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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
771

Algorithmes de graphes pour la découverte de la topologie d'un réseau énergétique par la connaissance de ses flots / Algorithm of graphs for topology discovery for a energy network from flot knowledges

Ehounou, Joseph 02 October 2018 (has links)
Dans les réseaux énergétiques, la connaissance des équipements, leurs emplacements et leursfonctions sont les prérequis à l’exploitation de l’infrastucture. En effet, tout opérateur disposed’une carte appelée schéma synoptique indiquant les connexions entre les équipements. À partirde cette carte, sont prises des décisions pour un fonctionnement optimal du réseau.Ce schéma synoptique peut être érronné parce que des opérations de maintenance sur le réseaun’auraient pas été retranscrites ou mal saisies. Et cela peut entrainer des coûts supplémentairesd’exploitation du réseau énergetique.Nous considérons le réseau électrique d’un Datacenter. Ce réseau est composé d’une topologiephysique modélisée par un DAG sans circuit et de mesures électriques sur ces arcs. La particularitéde ce réseau est que les mesures contiennent des erreurs et cette topologie est inconnue c’est-à-direles arcs sont connus mais les extrémités des arcs sont inconnues. Dans le cas où ces mesuressont correctes alors la corrélation des arcs induit la matrice d’adjacence du line-graphe du graphenon-orienté sous-jacent de notre DAG. Un line-graphe est un graphe dans lequel chaque sommet etson voisinage peuvent être partitionnés par une ou deux cliques et que chaque arête est couvertepar une clique. Cependant, avec la présence des erreurs de mesures, nous avons un graphe avecdes arêtes en plus ou en moins qui n’est pas nécessairement un line-graphe. Si ce graphe est unline-graphe alors il n’est pas le line-graphe de notre DAG. Notre problème est de découvrir cettetopologie en se basant sur ces mesures électriques.Nous débutons par une étude bibliographique des corrélations de mesures possibles afin dedéterminer celle qui est pertinente pour notre problème. Ensuite nous proposons deux algorithmespour résoudre ce problème. Le premier algorithme est l’algorithme de couverture et il déterminel’ensemble des cliques qui couvre chaque sommet de notre graphe. Le second algorithme estl’algorithme de correction. Il ajoute ou supprime des arêtes au voisinage d’un sommet non couvertde telle sorte que son voisinage soit partitionné en une ou deux cliques. Enfin, nous évaluons lesperformances de nos algorithmes en vérifiant le nombre d’arêtes corrigées et la capacité à retournerle graphe le plus proche du line-graphe de notre DAG. / In energy network, the knowledge of equipments, their locations and their functions are theimportant information for the distributor service operator. In fact, each operator has a networkplan often named synoptic schema. That schema shows the interconnexion between equipments inthe network. From this schema, some management decisions have taken for ensuring an optimalperformance of a network.Sometimes, a synoptic schema has some mistakes because the maintenance operations, such aschanged the connexion between equipments or replaced equipments, have not been updated orhave been written with errors. And these mistakes increase exploitation cost in the energy network.We consider an electric network of a datacenter. This network consists of physical topologymodelised by a DAG without circuit and measurements are on the edges of a DAG. The mainpoint of the network is that measurements are some mistakes and the topology is unknown i.ewe know edges but the nodes of edges are unknown. When measurements are correct then thecorrelations between pairwise edges provide the adjacency matrix of the linegraph of undirectedgraph of the DAG. A linegraph is a graph in which each node and the neighbor are partitionnedby one or deux cliques. However, with the mistakes in measurements, the obtained graph is nota linegraph because it contains more or less edges. If the obtained graph is a linegraph then it isa linegraph of the other DAG. Our problem is to discovery the topology of the DAG with somemistakes in measurements.We start by the state of art in the measurement correlations in order to choose the good methodfor our problem. Then, we propose two algorithms to resolve our problem. The first algorithmis the cover algorithm and it returns the set of cliques in the graph. The second algorithm is acorrection algorithm which adds or deletes edges in the graph for getting a nearest linegraph ofthe DAG. In the last, we evaluate the performances of the algorithms by checking the number ofedges corrected and the ability to return a nearest linegraph of the DAG.
772

Catégorisation des comportements de conduite en termes de consommation en carburant : une méthode de découverte de connaissances contextuelles à partir des traces d’interactions / Categorization of driving behavior in terms of fuel consumption

Traoré, Assitan 19 January 2017 (has links)
Cette thèse propose une méthode d'ingénierie des connaissances contextuelles qui permet la modélisation et l'identification du contexte explicatif d'un critère observé. Le contexte est constitué de connaissances explicatives situées permettant une représentation élicitée valide d'un objet dans la situation visée. Ces connaissances sont généralement découvertes lors de l'observation de la réalisation de l'activité dans laquelle cet objet est impliqué. Elles sont donc difficiles à décrire en début d'analyse d'une activité. Toutefois, elles restent nécessaires pour la définition, l'explication et la compréhension efficace d'une activité selon un critère observé caractérisant cette dernière. Cette thèse propose la définition progressive du contexte satisfaisant pour expliquer un critère observé lors de l'observation d'une activité. Cette recherche mobilise les traces d'interaction de l'activité analysée, précise la notion de contexte et exploite les méthodes de fouille de données pour réaliser la catégorisation et la classification d'un critère observé en distinguant les paramètres contextuels et non contextuels. L'environnement développé sur les principes des traces d'interaction, permet d'assister la découverte du contexte explicatif par une approche interactive, à l'aide des connaissances de l'analyste, de distinguer ce qui est contexte de ce qui ne l'est pas. Nous montrons qu'il est possible de construire un contexte valide, en le « découvrant » et en le formulant sous une forme générique, telle que proposée dans la littérature. Une application de la méthode a été effectuée en situation de conduite automobile pour modéliser et identifier le contexte explicatif de la consommation en carburant. En s'appuyant sur les connaissances existantes du domaine, la validation de la méthode est effectuée en étudiant qualitativement les connaissances produites sur la consommation réelle en carburant. La méthode est validée quantitativement en appliquant les règles de classifications établies sur des données collectées de l'activité de conduite. Cette illustration de l'analyse de l'activité de conduite automobile avec la méthode de découverte de connaissances contextuelles, pour déterminer le contexte explicatif de la consommation en carburant, a été effectuée à l'Ifsttar sur des données réelles collectées lors de l'activité de conduite en situation naturelle. Les expérimentations menées montrent des résultats encourageants et permettent d'envisager l'intégration de la méthode de découverte de connaissances contextuelles dans les pratiques des analystes de l'Ifsttar / This thesis proposes an engineering method of contextual knowledge that allows identification and modelling of explanatory context of observed criteria. The context consists of located explanatory knowledge allowing valid representation of an object in the covered situation. This knowledge is generally elicited when observing the activity performance in which the object is involved. They are therefore difficult to describe in the beginning of activity analysis but are necessary for the definition, explanation and effective understanding of an activity according to an observed criterion characterizing this activity. This thesis proposes a progressive definition of adequate context to explain an observed criterion during activity observation. The research mobilizes interaction traces of the analysed activity, clarify context notion and uses data mining methods for classification or categorization of an observed criterion by distinguishing contextual parameters and no contextual parameters. The developed environment, based on interaction traces principles, allows to assist explanatory context discovery by interactive approach, using context analyst knowledge. We demonstrate that it’s possible to build a valid context, by discovering it and by formulating it in a generic form as proposed in literature. An application of the method was performed in driving situation to identify and model the explanatory context of fuel consumption. The method validation is performed by studying produced knowledge on fuel consumption, qualitatively by relying on existing domain knowledge and quantitatively by applying classification rules established trough data collected from driving activity. This illustration of driving activity analysis with the contextual knowledge discovery method to determine explanatory context of fuel consumption was conducted at Ifsttar on real data, collected during driving activity in natural driving situation. The led experiments show encouraging results and allows considering the integration of contextual knowledge discovery method in Ifsttar analyst practices
773

Conhecimento prévio e aprendizagem significativa de conceitos históricos no ensino médio /

Alegro, Regina Celia. January 2008 (has links)
Orientador: José Augusto da Silva pontes Neto / Banca: Inês Amosso Dolci / Banca: Fátima Aparecida Dias Gomes Marin / Banca: Lúcia Helena Oliveira Silva / Banca: Raul Aragão Martins / Resumo: Esse estudo insere-se na linha de pesquisa Ensino, Aprendizagem Escolar e Desenvolvimento Humano e tem como pressuposto que as características dos conhecimentos prévios são determinantes para novas aprendizagens. Nessa perspectiva, tem por objetivo geral analisar os conteúdos substantivos de conhecimentos prévios apresentados por estudantes do Ensino Médio, na disciplina de História. Para tanto, investiga atributos desses conhecimentos que os alunos apresentam ao iniciarem o curso e descreve as variações das idéias dos estudantes ingressantes quando comparadas com aquelas dos concluintes do mesmo nível de ensino. A coleta de dados foi realizada por meio de diagrama aos moldes de mapa conceitual. A amostra constituiu-se de 73 diagramas elaborados por 143 estudantes matriculados em escolas públicas, sendo 37 diagramas de ingressantes e 36 diagramas de concluintes. A análise apoiou-se na teoria da aprendizagem significativa de Ausubel e colaboradores e em estudos e reflexões sobre os conhecimentos históricos como básicos para a determinação da consciência histórica. Os resultados indicam "descobrimento do Brasil" como o mais importante tema de ensino de História do Brasil, segundo os participantes, e três conjuntos de narrativas que expressam suas idéias sobre o tema: quadro descritivo do achado de Cabral; encontro de culturas; início do processo de confronto, ocupação e exploração que estão na origem de desenvolvimento econômico brasileiro. A leitura interpretativa dos diagramas apontou que estudantes ingressantes e concluintes apresentam idéias gerais incorporadoras assemelhadas, apenas com maior diferenciação conceitual ao final do Ensino Médio. Indicou também que os participantes da pesquisa, no seu contexto e condição de estudantes da educação básica, produzem significado e sentido ao construir narrativas sobre o tema. Os resultados ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study is inserts in the line of research Teaching, Learning School and Human Development and has the assumption that the characteristics of previous knowledge are determinant to new learning. In this perspective aims to analyze the general content for the substantive knowledge prior submitted by students from high school, in the discipline of history. For both, tried to identify attributes of the previous knowledge on the discipline of history those students presents when enter in the high school and describe the variations of previous ideas of the beginners students when compared with those of ending of this level of education. The search of data was done using the format diagram of conceptual map. The sample has been of 73 diagrams prepared by 143 students enrolled in public schools, and 37 diagrams of beginners and 36 diagrams of graduated students of high school. The analysis supported in the theory of meaningful learning of Ausubel and collaborators and in the researches and reflections on the historical knowledge of students as basic for the determination of historical conscience. The results show "Discovery of Brazil" as the most important issue of education of History of Brazil, according to participants, and three sets of narratives that express their ideas on the topic: descriptive framework of the finding of Cabral; meeting of cultures; start of the process of confrontation, occupation and exploitation that are the origin of economic development Brazil. The interpretative reading of diagrams indicated that beginners and graduated students have similar most general concepts, only with greater differentiation conceptual to the end of high school. It also states those participants of the research, in your context and condition of students of the basic education, produce meaning and direction to construct narratives on the theme... (Complete abstract click electronic access below) / Doutor
774

Etude de la formation des opportunités entrepreneuriales en Tunisie / How do entrepreneurial opportunities emerge and develop in the Tunisian context ?

Chaabouni, Haithem 25 October 2017 (has links)
L’objectif de cette thèse est d’apporter de nouveaux éclairages théoriques et empiriques sur la formation des opportunités entrepreneuriales. Pour mieux comprendre ce phénomène, nous avons mobilisé deux principales approches, l’approche de la découverte et l’approche de la création des opportunités. Une étude quantitative basée sur un questionnaire a été menée auprès d’entrepreneurs tunisiens afin de déterminer les facteurs de formation de l’opportunité entrepreneuriale. Les résultats montrent que dans le contexte tunisien, la découverte des opportunités est dominante étant donné que l’écosystème entrepreneurial tunisien ne favorise pas l’innovation et la création des opportunités. Ce travail de recherche contribue à la connaissance des pratiques de l’entrepreneuriat et des modes d’accompagnement des entrepreneurs. / The purpose of this thesis is to bring new theoretical and empirical insights about the formation of entrepreneurial opportunities. For getting a better understanding of this phenomenon, we have followed two main approaches: the discovery approach and the creation-of- opportunities approach. A quantitative research based on a questionnaire was conducted among a number of Tunisian entrepreneurs in order to identify the factors that have influenced on the formation of entrepreneurial opportunities. The results of the research show that the discovery of opportunities is prevalent given that the Tunisian entrepreneurial ecosystem does not promote innovation, and creation of opportunities. This research work contributes to the knowledge of entrepreneurial practices and the modes of coaching entrepreneurs.
775

Sistema de localização de serviços para domínios de segurança locais e remotos. / Service location system for local and remote security domains.

Sakuragui, Rony Rogério Martins 29 September 2006 (has links)
Um dos grandes avanços na área da computação nas últimas décadas refere-se aos sistemas distribuídos. O uso de tais sistemas tem crescido vertiginosamente nos últimos anos. Com o surgimento e uso de tecnologias de redes sem-fio, os sistemas ganharam mobilidade e dinamismo. Pessoas podem entrar ou sair de seus locais de trabalho, de entretenimento ou mesmo de suas casas com seus computadores móveis; redes podem ser formadas ou extintas conforme a dinâmica de um grupo de pessoas; e novos serviços podem ser disponibilizados ou interrompidos. Em sistemas como tais, um sistema de localização de serviços automático é fundamental para acompanhar as contínuas modificações na rede. A localização de serviços permite que, em uma rede de endereçamento estático ou dinâmico, dispositivos e serviços possam ser encontrados de modo completamente automático. A presente dissertação propõe um sistema de localização lógica (endereçamento) de serviços e dispositivos em uma rede local ou geograficamente distribuída, indo ao encontro às necessidades de controle de sistemas distribuídos dinâmicos, contribuindo ao mesmo tempo com questões de usabilidade e configuração automática de redes. O sistema, também, busca resolver questões relacionadas ao uso dos serviços entre redes protegidas por firewalls ou que utilizam configurações de NAT. / In the last decades, one of the most important progresses in computation is related to the distributed systems. The usage of these systems has increased a lot, in the last years. Due the emergence of wireless technologies, systems have acquired mobility and dynamism. People can enter or leave places, such as home, workplaces and entertainment spots, caring their mobile computers; networks can be formed or extinguished in accordance with the people dynamism; and new services can be available or interrupted. At these systems, a service location system is needed to keep track of the unceasing modifications in the network. The service location enables that services and devices can be found, at dynamic or static networks. This master thesis proposes a system for location of the logical addresses of services and devices at local or wide area networks. This work contributes to issues related to distributed systems control, usability and automatic network configuration. This system also solves questions related to service usage between networks using firewalls or NAT. Besides that, other points related to network interconnections in distributed systems, for example, using the Internet, are raised and solved.
776

Estratégias para aplicação de políticas parciais com motivação intrínseca. / Application strategies for intrinsic motivated options

Beirigo, Rafael Lemes 02 October 2014 (has links)
As técnicas de Aprendizado por Reforço permitem a solução de um problema através da escolha de ações que maximizem valores de recompensas recebidas que refletem a qualidade das ações tomadas pelo agente em um processo de tentativa e erro. Em problemas com estrutura hierárquica, a solução final depende do encadeamento de soluções para subproblemas aí presentes, sendo frequente a repetição de subproblemas nesse encadeamento. Nesses casos, a utilização de políticas parciais permite o aprendizado e armazenamento das soluções individuais para cada subproblema, que podem então ser utilizadas múltiplas vezes na composição de uma solução completa para o problema final, acelerando o aprendizado. Apesar de vantajosa, a utilização de políticas parciais necessita de definições por parte do projetista, o que representa uma sobrecarga. Para contornar esse problema, foram propostas técnicas de descoberta automática de políticas parciais, dentre as quais a utilização de motivação intrínseca se destaca por permitir ao agente aprender soluções de subproblemas úteis na solução do problema final sem a necessidade de se definir manualmente novas recompensas para esses subproblemas individualmente. Apesar de promissora, essa proposta utiliza um conjunto de componentes de aprendizado que ainda carece de investigação aprofundada acerca dos impactos individual e coletivo de cada componente, notadamente a aplicação das políticas parciais durante o aprendizado. Nesta dissertação são propostas duas abordagens para a aplicação de políticas parciais no Aprendizado por Reforço com Motivação Intrínseca: (i) armazenamento das políticas parciais em aplicação pelo agente e (ii) exploração interna à aplicação das políticas parciais. O impacto das propostas no desempenho de aprendizado é avaliado experimentalmente em um domínio com forte caracterização hierárquica. / Reinforcement Learning techniques allow an agent to learn the solution to a problem by interacting with the environment and executing actions, thus receiving rewards that reflect the value of the actions taken, on a process of trial and error. When a problem has a hierarchical structure, its final solution depends on several solutions to the subproblems it contains, and it is rather common the repetition of subproblems. On these cases, by using options it is possible to learn the solution to each subproblem individually, keeping and then using them multiple times to compose the complete solution to the problem, thus accelerating the learning process. But, despite this advantage, the use of options create the need for some definitions, what can represent a burden to the designer. To circumvent this problem, automatic option discovery techniques were proposed, among which the use of intrinsic motivation deserves special attention for allowing the agent to learn the solution of the subproblems, which are useful to compose the final solution, without the need to manually define new rewards to these subproblems individually. Despite being promising, this technique is built upon a set of several learning components that need a more deep investigation on the individual and collective impacts of each component, mostly the options application strategies during the learning process. On this work two modifications are proposed concerning the application process of options on the Intrinsically Motivated Reinforcement Learning: (i) storage of the history of the options applied by the agent and (ii) allow the agent to explore, even when following an option. These modifications were implemented on an algorithm present on the literature and evaluated on a domain with strong hierarchical characteristics.
777

Uma Proposta para Descoberta de Recursos na Computação Ubíqua com Suporte Semântico / A PROPOSAL FOR RESOURCE DISCOVERY IN UBIQUITOUS COMPUTING WITH SUPPORT SEMANTIC

