522 research outputs found
Resource management for heterogeneous computing systems: utility maximization, energy-aware scheduling, and multi-objective optimization
Includes bibliographical references.2015 Summer.As high performance heterogeneous computing systems continually become faster, the operating cost to run these systems has increased. A significant portion of the operating costs can be attributed to the amount of energy required for these systems to operate. To reduce these costs it is important for system administrators to operate these systems in an energy efficient manner. Additionally, it is important to be able to measure the performance of a given system so that the impacts of operating at different levels of energy efficiency can be analyzed. The goal of this research is to examine how energy and system performance interact with each other for a variety of environments. One part of this study considers a computing system and its corresponding workload based on the expectations for future environments of Department of Energy and Department of Defense interest. Numerous Heuristics are presented that maximize a performance metric created using utility functions. Additional heuristics and energy filtering techniques have been designed for a computing system that has the goal of maximizing the total utility earned while being subject to an energy constraint. A framework has been established to analyze the trade-offs between performance (utility earned) and energy consumption. Stochastic models are used to create "fuzzy" Pareto fronts to analyze the variability of solutions along the Pareto front when uncertainties in execution time and power consumption are present within a system. In addition to using utility earned as a measure of system performance, system makespan has also been studied. Finally, a framework has been developed that enables the investigation of the effects of P-states and memory interference on energy consumption and system performance
Conserved regulatory motifs at phenylethanolamine N-methyltransferase (PNMT) are disrupted by common functional genetic variation: an integrated computational/experimental approach
The adrenomedullary hormone epinephrine transduces environmental stressors into cardiovascular events (tachycardia and hypertension). Although the epinephrine biosynthetic enzyme PNMT genetic locus displays both linkage and association to such traits, genetic variation underlying these quantitative phenotypes is not established. Using an integrated suite of computational and experimental approaches, we elucidate a functional mechanism for common (minor allele frequencies > 30%) genetic variants at PNMT. Transcription factor binding motif prediction on mammalian PNMT promoter alignments identified two variant regulatory motifs, SP1 and EGR1, disrupted by G-367A (rs3764351), and SOX17 motif created by G-161A (rs876493). Electrophoretic mobility shifts of approximately 30-bp oligonucleotides containing ancestral versus variant alleles validated the computational hypothesis. Queried against chromaffin cell nuclear protein extracts, only the G-367 and -161A alleles shifted. Specific antibodies applied in electrophoretic gel shift experiments confirmed binding of SP1 and EGR1 to G-367 and SOX17 to -161A. The in vitro allele-specific binding was verified in cella through promoter reporter assays: lower activity for -367A haplotypes cotransfected by SP1 (p = 0.002) and EGR1 (p = 0.034); and enhanced inhibition of -161A haplotypes (p = 0.0003) cotransfected with SP1 + SOX17. Finally, we probed cis/trans regulation with endogenous factors by chromatin immunoprecipitation using SP1/EGR1/SOX17 antibodies. We describe the systematic application of complementary computational and experimental techniques to detect and document functional genetic variation in a trait-associated regulatory region. The results provide insight into cis and trans transcriptional mechanisms whereby common variation at PNMT can give rise to quantitative changes in human physiological and disease traits. Thus, PNMT variants in cis may interact with nuclear factors in trans to govern adrenergic activity
The Towuti Drilling Project:paleoenvironments, biological evolution, and geomicrobiology of a tropical Pacific lake
The Towuti Drilling Project (TDP) is an international research program, whose goal is to understand long-term environmental and climatic change in the tropical western Pacific, the impacts of geological and environmental changes on the biological evolution of aquatic taxa, and the geomicrobiology and biogeochemistry of metal-rich, ultramafic-hosted lake sediments through the scientific drilling of Lake Towuti, southern Sulawesi, Indonesia. Lake Towuti is a large tectonic lake at the downstream end of the Malili lake system, a chain of five highly biodiverse lakes that are among the oldest lakes in Southeast Asia. In 2015 we carried out a scientific drilling program on Lake Towuti using the International Continental Scientific Drilling Program (ICDP) Deep Lakes Drilling System (DLDS). We recovered a total of ∼ 1018 m of core from 11 drilling sites with water depths ranging from 156 to 200 m. Recovery averaged 91.7 %, and the maximum drilling depth was 175 m below the lake floor, penetrating the entire sedimentary infill of the basin. Initial data from core and borehole logging indicate that these cores record the evolution of a highly dynamic tectonic and limnological system, with clear indications of orbital-scale climate variability during the mid- to late Pleistocene
