Dynamic Adaptable Asynchronous Progress Model for MPI RMA Multiphase Applications

Casper is a process-based asynchronous progress model for MPI one-sided communication on multi- and many-core architectures. The one-sided communication is not truly one-sided in most MPI implementations: the target process still relies on software progress to complete incoming operations. Casper allows the user to specify an arbitrary number of cores dedicated to background ghost processes and transparently redirects the RMA operations to ghost processes by utilizing the PMPI redirection and MPI-3 shared-memory technologies. Although Casper benefits applications that suffer from lack of asynchronous progress, the operation redirection design might not support complex multiphase applications effectively, which often involve dynamically changing communication density and computing workloads. In this paper, we present an adaptive mechanism in Casper to address the limitation of static asynchronous progress in multiphase applications. We exploit two adaptive strategies, a user-guided strategy and a fully transparent and automatic strategy based on self-profiling and prediction, to dynamically reconfigure the asynchronous progress in Casper according to real-time performance characteristics during multiphase execution. We evaluate the adaptive approaches in both microbenchmarks and a real quantum chemistry application suite, NWChem, on the Cray XC30 supercomputer and an Intel Omni-Path cluster.This material was based upon work supported by the U.S. Dept. of Energy, Office of Science, Advanced Scientific Computing Research (SC-21), under contract DE-AC02- 06CH11357. The experimental resources for this paper were provided by the National Energy Research Scientific Computing Center (NERSC) on the Edison Cray XC30 supercomputer and by the Laboratory Computing Resource Center on the Bebop cluster at Argonne National Laboratory. Antonio J. Peña is co-financed by the Spanish Ministry of Economy and Competitiveness under Juan de la Cierva fellowship number IJCI-2015-23266.Peer ReviewedPostprint (author's final draft

Differences in depressive symptoms by rurality in Japan: a cross-sectional multilevel study using different aggregation units of municipalities and neighborhoods (JAGES)

[Background] Rurality can reflect many aspects of the community, including community characteristics that may be associated with mental health. In this study, we focused on geographical units to address multiple layers of a rural environment. By evaluating rurality at both the municipality and neighborhood (i.e., a smaller unit within a municipality) levels in Japan, we aimed to elucidate the relationship between depression and rurality. To explore the mechanisms linking rurality and depression, we examined how the association between rurality and depression can be explained by community social capital according to geographical units. [Methods] We used cross-sectional data from the 2016 wave of the Japan Gerontological Evaluation Study involving 144, 822 respondents aged 65 years or older residing in 937 neighborhoods across 39 municipalities. The population density quintile for municipality-level rurality and the quintile for the time required to reach densely inhabited districts for neighborhood-level rurality were used. We calculated the prevalence ratios of depressive symptoms by gender using a three-level (individual, neighborhood, and municipality) Poisson regression. Community social capital was assessed using three components: civic participation, social cohesion, and reciprocity. [Results] The prevalence of depressive symptoms was higher in municipalities with lower population density than those with the highest population density; the ratios were 1.22 (95% confidence intervals: 1.15, 1.30) for men and 1.22 (1.13, 1.31) for women. In contrast, when evaluating rurality at the neighborhood level, the prevalence of depressive symptoms was 0.9 times lower for men in rural areas; no such association was observed for women. In rural municipalities, community civic participation was associated with an increased risk of depressive symptoms. In rural neighborhoods, community social cohesion and reciprocity were linked to a lower risk of depressive symptoms. [Conclusions] The association between rurality and depression varied according to geographical unit. In rural municipalities, the risk of depression may be higher for both men and women, and the presence of an environment conducive to civic participation may contribute to a higher risk of depression, as observed in this study. The risk of depression in men may be lower in rural neighborhoods in Japan, which may be related to high social cohesion and reciprocity

PcpA, which is involved in the degradation of pentachlorophenol in Sphingomonas chlorophenolica ATCC39723, is a novel type of ring-cleavage dioxygenase

AbstractThe pentachlorophenol (PCP) mineralizing bacterium Sphingomonas chlorophenolica ATCC39723 degrades PCP via 2,6-dichlorohydroquinone (2,6-DCHQ). The pathway converting PCP to 2,6-DCHQ has been established previously; however, the pathway beyond 2,6-DCHQ is not clear, although it has been suggested that a PcpA plays a role in 2,6-DCHQ conversion. In this study, PcpA expressed in Escherichia coli was purified to homogeneity and shown to have novel ring-cleavage dioxygenase activity in conjunction with hydroquinone derivatives, and converting 2,6-DCHQ to 2-chloromaleylacetate

Crystal structure of the haloalkane dehalogenase from Sphingomonas paucimobilis UT26,

ABSTRACT: The haloalkane dehalogenase from Sphingomonas paucimobilis UT26 (LinB) is the enzyme involved in the degradation of the important environmental pollutant γ-hexachlorocyclohexane. The enzyme hydrolyzes a broad range of halogenated cyclic and aliphatic compounds. Here, we present the 1.58 Å crystal structure of LinB and the 2.0 Å structure of LinB with 1,3-propanediol, a product of debromination of 1,3-dibromopropane, in the active site of the enzyme. The enzyme belongs to the R/ hydrolase family and contains a catalytic triad (Asp108, His272, and Glu132) in the lipase-like topological arrangement previously proposed from mutagenesis experiments. The LinB structure was compared with the structures of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 and from Rhodococcus sp. and the structural features involved in the adaptation toward xenobiotic substrates were identified. The arrangement and composition of the R-helices in the cap domain results in the differences in the size and shape of the active-site cavity and the entrance tunnel. This is the major determinant of the substrate specificity of this haloalkane dehalogenase

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The transfer of artisan workshops and Gerechtsame-licenses among the shoemakers in the city of Innsbruck: Ein Forschungsberich

The central objective of this case study of shoemakers in Innsbruck (Austria) is to depict and analyse the various forms of social reproduction among urban artisans. In contradiction to the generally accepted assumption, about the Gerechtsame-license being passed on from father to sonor to a journeyman having married into the family, the author succeeds to show that during the 17th century this was rarely the case. And although the requirement of obligatory journeying was subsequently abandoned and a growing trend to less mobility increasingly characterised urban society, by the end of the 18th century the ratio of master artisans acquiring their Gerechtsame-license according to this pattern had still not reached more than 50 percent. The pattern of the Gerechtsame-transfer from one person to another was again to change drastically du ring the 19th century, when the reforms of the guild regulations and the new trades-legislation (the 1859 Gewerbeordnung) legalised the purchase of Gerechtsame-licenses for money.The central objective of this case study of shoemakers in Innsbruck (Austria) is to depict and analyse the various forms of social reproduction among urban artisans. In contradiction to the generally accepted assumption, about the Gerechtsame-license being passed on from father to sonor to a journeyman having married into the family, the author succeeds to show that during the 17th century this was rarely the case. And although the requirement of obligatory journeying was subsequently abandoned and a growing trend to less mobility increasingly characterised urban society, by the end of the 18th century the ratio of master artisans acquiring their Gerechtsame-license according to this pattern had still not reached more than 50 percent. The pattern of the Gerechtsame-transfer from one person to another was again to change drastically du ring the 19th century, when the reforms of the guild regulations and the new trades-legislation (the 1859 Gewerbeordnung) legalised the purchase of Gerechtsame-licenses for money