40 research outputs found

    Virulence of H5N1 virus in mice attenuates after in vitro serial passages

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    The virulence of A/Vietnam/1194/2004 (VN1194) in mice attenuated after serial passages in MDCK cells and chicken embryos, because the enriched large-plaque variants of the virus had significantly reduced virulence. In contrast, the small-plaque variants of the virus and the variants isolated from the brain of mice that were infected with the parental virus VN1194 had much higher virulence in mice. The virulence attenuation of serially propagated virus may be caused by the reduced neurotropism in mice. Our whole genome sequence analysis revealed substitutions of a total of two amino acids in PB1, three in PB2, two in PA common for virulence attenuated variants, all or part of which may be correlated with the virulence attenuation and reduced neurotropism of the serially propagated VN1194 in mice. Our study indicates that serial passages of VN1194 in vitro lead to adaptation and selection of variants that have markedly decreased virulence and neurotropism, which emphasizes the importance of direct analysis of original or less propagated virus samples

    H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation

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    Highly pathogenic avian influenza H5N1 virus has swept west across the globe and caused serious debates on the roles of migratory birds in virus circulation since the first large-scale outbreak in migratory birds of Lake Qinghai, 2005. In May 2006, another outbreak struck Lake Qinghai and six novel strains were isolated. To elucidate these QH06 viruses, the six isolates were subjected to whole-genome sequencing. Phylogenetic analyses show that QH06 viruses are derived from the lineages of Lake Qinghai, 2005. Five of the six novel isolates are adjacent to the strain A/Cygnus olor/Croatia/1/05, and the last one is related to the strain A/duck/Novosibirsk/02/05, an isolate of the flyway. Antigenic analyses suggest that QH06 and QH05 viruses are similar to each other. These findings implicate that QH06 viruses of Lake Qinghai may travel back via migratory birds, though not ruling out the possibility of local circulation of viruses of Lake Qinghai

    Course Recommendation Based on Enhancement of Meta-Path Embedding in Heterogeneous Graph

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    The main reason students drop out of online courses is often that they lose interest during learning. Moreover, it is not easy for students to choose an appropriate course before actually learning it. Course recommendation is necessary to address this problem. Most existing course recommendation methods depend on the interaction result (e.g., completion rate, grades, etc.). However, the long period required to complete a course, especially large-scale online courses in higher education, can lead to serious sparsity of interaction results. In view of this, we propose a novel course recommendation method named HGE-CRec, which utilizes context formation for heterogeneous graphs to model students and courses. HGE-CRec develops meta-path embedding simulation and meta-path weight fusion to enhance the meta-path embedding set, which can expand the learning space of the prediction model and improve the representation ability of meta-path embedding, thereby avoiding tedious manual setting of the meta-path and improving the effectiveness of the resulting recommendations. Extensive experiments show that the proposed approach has advantages over a number of existing baseline methods

    Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models

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    ABSTRACT: Methotrexate (MTX) is a substrate for numerous human ATP-binding cassette (ABC) efflux transporters, yet the impact of these transporters on MTX pharmacokinetics (PK) over a large dose range has not been examined. To investigate the effects of two transporters-ABC subfamily C member 2 (Abcc2; multidrug resistance protein 2) and ABC subfamily C member 3 (Abcc3; multidrug resistance protein 3)-involved in MTX hepatobiliary disposition in vivo, MTX plasma, urine, and feces concentrations were analyzed after 10, 50, and 200 mg/kg i.v. doses to groups of wild type (WT), Abcc2(؊/؊), and Abcc3(؊/؊) mice. The absence of Abcc2 caused a decrease in total clearance of MTX relative to WT mice at all dose levels yet was accompanied by compensatory increases in renal excretion and metabolism to 7-hydroxymethotrexate (7OH-MTX). In Abcc3(؊/؊) mice, total clearance was elevated at the two lower dose levels and was attributed to stimulation of biliary excretion and confirmed by elevated fecal excretion; however, at the high 200 mg/kg dose, clearance was severely retarded and could be attributed to hepatotoxicity because conversion to 7OH-MTX was diminished. The findings confirmed that both Abcc2 and Abcc3 significantly influenced the PK properties of MTX, and depending on the MTX dose and strain, alternate elimination pathways were elicited and saturable

    Edge detection in Cassini astronomy image using Extreme Learning Machine

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    Edge detection is often performed on disc-like object in Cassini astronomy images to accurately obtain the object’s center position. The existing edge extraction methods usually produce lots of false edge pixels because of noise and the interior details in disc-like objects. In the paper, an edge detection algorithm based on Extreme Learning Machine (ELM) is proposed for Cassini astronomy images. In the ELM model, a 28-D feature vector of a pixel in Cassini image is constructed as input, which consists of first and second derivatives and some Haar-like features, and a binary classifier is obtained as output that tells if the pixel is in edge. The experimental result shows that its performance is much better than traditional operators. The detected edge is closer to the actual contour. Its average accuracy is 0.9379. The algorithm can be applied to edge detection of disc-like objects in astronomy images
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