147 research outputs found

    FPGA Implementation of a General Space Vector Approach on a 6-Leg Voltage Source Inverter

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    A general algorithm of a Space Vector approach is implemented on a 6-leg VSI controlling a PM synchronous machine with three independent phases. In this last case, the necessity of controlling the zero-sequence current motivates the choice of a special family of vectors, different of this one used in Pulse Width Modulation (PWM) intersective strategy and in common Space Vector PWM (SVPWM). To preserve the parallelism of the algorithm and fulfill the execution time constraints, the implementation is made on a Field Programmable Gate Array (FPGA). Comparisons with more classical 2-level and 3-level PWM are provided.Fui8 within the SOFRACI projec

    Modeling of Hydro-Pneumatic Energy Storage Using Pump Turbines

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    Modelling of a hydro-pneumatic energy storage system is presented in this paper. Hydro pneumatic storage aims to combine the good efficiency of hydraulic energy conversion and the space flexibility of pneumatic storage. The project aims to model a prototype which uses a rotodynamic multi-stage pump-turbine to displace a virtual liquid piston to compress air. To facilitate mass and heat transfers between both phases, there is no separation between the water and the air. A dynamic model of the storage system is developed using block diagram methodology. It takes into account characteristic curves of the pump-turbine and thermodynamic equations. Modelling results show that vapour diffusion contributes to reducing compression final temperature. This implies an increase of storage efficiency. A test rig construction will begin at the end of autumn 2011. It will be electrically connected to the “Distributed Energies” platform of ‘’Arts et MĂ©tiers Paristech’’ in Lille.adem

    CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation?

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    CD9 belongs to the tetraspanin superfamily. Depending on the cell type and associated molecules, CD9 has a wide variety of biological activities such as cell adhesion, motility, metastasis, growth, signal transduction, differentiation, and sperm–egg fusion. This review focuses on CD9 expression by hematopoietic cells and its role in modulating cellular processes involved in the regulation of inflammation. CD9 is functionally very important in many diseases and is involved either in the regulation or in the mediation of the disease. The role of CD9 in various diseases, such as viral and bacterial infections, cancer and chronic lung allograft dysfunction, is discussed. This review focuses also on its interest as a biomarker in diseases. Indeed CD9 is primarily known as a specific exosome marker however, its expression is now recognized as an anti-inflammatory marker of monocytes and macrophages. It was also described as a marker of murine IL-10-competent Breg cells and IL-10-secreting CD9+ B cells were associated with better allograft outcome in lung transplant patients, and identified as a new predictive biomarker of long-term survival. In the field of cancer, CD9 was both identified as a favorable prognostic marker or as a predictor of metastatic potential depending on cancer types. Finally, this review discusses strategies to target CD9 as a therapeutic tool. Because CD9 can have opposite effects depending on the situation, the environment and the pathology, modulating CD9 expression or blocking its effects seem to be a new promising therapeutic strategy

    Modelling and experimental studies on hydro-pneumatic energy storage using pump-turbines

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    On propose ici un modĂšle fonctionnel d’un systĂšme de stockage hydro-pneumatique d’énergie ainsi que la comparaison entre le comportement simulĂ© et des observations expĂ©rimentales. L’intĂ©rĂȘt de ce type de stockage est de combiner le bon rendement de la conversion d’énergie hydraulique et la flexibilitĂ© spatiale du stockage pneumatique. Le prototype modĂ©lisĂ© utilise une pompe-turbine roto-dynamique multi-Ă©tagĂ©e dĂ©plaçant un piston liquide virtuel qui va comprimer l’air contenu dans un rĂ©servoir ‘’haute pression (HP)’’. Le modĂšle dynamique du systĂšme, dĂ©veloppĂ© sous forme de diagrammes fonctionnels, prend en compte les courbes caractĂ©ristiques de la machine hydraulique et les Ă©quations de la thermodynamique. Le modĂšle est complĂ©tĂ© par deux stratĂ©gies de commande afin de gĂ©rer la variation continue du point de fonctionnement : une stratĂ©gie de maintien du rendement et une autre basĂ©e sur la demande en puissance ; le paramĂštre commandĂ© est la vitesse de rotation de la machine. Par l’étude du modĂšle, deux points sensibles sont mis en relief : la dĂ©pendance du rendement de stockage au coefficient d’échange de chaleur du rĂ©servoir HP et les limites de la rĂ©gulation de puissance. Quelques solutions Ă  ces problĂšmes ont Ă©tĂ© Ă©tudiĂ©es. Les premiers rĂ©sultats expĂ©rimentaux donnent des observations qu’on retrouve par la modĂ©lisation. Ces observations vont servir Ă  recaler certains paramĂštres du modĂšle qui servira Ă  rĂ©aliser des Ă©tudes d’intĂ©gration dans le rĂ©seau Ă©lectrique. Le banc d’essais doit ĂȘtre prochainement connectĂ© au rĂ©seau de la plateforme â€˜â€™Ă©nergies reparties’’ du centre Arts et MĂ©tiers ParisTech de Lille

    CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

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    CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9+ IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9+ B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9+ B cells in human and mouse. The profile of CD9+ B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9+ B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19+CD9+ B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9+ B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9+ B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9+ B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients

    Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

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    Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3â€Č-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

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    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe
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