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  • 利用全基因组数据解码新型肺炎冠状病毒的进化和传播

    分类: 生物学 >> 病毒学 分类: 生物学 >> 生物进化论 分类: 生物学 >> 遗传学 提交时间: 2020-02-21

    摘要: Background. The outbreak of COVID-19 started in mid-December 2019 in Wuhan, Central China. Up to February 18, 2020, SARS-CoV-2 has infected more than 70,000 people in China, and another 25 countries across five continents. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to decode the evolution and human-to-human transmissions of SARS-CoV-2 in the recent two months. Methods. Alignment of coding-regions was conducted haplotype analyses using DnaSP. Substitution sites were analyzed in codon. Evolutionary analysis of haplotypes used NETWORK. Population size changes were estimated using both DnaSP and Arlequin. Expansion date of population size was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. Findings. Eight coding-regions have 120 substitution sites, including 79 non-synonymous and 40 synonymous substitutions. Forty-two non-synonymous substitutions changed the biochemical property of amino acids. No evident combination was found. Fifty-eight haplotypes were classified as five groups, and 31 haplotypes were found in samples from both China and other countries, respectively. The rooted network suggested H13 and H35 to be ancestral haplotypes, and H1 (and its descendent haplotypes including all samples from the Hua Nan market) was derived H3 haplotype. Population size of SARS-CoV-2 were estimated to have a recent expansion on 6 January 2020, and an early expansion on 8 December 2019. Interpretation. Genomic variations of SARS-CoV-2 are still low in comparisons with published genomes of SARS-CoV and MERS-CoV. Phyloepidemiologic analyses indicated the SARS-CoV-2 source at the Hua Nan market should be imported from other places. The crowded market boosted SARS-CoV-2 rapid circulations in the market and spread it to the whole city in early December 2019. Furthermore, phyloepidemiologic approaches have recovered specific direction of human-to-human transmissions, and the import sources of international infectious cases.

  • Heterogeneity in cancer stem cells

    分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11

    摘要: Accumulating evidence suggests that cancer stem cells (CSCs) are heterogeneous populations and their phenotypes are unstable. A number of intrinsic and extrinsic mechanisms contribute to CSC phenotypic variation. The existence of various CSC subpopulations which would lead to a rapid relapse after primary treatments might pose a problem for CSC targeted therapeutics. In order to develop more effective approaches to cancer therapeutics, more CSC-related surface markers or targeting molecules, as well as some novel targeting strategies should be explored. This review summarized the origin and performance of heterogeneity in CSCs and discussed their therapeutic implications. (c) 2014 Elsevier Ireland Ltd. All rights reserved.

  • Effective Treatment of Severe COVID-19 Patients with Tocilizumab

    分类: 医学、药学 >> 临床医学 提交时间: 2020-03-05

    摘要: Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, which spread rapidly and has become a world-wide public health challenge. We aimed to assess the efficacy of tocilizumab in severe patients with Corona Virus Disease-19 (COVID-19) and seek a new therapeutic strategy. Methods: The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between February 5 and February 14, 2020. The changes of clinical manifestations, CT scan image, and laboratory examinations were retrospectively analyzed. Findings: Within a few days, the fever returned to normal and all other symptoms improved remarkably. Fifteen of the 20 patients (75.0%) had lowered their oxygen intake and one patient need no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% patients (16/19). No obvious adverse reactions were observed. Nineteen patients (90.5%) have been discharged on average 13.5 days after the treatment with tocilizumab and the rest are recovering well. Interpretation: Tocilizumab is an effective treatment in severe patients of COVID-19, which provided a new therapeutic strategy for this fatal infectious disease.

  • Furin, a potential therapeutic target for COVID-19

    分类: 医学、药学 >> 药学 提交时间: 2020-02-23

    摘要: A novel coronavirus (SARS-CoV-2) infectious disease has broken out in Wuhan, Hubei Province since December 2019, and spread rapidly from Wuhan to other areas, which has been listed as an international concerning public health emergency. We compared the Spike proteins from four sources, SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that the SARS-CoV-2 virus sequence had redundant PRRA sequences. Through a series of analyses, we propose the reason why SARS-CoV-2is more infectious than other coronaviruses. And through structure based virtual ligand screening, we foundpotentialfurin inhibitors, which might be used in the treatment of new coronary pneumonia.

  • 武汉2019冠状病毒S蛋白可能存在Furin蛋白酶切位点

    分类: 生物学 >> 病毒学 提交时间: 2020-02-14

    摘要: 摘要:2019年12月,中国武汉报道了2019新型冠状病毒(2019 novel Coronavirus,2019-nCoV)引起的肺炎。基于基因组信息,我们前期研究结果显示2019-nCoV与SARS冠状病毒虽然同属于Beta冠状病毒B亚群(BB冠状病毒),但两种病毒差异很大,这一结果与两者临床症状差异一致。前期研究还发现了BB冠状病毒存在大量的可变翻译,并从分子水平揭示了BB冠状病毒变异快、多样性高的特点。本研究在国际上首次报道BB冠状病毒S蛋白上的一个重要突变,这个突变使2019-nCoV具有了一个可供Furin蛋白酶切的位点,是除鼠肝炎冠状病毒外所有的其它BB冠状病毒(包括SARS和SARS样(SARS-like)冠状病毒)所不具有的。这个突变有可能增强了2019-nCoV侵染细胞的效率,进而使其传播力显著大于SARS冠状病毒。由于这个突变,2019冠状病毒的包装机制也会不同于SARS等其它大部分Beta冠状病毒,而有可能与鼠肝炎冠状病毒、HIV、埃博拉病毒和一些禽流感病毒的包装机制相同。作为一个意外发现,一些禽流感病毒也可以通过突变获得Furin蛋白酶切位点。对这个重要突变的后续研究将为揭示2019-nCoV传播力强的原因,以及为药物、抗体和疫苗的开发等工作奠定基础。

  • 迁移学习研究进展

    分类: 计算机科学 >> 计算机应用技术 提交时间: 2016-05-03

    摘要: 近年来,迁移学习已经引起了广泛的关注。迁移学习是运用已存有的知识对不同但相关领域问题进行求解的新的一种机器学习方法。传统机器学习基于两个基本假设:(1) 用于学习的训练样本与新的测试样本满足独立同分布的条件;(2) 必须有足够可利用的训练样本才能学习得到一个好的分类模型。迁移学习降低了要求,目的是迁移已有的知识来解决目标领域中仅有少量或没有有标签样本数据时的学习问题。本文对迁移学习算法以及相关理论研究进展进行了综述,并介绍了我们在该领域所做的研究工作,特别是利用生成模型在概念层面建立迁移学习模型。最后指出了迁移学习下一步可能的研究方向。

  • 贝叶斯因子及其在JASP中的实现

    分类: 心理学 >> 心理统计 提交时间: 2018-05-08

    摘要: 统计推断在科学研究中起到关键作用,然而当前科研中最常用的经典统计方法——零假设检验(Null hypothesis significance test, NHST)却因难以理解而被部分研究者误用或滥用。有研究者提出使用贝叶斯因子(Bayes factor)作为一种替代和(或)补充的统计方法。贝叶斯因子是贝叶斯统计中用来进行模型比较和假设检验的重要方法,其可以解读为对零假设H0或者备择假设H1的支持程度。其与NHST相比有如下优势:同时考虑H0和H1并可以用来支持H0、不“严重”地倾向于反对H0、可以监控证据强度的变化以及不受抽样计划的影响。目前,贝叶斯因子能够很便捷地通过开放的统计软件JASP实现,本文以贝叶斯t检验进行示范。贝叶斯因子的使用对心理学研究者来说具有重要的意义,但使用时需要注意先验分布选择的合理性以及保持数据分析过程的透明与公开。

  • 大数据的核心问题与研究体系

    分类: 计算机科学 >> 计算机应用技术 提交时间: 2017-03-09

  • 深度学习概述

    分类: 计算机科学 >> 计算机应用技术 提交时间: 2016-05-03

    摘要: 深度学习是机器学习领域的一个新的研究方向,其核心思想在于模拟人脑的层级抽象结构,通过无监 督的方式从大规模数据(例如图像、声音和文本)中学习特征。近年来,深度学习在计算机视觉、语音识 别等研究领域取得的巨大成功使得研究者们对其寄予更多的关注。本文从深度学习的概念、发展历程、模 型、训练方法以及应用等几个方面对其进行概述,并对深度学习的未来发展做出展望。

  • PROSODIC BOUNDARIES EFFECT ON SEGMENT ARTICULATION IN STANDARD CHINESE:AN ARTICULATORY AND ACOUSTIC STUDY

    分类: 语言学及应用语言学 >> 语言学及应用语言学 提交时间: 2019-06-20

    摘要: This paper presents an electropalatographic (EPG) and acoustic study of prosodic boundaries effect on the domain-initial segments in Standard Chinese.1 Two speech sounds, namely, the voiceless unaspirated alveolar stop /t/ and the high front vowel /i/, were studied to examine the domain-initial strengthening in both spatial and temporal dimensions. The articulatory and acoustic parameters of the speech sounds were compared in initial positions of five prosodic constituents in Standard Chinese, namely, a Syllable, a Foot, an Immediate Phrase, an Intonational Phrase, and an Utterance. The results show that: (1) the production of the domain-initial consonantal gesture was prosodically encoded. The linguopalatal contact and the seal duration varied as a function of the prosodic boundary strength. The linguopalatal contact was dependent on the seal duration in a nonlinear fashion. Of the acoustic properties of the domain-initial stop, the total voiceless interval and voicing during closure were found to be reliable acoustic correlates that mark the hierarchical structure of the prosody. (2) At the release moment of the domain-initial stop, no consistent pattern was found to support the domain-initial strengthening. The linguopalatal contact of the vowel immediately following the domain-initial consonant did not show a clear trend of domain-initial strengthening; however, the phonatory features of vowels were indicative of pitch reset at major prosodic boundaries. These indicate that the domain-initial strengthening is restricted on the segment immediately following the boundary. In conclusion Standard Chinese strengthens the phonetic features of the domain-initial segments as a function of boundary strength, which serves as an important way to mark prosodic structure in Standard Chinese.

  • 我国科研人员对arXiv认知和使用的现状调查与分析

    分类: 图书馆学、情报学 >> 图书馆学 提交时间: 2016-03-14

    摘要: 【目的】了解中国用户对 arXiv预印本平台的认知、使用情况以及对 arXiv发展的意见建议。【方法】基于国内 9家高校及科研机构的教师、研究人员和研究生群体的问卷调查,作者获得 510份调查数据,并运用 SPSS等分析工具对调查数据进行分析。【结果】结果表明,我国科研人员对 arXiv的认知程度还不是很高,但熟悉 arXiv的国内科研人员已认识到在 arXiv上发布论文是占据成果首发权和征求同行意见的重要手段。【局限】在调查取样上仅限于中国 arXiv服务工作组的成员单位,非成员单位的 arXiv用户没有纳入。【结论】为了让 arXiv能够更多地惠及我国科研,中国 arXiv服务工作组需要采取更为积极的行动,加快推动 arXiv在国内更广泛深入的应用。

  • 基于语言结构功能的音位负担计算方法

    分类: 语言学及应用语言学 >> 语言学及应用语言学 提交时间: 2019-06-20

    摘要: 根据结构语言学的音位对立理论和以各种语言语料库为基础,进行了一系列的理论研究和数据分析,提出了音位结构功能负担的计算方法。计算步骤主要包括:1)音节对立频次统计;2)对立类型负担量计算;3)音位系统的负担量计算;4)音位的平均负担量计算。利用本方法,以汉语20个方言3000音节为研究对象,计算了对立类型负担量、音位系统负担量和音位的平均负担量在方言上的分布,并提出了音位负担量计算的基本理论。本方法可应用于语言音位功能研究、语言历史音变和演化研究以及语音工程的应用研究。

  • Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia

    分类: 医学、药学 >> 临床医学 提交时间: 2020-02-28

    摘要: A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China, Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improve the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China from Jan 23, 2020. to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients with COVID-19 pneumonia in 14 days without observed adverse effect. The pulmonary function and symptoms of all patients with COVID-19 pneumonia were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased and the overactivated cytokine-secreting immune cells CXCR3 CD4 T cells, CXCR3 CD8 T cells, and CXCR3 NK cells were disappeared in 3-6 days. And a group of CD14 CD11c CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level TNF-α is significantly decreased while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

  • Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells

    分类: 医学、药学 >> 临床医学 提交时间: 2020-02-27

    摘要: BackgroundThe COVID-19 cases increased very fast in the last two months. The mortality among critically ill patients, especially the elder ones, was relatively high. Considering that most of the dead patients were caused by severe inflammation response, it is very urgent to develop effective therapeutic agents and strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown very good capability to modulate immune response and repair the injured tissue with good safety. Case PresentationHere, we reported the treatment process and clinical outcome of a 65-year-old female critically ill COVID-19 patient infected with 2019-nCoV (now called SARS-CoV-2). The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic hUCMSCs.ConclusionsOur results suggested that the adoptive transfer therapy of hUCMSCs might be an ideal choice to be used or combined with other immune modulating agents to treat the critically ill COVID-19 patients.

  • COVID-19 outbreak increased risk of schizophrenia in aged adults

    分类: 心理学 >> 临床与咨询心理学 分类: 医学、药学 >> 预防医学与公共卫生学 提交时间: 2020-02-29

    摘要: We noticed an unusual increase of first-time patients with schizophrenia (F20) in January 2020 since the outbreak of COVID-19. The aim of this retrospective study is to validate this observation and find potential risk factors, if applicable. A total number of 13,783 records from outpatients in January 2020 were investigated thoroughly. Comparisons between incidence of schizophrenia in outpatients in January 2020 and similar periods of 2017-2019 were made to minimize seasonal influence. Relationship of incidence of schizophrenia and COVID-19 infections in China was calculated. Limited personal information (age, gender, approximate residence) was analyzed to find risk factors.After excluding seasonal factors such as Spring festival, a positive relationship between incidence of schizophrenia in first-time patients and countrywide epidemic situation was found. Statistical results further showed a significant increase of median age from 39 to 50 for first-time patients diagnosed with schizophrenia which is unusual. Meanwhile, a slight but not significant change was found in distribution of gender and approximate residence (urban/suburb). Our data supported that COVID-19 outbreak increased risk of schizophrenia in aged adults which is consistent with the fact that COVID-19 is more lethal to elders. We strongly appeal that public healthcare in countries either with or without infected patients should prepare in advance for potential risks in public mental health.

  • Lasso回归:从解释到预测

    分类: 心理学 >> 心理统计 提交时间: 2020-05-14

    摘要: 传统的最小二乘回归法关注于对当前数据集的准确估计,容易导致模型的过拟合,影响模型结论的可重复性。随着方法学领域的发展,涌现出的新兴统计工具可以弥补传统方法的局限,从过度关注回归系数值的解释转向提升研究结果的预测能力也愈加成为心理学领域重要的发展趋势。Lasso方法通过在模型估计中引入惩罚项的方式,可以获得更高的预测准确度和模型概化能力,同时也可以有效地处理过拟合和多重共线性问题,有助于心理学理论的构建和完善。

  • 新型冠状病毒(2019-nCoV)时空数据集及其典型应用

    分类: 测绘科学技术 >> 摄影测量与遥感技术 分类: 医学、药学 >> 预防医学与公共卫生学 分类: 统计学 >> 生物与医学统计学 提交时间: 2020-02-19

    摘要: 目前,新型冠状病毒(2019-nCoV)疫情正受到全球各科研工作者的广泛关注。然而,当前尚没有一个官方的渠道对2019-nCoV疫情数据进行实时开源,为了促进本次疫情相关的科研工作,本研究旨在为广大科研工作者提供权威的、开放的和多尺度的新型冠状病毒(2019-nCoV)时空数据集,为疫情监测、防控、预测和预警提供重要的数据来源。此外,该数据集还能应用于2019-nCoV疫情的多尺度、多时相制图和可视化,为疫情的空间分布、演化、趋势分析和模拟预测提供指导。

  • 生物磁受体蛋白MagR/IscA研究进展

    分类: 生物学 >> 分子生物学 提交时间: 2016-06-16

    摘要: 铁硫簇蛋白是一类重要的线粒体功能蛋白,在细胞能量代谢、电子传递、底物结合与激活、铁/硫存储、酶促反应、基因表达调控等诸多过程中均发挥了关键作用. 一旦铁硫簇组装及转运过程发生障碍,必将严重影响细胞内铁的稳态及铁硫蛋白的功能. 其中,分子量约 11-kDa 的 IscA,是铁硫蛋白亚家族 hesB 之一的高保守性成员,能结合铁离子及[2Fe-2S]簇,从而参与铁硫簇蛋白的合成,因此在铁硫簇组装蛋白系统中具有重要的作用. 更值得关注的是,2015 年谢灿和张生家各自研究组分别发现了 IscA1 具有独特的磁感应(magnetic sensor,MagS)与磁受体(magnetic receptor,MagR)功能. 尤为重要的是,通过外磁场刺激相关磁基因表达,能够调控神经活动及行为定位. 鉴于磁受体的独特功能并结合相关技术,遂将其统称为磁遗传学(磁基因学). 本文简要介绍 IscA 蛋白的始初发现与鉴定历程、进化保守性及其独特的生理生物学功能,并凝练出磁遗传假说机制调控模型.

  • 金庸小说人物的大五人格—基于文心系统的15部金庸小说分析

    分类: 心理学 >> 人格心理学 提交时间: 2018-02-12

    摘要: [目的]从心理学的角度全面分析金庸小说人物人格与创作阶段、性别之间的关系。[方法]本文通过创作阶段对金庸15部小说进行划分,采用基于数据挖掘的文学智能分析方法,通过中文心理分析系统对人物对话进行处理,得到人物的大五人格预测分数。[结果] 女性人物的神经质倾向高于男性人物;创作阶段影响小说人物的尽责性、外向性倾向。[局限]仅仅对小说中的人物进行了分析,没有和金庸本人生平经历和创作时代特点相结合。[结论]本文从心理学人格理论出发探讨金庸小说的人物描写特点,丰富了“金学”的研究成果,为研究金庸的人物刻画风格与偏好提供了新的视角。

  • Copula熵:理论和应用

    分类: 数学 >> 统计和概率 分类: 统计学 >> 数理统计学 分类: 信息科学与系统科学 >> 信息科学与系统科学基础学科 提交时间: 2023-11-29

    摘要: 统计独立性是统计学和机器学习领域的基础性概念,如何表示和度量统计独立性是该领域的基本问题。Copula理论提供了统计相关关系表示的理论工具,而Copula熵理论则给出了度量统计独立性的概念工具。本文综述了Copula熵的理论和应用,概述了其基本概念定义、定理和性质,以及估计方法。介绍了Copula熵研究的最新进展,包括其在统计学的九个基本问题(结构学习、关联发现、变量选择、因果发现、系统辨识、时延估计、域自适应、正态性检验和双样本检验等)上的理论应用。讨论了前四个理论应用之间的关系,以及其对应的深层次的相关性和因果性概念之间的联系,并将Copula熵的(条件)独立性度量框架与基于核函数和距离相关的同类框架进行了理论对比,又通过仿真和实际数据实验评估验证了Copula熵的实际优越性。简述了Copula熵在理论物理学、天体物理学、理论化学、化学信息学、材料学、水文学、气候学、气象学、环境学、生态学、动物形态学、农学、认知神经学、运动神经学、计算神经学、心理学、系统生物学、生物信息学、临床诊断学、老年医学、精神病学、公共卫生学、经济学、管理学、社会学、教育学、计算语言学、新闻传播学、法学、政治学、军事学、情报学,以及能源工程、食品工程、土木建筑、交通运输、制造工程、可靠性工程、化学工程、航空航天、车辆工程、电子工程、通信工程、高性能计算、测绘遥感和金融工程等领域的实际应用。