Enabling EASEY deployment of containerized applications for future HPC systems

The upcoming exascale era will push the changes in computing architecture from classical CPU-based systems in hybrid GPU-heavy systems with much higher levels of complexity. While such clusters are expected to improve the performance of certain optimized HPC applications, it will also increase the difficulties for those users who have yet to adapt their codes or are starting from scratch with new programming paradigms. Since there are still no comprehensive automatic assistance mechanisms to enhance application performance on such systems, we are proposing a support framework for future HPC architectures, called EASEY (Enable exASclae for EverYone). The solution builds on a layered software architecture, which offers different mechanisms on each layer for different tasks of tuning. This enables users to adjust the parameters on each of the layers, thereby enhancing specific characteristics of their codes. We introduce the framework with a Charliecloud-based solution, showcasing the LULESH benchmark on the upper layers of our framework. Our approach can automatically deploy optimized container computations with negligible overhead and at the same time reduce the time a scientist needs to spent on manual job submission configurations.Comment: International Conference on Computational Science ICCS2020, 13 page

Synchronization Landscapes in Small-World-Connected Computer Networks

Motivated by a synchronization problem in distributed computing we studied a simple growth model on regular and small-world networks, embedded in one and two-dimensions. We find that the synchronization landscape (corresponding to the progress of the individual processors) exhibits Kardar-Parisi-Zhang-like kinetic roughening on regular networks with short-range communication links. Although the processors, on average, progress at a nonzero rate, their spread (the width of the synchronization landscape) diverges with the number of nodes (desynchronized state) hindering efficient data management. When random communication links are added on top of the one and two-dimensional regular networks (resulting in a small-world network), large fluctuations in the synchronization landscape are suppressed and the width approaches a finite value in the large system-size limit (synchronized state). In the resulting synchronization scheme, the processors make close-to-uniform progress with a nonzero rate without global intervention. We obtain our results by ``simulating the simulations", based on the exact algorithmic rules, supported by coarse-grained arguments.Comment: 20 pages, 22 figure

Perivascular adipose tissue-derived nitric oxide compensates endothelial dysfunction in aged pre-atherosclerotic apolipoprotein E-deficient rats

BACKGROUND AND AIMS: Atherosclerosis is a major contributor to global mortality and is accompanied by vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is an established regulator of vascular function with emerging implications in atherosclerosis. We investigated the modulation of aortic relaxation by PVAT in aged rats with apolipoprotein E deficiency (ApoE-/-) fed a high-fat diet as a model of early atherosclerosis. METHODS AND RESULTS: ApoE-/- rats (N = 7) and wild-type Sprague-Dawley controls (ApoE+/+, N = 8) received high-fat diet for 51 weeks. Hyperlipidemia was confirmed in ApoE-/- rats by elevated plasma cholesterol (p < 0.001) and triglyceride (p = 0.025) levels. Early atherosclerosis was supported by increased intima/media thickness ratio (p < 0.01) and ED1-positive macrophage influx in ApoE-/- aortic intima (p < 0.001). Inflammation in ApoE-/- PVAT was characteristic by an increased [18F]FDG uptake (p < 0.01), ED1-positive macrophage influx (p = 0.0003), mRNA expression levels of CD68 (p < 0.001) and IL-1β (p < 0.01), and upregulated iNOS protein (p = 0.011). The mRNAs of MCP-1, IL-6 and adiponectin remained unchanged in PVAT. Aortic PVAT volume measured with micro-PET/CT was increased in ApoE-/- rats (p < 0.01). Maximal endothelium-dependent relaxation (EDR) to acetylcholine in ApoE-/- aortic rings without PVAT was severely impaired (p = 0.012) compared with controls, while ApoE-/- aortic rings with PVAT showed higher EDR than controls. All EDR responses were blocked by L-NMMA and the expression of eNOS mRNA was increased in ApoE-/- PVAT (p = 0.035). CONCLUSION: Using a rat ApoE-/- model of early atherosclerosis, we capture a novel mechanism by which inflammatory PVAT compensates severe endothelial dysfunction by contributing NO upon cholinergic stimulation

An All-Sky 2MASS Mosaic Constructed on the TeraGrid

The Montage mosaic engine supplies on-request image mosaic services for the NVO astronomical community. A companion paper describes scientific applications of Montage. This paper describes one application in detail: the generation at SDSC of a mosaic of the 2MASS All-sky Image Atlas on the NSF TeraGrid. The goals of the project are: to provide a value-added 2MASS product that combines overlapping images to improve sensitivity; to demonstrate applicability of computing at-scale to astronomical missions and surveys, especially projects such as LSST; and to demonstrate the utility of the NVO Hyperatlas format. The numerical processing of an 8 TB, 32-bit survey to produce a 64-bit, 20 TB output atlas presented multiple scalability and operational challenges. An MPI Python module, MYMPI, was used to manage the alternately sequential and parallel steps of the Montage process. This allowed us to parallelize all steps of the mosaic process: that of many, sequential steps executing simultaneously for independent mosaics and that of a single MPI parallel job executing on many CPUs for a single mosaic. The Storage Resource Broker (SRB) was used to archive the output results in the Hyperatlas. The 2MASS mosaics are now being assessed for scientific quality. Around 130,000 CPU-hours were used to complete the mosaics. The output consists of 1734 plates spanning 6◦ for each of 3 bands. Each of the 5202 mosaics is roughly 4 GB in size, and each has been tiled into a 12×12 array of 26 MB files for ease of handling. The total size is about 20 TB in 750,000 tiles

HNF1B and Endometrial Cancer Risk: Results from the PAGE study

We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P≥0.21) or between studies (P≥0.70). The ORper allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63×10−6) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77×10−7) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P≥0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors

Homozygous whole body Cbs knockout in adult mice features minimal pathology during ageing despite severe homocysteinemia

Deficiencies in Cystathionine-β-synthase (CBS) lead to hyperhomocysteinemia (HHCy), which is considered a risk factor for cardiovascular, bone and neurological disease. Moreover, CBS is important for the production of cysteine, hydrogen sulfide (H2 S) and glutathione. Studying the biological role of CBS in adult mice has been severely hampered by embryological disturbances and perinatal mortality. To overcome these issues and assess the effects of whole-body CBS deficiency in adult mice, we engineered and characterized a Cre-inducible Cbs knockout model during ageing. No perinatal mortality occurred before Cbs-/- induction at 10 weeks of age. Mice were followed until 90 weeks of age and ablation of Cbs was confirmed in liver and kidney but not in brain. Severe HHCy was observed in Cbs-/- (289 ± 58 µM) but not in Cbs+/- or control mice (<10 µM). Cbs-/- showed impaired growth, facial alopecia, endothelial dysfunction in absence of increased mortality, and signs of liver or kidney damage. CBS expression in skin localized to sebaceous glands and epidermis, suggesting local effects of Cbs-/- on alopecia. Cbs-/- showed increased markers of oxidative stress and senescence but expression of other H2 S producing enzymes (CSE and 3-MST) was not affected. CBS deficiency severely impaired H2 S production capacity in liver, but not in brain or kidney. In summary, Cbs-/- mice presented a mild phenotype without mortality despite severe HHCy. The findings demonstrate that HHCy is not directly linked to development of end organ damage

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype-phenotype associations, 26 represented phenotypes closely related to previously known genotype-phenotype associations, and 33 represented potentially novel genotype-phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits