Two-size moment Eulerian multi-fluid method describing the statistical trajectory crossing: modeling and numerical scheme

International audienceHigh fidelity modeling and simulation of turbulent dispersed two-phase flows is still a major challenge for many applications. Eulerian approaches are well suited for high performance computations of such flows. Recently, hybrid Eulerian methods that combine the multi-fluid approach-where the size is discretized-and the moment method were developed. On the one hand, in order to capture efficiently the size-polydispersion, two size moments were used on each interval of the size discretization (Two Size Moment method). On the other hand, the Anisotropic Gaussian (AG) velocity closure has been introduced as a relevant model to describe velocity dispersion occurring when the particles from the disperse phase have a significant inertia compared to the time scales of the flow, leading to particle trajectory crossings. The purpose of this contribution is to develop a model able to describe size and velocity dispersion, coupling the two-size moment Eulerian multi-fluid method and the anisotropic velocity closure. Adapted numerical schemes based on a relaxation method are provided. This new model (AG-TSM) is then evaluated on various test cases relevant to rocket propulsion and two-phase combustion

Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome

Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6–7 weeks (i.e. 2–3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1. Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms

Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB as Novel Risk Loci for Systemic Sclerosis

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10−5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10−8, OR = 0.69, 95% CI [0.60–0.79]; rs6457617, P = 1.14×10−7 and rs9275245, P = 1.39×10−7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10−5, OR = 1.36 [1.18–1.56]) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10−5) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10−10, OR:1.25), TNIP1 (P = 4.68×10−9, OR:1.31), and RHOB loci (P = 3.17×10−6, OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis

TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients

Introduction: Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH. Objective: To explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods: TGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results: No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions: This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Les agénésies des incisives latérales maxillaires (traitement multidisciplinaire)

BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Elaboration d'un registre local de recueil et d'étude des déficits immunitaires primitifs d'origine lymphocytaire de l'adulte

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Implication de la fibrilline-1 et bases génétiques de la sclérodermie systémique

Des donnees recentes montrant des anomalies de la Fibrilline-1 (FBN-1) et du TGFbeta font penser que la sclerodermie systemique (ScS) cette maladie pourrait appartenir au groupe des fibrillinopathies. L'etude cas-temoins du gene FBN1 a partir d'une cohorte de patients ScS Caucasiens Europeens n'a pas montre d'association. Par ailleurs, on a observe une diminution, in vivo, du reseau microfibrillaire dermique des patients ScS sans anomalie des fibroblastes dermiques. Les resultats de 1'etude de 1'Endogline (ENG), un recepteur du TGFbeta, ont souligne son interet dans la ScS. Le sequencage de ce gene ainsi que des recepteurs ALK1, TGFBR2 et BMPR2 n'a pas permis de detecter de mutations mais de suggerer 1'interet de tester certains variants. Les principaux resultats d'une strategic gene candidat (HIFJA, ACE, SLC6A4, TPH1, KCNA5, PTPN22, IRF5, STAT4) ont montre une association forte entre IRF5, STAT4 et la ScS, en particulier avec son phenotype fibrotique.Recent evidences suggested that Systemic sclerosis (SSc) could belong to fibrillinopathies because of Fibrillin-1 (FBN-1) and TGFbeta abnormalities inECM. First FBN-1 assessment, performed with a case-control study, did not detect association between FBN1 gene polymorphic markers and SSc. Then, we show a decrease of tissular FBN-1 microfibrillar network observed in the dermis of SSc patients but absence of in vitro alteration of synthesis, secretion and organization of microfibril network by fibroblasts. For TGFbeta pathway, subsequent analyses evaluate TGFbeta receptors with i) the study of Endoglin by case-control study and biochemical dosages it) sequencing of four TGFbeta receptors (ENG, ALK1, TGFBR2 and BMPR2). The most interesting results of the candidate gene strategy (HIFJA, ACE, SLC6A4, TPH1, KCNA5, PTPN22, IRF5, STAT4) were found for IRF5 and STAT4 genes which are associated with SSc and in particular with its fibrotic phenotype.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF