The aryl hydrocarbon receptor (AhR) binds synthetic and chemoprotective phytochemicals, and research in this laboratory has developed selective AhR modulators (SAhRMs) for treatment of breast cancer. Activation of the AhR through agonists such as TCDD inhibits hormone activation of several E2-responsive genes in breast cancer cell lines. In this study, inhibition of E2-induced proliferation and gene expression by TCDD has been investigated in the uterus of wildtype, ERKO and AhRKO mice. Cyclin D1, DNA polymerase ?, and VEGF mRNA levels are induced by E2 through ER? in the uterus as determined by in situ hybridization studies. TCDD down-regulated E2-induced cyclin D1 and DNA polymerase ? expression, but not E2-induced VEGF expression, in wild-type mice, but not AhRKO mice, confirming the role of the AhR. Furthermore, protein synthesis was not necessary for induction of cyclin D1 or DNA polymerase ?gene expression by E2 or inhibition of these responses by TCDD. Therefore, AhR-ER? crosstalk directly regulates the expression of genes involved in cell proliferation in vivo. AhR agonists induce down-regulation of ErbB family receptors in multiple tissues/organs suggesting possible inhibitory interactions with chemotherapeutic potential. Recently, it has been reported that the SAhRM 1,1??,2,2??-tetramethyldiindolylmethane inhibited DMBA-induced mammary tumor growth in rats and also inhibited MAPK and PI3-K pathways in human breast cancer cells. BT-474 and MDA-MB-453 cell lines are ErbB2-overexpressing breast cancer cells that express functional AhR and exhibit constitutive activation of MAPK and PI3-K pathways. Therefore, 1,1??,2,2??-tetramethyldiindolylmethane-induced inhibition of ErbB2 signaling was investigated in these cells lines and in the MMTV-c-neu mouse mammary tumor model, which overexpresses ErbB2 in the mammary gland. The growth of ErbB2 overexpressing cell lines and mammary tumors was inhibited by 1,1??,2,2??-tetramethyldiindolylmethane; however, modulation of MAPK or PI3-K pathways and cell cycle proteins nor induction of apoptosis by 1,1',2,2'-tetramethyldiindolylmethane was observed in the ErbB2overexpressing cell lines. Current studies are investigating mitochondrial effects of 1,1??,2,2??-tetramethyldiindolylmethane in the ErbB2-overexpressing cell lines, as well as continuing studies on gene expression profiles in the mammary glands of MMTV-c-neu mice to better understand and identify critical genes that are responsible for ErbB2-mediated transformation and growth of cancer cells/tumors.

Les travaux de cette thèse, menés dans le cadre du projet RNRT A3S, intègrent la notion de composants au sein d'une méthodologie de conception de plates-formes SoC (System on Chip), basée sur le langage de modélisation UML (Unified Modeling Language). Cette méthodologie propose un environnement de conception haut-niveau, basé sur le profil UML A3S, développé pour apporter la sémantique du domaine des systèmes temps réel embarqués et en particulier celle relative aux applications Radio Logicielle. Elle repose sur une approche MDA ou l'architecture est dirigée par les modèles où chaque modèle correspond à un niveau d'abstraction, à un niveau de raffinement particulier.<br /><br />Une chaîne UMTS a permis la validation de l'outil réalisé, en confrontant les résultats estimés de l'outil, à ceux mesurés sur une plate-forme temps réel hétérogène (multi-DSP, multi-FPGA). Une partie du travail s'est concentré sur l'identification des composants utiles à la conception des systèmes SoC, et de leurs caractéristiques, en adéquation avec le niveau d'abstraction considéré. Une autre partie des travaux a porté sur la définition des modèles UML, et donc du profil, qui définissent la sémantique des différents composants identifiés en fonction de la configuration (PIM, PSM), ainsi que leurs relations. Une réflexion a été nécessaire afin d'élaborer les diverses règles de vérification et modèles d'exécution qui permettent d'informer le concepteur de ses erreurs et de la faisabilité du système modélisé. Un modèle de système d'exploitation a également été inclus, enrichissant la liste des éléments (composants) déjà définis et démontrant l'extensibilité du profil.

