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

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 center, Creighton university Medical center, 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 24061-0315, 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.

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Industrial Biosystems Engineering and Biorefinery Systems

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生物工程学报 2008年第6期24卷 940-945页

作者： Shulin Chen Institute of Microbiology Chinese Academy of Sciences Beijing 1 O0101 ChinaDepartment of Biological Systems Engineering Washington State University USA

The concept of Industrial Biosystems Engineering (IBsE) was suggested as a new engineering branch to be developed for meeting the needs for science, technology and professionals by the upcoming bioeconomy. With emphasis on systems, IBsE builds upon the interfaces between systems biology, bioprocessing, and systems engineering. This paper discussed the background, the suggested definition, the theoretical framework and methodologies of this new discipline as well as its challenges and future development.

关键词：生物工程生物系统生物技术发展现状

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Azolla-A Model Organism for Plant Genomic Studies

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Genomics, Proteomics & Bioinformatics 2003年第1期1卷 15-25页

作者： Yin-Long Qiu, Jun Yu1 department of Ecology and Evolutionary Biology, university of Michigan, Ann Arbor, MI 48109-1048, usa 2 Beijing Genomics Institute, Chinese Academy of Scicences, Beijing 101300, China 3 university of washington Genome center, Seattle, WA 98195, usa department of Ecology and Evolutionary Biology University of Michigan Ann Arbor MI 48109-1048 USA. yqiu@bio.umass.edu

The aquatic ferns of the genus Azolla are nitrogen-fixing plants that have great potentials in agricultural production and environmental conservation. Azolla in many aspects is qualified to serve as a model organism for genomic studies because of its importance in agriculture, its unique position in plant evolution, its symbiotic relationship with the N2-fixing cyanobacterium, Anabaena azollae, and its moderate-sized genome. The goals of this genome project are not only to understand the biology of the Azolla genome to promote its applications in biological research and agriculture practice but also to gain critical insights about evolution of plant genomes. Together with the strategic and technical improvement as well as cost reduction of DNA sequencing, the deciphering of their genetic code is imminent.

关键词： Azolla nitrogen fixation genome model organism

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Inducible resistance to Fas-mediated apoptosis in B cells

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Cell Research 2000年第4期10卷 245-266页

作者： ROTHSTEIN THOMAS L departments of Medicine and Microbiology, and the Evans Memorial department of Clinical Research, Boston university Medical center, Boston, MA, usa 1departments of Medicine and Microbiology and the Evans Memorial Department of Clinical Research Boston University Medical Center Boston MA USA

Apoptosis produced in B cells through Fas (APO-1, CD95) triggering is regulated by signals derived from other surface receptors: CD40 engagement produces upregulation of Fas expres. sion and marked susceptibility to Fas-induced cell death, whereas antigen receptor engagement, or IL-4R engagement, inhibits Fas killing and in so doing induces a state of Fas-resistance, even in otherwise sensitive, CD40-stimulated targets. Surfaceim. munoglobulin and IL-4R utilize at least partially distinct pathways to produce Fas-resistance that differentially depend on PKC and STAT6, respectively. Further, surface immunoglob- "lin signaling for inducible Fas-resistance bypasses Bib, requires NF-GB, and entails new macromolecular synthesis. Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products, Bcl-xL and FLIP, and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule). faim was identified by differential display and exists in two alternatively spliced forms; maim-S is broadly expressed, but faim-L expression is tissue-specific. The FAIM sequence is highly evolu tionarily conserved, suggesting an important role for this molecule throughout phylogeny. Inducible resistance to Fas killing is hypothesized to protect foreign antigen-specific B cells during potentially hazardous interactions with FasL-bearing T cells, whereas autoreactive B cells fail to become Fas-resistant and are deleted via Fas-dependent cytotoxicity. Inadvertent or aberrant acquisition of Fas-resistance may permit autoreactive B cells to escape Fas deletion, and malignant lymphocytes to impede anti-tumor immunity.

