55 research outputs found

    Fast and accurate protein substructure searching with simulated annealing and GPUs

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    <p>Abstract</p> <p>Background</p> <p>Searching a database of protein structures for matches to a query structure, or occurrences of a structural motif, is an important task in structural biology and bioinformatics. While there are many existing methods for structural similarity searching, faster and more accurate approaches are still required, and few current methods are capable of substructure (motif) searching.</p> <p>Results</p> <p>We developed an improved heuristic for tableau-based protein structure and substructure searching using simulated annealing, that is as fast or faster and comparable in accuracy, with some widely used existing methods. Furthermore, we created a parallel implementation on a modern graphics processing unit (GPU).</p> <p>Conclusions</p> <p>The GPU implementation achieves up to 34 times speedup over the CPU implementation of tableau-based structure search with simulated annealing, making it one of the fastest available methods. To the best of our knowledge, this is the first application of a GPU to the protein structural search problem.</p

    Genetic Effects at Pleiotropic Loci Are Context-Dependent with Consequences for the Maintenance of Genetic Variation in Populations

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    Context-dependent genetic effects, including genotype-by-environment and genotype-by-sex interactions, are a potential mechanism by which genetic variation of complex traits is maintained in populations. Pleiotropic genetic effects are also thought to play an important role in evolution, reflecting functional and developmental relationships among traits. We examine context-dependent genetic effects at pleiotropic loci associated with normal variation in multiple metabolic syndrome (MetS) components (obesity, dyslipidemia, and diabetes-related traits). MetS prevalence is increasing in Western societies and, while environmental in origin, presents substantial variation in individual response. We identify 23 pleiotropic MetS quantitative trait loci (QTL) in an F16 advanced intercross between the LG/J and SM/J inbred mouse strains (Wustl:LG,SM-G16; n = 1002). Half of each family was fed a high-fat diet and half fed a low-fat diet; and additive, dominance, and parent-of-origin imprinting genotypic effects were examined in animals partitioned into sex, diet, and sex-by-diet cohorts. We examine the context-dependency of the underlying additive, dominance, and imprinting genetic effects of the traits associated with these pleiotropic QTL. Further, we examine sequence polymorphisms (SNPs) between LG/J and SM/J as well as differential expression of positional candidate genes in these regions. We show that genetic associations are different in different sex, diet, and sex-by-diet settings. We also show that over- or underdominance and ecological cross-over interactions for single phenotypes may not be common, however multidimensional synthetic phenotypes at loci with pleiotropic effects can produce situations that favor the maintenance of genetic variation in populations. Our findings have important implications for evolution and the notion of personalized medicine

    Determinants of premature mortality in a city population: An eight-year observational study concerning subjects aged 18–64

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    Background: Premature deaths constitute 31.1% of all deaths in Łódź. Analysis of the causes of premature deaths may be helpful in the evaluation of health risk factors. Moreover, findings of this study may enhance prophylactic measures. Material and Methods: In 2001, 1857 randomly selected citizens, aged 18-64, were included in the Countrywide Integrated Noncommunicable Diseases Intervention (CINDI) Programme. In 2009, a follow-up study was conducted and information on the subjects of the study was collected concerning their health status and if they continued to live in Łódź. The Cox proportional hazards model was used for evaluation of hazard coefficients. We adjusted our calculations for age and sex. The analysis revealed statistically significant associations between the number of premature deaths of the citizens of Łódź and the following variables: a negative self-evaluation of health - HR = 3.096 (95% CI: 1.729-5.543), poor financial situation - HR = 2.811 (95% CI: 1.183‑6.672), occurring in the year preceding the study: coronary pain - HR = 2.754 (95% CI: 1.167-6.494), depression - HR = 2.001 (95% CI: 1.222-3.277) and insomnia - HR = 1.660 (95% CI: 1.029-2.678). Our research study also found a negative influence of smoking on the health status - HR = 2.782 (95% CI: 1.581-4.891). Moreover, we conducted survival analyses according to sex and age with Kaplan-Meier curves. Conclusions: The risk factors leading to premature deaths were found to be highly significant but possible to reduce by modifying lifestyle-related health behaviours. The confirmed determinants of premature mortality indicate a need to spread and intensify prophylactic activities in Poland, which is a post-communist country, in particular, in the field of cardiovascular diseases

    Boosted Tree Ensembles for Artificial Intelligence Based Automated Valuation Models (AI-AVM)

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    10.1007/s11146-021-09861-1Journal of Real Estate Finance and Economic
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