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Background/aim: Heavy-ion irradiation seriously perturbs cellular homeostasis and thus damages cells. Vascular endothelial cells (ECs) play an important role in the pathological process of radiation damage. Protecting ECs from heavy-ion radiation is of great significance in the radioprotection of normal tissues. In this study, the radioprotective effect of ß-D-glucan (BG) derived from Saccharomyces cerevisiae on human umbilical vein endothelial cell (EA.hy926) cytotoxicity produced by carbon-ion irradiation was examined and the probable mechanism was established. Materials and methods: EA.hy926 cells were divided into seven groups: a control group; 1, 2, or 4 Gy radiation; and 10 µg/mL BG pretreatment for 24 h before 1, 2, or 4 Gy irradiation. Cell survival was assessed by colony formation assay. Cell cycles, apoptosis, DNA damage, and reactive oxygen species (ROS) levels were measured through flow cytometry. The level of malondialdehyde and antioxidant enzyme activities were analyzed using assay kits. The activation of NF-κB was analyzed using western blotting and a transcription factor assay kit. The expression of downstream target genes was detected by western blotting. Results: BG pretreatment significantly increased the survival of irradiated cells, improved cell cycle progression, and decreased DNA damage and apoptosis. The levels of ROS and malondialdehyde were also decreased by BG. Further study indicated that BG increased the antioxidant enzyme activities, activated Src, and promoted NF-κB activation, especially for the p65, p50, and RelB subunits. The activated NF-κB upregulated the expression of antioxidant protein MnSOD, DNA damage-response and repair-related proteins BRCA2 and Hsp90a, and antiapoptotic protein Bcl-2. Conclusion: Our results demonstrated that BG protects EA.hy926 cells from high linear-energy-transfer carbon-ion irradiation damage through the upregulation of prosurvival signaling triggered by the interaction of BG with its receptor. This confirms that BG is a promising radioprotective agent for heavy-ion exposure. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the bidirectional causal relationship between frailty and depression using Mendelian randomization (MR). Topics include the use of genetic data from Great Britain Biobank and TwinGen for frailty, the frailty, causally associated with an increased risk of depression, and emphasize the importance of early interventions and management for individuals affected by frailty and depression.

The article focuses on determining the preferred epitaxy for III-nitride semiconductors on wet-transferred graphene, showing that the favored approach is quasi-van der Waals epitaxy (quasi-vdWe). Topics include the choice between remote epitaxy, where nonchemical bonds couple the III-nitride/graphene interface, and quasi-van der Waals epitaxy (quasi-vdWe), where covalent bonds are dominant.

The functional maturation of neurons is a prolonged process that extends past the mitotic exit and is mediated by the chromatin-dependent orchestration of gene transcription programs. We find that expression of this maturation gene program in mouse cerebellar granule neurons (CGNs) requires dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), demonstrating a function for this chromatin modification beyond its role in cell fate specification. The developmental loss of H3K27me3 at promoters of genes activated as CGNs mature is facilitated by the lysine demethylase and ASD-risk gene, Kdm6b. Interestingly, inhibition of the H3K27 methyltransferase EZH2 in newborn CGNs not only blocks the repression of progenitor genes but also impairs the induction of mature CGN genes, showing the importance of bidirectional H3K27me3 regulation across the genome. These data demonstrate that H3K27me3 turnover in developing postmitotic neurons regulates the temporal coordination of gene expression programs that underlie functional neuronal maturation. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the activity of metformin in endometriosis, with a view to alleviating disease progression. Methods: A search was conducted using electronic databases such as CNKI, VIP, CBM, WANFANG, Embase, PubMed, Cochrane, and Web of Science from January 1980 to January 2022 for randomized trials involving any intrapartum fetal surveillance method. A network meta-analysis was performed within a frequentist framework, and it was assessed for quality and network inconsistency of the trials. A ninety-five percent confidence interval (CI) was used to report the relationship between metformin levels and patients with endometriosis. Results: Eight eligible studies which included 688 patients were evaluated in this meta-analysis. The primary indicators were treatment efficiency and CA-125 level. Metformin significantly increased treatment efficiency (SMD = 3.29, 95 % CI 2.01, 5.40, p < 0.00001). As expected, metformin also reduced the CA-125 level in endometriosis patients as a result (Odds Ratio, OR = -1.20, 95 % CI: -1.40 - 1.00, p < 0.00001). Conclusion: Metformin alleviates pains caused by endometriosis. However, some studies had scanty information about alleviating clinical symptoms other than basic medical research. More randomized controlled trials are needed to confirm treatment efficacy. [ABSTRACT FROM AUTHOR]

Objective: The aim was to evaluate the effectiveness and safety of the vapocoolants for vascular puncture in children and adults. Method: The search was carried out in PubMed, Web of Science, Embase and The Cochrane Library, from inception to March 2022. Randomized controlled trials comparing vapocoolants to control conditions for participants received intravenous cannulation or arterial puncture were included. Two reviewers independently performed selection of studies, data extraction, and assessment of risk of bias. The analysis was performed using fixed or random-effects model with mean differences or standardized mean difference and risk ratios. Results: A total of 25 studies involving 3143 participants were included. Compared with control conditions, vapocoolants may not decrease the pain of patients with arterial puncture (SMD = -0.36, 95% CI = -0.92 to -0.19, P = 0.20), but may more effectively relieve pain for adults received vein puncture (SMD = -0.65, 95% CI = -0.85 to -0.45, P < 0.00001). The application of vapocoolant increased the procedural difficulty of medical personnel (RR = 2.49, 95% CI = 1.62 to 3.84, P<0.000 1) and participants were more willing to use the spray in the future (RR = 1.88, 95% CI = 1.34 to 2.64, P = 0.0002). There was no significant difference for the first attempt success rate of the procedure and the occurrence of adverse events. Conclusions: Vapocoolant spray may relieve pain in adults received vein puncture and cannot cause severe side effects, but is ineffective in children. It also had no effect on patients with arterial puncture. In addition, the application of spray increases procedural difficulties for medical professionals, but does not decrease first attempt success rate, and many patients would like to use the spray again for pain relief in the future. Thus, more rigorous and large-scale studies are needed to determine its effectiveness in vascular access. [ABSTRACT FROM AUTHOR]

Proper regulation of the earth pressure on the bulkhead of earth-pressure balanced (EPB) shield tunneling machines is significant to ensure safe construction. This study proposes a procedure for regulating the bulkhead pressure by combining numerical simulations and data mining, and applies the procedure to a metro line constructed in sandy pebble stratum using EPB shield. Firstly, the relationship between the bulkhead pressure and the pressure on the tunnel face is carefully obtained from discrete element modeling, and the required supporting earth pressure is derived by considering the arching effect. Secondly, aided with the machine learning method, a model is constructed for predicting the average bulkhead pressure per ring according to the operational parameters (i.e., the average driving speed and the rotation speed of the screw conveyor). Given the target value of the bulkhead pressure, the optimal values of the operational parameters are obtained from the model. In addition, an autoregressive moving average stochastic process model is developed to monitor the real-time fluctuation of the bulkhead pressure and guide the actions taken in time to avoid dramatic fluctuations. The results indicate that the pressure difference between the tunnel face and the bulkhead is considerable, and the consideration of the arching effect can avoid overestimating the bulkhead pressure. A combination of the machine learning model and the stochastic process model provides a plausible performance in regulating the bulkhead pressure around the target value without dramatic fluctuation. [ABSTRACT FROM AUTHOR]

We establish the existence and uniqueness of viscosity solutions to the Dirichlet problem ∆∞hu = f(x, u), in Ω, u = q, on ∂Ω, where q ∈ C(∂Ω), h > 1, ∆ ∞hu = |Du| h−3 ∆∞u. The operator ∆∞u = ⟨D²uDu, Du⟩ is the infinity Laplacian which is strongly degenerate, quasilinear and it is associated with the absolutely minimizing Lipschitz extension. When the nonhomogeneous term f(x, t) is non-decreasing in t, we prove the existence of the viscosity solution via Perron’s method. We also establish a uniqueness result based on the perturbation analysis of the viscosity solutions. If the function f(x, t) is nonpositive (nonnegative) and non-increasing in t, we also give the existence of viscosity solutions by an iteration technique under the condition that the domain has small diameter. Furthermore, we investigate the existence and uniqueness of viscosity solutions to the boundary-value problem with singularity ∆∞hu = −b(x)g(u), in Ω, u > 0, in Ω, u = 0, on ∂Ω, when the domain satisfies some regular condition. We analyze asymptotic estimates for the viscosity solution near the boundary. [ABSTRACT FROM AUTHOR]

The ability to regulate gene activity spatially and temporally is essential to investigate cell-type- specific gene function during development and in postembryonic processes and disease models. The Cre/lox system has been widely used for performing cell and tissue-specific conditional analysis of gene function in zebrafish. However, simple and efficient methods for isolation of stable, Cre/lox regulated zebrafish alleles are lacking. Here, we applied our GeneWeld CRISPR-Cas9 targeted integration strategy to generate floxed alleles that provide robust conditional inactivation and rescue. A universal targeting vector, UFlip, with sites for cloning short homology arms flanking a floxed 2A-mRFP gene trap, was integrated into an intron in rbbp4 and rb1. rbbp4off and rb1off integration alleles resulted in strong mRFP expression,>99% reduction of endogenous gene expression, and recapitulated known indel loss-of- function phenotypes. Introduction of Cre led to stable inversion of the floxed cassette, loss of mRFP expression, and phenotypic rescue. rbbp4on and rb1on integration alleles did not cause phenotypes in combination with a loss-of- function mutation. Addition of Cre led to conditional inactivation by stable inversion of the cassette, gene trapping and mRFP expression, and the expected mutant phenotype. Neural progenitor Cre drivers were used for conditional inactivation and phenotypic rescue to showcase how this approach can be used in specific cell populations. Together these results validate a simplified approach for efficient isolation of Cre/lox-responsive conditional alleles in zebrafish. Our strategy provides a new toolkit for generating genetic mosaics and represents a significant advance in zebrafish genetics. [ABSTRACT FROM AUTHOR]

KDM6B-mediated epigenetic modification of the testicular regulator Dmrt1 has previously been identified as the primary switch of the male pathway in a temperature-dependent sex-determination (TSD) system; however, the molecular network of the female pathway has not yet been established. Here, we have functionally characterized for the first time an upstream regulator of the female pathway, the forkhead transcription factor FOXL2, in Trachemys scripta, a turtle species with a TSD system. FOXL2 exhibited temperature-dependent female-specific expression patterns before the onset of gonadal differentiation and was preferentially localized in ovarian somatic cells. Foxl2 responded rapidly to temperature shifts and estrogen. Importantly, forced expression of Foxl2 at the male-producing temperature led to male-to-female sex reversal, as evidenced by the formation of an ovary-like structure, and upregulation of the ovarian regulators Cyp19a1 and R-spondin1. Additionally, knockdown of Foxl2 caused masculinization at the femaleproducing temperature, which was confirmed by loss of the female phenotype, development of seminiferous tubules, and elevated expression of Dmrt1 and Sox9. Collectively, we demonstrate that Foxl2 expression is necessary and sufficient to drive ovarian determination in T. scripta, suggesting a crucial role of Foxl2 in female sex determination in the TSD system. [ABSTRACT FROM AUTHOR]

Background: In previous studies, a new Trichinella spiralis serine protease 1.1 (TsSP1.1) was identified in surface proteins of T. spiralis muscle larvae (ML) by proteomics analysis, but its functions in T. spiralis infection are unknown. The aim of this study was to investigate the roles of TsSP1.1 during larval intrusion of gut epithelium. Methods: From January 2019 to March 2021, complete TsSP1.1 cDNA sequence was cloned and expressed in Escherichia coli BL21 at the Department of Parasitology, Medical College of Zhengzhou University, Zhengzhou, China. Expression and location of TsSP1.1 in the parasite were investigated using indirect immunofluorescence assay (IIFA) and Western blotting. The in vitro intestinal epithelium cells (IECs) intrusion assay was used to ascertain the roles of TsSP1.1 during larval intrusion of IECs and gut epithelium. Results: TsSP1.1 was a surface and secretory protein, which was expressed at various T. spiralis stages, and principally localized at cuticle, stichosome and embryos of the nematode. rTsSP1.1 accelerated larval intrusion of IECs, whereas anti-rTsSP1.1 antibodies impeded larval intrusion. The acceleration and inhibtion was dose-dependently related to rTsSP1.1 and anti-TsSP1.1 antibodies. Block of the IIL with anti-rTsSP1.1 serum also impeded larval intrusion of gut mucosa. Conclusion: TsSP1.1 participates in T. spiralis intrusion of gut epithelium. [ABSTRACT FROM AUTHOR]

Porcine respiratory and reproductive syndrome (PRRS) is one of the most devastating infectious diseases of pigs, causing reproductive failures in sows and severe respiratory symptoms in piglets and growing pigs. MicroRNAs (miRNAs) are reported to play an essential role in virus–host interactions. In this study, we demonstrated that miR-451 enhanced type I interferon (IFN-I) production through targeting proteasome subunit β8 (PSMB8), therefore restricting PRRS virus (PRRSV) replication. We showed that the expression of PSMB8 was upregulated by PRRSV infection, and knockdown of PSMB8 inhibited PRRSV replication by promoting IFN-I production. Moreover, we demonstrated that PSMB8 interacted with the regulatory domain of IRF3 to mediate K48-linked polyubiquitination and degradation of IRF3. Also, importantly, we showed that PSMB8, as a target gene of miR-451, negatively regulated IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to modulate innate immune responses. IMPORTANCE Porcine respiratory and reproductive syndrome virus (PRRSV), as a huge threat to the swine industry, is a causative agent that urgently needs to be solved. The dissecting of PRRSV pathogenesis and understanding of the host–pathogen interaction will provide insights into developing effective anti-PRRSV strategies. In this study, we showed that miR-451 dramatically inhibited PRRSV replication by targeting proteasome subunit β8 (PSMB8), a subunit of the immunoproteasome. Mutation of PSMB8 is often related to autoinflammatory diseases due to the elevated IFN production. We revealed that PSMB8 downregulated IFN production by promoting IRF3 degradation. In addition, we showed that PRRSV infection upregulated PSMB8 expression. Taken together, our findings reveal that miR-451 is a negative regulator of PRRSV replication, and PSMB8, a target gene of miR-451, negatively regulates IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to regulate innate immune responses. [ABSTRACT FROM AUTHOR]

Traditional data centres often require additional energy to drive air conditioning fans etc. to dissipate heat due to the serious power generation problems of servers, which in effect raises the economic costs. Seawater, with its high specific heat capacity and fluidity, offers a viable research direction for reducing economic costs, and this paper is based on this problem. The study shows that it is feasible to use containers as the main structure of the data centre. The number of servers n 860 that can be tolerated by the cooling capacity of the container without considering the limit of geometrical constraints is obtained by calculation. Secondly, in order to enhance the heat dissipation capacity of the data centre, the 6 cm straight ribbed crown fin heat dissipation enclosure is proposed to have the best heat dissipation capacity when comparing various heat dissipation enclosure configurations. A comprehensive assessment model of material properties was established, and the weights of each straight index were determined by analytic hierarchy process, and then the metals were ranked according to the specific scores of each index. The results show that nickel alloys and aluminium alloys are the most suitable. [ABSTRACT FROM AUTHOR]

Genomic best linear unbiased prediction (GBLUP) is the most widely used model for genome-wide predictions. Interestingly, it is also possible to perform genome-wide association studies (GWAS) based on GBLUP. Although the estimated marker effects in GBLUP are shrunken and the conventional test based on such effects has low power, it was observed that a modified test statistic can be produced and the result of test was identical to a standard GWAS model. Later, a mathematical proof was given for the special case that there is no fixed covariate in GBLUP. Since then, the new approach has been called "GWAS by GBLUP". Nevertheless, covariates such as environmental and subpopulation effects are very common in GBLUP. Thus, it is necessary to confirm the equivalence in the general case. Recently, the concept was generalized to GWAS for epistatic effects and the new approach was termed rapid epistatic mixed-model association analysis (REMMA) because it greatly improved the computational efficiency. However, the relationship between REMMA and the standard GWAS model has not been investigated. In this study, we first provided a general mathematical proof of the equivalence between "GWAS by GBLUP" and the standard GWAS model for additive effects. Then, we compared REMMA with the standard GWAS model for epistatic effects by a theoretical investigation and by empirical data analyses. We hypothesized that the similarity of the two models is influenced by the relative contribution of additive and epistatic effects to the phenotypic variance, which was verified by empirical and simulation studies. [ABSTRACT FROM AUTHOR]

Half-sibling (HS) kinship testing is more difficult and complicated. This article describes a case where we sought to establish if three children with different mothers (one boy and two girls), shared a common father. The three children and their mother, as well as the suspected father's elder brother took part in the identification. To investigate the application of multiple genetic markers in HS kinship testing, autosomal STR, Y-STR, and X-STR was performed on blood samples from the individuals of interest C1 (female), M1 (mother of C1), C2 (male), M2 (mother of C2), C3 (female), M3 (mother of C3), and UC (elder brother of the suspected biological father). The 24 Y-STR haplotypes of C2 and UC were identical, confirming that they come from the same paternal line. Among the 27 X-STRs tested in C1 and C3, 18 of them had different paternal alleles, so C1 and C3 were excluded as half-sibling kinship.39 autosomal STR were calculated by ITO method, the HSI (or AI) of the pairs C1-C3, C2-C3, and C3-UC are <1, so HS kinship between C1 and C3, and between C2 and C3 can be excluded and avuncular kinship between C3 and UC can be excluded. The HSI (or AI) of the pairs C1-C2, C1-UC, and C2-UC are much >1, which may supports HS kinship between C1 and C2 and avuncular kinship between C1 and UC, and between C2 and UC.15 autosomal STR were calculated by discriminant function, DHS3 > DR3 between C1 and C2, and thus they could be HS. DHS3 < DR3 between C1 and C3, and between C2 and C3, so C1 and C3, and C2 and C3 may be unrelated individuals. Based on the above results, we can conclude that a HS relationship may be existed between C1 and C2. There may be a avuncular relationships between C1 and UC and between C2 and UC. HS relationships between C3 and C1 and between C3 and C2 as well as an avuncular relationship between C3 and UC were not supported by this study. The application of multiple genetic marker testing should be more regularly applied in the evaluation of HS and avuncular relationships. Increasing the number of related individuals tested when evaluating kinship relationships provides more data for better identification. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is one of the most malign brain tumors in adults. Temozolomide (TMZ) is an oral chemotherapy drug constituting the backbone of chemotherapy regimens utilized as first-line treatment of GBM. However, resistance to TMZ often leads to treatment failure. In the present study, we explored the expression and related mechanisms of nuclear enriched abundant transcript 1 (NEAT1) in glioma stem cells (GSCs). Quantitative real-time PCR (qRT-PCR) showed that NEAT1 was up-regulated in serum samples of GBM patients and GSCs isolated from U87, U251 cell lines. Functional experiments showed that NEAT1 knockdown restrained malignant behaviors of GSC, including proliferation, migration and invasion. Dual-luciferase assays identified let-7g-5p was a downstream target and negatively adjusted by NEAT1. Restoration of let-7g-5p impeded tumor progression by inhibiting proliferation, migration and invasion. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as a direct target of let-7g-5p, was positively regulated by NEAT1 and involved to affect the regulation of NEAT1 on GSCs' behaviors. In conclusion, our results suggested that NEAT1 promoted GSCs progression via NEAT1/let-7g-5p/MAP3K1 axis, which provided a depth insight into TMZ resistance mechanism. [ABSTRACT FROM AUTHOR]

The inhibitory and bactericidal activities of thyme oil against the foodborne multiple antibiotics-resistant Enterococcus faecalis biofilm were evaluated in this study. Gas chromatography-mass spectrometry revealed that more than 70% of the composition of thyme oil is thymol. Crystal violet staining assay showed that 128 and 256 mg/mL thyme oil significantly inhibited the biofilm formation of E. faecalis. The cell adherence of E. faecalis, as shown by its swimming and swarming motilities, was reduced by thyme oil. The exopolysaccharide (EPS) quantification assay showed that thyme oil inhibited the EPS synthesis in E. faecalis biofilms. The 3D-view observations through confocal laser scanning and scanning electron microscopy suggested that cell adherence and biofilm thickness were decreased in thyme oil-treated biofilms. Quantitative real-time analyses showed that the transcription of ebp and epa gene clusters, which were related to cell mobility and EPS production, was inhibited by thyme oil. Thus, thyme oil effectively inhibited the biofilm formation of E. faecalis by affecting cell adherence and EPS synthesis. Furthermore, 2,048 and 4,096 mg/mL thyme oil can effectively inactivate E. faecalis population in the mature E. faecalis biofilms by 5.75 and 7.20 log CFU/mL, respectively, after 30 min of treatment. Thus, thyme oil at different concentrations can be used as an effective antibiofilm or germicidal agent to control E. faecalis biofilms. [ABSTRACT FROM AUTHOR]

Motivation: Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bimultivariate genotype–phenotype associations. However, most existing SCCA methods are unsupervised, leading to an inability to identify diagnosis-specific genotype–phenotype associations. Results: In this article, we propose a new joint multitask learning method, named MT–SCCALR, which absorbs the merits of both SCCA and logistic regression. MT–SCCALR learns genotype–phenotype associations of multiple tasks jointly, with each task focusing on identifying one diagnosis-specific genotype–phenotype pattern. Meanwhile, MT– SCCALR cannot only select relevant SNPs and imaging QTs for each diagnostic group alone, but also allows the selection of those shared by multiple diagnostic groups. We derive an efficient optimization algorithm whose convergence to a local optimum is guaranteed. Compared with two state-of-the-art methods, MT–SCCALR yields better or similar canonical correlation coefficients and classification performances. In addition, it owns much better discriminative canonical weight patterns of great interest than competitors. This demonstrates the power and capability of MTSCCAR in identifying diagnostically heterogeneous genotype–phenotype patterns, which would be helpful to understand the pathophysiology of brain disorders. [ABSTRACT FROM AUTHOR]

In this paper, we shall study unilateral global bifurcation phenomenon for the following homogeneous Kirchhoff type problem (− ∫R 1 0∣u'∣2dx)u'' = λu3 + h(x, u, λ) in (0, 1),u(0) = u(1) = 0.As application of bifurcation result, we shall determine the interval of λ in which there exist nodal solutions for the following homogeneous Kirchhoff type problem (−∫R 10∣u'∣2dx)u'' = λ f(x, u) in (0, 1),u(0) = u(1) = 0,where f is asymptotically cubic at zero and infinity. To do this, we also establish a complete characterization of the spectrum of a homogeneous nonlocal eigenvalue problem. [ABSTRACT FROM AUTHOR]

The increase in the density of high-rise buildings is making urban air flow increasingly complex, and the wind environment conditions in urban public spaces are considerably changing. At present, few studies focus on the relationship between wind environment and the master plan of urban public spaces or attempt to improve the wind environment of public spaces from a landscape design perspective. To resolve this gap in information, this study explored the relationship among wind speed, seasonal comfort level in Nanjing, and different types of planting patterns. Computational fluid dynamics (CFD) software was used to quantify the seasonal wind environment of Xuanwumen Square in Nanjing. Three planting designs were created on the basis of the results, and their CFD results were compared among one another. Comparison results show that the second planting design provides the best wind environment, and its comfort levels are 2.26, 1.92, and 2.09 out of 5 in winter, summer, and total. Understanding of the relationship among different landscape designs and their impacts on wind environment supports designers in improving the wind environment of Xuanwumen Square in Nanjing. This study provides new insights into relating urban public space design with the quantitative research of wind environment in the future. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have gained central importance for the identification of candidate loci underlying complex traits. Single nucleotide polymorphism (SNP) markers are mostly used as genetic variants for the analysis of genotype-phenotype associations in populations, but closely linked SNPs that are grouped into haplotypes are also exploited. The benefit of haplotype-based GWAS approaches vs. SNP-based approaches is still under debate because SNPs in high linkage disequilibrium provide redundant information. To overcome some constraints of the commonly-used haplotype-based GWAS in which only consecutive SNPs are considered for haplotype construction, we propose a new method called functional haplotype-based GWAS (FH GWAS). FH GWAS is featured by combining SNPs into haplotypes based on the additive and epistatic effects among SNPs. Such haplotypes were termed functional haplotypes (FH). As shown by simulation studies, the FH GWAS approach clearly outperformed the SNP-based approach unless the minor allele frequency of the SNPs making up the haplotypes is low and the linkage disequilibrium between them is high. Applying FH GWAS for the trait flowering time in a large Arabidopsis thaliana population with whole-genome sequencing data revealed its potential empirically. FH GWAS identified all candidate regions which were detected in SNP-based and two other haplotype-based GWAS approaches. In addition, a novel region on chromosome 4 was solely detected by FH GWAS. Thus both the results of our simulation and empirical studies demonstrate that FH GWAS is a promising method and superior to the SNP-based approach even if almost complete genotype information is available. [ABSTRACT FROM AUTHOR]

Introduction: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. Methods: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29–50) and 10 non-smokers (ages 25–69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. Results: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. Conclusion: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement. [ABSTRACT FROM AUTHOR]

The aberrant hedgehog (Hh) pathway plays important roles in multiple cancer types, therefore serving as a promising drug target. Current clinically available hedgehog-targeted drugs act mostly by antagonizing the upstream component smoothened; however, both primary and acquired resistance to FDA-approved smoothened inhibitor (SMOi) drugs have been described. We have recently demonstrated that the BET inhibitor effectively suppresses SMOiresistant Hh-driven cancers through antagonizing transcription of GLI1 and GLI2, the core transcriptional factors of Hh pathway, suggesting epigenetic or transcriptional targeted therapy represents an anti-Hh therapeutic strategy that can overcome SMOi resistance. Here we performed an unbiased screening of epigenetic or transcriptional targeted small molecules to test their inhibitory effects on GLI1 and GLI2 transcription or cell viability of Hh-driven tumor lines. THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), is identified as the top hit in our screening. We then confirmed that antagonizing CDK7 by either small-molecule inhibitors or the CRISPR-Cas9 approach causes substantial suppression of GLI1 and GLI2 transcription, resulting in effective inhibition of Hh-driven cancers in vitro and in vivo. More importantly, antagonizing CDK7 retains inhibitory activity against Hh-driven cancers with almost all sofar described primary or acquired SMOi resistance. Furthermore, we reveal a synergy between CDK7 inhibition and BET inhibition on antagonizing aberrant Hh pathway and Hh-driven cancers that are either responsive or resistant to SMOi. Our results illustrate transcriptional inhibition through targeting CDK7 as a promising therapeutic strategy for treating Hh-driven cancers, especially those with primary or acquired resistance to SMOi drugs. [ABSTRACT FROM AUTHOR]

Working memory (WM) plays a crucial role in human brain functions. The application of brain connectivity analysis helps to understand the brain network properties in WM. Combination of functional and effective connectivity can provide new insights for exploring network attributes. Nevertheless, few studies have combined these two modes in WM. Near-infrared spectroscopy was used to investigate the connectivity properties in the prefrontal cortex (PFC) during n-back (0-back and 2-back) tasks by combining functional and effective connectivity analysis. Our results demonstrated that the PFC network showed small-world properties in bothWM tasks. The characteristic path length was significantly longer in the 2-back task than in the 0-back task, while there was no obvious difference in the clustering coefficient between two tasks. Regarding the effective connectivity, the Granger causality (GC) was higher for right PFC-left PFC than for left PFC-right PFC in the 2-back task. Compared with the 0-back task, GC of right PFC-left PFC was higher in the 2-back task. Our findings show that, along with memory load increase, long range connections in PFC are enhanced and this enhancement might be associated with the stronger information flow from right PFC to left PFC. [ABSTRACT FROM AUTHOR]

Assessment of disclosure risk is of paramount importance in data privacy research and applications. The concept of differential privacy (DP) formalizes privacy in probabilistic terms and provides a robust concept for privacy protection. Practical applications of DP involve development of DP mechanisms to release data at a pre-specified privacy budget. In this paper, we generalize the widely used Laplace mechanism to the family of generalized Gaussian (GG) mechanism based on the $l_p$ global sensitivity of statistical queries. We explore the theoretical requirement for the GG mechanism to reach DP at prespecified privacy parameters, and investigate the connections and differences between the GG mechanism and the Exponential mechanism based on the GG distribution. We also present a lower bound on the scale parameter of the Gaussian mechanism of $(\epsilon, \delta)$ -probabilistic DP as a special case of the GG mechanism, and compare the utility of sanitized results in the tail probability and dispersion between the Gaussian and Laplace mechanisms. Lastly, we apply the GG mechanism in three experiments and compare the accuracy of sanitized results in the $l_1$ distance and Kullback-Leibler divergence, and examine the prediction power of a SVM classifier constructed with the sanitized data relative to the original results. [ABSTRACT FROM AUTHOR]

Due to the intermittent power generation, wind farms integrated into the grid may cause a problem of large frequency fluctuation, when the capacity of load frequency control (LFC) is not enough to compensate the unbalance between the generation and the load demand. In this study, a new robust LFC strategy against load disturbance and wind power fluctuation is proposed to improve the disturbance-resistant performance of the power system with wind farms. First, a simplified model of the power system with wind farms is established without considering the accurate model information. Then, a control scheme based on the compensation of equivalent input disturbance (EID) is introduced, and a method of EID estimation is presented. The robust LFC design addresses various disturbances and internal/external uncertainties of power systems. Finally, to evaluate the effectiveness of the proposed method, two case studies are carried out and the performance comparisons with the classical proportional-integral-derivative control scheme are used to confirm the proposed method. [ABSTRACT FROM AUTHOR]

Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1-ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively. We found that ErbB4 deletion in adult mice impaired behavior and GABA release but had no effect on neuron numbers and morphology. On the other hand, some deficits due to the ErbB4 null mutation during development were alleviated by restoring ErbB4 expression at the adult stage. Together, our results indicate a critical role of NRG1-ErbB4 signaling in GABAergic transmission and behavior in adulthood and suggest that restoring NRG1- ErbB4 signaling at the postdevelopmental stage might benefit relevant brain disorders. [ABSTRACT FROM AUTHOR]

Background/Aims: Ventricular septal defects (VSDs) are one of the most common types of congenital heart malformations. Volume overload resulting from large VSDs can lead to heart failure (HF) and constitutes a major cause of pediatric HF with a series of often-fatal consequences. The etiology of VSD with HF is complex, and increasing evidence points toward a genetic basis. Indeed, we identified an L2483R mutation in the ryanodine receptor type 2 (RyR2) in a 2-month-old male patient with VSD with HF. Methods: We generated integration-free induced pluripotent stem cells from urine samples (UiPSCs) of this patient using Sendai virus containing the Yamanaka factors and characterized these cells based on alkaline phosphatase activity, pluripotency marker expression, and teratoma formation. Then, we induced the derived UiPSCs to rapidly and efficiently differentiate into functional cardiomyocytes through temporal modulation of canonical Wnt signaling with small molecules. Real-time PCR and immunofluorescence were used to verify the expression of myocardium-specific markers in the differentiated cardiomyocytes. The ultrastructure of the derived myocardial cells was further analyzed by using transmission electron microscopy. Results: The established UiPSC lines were positive for alkaline phosphatase activity, retained the RyR2 mutation, expressed pluripotency markers, and displayed differentiation potential to three germ layers in vivo. The UiPSC-derived cells showed hallmarks of cardiomyocytes, including spontaneous contraction and strong expression of cardiac-specific proteins and genes. However, compared with cardiomyocytes derived from H9 cells, they had a higher level of autophagy, implying that autophagy may play an important role in the development of VSD with HF. Conclusion: The protocol described here yields abundant myocardial cells and provides a solid platform for further investigation of the pathogenesis, pharmacotherapy, and gene therapy of VSD with HF. [ABSTRACT FROM AUTHOR]

To detect perimeter intrusion accurately and quickly, a stream computing technology was used to improve real-time data processing in perimeter intrusion detection systems. Based on the traditional density-based spatial clustering of applications with noise (T-DBSCAN) algorithm, which depends on manual adjustments of neighborhood parameters, an adaptive parameters DBSCAN (AP-DBSCAN) method that can achieve unsupervised calculations was proposed. The proposed AP-DBSCAN method was implemented on a Spark Streaming platform to deal with the problems of data stream collection and real-time analysis, as well as judging and identifying the different types of intrusion. A number of sensing and processing experiments were finished and the experimental data indicated that the proposed AP-DBSCAN method on the Spark Streaming platform exhibited a fine calibration capacity for the adaptive parameters and the same accuracy as the T-DBSCAN method without the artificial setting of neighborhood parameters, in addition to achieving good performances in the perimeter intrusion detection systems. [ABSTRACT FROM AUTHOR]

Phytophthora fruit rot, caused by Phytophthora cactorum, is an important disease of apple in China, often causing more than 50% fruit rot in rainy years. We examined the effects of temperature and moisture on the development of the disease and effects of the variables on zoospore release and germination, infection, and lesion development. In vitro, a temperature range of 5 to 20°C had no significant effects on zoospore release dynamics but did significantly affect the quantities of released zoospores. The largest quantity of zoospores was released at 9.9°C according to a fitted model. Zoosporangia released zoospores within 15 min at the test temperatures (0 to 20°C), which peaked at the fourth hour. Zoospores germinated in vitro, requiring free water, at temperatures from 5 to 35°C. The optimum germination temperature was 25.1°C according to a fitted model. The minimum wetness duration required for zoospores to complete the infection process and induce visible lesions on Fuji fruit was 0.40 h at the optimal temperature of 23.0°C according to the fitted model, whereas observed values were 4.5, 1.5, 0.5, 1.5 and 8.5 h at 10, 15, 20, 25, and 30°C, respectively. The number of zoospore infections on fruit at various temperatures and wetness durations were well fitted by the modified Weibull model; based on the model, the optimal temperature for zoospore infections was 23.0°C. Young apple fruit infected by zoospores developed visible lesions from 10 to 30°C, with a predicted optimum of 23.5°C; no lesions developed at 5 or 35°C. The shortest incubation period of the disease was 4 days. These results can be used to develop disease forecasting models for improved fungicide control. [ABSTRACT FROM AUTHOR]

With the acceleration of urbanisation and industrialisation, atmospheric particulate pollution has become one of the most serious environmental problems in China. In this study, green spaces in Baoji city were classified into different patterns on the basis of vegetation structural parameters, i.e., horizontal structure, vertical structure and vegetation type. Eleven types of green space with different structures were selected for investigating the relationships between atmospheric particulate matter (PM) concentration and green spaces with different vegetation structure, based on the "matrix effect" of environmental factors, i.e., location, time, wind velocity, temperature, humidity and area to the concentration of PM2.5 and PM10 in the green spaces. The results showed that: (1) Location, time, wind velocity, temperature and humidity had highly significant effects on the concentration of PM2.5 and PM10. In sunny and breeze weather conditions, PM2.5 and PM10 concentration increased with the wind velocity and humidity, and decreased with the temperature. The range of PM10 concentration was greater than the range of PM2.5 concentration. (2) Less than 2 hectares of the green space had no significant influence on the concentration of PM2.5 and PM10. (3) The concentration of PM2.5 and PM10 showed no significant difference between all the green spaces and the control group. There was no significant difference in the reduction of PM2.5 concentration between different structural green spaces, but there was a significant difference in the reduction of PM10 concentration. The above results will provide a theoretical basis and practical methods for the optimisation of urban green space structures for improving urban air quality effectively in the future. [ABSTRACT FROM AUTHOR]

We study the stochastic multi-armed bandit (MAB) problem in the presence of sideobservations across actions that occur as a result of an underlying network structure. In our model, a bipartite graph captures the relationship between actions and a common set of unknowns such that choosing an action reveals observations for the unknowns that it is connected to. This models a common scenario in online social networks where users respond to their friends' activity, thus providing side information about each other's preferences. Our contributions are as follows: 1) We derive an asymptotic lower bound (with respect to time) as a function of the bi-partite network structure on the regret of any uniformly good policy that achieves the maximum long-term average reward. 2) We propose two policies - a randomized policy; and a policy based on the well-known upper confidence bound (UCB) policies - both of which explore each action at a rate that is a function of its network position. We show, under mild assumptions, that these policies achieve the asymptotic lower bound on the regret up to a multiplicative factor, independent of the network structure. Finally, we use numerical examples on a real-world social network and a routing example network to demonstrate the benefits obtained by our policies over other existing policies. [ABSTRACT FROM AUTHOR]