Dilli, Renato Marques 11 March 2010 (has links)
Made available in DSpace on 2016-03-22T17:26:47Z (GMT). No. of bitstreams: 1 dm2_rdilli.pdf: 6543916 bytes, checksum: c1e5f8d9e3780088d192fcc2919a072b (MD5) Previous issue date: 2010-03-11 / In ubiquitous environments resources should be shared so that they can be accessed from anywhere and anytime. In this approach the process of resource discovery plays an important role in adequately satisfy the requests for resources. This paper presents the proposed EXEHDA-SD, EXEHDA-Semantic Discovery, which consists of a mechanism for resource discovery for ubiquitous computing, which combines technologies into its architecture for the semantic processing of requests for resources, increasing expressiveness in representation and consultation. The mechanism provides for the dynamics in which resources enter and leave the environment and pursue issues such as scalability and user preferences. In this sense, the work includes a study on mechanisms of resource discovery in the context of ubiquitous computing and technology for semantic processing with the intention of substantiating the architectural choices of the mechanism. The EXEHDA-SD was modeled to be prototyped as a service to the EXEHDA middleware, enabling the execution of search for resources located in the cells of the ubiquitous environment, in a scalable perspective, through the use of ontologies and tools for handling. Processing ontology expands the capacity for representation of environmental resources and their location. The use of semantic description of resources, among other things, facilitates the location of features similar to those requested. The model was compared with the state of the art, and its differential was discussed. Moreover, their functions were evaluated by three case studies / Em ambientes ubíquos os recursos devem estar compartilhados para que possam ser acessados de qualquer lugar e a qualquer momento. Nesta abordagem o processo de descoberta de recursos assume um importante papel em satisfazer adequadamente as requisições por recursos. Este trabalho apresenta a proposta do EXEHDA-SD, EXEHDASemantic Discovery, que consiste em um mecanismo de descoberta de recursos, para computação ubíqua, que agrega tecnologias em sua arquitetura para o processamento semântico de requisições por recursos, aumentando a expressividade na representação e consulta. O mecanismo prevê a dinamicidade em que os recursos entram e saem do ambiente e persegue aspectos como escalabilidade e preferências do usuário. Neste sentido, o trabalho desenvolvido contempla um estudo sobre mecanismos de descoberta de recursos no contexto da computação ubíqua e das tecnologias para processamento semântico com a intenção de fundamentar as escolhas arquiteturais do mecanismo. O EXEHDA-SD foi modelado para ser prototipado na forma de um serviço para o middleware EXEHDA, possibilitando a realização de pesquisas por recursos localizados nas células do ambiente ubíquo, em uma perspectiva escalável, através da utilização de ontologias e ferramentas para sua manipulação. O processamento de ontologias expande a capacidade de representação dos recursos do ambiente, bem como sua localização. A utilização de semântica na descrição dos recursos, dentre outros aspectos, facilita a localização de recursos similares ao solicitado. O modelo foi comparado com o estado da arte, e seu diferencial foi discutido. Outrossim, suas funcionalidades foram avaliadas por três estudos de caso
778

Agrupamento de dados fuzzy colaborativo / Collaborative fuzzy clustering

Coletta, Luiz Fernando Sommaggio 19 May 2011 (has links)
Nas últimas décadas, as técnicas de mineração de dados têm desempenhado um importante papel em diversas áreas do conhecimento humano. Mais recentemente, essas ferramentas têm encontrado espaço em um novo e complexo domínio, nbo qual os dados a serem minerados estão fisicamente distribuídos. Nesse domínio, alguns algorithmos específicos para agrupamento de dados podem ser utilizados - em particular, algumas variantes do algoritmo amplamente Fuzzy C-Means (FCM), as quais têm sido investigadas sob o nome de agrupamento fuzzy colaborativo. Com o objetivo de superar algumas das limitações encontradas em dois desses algoritmos, cinco novos algoritmos foram desenvolvidos nesse trabalho. Esses algoritmos foram estudados em dois cenários específicos de aplicação que levam em conta duas suposições sobre os dados (i.e., se os dados são de uma mesma npopulação ou de diferentes populações). Na prática, tais suposições e a dificuldade em se definir alguns dos parâmetros (que possam ser requeridos), podemn orientar a escolha feita pelo usuário entre os algoitmos diponíveis. Nesse sentido, exemplos ilustrativos destacam as diferenças de desempenho entre os algoritmos estudados e desenvolvidos, permitindo derivar algumas conclusões que podem ser úteis ao aplicar agrupamento fuzzy colaborativo na prática. Análises de complexidade de tempo, espaço, e comunicação também foram realizadas / Data mining techniques have played in important role in several areas of human kwnowledge. More recently, these techniques have found space in a new and complex setting in which the data to be mined are physically distributed. In this setting algorithms for data clustering can be used, such as some variants of the widely used Fuzzy C-Means (FCM) algorithm that support clustering data ditributed across different sites. Those methods have been studied under different names, like collaborative and parallel fuzzy clustring. In this study, we offer some augmentation of the two FCM-based clustering algorithms used to cluster distributed data by arriving at some constructive ways of determining essential parameters of the algorithms (including the number of clusters) and forming a set systematically structured guidelines as to a selection of the specific algorithm dependeing upon a nature of the data environment and the assumption being made about the number of clusters. A thorough complexity analysis including space, time, and communication aspects is reported. A series of detailed numeric experiments is used to illustrate the main ideas discussed in the study
779

Gaspar da Cruz e o tratado das coisas da China: Mundialização e Contatos Luso-Chineses no Século XVI / Gaspar da Cruz and his book \"Tratado das Coisas da China\": mundialization and Luso-Chinese interactions in the 16th century

Rezende, Daniel Ayres Arnoni 28 September 2018 (has links)
A presente dissertação tem como objetivo a análise do Tratado das Coisas da China (1570) de Frei Gaspar da Cruz, visando compreender a inserção desta literatura de viagem no processo de mundialização do século XVI, levado a cabo pelas naus da expansão ibérica, sobretudo portuguesa. A partir desta obra, pretende-se espelhar o processo de relações estabelecido entre portugueses e chineses, tomando a narrativa como registro histórico que constrói a imagem da China no século XVI. / This study encompasses the analysis of the book Tratado das Coisas da China by Friar Gaspar da Cruz, as an attempt to understand the addition of travel literature in the 16th century\'s mundialization process, which was undertaken by the Iberian maritime exploration led by Portugal during the Age of Discovery. Taking Gaspar da Cruz\'s work as basis, the study aims to mirror the Portuguese-Chinese relations established at the time, understanding travel narrative as a historical record that substantiates such relations, providing for an intercultural process with interlaced views.
780

Protein complexes in neurodegenerative diseases

Houston, Nicola Patricia January 2012 (has links)
The 14-3-3 family of proteins are important signalling proteins involved in a number of cellular processes. These include cell cycle regulation, apoptosis, signal transduction and cell signalling. There is also considerable evidence in the literature that 14-3-3 proteins play a vital role in the pathology of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s and Prion disease. The neurodegenerative disease of focus in this research is Spinocerebellar Ataxia Type 1 (SCA1). SCA1 is a polyglutamine-repeat disease and the interaction of the disease protein ataxin-1 with 14-3-3 proteins leads to the toxic accumulation and subsequent protein aggregation which is characteristic of this disease. This study focused on attempting to elucidate the structure of various domains of the disease protein and also in identifying potential inhibitors of this deleterious interaction. Unfortunately, structural studies were not successful due to a number of caveats encountered in the expression and purification of the ataxin-1 protein domains. By utilising computational methods and small molecule inhibitors, a number of potential lead compounds which possess the ability to at least partly disrupt the interaction of 14- 3-3ζ have been identified. As 14-3-3 proteins play roles in other neurodegenerative diseases, successful identification of potential drug lead treatments can have far reaching benefits in a number of neurodegenerative diseases including SCA1. Lipid rafts are also involved in neurodegenerative disease pathology. Lipid rafts are cholesterol and sphingolipid rich domains which organise the plasma membrane into discrete microdomains and act as signalling platforms and processing centres which attach specific proteins and lipids. A number of disease proteins are processed at these membrane regions, including those involved in Alzheimer’s, Parkinson’s and Prion disease. This processing is a step which is critical in the pathology of disease and abnormal processing leads to the formation of toxic protein aggregates. Previous research in the lab identified the association of low levels of the five main brain isoforms of 14-3-3 proteins with rafts. This study expanded on this to positively identify the presence of the two phospho-forms of 14-3-3, α and δ. The mechanism by which 14-3-3 proteins associate with rafts was also investigated, indicating that 14-3-3 associates with rafts via an unidentified raftbound protein(s). In addition, the phosphorylation status and quaternary structure of 14-3-3 in the presence of sphingolipids has been explored.

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