Understanding how chromosomes fold provides insights into the transcription regulation, hence, th... more Understanding how chromosomes fold provides insights into the transcription regulation, hence, the functional state of the cell. Using the next generation sequencing technology, the recently developed Hi-C approach enables a global view of spatial chromatin organization in the nucleus, which substantially expands our knowledge about genome organization and function. However, due to multiple layers of biases, noises and uncertainties buried in the protocol of Hi-C experiments, analyzing and interpreting Hi-C data poses great challenges, and requires novel statistical methods to be developed. This article provides an overview of recent Hi-C studies and their impacts on biomedical research, describes major challenges in statistical analysis of Hi-C data, and discusses some perspectives for future research.
To examine and quantify the potential dose-response relationship between red and processed meat c... more To examine and quantify the potential dose-response relationship between red and processed meat consumption and risk of all-cause, cardiovascular and cancer mortality. We searched MEDLINE, Embase, ISI Web of Knowledge, CINHAL, Scopus, the Cochrane library and reference lists of retrieved articles up to 30 November 2014 without language restrictions. We retrieved prospective cohort studies that reported risk estimates for all-cause, cardiovascular and cancer mortality by red and/or processed meat intake levels. The dose-response relationships were estimated using data from red and processed meat intake categories in each study. Random-effects models were used to calculate pooled relative risks and 95 % confidence intervals and to incorporate between-study variations. Nine articles with seventeen prospective cohorts were eligible in this meta-analysis, including a total of 150 328 deaths. There was evidence of a non-linear association between processed meat consumption and risk of all...
Scheme 2. Synthesis of the acid 5 a. a) TBSCl, imidazole; b) NaBH 4 , MeOH; c) MsCl, Et 3 N; d) t... more Scheme 2. Synthesis of the acid 5 a. a) TBSCl, imidazole; b) NaBH 4 , MeOH; c) MsCl, Et 3 N; d) tBuOK, 71 % yield over four steps; e) O 3 , Me 2 S; f) LiCH 2 CO 2 Et; g) 40 % HF; h) MsCl, Et 3 N, 45 % yield over four steps; i) CH 2 =CHCOCl, Et 3 N, 90 %; j) 10 mol % Grubbs' catalyst, 80 %; k) Me 2 A C H T U N G T R E N N U N G (CuCN)Li 2 , 94 %; l) LiAlH 4 , THF; m) AcCl, pyridine, then K 2 CO 3 , MeOH; n) Dess-Martin oxidation, 69 % yield over three steps; o) N-Propionylsultam, Et 2 BOTf, iPr 2 NEt, then TiCl 4 , 90 %; p) LiAlH 4 , THF, then DMP, PPTs, 67 %; q) Fmoc-l-proline, 2,4,6-trichlorobenzoyl chloride, DMAP, 90 %; r) TsOH, MeOH; s) TEMPO, NaClO; t) NaH 2 PO 4 , NaClO 2 , 81 % yield over three steps. TBS = tert-butyldimethylsilyl. DMAP = 4-dimethylaminopyridine; TEMPO = 2,2,6,6-tetramethylpiperidinyl-1-oxyl.
Background-Obesity is a prevalent disorder characterized as marked insulin resistance and low gra... more Background-Obesity is a prevalent disorder characterized as marked insulin resistance and low grade inflammation. We tested the hypothesis that obesity upregulates inflammatory markers in the submandibular gland in association with derangements of its architecture and predisposition to caries in obese Zucker rats. We also examined the potential impact of chromium picolinate (Cr(Pic)3), a nutritional supplement suggested to improve glycemic control, on the aforementioned parameters.
By employing united atom molecular dynamics simulation, we have investigated the effects of polym... more By employing united atom molecular dynamics simulation, we have investigated the effects of polymer-graphene interaction [Formula: see text] volume fraction of graphene [Formula: see text] thermodynamics of polymer matrix (rubbery versus glassy), interfacial interaction in the case of the same dispersion state, shape of nanoparticles (NPs) such as [Formula: see text] CNT and graphene at the same loading on the toughening efficiency of polymer nanocomposites. By beginning with the pure polymer, we observe that a plateau stress occurs at long chain length because entangled polymer chains in fibrils cannot become broken. We find that the work needed to dissipate during the failure increases with the increase of [Formula: see text] and [Formula: see text] and the yield point in the stress-strain behavior occurs at a smaller strain for an attractive NPs filled system compared to the pure case, attributed to the more mechanically heterogeneous environment. The thermodynamics of the polyme...
New affinity reagents were synthesized using alkene metathesis to directly modify the MeBmt side ... more New affinity reagents were synthesized using alkene metathesis to directly modify the MeBmt side chain of cyclosporin A. The reagents were used to detect novel cyclophilins from cellular extracts.
Motif discovery, which focuses on locating short sequence patterns associated with the regulation... more Motif discovery, which focuses on locating short sequence patterns associated with the regulation of genes in a species, leads to a class of statistical miss- ing data problems. These problems are discussed rst with reference to a hypothetical model, which serves as a point of departure for more realistic versions of the model. Some general results relating to modeling and
Proceedings of The National Academy of Sciences, 2005
Transcription regulation is controlled by coordinated binding of one or more transcription factor... more Transcription regulation is controlled by coordinated binding of one or more transcription factors in the promoter regions of genes. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. The number of sites and distances between the sites, however, vary greatly in a module. We propose a
International journal of clinical and experimental medicine, 2015
Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study ... more Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, P<0.00001) and improved the electrocardiography (OR=1.83, 95%...
Breast cancer-related lymphedema is associated with numerous adverse outcomes. This study investi... more Breast cancer-related lymphedema is associated with numerous adverse outcomes. This study investigated the extent clinical factors, lymphedema symptoms, lymphedema-related appearance, and coping strategies predicted quality of life. Female patients who underwent microsurgical treatment for lymphedema (n = 54) participated. Lymphedema symptoms were associated with physical and functional well-being, but not emotional and social well-being. Clinical factors and lymphedema-related appearance were not significantly associated with quality of life. Compared to adaptive coping strategies, maladaptive coping strategies (e.g. denial, venting, self-blame) were more strongly associated with quality of life. This suggests psychosocial interventions aimed at modifying maladaptive coping behaviors can potentially improve quality of life for this patient population.
Spin resonances can cause partial or full depolarization or spin-flip of a polarized beam. We stu... more Spin resonances can cause partial or full depolarization or spin-flip of a polarized beam. We studied 1st-, 2nd- and 3rd-order spin resonances with a 2.1 GeV/c vertically polarized proton beam stored in the COSY Cooler Synchrotron. We observed almost full spin-flip when crossing the 1st-order G*gamma=8nu<sub>y</sub> vertical-betatron-tune spin resonance and partial depolarization near some 2nd- and 3rd-order resonances. We observed
Physics of the Earth and Planetary Interiors, 1999
. The pressure-volume-temperature P-V-T behavior in SiO -stishovite has been studied using a DIA-... more . The pressure-volume-temperature P-V-T behavior in SiO -stishovite has been studied using a DIA-type, cubic-anvil T 0 previously from Brillouin scattering and diamond-anvil cell X-ray diffraction studies on single crystal stishovite and ultrasonic studies on polycrystalline specimens. q
Programmed Death-1 (PD-1) and its ligand, PD-L1, are regulators of immune/ inflammatory mechanism... more Programmed Death-1 (PD-1) and its ligand, PD-L1, are regulators of immune/ inflammatory mechanisms. We explored the potential involvement of PD-1/PD-L1 pathway in the inflammatory response and tissue damage in cardiac injury models. Ischemic-reperfused and cryoinjured hearts were processed for flow cytometry and immunohistochemical studies for determination of cardiac PD-1 and PD-L1 in the context of assessment of the growth arrest- and DNA damage-inducible protein 153 (GADD153) which regulates both inflammation and cell death. Further, we explored the potential ability of injured cardiac cells to influence proliferation of T lymphocytes. The isolated ischemic-reperfused hearts displayed marked increases in expression of PD-1 and PD-L1 in cardiomyocytes; however, immunofluorescent studies indicate that PD-1 and PD-L1 are not primarily co-expressed on the same cardiomyocytes. Upregulation of PD-1/PD-L1 was associated with a) marked increases in GADD153 and interleukin (IL)-17 but a m...
The crude processing of electronic waste (e-waste) has led to serious contamination in soils. Whi... more The crude processing of electronic waste (e-waste) has led to serious contamination in soils. While microorganisms may play a key role in remediation of the contaminated soils, the ecological effects of combined pollution (heavy metals, polychlorinated biphenyls and polybrominated diphenyl ethers) on the composition and diversity of microbial communities remain unknown. In this study, a suite of e-waste contaminated soils were collected from Guiyu, China, and the indigenous microbial assemblages were profiled by 16S rRNA high-throughput sequencing and clone library analysis. Our data revealed significant differences in microbial taxonomic composition between the contaminated and the reference soils, with Proteobacteria, Acidobacteria, Bacteroidetes and Firmicutes dominating the e-waste-affected communities. Genera previously identified as organic pollutants-degrading bacteria, such as Acinetobacter, Pseudomonas and Alcanivorax, were frequently detected. Canonical correspondence anal...
Proceedings of the ASP-DAC '99 Asia and South Pacific Design Automation Conference 1999 (Cat. No.99EX198), 1999
In the past two decades, the simulated annealing technique has been considered as a powerful appr... more In the past two decades, the simulated annealing technique has been considered as a powerful approach to handle many NP-hard optimization problems in VLSI designs. Recently, a new Monte Carlo and optimization technique, named simulated tempering, was invented and has been successfully applied to many scientific problems, from random field Ising modeling to the traveling salesman problem. It is designed to overcome the drawback in simulated annealing when the problem has a rough energy landscape with many local minima separated by high energy barriers. In this paper, we have successfully applied a version of relaxed simulated tempering to slicing floorplan design with consideration of both area and wirelength optimization. Good experimental results were obtained.
Loops in proteins are often involved in biochemical functions. Their irregularity and flexibility... more Loops in proteins are often involved in biochemical functions. Their irregularity and flexibility make experimental structure determination and computational modeling challenging. Most current loop modeling methods focus on modeling single loops. In protein structure prediction, multiple loops often need to be modeled simultaneously. As interactions among loops in spatial proximity can be rather complex, sampling the conformations of multiple interacting loops is a challenging task. In this study, we report a new method called multi-loop Distance-guided Sequential chain-Growth Monte Carlo (m-DiSGro) for prediction of the conformations of multiple interacting loops in proteins. Our method achieves an average RMSD of 1:93 Å for lowest energy conformations of 36 pairs of interacting protein loops with the total length ranging from 12 to 24 residues. We further constructed a data set containing proteins with 2, 3, and 4 interacting loops. For the most challenging target proteins with 4 ...
Understanding how chromosomes fold provides insights into the transcription regulation, hence, th... more Understanding how chromosomes fold provides insights into the transcription regulation, hence, the functional state of the cell. Using the next generation sequencing technology, the recently developed Hi-C approach enables a global view of spatial chromatin organization in the nucleus, which substantially expands our knowledge about genome organization and function. However, due to multiple layers of biases, noises and uncertainties buried in the protocol of Hi-C experiments, analyzing and interpreting Hi-C data poses great challenges, and requires novel statistical methods to be developed. This article provides an overview of recent Hi-C studies and their impacts on biomedical research, describes major challenges in statistical analysis of Hi-C data, and discusses some perspectives for future research.
To examine and quantify the potential dose-response relationship between red and processed meat c... more To examine and quantify the potential dose-response relationship between red and processed meat consumption and risk of all-cause, cardiovascular and cancer mortality. We searched MEDLINE, Embase, ISI Web of Knowledge, CINHAL, Scopus, the Cochrane library and reference lists of retrieved articles up to 30 November 2014 without language restrictions. We retrieved prospective cohort studies that reported risk estimates for all-cause, cardiovascular and cancer mortality by red and/or processed meat intake levels. The dose-response relationships were estimated using data from red and processed meat intake categories in each study. Random-effects models were used to calculate pooled relative risks and 95 % confidence intervals and to incorporate between-study variations. Nine articles with seventeen prospective cohorts were eligible in this meta-analysis, including a total of 150 328 deaths. There was evidence of a non-linear association between processed meat consumption and risk of all...
