ABSTRACT MICROARRAY APPLICATIONS FOR DETERMINATION OF THE EFFECTS OF EMODIN ON BREAST CANCER CELL LINES Ekenel Qomi, Emilia M.S., Department of Biotechnology Supervisor: Prof. Dr. Mesude Iscan Co-Supervisor: Assoc. Prof. Dr. Nursen &Ccedil / oruh February 2012, 191 pages Cancer is a genetic disease that is characterized by uncontrolled cells growth. Breast cancer is a type of cancer originating from breast tissue. Some breast cancers are sensitive to hormones such as estrogen which makes it possible to treat them by blocking the effects of these hormones in the target tissues. These require less aggressive treatment than hormone negative cancers. Breast cancers without hormone receptors, are higher-risk, and are treated more aggressively. The aim of our study is to investigate the effect of emodin on MCF-7 which is ER (estrogen receptor) positive, and MDA-MB-231 (ER negative) cancerous cell lines. Emodin which is a phytoestrogen component, extracted from rheum (genus) plant, has been reported to suppress the growth of tumor in some clinical situation, and it&rsquo / s found that emodin induced apoptosis through the decrease of Bcl-2/Bax ratio and the increase of cytoplasm cytochrome c concentration in human breast cancer Bcap-37 cells. Comparing the effect of emodin between ER positive and ER negative cells at the molecular level was investigated by Microarray analysis of gene expressions using Affymetrix Human Genome U133 plus 2.0 Array. The microarray data analysis was performed by using BRB-Array Tools, v.4.2.0. GST and its classes / Alpha, Mu, Pi, Theta, Sigma, Omega, Zeta and Kappa is our interested genes because of its role in regulating susceptibility to cancer, by their ability to metabolize reactive electrophilic intermediates to usually less reactive and more water soluble glutathione conjugates. And also its have a role in detoxifying the damage caused by oxidative stress which is a result of the radiotherapy. v The differentially expressed genes from emodin treated and untreated control breast cancer cell lines were compared after normalization and filtering and annotated, it was shown that the top 10 highly (significantly) varied genes belong to the biological processes such as (namely) cell cycle, cell division, cell proliferation, mitosis and meiosis, this insure the relation of emodin to the cell growth processes in the cancerous cells. The analysis of the change on the cell growth confirmed the anti-tumor effect of emodin. About the effect of emodin treatment on MCF-7 and MDA-MB-231 cancerous cell lines separately / Both cells its significant genes was belong to cell growth biological processes, in MCF-7 cells in-addition other biological processes was shown, for example / stimulus to estradoil response, and the metabolism of xenobiotic by cytochrome p450, so CYP1A1 gene code for a protein which is used in emodin metabolism. The varied gene number was nearly 4400 gene from the scatter plot result in MCF-7 cells while in MDA-MB-231 cells it was nearly 3400 gene, these result insured the effect of emodin as a phytoestrogenic component as MCF-7 cells are ER positive cells, so emodin bind to the ER in MCF-7 cells and affected more gene number than MDA-MB-231. More number of GST enzyme classes changed in MCF-7 cells than MDA-MB-231, and the effect of emodin as anti-cancer showed different change of GST genes between MCF-7 and MDA-MB-231. The results confirmed by network analysis done, to find the most related genes to our top 10 regulated gene list, and these genes were analyzed / most of them where in our gene list, and their regulation after emodin treatment analyzed and the result was supported to emodin as anti-tumor and phytoestrogenic component.

