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In the periphery, Foxp3 expression is considered sufficient to maintain natural regulatory CD4+ T-cell suppressive function. In this study, we challenge this model. Indeed, in mouse chimeras in which major histocompatibility complex (MHC) class II expression is restricted to the thymus, peripheral regulatory CD4+ T cells lack suppressive activity. In addition, regulatory CD4+ T cells recovered 5 days after transfer into recipient mice lacking expression of MHC class II molecules (self-deprived) are unable to inhibit the proliferative response of conventional CD4+ T cells both in vitro and in vivo. Disruption of TCR/MHC class II interactions rapidly leads to alterations in the regulatory CD4+ T-cell phenotype, the ability to respond to stimulation and to produce interleukin-10, and the transcriptional signature. Interestingly, self-deprivation does not affect Foxp3 expression indicating that in regulatory CD4+ T cells, self-recognition induces unique transcriptional and functional features that do not rely on Foxp3 expression.

In this paper, a physical model is proposed to estimate the TRIAC solder joint fatigue during power cycling. The lifetime prediction is based on the following assumptions: the case temperature swing (DTcase) is the main acceleration factor, the solder joints are the weakest materials in the non-insulated TO-220AB TRIAC package and the plastic strain within the solder layer due to shearing is the failure cause.

This paper presents the insulated TO-220AB TRIAC package aging when these devices are subjected to experimental power cycling test with various case temperature swings (Δ T case ). This study includes reliability tests set-up, results and failure analysis. An innovative failure analysis flow is proposed to identify the failure mechanism implied. This new failure analysis process flow is necessary due to the complex stack of these devices. Finally, thanks to the reliability tests and the complete failure analysis results, the thermal resistance ( R th ) change is correlated to the physical defect modification. This whole study gives the first data collection that is required to propose a lifetime prediction model for insulated TO-220AB TRIAC package during power cycling accelerated aging tests.

Background & Aims β-Catenin is an oncogene frequently mutated in hepatocellular carcinoma. In this study, we investigated target genes of β-catenin signaling in hepatocyte proliferation. Methods We studied transgenic mice displaying either inactivation or activation of the β-catenin pathway, focusing on analysis of liver proliferation due to aberrant β-catenin activation, and on the regeneration process during which β-catenin signaling is transiently activated. We localized in situ the various partners involved in proliferation or identified as targets of β-catenin in these transgenic and regenerating livers. We also performed comparative transcriptome analyses, using microarrays. Finally, we extracted, from deep-sequencing data, both the DNA regulatory elements bound to the β-catenin/Tcf nuclear complex and the expression levels of critical targets identified in microarrays. Results β-Catenin activation during liver regeneration occurred during G1/S cell cycle progression and allowed zonal extension of the normal territory of active β-catenin and panlobular proliferation. We found that β-catenin controlled both cell-autonomous and non-cell-autonomous hepatocyte proliferation, through direct transcriptional and complex control of cyclin D1 gene expression and of the expression of a new target gene, Tgfα. Conclusions We propose that β-catenin controls panlobular hepatocyte proliferation partly by controlling, together with its Tcf4 nuclear partner, expression of the pro-proliferation cyclin D1 and Tgfα genes. This study constitutes a first step toward understanding the oncogenic properties of this prominent signaling pathway in the liver.

This paper compares two strategies for replicating a put option used to synthetize a debt guarantee contract. The first strategy, super-replication, while maintaining the portfolio value greater or equal to a target value, minimizes the transaction cost of replicating a debt insurance put option by using dynamic linear programming. The second strategy replicates this put option by maximizing the guarantor's expected utility. A comparative study shows that both strategies give better results than the Leland (1985) method. If we use a risk-adjusted performance metric, the utility-based method performs best when transaction costs are relatively low. When transaction costs are relatively high, the two strategies yield similar results and still outperform Leland's.

Many papers exploiting the various MPPT (maximum power point tracking) techniques in PV (photovoltaic) applications, from the simple to the most complicated, can be found in literature. However, these techniques may not always be easy to implement in industrial applications. The main challenge of this paper is to model and implement the P & O (perturb and observe) algorithm in a low-cost PV-powered pumping system. To that end, a comparative investigation of the performance characteristics of the most popular MPPT methods, such as FOCV (fractional open circuit voltage), FSCC (fractional short circuit current), FLC (fuzzy logic control), ANN (artificial neural network) and INC (incremental conductance) is presented. This analysis is helpful to highlight the relevance of the P & O technique taking better account of complexity, difficulty of implementation and cost considerations in water pumping applications. The targeted PV-powered pumping system is based on a single-phase induction motor supplied by a three-phase inverter controlled by the DTC (direct torque control) technique. This stand-alone PV system is dedicated to water pumping, especially in rural areas that have no access to national grids but have sufficient amount of solar radiation. Simulation modeling (Matlab/Simulink) and experimental results are presented to demonstrate the relevance of the system.

Individuals, typically, are exposed to mixtures of environmental xenobiotics affecting multiple organs and acting through different xenosensors and pathways in species and cell-type specific manners. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and α-endosulfan are Persistent Organic Pollutants (POPs) and endocrine disruptors which act through different xenosensors and accumulate in the liver. Our objective in this HEALS study was to investigate the effects of the mixture of these POPs on gene expression in a human-derived hepatocyte cell line, HepaRG. We found that, in spite of having largely uncorrelated effects, TCDD and α-endosulfan, when mixed, alter the expression of genes. The combined effects of the mixture of the POPs significantly altered the expression of 100 genes (42 up- and 58 down-regulated) whereas the same concentration of either POP alone did not alter significantly the expression of these genes. For 32 other genes, selective inhibitory crosstalk between TCDD and α-endosulfan was observed. One of the POPs inhibited the effect, on gene expression, of the other in the mixture although, when used alone, that POP did not affect expression. The expression of another 82 genes was significantly altered (up- or down-regulated) by a single POP. The addition of the second POP either increased, in the same direction, the effect on gene expression or had no further effect. At low concentrations (0.2 nM TCDD and 1 μM α-endosulfan), the POPs still had significant effects and the levels of expression of the corresponding proteins were found to be affected for some genes. Particularly striking was the 80-90% inhibition, by the mixture, of the expression of a number of genes of several hepatic intermediary metabolic pathways (glycerolipid metabolism, FXR/RXR activation, glycolysis/gluconeogenesis, retinoid and bile acid biosynthesis), whereas each pollutant alone had only a moderate effect.

Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren’s syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR.In vitroactivation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.

Rectal infection of macaques by SIV is a model for rectal HIV transmission. We focus here on the digestive tract during days 7–14 of primary rectal infection by SIV in 15 rhesus macaques. Surprisingly, we did not detect productively infected cells in the rectosigmoid colon at early stages of viral dissemination. This strongly suggests that there is no massive viral amplification in the rectosigmoid colon prior to viral dissemination. As dissemination proceeds, productively infected T cells are observed in the rectosigmoid colon and small intestine, with rectosigmoid colon showing the heaviest viral load. Lymphoid follicles are infected prior to lamina propria at both sites. When viral dissemination is widespread, inflammatory infiltrates are visible in the rectosigmoid colon, but not in the small intestine. An important decrease in CD4+ T cells is then observed in the lamina propria of the rectosigmoid colon only.

The all-solid-state thin-film lithium microbatteries fulfill the requirements of a wide range of new markets and applications. Innovative due to the absence of liquid electrolyte, these systems are meant to replace conventional energy storage systems that cannot meet the size requirements of present and future microelectronic devices, such as smart cards, battery-assisted RFID tags, wireless sensor networks, Real-Time Clock back-up batteries, and multiple healthcare applications. Long-time leader in power technologies, STMicroelectronics has realized significant investments in the development of new miniaturized solutions for energy storage. This study focuses on the reliability performances of EnFilm™ HiCap batteries, characterized by 1x1 inch footprint and a nominal capacity of 700µA.h between 4.2V and 3.6V. The positive electrode material is made of lithium cobalt oxide (LiCoO2) and the solid electrolyte is a lithium phosphorus oxynitride (LiPON), a material originally developed and patented by Oak Ridge National Laboratories [1]. Both thin films are deposited by sputtering techniques. Despite many recent studies, the all-solid-state systems remain minority regarding liquid electrolyte Li-ion technologies. Today widely developed, the Li-ion batteries are extensively used in portable instruments especially due to their large capacities. However, the Li-ion systems present a few vulnerabilities. As highlighted by several studies, the graphite/electrolyte interface is considered by many researchers to be the major source of reliability issue, due to reactions between the anode and the electrolyte [2]. Indeed, many works reveal that a large irreversible capacity loss is initiated by the formation of an interfacial SEI film, resulting from the irreversible consumption of Li+. Hence, thin film batteries should present a great interest regarding reliability behavior, since no formation of SEI layer is expected. In this paper we propose to investigate further the ageing characteristics of all-solid-state Li/LiPON interface during an extended electrochemical cycling study. Experimentally, batteries were submitted to series of potentiodynamic charges and galvanostatic discharges (1.4C current rate) at a temperature of 60°C, in order to accelerate the ageing mechanisms. Electrochemical impedance spectroscopy (EIS) measurements were regularly performed at 30°C, in order to detect any evolution of each contributor of internal resistance [3]. The equivalent circuit shown in figure 1 was used to model the impedance data, so that some key physical parameters might be extracted, such as the exchange current density at Li/LiPON interface. As shown in figure 2, the impedance data analysis reveals the relatively great stability of interfacial contributions, even after 3000 cycles. These results prove that the solid character of the electrolyte confers to the system an electrochemical integrity for very long periods of use. Furthermore, the stability of the exchange current extracted for Li/electrolyte interface (table 1) reveals the absence of any chemical or morphological modifications, which are at the origin of most failures reported for liquid electrolyte Li-ion systems. To conclude, this paper highlights the reliability performances of all-solid-state thin film batteries technology, through the electrochemical characterization of the Li/LiPON interface at different steps of the cycle life. Besides, this study demonstrates that EIS measurement turns out to be a successful tool of failure mechanisms investigation and understanding. [1] X. Yu et al., J. Electrochem. Soc., 1997, 144, 524-532 [2]J. Vetter et al., A. J. Power Sources, 2005, 147, 269-281 [3] S. D.Fabre et al., J. Electrochem. Soc., 2011, 159, A104-A115