Heredity and cardiometabolic risk: naturally occurring polymorphisms in the human neuropeptide Y2 receptor promoter disrupt multiple transcriptional response motifs
The neuropeptide Y2 G-protein-coupled receptor (NPY2R) relays signals from PYY or neuropeptide Y toward satiety and control of body mass. Targeted ablation of the NPY2R locus in mice yields obesity, and studies of NPY2R promoter genetic variation in more than 10 000 human participants indicate its involvement in control of obesity and BMI. Here we searched for genetic variation across the human NPY2R locus and probed its functional effects, especially in the proximal promoter
Genes and environment: novel, functional polymorphism in the human cathepsin L (CTSL1) promoter disrupts a xenobiotic response element (XRE) to alter transcription and blood pressure
Cathepsin L (CTSL1) catalyzes the formation of peptides that influence blood pressure (BP). Naturally occurring genetic variation or targeted ablation of the Ctsl1 locus in mice yield cardiovascular pathology. Here, we searched for genetic variation across the human CTSL1 locus and probed its functional effects, especially in the proximal promoter
Loss of Skeletal Muscle Mass During Neoadjuvant Chemoradiotherapy Predicts Postoperative Mortality in Esophageal Cancer Surgery
Naturally Occurring Genetic Variants in Human Chromogranin A (CHGA) Associated with Hypertension as well as Hypertensive Renal Disease
Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 3′-UTR. In chromaffin cell-transfected CHGA 3′-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3′-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 3′-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects
Catecholamine Storage Vesicles: Role of Core Protein Genetic Polymorphisms in Hypertension
Hypertension is a complex trait with deranged autonomic control of the circulation. The sympathoadrenal system exerts minute-to-minute control over cardiac output and vascular tone. Catecholamine storage vesicles (or chromaffin granules) of the adrenal medulla contain remarkably high concentrations of chromogranins/secretogranins (or “granins”), catecholamines, neuropeptide Y, adenosine triphosphate (ATP), and Ca2+. Within secretory granules, granins are co-stored with catecholamine neurotransmitters and co-released upon stimulation of the regulated secretory pathway. The principal granin family members, chromogranin A (CHGA), chromogranin B (CHGB), and secretogranin II (SCG2), may have evolved from shared ancestral exons by gene duplication. This article reviews human genetic variation at loci encoding the major granins and probes the effects of such polymorphisms on blood pressure, using twin pairs to probe heritability and individuals with the most extreme blood pressure values in the population to study hypertension
Brain Potentials Highlight Stronger Implicit Food Memory for Taste than Health and Context Associations
Increasingly consumption of healthy foods is advised to improve population health. Reasons people give for choosing one food over another suggest that non-sensory features like health aspects are appreciated as of lower importance than taste. However, many food choices are made in the absence of the actual perception of a food's sensory properties, and therefore highly rely on previous experiences of similar consumptions stored in memory. In this study we assessed the differential strength of food associations implicitly stored in memory, using an associative priming paradigm. Participants (N = 30) were exposed to a forced-choice picture-categorization task, in which the food or non-food target images were primed with either non-sensory or sensory related words. We observed a smaller N400 amplitude at the parietal electrodes when categorizing food as compared to non-food images. While this effect was enhanced by the presentation of a food-related word prime during food trials, the primes had no effect in the non-food trials. More specifically, we found that sensory associations are stronger implicitly represented in memory as compared to non-sensory associations. Thus, this study highlights the neuronal mechanisms underlying previous observations that sensory associations are important features of food memory, and therefore a primary motive in food choice.</p
The Intention–Behavior Gap
© 2016 John Wiley & Sons LtdBitter personal experience and meta-analysis converge on the conclusion that people do not always do the things that they intend to do. This paper synthesizes research on intention–behavior relations to address questions such as: How big is the intention–behavior gap? When are intentions more or less likely to get translated into action? What kinds of problems prevent people from realizing their intentions? And what strategies show promise in closing the intention–behavior gap and helping people do the things that they intend to do?
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