303 research outputs found

    Investigation of Shear Stud Performance in Flat Plate Using Finite Element Analysis

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    Three types of shear stud arrangement, respectively featuring an orthogonal, a radial and a critical perimeter pattern, were evaluated numerically. A numerical investigation was conducted using the finite element software ABAQUS to evaluate their ability to resist punching shear in a flat plate. The finite element analysis here is an application of the nonlinear analysis of reinforced concrete structures using three-dimensional solid finite elements. The nonlinear characteristics of concrete were achieved by employing the concrete damaged plasticity model in the finite element program. Transverse shear stress was evaluated using finite element analysis in terms of shear stress distribution for flat plate with and without shear stud reinforcement. The model predicted that shear studs placed along the critical perimeter are more effective compared to orthogonal and radial patterns

    Naïve Bayes Classifier to Mitigate the DDoS Attacks Severity in Ad-Hoc Networks

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    Ad-Hoc networks are becoming more popular due to their unique characteristics. As there is no centralized control, these networks are more vulnerable to various attacks, out of which Distributed Denial of Service (DDoS) attacks are considered as more severe attacks. DDoS attack detection and mitigation is still a challenging issue in Ad-Hoc Networks. The existing solutions consider the fixed or dynamic threshold value to detect the DDoS attacks without any trained data, and very few existing solutions use machine learning algorithms to detect these attacks. However, existing solutions are inefficient to handle when DDoS attackers’ perform this attack through bursty traffic, packet size, and fake packets flooding. We have proposed DDoS attack severity mitigation solution. Out DDoS mitigation solution consists of new network node authentication module and naïve bayes classifier module to detect and isolate the DDoS attack traffic patterns. Our simulation results show that naïve bayes DDoS attack traffic classification out performs in the hostile environment and secure the legitimate traffic from DDoS attack

    Impact Resistance and Strength Reliability of Fiber-reinforced Concrete in Bending under Drop Weight Impact Load

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    This paper presents an experimental investigation on the Impact failure energy and strength reliability of fiber reinforced concrete (FRC) by using a simple drop weight test which was based on the testing procedure recommended by ACI committee 544. Two different steel fibers were used as the reinforcing material in various volume fractions such as 0%, 0.5%, 1.0% and 1.5% with a water cement ratio of 0.42. Furthermore, the two-parameter weibull distribution was used to analyze the experimental data in order to sort out a variation of test results. Using the weibull distribution, the impact failure strength reliability, in other words, the probability distribution according to which the concrete will fail, was obtained. The results indicated that the concrete containing a 1.5% volume fraction of fiber gave the best performance followed by 1.0% and 0.5% under impact loading. It was proven that the probabilistic distributions of the impact failure energy of seven types of samples approximately follow two-parameter Weibull distribution

    Positional identification of variants of Adamts16 linked to inherited hypertension

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    A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling B

    The in vivo endothelial cell translatome is highly heterogeneous across vascular beds

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    Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression after EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single-cell suspensions for fluorescence-activated cell sorting or single-cell RNA sequencing analysis. Comparison of our EC-TRAP with published single-cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole-tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole-tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions

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

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    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 complexit

    Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis

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    Abstract Background The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not. Methods and Results We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes. Conclusions In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.http://deepblue.lib.umich.edu/bitstream/2027.42/112500/1/12920_2010_Article_214.pd

    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

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    Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

    Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project

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    Neutrophils are a key component of innate immunity. Individuals with low neutrophil count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower absolute neutrophil count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC
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