Shear-induced quench of long-range correlations in a liquid mixture

A static correlation function of concentration fluctuations in a (dilute) binary liquid mixture subjected to both a concentration gradient and uniform shear flow is investigated within the framework of fluctuating hydrodynamics. It is shown that a well-known $|\nabla c|^2/k^4$ long-range correlation at large wave numbers $k$ crosses over to a weaker divergent one for wave numbers satisfying $k<(\dot{\gamma}/D)^{1/2}$, while an asymptotic shear-controlled power-law dependence is confirmed at much smaller wave numbers given by $k\ll (\dot{\gamma}/\nu)^{1/2}$, where $c$, $\dot{\gamma}$, $D$ and $\nu$ are the mass concentration, the rate of the shear, the mass diffusivity and the kinematic viscosity of the mixture, respectively. The result will provide for the first time the possibility to observe the shear-induced suppression of a long-range correlation experimentally by using, for example, a low-angle light scattering technique.Comment: 8pages, 2figure

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Bioelectrochemical systems for production of valuable compounds

The conversion of electrical current into valuable compounds by electrotrophic microorganisms represents one of the most promising applications of bioelectrochemical systems (BESs). The ability of electrotrophic microorganisms to directly accept electrons from an insoluble electrode greatly expands BES applications. Electrofermentation (EF) refers to electrically driven systems that use renewable carbon sources (e.g., glycerol) for the production of valuable compounds. In contrast, the concept of microbial electrosynthesis (MES) refers, specifically, to systems in which carbon dioxide (CO2) is used as the only carbon source. Fundamentals of the processes, such as the microorganisms involved and electron transfer mechanisms between electron donors and microorganisms, are presented in this chapter. In addition, this chapter summarizes the recent major applications in the field, as well as the main future challenges.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. This study was also supported by the FCT, within the scope of the project “INNOVsyn – Innovative strategies for syngas fermentation” (POCI01-0145-FEDER-031377) and under the scope of the project “MultiBiorefinery-multi-purpose strategies for broadband agro-forest and fisheries by-products valorization: a step forward for a truly integrated biorefinery” (POCI-01-0145-FEDER-016403).info:eu-repo/semantics/publishedVersio

Multicenter preclinical validation of BET inhibition for the treatment of pulmonary arterial hypertension

Rationale: Pulmonary arterial hypertension (PAH) is a degenerative arteriopathy that leads to right ventricular (RV) failure. BRD4 (bromodomain-containing protein 4), a member of the BET (bromodomain and extra-terminal motif) family, has been identified as a critical epigenetic driver for cardiovascular diseases. Objectives: To explore the therapeutic potential inPAHof RVX208, a clinically available BET inhibitor. Methods: Microvascular endothelial cells, smooth muscle cells isolated fromdistal pulmonary arteries of patientswith PAH, rats with Sugen54161hypoxia- ormonocrotaline1shunt-induced PAH, and rats with RV pressure overload induced by pulmonary artery banding were treated with RVX208 in three independent laboratories. Measurements and Main Results: BRD4 is upregulated in the remodeled pulmonary vasculature of patients with PAH, where it regulates FoxM1 and PLK1, proteins implicated in the DNA damage response. RVX208 normalized the hyperproliferative, apoptosisresistant, and inflammatory phenotype of microvascular endothelial cells and smooth muscle cells isolated from patients with PAH. Oral treatment with RVX208 reversed vascular remodeling and improved pulmonary hemodynamics in two independent trials in Sugen54161hypoxia-PAH and in monocrotaline1shunt-PAH. RVX208 could be combined safely with contemporaryPAHstandard of care. RVX208 treatment also supported the pressure-loaded RV in pulmonary artery banding rats. Conclusions: RVX208, a clinically available BET inhibitor, modulates proproliferative, prosurvival, and proinflammatory pathways, potentially through interactions with FoxM1 and PLK1. This reversed the PAH phenotype in isolated PAH microvascular endothelial cells and smooth muscle cells in vitro, and in diversePAH rat models. RVX208 also supported the pressure-loaded RV in vivo. Together, these data support the establishment of a clinical trial with RVX208 in patients with PAH