Objectives Although TB immunotherapy improves the results of conventional drug treatment, the effects of combining chemotherapy and immunotherapy have never been systematically evaluated. We used a comprehensive lung transcriptome analysis to directly compare the activity of combined chemotherapy and immunotherapy with that of single treatments in a mouse model of TB. Methods Mycobacterium tuberculosis-infected mice in the chronic phase of the disease (day 30) received: (i) isoniazid and rifampicin (drugs) daily for 30 days; (ii) DNA immunotherapy (DNA), consisting of four 100 μg injections at 10 day intervals; (iii) both therapies (DNA + drugs); or (iv) saline. The effects were evaluated 10 days after the end of treatment (day 70 post-infection). Results In all groups a systemic reduction in the load of bacilli was observed, bacilli became undetectable in the drugs and DNA + drugs groups, but the whole lung transcriptome analysis showed 867 genes exclusively modulated by the DNA + drugs combination. Gene enrichment analysis indicated that DNA + drugs treatment provided synergistic effects, including the down-regulation of proinflammatory cytokines and mediators of fibrosis, as confirmed by real-time PCR, ELISA, histopathology and hydroxyproline assay. Conclusions Our results provide a molecular basis for the advantages of TB treatment using combined chemotherapy and DNA immunotherapy and demonstrate the synergistic effects obtained with this strategy.

In this paper a creep deformation model has been developed for Type 321 stainless steel which has been based on a modified version of the creep model that is used in the French fast reactor design code RCC-MR. The model has been evaluated using: 1) constant load creep data covering the temperature range from 550°C to 650°C and 2) constant displacement, stress relaxation data obtained from creep-fatigue tests at 650°C. Samples in the heat-treatment conditions of solution-treated, aged, and simulated ‘heat affected zone’ have been assessed. The standard RCC-MR model was fitted to the constant load data and provided good predictions of forward creep. However, when this model was used to predict stress relaxation it was observed that the model significantly over predicted creep strain rates and therefore the level of stress drop during each cycle. During constant load tests the stress remains relatively constant (noting that true stress does increase a small amount prior to rupture). However, in relaxation tests the stress varies significantly over the dwell. Due to the poor predictions of stress relaxation it was hypothesised that the fitted model did not capture the stress dependence of creep appropriately. The RCC-MR model was therefore modified to include a primary and secondary threshold stress term that is a function of the accumulated creep strain. This work indicates that the RCC-MR model, modified to include threshold stresses, can be used to provide good predictions of both forward creep and stress relaxation in Type 321 stainless steel. Further work is required to validate this model on stress relaxation data at additional temperatures and lower start of dwell stresses.

Intra-uterine growth restriction (IUGR) dramatically increases the risk of bronchopulmonary dysplasia in preterm babies, a disease characterized by arrested alveolarization and abnormal microvascular angiogenesis. We have previously described a rodent low protein diet (LPD) model of IUGR inducing impaired alveolarization, but failed to demonstrate any modification of the classical factors involved in lung development. We performed a genome-wide microarray analysis in 120 rat pups with LPD-induced IUGR and their controls, at three key time points of the alveolarization process: postnatal day 4 (P4): start of alveolarization; P10: peak of the alveolarization process and P21: end of the alveolarization process. Results were analysed using Arraymining, DAVID and KEGG software and validated by qRT-PCR and western blots. Considering a cut-off of 2:1 as significant, 67 transcripts at P4, 102 transcripts at P10 and 451 transcripts at P21 were up-regulated, and 89 transcripts at P4, 25 transcripts at P10 and 585 transcripts at P21 were down-regulated. Automatic functional classification identified three main modified pathways, 'cell adhesion molecules', 'cardiac muscle contraction' and 'peroxisome proliferator-activated receptor' (PPAR). Protein analysis confirmed involvement of the PPAR pathway, with an increase of FABP4, an activator of this pathway, at P4 and an increase of adiponectin at P21. Other data also suggest involvement of the PPAR pathway in impaired alveolarization. Our results show that deregulation of the PPAR pathway may be an important component of the mechanism inducing impaired alveolarization observed in IUGR. The complete dataset is available as GEO profiles on the Gene Expression Omnibus (GEO) database ( www.ncbi.nih.gov/geo/, GEO Accession No. GSE56956).

This article deals with the development of an innovative low-loss monolithic AC switch based on super-gain BJT manufactured on silicon substrate. The GREMAN laboratory has started this study for ten years. Two main categories of AC switch are described: hybrid AC switch (based on the discrete association of 2 super-gain BJTs) and monolithic AC switch. The key criteria to design and process the monolithic power device are particularly discussed taking into consideration its application areas and its manufacturability.

International audience; This paper deals with a new approach to science and education regarding photovoltaic energy and applications. This teaching method is based on a Solar Production Simulator (SPS). This apparatus is able to reproduce the sun’s path on a small scale at all times of the year. The energy production is then estimated with different orientation and/or inclination of a solar sensor. The SPS provides students with the unique opportunity to learn, in a playful manner, the fundamental principles of photovoltaic energy. Several examples of practical work are detailed to give an accurate appreciation of many applications in the photovoltaic sector. A lot of applications could be studied such as implementation of solar position calculations, electrical characterization of solar cells with various technologies or tracking system programming.

International audience; This paper deals with an innovative low-loss AC switch, named as TBBS (transistor based bidirectional switch), based on the association of super-gain BJTs developed by the GREMAN laboratory. The main characterization results of the super-gain BJT are reminded to identify the key parameters that are essential to build the TBBS. A complete characterization database in static mode of this new AC switch is discussed. In particular, its forward and reverse-biased features have been measured to see the evolution of the DC current gain as a function of the current density. The TBBS makes sense when using the super-gain BJT (bipolar junction transistor) in reverse mode. It means that the reverse DC current gain has to be sufficient (at least higher than 1 compared with the conventional BJT one). This new AC switch is bidirectional in current and voltage, totally controllable (turn-on and turn-off) and the most attractive solution in terms of on-state power losses. Further, its manufacturing process is as easier as existing device such as triac.

International audience; This paper deals with the introduction of a highly doped N-type diffusion, called field stopper, in the bottom of each peripheral groove of double MESA-GLASS AC switch (e.g. Triac) to strengthen its reliability in more severe applications. From a set of high temperature and reverse bias (HTRB) tests, this new process flow allows multiplying the device lifetime by 11.3 compared to standard products when junction temperature and bias are fixed to 150 °C and 800 V AC respectively. An empirical acceleration model is proposed. This model is characterized by activation energy and voltage constant about 0.48 eV and 6.7 mV-1, respectively. Finally, we suggest that ionic conduction through the molding compound is the main physical phenomenon involved in the double MESA-GLASS AC switch aging.

We investigated the effects of the liver damage induced by flutamide in primary rat hepatocytes using liver microfluidic biochips. Flutamide is a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10 μM and 100 μM, were used to expose the hepatocytes for 24h under perfusion. Thanks to the maintenance of hepatocyte differentiation phenotype and to the biotransformation performance in the microfluidic cultures, the metabolic ratio analysis of hydroxyflutamide, flutamide-gluthatione and hydroxyflutamide-gluthatione productions demonstrated saturation of the drug's biotransformation process and the maintenance of a high level of flutamide at 100 μM when compared to 10 μM. A microarray analysis comparing flutamide (10 or 100 μM) with controls revealed a common response for both concentrations illustrated by modulating the expression of the mRNA of genes associated with mitochondrial perturbation, of the proliferator-activated receptors (Ppar) signaling, lipid and fatty acid metabolism, antioxidant defense, and cell death pathways, consistently with in vitro and in vivo reports. Additionally to literature reports, our integration of the transcriptomic profiles demonstrated a specific dose dependent response. We found at 10 μM a typical pro-survival/apoptosis network activation (through IGF/PDGFD upstream route and via a downstream up regulation in CREB5, BCL2, IKBKG routes in the PI3K/signaling). We also found a down regulation of mRNA levels in sugar and amino acid metabolism pathways. At 100 μM a typical necrosis switch was observed associated with a down regulation of the tight junctions' pathway, a cellular aggregation and a reduction of the cell viability. Altogether our data demonstrated the potential and the sensitivity of our liver microfluidic cultures to evaluate xenobiotic toxicity by improving in vitro analysis and reproducing both in vitro and in vivo results. Finally, we proposed two integrated synthetic networks to describe the response of rat hepatocytes to both exposure concentrations of flutamide.

We investigated metabolic clearances of phenacetin, midazolam, propranolol, paracetamol, tolbutamide, caffeine, and dextromethorphan by primary rat hepatocytes cultivated in microfluidic biochips. The levels of mRNA of the HNF4 α, PXR , AHR, CYP3A1 , and CYP1A2 genes were enhanced in the biochip cultures when compared with postextraction levels. We measured a high and rapid adsorption on the biochip walls and inside the circuit for dextromethorphan and midazolam, a moderate adsorption for phenacetin and propranolol, and a low adsorption for caffeine, tolbutamide, and paracetamol. Drug biotransformations were demonstrated by the formations of specific metabolites such as paraxanthyne (caffeine), paracetamol (phenacetin), 1-OH midazolam (midazolam), paracetamol sulfate (paracetamol and phenacetin), and dextrorphan (dextromethorphan). We used a pharmacokinetic model to estimate the adsorption and in vitro intrinsic drug clearance values. We calculated in vitro intrinsic clearance values of 0.5, 3, 12.5, 83, 100, 160, and 900 μL/min per 10 6 cells for the tolbutamide, caffeine, paracetamol, dextromethorphan, phenacetin, midazolam, and propranolol, respectively. A second model describing the liver as a well-stirred compartment predicted in vivo hepatic clearances of 0.1, 13.8, 30, 44.1, 61, 72, 85, and 61 mL/min per kg of body mass for the tolbutamide, caffeine, paracetamol, midazolam, dextromethorphan, phenacetin, and propranolol, respectively. These values appeared consistent with previously reported data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:706–718, 2014

Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma.

We investigated the behavior of primary rat hepatocytes in biochips using a microfluidic platform (the integrated dynamic cell culture microchip). We studied the effects of cell inoculation densities (0.2–0.5 × 106 cells/biochip) and perfusion flow rates (10, 25, and 40 µL/min) during 72 h of perfusion. No effects were observed on hepatocyte morphology, but the levels of mRNA and CYP1A2 activity were found to be dependent on the initial cell densities and flow rates. The dataset made it possible to extract a best estimated range of parameters in which the rat hepatocytes appeared the most functional in the biochips. Namely, at 0.25 × 106 inoculated cells cultivated at 25 µL/min for 72 h, we demonstrated better induction of the expression of all the genes analyzed in comparison with other cell densities and flow rates. More precisely, when primary rat hepatocytes were cultivated at these conditions, the time-lapse analysis demonstrated an over expression of CYP3A1, CYP2B1, ABCC1b and ABCC2 in the biochips when compared to the postextraction levels. Furthermore, the AHR, CYP1A2, GSTA2, SULT1A1, and UGT1A6 levels remained higher than 50% of the postextraction values whereas values of HNF4α, CEBP, and PXR remained higher than 20% during the duration of the culture process. Nevertheless, an important reduction in mRNA levels was found for the xenosensors CAR and FXR, and the related CYP (CYP2E1, CYP7A1, CYP3A2, and CYP2D2). CYP1A2 functionality was illustrated by 700 ± 100 pmol/h/106 cells resorufin production. This study highlighted the functionality in optimized conditions of primary rat hepatocytes in parallelized microfluidic cultures and their potential for drug screening applications. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:401–410, 2014

Cet article propose un retour d’experiences d’une nouvelle approche pedagogique de l’enseignement de l’electronique et du genie electrique menee au sein de Polytech Tours (ecole d’ingenieurs). Cette approche est fondee sur un projet intensif (trois semaines consecutives a plein temps dediees a l’etude et a la realisation d’un systeme industriel) realisee de maniere collective (33 eleves ingenieurs repartis en 3 groupes de 11 etudiants). L’etude a consiste a proceder a l’electrification d’un châssis de kart et a rendre le vehicule electrique performant. Les eleves ingenieurs ont entre autre justifie tous les elements composant le systeme de motorisation, assemble toutes les pieces du kart electrique, teste le bon fonctionnement de ce dernier et apporte une innovation technologique autour de la recuperation d’energie cinetique au freinage par l’intermediaire de super-condensateurs. Cette initiative, fortement appreciee des etudiants puisque chacun d’entre eux a joue un role actif dans la realisation du projet, a en outre ete saluee par la presse locale et regionale.

The functionality of primary rat hepatocytes was assessed in an Integrated Dynamic Cell Cultures in Microsystem (IDCCM) device. We characterized the hepatocytes over 96h of culture and evaluated the impact of dynamic cell culture on their viability, inducibility, and metabolic activity. Reverse Transcription quantitative Polymerase Chain Reaction (RTqPCR) was performed on selected genes: liver transcription factors ( HNF4α and CEBP ), nuclear receptors sensitive to xenobiotics ( AhR , PXR , CAR , and FXR ), cytochromes P450 (CYPs) ( 1A2 , 3A2 , 3A23 / 3A1 , 7A1 , 2B1 , 2C6 , 2C , 2D1 , 2D2 , and 2E1 ), phase II metabolism enzymes ( GSTA2 , SULT1A1 , and UGT1A6 ), ABC transporters ( ABCB1b and ABCC2 ), and oxidative stress related enzymes ( HMOX1 and NQO1 ). Microperfused-cultured hepatocytes remained viable and differentiated with in vivo -like phenotype and genotype. In contrast with postadhesion gene levels, the first 48h of perfusion enhanced the expression of xenosensors and their target CYPs. Furthermore, CYP3A1 , CYP2B1 , GSTA2 , SULT1A1 , UGT1A1 , ABCB1b , and ABCC2 were upregulated in IDCCM and reached above postextraction levels all along the duration of culture. Metabolic activities were also confirmed with the detection of metabolism rate and induced mRNAs after exposure to several inducers: 3-methylcholanthrene, caffeine, phenacetin, paracetamol,, and midazolam. Finally, this metabolic characterization confirms that IDCCM is able to maintain rat hepatocytes functions to investigate drug metabolism.

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In the periphery, Foxp3 expression is considered sufficient to maintain natural regulatory CD4(+) T-cell suppressive function. In this study, we challenge this model. Indeed, in mouse chimeras in which major histocompatibility complex (MHC) class II expression is restricted to the thymus, peripheral regulatory CD4(+) T cells lack suppressive activity. In addition, regulatory CD4(+) T cells recovered 5 days after transfer into recipient mice lacking expression of MHC class II molecules (self-deprived) are unable to inhibit the proliferative response of conventional CD4(+) T cells both in vitro and in vivo. Disruption of TCR/MHC class II interactions rapidly leads to alterations in the regulatory CD4(+) T-cell phenotype, the ability to respond to stimulation and to produce interleukin-10, and the transcriptional signature. Interestingly, self-deprivation does not affect Foxp3 expression indicating that in regulatory CD4(+) T cells, self-recognition induces unique transcriptional and functional features that do not rely on Foxp3 expression.

NF-κB, which comprises homo- and hetero-dimers of the five members of the Rel family, plays a crucial role in immunity to infection. The cRel and p50 subunits have been implicated in the development and function of the immune cells, but their in vivo importance remains poorly explored in sepsis. We aimed to study the impact of the combined loss of these two subunits on the innate response to infection in a cecal ligation and puncture model of sepsis. We have explored the possible defects in host defense, including pathogen clearance, bacterial phagocytosis and cytokine plasma release. We also performed gene profiling of cRel−/−p50−/− and wild-type LPS-stimulated peritoneal macrophages. Deficiency of cRel and p50 led to enhanced mortality to sepsis that was associated with defective macrophages phagocytosis, decreased bacterial clearance and moderate cytokine response. Transcription profile analysis revealed a common inflammatory response but a significant down-regulated transcription of genes encoding for pathogen recognition receptors and antimicrobial molecules, supporting the in vivo findings in mice. In conclusion, the cRel and p50 subunits of NF-κB play an important combined role in the innate response and are crucial for survival and pathogen clearance in polymicrobial sepsis.

Wafer handling during the manufacturing process introduces micro-cracks and flaws at the wafer edge. The aim of this work was to determine whether an initial crack would be able to propagate through the silicon active region of power devices when it is subjected to high electro-thermal loads during its application or during thermal cycling tests. We have determined the most critical crack propagation cases. These have been simulated using the ANSYS® FEA software and energy release rate G (ERR) has been calculated for different crack lengths, locations, or thermal loads, and then compared to the silicon critical ERR of the silicon. Temperature profiles that reproduce the typical device operation conditions are retrieved with electro-thermal simulation. Failure analysis performed on these power devices has revealed some typical propagation paths.

Supplemental materials : www.landesbioscience.com/journals/epigenetics/article/21495; Genomic imprinting characterizes genes with a monoallelic expression, which is dependent on the parental origin of each allele. Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. We used a high-throughput strategy by diverting the classical use of genotyping microarrays to compare the genotypes of mRNA/cDNA vs. genomic DNA to identify new genes presenting monoallelic expression, starting from human placental material. After filtering of data, we obtained a list of 1,082 putative candidate monoallelic SNPs located in more than one hundred candidate genes. Among these, we found known imprinted genes, such as IPW, GRB10, INPP5F and ZNF597, which contribute to validate the approach. We also explored some likely candidates of our list and identified seven new imprinted genes, including ZFAT, ZFAT-AS1, GLIS3, NTM, MAGI2, ZC3H12Cand LIN28B, four of which encode zinc finger transcription factors. They are, however, not imprinted in the mouse placenta, except for Magi2. We analyzed in more details the ZFAT gene, which is paternally expressed in the placenta (as ZFAT-AS1, a non-coding antisense RNA) but biallelic in other tissues. The ZFAT protein is expressed in endothelial cells, as well as in syncytiotrophoblasts. The expression of this gene is, moreover, downregulated in placentas from complicated pregnancies. With this work we increase by about 10% the number of known imprinted genes in humans.

Objet Dans le noyau interphasique, la chromatine est organisee en territoires chromosomiques (TC) [1] . Le lien entre cette organisation et la regulation de l’expression du genome reste meconnu. Afin de preciser cette organisation, nous avons etudie un modele de desorganisation : les aneuploidies en supposant que la presence d’un chromosome surnumeraire pouvait entrainer une perturbation de la distribution des TC, elle-meme conduisant a une modification de l’activite transcriptionnelle. Methodes Etude de la position des TC 18 et 21 par FISH 3D dans les noyaux interphasiques de fœtus aneuploides et temoins. Comparaison des volumes des noyaux et des TC. Parallelement, une analyse transcriptomique comparative pangenomique des cellules a ete realisee afin d’objectiver des deregulations d’expression. Resultats Nous n’avons pas observe de difference de positions des TC 18 et 21 entre les fœtus atteints et les temoins. Si les volumes nucleaires n’etaient pas modifies, ceux des TC l’etaient. Nous avons mis en evidence des modifications d’expression d’une partie des genes portes par les chromosomes d’interet ; mais egalement de genes sur les autres chromosomes. Discussion En cas d’aneuploidie, l’organisation des TC aneuploides dans le noyau semble globalement respectee. Il existerait cependant une diminution du volume de ces TC sans modification du volume des noyaux, interrogeant au detriment de quel compartiment, se fait cette compaction. L’analyse transcriptomique renforce l’idee d’une combinaison d’un effet de dosage genique et d’une rupture de l’homeostasie : aux genes deregules portes par les chromosomes trisomiques, s’ajoutent des modifications d’expression du reste du genome. Ces deregulations concernent de multiples voies impliquees dans le developpement mais aussi des genes au potentiel role dans l’apparition de traits phenotypiques. Conclusion Il semblerait exister un lien entre le desequilibre genique des chromosomes aneuploides et les deregulations de l’ensemble du genome. La participation de la reorganisation des TC reste a affiner.

Nowadays, the existing power devices (thyristors, Triacs, …) used to drive usual AC loads (e.g. washing machines, dimmers, …) are quite limited: no turn-off drive, small scale integration and high thermal dissipation. Within this framework, new architectures have to be developed. This paper summarizes the first results of the electrical characterization of a new high gain low loss 600V bipolar transistor. The static performances of our new bipolar transistor are compared with those obtained using some electrical simulations (Sentaurus). Combining two of these devices, we should be able to develop a new generation of AC power devices.

In this paper, we analyze the rise time and dwell time impact on 16A–600V high temperature Triacs reliability subjected to power cycling. Experimental tests, performed on two TO-220 packages (insulated or not), show that rise time and dwell time have a negligible contribution on Triacs lifetime. Failure analysis confirms that the physical failure mode (the die-attach fatigue) and the failure location (the solder joints) are similar when rise and dwell durations change. Thermo-mechanical simulations (ANSYS®) were performed to get a better understanding of the effects of various ramp and dwell values on solder joints plastic work and shear stress.

Spondyloarthritis (SpA) is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31–34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM) with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb) locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD) map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs) in 136 families (263 patients). The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9×10−5). Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients), and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value, Author Summary Spondyloarthritis (SpA) is a common variety of articular inflammatory disorder characterized by axial and/or peripheral arthritis, frequently associated with extra-articular manifestations such as psoriasis, uveitis, and inflammatory bowel diseases (ulcerative colitis or Crohn's disease (CD)). SpA is a complex disorder with high heritability. The MHC class I HLA-B27 allele is a very strong risk factor for its development, but other genetic factors located outside the MHC also play a role in disease susceptibility. By a previous whole-genome linkage investigation, we have demonstrated that a region located on the chromosome 9q31–34 was involved in SpA susceptibility. The present study aimed to further characterize this locus. Using a stepwise linkage and association approach, we identified a haplotype spanning 6 single-nucleotide polymorphisms strongly associated with SpA and located in a genomic region paralogous to the MHC, near to the TNFSF15 gene. Interestingly, polymorphisms of this gene have previously been shown to be associated with CD. This original finding offers a new research track for the understanding of SpA pathophysiology, which is still poorly understood, as well as new hope for diagnostic and therapeutic innovation.

This paper deals with the functional reliability study of a new 16 A - 600 V high-temperature TRIAC family, subjected to power cycles, simulating the component in harsh real operation conditions. The targeted application is a vacuum cleaner (1800 W - 230 V - 50 Hz). In this kind of application, one of the major issues for TRIAC, which leads to high mechanical stresses for the assembly, occurs when the switch turns-on in ldquojammed nozzle operationrdquo, i.e. when the tube is blocked. In that case, the TRIAC junction temperature reaches at most 180degC, higher than the maximum value specified by the manufacturer (i.e. 150degC). The aim of this study is to evaluate the TRIACs lifetime under these operation conditions. The thermal stresses generate local temperature variations and then, some mechanical stresses (assembly degradation). For TRIACs, the junction-to-case thermal resistance (Rth(j-c)) increase is the signature of such a damage. The lifetime has been studied and fitted with a Lognormale distribution. The components damages, due to the mechanical stresses, have been explained thanks to some qualitative two-dimensional thermo-mechanical simulations using finite elements (ANSYSreg).

This paper deals with thermal runaway that could occur for the new high-temperature TRIACs which are used with junction temperatures up to 160degC in transient state. The conditions to avoid thermal runaway for the specific case of alternative voltage are discussed. Experimental measurements are given and compared with a theoretical analysis.

