MRP

BACKGROUND/AIMS: BSEP, MRP2, and MDR3 are major hepatic canalicular transporters mediating bile secretion. Their expression in human liver during development has not been reported. METHODS: Human liver samples from fetus at gestational age 14–20 weeks, ...

A B S T R A C T Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinicalexperimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB. ß

The objective of this paper is to estimate the manufacturing and product costs by using activity-based costing (ABC) method in an advanced manufacturing system that is run under either material requirements planning (MRP) or just in time (JIT) system. ABC is a method that can overcome many of the limitations of traditional costing systems. This paper reports and discusses the implementation of the ABC alongside a mathematical and simulation model to estimate the manufacturing and product cost in an automated manufacturing system. The potential effects of manufacturing planning and control strategies implemented on financial structure of the manufacturing system are initially analysed. ABC has been used to model the manufacturing and product costs. An extensive analysis has been carried out to calculate the product costs under the two strategies. The comparison of the two strategies in terms of effects on the manufacturing and product costs are carried out to highlight the difference between the two strategies. r

Present day manufacturing resource planning (MRP) systems do not perform well in engineered-to-order (ETO) environments. A study of the use of MRP systems by ETO companies has led to the development of a new framework for manufacturing planning systems. New features allow better coordination of activities in the areas of engineering, material acquisition, production, and delivery. The new framework especially addresses the problem of planning with uncertain information which is characteristic of an ETO environment. r

Inventory management system for any company is essential to fulfil customer demands on time and in cost effective manner. Selection and implementation of inventory management system for any company management is vital. In this paper, we will discuss the most commonly used inventory management tools and using a real furniture company data as a case study, we will implement the inventory management system. In last, we will compare the implemented inventory management system with the existing system and infer the results.

Inventory management system for any company is essential to fulfil customer demands on time and in cost effective manner. Selection and implementation of inventory management system for any company management is vital. In this paper, we will discuss the most commonly used inventory management tools and using a real furniture company data as a case study, we will implement the inventory management system. In last, we will compare the implemented inventory management system with the existing system and infer the results.

Este material pretende brindar un acompañamiento para la realización de un Plan de Requerimiento de Materiales (PRM/MRP) simple, como parte de la lógica que se maneja (vía software) y se ejecuta en las empresas grandes; así como también aplicable para algún tipo de Microempresas.

Nota: Se muestra como PDF pero al descargarlo se presenta como Excel y editadle.

El concepto de MRP I, es bien sencillo, se trata de saber qué se debe aprovisionar y/o fabricar, en qué cantidad y qué momento para cumplir compromisos establecidos. En otras palabras Díaz A. 1993, resume estas ideas planteando que el sistema pretende conocer: ¿Qué materiales son requeridos?. ¿Cuánto se necesita de cada material?. ¿Cuándo cada material es requerido?.

The importance of drug transporters as one of the determinants of pharmacokinetics has become increasingly evident . While much research has been conducted focusing the role of drug transporters in the liver [2; 3; 4; 5] and kidney [2; 6; 7] less is known about the importance of uptake and efflux transporters identified in the intestine . Over the past years the effects of intestinal transporters have been studied using in vivo models, in situ organ perfusions, in vitro tissue preparations and cell lines. This review aims to describe up to date findings regarding the importance of intestinal transporters on drug absorption and bioavailability, highlighting areas in need of further research. Wu and Benet [9] proposed a Biopharmaceutics Drug Disposition Classification System (BDDCS) that allows the prediction of transporter effects on the drug disposition of orally administered drugs. This review also discusses BDDCS predictions with respect to the role of intestinal transporters and intestinal transporter-metabolizing enzyme interplay on oral drug pharmacokinetics.

