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

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.

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.

"In order to succeed in today’s global, competitive market, manufacturing industries need continuous improvements in their multi-disciplinary design processes. These improvements should result in expending fewer resources on the design process while achieving better quality and more environmentally friendly products. The current approach for improving design processes is mostly based on intuitive observations followed by incremental changes to the existing methodologies. However, today’s fast-paced world needs rapid incorporation of new technologies and methods into design methodologies. Recent advances in the application of Artificial Intelligence to design Multi-agent Design Systems in particular-provide an opportunity to accomplish this goal. The inter-disciplinary collaboration between Computer Science and Engineering Design provides the means to develop systematic and holistic approaches for constructing superior design methodologies. An innovative approach has been developed that is based on simulating the design process using a multi-agent system that mimics the behavior of the design team. The multi-agent system implements a knowledge-based model of design in which highly specialized knowledge from expert sources is applied to synthesize a design. The multi-agent system activates the pieces of design knowledge when they become applicable. The use of knowledge by agents is recorded by tracing the steps that the agents have taken during a design project. Many traces are generated by solving a large number of design projects that differ in their requirements. A set of design methodologies is constructed by using inductive learning techniques to generalize the traces generated. These methodologies then can be used to guide design teams through future design projects."

In today's networked world, information is widely distributed across many independent databases in heterogeneous formats. Integrating such information is a difficult task and has been adressed by several projects. However, previous integration solutions, such as the EVE-Project, have several shortcomings. Database contents and structure change frequently, and users often have incomplete information about the data content and structure of the databases they use. When information from several such insufficiently described sources is to be extracted and integrated, two problems have to be solved: How can we discover the structure and contents of and interrelationships among unknown databases, and how can we provide durable integration views over several such databases? In this dissertation, we have developed solutions for those key problems in information integration. The first part of the dissertation addresses the fact that knowledge about the interrelationships between databases is essential for any attempt at solving the information integration problem. We are presenting an algorithm called FIND2 based on the clique-finding problem in graphs and k-uniform hypergraphs to discover redundancy relationships between two relations. Furthermore, the algorithm is enhanced by heuristics that significantly reduce the search space when necessary. Extensive experimental studies on the algorithm both with and without heuristics illustrate its effectiveness on a variety of real-world data sets. The second part of the dissertation addresses the durable view problem and presents the first algorithm for incremental view maintenance in schema-restructuring views. Such views are essential for the integration of heterogeneous databases. They are typically defined in schema-restructuring query languages like SchemaSQL, which can transform schema into data and vice versa, making traditional view maintenance based on differential queries impossible. Based on an existing algebra for SchemaSQL, we present an update propagation algorithm that propagates updates along the query algebra tree and prove its correctness. We also propose optimizations on our algorithm and present experimental results showing its benefits over view recomputation.

The misfolding and aggregation of proteins is closely associated with more than fifty human disorders, including Alzheimer's and Parkinson's diseases, all of which are currently incurable and many represent a major threat to human life. The mechanism of protein aggregation is subject to extensive studies. The damaging effects associated with protein aggregation have been attributed to amyloidogenic species that are present during the misfolding process. In particular, oligomeric species are, however, intrinsically difficult to study as a consequence of their low abundance and highly heterogeneous nature. The first chapter of my thesis gives an introduction into the field of protein folding and misfolding with a focus on the study of protein aggregation, and toxic effects relevant to human disorders. The second chapter of my thesis describes the development of a methodology that enables the study of aggregate induced lipid bilayer permeability, possibly the most general mechanism of protein aggregate toxicity. Surface-tethered lipid vesicles functioning as optochemical probes sensitive to membrane integrity are imaged using total internal reflection microscopy. It is shown that oligomeric species of the 42-residue form of the Aβ peptide (Aβ42) are responsible for the membrane disruption. The methodology can be applied to the study of other proteins such as α-synuclein and tau, and the ability of antibodies and chaperones to counteract the aggregate induced lipid bilayer permeability can be assessed. Furthermore, lipid bilayer permeability induced by aggregates formed in human induced pluripotent stem cells can be studied. The third chapter presents a new approach for the measurement of protein aggregation kinetics by following the development of the lipid bilayer permeability over the course of the aggregation process of Aβ42. The aggregation kinetics can be modulated with molecular chaperones and pre-formed seed fibrils, which allows secondary nucleation to be identified as the process that drives the formation of species responsible for the lipid bilayer permeability. The fourth chapter describes the development of a three-pronged strategy to study the mechanism of α-synuclein amyloid formation. The aggregation is studied in the presence of lipid vesicles or pre-formed fibrils at neutral or acidic pH of the solution. The influence of single-point mutations on the aggregation of α-synuclein is described. Furthermore, the strategy is applied to the characterisation of the ability of antibodies and small molecules to inhibit the aggregation, and thus has the potential for the development of therapeutical agents. The work presented in the fifth chapter characterises the amyloid fibril populations formed by α-synuclein and mutational variants associated with familial Parkinson's disease. X-ray crystallography, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy and atomic force microscopy have all been applied to the analysis of these amyloid fibrils. Finally, the sixth chapter summarises the results described in this thesis and points out future opportunities in the context of fundamental and translational studies related to the research area of protein misfolding disorders.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2015-07-06T19:27:00Z No. of bitstreams: 1 JanainaConceicaoSutilLemos.pdf: 790058 bytes, checksum: 85e90c997855bb472d17380ce64d7c95 (MD5) / Made available in DSpace on 2015-07-06T19:27:00Z (GMT). No. of bitstreams: 1 JanainaConceicaoSutilLemos.pdf: 790058 bytes, checksum: 85e90c997855bb472d17380ce64d7c95 (MD5) Previous issue date: 2011-09-30 / Nenhuma / Com a crescente popularização dos dispositivos móveis nos últimos anos, há uma necessidade cada vez maior de conectividade e de serviços nas redes de computadores. Nesse contexto, as tecnologias para descoberta de serviços simplificam a interação entre usuários e dispositivos, facilitando as tarefas administrativas, principalmente quando existe a necessidade de adicionar novos equipamentos. Devido a grande diversidade de ambientes onde essas tecnologias podem ser utilizadas, surge também a necessidade de tratar as questões relacionadas a segurança e ao mesmo tempo, preservar a facilidade de uso do sistema. Neste trabalho é apresentado um sistema para descoberta segura de serviços em redes locais com arquitetura descentralizada, o Sec-SD (Secure Service Discovery Protocol). Através do uso de mecanismos para criptografia e autenticação, o Sec-SD visa estabelecer uma relação de confiança entre as partes envolvidas na descoberta de serviços antes da divulgação de informações relacionadas a estas, prevenindo assim os ataques causados pelo anúncio de falsos serviços, bem como o acesso a serviços restritos por usuários ilegítimos, objetivando ser ao mesmo tempo seguro e de fácil uso para humanos. O presente sistema permite que uma entidade atue simultaneamente como cliente e provedor de serviços, sem a necessidade de utilizar diretórios para anunciar serviços e/ou realizar buscas pelos mesmos, fazendo ainda com que a existência de provedores redundantes para um mesmo serviço seja tratada de forma a ser transparente para os usuários. Para validação, é avaliado o tráfego gerado pelas mensagens do Sec-SD e além disso, foi desenvolvido um protótipo, que é utilizado para integrar funcionalidades para descoberta segura de serviços no LP2P (Local Peer-to-Peer Protocol), que é uma plataforma para compartilhamento de arquivos P2P para redes locais desenvolvida no Grupo de Redes de Computadores e Sistemas Distribuídos do PIPCA – UNISINOS. / Given the growing popularity of mobile devices in recent years, there is an increasing need for connectivity and services in computer networks. In this context, service discovery technologies aim to simplify the interaction between users and devices, facilitating administrative tasks, especially when there is a need to add new equipments. Due to the diversity of environments where these technologies can be used, there also the need to address security issues and, at the same time, to preserv the usability of the system. This work presents a system for secure service discovery on local networks with decentralized architecture, called Sec-SD – Secure Service Discovery Protocol. Sec-SD makes use of cryptography and authentication mechanisms in order to allow only valid users to obtain information about the available services. In this way, is possible to prevent several attacks caused by the advertisement of false services and by service access performed by illegitimate users, aiming to be at the same time secure and easy-of-use for humans. This model allows the same entity to act simultaneously as a client and a service provider, without the use of any directory to register services and/or search for available services. The existence of redundant service providers is also addressed by the model in order to be transparent for human users. For validation, the traffic generated by the Sec-SD messages is evaluated and a prototype is used to provide secure service discovery facilities into a P2P file sharing focused in Local Area Networks called LP2P (Local Peer-to-Peer Protocol), that was developed at PIPCA - UNISINOS.

Nas últimas décadas, a capacidade das empresas de gerar e coletar informações aumentou rapidamente. Essa explosão no volume de dados gerou a necessidade do desenvolvimento de novas técnicas e ferramentas que pudessem, além de processar essa enorme quantidade de dados, permitir sua análise para a descoberta de informações úteis, de maneira inteligente e automática. Isso fez surgir um proeminente campo de pesquisa para a extração de informação em bases de dados denominado Knowledge Discovery in Databases – KDD, no geral técnicas de mineração de dados – DM – têm um papel preponderante. A obtenção de bons resultados na etapa de mineração de dados depende fortemente de quão adequadamente o preparo dos dados é realizado. Sendo assim, a etapa de extração de conhecimento (DM) no processo de KDD, é normalmente precedida de uma etapa de pré-processamento, onde os dados que porventura devam ser submetidos à etapa de DM são integrados em uma única relação. Um problema importante enfrentado nessa etapa é que, na maioria das vezes, o usuário ainda não tem uma idéia muito precisa dos dados que devem ser extraídos. Levando em consideração a grande habilidade de exploração da mente humana, este trabalho propõe uma técnica de visualização de dados armazenados em múltiplas relações de uma base de dados relacional, com o intuito de auxiliar o usuário na preparação dos dados a serem minerados. Esta técnica permite que a etapa de DM seja aplicada sobre múltiplas relações simultaneamente, trazendo as operações de junção para serem parte desta etapa. De uma maneira geral, a adoção de junções em ferramentas de DM não é prática, devido ao alto custo computacional associado às operações de junção. Entretanto, os resultados obtidos nas avaliações de desempenho da técnica proposta neste trabalho mostraram que ela reduz esse custo significativamente, tornando possível a exploração visual de múltiplas relações de uma maneira interativa. / In the last decades the capacity of information generation and accumulation increased quickly. With the explosive growth in the volume of data, new techniques and tools are being sought to process it and to automatically discover useful information from it, leading to techniques known as Knowledge Discovery in Databases – KDD – where, in general, data mining – DM – techniques play an important role. The results of applying data mining techniques on datasets are highly dependent on proper data preparation. Therefore, in traditional DM processes, data goes through a pre-processing step that results in just one table that is submitted to mining. An important problem faced during this step is that, most of the times, the analyst doesn’t have a clear idea of what portions of data should be mined. This work reckons the strong ability of human beings to interpret data represented in graphical format, to develop a technique to visualize data from multiple tables, helping human analysts when preparing data to DM. This technique allows the data mining process to be applied over multiple relations at once, bringing the join operations to become part of this process. In general, the use of multiple tables in DM tools is not practical, due to the high computational cost required to explore them. Experimental evaluation of the proposed technique shows that it reduces this cost significantly, turning it possible to visually explore data from multiple tables in an interactive way.

The complexity of biological systems constitute a significant problem for the development of biological models. This inspired the creation of a few Computational Scientific Discovery systems that attempt to address this problem in the context of metabolomics through the use of computers and automation. These systems have important limitations, however, like limited revision and experiment design abilities and the inability to revise refuted models. The goal of this project was to address some of these limitations. The system developed for this project, "Huginn", was based on the use of Abductive Logic Programming to automate crucial development tasks, like experiment design, testing consistency of models with experimental results and revision of refuted models. The main questions of this project were (1) whether the proposed system can successfully develop Metabolic Network Models and (2) whether it can do it better than its predecessors. To answer these questions we tested Huginn in a simulated environment. Its task was to relearn the structures of disrupted fragments of a state-of-the-art model of yeast metabolism. The results of the simulations show that Huginn can relearn the structure of metabolic models, and that it can do it better than previous systems thanks to the specific features introduced in it. Furthermore, we show how the design of extended crucial experiments can be automated using Answer Set Programming for the first time.

[pt] Em 1927, o escritor modernista Mário de Andrade (1893-1945) partiu da sua São Paulo para o Norte do país, a fim de conhecer e dar a conhecer um Brasil pouco explorado, muitas vezes homogeneizado na literatura de escritoresviajantes que o antecederam em empresa semelhante. Simbolicamente, o que resultou desta experiência foram notas que só viriam a ser coligidas em uma versão para-definitiva, provavelmente por volta de 1943. Sob a forma de um diário, a narrativa sobre a experiência da viagem pelo Norte compõe a primeira parte do livro O turista aprendiz, publicado na década de 70. Este trabalho tem por finalidade verificar as tensões entre essas duas camadas de tempo: o presente da reescrita e o passado como experiência da descoberta. Esta narrativa em palimpsesto, extremamente fragmentada, carecendo do apuro final de seu escritor, fez com que privilegiássemos os seus detalhes, alegorias, inflexões e, sublinhássemos as contradições e a ironia do pensamento marioandradino, elementos considerados imprescindíveis para a construção de sua biografia intelectual. / [en] In 1927, Modernist writer Mário de Andrade (1893-1945) left his city of São Paulo heading to Northern Brazil, in order tyo know and reveal a scarcely explored Brazil, often homogenized in the literature of traveling salesmen who had preceded him in such project. Symbolically, what resulted from this experience were notes that would only be collected in a parallel-definitive version around 1943. Under the form of a diary, the narrative about the facts of his trip through the northern region of his country composes the first part of his book The learning tourist, published in the seventies. This work intends to examine the tensions between those two layers of time: the present of the writing and the past as an experience of discovery. This narrative on palimpsest, extremely fragmented, lacking a final refurbishing by its author, allowed us to privilege its details, allegories, inflexions and, also, to underline its contradictions and the irony of Mario de Andrade s thought, elements that are considered to be indispensable for the building of his biography.