A constitutive model for unsaturated cemented soils under cyclic loading

On the basis of plastic bounding surface model, the damage theory for structured soils and unsaturated soil mechanics, an elastoplastic model for unsaturated loessic soils under cyclic loading has been elaborated. Firstly, the description of bond degradation in a damage framework is given, linking the damage of soil's structure to the accumulated strain. The Barcelona Basic Model (BBM) was considered for the suction effects. The elastoplastic model is then integrated into a bounding surface plasticity framework in order to model strain accumulation along cyclic loading, even under small stress levels. The validation of the proposed model is conducted by comparing its predictions with the experimental results from multi-level cyclic triaxial tests performed on a natural loess sampled beside the Northern French railway for high speed train and about 140 km far from Paris. The comparisons show the capabilities of the model to describe the behaviour of unsaturated cemented soils under cyclic loading

Three Dimensional Measurements of Asphaltene Deposition in a Transparent Micro-Channel

This study describes a novel experimental approach to directly measure the thicknesses of asphaltene deposits in micro-channels. The thickness of the asphaltene deposit is estimated using a visualization technique based on 3D digital microscopy. The working fluid is a mixture of n-heptane and dead oil. Induced by the addition of n-heptane, the asphaltenes present in crude oil phase separate at ambient temperature to form aggregates of asphaltene-rich phase. Part of the asphaltene aggregates deposit on the walls of the transparent micro-channel. A two-dimensional profile of the deposit across the channel at selected axial sections is measured. The influences of injection mixture volume on the growth of the thickness of deposited asphaltenes is investigated using two experimental conditions, (i) varying elapsed time at constant flow rate and (ii) increasing the flow rate at a constant elapsed time. In both cases the deposit thickness of asphaltene (δ) increases with the total injection volume (V). The experimental results obtained in this work provide new insights into the deposition process at the micro-scale level, which can be used to facilitate the development of more accurate numerical model for this applicatio

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Noise suppression in monolithically integrated Michelson interferometer

A novel monolithically integrated Michelson interferometer using intersecting twin-contact semiconductor optical amplifiers is proposed and implemented whereby the two arms are gain imbalanced to give enhanced noise suppression. Experimental OSNR improvements of 8.4 dB for pulses with durations 8 ps and by default ER of 14 dB are demonstrated for low driving currents of between 25 and 30 mA. This is believed to be the smallest Michelson interferometer to date