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Aplica??o do algoritmo de otimiza??o por col?nia de formigas sobre o problema do passeio do rob? seletivoOliveira J?nior, Edmilson Frank Machado 27 February 2012 (has links)
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Previous issue date: 2012-02-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This work seeks to propose and evaluate a change to the Ant Colony Optimization based on the results of experiments performed on the problem of Selective Ride Robot (PRS, a new problem, also proposed in this paper. Four metaheuristics are implemented,
GRASP, VNS and two versions of Ant Colony Optimization, and their results are analyzed by running the algorithms over 32 instances created during this work. The metaheuristics also have their results compared to an exact approach. The results show that the algorithm implemented using the GRASP metaheuristic show good results. The version of the multicolony ant colony algorithm, proposed and evaluated in this work, shows the best results / Este trabalho tem o objetivo de propor e avaliar uma variante para o algoritmo de col?nia de formigas baseando-se no resultado de experimentos executados sobre o problema do Passeio do Rob? Seletivo (PRS, um novo problema, tamb?m proposto neste
trabalho. S?o implementadas quatro metaheur?sticas, GRASP, VNS, e duas vers?es do Otimiza??o por Col?nia de Formigas, e analisados seus resultados executando-os sobre 32 inst?ncias criadas no trabalho. As metaheur?sticas tamb?m tem seu resultado comparado
com o de um algoritmo exato. Os resultados mostram que o algoritmo implementado utilizando a metaheur?stica GRASP apresenta bons resultados. A vers?o multi-col?nias do
algoritmo de col?nia de formigas, proposta e avaliada no trabalho, apresenta os melhores resultados
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Vieillesse et fragilité : le parcours et le devenir des personnes âgées de 75 ans ou plus hospitalisées pour fracture du col du fémur à Strasbourg / The career and future of persons aged 75 years or more for hip fracture in StrasbourgBenaim, Anne 03 September 2015 (has links)
L’état de santé des personnes âgées se dégrade, les niveaux de dépendance s’accroissent, induisant de profondes conséquences sur l’organisation sanitaire en France. Les fractures du col du fémur illustrent ce défi au regard de leur fort impact sur la qualité de vie et sur la morbi-mortalité des patients. Notre étude quantitative et qualitative, (Jan. 2012 - Jan. 2013) au sein du principal service de chirurgie orthopédique d’Alsace, a permis de retracer le parcours de soin de 107 patients âgés de 75 ans et plus. Notre principale conclusion est que le patient n’a que très peu de place dans le processus décisionnel de son parcours de soin. Cela est d’autant plus dommageable que cette fracture revêt une double signification: physique (besoin d’assistance accrue) et symbolique (dépendance anticipée). Notre étude interactionniste permet de dégager des pistes d’actions opérationnelles dans les domaines sanitaires, politiques et éthiques afin de limiter les effets délétères de cette pathologie. / In a context of depressed health-conditions for elderly people, the levels of dependency are rising. It induces deep consequences for the entire health care organisation. For instance, the fractures of the femoral neck (FFN) represent a healthcare challenge regarding their strong impact on patients’ quality of life and on their morbity-mortality. We conducted a qualitative and quantitative study (Jan. 2012- Jan. 2013) within the main department of orthopedic surgery in Alsace in order to track the healthcare paths of 107 patients of 75 years-old or more. Our main conclusion is that patients are poorly involved in the decisions for their care. This is all the more harmful because the FFN is in fact dual. It is both a physical (higher assistance needed) and a symbolic (earlier dependency) breakage. Our interactionist study identifies areas for pragmatic actions in health-care, public policies and ethic that could contribute to absorb / reduce the pernicious effects of this pathology.
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O Col?gio Nossa Senhora das Dores e o projeto educacional das Filhas da Caridade em Diamantina 1905-1925Loredo, Meirelle Aiane Almeida 20 October 2017 (has links)
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Previous issue date: 2017 / O objetivo central desse trabalho ? a an?lise do projeto educacional desenvolvido no Col?gio Nossa Senhora Das Dores em Diamantina, pelas Filhas da Caridade no per?odo de 1905 a 1925. J? os objetivos espec?ficos desse trabalho consistem em analisar o discurso ultramontano presente nas pr?ticas escolares do col?gio e identificar a influ?ncia das caracter?sticas institucionais da Congrega??o das Filhas da Caridade na forma??o da mocidade feminina. O educand?rio recebia alunas internas e externas e cuidava de meninas ?rf?s. As mo?as do Nossa Senhora das Dores eram preparadas para serem boas m?es, esposas e educadoras. Com rela??o ?s pr?ticas pedag?gicas desenvolvidas no col?gio, a presente pesquisa prop?e investig?-las utilizando-se do m?todo qualitativo. Como instrumento para a realiza??o da pesquisa foi utilizada an?lise documental e levantamento bibliogr?fico. Para tanto, prop?e-se investigar os dispositivos legais que foram institucionalizados para a efetiva??o desse projeto tanto no que concerne ?s leis do Estado, como as leis da Igreja e do pr?prio Col?gio. Sendo assim, o resultado da pesquisa ? ressaltar a import?ncia de discutir a organiza??o do ensino feminino e a sua tentativa de sistematiza??o dentro do quadro educacional, utilizando as mulheres como instrumento de expans?o desse novo discurso. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Educa??o, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The main objective of this work is the analysis of the educational project developed at the Col?gio Nossa Senhora das Dores in Diamantina by the daughters of charity from 1905 to 1925. The specific objectives of this work are to analyze the ultramontane discourse present in the school practices of the college and to identify the influence of the institutional characteristics of the Congregation of the Daughters of Charity in the formation of the female youth. The educational received internal and external students and take cared of orphaned girls. The girls of Nossa Senhora das Dores were prepared to be good mothers, wives and educators. With respect to the pedagogical practices developed in the college, the present research proposes to investigate them using the qualitative method. As an instrument for conducting the research will be used documentary analysis and bibliographic survey. In order to do so, it is proposed to investigate the legal documents that have been institutionalized for the realization of this project both with regard to the laws of the State, as well as the laws of the Church and of the College itself. Therefore, the expected result of the research is to emphasize the importance of discussing the organization of female teaching and its attempt to systematize within the educational framework, using women as an instrument to expand this new discourse.
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Inquisi??o em Vila Rica setecentista: aspectos das pr?ticas inquisitoriais no per?odo compreendido entre 1711 e 1750Colen, Dalvan Charbaje 20 September 2017 (has links)
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Previous issue date: 2017 / Este trabalho se desenvolveu atrav?s de pesquisas e contribui??es com a tem?tica Inquisi??o e seus aspectos Inquisitoriais, na busca de abstrair a atua??o do Tribunal do Santo Of?cio em Vila Rica - Minas Gerais, seus desdobramentos e experi?ncias nas primeiras d?cadas do s?culo XVIII. Ter acesso a documentos prim?rios da Inquisi??o, no inicio da forma??o territorial de Vila Rica viabilizou compreender mais a realidade do Santo Of?cio, os seus interesses e como atuavam, tendo em vista o car?ter m?ltiplo de julgador, controlador e repressor, atuando aparentemente como ide?rio da manuten??o da f? Cat?lica. Assim, selecionou-se Vila Rica, por se tratar de uma das principais Vilas no per?odo colonial do Brasil. Logo, houve delimita??o do espa?o e tempo; vale relatar que o principal expoente Inquisitorial em Vila Rica eram os Crist?os-Novos (1711-1750). / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Tecnologia, Sa?de e Sociedade, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / This work was developed through researches and contributions with the Inquisition and its Inquisitorial aspects, in the quest to abstract the actions of the Court of the Holy Office in Vila Rica - Minas Gerais, its developments and experiences in the first decades of the 18th century. Having access to primary documents of the Inquisition, at the beginning of the territorial formation of Vila Rica made it possible to understand more the reality of the Holy Office, its interests and how they acted, considering the multiple character of a judge, controller and repressor, apparently acting as maintenance of the Catholic faith. Thus, Vila Rica was selected because it is the main towns in the colonial period of Brazil. Therefore, there was delimitation of space and time; it is worth mentioning that the main Inquisitorial exponent in Vila Rica was the New-Christians (1711-1750).
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Testování pachových ohradníků pro odstrašení vydry říční (Lutra lutra) na sádkách Krajského školního hospodářství a zkušenosti s náhradami škod dle zákona č. 115/2000 Sb. / Testing of odour fences as protecting measure against otter on small ponds of fisheries KŠH ČB, Protivín and opinion with compensation of damages after law N.115/2000Sb.KOTLÍN, Vít January 2017 (has links)
The presented diploma thesis deals with the current issue of compensation for damages caused by European otter (Lutra lutra), namely the use of feasible preventive measures to eliminate damages and to ensure the entitlement to compensation in accordance with the law No 115/2000 Col. It also presents the results of practical testing of scent barrier systems as an alternative protective equipment agains unwanted predation in real conditions of fish storage pools.
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Développement d'un implant à géométrie variable pour le traitement des fractures du fémur proximal chez les personnes âgées / Development of an adjustable implant for proximal femoral fractures in the elderlyBillard, Rémi 21 February 2014 (has links)
Les fractures du fémur proximal de la personne âgée sont généralement fixées par des dispositifs d’ostéosynthèse. Pour les fractures particulières dites inter-trochantériennes, il est possible de fixer la fracture de manière intra-médullaire (à l’intérieur de l’os) ou de manière extra-médullaire (en dehors de l’os). Pour chaque type de traitement, les hôpitaux sont équipés des deux systèmes de fixation. Les différences de morphologie des individus impliquent l’existence de multiples références d’implants et donc de surcoûts en termes d’équipement. Dans ce travail de thèse, un implant original adaptable à la plupart des morphologies a été développé. Cet implant permettra non seulement d’offrir aux chirurgiens une souplesse au cours des interventions chirurgicales mais aussi de réduire de manière significative les stocks d’implants dans les hôpitaux. Le comportement mécanique de l’implant est étudié dans différents cas de fractures par deux approches complémentaires, une méthode numérique par Éléments Finis et une approche expérimentale mettant en oeuvre des techniques de stéréo-corrélation à partir d’images de caméras rapides. Les résultats des calculs numériques sont confrontés à ceux issus d’essais réalisés sur des fémurs synthétiques, puis cadavériques en laboratoire d’anatomie. Les comparaisons avec des implants existants montrent que ce nouveau concept d’implant permet une fixation plus stable des fragments osseux et une bonne compression du foyer de fracture. / Proximal femoral fractures in the elderly are generally fixed with osteosynthetic devices. For specific fractures called intertrochanteric, it is possible to fix the fracture in an intramedullary way (inside the bone) or in an extramedullary way (outside the bone). For each type of treatment, hospitals are equipped with the two fixing systems. The differences in physical characteristics between individuals imply the existence of multiple references implants and therefore additional costs in terms of equipment. In this thesis work,an original implant adaptable to most people has been developed. This implant will provide surgeons greater flexibility during surgery but also significantly reduce stocks implants in hospitals. The mechanical behavior of the implant is studied in different cases of fractures by two complementary approaches,a finite element analysis and an experimental study employing stereo-image correlation technique from images of high speed cameras. The results of the numerical calculation are compared with those derived from tests on synthetic femurs, then cadaver in anatomy laboratory. Comparisons with existing implants show that this new implant concept allows for a more stable fixation of bone fragments and a good compression of the fracture.
