Accelerated gas-liquid visible light photoredox catalysis with continuous-flow photochemical microreactors

In this protocol, we describe the construction and use of an operationally simple photochemical microreactor for gas-liquid photoredox catalysis using visible light. The general procedure includes details on how to set up the microreactor appropriately with inlets for gaseous reagents and organic starting materials, and it includes examples of how to use it to achieve continuous-flow preparation of disulfides or trifluoromethylated heterocycles and thiols. The reported photomicroreactors are modular, inexpensive and can be prepared rapidly from commercially available parts within 1 h even by nonspecialists. Interestingly, typical reaction times of gas-liquid visible light photocatalytic reactions performed in microflow are lower (in the minute range) than comparable reactions performed as a batch process (in the hour range). This can be attributed to the improved irradiation efficiency of the reaction mixture and the enhanced gas-liquid mass transfer in the segmented gas-liquid flow regime

Аналіз стійкості вибійних компоновок на проектній траєкторії

Рассмотрены основные причины, оказывающие дестабилизирующее влияние на роботу компоновок низа бурильной колонны. Проведён анализ процесса износа опорноцентрирующих элементов забойной компоновки и его влияния на изменение её конструктивных параметров. Получены графические зависимости, позволяющие оценить степень стойкости различных типов забойных компоновок на проектной траектории. Сделаны основные выводы, касающиеся поведения различных типов компоновок при воздействии на них дестабилизирующих факторовThe basic reasons, causing destabilizing influence on the work of drilling string assembly are reviewed. The analysis of wear out process of strong centralizing elements bottom drilling string assembly and its influence to change of its constructive properties is done. The graphic dependences, giving an opportunity to value the stage of firmness of different types of bottom drilling string assemblies on projected trajectory are given. The conclusion about conduct of different types of drilling string assemblies during influence on it destabilizing factors is draw

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Discovery of a Disrupting Open Cluster Far into the Milky Way Halo: A Recent Star Formation Event in the Leading Arm of the Magellanic Stream?

We report the discovery of a young (tau similar to 117 Myr), low-mass (M similar to 1200 M.), metal-poor ([Fe H] similar to -1.14) stellar association at a heliocentric distance D approximate to 28.7 kpc, placing it far into the Milky Way (MW) halo. At its present Galactocentric position (R, z) similar to (23, 15) kpc, the association is (on the sky) near the leading arm of the gas stream emanating from the Magellanic Cloud system, but is located approximate to 60 degrees from the Large Magellanic Cloud center on the other side of the MW disk. If the cluster is colocated with H I gas in the stream, we directly measure the distance to the leading arm of the Magellanic stream. The measured distance is inconsistent with Magellanic stream model predictions that do not account for ram pressure and gas interaction with the MW disk. The estimated age of the cluster is consistent with the time of last passage of the leading arm gas through the Galactic midplane; we therefore speculate that this star formation event was triggered by its last disk midplane passage. Most details of this idea remain a puzzle: the Magellanic stream has low column density, the MW disk at large radii has low gas density, and the relative velocity of the leading arm and MW gas is large. However it formed, the discovery of a young stellar cluster in the MW halo presents an interesting opportunity for study. This cluster was discovered with Gaia astrometry and photometry alone, but follow-up DECam photometry was crucial for measuring its properties.National Science Foundation (NSF) [AST-1813881]; Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory (NOAO) [2018A-0251]; Center for Computational AstrophysicsThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Taxonomy of the order Mononegavirales : update 2016

In 2016, the order Mononegavirales was emended through the addition of two new families (Mymonaviridae and Sunviridae), the elevation of the paramyxoviral subfamily Pneumovirinae to family status (Pneumoviridae), the addition of five free-floating genera (Anphevirus, Arlivirus, Chengtivirus, Crustavirus, and Wastrivirus), and several other changes at the genus and species levels. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV)

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Long-term thermal sensitivity of Earth’s tropical forests

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes