346 research outputs found

    Integrated engineering environments for large complex products

    Get PDF
    An introduction is given to the Engineering Design Centre at the University of Newcastle upon Tyne, along with a brief explanation of the main focus towards large made-to-order products. Three key areas of research at the Centre, which have evolved as a result of collaboration with industrial partners from various sectors of industry, are identified as (1) decision support and optimisation, (2) design for lifecycle, and (3) design integration and co-ordination. A summary of the unique features of large made-to-order products is then presented, which includes the need for integration and co-ordination technologies. Thus, an overview of the existing integration and co-ordination technologies is presented followed by a brief explanation of research in these areas at the Engineering Design Centre. A more detailed description is then presented regarding the co-ordination aspect of research being conducted at the Engineering Design Centre, in collaboration with the CAD Centre at the University of Strathclyde. Concurrent Engineering is acknowledged as a strategy for improving the design process, however design coordination is viewed as a principal requirement for its successful implementation. That is, design co-ordination is proposed as being the key to a mechanism that is able to maximise and realise any potential opportunity of concurrency. Thus, an agentoriented approach to co-ordination is presented, which incorporates various types of agents responsible for managing their respective activities. The co-ordinated approach, which is implemented within the Design Co-ordination System, includes features such as resource management and monitoring, dynamic scheduling, activity direction, task enactment, and information management. An application of the Design Co-ordination System, in conjunction with a robust concept exploration tool, shows that the computational design analysis involved in evaluating many design concepts can be performed more efficiently through a co-ordinated approach

    Common variants near MC4R are associated with fat mass, weight and risk of obesity.

    Get PDF
    To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

    Parental origin of sequence variants associated with complex diseases

    Get PDF
    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldEffects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.info:eu-repo/grantAgreement/EC/FP7/21807

    A Review of Fiber-Reinforced Injection Molding: Flow Kinematics and Particle Orientation

    Get PDF
    The existing flow and particle orientation models applicable to fiber- reinforced injection molding are reviewed. After a brief description of injection molding, previous studies on the flow kinematics and fiber reinforcement are presented. Basics of Hele-Shaw flows are described Including the commonly used viscosity models and foun tain flow effects. Some of the existing models for particle orientation are analyzed with particular emphasis on the amsotropic description of the material system. Concentration regions for short fiber suspensions are defined and relevant constitutive equations are dis cussed. A few example solutions are also given which describe the three-dimensional ori entation field for the filling of a sudden expansion cavity, depicting skin-core orientation structure.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    Meta-analysis of type 2 Diabetes in African Americans Consortium

    Get PDF
    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

    Novel genetic loci associated with hippocampal volume

    Get PDF
    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

    Measurement of the View the tt production cross-section using eÎŒ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

    Get PDF
    This paper describes a measurement of the inclusive top quark pair production cross-section (σttÂŻ) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σttÂŻ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σttÂŻ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

    Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

    Get PDF
    A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

    Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

    Get PDF
    A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter
    • 

    corecore