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Em nome da rep?blica: escolas e tradi??es modernasMoreira, Keila Cruz 21 March 2011 (has links)
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Previous issue date: 2011-03-21 / Our research aims to analyze some institutions of primary education in so-called First Republic in Natal/RN, when they were considered high standard institutions on training, dissemination and creation of national identity and republican traditions. Thus, we investigated to try to understand the creation of the new man and the invention of new traditions to confirm the status of republican modernity in two schools in Natal, the Colegio Americano, a private one, and a standard model of school, Augusto Severo, which is a public one. As a basis we have the history of institutions to analyze, paying close attention to consider the use of imitation in cultural patrimony as well as the use of strategies to distinguish. The concept of ownership follows, for present purposes, their focus of study on observation of diverse and contrasting use of these cultural objects, texts, readings and ideas from research institutions. For analysis of the link which occurs within the school environment, in every period of its history, we used the concept of school culture as a set of rules and practices which define knowledge to teach and conduct the introject. A culture that incorporates the school to keep a set with other religious cultures, political and popular of its time and space. In this sense, the educational institutions which we studied while showing what kind of in this work by preparing cultures, codes, different practices, and specific individuals they have, they were in important locations to provide modern cultural appropriation as a strategy for educational innovation and a factor of rationality and efficiency which could be observed and controlled, so gradually the modern school education was organized to produce its own society. As a challenge of affirmation and incorporating diverse social experiences to produce the modern, civilized man of the Republican time, the school, as part of the social life, which is singular in its practices, not only the set of reforms, decrees, laws and projects, but also as expressions of concept about life and society in terms of material, symbolic and cultural symbols in the social context in modernization. We focused on these two schools, because inside the wide cultural and material status of the city, they were the first republic schools which had the goal of having men and woman together culturally , with a view to adapting them to the modern movement to make them civilized / educated / rational . On this view, we would emphasize that this statement needs a reinvention as a new way through what is made at the schools which production of new spaces, practices, rites and what represents school, making and expressing a new identity, modern, different of the old symbols of the Empire. For this, nothing better than the organization of schooling, emphasizing on educating the individual and his/her responsibilities with the order and progress. We need to understand the past as a result of conflicts, including strengths and limitations within the historical and social context, and the invention of tradition as a process of formalization and ritualization of acts which want to perpetuate, as a reference to a group identity. These are practices and social educative representations which support the understanding of pedagogical and educational ideas at this historical moment, making a new way of being and doing in the Republican universe / Nossa pesquisa prioriza a an?lise das institui??es de ensino prim?rio na chamada Primeira Rep?blica em Natal/RN, enquanto inst?ncias privilegiadas na forma??o, divulga??o e cria??o da identidade nacional republicana e suas tradi??es. Assim, buscamos investigar e compreender a cria??o do homem novo e a inven??o de novas tradi??es para confirmarem o status de modernidade republicana dentro de duas institui??es escolares na cidade do Natal, o Col?gio Americano (de iniciativa privada) e o grupo escolar modelo, Augusto Severo (p?blica). Temos como base de an?lise a Hist?ria das institui??es, tendo o cuidado de considerar a imita??o do uso de bens culturais bem como o uso de estrat?gias de distin??o. A no??o de apropria??o segue, para fins deste trabalho, seu foco de estudo na observa??o do emprego diverso e contrastante dos mesmos bens culturais, textos, leituras e id?ias das institui??es pesquisadas. Para an?lise das rela??es que ocorrem dentro do ambiente escolar, em cada per?odo de sua hist?ria, utilizamos o conceito de cultura escolar, enquanto um conjunto de normas e pr?ticas que