A Comparative Analysis of the Molecular Interaction Techniques for In Silico Drug Design

International Journal of Peptide Research and Therapeutics - Computer Aided Drug Discovery (CADD) has become a vital tool for the rapid identification of new candidate molecules prior to their...     

基于VT K 的D IC OM 医学图像三维重建研究

医学图像三维重建技术利用二维医学图像序列重建出三维模型,为医生提供直观、全面、准确的病灶和正常组织信息．是当今医学影像领域研究的热点之一。VTK是国际上广泛应用的可视化工具包,具有优秀的架构和运行机制。本文研究了DICOM3．0标准,提出了正确解读DICOM医学图像的方法;深入VTK内部机制,解决了VTK和DICOM医学图像读取模块间的数据接口问题;在三维重建过程中,为解决数据量巨大、成像时间漫长、阶梯效应、交互性不强等问题,重点剖析了VTK的数据处理机制。并给出相关优化方法。实验结果表明本文提出的解决方案和优化方法实用可靠,为进一步开发医学三雏图形系统打下了基础。     

Fundamental Principles for CAD-based Ecological Assessments (9 pp)

Background Aims, and Scope. As products are, directly and indirectly, main sources for ecological impact, the overall enhancement of products' ecological behaviour is an important contribution to the protection of the Earth's biosphere. This is especially important in a world where the major economical system is based on a constant rise in industrial production, consumption, and disposal of products. The true ecological performance of a product can only be determined by consideration of the impact arising from the entire lifecycle, and by including all known impacts into the assessments. The state of technology provides a standardized framework for such life cycle assessments (LCA) in the ISO 14040 series (see ISO 1997), and numerous databases and software tools are available to support the conduction of LCA. To integrate ecological indicators into decisions of everyday product development, as natural as it is the case today with finite items, design, and costs, indicators based on a consideration of the product's entire life have to be generated with little effort and in short time. Methods This article describes the fundamental principles of a technology designed to integrate lifecycle information into common 3-dimensional product models, like the ones used within modern Computer Aided Design (CAD) systems. Thereby, ecological assessments can be effectively undertaken during product development, where most of the environmental lock-in of a product is defined (see Lewis et al. 2001). Overall effects of alterations in materials or other product properties can be assessed instantly, supporting on the spot decisions to reach an improved product design. Results Next to an information model that manages the product and process representation, the research on which this article is based also deals with the calculation of resulting indicators, database access to ecological indicators, a graphical user interface, and a synchronisation tool for the CAD system Pro/Engineer . The developed concepts have been implemented as a prototype software and validated in different stages. Conclusions The concepts described in this article are a foundation for tools that integrate ecological assessments into everyday product development, on the basis of 3-dimensional CAD systems. Reuse of existing CAD data, an improved understanding of the assessment structure by product developers, and an automated calculation of resulting indicators are approaches to largely enhance the efficiency of product-related ecological assessments.     

CAGE Displays Oncogenic Potential and Induces Cytolytic T Lymphocyte Activity

The cancer associated gene (CAGE) is a novel cancer/testis antigen. Over-expression of CAGE enhanced growth rates, promoted cell motility and led to an ROS scavenging effect which was accompanied by an induced catalase cavity. Further, peptides of CAGE induced cytolytic T lymphocytes (CTL) activity, and CD8⁺ T cells pre-sensitized with these peptides displayed cytotoxic effects against cancer cells expressing CAGE. These results suggest that CAGE would be a valuable target for the development of an anti-cancer vaccine.     

Role of CAGE, a novel cancer/testis antigen, in various cellular processes, including tumorigenesis, cytolytic T lymphocyte induction, and cell motility

A cancer-associated antigen gene (CAGE) was identified by serological analysis of a recombinant cDNA expression library (SEREX). The gene was identified by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera from patients with gastric cancer. CAGE was found to contain a D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. The CAGE gene is widely expressed in various cancer tissues and cancer cell lines. Demethylation plays a role in the activation of CAGE in certain cancer cell lines where the gene is not expressed. The functional roles of CAGE in tumorigenesis, the molecular mechanisms of CAGE expression, and cell motility are also discussed.     

Cancer/Testis Antigen CAGE Exerts Negative Regulation on p53 Expression through HDAC2 and Confers Resistance to Anti-cancer Drugs

The role of the cancer/testis antigen CAGE in drug resistance was investigated. The drug-resistant human melanoma Malme3M (Malme3M^R) and the human hepatic cancer cell line SNU387 (SNU387^R) showed in vivo drug resistance and CAGE induction. Induction of CAGE resulted from decreased expression and thereby displacement of DNA methyltransferase 1(DNMT1) from CAGE promoter sequences. Various drugs induce expression of CAGE by decreasing expression of DNMT1, and hypomethylation of CAGE was correlated with the increased expression of CAGE. Down-regulation of CAGE in these cell lines decreased invasion and enhanced drug sensitivity resulting from increased apoptosis. Down-regulation of CAGE also led to decreased anchorage-independent growth. Down-regulation of CAGE led to increased expression of p53, suggesting that CAGE may act as a negative regulator of p53. Down-regulation of p53 enhanced resistance to drugs and prevented drugs from exerting apoptotic effects. In SNU387^R cells, CAGE induced the interaction between histone deacetylase 2 (HDAC2) and Snail, which exerted a negative effect on p53 expression. Chromatin immunoprecipitation assay showed that CAGE, through interaction with HDAC2, exerted a negative effect on p53 expression in Malme3M^R cells. These results suggest that CAGE confers drug resistance by regulating expression of p53 through HDAC2. Taken together, these results show the potential value of CAGE as a target for the development of cancer therapeutics.     

Anti hyperglycaemic study of natural inhibitors for Insulin receptor

Diabetes is a metabolic disorder associated with either improper functioning of the beta-cells or wherein cells fail to use insulin properly. Insulin, the principal hormone regulates uptake of glucose from the blood into most of the cells except central nervous system. Therefore, deficiency of insulin or the insensitivity of its receptors plays a key role in all forms of diabetes. In the present work, attempt has been made to find out plant sources which show anti hyperglycaemic activity (AhG) (i.e. compounds that bring down the blood glucose level in the body). Ayurvedic plants showing AhG activity formed the basis of our study by using the platform of Computer Aided Drug Designing (CADD). Among 600 plants showing AhG activity, 500 compounds were selected and screened, out of which 243 compounds showed drug likeness property that can be used as therapeutic ligand/drug. Initial screening of such compounds was done based on their drug likeness or biochemical properties. Dynamic interaction of these molecules was captured through Protein-Ligand study. It also gave an insight of the binding pockets involved. Bench marking of all the parameters were done using the diabetic inhibitor drug, Glipizide. Pharmacokinetic studies of the compounds such as Aloins, Capparisine, Funiculosin and Rhein exhibited less toxicity on various levels of the body. As a conclusion these ligands can lay a foundation for a better anti-diabetic therapy.

Abbreviations

AhG - Anti hyperglycaemic, CADD - Computer Aided Drug Designing.     

The effectiveness of web-based, multimedia tutorials for teaching methods of human body composition analysis

This study examined the effectiveness of a series of Web-based, multimedia tutorials on methods of human body composition analysis. Tutorials were developed around four body composition topics: hydrodensitometry (underwater weighing), dual-energy X-ray absorptiometry, bioelectrical impedance analysis, and total body electrical conductivity. Thirty-two students enrolled in the course were randomly assigned to learn the material through either the Web-based tutorials only ("Computer"), a traditional lecture format ("Lecture"), or lectures supplemented with Web-based tutorials ("Both"). All students were administered a validated pretest before randomization and an identical posttest at the completion of the course. The reliability of the test was 0.84. The mean score changes from pretest to posttest were not significantly different among the groups (65.4 plus minus 17.31, 78.82 plus minus 21.50, and 76 plus minus 21.22 for the Computer, Both, and Lecture groups, respectively). Additionally, a Likert-type assessment found equally positive attitudes toward all three formats. The results indicate that Web-based tutorials are as effective as the traditional lecture format for teaching these topics.     

DeviceEditor visual biological CAD canvas

Background  

Biological Computer Aided Design (bioCAD) assists the de novo design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.     

树鼩脑三维结构重建的研究 Ⅲ.脑外形立体结构的计算机辅助绘图

作者曾经详细介绍过树鼩脑切片二维结构重建的数据采集、计算机处理数据的算法及图形生成技术。在此基础上,本文介绍树鼩脑三维结构重建的数学模型及其自动生成三维图形的基本技术与计算机绘图的部分结果。     

Identification and characterization of a novel cancer/testis antigen gene CAGE

We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. The corresponding gene was named cancer-associated gene (CAGE). PCR of human x hamster Radiation Hybrids showed localization of CAGE on the human chromosome Xp22. Transient transfection of CAGE showed predominantly nuclear localization. Both Western blot and plaque assay indicated seroreactivity of CAGE protein. We found that demethylation played a role in the activation of CAGE in some cancer cell lines that do not express it. Cell synchronization experiments showed that the expression of CAGE was related with cell cycle. This suggests that CAGE might play a role in cellular proliferation. Because CAGE is expressed in a variety of cancers but not in normal tissues except testis, this gene can be a target of antitumor immunotherapy.     

Some final responses to Dr. Waugh

OBJECTIVE: To describe alcohol disorders in the general Canadian population, using as a standard indicator the CAGE questionnaire (Have you felt you needed to cut down on your drinking? Have you felt annoyed by criticism of your drinking? Have you felt guilty about drinking? Have you felt you needed a drink first thing in the morning [eye-opener]?). DESIGN: Secondary analysis of data from Canada''s Alcohol and Other Drugs Survey (CADS), a national telephone survey conducted in 1994 of a representative sample of 12,155 people aged 15 years or more. PARTICIPANTS: The CAGE questionnaire was administered to 5894 drinkers who had consumed alcohol in the 12 months before the CADS survey. MAIN OUTCOME MEASURES: Respondents with positive (2 or more affirmative responses) and negative results on the CAGE questionnaire were compared as to demographic characteristics, alcohol consumption and harmful consequences of their drinking. Independent predictors of a positive result were identified by means of logistic regression analysis. RESULTS: A total of 5.8% of CAGE-tested current drinkers had a positive result on the past-year CAGE in 1994. The proportion of respondents reporting alcohol-related problems in one or more areas of their life was 7 times greater among drinkers with a positive result on the CAGE questionnaire than among those with a negative result (66.8% v. 9.5%) (p < 0.0001). When all demographic characteristics were controlled for simultaneously, male sex, residence in the Atlantic provinces, Quebec or the Prairies, single/never married or divorced/separated marital status, and low education level were found to be independent risk factors for a positive result on the CAGE questionnaire. About 85% of the respondents with a positive result had not sought help for their drinking. Applying the estimated sensitivity and specificity of the CAGE questionnaire in detecting alcohol dependence, as per criteria of the Diagnostic and Statistical Manual, in a general US population, the authors estimated that 4.1% of Canadians had an alcohol dependence in 1994. CONCLUSION: The large proportion of current drinkers with a positive result on the CAGE questionnaire who did not seek help for their drinking underscores the need for identification and brief interventions by physicians. Further research is needed to elucidate the underlying reasons for regional differences in CAGE status.     

CAGE,a cancer/testis antigen,induces c-FLIP<Subscript>L</Subscript> and Snail to enhance cell motility and increase resistance to an anti-cancer drug

Cancer associated gene (CAGE) regulates expression of epithelial-mesenchymal transition (EMT)-related proteins through extracellular regulated kinase (ERK), Akt and nuclear factor κB (NF-kB) in mouse B16F10 melanoma cells. Snail, a EMT-related protein, mediates the effect of CAGE on the induction of matrix metalloproteinase-2 (MMP-2) and cancer cell motility. C-Flice inhibitory protein mediates the effect of CAGE on the induction of MMP-2 and cell motility by the induction of Snail. CAGE was shown to protect cells against celastrol, an anti-cancer agent. Celastrol-resistant B16F10 melanoma cells had a higher expression level of c-FLIP_L and Snail as compared with a sensitive cell line. Youngmi Kim and Hyunmi Park contributed equally to this work.