Purpose: To study the effectiveness of exogenous erythropoietin (EPO) against chronic heart failure (CHF) with anemia, and its effect on serum hypersensitive C reaction protein (hs-CRP), homocysteic acid (Hcy ) and B-type natriuretic peptide (BNP). Methods: A total of 136 patients suffering from CHF with anemia from June 2015 to June 2017 were randomly divided into observation group (n = 68) and control group (n = 68). On the basis of conventional anti-heart failure therapy, the control group received oral ferrous sulfate tablets, while the observation group received oral ferrous sulfate tablets combined with EPO subcutaneous injection. Blood indices, cardiac function and serology were determined and tested in all patients before treatment, and at 4 months after treatment. Results: After treatment, hemoglobin (Hb), hematocrit (HCT), red blood cell (RBC), blood platelet count (PLT) and serum iron were significantly higher than those before treatment in the two groups; the levels in the observation group were significantly higher than those in control group (p <0.05). Following treatment, left ventricular ejection fraction (LVEF), and 6-minute walking distance in the observation group were significantly higher than those in the control group, while end-diastolic dimension (LVEDD), end-systolic dimension (LVESD) and cardiac functional grading in the observation group were significantly lower than those in the control group (p < 0.05). After treatment, hs-CRP, Hcy and BNP were significantly lower than pre-treatment values in the two groups, while the values for the observation group were significantly lower than those of control group (p <0.05). Correlation analysis showed that LVEF and Hb were negatively correlated with hs-CRP, Hcy and BNP (p <0.05). Conclusion: Serum hs-CRP, Hcy and BNP are involved in the occurrence and progression of CHF with anemia. Exogenous EPO can effectively improve anemia and cardiac function in these patients. [ABSTRACT FROM AUTHOR]

A total of 849 core samples collected from two drilling core STD235 and ZSQD289 in the northeastern South China Sea were analyzed for elemental composition including total organic carbon (TOC), total nitrogen (TN), stable carbon and nitrogen isotopic composition (δ13C, δ15N), and clay mineral composition. Based on clay mineral assemblages and organic geochemistry characteristics, it is supposed that the terrestrial source for sediments at STD235 and ZSQD289 is mainly from southwestern Taiwan. Moreover, the sedimentary organic matter of site ZSQD289 was probably directly inputted from southwestern Taiwan submarine canyon, while the sedimentary organic matter of core STD235 was probably transported by deep water current. The chronology suggested that it covered the record since ~19.7 and 34.6 ka BP in site STD235 and ZSQD289 respectively. Before the Last Glacial Maximum (LGM), high TOC/TN ratios with low δ13C and δ15N values might indicate that terrestrial organic input and nitrogen fixation was enhanced. During the LGM, gradually increased TOC, TN, δ13C, and δ15N values might result from the enhanced burial of organic carbon and higher marine primary production constrained by the strong winter monsoon. TOC/TN ratios and δ13C values generally present a decreased trend from LGM to Holocene (18 - 11 cal ka BP), strongly correlated to the terrestrial organic input and marine primary production reduced during this period. Since Holocene, the terrestrial organic input to both sites further reduced and maintained a low level, in according with a high sea level and a gradual intensified summer monsoon. [ABSTRACT FROM AUTHOR]

Smart sensor-equipped mobile devices sense, collect, and process data generated by the edge network to achieve intelligent control, but such mobile devices usually have limited storage and computing resources. Mobile cloud storage provides a promising solution owing to its rich storage resources, great accessibility, and low cost. But it also brings a risk of information leakage. The encryption of sensitive data is the basic step to resist the risk. However, deploying a high complexity encryption and decryption algorithm on mobile devices will greatly increase the burden of terminal operation and the difficulty to implement the necessary privacy protection algorithm. In this paper, we propose ENSURE (EfficieNt and SecURE), an efficient and secure encrypted search architecture over mobile cloud storage. ENSURE is inspired by edge computing. It allows mobile devices to offload the computation intensive task onto the edge server to achieve a high efficiency. Besides, to protect data security, it reduces the information acquisition of untrusted cloud by hiding the relevance between query keyword and search results from the cloud. Experiments on a real data set show that ENSURE reduces the computation time by 15% to 49% and saves the energy consumption by 38% to 69% per query. [ABSTRACT FROM AUTHOR]

Given the improvement of synthetic aperture radar (SAR) imaging technologies, the resolution of SAR image is largely improved and the variation of backscatter amplitude should be considered in SAR image processing. In this paper, considering the spatial geometric properties of SAR image in gray pixel space and the sample selection in the estimation of true signal, local directional property of each pixel is explored with the help of SAR sketching method, and two specially designed filters are integrated for adaptive speckle reduction of SAR images. Specifically, based on the sketch map of a SAR image, the orientation of the sketch point lying at each sketch segment is assigned to the corresponding pixel, and thus all pixels of the SAR image are classified as the directional pixels and the nondirectional pixels. For the directional pixels, given the significant directionality of its neighborhood, a geometricstructural block (GB) is built to center on it and GB-wised nonlocal means filter is designed to estimate the true values of all pixels contained in the GB. Moreover, using the local orientation, the whole image is adopted as the searching range to search the similar GBs. For the nondirectional pixels, based on the locally estimated equivalent number of looks, a novel pixel-based metric is proposed to determine the local adaptive neighborhood (AN) with which an AN-based filter is developed to estimate its true value. Besides, since some nondirectional pixels are contained in GBs, a Bayesian-based fusion strategy is designed for the fusion of their estimated values. In the experiments, three synthetic speckled images and five real SAR images [obtained with different resolutions (e.g., 3, 1, and 0.1 m) and different bands (e.g., X-band, C-band, and Ka-band)] are used for evaluation and analysis. Owing to the usage of local spatial geometric property and the combination of two different filters, the proposed method shows a reasonable performance among the comparison methods, in terms of the speckle reduction and the details' preservation. [ABSTRACT FROM AUTHOR]

An Nb3Sn cable-in-conduit (CIC) conductor with short twist pitch structure has been developed at Institute of Plasma Physics Chinese Academy of Sciences, Hefei, China, to meet the central solenoid model coil (CSMC) project of China fusion engineering test reactor (CFETR). 12 T magnetic field and 1.5 T/s field change are the most basic design target. The coupling loss characteristics of Nb3Sn CIC conductor is the key design requirement for CSMS because the deposited energy in magnets from ac losses can decrease the safe margin in the nuclear fusion device. In order to evaluate the coupling loss performance of the Nb3Sn CIC conductor, the ac loss measurement for Nb3Sn CIC conductor sample was carried out at SULTAN facility. This paper presents the specific structure design of the Nb3Sn CIC conductor and ac losses test results first. Then, the coupling losses characteristics are discussed with Multizones PArtial Shielding model and the key fit parameters are obtained from measurement results. Finally, two typical field cases are considered to evaluate the coupling loss energy of Nb3Sn CIC conductor for safe operation of the CFETR CSMC and the optimization of the cryogenic system. [ABSTRACT FROM AUTHOR]

Background: There is global health concern that the mass movement of pilgrims to and from Mecca annually could contribute to the international spread of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In China, about 11,000 Muslim pilgrims participate in the Hajj gathering in Mecca annually. This is the first report of MERS-CoV and respiratory virus molecular screening of returning pilgrims at points of entry in China from 2013 to 2015.Methods and Results: A total of 847 returning Hajj pilgrims participated in this study. The test results indicated that of the travelers, 34 tested positive for influenza A virus, 14 for influenza B virus, 4 for metapneumo virus, 2 for respiratory syncytial virus, and 3 for human coronavirus. There was a significant difference in the rates of positive and negative influenza virus tests between Hajj pilgrims with symptoms and those without. The detection rates of influenza virus were not significantly different among the three years studied, at 5.3, 6.0 and 6.3% for 2013, 2014 and 2015, respectively. DISCUSSION AND CONCLUSION: The MERS-CoV and respiratory viruses detection results at points of entry in China from 2013 to 2015 indicated that there were no MERS-CoV infection but a 5.7% positive influenza viruses in returning Chinese pilgrims. [ABSTRACT FROM AUTHOR]

Background: First generation bioethanol production utilizes the starch fraction of maize, which accounts for approximately 60% of the ash-free dry weight of the grain. Scale-up of this technology for fuels applications has resulted in a massive supply of distillers' grains with solubles (DGS) coproduct, which is rich in cellulosic polysaccharides and protein. It was surmised that DGS would be rapidly adopted for animal feed applications, however, this has not been observed based on inconsistency of the product stream and other logistics-related risks, especially toxigenic contaminants. Therefore, efficient valorization of DGS for production of petroleum displacing products will significantly improve the techno-economic feasibility and net energy return of the established starch bioethanol process. In this study, we demonstrate 'one-pot' bioconversion of the protein and carbohydrate fractions of a DGS hydrolysate into C4 and C5 fusel alcohols through development of a microbial consortium incorporating two engineered Escherichia coli biocatalyst strains. Results: The carbohydrate conversion strain E. coli BLF2 was constructed from the wild type E. coli strain B and showed improved capability to produce fusel alcohols from hexose and pentose sugars. Up to 12 g/L fusel alcohols was produced from glucose or xylose synthetic medium by E. coli BLF2. The second strain, E. coli AY3, was dedicated for utilization of proteins in the hydrolysates to produce mixed C4 and C5 alcohols. To maximize conversion yield by the co-culture, the inoculation ratio between the two strains was optimized. The co-culture with an inoculation ratio of 1:1.5 of E. coli BLF2 and AY3 achieved the highest total fusel alcohol titer of up to 10.3 g/L from DGS hydrolysates. The engineered E. coli co-culture system was shown to be similarly applicable for biofuel production from other biomass sources, including algae hydrolysates. Furthermore, the co-culture population dynamics revealed by quantitative PCR analysis indicated that despite the growth rate difference between the two strains, co-culturing didn't compromise the growth of each strain. The q-PCR analysis also demonstrated that fermentation with an appropriate initial inoculation ratio of the two strains was important to achieve a balanced co-culture population which resulted in higher total fuel titer. Conclusions: The efficient conversion of DGS hydrolysates into fusel alcohols will significantly improve the feasibility of the first generation bioethanol process. The integrated carbohydrate and protein conversion platform developed here is applicable for the bioconversion of a variety of biomass feedstocks rich in sugars and proteins. [ABSTRACT FROM AUTHOR]

To explore the debated phylogenetic relationship of two Hesperiidae subfamilies, Pyrginae and Eudaminae, and contribute to the understanding of the evolution of mitogenomic architecture in butterflies, we sequenced the complete mitogenome of Tag iades vajuna. The mitogenome is a typical circular duplex molecule of 15,359 bp. Apart from the standard 22 tRNAs, it has a tandem duplication of trnS(AGN) and trnE, which is unique in lepidopteran insects. Comparison with Ctenoptilum vasava indicates that the trnS1 duplication is not an ancestral state shared with other species of Tagiadini. Independent origin of the trnS1 duplications was further confirmed by the reconstruction of the ancestral character state based on the topology of the phylogram. Furthermore, comparative analysis of mitogenomes with and without tRNA duplications indicates that tRNA duplication does not alter the codon usage pattern. The mitogenome has negative AT- and GC-skews, and it is highly A+T-biased (79.7%). The AT-rich (or control) region (283 bp) contains "ATAGA" and "ATTTA" motifs. Regarding the phylogenetic analysis, we found that removal of the third codon position (3CP) from datasets used for the mitochondrial phylogenomics of Hesperiidae is likely to produce results that are more consistent: Pyrginae were rendered paraphyletic by Eudaminae in both analyses of the dataset from which the 3CP was removed (13 PCGs + all RNAs), but inclusion of the 3CP resulte d in a destabilized topology, resulting in both monophyly and polyphyly. We conc lude that even shallow-phylogenies of insects should pay close attention to compositional and mutational biases in mitogenomes. [ABSTRACT FROM AUTHOR]

Inkjet printing is a promising technology for the scalable fabrication of organic electronics because of the material conservation and facile patterning as compared with other solution processing techniques. In this study, we have systematically investigated the cross-sectional profile control of silver (Ag) electrode via inkjet printing. A facile methodology for achieving inkjet-printed Ag source/drain with improved profiles is developed. It is demonstrated that the printing conditions such as substrate temperature, drop spacing and printing layers affect the magnitude of the droplet deposition and the rate of evaporation, which can be optimized to greatly reduce the coffee ring effects for improving the inkjet-printed electrode profiles. Ag source/drain electrodes with uniform profiles were successfully inkjet-printed and incorporated into organic thin-film transistors (OTFTs). The resulting devices showed superior electrical performance than those without special treatments. It is noted to mention that the strategy for modulating the inkjet-printed Ag electrodes in this work does not demand the ink formulation or complicated steps, which is beneficial for scaling up the printing techniques for potential large-area/mass manufacturing. [ABSTRACT FROM AUTHOR]

To explore the debated phylogenetic relationship of two Hesperiidae subfamilies, Pyrginae and Eudaminae, and contribute to the understanding of the evolution of mitogenomic architecture in butterflies, we sequenced the complete mitogenome of Tag iades vajuna. The mitogenome is a typical circular duplex molecule of 15,359 bp. Apart from the standard 22 tRNAs, it has a tandem duplication of trnS(AGN) and trnE, which is unique in lepidopteran insects. Comparison with Ctenoptilum vasava indicates that the trnS1 duplication is not an ancestral state shared with other species of Tagiadini. Independent origin of the trnS1 duplications was further confirmed by the reconstruction of the ancestral character state based on the topology of the phylogram. Furthermore, comparative analysis of mitogenomes with and without tRNA duplications indicates that tRNA duplication does not alter the codon usage pattern. The mitogenome has negative AT- and GC-skews, and it is highly A+T-biased (79.7%). The AT-rich (or control) region (283 bp) contains "ATAGA" and "ATTTA" motifs. Regardi ng the phylogenetic analysis, we found that removal of the third codon position (3CP) from datasets used for the mitochondrial phylogenomics of Hesperiidae is likely to produce results that are more consistent: Pyrginae were rendered paraphyletic by Eudaminae in both analyses of the dataset from which the 3CP was removed (13 PCGs + all RNAs), but inclusion of the 3CP resulte d in a destabilized topology, resulting in both monophyly and polyphyly. We conc lude that even shallow-phylogenies of insects should pay close attention to compositional and mutational biases in mitogenomes. [ABSTRACT FROM AUTHOR]

Rapid and efficient analysis of fluoride ion is crucial to providing key information for fluoride ion hazard assessment and pollution management. In this study, we synthesized one symmetrical structure called 1,4-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene (1a) and two asymmetrical structures, namely 2-(4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl)-1H-phenanthro(9,10-d)imidazole (1b) and 2-(4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl)-1H-imidazo(4,5-f)(1,10)phenanthroline (1c), which served as an efficient anion sensor for fluoride ion over a wide range of other anions (Cl-, Br-, I-, NO3-, ClO4-, HSO4-, BF4-, and PF6-) owing to imidazole group in the main backbone. The absorption intensity of compound 1a at λmax 358 nm slightly decreased; however, a new band at λmax 414 nm appeared upon the addition of fluoride ion, while no evident change occurred upon the addition of eight other anions. The photoluminescence intensity of compound 1a at λmax 426 nm was nearly quenched and fluorescence emission spectra were broadened when fluoride ion was added into dimethyl sulfoxide (DMSO) solution of compound 1a. Compared with the optical behaviors of the DMSO solution of compound 1a in the presence of Bu4N+F-, compounds 1b and 1c exhibited considerable sensitivity to fluoride ion due to the increase in coplanarity. Furthermore, compared with the fluorescence emission behaviors of the DMSO solutions of compounds 1a and 1b in the presence of Bu4N+F-, compound 1c exhibited the most significant sensitivity to fluoride ion due to the charge transfer enhancement. Consequently, the detection limits of compounds 1a--1c increased from 5.47 x 10-6 M to 4.21 x 10-6 M to 9.12 x 10-7 M. Furthermore, the largest red shift (75 nm) of the DMSO solution compound 1c in the presence of fluoride ion can be observed. Our results suggest that the increase in coplanarity and the introduction of electron-withdrawing groups to the imidazole backbone can improve the performance in detecting fluoride ion. [ABSTRACT FROM AUTHOR]

