Structure of a Flat Plate Boundary Layer Subjected to Free-Stream Turbulence

International audienceThe structure near the flat plate leading edge of an incompressible boundary layer subjected to free-stream turbulence is investigated using large eddy simulation (LES) with a dynamic mixed subgrid-scale model. Free-stream turbulent intensities ranging from 1.5 to 10% are investigated. The evolutions of the velocity, temperature and turbulent intensity profiles inside the boundary layer and the characteristic length scales are analyzed and compared to a laminar flat plate boundary layer. The impact of the free-stream turbulence is examined for Reynolds numbers ranging from 0 (leading edge of the flat plate) to Re x =80,000 by using two consecutive spatial LESs. Bypass transition is found to occur in the early stage of the boundary layer development for all five cases presented here. The analysis indicates that the thermal turbulent structures transfer more energy and hence generate more thermal fluctuations in their wake than the dynamic structures

Validation of the Flexible and Rigid Cognitive Restraint Scales in a General French Population

International audienceDistinguishing between flexible and rigid cognitive restraint (CR) may be useful for understanding the role of CR in dietary behavior and weight status. This study aimed to translate and adapt the flexible and rigid CR scales to the French context and test their psychometric properties. Construct validity, internal consistency, and test–retest reliability were examined in a sample of 620 individuals. Confirmatory factor analysis of the scales found a two-factor structure (flexible CR: 12 items; rigid CR: 15 items) that provided a good fit and supported the initial solution (χ2 = 584.7, df = 322, CFI = 0.96, RMSEA = 0.052 [0.045, 0.059], TLI = 0.95). Higher flexible and rigid CR were associated with higher CR overall, emotional eating (TFEQ-R21) and eating disorders (SCOFF), and lower intuitive eating (IES-2). In addition, higher flexible CR was associated with lower impulsivity (BIS-11) while higher rigid CR was associated with higher uncontrolled eating (TFEQ-R21) and lower self-esteem (RSES), satisfaction with life (SWLS), and optimism (LOT-R). Flexible and rigid CR internal consistency was satisfactory (McDonald ω = 0.77 and 0.74, respectively) and test–retest reliability was good (ICC = 0.81 and 0.79, respectively). This study validated a flexible and rigid CR tool in a French population and confirmed that these two types of CR represent distinct eating behaviors. View Full-Tex

Structure, Dynamics, and Impact of Replication Stress–Induced Structural Variants in Hepatocellular Carcinoma

International audienceAbstract Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole-genome sequencing (WGS) to explore in depth the nature of structural variants (SV) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC displayed frequent intra-chromosomal and interchromosomal templated insertion cycles (TIC), likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are proximal to one another within the 3D genome. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induced continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics, and consequences of SV accumulation in tumors with oncogene-induced replication stress. Significance: Optical mapping and whole-genome sequencing integration unravels a unique signature of replication stress–induced structural variants that drive genomic evolution and the acquisition of driver events in CCN-HCC

Dispositional optimism is associated with weight status, eating behavior, and eating disorders in a general population‐based study

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Adeno-associated virus in the liver: natural history and consequences in tumor development

International audienceOBJECTIVE:Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35%-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. This study aimed to characterise the natural history of AAV infection in the liver and its consequence in tumour development.DESIGN:Viral DNA was quantified in tumour and non-tumour liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analysed using a DNAse/TaqMan-based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions.RESULTS:AAV DNA was detected in 21% of the patients, including 8% of the tumour tissues, equally distributed in two major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Episomal viral forms were found in 4% of the non-tumour tissues, frequently associated with viral RNA expression and human herpesvirus type 6, the candidate natural AAV helper virus. In 30 HCC, clonal AAV insertions were recurrently identified in CCNA2, CCNE1, TERT, TNFSF10, KMT2B and GLI1/INHBE. AAV insertion triggered oncogenic overexpression through multiple mechanisms that differ according to the localisation of the integration site.CONCLUSION:We provided an integrated analysis of the wild-type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations. Clonal AAV insertions were positive selected during HCC development on non-cirrhotic liver challenging the notion of AAV as a non-pathogenic virus