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BackgroundSchizophrenia and white blood cell count (WBC) are both complex and polygenic disease/traits. Previous evidence suggested WBC can lead to higher all-cause mortality, and some other evidence found elevated WBC in first-episode psychosis and chronic schizophrenia patients. However, prior observational findings may be confounded by antipsychotic exposures and their effects on WBC. Mendelian randomization (MR) is a useful method to examine the directional causal relationship between schizophrenia and WBC.MethodsWe performed a two-sample MR using summary statistics of the Psychiatric Genomics Consortium Schizophrenia Workgroup (N=130,644) and the Blood Cell Consortium (N=563,085). The MR methods included inverse variance weighted, ME Egger, weighted median, and MR-PRESSO, contamination mixture, and a novel approach called mixture model reciprocal causal inference (MRCI). False discovery rate was employed to correct for multiple testing.ResultsAfter correcting for horizontal pleiotropy, the MRCI method demonstrated that schizophrenia can cause by elevated lymphocyte count (OR=1.080; FDR adjusted p-value=0.026) and eosinophil count (OR=1.050; FDR adjusted p-value=0.026). The contamination mixture method showed that schizophrenia may cause elevated neutrophil counts (Beta=0.011 in unit of standard deviation of mean absolute neutrophil count; FDR adjusted p-value=0.045) and reduction of eosinophil count (Beta=-0.013 in unit of standard deviation of mean absolute eosinophil count; FDR adjusted p-value=0.045). Some further significant findings had been identified by conventional MR approaches and MR-PRESSO, but we interpreted those with cautious due to substantial heterogeneity and plausible pleiotropic effects identified.ConclusionThis MR study provided evidence that schizophrenia has causal relationships with altered differential WBC. Our findings support the role of WBC in influencing schizophrenia risk, and may concur with the hypothesis of neuroinflammation in schizophrenia.

The present study performed a continuous mode of bioleaching to investigate the leaching efficiency of Titanium (Ti) from bauxite residue using Penicillium Tricolor at between 4% and 12% pulp densities during a 120-day running. Obtained results of the current study showed that increased pulp density led to a decrease in biomass, dissolved oxygen, and amount of leaching Ti as well as an increase in pH value. Further, it was found that efficiency of bioleaching can be enhanced by increasing the rate of aeration, retention time, and concentration of carbon source. However, it was also evident that, at high pulp density, excessive agitation did not give an expected leaching efficiency but a collapse of biomass. In addition, results of the present study showed that the maximum leaching amount of Ti was 3202 mg/L with a corresponding leaching ratio of 50.35% during the whole bioleaching process. Moreover, it was noted that the biomass showed a significant negative correlation with the pH value and dissolved oxygen. However, the biomass showed a significant positive correlation with leaching amount of Ti and thus indicate that microbial metabolic activities are the uppermost factor affecting the continuous leaching performance.

Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 inChromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might controlThese results suggested that rs169884 might play a regulatory role for

The hydrolysis of Mg-based alloys and their hydrides with high abundance on the earth and low cost could produce hydrogen with high theoretical capacity and the formation of by-products that have no pollution to the environment. Hence, it has been regarded as one of the most promising way for hydrogen generation. Particularly, a gravimetric capacity of 6.4 wt% and 3.4 wt% H2 could be produced from the hydrolysis of pure Mg and MgH2, respectively, even when stoichiometric water is included for calculation. The formation of passive magnesium hydroxides with dense structure, however, could immediately interrupt the hydrolysis reaction of Mg/MgH2, which leads to ultralow yield and sluggish hydrogen generation rate. Recent studies have demonstrated that the hydrolysis reaction of Mg/MgH2 could be effectively enhanced in terms of both yield and kinetics by the formation of Mg-based alloys and their hydrides. This review aims to summarize the recent progress in the hydrolysis of Mg-based alloys and their hydrides and the involved hydrolysis mechanisms.

Due to their high theoretical specific capacity, metal hydrides are considered to be one of the most promising anode material for all-solid-state Li-ion batteries. Their practical application suffers, however, from the poor cycling stability and sluggish kinetics. Herein, we report the in situ fabrication of MgH

Grid impedance information occupies a fundamental and crucial position for the operation of grid-tied converters. Consequently, accurate and fast extraction of grid impedance is vital. The impulse injection method applied under the control loop of a grid-tied converter, which is commonly used to extract linear grid impedance online, is relatively reasonable in terms of device cost, measurement speed, simplicity, and design flexibility. However, the selection of impulse and design of impulse parameters mostly depend on rules of thumb, without theoretical guidance, leading to insufficient measurement accuracy in target frequency section and greatly burdening the system. To address these issues, a systematic guidance is proposed for analysis, design, and implementation of impulse-injection-based grid impedance identification. By comparing the spectra of several basic impulses with unipolar and bipolar forms and analyzing the impact when impulse parameters are altered, a guidance for impulse selection for different measurement scenarios is presented. Based on this guidance, an asymmetric bipolar sawtooth wave with a defined asymmetry ratio of $\boldsymbol{\rho } = 0.5$ is chosen in this article for broadband measurement of grid impedance. Furthermore, a related parameter design procedure with optimal injection position and instant is also proposed to reduce system burden and eliminate overmodulation when injecting the impulse. Finally, theoretical results are validated by experiments.

We address the visual comparison of multiple phylogenetic trees that arises in evolutionary biology, specifically between one reference tree and a collection of dozens to hundreds of other trees. We abstract the domain questions of phylogenetic tree comparison as tasks to look for supporting or conflicting evidence for hypotheses that requires inspection of both topological structure and attribute values at different levels of detail in the tree collection. We introduce the new visual encoding idiom of aggregated dendrograms to concisely summarize the topological relationships between interactively chosen focal subtrees according to biologically meaningful criteria, and provide a layout algorithm that automatically adapts to the available screen space. We design and implement the ADView system, which represents trees at multiple levels of detail across multiple views: the entire collection, a subset of trees, an individual tree, specific subtrees of interest, and the individual branch level. We benchmark the algorithms developed for ADView, compare its information density to previous work, and demonstrate its utility for quickly gathering evidence about biological hypotheses through usage scenarios with data from recently published phylogenetic analysis and case studies of expert use with real-world data, drawn from a summative interview study.

The nutritional design of personalized starchy foods has become a research hotspot in the field of food science. Driven by the immense functional and nutritional implications of starch-lipid binary interactions, this study is aimed at designing starch digestibility by controlling the interaction between starch and glycerol monostearate (GMS)/stearic acid (SA) using a hot-extrusion 3D printing (HE-3DP) environment. The results indicated that the thermal shear force in the HE-3DP environment promoted hydrophobic interactions between starch and lipids, forming a V-type starch-lipid complex with a compact and ordered structure, thus enhancing enzymatic resistance. Compared with GMS, SA with linear hydrophobic chains was inclined to compound with starch to form a more ordered structure. Interestingly, the slowly digestible starch (SDS) and resistant starch (RS) content reached 25.06% when the added SA content was 10%. Besides, correlations between the structural parameters and digestibility were established, which provided crucial information for designing nutritional starchy food systems using HE-3DP.

Recent developments of hot-extrusion 3D printing (HE-3DP) have made it possible to manipulate starch digestibility. This work investigated the regulating mechanism of starch-catechin (EC) interactions on rice starch digestibility during HE-3DP by using modern analytical techniques and computational models. The results showed that the HE-3DP processing with starch-EC interactions could significantly decrease the starch digestibility (p 0.05) due to the formation of ordered structures including short-range ordered structure, nano-aggregates and V-type crystalline structure. Meanwhile, molecular dynamics simulations were performed to reveal the mechanism of EC as an enzyme inhibitor to enhance the resistant starch contents of rice starch to 46.1%. Results showed that EC could loosely attach to starch chains, thereby facilitating binding to Trp59 of pancreatic α-amylase and preventing starch from binding to its active pocket. These findings provide useful structural information for EC to reduce starch digestibility in the HE-3DP environment.

Mendelian randomization using GWAS summary statistics has become a popular method to infer causal relationships across complex diseases. However, the widespread pleiotropy observed in GWAS has made the selection of valid instrumental variables problematic, leading to possible violations of Mendelian randomization assumptions and thus potentially invalid inferences concerning causation. Furthermore, current MR methods can examine causation in only one direction, so that two separate analyses are required for bi-directional analysis. In this study, we propose a ststistical framework, MRCI (Mixture model Reciprocal Causation Inference), to estimate reciprocal causation between two phenotypes simultaneously using the genome-scale summary statistics of the two phenotypes and reference linkage disequilibrium information. Simulation studies, including strong correlated pleiotropy, showed that MRCI obtained nearly unbiased estimates of causation in both directions, and correct Type I error rates under the null hypothesis. In applications to real GWAS data, MRCI detected significant bi-directional and uni-directional causal influences between common diseases and putative risk factors.

LCL resonance complicates the design of a current control loop and can even threaten its stability. Extensive approaches have been proposed to deal with this resonance, among which active damping (AD) schemes based on the feedback of a single filter variable have been shown to be effective and cost-efficient. This paper presents a study of such AD techniques, where a generalized approach to developing an AD controller by relating a control diagram to an equivalent circuit is proposed. Based on this approach, AD controller forms with any one of four commonly used filter variables to realize virtual resistors (VRs) in six different connections to the LCL filter are derived. Comparisons are then made between these 24 AD controller alternatives by considering the implementation complexity of the AD controller, the number of measuring sensors, and the effect of the AD controller on the power stage. Consequently, grid-side current feedback AD to realize a VR in parallel with the filter capacitor is selected as a considered alternative. Next, two issues associated with the practical implementation of the selected grid-side current feedback AD, caused by the second-order differential expression and the digital time delay, are discussed and solved. Finally, the selected AD method is analyzed in the discrete z -domain, and its effectiveness is experimentally verified.

The aim of this study was to investigate the changes of the microstructural, rheological and printing properties of rice starch-stearic acid (SA) paste during the hot-extrusion 3D printing (HE-3DP). The results showed that starch chains could complex with SA to form V-type crystalline structure and its molecular kinematic behaviors were changed under shear force, and crystalline structure were then embedded and rearranged to constitute an ordered sea-island structure, thus improving the rigidity and dynamic storage modulus of network structure, leading to the increased layer number. Interestingly, with the increase of SA addition, the network structure became weakened and the viscosity decreased which might due to the destroyed continuity and the breaking of entanglement and hydrogen bonding between starch chains, and finally impairing the printing accuracy of objects. Overall, this study provided important information for the application of lipid in the preparation of starch-based food by HE-3DP.

Diagnosing free electron laser (FEL) polarization is critical for polarization-modulated research such as x-ray free electron laser (XFEL) diffraction imaging and probing material magnetism. In an electron time-of-flight (eTOF)\ polarimeter, the flight time and angular distribution of photoelectrons were designed based on x-ray polarimetry for on-site diagnosis. However, the transverse position of x-ray FEL pulses introduces error into the measured photoelectron angular distribution. This work thus proposes a method to monitor the transverse position using an eTOF polarimeter and explains how to compensate for the error due to transverse position. A comprehensive numerical model is developed to demonstrate the feasibility of the compensation method, and the results reveal that a spatial resolution of 20 \(\mu\)m and a polarity improved by 0.5\% is possible with fully polarized FEL pulses. The impact of FEL\ pulses and a method to calibrate their linearity is also discussed., Comment: x-ray fel, e-TOF, position monitor, polarization

BackgroundThe evolving pandemic of COVID-19 is arousing alarm to public health. According to epidemiological and observational studies, coagulopathy was frequently seen in severe COVID-19 patients, yet the causality from specific coagulation factors to COVID-19 severity and the underlying mechanism remain elusive.MethodsFirst, we leveraged Mendelian randomization (MR) analyses to assess causal relationship between 12 coagulation factors and severe COVID-19 illness based on two genome-wide association study (GWAS) results of COVID-19 severity. Second, we curated clinical evidence supporting causal associations between COVID-19 severity and particular coagulation factors which showed significant results in MR analyses. Third, we validated our results in an independent cohort from UK Biobank (UKBB) using polygenic risk score (PRS) analysis and logistic regression model. For all MR analyses, GWAS summary-level data were used to ascertain genetic effects on exposures against disease risk.ResultsWe revealed that genetic predisposition to the antigen levels of von Willebrand factor (VWF) and the activity levels of its cleaving protease ADAMTS13 were causally associated with COVID-19 severity, wherein elevated VWF antigen level (P = 0.005, odds ratio (OR) = 1.35, 95% confidence interval (CI): 1.09-1.68 in the Severe COVID-19 GWAS Group cohort; P = 0.039, OR = 1.21, 95% CI: 1.01-1.46 in the COVID-19 Host Genetics Initiative cohort) and lowered ADAMTS13 activity (P = 0.025, OR = 0.69, 95% CI: 0.50-0.96 in the Severe COVID-19 GWAS Group cohort) lead to increased risk of severe COVID-19 illness. No significant causal association of tPA, PAI-1, D-dimer, FVII, PT, FVIII, FXI, aPTT, FX or ETP with COVID-19 severity was observed. In addition, as an independent factor, VWF PRS explains a 31% higher risk of severe COVID-19 illness in the UKBB cohort (P = 0.047, OR per SD increase = 1.31, 95% CI: 1.00-1.71). In combination with age, sex, BMI and several pre-existing disease statues, our model can predict severity risks with an AUC of 0.70.ConclusionTogether with the supporting evidence of recent retrospective cohort studies and independent validation based on UKBB data, our results suggest that the associations between coagulation factors VWF/ADAMTS13 and COVID-19 severity are essentially causal, which illuminates one of possible mechanisms underlying COVID-19 severity. This study also highlights the importance of dynamically monitoring the plasma levels of VWF/ADAMTS13 after SARS-CoV-2 infection, and facilitates the development of treatment strategy for controlling COVID-19 severity and associated thrombotic complication.