Scheme 2. Synthesis of the acid 5 a. a) TBSCl, imidazole; b) NaBH 4 , MeOH; c) MsCl, Et 3 N; d) t... more Scheme 2. Synthesis of the acid 5 a. a) TBSCl, imidazole; b) NaBH 4 , MeOH; c) MsCl, Et 3 N; d) tBuOK, 71 % yield over four steps; e) O 3 , Me 2 S; f) LiCH 2 CO 2 Et; g) 40 % HF; h) MsCl, Et 3 N, 45 % yield over four steps; i) CH 2 =CHCOCl, Et 3 N, 90 %; j) 10 mol % Grubbs' catalyst, 80 %; k) Me 2 A C H T U N G T R E N N U N G (CuCN)Li 2 , 94 %; l) LiAlH 4 , THF; m) AcCl, pyridine, then K 2 CO 3 , MeOH; n) Dess-Martin oxidation, 69 % yield over three steps; o) N-Propionylsultam, Et 2 BOTf, iPr 2 NEt, then TiCl 4 , 90 %; p) LiAlH 4 , THF, then DMP, PPTs, 67 %; q) Fmoc-l-proline, 2,4,6-trichlorobenzoyl chloride, DMAP, 90 %; r) TsOH, MeOH; s) TEMPO, NaClO; t) NaH 2 PO 4 , NaClO 2 , 81 % yield over three steps. TBS = tert-butyldimethylsilyl. DMAP = 4-dimethylaminopyridine; TEMPO = 2,2,6,6-tetramethylpiperidinyl-1-oxyl.
Background-Obesity is a prevalent disorder characterized as marked insulin resistance and low gra... more Background-Obesity is a prevalent disorder characterized as marked insulin resistance and low grade inflammation. We tested the hypothesis that obesity upregulates inflammatory markers in the submandibular gland in association with derangements of its architecture and predisposition to caries in obese Zucker rats. We also examined the potential impact of chromium picolinate (Cr(Pic)3), a nutritional supplement suggested to improve glycemic control, on the aforementioned parameters.
By employing united atom molecular dynamics simulation, we have investigated the effects of polym... more By employing united atom molecular dynamics simulation, we have investigated the effects of polymer-graphene interaction [Formula: see text] volume fraction of graphene [Formula: see text] thermodynamics of polymer matrix (rubbery versus glassy), interfacial interaction in the case of the same dispersion state, shape of nanoparticles (NPs) such as [Formula: see text] CNT and graphene at the same loading on the toughening efficiency of polymer nanocomposites. By beginning with the pure polymer, we observe that a plateau stress occurs at long chain length because entangled polymer chains in fibrils cannot become broken. We find that the work needed to dissipate during the failure increases with the increase of [Formula: see text] and [Formula: see text] and the yield point in the stress-strain behavior occurs at a smaller strain for an attractive NPs filled system compared to the pure case, attributed to the more mechanically heterogeneous environment. The thermodynamics of the polyme...
New affinity reagents were synthesized using alkene metathesis to directly modify the MeBmt side ... more New affinity reagents were synthesized using alkene metathesis to directly modify the MeBmt side chain of cyclosporin A. The reagents were used to detect novel cyclophilins from cellular extracts.
Motif discovery, which focuses on locating short sequence patterns associated with the regulation... more Motif discovery, which focuses on locating short sequence patterns associated with the regulation of genes in a species, leads to a class of statistical miss- ing data problems. These problems are discussed rst with reference to a hypothetical model, which serves as a point of departure for more realistic versions of the model. Some general results relating to modeling and
Proceedings of The National Academy of Sciences, 2005
Transcription regulation is controlled by coordinated binding of one or more transcription factor... more Transcription regulation is controlled by coordinated binding of one or more transcription factors in the promoter regions of genes. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. The number of sites and distances between the sites, however, vary greatly in a module. We propose a
International journal of clinical and experimental medicine, 2015
Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study ... more Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, P<0.00001) and improved the electrocardiography (OR=1.83, 95%...
Breast cancer-related lymphedema is associated with numerous adverse outcomes. This study investi... more Breast cancer-related lymphedema is associated with numerous adverse outcomes. This study investigated the extent clinical factors, lymphedema symptoms, lymphedema-related appearance, and coping strategies predicted quality of life. Female patients who underwent microsurgical treatment for lymphedema (n = 54) participated. Lymphedema symptoms were associated with physical and functional well-being, but not emotional and social well-being. Clinical factors and lymphedema-related appearance were not significantly associated with quality of life. Compared to adaptive coping strategies, maladaptive coping strategies (e.g. denial, venting, self-blame) were more strongly associated with quality of life. This suggests psychosocial interventions aimed at modifying maladaptive coping behaviors can potentially improve quality of life for this patient population.