The use of supertree has been largely applied recently, mainly because of its features for analysing lots of different types of data together, as well as uniting different tree topologies without overlapping sets of taxa. Using the Matrix Representation with Parsimony (MRP), a supertree was built for Coelurosauria (Dinosauria, Theropoda). A total of 12 trees from the literature were used and coded with the standard MRP and with the modification suggested by Purvis. The matrixes had 82 taxa and 196 chacaters and were analysed in the program PAUP* through a TBR search. The resulting trees were very akin either in their length, indexes and topologies. The standard MRP had more resolved trees and did not suffer from genre exclusion from their groups in a way opposing to the topologies found in the source papers, nor did it suffer with the appearance of novel clades as such the Purvis modification did for both. The latter seemed to have much of its problems caused from the exceeding missing data present in the matrix. For the standard MRP results, the group Alavrezsauridae is held as the sister-group of Paraves, while for the Purvis modification it appears as the sister-group of Therizinosauroidea + Oviraptorosauria.

J Jo os sé é M Mo on nz zó ó M Ma ar rc co o A mis padres. Un Sistema Solar Un Sistema Humano ÍNDICE PRÓLOGO _________________________________________________________7 PRÓLOGO ____________________________________________________________ 9 1. SISTÉMICA __________________________________________________15 1.1. El Pensamiento Sistémico en la empresa. _______________________________ 16 1.2. De Romario al Pensamiento de Sistemas. _______________________________ 22 1.3. El Mediterráneo visto por un sistémico. ________________________________ 27 1.4. ¿Brujas en Sort?. Una metáfora cibernética. ____________________________ 34 1.5. Apéndice Sistémica. Algunos textos seleccionados. _______________________ 40 2. ORGANIZACIÓN _____________________________________________54 2.1. Monjes, aviones y vacas sagradas. ______________________________________ 55 2.2. Productividad. Ese objeto del deseo. ____________________________________ 62 2.3. Productividad, competitividad y empleo._________________________________ 70 2.4. Las empresas de servicios y la Calitividad. _______________________________ 75 2.5. Teoría de las Limitaciones (TOC) aplicada a la Empresa. El Management del sentido común. _________________________________________________________ 79 2.6. Capacidad infinita vs. Capacidad. Una reflexión sobre los Erp's aplicados a la gestión de producción. ___________________________________________________ 95 3. CALIDAD ___________________________________________________104 3.1. ¿Calidad Total?. La verdad está ahí fuera. ______________________________ 105 3.2. Calidad Total en la decisión.__________________________________________ 112 3.3. Recéteme algo, lo que sea.____________________________________________ 121 4. ECONOMÍA _________________________________________________125 4.1. Crecimiento, desarrollo y calidad de vida._______________________________ 126 4.2. Cultura de la subvención. Círculo vicioso vs. virtuoso._____________________ 131 4.3. ¿Trabajar más o trabajar menos?. ____________________________________ 138 4.4. Metaeconomía. De Moisés a la semana de 35 horas. _______________________ 144 4.5. Un elefante llamado desempleo. Una aproximación sistémica al desempleo.____ 149 5. ECOLOGÍA _________________________________________________161 5.1. ¿Existe la responsabilidad ecológica?. __________________________________ 162 ¿ 5.2. La nave Tierra no tiene tubo de escape._________________________________ 167 5.3. Apéndice Ecología. El Gran Jefe de Washington hace saber... ____________ 173 6. POLÍTICA __________________________________________________178 6.1. Listas de espera en sanidad. ¿Problema de gestión o problema político?. ______ 179 6.2. Eficacia política. El fin de una ilusión. __________________________________ 183 6.3. Encuestas, mentiras y física cuántica. __________________________________ 187 6.4. Imaginación ¿al poder?. _____________________________________________ 192 7. JUEGOS ____________________________________________________196 7.1. El dilema de Felipe González desde la Teoría de Juegos. ___________________ 197 7.2. Aznar, González y el dilema del prisionero. _____________________________ 203 7.3. Se equivoca de ficha sr. Aznar.________________________________________ 211 7.4. Uso y abuso de la persuasión._________________________________________ 215 8. INFONOMÍA ________________________________________________218 8.1. Sistemas de Información en la empresa. ¿Coste o ventaja competitiva?._______ 219 8.2. Papá, ¿los ordenadores piensan?. _____________________________________ 229 8.3. ¿Quo vadis Internet?. _______________________________________________ 237 8.4. ¿Quo vadis Telefónica?. _____________________________________________ 244 8.5. Internet y Pymes. Señales del Futuro. __________________________________ 248 8.6. Factores Críticos de Éxito en la Implantación de un ERP. __________________ 254 9. META ______________________________________________________261 9.1. Diez años sin Krishnamurti.__________________________________________ 262 9.2. Axiomas, hipótesis y mitos en el caso Alcácer.____________________________ 268 9.3. Eutanasia. Una aproximación al conflicto. ______________________________ 273 9.4. Apéndice Eutanasia. Algunos textos para transcender el conflicto. ___________ 278 9.5. Hay un lugar donde la Navidad... _____________________________________ 282 9.6. No som res. Un breve adiós a José Monzó Fabra _________________________ 286 El Pensador Sistémico 7 PRÓLOGO El Pensador Sistémico 8 Lewis Carroll. Alicia en el país de las maravillas.

It is widely accepted in the brain computer interface (BCI) research community that neurological phenomena are the only source of control in any BCI system. Artifacts are undesirable signals that can interfere with neurological phenomena. They may change the characteristics of neurological phenomena or even be mistakenly used as the source of control in BCI systems. Electrooculography (EOG) and electromyography (EMG) artifacts are considered among the most important sources of physiological artifacts in BCI systems. Currently, however, there is no comprehensive review of EMG and EOG artifacts in BCI literature. This paper reviews EOG and EMG artifacts associated with BCI systems and the current methods for dealing with them. More than 250 refereed journal and conference papers are reviewed and categorized based on the type of neurological phenomenon used and the methods employed for handling EOG and EMG artifacts.

ABSTRACT
The objetive of this research is to know the technique of conducting POMOSDA (Pondok Modern Sumber Daya At-Taqwa) etawa goat farming, to engineer feed requirement become more efficient. The method used in this research using MRP method. By doing a quantitative approach, descriptive and associative type. It is said that the quantitative approach because the approach used in the proposed research, process, hypothesis, down to the field, data analysis and data conclusions up to the writing using aspects of measurement, calculation, formulas and certainty of numerical data. The results of this study concluded that the implementation of cultivation in Pomosda etawa farming is done intensively in continuous goat and scheduling goat baths regularly. With an output value of 203 million and an input value of 139,101,375 is feasible to work on but by maximizing dairy products. POMOSDA etawa farming needs are more easily fulfilled with their own land.

The intestinal mucosa is not simply a barrier allowing entry of compounds such as nutrients or chemicals, and restricting that of others. Intestinal cells and activities perform selective absorption, biotransformations and efflux back to the lumen. Furthermore, food substances affect both bioavailability and intestinal function. Some are able to act as transcriptional regulators and enzyme modulators.

This paper presents a mathematical formulation of a capacity constrained multistage inventory and production control problem. It argues that most practical multistage inventory and production control problems can be summarised in the formulation. The model has a strong connection to the model of Billington, McClain and Thomas (1983) and is also inspired of a paper from Bard and Golany (1991). The revised Billington/McClain/Thomas model is formulated in a dynamic programming recursion. A numerical solution to a simple problem is presented. A scheduling problem concerning capacity constrained models are enlightened. Further, the paper points to differences and relationships between this capacity constrained model, MRP, Kanban and Cover-Time Planning.

We report the screening of analogues of indomethacin to investigate the structure-activity relationship (SAR) of indomethacinmediated multidrug resistance associated protein-1 (MRP-1) inhibition. By examining the activities of compounds with minor variations of the parent structure, we were able to separate MRP-1, glutathione-S-transferase (GST), cyclooxygenase (COX)-1 and COX-2 inhibitory activities. Combination cytotoxicity assays were utilised to identify agents which possess synergistic potential in MRP-1-expressing cell lines. MRP-1 Inside Out Vesicles (IOVs) were utilised to demonstrate the ability of the indomethacin analogues to inhibit the pump directly. Most of the indomethacin analogues active as MRP-1 inhibitors were poor GST inhibitors when compared with the GST-inhibitory activity of indomethacin. Two of the MRP-1 inhibitory analogues were found to have no COX-1 inhibitory activity and low COX-2 inhibitory activity, suggesting potentially reduced clinical toxicity. One MRP-1 inhibitory indomethacin analogue was also found to have low COX-1 inhibitory activity, but significant COX-2 inhibitory activity, making this analogue again interesting in terms of low potential toxicity, but with the possibility of direct inhibitory effects on tumour growth. #