Du fait de leur complexité croissante, le développement des systèmes embarqués et temps réel nécessitent conjointement l'application de principes de génie logiciel et l'application de techniques formelles. Le travail développé pendant cette thèse propose une approche et des outils basés sur les modèles. Ces modèles, basés sur UML (Unified Modeling Language), permettent de définir un style architectural appelé SAIA (Sensors Actuators Independent Architecture) dont l'objectif est le développement et la mise au point de systèmes temps réel en intégrant l'évolution et la variabilité des plateformes. On entend ici par plateforme les services de communication entre le système et son environnement physique, c'est-à-dire des opérations de lecture et d'écriture via les capteurs et les actionneurs.<br /><br />Pour répondre à cet objectif, l'idée de SAIA est de séparer clairement le modèle de plateforme du modèle de l'application. À cette fin, SAIA propose l'introduction d'une plateforme de communication abstraite avec le processus. Cette plateforme abstraite est composée d'entrées et de sorties utiles pour effectuer le contrôle, mais indépendantes d'une technologie de capteurs/actionneurs particulière. L'application est développée en se basant sur les services fournis par la plateforme abstraite.%Une application temps réel ne peut pas être validée en ne considérant que ses aspects fonctionnels.<br />La stabilité d'une application de contrôle et sa qualité de contrôle sont, entre autres, dépendantes des caractéristiques temporelles de la plateforme abstraite. Cette dernière est donc composée d'un ensemble de services ainsi que d'une description de ses caractéristiques temporelles (notées QoS pour Quality of Service). La description de la QoS de la plateforme abstraite reflète le comportement temporel, sous forme de omega-expression régulière de la plateforme abstraite pour laquelle l'application a le comportement souhaité. Ainsi, nous avons d'un côté un modèle de la plateforme abstraite et de la QoS permettant la correction de l'application et de l'autre un modèle de la plateforme réelle dont la QoS a été analysée. Afin de connecter la plateforme abstraite à la plateforme réelle, SAIA s'appuie sur un connecteur complexe. Ce connecteur complexe est un assemblage de composants, décrit formellement par des automates temporisés réalisant des services de formatage, d'interprétation, de fusion de données et enfin d'adaptation de la QoS.<br />Le connecteur complexe possède un comportement et modifie donc la QoS de la plateforme réelle. Afin d'évaluer l'impact du connecteur complexe sur la QoS de la plateforme réelle, une analyse formelle basée sur la simulation exhaustive du connecteur complexe est réalisée. Il est alors nécessaire de s'assurer que cette QoS nouvellement évaluée satisfait la QoS de la plateforme abstraite et permet ainsi la réalisation d'un système correct. La vérification de cette satisfaction est basée sur l'établissement d'un contrat de QoS. Dans SAIA, l'établissement d'un contrat de QoS est basé sur une relation de satisfaction (équivalence de trace) entre systèmes à transitions étiquetés. Enfin, SAIA a été mis en oeuvre à plusieurs reprises dont, lors de deux concours d'implémentation de robots d'exploration terrestre dans le cadre de workshop satellites de RTSS (Real Time System Symposium).

Jörn Sieglerschmidt, Bibliotheksservice-Zentrum Baden Württemberg, Konstanz, führte seine Zuhörer durch die schwierigen Aufgaben bei der Vertextung von Museumsgut, wobei er deutlich machte, dass anders als im Bibliothekswesen die Grenzen zwischen Formal- und Sacherschließung fließend sind: http://titan.bsz-bw.de/cms/museen/musis/publ/sieglerschmidt_freiburg2007.pdf

Thesis (MA)--University of Stellenbosch, 2005. / Bibliography. Also available via the Internet.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-09-02T14:02:19Z No. of bitstreams: 1 SEBASTIÃO ESTEFÂNIO PINTO RABELO JÚNIOR - DISSERTAÇÃO PPGCC 2011..pdf: 13091249 bytes, checksum: 1cb0178385eb3bd7c5eb2d8c16dd72ac (MD5) / Made available in DSpace on 2018-09-02T14:02:19Z (GMT). No. of bitstreams: 1 SEBASTIÃO ESTEFÂNIO PINTO RABELO JÚNIOR - DISSERTAÇÃO PPGCC 2011..pdf: 13091249 bytes, checksum: 1cb0178385eb3bd7c5eb2d8c16dd72ac (MD5) Previous issue date: 2012-11-11 / Capes / Atualmente, quando se fala em UML, temos os diagramas de sequência como o mais popular entre os diagramas usados para descrever aspectos comportamentais de um software. Por outro lado, temos Java como uma das linguagens orientadas a objetos mais usada no mundo. Entretanto, não encontramos em nossas pesquisas um meio sistêmico para a verificação automática de conformidade entre modelos comportamentais e o código desenvolvido para atender esse modelo. Nesta dissertação, nós desenvolvemos uma abordagem capaz de verificar- esse tipo de conformidade. O uso dessa abordagem permitirá ajudai- desenvolvedores, analistas, e gerentes de projeto a manter a documentação do software atualizada, além de possibilitar a existência de um novo ponto de vista a respeito de defeitos na implementação de um sistema. Para dar suporte a essa verificação de conformidade nós desenvolvemos uma ferramenta baseada em Model Driven Architecture (MDA) capaz de gerar os testes de conformidade aqui apresentados. Além disso, esta dissertação traz uma avaliação da abordagem desenvolvida, a qual apresenta os principais resultados obtidos. / Currently, sequence diagrams are the most popular UML diagrams used to describe behavioral aspects of software systems. On the other hand, Java as one of the most popular object-oriented language used in lhe world. Despite that. there is no systematic approach to support verification between the behavioral design and the implemented source code. In this work, we propose an approach to verify this conformity. The use of this approach vvill help developers, architects, and engineers to maintain the software documentation updated. Its usage allows that the development team and managers to detect behavioral design implementation defects. We also present the tool support built for our approach using Model Driven Architecture (MDA) and a preliminary evaluation about this work.

Made available in DSpace on 2016-06-02T19:05:38Z (GMT). No. of bitstreams: 1 2623.pdf: 2743696 bytes, checksum: cc0c40ac7065c499f2cd408b70711f1d (MD5) Previous issue date: 2009-07-03 / Financiadora de Estudos e Projetos / This thesis presents an approach to Development based on Model-Driven Architecture, of Ubiquitous Applications Domain Software Product Lines. The approach uses Model-Driven Architecture to facilitate the modeling reuse of the same application in different architectures of the Ubiquitous Computing. With focus in the problem domain, the Software Product Lines core is developed and it is reused in the products construction. One of the assets that composed the Software Product Lines is the Ubiquitous Computing Framework, developed to attend the non functional requirements of Ubiquitous Computing. The CASE tool, called MVCASE, makes automatic part of the activities in the proposed approach. / Essa dissertação apresenta uma Abordagem para Desenvolvimento baseado em Model-Driven Architecture, de Linha de Produto de Software orientada a domínios de Aplicações Ubíquas. A abordagem utiliza a Model-Driven Architecture para melhor atender as diversidades de arquiteturas da Computação Ubíqua e facilitar o reuso. Com foco no domínio do problema, desenvolve-se o Core Asset, núcleo da Linha de Produto de Software, que é reutilizado na construção dos produtos derivados da linha. Um dos artefatos do Core Asset é Ubiquitous Computing Framework construído para atender os requisitos não funcionais da Computação Ubíqua. Uma ferramenta CASE, denominada MVCASE, automatiza grande parte do processo da Model-Driven Architecture, desde a modelagem até a geração parcial de código.

Made available in DSpace on 2016-06-02T19:06:09Z (GMT). No. of bitstreams: 1 5515.pdf: 2859644 bytes, checksum: 8f2473af784eb07ff38067a957051dde (MD5) Previous issue date: 2013-08-27 / Universidade Federal de Sao Carlos / Software systems are considered legacy when they were developed many years ago with outdated technologies and their maintenance process consumes a large amount of resources. One cause of these problems is the inadequate modularization of its crosscutting concerns. In this situation, an alternative is to modernize the system with a new language to provide better support for concern modularization. ADM (Architecture-Driven Modernization) is an OMG model-driven proposal to modernize legacy systems and consist of a set of metamodels in which the main metamodel is KDM (Knowledge Discovery Metamodel), which allows to represent all the characteristics of a system. The modernization process begins with reverse engineering to represent the legacy system in a KDM model. Thereafter, refactorings can be applied to the model and then generate the modernized code. However, the current proposals do not support crosscutting concerns modularization. This occurs because the first step is to identify the elements which contribute with the implementation of a particular concern and it is not supplied by ADM. In this sense, this dissertation presents an approach for mining crosscutting concerns in KDM models, thus establishing the first step towards to a Concern-Driven modernization. The approach is a combination of two techniques, a concern library and a modified K-means clustering algorithm, which comprises four steps where the input is a KDM model and the result is the same KDM model with annotated concerns and some log files. In addition, we developed an Eclipse plugin called CCKDM to implement the approach. An evaluation was performed involving three software systems. The results show that for systems using APIs to implement their concerns the developed technique is an effective method for identifying them, achieving good values of precision and recall. / Sistemas de software são considerados legados quando foram desenvolvidos há muitos anos com tecnologias obsoletas e seu processo de manutenção consome uma quantidade de recursos além da desejada. Uma das causas desses problemas é a modularização inadequada de seus interesses transversais. Quando se encontram nessa situação, uma alternativa é modernizar o sistema para novas linguagens que forneçam melhor suporte à modularização desse tipo de interesse. A ADM (Architecture-Driven Modernization) é uma proposta do OMG para a modernização orientada a modelos de sistemas legados, sendo composta por um conjunto de metamodelos, em que o principal é o KDM (Knowledge Discovery Metamodel), que permite representar todas as particularidades de um sistema. O processo de modernização inicia-se com a engenharia reversa, em que o sistema legado é inteiramente representado em KDM. Depois disso, pode-se aplicar refatorações nesse modelo e gerar o código modernizado. Entretanto, a proposta atual da ADM não inclui suporte para modularizar interesses transversais de um sistema. Isso ocorre porque o primeiro passo desse processo é minerar e encontrar os elementos que contribuem para a implementação de um dado interesse, e isso não é fornecido pela ADM. Nesse sentido, nesta dissertação é apresentada uma abordagem para mineração de interesses no metamodelo KDM, estabelecendo o primeiro passo para um processo de modernização dirigido a interesses. A abordagem de mineração proposta atua com uma combinação de duas técnicas; uma biblioteca de interesses e um algoritmo modificado K-means para agrupar strings similares. A abordagem inclui quatro passos onde a entrada é um modelo KDM e o resultado é o mesmo modelo KDM com os interesses anotados e mais alguns arquivos de registro. Além disso, desenvolveuse um plugin chamado CCKDM para o ambiente Eclipse que implementa a abordagem. Uma avaliação foi realizada envolvendo três sistemas de software. Os resultados da avaliação mostraram que para sistemas que utilizam APIs para implementar seus interesses a técnica desenvolvida é efetiva para a identificação deles, atingindo bons valores de precisão e cobertura.

Even though there are many software development and project management methodologies available, research and practice both show that IT software development projects still fail, and that the quality of software products does not always meet customers' expectations. There might be multiple causes for such failures, but some of these reasons can be seen to influence or create others. Therefore, the larger the project is, the higher its risk of failure, especially if the teams involved work remotely (distributed and outsourced). This increase in project complexity is considered the motivation for this paper. Similarly, there are other factors that can result in a project's failure and customers' dissatisfaction regarding software quality. All such factors identified by research conducted by organizations specializing in this area are analyzed in order to identify a common root of IT project failures. Once the root causes of these failures have been identified and analyzed, the goal of the Interface based software development methodology is to solve them. The solution offered by an Interface based software development methodology is to improve understanding of software requirements and to describe these requirements with interfaces in an object-oriented way. Interface based software development will support and drive development towards service-oriented architecture (SOA) and component-based development (CBD). The goal of interface based software development is to increase software testability and maintainability and to make it more easily feasible to execute various software development processes in parallel.

La capacidad de comunicación e integración que ofrece Internet, está facilitando el establecimiento y automatización de relaciones entre los participantes de los nuevos Modelos de Negocio electrónico. Aunque no existe una clasificación definitiva de éstos, es posible distinguir la integración de datos y funcionalidad como un requisito fundamental para la implementación de los mismos. Algunos de los casos más significativos lo constituyen empresas como Google y Amazon que ofrecen a sus socios sus plataformas tecnológicas a través de interfaces (APIs) basadas en servicios Web. Estas compañías establecen contratos de negocio que brindan la posibilidad de integración de sus plataformas con las aplicaciones Web de los socios. Así, los diversos servicios que ofrecen les están disponibles y establecen con ello una relación que redunda en beneficio mutuo. Tres actores básicos se pueden distinguir para lograr esta integración: los servicios Web, las aplicaciones Web y los procesos Negocio-a-Negocio. Los primeros, al facilitar la producción y consumo de datos y funcionalidad independientemente de la implementación tecnológica de los sistemas; los segundos, al ser el tipo más dominante de aplicación que se ejecuta en Internet; y los terceros, al definir los pasos necesarios para la realización de los diversos procesos del negocio. Desde el punto de vista del modelado conceptual, se encuentran diversas propuestas, la mayoría basadas en modelos UML, para la especificación de estos tres actores. No obstante que en múltiples casos es necesaria su participación mutua, se observa que en muchas de estas propuestas se focalizan en sólo alguno y escasamente se encuentran opciones que los incluyan a los tres. Por ejemplo, desde el punto de vista de la Ingeniería Web, se encuentra un número mínimo de métodos que consideran de manera conjunta en