Abstract
Motivation
Linkage disequilibrium (LD) decay is of great interest in population genetic studies. However, no tool is available now to do LD decay analysis from variant call format (VCF) ...files directly. In addition, generation of pair-wise LD measurements for whole genome SNPs usually resulting in large storage wasting files.
Results
We developed PopLDdecay, an open source software, for LD decay analysis from VCF files. It is fast and is able to handle large number of variants from sequencing data. It is also storage saving by avoiding exporting pair-wise results of LD measurements. Subgroup analyses are also supported.
Availability and implementation
PopLDdecay is freely available at https://github.com/BGI-shenzhen/PopLDdecay.
The efficiency of drug biosynthesis depends on different transcriptional regulatory pathways in Streptomyces, and the protein degradation system adds another layer of complexity to the regulatory ...processes. AtrA, a transcriptional regulator in the A‐factor regulatory cascade, stimulates the production of daptomycin by binding to the dptE promoter in Streptomyces roseosporus. Using pull‐down assays, bacterial two‐hybrid system and knockout verification, we demonstrated that AtrA is a substrate for ClpP protease. Furthermore, we showed that ClpX is necessary for AtrA recognition and subsequent degradation. Bioinformatics analysis, truncating mutation, and overexpression proved that the AAA motifs of AtrA were essential for initial recognition in the degradation process. Finally, overexpression of mutated atrA (AAA‐QQQ) in S. roseosporus increased the yield of daptomycin by 225% in shake flask and by 164% in the 15 L bioreactor. Thus, improving the stability of key regulators is an effective method to promote the ability of antibiotic synthesis.
Atomically ordered intermetallic nanoparticles are promising for catalytic applications but are difficult to produce because the high-temperature annealing required for atom ordering inevitably ...accelerates metal sintering that leads to larger crystallites. We prepared platinum intermetallics with an average particle size of <5 nanometers on porous sulfur-doped carbon supports, on which the strong interaction between platinum and sulfur suppresses metal sintering up to 1000°C. We synthesized intermetallic libraries of small nanoparticles consisting of 46 combinations of platinum with 16 other metal elements and used them to study the dependence of electrocatalytic oxygen-reduction reaction activity on alloy composition and platinum skin strain. The intermetallic libraries are highly mass efficient in proton-exchange-membrane fuel cells and could achieve high activities of 1.3 to 1.8 amperes per milligram of platinum at 0.9 volts.
The flexural cracking resistance of an asphalt concrete mixture used in a steel bridge deck pavement needs to be higher than that of one used in ordinary pavement. In this study, mechanical ...experimental tests were used to evaluate the influence of the aggregate strength on the flexural cracking behavior of epoxy asphalt concrete (EAC). The aggregate fracture area of beam cross sections was quantitatively analyzed by digital image processing, and crack propagation in the mixture was analyzed using fracture mechanics theory. The bending test results showed that the EAC containing high-strength aggregates exhibited the highest flexural cracking resistance among all of the aggregate mixtures under the same conditions. The use of high-strength aggregates led to a reduction in the aggregate fracture area, thereby improving the flexural cracking resistance of the mixture. The aggregate strength had a significant influence on the flexural cracking propagation behavior of the mixture. Fatigue test results at strain-controlled levels of 600-1200 με and 15 °C showed that the aggregate strength had no evident influence on the fatigue properties of the EAC. It is recommended that high-strength aggregates are used to increase the fracture resistance of aggregates and the flexural crack resistance of EACs.
AbstractObjectiveTo study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for ...coronavirus disease 2019 (covid-2019).DesignRetrospective case series.SettingSeven hospitals in Zhejiang province, China.Participants62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020.Main outcome measuresClinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification.ResultsOf the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days.ConclusionAs of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.
This paper establishes the global existence of classical solutions to systems of nonlinear wave equations with multiple speeds outside star-shaped regions satisfying time-independent inhomogeneous ...boundary conditions, provided that nonlinear terms obey the null condition. We first prove the existence and uniqueness of stationary solutions. Then we use the space-time estimates for perturbed wave equations in Metcalfe and Sogge (2007) to show that solutions of systems converge to stationary solutions as time goes to infinity.
Cholesteric liquid crystal (CLC) chiral superstructures exhibit unique features; that is, polychromatic and spin‐determined phase modulation. Here, a concept for digitalized chiral superstructures is ...proposed, which further enables the arbitrary manipulation of reflective geometric phase and may significantly upgrade existing optical apparatus. By encoding a specifically designed binary pattern, an innovative CLC optical vortex (OV) processor is demonstrated. Up to 25 different OVs are extracted with equal efficiency over a wavelength range of 116 nm. The multiplexed OVs can be detected simultaneously without mode crosstalk or distortion, permitting a polychromatic, large‐capacity, and in situ method for parallel OV processing. Such complex but easily fabricated self‐assembled chiral superstructures exhibit versatile functionalities, and provide a satisfactory platform for OV manipulation and other cutting‐edge territories. This work is a vital step towards extending the fundamental understanding and fantastic applications of ordered soft matter.
Digitalized chiral superstructures enable the generation, detection, and demultiplexing of optical vortices in a polychromatic, large‐capacity, and in situ way. Such complex but easily fabricated self‐assembled cholesteric liquid‐crystal superstructures provide a versatile platform for various cutting‐edge territories. This work brings new insights to both fundamental understanding and innovative applications of ordered soft matter.
Raw Pu-erh tea (RPT) needs ageing before drinking. However, the influence from environment and time of storage on chemical profile and flavor of RPT is unclear. In this study, the RPTs stored in ...wet-hot or dry-cold environment for 1–9 years were assessed using metabolomics based on UHPLC-Orbitrap-MS and global natural product social (GNPS) feature-based molecular networking as well as electronic tongue measurement. The results exhibited that the chemical profiles of RPTs were similar at an early stage but started to differentiate from each other at the 5th and the 7th year in wet-hot and dry-cold environments. The discriminating features including N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (flavoalkaloids), unsaturated fatty acids, lysophosphatidylcholines, flavan-3-ols, amino acids, and flavonol-O-glycosides among the three chemical profiles were discovered and analyzed by means of multivariate statistics, GNPS multilibraries matching, and SIRIUS calculation. The metabolomic data were consistent with the results obtained through electronic tongue measurement.
Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment ...outcome of GBM. In this study, we aimed to explore the function of verbascoside (VB) in GBM and its effects on GBM cell biological processes via let‐7g‐5p and HMGA2. Differentially expressed GBM‐related microRNAs (miRNAs) were initially screened. Different concentrations of VB were applied to U87 and U251 GBM cells, and 50 µmol/L of VB was selected for subsequent experiments. Cells were transfected with let‐7g‐5p inhibitor or mimic, and overexpression of HMGA2 or siRNA against HMGA2 was induced, followed by treatment with VB. The regulatory relationships between VB, let‐7g‐5p, HMGA2 and Wnt/β‐catenin signalling pathway were determined. The results showed that HMGA2 was a direct target gene of let‐7g‐5p. VB treatment or let‐7g‐5p overexpression inhibited HMGA2 expression and the activation of Wnt/β‐catenin signalling pathway, which further inhibited cell viability, invasion, migration, tumour growth and promoted GBM cell apoptosis and autophagy. On the contrary, HMGA2 overexpression promoted cell viability, invasion, migration, tumour growth while inhibiting GBM cell apoptosis and autophagy. We demonstrated that VB inhibits cell viability and promotes cell autophagy in GBM cells by up‐regulating let‐7g‐5p and down‐regulating HMGA2 via Wnt/β‐catenin signalling blockade.
Low‐dimensional lead halide perovskite materials recently have drawn much attention owing to the intriguing broadband emissions; however, the toxicity of lead will hinder their future development. ...Now, a lead‐free (C4H14N2)2In2Br10 single crystal with a unique zero‐dimensional (0D) structure constituted by InBr63− octahedral and InBr4− tetrahedral units is described. The single crystal exhibits broadband photoluminescence (PL) that spans almost the whole visible spectrum with a lifetime of 3.2 μs. Computational and experimental studies unveil that an excited‐state structural distortion in InBr63− octahedral units enables the formation of intrinsic self‐trapped excitons (STEs) and thus contributing the broad emission. Furthermore, femtosecond transient absorption (fs‐TA) measurement reveals that the ultrafast STEs formation together with an efficient intersystem crossing has made a significant contribution to the long‐lived and broad STE‐based emission behavior.
A lead‐free indium‐based (C4H14N2)2In2Br10 single crystal was synthesized and characterized; it has a unique 0D crystal structure. An intrinsic self‐trapped exciton‐based ultra‐broad photoluminescence has been observed as a result of an excited‐state structural distortion in InBr63− octahedrons.
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