The production planning and scheduling system used in refinery CIMS is discussed, where the production process, basic production characteristics, refinery production and administration, its activity types are introduced. An integrated refinery production plan and schedule system is put forward; its problem solving process is discussed in detail. A kind of integration framework used in the refinery CIMS and its computing environment are put forward and analysed. Finally, some conclusions are drawn out

Four new antigenic proteins located in Leishmania ribosomes have been characterized: S4, S6, L3 and L5. Recombinant versions of the four ribosomal proteins from Leishmania major were recognized by sera from human and canine patients suffering different clinical forms of leishmaniasis. The prophylactic properties of these proteins were first studied in the experimental model of cutaneous leishmaniasis caused by L. major inoculation into BALB/c mice. The administration of two of them, LmL3 or LmL5 combined with CpG-oligodeoxynucleotides (CpG-ODN) was able to protect BALB/c mice against L. major infection. Vaccinated mice showed smaller lesions and parasite burden compared to mice inoculated with vaccine diluent or vaccine adjuvant. Protection was correlated with an antigen-specific increased production of IFN-␥ paralleled by a decrease of the antigen-specific IL-10 mediated response in protected mice relative to non-protected controls. Further, it was demonstrated that BALB/c mice vaccinated with recombinant LmL3 or LmL5 plus CpG-ODN were also protected against the development of cutaneous lesions following inoculation of L. braziliensis. Together, data presented here indicate that LmL3 or LmL5 ribosomal proteins combined with Th1 inducing adjuvants, may be relevant components of a vaccine against cutaneous leishmaniasis caused by distinct species.

Retinoid X receptor-α (RXRα) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXRα deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0-to 5.4-fold in hepatocyte RXRα-null (H-RXRα-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid β-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXRα-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXRα-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXRα-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXRα-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXRα-null mice. In conclusion, these data suggest a critical role for RXRα in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury.

Más allá de la renovación pedagógica, se necesita una profunda transformación socioeducativa. Se defiende así, desde la praxis, la necesaria inserción de la educación en una trama cultural sociocrítica, en que intervienen como agentes clave los movimientos sociales y educativos, con una tarea común: la construcción de una `cultura transformadora´. Pensando en nuestra propia capacidad de actuación (incluyendo las iniciativas no plenamente coincidentes entre sí), se realiza finalmente una propuesta para conjugar las potencialidades de las redes y de los movimientos (educativos y sociales) e interactuar en espacios amplios de encuentro.

Further from a pedagogical renewal, there is a clear need of deep socio-educative transformation. We could base on praxis the necessary inclusion of Education within a sociocritic cultural frame, where social and educational movements take part as key agents to fulfill a common task: building a `transforming culture´. Thinking of our own capacity of acting upon a society (including initiatives which do not have the same exactly the same goals), the present article includes a proposal to combine the possibilities offered by networks and social and educative movements as well as interacting using wide meeting places.

Resumen:
Noël Burch puso las bases para la sistematización de los diferentes modelos de representación cinematográfica. El eje esencial de su argumentación, expuesto en El tragaluz del infinito, es que lo que distinguen los diferentes modelos es la posición de la mirada del espectador sobre la diégesis. Tomando en cuenta este punto de partida, Burch identifica dos modelos: el modelo de representación primitivo (MRP), regido por una mirada frontal y exterior al mundo diegético, y el modelo de representación institucional (MRI) que se caracteriza por la ubicuidad de una mirada interior a ese mundo. Partiendo de esta consideración metodológica de estudio, el presente artículo rastrea la coexistencia de ambos modelos en La ventana indiscreta de Alfred Hitchcock,concretamente cómo se articulan y cohabitan en el texto fílmico, así como la cristalización de un modelo tercero caracterizado por una mirada independizada y vinculada a la cámara.

Abstract:
Noël Burch stablished the basis for the systematization of the different models of cinematographic representation. The essential focus of his arguments, which were exposed in The skylight of infinity, is that the different models of representation are distinguished by the position of the viewer on the narration. Taking in account this starting point, Burch identifies two models: the Primitive Model of Representation (PMR), governed by a frontal glance which is out of the narrative world, and the Institutional Model of Representation (IMR) characterized by the ubiquity of a glance which is interior to that world. Starting by this methological consideration of study, this article traces the coexistence of both models in Alfred Hitchcock’s Rear Window; specifically how they cohabited and how they both were articulated in the filmic text. So as the crystallization of a third model characterized by an independent glance which is connected to the camera.

The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood-brain and blood-CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood-brain barrier and the choroid plexus, as well as provide recommendations for future research.

On s'intéresse au pilotage par une approche MRP, d'une chaîne logistique dédiée à la production de masse de produits fortement diversifiés. Il s'agit plus précisément de coordonner la production d'un ensemble de modules alternatifs montés sur un poste d'une ou plusieurs lignes d'assemblage final ainsi que celle des composants que ces modules comportent. Les niveaux de production de ces lignes sont stables. Les caractéristiques structurelles des demandes finales sont stables ou prévisibles. La production d'un composant est tirée par des réquisitions du Plan Directeur de Production (PDP) hors horizon gelé ne peut pas se faire à la commande dans le cadre classique de la MRP. On propose des solutions analytiques permettant de piloter la partie productive de la chaîne logistique par une approche MRP autorisant des productions partiellement ou totalement pour stock. On introduit également d'autres relations permettant de prendre en compte les aléas de qualité en production. Toutes ces solutions sont illustrées numériquement. ABSTRACT. This article focuses on the monitoring of a supply chain dedicated to the mass production of strongly diversified products. In particular we are interested in the part of this chain that contributes to the production of a set of alternative modules assembled on a work station of one or several assembly lines, whose production levels are stable. The customers' demand structures are assumed to be known. When the production of a component is drawn by requirements of the MPS that are beyond the frozen horizon, this component cannot be built-toorder. We provide and illustrate analytical solutions, adapted from the periodic order policies, to define scheduled orders of components to be produced partly or wholly to stock. Additional relations are provided to face disturbances induced by quality problems. MOTS-CLÉS : MRP, production à la commande, production pour stock, stock de sécurité, chaîne logistique, simulation de Monte Carlo.

Black hole and Grey hole attack is most happening attacks in Mesh networks. Mesh networks means nonstatic networks with making loops of networks with the help of active hotspots. In Wireless networks all the communication between the nodes is happening wirelessly and the nodes are so much resource constraint that it is difficult to employ any security solutions of other ad hoc networks. So they are attacked by malicious nodes. In black hole attack the attacker windup all the information and dropped it. In black hole attack, the series of RREQ (route request) and RREP (route reply) follows the smallest way of networking communication. The fault node always transmit RREP message as it receives RREQ, while managing the receivers sequence number. By the help of fault node packets are dropped. Sometimes fault node is authorised and otherwise it is unauthorised. Black hole attack is type of routing attack and can bring harm to whole network. Grey hole attack is the kind of denial of service attack. In this attack, the router which is mesh behave just not well and a subset of packets are forward and handle by receiver but leave by others. The presences of these attackers are hard to detect in wireless networks because over the wireless link the packets are lost due to bad channel quality. This paper deals with the study of analysis of delay occurs by these attack in Wireless Mesh networks and its types and also discuss about previous study by which we get idea about attack occurs in networks and also study various techniques to detect and prevent network from black hole and grey hole attack. Then we discuss about their result by using simulator OPNET.

