21 research outputs found
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health
ALSPEN-A mathematical model for thermal stresses in direct chill casting of aluminum billets
Stress formation in solidifying bodies. Solidification in a round continuous casting mold
Modeling of the peritectic reaction and macro-segregation in casting of low carbon steel
Thermomechanics of the cooling stage in casting processes: Three-dimensional finite element analysis and experimental validation
International audienceA thermomechanical three-dimensional (3-D) finite element analysis of solidification is presented. The heat transfer model is based on a multidomain analysis accounting for noncoincident meshes for the cast part and the different mold components. In each subdomain, a preconditioned conjugate gradient solver is used. The mechanical analysis assumes the mold is rigid. A thermoelastic-viscoplastic rheological model is used to compute the constrained shrinkage of the part, resulting in an effective local air gap width computation. At each time increment, a weak coupling of the heat transfer and mechanical analyses is performed. Comparisons of experimental measurements and model predictions are given in the case of a hollow cylindrical aluminum alloy part, showing a good quantitative agreement. An application to an industrial aluminum casting is presented, illustrating the practical interest of thermomechanical computations in solidification analysis