Spin resonances can cause partial or full depolarization or spin-flip of a polarized beam. We stu... more Spin resonances can cause partial or full depolarization or spin-flip of a polarized beam. We studied 1st-, 2nd- and 3rd-order spin resonances with a 2.1 GeV/c vertically polarized proton beam stored in the COSY Cooler Synchrotron. We observed almost full spin-flip when crossing the 1st-order G*gamma=8nu<sub>y</sub> vertical-betatron-tune spin resonance and partial depolarization near some 2nd- and 3rd-order resonances. We observed
Physics of the Earth and Planetary Interiors, 1999
. The pressure-volume-temperature P-V-T behavior in SiO -stishovite has been studied using a DIA-... more . The pressure-volume-temperature P-V-T behavior in SiO -stishovite has been studied using a DIA-type, cubic-anvil T 0 previously from Brillouin scattering and diamond-anvil cell X-ray diffraction studies on single crystal stishovite and ultrasonic studies on polycrystalline specimens. q
Programmed Death-1 (PD-1) and its ligand, PD-L1, are regulators of immune/ inflammatory mechanism... more Programmed Death-1 (PD-1) and its ligand, PD-L1, are regulators of immune/ inflammatory mechanisms. We explored the potential involvement of PD-1/PD-L1 pathway in the inflammatory response and tissue damage in cardiac injury models. Ischemic-reperfused and cryoinjured hearts were processed for flow cytometry and immunohistochemical studies for determination of cardiac PD-1 and PD-L1 in the context of assessment of the growth arrest- and DNA damage-inducible protein 153 (GADD153) which regulates both inflammation and cell death. Further, we explored the potential ability of injured cardiac cells to influence proliferation of T lymphocytes. The isolated ischemic-reperfused hearts displayed marked increases in expression of PD-1 and PD-L1 in cardiomyocytes; however, immunofluorescent studies indicate that PD-1 and PD-L1 are not primarily co-expressed on the same cardiomyocytes. Upregulation of PD-1/PD-L1 was associated with a) marked increases in GADD153 and interleukin (IL)-17 but a m...
The crude processing of electronic waste (e-waste) has led to serious contamination in soils. Whi... more The crude processing of electronic waste (e-waste) has led to serious contamination in soils. While microorganisms may play a key role in remediation of the contaminated soils, the ecological effects of combined pollution (heavy metals, polychlorinated biphenyls and polybrominated diphenyl ethers) on the composition and diversity of microbial communities remain unknown. In this study, a suite of e-waste contaminated soils were collected from Guiyu, China, and the indigenous microbial assemblages were profiled by 16S rRNA high-throughput sequencing and clone library analysis. Our data revealed significant differences in microbial taxonomic composition between the contaminated and the reference soils, with Proteobacteria, Acidobacteria, Bacteroidetes and Firmicutes dominating the e-waste-affected communities. Genera previously identified as organic pollutants-degrading bacteria, such as Acinetobacter, Pseudomonas and Alcanivorax, were frequently detected. Canonical correspondence anal...
Proceedings of the ASP-DAC '99 Asia and South Pacific Design Automation Conference 1999 (Cat. No.99EX198), 1999
In the past two decades, the simulated annealing technique has been considered as a powerful appr... more In the past two decades, the simulated annealing technique has been considered as a powerful approach to handle many NP-hard optimization problems in VLSI designs. Recently, a new Monte Carlo and optimization technique, named simulated tempering, was invented and has been successfully applied to many scientific problems, from random field Ising modeling to the traveling salesman problem. It is designed to overcome the drawback in simulated annealing when the problem has a rough energy landscape with many local minima separated by high energy barriers. In this paper, we have successfully applied a version of relaxed simulated tempering to slicing floorplan design with consideration of both area and wirelength optimization. Good experimental results were obtained.
Loops in proteins are often involved in biochemical functions. Their irregularity and flexibility... more Loops in proteins are often involved in biochemical functions. Their irregularity and flexibility make experimental structure determination and computational modeling challenging. Most current loop modeling methods focus on modeling single loops. In protein structure prediction, multiple loops often need to be modeled simultaneously. As interactions among loops in spatial proximity can be rather complex, sampling the conformations of multiple interacting loops is a challenging task. In this study, we report a new method called multi-loop Distance-guided Sequential chain-Growth Monte Carlo (m-DiSGro) for prediction of the conformations of multiple interacting loops in proteins. Our method achieves an average RMSD of 1:93 Å for lowest energy conformations of 36 pairs of interacting protein loops with the total length ranging from 12 to 24 residues. We further constructed a data set containing proteins with 2, 3, and 4 interacting loops. For the most challenging target proteins with 4 ...
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