LA CONCEPTION DE LA TECHNOLOGIE COMME BOITE NOIRE PAR LE CONTROLE DE GESTION BANCAIRE : LA MESURE DE LA PERFORMANCE OPERATIONNELLE DES AGENCES PAR LA METHODE DEA (DATA ENVELOPMENT ANALYSIS).

En intégrant la variable technologique, cet article décline les concepts d'" X Efficiency " et de " performance productive ". En recourant à l'axiomatique DEA, appliquée au secteur bancaire, les auteurs évaluent la productivité administrative de l'activité " Accueil guichet " de 42 agences.Benchmarking ; Contrôle de Gestion Bancaire ; Data Envelopment Analysis ; Efficience ; Management des Ressources Technologiques ; Performance productive ; Programmation linéaire ; Xefficiency

Comparative Localization and Functional Activity of the Main Hepatobiliary Transporters in HepaRG Cells and Primary Human Hepatocytes

The role of hepatobiliary transporters in drug-induced liver injury remains poorly understood. Various invivo and invitro biological approaches are currently used for studying hepatic transporters; however, appropriate localization and functional activity of these transporters are essential for normal biliary flow and drug transport. Human hepatocytes (HHs) are considered as the most suitable invitro cell model but erratic availability and inter-donor functional variations limit their use. In this work, we aimed to compare localization of influx and efflux transporters and their functional activity in differentiated human HepaRG hepatocytes with fresh HHs in conventional (CCHH) and sandwich (SCHH) cultures. All tested influx and efflux transporters were correctly localized to canalicular [bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), multidrug resistance protein 1 (MDR1), and MDR3] or basolateral [Na+-taurocholate co-transporting polypeptide (NTCP) and MRP3] membrane domains and were functional in all models. Contrary to other transporters, NTCP and BSEP were less abundant and active in HepaRG cells, cellular uptake of taurocholate was 2.2- and 1.4-fold and bile excretion index 2.8- and 2.6-fold lower, than in SCHHs and CCHHs, respectively. However, when taurocholate canalicular efflux was evaluated in standard and divalent cation-free conditions in buffers or cell lysates, the difference between the three models did not exceed 9.3%. Interestingly, cell imaging showed higher bile canaliculi contraction/relaxation activity in HepaRG hepatocytes and larger bile canaliculi networks in SCHHs. Altogether, our results bring new insights in mechanisms involved in bile acids accumulation and excretion in HHs and suggest that HepaRG cells represent a suitable model for studying hepatobiliary transporters and drug-induced cholestasi

Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals

Les stratégies d'alliances dans I'industrie agro-alimentaire française : des logiques contrastées

*Ecole Nationale Superieure Agronomique de Rennes 65 rue de Saint-Brieuc 35042 RENNES CEDEX (FRA) Diffusion du document : Ecole Nationale Superieure Agronomique de Rennes 65 rue de Saint-Brieuc 35042 RENNES CEDEX (FRA)The evolution of co-operative inter-firm relations over the last two decades has given rise to profuseliterature, in tl,e form of either theoretical analyses or empirical studies. The food processing industryhas been kept out of these studies and has never been included in any specific work on strategicalliances. As part of an ernpirical approach based on a database of 259 agreements reached between1988 and 1997, this paper confirms that alliances are a significant feature of this industry and that theyfollow two main logics, i.e., a vertical logic of value chain and a horizontal logic taking in account themarket dimension. This analysis offers a novel alliance classification and identifies specific factorscharacterising the practice of alliances within this sector. In particular, it highlights the need to take thespecificities of food processing activities into consideration, as well as the existence of a specifictechnological status and particular innovation practices.Au cours des deux dernières décennies, l'évolution des relations de coopération inter-firmes a suscitéune littérature abondante tant au niveau des analyses théoriques que des études empiriques. L'industrieagro-alimentaire est restée largement en marge de ces travaux et n'a jamais fait I'objet d'analysesspécifiques concernant la pratique des alliances stratégiques. Dans le cadre d'une démarche empirique,fondée sur l'exploitation d'une base de données recensant 259 accords conclus sur la période 1988 -7997, cet article confirme que les alliances constituent une pratique significative dans ce secteur etqu'elles obéissent à deux logiques principales, l'une verticale de chaîne de valeur et l'autre horizontalede marché. Cette analyse permet de proposer une typologie originale des alliances et de repérer lesfacteurs d'identité et de spécificité de cette pratique, dans ce secteur. En particulier, elle rappelle lanécessité de tenir compte des dimensions caractéristiques des métiers et des activités des firmes del'agro-alimentaire, et de l'existence d'un régime technologique et de modes d'innovation particuliers

Transcripts of ceruloplasmin but not hepcidin, both major iron metabolism genes, exhibit a decreasing pattern along portocentral axis of mouse liver

International audienc

Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix

Human hepatocytes are extensively needed in drug discovery and development. Stem cell-derived hepatocytes are expected to be an improved and continuous model of human liver to study drug candidates. Generation of endoderm-derived hepatocytes from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, is a complex, challenging process requiring specific signals from soluble factors and insoluble matrices at each developmental stage. In this study, we used human liver progenitor HepaRG-derived acellular matrix (ACM) as a hepatic progenitor-specific matrix to induce hepatic commitment of hPSC-derived definitive endoderm (DE) cells. The DE cells showed much better attachment to the HepaRG ACM than other matrices tested and then differentiated towards hepatic cells, which expressed hepatocyte-specific makers. We demonstrate that Matrigel overlay induced hepatocyte phenotype and inhibited biliary epithelial differentiation in two hPSC lines studied. In conclusion, our study demonstrates that the HepaRG ACM, a hepatic progenitor-specific matrix, plays an important role in the hepatic differentiation of hPSCs. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.

In the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the immune system, reproductive organs, and the endocrine system. The second part of this report reviews the application of in vitro culture systems to organ specific toxicity and evaluates the application of these systems both in industry for safety assessment and in government for regulatory purposes. Members of the working group (WG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cultures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation of human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment in each organ system, to organize and make available via the Internet complete in vivo toxicity data, including human data, containing dose, end points, and toxicokinetics. The WG also recommended that research should be supported to identify and to validate biological end points for target organ toxicity to be used in alternative toxicity testing strategies

Stratégies d'alliances et nouvelles frontières de la coopérative agro-alimentaire

*Ecole Nationale Superieure Agronomique de Rennes 65 rue de Saint-Brieuc 35042 RENNES CEDEX (FRA) Diffusion du document : Ecole Nationale Superieure Agronomique de Rennes 65 rue de Saint-Brieuc 35042 RENNES CEDEX (FRA)This document is based on the analysis of 70 alliances established between 1987 and 1999 by the co-operatives of the Brittany region. It analyses the consequences of this strategy on the agrofood co-operative boundaries. It shows the emergence of new cohesion forms regarding the business, geographical, strategical and governing dimensions. Their control represents a key challenge for the future of the co-operative system.A partir de l'étude de 70 alliances conclues sur la période 1987 - 1999 par les coopératives de la région Bretagne, l'objectif de ce document est d'analyser les conséquences de cette stratégie sur l'évolution des frontières de la coopérative agro-alimentaire. Il met en évidence l'émergence de nouvelles cohérences au plan des métiers, de l'organisation spatiale, de la stratégie et du gouvernement des coopératives, dont la maîtrise constitue un enjeu pour l'avenir du système coopératif

Advances in tetrahydropyrido[1,2-a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors.

International audienceAn efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro kinase activities and the best effects were obtained with lung and colon cell lines