sus propuestas los servicios Web y los procesos Negocio- a-Negocio. La mayoría de los métodos se centran en aplicaciones Web que ofrecen un espacio de navegación sobre grandes colecciones de datos, pero no permiten la integración de datos y funcionalidad de aplicaciones externas, como tampoco la exposición de su funcionalidad para consumo de otras. Por otro lado, desde el punto de los servicios Web, la mayor parte de las aproximaciones considera su especificación sin considerar su inclusión en aplicaciones Web o el papel que juega la interacción humana. La presente tesis ofrece una propuesta para el modelado conceptual de aplicaciones Web que integran datos y funcionalidad a partir de servicios Web, con consideraciones adicionales a los procesos Negocio-a-Negocio. La solución se expone en el contexto del método de Ingeniería Web Object Oriented Web Solutions (OOWS). Este método es la extensión para el modelado conceptual de aplicaciones Web del método clásico OO-Method. En su concepción original, OOWS ha sido diseñado para la consulta y actualización de datos, pero no para la integración de aplicaciones externas. La propuesta de esta tesis incluye un conjunto de adecuaciones y extensiones a sus primitivas conceptuales para la especificación de este tipo de aplicaciones. / Quintero Meza, RR. (2008). Desarrollo dirigido por modelos de aplicaciones web que integran datos y funcionalidad a partir se servicios web [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/1988 / Palancia

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and their presence in water bodies is documented. They discharge into surface water (SW) unmonitored, posing a threat to both aquatic and terrestrial lives. This is a challenge as not all populations have access to treated drinking water (TDW). The EDC contaminated serves as a route of exposure, together with ineffective treatment plants. Given the complexity of the endocrine system, EDCs may mimic or antagonise natural hormones or disrupt their synthesis, metabolism and excretion. The associated health effects include testicular dysgenesis syndrome, metabolic disorders and cancers. Policy and internationally standardised test methods are however sti ll limited. This study therefore aimed to assess the suitability of two assays used for screening estrogenic activity and one for androgenic activity in different water sources. The study consisted of two phases. In phase 1, water sample (tap, surface and treated wastewater) were collected from a catchment area in Pretoria. The samples and a spiked MilliQ laboratory water sample were extracted with solid phase extraction (SPE) and sent to Germany for distribution to participating laboratories. Samples (n=24) from six different countries were received to test for androgenic activity in the MDA-kb2 reporter gene assay. In phase 2, SW and TDW samples were collected from April 2015 until March 2016. The samples were filtered, extracted using SPE and assayed with the YES assay, T47D-KBluc reporter gene assay for estrogenic activity and MDA-kb2 reporter gene assay for androgenic activity. In phase 1, androgenic activity was detected in 4 out of 24 (21%) samples and ranged from 0.23 ± 0.040 ng/L to 0.008 ± 0.001 ng/L DHTEqs. In phase 2, estrogenic activity was detected in 16 out of 24 (67%) SW samples in the T47DKBluc reporter gene assay and ranged from 0.31 ± 0.05 pg/L to 10.51 ± 5.74 pg/L EEqs. It was below the detection limit (dl) in the YES assay. Androgenic activity was detected in 4 out of 24 (17%) SW samples, ranging from 0.0033 ± 0.0050 ng/L to 0.090 ± 0.040 ng/L DHTEqs. Androgenic and estrogenic activity was higher i n pretreatment samples compared to post-treatment in both treatment plants. In phase 1, the MDA-kb2 reporter gene assay was successfully applied to water samples from different sources. Androgenic activity was highest in treated wastewater. In phase 2, treatment plants proved to be effective in removing estrogens detected in the SW samples, as the TDW samples were below the dl. Estrogenic activity is within the ranges reported in other studies. Positive samples were below the 0.7 ng/L proposed trigger value for health risk assessments. Detected androgenic activity was lower in TDW samples compared to the SW samples supplying the two treatment plants indicating that they were both effective in removing the androgenic activity detected. Few studies have reported androgenic activity in tap water. This study strengthens the argument for using a battery of assays when monitoring endocrine activity as EDCs occur at low concentrations in mixtures. / Dissertation (MSc)--University of Pretoria, 2017. / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted