Asynchronous In Situ Processing with Gromacs: Taking Advantage of GPUs

International audienceNumerical simulations using supercomputers are producing an ever growing amount of data. Efficient production and analysis of these data are the key to future discoveries. The in situ paradigm is emerging as a promising solution to avoid the I/O bottleneck encountered in the file system for both the simulation and the analytics by treating the data as soon as they are produced in memory. Various strategies and implementations have been proposed in the last years to support in situ treatments with a low impact on the simulation performance. Yet, little efforts have been made when it comes to perform in situ analytics with hybrid simulations supporting accelerators like GPUs. In this article, we propose a study of the in situ strategies with Gromacs, a molecular dynamic simulation code supporting multi-GPUs, as our application target. We specifically focus on the computational resources usage of the machine by the simulation and the in situ analytics. We finally extend the usual in situ placement strategies to the case of in situ analytics running on a GPU and study their impact on both Gromacs performance and the resource usage of the machine. We show in particular that running in situ analytics on the GPU can be a more efficient solution than on the CPU especially when the CPU is the bottleneck of the simulation

Young people and political action: who is taking responsibility for positive social change?

A human rights perspective suggests that we are all responsible for ensuring the human rights of others, which in turn ensures that our own human rights are respected and protected. A convenience sample of 108 young people (41 males and 67 females) aged between 16 and 25 completed a questionnaire which asked about (a) levels of involvement in political activity and (b) sense of personal responsibility for ensuring that the human rights of marginalised groups (e.g. ethnic minorities, immigrants, lesbians and gay men) are protected. Findings showed that most respondents supported (in principle) the notion of human rights for all, but tended to engage in low key political activity (e.g. signing petitions; donating money or goods to charity) rather than actively working towards positive social change. Qualitative data collected in the questionnaire suggested three main barriers to respondents viewing themselves as agents of positive social change: (1) "It’s not my problem", (2) "It’s not my responsibility", and (3) a sense of helplessness. Suggestions for how political action might best be mobilised among young people are also discussed.</p

Formal Hecke algebras and algebraic oriented cohomology theories

In the present paper we generalize the construction of the nil Hecke ring of Kostant-Kumar to the context of an arbitrary algebraic oriented cohomology theory of Levine-Morel and Panin-Smirnov, e.g. to Chow groups, Grothendieck's K_0, connective K-theory, elliptic cohomology, and algebraic cobordism. The resulting object, which we call a formal (affine) Demazure algebra, is parameterized by a one-dimensional commutative formal group law and has the following important property: specialization to the additive and multiplicative periodic formal group laws yields completions of the nil Hecke and the 0-Hecke rings respectively. We also introduce a deformed version of the formal (affine) Demazure algebra, which we call a formal (affine) Hecke algebra. We show that the specialization of the formal (affine) Hecke algebra to the additive and multiplicative periodic formal group laws gives completions of the degenerate (affine) Hecke algebra and the usual (affine) Hecke algebra respectively. We show that all formal affine Demazure algebras (and all formal affine Hecke algebras) become isomorphic over certain coefficient rings, proving an analogue of a result of Lusztig.Comment: 28 pages. v2: Some results strengthened and references added. v3: Minor corrections, section numbering changed to match published version. v4: Sign errors in Proposition 6.8(d) corrected. This version incorporates an erratum to the published versio

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received "usual care".&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p=0.23, 95% CI -0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence.&lt;/p&gt

A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Menopause accelerates biological aging

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked