50 research outputs found

    A Delay Analysis of Mass Volume Train Security Detection Network

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    Mass volume train security detection network is a reliable and real-time onboard train communication network based on the train level and vehicle level Ethernet network, which will send and transmit large capacity status and fault diagnosis data, the event log data, passenger information which are stored in different vehicles equipments for fault diagnosis and intelligent maintenance. The topology structure and onboard devices logic relation of the train security detection network is presented. Then, a delay model of different topology structure is analysed, which indicate that the onboard ring network is superior to the bus network topology. Finally, the analysis is confirmed by simulation results. The research results will improve control and network function of train

    A Survey of Learned Indexes for the Multi-dimensional Space

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    A recent research trend involves treating database index structures as Machine Learning (ML) models. In this domain, single or multiple ML models are trained to learn the mapping from keys to positions inside a data set. This class of indexes is known as "Learned Indexes." Learned indexes have demonstrated improved search performance and reduced space requirements for one-dimensional data. The concept of one-dimensional learned indexes has naturally been extended to multi-dimensional (e.g., spatial) data, leading to the development of "Learned Multi-dimensional Indexes". This survey focuses on learned multi-dimensional index structures. Specifically, it reviews the current state of this research area, explains the core concepts behind each proposed method, and classifies these methods based on several well-defined criteria. We present a taxonomy that classifies and categorizes each learned multi-dimensional index, and survey the existing literature on learned multi-dimensional indexes according to this taxonomy. Additionally, we present a timeline to illustrate the evolution of research on learned indexes. Finally, we highlight several open challenges and future research directions in this emerging and highly active field

    Not All Negatives Are Worth Attending to: Meta-Bootstrapping Negative Sampling Framework for Link Prediction

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    The rapid development of graph neural networks (GNNs) encourages the rising of link prediction, achieving promising performance with various applications. Unfortunately, through a comprehensive analysis, we surprisingly find that current link predictors with dynamic negative samplers (DNSs) suffer from the migration phenomenon between "easy" and "hard" samples, which goes against the preference of DNS of choosing "hard" negatives, thus severely hindering capability. Towards this end, we propose the MeBNS framework, serving as a general plugin that can potentially improve current negative sampling based link predictors. In particular, we elaborately devise a Meta-learning Supported Teacher-student GNN (MST-GNN) that is not only built upon teacher-student architecture for alleviating the migration between "easy" and "hard" samples but also equipped with a meta learning based sample re-weighting module for helping the student GNN distinguish "hard" samples in a fine-grained manner. To effectively guide the learning of MST-GNN, we prepare a Structure enhanced Training Data Generator (STD-Generator) and an Uncertainty based Meta Data Collector (UMD-Collector) for supporting the teacher and student GNN, respectively. Extensive experiments show that the MeBNS achieves remarkable performance across six link prediction benchmark datasets

    Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody

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    手足口病是一种由人肠道病毒引起的全球性传染病,主要发生于5岁以下的婴幼儿,严重危害公众健康。根据获得的手足口病流行病学和病原学调查数据,目前认为CVA6与EV71和CVA16一样应作为优先的手足口病疫苗预防对象,亟需研制有效的预防和治疗方法。然而令人遗憾的是,目前对于CVA6的基础病毒学特别是结构生物学知识均缺乏足够了解,严重制约了相关研究的有效开展。 夏宁邵教授团队研究首次揭示了手足口病重要病原体柯萨奇病毒A组6型(CVA6)的病毒颗粒及其与中和抗体复合物的精确三维结构,为新型疫苗和治疗药物的研制提供了重要的理论基础。这项研究发现并精确描绘了CVA6的病毒颗粒及其与优势中和抗体的结构特征,首次完成了对CVA6的高精度“成像”,为新型疫苗和治疗药物研制提供了关键基础。 该研究工作在厦门大学分子疫苗学和分子诊断学国家重点实验室、国家传染病诊断试剂与疫苗工程技术研究中心科研平台完成。夏宁邵教授、颜晓东博士、程通副教授为该研究论文的共同通讯作者。颜晓东博士来自美国加州大学圣地亚哥分校,同时受聘为我校双聘教授。共同第一作者为徐龙发博士生、郑清炳工程师和李少伟教授。【Abstract】Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines.This work was supported by a grant from the National Natural Science Foundation of China (No. 31670933 and 81401669), the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2017ZX09101005-005-003), the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402-002-003) and the Natural Science Foundation of Fujian Province (No. 2015J05073). This work was also supported in part by funding to T.S.B. from the National Institutes of Health (Grant R37-GM33050). 研究工作也得到了国际病毒结构生物学权威专家美国加州大学洛杉矶分校周正洪教授的大力支持和帮助,获得了国家自然科学基金、新药创制国家科技重大专项、传染病防治国家科技重大专项和福建省自然科学基金的资助

    The COP9 signalosome regulates the Neurospora circadian clock by controlling the stability of the SCF(FWD-1) complex

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    The COP9 signalosome (CSN) promotes the function of SCF-type cullin-based ubiquitin ligase complexes in vivo. Paradoxically, removal of the Nedd8 modification of cullins by CSN inhibits the ubiquitin ligase activity of SCF complexes in vitro. Ubiquitination-mediated degradation of the Neurospora circadian clock protein FREQUENCY (FRQ) is critical for clock function. Ubiquitination of FRQ requires FWD-1, the substrate-recruiting subunit of an SCF complex. Here we show that disruption of a subunit of CSN (csn-2) impairs the degradation of FRQ and compromises its normal circadian expression. A FRQ-independent oscillator drives conidiation in the csn-2 mutant, resulting in a 2-d conidiation rhythm that persists in constant darkness (DD), constant light (LL), light-to-dark (LD) transitions, and temperature cycles. Strikingly, the levels of FWD-1 are drastically reduced in csn-2 mutant, explaining the impaired degradation of FRQ. Reduction of FWD-1 levels in the mutant requires its F-box, suggesting that its degradation is due to autoubiquitination. In addition, SKP-1 and CUL-1 of the SCF(FWD-1) complex are also unstable in the mutant. Therefore, our results establish an important role of CSN in the circadian clock of Neurospora. Our findings also reconcile the CSN paradox and suggest that a major function of CSN is to maintain the stability of SCF ubiquitin ligases in vivo

    Regulation of the Neurospora circadian clock by an RNA helicase

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    The eukaryotic circadian oscillators consist of autoregulatory negative-feedback loops. FRQ, WC-1, and WC-2 are three known components of the negative-feedback loop of the Neurospora circadian oscillator. FRQ represses its own transcription by interacting with the WC-1/WC-2 complex and inhibiting WC's role in transcriptional activation. Here we show that all FRQ associates with FRH, an essential DEAD box-containing RNA helicase in Neurospora. The budding yeast homolog of FRH, Dob1p/Mtr4p, is a cofactor of exosome, an important regulator of RNA metabolism in eukaryotes. Down-regulation of FRH by inducible expression of a hairpin RNA leads to low levels of FRQ but high levels of frq RNA and the abolishment of circadian rhythmicities. FRH is associated with the WC complex and this interaction is maintained in a frq null strain. Disruption of the FRQ–FRH complex by deleting a domain in FRQ eliminates the FRQ–WC interaction, suggesting that FRH mediates the interaction between FRQ and the WC complex. These data demonstrate that FRH is an essential component in the circadian negative-feedback loop and reveal an unexpected role of an RNA helicase in regulating gene transcription

    Numerical Analysis of Effect of Boundary Layer Characteristics on the Flow Field in S-shaped Inlet

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    In order to explore the effect of boundary layer thickness and pressure gradient on the performance of the flow field in the inlet, we design a high offset rate S-shaped inlet based on a certain unmanned aerial vehicle (UAV), and its author has analyzed the effect of boundary layer characteristics on the inlet with numerical simulation method. The suction of boundary layer which leads to separation zone not only becomes longer in the inlet, but also moves to the center plane of symmetry, the separation point of boundary layer appears in advance as pressure gradient increases. Considering the influence of the boundary layer, various performance parameters all exceeds that of the uniform entrance inlet conditions, especially the circumferential total pressure distortion of outlet increased by 58.2% at most, obviously can’t meet the engine to work properly, so we must consider and pay attention to the effect of the boundary layer characteristics on the flow field in the S-shaped inlet

    FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation

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    Phosphorylation of the Neurospora circadian clock protein FREQUENCY (FRQ) regulates its degradation and the proper function of the clock. The mechanism by which FRQ undergoes degradation has not been established. Here we show that FRQ is likely ubiquitylated in vivo, and its proper degradation requires FWD1, an F-box/WD-40 repeat-containing protein. In the fwd1 disruption strains, FRQ degradation is severely impaired, resulting in the accumulation of hyperphosphorylated FRQ. Furthermore, the circadian rhythms of gene expression and the circadian conidiation rhythms are abolished in these fwd1 mutants. Finally, FRQ and FWD1 interact physically in vivo, suggesting that FWD1 is the substrate-recruiting subunit of an SCF-type ubiquitin ligase responsible for FRQ ubiquitylation and degradation. Together with the recent finding that Slimb (the Drosophila homolog of FWD1) is involved in the degradation of the Period protein in flies, our results indicate that FWD1 regulates the degradation of FRQ in Neurospora and is an evolutionarily conserved component of the eukaryotic circadian clock
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