Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

A Class of Separation Axioms in Generalized Topology

The purpose of this paper is to introduce and study some new class of definitions like µ-point closure and gµ –regular space concerning generalized topological space. We obtain some characterizations and several properties of such definitions. This paper takes some investigations on generalized topological spaces with gµ –closed sets and gµ–closed sets.</jats:p

Optimal Control for Perishable Inventory with Partial Backlogging in a Supply Chain: MDP Approach

In this paper, we consider a continuous review perishable inventory control with partial backlogging at retailer in a two stage supply chain. The supply chain consists of a distribution center DC) and single retail-vendor (RV). Arrival of demands to a retailer node is assumed to be Poisson and lead times are exponentially distributed at retailer node and Distribution center with parameters µ0 and µ1 respectively. The items are supplied to the retailer in packs of fixed size. The system is formulated as a Markov Decision Process (MDP). A stationary cost structure is imposed and an optimal stationary policy is obtained by using Linear Programming technique. Numerical examples are provided to illustrate the problem.</jats:p

Deep Learning Based Intelligent Rail Track Health Monitoring System

This paper describes the possible way of monitoring the health of the rail track to increase the comfort and ride quality of rail transportation. The abnormalities present in the track are identified and rectified at the initial stage. In this paper, Convolutional Neural Network and Extreme Learning Machine Algorithm (CNN-ELMA) based rail track monitoring is proposed to estimate the exact abnormality. The micro-electro-mechanical sensor (MEMS) accelerometers are fixed in the axle box for measuring the acceleration signal. The location of abnormality is measured by a new sensing method even if the signal of the global positioning system (GPS) is absent. To pre-process the raw signal received from the accelerometer is done by using a Continuous Wavelet Transform (CWT). Then the high-level features are extracted using CNN with a square pooling architecture. To evaluate the performance of the proposed CNN-ELMA, it is simulated and compared with four other methods. The comparison results show that the proposed CNN-ELMA is an effective and accurate method useful for the maintenance department of railways. An experiment has been conducted for the four different abnormal locations and the performance of the proposed method is studied.</jats:p

Behaviour of Horizontal Connections in Precast Walls under Lateral Loading

The design of connections is one of the most important considerations in the structural design of precast concrete structures. The purpose of the connection is to transfer loads, restrain movement and provide stability. Within one joint there may be several load transfers, each one must be designed for adequate strength and ductility and appropriately detailed. The proposed investigation aims to achieve efficient horizontal connections in precast walls with improved structural performance under various loads. HYSD reinforcement dowels are used as connectors. The arrangement of dowels is varied to achieve the efficient load transfer in the walls. The experimental investigation on three precast wall and one monolithic wall depicts that the precast wall exhibits high strength than the monolithic wall specimen and structural performance were found to be better than the monolithic wall specimen and also the efficient load transfer is achieved in the precast wall.</jats:p