Reentrant peak effect and melting of a flux line lattice in 2H-NbSe<SUB>2</SUB>

A reentrant peak effect is observed through low field ac susceptibility measurements on the weakly pinned flux line lattice in single crystals of 2H-Nb Se2. The resulting phase diagram of the peak effect is strikingly similar to the theoretically predicted reentrant phase boundary which separates flux lattice and flux liquid phases. The broadening and ultimate disappearance of the peak effect at very low fields is consistent with the predicted crossover to a disordered glassy state in this field regime

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics

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Not AvailableThe present study examined the spatial market integration across four major potato markets, viz. Agra, Bengaluru, Delhi and Mumbai for the period January, 2005–March, 2018. Johansen’s multivariate co-integration approach has been applied to identify the possible market integration. The results of Johansen’s co-integration test for different markets revealed that all the six market pairs are co-integrated, demonstrating that the selected potato markets have long-run price linkage across them. To supplement the finding of Johansen’s co-integration analysis, we assessed the nature and extent of long run and short run causal relationship between the markets. The results of long run causality showed bidirectional causality for the market pairs: Agra ↔ Bengaluru, Agra ↔ Mumbai, Bengaluru ↔ Delhi and Bengaluru ↔ Mumbai, whereas for market pairs Agra→ Delhi and Mumbai→ Delhi have long-run unidirectional causality. To get the additional evidence as to whether and in which direction price transmission is occurring between the market pairs in short run, Wald test has been used.Not Availabl

Reconfigurable Computing and Electronic Nanotechnology

We examine the opportunities brought about by recent progress in electronic nanotechnology and describe the methods needed to harness them for building a new computer architecture. In this process we decompose some traditional abstractions, such as the transistor, into fine-grain pieces, such as signal restoration and input-output isolation. We also show how we can forgo the extreme reliability of CMOS circuits for low-cost chemical self-assembly at the expense of large manufacturing defect densities. We discuss advanced testing methods that can be used to recover perfect functionality from unreliable parts. We proceed to show how the molecular switch, the regularity of the circuits created by self-assembly and the high defect densities logically require the use of reconfigurable hardware as a basic building block for hardware design. We then capitalize on the convergence of compilation and hardware synthesis (which takes place when programming reconfigurable hardware) to propose the complete elimination of the instruction-set architecture from the system architecture, and the synthesis of asynchronous dataflow machines directly from high-level programming languages, such as C. We discuss in some detail a scalable compilation system that performs this task

Tartan: Evaluating spatial computation for whole program execution

Spatial Computing (SC) has been shown to be an energy-efficient model for implementing program kernels. In this paper we explore the feasibility of using SC for more than small kernels. To this end, we evaluate the performance and energy efficiency of entire applications on Tartan, a general-purpose architecture which integrates a reconfigurable fabric (RF) with a superscalar core. Our compiler automatically partitions and compiles an application into an instruction stream for the core and a configuration for the RF. We use a detailed simulator to capture both timing and energy numbers for all parts of the system. Our results indicate that a hierarchical RF architecture, designed around a scalable interconnect, is instrumental in harnessing the benefits of spatial computation. The interconnect uses static configuration and routing at the lower levels and a packet-switched, dynamically-routed network at the top level. Tartan is most energyefficient when almost all of the application is mapped to the RF, indicating the need for the RF to support most general-purpose programming constructs. Our initial investigation reveals that such a system can provide, on average, an order of magnitude improvement in energy-delay compared to an aggressive superscalar core on single-threaded workloads