon band-gap. This technique may offer
a promising approach to fabricate low-cost broadband silicon based detectors. (C)
2017 Elsevier B. V. All rights reserved.
Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia
favors malignant cell growth by providing energy to cancer cells. Clinical studies
also showed an increased risk of diabetes being associated with different types of
cancers. In addition, poorly regulated glucose metabolism in diabetic patients is
often found with increased levels of chronic inflammatory markers, e.g.,
interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, and emerging
evidence has highlighted activation of the immune response in the progression and
development of cancer cells. Therefore, uncontrolled proinflammatory responses
could conceivably create a chronic inflammatory state, promoting a tumor-favorable
microenvironment and potentially triggering immune overactivation and cancer
growth. To further understand how hyperglycemia contributes to immune
overactivation, the tumor microenvironment and the development of chronic
inflammation-associated tumors may provide insights into tumor biology and
immunology. This paper provides a brief introduction to hyperglycemia-associated
diseases, followed by a comprehensive overview of the current findings of
regulatory molecular mechanisms of glycosylation on proteoglycans in the
extracellular matrix under hyperglycemic conditions. Then, the authors discuss the
role of hyperglycemia in tumorigenesis (particularly in prostate, liver,
colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia
to chronic inflammation. The authors end with a brief discussion on the future
perspectives of hyperglycemia/tumorigenesis and potential applications of
alternative effective therapeutic strategies for hyperglycemia-associated cancers.
(C) 2016 Elsevier Ireland Ltd. All rights reserved.
The primary immunodeficiency (PID) diseases comprise a heterogeneous group of
inherited disorders of immune function. Technical advancements in whole-genome,
whole-exome, and RNA-sequencing have seen the explosion of genetic discoveries in
the field of PIDs. The present review aims to focus on a group of immunodeficiency
disorders associated with elevated levels of IgM (hyper IgM; HIGM) and provides a
clinical differential diagnosis. Most patients present for evaluation of
immunodeficiency due to recurrent infections, and laboratory studies show either a
clear isolated elevation of serum immunoglobulin M (IgM) with low or absent IgG,
IgA, and IgE. Alternatively, IgM levels may be normal or moderately elevated while
other serum immunoglobulins are reported below the norms for age but not absent.
Mechanistically, these disorders are recognized as defects in immunoglobulin (Ig)
class switch recombination (CSR). Importantly, to safeguard genetic stability, CSR
utilizes elements of the DNA repair machinery including multi-protein complexes
involved in mismatch repair (MMR). Therefore, it is not uncommon for defects in the
DNA repair machinery, to present with laboratory findings of HIGM. This review will
discuss clinical phenotypes associated with congenital defects associated with
HIGM. Clinical manifestations, relevant immunologic testing, inheritance pattern,
molecular diagnosis, presumed pathogenesis, and OMIM number, when annotated are
compiled. Accepted therapeutic options, when available, are reviewed for each
condition discussed. (C) 2016 American Academy of Allergy, Asthma & Immunology.
PurposeTo demonstrate the feasibility of mapping intracellular pH within the in
vivo rodent heart. Alterations in cardiac acid-base balance can lead to acute
contractile depression and alterations in Ca2+ signaling. The transient reduction
in adenosine triphosphate (ATP) consumption and cardiac contractility may be
initially beneficial; however, sustained pH changes can be maladaptive, leading to
myocardial damage and electrical arrhythmias. MethodsSpectrally selective
radiofrequency (RF) pulses were used to excite the HCO3- and CO2 resonances
individually while preserving signal from the injected hyperpolarized [1-C-
13]pyruvate. The large flip angle pulses were placed within a three-dimensional
(3D) imaging acquisition, which exploited CA-mediated label exchange between HCO3-
and CO2. Images at 4.5 x 4.5 x 5 mm(3) resolution were obtained in the in vivo
rodent heart. The technique was evaluated in healthy rodents scanned at baseline
and during high cardiac workload induced by dobutamine infusion. ResultsThe
intracellular pH was measured to be 7.150.04 at baseline, and decreased to 6.90 +/-
0.06 following 15 min of continuous -adrenergic stimulation. ConclusionsVolumetric
maps of intracellular pH can be obtained following an injection of hyperpolarized
[1-C-13]pyruvate. The new method is anticipated to enable assessment of stress-
inducible ischemia and potential ventricular arrythmogenic substrates within the
ischemic heart. Magn Reson Med 77:1810-1817, 2017. (c) 2016 The Authors Magnetic
Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
International Society for Magnetic Resonance in Medicine. This is an open access
article under the terms of the Creative Commons Attribution License, which permits
use, distribution and reproduction in any medium, provided the original work is
properly cited.
Two-person neuroscience, a perspective in understanding human social cognition and
interaction, involves designing immersive social interaction experiments as well as
simultaneously recording brain activity of two or more subjects, a process termed
"hyperscanning." Using newly developed imaging techniques, the interbrain
connectivity or hyperlink of various types of social interaction has been revealed.
Functional near-infrared spectroscopy (fNIRS)-hyperscanning provides a more
naturalistic environment for experimental paradigms of social interaction and has
recently drawn much attention. However, most fNIRS-hyperscanning studies have
computed hyperlinks using sensor data directly while ignoring the fact that the
sensor-level signals contain confounding noises, which may lead to a loss of
sensitivity and specificity in hyperlink analysis. In this study, on the basis of
independent component analysis (ICA), a source-level analysis framework is proposed
to investigate the hyperlinks in a fNIRS two-person neuroscience study. The
performance of five widely used ICA algorithms in extracting sources of interaction
was compared in simulative datasets, and increased sensitivity and specificity of
hyperlink analysis by our proposed method were demonstrated in both simulative and
real two-person experiments. (C) 2017 Society of Photo-Optical Instrumentation
Engineers (SPIE)
Depression and hypertension frequently present together in clinical practice.
Evaluating the interaction between depression and hypertension would help
stakeholders better understand the value of depression prevention in primary care.
This retrospective study aimed to evaluate the excessive burden of depression on
overall health and on health care utilization expenditure among hypertensive
patients. A total of 7019 hypertensive patients (ICD-9-CM: 401) were identified
from the 2012 Medical Expenditure Panel Survey (MEPS 2012) data, of which 936
patients had depression (ICD-9-CM: 311). Hypertension with depression was
associated with worse health status (physical component score, -3.97 [17.9%
reduction]; mental component score, -9.14 [9% reduction]), higher utilization of
health care services (outpatient visits, 6.4 [63.8% higher]; nights of
hospitalization, 0.9 [100% higher]; medication prescription, 22.6 [76.8% higher]),
and higher health care expenditures (inpatient, $1953.2 [72% higher]; prescription
drugs, $1995.5 [82% higher]).
Objective: To explore the effect of depression on the sleep quality, and the
circadian rhythm of ambulatory blood pressure in patients with essential
hypertension. Methods: A total of 73 older patients with hypertension were screened
for depression and divided into two groups. The Pittsburgh Sleep Quality Index
(PSQI) and the circadian rhythm of ambulatory blood pressure were compared between
the non-depressed (control) and depressed (case) group. Results: In the case group,
24 h ambulatory SBP and DBP, and nocturnal SBP and DBP were higher than in the
control group, and the circadian rhythm of non-dipper was higher (67.22% vs 40.13%,
P < 0.01). There was a positive correlation between PSQI and depression (r = 0.432,
P < 0.01). Conclusion: There was a significant correlation between sleep quality
and depression in older patients with hypertension. Depression increases the
circadian rhythm of non-dipper in older patients with hypertension. (C) 2017
Elsevier Ltd. All rights reserved.
Pressure overload has been shown to induce mitogen activated protein kinases
(MAPKs) and reactivate the atrial natriuretic factor in the heart. To test the
sensitivity of these signals to pressure overload, we assayed the activity of MAPKs
extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 in
protein lysates from the left ventricle (LV) or white blood cells (WBC) isolated
from aortic banded mice with varying levels of pressure overload. In separated mice
we measured atrial natriuretic factor mRNA levels by Northern blotting. As
expected, a significant induction of atrial natriuretic factor mRNA levels was
observed after aortic banding, and it significantly correlated with the trans-
stenotic systolic pressure gradient but not with the LV weight: body weight ratio.
In contrast, a significant correlation with systolic pressure gradient or LV
weight: body weight ratio was observed for all of the MAPK activity detected in LV
samples or WBCs. Importantly, LV activation of MAPKs significantly correlated with
their activation in WBCs from the same animal. To test whether MAPK activation in
WBCs might reflect uncontrolled blood pressure levels in humans, we assayed
extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38
activation in WBCs isolated from normotensive volunteers, hypertensive patients
with controlled blood pressure values, or hypertensive patients with uncontrolled
blood pressure values. Interestingly, in hypertensive patients with controlled
blood pressure values, LV mass and extracellular signal-regulated kinase
phosphorylation were significantly reduced compared with those in hypertensive
patients with uncontrolled blood pressure values. These results suggest that MAPKs
are sensors of pressure overload and that extracellular signal-regulated kinase
activation in WBCs might be used as a novel surrogate biomarker of uncontrolled
human hypertension. (Hypertension. 2010;55:137-143.)
Background: Hypertension has been associated to diabetes, and participates in the
development of diabetic complications. The spontaneously hypertensive rat (SHR) is
the gold standard model for the study of hypertension, and experimental diabetes
has been currently investigated in SHR. Wistar-Kyoto rat is usually taken as
control for SHR, however, regarding the glycemic homeostasis, WKY may be similar to
SHR, when compared to the standard Wistar rat, importantly affecting the
interpretation of data. Slc2a4 gene, which encodes the GLUT4 protein, is expressed
in insulin-sensitive tissues, such as muscle cells and adipocytes, and alteration
in Slc2a4/GLUT4 expression is inversely related to glycemic levels. We investigated
the effect of diabetes on the expression of Slc2a4/GLUT4 and glycemic control in
Wistar-Kyoto and SHR. Findings: Slc2a4 mRNA (Northern-blotting) and GLUT4 protein
(Western-blotting) were investigated in skeletal muscles (soleus and extensor
digitorum longus) of Wistar, Wistar-Kyoto and SHR, rendered or not diabetic for 1
month. Non-diabetic SHR shows hyperinsulinemia, and unaltered GLUT4 expression. The
hyperglycemia was significantly attenuated in diabetic Wistar-Kyoto and SHR,
compared to that observed in diabetic Wistar, although all of them presented the
same hypoinsulinemic levels. Besides, diabetes significantly reduced Slc2a4/GLUT4
in Wistar, as expected; however, that was not observed in diabetic Wistar-Kyoto and
SHR. Conclusions: Non-diabetic SHR is insulin resistant, despite unaltered GLUT4
expression. Diabetic Wistar-Kyoto and diabetic SHR presented high Slc2a4/GLUT4
expression in skeletal muscle, as compared to diabetic Wistar. This Slc2a4/GLUT4
regulation does not depend on insulin level and possibly protects the WKY and SHR
from severe glycemic impairment.
Hypertriglyceridemia (HTG) aggravates the course of acute pancreatitis (AP).
Intestinal barrier dysfunction is implicated in the pathogenesis of AP during which
dysbiosis of intestinal microbiota contributes to the dysfunction in intestinal
barrier. However, few studies focus on the changes in intestine during HTG-related
acute necrotizing pancreatitis (ANP). Here, we investigated the changes in
intestinal microbiota and Paneth cell antimicrobial peptides (AMPs) in HTG-related
ANP (HANP) in rats. Rats fed a high-fat diet to induce HTG and ANP was induced by
retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Rats
were sacrificed at 24 and 48 h, respectively. Pancreatic and ileal injuries were
evaluated by histological scores. Intestinal barrier function was assessed by
plasma diamine oxidase activity and D-lactate level. Systemic and intestinal
inflammation was evaluated by tumor necrosis factor alpha (TNF alpha), interleukin
(IL)-1 beta and IL-17A expression. 16S rRNA high throughput sequencing was used to
investigate changes in intestinal microbiota diversity and structure. AMPs (alpha-
defensin5 and lysozyme) expression was measured by real-time polymerase chain
reaction (PCR) and immunofluorescence. The results showed that compared with those
of normal-lipid ANP (NANP) groups, the HANP groups had more severe
histopathological injuries in pancreas and distal ileum, aggravated intestinal
barrier dysfunction and increased TNF alpha, IL-1 beta, and IL-17A expression in
plasma and distal ileum. Principal component analysis showed structural segregation
between the HANP and NANP group. alpha-Diversity estimators in the HANP group
revealed decreased microbiota diversity compared with that in NANP group. Taxonomic
analysis showed dysbiosis of intestinal microbiota structure. In the HANP group, at
phyla level, Candidatus_Saccharibacteria and Tenericutes decreased significantly,
whereas Actinobacteria increased. At genus level, Allobaculum, Bifidobacterium, and
Parasutterella increased significantly, while Alloprevotella, Anaerotruncus,
Candidatus_Saccharimonas, Christensenellaceae_R-7_group,
Rikenellaceae_RC9_gut_group, Ruminiclostridium_5, Ruminococcaceae_UCG-005, and
Ruminococcaceae_UCG-014 decreased. Compared with those in the NANP rats, mRNA
expression of lysozyme and alpha-defensin5 and protein expression of lysozyme
decreased significantly in the HANP rats. Moreover, in the NANP rats and the HANP
rats, Allobaculum abundance was inversely correlated with lysozyme expression,
while Anaerotruncus abundance was positively correlated with it by Spearman test.
In conclusion, intestinal microbiota dysbiosis and decreased AMPs of Paneth cells
might participate in the pathogenesis of intestinal barrier dysfunction in HANP.
The present study investigated the role of epidermal stem cell-expressed microRNA
let-7b in the pathogenesis of hypertrophied anal papillae. Hypertrophied anal
papillae were examined for the presence of epidermal stem cells. Epidermal stem
cells were identified using flow cytometry and immunofluorescent staining for the
cell surface markers, integrin alpha 6 and integrin beta 1 subunits. Expression
levels of microRNA let-7b in alpha 6+/beta 1+ and alpha 6-/beta 1-cells were
compared using reverse transcription-quantitative polymerase chain reaction and
northern blotting. Lentivirus-mediated expression of microRNA let-7b in epidermal
stem cells was utilized in order to study the effects of this microRNA on the cell
cycle proteins, cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4). MicroRNA
let-7b-overexpressing cells were examined using flow cytometry, in order to
determine the effects of the microRNA on cell cycle progression. alpha 6+/beta
1+epidermal stem cells were identified in hypertrophic anal papillae. Following
isolation and enrichment of the alpha 6+/beta 1+population, these cells were found
to have a rapid rate of proliferation in vitro. The expression of cell cycle-
related proteins was elevated in this population, compared with that in alpha
6-/beta 1-cells. The expression of microRNA let-7b in alpha 6+/beta 1+epidermal
stem cells was significantly lower than that in alpha 6-/beta 1-cells. Two microRNA
let-7b target genes, CCND1 and CDK4, were found to be upregulated in alpha 6+/beta
1+cells. When the exogenous precursor, microRNA let-7, was overexpressed in alpha
6+/beta 1+ epidermal stem cells, the cell proliferation rate was significantly
lower than that in cells expressing microRNA let-7 containing a mutated seed
sequence. The addition of exogenous microRNA let-7 resulted in an increased
expression level of mature microRNA let-7b, while the expression of CCND1 and CDK4
was reduced. Epidermal stem cells transfected with microRNA let-7b were arrested in
the G2/M phase and the percentage of cells in S-phase was significantly reduced. In
conclusion, let-7b expression results in upregulation of the cell cycle-related
proteins, CCND1 and CDK4, resulting in the excessive proliferation that leads to
the formation of hypertrophic anal papillae.
Objective: The current study examined whether (a) Attention-Deficit/Hyperactivity
Disorder (ADHD) symptoms were associated with dysregulation of stress-related
mechanisms, and (b) whether ADHD symptoms interact with affective disorders in
their association with dysregulated stress-related mechanisms. Methods: Data were
obtained from 2307 subjects participating in the Netherlands Study of Depression
and Anxiety. Stress-related mechanisms were reflected by the following biomarkers:
(1) hypothalamic pituitary -adrenal axis indicators (salivary cortisol awakening
curve, evening cortisol, cortisol suppression after a 0.5 mg dexamethasone
suppression test (DST)); (2) autonomic nervous system measures (heart rate, pre-
ejection period, respiratory sinus arrhythmia); (3) inflammatory markers (C-
reactive protein, interleukin-6, tumor necrosis factor-alpha); (4) brain-derived
neurotrophic factor. ADHD symptoms were measured using Conners' Adult ADHD Rating
Scale and used both dichotomous (High ADHD symptoms (yes/no)) and continuous
(Inattentive symptoms, Hyperactive/Impulsive symptoms, and the ADHD index).
Results: Regression analyses showed associations between High ADHD symptoms,
Inattentive symptoms, the ADHD index and a higher cortisol awakening curve, between
Hyperactive/Impulsive symptoms and less cortisol suppression after DST, and between
Inattentive symptoms and a longer pre-ejection period. However, the associations
with the cortisol awakening curve disappeared after adjustment for depressive and
anxiety disorders. No associations were observed between ADHD symptoms and
inflammatory markers or BDNF. ADHD symptoms did not interact with affective
disorders in dysregulation of stress-related mechanisms. Conclusion: Some
associations were observed between ADHD symptoms, the HPA-axis, and the pre-
ejection period, but these were mostly driven by depressive and anxiety disorders.
This study found no evidence that ADHD symptomatology was associated with
dysregulations in inflammatory markers and BDNF. Consequently, ADHD symptoms did
not confer an added risk to the disturbances of stress-related mechanisms in an -
already at-risk - population with affective disorders. (C) 2017 Elsevier Ltd. All
rights reserved.
The history of biochemistry and molecular biology is replete with examples of
erroneous theories that persisted for considerable lengths of time before they were
rejected. This paper examines patterns of dissolution of three such erroneous
hypotheses: The idea that nucleic acids are tetrads of the four nucleobases ('the
tetranucleotide hypothesis'); the notion that proteins are collinear with their
encoding genes in all branches of life; and the hypothesis that proteins are
synthesized by reverse action of proteolytic enzymes. Analysis of these cases
indicates that amassed contradictory empirical findings did not prompt critical
experimental testing of the prevailing theories nor did they elicit alternative
hypotheses. Rather, the incorrect models collapsed when experiments that were not
purposely designed to test their validity exposed new facts.
Drawing together social psychologists' concerns with equality and cognitive
psychologists' concerns with scientific inference, 6 studies (N = 841) showed how
implicit category norms make the generation and test of hypothesis about race
highly asymmetric. Having shown that Whiteness is the default race of celebrity
actors (Study 1), Study 2 used a variant of Wason's (1960) rule discovery task to
demonstrate greater difficulty in discovering rules that require specifying that
race is shared by White celebrity actors than by Black celebrity actors. Clues to
the Whiteness of White actors from analogous problems had little effect on
hypothesis formation or rule discovery (Studies 3 and 4). Rather, across Studies 2
and 4 feedback about negative cases-non-White celebrities-facilitated the discovery
that White actors shared a race, whether participants or experimenters generated
the negative cases. These category norms were little affected by making White
actors' Whiteness more informative (Study 5). Although participants understood that
discovering that White actors are White would be harder than discovering that Black
actors are Black, they showed limited insight into the information contained in
negative cases (Study 6). Category norms render some identities as implicit
defaults, making hypothesis formation and generalization about real social groups
asymmetric in ways that have implications for scientific reasoning and social
equality.
Microglial cells are phagocytic cells of the central nervous system (CNS) and have
been proposed to be a primary component of the innate immune response and maintain
efficient CNS homeostasis. Microglial cells are activated during various phases of
tissue repair and participate in various pathological conditions in the CNS.
Following spinal cord injury (SCI), anoxemia is a key problem that results in
tissue destruction. Hypoxia-inducible factor 1-alpha (HIF-1 alpha) may protect
hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions.
However, numerous studies have revealed that hypoxia upregulates HIF-1 alpha
expression leading to the death of microglial cells. The present study investigated
the alterations in HIF-1 alpha expression levels and the mechanism of autophagic
cell death mediated by HIF-1 alpha in microglial cells induced by hypoxia. Hypoxia
was demonstrated to induce HIF-1 alpha expression and autophagic cell death in
microglial cells. Enhanced autophagy reduced cell death during the initial stages
by restraining the functions of autophagy-associated genes (microtubule-associated
protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate and Beclin-1) and
modulating the expression of inflammatory cytokines (tumor necrosis factor-alpha
and interleukin-1 beta). Target value was determined by Cell Counting Kit 8 and
cell death by flow cytometry. Transmission electron microscopy, immunohistochemical
staining, reverse transcription-quantitative polymerase chain reaction, western
blotting, and ELISA were used for further analysis. However, increased expression
of HIF-1 alpha induced cell death and autophagic cell death in microglial cells.
Furthermore, the effects of the HIF-1 alpha inhibitor 2-methoxyestradiol and HIF-1
alpha small interfering RNA on the death and autophagy of microglial cells in vitro
were investigated. These investigations revealed the suppression of autophagy, the
decrease of cell viability and the increase of inflammatory cytokines results from
HIF-1 alpha inhibition or HIF-1 alpha silencing. In conclusion, the results
indicated that appropriate expression of HIF-1 alpha can ameliorate autophagic cell
death of microglial cells associated with hypoxia, and may provide a novel
therapeutic approach for SCI associated with microglial cell activation.
To perform pathogenic and pathological investigations on explosive epidemics of
Hyriopsis cumingii Lea in Hunan Province, China between 2005 and 2011. We isolated
pathogenic bacteria SJ-2 from naturally infected Hyriopsis cumingii Lea, and the
SJ-2 strain was artificial infected into the normal Hyriopsis cumingii Lea by axe
foot injection method. The strain was identified according to conventional
bacteriological isolation and identification and molecular biology methods, and
pathological changes caused by the bacteria in diseased mussel tissues were
observed. According to morphological and culture characteristics, physiological and
biochemical tests and 16S rDNA molecular identification, SJ-2 strain shares 99%
sequence identity with the type strain of Aeromonas veronii (A. Veronii). Results
for antibiotic susceptibility tests showed that among 50 drugs, A. Veronii was
highly sensitive to 15 drugs, moderately sensitive to 5 drugs, and showed drug
resistance to left drugs. Macroscopical lesions, pathological changes and
cytopathology were summarized. The pathogenic bacteria SJ-2 was isolated from
Hyriopsis cumingii Lea affected by explosive epidemic disease, and was identified
as A. Veronii. SJ-2 strain caused multi-organ lesions and function failure in
corresponding organs in the Hyriopsis cumingii Leal, resulting in gradually
decreased and disappeared normal physiological metabolism, and eventually death.
C1q is the target recognition sequence of the classical complement pathway and a
major link that connects innate and acquired immunity. In this study, a C1qDC
homolog, HcC1qDC5, from the triangle-shell pearl mussel (Hyriopsis cumingii) was
identified. The complete nucleotide sequence of HcC1qDC5 cDNA consists of a 5'-
untranslated terminal region (UTR) of 123 bp, a 3'-UTR of 105 bp with a poly(A)
tail, and an open reading frame (ORF) of 1344 bp, which encodes a polypeptide of
447 amino acids. HcC1qDC5 contains a signal peptide and three typical C1q domains.
The HcC1qDC5 gene was expressed in all tested tissues, with the highest expression
in the. mantle. Staphylococcus aureus or Vibrio parahaemolyticus infection
increased the mRNA transcript levels of HcC1qDC5 in the hepatopancreas and mantle.
The recombinant HcC1qDC5 protein could bind to Gram-negative and Gram-positive
bacteria as well as to different PAMPs (LPS and PGN). RNAi results showed that
HcC1qDC5 was involved in V. parahaemolyticus-induced HcTNF and HcWAP expression.
The combined results demonstrated that HcC1qDC5 participates in the innate immunity
of H. cumingii. (C) 2016 Elsevier Ltd. All rights reserved.
BACKGROUND: In order to study the novel genes related to rat embryonic
implantation, a novel implantation-associated gene, Iag-1, was identified and
characterized from rat uterus of early pregnancy. Iag-1 was initially derived from
suppressive subtracted hybridization of a cDNA library of rat uterus, which was
used to analyse differentially expressed genes between the preimplantation and
implantation period. METHODS:The full-length cDNA sequence of Iag-1 was cloned from
rat uterus on D5.5 of pregnancy by 5'- and 3'-RACE. The expression of Iag-1 in the
uterus of early pregnancy, pseudopregnancy, artificial decidualization and
activation of delayed implantation was detected by northern blotting, in situ
hybridization, western blotting and immunofluorescence. Endometrial stromal cells
(ESCs) were isolated from rat uterus. The effect of Iag-1 on ESCs proliferation and
apoptosis were determined by MTT assay, TUNEL and Hoechst staining. Apoptosis-
related proteins in ESCs were detected by western blotting. RESULTS: Differential
patterns of Iag-1 expression were detected in rat embryo and in the uterus during
the peri-implantation period. Iag-1 was specifically localized in glandular
epithelium and luminal epithelium. In contrast, the expression of Iag-1 was not
significantly altered in uterus of pseudopregnancy and artificial decidualization,
but was significantly increased in the uterus after activation of delayed
implantation. Stable expression of introduced Iag-1 inhibited the proliferation of
in vitro-cultured ESCs. Significant apoptosis was also detected in the ESCs
overexpressing Iag-1 , along with the enhancement of p53 and Bax protein
expression. CONCLUSIONS:Overexpression of Iag-1 can inhibit ESCs proliferation and
induce ESCs apoptosis, and p53 and Bax may play an important role in the process of
Iag-1-induced apoptosis.
The concepts developed by Ian Hacking during his lectures at the CollSge de France
(2000-2006) have provided an important contribution to the debates within the field
of philosophy of psychiatry. Professor at the Chair of Philosophy and History of
Scientific Concepts after Michel Foucault, Hacking is the author of a reflection on
the classification of mental disorders, which arises from the problem of the
natural kinds. In order to explain the case studies developed in Hacking's Paris
lectures, we first go back to the definition of a series of concepts, then we
discuss the status of his scientific metaphors. Finally we analyze the relationship
between the notions, respectively, of "transient mental illness" and "culture-bound
syndrome". We emphasize that the latter derives from the Canadian transcultural
psychiatry.
Introduction: Combination therapy with infliximab and immunomodulators is superior
to monotherapy, resulting in better outcomes and higher trough levels of
infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough
levels has not been adequately investigated. We evaluated the impact of concomitant
immunomodulation on adalimumab trough levels in patients on scheduled maintenance
therapy. Method: We conducted a prospective observational, cross-sectional study of
all inflammatory bowel disease patients on maintenance therapy who had adalimumab
trough levels measured between January 2013 and January 2016. Drug level and anti-
drug antibody measurements were performed on sera using a solid phase assay.
Pairwise comparison of means was used to compare trough levels in patients with and
without concomitant immune modulator therapy. Results: In total, 79 patients were
included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%)
were on alternate weeks. Median adalimumab trough levels were comparable in
patients with and without clinical remission (6.8 mu g/ml (IQR 5.6-8.1) versus 6.7
mu g/ml (IQR 3.9-8.1), respectively. Patients with an elevated faecal calprotectin
>250 mu g/g had lower adalimumab trough levels (median 6.7, IQR 3.9-8) compared to
patients with faecal calprotectin <250 mu g/g (median 7.7, IQR 6.1-8.1) though this
did not achieve statistical significance (p = .062). Median adalimumab trough
levels among patients on concurrent immunomodulators was 7.2 mu g/ml (IQR 5.7-8.1)
compared to those not on concurrent immunomodulator, 6.1 mu g/ml (IQR 2.7-7.7, p
= .0297). Conclusion: Adalimumab trough levels were significantly higher in
patients on concurrent immunomodulators during maintenance therapy. There was a
trend towards a lower adalimumab trough level in patients with elevated
calprotectin.
This paper presents an edge boosting method for I/O output buffer using signal
front detection digital control circuit. The presented architecture detects I/O
data or clock signal transitions and activates additional drive strength fingers in
the output buffer resulting in output current increase which improves the slew
rate, compensating for losses in transmission lines. The presented edge boosting
method can be used in the I/O circuits of such standards as DDR(Double Data Rate),
USB(Universal Serial Bus), PCI(Peripheral Component Interconnect) etc.
This paper deals with the susceptibility prediction of integrated circuits against
the conducted interference coupled on their power supply pins. An integrated
operational amplifier OP A694 is studied as a first case. The integrated circuit
electromagnetic (ICEM) model is used to describe the inner power distribution
network of OP A694 by theoretical study and experimental measurement. A curve
fitting method is proposed to obtain the ICEM model parameters from different kinds
of measurements without knowing the precise inner physical structure information of
OPA694. Then the direct power injection (DPI) experimental test is conducted to
measure the susceptibility of OP A694 to conducted sine-wave noise. And from the
immunity measurement, a common simulation susceptibility criterion is obtained.
Finally the whole simulation model of DPI setup including the ICEM model of OPA694
is established to predict its susceptibility and the model is perfectly verified in
a 200MHz frequency range.
Independent Component Analysis (ICA) - one of the basic tools in data analysis -
aims to find a coordinate system in which the components of the data are
independent. Most of existing methods are based on the minimization of the function
of fourth-order moment (kurtosis). Skewness (third-order moment) has received much
less attention. In this paper we present a competitive approach to ICA based on the
Split Gaussian distribution, which is well adapted to asymmetric data.
Consequently, we obtain a method which works better than the classical approaches,
especially in the case when the underlying density is not symmetric, which is a
typical situation in the color distribution in images. (C) 2017 Elsevier Ltd. All
rights reserved.
The structure of oceanic spreading centres and subsurface melt distribution within
newly formed crust is largely understood from marine seismic experiments. In
Iceland, however, sub-aerial rift elevation allows both accurate surface mapping
and the installation of large broadband seismic arrays. We present a study using
ambient noise Rayleigh wave tomography to image the volcanic spreading centres
across Iceland. Our high resolution model images a continuous band of low seismic
velocities, parallelling all three segments of the branched rift in Iceland. The
upper 10 km contains strong velocity variations, with shear wave velocities 0.5 km
s(-1) faster in the older non-volcanically active regions compared to the active
rifts. Slow velocities correlate very closely with geological surface mapping, with
contours of the anomalies parallelling the edges of the neo-volcanic zones. The
low-velocity band extends to the full 50 km width of the neo-volcanic zones,
demonstrating a significant contrast with the narrow (8 km wide) magmatic zone seen
at fast spreading ridges, where the rate of melt supply is similarly high. Within
the seismically slow rift band, the lowest velocity cores of the anomalies occur
above the centre of the mantle plume under the Vatnajtikull icecap, and in the
Eastern Volcanic Zone under the central volcano Katla. This suggests localisation
of melt accumulation at these specific volcanic centres, demonstrating variability
in melt supply into the shallow crust along the rift axis. Shear velocity
inversions with depth show that the strongest velocity contrasts are found in the
upper 8 km, and show a slight depression in the shear velocity through the mid
crust (10-20 km) in the rifts. Our model also shows less intensity to the slow rift
anomaly in the Western Volcanic Zone, supporting the notion that rift activity here
is decreasing as the ridge jumps to the Eastern Volcanic Zone. (C) 2017 The
Author(s). Published by Elsevier B.V.
Collodion baby is a severe form of congenital ichthyosis detected in neonatal
period. It often has a characteristic clinical picture. When evolution is not
fatal; it often causes dry Ichthyosis. Thanks to molecular biology techniques,
prenatal diagnosis can be made since the 10-12 weeks of amenorrhea, allowing
genetic counselling. Prognosis depends on several parameters, namely the degree of
the initial manifestation, the duration of desquamation, as well as underlying
Ichthyosis This rewiew of the literature which aims to clarify the diagnostic
aspects and therapeutic treatment as well as the role of the antenatal diagnosis is
based on a new observation of a collodion baby born at 34 weeks, of a parturient
woman having an index case and of infant deaths occurring in the first day of life.
FRMD7 mutations are associated with X-linked idiopathic congenital nystagmus (ICN);
however, the underlying mechanisms whereby mutations of FRMD7 lead to ICN remain
unclear. In a previous study, the first FRMD7 splice variant (FRMD7-S) was cloned
and identified, and FRMD7-S was hypothesized to play a significant role in neuronal
differentiation and development. The present study investigated a novel multiple
exon-skipping mRNA splice variant of FRMD7, termed FRMD7_SV2, which was detected in
NT2 cells using northern blotting. The mRNA expression levels of FRMD7_SV2 in the
developing human fetal brain were examined using reverse transcription polymerase
chain reaction (PCR), while the expression levels in NT2 cells treated with
retinoid acid (RA) or bone morphogenetic protein-2 were investigated using
quantitative PCR. The results revealed that the expression of FRMD7_SV2 was
spatially and temporally restricted in human fetal brain development, and was
upregulated upon RA-induced neuronal differentiation of the NT2 cells. These
results indicated that as a novel splice variant of FRMD7, FRMD7_SV2 may play a
role in neuronal development.
Interstitial lung diseases ( ILDs) are a heterogeneous group of lung disorders with
distinct clinical, radiological and morphological features. Among ILDs, idiopathic
pulmonary fibrosis ( IPF) is associated with the worst prognosis, with a survival
worse than many cancers, even after the advent of two anti- fibrotic drugs, shown
to halve disease progression. Reaching the correct diagnosis is crucial, as
pathogenesis, prognosis and treatment options differ substantially from other
interstitial fibrosing processes where immune overactivity plays a role in driving
fibrosis. However, a subgroup of patients with fibrotic lung disease mediated by
immune dysregulation can experience relentlessly progressive fibrosis despite
immunosuppressive treatment, and behave similarly to IPF. It is clear that even in
non IPF ILDs, phenotypes of relentlessly progressive disease exist, and molecular
pathways may overlap. One of the main challenges for the future is the use of high
throughput molecular biology techniques to stratify patients with progressive
fibrotic lung disease, in order to identify genetic, epigenetic and protein markers
to predict the individual patient's rate of progression and fundamental molecular
pathways involved. In this review, we will focus on the challenges in the diagnosis
and management of idiopathic pulmonary fibrosis as well as differences and areas of
overlap with other fibrotic ILDs, including fibrotic hypersensitivity pneumonitis,
connective tissue disease- associated ILD and interstitial pneumonia with
autoimmune features.
With the increasing installed capacity of wind power and the interdependencies
among multiple energy sectors, optimal operation of integrated energy systems (IES)
with combined cooling, heating and power (CCHP) is becoming more important. This
paper proposes an optimal dispatch strategy for IES with CCHP and wind power.
Natural gas system is modeled and its security constraints are integrated into the
optimal dispatch model. The gas shift factor (GSF(gas)) matrix for natural gas
system is derived to quantify the impact of gas supply and load at each node on the
gas flow through the pipelines so that the pipeline flow equation is linearized.
The objective function of the optimization model is to minimize the total operation
cost of IES. Then the model is transformed into mixed integer linear programming
(MILP) formulation to improve the computation efficiency. Numerical case studies
conducted demonstrate the lower operation cost of the proposed model facilitating
wind power integration. (C) 2016 Elsevier Ltd. All rights reserved.
Renal damage is the major cause of SLE associated mortality, and IFIT1 expression
was elevated in SLE cases in accordance of previous studies. Therefore, we
conducted an animal study to identify the role of IFIT1 expression in renal
pathological changes. 18 female MRL/lpr mice and same number of female BALB/c mice
were enrolled in present study. Quantitative analysis of urine protein, Complement
C3 and C4, and anti-ds DNA antibody were conducted. HE and PAS staining and TEM
analysis were employed to observe the pathological changes in renal tissue.
Significant elevation on urine protein and anti-dsDNA and reduction on Complement
C3 and C4 were observed in MRL/lpr mice when comparing the controls in same age.
Staining and TEM analysis observed several pathological changes in glomerulus among
MRL/lpr mice, including cellular enlargement, basement membrane thickening, and
increased cellularcasts. The linear regression analysis found the optical density
of IFIT1 was inversely associated with F-actin, Nephrin, and Podocin, but not
Synatopodin. In summary, IFIT1 expression is associated with podocytes damage, and
capable of suppressing some proteins essential to glomerular filtration.
In high power applications, proper gate control strategy for insulated gate bipolar
transistors (IGBTs) can increase their efficient and reliability. As to the feed-
back control strategy, the key issues are the control speed and control stability.
This paper proposed a new feed-back control method integrated in digital gate
driver for high power IGBT. It aims for controlling the current and voltage slope
suppressing the voltage overshoot and electromagnetic interference (EMI) in
switching transient. The digital gate driver for large power IGBT detects the
collector current and voltage in real time. Then the detected analog signal is
digitally sampled and sent to the digital core on board. An algorithm similar to
bang-bang control is deployed in forward control loop to adjust the gate drive
resistance. The control stability and robustness can be guaranteed as a result. The
whole detection and control process is accomplished in real time with only hundreds
of nanoseconds. Thus, the proposed control method can optimized the IGBT switching
transient with high reliability and time effectiveness. Experimental results
validate the feasibility of the proposed feed-back digital control method.
Since coal will be widely used in the next decades, mainly in the developing
countries such as China and India, carbon capture and storage (CCS) technologies
will have a key role in the containment of global warming. This paper presents a
techno-economic comparison between the most promising power generation technologies
for a CO2-free power generation in a short-term future. In particular, three
different power generation technologies have been considered in their conventional
(without CCS) and CO2-free configurations: (a) ultra supercritical (USC) pulverized
coal combustion, (b) oxy-coal combustion (OCC) and (c) integrated gasification
combined cycle (IGCC). Process simulation, based on Aspen Plus and Gate Cycle
commercial tools, allows to calculate plant performance, including the energy
penalty due to the CCS system (10.9% points for USC and 8.7% points for IGCC). In
parallel, a detailed economic assessment shows that, among the commercial-ready
technologies, USC could be the most convenient solution for power generation
without CCS (presenting a levelized cost of electricity - LCOE - of 38.6 (sic)/MW
h, significantly lower than 43.7 (sic)/MW h of IGCC), whereas IGCC becomes
competitive for CO2-free systems (with a LCOE of 59.6 (sic)/MW h, to be compared
with 63.4 (sic)/MW h of USC). Moreover, oxy-coal combustion, which is currently not
mature enough for commercial-scale applications, promises to become strongly
competitive for CCS applications due to its relatively low levelized cost of
electricity (62.8 (sic)/MW h). This kind of analysis typically presents strong
uncertainties, due to the variability of several key parameters (e.g. fuel and CCS
prices, determined by the fluctuation of the international markets, or an
improvement of the technologies). Therefore, a sensitivity analysis has been done
to determine the effects of these potential fluctuation or the improvement on the
economic performance of the plant. (C) 2017 Elsevier Ltd. All rights reserved.
Lymphocyte differentiation is set to produce myriad immune effector cells with the
ability to respond to multitudinous foreign substances. The uniqueness of this
developmental system lies in not only the great diversity of cellular functions
that it can generate but also the ability of its differentiation intermediates and
mature effector cells to expand upon demand, thereby providing lifelong immunity.
Surprisingly, the goals of this developmental system are met by a relatively small
group of DNA-binding transcription factors that work in concert to control the
timing and magnitude of gene expression and fulfill the demands for cellular
specialization, expansion, and maintenance. The cellular and molecular mechanisms
through which these lineage-promoting transcription factors operate have been a
focus of basic research in immunology. The mechanisms of development discerned in
this effort are guiding clinical research on disorders with an immune cell base.
Here, I focus on IKAROS, one of the earliest regulators of lymphoid lineage
identity and a guardian of lymphocyte homeostasis.
IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in
several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-
enhancing effects. On the other hand, IL-27 demonstrated immune regulatory
activities and inhibition of auto-immunity in mouse models. Also, we reported that
IL-27, similar to IFN-gamma, induces the expression of IL-18BP, IDO and PD-L1
immune regulatory molecules in human cancer cells. Here, a proteomic analysis
reveals that IL-27 and IFN-gamma display a broad overlap of functions on human
ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine
treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines,
while a smaller number (176) were differentially modulated. The most up-regulated
proteins were common to both IFN-gamma and IL-27. In addition, functional analysis
of IL-27-regulated protein networks highlighted pathways of interferon signaling
and regulation, antigen presentation, protection from natural killer cell-mediated
cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid
catabolism and regulation of viral protein levels. Importantly, we found that IL-27
induced HLA class I molecule expression in human cancer cells of different
histotypes, including tumor cells showing very low expression. IL-27 failed only in
a cancer cell line bearing a homozygous deletion in the B2M gene. Altogether, these
data point out to a broad set of activities shared by IL-27 and IFN-gamma, which
are dependent on the common activation of the STAT1 pathway. These data add further
explanation to the anti-tumor activity of IL-27 and also to its dual role in immune
regulation.
Accumulated data have shown that alternatively activated macrophage exerts a
modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a
critical modulator in adaptive and innate immune, has been implicated in
autoimmunity and inflammation. Previously, we have reported that IL-33 functions as
a protective modulator in TNBS-induced colitis, which is closely related to a Th1-
to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33 primes
macrophage into alternatively activated macrophages (AAM) in TNBS-induced colitis.
The strong polarized effect of IL-33 was tightly associated with the markedly
increased induction of Th2-type cytokines. To confirm the beneficial effects of AAM
induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice were transferred
to recipient mice with TNBS colitis. The adoptive transfer resulted in prominent
inhibition of disease activity and inflammatory cytokines in the TNBS-treated mice.
In conclusion, our data provide clear evidence that IL-33 plays a protective role
in TNBS-induced colitis, which is closely related to AAM polarization.
Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology,
mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to
be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes
immature immune cell arrest. Interestingly, in recent years, certain studies have
strongly suggested that the role of IL-7 is far beyond the field of immunology, it
might have direct or indirect effect on cancer. This review aims to summarize the
role of IL-7 in immunity and its role in the pathogenesis of neoplasia.
The problem of the secure transmission of digital image has paid more and more
attention to the network and this paper designs a special image encryption scheme.
Image encryption scheme is designed based on the hyper chaos of generalized five-
order Henon mapping and five-order cellular neural network (CNN) system. Firstly,
the chaotic sequence X, which is regarded as the initial conditions of CNN system,
is generated by the five-order generalized Henon mapping. Then another chaotic
sequence Y is produced by the CNN system. At last, the cipher image is generated by
the transformation of random sequence Y and the original image. Toward the end, the
paper makes the simulation experiment and draws a conclusion that the algorithm of
image encryption has strong attack resistance, good safety, and suitable to spread
in the network through analyzing the statistical characteristics of the image
information entropy, correlation and histogram as well as the key space and the
sensitivity.
We propose an analog front-end integrated circuit (IC) design for a readout IC
(ROIC), which applies a fixed-voltage-bias sensing method with a capacitance
transimpedance amplifier (CTIA) to an input stage in order to simplify the circuit
structure of the ROIC and the IR sensor characteristic control. For a sample-and-
hold stage, in order to display and control a signal detected by the IR sensor
using a 2-D focal plane array, a differential delta sampling circuit is proposed,
which effectively removes the fixed pattern noise. In addition, a two-stage
variable-gain amplifier equipped with a rail-to-rail fully differential operational
amplifier is applied to the ROIC to achieve high voltage sensitivity. The output
characteristic of the proposed device is 30.84 mV/K and the linearity error rate is
less than 0.07%. After checking the performance of the ROIC using an HSPICE
simulation, the chip is manufactured and measured using the United Microelectronics
Corporation Japan 0.35-mu m standard CMOS process to confirm that the simulation
results from the actual design are in close agreement with the measurement results.
Sound and image compete in It Can Pass Through the Wall, as in Fritz Lang's M
(1931), to create tension between what is seen and what is heard. This disconnect
between image and sound draws attention to the limits of the visual and the
possibilities of the audible.
Background and objectives: Literature suggests that imagery rescripting (ImRs) is
an effective psychological intervention. Methods: We conducted a meta-analysis of
ImRs for psychological complaints that are associated with aversive memories.
Relevant publications were collected from the databases Medline, Psychlnfo, and Web
of Science. Results: The search identified 19 trials (including seven randomized
controlled trials) with 363 adult patients with posttraumatic stress disorder
(eight trials), social anxiety disorder (six trials), body dysmorphic disorder (two
trials), major depression (one trial), bulimia nervosa (one trial), or obsessive
compulsive disorder (one trial). ImRs was administered over a mean of 4.5 sessions
(range, 1-16). Effect size estimates suggest that ImRs is largely effective in
reducing symptoms from pretreatment to post-treatment and follow-up in the overall
sample (Hedges' g = 1.22 and 1.79, respectively). The comparison of ImRs to passive
treatment conditions resulted in a large effect size (g = 0.90) at posttreatment.
Finally, the effects of ImRs on comorbid depression, aversive imagery, and
encapsulated beliefs were also large. Limitations: Most of the analyses involved
pre-post comparisons and the findings are limited by the small number of randomized
controlled trials. Conclusions: Our findings indicate that ImRs is a promising
intervention for psychological complaints related to aversive memories, with large
effects obtained in a small number of session. (C) 2016 Elsevier Ltd. All rights
reserved.
Imaginative resistance refers to a perceived inability or unwillingness to enter
into fictional worlds that portray deviant moralities (Gendler, 2000): we can all
easily imagine that dragons exist, but many people feel incapable of imagining
fictional worlds in which morality works differently. Although this phenomenon has
received much attention from philosophers, no one has attempted to operationalize
the construct in a self-report scale. In Study 1, we developed the Imaginative
Resistance Scale (IRS), investigated its relationship to theoretically related
constructs, and confirmed its structure and reliability (r(alpha) = 0.92) in a
large sample. In Study 2, we asked participants to rate scenarios expected to
provoke imaginative resistance and predicted these ratings from the IRS and its
validity measures. IRS scores accounted for variability in ease of imagining these
scenarios over and above gender, political orientation, and three related measures.
The results are discussed in terms of theories of imaginative resistance and
directions for future research. (C) 2017 Elsevier Ltd. All rights reserved.
Phagocytes display marked heterogeneity in their capacity to induce and control
acute inflammation. This has a significant impact on the effectiveness of
antimicrobial immune responses at different tissue sites as well as their
predisposition for inflammation-associated pathology. Imaging flow cytometry
provides novel opportunities for characterization of these phagocyte populations
through high spatial resolution, statistical robustness, and a broad range of
quantitative morphometric cell analysis tools. This study highlights an integrative
approach that brings together new tools in imaging flow cytometry with conventional
methodologies for characterization of phagocyte responses during acute
inflammation. We focus on a comparative avian in vivo challenge model to showcase
the added depth gained through these novel quantitative multiparametric approaches
even in the absence of antibody-based cellular markers. Our characterization of
acute inflammation in this model shows significant conservation of phagocytic
capacity among avian phagocytes compared to other animal models. However, it also
highlights evolutionary divergence with regards to phagocyte inflammation control
mechanisms based on the internalization of apoptotic cells. (C) 2016 Published by
Elsevier Inc.
Regulation of eukaryotic transcription in vivo occurs at distinct stages. Previous
research has identified many active or repressive transcription factors (TFs) and
core transcription components and studied their functions in vitro and in vivo.
Nonetheless, how individual TFs act in concert to regulate mRNA gene expression in
a single cell remains poorly understood. Direct observation of TF assembly and
disassembly and various biochemical reactions during transcription of a single-copy
gene in vivo is the ideal approach to study this problem. Research in this area
requires developing novel techniques for single-cell transcription imaging and
integrating imaging studies into understanding the molecular biology of
transcription. In the past decade, advanced cell imaging has enabled unprecedented
capabilities to visualize individual TF molecules, to track single transcription
sites, and to detect individual mRNA in fixed and living cells. These studies have
raised several novel insights on transcriptional regulation such as the "hit-and-
run" model and transcription bursting that could not be obtained by in vitro
biochemistry analysis. At this point, the key question is how to achieve deeper
understandings or discover novel mechanisms of eukaryotic transcriptional
regulation by imaging transcription in single cells. Meanwhile, further technical
advancements are likely required for visualizing distinct kinetic steps of
transcription on a single-copy gene in vivo. This review article summarizes recent
progress in the field and describes the challenges and opportunities ahead. (C)
2016 Elsevier Ltd. All rights reserved.
Imbalance data are defined as a dataset whose proportion of classes is severely
skewed. Classification performance of existing models tends to deteriorate due to
class distribution imbalance. In addition, over-representation by majority classes
prevents a classifier from paying attention to minority classes, which are
generally more interesting. An effective ensemble classification method called
RHSBoost has been proposed to address the imbalance classification problem. This
classification rule uses random undersampling and ROSE sampling under a boosting
scheme. According to the experimental results, RHSBoost appears to be an attractive
classification model for imbalance data. (C) 2017 Elsevier B.V. All rights
reserved.
While much literature has examined immigrants' health in Canada, less attention has
focused specifically on the life stress, an important yet understudied post-
migration challenge which may lead to poor coping strategies and negative health
consequences. For this study, the pooled 2009-2014 Canadian Community Health Survey
(CCHS) was analyzed, using multilevel logistic regression to examine the
compositional effects (at an individual level) and areal effects (at a CMA/CA
level) on reported high life stress. Separate models have been run for immigrants
and non-immigrants for comparative purposes. The results reveal different ways in
which select individual socioeconomic and lifestyle factors affect life stress. A
statistically significant yet small areal effect at the CMA/CA level on life stress
was identified for both immigrants and non-immigrants. When comparing immigrants to
non-immigrants, factors such as smoking, length of residency in Canada, and mental
health status were found to be particularly informative for predicting high life
stress among immigrants. A Healthy Immigrant Effect (HIE) is partially evident, as
immigrants with a longer stay in Canada are more likely to be highly stressed than
recent arrivals. The areal effect on variances in high life stress is minimal,
suggesting the importance of focusing on individual-level effects as stress
predictors.
It is commonly known that enzymatic transformations are considerably more specific
than classical chemical reactions which usually lead to formation of byproducts.
That is why the enzymes are a powerful tool in the field of analytical chemistry.
The main problems occurring while working with enzymes stem from their relatively
high price and sensitivity to non-physiological conditions. The above mentioned
disadvantages may be overcome through enzyme immobilization which allows for
reusing the biocatalyst as long as it retains its activity. When the immobilization
is performed correctly the enzymes are more stable and also more resistant to
denaturation. Such an approach in combination with additional benefits of
miniaturization, heterogeneous catalysis and flow-mode operation contributes to the
various applications of the Immobilized Enzyme Reactors (IMERs) in particular,
microfluidic (mu-IMERs). In the present review various types of mu-IMERs were
described. Particular attention was paid to techniques of their preparation
including immobilization strategies and technical solutions connected with their
applications using both capillary and chip format. (C) 2016 Elsevier B.V. All
rights reserved.
Background: In October 2010, a pharmacist-driven stewardship program was
implemented at the Brigham and Women's Hospital to ensure continued adherence to
the prescribing guideline, focusing on indications for intravenous immune globulin
(IVIG) use and dosing per ideal body weight. Objective: The primary objective was
to describe an IVIG stewardship program at a tertiary academic medical center.
Methods: This was a prospective, observational study from January 2013 through
December 2014. All patients ordered to receive IVIG during the defined study period
were included. The intervention assessed describes a pharmacist-driven IVIG
stewardship program for medication approval. The primary end point was guideline
compliance based on indication, dose, dosing weight, and frequency. Secondary end
points included the number of patients receiving IVIG, indications, orders
discontinued as a result of guideline nonadherence, and total amount dispensed.
Results: A total of 418 patients were identified during the study time frame. The
top indications were: hypogammaglobulinemia in bone marrow transplantation and
hematological malignancy (50.7%), acute solid organ rejection (11.8%), and immune
thrombocytopenia with bleeding (10.1%). In all, 12 patients (2.9%) received IVIG
for an indication nonadherent with the IVIG prescribing guideline; 9 patients
(2.2%) and 2 patients (0.5%), respectively, received a different dose or frequency
per the prescribed indication; and 12 orders (2.9%) for indications nonadherent to
the guideline were discontinued. A total of 26033 g of IVIG were dispensed during
the study period. Conclusions: An IVIG stewardship program, including an
institution-specific prescribing guideline and a pharmacist-driven stewardship
program, may ensure guideline compliance for appropriateness of indication and dose
at an academic medical center.
Background. Oxytetracycline (OTC), which is largely employed in zootechnical and
veterinary practices to ensure wellness of farmed animals, is partially absorbed
within the gastrointestinal tract depositing in several tissues. Therefore, the
potential OTC toxicity is relevant when considering the putative risk derived by
the entry and accumulation of such drug in human and pet food chain supply. Despite
scientific literature highlights several OTC-dependent toxic effects on human and
animal health, the molecular mechanisms of such toxicity are still poorly
understood. Methods. Here, we evaluated DNA damages and epigenetic alterations by
quantitative reverse transcription polymerase chain reaction, quantitative
polymerase chain reaction, chromatin immuno-precipitation and Western blot
analysis. Results. We observed that human peripheral blood mononuclear cells
(PBMCs) expressed DNA damage features (activation of ATM and p53, phosphorylation
of H2AX and modifications of histone H3 rnethylation of lysine K4 in the chromatin)
after the in vitro exposure to OTC. These changes are linked to a robust
inflammatory response indicated by an increased expression of Interferon (IFN)-
gamma and type 1 superoxide dismutase (SOD1). Discussion. Our data reveal an
unexpected biological in vitro activity of OTC able to modify DNA and chromatin in
cultured human PI3MC. In this regard, OTC presence in foods of animal origin could
represent a potential risk for both the human and animal health.
Harnessing the immune system to eradicate malignant cells is becoming a most
powerful new approach to cancer therapy. FDA approval of the immunotherapy-based
drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA- 4), and more
recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for
the treatment of multiple types of cancer has greatly advanced research and
clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical
trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen
receptor (CAR), have shown promising clinical results for patients with metastatic
cancer. Current success of cancer immunotherapy is built upon the work of cancer
antigens and co-inhibitory signaling molecules identified 20 years ago. Among the
large numbers of target antigens, CD19 is the best target for CAR T cell therapy
for blood cancer, but CAR-engineered T cell immunotherapy does not yet work in
solid cancer. NY-ESO-1 is one of the best targets for TCR-based immunotherapy in
solid cancer. Despite the great success of checkpoint blockade therapy, more than
50% of cancer patients fail to respond to blockade therapy. The advent of new
technologies such as next-generation sequencing has enhanced our ability to search
for new immune targets in onco-immunology and accelerated the development of
immunotherapy with potentially broader coverage of cancer patients. In this review,
we will discuss the recent progresses of cancer immunotherapy and novel strategies
in the identification of new immune targets and mutation-derived antigens
(neoantigens) for cancer immunotherapy and immunoprecision medicine.
Both microRNAs and T helper (Th) cells involve in autoimmune diseases and their
effects and interactions in immune thrombocytopenia (ITP) remain unclear. In the
present study, we investigated the expression profiles of seven immune-related
microRNAs (miR-155, 146a, 326, 142-3p, 17-5p, 21 and 181a) and the frequencies of
four Th cells (Th1, Th2, Th17 and Treg) in peripheral blood mononuclear cell
(PBMCs) of ITP patients and healthy controls. Platelet autoantibodies specific for
GPIIb/IIIa or GPIb/IX were measured using MAIPA method. The regulating effect of
miR-146a on Th differentiation was evaluated after using agomir. Our results showed
that the expression of miR-146a, miR-326 or miR-142-3p in ITP patients was lower
than that of controls. The frequencies of Treg cells were decreased, whereas the
frequencies of Th17 and Th22 cells were increased significantly in ITP patients
compared to those in controls. The expression levels of miR-142-3p and miR-146a
were negatively correlated with Th17 cells, respectively. The expression of miR-
146a was positively correlated with the frequencies of Treg cells and platelet
counts. No significant correlation was found between the miRNAs expression and
different autoantibody groups. The up-regulated miR-146a expression with agomir
contributed to the differentiation of Th17 and Treg in ITP patients. Moreover, miR-
146a was increased in the presence of DEX in PBMCs of ITP patients in vitro. Our
study represents the abnormal expression profile of immune-related miRNAs in ITP
patients, and miR-146a may be involved in Tregs differentiation and function.
In the broad field of autoimmunity and clinical immunology, experimental evidence
over the past few years have demonstrated several connections between the immune
system and the nervous system, both central and peripheral, leading to the
definition of neuroimmunology and of an immune-brain axis. Indeed, the central
nervous system as an immune-privileged site, thanks to the blood-brain barrier, is
no longer a dogma as the barrier may be altered during chronic inflammation with
disruptive changes of endothelial cells and tight junctions, largely mediated by
adenosine receptors and the expression of CD39/CD73. The diseases that encompass
the neuroimmunology field vary from primary nervous diseases such as multiple
sclerosis to systemic conditions with neuropsychiatric complications, such as
systemic lupus erythematosus or vasculitidies. Despite potentially similar clinical
manifestations, the pathogenesis of each condition is different, but the
interaction between the ultra-specialized structure that is the nervous system and
inflammation mediators are crucial. Two examples come from antidsDNA cross-reacting
with anti-N-Methyl-o-Aspartate receptor (NMDAR) antibodies in neuropsychiatric
lupus or the new family of antibody-associated neuronal autoimmune diseases
including classic paraneoplastic syndromes with antibodies directed to
intracellular antigens (Hu, Yo, Ri) and autoimmune encephalitis. In the case of
multiple sclerosis, the T cell paradigm is now complicated by the growing evidence
of a B cell involvement, particularly via aquaporin antibodies, and their influence
on Thl and Th17 lineages. Inspired by a productive AARDA-sponsored colloquium among
experts we provide a critical review of the literature on the pathogenesis of
different immune-mediated diseases with neurologic manifestations and we discuss
the basic immunology of the central nervous system and the interaction between
immune cells and the peripheral nervous system. (C) 2016 Elsevier Ltd. All rights
reserved.
Given immunity's general role in the organism's economy-both in terms of its
internal environment as well as mediating its external relations-immune theory has
expanded its traditional formulation of preserving individual autonomy to one that
includes accounting for nutritional processes and symbiotic relationships that
require immune tolerance. When such a full ecological alignment is adopted, the
immune system becomes the mediator of both defensive and assimilative environmental
intercourse, where a balance of immune rejection and tolerance governs the complex
interactions of the organism's ecological relationships. Accordingly, immunology,
which historically had affiliated with the biology of individuals, now becomes a
science concerned with the biology of communities. With this translocation, the
ontological basis of the organism is undergoing a profound change. Indeed, the
recent recognition of the ubiquity of symbiosis has challenged the traditional
notions of biological individuality and requires a shift in the metaphysics
undergirding biology, in which a philosophy of the organism must be characterized
by ecological dialectics "all-the-way-down.".
Guillain-Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of
unknown cause. However, about a quarter of GBS patients have suffered a recent
bacterial or viral infection, and axonal forms of the disease are especially common
in these patients. Proteomics is a good methodological approach for the discovery
of disease biomarkers. Until recently, most proteomics studies of GBS and other
neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid
(CSF). However, serum represents an attractive alternative to CSF because it is
easier to sample and has potential for biomarker discovery. The goal of this
research was the identification of serum biomarkers associated with recovery from
GBS. To address this objective, a quantitative proteomics approach was used to
characterize differences in the serum proteome between a GBS patient and her
healthy identical twin in order to lessen variations due to differences in genetic
background, and with additional serum samples collected from unrelated GBS (N = 3)
and Spinal Cord Injury (SCI) (N = 3) patients with similar medications. Proteomics
results were then validated by ELISA using sera from additional GBS patients (N =
5) and healthy individuals (N = 3). All GBS and SCI patients were recovering from
the acute phase of the disease. The results showed that Piccolo, a protein that is
essential in the maintenance of active zone structure, constitutes a potential
serological correlate of recovery from GBS. These results provided the first
evidence for the Piccolo's putative role in GBS, suggesting a candidate target for
developing a serological marker of disease recovery.
Phytohemagglutinin (PHA)-induced skin swelling response is widely used as a rough
surrogate of integrative cell-mediated and innate immunity across multiple
vertebrate taxa due to its simplification and feasibility. However, little is known
whether there are sex and interspecific differences of immune responsiveness to PHA
in ectotherms, especially for anurans. Therefore, we studied sex and species
differences of PHA response in three anurans, Asiatic toads (Bufo gargarizans),
Dark-spotted frogs (Pelophylax nigromaculatus) and Mongolian toads (Pseudepidalea
raddei), captured in northern regions of Anhui Province (China). Footpad thickness
was measured prior to (0 h) and after (6, 12, 24, 48 and 72 h) a PHA injection and
normalized against saline injection in the opposite footpad. Body mass was recorded
at the beginning (0 h) and end of each assay (72 h). Results showed effects of PHA
assay, sex and taxa on body mass. Relative maximum swelling response (PHA(max))
ranged from 18.58-29.75%, 9.77 to 20.56% and 21.97 to 31.78% and its occurrence
over time was apparent 10.6-19.72 h, 7.74-14.01 h and 17.39-23.94 h postinjection
for Asiatic toads, Dark-spotted frogs and Mongolian toads, respectively. Finally,
the magnitude or timing of PHAmax in Dark-spotted frogs was significantly thinner
and faster than in Mongolian toads, and Asiatic toads had an in-between value, not
different from the other two species. The magnitude of PHA(max) was significantly
positively correlated with the timing ofPHAmax considering individuals altogether,
but not when analyzed within species. Our results indicate that male and female
anuran species respond similarly to PHA antigen stimulation, but the magnitude and
timing of PHAmax is species-specific. Briefly, we provide new evidence for the
suitability of PHA assay in non-model anuran species with different body sizes, and
exhort the need to further investigate the nature of PHA assay at the hematological
and histological levels in order to extend its application in ecoimmunological
studies of amphibians.
Since the mid 1970s, when membrane modules became available, plasma separation
techniques have gained in importance especially in the past few years. The
advantages of this method are a complete separation of the corpuscular components
from the plasma and due to increased blood flow rate and higher efficacy. Systemic
autoimmune diseases based on an immune pathogenesis produce autoantibodies and
circulating immune complexes, which cause inflammation in the tissues of various
organs. In most cases, these diseases have a poor prognosis without treatment.
Therapeutic apheresis (TA) in combination with immunosuppressive therapies has led
to a steady increase in survival rates over the last 40years. The updated
information on immunology and molecular biology of different immunologic diseases
are discussed in relation to the rationale for apheresis therapy and its place in
combination with other modern treatments. The different diseases can be treated by
various apheresis methods such as therapeutic plasma exchange (TPE) with
substitution solution, or with online plasma or blood purification using adsorption
columns, which contain biological or non-biological agents. Here, the authors
provide an overview of the most important pathogenic aspects indicating that TA can
be a supportive therapy in systemic autoimmune diseases such as renal and
neurological disorders. For the immunological diseases that can be treated with TA,
the guidelines of the German Working Group of Clinical Nephrology and of the
Apheresis Committee of the American Society for Apheresis are cited.
During a long time, immunofluorescence has been neglected to benefit of molecular
biology especially genetics, transcriptomics, and proteomics analyses. These
techniques give good results on cell culture but for organs that are made of
numerous cells with several compartments, various states of differentiation as in
epidermis, immunohistochemistry is always relevant. Double (triple) staining by
immunofluorescence allows positive cells identification in complex cell structure
(for example, pericytes and endothelial cells in vessels) and subcellular
localizations. In order to, due to improvement of antibodies avoiding especially
species cross-reactions, microscopy and specific softwares, quality of staining,
and acquired images have been upgraded. Consequently, this technique permits, as
molecular biology analyses, quantification of the level of expression as intensity
of fluorescence can be measured in each cells and each compartments (nuclear,
cytoplasmic). In order to immunofluorescence on cells and tissue needs few
materials and gives at the same times qualitative and quantitative results and must
be used more widely especially when a mutation was associated to a disease.
Within the past 10 years, several investigators have reported the presence of
immunoglobulin G in brain neurons. However, because immunoglobulin molecules were
only known to be produced by B-lymphocytes, it was suspected that the neurons were
taking immunoglobulin G up from the extracellular fluid. The aim of this study was
to determine whether immunoglobulin G was actually being produced by the neurons.
By immunohistochemistry and Western blotting analysis, we found that immunoglobulin
G was also present in adult mouse brain neurons and isolated neonatal mouse
neurons, respectively. More importantly, by in situ hybridization, Northern
blotting and single cell reverse transcriptase polymerase chain reaction, the
transcripts of rearranged immunoglobulin gamma chain and K chain were also found in
adult mouse brain neurons. Further, confocal imaging of primary culture neurons
showed that immunoglobulin G immunoreactivity was localized in the neuron
cytoplasm, axons and dendrites. Immunoglobulin G extracted from the primary culture
neurons could also be detected by Western blotting. Furthermore, the results of
sulphur-35 or iodine-125 pulse-labeled immunoprecipitation provided additional
confirmation that brain neurons could produce immunoglobulin G. Taken together, the
results indicated that immunoglobulin G originated from both early generated and
adult mouse neurons. Although the bioactivity of neuron-derived immunoglobulin G
was not yet clear, we believed that immunoglobulin G might play an important role
in neuronal development. (C) 2007 Elsevier Ltd. All rights reserved.
We found that stem-cell leukemia (SCL), also known as T cell acute-lymphocytic
leukemia (Tal-1) gene expression, was upregulated in the maturing rat testis.
Strong expression of Tal-1 was detected in the normal maturing rat testis by
Northern blotting. Western blotting revealed the protein size to be about 34 kDa.
Protein expression was wide-spread in spermatocytes, spermtids and spermatogonia in
accordance with the seminiferous epithelium cycle, as determined by an analysis of
immunohistochemistry. Gene expression of Tal-1 regulatory gene, NKX3.1, was
negatively correlated with Tal-1 expression. Human Tal-1 expression in the maturing
testis as well as in bone marrow was observed, which suggests that the gene product
is a novel cancer-testis antigen candidate. Taken together, TAL-1 may be involved
in cell division, morphological changes, and the development of spermatogenic cells
in the normal rat testis.
This report investigated the possible participation of canine distemper virus (CDV)
in an eight-year-old, male, Akita dog with neuromuscular disease. Clinically, there
was tetraparesis, muscular atrophy, generalized weakness, intolerance to exercise,
and diminished or absent spinal reflexes. The dog was serologically negative for
Toxoplasma gondii. Necropsy confirmed generalized muscular atrophy. Histopathology
revealed white matter demyelinating encephalitis, generalized atrophy and fibrosis
of skeletal muscle fibers, myocardial atrophy and fibrosis, loss and demyelination
of peripheral nerve fibers, axonal degeneration, endoneural fibrosis, and
interstitial pneumonia. Immunohistochemistry identified CDV antigens within the
cerebellum, spinal cord, skeletal muscle, lungs, and spleen. RT-PCR and direct
sequencing amplified the CDV nucleoprotein gene from the cerebellum and sciatic
nerves. Collectively, these findings suggest that this dog demonstrated systemic
canine distemper that also affected the muscular system and probably triggered the
manifestations of the neuromuscular disease observed in this case. (C) 2016 PVJ.
All rights reserved
Background: The identification of immunogenic regions on the surface of antigens,
which are able to be recognized by antibodies and to trigger an immune response, is
a major challenge for the design of new and effective vaccines. The prediction of
such regions through computational immunology techniques is a challenging goal,
which will ultimately lead to a drastic limitation of the experimental tests
required to validate their efficiency. However, current methods are far from being
sufficiently reliable and/or applicable on a large scale. Results: We developed
SEPIa, a B-cell epitope predictor from the protein sequence, which is sufficiently
fast to be applicable on a large scale. The originality of SEPIa lies in the
combination of two classifiers, a naive Bayesian and a random forest classifier,
through a voting algorithm that exploits the advantages of both. It is based on 13
sequence-based features, whose values in a 9-residue sequence window are compiled
to predict the epitope/non-epitope state of the central residue. The features are
related to the type of amino acid, its conservation in homologous proteins, and its
tendency of being exposed to the solvent, soluble, flexible, and disordered. The
highest signal is obtained from statistical amino acid preferences, but all 13
features contribute non-negligibly in the predictor. SEPIa's average prediction
accuracy is limited, with an AUC score (area under the receiver operating
characteristic curve) that reaches 0.65 both in 10-fold cross-validation and on an
independent test set. It is nevertheless slightly higher than that of other methods
evaluated on the same test set. Conclusions: SEPIa was applied to a test protein
whose epitopes are known, human beta 2 adrenergic G-protein-coupled receptor, with
promising results. Although the actual AUC score is rather low, many of the
predicted epitopes cluster together and overlap the experimental epitope region.
The reasons underlying the limitations of SEPIa and of all other B-cell epitope
predictors are discussed.
Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune
system. They recognize antigens with high specificity and are indispensable for
immunological memory following pathogen exposure or vaccination. The constant,
crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions
such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity,
and antibody-dependent cell-mediated phagocytosis. These functions are regulated by
a single N-linked, biantennary glycan of the heavy chain, which resides just below
the hinge region, and the presence of specific sugar moieties on the glycan has
profound implications on IgG effector functions. Emerging knowledge of how Fc
glycans contribute to IgG structure and functions has opened new avenues for the
therapeutic exploitation of defined antibody glycoforms in the treatment of cancer
and autoimmune diseases. Here, we review recent advances in understanding
proinflammatory IgG effector functions and their regulation by Fc glycans.
In this paper we present a simple mathematical model of cancer growth. The model is
discrete, it is a linear map (T) on three dimensional Eucledian vector space. But
for some values of the parameters there exists a linear vector field on three
dimensional Eucledian vector space whose time one map is T. We can analyze what
happens to the flow of this vector field on one of the coordinate hyperplanes (see
Fig. 5 in Sect. 4). In words this figure depicts, that if you have a bad ratio of
growth inhibitor to growth factor cancer grows and if you have a good ratio cancer
is eradicated. We can modify the dynamical system to model giving chemo therapy or
immune therapy and discuss the consequences. We fit the model predictions to a
Gompertz function and this gives a good fit for some values of the parameters (see
Figs. 1, 2, 3 and 4). A main topic of the present paper is a mass action kinetic
model for cancer growth. This gives a three dimensional ODE model, for which the
first orthant is positively invariant. We discretize the linearization of this
nonlinear ODE and with appropriate parameter definitions we recover the model T of
Sect. 1. For some parameter values the model T induces a two dimensional map of the
plane, see Sect. 5 .
Despite having been much debated, it is now well established that the immune system
plays an essential role in the fight against cancer. In this article, we will
highlight the implication of the immune system in the control of tumor growth and
describe the major components of the immune system involved in the antitumoral
immune response. The immune system, while exerting pressure on tumor cells, also
will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as
they develop. Finally, we will illustrate the numerous mechanisms of immune
suppression that take place within the tumoral microenvironment which allow tumor
cells to escape control from the immune system. The increasingly precise knowledge
of the brakes to an effective antitumor immune response allows the development of
immunotherapy strategies more and more innovating and promising of hope. (C) 2016
Published by Elsevier Masson SAS.
Peripartum cardiomyopathy is a heart failure syndrome occurring late in pregnancy
or during the early post-natal period. The pathophysiology of peripartum
cardiomyopathy is not fully understood and various mechanisms have been postulated
including an underlying inflammatory process. We here report four cases presenting
with acute left ventricular systolic dysfunction. Three out of four of the patients
presented with a left ventricular ejection fraction <30% and one with a left
ventricular ejection fraction of 35%. All made a full clinical recovery following
treatment with high-dose intravenous steroids. This case series adds to the growing
body of evidence for the role for immunosuppressants in the management of
peripartum cardiomyopathy.
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a
reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)],
producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the
standard of care for CML patients and exert a dual mode of action: direct
oncokinase inhibition and restoration of effector-mediated immune surveillance,
which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy.
TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib
induce a high rate of deep molecular response (DMR, BCR-ABL1 <= 0.01%) in CML
patients. As a result, the more recent goal of therapy in CML treatment is to
induce a durable DMR as a prelude to successful treatment-free remission (TFR),
which occurs in approximately half of all CML patients who cease TKI therapy. The
lack of overt relapse in such patients has been attributed to immunological control
of CML. In this review, we discuss an immunological timeline to successful TFR,
focusing on the immunology of CML during TKI treatment; an initial period of immune
suppression, limiting antitumor immune effector responses in newly diagnosed CML
patients, linked to an expansion of immature myeloid-derived suppressor cells and
regulatory T cells and aberrant expression of immune checkpoint signaling pathways,
including programmed death-1/programmed death ligand-1. Commencement of TKI
treatment is associated with immune system re-activation and restoration of
effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML
patients, albeit with differing frequencies in concert with differing levels of
molecular response achieved on TKI. DMR is associated with maximal restoration of
immune recovery in CML patients on TKI. Current data suggest a net balance between
both the effector and suppressor arms of the immune system, at a minimum involving
mature, cytotoxic CD56d"n NK cells may be important in mediating TFR success.
However, a major goal remains in CML to identify the most effective pathways to
target to maximize an advantageous immune response and promote TFR success.
The immune system is a critical component in defense against viral, bacterial,
parasitic, and fungal diseases. Immunological mechanisms, including immunological
mediators, innate immunity, cell-mediated immunity, and humoral-mediated immunity,
serve to maintain homeostasis and protect the host from disease. Immunological
variation can impact defense mechanisms, however. Two factors in particular that
can influence immune function are the single nucleotide polymorphisms (SNPs) and
aging. SNPs affecting inflammatory cytokines are an important modifier involved in
a number of diseases such as asthma, periodontal disease, atherosclerosis, diabetic
retinopathy, psoriasis, and osteoporosis. Age-related alterations to the immune
system have also been studied and documented. The genetic makeup of different
strains of mice and the age of these different strains cause large differences in
susceptibility to infection, with influenza virus infection among the most widely
studied. The mechanism of these differences due to either genetics or age is not
known but can be investigated in strain-and age-specific infectious disease models.
The immune system of vertebrates confers protective mechanisms to the host through
the sensing of stress-induced agents expressed during infection or cell stress.
Among them, the first line of host defense composed of the innate immune sensing of
these agents by pattern recognition receptors enables downstream adaptive immunity
to be primed, mediating the body's appropriate response to clear infection and
tissue damage. Mitochondria are bacteria within that allowed the emergence of
functional eukaryotic cells by positioning themselves as the cell powerhouse and an
initiator of cell death programs. It is striking to consider that such ancestral
bacteria, which had to evade host defense at some point to develop evolutionary
endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting
the immune system against various insults including infection by other pathogens.
Mitochondria have indeed become critical regulators of innate immune responses to
both pathogens and cell stress. They host numerous modulators, which play a direct
role into the assembly of innate sensing machineries that trigger host immune
response in both sterile and non-sterile conditions. Several lines of evidence
indicate the existence of a complex molecular interplay between mechanisms involved
in inflammation and metabolism. Mitochondrial function seems to participate in
innate immunity at various stages as diverse as the transcriptional regulation of
inflammatory cytokines and chemokines and their maturation by inflammasomes. Here,
we review the mechanisms by which mitochondria orchestrate innate immune responses
at different levels by promoting a cellular metabolic reprogramming and the
cytosolic immune signaling cascades. (C) 2016 Elsevier Ltd. All rights reserved.
Hundreds of intracellular peptides that are neither antigens nor neuropeptides are
present in mammalian cells and tissues. These peptides correspond to fragments of
cytosolic, nuclear or mitochondrial proteins. Proteasome inhibition affects the
levels of the intracellular peptides in human cell lines. Here, the effect of
immuneproteasome expression on the intracellular peptide profile was evaluated, and
its functional significance was investigated. The expression of the
immuneproteasome in HeLa cells was induced by interferon gamma treatment, and the
relative concentrations of the intracellular peptides were compared to those of the
control cells using isotope labeling and electron spray mass spectrometry. One of
the peptides identified, VGSELIQKY (EL28), corresponds to amino acids 251-259 of
the human 19S ATPase regulatory subunit 4. This peptide was increased in the
extracts of HeLa cells that had been treated with interferon gamma compared to
those of control cells. In vitro, EL28 increased the chymotrypsin, trypsin and
caspase-like proteasome activities. In vivo, when covalently linked to a cell-
penetrating peptide, EL28 potentiated the ability of interferon gamma to stimulate
the expression of the immuneproteasome beta 5i subunit and to increase the
proliferation of CD8 + T-cells. The EL28/cell-penetrating peptide construct also
improved and positively modulated the secondary IgG anti-bovine serum albumin
immune responsiveness elicited in high antibody-responder mice. Together, these
results suggest that EL28 is a functional intracellular peptide that can potentiate
interferon gamma activity. Biological significance: The functional identification
of EL28 advances our understanding regarding the bioactive peptides generated by
limited proteolysis within cells. (C) 2016 Elsevier B.V. All rights reserved.
Aims: The aim of this study was to verify the suitable use of candidate
'probiotics' selected by in vitro tests and the importance of in vivo assays to
nominate micro-organisms as probiotics and alternative prophylactic treatments for
Salmonella Typhimurium infection. Methods and Results: Thirty-three lactic acid
bacteria (LAB) isolated from foal's faeces were assessed based on the main
desirable functional in vitro criteria. Based on these results, Pediococcus
pentosaceus strain 40 was chosen to evaluate its putative probiotic features in a
mouse model of Salmonella infection. Daily intragastric doses of Ped. pentosaceus
40 for 10 days before and 10 days after Salmonella challenge (10(6) CFU of Salm.
Typhimurium per mouse) led to a significant aggravation in mouse health by
increasing weight loss, worsening clinical symptoms and anticipating the time and
the number of deaths by Salmonella. Pediococcus pentosaceus modulated cell-mediated
immune responses by up-regulation of the gene expression of the proinflammatory
cytokines IFN-gamma and TNF-alpha in the small intestine. Conclusion: The usual
criteria were used for in vitro screening of a large number of LAB for desirable
probiotic functional properties. However, the best candidate probiotic strain
identified, Ped. pentosaceus #40, aggravated the experimental disease in mice.
Significance and Impact of the Study: These findings emphasize the need for
prophylactic or therapeutic effectiveness to be demonstrated in in vivo models to
make precise health claims.
Flow cytometry is a method widely used to quantify suspended solids such as cells
or bacteria in a size range from 0.5 to several tens of micrometers in diameter. In
addition to a characterization of forward and sideward scatter properties, it
enables the use of fluorescent labeled markers like antibodies to detect respective
structures. Using indirect antibody staining, flow cytometry is employed here to
quantify birch pollen allergen (precisely Bet v 1)-loaded particles of 0.5 to 10 mu
m in diameter in inhalable particulate matter (PM10, particle size0.5 mu m.
Neutrophil extracellular traps are networks of DNA, histones and neutrophil
proteins released in response to infectious and inflammatory stimuli. Although a
component of the innate immune response, NETs are implicated in a range of disease
processes including autoimmunity and thrombosis. This protocol describes a simple
method for canine neutrophil isolation and quantification of NETs using a
microplate fluorescence assay. Blood is collected using conventional venipuncture
techniques. Neutrophils are isolated using dextran sedimentation and a density
gradient using conditions optimized for dog blood. After allowing time for
attachment to the wells of a 96 well plate, neutrophils are treated with NET-
inducing agonists such as phorbol-12-myristate-13-acetate or platelet activating
factor. DNA release is measured by the fluorescence of a cell-impermeable nucleic
acid dye. This assay is a simple, inexpensive method for quantifying NET release,
but NET formation rather than other causes of cell death must be confirmed with
alternative methods.
Lymphocytes respond to a variety of stimuli by activating intracellular signaling
pathways, which in turn leads to rapid cellular proliferation, migration and
differentiation, and cytokine production. All of these events are tightly linked to
the energy status of the cell, and therefore studying the energy-producing pathways
may give clues about the overall functionality of these cells. The extracellular
flux analyzer is a commonly used device for evaluating the performance of
glycolysis and mitochondrial respiration in many cell types. This system has been
used to study immune cells in a few published reports, yet a comprehensive protocol
optimized particularly for lymphocytes is lacking. Lymphocytes are fragile cells
that survive poorly in ex vivo conditions. Oftentimes lymphocyte subsets are rare,
and working with low cell numbers is inevitable. Thus, an experimental strategy
that addresses these difficulties is required. Here, we provide a protocol that
allows for rapid isolation of viable lymphocytes from lymphoid tissues, and for the
analysis of their metabolic states in the extracellular flux analyzer. Furthermore,
we provide results of experiments in which the metabolic activities of several
lymphocyte subtypes at different cell densities were compared. These observations
suggest that our protocol can be used to achieve consistent, well-standardized
results even at low cell concentrations, and thus it may have broad applications in
future studies focusing on the characterization of metabolic events in immune
cells.
Fluorescence-activated cell sorting (FACS) is a technique to purify specific cell
populations based on phenotypes detected by flow cytometry. This method enables
researchers to better understand the characteristics of a single cell population
without the influence of other cells. Compared to other methods of cell enrichment,
such as magnetic-activated cell sorting (MCS), FACS is more flexible and accurate
for cell separation due to the ability of phenotype detection by flow cytometry. In
addition, FACS is usually capable of separating multiple cell populations
simultaneously, which improves the efficiency and diversity of experiments.
Although FACS has some limitations, it has been broadly used to purify cells for
functional studies in both in vitro and in vivo settings. Here we report a protocol
using fluorescence-activated cell sorting to isolate a very rare population of
immune cells, plasmacytoid dendritic cells (pDC), with high purity from the bone
marrow of lupus-prone mice for in vitro functional studies of pDC.
The methods described herein for activation of naive CD4(+) T cells in suspension
and their adherence in coverslips for confocal microscopy analysis allow the
spatial localization and visualization of gangliosides involved in CD4(+) T cell
activation, that complement expression profiling experiments such as flow
cytometry, western blotting or real-time PCR. The quantification of ganglioside
expression through flow cytometry and their cellular localization through
microscopy can be obtained by the use of anti-ganglioside antibodies with high
affinity and specificity. Nonetheless, an adequate handling of cells in suspension
involves the treatment of culture plates to promote the necessary adherence
required for fluorescence or confocal microscopy acquisition. In this work, we
describe a protocol for determining GD3 and GD2 ganglioside expression and
colocalization with the TCR during naive CD4(+) T cell activation. Also, real-time
PCR experiments using < 40,000 cells are described for the determination of the GD3
and GM2/GD2 synthase genes, demonstrating that gene analysis experiments can be
performed with a low number of cells and without the need of additional low input
RNA kits.
Autoimmune diseases arise due to the loss of immunological self-tolerance.
Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance.
Tregs represent about 5 - 10% of the mature CD4+ T cell subpopulation in mice and
humans, with about 1 - 2% of those Tregs circulating in the peripheral blood.
Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs,
which have a potential to be used for cell-based therapies of autoimmune diseases.
Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i.e.,
iPSC-Tregs). The method is based on incorporating the transcription factor FoxP3
and an Ag-specific T cell receptor (TCR) into iPSCs and then differentiating on OP9
stromal cells expressing Notch ligands delta-like (DL) 1 and DL4. Following in
vitro differentiation, the iPSC-Tregs express CD4, CD8, CD3, CD25, FoxP3, and Ag-
specific TCR and are able to respond to Ag stimulation. This method has been
successfully applied to cell-based therapy of autoimmune arthritis in a murine
model. Adoptive transfer of these Ag-specific iPSC-Tregs into Ag-induced arthritis
(AIA)bearing mice has the ability to reduce joint inflammation and swelling and to
prevent bone loss.
Helper T cell development and function must be tightly regulated to induce an
appropriate immune response that eliminates specific pathogens yet prevents
autoimmunity. Many approaches involving different model organisms have been
utilized to understand the mechanisms controlling helper T cell development and
function. However, studies using mouse models have proven to be highly informative
due to the availability of genetic, cellular, and biochemical systems. One genetic
approach in mice used by many labs involves retroviral transduction of primary
helper T cells. This is a powerful approach due to its relative ease, making it
accessible to almost any laboratory with basic skills in molecular biology and
immunology. Therefore, multiple genes in wild type or mutant forms can readily be
tested for function in helper T cells to understand their importance and mechanisms
of action. We have optimized this approach and describe here the protocols for
production of high titer retroviruses, isolation of primary murine helper T cells,
and their transduction by retroviruses and differentiation toward the different
helper subsets. Finally, the use of this approach is described in uncovering
mechanisms utilized by microRNAs (miRNAs) to regulate pathways controlling helper T
cell development and function.
The ribosomal spacer PCR (RS-PCR) is a highly resolving and robust genotyping
method for S. aureus that allows a high throughput at moderate costs and is,
therefore, suitable to be used for routine purposes. For best resolution, data
evaluation and data management, a miniaturized electrophoresis system is required.
Together with such an electrophoresis system and the in-house developed software
(freely available here) assignment of the pattern of bands to a genotype is
standardized and straight forward. DNA extraction is simple (boiling prep),
setting-up of the reactions is easy and they can be run on any standard PCR
machine. PCR cycling is common except prolonged ramping and elongation times.
Compared to spa typing and Multi Locus Sequence Typing (MLST), RS-PCR does not
require DNA sequencing what simplifies the analysis considerably and allows a high
throughput. Furthermore, the resolution for bovine strains of S. aureus is at least
as good as spa typing and better than MLST or pulsed-field gel electrophoresis
(PFGE). The RS-PCR data base includes presently a total of 141 genotypes and
variants. The method is highly associated with the virulence gene pattern,
contagiosity and pathogenicity of S. aureus strains involved in bovine mastitis. S.
aureus genotype B (GTB) is contagious and causes herds problems causing large costs
in the Switzerland and other European countries. All the other genotypes observed
in Switzerland infect individual cows and quarters. Genotyping by RS-PCR allows the
reliable prediction of the epidemiological and the pathogenic potential of S.
aureus involved in bovine intramammary infection (IMI), two key factors for
clinical veterinary medicine. Because of these beneficial properties together with
moderate costs and a high sample throughput the goal of this publication is to give
a detailed, step-by-step protocol for easily establishing and running RS-PCR for
genotyping S. aureus in other laboratories.
Dendritic cells (DCs) recognize foreign structures of different pathogens, such as
viruses, bacteria, and fungi, via a variety of pattern recognition receptors (PRRs)
expressed on their cell surface and thereby activate and regulate immunity. The
major function of DCs is the induction of adaptive immunity in the lymph nodes by
presenting antigens via MHC I and MHC II molecules to naive T lymphocytes.
Therefore, DCs have to migrate from the periphery to the lymph nodes after the
recognition of pathogens at the sites of infection. For in vitro experiments or DC
vaccination strategies, monocyte-derived DCs are routinely used. These cells show
similarities in physiology, morphology, and function to conventional myeloid
dendritic cells. They are generated by interleukin 4 (IL-4) and
granulocytemacrophage colony-stimulating factor (GM-CSF) stimulation of monocytes
isolated from healthy donors. Here, we demonstrate how monocytes are isolated and
stimulated from anti-coagulated human blood after peripheral blood mononuclear cell
(PBMC) enrichment by density gradient centrifugation. Human monocytes are
differentiated into immature DCs and are ready for experimental procedures in a
non-clinical setting after 5 days of incubation.
Lymphocyte proliferation in response to antigenic or mitogenic stimulation is a
readily quantifiable phenomenon useful for testing immunomodulatory (i.e.,
immunosuppressive or immunostimulatory) chemical compounds and biologics. One of
the earliest steps during mitogenesis is cell enlargement or blastogenic
transformation, whereupon the cell volume increases before division. It is usually
detectable in the first several hours of T-lymphocyte stimulation. Here, we
describe a rapid method to quantify blastogenesis in T lymphocytes isolated from
mouse spleens and human peripheral blood mononuclear cells (PBMCs) using an
automated cell counter. Various commonly used proliferation assays for the most
part are laborious and only reflect the overall population effect rather than
individual cellular effects within a population. In contrast, the presented
automated cell counter assay provides rapid, direct, and precise measurements of
cell diameters that can be used for assessing the effectiveness of various mitogens
and immunomodulatory drugs in vitro.
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of
autoimmune diseases such as multiple sclerosis (MS) and its animal model
experimental autoimmune encephalomyelitis (EAE). This process is characterized by
the transmigration of activated T cells across brain endothelial cells (ECs), the
main constituents of the BBB. However, the consequences on brain EC function upon
interaction with such T cells are largely unknown. Here we describe an assay that
allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function
and barrier integrity during the interaction with T cells over time. The assay
makes use of impedance cell spectroscopy, a powerful tool for studying EC monolayer
integrity and permeability, by measuring changes in transendothelial electrical
resistance (TEER) and cell layer capacitance (Ccl). In direct contact with ECs,
stimulated but not naive T cells are capable of inducing EC monolayer dysfunction,
as visualized by a decrease in TEER and an increase in Ccl. The assay records
changes in EC monolayer integrity in a continuous and automated fashion. It is
sensitive enough to distinguish between different strengths of stimuli and levels
of T cell activation and it enables the investigation of the consequences of a
targeted modulation of T cell-EC interaction using a wide range of substances such
as antibodies, pharmacological reagents and cytokines. The technique can also be
used as a quality control for EC integrity in in vitro T-cell transmigration
assays. These applications make it a versatile tool for studying BBB properties
under physiological and pathophysiological conditions.
The hallmark of humoral immunity is to generate functional ASCs, which synthesize
and secrete Abs specific to an antigen (Ag), such as a pathogen, and are used for
host defense. For the quantitative determination of the functional status of the
humoral immune response of an individual, both serum Abs and circulating ASCs are
commonly measured as functional readouts. In humans, peripheral blood is the most
convenient and readily accessible sample that can be used for the determination of
the humoral immune response elicited by host B cells. Distinct B-cell subsets,
including ASCs, can be isolated directly from peripheral blood via selection with
lineage-specific Ab-conjugated microbeads or via cell sorting with flow cytometry.
Moreover, purified naive and memory B cells can be activated and differentiated
into ASCs in culture. The functional activities of ASCs to contribute to Ab
secretion can be quantified by ELISpot, which is an assay that converges enzyme-
linked immunoabsorbance assay (ELISA) and western blotting technologies to enable
the enumeration of individual ASCs at the singlecell level. In practice, the
ELISpot assay has been increasingly used to evaluate vaccine efficacy because of
the ease of handling of a large number of blood samples. The methods of isolating
human B cells from peripheral blood, the differentiation of B cells into ASCs in
vitro, and the employment of ELISpot for the quantification of total IgM-and IgG-
ASCs will be described here.
Peptide-major histocompatibility complex class I (pMHC-I) tetramers have been an
invaluable tool to study CD8(+) T-cell responses. Because these reagents directly
bind to T-cell receptors on the surface of CD8(+) T-lymphocytes, fluorochrome-
labeled pMHC-I tetramers enable the accurate detection of antigen (Ag)-specific
CD8(+) T-cells without the need for in vitro re-stimulation. Moreover, when
combined with multi-color flow cytometry, pMHC-I tetramer staining can reveal key
aspects of Ag-specific CD8(+) T-cells, including differentiation stage, memory
phenotype, and activation status. These types of analyses have been especially
useful in the field of HIV immunology where CD8(+) T-cells can affect progression
to AIDS. Experimental infection of rhesus macaques with simian immunodeficiency
virus (SIV) provides an invaluable tool to study cellular immunity against the AIDS
virus. As a result, considerable progress has been made in defining and
characterizing T-cell responses in this animal model. Here we present an optimized
protocol for enumerating SIV-specific CD8(+) T-cells in rhesus macaques by pMHC-I
tetramer staining. Our assay permits the simultaneous quantification and memory
phenotyping of two pMHC-I tetramer+ CD8(+) T-cell populations per test, which might
be useful for tracking SIV-specific CD8(+) T-cell responses generated by
vaccination or SIV infection. Considering the relevance of nonhuman primates in
biomedical research, this methodology is applicable for studying CD8(+) T-cell
responses in multiple disease settings.
Regulatory T cells (Tregs) are an integral part of peripheral tolerance,
suppressing immune reactions against self-structures and thus preventing autoimmune
diseases. Clinical approaches to adoptively transfer Tregs, or to deplete Tregs in
cancer, are underway with promising first outcomes. Because the number of naturally
occurring Tregs (nTregs) is very limited, studying certain Treg features using in
vitro induced Tregs (iTregs) can be advantageous. To date, the best although not
absolutely specific protein marker to delineate Tregs is the transcription factor
FOXP3. Despite the importance of Tregs including non-redundant roles of
peripherally induced Tregs, the protocols to generate iTregs are currently
controversial, particularly for human cells. This protocol therefore describes the
in vitro differentiation of human CD4+FOXP3+ iTregs from human naive T cells using
a range of Treg-inducing factors (TGF-beta plus IL-2 only, or their combination
with retinoic acid, rapamycin or butyrate) in parallel. It also describes the
phenotyping of these cells by flow cytometry and qRT-PCR. These protocols result in
reproducible expression of FOXP3 and other Treg signature genes and enable the
study of general FOXP3-regulatory mechanisms as well as protocol-specific effects
to delineate the impact of certain factors. iTregs can be utilized to study various
phenotypic aspects as well as molecular mechanisms of Treg induction. Detailed
molecular studies are facilitated by relatively large cell numbers that can be
obtained. A limitation for the application of iTregs is the relative instability of
FOXP3 expression in these cells compared to nTregs. iTregs generated by these
protocols can also be used for functional assays such as studying their suppressive
function, in which iTregs induced by TGF-beta plus retinoic acid and rapamycin
display superior suppressive activity. However, the suppressive capacity of iTregs
can differ from nTregs and the use of appropriate controls is crucial.
Bacterial biofilms frequently form on fungal surfaces and can be involved in
numerous bacterial-fungal interaction processes, such as metabolic cooperation,
competition, or predation. The study of biofilms is important in many biological
fields, including environmental science, food production, and medicine. However,
few studies have focused on such bacterial biofilms, partially due to the
difficulty of investigating them. Most of the methods for qualitative and
quantitative biofilm analyses described in the literature are only suitable for
biofilms forming on abiotic surfaces or on homogeneous and thin biotic surfaces,
such as a monolayer of epithelial cells. While laser scanning confocal microscopy
(LSCM) is often used to analyze in situ and in vivo biofilms, this technology
becomes very challenging when applied to bacterial biofilms on fungal hyphae, due
to the thickness and the three dimensions of the hyphal networks. To overcome this
shortcoming, we developed a protocol combining microscopy with a method to limit
the accumulation of hyphal layers in fungal colonies. Using this method, we were
able to investigate the development of bacterial biofilms on fungal hyphae at
multiple scales using both LSCM and scanning electron microscopy (SEM). This report
describes the protocol, including microorganism cultures, bacterial biofilm
formation conditions, biofilm staining, and LSCM and SEM visualizations.
The lungs are constantly exposed to the external environment, which in addition to
harmless particles, also contains pathogens, allergens, and toxins. In order to
maintain tolerance or to induce an immune response, the immune system must
appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in
maintaining a delicate balance to initiate immunity when required without causing
collateral damage to the lungs due to an exaggerated inflammatory response. While
there is a detailed understanding of the phenotype and function of immune cells
such as DCs in human blood, the knowledge of these cells in less accessible
tissues, such as the lungs, is much more limited, since studies of human lung
tissue samples, especially from healthy individuals, are scarce. This work presents
a strategy to generate detailed spatial and phenotypic characterization of lung
tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling
of endobronchial biopsies. Several small biopsies can be collected from each
individual and can be subsequently embedded for ultrafine sectioning or
enzymatically digested for advanced flow cytometric analysis. The outlined
protocols have been optimized to yield maximum information from small tissue
samples that, under steady-state conditions, contain only a low frequency of DCs.
While the present work focuses on DCs, the methods described can directly be
expanded to include other (immune) cells of interest found in mucosal lung tissue.
Furthermore, the protocols are also directly applicable to samples obtained from
patients suffering from pulmonary diseases where bronchoscopy is part of
establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD),
sarcoidosis, or lung cancer.
A number of methods exist for the transformation of B lymphocytes by the Epstein
Barr virus in vitro into immortalized cell lines. We have developed a new method
with a powerful and simple strategy for the establishment of B-LCLs, the red blood
cell lysis method. This method simplified the PBMC separation procedure with red
blood cell removal, and used as little as 0.5 mL of whole blood for establishing
EBV-immortalized cell lines, which can proliferate to large cell numbers in a
relatively short amount time with a 100% success rate. The method is simple,
reliable, time saving, and applicable to treating a large number of the clinical
samples.
Reporter mice have been widely used to observe the localization of expression of
targeted genes. This protocol focuses on a strategy to establish a new transgenic
reporter mouse model. We chose to visualize interleukin (IL) 22 gene expression
because this cytokine has important activities in the intestine, where it
contributes to repair tissues damaged by inflammation. Reporter systems offer
considerable advantages over other methods of identifying products in vivo. In the
case of IL-22, other studies had first isolated cells from tissues and then re-
stimulated the cells in vitro. IL-22, which is normally secreted, was trapped
inside cells using a drug, and intracellular staining was used to visualize it.
This method identifies cells capable of producing IL-22, but it does not determine
whether they were doing so in vivo. The reporter design includes inserting a gene
for a fluorescent protein (tdTomato) into the IL-22 gene in such a way that the
fluorescent protein cannot be secreted and therefore remains trapped inside the
producing cells in vivo. Fluorescent producers can then be visualized in tissue
sections or by ex vivo analysis through flow cytometry. The actual construction
process for the reporter included recombineering a bacterial artificial chromosome
that contained the IL-22 gene. This engineered chromosome was then introduced into
the mouse genome. Homeostatic IL-22 reporter expression was observed in different
mouse tissues, including the spleen, thymus, lymph nodes, Peyer's patch, and
intestine, by flow cytometry analysis. Colitis was induced by T-cell
(CD4(+)CD45RBhigh) transfer, and reporter expression was visualized. Positive T
cells were first present in the mesenteric lymph nodes, and then they accumulated
inside the lamina propria of the distal small intestine and colon tissues. The
strategy using BACs gave good-fidelity reporter expression compared to IL-22
expression, and it is simpler than knock-in procedures.
The stimulation of immune responses is a common tool in invertebrate studies to
examine the efficacy and the mechanisms of immunity. This stimulation is based on
the injection of non-pathogenic particles into insects, as the particles will be
detected by the immune system and will induce the production of immune effectors.
We focus here on the stimulation of the melanization response in the mosquito
Anopheles gambiae. The melanization response results in the encapsulation of
foreign particles and parasites with a dark layer of melanin. To stimulate this
response, mosquitoes are inoculated with beads in the thoracic cavity using
microcapillary glass tubes. Then, after 24 hr, the mosquitoes are dissected to
retrieve the beads. The degree of melanization of the bead is measured using image
analysis software. Beads do not have the pathogenic effects of parasites, or their
capacity to evade or suppress the immune response. These injections are a way to
measure immune efficacy and the impact of immune stimulations on other life history
traits, such as fecundity or longevity. It is not exactly the same as directly
studying host-parasite interactions, but it is an interesting tool to study
immunity and its evolutionary ecology.
It is now well known that T lymphocytes play a critical role in the development of
several cardiovascular diseases(1,2,3,4,5). For example, studies from our group
have shown that hypertension is associated with an excessive accumulation of T
cells in the vessels and kidney during the development of experimental
hypertension(6). Once in these tissues, T cells produce several cytokines that
affect both vascular and renal function leading to vasoconstriction and sodium and
water retention(1,2). To fully understand how T cells cause cardiovascular and
renal diseases, it is important to be able to identify and quantify the specific T
cell subsets present in these tissues. T cell subsets are defined by a combination
of surface markers, the cytokines they secrete, and the transcription factors they
express. The complexity of the T cell population makes flow cytometry and
intracellular staining an invaluable technique to dissect the phenotypes of the
lymphocytes present in tissues. Here, we provide a detailed protocol to identify
the surface and intracellular markers (cytokines and transcription factors) in T
cells isolated from murine kidney, aorta and aortic draining lymph nodes in a model
of angiotensin II induced hypertension. The following steps are described in
detail: isolation of the tissues, generation of the single cell suspensions, ex
vivo stimulation, fixation, permeabilization and staining. In addition, several
fundamental principles of flow cytometric analyses including choosing the proper
controls and appropriate gating strategies are discussed.
Monoclonal antibodies are universal binding molecules and are widely used in
biomedicine and research. Nevertheless, the generation of these binding molecules
is time-consuming and laborious due to the complicated handling and lack of
alternatives. The aim of this protocol is to provide one standard method for the
generation of monoclonal antibodies using hybridoma technology. This technology
combines two steps. Step 1 is an appropriate immunization of the animal and step 2
is the fusion of B lymphocytes with immortal myeloma cells in order to generate
hybrids possessing both parental functions, such as the production of antibody
molecules and immortality. The generated hybridoma cells were then recloned and
diluted to obtain stable monoclonal cell cultures secreting the desired monoclonal
antibody in the culture supernatant. The supernatants were tested in enzyme-linked
immunosorbent assays (ELISA) for antigen specificity. After the selection of
appropriate cell clones, the cells were transferred to mass cultivation in order to
produce the desired antibody molecule in large amounts. The purification of the
antibodies is routinely performed by affinity chromatography. After purification,
the antibody molecule can be characterized and validated for the final test
application. The whole process takes 8 to 12 months of development, and there is a
high risk that the antibody will not work in the desired test system.
Murine full-thickness skin transplantation is a well-established in vivo model to
study alloimmune response and graft rejection. Despite its limited application to
humans, skin transplantation in mice has been widely employed for transplantation
research. The procedure is easy to learn and perform, and it does not require
delicate microsurgical techniques nor extensive training. Moreover, graft rejection
in this model occurs in a very reproducible immunological reaction and is easily
monitored by direct inspection and palpation. In addition, secondary skin
transplantation with donor-matched or third-party skin grafts can be performed on
more complex transplant models as an alternative and uncomplicated method to assess
donor-specific tolerance. The complications are low and are in general limited to
anesthesia overdose or respiratory distress after the procedure. Graft failure, on
the other hand, occurs commonly as a result of poor preparation of the graft,
incorrect positioning in the graft bed, or inappropriate placement of the bandage.
In this article, we present a protocol for full-thickness skin transplantation in
mice and describe the important steps necessary for a successful procedure.
Neutrophils (PMN) are best known for their phagocytic functions against invading
pathogens and microorganisms. They have the shortest half-life amongst leukocytes
and in their non-activated state are constitutively committed to apoptosis. When
recruited to inflammatory sites to resolve inflammation, they produce an array of
cytotoxic molecules with potent antimicrobial killing. Yet, when these powerful
cytotoxic molecules are released in an uncontrolled manner they can damage
surrounding tissues. In recent years however, neutrophil versatility is
increasingly evidenced, by demonstrating plasticity and immunoregulatory functions.
We have recently identified a new neutrophil-derived subpopulation, which develops
spontaneously in standard culture conditions without the addition of
cytokines/growth factors such as granulocyte colony-stimulating factor
(GM-CSF)/interleukin (IL)-4. Their phagocytic abilities of neutrophil remnants
largely contribute to increase their size immensely; therefore they were termed
giant phagocytes (G phi). Unlike neutrophils, G phi are long lived in culture. They
express the cluster of differentiation (CD) neutrophil markers
CD66b/CD63/CD15/CD11b/myeloperoxidase (MPO)/neutrophil elastase (NE), and are
devoid of the monocytic lineage markers CD14/CD16/CD163 and the dendritic
CD1c/CD141 markers. They also take-up latex and zymosan, and respond by oxidative
burst to stimulation with opsonized-zymosan and PMA. G phi also express the
scavenger receptors CD68/CD36, and unlike neutrophils, internalize oxidized-low
density lipoprotein (oxLDL). Moreover, unlike fresh neutrophils, or cultured
monocytes, they respond to oxLDL uptake by increased reactive oxygen species (ROS)
production. Additionally, these phagocytes contain microtubule-associated protein-1
light chain 3B (LC3B) coated vacuoles, indicating the activation of autophagy.
Using specific inhibitors it is evident that both phagocytosis and autophagy are
prerequisites for their development and likely NADPH oxidase dependent ROS. We
describe here a method for the preparation of this new subpopulation of long-lived,
neutrophil-derived phagocytic cells in culture, their identification and their
currently known characteristics. This protocol is essential for obtaining and
characterizing G phi in order to further investigate their significance and
functions.
Although originally developed for predicting transfusion outcomes of serologically
incompatible blood, the monocyte monolayer assay (MMA) is a highly versatile in
vitro assay that can be modified to examine different aspects of antibody and Fc
gamma receptor (Fc gamma R)-mediated phagocytosis in both research and clinical
settings. The assay utilizes adherent monocytes from peripheral blood mononuclear
cells isolated from mammalian whole blood. MMA has been described for use in both
human and murine investigations. These monocytes express Fc gamma Rs (e.g., Fc
gamma RI, Fc gamma RIIA, Fc gamma RIIB, and Fc gamma RIIIA) that are involved in
immune responses. The MMA exploits the mechanism of Fc gamma R-mediated
interactions, phagocytosis in particular, where antibody-sensitized red blood cells
(RBCs) adhere to and/or activate Fc gamma Rs and are subsequently phagocytosed by
the monocytes. In vivo, primarily tissue macrophages found in the spleen and liver
carry out Fc gamma R-mediated phagocytosis of antibody-opsonized RBCs, causing
extravascular hemolysis. By evaluating the level of phagocytosis using the MMA,
different aspects of the in vivo Fc gamma R-mediated process can be investigated.
Some applications of the MMA include predicting the clinical relevance of allo-or
autoantibodies in a transfusion setting, assessing candidate drugs that promote or
inhibit phagocytosis, and combining the assay with fluorescent microscopy or
traditional Western immunoblotting to investigate the downstream signaling effects
of Fc gamma R-engaging drugs or antibodies. Some limitations include the
laboriousness of this technique, which takes a full day from start to finish, and
the requirement of research ethics approval in order to work with mammalian blood.
However, with diligence and adequate training, the MMA results can be obtained
within a 24-h turnover time.
Cells release small extracellular vesicles (EVs) into the surrounding media. Upon
virus infection cells also release virions that have the same size of some of the
EVs. Both virions and EVs carry proteins of the cells that generated them and are
antigenically heterogeneous. In spite of their diversity, both viruses and EVs were
characterized predominantly by bulk analysis. Here, we describe an original
nanotechnology-based high throughput method that allows the characterization of
antigens on individual small particles using regular flow cytometers. Viruses or
extracellular vesicles were immunocaptured with 15 nm magnetic nanoparticles (MNPs)
coupled to antibodies recognizing one of the surface antigens. The captured virions
or vesicles were incubated with fluorescent antibodies against other surface
antigens. The resultant complexes were separated on magnetic columns from unbound
antibodies and analyzed with conventional flow cytometers triggered on
fluorescence. This method has wide applications and can be used to characterize the
antigenic composition of any viral-and non-viral small particles generated by cells
in vivo and in vitro. Here, we provide examples of the usage of this method to
evaluate the distribution of host cell markers on individual HIV-1 particles, to
study the maturation of individual Dengue virions (DENV), and to investigate
extracellular vesicles released into the bloodstream.
B cells reactive with a specific antigen usually occur at a frequency of <0.05% of
lymphocytes. For decades researchers have sought methods to isolate and enrich
these rare cells for studies of their phenotype and biology. Approaches are
inevitably based on the principle that B cells recognize native antigen by virtue
of cell surface receptors that are representative in specificity of antibodies that
will eventually be secreted by their differentiated daughters. Perhaps the most
obvious approach to the problem involves use of fluorochrome-conjugated antigens in
conjunction with fluorescence-activated cell sorting (FACS). However, the utility
of these methods is limited by cell frequency and the achievable rate of analysis
and isolation by electronic sorting. A novel method to enrich rare antigen-specific
B cells using magnetic nanoparticles that results in high yield enrichment of
antigen-reactive B cells from large starting cell populations is described. This
method enables improved monitoring of the phenotype and biology of antigen reactive
cells before and following in vivo antigen encounter, such as after immunization or
during development of autoimmunity.
Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in
tumor control. In order to carry out this function, the cell surface-expressed T-
cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-
restricted tumor-derived peptides (pHLA). However, we and others have shown that
most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms
that define this poor recognition could aid in the development of new targeted
therapies that circumnavigate these shortcomings. Indeed, present therapies that
lack this molecular understanding have not been universally effective. Here, we
describe methods that we commonly employ in the laboratory to determine how the
nature of the interaction between TCRs and pHLA governs T-cell functionality. These
methods include the generation of soluble TCRs and pHLA and the use of these
reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-
cell staining with pHLA multimers. Using these approaches and guided by structural
analysis, it is possible to modify the interaction between TCRs and pHLA and to
then test how these modifications impact T-cell antigen recognition. These findings
have already helped to clarify the mechanism of T-cell recognition of a number of
cancer antigens and could direct the development of altered peptides and modified
TCRs for new cancer therapies.
The intestine displays an architecture of repetitive crypt structures consisting of
different types of epithelial cells, lamina propia containing immune cells, and
stroma. All of these heterogeneous cells contribute to intestinal homeostasis and
participate in antimicrobial host defense. Therefore, identifying a surrogate model
for studying immune response and antimicrobial activity of the intestine in an in
vitro setting is extremely challenging. In vitro studies using immortalized
intestinal epithelial cell lines or even primary crypt organoid culture do not
represent the exact physiology of normal intestine and its microenvironment. Here,
we discuss a method of culturing mouse colon tissue in a culture dish and how this
ex vivo organ culture system can be implemented in studies related to antimicrobial
host defense responses. In representative experiments, we showed that colons in
organ culture express antimicrobial peptides in response to exogenous IL-1 beta and
IL-18. Further, the antimicrobial effector molecules produced by the colon tissues
in the organ culture efficiently kill Escherichia coli in vitro. This approach,
therefore, can be utilized to dissect the role of pathogen-and danger-associated
molecular patterns and their cellular receptors in regulating intestinal innate
immune responses and antimicrobial host defense responses.
Fluorescence correlation spectroscopy (FCS) is a powerful technique for studying
the diffusion of molecules within biological membranes with high spatial and
temporal resolution. FCS can quantify the molecular concentration and diffusion
coefficient of fluorescently labeled molecules in the cell membrane. This technique
has the ability to explore the molecular diffusion characteristics of molecules in
the plasma membrane of immune cells in steady state (i.e., without processes
affecting the result during the actual measurement time). FCS is suitable for
studying the diffusion of proteins that are expressed at levels typical for most
endogenous proteins. Here, a straightforward and robust method to determine the
diffusion rate of cell membrane proteins on primary lymphocytes is demonstrated. An
effective way to perform measurements on antibody-stained live cells and commonly
occurring observations after acquisition are described. The recent advancements in
the development of photostable fluorescent dyes can be utilized by conjugating the
antibodies of interest to appropriate dyes that do not bleach extensively during
the measurements. Additionally, this allows for the detection of slowly diffusing
entities, which is a common feature of proteins expressed in cell membranes. The
analysis procedure to extract molecular concentration and diffusion parameters from
the generated autocorrelation curves is highlighted. In summary, a basic protocol
for FCS measurements is provided; it can be followed by immunologists with an
understanding of confocal microscopy but with no other previous experience of
techniques for measuring dynamic parameters, such as molecular diffusion rates.
Human noroviruses are a leading cause of epidemic and sporadic gastroenteritis
worldwide. Because most infections are either spread directly via the person-to-
person route or indirectly through environmental surfaces or food, contaminated
fomites and inanimate surfaces are important vehicles for the spread of the virus
during norovirus outbreaks. We developed and evaluated a protocol using macrofoam
swabs for the detection and typing of human noroviruses from hard surfaces.
Compared with fiber-tipped swabs or antistatic wipes, macrofoam swabs allow virus
recovery (range 1.2-33.6%) from toilet seat surfaces of up to 700 cm(2). The
protocol includes steps for the extraction of the virus from the swabs and further
concentration of the viral RNA using spin columns. In total, 127 (58.5%) of 217
swab samples that had been collected from surfaces in cruise ships and long-term
care facilities where norovirus gastroenteritis had been reported tested positive
for GII norovirus by RT-qPCR. Of these 29 (22.8%) could be successfully genotyped.
In conclusion, detection of norovirus on environmental surfaces using the protocol
we developed may assist in determining the level of environmental contamination
during outbreaks as well as detection of virus when clinical samples are not
available; it may also facilitate monitoring of effectiveness of remediation
strategies.
Cell-specific restriction of viral replication without concomitant attenuation can
benefit vaccine development, gene therapy, oncolytic virotherapy, and understanding
the biological properties of viruses. There are several mechanisms for regulating
viral tropism, however they tend to be virus class specific and many result in
virus attenuation. Additionally, many viruses, including picornaviruses, exhibit
size constraints that do not allow for incorporation of large amounts of foreign
genetic material required for some targeting methods. MicroRNAs are short, non-
coding RNAs that regulate gene expression in eukaryotic cells by binding
complementary target sequences in messenger RNAs, preventing their translation or
accelerating their degradation. Different cells exhibit distinct microRNA
signatures and many microRNAs serve as biomarkers. These differential expression
patterns can be exploited for restricting gene expression in cells that express
specific microRNAs while maintaining expression in cells that do not. In regards to
regulating viral tropism, sequences complementary to specific microRNAs are
incorporated into the viral genome, generally in the 3' non-coding regions,
targeting them for destruction in the presence of the cognate microRNAs thus
preventing viral gene expression and/or replication. MicroRNA-targeting is a
technique that theoretically can be applied to all viral vectors without altering
the potency of the virus in the absence of the corresponding microRNAs. Here we
describe experimental methods associated with generating a microRNA-targeted
picornavirus and evaluating the efficacy and specificity of that targeting in
vitro. This protocol is designed for a rapidly replicating virus with a lytic
replication cycle, however, modification of the time points analyzed and the
specific virus titration readouts used will aid in the adaptation of this protocol
to many different viruses.
The female reproductive tract (FRT) mucosal immune system serves as the first line
of defense. Better knowledge of the genital mucosa is therefore essential for
understanding pathogenicity of different pathogens including HIV. Gamma delta (GD)
T cells are the prototype of 'unconventional' T cells and represent a relatively
small subset of T cells defined by their expression of heterodimeric T-cell
receptors (TCRs) composed of gamma and delta chains. This sets them apart from the
classical and much better known CD4(+) helper T cells and CD8(+) cytotoxic T cells
that are defined by alpha-beta TCRs. GD T cells often show tissue-specific
localization and are enriched in epithelium. GD T cells orchestrate immune
responses in inflammation, tumor surveillance, infectious disease, and
autoimmunity. Here, we present a method to reproducibly isolate and analyze human
endocervical intraepithelial GD T lymphocytes. We have used endocervical cytobrush
samples from women participating in the Women's Interagency HIV Infection Study
(WIHS). Knowledge about GD T cells interactions during conditions in which there is
an insult to the vaginal mucosal could be applied to any clinical study in which
mucosal vulnerability is addressed, including the development of vaginal
microbicides. In addition, knowledge about mucosal GD T cell responses has
potential for application of GD T cell-based immune therapy in treating infectious
diseases.
The commonality of antibiotic usage in medicine means that understanding the
resulting consequences to the host is vital. Antibiotics often decrease host
microbiome community diversity and alter the microbial community composition. Many
diseases such as antibiotic-associated enterocolitis, inflammatory bowel disease,
and metabolic disorders have been linked to a disrupted microbiota. The complex
interplay between host, microbiome, and antibiotics needs a tractable model for
studying host-microbiome interactions. Our freshwater vertebrate fish serves as a
useful model for investigating the universal aspects of mucosal microbiome
structure and function as well as analyzing consequential host effects from
altering the microbial community. Methods include host challenges such as infection
by a known fish pathogen, exposure to fecal or soil microbes, osmotic stress,
nitrate toxicity, growth analysis, and measurement of gut motility. These
techniques demonstrate a flexible and useful model system for rapid determination
of host phenotypes.
High-throughput screening (HTS) is currently the mainstay for the identification of
chemical entities capable of modulating biochemical reactions or cellular
processes. With the advancement of biotechnologies and the high translational
potential of small molecules, a number of innovative approaches in drug discovery
have evolved, which explains the resurgent interest in the use of HTS. The oncology
field is currently the most active research area for drug screening, with no major
breakthrough made for the identification of new immunomodulatory compounds
targeting transplantation-related complications or autoimmune ailments. Here, we
present a novel in vitro murine fluorescent-based lymphocyte assay easily adapted
for the identification of new immunomodulatory compounds. This assay uses T or B
cells derived from a transgenic mouse, in which the Nur77 promoter drives GFP
expression upon T-or B-cell receptor stimulation. As the GFP intensity reflects the
activation/ transcriptional activity of the target cell, our assay defines a novel
tool to study the effect of given compound(s) on cellular/biological responses. For
instance, a primary screening was performed using 4,398 compounds in the absence of
a "target hypothesis", which led to the identification of 160 potential hits
displaying immunomodulatory activities. Thus, the use of this assay is suitable for
drug discovery programs exploring large chemical libraries prior to further in
vitro/in vivo validation studies.
The interferon regulatory factor 5 (IRF5) is crucial for cells to determine if they
respond in a pro-inflammatory or anti-inflammatory fashion. IRF5's ability to
switch cells from one pathway to another is highly attractive as a therapeutic
target. We designed a decoy peptide IRF5D with a molecular modeling software for
designing small molecules and peptides. IRF5D inhibited IRF5, reduced alterations
in extracellular matrix, and improved endothelial vasodilation in the tight-skin
mouse (Tsk/+). The K-d of IRF5D for recombinant IRF5 is 3.72 +/- 0.74 x 10(-6) M as
determined by binding experiments using biolayer interferometry experiments.
Endothelial cells (EC) proliferation and apoptosis were unchanged using increasing
concentrations of IRF5D (0 to 100 mu g/mL, 24 h). Tsk/+ mice were treated with
IRF5D (1 mg/kg/d subcutaneously, 21 d). IRF5 and ICAM expressions were decreased
after IRF5D treatment. Endothelial function was improved as assessed by
vasodilation of facialis arteries from Tsk/+ mice treated with IRF5D compared to
Tsk/+ mice without IRF5D treatment. As a transcription factor, IRF5 traffics from
the cytosol to the nucleus. Translocation was assessed by immunohistochemistry on
cardiac myocytes cultured on the different cardiac extracellular matrices. IRF5D
treatment of the Tsk/+ mouse resulted in a reduced number of IRF5 positive nuclei
in comparison to the animals without IRF5D treatment (50 mu g/mL, 24 h). These
findings demonstrate the important role that IRF5 plays in inflammation and
fibrosis in Tsk/+ mice.
The liver plays a decisive role in the regulation of systemic inflammation. In
chronic kidney disease in particular, the liver reacts in response to the uremic
milieu, oxidative stress, endotoxemia and the decreased clearance of circulating
proinflammatory cytokines by producing a large number of acute-phase reactants.
Experimental tools to study inflammation and the underlying role of hepatocytes are
crucial to understand the regulation and contribution of hepatic cytokines to a
systemic acute phase response and a prolonged pro-inflammatory scenario, especially
in an intricate setting such as chronic kidney disease. Since studying complex
mechanisms of inflammation in vivo remains challenging, resource-intensive and
usually requires the usage of transgenic animals, primary isolated hepatocytes
provide a robust tool to gain mechanistic insights into the hepatic acute-phase
response. Since this in vitro technique features moderate costs, high
reproducibility and common technical knowledge, primary isolated hepatocytes can
also be easily used as a screening approach. Here, we describe an enzymatic-based
method to isolate primary murine hepatocytes, and we describe the assessment of an
inflammatory response in these cells using ELISA and quantitative real-time PCR.
NK cell cytotoxicity is a widely used measure to determine the effect of outside
intervention on NK cell function. However, the accuracy and reproducibility of this
assay can be considered unstable, either because of user's errors or because of the
sensitivity of NK cells to experimental manipulation. To eliminate these issues, a
workflow that reduces them to a minimum was established and is presented here. To
illustrate, we obtained blood samples, at various time points, from runners (n = 4)
that were submitted to an intense bout of exercise. First, NK cells are
simultaneously identified and isolated through CD56 tagging and magnetic-based
sorting, directly from whole blood and from as little as one milliliter. The sorted
NK cells are removed of any reagent or capping antibodies. They can be counted in
order to establish an accurate NK cell count per milliliter of blood. Secondly, the
sorted NK cells (effectors cells or E) can be mixed with 3,3'-
Diotadecyloxacarbocyanine Perchlorate (DiO) tagged K562 cells (target cells or T)
at an assay-optimal 1: 5 T: E ratio, and analyzed using an imaging flow-cytometer
that allows for the visualization of each event and the elimination of any false
positive or false negatives (such as doublets or effector cells). This workflow can
be completed in about 4 h, and allows for very stable results even when working
with human samples. When available, research teams can test several experimental
interventions in human subjects, and compare measurements across several time
points without compromising the data's integrity.
Lipid analysis performed by high performance thin layer chromatography (HPTLC) is a
relatively simple, cost-effective method of analyzing a broad range of lipids. The
function of lipids (e. g., in host-pathogen interactions or host entry) has been
reported to play a crucial role in cellular processes. Here, we show a method to
determine lipid composition, with a focus on the cholesterol level of primary
blood-derived neutrophils, by HPTLC in comparison to high performance liquid
chromatography (HPLC). The aim was to investigate the role of lipid/cholesterol
alterations in the formation of neutrophil extracellular traps (NETs). NET release
is known as a host defense mechanism to prevent pathogens from spreading within the
host. Therefore, blood-derived human neutrophils were treated with methyl-beta-
cyclodextrin (M beta CD) to induce lipid alterations in the cells. Using HPTLC and
HPLC, we have shown that M beta CD treatment of the cells leads to lipid
alterations associated with a significant reduction in the cholesterol content of
the cell. At the same time, M beta CD treatment of the neutrophils led to the
formation of NETs, as shown by immunofluorescence microscopy. In summary, here we
present a detailed method to study lipid alterations in neutrophils and the
formation of NETs.
The identification of an antigenic epitope by the immune system allows for the
understanding of the protective mechanism of neutralizing antibodies that may
facilitate the development of vaccines and peptide drugs. Peptide scanning is a
simple and efficient method that straightforwardly maps the linear epitope
recognized by a monoclonal antibody (mAb). Here, the authors present an epitope
determination methodology involving serially truncated recombinant proteins,
synthetic peptide design, and dot-blot hybridization for the antigenic recognition
of nervous necrosis virus coat protein using a neutralizing mAb. This technique
relies on the dot-blot hybridization of synthetic peptides and mAbs on a
polyvinylidene fluoride (PVDF) membrane. The minimum antigenic region of a viral
coat protein recognized by the RG-M56 mAb can be narrowed down by step-by-step
trimmed peptide mapping onto a 6-mer peptide epitope. In addition, alanine scanning
mutagenesis and residue substitution can be performed to characterize the binding
significance of each amino acid residue making up the epitope. The residues
flanking the epitope site were found to play critical roles in peptide conformation
regulation. The identified epitope peptide may be used to form crystals of epitope
peptide-antibody complexes for an x-ray diffraction study and functional
competition, or for therapeutics.
One important feature of the major opportunistic human pathogen Staphylococcus
aureus is its extraordinary ability to rapidly acquire resistance to antibiotics.
Genomic studies reveal that S. aureus carries many virulence and resistance genes
located in mobile genetic elements, suggesting that horizontal gene transfer (HGT)
plays a critical role in S. aureus evolution. However, a full and detailed
description of the methodology used to study HGT in S. aureus is still lacking,
especially regarding natural transformation, which has been recently reported in
this bacterium. This work describes three protocols that are useful for the in
vitro investigation of HGT in S. aureus: conjugation, phage transduction, and
natural transformation. To this aim, the cfr gene (chloramphenicol/florfenicol
resistance), which confers the Phenicols, Lincosamides, Oxazolidinones,
Pleuromutilins, and Streptogramin A (PhLOPSA)-resistance phenotype, was used.
Understanding the mechanisms through which S. aureus transfers genetic materials to
other strains is essential to comprehending the rapid acquisition of resistance and
helps to clarify the modes of dissemination reported in surveillance programs or to
further predict the spreading mode in the future.
Inflammation is a local response to infection and tissue damage mediated by
activated macrophages, monocytes, and other immune cells that release cytokines and
other mediators of inflammation. For a long time, humoral and cellular mechanisms
have been studied for their role in regulating the immune response, but recent
advances in the field of immunology and neuroscience have also unraveled specific
neural mechanisms with interesting therapeutic potential. The so-called cholinergic
anti-inflammatory pathway (CAP) has been described to control innate immune
responses and inflammation in a very potent manner. In the early 2000s, Tracey and
collaborators developed a technique that stimulates the vagus nerve and mimics the
effect of the pathway. The methodology is based on the electrical stimulation of
the vagus nerve at low voltage and frequency, in order to avoid any side effects of
overstimulation, such as deregulation of heart rate variability. Electrical devices
for stimulation are now available, making it easy to set up the methodology in the
laboratory. The goal of this research was to investigate the potential involvement
of prostaglandins in the CAP. Unfortunately, based on earlier attempts, we failed
to use the original protocol, as the induced inflammatory response either was too
high or was not suitable for enzymatic metabolism properties. The different
settings of the original surgery protocol remained mostly unchanged, but the
conditions regarding inflammatory induction and the time point before sacrifice
were improved to fit our purposes (i. e., to investigate the involvement of the CAP
in more limited inflammatory responses). The modified version of the original
protocol, presented here, includes a longer time range between vagus nerve
stimulation and analysis, which is associated with a lower induction of
inflammatory responses. Additionally, while decreasing the level of
lipopolysaccharides (LPS) to inject, we also came across new observations regarding
mechanistic properties in the spleen.
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex
and poorly understood immunopathogenesis. However, a pathogenic role for the T
helper type 17 (Th17) axis was demonstrated by many studies, while regulatory T
cells (T-regs) were shown to mediate protection. Recently, we and others
characterized a novel and independent T cell population expressing both the T-reg
characteristic transcription factor forkhead box protein 3 (FoxP3) and the Th17-
defining retinoic acid receptor-related orphan nuclear receptor t (RORt). Studies
in a model of acute glomerulonephritis unveiled potent regulatory, but also
proinflammatory, functions of RORt(+)FoxP3(+) T-regs. This bi-functional nature
prompted us to suggest the name biT(regs)'. Importantly, the pathogenic biT(reg)
effects were dependent upon expression of RORt. We thus aimed to evaluate the
contribution of RORt(+)FoxP3(+) biT(regs) to pristane-induced SLE and explored the
therapeutic potential of interference with RORt activation. Our analyses revealed
expansion of IL-17 producing biT(regs) in a distinctive time-course and organ-
specific pattern, coincident with the development of autoimmunity and tissue
injury. Importantly, specific ablation of RORt activation in endogenous biT(regs)
resulted in significant amelioration of pristane-induced pulmonary vasculitis and
lupus nephritis. As potential mechanisms underlying the observed protection, we
found that secretion of IL-17 by biT(regs) was abrogated completely in
FoxP3(Cre)xRORC(fl/fl) mice. Furthermore, T-regs showed a more activated phenotype
after cell-specific inactivation of RORt signalling. Finally, and remarkably,
biT(regs) were found to potently suppress anti-inflammatory Th2 immunity in a RORt-
dependent manner. Our study thus identifies biT(regs) as novel players in SLE and
advocates RORt-directed interventions as promising therapeutic strategies.
The MHC class II (MHCII) processing pathway presents peptides derived from
exogenous or membrane-bound proteins to CD4+ T cells. Several studies have shown
that glycopeptides are necessary to modulate CD4+ T cell recognition, though
glycopeptide structures in these cases are generally unknown. Here, we present a
total of 93 glycopeptides from three melanoma cell lines and one matched EBV-
transformed line with most found only in the melanoma cell lines. The glycosylation
we detected was diverse and comprised 17 different glycoforms. We then used
molecular modeling to demonstrate that complex glycopeptides are capable of binding
the MHC and may interact with complementarity determining regions. Finally, we
present the first evidence of disulfide-bonded peptides presented by MI-ICIL This
is the first large scale study to sequence glyco- and disulfide bonded MHCII
peptides from the surface of cancer cells and could represent a novel avenue of
tumor activation and/or immunoevasion.
The evolutionarily conserved protein kinase p38 mediates innate resistance to
environmental stress and microbial infection. Four p38 isoforms exist in mammals
and may have been co-opted for new roles in adaptive immunity. Murine T cells
deficient in p38, the ubiquitously expressed p38 isoform, showed no readily
apparent cell-autonomous defects while expressing elevated amounts of another
isoform, p38. Mice with T cells simultaneously lacking p38 and p38 displayed
lymphoid atrophy and elevated Foxp3(+) regulatory T cell frequencies. Double
deficiency of p38 and p38 in naive CD4(+) T cells resulted in an attenuation of
MAPK-activated protein kinase (MK)-dependent mTOR signaling after T cell receptor
engagement, and enhanced their differentiation into regulatory T cells under
appropriate inducing conditions. Pharmacological inhibition of the p38-MK-mTOR
signaling module produced similar effects, revealing potential for therapeutic
applications.
Objectives Acute pancreatitis is characterized by a systemic inflammatory response.
We hypothesized that the fundamental inflammatory response observed during the
initial stages of all acute pancreatitis is not a Th1 but rather a Th17 response.
Methods Seven patients with mild AP presenting within three days of symptom onset
were recruited. Peripheral blood was drawn for five consecutive days and plasma
Th1/Th2/Th17 cytokine levels compared to eleven healthy controls. Plasma cytokine
measurements were performed using Th1/ Th2/Th17 Cytokine Bead Array assay and data
quantified using FCAP Array software. Results IL-6 levels were significantly
elevated in AP patients compared to controls; IL-10 levels were significantly
elevated by day 3; IL17A levels increased on day 2 and significantly elevated at
day 3 compared to controls declining to non-significant levels by day 4. IFN gamma
and TNF alpha levels were low at all time-points. Conclusion IL-17A and IL-10 (an
anti-inflammatory cytokine implicated in suppressing Th17 cytokines secreted by
macrophages and T cells) were elevated by day 3. In addition IL-6, which helps
drive development of Th17 cells, was significantly elevated at all time-points.
These preliminary results imply that the underlying AP induced systemic
inflammation is polarized to a Th17 rather than a Th1 response.
Introduction Seldom cutaneous leishmaniasis (CL) may present as a lasting and
active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T
helper (Th1) cells are assumed the most important factor in the outcome of the
disease. The present study aims to assess some molecular defects that potentially
contribute to Th1 impairment in NHCL. Methods and analysis This prospective
observational study will be implemented among five groups. The first and second
groups comprise patients afflicted with non-healing and healing forms of CL,
respectively. The third group consists of those recovered participants who have
scars as a result of CL. Those participants who have never lived or travelled to
endemic areas of leishmaniasis will comprise the fourth group. The fifth group
comprises participants living in hyperendemic areas for leishmaniasis, although
none of them have been afflicted by CL. The aim is to recruit 10 NHCL cases and 30
participants in each of the other groups. A leishmanin skin test (LST) will be
performed to assess in vivo immunity against the Leishmania infection. The cytokine
profile (interleukin (IL)-12p70, interferon (IFN)-, C-X-C motif chemokine ligand
(CXCL)-11 and IL-17a) of the isolated peripheral blood mononuclear cells (PBMCs)
will be evaluated through ELISA. Real-time PCR will determine the C-X-C motif
chemokine receptor (CXCR)-3 and IL-17a gene expression and expression of IL-12R1
will be assessed by flow cytometry. Furthermore, IL-12B and IL-12RB1 mutation
analysis will be performed. Discussion It is anticipated that the outcome of the
current study will identify IL-12B and IL-12RB1 mutations, which lead to persistent
lesions of CL. Furthermore, our expected results will reveal an association between
NHCL and pro-inflammatory cytokines (IL-12p70, IFN- IL-17a and CXCL-11), as well as
CXCR-3 expression. Ethics and dissemination This study has been approved by a local
ethical committee. The final results will be disseminated through peer-reviewed
journals and scientific conferences.
Advances in clinical immunology in the past year included the report of practice
parameters for the diagnosis and management of primary immunodeficiencies to guide
the clinician in the approach to these relatively uncommon disorders. We have
learned of new gene defects causing immunodeficiency and of new phenotypes
expanding the spectrum of conditions caused by genetic mutations such as a specific
regulator of telomere elongation (RTEL1) mutation causing isolated natural killer
cell deficiency and mutations in ras-associated RAB (RAB27) resulting in
immunodeficiency without albinism. Advances in diagnosis included the increasing
use of whole-exome sequencing to identify gene defects and the measurement of serum
free light chains to identify secondary hypogammaglobulinemias. For several primary
immunodeficiencies, improved outcomes have been reported after definitive therapy
with hematopoietic stem cell transplantation and gene therapy.
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory
infections, particularly in children. Much information regarding the immune
response to RSV comes from animal models and in vitro studies. Here, we provide a
comprehensive description of the human immune response to RSV infection, based on a
systematic literature review of research on infected humans. There is an initial
strong neutrophil response to RSV infection in humans, which is positively
correlated with disease severity and mediated by interleukin-8 (IL- 8). Dendritic
cells migrate to the lungs as the primary antigen-presenting cell. An initial
systemic T-cell lymphopenia is followed by a pulmonary CD8(+) T-cell response,
mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV
IgG and IgA are protective. B-cell-stimulating factors derived from airway
epithelium play a major role in protective antibody generation. Gamma interferon
(IFN-gamma) has a strongly protective role, and a Th2-biased response may be
deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5
and CCL-3), and local innate immune factors (including cathelicidins and IFN-
lambda) contribute to pathogenesis. In summary, neutrophilic inflammation is
incriminated as a harmful response, whereas CD8(+) T cells and IFN-gamma have
protective roles. These may represent important therapeutic targets to modulate the
immunopathogenesis of RSV infection.
We consider the general problem of sensitive and specific discrimination between
biochemical species. An important instance is immune discrimination between self
and not-self, where it is also observed experimentally that ligands just below the
discrimination threshold negatively impact response, a phenomenon called
antagonism. Wecharacterize mathematically the generic properties of such
discrimination, first relating it to biochemical adaptation. Then, based on basic
biochemical rules, we establish that, surprisingly, antagonism is a generic
consequence of any strictly specific discrimination made independently from ligand
concentration. Thus antagonism constitutes a 'phenotypic spandrel': a phenotype
existing as a necessary by-product of another phenotype. We exhibit a simple
analytic model of discrimination displaying antagonism, where antagonism strength
is linear in distance from the detection threshold. This contrasts with traditional
proofreading based models where antagonism vanishes far from threshold and thus
displays an inverted hierarchy of antagonism compared to simpler models. The
phenotypic spandrel studied here is expected to structure many decision pathways
such as immune detection mediated by TCRs and FC epsilon RIs, as well as endocrine
signalling/disruption.
Vaccination has saved more lives than any other medical procedure. Pathogens have
now evolved that have not succumbed to vaccination using the empirical paradigms
pioneered by Pasteur and Jenner. Vaccine design strategies that are based on a
mechanistic understanding of the pertinent immunology and virology are required to
confront and eliminate these scourges. In this perspective, we describe just a few
examples of work aimed to achieve this goal by bringing together approaches from
statistical physics with biology and clinical research.
The ability of the adaptive immune system to respond to arbitrary pathogens stems
from the broad diversity of immune cell surface receptors. This diversity
originates in a stochastic DNA editing process (VDJ recombination) that acts on the
surface receptor gene each time a new immune cell is created from a stem cell. By
analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and
thymus of mice of different ages, we quantify the changes in the VDJ recombination
process that occur from embryo to young adult. We find a rapid increase with age in
the number of random insertions and a dramatic increase in diversity. Because the
blood accumulates thymic output over time, blood repertoires are mixtures of
different statistical recombination processes, and we unravel the mixture
statistics to obtain a picture of the time evolution of the early immune system.
Sequence repertoire analysis also allows us to detect the statistical impact of
selection on the output of the VDJ recombination process. The effects we find are
nearly identical between thymus and blood, suggesting that our analysis mainly
detects selection for proper folding of the TCR receptor protein. We further find
that selection is weaker in laboratory mice than in humans and it does not affect
the diversity of the repertoire.
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed
the hypothesis that the immune system can control many cancers across various
histologies, in some cases producing durable responses in a way not seen with many
small molecule drugs. However, only less than 25% of all patients do respond to
immunooncology drugs and several resistance mechanisms have been identified (e.g.
T-cell exhaustion, overexpression of caspase-8 and beta-catenin, PD-1/PD-L1 gene
amplification, MHC-I/II mutations). To improve response rates and to overcome
resistance, novel second- and third-generation immuno-oncology drugs are currently
evaluated in ongoing phase I/II trials (either alone or in combination) including
novel inhibitory compounds (e.g. TIM-3, VISTA, LAG-3, IDO, KIR) and newly developed
co-stimulatory antibodies (e.g. CD40, GITR, OX40, CD137, ICOS). It is important to
note that co-stimulatory agents strikingly differ in their proposed mechanism of
action compared with monoclonal antibodies that accomplish immune activation by
blocking negative checkpoint molecules such as CTLA-4 or PD-1/PD-1 or others.
Indeed, the prospect of combining agonistic with antagonistic agents is enticing
and represents a real immunologic opportunity to 'step on the gas' while 'cutting
the brakes', although this strategy as a novel cancer therapy has not been
universally endorsed so far. Concerns include the prospect of triggering cytokine-
release syndromes, autoimmune reactions and hyper immune stimulation leading to
activation-induced cell death or tolerance, however, toxicity has not been a major
issue in the clinical trials reported so far. Although initial phase I/II clinical
trials of agonistic and novel antagonistic drugs have shown highly promising
results in the absence of disabling toxicity, both in single-agent studies and in
combination with chemotherapy or other immune system targeting drugs; however,
numerous questions remain about dose, schedule, route of administration and
formulation as well as identifying the appropriate patient populations. In our
view, with such a wealth of potential mechanisms of action and with the ability to
fine-tune monoclonal antibody structure and function to suit particular
requirements, the second and third wave of immuno-oncology drugs are likely to
provide rapid advances with new combinations of novel immunotherapy (especially co-
stimulatory antibodies). Here, we will review the mechanisms of action and the
clinical data of these new antibodies and discuss the major issues facing this
rapidly evolving field. (C) 2017 Elsevier Ltd. All rights reserved.
The development of an immuno-PCR assay for quantitation of low amounts of anti-
glycan human antibodies is described. The sensitivity of the assay for
determination of low-affinity anti-Le(C) IgM has been found to be 4 ng/ml (similar
to 100 pg per sample), thus being two orders of magnitude higher compared to the
conventional ELISA with the same antigen.
Primary cutaneous gamma delta T-cell lymphoma (PCGD TCL), an aggressive type of
lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have
occasionally observed changes in T-cell antigen expression (immunophenotypic [IP]
shift) over time, a phenomenon that is considered rare in T-cell lymphoma including
cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL
for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL
with consecutive biopsies to perform a comprehensive immunohistochemical analysis
of paired specimens. A median of 12 markers per case was tested. We evaluated the
percentage of neoplastic lymphocytes and determined the differential expression of
antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL
with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen,
whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7
(31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8
(36.4%). Molecular analysis of TCR gamma showed identically sized monoclonal
rearrangements between biopsy pairs in 4/4 (100%) patients. There was no
correlation between IP shifts and the clinical appearance of lesions,
histopathologic or cytologic features, or molecular rearrangements. IP shifts are
common in PCGD TCL, occurring in all patients in this study and involving a variety
of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and
are without obvious clinical or morphologic correlates. The occurrence of IP shifts
in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP
shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a
second neoplasm, and molecular studies can be used to determine clonal identity.
Background: The immunoprecipitation (IP) assay is a valuable molecular biology tool
applied across a breadth of fields. The standard assay couples IP to immunoblotting
(IP/IB), a procedure severely limited as it is not easily scaled for high-
throughput analysis. Results: Here we describe and characterize a new methodology
for fast and reliable evaluation of an immunoprecipitation reaction. FLIP
(FLuorescence IP) relies on the expression of the target protein as a chromophore-
tagged protein and couples IP with the measurement of fluorescent signal coating
agarose beads. We show here that FLIP displays similar sensitivity to the standard
IP/IB procedure but is amenable to high-throughput analysis. We applied FLIP to the
screening of mouse monoclonal antibodies of unknown behavior in IP procedures. The
parallel analysis of the considered antibodies using FLIP and IP/western shows good
correlation between the two procedures. We also show application of FLIP using
unpurified antibodies (hybridoma supernatant) and we developed a publicly available
tool for the easy analysis and quantification of FLIP signals. Conclusions:
Altogether, our characterizations of this new methodology show that FLIP is an
appealing and reliable tool for any application of high-throughput IP.
Throughout their life animals progressively accumulate mostly detrimental changes
in cells, tissues and their functions, causing a decrease in individual performance
and ultimately an increased risk of death. The latter may be amplified if it also
leads to a deterioration of the immune system which forms the most important
protection against the permanent threat of pathogens and infectious diseases. Here,
we investigated how four baseline innate immune parameters (natural antibodies,
complement activity, concentrations of haptoglobin and concentrations of nitric
oxide) changed with age in free-living great tits (Parus major). We applied both
cross-sectional and longitudinal approaches as birds were sampled for up to three
years of their lives. Three out of the four selected innate immune parameters were
affected by age. However, the shape of the response curves differed strongly among
the innate immune parameters. Natural antibody levels increased during early life
until mid age to decrease thereafter when birds aged. Complement activity was
highest in young birds, while levels slightly decreased with increasing age.
Haptoglobin levels on the other hand, showed a linear, but highly variable increase
with age, while nitric oxide concentrations were unaffected by age. The observed
differences among the four studied innate immune traits not only indicate the
importance of considering several immune traits at the same time, but also
highlight the complexity of innate immunity. Unraveling the functional significance
of the observed changes in innate immunity is thus a challenging next step. (C)
2017 Elsevier Inc. All rights reserved.
Treatment of cancer patients involves a multidisciplinary approach including
surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic
disease are treated with combination chemotherapies or targeted agents. These
cytotoxic agents have good response rates and achieve palliation; however, complete
responses are rarely seen. The field of cancer immunology has made rapid advances
in the past 20 years. Recently, a number of agents and vaccines, which modulate the
immune system to allow it to detect and target cancer cells, are being developed.
The benefit of these agents is twofold, it enhances the ability the body's own
immune system to fight cancer, thus has a lower incidence of side effects compared
to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of
patients with metastatic disease are cured by immunotherapy or achieve durable
responses lasting for a number of years. In this article, we review the FDA-
approved immunotherapy agents in the field of genitourinary malignancies. We also
summarize new immunotherapy agents being evaluated in clinical studies either as
single agents or as a combination.
p53 was reported to be an attractive immunotherapy target because it is mutated in
approximately half of human cancers, resulting in its inactivation and often
accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC
molecules and may act as tumor-associated epitopes which could be targeted by p53-
specific T cells. Interestingly, it was recently shown that there is a lack of
significant correlation between p53 expression levels in tumors and their
recognition by p53-TCR transduced T cells. To better understand the influence of
the mutational status of p53 on its presentation by the MHC system and on T cell
antitumor reactivity, we generated several mutant p53 constructs and expressed them
in HLA-A2(+)/p53(-) cells. Upon co-culture with p53-specific T cells, we measured
the specific recognition of p53-expressing target cells by means of cytokine
secretion, marker upregulation and cytotoxicity, and in parallel determined p53
expression levels by intracellular staining. We also examined the relevance of
antigen presentation components on p53 recognition and the impact of mutant p53
expression on cell-cycle dynamics. Our results show that selected p53 mutations
altering protein stability can modulate p53 presentation to T cells, leading to a
differential immune reactivity inversely correlated with measured p53 protein
levels. Thus, p53 may behave differently than other classical tumor antigens and
its mutational status should therefore be taken into account when elaborating
immunotherapy treatments of cancer patients targeting p53.
The ac impedance spectroscopy measurements are predominantly taken by using
impedance analyzers based on analog auto-balancing bridge. However, those bench-top
analyzers are generally complicated, bulky and expensive, thus limiting their usage
in industrial field applications. This paper presents the development of a compact
wideband precision measurement system based on digital auto-balancing bridge. The
methods of digital auto-balancing bridge and digital lock-in amplifier are analyzed
theoretically. The overall design and several key sections including null detector,
direct digital synthesizer-based sampling clock, and digital control unit are
introduced in detail. The results show that the system achieves a basic measurement
accuracy of 0.05% with a frequency range of 20 Hz-2 MHz. The advantages of
versatile measurement capacity, fast measurement speed, small size and low cost
make it quite suitable for industrial field applications. It is demonstrated that
this system is practical and effective by applying in determining the impedance-
temperature characteristic of a motor starter PTC thermistor.
Current sources are critical for the performance of bioimpedance health monitoring
device. The challenging features for a high accuracy and wide bandwidth voltage
controlled current source are stable and safe current magnitudes. Corresponding to
the typical measurement requirements, it should allow typical load impedances in
the range from 100 Omega to 10 k Omega and have high output impedance of
approximately 10 M Omega at 5 kHz and 1 M Omega at high frequencies up to 1 MHz
without harmonics and influence of stray capacitances. Generalized impedance
converters and negative impedance converters help to reduce the influence of stray
capacitances. In this study, we compare between two types of voltage controlled
current sources for grounded loads: Howland and Tietze circuits. Based on this
study, we suggest an improved Howland circuit in inverting dual configuration with
a negative feedback using the high bandwidth amplifier AD8021. With this
configuration, a better accuracy is reached at higher frequencies up to 1 MHz. With
the addition of compensation capacitor to the operational amplifier, this circuit
configuration is capable to maintain approximately constant current amplitude
within an accuracy of less than 0.022% at both low and high frequencies up to 1
MHz. (C) 2015 Elsevier Ltd. All rights reserved.
Purpose:The aim of the present study was to mimic the hierarchical structure of
bone tissues by simple sandblasting/acid-etching and anodization to investigate the
effects of such surface characteristics on proliferation and differentiation of
osteoblasts in high glucose concentrations. By the way, the effects of high glucose
levels on osteoblast functions were tested.Methods:MC3T3-E1 cells cultured on sand-
blasted and acid-etched (SLA) surface and nano-modified SLA (NMSLA) surface were
subjected to normal serum (NS) and diabetic serum (DS), respectively. The surface
characteristics were evaluated by scanning electron microscopy. Cell proliferation
was assessed using MTT assay. The levels of alkaline phosphatase (ALP) activity and
mineralization were measured and compared. Real-time polymerase chain reaction was
applied to detect the expression levels of osteogenic genes.Results:NMSLA
significantly increased cell proliferation at time points ranging from 3 to 7 days
under both serums. Cells cultured on NMSLA surfaces displayed significantly higher
ALP activities and mineralization. The expression levels of Runx2 (indicates runt-
related protein 2), collagen I (COL1), and osteocalcin (OCN) were notably increased
on NMSLA surface compared with SLA surface. Moreover, we found that high glucose
increased osteoblast proliferation but decreased differentiation of osteoblast
slightly.Conclusion:The hierarchical micro/nano-structured titanium surface has a
favorable biocompatibility on simultaneously improving osteoblast proliferation and
differentiation in diabetic serum.
OBJECTIVE: The aim of this in vivo study was to evaluate two different types of
implant-abutment connections: screwed connection and cemented connection, analyzing
peri-implant bacteria microflora as well as other clinical parameters. PATIENTS AND
METHODS: Twenty implants were selected, inserted in 20 patients, 10 with a screwed
implant-abutment connection (Group 1) and 10 with a cemented implant-abutment
connection (Group 2). The peri-implant microflora was collected, after at least 360
days from the prosthetic rehabilitation, using paper points inserted in peri-
implant sulcus for 30 s. Polymerase chain reaction (PCR) Real-time analyzed the
presence of 9 bacteria periodontal-pathogens and Candida albicans. RESULTS: Our
findings showed that bacteria colonized all Groups analyzed, the average bacterial
count was 3.7 E + 08 (+/- 1.19) in Group 1, compared to 2.1 E + 08 (+/- 0.16) in
Group 2; no statistically significant differences were observed (p >0.0.5). In
Group 1, however, bacterial colonization of peri-implant sulci was over the
pathogenic threshold for 5 bacteria, indicating a high-risk of peri-implantitis.
Also in Group 2, results showed a microflora composed by all bacteria analyzed but,
in this case, bacterial colonization of peri-implant sulci was over the pathogenic
threshold for only 1 bacterium, indicating a lower risk of peri-implantitis.
Moreover, clinical parameters (PPD >3 mm and m SBI >0) confirmed a greater risk of
peri-implantitis in Group 1 compared to Group 2 (p < 0.05). CONCLUSIONS: We
concluded that, also after only 360 days, implants with screwed connection showed a
higher risk of peri-implantitis that implants with cemented connection.
The present study is the first report providing evidence for a physiological role
of a truncated form of the mRNA cap-binding protein eIF4E1 (eukaryotic initiation
factor 4E1). Our initial observation was that eIF4E, which mediates the mRNA cap
function by recruiting the eIF4F complex (composed of eIF4E, 4G and 4A), occurs in
two forms in porcine endometrial tissue in a strictly temporally restricted
fashion. The ubiquitous prototypical 25 kDa form of eIF4E was found in
ovariectomized and cyclic animals. A new stable 23 kDa variant, however, is
predominant during early pregnancy at the time of implantation. Northern blotting,
cDNA sequence analysis, in vitro protease assays and MS showed that the 23 kDa form
does not belong to a new class of eIF4E proteins. It represents a proteolytically
processed variant of eIF4E1, lacking not more than 21 amino acids at the N-
terminus. Steroid replacements indicated that progesterone in combination with 17
beta-oestradiol induced the formation of the 23 kDa eIF4E. Modified cell-free
translation systems mimicking the situation in the endometrium revealed that,
besides eIF4E, eIF4G was also truncated, but not eIF4A or PABP [poly(A)binding
protein]. The 23 kDa form of eIF4E reduced the repressive function of 4E-BP1
(eIF4E-binding protein 1) and the truncated eIF4G lacked the PABP-binding site.
Thus we suggest that the truncated eIF4E provides an alternative regulation
mechanism by an altered dynamic of eIF4E/4E-BP1 binding under conditions where 4E-
BP1 is hypophosphorylated. Together with the impaired eIF4G-PABP interaction, the
modified translational initiation might particularly regulate protein synthesis
during conceptus attachment at the time of implantation.
Implicit evaluations reflect people's gut response toward an attitude object and
are based on associative processes. They are the starting ground for more
reflective processes and subsequent explicit evaluations. The present research
examined determinants and consequences of implicit evaluations in a rape case.
Situational (i.e. specifics of the rape case) and personal factors (i.e. rape myth
acceptance) were demonstrated to influence both explicit and implicit judgments of
the rape case. Moreover, sex of participant influenced participants' implicit
evaluations but affected explicit judgments only indirectly via the implicit
evaluation. People's gut response was shown to affect their explicit judgment of
the case, and this effect was particularly pronounced for people with a low need
for cognition (i.e. people who do not like to engage in effortful processing). The
discussion focuses on the role of implicit cognition and implicit biases in
judicial decision-making.
This article reviews the Sex with Children (SWCH) scale and compares its
psychometric properties to alternative measures in the field. Examination of the
scale indicates that it is one of several instruments which do not proportionally
tap into all implicit theory schemas that have been proposed in the literature.
This does not help clinicians who aim to target pro-offending schema since the
scale appears to neglect certain types of beliefs that are considered to be
important in the investigation of child molester cognition. Similar to many other
instruments in the field, the SWCH scale is unlikely to identify offenders who
outwardly endorse child abuse items, and its discriminant validity may be better
viewed as a capacity to differentiate those who disagree less from those who
disagree more. The scale possesses excellent reliability properties compared to
other instruments. However, recently reported area under the curve calculations
indicate that the scale's predictive power for sexual and violent reconviction is
no better than chance. It would be useful to develop the SWCH scale so that it does
not under-represent important types of pro-offending schema. Copyright (c) 2014
John Wiley & Sons, Ltd.
The transcription factor hepatocyte nuclear factor 1 beta (HNF1 beta) is
ubiquitously overexpressed in ovarian clear cell carcinoma (CCC) and is a potential
therapeutic target. To explore potential approaches that block HNF1 beta
transcription we have identified and characterised extensively the nuclear
localisation signal (NLS) for HNF1 beta and its interactions with the nuclear
protein import receptor, Importin-alpha. Pull-down assays demonstrated that the DNA
binding domain of HNF1 beta interacted with a spectrum of Importin-alpha isoforms
and deletion constructs tagged with eGFP confirmed that the HNF1 beta(KKMRRNR235)-
K-229 sequence was essential for nuclear localisation. We further characterised the
interaction between the NLS and Importin-alpha using complementary biophysical
techniques and have determined the 2.4 angstrom resolution crystal structure of the
HNF1 beta NLS peptide bound to Importin-alpha. The functional, biochemical, and
structural characterisation of the nuclear localisation signal present on HNF1 beta
and its interaction with the nuclear import protein Importin-alpha provide the
basis for the development of compounds targeting transcription factor HNF1 beta via
its nuclear import pathway. (C) 2016 MRC Laboratory of Molecular Biology. Published
by Elsevier Inc.
As maize was domesticated in Mexico around 9,000years ago, local farmers have
selected and maintained seed stocks with particular traits and adapted to local
conditions. In the present day, many of these landraces are still cultivated;
however, increased urbanization and migration from rural areas implies a risk that
this invaluable maize germplasm may be lost. In order to implement an efficient
mechanism of conservation in situ, the diversity of these landrace populations must
be estimated. Development of a method to select the minimum number of samples that
would include the maximum number of alleles and identify germplasm harboring rare
combinations of particular alleles will also safeguard the efficient ex-situ
conservation of this germplasm. To reach this goal, a strategy based on SSR
analysis and a novel algorithm to define a minimum collection and rare genotypes
using landrace populations from Puebla State, Mexico, was developed as a proof of
concept for methodology that could be extended to all maize landrace populations in
Mexico and eventually to other native crops. The SSR-based strategy using bulked
DNA samples allows rapid processing of large numbers of samples and can be set up
in most laboratories equipped for basic molecular biology. Therefore, continuous
monitoring of landrace populations locally could easily be carried out. This
methodology can now be applied to support incentives for small farmers for the in
situ conservation of these traditional cultivars.
Corneal immunoimaging and neuroimaging approaches facilitate in vivo analyses of
the cornea, including high-resolution imaging of corneal immune cells and nerves.
This approach facilitates the analyses of underlying immune and nerve alterations
not detected by clinical slit-lamp examination alone. In this review, we describe
recent work performed in our translational ocular immunology center with a focus on
"bench-to-bedside" and "bedside-to-bench" research. The ability to visualize
dendritiform immune cells (DCs) in patients with laser in vivo confocal microscopy
(IVCM), recently discovered in the central murine cornea, has allowed us to
demonstrate their utility as a potential surrogate biomarker for inflammatory
ocular surface diseases. This biomarker for inflammation allows the measurement of
therapeutic efficacy of anti-inflammatory drugs and its utility as an endpoint in
clinical trials with high interobserver agreement. IVCM image analyses from our
studies has demonstrated a significant increase in DC density and size in ocular
disease, a positive correlation between DC density and clinical signs and symptoms
of disease and pro-inflammatory tear cytokines, and a strong negative correlation
between DC density and subbasal nerve density. In conjunction with preclinical
research investigating the inflammatory state in a partial or fully denervated
cornea, our results indicated that corneal nerves are directly involved in the
regulation of homeostasis and immune privilege in the cornea.
Inbreeding, reproduction between relatives, often impinges on the health and
survival of resulting offspring. Such inbreeding depression may manifest itself
through immunological costs as inbred individuals suffer increased propensity to
disease, infection and parasites compared to outbred conspecifics. Here, we assess
how the intestinal parasite loads of wild banded mongooses (Mungos mungo) vary with
pedigree inbreeding coefficient (f) and standardized multi-locus heterozygosity. We
find a significant association between increased heterozygosity and lower parasite
loads; however, this correlation does not stand when considering f. Such findings
may be explained by local genetic effects, linkage between genetic markers and
genes influencing parasite burdens. Indeed, we find heterozygosity at certain loci
to correlate with parasite load. Although these tentative local effects are lost
following multiple test correction, they warrant future investigation to determine
their strength and impact. We also suggest frequent inbreeding within banded
mongooses may mean heterozygosity is a better predictor of inbreeding than pedigree
f. This is because inbreeding facilitates linkage disequilibrium, increasing the
chances of neutral markers representing genome-wide heterozygosity. Finally,
neither f nor heterozygosity had a significant influence on the loads of two
specific gastrointestinal parasites. Nevertheless, more heterozygous individuals
benefited from reduced overall parasitic infection and genetic diversity appears to
explain some variation in parasite burdens in the banded mongoose.
Residential domestic hot water energy consumption represented 16% of the EU
household heating demand in 2013. With the improvement of the building insulation
envelope, domestic hot water contribution to energy consumption is expected to
increase significantly, with values between 20% and 32% in single family buildings,
and between 35% to almost 50% in multifamily buildings. This energy, currently lost
to the environment, can be recovered by waste water heat recovery systems inside
buildings (in building solutions). While most publications in this field focus on
shower heat recovery and on waste water as heat source for heat pumps, the detailed
impact of waste water heat recovery at a city scale by aggregating building data
has not been addressed yet. Furthermore, waste water heat recovery potential and
relevance was not yet quantified as a function of the specific inhabitant and
household numbers, end-use occurrence, and building type and age. A method to
quantify the building-specific energy cost and energy saving potentials, based on
pinch analysis, at the urban scale of in-building waste water heat recovery systems
is therefore proposed. A complementary method to spatially allocate and
characterise grey water streams as to thermal load and temperature levels in
function of the building specificities is also developed. These methods are applied
in two case studies, first as retrofitting solution in a city in Luxembourg and,
second, as optimisation measure for high efficiency residential buildings. Grey
water heat recovery would reduce the residential fuel consumption of the city by
63%. An integrated approach combining grey water heat recovery for hot water
preheating and a heat pump yields up to 28% and 41% electricity savings for passive
single family houses and multifamily buildings, respectively. With the detailed
characterisation of various grey water streams as a function of inhabitant number
and end -use occurrence, the quantification of the energy savings and costs through
heat recovery is improved. The outcomes of urban energy and cost assessments
concerning grey water heat recovery are more specific, as the results at building
level are aggregated to the considered geographical scope. The proposed method
therefore complements current urban energy and cost assessments with the detailed
integration of in -building grey water heat recovery systems. (C) 2017 Published by
Elsevier Ltd.
The purpose of the study was to investigate types of childhood abuse in a sample of
60 inmates and to explore the relationships between childhood abuse, criminality,
and drug addiction. Overall, the sample inmates came from risky families with a
high prevalence of crime, drug addiction, and mental health problems. The results
showed that a history of child abuse was common, and emotional neglect was more
prevalent than physical, emotional, or sexual abuse. The odds for childhood abuse
were higher among inmates whose fathers had been addicted to drugs and involved in
crime, and whose siblings suffered from mental health problems.
Neuroimaging techniques have greatly enhanced the understanding of neurodiversity
(human brain variation across individuals) in both health and disease. The ultimate
goal of using brain imaging biomarkers is to perform individualized predictions.
Here we proposed a generalized framework that can predict explicit values of the
targeted measures by taking advantage of joint information from multiple
modalities. This framework also enables whole brain voxel-wise searching by
combining multivariate techniques such as ReliefF, clustering, correlation-based
feature selection and multiple regression models, which is more flexible and can
achieve better prediction performance than alternative atlas-based methods. For 50
healthy controls and 47 schizophrenia patients, three kinds of features derived
from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy)
were extracted and fed into a regression model, achieving high prediction for both
cognitive scores (MCCB composite r = 0.7033, MCCB social cognition r = 0.7084) and
symptomatic scores (positive and negative syndrome scale [PANSS] positive r =
0.7785, PANSS negative r = 0.7804). Moreover, the brain areas likely responsible
for cognitive deficits of schizophrenia, including middle temporal gyrus,
dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with
different weights, as well as regions predicting PANSS symptoms, including
thalamus, striatum and inferior parietal lobule, pinpointing the potential
neuromarkers. Finally, compared to a single modality, multimodal combination
achieves higher prediction accuracy and enables individualized prediction on
multiple clinical measures. There is more work to be done, but the current results
highlight the potential utility of multimodal brain imaging biomarkers to
eventually inform clinical decision-making. (C) 2016 Elsevier Inc. All rights
reserved.
Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to be
used for the study of underlying molecular biology of disease, therapeutic drug
screening, and transplant-based regenerative medicine. However, methods for the
directed differentiation of skeletal muscle for these purposes remain scarce and
incomplete. Here, we present a novel, small molecule-based protocol for the
generation of multinucleated skeletal myotubes using eight independent iPSC lines.
Through combinatorial inhibition of phosphoinositide 3-kinase (PI3K) and glycogen
synthase kinase 3 beta (GSK3 beta) with addition of bone morphogenic protein 4
(BMP4) and fibroblast growth factor 2 (FGF2), we report up to 64% conversion of
iPSCs into the myogenic program by day 36 as indicated by MYOG(+) cell populations.
These cells began to exhibit spontaneous contractions as early as 34 days in vitro
in the presence of a serum-free medium formulation. We used this protocol to obtain
iPSC-derived muscle cells from frontotemporal dementia (FTD) patients harboring
C9orf72 hexanucleotide repeat expansions (rGGGGCC), sporadic FTD, and unaffected
controls. iPSCs derived from rGGGGCC carriers contained RNA foci but did not vary
in differentiation efficiency when compared to unaffected controls nor display
mislocalized TDP-43 after as many as 120 days in vitro. This study presents a
rapid, efficient, and transgene-free method for generating multinucleated skeletal
myotubes from iPSCs and a resource for further modeling the role of skeletal muscle
in amyotrophic lateral sclerosis and other motor neuron diseases.
A new electronic interface for inductive sensors is presented. The proposed circuit
is basically a current-feedback operational-amplifier (CFOA)-based sinusoidal
oscillator circuit. The circuit uses only one externally connected inductor and
exploits to advantage the internal poles of the CFOA. Sinusoidal oscillation at
frequency of 122.1 MHz was obtained using the AD844 CFOA and an inductor of
inductance = 0.14 mu H with peak-to-peak output voltage = 700 mV.
Industrial waste heat may be one of the answers to future energy demands. Depending
on the temperature, industrial waste heat may be used to produce electricity or
meet cooling or heating demands at different temperature levels. However, in order
to estimate the influence the waste heat may have in future energy systems, the
magnitude of the industrial waste heat in the different countries need to be
estimated. For Germany, so far, only top-down analyses of the waste heat potential
exist, using key figures derived from other studies in other countries. In this
paper, the first bottom-up approach for estimating the industrial waste heat
potential in Germany is presented. For this approach, an algorithm to evaluate and
test the mandatory emission report data from German production companies was
developed. In a second step, round about 81,000 data sets have been evaluated to
calculate a conservative and lower boundary value for the industrial waste heat. As
this conservative, lower boundary based on the collected data from the German
industry, the waste heat volume was evaluated as 127 PJ/a or 13 % of the industrial
fuel consumption. Results were used to derive key figures with which the missing
share of the data was approximated.
Exogenous oxytocin administration is widely reported to improve social cognition in
human and nonhuman primate adults. Risk factors of impaired social cognition,
however, emerge in infancy. Early interventions-when plasticity is greatest-are
critical to reverse negative outcomes. We tested the hypothesis that oxytocin may
exert similar positive effects on infant social cognition, as in adults. To test
this idea, we assessed the effectiveness of acute, aerosolized oxytocin on two
foundational social cognitive skills: working memory (i.e., ability to briefly hold
and process information) and social gaze (i.e., tracking the direction of others'
gaze) in 1-month-old nursery-reared macaque monkeys (Macaca mulatta). We did not
predict sex differences, but we included sex as a factor in our analyses to test
whether our effects would be generalizable across both males and females. In a
double-blind, placebo-controlled design, we found that females were more socially
skilled at baseline compared to males, and that oxytocin improved working memory
and gaze following, but only in males. These sex differences, while unexpected, may
be due to interactions with gonadal steroids and may be relevant to sexually
dimorphic disorders of social cognition, such as male-biased autism spectrum
disorder, for which oxytocin has been proposed as a potential treatment. In sum, we
report the first evidence that oxytocin may influence primate infant cognitive
abilities. Moreover, these behavioral effects appear sexually dimorphic,
highlighting the importance of considering sex differences. Oxytocin effects
observed in one sex may not be generalizable to the other sex.
Background Child abuse is a health and social problem, and few screening
instruments are available for the detection of risk in primary health care. The aim
was to develop a screening instrument to be used by professionals in the public
health care sector, thus enabling the detection of infants and toddlers at risk of
emotional and physical abuse and neglect, and to provide evidence for the
feasibility of the instrument in Cyprus, Greece and Spain. Method A total of 50
health professionals from paediatric public health-care centres in the three
countries were involved in a three-step process for guiding the development of the
screening tool and its application. Results A nine-item screening tool, consisting
of items assessing relational emotional abuse, physical abuse and other risk
factors, was developed. The screening tool was applied on a total of 219 families
with 0 to 3-year-old children attending public health centres in the three
countries. Clinicians reported that they agreed on the inclusion of the questions
(86.4-100%) and that they found the questions to be useful for the clinical
evaluation of the family (63.2-100%). Conclusion The screening tool shows
considerable face validity and was reported feasible by an international set of
clinicians.
Individual differences in early attention are associated with later social,
cognitive, and emotional development, and attentional deficits in the first year
are associated with risk for developmental disorders such as Autism Spectrum
Disorder (ASD). The First Year Inventory (FYI; Baranek, Watson, Crais, & Reznick,
2003) was developed to identify 12-month-olds at risk for an ASD diagnosis. The
current study identifies FYI items that reflect aspects of early attention that
might predict future typical and atypical social, cognitive, and emotional
development. Using a series of theoretical and statistical methods, we developed 3
attention-based constructs from the FYI: Responding to Social Attention (RSA),
Initiating Social Attention (ISA), and Nonsocial Sensory Attention (NSA). A
database with completed FYIs was analyzed using these constructs to determine the
strength of relations among items. Cronbach's alpha analyses indicated good
internal consistency, and item distribution was further supported using a
confirmatory factor analysis. Data analyses showed statistically significant
relations between the scores on these domains at 12 months and subsequent social
responsiveness scores at 3 years. Analyses demonstrating the statistical and
predictive validity of these 3 FYI attention constructs support their use for
innovative explorations of infant behavioral patterns that can be used to predict
typical and atypical individual trajectories in the development of later social,
cognitive, and emotional skills.
The objective of this study was to develop a new elaborate method to evaluate
infants' liking of foods that could be applied at home and to compare the results
of this elaborate method with those of a basic method. Mothers of infants aged 4 to
7 (n = 44) and 12-15 months (n = 46) participated in this study. For the basic
method, mothers were asked to assess their infant's global liking at the end of a
meal. Then, for the elaborate method, mothers received detailed instructions on how
to feed their infant, how infants might express like/dislike and when to stop the
meal. During the first nine spoons, they were asked to report the presence/absence
of positive and negative behaviours after each spoon, and the infant's initial
liking was reported after each triplet of spoons. They also assessed their infant's
global liking at the end of the meal. Both methods were applied using three
commercial familiar baby foods adapted to each age range. In 4-7-month-olds, the
elaborate method showed a significant difference across products for liking,
whereas the basic method did not show any difference. In 12-15-month-olds, the
elaborate method showed more differences across products for liking than the basic
method. In both age groups, negative behaviours, despite being less frequently
reported, provided better liking discrimination than positive behaviours. In
conclusion, the elaborate method produced better product liking discrimination than
the basic method by focusing maternal attention on infants' eating behaviours since
the first spoons. (C) 2017 Elsevier Ltd. All rights reserved.
Infant-directed speech (IDS) is the particular voice register observed in the
majority of parents in interaction with their infants and differs from natural
speech used in conversations with adults by showing exaggerated prosodic features.
These prosodic features are supposed to have effects on regulating infant arousal
and attention, fostering infant pre-linguistic and linguistic competences and
enhancing the expression of positive affect. The present set of meta-analyses was
conducted to test these associations and the role of moderators during the first
two years of infant life. The results confirmed an overall association between IDS
prosody and infant outcomes with prosodic values typical of IDS associated with
better outcomes. This association was confirmed for attentional, pre-linguistic and
linguistic outcomes with a greater effect on pre-linguistic than linguistic
outcomes. An insufficient number of studies was found to test the association with
infant emotion expression. Many limitations in the existing body of literature were
found, such as a lack of empirical papers exploring IDS prosody in relation to
infant outcomes using natural observations. The results and limitations were
discussed in light of the necessity to examine the interplay between the quality of
IDS prosody and other aspects of parental communicative and care giving
competences. To do so, the contribution of scholars from different fields is needed
with the aim to fully understand the multidimensional determinants and influential
mechanisms of IDS. (C) 2017 Elsevier Inc. All rights reserved.
Overall analysis and understanding of mechanisms are of great importance for
treatment of infantile pneumonia due to its high morbidity and mortality worldwide.
In this study, we preliminarily explored the function and mechanism of focal
adhesion kinase (FAK) in regulation of inflammatory response induced by
lipopolysaccharides in A549 cells. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcription
polymerase chain reaction, and Western blot analysis were used to explore the
correlation of FAK expression with cell apoptosis, viability, and the inflammatory
cytokine activity in A549 cells. The results showed that knockdown of FAK enhanced
cell viability, suppressed apoptosis, and decreased inflammatory cytokine activity.
In addition, downregulation of FAK could activate the Wnt and nuclear factor kappa
B signaling pathways. These findings suggest that FAK might be involved in
progression of infantile pneumonia and could be a new therapeutic target for this
disease.
Legislation in the United States, such as the Child Abuse Prevention and Treatment
Act and the Individuals With Disabilities Education Improvement Act, mandates
service system collaboration to meet the complex needs of young children with
disabilities who have experienced abuse. This literature review examines extant
literature related to young children with disabilities who have experienced abuse.
Gaps in the literature are identified and future directions are discussed.
Context: The human papillomaviruses (HPVs) are a major global health burden,
playing a part in diseases ranging from genital warts to malignancies such as
penile cancer in men and cervical cancer in women. Objective: To explore the
molecular biology and epidemiology of HPV infection; the diseases linked to it; and
current prevention strategies, including the potential role of vaccination.
Evidence acquisition: The relevant papers, reviews, and guidelines pertaining to
the topics were collected for the purpose of this review from PubMed and online
guidelines resources including the European Association of Urology and the Centers
for Disease Control and Prevention. Evidence synthesis: The current knowledge on
genital HPV in men is explained and summarised. Conclusions: There is an urgent
need for more data on the incidence and persistence of HPV at the different
anatomic sites, the incidence of external genital lesions, and the types of HPV in
these lesions. This will allow a more comprehensive understanding of the natural
history of HPV infection and its progression to both benign and malignant disease
in men and will help formulate the development and implementation of vaccination
programs. Patient summary: This review explores the molecular biology and
epidemiology of human papillomavirus (HPV) infection; the diseases linked to it;
and current prevention strategies, including the potential role of vaccination.
There is an urgent need for more data on the incidence and persistence of HPV at
the different anatomic sites, the incidence of external genital lesions, and the
types of HPV in these lesions. (C) 2016 European Association of Urology. Published
by Elsevier B.V. All rights reserved.
Unravelling the molecular mechanisms of disease manifestations is important to
understand pathologies and symptom development in plant science. Bacteria have
evolved different strategies to manipulate their host metabolism for their own
benefit. This bacterial manipulation is often coupled with severe symptom
development or the death of the affected plants. Determining the specific bacterial
molecules responsible for the host manipulation has become an important field in
microbiological research. After the identification of these bacterial molecules,
called "effectors," it is important to elucidate their function. A straightforward
approach to determine the function of an effector is to identify its proteinaceous
binding partner in its natural host via a yeast two-hybrid (Y2H) screen. Normally
the host harbors numerous potential binding partners that cannot be predicted
sufficiently by any in silico algorithm. It is thus the best choice to perform a
screen with the hypothetical effector against a whole library of expressed host
proteins. It is especially challenging if the causative agent is uncultivable like
phytoplasma. This protocol provides step-by-step instructions for DNA purification
from a phytoplasma-infected woody host plant, the amplification of the potential
effector, and the subsequent identification of the plant's molecular interaction
partner with a Y2H screen. Even though Y2H screens are commonly used, there is a
trend to outsource this technique to biotech companies that offer the Y2H service
at a cost. This protocol provides instructions on how to perform a Y2H in any
decently equipped molecular biology laboratory using standard lab techniques.
The demand for expertise in pathology for the diagnosis of infectious diseases (ID)
is continually growing, due to an increase in ID in immunocompromised patients and
in the (re)-emergence of common and uncommon diseases, including tropical
infections and infections with newly identified microbes. The microbiology
laboratory plays a crucial role in diagnosing infections, identifying the
responsible infectious agents and establishing sensitivity of pathogens to drug
therapy. Pathology, however, is the only way to correlate the presence of an
infectious agent with the reaction it evokes at cell and tissue level. For
pathologists working in the field of ID pathology, it is essential to dispose of
competence in cell and tissue pathology as well as in microbiology. Expertise in ID
includes understanding of taxonomy and classification of pathogens as well as
morphological criteria supporting their identification. Moreover, ID pathologists
must master the methods used to detect pathogens in fixed cell and tissue samples,
notably immunohistochemistry, in situ hybridization and the polymerase chain
reaction. Paradoxically, the increasing frequency of lesions caused by pathogens
and diagnosed in a pathology laboratory appears to be paralleled by a gradual loss
of expertise of pathologists in the field of infectious and tropical diseases. We
contend that this may be due at least in part to the continuously increasing number
of samples of tumor tissue pathologists deal with and the rapidly expanding number
of tissue based biomarkers with predictive value for new anti-cancer therapies. In
this review, we highlight current and future issues pertaining to ID pathology, in
order to increase awareness of its importance for surgical and molecular pathology.
The intention is to contribute to the development of best practice in ID pathology.
Background: Infertility is one of the major social issues. Due to the asymptomatic
cervical infection associated with Staphylococcus aureus (S. aureus), the majority
of patients remain undiagnosed. The present study intended to assess the frequency
of S. aureus isolated from infertile women's endocervix in northwest Iran.
Materials and Methods: In a descriptive cross sectional study, specimens were
randomly collected during vagina examination using a sterile speculum and swabbing.
After performance of antibiotic susceptibility testing, polymerase chain reaction
(PCR) was used to identify methicillin-resistance S. aureus (MRSA) and toxic shock
syndrome toxin-1 (TSST-1). Results: About 26 (26%) and 9 (9%) women's urogenital
tracts were colonized by S. aureus and Candida spp., respectively, of which three
(11.5%) patients were infected with fungi and S. aureus, simultaneously. Antibiotic
susceptibility results showed high activity of vancomycin and co-trimoxazole on
isolates. Regarding PCR results, mecA sequences were detected in 7 (26.9%) strains,
whilst the tst gene encoding TSST-1 was not detected in any of clinical strains.
Conclusion: The prevalence of S. aureus was very high in infertile women.
Therefore, it demands all patients undergoing infertility treatment to be
investigated thoroughly for this type of infection.
This paper addresses a significant paradox in biomaterials science;
biocompatibility phenomena have been experienced and described for over 50 years
but without an agreed understanding of the framework of mechanisms that control the
events that occur when a biomaterial is exposed to the tissues of the human body.
The need for such an understanding has become more urgent as biomaterials are now
used in wide-ranging applications such as tissue engineering, drug and gene
delivery, and imaging contrast agents. A detailed analysis of these phenomena,
especially in terms of clinical outcomes rather than in vitro experiments,
determines that two overarching mechanisms, mechanotransduction and sterile
inflammation associated with damage associated molecular patterns, are responsible
for the vast majority of phenomena. In contrast, interfacial interactions, for so
long being assumed to play pivotal roles in biocompatibility, especially relating
to protein adsorption, are actually relatively unimportant unless, through
conformational changes, they are able to participate in 3D ECM development.
Critical to this new view of biocompatibility is the fact that the combination of
mechanotransduction and sterile inflammation, especially focusing on inflammasome
activation and the immunology of the balance between inflammation and fibrosis,
allows biomaterials science to encompass mechanisms of innate and adaptive immunity
without recourse to the traditional implications of pathogen induced responses of
the immune system. In this way, a system of biocompatibility pathways can be
generated; these are able to explain a wide range of clinical biocompatibility
challenges, including nanoparticle translocation and internalization, intraocular
lens opacification, leukocyte dominated responses to metallic wear debris in joint
replacement, stem cell differentiation of nanostructured hydrogels, tissue
responses to incontinence meshes, and restenosis of intravascular stents. Perhaps
even more importantly, the identification of these molecular pathways of
biocompatibility offers prospects of the control of the host response by targeting
specific points in these pathways, for example the inhibition of epithelial to
mesenchymal transformation that can result in excessive fibrosis, and the
inhibition of activation of the NLRP3 inflammasome following exposure to
biomaterial-induced stresses; this should lead to a more effective translation of
biocompatibility understanding into better clinical outcomes.
Inflammation in the retinal pigment epithelium is an important contributor to the
pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated
from the root of Scutellaria baicalensis and has multiple pharmacological effects,
including anti-inflammatory effects. The present study sought to determine if the
pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE-19
cells were pre-conditioned with different concentrations of wogonin (0-50 mu M)
prior to induction of inflammation with LPS (2 mu g/ml). Transepithelial electrical
resistance analysis demonstrated that 24 h treatment with 10 and 50 mu M wogonin
ameliorated LPS-induced changes. Reverse transcription-quantitative polymerase
chain reaction (RT-qPCR) and immunofluorescence analyses revealed that wogonin
restrained LPS-induced tight junction proteins, claudin-1 and ZO-1. LPS-induced
upregulation of inflammatory mediators in ARPE-19 cells, including IL-1 beta, IL,-
6, IL,-8, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and TNF-
alpha was reduced after pre-treatment with wogonin. In addition, RT-qPCR and
western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS-
stimulated ARPE-19 cells. This is a novel mechanism indicating that pre-treatment
with wogonin could attenuate the TLR4/NF-kappa B-mediated inflammatory response in
LPS-stimulated ARPE-19 cells, and thus could be a potential therapy for the
treatment of AMD.
ObjectiveEstablish whether inflammatory biomarkersserum amyloid A (SAA), C-reactive
protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-)are related
to key symptoms of depression, including anxiety and fatigue, in a cross-sectional,
out-patient setting to identify biomarkers that reflect psychiatric symptomatology
in a naturalistic, real-life population. MethodsWe measured SAA, CRP, IL-6, and
TNF- in plasma samples from 89 adult psychiatric out-patients by multiplex, high-
sensitivity electrochemiluminescent assays. Psychiatric symptoms were evaluated
using the Hamilton Depression Rating Scale (HAMD-17), the Patient Health
Questionnaire (PHQ-9), and the Center for Epidemiological Studies Depression Scale
(CES-D). ResultsPlasma SAA was most robustly associated with depressive symptoms
across diagnostic boundaries in this cohort of out-patients. Elevated SAA was
significantly associated with higher total scores on the HAMD-17 scale and
correlated with multiple scale items that rated symptoms of fatigue and depressed
mood, but not with anxiety-related items. ConclusionsSAA might constitute a cross-
diagnostic marker indicative of depressed mood and fatigue in a naturalistic
patient setting. Because SAA activates Toll-like receptors 2 and 4, present on
macrophages and glial cells, its association with depression severity could also
implicate this inflammatory mediator in the pathogenesis of mood disorders.
Recent studies indicate that the immune system adaptation during pregnancy could
play a significant role in the pathophysiology of perinatal depression. The aim of
this study was to investigate if inflammation markers in a late pregnancy plasma
sample can predict the presence of depressive symptoms at eight weeks postpartum.
Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and
7-23 days respectively) comprising 63 individuals with postpartum depressive
symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS >= 12)
and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228
controls were analyzed with an inflammation protein panel using multiplex proximity
extension assay technology, comprising of 92 inflammation-associated markers. A
summary inflammation variable was also calculated. Logistic regression, LASSO and
Elastic net analyses were implemented. Forty markers were lower in late pregnancy
among women with depressive symptoms postpartum. The difference remained
statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and
IL-10, after Bonferroni correction. The summary inflammation variable was ranked as
the second best variable, following personal history of depression, in predicting
depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1
were validated in relation to methylation status of loci in the respective genes in
a different population, using openly available data. This explorative approach
revealed differences in late pregnancy levels of inflammation markers between women
presenting with depressive symptoms postpartum and controls, previously not
described in the literature. Despite the fact that the results do not support the
use of a single inflammation marker in late pregnancy for assessing risk of
postpartum depression, the use of STAM-BP or the novel notion of a summary
inflammation variable developed in this work might be used in combination with
other biological markers in the future. (C) 2017 The Authors. Published by Elsevier
Ltd.
Purpose To evaluate the prevalence of large drusen in a uveitis clinic population.
Design Retrospective, cohort study. Methods Patients with primary, non-infectious
uveitis 55years or older who were seen at the National Eye Institute of the
National Institutes of Health from 2004 through August 2013 were reviewed using
electronic medical records and photographic databases. Patients were classified as
having age-related macular degeneration (AMD) if either eye had large drusen,
geographic atrophy or neovascular AMD according to definitions used by the Eye
Diseases Prevalence Research Group (EDPRG). The expected number of cases and
standardised mortality ratio (SMR) for large drusen were estimated based on EDPRG
estimates. Results We identified 177 patients aged 55years as having primary non-
infectious uveitis; 170 (96.0%) had gradable fundus photos. Average age was
65.07.5years (range 55-87), and 87 were non-Hispanic white, 66 non-Hispanic black,
6 Hispanic white and 11 of other race/ethnicity. Large drusen were identified in
four patients (2.4%; 95% CI 0.6 to 6.0). No patients were identified to have late
AMD. In the uveitis cohort, the SMR for cases of large drusen, which was adjusted
for age, was calculated to be 0.32 (95% CI 0.12 to 0.70) for the whole cohort, 0.28
(95% CI 0.09 to 0.79) for non-Hispanic whites and 0.46 (95% CI 0.14 to 1.29) for
non-Hispanic blacks. Conclusions Large drusen prevalence among patients with
uveitis 55years of age appears less than the prevalence in the general US
population after accounting for differences in age distribution, especially for
non-Hispanic whites. Although the racial and gender distribution in this study
population is not directly representative of the general US population, results of
this study suggest possible sparing of patients with uveitis from AMD. A larger
systematic study with greater power would be needed to confirm these findings.
Purpose Kyrieleis retinal periarteritis reflects the severe intraocular
inflammation experienced by the eye. Its aetiology has not been well established,
since only nine cases have been reported and there is no pathological study
available in the literature. We determine the pathogenesis of Kyrieleis
periarteritis based on interpretation of multimodal imaging findings. Methods
Charts of patients with Kyrieleis arteritis seen between 2006 and 2014 were
retrieved from eight uveitis referral centres throughout the world. Follow-up
ranged from 5 to 12months. Results Twenty-five eyes with Kyrieleis arteritis from
25 patients were included in the study. Nineteen patients (72%) were male and six
(28%) were female. Twenty-three patients were diagnosed with toxoplasmosis
retinochoroiditis and two patients had cytomegalovirus retinitis. Fluorescein
angiography, fundus autofluorescence and indocyanine green angiography were
performed on 25/25 (100%) eyes. In eight eyes (32%), baseline spectral domain
optical coherence tomography (SD-OCT) scans were performed along the segmental
Kyrieleis arteritis. Fluorescein angiography showed early hypofluorescence and
intermediate hyperfluorescence associated with the areas of focal arteritis,
whereas indocyanine green angiography of these accumulations showed early
hypofluorescence and late hyperfluorescence. Fundus autofluorescence revealed an
increased autofluorescence of the vessels corresponding to the Kyrieleis plaques,
while SD-OCT scans along the segmental Kyrieleis arteritis showed hyperreflectivity
of the vessel wall. Conclusions These imaging modalities provide in vivo, quasi-
histologic images demonstrating that Kyrieleis plaques are characterised by an
inflammatory involvement within the vessels' endothelium.
Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity
account for a great part of neonatal morbidity and mortality. Inflammation may
cause preterm labor, with the involvement of different mediators that produce
diverse aspects of the inflammatory response. Although bacteria are considered to
be the main trigger for intrauterine infection/inflammation, immunological factors
also appear to be involved. Recently, molecular genetic studies have helped us
better understand the underlying pathophysiologic processes. During mammalian
pregnancy, maternal-fetal tolerance involves a number of immunosuppressive factors
produced by placenta. Recently, placenta-derived exosomes have emerged as new
immune regulators in the maternal immune tolerance. This review focuses on the
specific immune parameters that become altered during human pregnancy, the identity
and function of some immune modulators that have been best characterized to date,
as well as a comprehensive evaluation of the pregnancy-associated mechanisms that
downregulate proinflammatory immunity to a level sufficient to prevent the
triggering of premature common pathway of labor and damage to developing organs.
Objective: To examine differences in inflammation markers in sexually active versus
abstinent women and observe changes in inflammation markers across the menstrual
cycle. Cycle-related immune fluctuations may have evolved to reduce interference
with conception. If so, reproductively active (i.e., sexually active) women should
show the most variability in cytokine expression. Design: Participants provided
serum samples at menses and ovulation (from which cytokines were assayed) and
saliva samples at menses and during follicular, ovulation, and luteal phases (from
which C-reactive protein [CRP] was assayed). Participants self reported intercourse
frequency during the study. Setting: Academic research laboratory. Patient(s):
Thirty-two healthy, naturally cycling premenopausal women (sexually active, n = 15;
abstinent, n = 17). Intervention(s): Observational study. Main Outcome Measure(s):
Levels of proinflammatory cytokines (interleukin-6 [IL-6], interferon gamma [IFN-
7], tumor necrosis factor-alpha [INF-alpha]), an anti-inflammatory cytokine
(interleukin-4 [IL-41), and a marker of total inflammation (CRP). Result(s):
Sexually active women had higher levels of all of the immune markers measured,
including both pro- and antiinflammatory cytokines, than abstinent women. Relative
to sexually active women, abstinent women had less change across the menstrual
cycle in levels of CRP. Among sexually active women, higher intercourse frequency
predicted greater midcycle decreases in CRP, IL-6, and IFN-7 and midcycle increases
in IL-4. Conclusion(s): Sexual activity may stimulate a complex interaction between
pro- and anti-inflammatory cytokines that subsequently drives midcycle declines in
inflammation. (C)2016 by American Society for Reproductive Medicine.
Transfusion of blood cell components is frequent in the therapeutic arsenal; it is
globally safe or even very safe. At present, residual clinical manifestations are
principally inflammatory in nature. If some rare clinical hazards manifest as acute
inflammation symptoms of various origin, most of them linked with conflicting and
undesirable biological material accompanying the therapeutic component (infectious
pathogen, pathogenic antibody, unwanted antigen, or allergen), the general feature
is subtler and less visible, and essentially consists of alloimmunization or
febrile non-hemolytic transfusion reaction. The present essay aims to present
updates in hematology and immunology that help understand how, when, and why
subclinical inflammation underlies alloimmunization and circumstances
characteristic of red blood cells and - even more frequently - platelets that
contribute inflammatory mediators. Modern transfusion medicine makes sustained
efforts to limit such inflammatory hazards; efforts can be successful only if one
has a clear view of each element's role.
Inflammation is an elaborate reflex response of the body to the action of harmful
agents. This reaction manifests itself in the form of functional and structural
changes of vascular tissues. The inflammatory response is the result of the human
evolutionary process. It has three main stages, which are closely related to each
other and evolve simultaneously: tissue dystrophy (alteration); impairment of blood
circulation (transudation of fluid and migration of leukocytes) and multiplication
of cellular elements (proliferation). These phenomena express both a disturbance of
biological activity in body tissues and the defense mechanisms to restore the
damaged areas. There are two interrelated processes which are often inseparable
from each other in the inflammatory response. First, there is the pathological
process itself, the tissue damage in form of dystrophy, necrobiosis or necrosis.
Second, there is the physiological mechanism of defense, the process of recovery or
the physiological response against the disease", manifested as exudation,
phagocytosis and proliferation. Simultaneity of both processes is characteristic to
inflammatory processes.
BackgroundPatterns of influenza molecular viral shedding following influenza
infection have been well established; predictors of viral shedding however remain
uncertain. ObjectivesWe sought to determine factors associated with peak molecular
viral load, duration of shedding, and viral area under the curve (AUC) in children
and adult Hutterite colony members with laboratory-confirmed influenza. MethodsA
cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal
swabs were collected during three influenza seasons (2007-2008 to 2009-2010) from
both symptomatic and asymptomatic individuals infected with influenza. Samples were
tested by real-time reverse-transcription polymerase chain reaction for influenza A
and influenza B, and the viral load was determined for influenza A-positive
samples. ResultsFor seasonal H1N1, younger age was associated with a larger AUC,
female sex was associated with decreased peak viral load and reduced viral shedding
duration, while the presence of comorbidity was associated with increased peak
viral load. For H3N2, younger age was associated with increased peak viral load and
increased AUC. For pandemic H1N1, younger age was associated with increased peak
viral load and increased viral AUC, female sex was associated with reduced peak
viral load, while inapparent infection was associated with reduced peak viral load,
reduced viral shedding duration, and reduced viral AUC. ConclusionsPatterns of
molecular viral shedding vary by age, sex, comorbidity, and the presence of
symptoms. Predictor variables vary by influenza A subtype.
H9N2 Influenza subtype has emerged in Tunisia causing epidemics in poultry and
resulting in major economic losses. New mutations in their hemagglutinin and
neuraminidase proteins were acquired, suggesting their potential to directly infect
humans. Effective surveillance tools should be implemented to help prevent
potential spillover of the virus across species. We have developed a highly
sensitive real time immuno-polymerase chain reaction (RT-I-PCR) method for
detecting H9N2 virus. The assay applies aptamers as ligands to capture and detect
the virus. First, a panel of specific ssDNA aptamers was selected via a one step
high stringency protocol. Next, the panel of selected aptamers was characterized
for their affinities and their specificity to H9N2 virus. The aptamer showing the
highest binding affinity to the virus was used as ligand to develop a highly
sensitive sandwich Aptamer I-PCR. A 3-log increase in analytical sensitivity was
achieved as compared to a routinely used ELISA antigen test, highlighting the
potential of this approach to detect very low levels of virus particles. The test
was validated using clinical samples and constitutes a rapid and a label-free
platform, opening a new venue for the development of aptamer based viability
sensing for a variety of microorganisms of economic importance in Tunisia and
surrounding regions. (C) 2017 Elsevier B.V. All rights reserved.
Caregivers of children living with HIV/AIDS (CLWHA) face unique challenges due to
disease-related stigma and discrimination, isolation from society, financial
constraints, grief and mortality of loved one. A descriptive cross-sectional study
was conducted at Udupi ART centre to assess the caregiver burden, psychological
distress and their associated factors among the caregivers of CLWHA in Udupi
District. The convenience sampling technique was used to collect the data from 171
caregivers and analysed with the help of SPSS version 15.0. Majority of caregivers
were female (64.9%) with mean age of 38.1 +/- 9.6 years. About 64.3% caregivers
were HIV-positive and 63.2% were biological parents of CLWHA. Mild-to-severe
caregiver burden on Zarit Burden Inventory (ZBI) was reported among 84.8% of
caregivers, and mild-to-severe psychological distress on General Health
Questionnaire (GHQ-12) was reported among 49.7% caregivers. Relationship with child
was found to be a significant predictor of caregiver burden as compared to other
relatives/foster (P<0.001). Relationship with child (P 0.004), Alcohol use (P
0.008) and Schooling of children (P 0.049) were reported as significant predictors
of psychological distress. Study concludes that caregiver burden and psychological
distress were high among caregivers of CLWHA. Psychological problems of caregivers
need to be addressed and integrated along with the clinical care of HIV-infected
children at ART centres.
Anxiety and depression, which are highly prevalent in adolescence, are both
characterized by a negative attentional bias. As Attentional Bias Modification
(ABM) can reduce such a bias, and might also affect emotional reactivity, it could
be a promising early intervention. However, a growing number of studies also report
comparable improvements in both active and placebo groups. The current study
investigated the effects of eight online sessions of visual search (VS) ABM
compared to both a VS placebo-training and a no-training control group in
adolescents with heightened symptoms of anxiety and/or depression (n = 108).
Attention bias, interpretation bias, and stress-reactivity were assessed pre- and
post-training. Primary outcomes of anxiety and depressive symptoms, and secondary
measures of emotional resilience were assessed pre- and post-training and at three
and six months follow-up. Results revealed that VS training reduced attentional
bias compared to both control groups, with stronger effects for participants who
completed more training sessions. Irrespective of training condition, an overall
reduction in symptoms of anxiety and depression and an increase in emotional
resilience were observed up to six months later. The training was evaluated
relatively negatively. Results suggest that online ABM as employed in the current
study has no added value as an early intervention in adolescents with heightened
symptoms. (C) 2017 The Authors. Published by Elsevier Ltd.
In order to realize the human body temperature fast and non-contact measurement, an
infrared thermometer is designed. The infrared human body temperature sensor is
mainly used to convert the human body's infrared into voltage signal, an
operational amplifier to amplify the signal, filter circuit to filter the signal,
the analog signal into digital signal by the A/D conversion circuit, data
processing by the MCU, LCD display and voice reporting body temperature and time,
so the human body non-contact measurement is realized. The experimental results
show that: the device can realize the temperature and time of acquisition, the
measurement error is not more than 0.5 degrees C, voice broadcast and liquid
crystal display the temperature and time, overrun alarm and other functions.
Infrastructure services are essential to human development. Yet, the drivers of
service access at a global scale remain largely unexplored. This paper presents
trends and global patterns in access to water, sanitation, electricity, and
telephony services. Using a panel data set from 1990 to 2010, we empirically
explore plausible determinants of access rates to key infrastructure services.
Although per-capita GDP is correlated with access rates, access still varies
significantly at comparable income levels. Much of this variation is explained by
differences in population density. Access levels are higher for urban areas and
highest for water, followed by sanitation, electricity, and telephony. (c) 2017
Elsevier Ltd. All rights reserved.
Production of human papillomavirus type 16 major capsid protein L1 in
undifferentiated cells is negatively regulated by several yet unidentified cis-
acting inhibitory RNA elements, among which a major element is located within the
first 514 nucleotides of the L1-mRNA. By Northern blotting we examined effect of
the major element on the steady-state level of mRNA transiently transcribed in 293T
cells from the firefly luciferase (Fluc) gene combined with the L1 DNA fragment
encoding the major element. As reported previously, the element down-regulated
steady-state level of the mRNA. The most efficient down-regulation was achieved by
insertion of the element near the 5' end of mRNA, resulting in an undetectable
level of the mRNA. The longer the distance from the 5' end of the mRNA to the
element, the weaker the down-regulation. The half-life of the mRNA having the
element was similar to that of normal Fluc-mRNA. When the element near the 5' end
was removed by splicing, the steady-state level of the resultant mRNA was raised to
a readily detectable level. The steady-state level of RNA synthesized by RNA
polymerase-I was not influenced by the presence of the element. Taken together, it
is suggested that DNA region encoding the major inhibitory element does not disturb
transcription and that the pre-mRNA is degraded by an RNA element-mediated
mechanism after the splicing step in the course of mRNA maturation.
Scholars have hypothesized that victimization elicits distinctive effects on
women's pathways to prison and subsequent prison maladjustment, but few researchers
have investigated gender differences in this relationship. Using nationally
representative samples of men and women housed in state prisons, we examine gender
differences in the effects of experiencing different types of nonstranger
victimization prior to prison on inmate maladjustment. Results indicate that pre-
prison nonstranger victimization affects men's and women's maladjustment similarly,
with some gender differencesspecifically, the effect of being physically assaulted
by a nonstranger as an adult on violent misconduct was stronger among men, as was
the effect of child abuse on men's depressive symptoms. Our findings suggest the
effects of experiencing nonstranger victimization prior to incarceration on prison
maladjustment may be gender-neutral more so than gender-specific. Based on our
findings, nonstranger victimization should be deemed important in theories of men's
maladjustment as well as in theories of women's maladjustment.
The aim of this study was to examine the gender differences in various types of
childhood abuse and family history of crime, substance abuse, and mental health
problems. Our study was conducted among 110 Israeli female and male inmates (50
female and 60 male inmates). The findings indicated a higher rate of multiple types
of childhood abuse among the female inmates compared with the male inmates. The
findings also revealed that female inmates reported more prevalence of parents'
substance abuse, crime, and family's mental health problems than the male inmates
did. Moreover, the female inmates reported higher rates of emotional, physical, and
sexual abuse associated with family history variables compared with the male
inmates. Furthermore, the findings indicated that female inmates whose siblings
were involved in substance abuse and crime reported higher rates of sexual and
emotional abuse compared with the male inmates. We discussed the implications of
these findings.
Background: Growing evidence emphasizes the relevance of sphingolipids for
metabolism and immunity of antigen-presenting cells (APC). APCs are key players in
balancing tolerogenic and encephalitogenic responses in immunology. In contrast to
the well-known prominent effects of sphingosine-1-phosphate (S1P) on lymphocyte
trafficking, modulatory effects on APCs have not been fully characterized. Methods:
Frequencies and activation profiles of dendritic cell (DC) subtypes, monocytes, and
T cell subsets in 35 multiple sclerosis (MS) patients were evaluated prior and
after undergoing fingolimod treatment for up to 24 months. Impact of fingolimod and
S1P on maturation and activation profile, pro-inflammatory cytokine release, and
phagocytotic capacity was assessed in vitro and ex vivo. Modulation of DC-dependent
programming of naive CD4+ T cells, as well as CD4+ and CD8+ T cell proliferation,
was also investigated in vitro and ex vivo. Results: Fingolimod increased
peripheral slanDC count-CD1+ DC, and monocyte frequencies remained stable. While
CD4+ T cell count decreased, ratio of Treg/Th17 significantly increased in
fingolimod-treated patients over time. CD83, CD150, and HLADR were all inhibited,
but CD86 was upregulated in DCs after incubation in the presence of fingolimod.
Fingolimod but not S1P was associated with reduced release of pro-inflammatory
cytokines from DCs and monocytes in vitro and ex vivo. Fingolimod also inhibited
phagocytic capacity of slanDCs and monocytes. After fingolimod, slanDCs
demonstrated reduced potential to induce interferon-gamma-expressing Th1 or IL-17-
expressing Th17 cells and DC-dependent T cell proliferation in vitro and in
fingolimod-treated patients. Conclusions: We present the first evidence that S1P-
directed therapies can act additionally as immunomodulators that decrease the pro-
inflammatory capabilities of APCs, which is a crucial element in DC-dependent T
cell activation and programming.
Phagocytosis and autophagy in macrophages have been shown to be essential to both
innate and adaptive immunity. Lysosomes are the main catabolic subcellular
organelles responsible for degradation and recycling of both extracellular and
intracellular material, which are the final steps in phagocytosis and autophagy.
However, the molecular mechanisms underlying lysosomal functions after infection
remain obscure. In this study, we conducted a quantitative proteomics analysis of
the changes in constitution and glycosylation of proteins in lysosomes derived from
murine RAW 264.7 macrophage cells treated with different types of pathogens
comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses (herpes
simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus, VSV). In
total, 3,704 lysosome-related proteins and 300 potential glycosylation sites on 193
proteins were identified. Comparative analysis showed that the aforementioned
pathogens induced distinct alterations in the proteome of the lysosome, which is
closely associated with the immune functions of macrophages, such as toll-like
receptor activation, inflammation and antigen-presentation. The most significant
changes in proteins and fluctuations in glycosylation were also determined.
Furthermore, Western blot analysis showed that the changes in expression of these
proteins were undetectable at the whole cell level. Thus, our study provides unique
insights into the function of lysosomes in macrophage activation and immune
responses.
Purpose of review The purpose of this review is to summarize recent advances in our
understanding of the complex immunology of intestinal transplantation and allograft
rejection. Recent findings Recent findings highlight the importance of the
intestinal microbiome for intestinal homeostasis and the role of newly discovered
innate lymphoid cells in intestinal transplantation. In addition, the role of host
antimicrobial Th17 responses in the pathogenesis of inflammatory bowel diseases and
intestinal allograft rejection has been further elucidated. Summary Research on the
complex immune system of the intestine has continued to reveal more intricacies and
connections with each study performed, making treatment of intestinal transplant
patients more multifaceted. The interaction, communication, and relationships
between areas such as the microbiome, innate lymphoid cells, and Th17 cells reveal
possible targets for therapy and further areas requiring ongoing research.
Gap junctions are clusters of intercellular channels that are associated with
embryonic development and neural signaling. Innexins, invertebrate gap junction
proteins, have been identified in Drosophila and Caenorhabditis. Here, we report
the isolation and characterization of two novel members of the insect innexin
family, Bm inx2 and Bm inx4, from embryos of the silkworm, Bombyx mori, during the
germ-band formation stage. Bm inx2 is a single copy gene with one exon, while Bm
inx4 is a single copy gene with four exons and three introns. The predicted
proteins show structural similarities with other innexin family members, including
four transmembrane (TM) domains, two extracellular loops (ELs), one cytoplasmic
loop (CL), and typical conserved amino acids. Bm inx2 is phylogenetically
orthologous to the other insect inx2 genes, but Bm inx4 is not orthologous to any
known innexin including Dm inx4. Interestingly, Northern blotting and in situ
hybridization showed that Bm inx2 was variously expressed across all developmental
stages and in various tissues, with high expression seen in the nervous system at
the time of embryogenesis. In contrast, Bm inx4 was transiently expressed at the
germ-band formation stage of embryogenesis, and was specifically expressed in the
ovary and testis during the larval and pupal stages. The isolation and
characterization of these novel genes should form the basis for further study of
the functional events that occur during development and neuronal communication in
B. mori. (c) 2007 Published by Elsevier Ltd.
Recent work has demonstrated the importance of post-transcriptional gene regulation
in toxic responses. In the present study, we used two rat models to investigate
mRNA translation in the liver following xenobiotic-induced toxicity. By combining
polysome profiling with genomic methodologies, we were able to assess global
changes in hepatic mRNA translation. Dio3 (iodothyronine deiodinase type III) was
identified as a gene that exhibited specific translational repression and had a
functional role in a number of relevant canonical pathways. Western blot analysis
indicated that this repression led to reduced D3 (the protein expressed by Dio3)
levels, enhanced over time and with increased dose. Using Northern blotting
techniques and qRT-PCR (quantitative reverse transcription-PCR), we confirmed
further that there was no reduction in Dio3 mRNA, suggesting that translational
repression of Dio3 is an important determinant of the reduced D3 protein expression
following liver damage. Finally, we show that drug-induced hepatotoxicity appears
to cause localized disruptions in thyroid hormone levels in the liver and plasma.
We suggest that this leads to reduced translation of Dio3 mRNA, which results in
decreased D3 production. It may therefore be possible that this is an important
mechanism by which the liver can, upon early signs of damage, act rapidly to
maintain its own energy equilibrium, thereby avoiding global disruption of the
hypothalamic-pituitary-thyroid axis.
Cadmium-free quantum dots (QDs) have attracted great attention in biological and
biomedical applications due to their less content of toxic metals, but their
potential toxicity investigations on molecular biology level are rarely involved.
Since few studies have addressed whether InP/ZnS QDs could bind and alter the
structure and function of human serum albumin (HSA), in vitro interaction between
InP/ZnS QDs and HSA was systematically characterized by multispectroscopic
approaches. InP/ZnS QDs could quench the intrinsic fluorescence of HSA via static
mode. The binding site of InP/ZnS QDs was mainly located at subdomain IIA of HSA.
Some thermodynamic parameters suggested that InP/ZnS QDs interacted with HSA mainly
through electrostatic interactions. As further revealed by three dimensional
spectrometry, FT-IR spectrometry and circular dichroism technique, InP/ZnS QDs
caused more global and local conformational change of HSA than CdSe/ZnS QDs, which
illustrated the stronger binding interaction and higher potential toxicity of
InP/ZnS QDs on biological function of HSA. Our results offer insights into the in
vitro binding mechanism of InP/ZnS QDs with HSA and provide important information
for possible toxicity risk of these cadmium-free QDs to human health. (C) 2016
Elsevier B.V. All rights reserved.
Inpp5f-v3 is a transcriptional variant of Inpp5f (inositol polyphosphate-5-
phosphatase F) and locates in distal mouse chromosome 7. It is a paternally
expressed imprinted gene in mouse. In this study, we examined the spatiotemporal
patterns of Inpp5f-v3 gene during the mouse development. The northern blotting
analysis revealed that only one transcript approx 2.7 kb of Inpp5f-v3 was detected
in brain. The signals were only observed in brain by the whole-mount in situ
hybridization at embryonic day 11.5 (E11.5). The results of quantitative real-time
PCR (QRT-PCR) showed that the expression of Inpp5f-v3 increased gradually from the
E11.5 to E17.5 and reached the highest at E17.5, then decreased at E18.5 during the
brain development. Inpp5f-v3 gene was strongly expressed in the cerebral cortex,
olfactory bulb, external germinal layer of cerebellum and ventricular zone (Vz)
during the embryonic development (E15.5-E19.5), whereas the expression increased in
the olfactory bulb and the cerebellum after birth by using in situ hybridization.
The results also demonstrated that the expression of Inpp5f-v3 gene mainly located
in olfactory bulb and hippocampus at postnatal day 7 (P7) and adulthood. These
results suggest that Inpp5f-v3 is specifically expressed in mouse brain, and may
function in the development of mouse brain.
Although some novel antimicrobial peptides (AMP) have been successfully isolated
from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these
peptides are still elusive. The homolog of NF-kappa B transcription factor Relish,
designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of
BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids.
Similar to Drosophila Relish and the mammalian p100, it is a compound protein
containing a conserved Rel homology domain, an IPT (Ig-like, plexins, transcription
factors) domain and an I kappa B-like domain (four ankyrin repeats), the nuclear
localization signal RKRRR is also detected at the residues 449-453, suggesting that
it has homology to Relish and it is a member of the Rel family of transcription
activator proteins. Reverse transcription quantitative polymerase chain reaction
analysis reveals that BdRelish mRNAs are detected in different quantities from
various tissues and the highest transcription level of BdRelish is determined in
fat body. The injection challenge of Escherichia coli and Staphylococcus aureas
significantly upregulated the expression of BdRelish. The injection of BdRelish
dsRNA markedly reduced the expression of BdRelish and decreased the transcription
magnitude of antimicrobial peptides. Individuals injected BdRelish dsRNA died at a
significantly faster rate compared with the control groups. Therefore, BdRelish is
vital for the transcription of AMPs to attack the invading bacteria.
The kissing bug Rhodnius prolixus is both an important vector of Chagas' disease
and an interesting model for investigation into the field of physiology, including
lipid metabolism. The publication of this insect genome will bring a huge amount of
new molecular biology data to be used in future experiments. Although this work
represents a promising scenario, a preliminary analysis of the sequence data is
necessary to identify and annotate the genes involved in lipid metabolism. Here, we
used bioinformatics tools and gene expression analysis to explore genes from
different genes families and pathways, including genes for fat breakdown, as
lipases and phospholipases, and enzymes from beta-oxidation, fatty acid metabolism,
and acyl-CoA and glycerolipid synthesis. The R. prolixus genome encodes 31 putative
lipase genes, including 21 neutral lipases and 5 acid lipases. The expression
profiles of some of these genes were analyzed. We were able to identify nine
phospholipase A2 genes. A variety of gene families that participate in fatty acid
synthesis and modification were studied, including fatty acid synthase, elongase,
desaturase and reductase. Concerning the synthesis of glycerolipids, we found a
second isoform of glycerol -3-phosphate acyltransferase that was ubiquitously
expressed throughout the organs. Finally, all genes involved in fatty acid beta-
oxidation were identified, but not a long-chain acyl-CoA dehydrogenase. These
results provide fundamental data to be used in future research on insect lipid
metabolism and its possible relevance to Chagas' disease transmission. (C) 2016
Elsevier B.V. All rights reserved.
Mythimna separata walker (Lepidoptera: Noctuidae) is a polyphagous pest of nearly
100 families of more than 300 kinds of food and industrial crops. So far, both
nucleotide and protein sequence information has been rarely available in database
for M. separata, strictly limiting molecular biology research in this insect
species. In this study, we carried out a transcriptome sequencing for M. separata.
The sequencing and subsequent bioinformatics analysis yielded 69,238 unigenes,
among which 45,227 unigenes were annotated to corresponding functions by blasting
with high homologous genes in database, giving annotation rate of 65.32%. Several
lepidopteran insects gave best matches with the transcriptome data. To gain insight
into the mechanism of insecticide resistance in M. separata, 15 families of genes
encoding insecticide resistance-related proteins were investigated. Substantial
numbers of unigenes in these families were identified in the transcriptome data,
and 17 out of 21 selected unigenes were successfully amplified. Expressions of most
of these genes were detected at larval stages and in gut tissue, as was consistent
with their putative involvement in insecticide resistance. Our study provides most
comprehensive transcriptome data for M. separata to date, and also provides
reference sequence information for other Noctuidae family insects.
We examined the extent to which emerging adults engage in different behaviors on
Instagram, a popular social networking site, to gain attention and validation from
others via "likes." We also examined individual differences in the frequency of
like-seeking behavior and motives for Instagram use as mediators of these
relationships. Participants (N = 198 and 265 (replication study)) were recruited
via an online crowdsourcing portal to complete a survey. Results demonstrated that,
as predicted, participants engaged in an assortment of different like-seeking
behaviors. Further, a two-factor solution emerged, with like-seeking behavior
separated by whether they were normative (i.e., common or accepted, e.g., using
filters or hashtags) or deceptive (e.g., buying likes or changing one's appearance
in photos using software). Deceptive like-seeking was predicted by stronger
narcissism and a weaker sense of peer belonging, whereas normative like-seeking was
predicted by stronger narcissism and a stronger sense of peer belonging. Further,
consistent with hypotheses, significant mediators of the relation between
narcissism and deceptive like-seeking included motives to use Instagram to increase
popularity and showcase creativity. Results help to identify young people who are
more susceptible to engaging in deceptive, potentially harmful acts to gain
attention and validation on Instagram. (C) 2017 Elsevier Ltd. All rights reserved.
In an effort to enhance instruction and reach more students, educators design
engaging online learning experiences, often in the form of online videos. While
many instructional videos feature a picture-inpicture view of instructor, it is not
clear how instructor presence influences learners' visual attention and what it
contributes to learning and affect. Given this knowledge gap, this study explored
the impact of instructor presence on learning, visual attention, and perceived
learning in mathematics instructional videos of varying content difficulty. Thirty-
six participants each viewed two 10-min-long mathematics videos (easy and difficult
topics), with instructor either present or absent. Findings suggest that instructor
attracted considerable visual attention, particularly when learners viewed the
video on an easy topic. Although no significant difference in learning transfer was
found for either topic, participants' recall of information from the video was
better for easy topic when instructor was present. Finally, instructor presence
positively influenced participants' perceived learning and satisfaction for both
topics and led to a lower level of self-reported mental effort for difficult topic.
(C) 2017 Elsevier Ltd. All rights reserved.
An area-efficient self-trimming technique for precision chopper-stabilized
instrumentation amplifier (IA) is presented. The amplifier uses a reconfigurable
differential pair for the input stage and it is automatically configured to reduce
the mismatch of the differential pair, suppressing the chopper ripple. To confirm
the effectiveness of the proposed scheme, an IA with the complete calibration logic
is fabricated in a standard 180-nm CMOS and achieves active area, less than offset
voltage, input-referred noise, and current consumption. The noise efficiency factor
of the amplifier is 7.2.
The article considers design features of the main modifications of analog interface
for sensor systems, implemented on the base of differential difference op amps
(DDA). Unlike classical structures of instrumentation amplifiers (IA) with junction
coupling of stages, the suggested circuit solutions give small suppression of
offset voltage (<= 30 mu V) and provide common-mode rejection more than -97dB in
conditions of radiation and low temperature effects. Feeding of inherent
compensation circuits of parasitic impedances of IA circuit according to the
algorithm extends its bandwidth by a factor of 3-5. The article suggests new
modifications of two-stage DDAs with higher voltage gain.
Previous studies in our laboratory have shown that one of the earliest events
during hepatocarcinogenesis in the albumin SV40 T antigen (Alb SV40 T Ag)
transgenic rat is the duplication of chromosome 1q3.7-4.3, a region which contains
the imprinted and coordinately regulated genes lgf2 and H19. We have also shown
that this duplication is associated with the biallelic expression of the normally
monoallelically-expressed H19. These results, however, are seemingly at odds with
studies in the mouse that have shown a conservation of fetal regulatory patterns of
these two genes in hepatic neoplasms. We therefore aimed in this study to determine
the allelic origin of lgf2 expression in hepatocellular carcinomas of the Ab SV40 T
Ag transgenic rat. Sprague-Dawley Alb SV40 T Ag transgenic rats and Brown Norway
rats were reciprocally mated and the expression of lgf2 in hepatocellular
carcinomas of the resulting F, transgene-positive female rats was analyzed by
Northern blotting and RT-PCR. We determined that lgf2 was expressed exclusively
from the paternal allele, which prompted the study (by the same methods) of the
allelic origin of H19 in the same hepatocellular carcinomas in order to determine
if the two genes remained coordinately regulated. our results demonstrate fetal-
like re-expression of lgf2 and deregulation of H19 in singular hepatocellular
carcinomas of the rat. These results imply that another regulatory mechanism other
than the generally accepted ICR/CTCF mechanism may play a role in the control of
lgf2 and H19 expression. (C) 2007 Wiley-Liss, Inc.
Liu S, Liu R, Chiang Y, Song L, Li X, Jin T, Wang Q. Insulin detemir enhances
proglucagon gene expression in the intestinal L cells via stimulating beta-catenin
and CREB activities. Am J Physiol Endocrinol Metab 303: E740-E751, 2012. First
published July 17, 2012; doi:10.1152/ajpendo.00328.2011.-Insulin therapy using
insulin detemir (d-INS) has demonstrated weight-sparing effects compared with other
insulin formulations. Mechanisms underlying these effects, however, remain largely
unknown. Here we postulate that the intestinal tissues' selective preference allows
d-INS to exert enhanced action on proglucagon (Gcg) expression and the production
of glucagon-like peptide (GLP)-1, an incretin hormone possessing both glycemia-
lowering and weight loss effects. To test this hypothesis, we used obese type 2
diabetic db/db mice and conducted a 14-day intervention with daily injection of a
therapeutic dose of d-INS or human insulin (h-INS) in these mice. The body weight
of the mice after 14-day daily injection of d-INS (5 IU/kg) was decreased
significantly compared with those injected with the same dose of h-INS or saline.
The weight-sparing effect of d-INS was associated with significantly elevated
circulating levels of total GLP-1 and reduced food intake. Histochemistry analysis
demonstrated that d-INS induced rapid phosphorylation of protein kinase B (Akt) in
the gut L cells of normal mice. Western blotting showed that d-INS stimulated Akt
activation in a more rapid and enhanced fashion in the mouse distal ileum compared
with those by h-INS. In vitro investigation in primary fetal rat intestinal cell
(FRIC) cultures showed that d-INS increased Gcg mRNA expression as determined by
Northern blotting and real-time RT-PCR. Consistent with these in vivo
investigations, d-INS significantly increased GLP-1 secretion in FRIC cultures.
Consistently, d-INS was also shown to induce rapid phosphorylation of Akt in the
clonal gut cell line GLUTag. Furthermore, d-INS increased beta-catenin
phosphorylation, its nuclear translocation, and enhanced cAMP response element-
binding protein (CREB) phosphorylation in a phosphatidylinositol 3-kinase and/or
mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-
sensitive manner. We suggest that the weight-sparing benefit of d-INS in mice is
related to its intestinal tissues preference that leads to profound stimulation of
Gcg expression and enhanced GLP-1 secretion in intestinal L cells, potentially
involving the activation of insulin/beta-catenin/CREB signaling pathways.
This study examines the expression of the insulin-like growth factor type 1
receptor (TGF-1R) in colorectal neoplasia. Previous studies have shown that the
IGF-1R is expressed at high levels in normal embryonic stem cells and in many
cancer phenotypes. However, lower IGF-1R levels are expressed in some advanced
cancer phenotypes. The timing of and the reasons for these changes in expression
during the evolution of a cancer are not understood. Here, we examine IGF-1R
expression in the evolution of colorectal cancer by means of Northern blotting and
immunohistochemistry validated by tissue and reagent controls and Western blotting.
We show for the first time that (1) in normal colorectal crypts, epithelial stem
cells in the basal crypt region express high IGF-1R levels, which decrease to low
levels when these cells migrate to and differentiate in the mid and upper crypt
regions; (2) in tumor initiation in aberrant crypt foci, all of the transformed
cells express high levels of the IGF-1R at stem cell levels throughout the crypt
axis; (3) in tumor progression in adenomatous and cancerous crypts, tumor cells of
an epithelial type morphology express high levels of the IGF-1R; (4) in advanced
cancers, low levels of the IGF-1R are expressed in invasive foci where cancer cells
dedifferentiate to a mesenchymal-type morphology and show a loss of cell adhesion.
Interestingly, these cells can form an alternating pattern with mesenchymal type
cells that show cell adhesion and high levels of IGF-1R expression. In summary,
this study shows that high-level IGF-1R expression in colorectal neoplasia is
initiated by an abnormality of stem cell programed differentiation in the aberrant
crypt focus. However, low-level IGF-1R expression is found in some invasive cancers
where it is consequent to cancer cell dedifferentiation to a mesenchymal type
morphology with loss of cell adhesion. Crown Copyright (c) 2007 Published by
Elsevier Inc. All rights reserved.
Insulin receptor substrates (IRSs) are well known to play crucial roles in
mediating intracellular signals of insulin-like growth factors (IGFs)/insulin.
Previously, we showed that IRS-1 forms high molecular mass complexes containing
RNAs. To identify RNAs in IRS-1 complexes, we performed ultraviolet (UV) cross-
linking and immunoprecipitation analysis using HEK293 cells expressing FLAG IRS-1
and FLAG IRS-2. We detected the radioactive signals in the immunoprecipitates of
FLAG IRS-1 proportional to the UV irradiation, but not in the immunoprecipitates of
FLAG IRS-2, suggesting the direct contact of RNAs with IRS-1. RNAs cross-linked to
IRS-1 were then amplified by RT-PCR, followed by sequence analysis. We isolated
sequence tags attributed to 25 messenger RNAs and 8 non-coding RNAs, including
small nucleolar RNAs (snoRNAs). We focused on the interaction of IRS-1 with U96A
snoRNA (U96A) and its host Rack1 (receptor for activated C kinase 1) pre-mRNA. We
confirmed the interaction of IRS-1 with U96A, and with RACK1 pre-mRNA by
immunoprecipitation with IRS-1 followed by Northern blotting or RT-PCR analyses.
Mature U96A in IRS-1 / mouse embryonic fibroblasts was quantitatively less than WT.
We also found that a part of nuclear IRS-1 is localized in the Cajal body, a
nuclear subcompartment where snoRNA mature. The unanticipated function of IRS-1 in
snoRNA biogenesis highlights the potential of RNA-associated IRS-1 complex to open
a new line of investigation to dissect the novel mechanisms regulating
IGFs/insulin-mediated biological events.
This paper presents a nonlinear control technique based on feedback Relay systems
for photovoltaics applications in converters and inverters. Describes the design of
the control law from the state equations of Buck converter, the analysis of limit
cycles, stability of the systems to obtain digital control law for further
simulation and implementation in programmable logic devices (PLD). We performed the
programming of the control technique in hardware description language (VHDL), later
we implement in a CPLD and development the prototype of a Buck converter. Finally
simulations and tests to the prototype were realized, obtaining optimal results of
performance.
We investigate analog single event transient (ASET) generation in an LM124
operational amplifier using focused pulsed x-rays and 800 nm femtosecond laser
pulses. We report improvements that have been made to the pulsed x-ray experimental
apparatus which include normal incidence geometry and a high speed x-ray chopper
that allows us to reduce the pulse repetition frequency of the synchrotron derived
x-ray pulse train. The addition of the chopper allows us to measure ASETs that have
long relaxation times. We show that ASETs can be generated through metallization on
the LM124, and that for equivalent pulse energy incident on the part, the x-ray
response from areas covered by metal (and inaccessible to the laser) are different
than the x-ray response from areas with no metallization, i.e. "metal-free". We use
the laser pulses to generate ASETs at the same metal-free locations of x-ray
induced ASETs. The shapes of the ASETs generated by the two methods are compared.
We use the differences seen from the two generation methods to estimate the charge
generation/collection produced by the pulsed x-rays and then estimate what LET this
would correspond to for heavy ions. This work shows that pulsed x-rays can be used
to characterize analog devices for single event effects.
The increasing share of variable renewable energy sources and the improving
requirements on system security and reliability are calling for important changes
in our energy systems. The synergies between energy supply networks are of great
importance to satisfy the development of the integrated energy system (IES). Hence
this paper presents the study of the coordinated scheduling strategy (CSS), in
which, the models of the electricity network and gas network are developed in
detail, and the operation constraints of the networks are fully considered. The
purpose of the CSS is to optimize the conflicting benefits of the electricity
network arid gas network for daily operation of the IES, while satisfying the
operation constraints. In the CSS, a multi-objective optimization algorithm is
applied to obtain a Pareto-optimal solution set, and a multiple attribute decision
analysis (MADA) using interval evidential reasoning (IER) is developed to determine
a final optimal daily operation solution for the IES. Simulation studies are
conducted on an IES consisting of a modified IEEE 30-bus electricity network and a
15-node gas network to verify the effectiveness of the CSS, and to evaluate the
interdependency between the electricity network and gas network. (C) 2016 Published
by Elsevier Ltd.
An integrated photo-bioelectrochemical (IPB) system is innovative through
integrating microbial fuel cells (MFCs) with algal bioreactors for simultaneous
organics degradation, nutrient removal, and bio-energy production. A mathematical
model has been developed for simulating and understanding the performance of the
IPB system. The model inputs include influent COD (chemical oxygen demand), NH-N,
total phosphorus, external resistance and flow rate, while the outputs include the
biomass growth, COD degradation, nutrient removal, and electricity generation. The
determination of unknown model parameters was assisted with sensitivity analysis.
Satisfactory model fitting and validation was achieved, with low root-mean-square
error of 5.6% and 0.2%, respectively, for biomass concentration and current
generation under varied COD input. The simulated results suggested that the organic
input and flow rate had more significant impacts on the growth of algal biomass
than other input factors, while COD, flow rate and external resistance were of
importance for current generation. The optimal condition for improving this
particular IPB system was predicted to have a COD concentration above 150 mg L-1
and the flow rate at 0.1 mL min(-1). This IPB model is the first attempt of the
kind for the optimization of an integrated bioprocess of electrochemical reactions
and algal growth. (C) 2017 Elsevier Ltd. All rights reserved.
Solar energy for building applications may significantly reduce the conventional
energy consumption and the related carbon dioxide emissions. The comprehensive
utilization of integrated solar thermal and photovoltaic systems is undoubtedly a
subject of interest. In the present paper, an optimization model was proposed for
integrated solar energy systems, aiming to figure out the optimal utilization and
economical efficiency of solar energy resources for buildings in cold plateau
areas. A case study in Lhasa city was further carried out in order to evaluate the
energy and economic performance of the developed model. The results indicated that
solar photovoltaic systems are preferred than solar thermal systems for typical
office buildings in cold plateau areas with rich solar energy resources. In
addition, a sensitivity analysis was performed to investigate the influences of
financial subsidies and commercial electricity prices on the system economical
performance. Furthermore, life cycle assessment was conducted to compare and
analyze the performances of an optimization system and a conventional system. (C)
2016 Elsevier Ltd. All rights reserved.
Engaging undergraduates in research is essential for teaching them to think like
scientists, and it has become a desired component of classroom and laboratory
instruction. Research projects that span an entire semester expose students to a
variety of concepts and techniques and allow students to use experiments to learn
scientific principles, understand why specific techniques are applicable,
critically analyze varied data, and examine how experimentation leads to acquiring
knowledge. To provide an experience with these features, a semester long research
project was integrated into a combined lecture and laboratory course, Molecular
Biology. The project utilized the zebrafish model to examine gene expression during
embryonic development and required students to develop and test hypotheses about
the timing of expression of previously uncharacterized genes. The main goals for
the project were to provide opportunities for students to develop critical thinking
skills required for conducting research and to support the content goals of the
course. To determine whether these goals were met, student performance on the steps
of the project and related pre-test and post-test questions was examined. (C) 2016
by The International Union of Biochemistry and Molecular Biology
Integrative medicine (IM) has received increasing attention since the 1990s, but
few studies have explored the key factors of the IM model in health care. This
study aimed to describe the IM model in leading centers operating in the USA and
Germany. A 28-item structured survey and semi-structured interviews were conducted
in six centers providing integrative medicine in the USA and Germany, and were
analyzed using a convergent mixed-method approach. The elements in common across
all six centers were the following: (1) involvement of general physicians (GP) in
delivering complementary and alternative medicine (CAM) services; (2) requirement
for GP or medical referral or recommendation to CAM services; (3) involvement of an
integrative physician (IP) as a "gatekeeper"; (4) focus on research, education, and
clinical practice; and (5) ongoing academic activities. The key elements
differentiating the two countries were the following: (1) level of requirements for
GP referral to CAM services; (2) differences in IM service delivery, including
treatment modalities used; (3) accessibility of CAM services to patients; (4)
interaction between team members and patients; (5) perception of CAM/IM; and (6)
perception of patient-centered care. Themes underpinning these elements are the
following: cultural aspects in conceptualizing IM health care; communication within
IM programs; and resource availability for delivering IM services, which impacts
patient engagement and team collaboration in the IM framework. Delivering IM health
care requires a model of care that encourages interaction between all stakeholders.
Developing a comprehensive conceptual framework to support IM practice is required
to facilitate efficient and safe patient care.
When lepidopteran larvae are infected by a large quantity of pathogens or
parasitized by nonadaptive parasitoids hemocytes in the hemocoel will encapsulate
these foreign invaders Cellular encapsulation requires hemocytes particularly
plasmatocytes to change their states from nonadhesive spherical cells into adhesive
spreading cells However It is unclear how the changes of plasmatocytes are
regulated Here we report that the integrin beta 1 subunit from hemocytes of
Ostrinia furnacalis (Ofint beta 1) plays an important role in regulating the
spreading of plasmatocytes The full length cDNA sequence (4477 bp) of Ofint beta 1
was cloned from hemocytes Phylogenetic analysis showed that Ofint beta 1 belonged
to the integrin beta PS family of Drosophila melanogaster with highest sequence
identity (78 7%) to the beta-integrin of Pseudoplusia includens Structural analysis
of the deduced amino acid sequence indicated that Ofint beta 1 had similar
functional domains to known beta-integrins in other lepidopteran insects RT-PCR
Northern blotting Western blotting and immunohistochemical analyses showed that
OfINT beta 1 was expressed mainly in hemocytes especially in plasmatocytes and
weakly in fat body Malpighian tubes and epidermis After hemocytes had spread onto
slides fewer antibodies to OfINT beta 1 bound to the surface of plasmatocytes
Furthermore anti-OfINT beta 1 serum clearly inhibited the spreading of
plasmatocytes Together these results indicate that OfINT beta 1 may play an
important role in regulating the spreading of plasmatocytes (C) 2010 Elsevier Ltd
All rights reserved
We outline an evolutionary-embodied-epistemological (EEE) account of intellectual
arrogance (IA), proposing that people psychologically experience their important
beliefs as valued possessions - mental materialism - that they must fight to keep -
ideological territoriality - thereby disposing them toward IA. Nonetheless, IA
should still vary, being higher among people taking a hostile and domineering
epistemic stance (rejecting reality, resisting evidence) than among those taking an
open and deferential one (embracing reality, respecting evidence). Such variations
can be predicted from people's standing on the communion-agency circumplex at
multiple levels of analysis (i.e. from their social inclusion and status;
dispositional warmth and competence; and behavioral amiability and assertiveness).
Using pre-validated indices of mental materialism and ideological territoriality,
and an argument evaluation task permitting the quantification of rational
objectivity and egotistical bias, we obtained consistent correlational evidence
that, as hypothesized, IA is the highest when agency is high and communion low,
validating the EEE account.
Several studies have demonstrated that mothers with intellectual disability (ID)
have a higher prevalence of mental health illness, lower socio-economic status, and
a higher risk of alcohol and drug use compared to mothers without ID. The children
of mothers with ID are over-represented in child protection and legal proceedings
but are generally a less studied group than the mothers. The aim of this study was
to investigate if children born to mothers with ID had an increased risk of being
diagnosed with mental illness, injuries, and violence compared with children of
mothers without ID. The study comprised a population based cohort of children born
in Sweden between 1999 and 2005. Data were collected from the Medical Birth
Register and linked with two other national registers; ICD-10 codes were used for
medical diagnoses, including ID. The children were followed from birth to seven
years of age. In total, 478,577 children were included, of whom 2749 were born to
mothers with ID. Children of mothers with ID were at a greater risk of having
mental health problems (adjusted odds ratio (OR)= 2.02; 95% confidence interval
(CI) = 1.74-2.35) and ID (OR = 4.14; CI = 2.95-5.82) in early childhood. They had
an increased risk for injuries due to falls (OR = 1.15; CI 1.04-1.27). The largest
risk related to trauma was violence and child abuse (OR =3.11; CI = 1.89-5.12). In
conclusion, children of mothers with ID had an increased risk for injuries,
violence, and child abuse. We therefore suggest that parents with ID should receive
evidence based support so that their children receive the best care and protection.
(C) 2017 The Author(s). Published by Elsevier Ltd.
The paper proposes to evaluate achievement of main results in operation of
intellectual mechatronic systems with digital control by the obtained information
effect. In this respect, common information requirements with intellectual
components are considered as a basic information factor which influences on the
process of mechatronic system designing. Therefore, some parameters have been
accentuated and they can help to provide rather complete description of the
processes used for obtaining and using systematic information within the volume of
the intellectual mechatronic system. Conformity degree of control vector parameters
synthesized by the system and identification results of its current states have
been selected as an information criterion of the control efficiency. A set of
expected probability values for location of each parameter of an control object and
a mechatronic system within the required tolerances has been used for formation of
possible states. The paper shows that when a complex information description of the
system is used then it is expedient to use an expert assessment of selection
probability for allowable control vectors which ensure a system transfer to
favorable states. This approach has made it possible to pinpoint main information
and technical specifications of the intellectual mechatronic system: structural
construction (informational and technical compatibility and information matching of
its components); control object (uncertainty of its state and information vector,
information capacity of the mechatronic system); control actions (their hierarchy
and entropic balance of control process, managerial resource of mechatronic
system); functioning result (informational effect and control efficiency criterion,
probabilistic selection of system states). In accordance with the fulfilled
analysis it is possible to note the most effective directions for practical use of
the proposed informational approach for creation of the intellectual mechatronic
system: comparison of alternative design solutions based on the analysis of
calculation assessments on unconditional entropy of the control object and the
system; simulation with the aim to accept a final systematic option while
constructing digital controlling block of the created system; complex application
of experts' knowledge, most comprehensive introduction of knowledge to the process
of mechatronic system designing.
Interconnected electricity networks, or Supergrids, are considered as a possible
solution to tackle challenges associated with near and far-future supply of
electricity. These include, but are not limited to, reducing Green House Gas
emissions and reliance on non-renewable fossil fuels. Supergrids can help to tackle
these challenges, for example, by providing a reliable interconnection platform for
wider application (and development) of renewable technologies. However, there is a
range of risks and uncertainties associated with selecting appropriate
interconnections. Heretofore these have been a hindrance to developing
interconnections and therefore a Risk-Based Framework (RBF) which addresses these
risks and uncertainties could encourage the wider uptake of Supergrids. This paper
presents for the first time such a robust framework. The RBF comprises of four
stages; (1) initial screening for selecting candidate countries, (2) risk
identification, (3) risk semi-quantification and (4) risk quantification. In stage
4 the uncertainties associated with the identified risks are quantified using a
cost-risk model under uncertainty based on a whole life appraisal approach. The
usefulness of the approach, demonstrated using the UK as a case study, showed that
greatest cost risks are associated with (a) regulatory framework, and (b) changes
in energy policy. The most desirable interconnection option for the UK was
identified as France. (C) 2017 Elsevier Ltd. All rights reserved.
This paper presents a low power, compact, and low-complexity pulse-width
modulation-based interface circuit for capacitive MEMS sensors. The circuit is
designed using a ring oscillator, an RC controlled pulse generator with high-pass
filter, and a self-tuning inverter comparator to produce pulse width, which is
proportional to differential capacitance and independent of parasitic capacitance.
The high-pass filter is utilized to reduce the bandwidth of noise sources. The
circuit provides control over sensitivity, dynamic range, and nominal point for the
capacitance measurement by selecting controlling parameters, such as resistance of
the RC pulse generator, biasing voltage of the self-tuning inverter comparator, and
a reference capacitor using digital control signals. The circuit provides high
linearity with higher sensitivity and lower power consumption. The sensitivity of
the circuit is 0.56 to 3.62 mu s/pF depending on the controlling parameters. The
maximum dynamic sensing range is 22 to 270 pF depending on the controlling
parameters. The interface circuit is designed and fabricated using the United
Microelectronics Corporation (UMC) 0.18-mu m CMOS technology. It occupies an active
area of 0.17 mm(2) and consumes 98 mu W. A capacitive MEMS-based pressure sensor is
also connected with the interface circuit to measure pressure throughout the
digestive tract. The sensitivity for pressure from 101 to 200 kPa is 60 ns/kPa and
from 50 to 101 kPa is 23 ns/kPa.
This paper presents a closed-loop interface for micro-machined accelerometer sensor
based on a force-feedback sigma-delta loop. A high-order closed-loop accelerometer
interface circuit is investigated, and a time-shared multiplexing electrostatic
feedback technique is used to eliminate feedthrough between feedback signals and
pick-up charge signals. A low noise capacitance detection circuit is proposed with
correlated-double-sampling technique to eliminate the 1/f noise and offset of
operational amplifier. The interface is fabricated in a standard 0.5 mu m CMOS
process and the active circuit area is about 13 mm(2). The chip consumes 20 mW from
a 5 V supply with a sampling clock of 250 kHz. The average noise floor of the
digital accelerometer is about -115 dBV/Hz(1/2) over a 1.5 kHz bandwidth.
Corresponding to a sensitivity of 302 mV/g, the measured resolution of the
accelerometer system is about 6 mu g/Hz(1/2). The nonlinearity is 0.085 %. The
figure of merit shows that the proposed sigma-delta interface achieves a good
performance.
Prunus necrotic ringspot virus (PNRSV) is a common pollen-borne virus that can
infect many Prunus species. While some strains cause serious adverse effects (e.g.,
rugose mosaic virus), many strains are relatively symptomless in sweet cherry
(Prunus avium). However, even symptomless strains can cause adverse reactions in
some cherry rootstocks, such as Gisela T (Gi) 7 (P. cerasus x P. canescens). Using
interfering RNAs (RNAi) to induce gene silencing, the rootstocks Gi6 (PNRSV-
tolerant) and Gi7 (PNRSV-sensitive) were transformed with the RNAi vector pART27-
PNRSV containing an inverted repeat (IR) region of PNRSV, using Agrobacterium
tumefaciens strain EHA105. This yielded 19 independent transgenic events for Gi6
and three for Gi7. Regenerated plants exhibited a normal phenotype. The presence of
the PNRSV-fragment was confirmed by Southern blot. Northern blotting revealed the
presence of small interfering RNAs (siRNA) in five of ten transgenic events tested.
The transgenic lines were then inoculated with a combination of PNRSV and Prune
Dwarf Virus (PDV). After one year, the transgenic Gi7 showed no infection symptoms
and was negative for PNRSV in ELISA assays. Non-transgenic Gi7 plants developed
serious virus infection symptoms and died. Even though Gi6 is tolerant of PNRSV,
inoculation still caused infection, making it a symptomless carrier. In contrast,
the inoculated transgenic Gi6 remained negative for PNRSV in ELISA assays. These
results indicate RNAi-mediated gene silencing is effective in inducing virus
resistance for cherry rootstocks, which may be useful for conferring virus
resistance to commercial scions while producing non-genetically modified fruits.
Aim: A number of adipocytokines have been suggested to be involved in the
disruption of glucose metabolism, and also in the development of various diabetic
complications. We attempted to identify and analyze additional adipocytokines, to
better understanding the roles of adipocytes and adipocytokines. Methods: An oligo-
capping signal sequence trap, developed in our laboratory for screening the cDNAs
of secretory proteins, was used to sreen cDNAs expressed in mouse white adipose
tissue. Profiles of the genes identified in mice and cultured cells were further
investigated by northern blotting and luciferase assay. Results: A cDNA fragment of
interferon-stimulated gene 12b (ISG12b) was obtained in the search. A northern blot
analysis revealed ISG12b to be highly expressed in white adipose tissue. Interferon
a (IFN alpha) was shown to induce ISG12b expression in the adipose tissue of BL6
mice in vivo, and also in a 3T3-L1 preadipocyte cell line in vitro. The level of
ISG12b was higher in mature adipocytes than in preadipocytes. A promoter analysis
demonstrated that the 369bp upstream from the transcription initiation site of
ISG12b mRNA contain strong promoter activity, and the interferon-stimulated
response elements (ISREs) were not present within the 5593bp upstream region.
Conclusion: ISG12b is an additional candidate for a adipocytokine induced to
express in adipose tissue by interferon.
The concept of intergenerational transmission of intimate partner violence (IPV)
has been an important topic of research. Experts have contended that this brutal
path in which violence is transmitted to subsequent generations may be avoidable.
This study examined whether public perceptions of the legal regulation of IPV and
the certainty of sanction deter the prevalence of IPV. Data from 3,800 households
were obtained from a nationwide survey conducted in South Korea. Due to a skewed
distribution of the prevalence of IPV, this study applied a zero-inflated Poisson
(ZIP) model, which has been shown to address issues of skewed count variables. In
addition, use of a ZIP model allowed us to examine factors associated with the
occurrence and frequency of IPV. Results showed that child abuse experience and
perceptions of the law were associated with the occurrence of IPV. Individuals who
experienced child abuse were more likely to perpetrate IPV, whereas those aware of
the law were less likely to perpetrate IPV. Witnessing IPV between parents was
associated with an increased frequency of IPV. Results suggest that by increasing
awareness of laws against domestic violence, IPV may be reduced or prevented.
We examined the intergenerational transmission of parent-child relationship
qualities in a population-based Finnish sample of 1418 participants (G2) and their
mothers (G1). At baseline, G1 (Mage=38) reported qualities of the parent-child
relationship in terms of emotional warmth and acceptance towards G2 (age range 3-
18). After 28years, G2 (Mage=39) rated the qualities of the parent-child
relationship regarding their own children using the same questionnaire. Emotional
warmth and acceptance were transmitted across generations even after controlling
for demographic and family characteristics in both generations. The transmission
was stronger for emotional warmth than acceptance. For emotional warmth,
intergenerational transmission was stronger for men than women. The findings
provide evidence for the long-term transmission of parenting quality across
generations.
An accurate inter-laboratory comparison (ILC) concerning the electrical quantities
in low frequency between the laboratory for the calibration of multifunction
electrical instruments of the National Institute of Metrology Research (INRIM) and
a secondary high level electrical calibration laboratory was performed with
satisfactory results. The instrument involved in the ILC was a top class
multifunction electrical calibrator, chosen for its wide measurement fields and its
excellent definability requiring therefore very small uncertainties to calibrate
it. This ILC was the first high accuracy comparison exercise at INRIM involving a
grid of about one hundred and thirty measurement points. The ILC allowed to check
adequately the measurement capabilities, techniques and uncertainties of this
secondary laboratory. Attention was paid to evaluate the correlated terms between
the two laboratories measurements. The calibrator showed high stability and
resulted more appropriate than fixed standards or than a 8.5 digits multimeter to
the aim of the ILC. (C) 2017 Elsevier Ltd. All rights reserved.
This paper proposes a new phase current reconstruction technique for interleaved
three-phase bidirectional dc-dc converters using a single current sensor. In the
proposed current reconstruction algorithm, a single current sensor is employed at
the dc-link, and the dc-link current information is sampled at either the peak or
valley point of the pulse-width modulation (PWM) carriers regularly. From the
obtained current information, all phase currents are reconstructed in a single PWM
cycle. After that, the digital current controller is applied to achieve current
balancing in each phase. Compare to the previous multiple current sensor method,
the proposed strategy reduces the number of the current sensors in the interleaved
three-phase bidirectional converter as well as reducing potential current sensing
error caused by non-ideal characteristics of the multiple current sensors. The
effectiveness of the proposed method is verified from the experiments based on a
3kW three-phase bidirectional converter prototype for the automotive battery
charging application.
The interleaved multilevel DC-DC converters have advantages of low voltage stress
of the switches and diodes and reduction of filter size. Particularly series input
parallel output (ISOP) configuration is well suited for high output voltage and
large output current application but input series output series (ISOS)
configuration enable the utilization of low voltage rating switches in high voltage
input and high voltage output applications that require galvanic isolation. The
series connection of the isolated DC-DC converters at the input side also can be
used for higher voltage application. While multilevel topology offers many new
features, it also necessitates a balance control of the input capacitors. The paper
describes the operating principles of the balancing circuit, analyzes the
fundamental relationships, introduces principles of the operation of the circuit.
The paper shows experimental results based on a few practical application examples.
The paper discusses design of the transformer with balancing winding for ISOP, ISOS
and parallel connection of the DC-DC converters to provide independent voltage
balancing of input capacitors.
Interleukin-1 (IL-1beta) beta and major histocompatibility complex (MHC) play an
important role during pregnancy. Expression of non-classical class MHC II RT1-DM
antigen and classical class MHC I RT1-A antigen induced by IL-1beta was examined by
Northern blotting, Western blotting and immunohistochemistry. IL-1beta treatment
significantly increased the expression of RT1-A and RT1-DM in early and mid
pregnancy. In late pregnancy, expression of RT1-DM significantly increased in uteri
and decreased in placenta. Immunohistochemical studies indicated that, in early
pregnancy, RT1-DM protein mainly localized to luminal and glandular uterine
epithelium, and RT1-A was present in deciduas basalis, outer layer of luminal
epithelium and glandular epithelium. During mid and late pregnancy, RT1-DM was
present in maternal blood vessels and syncytio-trophoblast of labyrinthine zone,
and RT1-A was present in maternal blood vessels and trophoblastic epithelium of the
labyrinthine layers. These findings show that exogenous IL-1beta affects expression
of RT1-DM and RT1-A and does not affect the localization of corresponding molecules
during pregnancy.
AIM: To identify the effects of interleukin (IL) -13 on retinal pigment epithelial
(RPE) cells and the IL -13 level in aqueous humor of age-related macular
degeneration (AMD) patients. METHODS: IL -13 levels in aqueous humor specimens from
AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19
cells were treated with 10 ng/mL IL -13 for 12, 24, and 48h. The cell proliferaton
was evaluated by the MTS method. The mRNA and protein levels of alpha-SMA and ZO-1
were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and
Western blot respectively. The expression of tumor necrosis factor-alpha (TNF-
alpha), transforming growth factor-beta (TGF-beta)and vascular endothelial growth
factor (VEGF) were assessed by ELISA. RESULTS: IL -13 levels in the aqueous humor
of patients with AMD were significantly higher than those in the control (167.33
+/- 17.64 vs 27.12 +/- 5.65 pg/mL; P<0.01). In vitro, IL -13 of high concentrations
(10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. a-SMA mRNA in ARPE-19
cell were increased (1.017 +/- 0.112 vs 1.476 +/- 0.168; P<0.001) and ZO-1
decreased (1.051 +/- 0.136 vs 0.702 +/- 0.069; P<0.001) after treated with 10 ng/mL
IL -13 for 48h. The protein expression of a-SMA and ZO-1 also showed the same
tendency (a-SMA: P=0.038; ZO-1: P=0.008). IL -13 significantly reduced the level of
TNF-a (44.7 +/- 01.67 vs 31.79 +/- 3.53 pg/mL; P=0.005) at 48h, but the level of
TGF-I32 was significantly increased from 34.44 +/- 2.92 to 57.61 +/- 6.31 pg/mL at
24h (P=0.004) and from 61.26 +/- 1.11 to 86.91 +/- 3.59 pg/mL at 48h (P<0.001).
While expressions of VEGF didn't change after IL -13 treatment. CONCLUSION: IL -13
in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be
associated with AMD.
Objective Limited data exist on child abuse-related immune variation during
pregnancy, despite implications for maternal and infant health and extensive data
showing that abuse history and depression are related to increased inflammation in
other populations. This study examined associations among child abuse, depression,
circulating levels of inflammatory markers, and perinatal health in pregnant
adolescents, a group at high risk for childhood abuse and poor birth outcomes.
Methods Pregnant teenagers (n = 133; 14-19 years; 89.5% Latina) reported on abuse
and depression and had two blood draws (24-27 and 34-37 gestational weeks, second
and third trimesters, respectively) for interleukin-6 (IL-6) and C-reactive
protein; birth outcomes were collected. Results Abuse and depression interacted to
predict higher IL-6 at second trimester (B = 0.006, p = .011) such that severely
abused adolescents with high depression had higher IL-6 relative to severely abused
adolescents with low depression; depression did not differentiate IL-6 levels for
those with low abuse severity. Abuse and IL-6 also interacted to predict
gestational age at birth (B = 0.004, p = .040) such that those with low abuse and
high IL-6 and those with high abuse and low IL-6 had infants with earlier
gestational age at birth. Cortisol at the second trimester mediated the association
between IL-6 and gestational age at birth (indirect effect estimate=-0.143, p
< .039). Conclusions Depression severity distinguished IL-6 levels among more
severely abused pregnant Latina adolescents, but it was unrelated to IL-6 among
less severely abused adolescents. Cortisol explained the relationship between IL-6
and earlier gestational age at birth. Multiple adversities and inflammation may
influence birth outcomes and potentially affect intergenerational health.
A novel independent Th-cell subset, characterized by high expression of interleukin
(IL)-9, has been recognized as the "Th9" subset. Although Th9 cells are important
in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We
therefore first determined whether Th9 cells were presentin a mouse model of AR. We
then investigated the their involvement in the distribution of CD4+ T-cell subsets
and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9
Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR
in BALB/c mice. We measured nasal rubbing motion, sneezing and eosinophils, as well
as the Th1 (Th1 cell percentage, Ifn-gamma. mRNA/protein, T-bet mRNA), Th2 (Th2
cell percentage, Il-4 mRNA/protein, Gata3 mRNA), Th9 (Th9 cell percentages Il-9
mRNA/protein, PU. 1 and Irf4 mRNA), Th17 (Th17 cell percentage, Il-17 mRNA/protein,
Ror.t mRNA), and Treg (Treg cell percentage, Foxp3 mRNA) responses in the nasal
mucosa. Treatment with anti-IL-9 Abs markedly reduced nasal rubbing, sneezing,
eosinophil infiltration, and Th2, Th9, and Th17 responses, and increased the Treg
response. Our findings emphasize the importance of IL-9/Th9 in the pathogenesis of
AR, and suggest that anti-IL-9 Ab treatment may be an effective therapeutic
strategy for AR.
Wind power generation of electricity has gained popular support because of its low
environmental impact and its low costs relative to other renewable energy sources.
However, concerns have been raised in the power sector that wind power generation
will come at the price of increased damage to other power generators. Wind power
generation is naturally volatile which requires other power sources to start up and
shut down in accordance with weather conditions, which for instance coal or gas
generators are in general not built to do. The previous literature has used
simulations to show that the damage done and the associated costs can be
substantial. We use a dataset containing all reported failures in the Nordic
electricity market Nord Pool and data for Danish wind power generation. The
analysis shows that for both Denmark and the rest of Nord Pool the short-term costs
associated with the volatility of wind power generation are non-significant. (C)
2016 Elsevier Ltd. All rights reserved.
This paper refers to recovering waste heat from the hot gases exhausted by internal
combustion engines (ICEs) driving electric generators (EGs) at full and partial
load. The topic is of particular interest for developing countries where electric
grids are underdeveloped or missing and electricity is generated locally by using
classical fuels. The heat recovery system is based on an Organic Rankine Cycle
(ORC). A novel method is proposed for the optimum design of ORC-based systems
operating in combination with ICE at partial EG loads. First, ORC-based systems
coupled with ICEs operating at full EG load is treated. Specific results for the
operation at full EG load are as follows: (i) the optimum superheating increment
ranges between 30 and 40 degrees C, depending on the type of the working fluids;
(ii) a pinch point temperature difference exits between the flue gas temperature
and the working fluid at the evaporator inlet; (iii) the total area of the
evaporator is very close to the total area of the condenser, a fact which
facilitates manufacturing; (iv) the surface area of the preheater zone is about 75%
of the total surface area, while those of the boiler zone and superheater zone is
about 13.5% and 11.5%, respectively. Second, the case of the ORC-based systems
coupled with ICEs operating at partial EG load is considered. Specific results for
this case are as follows: (v) the net power may be maximized by optimizing the
working fluid mass flow rate; (vi) when the ICE is coupled with an ORC-based
system, the overall thermal efficiency of the combined system, eta(ICE-ORC), is
higher than the thermal efficiency of the ICE operating alone. As an example, for
the case treated here, 'eta(ICE-ORC) is higher than Hits. by 6.00%, 5.85% and
5.91%, for EG loads of 100%, 75% and 50%, respectively. (C) 2017 Elsevier Ltd.
Background: The world's top three cereals, based on their monetary value, are rice,
wheat, and corn. In cereal crops, DNA extraction is difficult owing to rigid non-
cellulose components in the cell wall of leaves and high starch and protein content
in grains. The advanced techniques in molecular biology require pure and quick
extraction of DNA. The majority of existing DNA extraction methods rely on long
incubation and multiple precipitations or commercially available kits to produce
contaminant-free high molecular weight DNA. Results: In this study, we compared
three different methods used for the isolation of high-quality genomic DNA from the
grains of cereal crop, Zea mays, with minor modifications. The DNA from the grains
of two maize hybrids, M10 and M321, was extracted using extraction methods DNeasy
Qiagen Plant Mini Kit, CTAB-method (with/ without 1% PVP) and modified Mericon
extraction. Genes coding for 45S ribosomal RNA are organized in tandem arrays of up
to several thousand copies and contain codes for 18S, 5.8S and 26S rRNA units
separated by internal transcribed spacers ITS1 and ITS2. While the rRNA units are
evolutionary conserved, ITS regions show high level of interspecific divergence and
have been used frequently in genetic diversity and phylogenetic studies. In this
study, the genomic DNA was then amplified with PCR using primers specific for ITS
gene. PCR products were then visualized on agarose gel. Conclusion: The modified
Mericon extraction method was found to be the most efficient DNA extraction method,
capable to provide high DNA yields with better quality, affordable cost and less
time.
Background Working with victims and perpetrators of child sexual abuse has been
shown to cause secondary traumatic stress (STS) in child protection professionals.
Aims To examine the role of gender and personality on the development of secondary
trauma responses. Methods A study of Internet child abuse investigators (ICAIs)
from two UK police forces. Participants completed a personality test together with
tests for anxiety, depression, burnout, STS and post-traumatic stress disorder to
assess secondary trauma. The data were normally distributed and the results were
analysed using an independent t-test, Pearson correlation and linear regression.
Results Among 126 study subjects (50 females and 75 males), there was a higher
incidence of STS in investigators who were female, introverted and neurotic.
However, there were lower levels of STS in the participants in this study than
those found in other studies. Conclusions Psychological screening and surveillance
of ICAI teams can help to identify risk factors for the development of STS and
identify where additional support may be required.
Control over digital transactions has steadily risen in recent years, to an extent
that puts into question the Internet's traditional openness. To investigate the
origins and effects of such change, the paper formally models the historical
evolution of digital control. In the model, the economy-wide features of the
digital space emerge as a result of the endogenous adaptation (co-evolution) of
users' preferences (culture) and platform designs (technology). The model shows
that: a) in the digital economy there exist two stable cultural-technological
equilibria: one with intrinsically motivated users and low control; and the other
with purely extrinsically motivated users and high control; b) before the opening
of the Internet to commerce, the emergence of a low-control-intrinsic-motivation
equilibrium was favored by the specific set of norms and values that formed the
early culture of the networked environment; and c) the opening of the Internet to
commerce can indeed cause a transition to a high-control-extrinsic-motivation
equilibrium, even if the latter is Pareto inferior. Although it is too early to say
whether such a transition is actually taking place, these results call for a great
deal of attention in evaluating policy proposals on Internet regulation.
Interpersonal space is a nonverbal indicator of affiliation and closeness. In this
study we investigated the effects of oxytocin (OT), a neuropeptide known for its
social role in humans, on interpersonal space. In a double blind placebo controlled
study we measured the effect of intranasal OT on the personal distance preferences
of different familiar (friend) and unfamiliar (stranger) protagonists. Behavioral
results showed that participants preferred to be closer to,a friend than to a
stranger. Intranasal OT was associated with an overall distancing effect, but this
effect was significant for the stranger and not for the friend. The imaging results
showed interactions between treatment (OT, placebo) and protagonist (friend,
stranger) in regions that mediate social behavior including the dorsomedial
prefrontal cortex (dmPFC), a region associated with the mentalizing system.
Specifically, OT increased activity in the dmPFC when a friend approached the
participants but not when a stranger approached. The results indicate that the
effect of OT on interpersonal space greatly depends on the participant's
relationship with the protagonist. This supports the social salience theory,
according to which OT increases the salience of social cues depending on the
context. (C) 2016 Elsevier Ltd. All rights reserved.
The problem of inter-regional interchange scheduling in the presence of stochastic
generation and load is considered. An interchange scheduling technique based on a
two-stage stochastic minimization of expected operating cost is proposed. Because
directly solving the stochastic optimization is intractable, an equivalent problem
that maximizes the expected social welfare is formulated. The proposed technique
leverages the operator's capability of forecasting locational marginal prices and
obtains the optimal interchange schedule without iterations among operators.
Several extensions of the proposed technique are also discussed.
This paper illustrates the development, up to prototype stage, of an
electromechanical actuation system for a medium-voltage vacuum contactor. Such
development is carried out using a multi-domain simulation-based mechatronic
approach, i.e. developing coordinated sub-models for the mechanism linking the
actuator to the movable parts of the interrupter, the rotational electromagnetic
actuator, and the power and control electronic circuit supplying the actuator and
governing the system via a digital control unit. After a preliminary analysis, the
modeling, design and check of the parts via coordinated simulations is presented. A
prototype of the system, manufactured to validate the design procedure is finally
presented.
Intervertebral disc degeneration (IDD) is considered to be the main cause of many
spinal disorders; however, its underlying pathophysiology is not clearly
understood. Recent studies indicate that excessive mechanical loading may serve a
major role in the initiation of IDD. The aim of the present study was to explore
the effect of noninvasive cumulative axial loading on the intervertebral discs of
the lumbar spine using a novel rabbit model. Rabbits in the experimental group were
placed into individual tubes specifically designed to force maintenance of an
upright posture and were loaded with a heavy collar to increase the intradiscal
pressure of their lumbar spine. Radiograph imaging and magnetic resonance imaging
(MRI) was performed every 4 weeks to provide evidence of disc degeneration. At the
end of the experiment, the animals were sacrificed and disc specimens were
harvested for quantitative polymerase chain reaction and histological analysis. MRI
results revealed significant and progressive reductions in the signal intensities
of lumbar discs in the experimental group compared with the control group
throughout the 14-week study period. The expression level of type I collagen was
significantly increased and the expression levels of type II collagen and aggrecan
were significantly decreased in the experimental group compared with the control
group (P<0.05). Histological examination revealed marked structural changes in the
experimental group, including fibrocartilage-like tissue ingrowth and accelerated
fibrotic changes of the nucleus pulposus. The results of the present study indicate
that noninvasive cumulative axial load is able to induce accelerated degenerative
changes in rabbit lumbar discs, which may provide useful information for the
establishment of a novel animal model of IDD for the research of IDD in humans.
Background and aims Little is known about the intestinal epithelial expression and
secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and
monocytes. We aimed to study CXCL10 gene expression and regulation by the pro-
inflammatory cytokines interleukin (IL)-1 beta, interferon (IFN)-gamma and tumour
necrosis factor (TNF)-alpha in intestinal epithelial cell lines. Materials and
methods CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29 and
DLD1 human colon epithelial cells, treated with IL-1 beta, TNF-alpha, IFN-gamma
alone or in combination with each other by real-time polymerase chain reaction
(PCR), Northern blotting and enzyme-linked immunoabsorbent assay (ELISA). Transient
transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10-kappa B2 mutant promoter
and gelshifts and supershifts for nuclear factor (NF)-kappa B were also performed.
Results Real-time PCRs and ELISA experiments revealed that IL-1 beta was the
strongest and earliest inducer of CXCL10 messenger ribonucleic acid (mRNA)
expression and protein secretion in Caco-2 cell line, whereas INF-gamma had a
delayed kinetics. There was a strong synergistic effect of either TNF-alpha or IL-1
beta with IFN-gamma both on CXCL10 mRNA expression and protein secretion in all
three cell lines. Real-time PCR and ELISA experiments using a specific NF-kappa B
inhibitor and transfection experiments with a NF-kappa B-binding defective CXCL10
promoter construct revealed that the induction of CXCL10 by IL-1 beta and its
synergism with IFN-gamma is NF-kappa B dependent. Conclusion These data demonstrate
that in colonic epithelial cells, depending on the cellular context and utilizing
the NF-kappa B pathway, IL-1 beta alone and/or in synergism with IFN-gamma may play
a major role in the induction of CXCL10.
Mast cells are innate immune cells that respond rapidly to infection in barrier
tissues such as the skin and intestinal mucosa. Expulsion of parasitic worms in the
gut involves a robust type 2 host response, and an acute mastocytosis is often
generated at the site of infection. However, the role of mast cells in resistance
to worm infections appears to be parasite specific. Mast cells are also involved in
tissue repair, but the long-term contribution of mast cell activation after worm
expulsion has not been definitively studied. In this issue of European Journal of
Immunology, Sorobetea et al. [ Eur. J. Immunol. 2017. 47: 257-268] demonstrate that
activated mast cells persist in the large intestinal lamina propria and
intraepithelial compartment long after worm expulsion, resulting in continued local
and systemic presence of the mast cell protease mast cell protease 1 (MCPt-1) and
enhanced intestinal permeability. In this commentary, we discuss these findings in
the wider context of mast cell function in health and disease.
In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are
removed by apoptosis, and the adult epithelial stem (AE) cells appear
concomitantly. They proliferate and differentiate to form the adult epithelium
(Ep). Thyroid hormone (TH) is well established to trigger this remodeling by
regulating the expression of various genes including Notch receptor. To study the
role of Notch signaling, we have analyzed the expression of its components,
including the ligands (DLL and Jag), receptor ( Notch), and targets ( Hairy), in
the metamorphosing intestine by real-time reverse transcription-polymerase chain
reaction and in situ hybridization or immunohistochemistry. We show that they are
up-regulated during both natural and TH-induced metamorphosis in a tissue-specific
manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover,
upregulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a
c-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-
induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed
by GSI treatment. Our results suggest that Notch signaling plays a role in stem
cell development by regulating the expression of Hairy genes during intestinal
remodeling. Furthermore, we show with organ culture experiments that prolonged
exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory
cells and reduction of absorptive cells. Our findings here thus provide evidence
for evolutionarily conserved role of Notch signaling in intestinal cell fate
determination but more importantly reveal, for the first time, an important role of
Notch pathway in the formation of adult intestinal stem cells during vertebrate
development.
The postnatal development of intestine is associated with a decline in brush border
lactase activity in rodents. This is similar to adulthood hypolactasia, a
phenomenon prevalent in humans worldwide. In the present study, the effect of
luminal proteases from adult rat intestine was studied in vitro on intestinal
lactase activity in saline control, thyroxine, insulin and cortisone treated rat
pups. Lactase levels were determined by enzyme analysis and Western blotting. mRNA
levels encoding lactase were determined by Northern blotting. Administration of
thyroxine for 4 days reduced (P < 0.05) lactase activity, but insulin treatment had
no effect in 8-day-old rat intestine. However, cortisone administration augmented
(P < 0.01) lactase activity, under these conditions. Western blot analysis showed
decreased lactase signal corresponding to 220-kDa protein band in thyroxine treated
animals. However, the intensity of lactase signal was high in cortisone treated
animals compared to controls. mRNA levels encoding lactase showed a 6.8-kb mRNA
transcript in saline and hormone treated rats. mRNA levels encoding lactase were
increased in cortisone treated animals but were reduced in thyroxine injected pups
compared to controls. Microvillus membranes from saline (P < 0.01) and thyroxine (P
< 0.05) or insulin (P < 0.01) treated rats upon incubation with luminal wash from
adult rat intestine showed a significant decline in lactase activity. These
findings suggest that thyroxine, insulin or cortisone induced changes in lactase
expression in suckling rat intestine make it susceptible to luminal proteases,
which may in part be responsible for observed maturational decline in lactase
activity in adult rat intestine.
This study examined the associations between intimate partner violence (IPV) during
pregnancy, mother-to-infant bonding failure, and postnatal depressive symptoms at 1
month postnatal. This study also examined if these relationships would be mediated
by antenatal depressive symptoms. This study was a prospective cohort study that
investigated effects between the third trimester of pregnancy and 1 month after
childbirth. The Japanese version of the Index of Spouse Abuse (ISA), the Japanese
version of the Mother-Infant Bonding Scale (MIBS), and the Japanese version of the
Hospital Anxiety and Depression Scale (HADS) were used to measure IPV during
pregnancy, bonding failure with infants, and depressive symptoms during pregnancy
and the postnatal period respectively. Structural equation modeling (SEM) was used
to find the associations between those four variables. The final path model of the
SEM showed good fit with the data. IPV during pregnancy was associated with mother-
to-infant bonding failure at 1 month postnatal, whereas IPV during pregnancy was
not significantly associated with postnatal depressive symptoms at 1 month
postnatal. In addition, this study demonstrated that the associations between IPV
during pregnancy, mother-to-infant bonding failure, and postnatal depressive
symptoms at 1 month postnatal were mediated by antenatal depressive symptoms. The
results of this study indicated the need for interventions for IPV and
psychological health care for abused pregnant women to prevent antenatal depressive
symptoms in prenatal health settings. Those interventions by perinatal health
professionals would help to prevent bonding failure with infants and postnatal
depressive symptoms after childbirth.
Intimate partner violence (IPV) has potentially severe and long-lasting mental
health consequences for survivors, including elevated symptoms and diagnoses of
posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder
(GAD). The current study examined the relationship between three self-report
measures of psychological distress and ratings obtained from the corresponding
clinician-administered measures in women seeking assessment for mental health
problems following IPV (N = 185). PTSD symptoms were assessed using the self-report
Impact of Event Scale-Revised (IES-R) and the interview-based Clinician-
Administered PTSD Scale (CAPS). Depression symptoms were assessed using the self-
report Beck Depression Inventory-II (BDI-II) and the depressive disorders sections
from the clinician-administered Anxiety Disorders Interview Schedule-IV (ADIS-IV).
Anxiety symptoms were assessed using the self-report Beck Anxiety Inventory (BAI)
and the clinician-administered GAD section from the ADIS-IV. Results indicated that
psychological distress was prevalent in the sample, with 27% receiving a PTSD
diagnosis, 40% diagnosed with a depressive disorder, and 55% meeting criteria for
GAD. Although each self-report measure was significantly and positively correlated
with its corresponding clinician-administered measure, rates of diagnostic
concordance were mixed. The BDI-II showed a high degree of agreement with the ADIS-
IV depression section, but the IES-R and the CAPS were discordant at classifying
PTSD. The BAI had acceptable sensitivity but poor specificity in relation to the
ADIS-IV GAD section. These findings suggest that multiple assessment modalities
should be considered when rating symptoms and estimating the prevalence of
diagnoses among survivors of IPV.
Intimate partner violence (IPV) and teen dating violence (TDV) are widespread,
preventable public health problems in the United States. Children exposed to IPV
between their caregivers and adolescent victims of TDV suffer not only immediate
risks to their physical safety, but also long-term health sequelae. The emergency
department presents a unique opportunity for physicians to screen for various forms
of family violence and intervene on behalf of the victims. Screening for IPV and
TDV is widely recommended by national health organizations including the American
College of Emergency Physicians. Effective screening protocols require a
multidisciplinary approach informed by knowledge of local community resources.
Intracerebral hemorrhage (ICH) is a lifethreat-ening type of stroke. Previous
studies have reported that bone marrow mesenchymal stem cells (BMSCs) may exert
beneficial effects on the treatment of ICH. However, it remains unknown whether the
neuroprotection exerted by BMSCs on ICH is due to the differentiation of BMSCs, or
the trophic factors secreted into their conditioned medium (CM). In addition,
growth-associated protein-43 (GAP-43) is a protein associated with neurite
extension, which may be considered a prospective therapeutic target in the
treatment of ICH. The present study investigated whether administration of BMSC-CM
could be considered as an alternative to the established treatment of direct BMSC
transplantation; in addition, the underlying mechanisms were evaluated.
Neurological function tests, brain water content, reverse transcription -
quantitative polymerase chain reaction and western blotting were used in present
study. The current study indicated that the neuroprotective effects of BMSC
implantation and BMSC-CM treatment are similar, and that both decrease the severity
of post-ICH cerebral edema, as well as improving neurological functions. At the
molecular level, treatment with BMSC-CM resulted in a marked elevation in the
expression of GAP-43 and interleukin (IL) -10, in addition to a significant
reduction in the expression levels of IL-1a, tumor necrosis factor-a and IL-6.
Following application of a phosphorylated-extracellular signal-regulated kinase
(ERK1/2) inhibitor, PD98059, in a BMSC-CM rat model, the mRNA and protein
expression levels of GAP-43 were significantly attenuated. Therefore, the findings
of the present study demonstrated that treatment with BMSC-CM may be an alternative
to direct BMSC transplantation in a rat model of ICH. The mechanism underlying
BMSC-CM-mediated neuroprotection may be associated with anti-inflammatory effects,
as well as activation of GAP-43 transcription and expression through ERK-1/2
phosphorylation. Therefore, the ERK-1/2-GAP-43 signaling pathway may be considered
a potential novel application target of BMSC-CM for the treatment of neurological
diseases.
OBJECTIVE Benign external hydrocephalus (BEH) is an enlargement of the subarachnoid
spaces (SASs) that can be seen in young children. It is controversial whether
children with BEH are predisposed to developing subdural hemorrhage (SDH) with or
without trauma. This issue is clinically relevant as a finding of unexplained SDH
raises concerns about child abuse and often prompts child protection and law
enforcement investigations. METHODS This retrospective study included children (1-
24 months of age) who underwent head CT scanning after an accidental fall of less
than 6 feet. Head CT scans were reviewed, cranial findings were documented, and the
SAS was measured and qualitatively evaluated. Enlarged SAS was defined as an
extraaxial space (EAS) greater than 4 mm on CT scans. Clinical measurements of head
circumference (HC) were noted, and the head circumference percentile was
calculated. The relationship between enlarged SAS and HC percentile, and enlarged
SAS and intracranial hemorrhage (ICH), were investigated using bivariate analysis.
RESULTS Of the 110 children included in this sample, 23 had EASs greater than 4 mm.
The mean patient age was 6.8 months (median 6.0 months). Thirty-four patients
(30.9%) had ICHs, including subarachnoid/subpial (6.2%), subdural (6.2%), epidural
(5.0%), and unspecified extraaxial hemorrhage (16.5%). Enlarged SAS was positively
associated with subarachnoid/subpial hemorrhage; there was no association between
enlarged SASs and either SDH or epidural hemorrhage. A larger SAS was positively
associated with larger HC percentile; however, HC percentile was not independently
associated with ICH. CONCLUSIONS Enlarged SAS was not associated with SDH, but was
associated with other ICHs. The authors' findings do not support the theory that
BEH predisposes children to SDH with minor accidental trauma.
Objective: The objective was to describe the endometrial milieu of stable
transplant patients and healthy women before and after levonorgestrel intrauterine
system (LNG-IUS) insertion. Study design: Women between 18 and 45 years of age
desiring LNG-IUS insertion were enrolled with a 2:1 ratio of healthy to stable
solid organ transplant patients. The first visit entailed a blood draw, uterine
lavage and endometrial biopsy followed by LNG-IUS insertion. Follow-up visit
involved a repeat serum draw, uterine lavage and endometrial biopsy. Cytokine
levels were measured in the uterine lavage and serum by quantifying inflammatory
biomarkers. Immunohistochemistry staining was performed on the endometrial tissue
to measure macrophage levels. Statistical analysis included a nonparametric
analysis that compared medians of the marker levels before and after intrauterine
device (IUD) insertion within the group and between the two groups. Results:
Sixteen participants completed the study: 5 solid organ transplant patients and 11
healthy patients. For the serum, there were no marked changes in the cytokines or
soluble receptor levels in either group after IUD insertion. However, in the
uterine lavage, there was an increase in cytokine levels post-IUD insertion for
both healthy and transplant women. For the endometrial tissue, there was evidence
of macrophage activity in both groups after device insertion. Conclusions: This
pilot study investigated the uterine environment of the transplant patient
population. Findings have pointed to the strong local inflammatory response
following LNG-IUS insertion for the transplant recipients. In addition, these
preliminary findings will help power a larger study that can investigate the safety
and effectiveness of the IUD in this patient population. (C) 2016 The Authors.
Published by Elsevier Inc.
The development of multi-photon intravital microscopy, in particular two-photon
microscopy (2PM), has been a breakthrough technique for deep-tissue imaging of
dynamic cell behavior inside live organisms and has substantially advanced the
field of immunology. However, intravital time-lapse imaging over prolonged time
periods is complicated by slow tissue drifts caused by vital activity, leading to
shifting fields of views and making the acquired image sequence partially or
completely unanalyzable. To solve this issue, we have established a system that
performs continuous drift offset correction in real time using fine pattern
matching during 2PM acquisition. We incorporated an extensive use of graphical
processing unit (CPU) for high-speed computing required for real time correction
during data acquisition. This allowed us to perform prolonged acquisitions and
increase the proportion of analyzable datasets to nearly 100% in lymphoid and non -
lymphoid tissues. Considering the straightforward implementation of our newly
developed system, we anticipate that it will be applicable for other users
interested in improving the quality of live imaging data acquisition. (C) 2016
Elsevier B.V. All rights reserved.
The present work was aimed at developing vector construct(s) suitable for restoring
fertility in transgenic male sterile tobacco plants expressing male-sterility-
inducing ORFH522 in tapetal cell layer (Nizampatnam et al. Planta 229:987-1001,
2009). PTGS vectors that could produce either intron spliced hairpin RNA against
the orfH522 or induce silencing of orfH522 by heterologous 3'UTR region were
developed using the selected 316 bp (orf316) fragment of orfH522. The constructs
were independently mobilized into Agrobacterium and used for transforming tobacco.
The T(1) generation plants carrying the restorer gene cassettes in homozygous
condition were identified and crossed with the male sterile transgenic tobacco
plants to obtain the hybrid seeds. PCR analysis of hybrid plants indicated
segregation for the sterility inducing cassette while all the plants carried the
restorer cassette. Hybrid plants produced fertile pollen grains and formed normal
capsules upon selfing. Further molecular analyses of these hybrid plants with RT-
PCR, Northern blotting and siRNA detection, revealed that intron interrupted
hairpin RNA (ihp-RNA) mediated gene silencing was more effective compared to
silencing by heterologous 3'UTR (SHUTR) as indicated by the complete degradation of
orfH522 transcripts and formation of higher levels of orf316 specific siRNA
molecules in plants carrying ihp-RNA restorer construct. Segregation analyses of
F(2) (selfed hybrid) plants confirmed the co-segregation of gene cassettes and the
traits in Mendelian di-hybrid ratio (9:3:3:1). Taken together, the results
established that intron hairpin and transitive RNAi mediated silencing of orfH522
transcripts restored fertility in transgenic male sterile tobacco plants expressing
orfH522 and ihp-RNA was more efficient in silencing orfH522 transcripts.
Since the European Union enforced the ban on antibiotic growth promoters in 2006,
the research has been focused on natural feed additives which would have a proven
positive impact on both production and animal health. Inulin is both the most
commonly used and the most effective probiotic additive. The mechanism of inulin
interactions with the avian body is complex, multidirectional and not fully
understood. Despite a number of unresolved issues, many authors have demonstrated
the positive impact of inulin on the host organism. Dietary supplementation of
poultry feeding with inulin contributes to the modulation of intestinal microbiota
through favouring a quick proliferation of beneficial Bifidobacterium and
Lactobacillus strains and inhibiting the growth of pathogenic microbes. There are
indications that inulin-provoked changes in the host gut microbiota in poultry may
alter the structure and histomorphology of the intestinal mucosa and improve its
absorption capacity in poultry. It has also been demonstrated that inulin may
affect the immune system and the systemic metabolism of minerals and lipids. The
reports on inulin effects on the body and performance of poultry are often
contradictory, as the effectiveness of this prebiotic is strongly dependent on the
type and dose used, and the duration of its administration.
Aims and Objectives:Recent studies show that lobular carcinoma in situ (LCIS) and
invasive lobular carcinoma (ILC) share similar genetic molecular biology. There are
increasing concerns regarding the biological significance of LCIS. The aim of this
study is to investigate whether the presence of coexisting LCIS in ILC affects
tumor biology and behavior and to correlate it with other clinicopathologic
parameters.Materials and Methods:In this study, 254 cases of ILC were included.
Clinicopathologic parameters and immunohistochemical stains for estrogen receptor
(ER), progesterone receptor (PR), E-cadherin, human epidermal growth factor
receptor (HER2), and MIB-1 of 254 ILC cases were retrieved. The patient with ILC
and coexisting LCIS were compared with pure ILC cases with respect to different
clinicopathologic parameters.Results:Of the 254 cases, 107 cases were pure ILC and
147 cases were ILC with coexisting LCIS. Seventy-six (76/184, 41.32%) cases showed
axillary lymph node metastases. Lymph node metastasis was absent in 108 cases,
micrometastasis was present in 5 cases, and stage N1, N2, N3 in 51, 5, and 15
cases, respectively. Nodal involvement, locoregional and distant recurrence of ILC
with LCIS were less frequent compared with ILC without LCIS with P-value of 0.034
and 0.007, respectively. The presence of coexisting LCIS in ILC predicted higher
disease-free survival (DFS) compared with pure ILC (P=0.034, log-rank test). When
divided into different strata, ER-positive ILC cases with associated LCIS cases
showed better DFS than ER-positive pure ILC cases (P=0.021, log-rank test).
Similarly, ILC cases with LCIS in patient less than 50 years showed better DFS than
the patient less than 50 years with pure ILC (P=0.045, log-rank
test).Conclusions:In conclusion, ILC coexisting with lobular carcinoma in situ
(ILC+LCIS) is characterized by less nodal involvement, lower locoregional, and
distant recurrence and better DFS than pure ILC. When divided into different
strata, ER-positive and less than 50-year groups with ILC+LCIS show even
significant better DFS than pure ILC. These findings suggest that there is
biological significance of coexisting LCIS in ILC and that this may have more
effect on tumor aggressiveness in certain strata of ILC.
In this paper a twofold inverse problem for orthogonal matrix functions in the
Wiener class is considered. The scalar-valued version of this problem was solved by
Ellis and Gohberg in 1992. Under reasonable conditions, the problem is reduced to
an invertibility condition on an operator that is defined using the Hankel and
Toeplitz operators associated to the Wiener class functions that comprise the data
set of the inverse problem. It is also shown that in this case the solution is
unique. Special attention is given to the case that the Hankel operator of the
solution is a strict contraction and the case where the functions are matrix
polynomials. (C) 2017 Elsevier Inc. All rights reserved.
An indirect hysteresis voltage digital control is proposed for single-phase half-
bridge inverters. Because of the slow response to the switching modulation, it is
difficult to control the voltage by hysteresis method directly. In this study, the
output voltage is controlled indirectly by using the adaptive band hysteresis
current control, which is fast response, robustness, and independent on the system
parameters. The reference current is computed based on the desired reference output
voltage, and the hysteresis band is controlled to maintain the switching frequency
at a constant value. Simulation results show good performances of the proposed
control method in both cases: ac and dc reference output voltage.
The model of a voltage source inverter depends on its output filter. The parameters
of this filter can differ significantly from their nominal values due to power
losses in the core of the output coil and changes in its inductance. Only Multi-
Input-Single-Output control systems can effectively reduce inverter output voltage
distortions for a standard nonlinear rectifier RC load. However, their design
requires knowledge of the actual values of the inverter parameters. The novelty of
the paper is that it connects the designs of two MISO control systems with a method
of the automated measurements of the voltage source inverter parameters. The
breadboard verification is also included.
Voltage inverters are the most common kind of actuator to interface with variable
frequency electrical systems. They are usually driven by a modulation block that
provides the gating signals for the switches. Direct digital control avoids the
modulation block, being the gating signals directly produced by the controller. In
such configuration, the control of the electrical system is a discrete time and
quantized-actuation problem. This paper analyzes the harmonic content in sinusoidal
steady state resulting from such configuration. The analysis illustrates the higher
harmonic content, providing lower bounds for such content in the case of low ratios
of commutation to fundamental frequencies. Also, the dependence of harmonic content
with duty cycle and with commutation losses is exposed. The findings apply to
different kind of control structures, regardless of its design or tuning
parameters. Some of them are experimentally compared. A two-level three-phase
inverter is used in the analysis for its relevance and simplicity although the
procedure can be applied to any number of phases or levels. (C) 2016 International
Association for Mathematics and Computers in Simulation (IMACS). Published by
Elsevier B.V. All rights reserved.
This study deals with the design of a load sensorless multi-loop control system for
the stand-alone inverter. In the proposed strategy, only the inverter current is
measured, which is practically required for both control and protection purposes,
then the load voltage and current are both estimated using the linear Kalman filter
algorithm, and the gradient descent adaptive control method, respectively. The
estimated quantities are used as feedback signals of an inner-outer double-loop
controller, which uses a proportional-resonant outer-controller to regulate the
output voltage with minimum steady-state error and a simple proportional inner-
controller to provide active damping and improve the transient performance. The
controller parameters are designed in the frequency domain based on the required
bandwidth and stability margin. Furthermore, the controllability and observability,
as well as the stability of overall digital control system, including the dynamics
of estimators, are analytically investigated. Simulation and experimental results,
with a 600 VA prototype, confirm the theoretical achievements and illustrate the
excellent performance of the proposed estimation and control scheme.
Statin-induced skeletal muscle damage in rats is associated to the reduction of the
resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel
expression. These drugs also affect the ClC-1 regulation by increasing protein
kinase C (PKC) activity, which phosphorylate and close the channel. Also the
intracellular resting calcium (restCa) level is increased. Similar alterations are
observed in skeletal muscles of aged rats, suggesting a higher risk of statin
myotoxicity. To verify this hypothesis, we performed a 4-5-weeks atorvastatin
treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-
intracellular microelectrodes technique as well as transcript and protein
expression of different genes sensitive to statins by quantitative real-time-PCR
and western blot analysis. The restCa was measured using FURA-2 imaging, and
histological analysis of muscle sections was performed. The results show a marked
reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein
expression in atorvastatin-treated aged rats, with respect to treated adult
animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be
involved in ClC-1 expression changes. The activity of PKC was also increased and
further modulate the gCl in treated aged rats. In parallel, a marked reduction of
the expression of glycolytic and mitochondrial enzymes demonstrates an impairment
of muscle metabolism. No worsening of restCa or histological features was found in
statin-treated aged animals. These findings suggest that a strong reduction of gCl
and alteration of muscle metabolism coupled to muscle atrophy may contribute to the
increased risk of statin-induced myopathy in the elderly. (C) 2016 Elsevier Inc.
All rights reserved.
Deep eutectic solvents (DESs) have been touted recently as potential alternatives
to ionic liquids (Is). Although they possess core characteristics that are similar
to those of Its (e.g., low volatility, non-flammability, low melting points, low
vapor pressure, dipolar nature, chemical and thermal stability, high solubility,
and tuneability), DESs are superior in terms of the availability of raw materials,
the ease of storage and synthesis, and the low cost of their starting materials. As
such, they have become the subject of intensive research in various sectors,
notably the chemical, electrochemical, and biological sectors. To date, the
applications of DESs have shown great promise, especially in the medical and
biotechnological fields. In spite of these various achievements, the safety concern
for these mixtures must be sufficiently addressed. Indeed, in order to exploit the
vast array of opportunities that DESs offer to the biological industry, first, they
must be established as safe mixtures. Hence, the biotechnological applications of
DESs only can be implemented if they are proven to have negligible or low toxicity
profiles. This review is the first of its kind, and it discusses two current
aspects of DES-based research. First, it describes the properties of these mixtures
with ample focus on their toxicity profiles. Second, it provides an overview of the
breakthroughs that have occurred and the foreseeable prospects of the use of DESs
in various biotechnological and biological applications. (C) 2016 Elsevier Inc. All
rights reserved.
Flowers are the main sexual reproductive organs in plants. The shapes, colours and
scents of corolla of plant flowers are involved in attracting insect pollinators
and increasing reproductive success. The process of corolla senescence was
investigated in Ipomoea purpurea (Convolvulaceae) in this study. In the research
methods of plant anatomy, cytology, cell chemistry and molecular biology were used.
The results showed that at the flowering stage cells already began to show
distortion, chromatin condensation, mitochondrial membrane degradation and
tonoplast dissolution and rupture. At this stage genomic DNA underwent massive but
gradual random degradation. However, judging from the shape and structure, aging
characteristics did not appear until the early flower senescence stage. The
senescence process was slow, and it was completed at the late stage of flower
senescence with a withering corolla. We may safely arrive at the conclusion that
corolla senescence of I.purpurea was mediated by programmed cell death (PCD) that
occurred at the flowering stage. The corolla senescence exhibited an obvious
temporal rhythm, which demonstrated a high degree of coordination with pollination
and fertilization.
Intimate partner violence (IPV) in sub-Saharan Africa affects 36% of the
population. Several African countries rank among the highest globally. In this
article, we present evidence on the prevalence, determinants, and impact of IPV
across several sub-Saharan African countries interpreted against the backdrop of
social ecological theory. We also describe prevention or intervention programs
tested in different regions of Africa, selecting only those programs which were
published in a journal outlet and which met a high criteria of implementation and
methodology (n = 7). Based on our review of the empirical literature, some risk
factors for violence documented in Western societies are the same in Africa,
including poverty, drinking, a past history of child abuse or posttraumatic stress
disorder, and highly traditional gender role beliefs. Low education is also
associated with IPV for both women and men. In Africa, partner abuse intersects
with the HIV pandemic, making violence prevention especially urgent. African
programs to prevent IPV are often incorporated with HIV prevention; community
building and community engagement are emphasized more in Africa than in North
America or Europe, which invoke more individually focused approaches. Some programs
we review lowered HIV exposure in women; others contributed to reduced violence
perpetration among men. The programs show sufficient promise to recommend
replication and dissemination in sub-Saharan Africa.
Iris yellow spot virus (IYSV), an emerging disease of onion crops, was identified
by transmission electron microscopy, enzyme linked immunosorbent assay, and reverse
transcription polymerase chain reaction in Costa Rica. Onion plants had straw-
colored, elongated lesions and tip dieback. Costa Rican IYSV nucleocapsid partial
sequences (15 isolates) grouped with isolates from North and Central America and
from New Zealand.
This essay will examine the expos of the realities regarding poverty, immorality
and sexual crime in the Irish Free State by the radical journal Honesty (1925-
1931). Honesty was edited by the socialist republican James W. Upton, a man with a
longstanding commitment to the rights of women and the poor. Upton was by instinct
anti-establishment in an era when the country's religio-political leadership was
insecure and keen to manage the Free State's news agenda. Something they attempted
in the service of projecting what was viewed as an ideologically acceptable image
of life in the Free Sate, to both domestic and foreign audiences. Upton viewed this
policy as a manifestation of the social and political cant favoured by the Free
State's leadership, which was aided and abetted by, and gave succour to, the
hypocrisy of wider bourgeois Free State society. A coalition of forces, Upton
reasoned, that damaged the interests of the most vulnerable sections of Irish
society, in particular, the nation's women and children living on or below the
breadline. However, notwithstanding it radicalism and reputation in the Free State,
Honesty has been largely lost to the history of Irish journalism.
Iron deficiency continues to be the most prevalent micronutrient deficit worldwide.
Since iron is involved in several processes including myelination, dopamine
neurotransmission and neuronal metabolism, the presence of iron deficiency anemia
(IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce
data regarding whether these effects would extend to former iron deficient anemic
human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel
technique to explore patterns of functional connectivity. Default Mode Network
(DMN), one of the resting state networks, is deeply involved in memory, social
cognition and self-referential processes. The four core regions consistently
identified in the DMN are the medial prefrontal cortex, posterior
cingulate/retrosplenial cortex and left and right inferior parietal cortex.
Therefore to investigate the DMN in former iron deficient anemic adults is a
particularly useful approach to elucidate de long term effects on functional brain.
We conducted this research to explore the connection between IDA in infancy and
altered patterns of resting state brain functional networks in young adults.
Resting-state fMRI studies were performed to 31 participants that belong to a
follow-up study since infancy. Of them, 14 participants were former iron deficient
anemic in infancy and 17 were controls, with mean age of 21.5 years (+/- 1.5) and
54.8% were males. Resting-state fMRI protocol was used and the data was analyzed
using the seed based connectivity statistical analysis to assess the DMN. We found
that compared to controls, former iron deficient anemic subjects showed posterior
DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas
they exhibited increased anterior DMN connectivity to the right PCC. Differences
between groups were also apparent in the left medial frontal gyrus, with former
iron deficient anemic participants having increased connectivity with areas
included in DMN and dorsal attention networks. These preliminary results suggest
different patterns of functional connectivity between former iron deficient anemic
and control young adults. Indeed, IDA in infancy, a common nutritional problem
among human infants, may turn out to be important for understanding the mechanisms
of cognitive alterations, common in adulthood.
Objective: To evaluate the transepithelial transport of sodium, glucose, potassium,
and water and the mRNA level of the sodium-glucose cotransporter (SGLT1) and the
facilitated sugar transporter (GLUT2) in the small intestine of iron-deficient
rats. Methods: After 6 wk of receiving diets with low or normal iron content, rats
(Wistar-EPM) were subjected to two experiments: 1) evaluation of the
transepithelial transport of sodium, glucose, potassium, and water by an "in vivo"
experimental model of intestinal perfusion and 2) determination of relative SGLT1
and GLUT2 mRNA levels in the proximal, intermediate, and distal portions of the
small intestine by the northern blotting technique. Results: Hemoglobin and hepatic
iron levels were statistically lower in the anemic rats. The mean transepithelial
transports of sodium (-33.0 mu Eq . min(-1) . cm(-1)), glucose (426.0 mu M . min(-
1) . cm(-1)), and water (0.4 mu L . min(-1) . cm(-1)) in the small intestine of the
anemic rats were significantly lower than in the control group (349.1 mu Eq . min(-
1) cm(-1), 842.6 mu M . min(-1) . cm(-1), and 4.3 mu l . min(-1) cm(-1),
respectively, P < 0.05). The transepithelial transport of potassium was similar for
both groups. The relative SGLT1 mRNA levels of the anemic rats in the intermediate
(1.796 +/- 0.659 AU) and distal (1.901 +/- 0.766 AU) segments were significantly
higher than the values for the control rats (intermediate 1.262 +/- 0.450 AU,
distal 1.244 +/- 0.407 AU). No significant difference was observed for the relative
SLGT1 mRNA levels in the proximal segment or for the GLUT2 mRNA levels in all
segments. Conclusion: Iron deficiency decreases the absorption of glucose, sodium,
and water and increases SGLT1 mRNA in the intermediate and distal segments of the
small intestine of rats. (C) 2011 Elsevier Inc. All rights reserved.
Electrocoagulation with an iron-air fuel cell is an innovative arsenate removal
system that can operate without an external electricity supply. Thus, this
technology is advantageous for treating wastewater in remote regions where it is
difficult to supply electricity. In this study, the possibility of real
applications of this system for arsenate treatment with electricity production was
verified through electrolyte effect investigations using a small-scale fuel cell
and performance testing of a liter-scale fuel cell stack. The electrolyte species
studied were NaCl, Na2SO4, and NaHCO3. NaCl was overall the most effective
electrolyte for arsenate treatment, although Na2SO4 produced the greatest
electrical current and power density. In addition, although the current density and
power density were proportional to the concentrations of NaCl and Na2SO4, the use
of concentrations above 20 mM of NaCl and Na2SO4 inhibited arsenate treatment due
to competition effects between anions and arsenate in adsorption onto the iron
hydroxide. The dominant iron hydroxide produced at the iron anode was found to be
lepidocrocite by means of Raman spectroscopy. A liter-scale four-stack iron-air
fuel cell with 10 mM NaCl electrolyte was found to be able to treat about 300 L of
1 ppm arsenate solution to below 10 ppb during 1 day, based on its 60-min treatment
capacity, as well as produce the maximum power density of 250 mW/m(2). (C) 2017
Elsevier Ltd. All rights reserved.
Irrigation water has been recognized as an important microbial risk factor for
fruits and vegetables in many production areas, but there is still a lack of
information about how the microbiological quality of different irrigation water
sources and climatic conditions influence the safety of vegetables produced in
Brazil. This study evaluated the distribution of generic E. coli and the prevalence
of E. coil O157:H7 in two different water sources (ponds and streams bordering
farmlands and urban areas) used for irrigation and on commercially produced
lettuces in Southern Brazil. We also evaluated the effect of agricultural factors
and meteorological conditions in the potential contamination of water and produce
samples. A longitudinal study was conducted on four farms during a year (July 2014
to August 2015). The results showed generic E. coli prevalence of 84.8% and 38.3%
in irrigation water samples and on lettuces, respectively, indicating irrigation
water as an important source of contamination of lettuces. No significant
differences were detected in the counts of E. coli between the two different
surface water sources. The climatic conditions, particularly rainfall and
environmental temperature, have influenced the high concentration of E. coil. The
highest loads of E. coil in irrigation water and on lettuces were found during the
warmest time of the year. E. coli O157:H7 was detected by qualitative polymerase
chain reaction (qPCR) in 13 water samples but only 4 were confirmed by isolation in
culture media. (C) 2017 Elsevier Ltd. All rights reserved.
BackgroundIrritability, a frequent complaint in children with psychiatric
disorders, reflects increased predisposition to anger. Preliminary work in
pediatric clinical samples links irritability to attention bias to threat, and the
current study examines this association in a large population-based sample.
MethodsWe studied 1,872 children (ages 6-14) using the Development and Well-Being
Assessment (DAWBA), Childhood Behavior Checklist (CBCL), and dot-probe tasks.
Irritability was defined using CBCL items that assessed temper tantrums and hot
temper. The dot-probe task assessed attention biases for threat-related (angry
face) stimuli. Multiple regression analysis was used to assess specificity of
associations to irritability when adjusting for demographic variables and co-
occurring psychiatric traits. Propensity score matching analysis was used to
increase causal inference when matching for demographic variables and co-occurring
psychiatric traits. ResultsIrritability was associated with increased attention
bias toward threat-related cues. Multiple regression analysis suggests associations
between irritability and threat bias are independent from demographic variables,
anxiety, and externalizing traits (attention-deficit/hyperactivity, conduct, and
headstrong/hurtful), but not from broad internalizing symptoms. Propensity score
matching analysis indicated that this association was found for irritable versus
nonirritable groups matched on demographic and co-occurring traits including
internalizing symptoms. ConclusionsIrritability in children is associated with
biased attention toward threatening information. This finding, if replicated,
warrants further investigation to examine the extent to which it contributes to
chronic irritability and to explore possible treatment implications.
Objective: The genetic surroundings of blaCTX-M-15 in Escherichia coli recovered
from faeces of travellers returning to the UK from overseas were compared with
those among established UK strains to provide further insights into the spread of
bla(CTX-M-15) in the UK. Methods: From August 2006 to January 2008, 1031 faecal
specimens were collected at the North West London NHS Trust from general practice
patients with a clinical history of diarrhoea following recent international
travel. Cefuroxime-resistant E. coli were isolated on cystine-lactose-electrolyte
deficient agar and those that produced extended-spectrum beta-lactamases (ESBLs)
were identified by double disc synergy test (DDST). The molecular environments
surrounding bla(CTX-M-15) were investigated by PCR, DNA sequencing, gene cloning
and northern blotting. Results: 182/1031 (18%) E. coli isolated from returning
travellers gave a positive DDST, and were confirmed by PCR to produce CTX-M ESBLs;
174 (96%) had blaCTX-M-15, including 21 belonging to clone ST131. Among these 174
isolates, the environment upstream of blaCTX-M-15 consisted of either: (i) an
intact ISEcp1 (n=108); (ii) various lengths of truncated ISEcp1 (n=58); or (iii) a
24 bp remnant of ISEcp1 (n=8). Two different promoters were found to transcribe
bla(CTX-M-15), resulting in different levels of cephalosporin resistance.
Conclusion: E. coli with CTX-M-15 ESBL from returning travellers harboured
previously seen UK bla(CTX-M-15) genetic environments (intact or 24 bp remnant of
ISEcp1) as well as bla(CTX-M-15) genetic environments previously unseen in the UK
(various lengths of truncated ISEcp1), which suggest overseas acquisition and
highlight the difficulty of control in a time of population mobility and travel.
Islamic State of Iraq and Syria (ISIS) has recently carried out atrocities both in
the Middle East and localized terror attacks in several western countries killing
hundreds and wounding thousands. Many executions and attacks were broadcast within
clever media campaigns containing warnings of future attacks. We examined anxiety
of a future ISIS threat along with its association to self-reported sleep
difficulties in a sample of adult Israelis (N = 1007). We demonstrated this
association in different models beyond the effects of additional potential
variables which have been noted to affect sleep, such as reported health, exposure
to terror, exposure to ISIS media, psychological variables such as general anxiety,
depression and post-traumatic stress disorder symptoms. In all cases, a strong
positive relationship between ISIS anxiety and sleep symptoms was obtained. Issues
concerning the relationship between anxiety of a future threat and sleep symptoms,
as well as the notion of sleep difficulties being a marker for such anxiety, are
discussed. (C) 2017 Elsevier Ltd. All rights reserved.
The genes encoding monomer- and dimer-type isocitrate dehydrogenase (IDH) isozymes
from a psychrotrophic bacterium, Pseudomonas psychrophila, were cloned and
sequenced. Open reading frames of the genes were 2,226 and 1,257 bp in length and
corresponded to polypeptides composed of 741 and 418 amino acids, respectively. The
deduced amino acid sequences showed high sequence identity with those of
psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea, (about 70%
identity) and the respective types of the putative IDH genes from other bacteria of
genus Pseudomonas (more than 80% identity). The two genes were located in opposite
direction from each other with a spacer of 463 bases in the order of dimeric and
monomeric IDH genes on the chromosomal DNA, but analyses of northern blotting and
5'-terminal regions of the mRNAs revealed that they are transcribed independently.
The expression of monomer- and dimer-type IDH genes in C. maris are known to be
cold- and acetate-inducible, respectively, while only slight inductions by low
temperature and/or acetate were observed in the expression of the P. psychrophila
monomer- and dimer-type IDH genes. Both of these IDH isozymes overproduced in
Escherichia coli showed mesophilic properties, in contrast with monomer- and dimer-
type IDHs of C. maris as cold adapted and mesophilic enzymes, respectively. The
substitution of Glu55 residue in the P. psychrophila monomeric IDH for Lys, which
is the corresponding residue conserved between the cold-adapted monomeric IDHs from
C. maris and C. psychrerythraea, by site-directed mutagenesis resulted in the
decreased thermostability and the lowered optimum temperature of activity,
suggesting that this residue is involved in the mesophilic properties of the P.
psychrophila monomeric IDH.
Which issues do political parties emphasize in campaigns? Selecting the issues to
emphasize in campaigns is treated with the same importance as policy positioning.
Nevertheless, little attention has been paid to understanding parties' strategies
of issue competition in presidential elections under multiparty systems. By
analyzing statements of presidential candidates in the 2002, 2007, and 2012 Korean
presidential debates, we find that presidential candidates use their issue emphasis
strategies differently in presidential elections according to party size and
ideological relationships with other parties. Specifically, a small party's
candidates have been more likely than mainstream parties' candidates to pursue
their issue ownership advantage. In addition, a mainstream party's candidates have
emphasized the issues of a small party more than those of his own party when the
two parties have had a similar ideological foundation, whereas, when there were no
such ideological similarities, a mainstream party's candidate has only focused on
issues of the mainstream party. Our results imply that the political communication
used by political parties and candidates is conditioned not only by political
contexts such as electoral systems or party systems but also by the size and
ideology of parties.
Background: Itraconazole has been proved therapeutically effective against a
variety of human cancers. This study assessed the effect of itraconazole on the
Hedgehog (Hh) pathway and proliferation of human gastric cancer cells. Methods:
CCK-8 assay and colony formation assay were used to assess the effects of
itraconazole on proliferation of gastric cancer cells. The expression of Hh
signaling components in gastric cancer cells treated with itraconazole was
evaluated by reverse-transcription polymerase chain reaction, immunoblotting and
dual luciferase assay. Tumor xenograft models were used to assess the inhibitory
effect of itraconazole on the proliferation of gastric cancer cells in vivo.
Results: Itraconazole could remarkably inhibit the proliferation of gastric cancer
cells. When in combination with 5-FU, itraconazole significantly reduced the
proliferation rate of cancer cells. Furthermore, itraconazole could regulate the
G1-S transition and induce apoptosis of gastric cancer cells. Hh signaling was
abnormally activated in human gastric cancer samples. In vitro, studies showed that
the expression of glioma-associated zinc finger transcription factor 1 (Gli1) was
decreased at both transcriptional and translational levels after treatment with
itraconazole. Dual luciferase assay also indicated that itraconazole could inhibit
the transcription of Gli1. In vivo studies demonstrated that monotherapy with
itraconazole by oral administration could inhibit the growth of xenografts, and
that itraconazole could significantly enhance the antitumor efficacy of the
chemotherapeutic agent 5-FU. Conclusions: Hh signaling is activated in gastric
tumor and itraconazole can inhibit the growth of gastric cancer cells by inhibiting
Gli1 expression.
Imprinted genes control fetal and placental growth in mice and in rare human
syndromes, but the role of these genes in sporadic intrauterine growth restriction
(IUGR) is less well-studied. We measured the ratio of mRNA from a maternally
expressed imprinted gene, PHLDA2, to that from a paternally expressed imprinted
gene, MEST, by Northern blotting in 38 IUGR-associated placentae and 75 non-IUGR
placentae and found an increase in the PHLDA2/MEST mRNA ratio in IUGR (p = 0.0001).
Altered expression of PHLDA2 and MEST was not accompanied by changes in DNA
methylation within their imprinting centers, and immunohistochemistry showed PHLDA2
protein appropriately restricted to villous and intermediate cytotrophoblast in the
IUGR placentae. We next did a genome-wide survey of mRNA expression in 14 IUGR
placentae with maternal vascular under-perfusion compared to 15 non-IUGR placentae
using Affymetrix U133A microarrays. In this series six imprinted genes were
differentially expressed by ANOVA with a Benjamini-Hochberg false discovery rate of
0.05, with increased expression of PHLDA2 and decreased expression of MEST, MEG3,
GATM, GNAS and PLAGL1 in IUGR placentae. At lower significance, we found IGF2 mRNA
decreased and CDKN1C mRNA increased in the IUGR cases. We confirmed the significant
reduction in MEG3 non-translated RNA in IUGR placentae by Northern blotting. In
addition to imprinted genes, the microarray data highlighted non-imprinted genes
acting in endocrine signaling (LEP, CRH, HPGD, INHBA), tissue growth (IGF1), immune
modulation (INDO, PSG-family genes), oxidative metabolism (GLRX), vascular function
(AGTR1, DSCR1) and metabolite transport (SLC-family solute carriers) as
differentially expressed in IUGR vs. non-IUGR placentae.
A total of 7778 host-seeking adult Dermacentor reticulatus (Ixodida: Ixodidae)
ticks were examined for the prevalence of Francisella tularensis holarctica
(Thiotrichales: Francisellaceae) in a natural focus of tularaemia in the floodplain
forest-meadow ecosystem along the lower reaches of the Dyje (Thaya) river in South
Moravia (Czech Republic) between 1995 and 2013. Ticks were pooled (10 specimens per
pool) and their homogenates inoculated subcutaneously in 4-week-old specific
pathogen-free mice. Dead mice were sectioned, their spleens cultivated on
thioglycollate-glucose-blood agar and impression smears from the spleen, liver and
heart blood were Giemsa-stained. Sixty-four pools were positive for F.tularensis:
the overall minimum infection rate (MIR) was 0.82%. Overall MIRs for the 4714
female and 3064 male D.reticulatus examined were 0.89 and 0.72%, respectively; MIRs
fluctuated across years between 0.0 and 2.43%. The estimated bacterial load in
infected ticks varied from 0.84 to 5.34 log(10) infectious F.tularensis cells per
tick (i.e. from about seven to 220000 cells). Ticks with low loads were more
prevalent; more than 1000 infectious cells were detected in 24 ticks (0.3% of all
ticks and 37.5% of infected ticks). Monitoring of D.reticulatus for the presence
and cell numbers of F.tularensis may be a valuable tool in the surveillance of
tularaemia.
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which
transduces cytokine and growth factor signalling. Analysis of TYK2 loss-of-function
revealed its important role in immunity to infection, (auto-) immunity and (auto-)
inflammation. TYK2-deficient patients unravelled high similarity between mice and
men with respect to cellular signalling functions and basic immunology. Genome-wide
association studies link TYK2 to several autoimmune and inflammatory diseases as
well as carcinogenesis. Due to its cytokine signalling functions TYK2 was found to
be essential in tumour surveillance. Lately TYK2 activating mutants and fusion
proteins were detected in patients diagnosed with leukaemic diseases suggesting
that TYK2 is a potent oncogene. Here we review the cell intrinsic and extrinsic
functions of TYK2 in the characteristics preventing and enabling carcinogenesis. In
addition we describe an unexpected function of kinase-inactive TYK2 in tumour
rejection. (C) 2015 The Authors. Published by Elsevier Ltd.
Certain special biological characteristics of Japanese quails (Coturnix coturnix
japonica) could enable quicker and less expensive laboratory experiments than
similar studies using mice or chickens. Moreover, due to some physiological
similarities with humans, quails have been recognized as an ideal laboratory model
for experiments in some fields such as immunology, endocrinology, and reproductive
biology. The aim of this study was to acquire normal ultrasonographic images of
reproductive organs of female Japanese quails in order to facilitate laboratory
experiments on reproductive biology and to determine a non-invasive in-life
alternative to carcass analysis. Thirty female Japanese quails of different ages
were used for ultrasound scanning of ovaries, follicles, ova, oviducts and eggs. In
addition, five quails were euthanized for experiments using a direct standoff
imaging technique. It was possible to identify different sizes of follicles ranging
from small white follicles (0.14cm) to large yellow follicles (2.57cm), post-
ovulatory follicles (POFs), ova at various stages of development, oviducts, and
also eggs within the oviducts. These findings demonstrate that ultrasound scanning
of female Japanese quail reproductive organs might be a beneficial diagnostic tool
for applications such as studying reproductive physiology, anticipating the
beginning or the end of the breeding season, detecting any pathological disorders
easily, and identifying non-productive females which could lead to more cost-
efficient laboratory procedures.
JC polyomavirus-associated nephropathy (JC-PVAN) is a rare but challenging cause of
renal dysfunction. We report JC-PVAN in a renal allograft recipient and highlight
the obstacles in definitive diagnosis of this disease entity. A deceased-donor
renal transplant recipient was diagnosed with JC polyomavirus nephritis 4 years
after transplantation. Immunosuppressive agents were subsequently reduced,
resulting in an initial stabilization of renal function. We present this
interesting case and discuss the challenges with diagnosing and treating this rare
entity.
Jet electrochemical machining is a promising shaping method that has the potential
to replace traditional sinking ECM in the industry owing to its flexibility and
stability. However, its machining quality is impaired by the occurrence of a unique
phenomenon (i.e., the anode cannot be uniformly dissolved with high nozzle travel
rate). This paper aims to analyze this unique phenomenon from the viewpoint of
anodic behavior and to select the optimum travel rate parameter window. The anodic
behavior of TB6 titanium alloy in sodium chloride solution was investigated by
linear sweep voltammetry, cyclic voltammetry, electrochemical impedance
spectroscopy and chronoamperometry. A time-dependent mechanism of pitting/large
localized corrosion/polishing for the anodic interface structure was developed. The
full electricity quantity of the equivalent oxide layer capacitor, Q, was proposed
as a criterion for the initiation of uniform dissolution state. Subsequently, a
novel model that incorporates the parameter Q was developed to account for the
effect of anodic behavior. This model is able to predict the machined profile as
well as the localized corrosion range. Finally, the effect of nozzle travel rate on
jet ECM performance was investigated, and a nozzle travel rate of 10 to 25 mu m s(-
1) was selected as the optimum parameter window in the present work. (C) 2017
Elsevier Ltd. All rights reserved.
Although the role of social cognition in leadership perception has been emphasized
frequently in recent years, research using this approach in an organizational
context is rare. This study investigated subordinates' perceptions of their
managers as leaders (that is, to what extent they perceive their manager as a
leader) as a potential mediating factor explaining the relationship between
managers' self-monitoring and their subordinates' attitudes toward their
organizations. The study was carried out with middle-level managers (N=64) and
their subordinates (N=210) from various business organizations in Turkey. Results
indicate that subordinates' leadership perceptions of their managers mediate the
relationship between managers' self-monitoring and their subordinates' affective
and normative organizational commitment. These results provide insight into some of
the antecedents and outcomes of leadership perception.
The current study measured adults' P350 and N170 ERPs while they interacted with a
character in a virtual reality paradigm. Some participants believed the character
was controlled by a human (avatar condition, n=19); others believed it was
controlled by a computer program (agent condition, n=19). In each trial,
participants initiated joint attention in order to direct the character's gaze
toward a target. In 50% of trials, the character gazed toward the target (congruent
responses), and in 50% of trials the character gazed to a different location
(incongruent response). In the avatar condition, the character's incongruent gaze
responses generated significantly larger P350 peaks at centro-parietal sites than
congruent gaze responses. In the agent condition, the P350 effect was strikingly
absent. Left occipitotemporal N170 responses were significantly smaller in the
agent condition compared to the avatar condition for both congruent and incongruent
gaze shifts. These data suggest that beliefs about human agency may recruit
mechanisms that discriminate the social outcome of a gaze shift after approximately
350ms, and that these mechanisms may modulate the early perceptual processing of
gaze. These findings also suggest that the ecologically valid measurement of social
cognition may depend upon paradigms that simulate genuine social interactions.
This paper presents an optimal bid submission in a day-ahead electricity market for
the problem of joint operation of wind with photovoltaic power systems having an
energy storage device. Uncertainty not only due to the electricity market price,
but also due to wind and photovoltaic powers is one of the main characteristics of
this submission. The problem is formulated as a two-stage stochastic programming
problem. The optimal bids and the energy flow in the batteries are the first-stage
variables and the energy deviation is the second stage variable of the problem.
Energy storage is a way to harness renewable energy conversion, allowing the store
and discharge of energy at conveniently market prices. A case study with data from
the Iberian day-ahead electricity market is presented and a comparison between
joint and disjoint operations is discussed. (C) 2017 Elsevier Ltd. All rights
reserved.
Tunneling field-effect transistors (TFETs) are gaining attention because of their
good scalability and low leakage current. However, they suffer from low on-state
current and severe ambipolar conductivity. To address these issues, in this paper,
we have proposed a novel junctionless nanowire TFET with induced source side
tunneling realized by a hetero-gate-dielectric (HGD JN-TFET). This approach induces
a local dip in the conduction band edge at the tunneling junction leading to an
abrupt transition between the on and off-states as well as subthreshold swing (SS)
as low as 45 mV/dec at low drain voltages. The proposed structure provides I-on of
8.7 x 10(-6) A/mu m and I-off of 1.1 x 10(-11) A/mu m. Also, we have shown that the
length of high-k gate insulator as well as its dielectric constant can
significantly affect the performance and power efficiency of this device.
In the realm of state trial courts, child abuse and neglect (dependency)
proceedings are unique. Dependency proceedings place courts in the position, not of
determining an ultimate result, but of overseeing the ongoing actions of a state
agency. The court proceedings can continue on up to twenty-one years without a
culminating trial. We must revise our rules of appellate procedure to protect
review of dependency decisions so that children and families have the access to
justice they deserve.
With the increasing incidence and prevalence of antibiotic contamination in animal-
derived food and drug resistance around the world, early and specific detection of
antibiotic residues has garnered significant attention. Herein, for the first time,
we devise a facile, label free and portable aptasensor for quantitative
determination of Kanamycin (KANA) by electrochemical impedance spectroscopy (EIS),
which accompanying the assembly of in-vitro selected single strand DNA (ssDNA)
anti-KANA-aptamer functionalized screen printed carbon electrodes (SPCEs) used as
transducer. The target detection is based on specific recognition by KANA-aptamer
covalently immobilized on SPCEs surface. The surface morphology and electrochemical
properties of aptasensor were characterized using Fourier transform infrared
spectroscopy (FT-IR), scanning electron microscopy (SEM), atomic force microscopy
(AFM), cyclic voltammetry (CV) and EIS. Under optimized experimental conditions,
the devised aptasensor exhibited a dynamic range 1.2-600 ngmL(-1) with linearity
1.2-75 ngmL(-1) and limit of detection (LOD) 0.11 ng mL(-1) (S/N =3) of KANA. The
developed aptasensor are endowed with a good selectivity and specificity to KANA
without interference from competitive analogues (streptomycin and gentamicin). For
practical application, the aptasensor performance was verified in spiked milk
samples and the acceptable recovery percentage of 96.88-100.5% (%RSD = 4.56, n=3)
was obtained in milk samples. (C) 2017 Elsevier B.V. All rights reserved.
Seed germination and early seedling establishment are critical stages during a
plants life cycle. These stages are precisely regulated by multiple internal
factors, including phytohormones and environmental cues such as light. As a family
of small molecules discovered in wildfire smoke, karrikins (KARs) play a key role
in various biological processes, including seed dormancy release, germination
regulation, and seedling establishment. KARs show a high similarity with
strigolactone (SL) in both chemical structure and signaling transduction pathways.
Current evidence shows that KARs may regulate seed germination by mediating the
biosynthesis and/or signaling transduction of abscisic acid (ABA), gibberellin (GA)
and auxin [indoleacetic acid (IAA)]. Interestingly, KARs regulate seed germination
differently in different species. Furthermore, the promotion effect on seedling
establishment implies that KARs have a great potential application in alleviating
shade avoidance response, which attracts more and more attention in plant molecular
biology. In these processes, KARs may have complicated interactions with
phytohormones, especially with IAA. In this updated review, we summarize the
current understanding of the relationship between KARs and SL in the chemical
structure, signaling pathway and the regulation of plant growth and development.
Further, the crosstalk between KARs and phytohormones in regulating seed
germination and seedling development and that between KARs and IAA during shade
responses are discussed. Finally, future challenges and research directions for the
KAR research field are suggested.
Ganoderma lingzhi is a kind of precious medicinal mushroom. MicroRNAs (miRNAs) play
an important role in the regulation of a broad range of biological processes. In
this study, we first report on the miRNAs of the G. lingzhi sporocarp. In total,
132 known miRNAs and 34 putative candidate (PC) miRNAs were identified for the
first time in G. lingzhi sporocarp. Through target gene prediction, 111 of 132
known miRNAs had targeted genes, 58 of them had more than one, and most predicted
targeted genes might be regulated by more than one miRNA; functional enrichment by
KEGG analysis demonstrated that target genes related to cancer and signal
transduction occupied the largest proportion. A total of seven miRNAs (four known
miRNAs and three PC miRNAs) that had high abundance were selected for expression
confirmation by quantitative real-time PCR (qRT-PCR) and northern blotting. This is
the first comprehensive study of the miRNA composition in G. lingzhi, which
resulted in the addition of a significant number of novel miRNA sequences to
miRBase and laid the foundation for further understanding of the function of miRNAs
in the regulation of G. lingzhi. (c) 2016 Published by Elsevier B.V. on behalf of
The Mycological Society of Japan.
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway
activation through influencing structure of the primary cilium. Here we show that
Kif7 is required for normal T-cell development, despite the fact that T-cells lack
primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency
increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces
differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to
mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage.
Expression of CD5, which correlates with TCR signal strength, was reduced on DP and
mature CD4 and CD8 cells, as a result of thymocyte-intrinsic Kif7-deficiency, and
Kif7-deficient T-cells from radiation chimeras activated less efficiently when
stimulated with anti-CD3 and anti-CD28 in vitro. Kif7-deficient thymocytes showed
higher expression of the Hedgehog target gene Ptch1 than WT, but were less
sensitive to treatment with recombinant Shh, and Kif7-deficient T-cell development
was refractory to neutralisation of endogenous Hh proteins, indicating that Kif7-
deficient thymocytes were unable to interpret changes in the Hedgehog signal. In
addition, Kif7-deficiency reduced cell-surface MHCII expression on thymic
epithelial cells.
Natural killer (NK) cell activity is regulated by activating and inhibitory signals
transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR
gene repertoire among individuals may affect disease outcome. Sepsis development
and severity may be influenced by genetic factors affecting the immune response.
Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I
ligands in critical patients, aiming to identify patterns that could be associated
with sepsis. Male and female patients (ages ranging between 14 and 94 years-old)
were included. DNA samples from 211 patients with sepsis and 60 controls (critical
care patients with no sepsis) collected between 2004 and 2010 were included and
genotyped for KIR genes using the polymerase chain reaction method with sequence-
specific oligonucleotide (PCR-SSO), and for HLA genes using the polymerase chain
reaction method with sequence-specific primers (PCR-SSP). The frequencies of
activating KIR2DS1 and KIR3DS1 in sepsis patients when compared to controls were
41.23% versus 55.00% and 36.49% versus 51.67% (p = 0.077 and 0.037 respectively
before Bonferroni correction). These results indicate that activating KIR genes
2DS1 and 3DS1 may more prevalent in critical patients without sepsis than in
patients with sepsis, suggesting a potential protective role of activating KIR
genes in sepsis. (C) 2017 American Society for Histocompatibility and
Immunogenetics. Published by Elsevier Inc. All rights reserved.
Kin17 DNA and RNA binding protein (Kin17) is a highly conserved protein that
participates in DNA replication, DNA repair and cell cycle progression. Recently,
the tumor-promoting function of Kin17 has been demonstrated and increasingly
studied. In the present study, the role of Kin17 in the invasion and metastasis of
non-small cells lung cancer (NSCLC) was investigated. Elevated Kin17 mRNA and
protein expression was identified in a total of 97 NSCLC and benign lung lesion
tissue specimens. Kin17 overexpression was significantly correlated with high tumor
grade and lymph node metastasis, indicating poor patient prognosis. Scratch and
Transwell assays demonstrated that the knockdown of KIN17 inhibited the ability of
NSCLC cells to migrate and invade. Furthermore, reverse transcription-quantitative
polymerase chain reaction and western blot analyses confirmed that knockdown of
KIN17 decreased the expression of matrix metalloproteinase 7, epidermal growth
factor receptor and v-myc avian myelocytomatosis viral oncogene homolog. The
results of the present study indicate that Kin17 is markedly overexpressed in NSCLC
tissues compared with benign lung lesion and peritumoral tissue. The upregulation
of KIN17 may serve an important role in the metastasis of NSCLC cells. These
results indicate that Kin17 is a novel diagnostic and prognostic biomarker of
NSCLC, in addition to being a potential therapeutic target for the treatment of
patients with NSCLC.
Genetic factors have a great role in the pathogenesis of autoimmune diseases by
cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs)
are cell surface proteins on NK cells whose association with major
histocompatibility complex-I regulates their killing function. The aim of this
study was to provide information on the possible association between KIR and human
leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian
population. A total of 279 systemic sclerosis patients and 451 healthy controls
were enrolled in this case-control study in order to determine the presence or
absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by
polymerase chain reaction using the specific sequence primer method (PCR-SSP).
Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4
genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-
gene interactions were also analyzed, and significant confounding effects were seen
between involved genes in these two combinations: "KIR3DL1; HLA-BW4-Thr80" and
"KIR3DL1 -HLA-BW4-A1." None of single KIR genes showed significant effect on the
risk of SSc. We conclude that there is an important relationship between KIR genes
and their HLA ligands with incidence rate of systemic sclerosis in Iranian
population. The powerful role of a number of discovered KIR/HLA compounds such as
activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of
the interplay between activating or inhibitory KIR genes with HLA ligands as a
critical index of systemic sclerosis predisposition.
Background:The klf10 gene could indirectly modify gamma-globin chain production and
hence the level of fetal hemoglobin (HbF) ameliorating the phenotype of beta-
hemoglobinopathies and the response to hydroxycarbamide (hydroxyurea [HU]) therapy.
In this study, we aimed to evaluate the frequency of different genotypes for the
klf10 gene in beta-thalassemia major (B-TM), beta-thalassemia intermedia (B-TI),
and sickle cell disease (SCD) patients by polymerase chain reaction and to assess
its relation to disease phenotypes and HU response. Methods:This cross-sectional
study included 75 patients: 50 B-TM, 12 SCD, and 13 B-TI patients (on stable HU
dose). The relation of the klf10 gene polymorphism (TIEG, TIEG1, EGR alpha)
(rs3191333: c*0.141C >T) to phenotype was studied through baseline mean corpuscular
volume, HbF, and transfusion history, whereas evaluation of response to HU therapy
was carried out clinically and laboratory. Results:The frequency of the mutant
klf10 genotype (TT) and that of the mutant allele (T) was significantly higher
among B-TM patients compared with those with B-TI and SCD patients. Only homozygous
SCD patients for the wild-type allele within the klf10 gene had a significantly
lower transfusion frequency. The percentage of HU responders and nonresponders
between different klf10 polymorphic genotypes among B-TI or SCD patients was
comparable. Conclusions:Although the klf10 gene does not play a standalone role as
an HbF modifier, our data support its importance in ameliorating phenotype among
beta-hemoglobinopathies.
Sustainability science is a solution-oriented discipline. Yet, there are few
theory-rich discussions about how this orientation structures the efforts of
sustainability science. We argue that Niklas Luhmann's social system theory, which
explains how societies communicate problems, conceptualize solutions, and identify
pathways towards implementation of solutions, is valuable in explaining the general
structure of sustainability science. From Luhmann, we focus on two key concepts.
First, his notion of resonance offers us a way to account for how sustainability
science has attended and responded to environmental risks. As a product of
resonance, we reveal solution-oriented research as the strategic coordination of
capacities, resources, and information. Second, Luhmann's interests in self-
organizing processes explain how sustainability science can simultaneously advance
multiple innovations. The value logic that supports this multiplicity of self-
organizing activities as a recognition that human and natural systems are complex
coupled and mutually influencing. To give form to this theoretical framework, we
offer case evidence of renewable energy policy formation in Texas. Although the
state's wealth is rooted in a fossil-fuel heritage, Texas generates more
electricity from wind than any US state. It is politically antagonistic towards
climate-change policy, yet the state's reception of wind energy technology
illustrates how social and environmental systems can be strategically aligned to
generate solutions that address diverse needs simultaneously. This case
demonstrates that isolating climate change-as politicians do as a separate and
discrete problem-is incapable of achieving sustainable solutions, and resonance
offers researchers a framework for conceptualizing, designing,
Epistemic contextualism is one of the most hotly debated topics in contemporary
epistemology. Contextualists claim that know' is a context-sensitive verb
associated with different evidential standards in different contexts.
Contextualists motivate their view based on a set of behavioural claims. In this
paper, I show that several of these behavioural claims are false. I also show that
contextualist test cases suffer from a critical confound, which derives from
people's tendency to defer to speakers' statements about their own mental states.
My evidence consists in results from several behavioural experiments. I conclude
that contextualism is an idle hypothesis and I propose some general methodological
lessons.
Lung cancer remains the leading cause of cancer-related deaths in both men and
women. However, the discovery of several oncogenic driver mutations and the
development of immune checkpoint inhibitors resulted in improved clinical outcomes
for most patients. Although activating KRAS mutations are the most common recurring
molecular events in lung adenocarcinoma, little progress has been made during the
past decades with no new agents being approved for this indication. The elucidation
of the underlying biology of this diverse patient subgroup offers great potential
and renewed hope regarding the rational development, rigorous evaluation and
subsequent approval of novel targeted agents and combinations which will
effectively suppress compensatory escape routes and the emergence of resistance,
issues that have plagued previous attempts. Here, we review in a structured manner
all aspects of KRAS positive non small cell lung cancer, including the molecular
biology, clinicopathologic characteristics, the prognostic and predictive value of
KRAS mutations, as well as previous and contemporary approaches towards the
treatment of this elusive target. (C) 2016 Elsevier Ireland Ltd. All rights
reserved.
In recent years, molecular biology has proven to be a great asset in our
understanding of mechanisms in genodermatoses. However, bench to bedside
translation research lags far behind. Advances in lab-on-a chip technologies
enabled programmable, reconfigurable, and scalable manipulation of a variety of
laboratory procedures. Sample preparation, microfluidic reactions, and continuous
monitoring systems can be integrated on a small chip. These advantages have
attracted attention in various fields of clinical application including diagnosis
of inherited skin diseases. This review lists an overview of the underlying genes
and mutations and describes prospective application of lab-on-a-chip technologies
as solutions to challenges for point-of-care genodematoses diagnosis. (C) 2016
Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative
Dermatology.
Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in
shorter time and with lower reagent consumption than a standard laboratory. Their
miniaturization interferes with the multiple functions that the biochemical
procedures require. In order to address this issue, our paper presents, for the
first time, the integration on a single glass substrate of different thin film
technologies in order to develop a multifunctional platform suitable for on-chip
thermal treatments and on-chip detection of biomolecules. The proposed System on-
Glass hosts thin metal films acting as heating sources; hydrogenated amorphous
silicon diodes acting both as temperature sensors to monitor the temperature
distribution and photosensors for the on-chip detection and a ground plane ensuring
that the heater operation does not affect the photodiode currents. The sequence of
the technological steps, the deposition temperatures of the thin films and the
parameters of the photolithographic processes have been optimized in order to
overcome all the issues of the technological integration. The device has been
designed, fabricated and tested for the implementation of DNA amplification through
the Polymerase Chain Reaction (PCR) with thermal cycling among three different
temperatures on a single site. The glass has been connected to an electronic system
that drives the heaters and controls the temperature and light sensors. It has been
optically and thermally coupled with another glass hosting a microfluidic network
made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR
process chamber. The successful DNA amplification has been verified off chip by
using a standard fluorometer. (C) 2016 Elsevier B.V. All rights reserved.
Purpose: Labor is thought to positively influence immune system development in the
offspring, but studies investigating the impact of different modes of delivery on
maternal immune system cells are scarce. Therefore, the aim of this study was to
investigate the effect of labor on maternal peripheral blood T-cell subsets and on
the recently described regulatory T and B cells. Methods: Cross-sectional study
comparing the absolute counts and percentages of peripheral blood T-cell subsets
(maturation and activation profiles) and regulatory T and B cells between healthy
pregnant women who delivered their newborns via elective cesarean (no labor; n =
14) and those who had a spontaneous vaginal delivery (after labor; n = 18). The
cells were characterized using flow cytometry. Results: We found that compared to
the women who had elective cesareans, those who had spontaneous vaginal deliveries
had significantly (P < .05) lower absolute counts of B cells (median [cells/L]: 146
[interquartile range, IQR = 49] vs 192 [IQR = 65]) and natural killer-like T (NKT-
like) cells (median [cells/L]: 154 [IQR = 125] vs 224 [IQR = 117]) in the
peripheral blood. No further significant differences, particularly in regulatory T
and B cells, were identified between the study groups. Conclusion: Labor does not
seem to have a major impact on maternal peripheral blood T-cell subsets or
regulatory T and B cells.
Medical biochemistry is the usual name for clinical biochemistry or clinical
chemistry in Serbia, and medical biochemist is the official name for the clinical
chemist (or clinical biochemist). This is the largest sub-discipline of the
laboratory medicine in Serbia. It includes all aspects of clinical chemistry, and
also laboratory hematology with coagulation, immunology, etc. Medical biochemistry
laboratories in Serbia and medical biochemists as a profession are part of Health
Care System and their activities are regulated through: the Health Care Law and
rules issued by the Chamber of Medical Biochemists of Serbia. The first continuous
and organized education for Medical Biochemists (Clinical Chemists) in Serbia dates
from 1945, when the Department of Medical Biochemistry was established at the
Pharmaceutical Faculty in Belgrade. In 1987 at the same Faculty a five years
undergraduate study program was established, educating Medical Biochemists under a
special program. Since the academic year 2006/2007 the new five year undergraduate
(according to Bologna Declaration) and four-year postgraduate program according to
EC4 European Syllabus for Postgraduate Training in Clinical Chemistry and
Laboratory Medicine has been established. The Ministry of Education and Ministry of
Public Health accredited these programs. There are four requirements for practicing
medical biochemistry in the Health Care System: University Diploma of the Faculty
of Pharmacy (Study of Medical Biochemistry), successful completion of the
professional exam at the Ministry of Health after completion of one additional year
of obligatory practical training in the medical biochemistry laboratories,
membership in the Serbian Chamber of Medical Biochemists and licence for skilled
work issued by the Serbian Chamber of Medical Biochemists. In order to present
laboratory medical biochemistry practice in Serbia this paper will be focused on
the following: Serbian national legislation, healthcare services organization, sub-
disciplines of laboratory medicine and medical biochemistry as the most
significant, education in medical biochemistry, conditions for professional
practice in medical biochemistry, continuous quality improvement, and
accreditation. Serbian healthcare is based on fundamental principles of universal
health coverage and solidarity between all citizens.
Background: In clinical practice, laboratory results are often important for making
diagnostic, therapeutic, and prognostic decisions. Interpreting individual results
relies on accurate reference intervals and decision limits. Despite the
considerable amount of resources in clinical medicine spent on elderly patients,
accurate reference intervals for the elderly are rarely available. The SENIORLAB
study set out to determine reference intervals in the elderly by investigating a
large variety of laboratory parameters in clinical chemistry, hematology, and
immunology. Methods/design: The SENIORLAB study is an observational, prospective
cohort study. Subjectively healthy residents of Switzerland aged 60 years and older
were included for baseline examination (n=1467), where anthropometric measurements
were taken, medical history was reviewed, and a fasting blood sample was drawn
under optimal preanalytical conditions. More than 110 laboratory parameters were
measured, and a biobank was set up. The study participants are followed up every 3
to 5 years for quality of life, morbidity, and mortality. The primary aim is to
evaluate different laboratory parameters at age-related reference intervals. The
secondary aims of this study include the following: identify associations between
different parameters, identify diagnostic characteristics to diagnose different
circumstances, identify the prevalence of occult disease in subjectively healthy
individuals, and identify the prognostic factors for the investigated outcomes,
including mortality. Discussion: To obtain better grounds to justify clinical
decisions, specific reference intervals for laboratory parameters of the elderly
are needed. Reference intervals are obtained from healthy individuals. A major
obstacle when obtaining reference intervals in the elderly is the definition of
health in seniors because individuals without any medical condition and any
medication are rare in older adulthood. Reference intervals obtained from such
individuals cannot be considered representative for seniors in a status of age-
specific normal health. In addition to the established methods for determining
reference intervals, this longitudinal study utilizes a unique approach, in that
survival and long-term well-being are taken as indicators of health in seniors.
This approach is expected to provide robust and representative reference intervals
that are obtained from an adequate reference population and not a collective of
highly selected individuals.
The opportunity to engage in scientific research is an important, but often
neglected, component of undergraduate training in biology. We describe the
curriculum for an innovative, course-based undergraduate research experience (CURE)
appropriate for a large, introductory cell and molecular biology laboratory class
that leverages students ' high level of interest in cancer. The course is highly
collaborative and emphasizes the analysis and interpretation of original scientific
data. During the course, students work in teams to characterize a collection of
mutations in the human p53 tumor suppressor gene via expression and analysis in
yeast. Initially, student pairs use both qualitative and quantitative assays to
assess the ability of their p53 mutant to activate expression of reporter genes,
and they localize their mutation within the p53 structure. Through facilitated
discussion, students suggest possible molecular explanations for the
transactivation defects displayed by their p53 mutants and propose experiments to
test these hypotheses that they execute during the second part of the course. They
use a western blot to determine whether mutant p53 levels are reduced, a DNA-
binding assay to test whether recognition of any of three p53 target sequences is
compromised, and fluorescence microscopy to assay nuclear localization. Students
studying the same p53 mutant periodically convene to discuss and interpret their
combined data. The course culminates in a poster session during which students
present their findings to peers, instructors, and the greater biosciences
community. Based on our experience, we provide recommendations for the development
of similar large introductory lab courses. (C) 2016 The Authors Biochemistry and
Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of
International Union of Biochemistry and Molecular Biology, 45(2): 161-178, 2017.
Regional labour force participation across the European Union: a time-space
recursive modelling approach with endogenous regressors. Spatial Economic Analysis.
Although there is an abundant regional labour market literature taking a spatial
perspective, only a few studies have explored extending the analysis of labour
force participation with spatial effects. This paper revisits this important issue,
proposing a time-space recursive modelling approach that builds on and appraises
Fogli and Veldkamp's methodology from 2011 and finding for the United States that
participation rates vary with past values in nearby regions. Major shortcomings in
their study are corrected for, including stationarity and the control for
endogenous regressors other than the time and space-time-lagged dependent variable
using system generalized method of moments (GMM). The paper also highlights
interaction effects among explanatory variables for the first time in this context.
Using a panel of 108 regions across the European Union over 1986-2010, the results
for total, male and female participation rates throw a new light on the socio-
economic relevance of different determinants. Importantly, characteristics in
neighbouring regions play a significant role, and neglecting endogeneity is found
to have serious consequences, underlining increased attention on the specification
and estimation of spatial econometric models with endogenous regressors.
The taxonomic differentiation among lactic acid bacteria (LAB) using only
phenotypic methods is inadequate. In the past, several phenotypic techniques have
been applied in identification of different species of LAB from Nigerian indigenous
fermented foods. In this study, two less-expensive and rapid molecular techniques
were employed in the identification and differentiation of LAB species isolated
from some Nigerian fermented foods: gari (cassava mash), fufu (cassava dough) and
ogi (maize gruel) to avoid the common errors that are synonymous with the use of
conventional methods. The size of the amplified products for the LAB species using
universal primers fD1 and rD1 was about 1500 bp. The differentiation of the three
predominant LAB, Lactobacillus plantarum, Pediococcus pentosaceus and Weissella
confusa to species level was performed by intergenic transcribed spacer (ITS-PCR)
and amplified ribosomal DNA restriction analysis (ARDRA) using three restriction
endonucleases: HinfI, HaeIII and RsaI. In summary, the study demonstrated that the
ARDRA and ITS-PCR analysis are simple, fast and efficient methods that can be used
for the routine identification and rapid differentiation of LAB species which are
often regularly used as probiotics, starter culture and biopreservative in
fermented foods consumed since they are generally regarded as safe (GRAS). (C) 2016
Elsevier Ltd. All rights reserved.
The aim of this study was to compare the concentration of salivary immunoglobulin A
(IgA) and the selected interleukins (IL)-1 beta, IL-6, IL-8 and IL-10 in young
individuals with presence and non-presence of Lactobacillus reuteri in saliva after
a three-week intervention with probiotic lozenges. The study group consisted of 47
healthy individuals aged 18-32 years with no clinical signs of oral inflammation.
In a randomised, double-blind, placebo-controlled, cross-over trial participants
ingested two lozenges per day containing two strains of the probiotic bacterium L.
reuteri or placebo lozenges. The intervention and wash-out periods were three
weeks. Stimulated and unstimulated whole saliva was collected at baseline and
immediately after termination of the intervention periods. The samples were
analysed for total protein, salivary IgA and selected cytokines. In this extended
analysis, data were collected by analysing baseline and follow-up saliva samples
related to ingestion of the probiotic lozenges for the presence of L. reuteri
through DNA-extraction, PCR-amplification and gel-electrophoresis. At baseline, 27%
of the individuals displayed presence of L. reuteri and 42% were positive
immediately after the three-week probiotic intervention. Individuals with presence
of L. reuteri in saliva had significantly higher (P<0.05) concentrations of
salivary IgA and %IgA/protein at the termination of the probiotic intake compared
with non-presence. No differences in the cytokine levels were observed. In
conclusion, detectable levels of L. reuteri in saliva coincided with higher
concentrations of salivary IgA and %IgA/protein in stimulated whole saliva after
the three-week daily intake of probiotic lozenges. Our findings suggest that
monitoring the presence of probiotic candidates in the oral environment is
important to interpret and understand their possible immune-modulating role in
maintaining oral health.
Tuberculosis (TB) remains among the most deadly diseases in the world. The only
available vaccine against tuberculosis is the bacille Calmette-Guerin (BCG)
vaccine, which does not ensure full protection in adults. There is a global urgency
for the development of an effective vaccine for preventing disease transmission,
and it requires novel approaches. We are exploring the use of lactic acid bacteria
(LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the
successful expression and surface display of a Mycobacterium tuberculosis fusion
antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus
plantarum. The AgE6 fusion antigen was targeted to the bacterial surface using two
different anchors, a lipoprotein anchor directing the protein to the cell membrane
and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of
the two anchors induced antigen-specific proliferative responses in lymphocytes
purified from TB-positive donors. Similarly, both strains induced immune responses
in mice after nasal or oral immunization. The impact of the anchoring strategies
was reflected in dissimilarities in the immune responses generated by the two L.
plantarum strains in vivo. The present study comprises an initial step toward the
development of L. plantarum as a vector for M. tuberculosis antigen delivery.
IMPORTANCE This work presents the development of Lactobacillus plantarum as a
candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top
infectious diseases worldwide, and the only available vaccine, bacille Calmette-
Guerin (BCG), fails to protect adults and adolescents. Direct antigen delivery to
mucosal sites is a promising strategy in tuberculosis vaccine development, and
lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles
for mucosal immunization. We have engineered L. plantarum strains to produce a
Mycobacterium tuberculosis fusion antigen and to anchor this antigen to the
bacterial cell wall or to the cell membrane. The recombinant strains elicited
proliferative antigenspecific T-cell responses in white blood cells from
tuberculosis-positive humans and induced specific immune responses after nasal and
oral administrations in mice.
PCR detection and quantification of vaginal lactobacilli remains problematic
because of the high level of genetic heterogeneity and taxonomic complexity within
the genus Lactobacillus. The aim of the present study was to identify conserved
sequences among the genomes of major species of vaginal lactobacilli that could be
used for the development of a PCR-based method for quantitative determination of
vaginal microbiota-specific lactobacilli. Comparative analysis of the genomes of
several species of vaginal lactobacilli allowed us to identify conserved regions in
the rplK gene, which encodes ribosomal protein L11, and to design group-specific
PCR primers and a probe for selected species from the L acidophilus complex,
including major vaginal lactobacilli Lactobacillus crispatus, L gasseri, L iners
and L jensenii as well as other species that are less common in vaginal microbiota.
The applicability of the new assay in routine diagnostic testing was evaluated
using a set of clinical samples. The assay was able to detect and quantify vagina-
associated lactobacilli within a wide range of initial DNA template concentrations,
indicating promising potential for clinical applications. (C) 2016 Elsevier Ltd.
All rights reserved.
In the study of engineering, experimentation plays a great role in understanding
the concepts. Teaching in engineering is always challenging as theoretical study
should be augmented with experiments so that students get a feel of the real life
applications of the concepts they study. Automation and control laboratory is an
area where students can not verify the ladder diagrams; they develop for various
applications, unless they have a Programmable Logic Controller, PLC in the lab. But
the new concept of virtual lab has enabled us to teach the concepts of ladder
diagrams and development of control systems using PLC very easily. Students could
develop ladder diagrams and design digital control systems using the simulation
environment given in the virtual lab platform and implement the logics developed by
them. Study carried out at institute and the exit surveys shows that the students
are more convinced about the results, as they could test them on a platform.
This article shows how Lamarckism was essential in the birth of the French school
of molecular biology. We argue that the concept of inheritance of acquired
characters positively shaped debates surrounding bacteriophagy and lysogeny in the
Pasteurian tradition during the interwar period. During this period the typical
Lamarckian account of heredity treated it as the continuation of protoplasmic
physiology in daughter cells. F,lix d'H,relle applied this conception to argue that
there was only one species of bacteriophage and Jules Bordet applied it to develop
an account of bacteriophagy as a transmissible form of autolysis and to analyze the
new phenomenon of lysogeny. In a long-standing controversy with Bordet, EugSne
Wollman deployed a more morphological understanding of the inheritance of acquired
characters, yielding a particulate, but still Lamarckian, account of lysogeny. We
then turn to Andr, Lwoff who, with several colleagues, completed Wollman's research
program from 1949 to 1953. We examine how he gradually set aside the Lamarckian
background, finally removing inheritance of acquired characters from the resulting
account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex
dual role of Lamarckism as it moved from an assumed explanatory framework to a
challenge that the nascent molecular biology had to overcome.
Correct identification of medicinal plant ingredients is essential for their safe
use and for the regulation of herbal drug supply chain. Loop-mediated isothermal
amplification (LAMP) is a recently developed approach to identify herbal medicine
species. This novel molecular biology technique enables timely and accurate
testing, especially in settings where infrastructures to support polymerase chain
reaction facilities are lacking. Studies that used this method have altered our
view on the extent and complexity of herbal medicine identification. In this
review, we give an introduction into LAMP analysis, covers the basic principles and
important aspects in the development of LAMP analysis method. Then we presented a
critical review of the application of LAMP-based methods in detecting and
identifying raw medicinal plant materials and their processed products. We also
provide a practical standard operating procedure (SOP) for the utilization of the
LAMP protocol in herbal authentication, and consider the prospects of LAMP
technology in the future developments of herbal medicine identification and the
challenges associated with its application.
Pratylenchus zeae parasitizes various crops and damages the host roots, resulting
in decreased yield and quality of the host plants. Alignments of mitochondrial DNA
(mtDNA) Cytochrome Oxidase I (COI (TM)) sequences revealed the genetic variation
among Pratylenchus species. The results indicated 0.2-2.4% intraspecific variations
for mtDNA COI sequences among eight P. zeae populations, and 25.4-35.1%
interspecific variations between P. zeae and other Pratylenchus species. Based on
the mtDNA COI (TM) region, a loop-mediated isothermal amplification (LAMP) assay
was developed for the rapid and specific detection of P. zeae. The optimal
conditions for the LAMP assay were 64 A degrees C for 40 min. The LAMP products
were confirmed using conventional polymerase chain reaction (PCR), analysis with
the restriction enzyme Bam HI and visual inspection by adding SYBR Green I to the
products. The LAMP assay could detect P. zeae populations from different hosts and
different geographical origins specifically. The LAMP assay was also sensitive,
detecting 0.1 individual P. zeae, which was 10 times more sensitive than
conventional PCR. This is the first report of the detection of Pratylenchus spp.
using LAMP. In addition, the results also suggested that use of the COI gene might
allow for good resolution at the Pratylenchus species level.
There are two adult life history types among lamprey species, nonparasitic and
parasitic, with the former commencing the final interval of sexual maturation
immediately after metamorphosis. There are no extensive studies that directly
compare hormone profiles during the life cycles of nonparasitic and parastic
lamprey species, yet such data may explain differences in development, reproductive
maturation, and feeding status. The present study uses immunohistochemistry to show
the life cycle profiles for gonadotropin-releasing hormones (GnRH-I and -III) in
the brain of the nonparasitic species, the American brook lamprey, Lampetra
appendix, for comparison with the extensive, published, immunohistochemical data on
these hormones in the parasitic species, the sea lamprey, Petromyzon marinas. The
complete cDNAs for the two lamprey prohormones, proopiocortin (POC), and
proopiomelanotropin (POM), were cloned for L. appendix and both nuclectide and
deduced amino acid sequences were compared with those previously published for P.
marinas. The POC and POM cDNAs for both species were used in expression studies,
with Northern blotting, throughout their life cycles. Although GnRH-I and -III
immunohistochemistry revealed a similar distribution of immunoreactive cells and
fibers in the two species during the life cycles, a qualitative evaluation of
staining intensity in L. appendix, implied early activity in the brains of
metamorphosis of this species, particularly in GnRH-I. GnRH-III seems to be
important in larval life and early metamorphosis in both species. A novel feature
of this immunohistochemical study is the monthly observations of the distribution
and relative intensity of the two GnRHs during the critical period of final sexual
maturation that lead to spawning and then the spent animal. L. appendix POC and POM
nucleotide sequences had 92.9 and 94.6% identity, respectively, with P. marinus POC
and POM and there was an earlier increase in their expression during metamorphosis
and postmetamorphic life. Since there was some correlation between the timing of
metamorphic development, gonad maturation, and brain irGnRH intensity with POC and
POM expression in L. appendix, it was concluded that these prohormones yield
posttranslational products that likely play a substantial role in development and
maturation events that lead to the nonparasitic adult life history of this species.
(c) 2005 Elsevier Inc. All rights reserved.
A simple experimental setup for measuring Planck's constant, using Landauer
quantization of the conductance between touching gold wires, is described. It
consists of two gold wires with thickness of 500 mu m and 1.5 cm length, and an
operational amplifier. The setup costs less than $30 and can be realized in every
teaching laboratory in two weeks. The use of an oscilloscope is required.
Over the years, the restorative benefits of the natural environment have been taken
seriously. These restorative effects continue to be verified in research from both
the psychological and physiological perspectives. The latest functional magnetic
resonance imaging (fMRI) technology provides an opportunity to further explore the
psychophysiological aspects of these benefits from the natural environment. This
study aimed to compare the restorative value of four types of landscape
environments (urban, mountain, forest, and water) through questionnaires and by
investigating the relationship between the different environments and brain region
activity by means of fMRI. Based on a one-way analysis of variance, a significant
difference was found between the restorative value of the urban and natural
environments the most value being in the water and mountain environments and least
in the urban environment. In support of this psychological result, the brain was
found to respond similarly, showing increased activity in the visual and
attentional focus areas when an urban environment is viewed as opposed to a natural
environment. These findings reveal a new approach to test the restorative value of
an environment and support the restorative effect of the natural environment. (C)
2017 The Authors. Published by Elsevier B.V.
The Tropical Montane Cloud Forest (TMCF) is a hydrologically unique and highly
vulnerable ecosystem to changes in land-use and climate. Assessing the impacts of
these changes needs to consider soil-water dynamics. In particular, the organic
layer and its functioning requires attention because its difference in water
retention characteristics and root density compared to the underlying mineral
soils. A higher root density and a higher water storage capacity of the organic
layer compared to the mineral soils suggests that most nutrient and water uptake
occurs in this layer. However, hydraulic properties of mineral soils and their
impact on hydrology of TMCFs have been poorly studied. Here we provide organic
layer water retention curves for TMCF soils that were measured in the laboratory.
With these data we assessed the potential land-use and climate change impacts on
TMCF soil moisture dynamics. From the land-use change perspective, we estimated the
water storage capacity loss by slash-and-burn deforestation practices. These
estimates show that the storage loss ranges from 35 to 59 mm when TMCFs are
converted to pastures. This is several times higher than the estimated TMCF canopy
storage capacity (2 to 5 mm). Therefore, the higher peak flow observations in
deforested catchments might not only be explained by a decreasing canopy water
storage but also likely due to a decreasing soil water storage. From the climate
change perspective, we evaluated the effect of contrasting dry season conditions on
soil moisture and transpiration using a 1-D water-flow model, and assessed the
sensitivity of these hydrological variables to uncertainties in saturated hydraulic
conductivity. Although transpiration was not limited by soil moisture during the
mild dry season, it was affected during the severe dry season and continued to
decline under expected climate change with the prolongation of dry spells. Our
results show that the organic layer is a key element in TMCF's hydrological
functioning and call for an increased focus on the role of organic soils when
evaluating effects of land-use change. (C) 2017 Elsevier B.V. All rights reserved.
A closed loop frequency tracking electronics circuit has been proposed for the
measurement of pressure and temperature using a newly developed Langasite (LGS)
piezo crystals. The ambient force and heat applied on the LGS crystal produces the
shift in its resonant frequency. The proposed closed loop electronics tracks the
shift in resonant frequency and measures the pressure and temperature by relating
to the difference in frequency shift. The steady state oscillation condition of the
resonator circuit is analytically derived and experimentally verified. The
experimental setup consists of an operational amplifier based resonator circuit
connected to the langasite piezo crystal placed between a double side diametric
forces loading device with temperature controller bath. The diametric force applied
on the LGS crystal produces the frequency shift in its fundamental mechanical
vibration mode (Cmode). Similarly, the change in temperature produces the frequency
shift in its second mechanical vibrational mode (Bmode). The frequency shifts are
measured using two separate closed loop resonator electronics for two different
measurand. Whenever the force on the LGS crystal is changed by the external unknown
pressure, an additional intrinsic material property change is added to the piezo
and changes the fundamental oscillating resonant frequency. The closed loop
resonant circuit tracks the change in resonance frequency and vibrates the LGS with
the new resonance frequency depends on the external pressure strength. Similar
procedure is followed for temperature induce frequency tracking measurement also.
The proposed frequency tracking electronics concept is simple and it is found that
it has high sensitivity and linearity.
When two targets are presented within approximately 500 ms of each other in the
context of rapid serial visual presentation (RSVP), participants' ability to report
the second target is reduced compared to when the targets are presented further
apart in time. This phenomenon is known as the attentional blink (AB). The AB is
increased in magnitude when the first target is emotionally arousing. Emotionally
arousing stimuli can also capture attention and create an AB-like effect even when
these stimuli are presented as to-be-ignored distractor items in a single-target
RSVP task. This phenomenon is known as emotion-induced blindness (EIB). The
phenomenological similarity in the behavioral results associated with the AB with
an emotional T1 and EIB suggest that these effects may result from similar
underlying mechanisms - a hypothesis that we tested using event-related electrical
brain potentials (ERPs). Behavioral results replicated those reported previously,
demonstrating an enhanced AB following an emotionally arousing target and a clear
EIB effect. In both paradigms highly arousing taboo/sexual words resulted in an
increased early posterior negativity (EPN) component that has been suggested to
represent early semantic activation and selection for further processing in working
memory. In both paradigms taboo/sexual words also produced an increased late
positive potential (LPP) component that has been suggested to represent
consolidation of a stimulus in working memory. Therefore, ERP results provide
evidence that the EIB and emotion-enhanced AB effects share a common underlying
mechanism.
It is shown that negative capacitance (NC) circuits can be systematically used to
improve the gain-bandwidth product of the operational amplifiers (opamps). The NC
circuit moves the nondominant pole of the opamp to higher frequency by decreasing
the parasitic capacitance of the critical node. The impedance at the input of the
NC circuits is neither purely capacitive nor negative at all frequencies. A design
guide is presented by deriving the circuit model for a conventional NC circuit and
investigating the extent of the improvement that can be achieved in a circuit by
the use of the NC circuit. The model is then used to present the design guide for
widebanding the multistage opamps with large capacitive loads. Based on the
proposed method, a three-stage opamp with a 15-nF capacitive load was designed and
fabricated in a 0.18-mu m CMOS process. The measurements confirm that the opamp
satisfies the design target of 1.5-MHz bandwidth at the power consumption of 75 mu
W.
The EU Large Combustion Plant Directive (LCPD) is a major but largely unstudied
environmental regulation. Most of the 1585 large combustion plants in this analysis
are electricity supply plants or combined heat and power plants. We find that,
controlling for country characteristics and plant size, plants in the electricity
supply, combined heat and power, district heating, and paper industries have a
higher probability of being opted-out of the emission limit values (ELVs), which
necessitates eventual plant closure. Controlling for plant size and industry,
increasing the amount of solid fuel or natural gas utilized at a plant is
associated with a decreased likelihood of being opted-out of the ELVs. (C) 2017
Elsevier Ltd. All rights reserved.
We present a scalable computing framework for the solution stochastic
multiobjective optimization problems. The proposed framework uses a nested
conditional value-at-risk (hCVaR) metric to find compromise solutions among
conflicting random objectives. We prove that the associated nCVaR minimization
problem can be cast as a standard stochastic programming problem with expected
value (linking) constraints. We also show that these problems can be implemented in
a modular and compact manner using PLASM (a Julia-based structured modeling
framework) and can be solved efficiently using PIPS-NLP (a parallel nonlinear
solver). We apply the framework to a CHP design study in which we seek to find
compromise solutions that trade-off cost, water, and emissions in the face of
uncertainty in electricity and water demands. (C) 2017 Elsevier Ltd. All rights
reserved.
Large-array resistive sensors have found a variety of applications from industrial
instrumentation to medical wearable applications. In such large-array sensors,
several non-idealities limit the accuracy of the readout circuit. In this paper,
after analyzing the crosstalk error caused by the input offset voltage and input
bias current of the operational amplifier, a novel double-sampling technique is
proposed to considerably reduce the error. Spice simulation results of a 20 x 20
array confirm that for a 1-M Omega resistance, the proposed technique can decrease
the maximum measureable relative error from 20% to 0.089%. Furthermore, the
measurement results of a 20 x 20 array confirm that for a resistance value of 19 M
Omega being measured, the proposed technique can reduce the error from 84% to
0.69%.
Background. It has become evident that increased nitric oxide (NO) generation may
be associated with production of reactive oxygen species, such as peroxynitrite
(ONOO-). Peroxynitrite has been postulated to be responsible for several of the
cytotoxic effects previously ascribed to NO. Since cellular arginine uptake has
been shown to modulate nitric oxide synthase activity, we were intrigued to study
the effect of ONOO- on arginine traffic in renal mesangial cells. Methods. Arginine
uptake, CAT-1 and CAT-2 mRNA expression by northern blotting analysis, and CAT-1
protein content using western blotting were determined in mesangial cells pre-
treated with peroxynitrite (0.1 and 0.5 mM) for 2 h. Results. Peroxynitrite induced
a significant increase in arginine uptake and CAT-2 mRNA expression compared with
untreated cells. In contrast, CAT-1 mRNA expression and protein abundance were
diminished. Conclusions. In rat mesangial cells, peroxynitrite augments arginine
uptake via augmentation of CAT-2 while decreasing CAT-1 expression.
The aim of this work was to elucidate the immunopathological mechanisms of how
helminths may influence the course of a viral infection, using a murine model.
Severe virulence, a relevant increase in the virus titres in the lung and a higher
mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice,
compared with VACV mono-infected mice. Immunopathological analysis suggested that
the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells
producing IFN-gamma, and the robust pulmonary inflammation were associated with the
increase of morbidity/mortality in co-infection and subsequently with the negative
impact of concomitant pulmonary ascariasis and respiratory VACV infection for the
host. On the other hand, when evaluating the impact of the co-infection on the
parasitic burden, co-infected mice presented a marked decrease in the total number
of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infettion.
Taken together, our major findings suggest that Ascaris and VACV co-infection may
potentiate the virus-associated pathology by the down modulation of the VACV-
specific immune response. Moreover, this study provides new evidence of how
helminth parasites may influence the course of a coincident viral infection. (C)
2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights
reserved.
The laryngeal carcinoma related gene 1 (LCRG1) has been implicated as a tumor
suppressor in laryngeal cancer. However, the microRNAs (small non-coding RNAs of
approximately 22 nucleotides in length) that regulate LCRG1 expression remain
elusive. In this study, quantitative PCR analysis first showed that the average
level of miR-21-5p was elevated in primary laryngeal carcinoma tissues compared to
paired adjacent non-tumor tissues. Thus, we explored the potential regulation of
miR-21-5p on LCRG1. PITA algorithm predicted that two sites within LCRG1 mRNA
3'UTR, which reside at +743 position and +938 position, respectively, might be
targeted by miR-21-5p. Dual luciferase reporter assay confirmed that miR-21-5p
mimic specifically decreased luciferase activity of the reporter harboring
3'UTR+743 target site. With respect to the 3'UTR+938 site, the influence of miR-21-
5p on luciferase activity was not sequence specific. Further, we observed that miR-
21-5p mimic transfection decreased the LCRG1 protein in human laryngeal carcinoma
Hep2 cells as indicated by Western blotting analysis, and promoted cell growth,
migration and invasion as evidenced by MTT assay and transwell migration assay and
matrigel invasion assay. Of note, the effects of miR-21-5p inhibitor treatment are
opposite to those of the miR-21-5p mimic. Taken together, this study identifies
that the tumor suppressor LCRG1 is targeted by the oncogenic miR-21-5p. This
finding may help us to better understand the dysregulation of cancer-associated
genes associated with microRNAs and eventually improve the diagnosis and target
therapy for laryngeal carcinoma.
Objective. To determine the presence of human papillomavirus (HPV) in head and neck
squamous cell carcinoma, specifically in the larynx without the bias of other
sublocations, and to describe the different serotypes of HPV and their impact on
overall and disease-free survival after 10-year follow-up. Study Design.
Retrospective case series with chart review of ear, nose, and throat oncologic
database. Setting. Academic tertiary care hospital. Subjects. A total of 123
samples of larynx squamous cell carcinoma were included, only from the glottis and
treated only with surgery between 1977 and 2005. Methods. DNA extraction was
carried out by polymerase chain reaction, and subsequent visualization was
performed in low-density arrays. Results were compared with histologic,
clinicopathologic, and survival parameters, with a 10-year follow-up. Results. HPV
DNA was detected in 22.76% (n = 28) of the samples. Eleven genotypes were detected,
2 of which had never been described in the larynx (HPV43 and HPV62). No increasing
trend of HPV was observed over time. HPV presence did not correlate with better
survival during the follow-up. Smoking was proven as an independent factor in
relation to the presence of HPV. Conclusion. HPV may represent a notable factor in
the development of a subset of laryngeal squamous cell carcinoma without
significant influence on overall and disease-free survival. More studies, including
oncogene transcription proteins, would be necessary to draw more relevant
conclusions about the relevance of HPV infection in the larynx.
Laser ablation in liquid (LAL) has received considerable attention over the last
decade, and is gradually becoming an irreplaceable technique to synthesize
nanocrystals and fabricate functional nanostructures because it can offer effective
solutions to some challenges in the field of nanotechnology. The goal of this
review is to offer a comprehensive summary of recent developments of LAL in
nanocrystal synthesis and nanostructure fabrication. First, we will introduce the
fundamental processes of microsecond, nanosecond, and femtosecond LAL, and how the
active species act differently in plasma, cavitation bubbles, and droplets in the
different LAL processes. Second, a variety of LAL-based techniques for
nanomaterials synthesis and processing are presented, such as electric-, magnetic-,
and temperature-field LAL, as well as electrochemically assisted LAL, pulsed laser
deposition in liquid, and laser writing of nanopatterns in liquid. Third, new
progress in LALgenerated nanomaterials is described. Fourth, we emphasize five
applications of LALgenerated nanomaterials that have emerged recently in the fields
of optics, magnetism, environment, energy, and biomedicine. Finally, we consider
the core advantages of LAL, the limitations of LAL and corresponding solutions, and
the future directions in this promising research area. (C) 2017 The Author(s).
Laser-based additive manufacturing has attracted much attention as a promising 3D
printing method for metallic components in recent years. However, surface roughness
of additive manufactured components has been considered as a challenge to achieve
high performance. In this work, we demonstrate the capability of fiber laser in
polishing rough surface of additive manufactured Ti-based alloys as Ti-6A1-4V and
TC11. Both as-received surface and laser-polished surfaces as well as cross-section
subsurfaces were analyzed carefully by White-Light Interference, Confocal
Microscope, Focus Ion Beam, Scanning Electron Microscopy, Energy Dispersive
Spectrometer, and X-ray Diffraction. Results revealed that as-received Ti-based
alloys with surface roughness more than 5 ism could be reduce to less than 1 pm
through laser polishing process. Moreover, microstructure, microhardness and wear
resistance of laser-polished zone was investigated in order to examine the thermal
effect of laser polishing processing on the substrate of additive manufactured Ti
alloys. This proof-of-concept process has the potential to effectively improve the
surface roughness of additive manufactured metallic alloy by local polishing method
without damage to the substrate.
Late-life depression (LLD) is a common emotional and mental disability in the
elderly population characterized by the presence of depressed mood, the loss of
interest or pleasure in daily activities, and other depression symptoms. It has a
serious effect on the quality of life of elderly individuals and increases their
risk of developing physical and mental diseases. It is an important area of
research, given the growing elderly population. Brain functional connectivity
modifications represent one of the neurobiological biomarker for LLD even if to
date remains poorly understood. In our study, we enrolled 10 elderly patients with
depressive symptoms compared to 11 age-matched healthy controls. All participants
were evaluated by means of neuropsychological tests and underwent the same
functional magnetic resonance imaging (fMRI) protocol to evaluate modifications of
brain resting state functional connectivity. Between-group differences were
observed for the Geriatric Depression Scale and Hamilton Depression Rating Scale,
with higher scores for patients with LLD. Voxel-wise, 1-way analysis of variance
revealed between-group differences in left frontoparietal network (lFPN) and
sensory motor network (SMN): Increased intrinsic connectivity in the LLD group was
observed in the left dorsolateral prefrontal cortex and in the left superior
parietal lobule of the lFPN and increased intrinsic connectivity in the LLD group
was observed in the bilateral primary somatosensory cortex of the SMN. Our findings
support the use of resting state fMRI as a potential biomarker for LLD; even if to
confirm the relationship between brain changes and the pathophysiology of LLD,
longitudinal neuroimaging studies are required.
A novel three-dimensional DNA-AuNPs network structure amplification strategy was
employed to design a lateral flow biosensor by introducing streptavidin coated gold
nanoparticles (Au-SA) in this paper. They act as amplification probes which
aggregate numerous gold nanoparticles (AuNPs) on test line by forming a
threedimensional DNA-AuNPs network structure in the presence of target. Sensitive
detection of nucleic acid with point-of-care analysis is significant for infectious
agent, early diagnosis and treatment of genetic diseases. The use of these
particles in rapid ultrasensitive point of care (POC) lateral flow assays lead to a
linear range from 0.1 pM to 250 nM with a limit of detection of 0.01 pM without
polymerase chain reaction (PCR). The proposed method could increase the sensitivity
by 4 orders of magnitudes than traditional sandwich assays labeled with AuNPs.
Furthermore, the assay owns good reproducibility and stability, which will prove
practical diagnostic applications.
IntroductionThe etiological diagnosis of pleural effusion is a difficult task
because the diagnostic tools can only establish a definitive etiological diagnosis
in at most 76% of cases. ObjectivesTo verify the diagnostic accuracy of the latex
agglutination test (LAT) for the etiological diagnosis of pleural effusions caused
by Streptococcus pneumoniae and Haemophilus influenzae type b. MethodsAfter
thoracocentesis, paired fresh samples of pleural fluid from 418 children and
adolescents were included in this investigation. They were tested blindly and
simultaneously through counterimmunoelectrophoresis (CIE) and LAT for both
bacteria. Sensitivity, specificity, predictive values and likelihood ratios (LR)
were calculated taking CIE as a reference standard. ResultsThe sensitivity and
specificity of LAT was 100% (95% confidence interval, 94.4%-100%) and 83.3% (95%
confidence interval, 79.0%-87.0%), respectively, whereas the positive (calculated
from Bayes' theorem) and negative predictive values were, respectively, lower than
1% and 100% (95% confidence interval, 98.8%-100%). Positive and negative LR were
6.0 (95% confidence interval, 4.7-7.6) and zero, respectively. ConclusionsOur
results suggest that LAT is a useful tool for the etiological diagnosis of pleural
effusion. It is a reliable, rapid, simple to perform and shows an excellent yield
in our studied population, helping to prescribe appropriate antibiotics for this
clinical condition.
This paper examined the prevalence of depressive symptomotology among women of
Mexican ancestry (N = 205), over the age of 18, of diverse incomes and nativity. We
examined differences in rates of diagnosis by Spanish/English preference and the
sensitivity and specificity of three common measures: the Patient Health
Questionnaire (PHQ9), the Kessler Psychological Distress Scale (K-10), and
depression questions from the Composite International Diagnostic Interview, Short
Form (MDD CIDI-SF); PHQ9 was used as the "gold standard" measure. Results indicated
18-32 % of participants met criteria for depression with higher rates found among
Spanish preference participants. The K-10 had significantly higher sensitivity
(0.81) but lower specificity (0.79) than the MDD CIDI-SF items (0.57 and 0.89,
respectively). This study suggests that the K-10 and MDD CIDI-SF measures are
complementary to each other for screening of depressive symptomatology.
Implications for cultural and linguistic assessment of depression are further
discussed.
Objective: The purpose of this study was to present a case report and review the
relevant literature on laxative-induced dermatitis being mistaken for scald injury
and child abuse. Case: A 33-month-old girl presented with partial thickness burn to
the buttocks and perineum, which were suspected to be caused by child abuse. On
further investigation, the parents had been administering large doses of laxatives
to the child for chronic constipation. Discussion: Child abuse by burning has
characteristic physical examination findings, which differ from the pattern of
laxative-induced dermatitis that has been reported in the literature. Diapers
appear to be a risk factor for laxative-induced dermatitis. Surprisingly, the dose
of laxative does not correlate with the severity of the burn injury. All physicians
must be aware of the possibility of laxative-induced dermatitis mimicking scald
burn injury to the buttocks. Parents should be educated about the risk of
administering over-the-counter laxatives to children.
With the increasing applications of ionic liquids (ILs), the toxicity of ILs has
drawn increasing attention in recent years, especially the influences of different
anions and alkyl-chain lengths on the acute toxicity to aquatic organisms. We
performed a study on the acute toxicity of 1-alkyl-3-methylimidazolium nitrate
([C(n)mim]NO3] (n = 2, 4, 6, 8, 10, 12)), 1-hexyl-3-methylimidazolium ILs
([C(6)mim]R (R = Cl-, Br-, BF4-, PF6-)) to zebrafish (Danio rerio). We also
evaluated the sensibility of the investigated animals and the stability of ILs in
water via high performance liquid chromatography (HPLC, Agilent 1260, Agilent
Technologies Inc., USA) to prove the reliability of the present study. The results
illustrated that the test zebrafish (Danio rerio) were sensitive to the reference
toxicant and that the investigated ILs in water were stable. The 50% lethal
concentration (LC50) was used to represent the acute toxicity to zebrafish (Dario
rerio). The present study showed that the highest toxic IL is [C(12)mim]NO3 and the
lowest toxic IL is [C(2)mim]NO(3)on Danio rerio. The LC(50)s for ILs with different
anions had similar values. Accordingly, we believe that ILs with different alkyl-
chain lengths cause greater effects than other anions on acute toxicity to aquatic
organisms. Furthermore, the present study can also provide scientific methods for
future studies to select and assess ILs.
The growing demand for electric vehicles entails an increased consumption of
critical energetic and non-energetic abiotic resources, necessary for an optimal
performance of the vehicle. The depletion of these resources and the future
availability to meet their demand appears to be a potential limitation for the
expansion of the electrified vehicle industry. The goal of this study is to perform
a detailed life cycle analysis, including manufacturing, use and disposal, of key
components of EV powertrains, identifying materials and processes responsible for
abiotic depletion impact. This study also investigates the sensitivity of the
results to the choice of Life Cycle Assessment (LCA) impact methods. For this, a
LCA is performed on an integrated electric drive, by considering seven impact
methods. Results show that energetic resources consumption generate the largest
impact, followed by metals and lastly by mineral resources. The consumption of
electricity in each life cycle is a crucial factor in the generation of total
impact. There are agreements among methods on the materials and processes
contributing the most to depletion, given the differences in approach used by each
impact method. (C) 2016 Elsevier B.V. All rights reserved.
Purpose Application of zero valent iron nanoparticles is an innovative technology
for ground water treatment and soil remediation. There are several methods to
synthesise nano scale zero valent iron (nZVI), namely through bottom-up methods
which consists on chemical reactions using strong reducing agents. In this work,
the environmental impacts and costs were determined for two methods, namely the
traditional one that uses sodium borohydride and the green method that uses
extracts obtained from natural products. Methods The consideration of environment
and economic aspects in the earlier stages of the synthesis processes and in the
development of new materials is of great importance since it can help to decide if
alternative methods are promising and should be further developed aiming more
sustainable processes. In this work, life cycle assessment (LCA) was used as an
ecodesign strategy evaluating environmental performance of the two synthesis
methods, identifying critical stages of the synthesis processes of nZVI. An
economic evaluation and a sensitivity analysis considering a different scenario for
electricity production were also performed. Results and discussion The results
obtained in this study showed that the green synthesis method presents lower
environmental impacts than the traditional one, roughly 50% lower in the first
scenario. In the second scenario, environmental impact of green synthesis
corresponds to 38% of the environmental impact of traditional synthesis. In the
green method, the critical stage is the extraction process which is closely related
to the electricity production. In the traditional method, the reactant use is the
critical stage that is related to the production of sodium borohydride. The
economic evaluation indicated that the traditional synthesis method is much more
expensive than the green synthesis (roughly eight times higher). Conclusions From
the results obtained, it is possible to conclude that the green synthesis method
presents lower environmental impacts in both scenarios and lower costs than the
traditional synthesis.
Lead (Pb) in public drinking water supplies has garnered much attention since the
outset of the Flint water crisis. Pb is a known hazard in multiple environmental
matrices, exposure from which results in long-term deleterious health effects in
humans. This discussion paper aims to provide a succinct account of environmental
Pb exposures with a focus on water Pb levels (WLLs) in the United States. It is
understood that there is a strong correlation between WLLs and blood Pb levels
(BLLs), and the associated health effects. However, within the Flint water crisis,
more than water chemistry and Pb exposure occurred. A cascade of regulatory and
bureaucratic failures culminated in the Flint water crisis. This paper will discuss
pertinent regulations and responses including their limitations after an overview
of the public health effects from Pb exposure as well as discussion on our
limitations on monitoring and mitigating Pb in tap water. As the Flint water crisis
also included increased Legionnares' disease, caused by Legionella pneumophila,
this paper will discuss factors influencing L. pneumophila growth. This will
highlight the systemic nature of changes to water chemistry and public health
impacts. As we critically analyze these important aspects of water research, we
offer discussions to stimulate future water quality research from a new and
systemic perspective to inform and guide public health decision-making. (C) 2017
Elsevier B.V. All rights reserved.
Eliminating the leakage current is one of the most important issues for
transformerless three-phase photovoltaic (PV) systems. In this paper, the leakage
current elimination of a three-phase four-leg PV inverter is investigated. With the
common-mode loop model established, the generation mechanism of the leakage current
is clearly identified. Different typical carrier-based modulation methods and their
corresponding common-mode voltages are discussed. A new modulation strategy with
Boolean logic function is proposed to achieve the constant common-mode voltage for
the leakage current reduction. Finally, the different modulation methods are
implemented and tested on the TMS320F28335 DSP +XC3S400 FPGA digital control
platform. The experimental results verify the effectiveness of the proposed
solution.
The human left inferior parietal lobule (LIPL) plays a pivotal role in many
cognitive functions and is an important node in the default mode network (DMN).
Although many previous studies have proposed different parcellation schemes for the
LIPL, the detailed functional organization of the LIPL and the exact correspondence
between the DMN and LIPL subregions remain unclear. Mounting evidence indicates
that spontaneous fluctuations in the brain are strongly associated with cognitive
performance at the behavioral level. However, whether a consistent functional
topographic organization of the LIPL during rest and under task can be revealed
remains unknown. Here, they used resting- state functional connectivity (RSFC) and
task- related coactivation patterns separately to parcellate the LIPL and
identified seven subregions. Four subregions were located in the supramarginal
gyrus (SMG) and three subregions were located in the angular gyrus (AG). The
subregion- specific networks and functional characterization revealed that the four
anterior subregions were found to be primarily involved in sensorimotor processing,
movement imagination and inhibitory control, audition perception and speech
processing, and social cognition, whereas the three posterior subregions were
mainly involved in episodic memory, semantic processing, and spatial cognition. The
results revealed a detailed functional organization of the LIPL and suggested that
the LIPL is a functionally heterogeneous area. In addition, the present study
demonstrated that the functional architecture of the LIPL during rest corresponds
with that found in task processing. (C) 2017Wiley Periodicals, Inc.
Forensic clinical anatomy is a new practical application of the discipline of
Clinical Anatomy for ascertaining and evaluating medicolegal questions. In
particular, individual anatomy (normal anatomy, anatomical variations, age-,
disease-, or surgery-related modifications) can acquire significant relevance in
various fields of legal medicine such as child abuse, sudden death, medical
responsibility and/or liability, personal injury and damage. Anatomical data of
forensic interest frequently arise from the correct application of methods of
ascertainment; anatomical methods may then be required for further comprehensive
analysis. The rigorous interpretation of anatomical data, derived from the
ascertainment phase and analyzed on the basis of pertinent literature, can be
pivotal for the correct application of evaluation criteria in various forensic
contexts. Clin. Anat. 30:2-5, 2017. (c) 2016 Wiley Periodicals, Inc.
The Rhizobia are collectively comprised of gram negative soil bacteria that have
the ability to form symbiotic nitrogen-fixing root and/or stem nodules in
association with leguminous plants. The taxonomy of these bacteria is continually
in a state of flux, in large part due to rapid development of refined molecular
biology techniques. The isolation and characterization of new, and often different,
legumes-nodulating bacteria on a variety of plant hosts has resulted in the naming
of many new rhizobial species. Here we update the taxonomy of the legume-nodulating
bacteria and describe newly identified rhizobia capable of nodulating edible
legumes and legume trees. In 1990, there was only one bacterial species that was
known to nodulate common bean worldwide (Rhizobium leguminosarum sv. phaseoli), one
species that nodulated faba bean (Rhizobium leguminosarum sv. viciae), and two
species that nodulated soybean (Bradyrhizobium japonicum and Rhizobium fredii).
Today, nearly 14, 11, 6, 5, 5, 4, 3 and 2 species have been defined that are
capable of nodulating common bean, soybean, cowpea, chickpea, peanut, lentils, faba
bean and pea, respectively. The recent use of whole genome based taxonomy
(genomotaxonomy) will surely change how we define this important group of bacteria.
The identification of several rhizobial species that are able to nodulate and fix
nitrogen with edible legumes may enhance the production of these crops and can
compensate for worldwide deficiencies in human nutritional needs in the future.
Background: Leishmania use exosomes to communicate with their mammalian hosts and
these secreted vesicles appear to contribute to pathogenesis by delivering protein
virulence factors to macrophages. In other eukaryotes, exosomes were found to carry
RNA cargo, such as mRNAs and small non-coding RNAs, capable of altering recipient
cell phenotype. Whether leishmania exosomes also contain RNAs which they are able
to deliver to bystander cells is not known. Here, we show that leishmania exosomes
indeed contain RNAs and compare and contrast the RNA content of exosomes released
by Leishmania donovani and Leishmania braziliensis. Results: We purified RNA from
exosomes collected from axenic amastigote culture supernatant and found that when
compared with total leishmania RNA, exosomes mainly contained short RNA sequences.
Exosomes with intact membranes were capable of protecting their RNA cargo from
degradation by RNase. Moreover, exosome RNA cargo was delivered to host cell
cytoplasm in vitro. Sequencing of exosomal RNA indicated that the majority of cargo
sequences were derived from non-coding RNA species such as rRNA and tRNA. In depth
analysis revealed the presence of tRNA-derived small RNAs, a novel RNA type with
suspected regulatory functions. Northern blotting confirmed the specific and
selective enrichment of tRNA-derived small RNAs in exosomes. We also identified a
number of novel transcripts, which appeared to be specifically enriched in exosomes
compared to total cell RNA. In addition, we observed the presence of sequences
mapping to siRNA-coding regions in L. braziliensis, but not in L. donovani
exosomes. Conclusions: These results show that leishmania exosomes are selectively
and specifically enriched in small RNAs derived almost exclusively from non-coding
RNAs. These exosomes are competent to deliver their cargo of novel, potential small
regulatory RNAs to macrophages where they may influence parasite-host cell
interactions. The remarkably high degree of congruence in exosomal RNA content
between L. donovani and L. braziliensis, argues for the presence of a conserved
mechanism for exosomal RNA packaging in leishmania. These findings open up a new
avenue of research on non-canonical, small RNA pathways in this trypanosomatid,
which may elucidate pathogenesis and identify novel therapeutic approaches.
Leishmaniasis is an arthropod-borne disease that affects approximately 2 million
people worldwide annually. The aims of this study were to detect the presence of
Leishmania (Kinetoplastida: Trypanosomatidae) DNA and the feeding preferences of
probable vector species in an endemic focus of Leishmania infantum in Turkey.
Entomological sampling was performed in August and October 2015 in Aydn province,
where cases of human and canine leishmaniasis have been reported previously. A
total of 1059 sandfly specimens comprising nine species belonging to two genera,
Phlebotomus and Sergentomyia (both: Diptera: Psychodidae), and five subgenera of
the Phlebotomus genus (Phlebotomus, Paraphlebotomus, Larroussius, Adlerius and
Transphlebotomus) were collected in five villages. Among all Phlebotomus specimens,
Phlebotomus neglectus (39%) was noted as the most abundant species, followed by
Phlebotomus tobbi (18%). LeishmaniaDNA was detected in pools from P.neglectus,
P.tobbi and Sergentomyia dentata by kDNA polymerase chain reaction (PCR).
LeishmaniaDNA from Phlebotomus specimens was identified as L.infantum, but
LeishmaniaDNA from Sergentomyia spp. could not be identified to species level by
ITS-1 real-time PCR. The detection of LeishmaniaDNA in wild-caught P.neglectus and
the high percentage (24.2%) of human DNA in engorged specimens suggests that
P.neglectus is probably an important vector species for L.infantum in Aydn
province.
Transmission of canine leishmaniosis (CanL) is described in three consecutive
generations of female Boxers living in a non-endemic environment in the Czech
Republic. Infection of the first generation female likely occurred during a
breeding visit to Italy and the dog died with typical clinical signs of the disease
but without definitive laboratory diagnosis. The second and third generation
offsprings never left the Czech Republic, suffered from clinical CanL confirmed by
polymerase chain reaction and serology, and were apparently infected by
transplacental transmission. Persistence of CanL in the Czech Republic over 7 years
with a suspected origin in an endemic region and progression of infection through
subsequent generations in a non-endemic country exemplifies that this disease may
establish itself also in areas where no obvious vectors are present. (C) 2017
Published by Elsevier B.V.
Lemur tyrosine kinase-3 (LMTK3) is a member of the serine/threonine tyrosine kinase
family, which is thought to be involved in tumor progression and prognosis. The
purpose of the present study was to determine the diagnostic significance and
therapeutic targets in thyroid cancer. ELISA assay was used to detect the protein
expression of serum LMTK3. Immunohistochemistry and reverse transcription-
quantitative polymerase chain reaction were employed to measure the expression of
LMTK3. Flow cytometry was used to determine the cell cycle. Transwell assay was
used to measure the invasion and migration of SW579 cells and terminal
deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect cell
apoptosis. The LMTK3 level was positively associated with disease stage and
pathological type, whereas there was no correlation between LMTK3 level and gender,
age, tumor size or lymph node metastasis. The serum LMTK3 level was significantly
increased in 102 thyroid carcinoma patients compared with 52 benign thyroid tumor
patients and 50 healthy volunteers (P= 0.001). The protein and mRNA expression of
LMTK3 was markedly higher in thyroid cancer patients compared with patients with
benign thyroid tumors. Notably, LMTK3 knockdown retarded proliferation, invasion
and migration in SW579 cells. In addition, downregulation of LMTK3 promoted
apoptosis in SW579 cells. These findings indicated that LMTK3 knockdown retards the
growth of thyroid cancer cells partly through inhibiting proliferation, invasion,
migration and inducing apoptosis in SW579 cells. It may serve as a useful
diagnostic biomarker and a novel therapeutic target for patients with thyroid
cancer.
Objectives: To investigate whether LEP G2548A and LEPR Q223R polymorphisms
influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of
simvastatin treatment in Chinese patients with primary hyperlipidemia. Methods: We
used an extreme sampling approach by selecting 212 individuals from the top and
bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in
each group of good or bad response) from a total of 734 samples with primary
hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum
lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping
was carried out using polymerase chain reaction-restriction fragment length
polymorphism. Results: More patients in the good response group (27%) had LEPR
Q223R than in the bad response group (16%, P =.046). Secondary stratified analyses
showed that patients carrying the RR genotype of the LEPR Q223R gene had
significantly higher high-density lipoprotein cholesterol levels than those with
the QR genotype at baseline (P = .034) among good responders. After 29 consecutive
days of treatment with simvastatin, patients carrying the RR genotype had a
significantly larger decrease in triglycerides (change: -0.74 +/- 0.92, P =.036)
and total cholesterol levels (change: -1.77 +/- 0.68, P = .023) compared with those
carrying QR genotype among bad responders. After Bonferroni correction, the results
were not statistically significant. Conclusion: LEPR Q223R polymorphism, but not
LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with
primary hyperlipidemia.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According
to official reports from 121 countries across five WHO regions, there were 213 899
newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral
nerves, it can present across a spectrum of clinical and histopathological forms
that are strongly influenced by the immune response of the infected individuals.
These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-
specific Th1, but also a Th17, response that limits M. leprae multiplication,
through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory
responses that do not control M. leprae replication but rather allow bacterial
dissemination. The interpolar borderline clinical forms present with similar, but
less extreme, immune biases. Acute inflammatory episodes, known as leprosy
reactions, are complications that may occur before, during or after treatment, and
cause further neurological damages that can cause irreversible chronic
disabilities. This review discusses the innate and adaptive immune responses, and
their interactions, that are known to affect pathogenesis and influence the
clinical outcome of leprosy.
Leptospirosis is a systemic infection that causes, among others, acute kidney
injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and
reproductive loss. In an effort to reduce uterine inflammatory responses induced by
Leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and
astragalin in a mouse model. Our results showed that treatment with emodin, thymol,
and astragalin alleviated uterine inflammation induced by leptospira infection via
suppression of pro-inflammatory cytokine expression and prevented tissue damage.
Furthermore, we used primary endometrium epithelial cells to show that treatment
with these chemicals inhibited the expression of proinflammatory cytokines TNF-
alpha, IL-1 beta, and IL-6 using enzyme-linked immunosorbent assay and quantitative
polymerase chain reaction. Western blot results showed that these chemicals
suppressed the phosphorylation of p38, p65, extracellular signal-regulated kinase,
and c-Jun N-terminal kinase. These results indicate that treatment with emodin,
thymol, and astragalin suppressed inflammatory response by regulating NF-kappa B
and mitogen-activated protein kinase signaling pathways in leptospira-infected
uterine and endometrium epithelial cells of mice.
With the increasing use of real-time PCR techniques, Leptospira isolation has
mostly been abandoned for the diagnosis of human leptospirosis. However, there is a
great value of collecting Leptospira isolates to better understand the epidemiology
of this complex zoonosis and to provide the researchers with different isolates. In
this study, we have successfully isolated different Leptospira strains from
BacT/Alert aerobic blood culture bottles and suggest that this privileged
biological material offers an opportunity to isolate leptospires. (C) 2017 Elsevier
Inc. All rights reserved.
Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder of purine metabolism
caused by a mutation in Xq26.2-q26.3 (OMIM 308000.0004). The presence of the
diagnostic triad, i.e. signs of self-injurious behavior (SIB) and results of
pedigree analysis and novel molecular biology & genetic testing, confirms the
diagnosis of LNS. With a level of hypoxanthine guanine phosphoribosyl-transferase 1
(HPRT1) enzyme activity < 2%, patients develop neurological, neurocognitive, and
neuromotor symptoms along with SIB. Described here is a case of 4-year-old boy who
was diagnosed with LNS. The boy displayed SIB, i.e. biting of the lips and fingers,
and he had cerebral venous sinus thrombosis caused by LNS.
In human leukaemia, resistance to chemotherapy leads to treatment ineffectiveness
or failure. Previous studies have indicated that cancers with increased levels of
aerobic glycolysis are insensitive to numerous forms of chemotherapy and respond
poorly to radiotherapy. Whether glycolysis serves a key role in drug resistance of
leukaemia cells remains unclear. The present study systematically investigated
aerobic glycolytic alterations and regulation in K562/adriamycin (ADM) multidrug-
resistant (MDR) and ADM-sensitive K562 leukaemia cells in normoxia, and the
association between drug resistance and improper glycometabolism. The cell
proliferating activity was assessed with an MTT colorimetric assay, glycolysis,
including glucose consumption, lactate export and key-enzyme activity was
determined by corresponding commercial testing kits. The expression levels of
hexokinase-II (HK-II), lactate dehydrogenase A (LDHA), glucose transporter-4 (GLUT-
4), AKT, p-AKT473/308, mammalian target of rapamycin (mTOR), p-mTOR, c-Myc and
hypoxia-inducible factor-1 alpha (HIF-1 alpha) were analyzed by western blot or
reverse transcription-quantitative polymerase chain reaction (RT-qPCR). K562/ADM
cells exhibited increased glucose consumption and lactate accumulation, increased
lactate dehydrogenase, hexokinase and pyruvate kinase activities, and reduced
phosphofructokinase activity. In addition, K562/ADM cells expressed significantly
more HK-II and GLUT-4. Notably, inhibition of glycolysis effectively killed
sensitive and resistant leukaemia cells and potently restored the sensitivity of
MDR cells to the anticancer agent ADM. The AKT serine/threonine kinase
(AKT)/mechanistic target of rapamycin (mTOR) signalling pathway, a crucial
regulator of glycometabolic homeostasis, mediated over-activation and upregulation
of c-Myc expression levels in K562/ADM cells, which directly stimulated glucose
consumption and enhanced glycolysis. In conclusion, the present study demonstrated
that MDR leukaemia cells exhibit increased aerobic glycolytic activity and that
this may be responsible for resistance to chemotherapeutics in leukaemia MDR cells
via activation of the AKT-mTOR-c-Myc signalling pathway. Therefore, inhibition of
aerobic glycolysis may be a potential therapeutic strategy to efficiently treat
multidrug resistance in relapsed or refractory leukaemia and cancers.
To observe the biological characteristic and the prognoses in patients with acute
erythroleukemia (AEL). The results of 167 patients with newly diagnosed AEL, from
January 2004 and June 2014 in the department of Hematology, Shandong Province
Chinese Medicine Hospital, were reviewed by morphology, immunology, cytogenetics,
molecular biology. Flow cytometry analysis indicated that CD13 (96.1 %), CD33 (95.1
%), CD117 (87.4 %) and CD34 (79.4 %) were highly expressed in AEL. 56 of 148 (37.8
%) AEL patients had a variety of cytogenetic abnormalities, 27 of 148 (18.2 %)
patients were complex karyotype (abnormal involving 3 or more chromosomes), the
abnormalities of chromosomes 3, 5, 7 and 8 were more frequently involved and the
most common one was +8, accounting for 35.7 % of all abnormal karyotype, followed
by 5q- (17.9 %). Mutation analysis showed CEBPA mutation ratio of AEL patients was
44.0 % (11/25), that of NPM1as 15.4 % (4/26). Initial induced remission rate of AEL
was 56.6 % (30/53), compared by 33.3 % (4/12) of MDSM6. Survival analysis was shown
that the overall survival in female was better than that in male (P = 0.047). The
overall survival time of transplantation group was significantly longer than
chemotherapy group (P = 0.000). The OS of 13-39 years old group was the best, 40-49
years old group took second place, >50 years old group appeared to be the worst.
Patients with AML-M-6 had dysplasia in varying degrees in granulocyte, erythrocyte
and megakaryocyte series. Periodic acid-Shiff reaction staining in polychromatic
erythroblast and ortho-chromatic erythroblast had a specificity in the diagnosis of
AEL. AEL had its own unique biological features, and allogeneic hematopoietic stem
cell transplantation could significantly improve its poor prognosis.
This paper sets forth a novel approach to calculate the levelized cost of
electricity (LCOE) using a probabilistic model that accounts for endogenous input
parameters. The approach is applied to the example of a nuclear and gas power
project. Monte Carlo simulation results show that a correlation between input
parameters has a significant effect on the model outcome. By controlling for
endogeneity, a statistically significant difference in the mean LCOE estimate and a
change in the order of input leverages is observed. Moreover, the paper discusses
the role of discounting options and external costs in detail. In contrast to the
gas power project, the economic viability of the nuclear project is considerably
weaker. (C) 2017 Elsevier Ltd. All rights reserved.
Analysis of microarray data obtained by comparing gene expression between 2-week-
old infant and 7-week-old mature SD rat testes revealed novel targets involved in
tumor suppression. Reverse-transcription polymerase chain reaction and Northern
blotting indicated that Tusc3 gene expression was upregulated in the normal
maturing testis and prostate and other organs such as the cerebrum and ovary. Tumor
suppressor candidate 3 protein expression was detected in these same organs at a
size of about 40 kDa, in accord with the predicted molecular size. In situ
hybridization and immunohistochemistry showed that mRNA and protein localization
were prevalent in the testis spermatocytes and interstitial cells such as the
Leydig cells, as well as prostate epithelial cells. These data suggest that TUSC3
is deeply involved in spermatogenesis in the testis, inducing sperm differentiation
and maturation, and plays a role in normal prostate development and tumor
suppression.
Individuals are not merely passive vessels of whatever beliefs and opinions they
have been exposed to; rather, they are attracted to belief systems that resonate
with their own psychological needs and interests, including epistemic, existential,
and relational needs to attain certainty, security, and social belongingness. Jost,
Glaser, Kruglanski, and Sulloway (2003) demonstrated that needs to manage
uncertainty and threat were associated with core values of political conservatism,
namely respect for tradition and acceptance of inequality. Since 2003 there have
been far more studies on the psychology of left-right ideology than in the
preceding half century, and their empirical yield helps to address lingering
questions and criticisms. We have identified 181 studies of epistemic motivation
(involving 130,000 individual participants) and nearly 100 studies of existential
motivation (involving 360,000 participants). These databases, which are much larger
and more heterogeneous than those used in previous meta-analyses, confirm that
significant ideological asymmetries exist with respect to dogmatism,
cognitive/perceptual rigidity, personal needs for order/structure/closure,
integrative complexity, tolerance of ambiguity/uncertainty, need for cognition,
cognitive reflection, self-deception, and subjective perceptions of threat.
Exposure to objectively threatening circumstances-such as terrorist attacks,
governmental warnings, and shifts in racial demography-contribute to modest
"conservative shifts" in public opinion. There are also ideological asymmetries in
relational motivation, including the desire to share reality, perceptions of
within-group consensus, collective self-efficacy, homogeneity of social networks,
and the tendency to trust the government more when one's own political party is in
power. Although some object to the very notion that there are meaningful
psychological differences between leftists and rightists, the identification of
"elective affinities" between cognitive-motivational processes and contents of
specific belief systems is essential to the study of political psychology.
Political psychologists may contribute to the development of a good society not by
downplaying ideological differences or advocating "Swiss-style neutrality" when it
comes to human values, but by investigating such phenomena critically, even-or
perhaps especially-when there is pressure in society to view them uncritically.
To decrease the use of fossil fuels and face the energetic demand, the integration
of renewable energy is a necessary step. Part of this renewable energy can be
supplied by the production of electricity from photovoltaic panels and windfarms.
The massive use of these intermittent energies will lead to overproduction periods,
and there is consequently a need to convert this surplus of electricity into a
storable form of energy. Power-to-gas (PtG) technology consists in using
electricity to convert water into hydrogen by electrolysis, and then to synthetize
methane from carbon dioxide and hydrogen. Techno-economic and Life Cycle Assessment
of methane production via the combination of anaerobic digestion and PtG technology
have been applied to sewage sludge valorization. Process studies and equipment
design have been addressed considering already available technologies. Sensitivity
analyses have been done on biogas upgrading technologies, electricity prices,
annual operation time and composition of the electricity mix with also a comparison
between PtG and direct injection. It appears that the more the electricity is
expensive, the longer the operation time of the methanation process must be to be
competitive with injection of methane from biogas. Reduction of electricity
consumption of the electrolysis step decreases production costs. Even if the
current context does not feature adapted conditions to ensure an economically
viable chain, the evolution of the energetic context in the next few years as well
as the expected technological improvements will contribute to overall cost
reduction. From an environmental point of view, continuous PtG generates more
greenhouse gases than direct injection, but intermittent operation with use of
renewable electricity can significantly reduce GHG emissions. From an endpoint
impacts perspective, impact from continuous PtG are higher than biogas upgrading,
but much lower than fossil energy. Future development of low electricity
consumption of the electrolysis process, and integration of renewable credits from
CO2 valorization can increase the competitiveness of this technology. (C) 2016
Published by Elsevier Ltd.
Electrical arcs emit extremely high intensity light across a wide spectrum that can
damage eye delicate structures, such as the cornea or the retina. Developing
industry safety standards to mitigate light hazards is a critical component of arc
flash safety. Accurate measurement of light intensity is the first step in
understanding the level of eye protection needed. Traditionally, light measurement
devices are an assembly of light detecting resistors made from cadmium sulfide
(CdS) or silicon (Si) cells. However, their response times are inadequate for
capturing the peak light intensity or the dynamic changes during the initial arc
flash. In addition, the brightness of an arc flash is greater than the measurable
light levels from traditional light measurement devices. Furthermore the light
sensitivity of traditional sensors does not match the Commission Internationale de
l'Eclairage (CIE) luminosity function V(lambda) curve, which defines the human
eye's sensitivity to bright light as a function of wavelength under typical ambient
light conditions. This paper discusses a novel light measurement technique to
overcome the limitations of traditional approaches. This design is capable of
measuring the light intensity of the arc flash as perceived by human eyes. These
results can be used to evaluate the potential of an arc flash to harm the eyes.
The use of laser microbeams and optical tweezers in a wide field of biological
applications from genomic to immunology is discussed. Microperforation is used to
introduce a welldefined amount of molecules into cells for genetic engineering and
optical imaging. The microwelding of two cells induced by a laser microbeam
combines their genetic outfit. Microdissection allows specific regions of genomes
to be isolated from a whole set of chromosomes. Handling the cells with optical
tweezers supports investigation on the attack of immune systems against diseased or
cancerous cells. With the help of laser microbeams, heart infarction can be
simulated, and optical tweezers support studies on the heartbeat. Finally, laser
microbeams are used to induce DNA damage in living cells for studies on cancer and
ageing.
Conversion of lignocellulosic biomass to electricity using fuel cell technologies
is a promising but challenging research topic for sustainable electricity
production. This is because that lignocellulosic biomass generally cannot be
directly used as a fuel for electricity generation in a conventional fuel cell with
high efficiency. Typical fuel cells that can convert lignocellulosic biomass to
electricity under mild conditions (< 100 degrees C) include microbial fuel cells
(MFC) and novel direct biomass fuel cells (DBFC) such as that mediated by polyoxo-
metalates (POMs) developed recently. However, the efficiency and power output for
these low-temperature fuel cells still need to be improved for practical
applications. In this review, we focus on the research advances of electricity
generation in fuel cells that can be operated at low temperatures. More
specifically, we discussed the progress, challenge and perspectives of biomass-
fueled MFCs. Recent interesting researches on DBFC were also highlighted in terms
of the efficiency, principles, and technological obstacles. As concluded in this
work, lignocellulosic biomass is a promising feedstock for fuel cells because it is
renewable, carbon neutral, and sustainable. However, the power density of
lignocelluose-fueled MFC are usually far below that required for commercial
applications. Improving fermentable sugar release from lignocellulosic biomass and
increasing the cell output power are the main research points. DBFC can obtain a
high theoretical exergy recovery; however, it is still in its early stage of
development with low efficiency. More research should be focused on the electrode
development, cell design, parameter optimization, process integration, as well as
understanding fundamental process mechanisms.
Expression profiling of miRNAs has the ability to reveal the essence of somatic
embryogenesis (SE). qRT-PCR is one of the most commonly used techniques for dynamic
miRNA detection but requires optimal reference genes for data reliability. This is
the first report on reference gene validation for miRNA expression normalization in
Lilium (Lilium pumilum DC. Fisch. and Lilium davidii var. unicolor). In this study,
seventeen miRNAs together with two snRNAs (U4, U6), one rRNA (5S rRNA) and three
protein-coding genes (FP, ACT, GAPDH) were selected as reference candidates, and
their expression stability was validated by qRT-PCR among eleven developing SE
cultures in two lilies. Four normalization algorithms, including geNorm,
BestKeeper, NormFinder and RefFinder, were also used to evaluate the stability of
the reference candidates. For Lilium pumilum DC. Fisch., lpu-miR159a was the
optimal reference gene during SE, followed by lpu-miR408b, while U6 was the least
stable reference candidate. For Lilium davidii var. unicolor, FP presented greater
stability than did half of the miRNA candidates, but the best reference gene was
lda-miR162, followed by lda-miR159a. Further analysis of the expression level of
miR156 and miR529 was used to evaluate the validity of the reference genes in both
lilies. In general, miRNAs are superior to common protein-coding genes and
snRNAs/rRNAs as reference genes for miRNA expression normalization during Lilium
SE, and the most suitable reference miRNA is different between two species in the
same Lilium genus. This is a pioneer study using suitable miRNAs as reference genes
in Lilium and constitutes a small but essential step for the further exploration of
miRNA function in Lilium, thus offering valuable references for other plants.
Many of the great morphologists of the nineteenth century marvelled at similarities
between the limbs of diverse species, and Charles Darwin noted these homologies as
significant supporting evidence for descent with modification from a common
ancestor. Sir Richard Owen also took great care to highlight each of the elements
of the forelimb and hindlimb in a multitude of species with focused attention on
the homology between the hoof of the horse and the middle digit of man. The ensuing
decades brought about a convergence of palaeontology, experimental embryology and
molecular biology to lend further support to the homologies of tetrapod limbs and
their developmental origins. However, for all that we now understand about the
conserved mechanisms of limb development and the development of gross morphological
disturbances, little of what is presented in the experimental or medical literature
reflects the remarkable diversity resulting from the 450 million year experiment of
natural selection. An understanding of conserved and divergent limb morphologies in
this new age of genomics and genome engineering promises to reveal more of the
developmental potential residing in all limbs and to unravel the mechanisms of
evolutionary variation in limb size and shape. In this review, we present the
current state of our rapidly advancing understanding of the evolutionary origin of
hands and feet and highlight what is known about the mechanisms that shape diverse
limbs. This article is part of the themed issue 'Evo-devo in the genomics era, and
the origins of morphological diversity'.
Limonium bicolor, a typical recretohalophyte, has a specialized salt-secreting
structure in the epidermis called the salt gland and plays a significant role in
improving saline land. Understanding the molecular mechanisms of salt secretion and
salt gland development requires an efficient L. bicolor transformation system,
which is described in this report. Leaf explants were incubated with Agrobacterium
tumefaciens strain EHA105 harboring the plasmid pTCK303 containing the beta-
glucuronidase gene (GUS) as the transgene reporter and the hygromycin B resistance
gene as a selectable marker. Up to 96.9% of leaves were induced to regenerate
shoots on an Murashige and Skoog (MS) medium supplemented with 4.4 mu M 6-
benzyladenine and 1.1 mu M alpha-naphthaleneacetic acid; roots were induced on the
MS medium containing 2.5 mu M indole-3-butyric acid. This tissue culture system was
suitable for Agrobacterium-mediated transformation of L. bicolor. Pre-cultivated
explants (2 d old) were incubated with Agrobacterium (0.6-0.7 at OD600) in a
shaking culture for 20 min; the explants and bacterium were co-cultivated for 4 d
in the dark before the explants were transferred to a selection medium containing 8
mg/L hygromycin B and 600 mg/L piperacillin sodium (added to prevent continued
Agrobacterium growth). Histochemical assays and PCR to detect the GUS gene showed
that transformation frequency was 4.43%. Quantitative PCR and Northern blotting
further verified the integration and presence of the GUS gene in L. bicolor. This
is the first report of an Agrobacterium-based transformation system for L. bicolor.
The system will facilitate a research on the identity and function of genes
involved in salt gland development and salt secretion.
Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating the
biological functions and underlying molecular mechanisms of glioma. Here, we
investigated the expression level and biological function of linc-OIP5 in glioma.
In the current study, we used quantitative real-time polymerase chain reaction
(qRT-PCR) to determine the expression of linc-OIP5 in glioma tissues and in
adjacent normal tissues. Level of linc-OIP5 was up-regulated in glioma tissues and
significantly correlated with the advanced tumor stage (III/IV). Subsequently, the
efficacy of knockdown of linc-OIP5 by linc-OIP5-small interfering RNA (siRNA) was
evaluated in vitro, and we found that knockdown of linc-OIP5 can inhibit glioma
cells proliferation, migration in vitro and tumor formation in vivo. Further
mechanistic studies revealed the effect of linc-OIP5 knockdown on glioma cell
phenotype at least partially through down-regulation of YAP and inhibition of Notch
signaling pathway activity. Thus, our study provides evidence that linc-OIP5 is a
potential therapeutic target and novel molecular biomarker for glioma. (C) 2017
Published by Elsevier B.V.
A quickest change detection (QCD) algorithm is proposed to address the problem of
detecting and identifying line outages in a power system. The statistics of
electricity demand are assumed to be known and propagated through a linearized
model of the equations describing the power flow balance at each node of the
network. The proposed algorithm incorporates the transient dynamics of the power
system following a line outage and is applied to the measurements of voltage phase
angles, which are collected using phasor measurement units. This adaptive algorithm
is developed by treating the QCD problem as a dynamic composite hypothesis testing
problem. It is shown to have superior performance compared with other line outage
detection algorithms previously proposed in the literature. Case studies
demonstrating this gain in performance are illustrated through the IEEE 118-bus
test system.
The control system described in this work implements automatically a digital
controller that achieves the highest possible cross-over frequency for the
specified phase margin by applying a design method based on the measured frequency
response of the DC/DC converter, identified by the system itself. The algorithms
for the design, identification process and control of the converter are implemented
on a SoC (System on Chip). The proposed algorithm to calculate the controller is
described and the identification process and the designed compensator are validated
through measurements on an actual converter.
A digital dual-mode linear quadratic regulator (LQR) with feedforward optimal
controller is presented, which allows voltage control of a boost converter for
wide-load-range condition, whether in continuous conduction mode (CCM) or in
discontinuous conduction mode (DCM). Based on the conventional LQR method, the
proposed controller is designed and makes the following two improvements. First, in
order to eliminate the phase error caused by right-half-phase zero emerged in non-
minimum phase boost converter, a feedforward controller is implemented by zero
phase error tracking control technique because the inverse of non-minimum phase
system is unstable. Second, since the models of DC-DC converter in CCM or DCM are
different, the proposed control strategy allows boost converter to autonomously
operate in CCM or DCM controller by utilising a mode detector. The proposed mode
detector greatly enhances the control performance in both operating modes. Finally,
the proposed controller has been implemented for voltage control of a boost
converter. The simulation and experimental results show the proposed controller
offers better performance in both transient response and frequency response than
the conventional LQR controller.
Aim: Endothelial lipase (EL) is a member of the lipoprotein lipase family that
regulates HDL metabolism. EL is known to act as a bridging molecule for monocytes
or lipoproteins in vascular endothelial cells. We investigated the role and
regulatory mechanisms of EL expression in macrophages. Methods: Macrophages
originating from wild-type (EL+/+) and EL-deficient (EL-/-) mice were stimulated
with lipopolysaccharide (LPS). The expression of EL mRNA was evaluated by northern
blotting. DiI-LDL was used to measure the uptake of native low-density lipoprotein
(nLDL). Results: LPS increased EL mRNA levels by increasing intracellular oxidative
stress in the macrophages. LPS did not affect EL expression in macrophages derived
from Toll-like receptor 4 (TLR4) gene mutant mice, C3H/HeJ. The uptake of nLDL
after LPS-treatment was significantly lower in macrophages from EL-/- mice than
those from EL+/+ mice. Simvastatin suppressed the LPS-induced upregulation of EL
expression and uptake of nLDL. Conclusions: EL expression is upregulated by LPS via
TLR4 and promotes the uptake of nLDL by macrophages. Simvastatin inhibits the LPS-
induced up-regulation and uptake in macrophages. Thus, our findings provide a novel
role for EL in lipoprotein metabolism and would expand the range of anti-
atherogenic effects of statins.
Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal
intercellular signal transmitter in the immune system by recruiting lymphocytes
from the thymus and secondary lymphoid tissues. The plasma S1P concentration is
maintained by the supply of S1P from erythrocytes. Previously, we showed that S1P
release from erythrocytes is mediated by an ATP-dependent transporter. In this
study, we attempted to establish a rapid and reliable method for measuring the S1P
transport activity in erythrocytes by using a fluorescent S1P analog, 7-nitro-2-
1,3-benzoxadiazol-4-yl (NBD)-labeled S1P. NBD-S1P was released from erythrocytes in
a time-dependent manner. The NBD-S1P release was reduced after exposure to
glyburide, which is an inhibitor of the S1P transporter in erythrocytes. Moreover,
the release of NBD-S1P and S1P from erythrocytes was competitively inhibited by
intracellular S1P and NBD-S1P, respectively. These results showed that the
erythrocyte S1P transporter exports NBD-S1P. We optimized the sample-preparation
conditions and lipid extraction to increase the sensitivity of the assay.
Furthermore, we successfully measured NBD-S1P release without lipid extraction by
decreasing the concentration of BSA in the assay buffer to 0.1%. This method will
be useful for the high-throughput screening of S1P transporter inhibitors using
conventional fluorometers.
Lipid biosynthesis and its regulation have been studied mostly in the nonoleaginous
yeast Saccharomyces cerevisiae that serves as a model for eukaryotic cells. On the
other hand, the yeast Yarrowia lipolytica has been put forward as a model for
oleaginous microorganisms because its genetics is known and tools for its genetic
manipulation are becoming increasingly available. A comparison of the lipid
biosynthetic pathways that function in these two microorganisms shows many
similarities in key biosynthetic and regulatory steps. An example is the enzyme
phosphatidic acid phosphatase that controls the synthesis of triacylglycerol (TAG)
in both yeasts. Controlling the TAG synthesis is crucial for metabolic engineering
efforts that aim to increase the production of microbial lipids (i.e. single cell
oils) because TAG comprises the final product of these processes. At the same time
the comparison reveals fundamental differences (e.g. in the generation of acetyl-
CoA for lipid biosynthesis) stemming from the oleaginous nature of Y. lipolytica.
These differences warranty more studies in Y. lipolytica where the biochemistry and
molecular biology of oleaginicity can be further explored.
Changes in chromatin structure regulate gene expression and genome maintenance.
Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are
key modulators of chromatin structure. Previous work indicated that cholesterol, a
ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential
function for lipids in modulating chromatin architecture. However, the molecular
mechanisms of cholesterol's action on chromatin structure have remained unclear.
Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin
fibers reconstituted in vitro and characterized in silico the cholesterol binding
to the nucleosome. Our findings support that cholesterol assists 10 and 30 nm
chromatin formation and induces folding of long chromatin fibers as a result of
direct interaction of the cholesterol to six nucleosomal binding sites.
In crustaceans, the fascinating processes of maturation, reproductive molting and
carapace coloration are regulated by hydrophobic molecules. Interestingly, most of
the molecules are ligands of lipocalin. To understand the role of lipocalin in the
aforementioned processes at molecular level, we isolated a cDNA that belongs to the
lipocalin family, from a central nervous system cDNA library of Macrobrachium
rosenbergii. We monitored the spatial and temporal distributions of the mRNA by
using Northern Blotting analysis. Our results demonstrated that this gene expresses
abundantly in the subepidermal adipose tissue, while faintly in the hepatopancreas
and central nervous system. However, no signal was detected in other tissues
including muscle, gill and ovary. Its expression levels in subepidermal adipose
tissue during various stages of maturation as well as through the whole molting
cycle showed that prawn lipocalin is involved in sexual maturation, as the maximal
level was observed just after molt. (C) 2007 Published by Elsevier Inc.
Important insights into the role of interfacial composition and structure in
controlling the digestion of oil-water emulsions have been gained in the last
decade. The driving interest relies on: i) the necessity of controlling the
digestion of lipids to decrease or delay fat intake to address the obesity crisis
existing worldwide and ii) assuring the bioaccessibility of bioactive emulsified
lipids or hydrophobic bioactive compounds. This article mainly reviews the
relationship between the composition and structure of protein and polysaccharides
stabilized emulsions and their susceptibility to in vitro lipolysis. The analysis
concentrates on emulsions where (1) proteins or (2) polysaccharides are used as
single emulsifiers, (3) emulsions stabilized by protein-polysaccharide conjugates,
(4) protein-polysaccharide multilayer emulsions where the primary emulsion is
formed by a protein, (5) protein-polysaccharide emulsions where proteins are the
main emulsifiers and the polysaccharides perform as stabilizers. The mechanisms
involved in the control of the rate and extent of lipolysis are discussed with
special attention given to the interactions between emulsions components and bile
salts as a critical point for controlling lipids digestion. (C) 2016 Elsevier Ltd.
All rights reserved.
Previous studies have reported that lipoxin A(4) (LXA(4)) may exert a
renoprotective effect on ischemia/reperfusion injury in various animal models. The
underlying mechanism of LXA(4)-induced renoprotection during ischemia/reperfusion
injury remains to be elucidated. The present study investigated LXA4-induced
protection on renal tubular cells subjected to hypoxia/reoxygenation (H/R) injury,
and determined the effects of peroxisome proliferator-activated receptor-gamma
(PPAR gamma) and heme oxygenase-1 (HO-1) on LXA(4) treatment. HK-2 human tubular
epithelial cells exposed to H/R injury were pretreated with LXA4, signal molecule
inhibitors or the HO-1 inhibitor zinc protoporphyrin-IX, or were transfected with
PPAR. small interfering RNA (siRNA) or nuclear factor E2-related factor 2 (Nrf2)
siRNA. The protein and mRNA expression levels of PPAR. and HO-1 were analyzed using
western blotting and reverse transcription-quantitative polymerase chain reaction.
Binding activity of Nrf2 to the HO-1 E1 enhancer was determined using chromatin
immunoprecipitation. Nrf2 binding to the HO-1 antioxidant responsive element (ARE)
was assessed using electrophoretic mobility shift assay. Preincubation of cells
with LXA(4) exposed to H/R injury led to a decreased production of inducible
nitrogen oxide synthase, malondialdehyde,gamma-glutamyl transpeptidase, leucine
aminopeptidase and N-acetyl-gamma-glucosaminidase. In addition, LXA(4) pretreatment
increased cell viability, protein and mRNA expression levels of PPAR. and HO-1 and
PPAR. and HO-1 promoter activity. SB20358 is a p38 mitogen-activated protein kinase
(p38 MAPK) pathway inhibitor, which reduced LXA(4)-induced PPAR. expression levels.
LXA4 treatment upregulated p38 MAPK activation, Nrf2 nuclear translocation and
increased binding activity of Nrf2 to HO-1 ARE and E1 enhancer in cells exposed to
H/r injury. Transfection of thecells with PPAR gamma siRNA reduced the LXA(4)-
induced Nrf2 translocation. Transfection of the cells with PPAR. siRNA or Nrf2
siRNA also reduced the LXA(4)-induced increase in HO-1 expression. In conclusion,
LXA(4)-induced protection of renal tubular cells against H/R injury was associated
with the induction of PPAR. and HO-1, via activation of the p38 MAPK pathway, as
well as Nrf2 nuclear translocation and binding to HO-1 ARE and E1 enhancer.
Therefore, LXA(4)-induced renoprotection is associated with activation of the p38
MAPK/PPAR gamma/Nrf2-ARE/HO-1 pathway.
Objectives: Epidermal growth factor receptor (EGFR) mutation testing is a companion
diagnostic to determine eligibility for treatment with EGFR tyrosine kinase
inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-
based EGFR testing by digital polymerase chain reaction (dPCR), which enables
accurate quantification of target DNA, has shown promise as a minimally invasive
diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation
test developed using chip based dPCR-based detection of 3 EGFR mutations (exon 19
deletions, L858R in exon 21, and T790M in exon 20). Materials and methods: Forty-
nine patients with NSCLC harboring EGFR-activating mutations were enrolled, and
circulating free DNAs (cfDNAs) were extracted from the plasma of 21 and 28 patients
before treatment and after progression following EGFR-TKI treatment, respectively.
Results: Using reference genomic DNA containing each mutation, the detection limit
of each assay was determined to be 0.1%. The sensitivity and specificity of
detecting exon 19 deletions and L858R mutations, calculated by comparing the
mutation status in the corresponding tumors, were 70.6% and 93.3%, and 66.7% and
100%, respectively, showing similar results compared with previous studies. T790M
was detected in 43% of 28 cfDNAs after progression with EGFR-TKI treatment, but in
no cfDNAs before the start of the treatment. Conclusion: This chip-based dPCR assay
can facilitate detection of EGFR mutations in cfDNA as a minimally invasive method
in clinical settings. (C) 2017 Elsevier B.V. All rights reserved.
Background. The use of plasma as a "liquid biopsy" has gained increasing attention.
The purpose of the present study was to evaluate the diagnostic and prognostic
utility of the perioperative detection and quantitation of mRNAs encoding human
telomerase reverse transcriptase (hTERT) and glyceraldehyde 3-phosphate
dehydrogenase (GAPDH) in plasma from patients with cancer of the larynx or
hypopharynx. Methods. We recruited 47 patients with laryngeal cancer and 2 patients
with hypopharyngeal cancer, plus 27 healthy subjects. A blood sample was taken from
each patient before and after surgical resection of the tumor. We quantified hTERT
mRNA and GAPDH mRNA in plasma by real-time polymerase chain reaction (PCR).
Results. Detection of hTERT mRNA before surgery had diagnostic value (sensitivity,
22%; specificity, 100%). Detection was more frequent in patients with supraglottic
tumors than glottic tumors (p = .02) and was related to subsequent recurrence (p
= .02). Preoperative levels of hTERT mRNA in plasma were higher in patients with
subsequent recurrence (p = .046) and/or metastases (p = .047). The disease-free
survival (DFS) and overall survival (OS) of patients with plasma samples positive
for hTERT mRNA was poorer than that of patients with negative samples. Mean levels
of plasma GAPDH mRNA in untreated patients were higher than in healthy subjects (p
< .001). Conclusion. Detection and quantitation of hTERT and GAPDH mRNA in
patients' plasma might be clinically significant in cases of laryngeal and
hypopharyngeal cancer. (C) 2017 Wiley Periodicals, Inc.
This paper proposes a positive temperature coefficient (PTC) self-heating method,
in which EVs can be operated independently of external power source at low
temperature, with a lithium-ion battery (LIB) pack discharging electricity to
provide PTC material with power. Three comparative heating experiments have been
carried out respectively. With charge/discharge tests implemented, results
demonstrate the superiority of the self-heating method, proving that the discharge
capability, especially the discharge capacity of the self-heated pack is better
than that of the external power heated pack. In order to evaluate the heating
effect of this method, further studies are conducted on temperature distribution
uniformity in the heated pack. Firstly, a geometric model is established, and heat-
generation rate of PTC materials and LIB are calculated. Then, thermal
characteristics of the self-heating experiment processes are numerically simulated,
validating the accuracy of our modeling and confirming that temperature
distributions inside the pack after heating are kept in good uniformity. Therefore,
the PTC self-heating method is verified to have a significant effect on the
improvement of performance of LIB at low temperature.
The limited number of oral vaccines currently approved for use in humans and
veterinary species clearly illustrates that development of efficacious and safe
oral vaccines has been a challenge not only for fish immunologists. The
insufficient efficacy of oral vaccines is partly due to antigen breakdown in the
harsh gastric environment, but also to the high tolerogenic gut environment and to
inadequate vaccine design. In this review we discuss current approaches used to
develop oral vaccines for mass vaccination of farmed fish species. Furthermore,
using various examples from the human and veterinary vaccine development, we
propose additional approaches to fish vaccine design also considering recent
advances in fish mucosal immunology and novel molecular tools. Finally, we discuss
the pros and cons of using the zebrafish as a pre-screening animal model to
potentially speed up vaccine design and testing for aquaculture fish species. (C)
2016 The Authors. Published by Elsevier Ltd.
BACKGROUND & AIMS: Choline kinase a ( CHKA) catalyzes conversion of choline to
phosphocholine and can contribute to carcinogenesis. Little is known about the role
of CHKA in the pathogenesis of hepatocellular carcinoma ( HCC). METHODS: We
performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-
tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and
non-tumor-adjacent tissues from patients who received surgery in Shanghai, China
from January 2006 through December 2009; 48 sets of specimens ( HCC and non-tumor-
adjacent tissues) were also analyzed. CHKA gene copy number was quantified and
findings were validated by quantitative reverse transcription polymerase chain
reaction analysis. CHKA messenger RNA and protein levels were determined by
polymerase chain reaction, immunohistochemical, and immunoblot analyses. CHKA was
examined in 2 hepatocyte cell lines and 7 HCC-derived cell lines, and knocked down
with small interfering RNAs in 3 HCC cell lines. Cells were analyzed in
proliferation, wound healing, migration, and invasion assays. Cells were injected
into tail veins of mice and tumor growth and metastasis were quantified.
Immunoprecipitation and immunofluorescence assays were conducted to determine
interactions between CHKA and the epidermal growth factor receptor ( EGFR) and the
mechanistic target of rapamycin complex 2. RESULTS: Levels of CHKA messenger RNA
were frequently increased in HCC tissues compared with nontumor tissues; increased
expression was associated with amplification at the CHKA loci. Tumors that
expressed high levels of CHKA had more aggressive phenotypes, and patients with
these tumors had shorter survival times after surgery compared to patients whose
tumors expressed low levels of CHKA. HCC cell lines that stably overexpressed CHKA
had higher levels of migration and invasion than control HCC cells, and formed
larger xenograft tumors with more metastases in mice compared to HCC cells that did
not overexpress CHKA. CHKA was required for physical interaction between EGFR and
mechanistic target of rapamycin complex 2. This complex was required for HCC cells
to form metastatic xenograft tumors in mice and to become resistant to EGFR
inhibitors. CONCLUSIONS: We found levels of CHKA to be increased in human HCCs
compared to nontumor tissues, and increased expression to be associated with tumor
aggressiveness and reduced survival times of patients. Overexpression of CHKA in
HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and
ability to form metastatic tumors in mice by promoting interaction of EGFR with
mechanistic target of rapamycin complex 2.
Multiple long non-coding RNAs (lncRNAs) have been demonstrated to be involved in
liver disease. Increased cyclooxygenase-2 (COX-2) levels have also been reported to
be involved in the progression of liver cirrhosis. In the present study, the
correlations between lncRNA-COX-2 RNA expression levels, COX-2 mRNA expression
levels and liver fibrosis were examined. Liver fibrosis was induced by
intraperitoneal injection of carbon tetrachloride (CCl4) in mice for 2months (CCl4-
2M) or 3months (CCl4-3M). Liver histopathological evaluation was conducted using
hematoxylin and eosin and Masson trichrome staining. Hepatic expression of COX-2
and lncRNA-COX-2 was evaluated by reverse transcriptionquan-titative polymerase
chain reaction and immunohistochemical staining. Compared with the control group,
fibrotic areas were increased four and nine times in the CCl4-2M group and the
CCl4-3M group, respectively. LncRNA-COX-2 and COX-2 upregulation were observed in
the cirrhotic liver. COX-2 mRNA expression levels and lncRNA-COX-2 RNA expression
levels were significantly positively correlated with the fibrotic area. In
addition, COX-2 mRNA expression was significantly positively correlated with
lncRNA-COX-2 expression. These results suggest that expression of COX-2 and lncRNA-
COX-2 increased with the progression of liver fibrosis. LncRNA-COX-2 may
potentially be considered as a novel therapeutic target for liver fibrosis.
Background & Aims: Induction of donor-specific immune tolerance is a good
alternative to chronic life-long immunosuppression for transplant patients. Donor
major histocompatibility complex (MHC) molecules represent the main targets of the
allogeneic immune response of transplant recipients. Liver targeted gene transfer
with viral vectors induces tolerance toward the encoded antigen. The aim of this
work was to determine whether alloantigen gene transfer to hepatocytes induces
tolerance and promotes graft acceptance. Methods: C57BL/6 (H-2b) mice were treated
with adeno-associated viral (AAV) vector targeting the expression of the MHC class
I molecule H-2K(d) to hepatocytes, before transplantation with fully allogeneic
pancreatic islet from BALB/c mice (H-2d). Results: AAV H-2K(d) treated mice were
tolerant to the alloantigen, as demonstrated by its long-term expression by the
hepatocytes, even after a highly immunogenic challenge with an adenoviral vector.
After chemical induction of diabetes, the AAV treated mice had significantly
delayed rejection of fully allogeneic pancreatic islet grafts, with more than 40%
of recipients tolerant (>100 days). AAV-mediated expression of H-2Kd in the liver
induced the local expansion of CD8(+) T lymphocytes with allospecific suppressive
properties. The adoptive transfer of these liver-generated CD8(+) Tregs into naive
diabetic mice promoted the long-term survival of allogeneic pancreatic islet
grafts. Conclusion: AAV-mediated long-term expression of a single MHC class I
molecule in the liver induces the generation of a subset of allo-specific CD8(+)
Treg cells, which promote tolerance toward fully allogeneic graft. Liver gene
transfer represents a promising strategy for in vivo induction of donor-specific
tolerance. Lay summary: The liver has a special immune system, biased toward
tolerance. In this study, we investigated the possibility of harnessing this
property of the liver to induce tolerance to an allogeneic transplantation. We
demonstrate for the first time that the in vivo gene transfer of an allogeneic
antigen with an adeno-associated viral vector to mouse hepatocytes induces the
expansion of a population of CD8(+) regulatory T lymphocytes. These Tregs are then
instrumental in preventing the rejection of allogeneic pancreatic islets
transplanted in these animals. Allogeneic transplantation is the main treatment for
the end-stage diseases of a number of organs. Life-long immunosuppressive
treatments are still required to limit graft rejection, and these treatments
exhibit serious side effects. Our present findings open a new avenue for promoting
allo-specific tolerance via in vivo induction of CD8(+) Treg expansion. (C) 2016
European Association for the Study of the Liver. Published by Elsevier B. V. All
rights reserved.
Recent years have seen a growing interest in PBC within the scientific community,
healthcare providers and industries, coupled with great advances in the
understanding of the molecular and genetic basis and the natural history of the
disease. Several disease-modifying agents targeting the immune-mediated response
and bile-acid therapies are at different stages of development, some with promising
results. A new drug, obeticholic acid, has been recently registered in the US and
Europe as a second-line treatment in refractory PBC. International cohort studies
have highlighted a disease heterogeneity, and so the need to provide patients with
a more personalised management based on their risk of disease progression. Major
challenges remain the development of surrogate endpoints in clinical trials
acceptable to regulatory authorities, in a disease with a relatively low rate of
events; and the development of clinical tools for patient's risk stratification and
selection of those with greatest potential benefit from second-line therapies.
The tumor microenvironment (TME) in the liver plays an important role in primary
and metastatic liver tumor formation and tumor growth promotion. Cellular and non-
cellular components of the TME significantly influence tumor development, growth,
metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular
components of the TME in the liver not only consist of infiltrating immune cells,
but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC)
and hepatic stellate cells (HSC), which promote tumor growth by negatively
regulating tumor-associated immune responses. In this review, we characterize cells
of the TME with pro-and anti-tumor function in primary and metastatic liver tumors.
Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite
the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic
approaches targeting the TME could unleash tumor-specific immune responses to
improve survival of liver cancer patients. Published by Elsevier Inc.
Background: Previous studies have indicated that Tec tyrosine kinase is
differentially expressed in the regenerating liver. The purpose of the present
study was to further investigate the potential involvement of Tec tyrosine kinase
in hepatocyte proliferation and liver regeneration. Methods: Tec kinase gene
expression after partial (two-thirds) hepatectomy was examined by representational
difference analysis. Tissue distribution and potential involvement of Tec kinase in
liver regeneration and hepatocyte proliferation were then determined by northern
blotting, reverse transcription-polymerase chain reaction (RT-PCR), and western
blotting. Full-length rat Tec cDNA was cloned. Results: Using this cDNA as the
probe, northern blotting showed that Tec was specifically expressed in liver and
kidney, the highest expression of Tec being detected in embryonic day 15-19 fetal
livers. In contrast, the expression level of Tec in adult and neonatal rat livers
was significantly decreased. Similar results were obtained from western blotting
analyzes. It was thus hypothesized that Tec might be involved in hepatocyte
proliferation. To test this hypothesis, Tec expression was examined in regenerating
rat livers. An increase in Tec expression and activation of Tec kinase were
observed within 1 h after partial hepatectomy. Moreover, it has been shown that
hepatocyte growth factor (HGF) dramatically induces Tec expression in primary rat
hepatocytes. Additionally, it was observed that Tec gene expression in serum-
starved liver tumor cell line HepG2 was substantially decreased. Stimulation with
10% fetal bovine serum and insulin but not epidermal growth factor resulted in
dramatic elevation of Tec expression in these cells. Conclusion: Tec is an
inducible early response gene that might enhance hepatocyte proliferation and liver
regeneration.
The aim of this single-center cross-sectional study was to detect the prevalence of
selected periodontal pathogenic bacteria and active matrix metalloproteinase-8
(aMMP-8) level in patients before (preLTx) and after liver transplantation
(postLTx). Periodontal pocket depth (PPD) and clinical attachment loss (CAL) were
assessed. Subgingival biofilm samples were analyzed using polymerase chain reaction
(PCR) to detect 11 common periodontal pathogens. Gingival crevicular fluid (GCF)
samples were analyzed with enzyme-linked immunosorbent assay (ELISA) to determine
aMMP-8 level and assigned to a scoring system: score 0: 0-8 ng/ml, score 1: 8-20
ng/ml, and score 2: >20 ng/ml. The following were used for the statistical
analysis: t test, Mann-Whitney U test, Fishers test (alpha = 5 %). In total, 110
patients (preLTx: n = 35, postLTx: n = 75) could be included in the study.
Periodontal findings were not significantly different between groups. In
microbiological analysis, a significantly higher prevalence of Campylobacter rectus
in preLTx group was detected (p = 0.03). Significantly more patients with score 0
in postLTx group (p = 0.024) and significantly more patients with score 1 in preLTx
group were found (p = 0.004). Furthermore, aMMP-8 concentrations for patients with
moderate periodontitis were significantly lower in postLTx group compared to preLTx
group (p = 0.045). Additionally, in postLTx group, aMMP-8 concentration was
significantly higher in patients with severe periodontitis compared to those with
no/mild periodontitis (p = 0.016). LTx appears to affect aMMP-8 level, but not
bacterial findings in patients after LTx. Determination of aMMP-8 level in patients
after LTx with immunosuppressive medication might lead to wrong interpretation of
the results.
In this paper, an adaptive synchronous rectifier (SR) driving scheme for the LLC
resonant converters using the ripple counter concept is proposed, along with two
methods of implementation. With the proposed scheme, the SR drain to source voltage
is sensed to detect the body diode conduction, based on which the SR on-time can be
well tuned to eliminate the body diode conduction. One proposed implementation
tunes the SR on-time every switching cycle based on the ripple detection; another
proposed implementation tunes the SR on-time every nth switching cycle (n = 1, 2,
3...) based on the ripple counter, which is suitable for the high frequency LLC
converters. The proposed SR driving scheme has the simple implementation, requires
only low-cost digital controllers and occupies very few controller resources. More
importantly, since the digital controllers have already been widely adopted in the
control of the LLC converters, the proposed adaptive SR driving method can be
embedded into these digital controllers with little extra cost. Furthermore, how to
integrate the proposed SR driving method with closed-loop control is explained in
details. Experimental results are demonstrated on a 130kHz LLC converter with
100MHz microcontroller (MCU) and a 500kHz LLC converter with a 60MHz MCU and a
ripple counter.
in this paper, the dynamics of the half-bridge LLC resonant converter are
investigated based on the small signal model and a piecewise PI regulation is
studied and derived by simulation. Small-signal dynamics of the circuit under
consideration contain many factors that may affect regulation accuracy and
performance of digitally controlled regulators. The load factor is specifically
addressed here. The objective of this paper is to introduce a digital piecewise PI
compensation to achieve time-optimal response to an external disturbance such as a
step load transient.
Long non-coding RNAs (lncRNAs), which represent a new frontier in molecular
biology, play important roles in regulating gene expression at epigenetic,
transcriptional and post-transcriptional levels. More and more lncRNAs have been
found to play important roles in normal cell physiological activities, and
participate in the development of varieties of tumors and other diseases.
Previously, we have only been able to determine the function of lncRNAs through
multiple mechanisms, including genetic imprinting, chromatin remodeling, splicing
regulation, mRNA decay, and translational regulation. Application of technological
advances to research into the function of lncRNAs is extremely important. The major
tools for exploring lncRNAs include microarrays, RNA sequencing (RNA-seq), Northern
blotting, real-time quantitative reverse transcription-polymerase chain reaction
(qRT-PCR), fluorescence in situ hybridization (FISH), RNA interference (RNAi), RNA-
binding protein immunoprecipitation (RIP), chromatin isolation by RNA purification
(ChIRP), crosslinking-immunopurification (CLIP), and bioinformatic prediction. In
this review, we highlight the functions of lncRNAs, and advanced methods to
research lncRNA-protein interactions.
Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis
and prognosis of sporadic colorectal cancer. This study aimed to characterize the
expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage
colon cancer (CC). The microsatellite instability (MSI) status was examined by a
multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The
differentially expressed lncRNAs and mRNAs were determined by bioinformatic
analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by
quantitative real-time polymerase chain reaction (qRT-PCR). We found that 16 out of
67 CC had MSI-L CC and 7 with MSI-H. In comparison with that in five non-tumor
colonic samples, microarray indicated that 1492 lncRNAs and 1639 mRNAs were
upregulated while 1804 lncRNAs and 1073 mRNAs downregulated in four pMMR early-
stage CC. Bioinformatic analyses revealed that the differentially expressed mRNAs
were involved in the process of cell division, angiogenesis, apoptotic,
differentiation, the PI3K-Akt/p53/TNF pathways and others. The co-expression lncRNA
and mRNA networks indicated five hot spots with significantly high co-expression
degrees. Further quantitative RT-PCR revealed that 4 out of 6 lncRNAs were
significantly upregulated while the other 2 lncRNAs were downregulated in the CC.
Stratification analysis demonstrated that 5 out of 6 lncRNAs were significantly
associated with TNM stage and/or distant metastasis in this population.
Differentially expressed lncRNAs were significantly associated with clinical
features of patients with pMMR CC and may participate in the tumorigenesis of pMMR
CC.
Loki Patera is one of the most dramatically time-variable volcanic features on Io,
exhibiting episodic brightening events every 1-3 years that may produce over 15% of
lo's global heat flow. We observed three such brightening events with adaptive
optics imaging at the Keck and Gemini N telescopes over the course of 70 nights of
observation in 2013-2016. The high cadence and multi-wavelength nature of the
observations provides constraints on models for activity at Loki Patera. The Matson
et al. (2006) model for Loki Patera as an overturning basaltic magma sea is adapted
to fit the observations of all three events. In particular, we adjust the details
of the overturn progression, and modify the lava thermal properties to include
dependencies on temperature and porosity, to improve the fit to the data. The
preferred models find overturn front propagation velocities of 1.2-1.7 km/day,
corresponding to resurfacing rates of 1500-2200 m(2)/s. The time intervals of 440-
540 days between successive events are roughly consistent with the 540-day period
calculated by Rathbun et al. (2002) for events prior to 2001. The best coverage was
obtained for the 2016 brightening; model fits to this event require a lava bulk
thermal conductivity of 0.55-0.75 W/m/K, with the best fit obtained for a value of
similar to 0.7 W/m/K and an average porosity that decreases during cooling. For all
three events, the overturn front appears to propagate around the patera in the
clockwise direction, opposite to what has been inferred for past brightening
events. There is evidence that the overturn may be more complex than a single
propagating wave, perhaps involving multiple simultaneous resurfacing waves as well
as portions of the patera that are active even after the nominal bright phase has
ended. The measured intensities are anomalously low when Loki Patera is viewed at
high emission angles, suggestive of topographic shadowing due to a raised area or
the edge of the depression in which the magma sea resides. (C) 2017 Elsevier Inc.
All rights reserved.
There is an unmet need for herbal medicine identification using a fast, sensitive,
and easy-to-use method that does not require complex infrastructure and well-
trained technicians. For instance, the detection of adulterants in Lobelia
chinensis herbal product has been challenging, since current detection technologies
are not effective due to their own limits. High Resolution Melting (HRM) has
emerged as a powerful new technology for clinical diagnosis, research in the food
industry and in plant molecular biology, and this method has already highlighted
the complexity of species identification. In this study, we developed a method of
species specific detection of L. chinensis using HRM analysis combined with
internal transcribed spacer 2. We then applied this method to commercial products
purporting to contain L. chinensis. Our results demonstrated that HRM can
differentiate L. chinensis from six common adulterants. HRM was proven to be a fast
and accurate technique for testing the authenticity of L. chinensis in herbal
products. Based on these results, a HRM approach for herbal authentication is
provided .
In the last decade, China has implemented more public-private partnership (PPP)
projects in the water sector compared to other sectors. However, efficient
management of risks in these projects remains problematic. While there have been
many studies that have examined risks associated with PPPs in China, the experience
of local governments with risks has received little or no attention in the
literature. Moreover, the stages at which the risks are significant and how these
risks are interrelated have not been researched. This paper examines risks as
experienced from the local government's perspective and how they manifest across
five PPP stages: (1) feasibility, (2) procurement, (3) construction, (4) operation,
and (5) transfer. The interrelationship between the risks across the PPP stages is
also examined. Data was collected via questionnaire surveys and interviews, and it
was analyzed using quantitative and qualitative analysis. The findings reveal
critical risk for local governments and how their impacts vary across project
stages. Some of the risks influence other risks both within and across the five PPP
stages. The findings provide significant insight into the dynamic nature risks in
PPP water projects, which has important implications for practitioners when
developing risk mitigation strategies. (C) 2017 American Society of Civil
Engineers.
The skin can serve as an interstitial Na+ reservoir. Local tissue Na+ accumulation
increases with age, inflammation and infection. This increased local Na+
availability favors pro-inflammatory immune cell function and dampens their anti-
inflammatory capacity. In this review, we summarize available data on how NaCl
affects various immune cells. We particularly focus on how salt promotes pro-
inflammatory macrophage and T cell function and simultaneously curtails their
regulatory and anti-inflammatory potential. Overall, these findings demonstrate
that local Na+ availability is a promising novel regulator of immunity. Hence, the
modulation of tissue Na+ levels bears broad therapeutic potential: increasing local
Na+ availability may help in treating infections, while lowering tissue Na+ levels
may be used to treat, for example, autoimmune and cardiovascular diseases.
In order to obtain very precise measurements of the position of agents located at a
considerable distance using a sensor system based on position sensitive detectors
(PSD), it is necessary to analyze and mitigate the factors that generate
substantial errors in the system's response. These sources of error can be divided
into electronic and geometric factors. The former stem from the nature and
construction of the PSD as well as the performance, tolerances and electronic
response of the system, while the latter are related to the sensor's optical
system. Here, we focus solely on the electrical effects, since the study, analysis
and correction of these are a prerequisite for subsequently addressing geometric
errors. A simple calibration method is proposed, which considers PSD response,
component tolerances, temperature variations, signal frequency used, signal to
noise ratio (SNR), suboptimal operational amplifier parameters, and analog to
digital converter (ADC) quantitation SNRQ, etc. Following an analysis of these
effects and calibration of the sensor, it was possible to correct the errors, thus
rendering the effects negligible, as reported in the results section.
The reliance on sales taxation has increased in both states and counties. This
study aggregated county-level data and empirically explored the associations
between state-local sales taxes and economic activity by industry types in county
governments for the period of 1990-2013. The results revealed negative associations
of sales tax rates with economic activity, especially in the manufacturing
industry. Further, the findings provided the spatial dependence of economic
activity across counties as a form of possible spillover. This study suggests that
policymakers should pay attention to how the manufacturing and retail industries
respond to any changes in sales tax rates for business activity.
The prosperity of location-based services (LBSs) makes more and more people pay
close attention to personal privacy. In order to preserve users privacy, several
schemes utilized a trusted third party (TTP) to obfuscate users, but these schemes
were suspected as the TTP may become the single point of failure or service
performance bottleneck. To alleviate the suspicion, schemes with collaborative
users to achieve k-anonymity were proposed. In these schemes, users equipped with
short-range communication devices could communicate with adjacent users to
establish an anonymous group. With this group, the user can obfuscate and hide
herself behind at least k - 1 other users. However, these schemes are usually more
effcient in snapshot services than continuous ones. To cope with the inadequacy,
with the help of caching in mobile devices, we propose a query information blocks
random exchange and results caching scheme (short for CaQBE). In this scheme, a
particular user is hidden behind collaborative users in snapshot service, and then
the caches further preserve the privacy in continuous service. In case of the
active adversary launching the query correlation attack and the passive adversary
launching the impersonation attack, a random collaborative user selection and a
random block exchange algorithm are also utilized. Then based on the feature of
entropy, a metric to measure the privacy of the user against attacks from the
active and passive adversaries is proposed. Finally, security analysis and
experimental comparison with other similar schemes further verify the optimal of
our scheme in effectiveness of preservation and effciency of performance.
This study examined the incidence of PTSD and psychiatric co-morbidity among women
who experienced stillbirth and investigated the relationship between locus of
control, trauma characteristics of stillbirth, posttraumatic cognitions, PTSD and
co-morbid psychiatric symptoms following stillbirth. Fifty women recorded
information on stillbirth experiences, and completed the Posttraumatic Stress
Diagnostic Scale, General Health Questionnaire-28, Edinburgh Post-natal Depression
Scale, Rotter's Locus of Control Scale and the Posttraumatic Cognitions Inventory.
60, 28 and 12 % met the diagnostic criteria for probable full-PTSD, partial and no-
PTSD respectively. Sixty-two percent and 54 % scored at or above the cutoff of the
General Health Questionnaire-28 and postnatal depression respectively. Women who
experienced stillbirth reported significantly more psychiatric co-morbid and post-
natal depressive symptoms than the comparison group. Both groups were similar in
locus of control. Women who experienced stillbirth reported negative cognitions
about the self the most. After adjusting for postnatal depression, trauma
characteristics were significantly correlated with Posttraumatic cognitions which,
in turn, were significantly correlated with PTSD and psychiatric co-morbidity.
Locus of control was not significantly correlated with psychological outcomes.
Mediational analyses showed that negative cognitions about self mediated the
relationship between trauma characteristics and psychiatric co-morbidity only.
Women reported a high incidence of probable PTSD and co-morbid psychiatric symptoms
following stillbirth. Stillbirth trauma characteristics influenced how they
negatively perceived themselves. This then specifically influenced general
psychological problems rather than PTSD symptoms.
In this paper, we propose a multi-cue object representation for image
classification using the standard bag-of-words model. Ever since the success of the
bag-of-words model for image classification, several modifications of it have been
proposed in the literature. These variants target to improve key aspects, such as
efficient and compact dictionary learning, advanced image encoding techniques,
pooling methods, and efficient kernels for the final classification step. In
particular, "soft-encoding" methods such as sparse coding, locality constrained
linear coding, Fisher vector encoding, have received great attention in the
literature, to improve upon the "hard-assignment" obtained by vector quantization.
Nevertheless, these methods come at a higher computational cost while little
attention has been paid to the extracted local features. In contrast, we propose a
novel multi-cue object representation for image classification using the simple
vector quantization, and show highly competitive classification performance
compared to state-of-the-art methods on popular datasets like Caltech-101 and MICC
Flickr-101. Apart from the object representation, we also propose a novel keypoint
detection scheme that helps to achieve a classification rate comparable to the
popular dense keypoint sampling strategy, at a much lower computational cost. (C)
2017 Elsevier Ltd. All rights reserved.
This article explores the ways in which London lives were written together during
the Romantic period, considering representations across different genres and media
including: poetry by William Wordsworth, Richard Horwood's house-by-house Plan of
the city (1792-9), Fores's New Guide for Foreigners ([?1789]), the 1788 volume of
Harris's List of Covent Garden Ladies, Richard Phillips' Modern London (1804) and
Pierce Egan's Life in London (1820-1). It pays particular attention to recovering
evidence of marginalised individuals, whose lives were never written at book or
article length, but of whom traces survive in glimpses and in aggregated forms such
as plate series and directories. It also discusses the life writing of communities
through the representation of common knowledge and the use of statistics,
contrasting the confident assertions of knowledge made in guides, mapping and
topography with the more conflicted and fragmented modes common in poetry and
novels. Through examining these issues, it contends that there are considerable
benefits in thinking of life writing as being intrinsic to a far wider range of
discourses than the standard biographical and autobiographical modes, arguing that
a broader conception is invaluable for recovering occluded existences, modelling
collective experience and understanding the hierarchies implicit in the ways in
which lives are culturally inscribed.
Social attachment is a biological and affective need. When this need is not met,
people experience loneliness. Loneliness is associated with impaired social
cognition, and is a risk factor for broad based morbidity across the adult lifespan
even after controlling for multiple factors. However, little is known about
loneliness in schizophrenia. Eighty-seven non-depressed individuals with
schizophrenia or schizoaffective disorder (including 51 inpatients) and 58 control
subjects completed the revised UCLA Loneliness scale. Social cognition was assessed
with a self-report questionnaire and a performance-based task. Social trait
perception was assessed with a facial task. Comorbid medical diagnoses were
available for all inpatients. Patients reported greater loneliness levels than
controls, while in- and out-patients did not significantly differ. In patients,
loneliness was associated with self-report measures of social cognition. Patients'
loneliness scores predicted a diagnosis of drug abuse/dependence, number of drugs
used, hypertension and abnormal hemoglobin A1c levels. Patients experienced higher
levels of loneliness than controls, independently of their objective social
isolation. Loneliness did not rely on the same psychological processes in patients
than in controls. Loneliness in schizophrenia is a symptom that deserves more
scrutiny, particularly as it relates to the high prevalence of metabolic syndrome
in this population.
Long non-coding RNAs (lncRNAs) have emerged recently as important factors in
regulating fundamental biological processes. Alterations in the expression and
function of lncRNAs have been observed to promote tumor formation, progression and
metastasis. Although downregulation of the expression levels of LET lncRNA in
several tumors has been reported, its role in gastric cancer remains unknown. The
aim of the present study was to investigate the expression and function of LET in
gastric cancer development. The expression levels of LET in 37 pairs of gastric
cancer and adjacent non-tumor tissues were detected by reverse transcription-
quantitative polymerase chain reaction (RT-qPCR). In addition, LET expression in
gastric cancer cell lines was analyzed by RT-qPCR assay analysis. Furthermore, the
impact of LET on cell proliferation, migration and apoptosis were detected using
the cell counting kit-8, wound scratch and ELISA assays, respectively. The results
demonstrated that the expression level of LET was downregulated in gastric cancer
tissues and cell lines (SGC-7901 and MGC-803) compared with normal tissues and a
normal human gastric epithelial cell line (GES-1). Restoration of LET expression
using a synthesized recombinant overexpression vector transfected into SGC-7901 and
MGC-803 cells, significantly inhibited cell proliferation and migration, and
promoted cell apoptosis in vitro. The present study is the first to demonstrate
that LET may function as a tumor suppressor in gastric cancer. The results indicate
that LET may be a promising biomarker and/or a therapeutic target for gastric
cancer.
This paper introduces a high power density step-up converter for LED applications,
based on a hybrid serial-output (HSO) architecture [1], which is suitable for on-
chip implementation. In this system, the output voltage is formed by stacking the
output of a switched-capacitor (SC) converter on top of a boost converter output.
The high power density SC converter processes around a half of the power of the
system and is left unregulated. The boost converter processes the remainder of the
power and regulates the output voltage. In comparison with conventional boost-based
solutions, the introduced boost-SC HSO drastically reduces the passive component
volume and decreases peak voltage stress of switches. Experimental results obtained
with a 3.7 V to 13 V, 2.6 W, 1080 kHz prototype show that the introduced SC-boost
HSO converter has about three times smaller reactive component area than a
conventional boost having the same power processing efficiency.
Xyloglucan endotransglycosylase (XET) catalyses the transglycosylation of
xyloglucan, the major hemicellulose polymer, which has been thought to mediate the
cross-linkining of cellulose microfibrils in cellular walls and proposed to be
involved in the control of cell wall relaxation. To understand the relationship
between longan fruit growth and XET gene expression patterns, three XET genes from
fruit were identified and then their expression profiles in pericarp and aril
tissues of fruit at different development stages were investigated. Three full-
length cDNAs of 1077, 1093 and I IS I bp encoding XETs, named DIXET1, DIXET2 and
DIXET3, respectively, were isolated from expanding fruit using RT-PCR and RACE-PCR
(rapid amplification of cDNA ends) methods. Northern blotting analysis showed that
three DIXET mRNAs exhibited different patterns during fruit growth and development.
Accumulation of MET] kept changeable during the fruit growth and development, DI-
XET2 mRNA accumulations in the pericarp, and in the aril increased gradually
following fruit growth during the whole fruit developmental stage. In addition,
DIXET3 did not accumulate in the pericarp during the whole fruit development stage,
but it could be detected in the aril of fruit during the rapid aril growth stage
(63-74 DAA). These results indicated that DIXET2 was associated with growth of
pericarp and aril in longan fruit, while DIXET1 was related to pericarp growth and
DIXET3 was primarily responsible for aril growth. To further characterize the
expressions of three XETs regulated by plant growth substances, alpha-naphthalene
acetic acid (NAA) and thidiazuron (TDZ) were used to treat longan fruit at 21 DAA
and 56 DAA when pericarp, and aril grew rapidly respectively, it was found that
treatment at 21 DAA, only TDZ increased the accumulation of DIXET2 mRNA at 12 h
after treatment. However, both NAA and TDZ increased the accumulation of DIXET3
after 36 h treatment, although DIXET-3 did not accumulate in the whole fruit.
While, treatment at 56 DAA, both NAA and TDZ increased the accumulations of DIXETs
in aril except DIXET3 in aril by NAA treatment. In addition. the expression
patterns of the three XETs showed different tissue specificity. These results
suggested that XET genes played a different role in longan fruit growth and showed
different response to plant growth substances which existed difference at different
growth stage. (C) 2007 Published by Elsevier Ireland Ltd.
Soya bean (Glycine max (L.) Merr.) is sought after for both its oil and protein
components. Genetic approaches to add value to either component are ongoing efforts
in soya bean breeding and molecular biology programmes. The former is the primary
vegetable oil consumed in the world. Hence, its primary usage is in direct human
consumption. As a means to increase its utility in feed applications, thereby
expanding the market of soya bean coproducts, we investigated the simultaneous
displacement of marine ingredients in aquafeeds with soya bean-based protein and a
high Omega-3 fatty acid soya bean oil, enriched with alpha-linolenic and
stearidonic acids, in both steelhead trout (Oncorhynchus mykiss) and Kampachi
(Seriola rivoliana). Communicated herein are aquafeed formulations with major
reduction in marine ingredients that translates to more total Omega-3 fatty acids
in harvested flesh. Building off of these findings, subsequent efforts were
directed towards a genetic strategy that would translate to a prototype design of
an optimal identity-preserved soya bean-based feedstock for aquaculture, whereby a
multigene stack approach for the targeted synthesis of two value-added output
traits, eicosapentaenoic acid and the ketocarotenoid, astaxanthin, were introduced
into the crop. To this end, the systematic introduction of seven transgenic
cassettes into soya bean, and the molecular and phenotypic evaluation of the
derived novel events are described.
Oxidative stress is suggested to be central to the ageing process, with endogenous
antioxidant defence and repair mechanisms in place to minimize damage.
Theoretically, supplementation with exogenous antioxidants might support the
endogenous antioxidant system, thereby reducing oxidative damage, ageing-related
functional decline and prolonging life- and health-span. Yet supplementation trials
with antioxidants in animal models have had minimal success. Human epidemiological
data are similarly unimpressive, leading some to question whether vitamin C, for
example, might have pro-oxidant properties in vivo. We supplemented cold exposed (7
12 degrees C) female C57BL/6 mice over their lifespan with vitamin C (ascorbyl-2-
polyphosphate), widely advocated and self administered to reduce oxidative stress,
retard ageing and increase healthy lifespan. No effect on mean or maximum lifespan
following vitamin C treatment or any significant impact on body mass, or on
parameters of energy metabolism was observed. Moreover, no differences in
hepatocyte and lymphocyte DNA oxidative damage or hepatic lipid peroxidation was
seen between supplemented and control mice. Using a DNA macroarray specific for
oxidative stress-related genes, we found that after 18 months of supplementation,
mice exhibited a significantly reduced expression of several genes in the liver
linked to free-radical scavenging, including Mn-superoxide dismutase. We confirmed
these effects by Northern blotting and found additional down-regulation of
glutathione peroxidase (not present on macroarray) in the vitamin C treated group.
We suggest that high dietary doses of vitamin C are ineffective at prolonging
lifespan in mice because any positive benefits derived as an antioxidant are offset
by compensatory reductions in endogenous protection mechanisms, leading to no net
reduction in accumulated oxidative damage. (c) 2006 Elsevier Ireland Ltd. All
rights reserved.
One of the important topics in morphometry that received high attention recently is
the longitudinal analysis of shape variation. According to Kendall's definition of
shape, the shape of object appertains on non-Euclidean space, making the
longitudinal study of configuration somehow difficult. However, to simplify this
task, triangulation of the objects and then constructing a non-parametric
regression-type model on the unit sphere is pursued in this paper. The prediction
of the configurations in some time instances is done using both properties of
triangulation and the size of great baselines. Moreover, minimizing a Euclidean
risk function is proposed to select feasible weights in constructing smoother
functions in a non-parametric smoothing manner. These will provide some proper
shape growth models to analysis objects varying in time. The proposed models are
applied to analysis of two real-life datasets.
Background: Little is known about the course of depression in midlife women. This
study aims to identify factors that distinguish risk factors for persistent or
recurrent depression from those of a milder course across 13-years of follow-up.
Methods: 297 Black and White premenopausal women aged 42-52 were enrolled at the
Study of Women's Health Across the Nation Pittsburgh site. Psychiatric interviews
obtained information on lifetime psychiatric diagnoses at baseline and occurrences
of depression annually. We identified four depression patterns: 91(31%) had
Persistent/recurrent major depressive disorder (MDD), 27(9%) Single Episode MDD, 35
(12%) Minor Depression (minD) only, 144(48%) No Depression. We compared baseline
risk factors for the Persistent/recurrent MDD group with each of the other three.
Results: A lifetime history of major or minor depression (p-values =.001-.08) and
2+ very upsetting life events in the previous year (p-values=.003-.04) were more
likely to be reported by women in the Persistent/recurrent group than in the other
three. The Persistent/recurrent group was more likely to report a family history of
depression (p=.03) than the MinD group, and to report current sleep problems
(p=.002) at baseline than the Single Episode MDD group. Limitations: Small numbers
of women with minD or a Single Episode MDD. Childhood maltreatment and family
depression history were retrospectively reported. Conclusions: A
Persistent/recurrent depression course is common during midlife. In addition to
personal and family histories of depression, providers of midlife health care
should recognize that current sleep problems and recent very upsetting events are
strong risk factors for a pernicious depression course. (C) 2016 Elsevier B.V. All
rights reserved.
The quality of the caregiver-child relationship is key to the well-being of
children but assumptions based on research in western countries about the benefits
of different types of substitute care may be questionable when applied elsewhere.
This study assessed the quality of caregiver-child relationships and their
association with child abuse in foster and residential care in Nigeria. The
findings are relevant to European and North American countries as 4% of those
looked after and 6% of care entrants in England are of African heritage and it is
too easy to draw wrong conclusions about the care they might have received in their
own countries. The study scrutinised 314 children aged 7-17 years from foster (157)
and residential care settings (157) and assessed the caregiver-child relationship
using the Positive Relationship Scale. The child abuse measure covered physical,
sexual and emotional components and aggregated these into a single score. The
subsequent analysis explored differences in child abuse between foster and
residential care and the significance of other factors influencing levels of child
abuse. It was found that the children in residential care had more positive
relationships with caregivers than did those in foster care, even though abuse
occurred in both settings. There were no gender differences in experiences of child
abuse in either setting but children under the age of 12 were significantly more
likely to have been abused while in care than those over this age. For children in
residential care, age was the most significant factor associated with abuse. As
these findings provide a perspective on children in substitute care in a West
African city, they may be useful to social workers elsewhere who are responsible
for children of African heritage, as they suggest that abuse often occurs in foster
homes and that child-carer relationships in residential establishments can be good.
Membrane type1 matrix metalloproteinase (MT1-MMP) is implicated in pericellular
proteolysis, and, together with tissue inhibitor of matrix metalloproteinases-2
(TIMP-2), in the activation of pro-matrix metalloproteinase-2 on the cell surface.
It is expressed on the cell surface either activated or as a proenzyme. A soluble
form of MT1-MMP (sMT1-MMP) has been previously identified in periprosthetic tissues
and fluid of patients with loose arthroplasty endoprostheses. The aim of this study
was to examine periprosthetic tissues and fluids from patients with loose
arthroplasty endoprostheses, as well as tissues and fluids from patients with other
disorders, for the presence of sMT1-MMP, and to investigate its activation state
and possible role. With antibody against MT1-MMP, a protein with molecular mass of
similar to 57kDa was detected by western blotting in all samples tested,
representing a soluble form of MT1-MMP, which cannot be ascribed to alternative
splicing, as northern blotting showed only one transcript. With various biochemical
methods, it was shown that this species occurs in a latent form bearing the N-
terminal prodomain, and, additionally, it is bound to TIMP-2, which appeared to be
bound via its C-terminal domain to a site different from the active site. Cell
ELISA and immunohistochemical analysis revealed that, besides fibroblasts, all
other cells, such as inflammatory, epithelial, endothelial, giant and cancer cells,
express MT1-MMP on their plasma membrane as a proenzyme. Taking into account the
proteolytic abilities of MT1-MMP, the latent sMT1-MMP-TIMP-2 complex could be
considered as a new interstitial collagenase. However, the exact role, the
production mechanism and the cell origin of this complex remain to be elucidated.
A digital low dropout regulator (D-LDO) manages to operate at low voltage and scale
with process. But, the tradeoff between current efficiency and transient response
speed limits its applications. In this work, a coarse-fine-tuning technique with
burst-mode operation is employed to advance this trade-off. Once the output voltage
under/overshoot is detected, the power MOS array changes with x16 unit size at 500
MHz sampling frequency for a fixed time, comparing with xi size and 50 MHz in
steady state. The limit cycle oscillation (LCO) in steady state is reduced by a
feed-forward compensation zero with negligible power and area overheads. The
proposed D-LDO is simulated in a 65 nm CMOS process, achieving a 60 mV voltage
undershoot and 0.36 ps FOM of speed with a 60 mu A quiescent current, and mode-1
LCO in steady state.
In this paper, a low voltage low dropout (LDO) regulator is designed and simulated
in 0.13 mu m CMOS technology, which converts an input voltage of 1.2V into a stable
regulated output voltage of 1.1 V using Ng-Spice circuit simulator. The two stage
operational amplifier (Op-Amp) is used as an error amplifier (EA). Here, the
Artificial Bee Colony (ABC) evolutionary algorithm based optimizer is demonstrated
for solving the problem of the device sizing and other parameters of Op-Amp and
optimization. This approach for designing two stage Op-Amp circuit does not require
any analytical calculations and handles non-linear effects of sub-micron devices
very effectively. The designed LDO is tested for a change in load current for 0-100
mA and it is found that the power supply rejection ratio (PSRR) is found to be 78.5
dB at 1 KHz and 28.7 dB at 10 MHz. The settling time of less than 1 mu sec observed
during testing of line and load regulations.
As a driven accelerator, the CYCIAE-100 cyclotron is designed by China Institute of
Atomic Energy for the Beijing Radio Ion-beam Facility project. The cyclotron RF
system is designed to use two RF power sources of 100 kW to drive two half-
wavelength cavities respectively. Two Dee accelerating electrodes are kept
separately from each other inside the cyclotron, while their accelerating voltages
are maintained in phase by the efforts of LLRF control. An analog-digital hybrid
LLRF system has been developed to achieve cavity tuning control, dee voltage
amplitude and phase stabilization etc. The analog subsystems designs are focused on
RF signal up/down conversion, tuning control, and dee voltage regulation. The
digital system provides an RF signal source, aligns the cavity phases and maintains
a Finite State Machine. The digital parts combine with the analog functions to
provide the LLRF control. A brief system hardware introduction will be given in
this paper, followed by the review of several major characteristics of the digital
control in the 100 MeV cyclotron LLRF system. The commissioning is also introduced,
and most of the optimization during the process was done by changing the digital
parts. (C) 2016 Elsevier B.V. All rights reserved.
The study was carried out in 48 poultry flocks to elucidate the roles of various
complicating pathogens involved along with Newcastle disease (ND)/ low pathogenic
avian influenza (LPAI) outbreaks. Necropsy was conducted and samples were collected
for the isolation of Newcastle disease virus (NDV), Influenza A virus, infectious
bronchitis virus (IBV), pathogenic bacteria; molecular detection of infectious
laryngotracheitis virus (ILTV), fowl adeno virus (FAV), chicken anaemia virus
(CAV), Mycoplasma synoviae (MS) and Mycoplasma gallisepticum (MG). The isolation
results confirmed that 18/48 flocks (37%) were positive for the presence of
hemagglutinating agents. Out of 18 hemagglutination (HA) positive flocks, 11 flocks
(61%) were positive for both avian influenza virus (AIV) and NDV; 4 flocks (22%)
were positive for NDV; and 3 flocks (17%) were positive for AIV. Sequence analysis
of hemagglutinin and neuraminidase genes of AIV revealed that all were belonging to
LPAI-H9N2 subtype. Sequence analysis of F gene of NDV revealed that they belong to
virulent type. The PCR results confirmed the presence of three to seven etiological
agents (CAV, FAV, ILTV, MG, MS and avian pathogenic E. coli along with LPAI/NDV
from all the 18 HA-positive flocks. The detection rate of triple, quadruple,
quintuple, sextuple and sevenfold infections was 17% (3 flocks), 28% (5 flocks),
11%, (2 flocks) 28% (5 flocks) and 17% (3 flocks), respectively. In conclusion, the
disease complex involved more than one pathogen, primarily resulting from the
interplay between LPAI-H9N2 and NDV; subsequently this could be exacerbated by co-
infection with other agents which may cause exacerbated outbreaks that may
otherwise go undetected in field.
This paper proposes a low power and low output ripple regulator for radio frequency
identification tags. The inner blocks of regulator is supplied from elementary
stages output of rectifier. The proposed operational amplifier works on AB class
and its bias is in adaptive biasing form. The bandgap reference and sampling
voltage resistors used in this paper are completely designed with transistors which
culminate in low power dissipation. The regulator output voltage is 1.07 V, while
the output ripple is +/- 1.1 mV. The value of line regulation, power supply
rejection ratio, and regulator efficiency are 5.5 mV/V, 45.2 dB, and 71.3%,
respectively. A 111 mu W power consumption has been calculated with 20 K omega
load. The simulation is done with the help of Cadence software in 0.18 mu m CMOS
technology, while its operational frequency is 960 MHz. The layout of the proposed
regulator is 0.00125 mm(2).
We are developing a fully depleted silicon-on-insulator (FD-SOI) CMOS readout
integrated circuit (ROIC) operated at temperatures below 4 K. Its application is
planned for the readout circuit of high-impedance far-infrared detectors for
astronomical observations. We designed a trans-impedance amplifier (TIA) using a
CMOS operational amplifier (OPAMP) with FD-SOI technique. The TIA is optimized to
readout signals from a germanium blocked impurity band (Ge BIB) detector which is
highly sensitive to wavelengths of up to 200 m. For the first time, we demonstrated
the FD-SOI CMOS OPAMP combined with the Ge BIB detector at 4.5 K. The result
promises to solve issues faced by conventional cryogenic ROICs.
Temperature is the bottleneck for the anaerobic treatment of domestic wastewater in
temperate climates. Most previous attempts to achieve anaerobic treatment at low
temperatures have attempted to acclimatize mesophilic sludge and have failed at
temperatures below 10-13 degrees C. We describe an alternative approach using
communities from environments that have been exposed to low temperatures over
evolutionary time-scales as seed for such reactors. Batch reactors were inoculated
with a mixture of soils and sediments from the high Arctic and an Alpine lake to
treat UV-sterilized raw domestic wastewater at 4, 8 and 15 degrees C. To evaluate
the intrinsic treatment capacity of the bacteria the specific rates of
methanogenesis and hydrolysis were evaluated. Specific methanogenic activity at 4,
8 and 15 degrees C was 63, 7.6 and 10.3 fmol CH4 cell(-1) day(-1) respectively.
Specific putative hydrolysis rates were 76.2, 186.6 and 251.9 fgrams COD cell(-1)
day(-1). Hydrolysis was twice as temperature sensitive as methanogenesis (Q(10):
4.62 and 1.57 respectively). The specific rates are over ten times higher than we
have previously observed in microcosms fed with settled wastewater at the same
temperatures. The results imply that inoculating reactors with cold-adapted
communities is a promising way to develop biomass capable of treating anaerobic
wastewater treatment at low temperatures whilst achieving an effluent that conforms
to the EC Directive COD standards. Large-scale reactors are feasible if
satisfactory cell concentrations can be achieved. (C) 2017 Published by Elsevier
Ltd.
In plants, low temperatures can activate the CBF cold response pathway playing a
prominent role in cold acclimation by triggering a set of cold-related gene
expressions. CBF homologous gene, designated as LpCBF3, from a cold-tolerant
perennial ryegrass (Lolium perenne L.) accession was identified. It carries the
sequences for nuclear localization signal (NLS), AP2 DNA-binding domains and an
acidic activation present in most of the plant CBF proteins. Southern analysis
indicated the presence of three homologs of LpCBF3 gene in perennial ryegrass
genome, and only one amino acid variation in LpCBF3 protein between cold-tolerant
and -sensitive perennial ryegrass accessions. In their putative promoter regions,
some differential regions were found. Northern blotting and RT-PCR analysis found
that LpCBF3 reached the highest expression after 1.5 h of cold treatment (4C). The
COR homologous gene, a downstream gene of CBF, can be expressed in the plant stem
of cold-tolerant perennial ryegrass accessions without cold treatment. Without cold
treatment, the COR gene cannot be activated in cold-sensitive perennial ryegrass
accessions. Cold treatment can prompt expression levels of COR homologous genes in
both perennial ryegrass accessions. In transgenic Arabidopsis, the overexpression
of LpCBF3 with the 35S promoter resulted in dwarf-like plants, later flowering and
greater freezing tolerance.
Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase
activating protein (TAGAP) polymorphisms might influence the susceptibility to
celiac disease. Therefore, we performed a meta-analysis by identifying relevant
studies to estimate the risks of these polymorphisms on celiac disease. Methods:
The PubMed, Web of Science and Embase databases were searched (up to October 2016)
for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis
included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A
allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI:
1.22-1.30) and 1.17 (95% CI: 1.14-1.21), respectively, which contributed to
increased risks in all celiac disease patients by 10.72% and 6.59%, respectively.
The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-
dominant model would be suitable for both gene effects. Conclusions: This meta-
analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are
potential risk factors for celiac disease in European and American. Prospective
studies and more genome-wide association studies (GWAS) are needed to confirm these
findings, and some corresponding molecular biology experiments should be carried
out to clarify the pathogenic mechanisms of celiac disease.
Objective: This case-control study explored correlations between LP-PLA2 gene
polymorphisms (A379V, V279F, and R92H) and susceptibility and severity of acute
pancreatitis (AP) in a Chinese population. Materials and Methods: From October 2013
to October 2015, 94 AP patients were chosen as the case group. According to the
Acute Physiology and Chronic Health Evaluation (APACHE) II score standard, AP
patients were divided into a mild AP (MAP) group (n = 46) and severe AP (SAP) group
(n = 48). The 48 SAP patients were further divided into an SAP with multiple organ
dysfunction syndrome (MODS) group (n = 42) and SAP without MODS group (n = 6).
Meanwhile, 96 healthy subjects who received physical examinations at the study
hospitals were selected as the control group. Serum lipoprotein-associated
phospholipase A2 (LP-PLA2) levels were detected by an enzyme-linked immunosorbent
assay (ELISA). The A379V (s1051931), V279F (rs16874954), and R92H (rs13989)
polymorphisms of the LP-PLA2 gene were detected by polymerase chain reaction-
restriction fragment length polymorphism (PCR-RFLP). Results: There were
significant differences in the frequencies of the LP-PLA2 gene polymorphisms
between the AP group and the control group. The distribution of V279F-AA+AC
genotype and R92H-AA+AG genotype in the AP group was higher than that in the
control group, whereas the SAP group and SAP with MODS group distributions were
higher than those in the MAP group and SAP without MODS group (both p < 0.05). G-C-
A, G-A-G, and G-C-G haploids formed by A379V, V279F, and R92H may be associated
with AP susceptibility. LP-PLA2 gene polymorphisms could affect serum LP-PLA2
level, whereas the V279F-A allele gene, the R92H-A allele gene, serum LP-PLA2
level, and serum amylase may be independent risk factors for AP (all p < 0.05).
Conclusion: These results demonstrated that the LP-PLA2 gene polymorphisms, V279F
and R92H, may be associated with susceptibility to and severity of AP.
Histone methylation is a complicate and dynamic epigenetic modification that
regulates gene transcription, chromosomal structure and cell differentiation. Here,
we discovered the interaction between the H3K4 demethylase, lysine specific
demethylase 1 (LSD1, an important component of CoREST repressor complex) and the
H3K27 methyltransferase, enhancer of zeste homolog 2 (EZH2, an essential component
of PRC2). Immuno-precipitation and GST-pull down assay were performed to observe
the interaction between the proteins. The MCF-7 cells were cultured and transfected
with the siRNA. The mRNA and proteins were examined by using the real-time
polymerase chain reaction (RT-PCR) and western blot assay, respectively. HPLC and
LC-MS/MS analysis were performed to purify the proteins. RTPCR- based quantitative
ChIP analysis were performed. LSD1 interacts with histone modification protein EZH2
in MCF-7 cells. LSD1 and EZH2 target a few common genes. LSD1 knockdown and EZH2
knockdown affect protein expression. LSD1 knockdown and EZH2 knockdown affect the
proteins involving in IFN signaling pathway. LSD1 and EZH2 modify histone
methylation at IRF9 gene locus. We systematically analyzed the proteins that are
affected by either LSD1 or EZH2 knockdown with proteomic approaches and identified
that the interferon pathway and some other pathways are commonly affected. The
interaction between LSD1 and EZH2 stabilizes the binding of LSD1 to the promoter
region of IRF9, which is a key transcription factor of the interferon pathway. In
conclusion, our study revealed that the coordination between histone demethylases
and methyl-transferases might serve as a double lock system to suppress the
expression of interferon stimulated genes. (C) 2017 Published by Elsevier Masson
SAS.
Pricing and hedging exotic options using local stochastic volatility models drew a
serious attention within the last decade, and nowadays became almost a standard
approach to this problem. In this paper we show how this framework could be
extended by adding to the model stochastic interest rates and correlated jumps in
all three components. We also propose a new fully implicit modification of the
popular Hundsdorfer and Verwer and Modified Craig-Sneyd finite-difference schemes
which provides second-order approximation in space and time, is unconditionally
stable and preserves positivity of the solution, while still has a linear
complexity in the number of grid nodes.
The blow fly, Lucilia cuprina (Wiedemann, 1830) is a parasitic insect of major
global economic importance. Maggots of this fly parasitize the skin of animal
hosts, feed on excretions and tissues, and cause severe disease (flystrike or
myiasis). Although there has been considerable research on L. cuprina over the
years, little is understood about the molecular biology, biochemistry and genetics
of this parasitic fly, as well as its relationship with its hosts and the disease
that it causes. This Situation might change with the recent report of the draft
genome and transcriptome of this blow fly, which has given new and global insights
into its biology, interactions with the host animal and aspects of insecticide
resistance at the molecular level. This genomic resource will likely enable many
fundamental and applied research areas in the future. The present article gives a
background on L. cuprina and myiasis, a brief account of past and current
treatment, prevention and control approaches, and provides a perspective on the
impact that the L cuprina genome should have on future research of this and related
parasitic flies, and the design of new and improved interventions for myiasis. (C)
2016 Elsevier Inc. All rights reserved.
Objective: The objective of this study was to construct a recombinant vector
expressing siRNA targetedly inhibiting aquaporin 3 (AQP3), and to evaluate the
effects of AQP3 inhibition on the proliferation and invasion of XWLC-05 human lung
cancer cells. Methods: We obtained human AQP3 sequence from the Genbank and
established the recombinant vector expressing siRNA targeting AQP3. After the
transfection of the recombinant vectors, the expression of AQP3 was determined by
RT-PCR and western blot. The MTS assay, flow cytometry and Transwell assay were
conducted to detect the proliferation, cell cycle process, apoptosis and invasion
of XVVLC-05 cells. Then the activity of metal matrix proteinase (MMP) 2 was
determined by gelatin zymography. Tumor formation in vivo experiments were also
conducted in nude mice. Results: RNA interference (RNAi) of AQP3 substantially
suppressed the XWLC-05 cell proliferation and invasion, blocked the cell cycle
progressing and promoted cell apoptosis. In addition, the activity of MMP2 was
remarkably attenuated in RNAi group. AQP3 RNAi did not affect the tumor formation
rate in nude mice but reduced the tumor growth. Conclusion: The inhibition of AQP3
retarded the growth and invasiveness of XWLC-05 lung cancer cells and decreased the
activity of MMP2. (C) 2017 Elsevier Inc. All rights reserved.
Background: The mechanisms involved in lung cancer (LC) progression are poorly
understood making discovery of successful therapies difficult. Adaptor proteins
play a crucial role in cancer as they link cell surface receptors to specific
intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain
adaptor protein implicated in the pathophysiology of numerous pulmonary diseases.
To date, the role of ITSN-1s in LC has not been studied. Methods: Human LC cells,
human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct
(A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and
morphological studies. In addition scratch assay with time lapse microscopy and in
vivo xenograft tumor and mouse metastasis assays were performed. Results: ITSN-1s,
a prevalent protein of lung tissue, is significantly downregulated in human LC
cells and LC tissue. Restoring ITSN-1s protein level decreases LC cell
proliferation and clonogenic potential. In vivo studies indicate that
immunodeficient mice injected with A549 + ITSN-1s cells develop less and smaller
metastatic tumors compared to mice injected with A549 cells. Our studies also show
that restoring ITSN-1s protein level increases the interaction between Cbl E3
ubiquitin ligase and Eps8 resulting in enhanced ubiquitination of the Eps8
oncoprotein. Subsequently, downstream unproductive assembly of the Eps8-mSos1
complex leads to impaired activation of the small GTPase Rac1. Impaired Rac1
activation mediated by ITSN-1s reorganizes the cytoskeleton (increased thick actin
bundles and focal adhesion (FA) complexes as well as collapse of the vimentin
filament network) in favor of decreased LC cell migration and metastasis.
Conclusion: ITSN-1s induced Eps8 ubiquitination and impaired Eps8-mSos1 complex
formation, leading to impaired activation of Rac1, is a novel signaling mechanism
crucial for abolishing the progression and metastatic potential of LC cells.
During the peripartum period, the lung must respond to dramatic changes in
circulating hormones, nutritional factors, and physiologic signals during its
tran