本論文的目的是希望能以模型驅動方式，利用既有本體論提供的知識，快速產生與之相關的網路服務應用。我們的方法是先將本體論知識轉換為符合EMF超模型規格的中性模型，這些模型經人為修正與轉換之後，利用EMF和我們實作的產生器，即可從模型生成模型實作以及網路服務的WSDL與OWL-S描述檔。在產生出WSDL後，就可以用AXIS提供的工具，從WSDL的介面描述中生成網路服務的通訊端點實作。我們的系統整合了AXIS與EMF產出的程式碼，使系統能夠產生出比原本AXIS產出的實作更為完整的功能。最後，部分實作所缺之邏輯處理部份，則需由程式開發人員再予補足，即能建構出完整的網路服務。我們提出的這套方法與開發工具，讓開發人員能善用本體論知識，經由模型驅動的設計方式，快速地建構出網路服務系統。 / In this thesis we propose a model-driven approach by which we can make use of existing ontology knowledge to help construct a partial implementation of web services on related domains. The idea is to use existing formal ontologies for an application domain as the basis of requirement and system analysis. Our system then transforms these ontologies into platform neutral models conforming to the EMF metamodel, which, after additional refinements, can be used to construct platform dependent web service models as well as a partial implementation by following the typical MDA process with supporting tools. Finally, developers need only fulfill the lacked service logic and a complete web service can be obtained. In addition to providing and integrating supporting tools, the main contribution of our system is to leverage ontology for rapid construction of web services.

Daugeliui įmonių ar organizacijų reikalingos informacinės sistemos, skirtos valdytį jų procesus duomenis. Darbe analizuojamos verslo procesų, transakcijų modeliavimo galimybės, technologijos, standartai: RUP, UML, XML (XMI), MERODE, R. Gusto, WAE, BPMN, MDA, Agile. Deliau analizuojamas verslo procesų modelis ir jo plėtinys BPMN. Pateikti pasiųlymai notacijos išplėtimui duomenų objektais, modelių ir elementų interpretacija modeliuojant o modelius panaudojant kodo generavime. Sudarytas ir ištestuotas pilnai funkcionuojančio ir dalykinę sritį atitinkančio kodo generavimo algoritmas. / In nowadays a lot of business companies and organizations are using information systems. This paper analyses business transactions, tools and technologies for transactions and process modelling of information and enterprise systems. Analyzed popular technologies like UML and its extensions, RUP, XMI, MDA. Familiarized with MERODE and Agile methods. More closely analyzed BPMN notation and its possibilities for code generation. BPMN notation augment with data objects for better code generation solutions. It also gives better understanding of data flows and influence of business process and transactions. Defined process and transactions modelling strategy which allows better code generations solution too. Made-up, practically materialized ant tested code generation algorithm.

Dans le cycle de vie logiciel nous avons principalement les activités (1) de pré-développement (l'analyse des besoins, les spécifications, la conception architecturale et la conception détaillée), (2) de développement (l'implémentation, le prototypage, les tests unitaires et les tests d'intégration) et (3) de post-développement (déploiement). Le déploiement de logiciel couvre l'ensemble des activités post-développement. Les activités de déploiement permettent de rendre une application utilisable. Elles sont identifiées comme cycle de vie de déploiement couvrant l'archivage des logiciels, leur chargement, leur installation sur les sites clients, leur configuration, leur activation ainsi que leur mise à jour. Le développement de systèmes à composants a permis de mieux identifier cette partie du cycle de vie global du logiciel, comme le montrent de nombreux travaux industriels et académiques. Cependant ces travaux sont en général développés de manière ad' hoc, spécifiques à une plate-forme donnée. Peu flexibles, ils s'adaptent difficilement aux stratégies des entreprises. Les systèmes de déploiement comme le montrent ceux supportés par les environnements de type intergiciel CCM, .Net, EJB développent de manière spécifique les mécanismes et outils de déploiement et introduisent des choix prédéfinis et figés de stratégies de déploiement. Nos travaux se situent dans le contexte de logiciels à base de composants distribués et portent sur la proposition d'un environnement générique pour supporter leur déploiement. C'est une nouvelle génération de systèmes proposée essentiellement par le monde académique de génie logiciel qui s'est approprié la problématique de déploiement à large échelle. Dans ce contexte, nous proposons une approche basée sur l'ingénierie dirigée par les modèles où nous introduisons les abstractions nécessaires pour décrire les logiciels à déployer, les infrastructures de déploiement, les stratégies de déploiement ainsi que le processus de déploiement avec l'identification et l'ordonnancement des activités à accomplir et le support pour leur exécution.