关键词： Apoptosis Fas B lymphocytes FAIM FLIP Bcl-XL surface immunoglobulin IL-4R CD40 autoreactivity

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Progress of gastric cancer etiology:N-nitrosamides in the 1990s

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World Journal of Gastroenterology 2000年第4期6卷 613-618页

作者： Da Jun Deng Laboratory of cancer Etiology,Beijing Medical university School of oncology& Beijing Institute for cancer Research,100034,China 北京医科大学北京

Stomach carcinoma is still the leading cause of cancer death in China and the second one in the world. Its possible causes include: A) chemical factors such as intragastric formation of N-nitroso compounds (NOC) and high salt intake; B ) biological factors such as infection of Helicobacter pylori and biotoxins intake; and C ) nutritional factors such as deficiency of vitamin C, selenium, and other antioxidants. Nitrogenous precursors of NOC, e.g., alkylamines, alkylureas, alkylguanidines, and alkylamides, occur widely in nature and potential nitrosating agents, e.g., nitrite (NO2-) and NOx (the gaseous oxides of nitrogen ) are similarly widespread. Relationship between exposure to NOC and causes of human cancer was investigated extensively ten years ago. Results indicated that the exposures of NOC might contribute to the occurrences of malignancy in the upper digestive tracts including stomachs. It was also observed that both high salt intake and deficiency of some micronutrients enhanced NOC-induced carcinogenicity. Recent studies show that infection of H. pylori can lead to atrophic gastritis and achlorhydria, and promote endogenous formation of NOC indirectly[1] . Much attention has been paid to stomach cancer and NOC regarding the characterization of natural N-nitrosamides in human environment in the 1990s.

关键词： stomach neoplasms/etiology nitroso compounds nitrosamides/nitrosourea epidemiology chromatography liquid microorganisms

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Expression of hepatitis B virus surface antigen in 120 Hodgkin's lymphoma patients

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Chinese Journal of cancer 2010年第8期29卷 735-740页

作者： Miao-Zhen Qiu1,2, Dan-Yun Ruan1,2, Zhi-Qiang Wang1,2, Hui-Yan Luo1,2, Kai-Yuan Teng1,2, Zhong-Jun Xia1,3, Yue Lu1,3, Hui-Qiang Huang1,2, Wen-Qi Jiang1,2, Rui-Hua Xu1,2 1 State Key Laboratory of oncology in South China, Sun Yat-sen university cancer center, Guangzhou, Guangdong 510060, P. R. China 2 department of Medical oncology, Sun Yat-sen university cancer center, Guangzhou, Guangdong 510060, P. R. China 3 department of Hematology oncology, Sun Yat-sen university cancer center, Guangzhou, Guangdong 510060, P. R. China Sun Yat-sen university cancer center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Background and Objective: Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient. Methods: Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen university cancer center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis. Results: Of the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen (HBsAg)-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (Ⅰ+Ⅱ) and advanced-stage (Ⅲ+Ⅳ) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P 4.8%, P=0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P=0.006 and 0.014, respectively). Conclusions: The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

关键词：乙肝病毒表面抗原淋巴瘤患者乙肝表面抗原多因素分析金病毒感染肝炎病毒

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Effect of Recql5 deficiency on the intestinal tumor susceptibility of Apc^(min) mice

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World Journal of Gastroenterology 2010年第12期16卷 1482-1486页

作者： Yiduo Hu,Xincheng Lu,Guangbin Luo,department of Genetics,Case Comprehensive cancer center and university Hospitals of Cleveland,Case Western Reserve university,Cleveland,OH 44106,United States Yiduo Hu,department of cancer Biology,Dana-Farber cancer Institute,Boston,MA 02115,United States department of Genetics Case Comprehensive Cancer Center and University Hospitals of Cleveland Case Western Reserve University 10900 Euclid Avenue Cleveland OH 44106 United States. guangbin.luo@case.edu

AIM:To investigate whether Recql5,a DNA helicase that plays an important role in the maintenance of genome integrity,is a tumor suppressor in the gastrointestinal tract in ***:We generated cohorts of both Recql5-proficient and Recql5-deficient Apcmin/+mice and compared the tumor susceptibility in their gastrointestinal ***:Recql5 deficiency in Apcmin/+mice resulted in a significant increase in the tumor incidence in both the colon(P=0.0162)and the small intestine(P<0.01).These findings have provided the first genetic evidence for a tumor suppression role of Recql5 in the gastrointestinal tract of ***,since mouse Recql5 and human RECQL5 are highly conserved,these findings also suggest that RECQL5 may be a tu-mor suppressor for human colon ***:Recql5 has a tumor suppression role in the mouse gastrointestinal tract.

关键词： Recql5 Apc Tumor suppressor Genome instability Colon cancer Apcmin/+mice

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Discrete Element Modeling of Asphalt Concrete Cracking Using a User-def ined Three-dimensional Micromechanical Approach

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Journal of Wuhan university of Technology(Materials Science) 2011年第6期26卷 1215-1221页

作者：陈俊 College of Civil and Transportation Engineering Hohai University

We established a user-defined micromechanical model using discrete element method （DEM） to investigate the cracking behavior of asphalt concrete （AC）. Using the ＂Fish＂ language provided in the particle flow code in 3-Demensions （PFC3D）, the air voids and mastics in asphalt concrete were realistically built as two distinct phases. With the irregular shape of individual aggregate particles modeled using a clump of spheres of different sizes, the three-dimensional （3D） discrete element model was able to account for aggregate gradation and fraction. Laboratory uniaxial complex modulus test and indirect tensile strength test were performed to obtain input material parameters for the numerical simulation. A set of the indirect tensile test were simulated to study the cracking behavior of AC at two levels of temperature, i e, -10 ℃ and 15 ℃. The predicted results of the numerical simulation were compared with laboratory experimental measurements. Results show that the 3D DEM model is able to predict accurately the fracture pattern of different asphalt mixtures. Based on the DEM model, the effects of air void content and aggregate volumetric fraction on the cracking behavior of asphalt concrete were evaluated.

关键词： discrete element method asphalt concrete cracking behavior three-dimensional simulation micromechanics

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Science Letters:Radio frequency heating: a potential method for post-harvest pest control in nuts and dry products

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Journal of Zhejiang university-Science A(Applied Physics & Engineering) 2004年第10期 3-8页

作者： WANG Shao-jin, TANG Ju-ming(department of Biological Systems Engineering, washington State university, Pullman, WA 99164-6120, usa) department of Biological Systems Engineering Washington State University Pullman WA 99164-6120 USA

The multi-billion dollar US tree nut industries rely heavily on methyl bromide fumigation for postharvest insect control and are facing a major challenge with the mandated cessation by 2005 of its use for most applications. There is an urgent need to develop effective and economically viable alternative treatments to replace current phytosanitary and quarantine practices in order to maintain the competitiveness of US agriculture in domestic and international markets. With the reliable heating block system, the thermal death kinetics for fifth-instar codling moth, Indianmeal moth, and navel orangeworm were determined at a heating rate of 18℃/min. A practical process protocol was developed to control the most heat resistant insect pest, fifth-instar navel orangeworm, in in-shell walnuts using a 27 MHz pilot scale radio frequency (RF) system. RF heating to 55℃ and holding in hot air for at least 5 min resulted in 100% mortality of the fifth-instar navel orangeworm. Rancidity, sensory qualities and shell

关键词： Disinfestation Heat Nut Postharvest Radio frequency

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Some results on numerical divided difference formulas

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Science China Mathematics 2005年第11期48卷 1441-1450页

作者： Wang Xinghua,Wang Heyu & Ming-Jun Lai department of Mathematics, Zhejiang university, Hangzhou 310028, China Computing center, Zhejiang university, Hangzhou 310012, China department of Mathematics, university of Georgia, Athens, GA 30602-7403, usa 1. department of Mathematics Zhejiang University 310028 Hangzhou China 2. Computing center Zhejiang University 310012 Hangzhou China 3. department of Mathematics University of Georgia 30602-7403 Athens GA USA

The remainder estimates of numerical divided difference formula are given for the functions of lower and higher smoothness, respectively. Then several divided difference formulas with super-convergence are derived wit... 详细信息

关键词： numerical divided difference remainder estimate functions of lower smoothness sufficiently smooth functions super convergence.

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