405 research outputs found

    CUDA Implementation of a Navier-Stokes Solver on Multi-GPU Desktop Platforms for Incompressible Flows

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    Graphics processor units (GPU) that are traditionally designed for graphics rendering have emerged as massively-parallel co-processors to the central processing unit (CPU). Small-footprint desktop supercomputers with hundreds of cores that can deliver teraflops peak performance at the price of conventional workstations have been realized. A computational fluid dynamics (CFD) simulation capability with rapid computational turnaround time has the potential to transform engineering analysis and design optimization procedures. We describe the implementation of a Navier-Stokes solver for incompressible fluid flow using desktop platforms equipped with multi-GPUs. Specifically, NVIDIA’s Compute Unified Device Architecture (CUDA) programming model is used to implement the discretized form of the governing equations. The projection algorithm to solve the incompressible fluid flow equations is divided into distinct CUDA kernels, and a unique implementation that exploits the memory hierarchy of the CUDA programming model is suggested. Using a quad-GPU platform, we observe two orders of magnitude speedup relative to a serial CPU implementation. Our results demonstrate that multi-GPU desktops can serve as a cost-effective small-footprint parallel computing platform to accelerate CFD simulations substantially. I. Introductio

    Glycemic Control, Complications, and Death in Older Diabetic Patients: The Diabetes and Aging Study

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    OBJECTIVE—To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study (2004–2008) of 71,092 patients with type 2 diabetes, aged 60years,enrolledinKaiserPermanenteNorthernCalifornia.WespecifiedCoxproportionalhazardsmodelstoevaluatetherelationshipsbetweenbaselineglycatedhemoglobin(A1C)andsubsequentoutcomes(nonfatalcomplications[acutemetabolic,microvascular,andcardiovascularevents]andmortality).RESULTSThecohort(aged71.067.4years[means6SD])hadameanA1Cof7.061.260 years, enrolled in Kaiser Per-manente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality). RESULTS—The cohort (aged 71.06 7.4 years [means6 SD]) had a mean A1C of 7.06 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C.6.0 % (e.g., adjusted hazard ratio 1.09 [95 % CI 1.02–1.16] for A1C 6.0–6.9 % and 1.86 [1.63–2.13] for A1C 11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C,6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0 % (e.g., 0.83 [0.76–0.90] for A1C 7.0–7.9%) and higher at A1C11.011.0 % (1.31 [1.09–1.57]). Risk of any end point (compli-cation or death) became significantly higher at A1C 8.0%. Patterns generally were consistent across age-groups (60–69, 70–79, and $80 years). CONCLUSIONS—Observed relationships between A1C and combined end points suppor

    Plasmon oscillations in ellipsoid nanoparticles: beyond dipole approximation

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    The plasmon oscillations of a metallic triaxial ellipsoid nanoparticle have been studied within the framework of the quasistatic approximation. A general method has been proposed for finding the analytical expressions describing the potential and frequencies of the plasmon oscillations of an arbitrary multipolarity order. The analytical expressions have been derived for an electric potential and plasmon oscillation frequencies of the first 24 modes. Other higher orders plasmon modes are investigated numerically.Comment: 33 pages, 12 figure

    Serum MicroRNA Expression Profile Distinguishes Enterovirus 71 and Coxsackievirus 16 Infections in Patients with Hand-Foot-and-Mouth Disease

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    Altered circulating microRNA (miRNA) profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand-foot-and-mouth disease (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC) curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p) were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC) values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR-545, and miR-140-5p) were significantly increased in patients with CVA16 versus those with EV71 (p<0.05). Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections

    An FDA bioinformatics tool for microbial genomics research on molecular characterization of bacterial foodborne pathogens using microarrays

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    <p>Abstract</p> <p>Background</p> <p>Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed a genomics tool, ArrayTrack<sup>TM</sup>, which provides extensive functionalities to manage, analyze, and interpret genomic data for mammalian species. ArrayTrack<sup>TM</sup> has been widely adopted by the research community and used for pharmacogenomics data review in the FDA’s Voluntary Genomics Data Submission program. </p> <p>Results</p> <p>ArrayTrack<sup>TM</sup> has been extended to manage and analyze genomics data from bacterial pathogens of human, animal, and food origin. It was populated with bioinformatics data from public databases such as NCBI, Swiss-Prot, KEGG Pathway, and Gene Ontology to facilitate pathogen detection and characterization. ArrayTrack<sup>TM</sup>’s data processing and visualization tools were enhanced with analysis capabilities designed specifically for microbial genomics including flag-based hierarchical clustering analysis (HCA), flag concordance heat maps, and mixed scatter plots. These specific functionalities were evaluated on data generated from a custom Affymetrix array (FDA-ECSG) previously developed within the FDA. The FDA-ECSG array represents 32 complete genomes of <it>Escherichia coli</it> and<it> Shigella.</it> The new functions were also used to analyze microarray data focusing on antimicrobial resistance genes from <it>Salmonella</it> isolates in a poultry production environment using a universal antimicrobial resistance microarray developed by the United States Department of Agriculture (USDA).</p> <p>Conclusion</p> <p>The application of ArrayTrack<sup>TM</sup> to different microarray platforms demonstrates its utility in microbial genomics research, and thus will improve the capabilities of the FDA to rapidly identify foodborne bacteria and their genetic traits (e.g., antimicrobial resistance, virulence, etc.) during outbreak investigations. ArrayTrack<sup>TM</sup> is free to use and available to public, private, and academic researchers at <url>http://www.fda.gov/ArrayTrack</url>. </p

    Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo

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    Connective tissue growth factor (CCN2) is a major pro-fibrotic factor that frequently acts downstream of transforming growth factor beta (TGF-β)-mediated fibrogenic pathways. Much of our knowledge of CCN2 in fibrosis has come from studies in which its production or activity have been experimentally attenuated. These studies, performed both in vitro and in animal models, have demonstrated the utility of pharmacological inhibitors (e.g. tumor necrosis factor alpha (TNF-α), prostaglandins, peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists, statins, kinase inhibitors), neutralizing antibodies, antisense oligonucleotides, or small interfering RNA (siRNA) to probe the role of CCN2 in fibrogenic pathways. These investigations have allowed the mechanisms regulating CCN2 production to be more clearly defined, have shown that CCN2 is a rational anti-fibrotic target, and have established a framework for developing effective modalities of therapeutic intervention in vivo

    Global matrix 2.0:Report card grades on the physical activity of children and youth comparing 38 countries

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    The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the world's population). Nine common indicators were used (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior, Family and Peers, School, Community and the Built Environment, and Government Strategies and Investments), and all Report Cards were generated through a harmonized development process and a standardized grading framework (from A = excellent, to F = failing). The 38 Report Cards were presented at the International Congress on Physical Activity and Public Health in Bangkok, Thailand on November 16, 2016. The consolidated findings are summarized in the form of a Global Matrix demonstrating substantial variation in grades both within and across countries. Countries that lead in certain indicators often lag in others. Average grades for both Overall Physical Activity and Sedentary Behavior around the world are D (low/poor). In contrast, the average grade for indicators related to supports for physical activity was C. Lower-income countries generally had better grades on Overall Physical Activity, Active Transportation, and Sedentary Behaviors compared with higher-income countries, yet worse grades for supports from Family and Peers, Community and the Built Environment, and Government Strategies and Investments. Average grades for all indicators combined were highest (best) in Denmark, Slovenia, and the Netherlands. Many surveillance and research gaps were apparent, especially for the Active Play and Family and Peers indicators. International cooperation and cross-fertilization is encouraged to address existing challenges, understand underlying determinants, conceive innovative solutions, and mitigate the global childhood inactivity crisis. The paradox of higher physical activity and lower sedentary behavior in countries reporting poorer infrastructure, and lower physical activity and higher sedentary behavior in countries reporting better infrastructure, suggests that autonomy to play, travel, or chore requirements and/or fewer attractive sedentary pursuits, rather than infrastructure and structured activities, may facilitate higher levels of physical activity.</p

    A Novel Adaptive Method for the Analysis of Next-Generation Sequencing Data to Detect Complex Trait Associations with Rare Variants Due to Gene Main Effects and Interactions

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    There is solid evidence that rare variants contribute to complex disease etiology. Next-generation sequencing technologies make it possible to uncover rare variants within candidate genes, exomes, and genomes. Working in a novel framework, the kernel-based adaptive cluster (KBAC) was developed to perform powerful gene/locus based rare variant association testing. The KBAC combines variant classification and association testing in a coherent framework. Covariates can also be incorporated in the analysis to control for potential confounders including age, sex, and population substructure. To evaluate the power of KBAC: 1) variant data was simulated using rigorous population genetic models for both Europeans and Africans, with parameters estimated from sequence data, and 2) phenotypes were generated using models motivated by complex diseases including breast cancer and Hirschsprung's disease. It is demonstrated that the KBAC has superior power compared to other rare variant analysis methods, such as the combined multivariate and collapsing and weight sum statistic. In the presence of variant misclassification and gene interaction, association testing using KBAC is particularly advantageous. The KBAC method was also applied to test for associations, using sequence data from the Dallas Heart Study, between energy metabolism traits and rare variants in ANGPTL 3,4,5 and 6 genes. A number of novel associations were identified, including the associations of high density lipoprotein and very low density lipoprotein with ANGPTL4. The KBAC method is implemented in a user-friendly R package

    Rare Copy Number Variants Observed in Hereditary Breast Cancer Cases Disrupt Genes in Estrogen Signaling and TP53 Tumor Suppression Network

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    Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 BRCA1, BRCA2, and PALB2 mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (P = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and TP53 centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer
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