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LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

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Progress in Natural Science:Materials International 2006年第1期16卷 30-38页

作者： DENG Hongwen1,2.3 and GAO Guimin2.4 (1.Laboratory of molecular and Statistical Genetics, College of Life Sciences, Hunan Normal university, Changsha 410081, China 2.Osteoporosis Research {2., Creighton university Medical {2., Omaha NE 68131, USA 3. Department of Biomedical Sciences, Creighton university, Omaha NE 68131, USA 4. Virginia Bioin format ics Institute and Department of Statistics, Virginia Polytechnic Institute and State university, Blacksburg VA 2.061-0315, USA) [a]Laboratory of molecular and Statistical Genetics College of Life Sciences Human National University Changsha China [b]Osteoporosis Research center Creighton University Medical Center Omaha NE USA [c]Department of Biomedical Sciences Creighton University Omaha NE USA [d]Virginia Bioinformatics Institute and Department of Statistics Virginia Polytechnic Institute and State University Blacksburg VA USA

The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.

Internalization and distribution of three α1-adrenoceptor subtypes in HEK2.3A cells before and after agonist stimulation

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Acta Pharmacologica Sinica 2007年第3期28卷 359-366页

作者： Shu-yi WANG~2.Yao SONG~2.Ming XU~2.Qi-hua HE~3 Qi-de HAN~2.You-yi ZHANG~(2.4)2.Institute of Vascular Medicine,Peking university Third Hospital and Key Laboratory of molecular Cardiovascular Sciences,Ministry of Education,Beijing 100083,China 2.{2. of Medical Analysis,Peking university,Health Science {2.,Beijing 100083,China Institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100083 China center of Medical Analysis Peking University Health Science Center Beijing 100083 China

Aim:To examine the subcellular distribution of the 3 α1-adrenoceptor（α1-AR）subtypes and their internalization and trafficking upon agonist stimulation in hu-man embryonic kidney 2.3A ***:Confocal real-time imaging,enzymelinked immunosorbent assay（ELISA）and whole cell[3H]-prazosin binding assaywere applied to detect the distribution and localization of the 3 α1B-AR ***:α1A-AR was found both on the cell surface and in the cytoplasm;α1B-AR,however,was predominantly detected on the cell surface,while α1D-AR wasdetected mainly in the intracellular *** stimulation withphenylephrine,localization changes were detected by confocal microscopy forα1A-and α1B-AR, but the localization of α1D-AR were *** promoted a more rapid internalization of α1B-AR than α1A-AR.α1D-ARinternalization was detected only by *** cell[3H]-prazosin bindingassay showed that α1A-AR functional receptors were detected both on the cellsurface and in the cytoplasm;α1B-AR,however,were detected predominantly onthe cell surface,while α1D-AR were detected mainly in intracellular *** stimulation promoted internalization of α1A-and α***:Phenylephrine stimulation induced changes in the localization of the3α1-AR.

关键词： adrenoceptor agonist stimulation confocal image enzyme-linked immunosorbent assay [~3H]-prazosin binding assay internalization subcellular distribution subtype

The effect of hydrogen on the electronic structure of kink in bcc iron

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Science China(Technological Sciences) 2009年第5期52卷 1212-1218页

作者： CHEN LiQun1,QIU ZhengChen1,YU Tao2.& WANG ChongYu2.3,4 1 College of Sciences,Central South university of Forestry and Technology,Changsha 410004,China 2.Central Iron and Steel Research Institute,Beijing 100081,China 3 Department of Physics,tsinghua university,Beijing 100084,China 4 International center for Materials Physics,Chinese Academy of Sciences,Shenyang 110016,China 1. College of Sciences Central South University of Forestry and Technology Changsha 410004 China 2. Central Iron and Steel Research Institute Beijing 100081 China 3. Department of Physics Tsinghua University Beijing 100084 China 4. International center for Materials Physics Chinese Academy of Sciences Shenyang 110016 China

The electronic structures of kinks in the [100](010) and 1/2.111](-110) edge dislocations in bcc iron containing hydrogen are investigated by means of the first-principles DMol method and the discrete variational *** effects of hydrogen on the kinks are *** results show that hydro-gen forms weak bonding states with its neighboring host atoms,and since hydrogen draws charge from its neighboring host atoms,the interactions between most of the host atoms are weakened com-pared with those of the corresponding atomic pairs in the clean *** indicates that the migration of kink,*** motion of dislocation,is easier in the doping hydrogen kink than in the clean kink,which may be the solid solution softening effect resulting from the impurity hydrogen.

关键词： electronic structure dislocation kink impurity

molecular hosts for triplet emitters in organic light-emitting diodes and the corresponding working principle

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Science China Chemistry 2010年第8期53卷 1679-1694页

作者： MI BaoXiu1,2.GAO ZhiQiang1,LIAO ZhangJin2.HUANG Wei2.& CHEN Chin Hsin3 1Jiangsu Engineering center for Flat-Panel Displays & Solid-State Lighting School of Materials Science & Engineering,Nanjing university of Posts & Telecommunications,Nanjing 2.0046,China 2.ey Laboratory for Organic Electronics & Information Displays (KLOEID),Institute of Advanced Materials (IAM),Nanjing university of Posts & Telecommunications,Nanjing 2.0046,China 3Display Institute,Microelectronics and Information Systems Research center,National Chiao Tung university Hsinchu,Hsinchu,300 China 1. Jiangsu Engineering center for Flat-Panel Displays & Solid-State Lighting School of Materials Science & Engineering Nanjing University of Posts & Telecommunications Nanjing 210046 China2. Key Laboratory for Organic Electronics & Information Displays (KLOEID) Institute of Advanced Materials (IAM) Nanjing University of Posts & Telecommunications Nanjing 210046 China3. Display Institute Microelectronics and Information Systems Research Center National Chiao Tung University Hsinchu Hsinchu 300 China

This paper summarizes the mechanism and routes for excitation of triplet emitters in dopant emission based phosphorescent organic light-emitting diodes (PhOLEDs),providing a comprehensive overview of recent progress in molecular hosts for triplet emitters in ***,based on the nature of different hosts,e.g.,hole transporting,electron transporting or bipolar materials,in which the dopant emitters can be hosted to generate phosphorescence,the respective device performances are summarized and *** are given to the relationships among the molecular structure,thermal stability,triplet energy,carrier mobility,molecular orbital energy level and their corresponding device performances.

关键词： phosphorescent organic light-emitting diodes (OLEDs) working principle electrophosphorescence hosts triplet emitter

Microstructure and Mechanical Properties of Heat-treated GeSb_2.e_4 Thin Films

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Journal of Wuhan university of Technology(Materials Science) 2007年第2期22卷 196-200页

作者：丁建宁解国新 Micro/Nano Science & Technology center Jiangsu University State Key Laboratory of Tribology Tsinghua University

The effect of annealing on microstructure, adhesive and frictional properties of GeSb2.e4 films were experimentally studied. The GeSb2.e4 films were prepared by radio frequency （RF） magnetron sputtering, and annealed at 2.0℃ and 340℃ under vacuum circumstance, respectively. The adhesion and friction experiments were mainly conducted with a lateral force microscope （LFM） for the GeSb2.e4 thin films before and after annealing. Their morphology and phase structure were analyzed by using atomic force microscopy （AFM） and X-ray Diffraction （XRD） techniques, and the nanoindention was employed to evaluate their hardness values. Moreover, an electric force microscope （EFM） was used to measure the surface potential. It is found that the deposited GeSb2.e4 thin film undergoes an amorphous-to-fcc and fcc-to-hex structure transition; the adhesion has a weaker dependence on the surface roughness, but a certain correlation with the surface potential of GeSb2.e4 thin films. And the friction behavior of GeSb2.e4 thin films follows their adhesion behavior under a lower applied load. However, such a relation is replaced by the mechanical behavior when the load is relatively higher. Moreover, the GeSb2.e4 thin film annealed at 340℃ presents a lubricative property.

关键词： GeSb2.e4 films annealing microstructure mechanical properties friction

Evidence of DNA-Ligand Binding with Different Modes Studied by Spectroscopy

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Chinese Chemical Letters 2000年第2期11卷 147-148页

作者： Xue Mei WANGI1 Xian Lun JIANG1 Zu Hong LU1 Hong Yuan CHEN2.(1National Lab of molecular and Biomolecular Electronics, Southeast {2., Nanjing 2.0096 2.epartment of Chemistry, Nanjing {2., Nanjing 2.0094) Southeast Univ Natl Lab Mol & Biomol Elect Nanjing 210096 Peoples R China Nanjing Univ Dept Chem Nanjing 210094 Peoples R China

The binding behavior of several fluorescence dyes to calf thymus DNA has been studied by absorption, fluorescence and atomic force microscopy (AFM), which could provide direct evidence of formation modes and the corre... 详细信息

关键词： atomic force microscopy (AFM) absorption spectroscopy fluorescence DNA interaction

Interferon-α enhances sensitivity of human osteosarcoma U2.S cells to doxorubicin by p53-dependent apoptosis

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Acta Pharmacologica Sinica 2007年第11期28卷 1835-1841页

作者： Xiang-wei YUAN~2.Xiao-feng ZHU~(3,5),Xiu-fang HUANG~4,Pu-yi SHENG~2.Ai-shan HE~2.Zi-bo YANG~2.Rong DENG~3,Gong-kanFENG~3,Wei-ming LIAO~(2.5)~2.Department of Orthopedic Surgery,The First Affiliated Hospital,Sun Yat-sen university,Guangzhou 510080,China ~3 State Key Laboratoryof Oncology in South China,Cancer center,Sun Yat-sen university,Guangzhou 510060,China ~4 Department of Pathology,The AffiliatedJiangmen Hospital,Sun Yat-sen university,Jiangmen 52.030,China Department of Orthopedic Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China State Key Laboratory of Oncology in South China Cancer Center Sun Yat-sen University Guangzhou 510060 China Department of Pathology The Affiliated Jiangmen Hospital Sun Yat-sen University Jiangmen 529030 China

Aim:To determine whether interferon-α(IFNα) can enhance doxorubicinsensitivity in osteosarcoma cells and its molecular ***:Cellviability was evaluated using 3-(4,5-dimethylthiazol-2.yl)-2.5-diphenyltetrazoliumbromide *** was studied using Flow cytometry analysis,Hoechst332.8 staining,DNA fragmentation assay,as well as the activation ofcaspase-3 and poly (ADP-ribose) *** expression was detectedby Western *** dependence of p53 was determined using ***:IFNα increased doxorubicin-induced cytotoxicity to a muchgreater degree through apoptosis in human osteosarcoma p53-wild U2.S cells,but not p53-mutant MG63 ***α markedly upregulated p53,Bax,Mdm2.andp2.,downregulated Bcl-2.and activated caspase-3 and PARP cleavage in re-sponse to doxorubicin in U2.S ***,the siRNA-mediated silencing ofp53 significantly reduced the IFNα/doxorubicin combination-induced cytotoxic-ity and PARP ***:IFNα enhances the sensitivity of humanosteosarcoma U2.S cells to doxorubicin by p53-dependent *** propercombination with IFNα and conventional chemotherapeutic agents may be a ra-tional strategy for improving the treatment of osteosarcoma with functional p53.

关键词： Interferon-α doxorubicin apoptosis p53 osteosarcoma

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高准确度的钙离子光频标

物理学报 2018年第16期67卷 155-164页

作者：管桦黄垚李承斌高克林中国科学院武汉物理与数学研究所波谱与原子分子物理国家重点实验室武汉430071 中国科学院武汉物理与数学研究所中国科学院原子频标重点实验室武汉430071 中国科学院冷原子物理中心(武汉) 武汉430071

近年来,冷原子技术和激光技术促进了高精度光频标的发展,有望在建立时间基准、推动基础研究和满足国家需求等方面发挥重要的作用.本文介绍了中国科学院武汉物理与数学研究所近年来在高准确度钙离子(^(40)Ca^+)光频标研究方面的进展:采... 详细信息

近年来,冷原子技术和激光技术促进了高精度光频标的发展,有望在建立时间基准、推动基础研究和满足国家需求等方面发挥重要的作用.本文介绍了中国科学院武汉物理与数学研究所近年来在高准确度钙离子(^(40)Ca^+)光频标研究方面的进展:采用新的ULE腔系统,实现了72. nm钟跃迁激光器1—100 s的频率稳定度均优于2.10^(-15),通过对外场和环境效应的控制及克服,特别是囚禁离子运动效应的抑制,获得单个钙离子光频标的不确定度优于5.5×10^(-17);通过两台光频标的比对,测得2.000 s的稳定度也进入10^(-17)量级;基于高精度钙离子光频标平台,进行了相关精密测量的工作,包括:基于全球定位系统的超高精度远程光频绝对值测量方案,第二次测量了钙离子的光频跃迁绝对值,该测量结果再次被国际时间频率咨询委员会采纳,更新了钙离子的频率推荐值;精确测量了钙离子的钟跃迁魔幻波长,由此提出新型的全光囚禁离子光频标的方法;精密测量了钙离子的亚稳态寿命等参数.以上工作推动了基于冷原子的精密测量工作.

关键词：光频标精密测量钙离子魔幻波长

PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers:Preparation,Characterization and Release in vitro

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Journal of Wuhan university of Technology(Materials Science) 2007年第1期22卷 112-116页

作者：刘卫杨祥良 College of Life Science and Technology Huazhong University of Science and Technology

To assess the merits of PEGylated poly （lactic-co-glycolic acid）（PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 2.0 nm and zeta potential less than -2. mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

关键词： tumor necrosis factor-α receptor blocking peptide PEG-PLGA stealth nanoparticles ring-opening polymerization controlled and sustained drug release