Background: Almonds can decrease glycemic index of co-consumed foods and are a rich source for oleic acid and a-tocopherol. The aim of the randomized, crossover, controlled feeding trial was to examine whether as compared to NCEP step II diet as control (CON), ~60 g/d almonds (ALM) added to CON would improve glucoregulation and cardiovascular disease (CVD) risk factors in 33 Chinese T2DM patients. Methods: Forty T2DM patients were enrolled and randomly assigned to receive CON or ALM for 12 wks after a 2-wk. run-in period. Blood and urine samples were collected in the beginning and at the end of each dietary intervention phase for the assessment of biomarkers of glucoregulation, lipid profile, inflammation, and oxidative stress. Results: While ALM had a better overall nutritional quality than CON, neither ALM nor CON improved the glycemic status as the primary study outcome and other CVD risk factors, except the circulating nitric oxide being decreased by ALM compared to CON. Among 27 of 33 patients with the baseline HbA1c ≤.8, ALM decreased post-interventional fasting serum glucose and HbA1c by 5.9% and 3.0% as compared to that of CON, respectively (P = 0.01 and 0.04). Mean total and LDL-cholesterol concentrations were not changed by both diets. Conclusions: These results suggest almonds incorporated into healthful diets can improve glycemic status in diabetic patients with a better glycemic control. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the frequency of RASSF1A hypermethylation in patients with acute myeloid leukemia (AML), in an attempt to modify the current molecular model for disease prognosis. Materials and methods: Aberrant RASSF1A promoter methylation levels were assessed in 226 newly diagnosed non-M3 AML patients and 30 apparently healthy controls, by quantitative methylation-specific polymerase chain reaction. Meanwhile, RASSF1A mRNA levels were detected by real-time quantitative polymerase chain reaction. Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic aberrations were assessed. Finally, associations of RASSF1A hypermethylation with clinical outcomes were evaluated. Results: RASSF1A hypermethylation was observed in 23.0% of patients with non-M3 AML (52/226), but not in controls. Meanwhile, hypermethylation of the RASSF1A promoter was significantly associated with ASXL1 mutation. Furthermore, the log-rank test revealed that RASSF1A hypermethylation indicated decreased relapse-free survival (RFS) and overall survival (OS) in patients with non-M3 AML (P=0.012 and P=0.014, respectively). In multivariate analysis, RASSF1A hypermethylation was an independent prognostic factor for RFS (P=0.040), but not for OS (P=0.060). Conclusion: Hypermethylation of the RASSF1A promoter is associated with ASXL1 mutation in non-M3 AML patients, likely indicating poor outcome. These findings provide a molecular basis for stratified diagnosis and prognostic evaluation. [ABSTRACT FROM AUTHOR]

Previous studies have shown that our understanding of species diversity within Diaporthe (syn. Phomopsis) is limited. In this study, 49 strains obtained from different countries were subjected to DNA sequence analysis. Based on these results, eight new species names are introduced for lineages represented by multiple strains and distinct morphology. Twelve Phomopsis species previously described from China were subjected to DNA sequence analysis, and confirmed to belong to Diaporthe. The genus Diaporthe is shown to be paraphyletic based on multi-locus (LSU, ITS and TEF1) phylogenetic analysis. Several morphologically distinct genera, namely Mazzantia, Ophiodiaporthe, Pustulomyces, Phaeocytostroma, and Stenocarpella, are embedded within Diaporthe s. lat., indicating divergent morphological evolution. However, splitting Diaporthe into many smaller genera to achieve monophyly is still premature, and further collections and phylogenetic datasets need to be obtained to address this situation. [ABSTRACT FROM AUTHOR]

In this paper, we study a uniqueness question of meromorphic functions of certain differential polynomials that share a nonzero finite value or have the same fixed points with the same of L-functions. The results in this paper extend the corresponding results from Steuding [12, p. 152], Li [7], Fang [1] and Yang-Hua [14]. [ABSTRACT FROM AUTHOR]

Energy efficiency is a significant topic in cloud computing. Dynamic consolidation of virtual machines (VMs) with live migration is an important method to reduce energy consumption. However, frequent VM live migration may cause a downtime of service. Therefore, the energy save and VM migration are two conflict objectives. In order to efficiently solve the dynamic VM consolidation, the dynamic VM placement (DVMP) problem is formed as a multiobjective problem in this paper. The goal of DVMP is to find a placement solution that uses the fewest servers to host the VMs, including two typical dynamic conditions of the assignment of new coming VMs and the re-allocation of existing VMs. Therefore, we propose a unified algorithm based on an ant colony system (ACS), termed the unified ACS (UACS), that works on both conditions. The UACS firstly uses sufficient servers to host the VMs and then gradually reduces the number of servers. With each especial number of servers, the UACS tries to find feasible solutions with the fewest VM migrations. Herein, a dynamic pheromone deposition method and a special heuristic information strategy are also designed to reduce the number of VM migrations. Therefore, the feasible solutions under different numbers of servers cover the Pareto front of the multiobjective space. Experiments with large-scale random workloads and real workload traces are conducted to evaluate the performance of the UACS. Compared with traditional heuristic, probabilistic, and other ACS based algorithms, the proposed UACS presents competitive performance in terms of energy consumption, the number of VM migrations, and maintaining quality of services (QoS) requirements. [ABSTRACT FROM AUTHOR]

Background: The inability of patients to accurately and completely recount their clinical status between clinic visits reduces the clinician's ability to properly manage their patients. One way to improve this situation is to collect objective patient information while the patients are at home and display the collected multi-day clinical information in parallel on a single screen, highlighting threshold violations for each channel, and allowing the viewer to drill down to any analog signal on the same screen, while maintaining the overall physiological context of the patient. All this would be accomplished in a way that was easy for the clinician to view and use.Methods: Patients used five mobile devices to collect six heart failure-related clinical variables: body weight, systolic and diastolic blood pressure, pulse rate, blood oxygen saturation, physical activity, and subjective input. Fourteen clinicians practicing in a heart failure clinic rated the display using the System Usability Scale that, for acceptability, had an expected mean of 68 (SD, 12.5). In addition, we calculated the Intraclass Correlation Coefficient of the clinician responses using a two-way, mixed effects model, ICC (3,1).Results: We developed a single-screen temporal hierarchical display (VISION) that summarizes the patient's home monitoring activities between clinic visits. The overall System Usability Scale score was 92 (95% CI, 87-97), p < 0.0001; the ICC was 0.89 (CI, 0.79-0.97), p < 0.0001.Conclusion: Clinicians consistently found VISION to be highly usable. To our knowledge, this is the first single-screen, parallel variable, temporal hierarchical display of both continuous and discrete information acquired by patients at home between clinic visits that presents clinically significant information at the point of care in a manner that is usable by clinicians. [ABSTRACT FROM AUTHOR]