It is widely accepted in the brain computer interface (BCI) research community that neurological phenomena are the only source of control in any BCI system. Artifacts are undesirable signals that can interfere with neurological phenomena. They may change the characteristics of neurological phenomena or even be mistakenly used as the source of control in BCI systems. Electrooculography (EOG) and electromyography (EMG) artifacts are considered among the most important sources of physiological artifacts in BCI systems. Currently, however, there is no comprehensive review of EMG and EOG artifacts in BCI literature. This paper reviews EOG and EMG artifacts associated with BCI systems and the current methods for dealing with them. More than 250 refereed journal and conference papers are reviewed and categorized based on the type of neurological phenomenon used and the methods employed for handling EOG and EMG artifacts. This study reveals weaknesses in BCI studies related to reporting the methods of handling EMG and EOG artifacts. Most BCI papers do not report whether or not they have considered the presence of EMG and EOG artifacts in the brain signals. Only a small percentage of BCI papers report automated methods for rejection or removal of artifacts in their systems. As the lack of dealing with artifacts may result in the deterioration of the performance of a particular BCI system during practical applications, it is necessary to develop automatic methods to handle artifacts or to design BCI systems whose performance is robust to the presence of artifacts.

The objective of this paper is to estimate the manufacturing and product costs by using activity-based costing (ABC) method in an advanced manufacturing system that is run under either material requirements planning (MRP) or just in time (JIT) system. ABC is a method that can overcome many of the limitations of traditional costing systems. This paper reports and discusses the implementation of the ABC alongside a mathematical and simulation model to estimate the manufacturing and product cost in an automated manufacturing system. The potential effects of manufacturing planning and control strategies implemented on financial structure of the manufacturing system are initially analysed. ABC has been used to model the manufacturing and product costs. An extensive analysis has been carried out to calculate the product costs under the two strategies. The comparison of the two strategies in terms of effects on the manufacturing and product costs are carried out to highlight the difference between the two strategies.

In the context of very extensive phylogenies, the debate concerning the best methodological approach and the growing use of taxonomic congruence is well known. Despite being well documented in the literature by the usage of hypothetical data, empirical tests capable of evaluating its efficiency are still limited. In the attempt to elucidate the matter, a single matrix for Theropoda was split into smaller matrices, which were analysed separately and then merged together with the MRP supertree method, in order to compare both results. The framework used to separate the characters was the disarticulation order. The supertree resulted in a topology similar to that of the original matrix, and the analyses of each anatomical class points that elements such as the cranium are more informative, although they should not be used alone to assess the phylogeny of the group. The method was then applied to a real fossil example: the Prolacertiformes. The results differed from one another, but they indicate that the group is not monophyletic, although some families are robust and the origins of Pterosauria and Arhosauria are still not solved. In fact, only a thorough revision of the group can help to clarify its phylogenetic relationships.

This paper presents a teaching system for Higher Education Institutions in careers such as logistics, supply chain, internal logistics and related fields, through the understanding of mathematical procedures oriented to simulation. Presenting a case study of material requirements planning (MRP) that provides a production and supply schedule, according to the sales forecasts of a Distribution Centre (CEDIS): The production standards and delivery times of the suppliers, which respond to the What, how much and When to supply. (Velasco Flores, 2017): MRP is a set of techniques that uses bill of materials data, inventory data and the master production plan to calculate material requirements. It suggests releasing material replenishment orders and rescheduling open orders, based on the time lag. (APICS, 2019): The MRP I mathematical procedure presented in this research is based on two fundamental aspects: 1. It refers to finished products. 2. This system is carried out according to the needs of each item (independent demands and product structure): MRP I is based on the calculation of the net needs of the articles and components, introducing a factor not considered in the traditional methods of stock management, which ultimately leads to modulate the time, with due planning with respect to its use, to subsequently simulate it in a software.

Herbicide safeners are known to protect monocotyledonous crops from herbicide injury by accelerating the metabolism of herbicides. We have investigated the effects of the safener cloquintocetmexyl, which protects small-grain cereals against the graminicidal herbicide, clodinafop-propargyl. Subtractive suppression hybridisation was used to identify wheat genes which are up-regulated by treatment not only with cloquintocet-mexyl but also with phenobarbital, which is known to stimulate xenobiotic metabolism in animals and plants. DNA sequences of five glutathione transferases (GSTs) belonging to three different classes and a multidrug resistance associated protein (MRP) homologue were identified in the screen. The chemical inducibility of these clones was confirmed by Northern analysis. The MRP protein was shown to be induced by treatments with cloquintocet-mexyl and phenobarbital and to be localised to the tonoplast. Since clodinafop-propargyl is not known to be metabolised by glutathionylation, the significance of GST induction is interpreted in terms of a generalised response to chemical stress, particularly the generation of active oxygen species.

The presence of P-glycoprotein (P-gp) and multiple drug resistance-associated protein (MRP) was examined in four human pancreatic adenocarcinoma cell lines (PANC-1, BxPC-3, AsPC-1, and Capan-1). Cellular accumulation of rhodamine 123 and [3H]vincristine were used to determine functional activity of P-gp and MRP, respectively. None of the cells showed any evidence of P-gp in the rhodamine 123 cellular accumulation assays. In contrast, PANC-1, BxPC-3 and AsPC-1 did display an increased accumulation of [3H]vincristine following treatment with either cyclosporin A or verapamil. Western blot analysis confirmed the expression of MRP, and little, if any, measurable P-gp in the cell lysates. These studies suggest that intrinsic drug resistance in pancreatic duct cancer may be due in part to the presence of MRP.

The treatment of alkylating cytotoxic drug cisplatin is often limited by high incidence rate of resistance. In the present study, the potential involvement of the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are retaining 25-fold higher levels of GSH than murine fibroblasts, could be sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells resulted in severe degree of GSH depletion and exacerbated cytotoxicity following cisplatin treatment compared to scrambled RNA control. In conclusion, we propose that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to oxidants, cytotoxic chemicals, and radiation.

Chloroacetanilide herbicides are among the most commonly used herbicides in agriculture. Several studies have demonstrated a number of them to be carcinogenic. ATP binding cassette (ABC) transporters are efflux pumps expressed in cell membranes, which form an important wall of defense against xenobiotics from different sources. We tested the interaction of the herbicides acetochlor, alachlor, dimetachlor, metazachlor, metolachlor, propachlor and prynachlor with human multidrug resistance transporters MDR1, MRP1, MRP2 and BCRP. A number of metabolites were studied for interaction with MRP1, MRP2 and MRP3. Transporter interactions were studied by measuring ATPase activity, inhibition of fluorescent dye efflux and vesicular transport. Also inhibition of MDR1 was monitored by measuring digoxin transport on Caco-2 monolayers and paclitaxel toxicity on K562-MDR cells. Acetochlor, alachlor, metolachlor and metazachlor showed specific interactions with MDR1. Digoxin permeability and paclitaxel cytotoxicity studies revealed that these herbicides are potent inhibitors of MDR1 that can modulate drug absorption and cause chemosensitization of cells. MRP1 was demonstrated to transport an important intermediate of the acetochlor detoxification pathway. Several specific interactions were shown when studying the interaction of chloroacetanilides with human transporter proteins. This study suggests an important role for transporter proteins in hazard prediction of agrochemicals and demonstrates how transporter interactions can be easily detected using in vitro screening methods.

A B S T R A C T ATP-binding cassette (ABC) transporters constitute a ubiquitous superfamily of membrane proteins responsible for the translocation of several substances across membranes using the chemical energy provided by ATP hydrolysis. ABC transporters participate in many physiological and pathophysiological processes, including cholesterol and lipid transportation and multidrug resistance. Oxysterols are the products of cholesterol oxidation, formed by both enzymatic and non-enzymatic mechanisms. The role of oxysterols in cholesterol metabolism and several diseases has been widely investigated, but many questions remain to be answered. Several lines of evidence link ABC transporter functions with cholesterol and oxysterol metabolism. This review discusses ABC transporters, oxysterols, and how they interact with each other. ß