No abstract available. / Thesis (M.A.)-University of Durban-Westville, 2003.

It can be argued that critical scholarship has not satisfactorily commented on the portrayal of women in South African theatre by male playwrights. This dissertation will examine the presentation of the female voice in the selected plays of two playwrights, namely Athol Fugard and Zakes Mda, coming from different socio-historical and cultural backgrounds. This comparative study will re-interrogate the selected representative texts from a feminist perspective, and will compare Fugard's subversive distrust of the female voice juxtaposed against Mda's refreshing celebration of the female presence in the selected plays. Fugard and Mda's female characters are generally seen by their readers, audiences and critics such as Andrew Hom, Marcia Blumberg and Dennis Walder as fundamentally vital, irrepressible and certainly more admirable than their male counterparts, as it is ultimately their quest for symbiosis and affirmation of the self which precludes any passive spectatorship on the part of the audience. However, paradoxically and ironically, it is Fugard, writing from a relatively privileged white male position, who consistently places his female characters in positions where their distinct inner strength is continually undermined. Despite their cognitive ability to engage with their situation, they are seldom permitted to triumph over the bleakness of their lives, but in fact are rendered emotionally impotent in the face of insurmountable existential isolation. Always situated within an interdependent relationship absent of hope and love, Fugard's women characters are never allowed to forget the role they are expected to assume in a patriarchal society rife with political and racial overtones. This very impasse in which they are placed by Fugard generally resonates strongly with the audience, who can identify or empathise with the women, but who are not afforded an imaginative escape by Fugard. Mda's female characters are created and portrayed within a similar political and universal system which perpetuates their exclusion from power and keeps them in servitude. However, unlike the ultimately silenced women in Fugard' splays, Mda, writing partly from a historically marginalised position himself, empowers his female characters with the freedom to confront and articulate their emotions and perceptions. His female characters are inscribed in a multiplicity of social positions, within which they most often find a solution to their problems and demand an outcome which is not only determined by outsiders, but by their own inner strength. Although they are less fettered by class and ideological constraints, they are however more naively drawn than Fugard's female characters. Whilst Fugard' s female characters in the selected plays are, without exception, left on the periphery of the play as the ultimate victims of their inescapable circumstances, the female characters created by Mda more often than not dominate the stage by virtue of their indomitable resilience, rather than resignation. This dissertation will also examine Fugard and Mda's presentation of their female characters as wholly a male's construct, set in a political context which subtextually interrogates race and gender. The implied assumption concerning the authority of the male writer over women's narratives will also therefore be questioned. Reference to Fugard and Mda's own personal histories as well as their other non-fictional writing will be seen as relevant in this regard. In conclusion, this dissertation will focus on the artificially imposed passivity of Fugard' s confined and limited female characters, and will compare this to Mda's empowerment of his female characters through critical awareness. The provocative issues of voice and violence as agency in both Fugard and Mda's discourse will be viewed, in particular, from within an apartheid system of governance. / Thesis (M.A.)-University of Durban-Westville, 2002.

ABSTRACT EFFECT OF SALT STRESS ON ANTIOXIDANT DEFENSE SYSTEMS OF SENSITIVE AND RESISTANT CULTIVARS OF LENTIL Cicerali, Iin Nur M.Sc., Department of Biotechnology Supervisor: Prof. Dr. Meral Y&uuml / cel Co-supervisor: Asst. Prof. Dr. F&uuml / sun (nci) Eyidoan June 2004, 90 pages In this study, two lentil cultivars (Lens culinaris, Medik.) (ILL5582-salt tolerant and ILL590) were characterized and compared due to their NaCl susceptibility and antioxidant mechanism was examined under laboratory conditions. Physiological parameters such as wet-dry weight, root-shoot lengths, cell membrane stability, lipid peroxidation in terms of malondialdehyde (MDA), H2O2, proline contents were determined. The activities of antioxidant enzymes such as superoxide dismutase (SOD: EC 1.15.1.1), catalase (CAT: EC 1.11.1.6), ascorbate peroxidase (APX: EC 1.11.1.11) and glutathione reductase (GR: EC 1.6.4.2) were examined and analyzed in 14 days old plant seedlings after 9 days of normal growth and 5 days of 100mM and 200mM NaCl stress conditions. Shoot-root length and wet-dry weight percent decrease were more in ILL590. Especially shoot tissues were affected more from the stress conditions when compared to root tissues. ii According to malondialdehyde (MDA) content and membrane stability results, lipid peoxidation was higher in ILL590 and significant increases were observed in shoot tissues. Proline concentration showed a remarkable increase in salt concentration dependent manner. Higher concentrations of proline in ILL5582 might be the reason of higher salt tolerance when compared to ILL590. Among the antioxidant enzymes SOD was the one which showed highest activity increase. At organ level roots showed highest activity when compared to leaves. In the organelle higher activity percent contribution was achieved by cytosolic Cu/ZnSOD isozyme. Higher percent increase of this isozyme was observed in ILL5582. This might be one of the tolerance mechanisms that get activated against NaCl stress. APX activity showed similar alterations in both cultivars. In leaf tissues significant increase was observed but in root tissues ascorbate peroxidase activity did not change significantly. Glutathione Reductase activity increase was significant in both cultivars leaf tissues but although ILL5582 showed a stress concentration dependent increase, ILL590 did not. The activity of CAT enzyme in leaf and root tissues of both cultivars did not significantly change under increasing salt stress conditions. The results suggested that the leaves were more susceptible to salt stress. Also when two cultivars were compared ILL5582 was found to be more tolerant against salt stress than ILL590 under laboratory conditions and SOD enzyme seemed to be the most active component of the salt tolerant mechanism.

L'ordre dels primats inclou l'home i els seus parents més propers. Actualment, més de la meitat dels primats no humans es troben en perill d'extinció, principalment com a conseqüència de l'activitat humana. Això doncs, l'estudi dels primats és de gran rellevància des de dos punts de vista ben diferents, tant a nivell de conservació de les espècies com en biomedicina, genòmica comparada i evolució. El treball de tesi doctoral presentat aquí s'emmarca dins d'aquest context bilateral i pretén ser una aportació tant pel que fa al desenvolupament i aplicació d'eines moleculars per a la conservació de les espècies de primat com per a l'estudi de l'evolució d'aquests éssers.Aquest estudi es divideix en cinc apartats principals. Comença amb una Introducció en què descriu la diversitat que amaga l'ordre dels primats, el gran ventall de possibilitats que obre la genètica de la conservació, la importància de les duplicacions en l'evolució de les espècies i la història del cromosoma Y. A continuació s'estableixen els Objectius fonamentals proposats en aquesta tesi. Les fites principals són: determinar l'aplicabilitat de la tècnica de l'MDA sobre mostres no invasives, contribuir a desenvolupar un microarray de miniseqüència per a l'estudi dels primats i desemmascarar la història evolutiva de la família gènica RPS4Y en primats.El cos principal de la tesi està format pels tres capítols que constitueixen l'apartat dels Resultats. En el primer treball, publicat a "Biotechnology Journal" amb el títol "Sequence quality is maintained after multiple displacement amplification of non-invasively obtained macaque semen DNA", s'analitza la possibilitat d'aplicar la tècnica d'amplificació de genomes complets Multiple Displacement Amplification (MDA) amb mostres recol·lectades de manera no invasiva. Amb aquest estudi s'ha pogut demostrar que els productes d'MDA obtinguts a partir de mostres no invasives de semen de macaco són adequades per a la realització d'estudis genètics. En el segon treball, titulat "A microarray system for Y-chromosomal and mitochondrial SNP analysis in chimpanzee populations" i enviat a Molecular Ecology, s'ha desenvolupat un "microarray" de miniseqüència per estudiar la variabilitat de les poblacions de ximpanzé, ja siguin captives com en estat salvatge. El "microarray" inclou SNPs tant de cromosoma Y i com de gens mitocondrials, de manera que permet analitzar simultàniament la línia paterna i la línia materna, informació que és de gran interès quan s'estudien espècies en què mascles i femelles presenten diferent patró de migració, com els ximpanzés. Finalment, en el tercer estudi es descriu la història evolutiva dels gens RPS4Y dins de la filogènia dels primats. S'ha pogut determinar en 35 milions d'anys el moment de la duplicació que originà el gen RPS4Y2 i s'ha proposat que el seu manteniment en el genoma es deu a l'adquisició d'una nova funció relacionada amb l'espermatogènesi, almenys en el llinatge humà. Aquests resultats es troben recollits a l'article titulat "Molecular evolution of primate RPS4Y gene family" enviat a la revista "Molecular Biology and Evolution".Finalment, els resultats obtinguts durant el desenvolupament d'aquesta tesi es discuteixen d'una manera general dins l'apartat del Resum global. La memòria acaba amb les Conclusions més rellevants a què s'ha pogut arribar, exposades de manera específica i resumida. / Primate order includes humankind and its closest relatives. Nowadays, more than half of nonhuman primates are in peril, mainly due to human activities. Therefore, primate studies are of great interest from two important points of view, both for species conservation purposes and also in biomedicine, comparative genomics, and evolution.The aim of this thesis is to contribute both to the conservation of primate species and to the study of their evolution.This thesis includes the results of three different studies, already published or in preparation. The first study analyses the Multiple Displacement Amplification (MDA) technique in order to test its applicability on non-invasively collected samples. We have demonstrated that MDA products obtained from non-invasively collected macaque semen are suitable to carry out genetic analyses. In the second study we have developed a minisecuencing microarray to study the genetic variability in chimpanzee populations, both captive and wild-living. The microarray includes SNPs from the Y chromosome and from mitochondrial genes, so that it allows to simultaneously analyse the paternal and maternal lineages. Finally, the third study aimed to describe the evolution of primate RPS4Y genes. We have dated in 35 million years the origin of RPS4Y2 and we proposed a neofunctionalization process as the reason of its maintenance in the genome.

Previous studies have shown that the upregulation of CD151 and β1 is associated with poor prognosis in many cancers such as breast cancer. Studies have provided evidence that these proteins are associated with the adhesion and migration of tumor cells. In this study, a microfluidic flow chamber was utilized to determine how CD151 and β1 affected the firm and initial adhesion of metastatic breast cancer cells to a planar endothelial monolayer under shear stress. This system mimicked the adhesion of metastatic breast cancer cells to the endothelial cells of the circulatory system. CD151 and β1 increased the firm adhesion of metastatic breast cancer cells onto an endothelial monolayer when subjected to high shear stresses. CD151 and β1 increased the initial adhesion of metastatic breast cancer cells onto an endothelial monolayer. A transwell assay was utilized to determine how CD151 and β1 affected random migration through different matrixes and random transendothelial migration. CD151 and β1 decreased the random migration of metastatic breast cancer cells through matrices. Additionally, background information is provided related to the metastatic cascade, how it can be modeled with microfluidics, and how CD151 and β1 have been known to effect cancer and metastasis.