definem conhecimentos a ensinar e condutas a introjetar. Uma cultura que incorpora o fazer escolar, mantendo um conjunto com outras culturas religiosas, pol?ticas e populares de seu tempo e espa?o. Nesse sentido, as institui??es educativas estudadas neste trabalho, ao disporem de culturas, c?digos, pr?ticas diferenciadas, singulares e espec?ficas, constitu?ram-se em locais privilegiados para se darem apropria??es culturais modernas, como estrat?gia de inova??o educacional e fator de racionalidade e efici?ncias, observ?veis e control?veis. Paulatinamente, a educa??o escolar moderna, se organizava ao produzir a pr?pria sociedade. No desafio da afirma??o e incorpora??o de diversas experi?ncias sociais para produzir o homem republicano moderno e civilizado, a escola, como parte do social, singularizava em suas pr?ticas, n?o somente o conjunto de reformas, decretos, leis e projetos, mas express?es de concep??es de sociedade e vida no plano material, simb?lico e cultural, no contexto social em moderniza??o. Detemo-nos nessas duas institui??es porque dentro do diverso estado material e cultural da cidade foram as primeiras escolas republicanas que objetivavam homogeneizar culturalmente homens e mulheres na perspectiva de adequ?-los ao movimento da modernidade para faz?-los civilizados/educados/racionais. Sobre esse prisma conv?m destacar que essa reinven??o necessita de uma afirma??o como nova forma escolar atrav?s da produ??o de novos espa?os, pr?ticas, ritos e s?mbolos escolares, produzindo e expressando uma nova identidade, o moderno, contr?rio aos s?mbolos ultrapassados do Imp?rio. Para tanto, nada melhor do que a organiza??o da instru??o escolar, com ?nfase na forma??o do indiv?duo, e suas responsabilidades com a ordem e o progresso. ? entendermos o passado como resultado dos conflitos, com suas potencialidades e limites dentro do contexto hist?rico e social e a inven??o de tradi??es enquanto processo de formaliza??o e ritualiza??o de atos que se quer perpetuar como refer?ncia de identidade a um grupo. S?o essas pr?ticas e as representa??es s?cio-educativas que favoreceram a compreens?o das id?ias pedag?gico-educacionais nesse momento hist?rico, destinadas a formar um novo modo de ser e fazer no universo republicano
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O conhecimento em administra??o: uma cartografia das perspectivas epistemol?gicasSouza, Catarina da Silva 29 April 2016 (has links)
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Previous issue date: 2016-04-29 / ministra??o, que recebe sobremodo influ?ncias de uma colonialidade do
pensamento, que subjaz a outras possibilidades de vis?es, numa perspectiva mais
cr?tica e reflexiva acerca das quest?es organizacionais e suas implica??es no
contexto sociocultural, expressas tanto nos itiner?rios das ideias, como na l?gica
produtivista do pensamento linear, bem como na forma??o utilitarista dos cursos das
escolas superiores. T?m-se como objetivo elaborar uma cartografia simb?lica das
ideias do conhecimento em administra??o na tentativa de identificar aproxima??es
com o conhecimento regula??o, mas tamb?m pistas de aproxima??es com o
conhecimento emancipa??o. Prop?e-se mapear as perspectivas epistemol?gicas do
conhecimento em Administra??o no Brasil, tendo como aporte te?ricoepistemol?gico
autores cl?ssicos e contempor?neos que discutem a descoloniza??o
do pensamento, destacando-se a proposta de Boaventura de Sousa Santos ao
trabalhar como contraponto a esse colonialismo hegem?nico a ?epistemologia do
sul?, complementada por outros referentes epist?micos de Santos, quais sejam os
conceitos de Sociologia das Aus?ncias, Sociologia das Emerg?ncias, Ecologia dos
saberes, e Tradu??o, al?m de referentes de outros autores do movimento
Modernidade/Colonialidade. Para compreender a constitui??o desse conhecimento,
examinam-se, como campo emp?rico, as experi?ncias encontradas no Col?quio
Internacional de Epistemologia e Sociologia da Ci?ncia da Administra??o (2011-
2015). Enquanto estrat?gia de pesquisa configuram-se os dados da pesquisa
emp?rica em uma cartografia simb?lica, conforme proposta por Santos (2009a), por
ela permitir a demonstra??o das ?[...] virtualidades anal?ticas e te?ricas de uma
abordagem sociol?gica que tome por matriz de refer?ncia a constru??o e a
representa??o do espa?o?. Constata-se uma atualiza??o das perspectivas
epistemol?gicas do conhecimento em administra??o, no sentido de buscar as bases
epist?micas que fomentam sua constitui??o, bem como; compress?o e dialogo com
outras ?reas do conhecimento e suas estrat?gias metodol?gicas. Destaque para
tem?ticas como gest?o p?blica, economia solid?ria, racionalidade e dom?nios
espec?ficos da administra??o, como finan?as, empreendedorismo e estrat?gia.
Verifica-se o alinhamento ao conhecimento regula??o, todavia; h? aproxima??es ao
conhecimento emancipa??o iminente ?s reflex?es do pensamento cr?tico em
administra??o. / We study the epistemological perspectives of knowledge production
Administration, which seems to receive greatly influences a coloniality of thought
which underlies other possibilities visions in a more critical and reflective perspective
on organizational issues and their implications for the socio-cultural context,
expressed both on the routes of ideas, as in the productivist logic of linear thinking
and the utilitarian training courses of higher education. There have as objective to
elaborate a symbolic mapping of knowledge management ideas in an attempt to
identify approaches with knowledge regulation, but also approaches slopes with
knowledge emancipation. It is proposed to map the epistemological perspectives of
knowledge in Administration in Brazil, with the theoretical and epistemological
contribution classic and contemporary authors propose the decolonization of thought,
especially the proposal of Boaventura de Sousa Santos to work as opposed to this
colonialism hegemonic the "southern epistemology", complemented by other
epistemic referents of Santos, namely the concepts of Sociology of Absences,
Sociology of Emergencies, ecology of knowledge, and translation, as well as
regarding other authors of Modernity / Coloniality movement. To understand the
constitution of this knowledge, it looks as empirical field, the experiences found in the
International Colloquium on Epistemology and Sociology of Management Science
(2011-2015). While research strategy configure the data of empirical research in a
symbolic cartography, as proposed by Santos (2009a), for it allows the
demonstration of "[...] analytical and theoretical virtues of a sociological approach to
take for matrix reference to construction and representation of space?. There has
been an update to the epistemological perspectives of knowledge in administration,
in order to seek the epistemic bases that promote their constitution, as well as;
compression and dialogue with other areas of knowledge and methodologies
strategies. Highlighting issues such as public management, solidarity economy,
rationality and specific areas of management such as finance, entrepreneurship and
strategy. Check the alignment knowledge regulation, however; There are approaches
to knowledge imminent emancipation to the reflections of critical thinking in
management.
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Otimiza??o de controladores Fuzzy Tipo-2 intervalares utilizando meta-heur?sticasCavalcante, M?rio S?rgio Freitas Ferreira 27 June 2017 (has links)
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Previous issue date: 2017-06-27 / Industrialmente, diversas estrat?gias e algoritmos de controle j? s?o utilizadas e registradas
na literatura. Entre as t?cnicas existentes, os controladores fuzzy destacam-se
pela sua capacidade de tratar de severas n?o linearidades presentes em plantas reais e por
conseguir representar o conhecimento especialista, que ? impreciso e inexato matematicamente.
Este trabalho estudou dois tipos de controladores fuzzy existentes, baseados
no modelo Sugeno, sendo fuzzy tipo-1, aqui classificado como fuzzy convencional, e o
fuzzy tipo-2. Devido a complexidade em sintonizar controladores fuzzy que apresentam
uma grande quantidade de par?metros, esse trabalho se prop?e a testar diferentes m?todos
de otimiza??o meta-heur?sticos para a sintonia de controladores. Para validar os controladores
obtidos foi utilizado um servo motor-DC da Quanser, um problema de controle
que requer precis?o e velocidade na corre??o do erro de segmento da refer?ncia. Com o
intuito de comparar o comportamento dos controladores, otimizou-se um controlador PI
para cada um dos sistemas. Para quantificar e qualificar cada controlador foram utilizados
tr?s ?ndices de avalia??o, ITEA, IEA e o ?ndice de Goodhart, este ?ltimo utilizado por
levar em considera??o tamb?m o sinal de controle aplicado na planta. Pela an?lise dos resultados
obtidos, o controlador fuzzy tipo-2 apresentou ganho significativo para o controle
dessa planta, quando otimizado com o m?todo PSO. Pelos resultados, pode-se tamb?m inferir
que o algoritmo das formigas n?o mostrou-se adequado para esse problema, com a
fun??o de avalia??o proposta. / Differents stategies and control algorithms are already tested and registered by industry.
