Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

Oxysterols direct B-cell migration through EBI2

EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein-Barr-virus infection. Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism. The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors. Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7α,25-dihydroxycholesterol (OHC), with a dissociation constant of 450?pM for EBI2. In vitro, 7α,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7α,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7α,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7α,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.     

Q235钢的直接电加热渗硼研究

通过Q235钢直接电加热洛硼工艺试验，研究了Q235钢渗硼层的生长规律、组织组成、渗层深度分布状态和硬度分布状态，并与其在电阻炉中加热作了比较。探讨了电磁场对渗硼深度的影响。结果发现：直接电加热可以充分发挥电磁场的化学催渗和物理催渗作用。提高渗层质量，加速渗硼过程，缩短渗硼周期。     

试论英语专业词汇教学的综合技能培养

基于对国内外词汇教学的相关理论的分析探讨和实践认识,本文针对英语专业的词汇教学提出了几点具体而有效的教学方法,如词块链接输入教学,词块输出导向教学等。旨在于强调英语专业词汇学习的根本原则应是培养学习者理解和运用词汇的语言能力,最终达到提高英语综合技能素质的教学目的。     

An integrative model and analysis of cell cycle in fission yeast

Cell cycle is a programmed process, during which a cell proliferates to two daughter cells. The eukaryotic or-ganisms share the same characters, such as four cycle phases G1, S, G2 and M, the evolutionally conserved cell cycle proteins and its dependent kinases, and the check-points mechanism[1,2]. Due to the different functions and the complicated interactions of these proteins involved in cell cycle, it is very difficult to understand the regulatory mechanism of cell cycle in a whole sense …     

工业化住宅系统的建模和整体优化分析

根据我国住宅产业现代化的需要，用大系统控制理论讨论了工业化住宅系统的结构模型、邻接矩阵、状态方程组及知识模型，构建了工业化住宅系统的集成模型，提出了工业化住宅系统的优化设计原则和目标函数，分析了工业化住宅形成过程中的多级递阶协调控制结构，并指出工业化住宅提供了整体优化的住宅建设新模式，可通过在线控制工业化住宅系统的信息流、物质流和资金流达到整体优化住宅建设系统的目的．     

仪器分析实验教学立体优化的探索与实践

在仪器分析实验教学中,从实验仪器管理模式、实验仪器开放模式、实验教学过程管理和考核体系几方面进行了全面优化改革。在实验仪器管理上,采取了同类仪器集中管理的措施,同时实现了师资力量的合理分配;为了进一步有效提高实验教学质量,在实验仪器开放过程中,面向学生采用"一人一器"的实验开放模式,并在教学过程中提出了实验内容"一体化"、"小导师"制等改革新举措。立体化的仪器分析实验教学模式,突出了学生的主体性,培养其创新意识和科学研究能力,取得了良好的教学效果。     

基于最长次长匹配分词的一体化中文词法分析

针对当前大多数词法分析系统流水线式处理方式存在的不足,提出一种一体化同步词法分析机制.在最长次长匹配分词的基础上,在切分有向图中增加词性信息和候选未登录词节点,并拓展隐马尔可夫模型,在切分有向图内同步完成分词、歧义消解、未登录词识别和词性标注等词法分析任务.实现了分词与词性标注的一体化、未登录词识别与分词的一体化以及不确定词性未登录词处理的一体化.一体化机制使词法分析中各步骤实现真正意义上的同步完成,充分利用上下文词法信息提高整体精度并保证了系统的高效性,避免了各步骤间的冲突.开放测试表明,系统综合测试的F值为98.03%.     

山苦菜嫩茎直接分化无性系的建立

为了保护山苦菜资源,满足人们对种苗栽培的需求,分别以山苦菜茎尖、叶片、叶柄和无芽嫩茎为外植体,进行直接分化不定芽的诱导培养.结果表明:嫩茎是直接分化出不定芽的理想材料,最佳分化培养基为MS+BA 0.5mg/L+IBA 0.5mg/L+KT 0.5mg/L+蔗糖30g/L;1/4MS+IAA 0.2mg/L+蔗糖20g/L是分化芽生根的理想培养基;山苦菜再生苗移栽的理想基质是1/2园土+1/2河沙,移栽成活率为98.4%,移栽成活苗定植的成活率为98.8%.本实验证明:在适宜条件下可由嫩茎直接分化建立起山苦菜无性系.     

瓢虫干标本基因组DNA的提取及RAPD分析

实验对保存多年的瓢虫干标本进行了基因组 ＤＮＡ提取和 ＲＡＰＤ－ＰＣＲ扩增。结果显示 ＤＮＡ分子的提取与保存年代长短无直接关系;ＲＡＰＤ－ＰＣＲ增产物经琼脂糖凝胶电泳检测,分子量大小约为 １９８４ｂｐ～６３０ｂｐ;不同种瓢虫的 ＤＮＡ用同一引物,扩增片段是多态表现,同一种瓢虫的干标本保存时间虽不同,但扩增产物中均具有相同的ＤＮＡ片段。     

大跨度桥梁颤振时域的直接分析法

文章采用三维空间内单位脉冲响应函数描述自激力的方法,改进传递函数最小二乘法的拟合方法,从自激力时域描述公式中分离出气动质量,使得公式中的时间历程与当前时间无关,消除了迭代计算中由自激力时域公式引起的荷载非线性,提高了计算速度和计算精度;通过ANSYS实现颤振时程分析,以具有理想平板截面的简支梁和马鞍山长江大桥右汊桥为例...     

混凝土单轴直接拉伸受力分析

对3种直接拉伸试验方式(内埋式、外夹式和粘贴式)下混凝土试件各点的应力分布状况进行了有限元数值分析,对获得混凝土单轴直接拉伸应力-应变全曲线所需的条件进行了探讨,并对试件在两端粘贴受力方式下辅以刚性架装置后刚性架拉杆刚度、位置对试件受力的影响进行了研究.结果表明:两端粘贴加载方式可使试件各点应力分布更加均匀,应力集中程度较低;减小刚性架的高度、增大刚性架的截面积有利于获得完整的应力-应变全曲线.     

克隆植物珠芽蓼基因组DNA的提取及RAPD鉴定

高原植物体内所含有的酚类、多糖、色素等次生代谢物质严重影响提取其基因组DNA的得率和纯度,是导致后续分子操作失败的主要原因.运用一种新改进的CTAB法对变色硅胶保存的高原植物珠芽蓼(Polygonumviviparum)叶片进行基因组DNA的提取,采取常温下沉淀DNA,增加洗涤沉淀的体积分数为70%乙醇用量和洗涤时间等措施,有效地去除了酚类、多糖、色素等物质的干扰,减少了褐化现象的发生.样品检测所得DNA片段均在48 kb左右,电泳谱带呈线状,无拖尾现象;紫外分光光度计检测,A260nm/A280nm值在1.7~1.9之间.RAPD扩增结果表明,此方法提取的DNA无论在质量和纯度上都较理想.     

车载序列影像直接相对定向质量

为验证地面大转角、小面幅序列数码影像直接相对定向质量.推导了一套基于SIFT特征匹配的计算机视觉分析方法,解算过程简洁明了.研究结果表明:基于计算机视觉方法能够有效解决大转角影像、特别是车载序列数码影像相对定向中的匹配难题,解算结果比较稳定;从目前的结果来看,直接相对定向质量还不高,但研究方法对室内移动机器人环境感知、无人驾驶等导航领域具有一定的借鉴价值;最后分析了制约其质量的主要原因,为今后分析和提高视觉量测质量提供了一条思路.     

基于FSPMM的直驱型纯电动汽车驱动桥设计

以一种新型开关磁通永磁电机为动力源驱动装置,介绍了新型开关磁通永磁电机的工作原理、结构参数和设计过程,结合汽车主减速器、差速器和电机,实现电动汽车的直驱设计。利用有限元分析软件对电机的结构参数进行优化,对输出特性进行仿真,结果表明,所设计的开关磁通永磁电机具有较好的鲁棒性和较高的转矩功率密度,满足纯电动汽车的运行要求。     

一个基于信号分析的直和分解定理

根据经典Fourier分析中关于L^2（R^2）的直和分解,利用近期信号分析中由Mo bius变换引出的一系列结果,得到了更为广泛的直和分解,证明了其所有子空间在Fourier变换下保持不变,并且推出了其子空间里任意函数Fourier变换的具体表达式。