Journal of Reproductive Immunology 101–102 (2014) 6–17 11 with the Bishop of Oxford Samuel Wilberforce concerning the validity of Darwin’s theory of evolution. It was the liberating force of science versus the authoritarian view of religion that Man was a unique creation of God, and hence distinct and different from all animal species. Sciencewon.As yet, there are still somewhosteadfastly refuse to consider that what has been learned from the study of pregnancy in animals has any relevance towhat happens in human reproduction and its maladies. This has not had an impact on the increasing amounts of grant monies given to the study of animal models of human disease. In this debate, it is first necessary to review the proper use of animal analogmodels of human disease, and to emphasize the fallacy of uncritical extrapolation from animals to humans. Nevertheless, careful consideration of the structure and composition of the feto-maternal interface in mice, rats, and humans indicates rather striking homologies. Indeed, the similarities appear to outweigh the differences, save for minor details. Further, an in-depth consideration of the implications of a currently popular hypothesis concerning the function of humanuterineNK cells at the feto-maternal interface in healthy and disordered pregnancy appears to reveal a major flaw in the proposed mechanism and its importance. Indeed, the existing data support the alternative view that findings in animal models may indeed be quite relevant to human pregnancy problems. The importance of a rigorous scientific approach to the use of both animal and human data is emphasized. http://dx.doi.org/10.1016/j.jri.2013.12.015

Cet article decrit une nouvelle approche pedagogique pour l’enseignement des connaissances de base de l'energie solaire et des applications photovoltaiques. Cette methode d'enseignement experimentale et interactive permet aux etudiants et aux concepteurs de systemes photovoltaiques de manipuler un simulateur de production solaire. Cet outil de simulation reproduit a echelle reduite la trajectoire du soleil quelle que soit la periode de l’annee. La production d'energie est ensuite calculee pour differentes inclinaisons et orientations d'un capteur solaire. Le simulateur offre aux etudiants l'occasion d'acquerir d’une facon ludique les fondamentaux de l’energie photovoltaique. Plusieurs exemples de travaux pratiques sont detailles afin de donner une vue d'ensemble des exercices d'apprentissage qui pourraient etre faits par les etudiants pour decouvrir les multiples applications du photovoltaique. A titre d’exemple, de nombreux cas d’etudes peuvent etre traites tels que la mise en oeuvre des calculs de position du soleil, la caracterisation electrique des cellules solaires avec differentes technologies ou encore la programmation de suiveurs du point de puissance maximale.

International audience

International audience; The management of electricity demand still raises a huge interest for end-users at the household level. Smart home electricity management systems (HEMS) have recently emerged both to warrant uninterruptible power and high power quality, and decrease the cost of electricity consumption by either shifting it in off peak time or smoothing it. Such systems require a bidirectional DC-AC converter, specifically when the energy flows from a DC source (e.g., batteries) to an AC one (i.e., the AC grid), and vice versa. This article highlights the relevance of a bidirectional DC-AC converter based on sinusoidal waveforms from the generation of sine half-waves. Such a converter is composed of a DC-DC stage equivalent to an adjustable output voltage source and a DC-AC stage (H-bridge) which are in series. The results of a complete experimental procedure prove the feasibility to warrant a high efficiency (higher than 95%) of the whole converter, and a high power quality of the output signals in terms of total harmonic distortion, while avoiding the use of a bulky filter, as is the case with a conventional H-bridge. Keywords Smart home electricity management systems; bidirectional DC-AC converter; high efficiency; high power quality.

National audience; Cet article décrit la mise en oeuvre d'une nouvelle approche pédagogique de l'enseignement de l'électronique et du génie électrique menée au sein du Département Électronique et Énergie de l'école Polytechnique de l'Université François Rabelais de Tours. Cette approche est fondée sur un projet intensif qui est planifié durant 3 se-maines consécutives à plein temps et dédié à l'étude et à la réalisation d'un système industriel. Ce projet est réalisé de manière collective : 33 élèves ingénieurs sont répartis en 3 groupes de 11 étudiants. L'étude a consisté à électrifier un châssis de kart et à rendre le véhicule électrique opérationnel dans le temps imparti. Les élèves ingénieurs ont entre autre justifié tous les éléments composant le système de motorisation, assemblé toutes les pièces du kart électrique et testé le bon fonctionnement de ce dernier. Cette initiative pédagogique, fortement appréciée des étudiants puisque chacun d'entre eux a joué un rôle actif dans la réalisation du projet, a en particulier été saluée par la presse locale et régionale.

Introduction This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls. Methods MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences. Results The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P 1.5). Four selected genes were validated by qRT-PCR: ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2. Conclusion This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses. Electronic supplementary material The online version of this article (doi:10.1186/s13075-014-0417-0) contains supplementary material, which is available to authorized users.