Among the existing techniques, fuzzy controllers stand out for their ability to deal with
nonlinearities present in real plants. Another fuzzy also allows to best represent expert
knowledge, which is mathematically inaccurate. This proposal studied the two types of
fuzzy controllers, based on Sugeno Model, the fuzzy type-1 is classified as conventional
fuzzy and fuzzy type-2. In this study is used optimization techniques seeking to tune controllers
in order to solve one of the biggest problem in fuzzy logic, its tunning. Ant colony,
particle swarm and genetic algorithm are used and evaluated to this problem. A servo
motor-dc is used to validate fuzzys controllers and pi controller obtained by optimization
tecniques. In order to quantify and qualify each controller, three indices were used IEA,
ITEA and Goodhart index. The results obtained prove that the type-2 fuzzy controller presented
significant gain for the control of this plant, when optimized with the PSO method.
From the results, it can also be inferred that the ant algorithm was not adequate for this
problem, with the proposed evaluation function.
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Exploration de nouvelles voies thérapeutiques contre le cancer du col de l'utérus : approche combinée par adénovirus et ARN interférence / Adenovirus mediated RNA interference as new therapeutic tool against cervical cancerBonetta, Anaëlle 16 January 2013 (has links)
Le cancer du col de l’utérus est le troisième cancer le plus fréquent chez la femme, dont l’agent étiologique majeur est l’infection par les papillomavirus humain (notamment HPV-16 et 18), qui sont de petits virus infectant les épithéliums muqueux et cutanés, et pouvant induire la formation de tumeurs. L’inducteur majeur du processus oncogène est le processus d’intégration des régions codantes pour les oncoprotéines E6 et E7, au sein de la cellule hôte suite à l’infection. Elles interférent avec le cycle cellulaire et induisent notamment l’immortalisation, voire la transformation des cellules. Les fonctions les plus connue de ces deux oncoprotéines sont la dégradation des suppresseurs de tumeur p53 et pRb, respectivement. Mon travail de thèse à consisté en la mise au point des vecteurs adénoviraux exprimant des miARN dirigés contre l’oncoprotéine E6. Exprimés in vitro ils induisent l’induction de la mort cellulaire par apoptose des cellules tumorales traitées, via l’activation de la voie de caspases, et in vivo permettent le ralentissement de la croissance de tumeurs xénogreffées à des souris Nude. De plus, la stratégie thérapeutique adénovirale a montré ses extensions possibles sur d’autres types de cancers HPV-positifs, mais également via l’expression de différentes moléculaires thérapeutiques, visant à empêcher l’interaction des oncoprotéines telles qu’E6 avec leurs partenaires cellulaires et ainsi les empêcher d’exercer les activités biologiques impliquées dans le développement de cancers. Pour finir, les adénovirus peuvent également être vu comme des outils d’extinction fonctionnels d’E6 et permettant d’étudier les répercutions sur d’autres processus cellulaires. / Cervical cancer is the third most common female cancer. Infection by human papillomavirus (mainly HPV-16 and 18), with tropisms for mucosal or cutaneous squamous surfaces, is the major etiological agent implicated in cancer and tumor development. After infection, the oncogenic process is triggered by integration of oncoproteins E6 and E7 coding regions into the host cell genome. After integration, these oncoproteins interfere with the cell cycle and induce immortalization and cellular transformation of normal cells. The best known function of these two oncoproteins is the degradation of tumors suppressors p53 and pRb respectively. My thesis project consisted in the development of adenoviral vectors expressing miRNA directed against E6 oncoprotein. Their in vitro expression resulted in cellular death by apoptosis of the treated tumor cells, and allowed reduction of tumor growth in vivo in nude mice xenografts. In addition, the adenoviral therapeutical strategy showed its possible extensions on other types of HPV-positive cancers, but also through the possible expression of different therapeutic molecules aimed at preventing the interaction of viral oncoproteins, such as E6, with their cellular partners. These abolished interactions prevent oncoproteins from exercising their biological activities implicated in the development of cancers. In conclusion, we can say that adenoviruses can also be seen as functional tools suppressing E6 and enabling to highlight the repercussions of its suppression on other cellular processes.
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