Submitted by Gisele Lamberti Zanirato null (gisele_zanirato@yahoo.com.br) on 2017-07-07T15:51:00Z No. of bitstreams: 1 Diss Gisele L Zanirato rep.pdf: 1048307 bytes, checksum: 64d1df70f421a6b3857410fbad214c61 (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-07-13T17:37:01Z (GMT) No. of bitstreams: 1 zanirato_gl_me_sjrp.pdf: 1048307 bytes, checksum: 64d1df70f421a6b3857410fbad214c61 (MD5) / Made available in DSpace on 2017-07-13T17:37:01Z (GMT). No. of bitstreams: 1 zanirato_gl_me_sjrp.pdf: 1048307 bytes, checksum: 64d1df70f421a6b3857410fbad214c61 (MD5) Previous issue date: 2017-06-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Com a expansão dos centros urbanos e das atividades agrícolas, as áreas do bioma Cerrado no estado de São Paulo vêm sendo transformadas em paisagens altamente fragmentadas constituídas em grande parte por fragmentos pequenos. A perda e a fragmentação do habitat tem sido um dos principais fatores responsáveis pelo declínio populacional e pela extinção local de espécies com baixa densidade populacional, baixa taxa de reprodução, alta demanda por espaço e especialista alimentar, como o tamanduá-bandeira (Myrmecophaga tridactyla). É conhecido que algumas espécies de mamíferos modificam seus padrões de atividade frente às perturbações antrópicas e até em relação aos efeitos da perda de habitat. Diante disso, os objetivos deste estudo foram avaliar se a área e o isolamento do fragmento, a porcentagem de vegetação nativa e a disponibilidade hídrica da paisagem são importantes para explicar a ocupação dos fragmentos pelo tamanduá-bandeira, e verificar se há diferenças no padrão de atividade entre as populações de tamanduás que ocupam os fragmentos menores (< 2.015 ha) e a população que ocupa o fragmento maior (10.285 ha). Os dados de presença e ausência dos tamanduás-bandeira em cada um dos vinte fragmentos de vegetação nativa localizados no nordeste do estado de São Paulo foram coletados através de armadilhas fotográficas. A influência da temperatura e da pluviosidade na probabilidade de detecção dos tamanduás e a importância das variáveis de fragmento e de paisagem na probabilidade de ocupação dos fragmentos pela espécie foram avaliadas através de modelos de ocupação de estação única. O Critério de Informação de Akaike corrigido (AICc) foi utilizado para a seleção dos melhores modelos e o teste de Mardia Watson Wheeler foi usado para verificar possíveis diferenças no padrão de atividade entre as populações que ocupam os fragmentos menores e a população presente no fragmento maior. O padrão de atividade dos tamanduás não foi influenciado pela área do fragmento, no entanto, a probabilidade de ocupação dos fragmentos pela espécie foi maior nos fragmentos com áreas maiores e em fragmentos com maior porcentagem de vegetação nativa ao redor. Portanto, a conservação de fragmentos maiores e de fragmentos com maior porcentagem de vegetação nativa ao redor é de grande importância para a conservação de tamanduás-bandeira no nordeste do estado de São Paulo. / With the expansion of urban areas and agricultural activities, the Cerrado’s areas in São Paulo state have been transformed in highly fragmented landscapes consisting largely of small fragments. Habitat loss and fragmentation have been one of the main factors responsible for population decline and local extinction of species with low population density, low reproduction rate, high spatial demand and diet specialist, such as the giant anteater (Myrmecophaga tridactyla). It is known that some species of mammals modify their activity patterns in face of anthropic disturbances and even in relation to the habitat loss effects. On this, the aims of this study were to evaluate if the patch’s area and the isolation, the native vegetation percentage and water availability in the landscape are important to explain the patches occupancy by the giant anteater, and verify if there are differences in the activity pattern between the anteaters populations that inhabit the smaller patches (<2,015 ha) and the population that occupies the larger patch (10,285 ha). The presence and absence data of the giant anteaters in each one of the twenty patches of native vegetation located in the northeast of the São Paulo state were collected through camera traps. The temperature and rainfall influence on the detection probability of the anteaters and the importance of the patch and landscape variables on the occupancy probability of the patches by the species were evaluated through single-season occupancy models.The corrected Akaike Information Criterion (AICc) was used to select the best models and the Mardia Watson Wheeler test was used to verify possible differences in the activity pattern between the populations that inhabit the smaller patches and the population present in the larger patch. The activity pattern of the anteaters was not influenced by the patch’s area, however, the occupancy probability of the patches by the species was higher in the larger patches and in patches with higher native vegetation percentage around. Therefore, the conservation of larger patches and of the patches with higher native vegetation percentage around them is of great importance for the anteater conservation in the northeast of the São Paulo state.

Orientador: Mirela Tinucci Costa / Banca: Gisele Fabrino Machado / Banca: Gervásio Henrique Bechara / Resumo: O tumor ósseo de células gigantes apresenta 3 diferentes tipos celulares, sendo duas estromais: fibroblastos neoplásicos e células mononucleares; e o terceiro tipo, células gigantes. Propôs-se que este tumor é de linhagem monócito-macrofágica e acredita-se que as células gigantes se formam por fusão de células mononucleares. Aparentemente os fibroblastos neoplásicos que expressam o fator transformador de crescimento TGF"beta"1 estão envolvidos no recrutamento das células gigantes para o tumor. Com o intuito de compreender melhor a histogênese, o envolvimento do estrógeno e a expressão de receptores TGF"beta"1, foi realizado este estudo em casos deste tumor em gatos domésticos. Para tanto foi utilizado o método imuno-enzimático Streptoavidina-biotina utilizando-se o anticorpo primário anti-vimentina, clone 3B4 (Dako A/s, Denmark); o anticorpo marcador de macrófago, MAC387 (Dako A/s, Denmark); o anticorpo para receptores de estrógeno, clone 15D (Dako A/s, Denmark) e o anticorpo marcador para TGF"Beta"1 (Santa Cruz Biotechnology). Os resultados foram analisados pela porcentagem e desvio padrão de células marcadas para cada anticorpo e permitiram concluir que: o TOCG de gatos domésticos, assim como em humanos, tem origem mesenquimal e expressa receptores de estrógeno e de TGF 1 e as células gigantes do tumor não reagem com o clone 387, marcador de células de linhagem mielomonocítica. / Abstract: Giant cell tumor of bone are composed of 3 different cell types: round mononuclear stromal cells, spindle-shaped mononuclear stromal cells, and giant cells. Some authors assert giant cell could arise by fusion of mononuclear cell mielomonocytic. Aparently neoplasic fibroblast that expression TGF is involved in the recruitment of giant cells from tumor. For better understand of histogenesis, the involved of receptors estrogen and of expression of TGF receptors, achieved this study in this cases tumor in domestics cats. By using the immune-enzymatic Streptoavidin- biotin using the primary antibody anti-vimentin, clone VIM 3B4 (Dako A/s, Denmark); antibody myeloid/histocyte clone MAC 387 (Dako A/s, Denmark); antibody estrogen receptor clone 1D5 (Dako A/s, Denmark) and the antibody TGFb1 (Santa Cruz Biotechnology). The results analyzed for percent and standara deviation of marks cells for each antibody and permissive to come to a conclusion: the GCT of bone in domestic cats, like humans, has mesenchymal origin and has expression of estrogen receptors and of TGF"beta", and giants cells this tumor not react with the clone 387, mark the cells myeloidmonocyte lineage. / Mestre

[pt] Amperímetros convencionais devem ser inseridos em série com o elemento no qual se deseja medir a corrente, constituindo uma forma de medição invasiva. Amperímetros alicate, baseados em bobinas, realizam medições de forma não invasiva, mas são limitados a correntes alternadas. Para medição de correntes contínuas, amperímetros baseados no efeito Hall são utilizados, mas possuem baixo nível de tensões de saída e pouca estabilidade em relação à temperatura. O objetivo desta dissertação foi desenvolver um protótipo de amperímetro baseado em magnetômetros de magnetorresistência gigante (GMR) capaz de medir correntes contínuas, de forma não invasiva e com alta resolução em relação aos amperímetros alicate. A metodologia dividiu-se em: (i) utilização de dois magnetômetros GMR para medir o campo magnético gerado pela corrente elétrica em um condutor; (ii) projeto e implementação de um solenoide para polarizar os sensores na faixa de operação linear; (iii) aprimoramento e desenvolvimento de circuitos eletrônicos dedicados à excitação e leitura dos GMRs; (iv) implementação de algoritmos para solução do problema inverso, isto é, a partir da saída do circuito, em mV, estimar a corrente que passa pelo condutor e a distância entre este e o amperímetro. Foram realizados 60 testes, com correntes variando de -3 A a 3 A, com passos de 0,1 A. O protótipo foi capaz de estimar a corrente elétrica com incerteza expandida, do tipo A, de 0,091 A e 0,07 cm para a distância. Os resultados comprovam a viabilidade da realização de medições de corrente, por aproximação, utilizando sensores GMR. / [en] Conventional ammeters should be inserted in series with the element in which the current is to be measured, thus constituting an invasive measurement form. Clamp ammeters, based on coils, are able to measure non-invasively but are limited to alternating currents. For measurement of direct currents, Hall-based ammeters are used, but have low output voltages and little temperature stability. Thus, the objective of this dissertation was to develop a prototype based on giant magnetoresistance (GMR) magnetometers capable of measuring direct currents, non-invasively and with high resolution in relation to clamp ammeters. The methodology was divided into: (i) the use of two GMR magnetometers to measure the magnetic field generated by the electric current in a conductor; (ii) design and implementation of a solenoid to polarize the sensors in the linear operating range; (iii) improvement and development of electronic circuits dedicated to the excitation and reading the GMRs; (iv) implementation of algorithms to solve the inverse problem, that is, from the outputs of the circuit, in mV, estimate the current passing through the conductor and the distance between it and the ammeter. Sixty tests were performed, with currents varying from -3 A to 3 A, with steps of 0.1 A. The prototype was able to estimate the electrical current with type A expanded uncertainty of 0.091 A and 0.07 cm for the distance. The results demonstrate the feasibility of conducting current measurements by approximation using GMR sensors.

Central giant cell granuloma (CGCG) is an uncommon pathology of the maxillary bones, which has diverse clinical behavior. It can be treated either by surgical removal or by conservative methods such as systemic daily application of calcitonin and intralesional injections of corticosteroids. Recurrence of lesions seems to vary according to its clinical behavior, location and treatment modality. The aim of this study was to evaluate the recurrence rate of the CGCG of the jaws and its associated factors through a systematic review and meta-analyses. An electronic search in PubMed and Scopus databases was conducted in order to identify observational studies, published in English, that reported the recurrence rate of CGCG of the jaws regardless of treatment modality. In addition, a hand search of cross-references was also carried out identify additional studies. We excluded studies that did not report the main outcome of interest, with less than five cases and studies not available for full text review. Twenty-one studies, published between 1973 and 2011 met eligibility criteria and were included in this review. We observed a global recurrence rate of 13.4% (8.4%-19.1%, 95% CI). Surgical curettage showed the higher recurrence rate (15.8%, 10.7 – 21.7 95%CI), followed by calcitonin administration (9.7%, 0.0 – 31.8 95% CI) and surgical resection (0.16%, 0.0 – 0.07 95%CI). Lesion location was not associated with a higher risk of recurrence (RR = 1.7, 0.97 – 2.9, 95% CI). The results of this systematic review showed a high risk of lesion recurrence of aggressive CGCG treated with surgical curettage. / A lesão central de células gigantes (LCCG) é uma patologia incomum dos maxilares que apresenta comportamento clínico bastante variável. As modalidades terapêuticas para esta lesão variam desde tratamentos conservadores, com o uso de calcitonina e corticosteróides, a abordagens cirúrgicas mais radicais. As taxas de recidiva parecem variar de acordo com o comportamento clínico das lesões, tratamento indicado e localização. O objetivo deste trabalho foi, através de uma revisão sistemática com metanálise, avaliar as taxas de recidiva da LCCG dos maxilares e seus fatores associados. A revisão sistemática da literatura foi conduzida utilizando-se de busca eletrônica pelas bases de dados PubMed e Scopus. A lista de referências de todos os estudos elegíveis foi manualmente analisada para identificar estudos adicionais a serem incluídos. Foram incluídos estudos observacionais, publicados em língua inglesa, que relataram a taxa de recidiva da LCCG dos maxilares independente do tipo de tratamento realizado. Foram excluídos os estudos com menos de 5 casos, aqueles em que o desfecho de interesse não foi relatado e os artigos não disponíveis para leitura na íntegra. A heterogeneidade estatística entre os estudos foi analisada através do teste Q de Cochran e do índice I2 de Higgins e Thompson. As taxas de recidiva foram calculadas através de um modelo de efeitos randômicos após transformação do tipo Freeman-Tukey. O risco relativo para recidiva de acordo com comportamento clínico e localização das lesões foi calculado pelo método de Mantel-Haenszel. Foram incluídos 21 estudos observacionais, publicados entre 1973 e 2011. Foi observada uma taxa global de recidiva de 13.4% (IC 95% 8.4-19.1). Os pacientes tratados através de curetagem, ressecção cirúrgica e calcitonina tiveram taxas de recidiva de 15.8% (IC 95% 10.7-21.7), 0.16% (IC 95% 0.0-0.07) e 9.7% (0.0-31.8%), respectivamente. As lesões de comportamento agressivo tiveram um risco relativo para recidiva de 3.1 (IC 95% 1.7-5.7). Não foi observado aumento do risco em relação à localização da lesão (RR = 1.7; IC 95% 0.97-2.9). Desta forma, os resultados desta meta-análise indicam um risco elevado de recidiva em LCCG de comportamento agressivo e tratadas através de curetagem.

La découverte des virus géants il y a une dizaine d’années a véritablement bouleversé notre perception du monde viral. Cette découverte a ouvert un débat sur l’origine et l’histoire évolutive de ces virus, et ravivé celui portant sur la nature des virus : peuvent-ils être considérés comme vivants ?J'ai caractérisé un nouveau Marseilleviridae, isolé à partir d’un échantillon prélevé en Nouvelle-Calédonie, appelé Noumeavirus. Les Marseilleviridae sont des grands virus à ADN, qui possèdent des particules à symétrie icosaédrique d’environ 200 nm de diamètre, et des génomes à ADN double-brin de plus de 300 kb. Différentes approches de génomique, protéomique, ainsi que l’étude du cycle infectieux ont montré que le cycle infectieux de ces virus n’était pas indépendant du noyau cellulaire mais recrutait transitoirement les fonctions nucléaires à l’usine virale.J'ai également caractérisé un nouveau Pandoravirus, isolé à partir d’un échantillon prélevé en Nouvelle-Calédonie, appelé Pandoravirus neocaledonia. Les Pandoravirus possèdent une morphologie unique au sein des virus, ainsi qu’un génome colossal à ADN double-brin de 2.5 Mb. Des études comparatives avec d’autres Pandoravirus ont été réalisées en combinant plusieurs approches, afin de mieux comprendre les caractéristiques de ces virus inédits. La morphologie étonnante de ces virus nous a poussés à étudier la nature de leur enveloppe, constituée d’un réseau de fibres formant des structures lamellaires. Se pourrait-il que les Pandoravirus, contrairement aux autres virus, détournent la machinerie cellulaire pour construire leurs particules ? Dans ce cas, quelle serait leur place dans l’histoire évolutive des virus ? / The discovery of giant viruses about a decade ago has truly shaken our perception of the viral world. This discovery has initiated a debate on the origin and evolutionary history of these viruses, and it revived the debate on their nature: are viruses alive?I characterized a new Marseilleviridae, isolated from a sample collected in New-Caledonia, named Noumeavirus. The Marseilleviridae are large DNA viruses that have icosahedral particles of about 200 nm in diameter, and double-stranded DNA genomes of more than 300 kb. Various approaches, such as genomics, proteomics and the study of the infectious cycle, allowed us to reveal that the infectious cycle of these viruses was not independent from the cell nucleus as we thought, but was transiently recruiting nuclear functions to the viral factory.I also characterized a new Pandoravirus, isolated from a sample collected in New-Caledonia, named Pandoravirus neocaledonia. Pandoraviruses have a unique morphology and a gigantic double-stranded DNA genome of about 2.5 Mb. Comparative studies with other Pandoraviruses were performed using several approaches to better understand the characteristics of these original viruses. The astonishing morphology of these viruses led us to investigate the nature of their envelope, which is made of a mesh of fibers forming lamellar structures. Is it possible that Pandoraviruses, unlike other viruses, hijack the cellular machinery to build their particles? In this case, what would be their place in the evolutionary history of viruses?

A l'instar de la sismologie terrestre, l'astérosismologie est l'étude des tremblements d'étoiles. Ces vibrations internes sont observées via les variations de luminosité (ou de vitesse) qui se manifestent à leurs surfaces. A partir de ces séries temporelles, on calcule les spectres de puissance qui contiennent une véritable mine d'informations. En particulier, pour les pulsateurs de types solaires, nous pouvons observer le signal de la granulation ainsi que les modes propres d'oscillations stellaires qui sont tous deux une conséquence directe de la convection dans l'enveloppe de l'étoile. L'astérosismologie permet de sonder l'intérieur des étoiles comme une échographie. Par ailleurs, avec les grands relevés de photométrie spatiale CoRoT et Kepler, un nouveau champ d'application pour la sismologie est apparu. En effet, il est possible de caractériser au premier ordre les spectres d'oscillations des pulsateurs de types solaires à partir de quelques indices que nous appellerons indices sismiques. Ces derniers permettent via des relations simples d'estimer les paramètres fondamentaux de ces étoiles. Cela fait de l'astérosismologie un outil très puissant pour l'étude des populations stellaires.Dans la perspective du développement de la base de données Stellar Seismic Indices (SSI - Ouverture de la base SSI prévue pour l'été 2016. Lien vers la base: http://ssi.lesia.obspm.fr/), l'objet de ma thèse a été de développer une méthode automatique capable d'extraire simultanément les indices sismiques et les paramètres caractérisant la granulation des pulsateurs de types solaires. Cette méthode, appelée MLEUP, a été pour l'instant optimisée pour les géantes rouges car CoRoT et Kepler ont observé plusieurs dizaines de milliers de géantes rouges contre quelques centaines de pulsateurs de type solaire de séquence principale. Le MLEUP présente un avantage majeur par rapport à la plupart des méthodes existantes : il utilise le patron universel d'oscillations (UP) des géantes rouges comme modèle d'ajustement du spectre d'oscillations, ce qui permet d'analyser le spectre non lissé, donc non dégradé, et d'ajuster simultanément la composante de granulation et celle des oscillations par l'estimation du maximum de vraisemblance (MLE). Le MLEUP a dans un premier temps été testé par des simulations Monte Carlo afin de quantifier ses performances. Ces dernières se sont révélées très bonnes, avec de faibles biais et dispersions. Dans un second temps, nous avons appliqué le MLEUP à plus de 36.500 étoiles observées par CoRoT et Kepler, parmi lesquelles nous obtenons les indices sismiques et les paramètres de la granulation pour plus de 13.500 étoiles. Ces résultats ont d'ores et déjà été utilisés dans plusieurs travaux et leur utilisation devrait s'intensifier rapidement. / Like terrestrial seismology, asteroseismology is the study of star quakes. These internal vibrations are detected by observing the luminosity (or velocity) variations at the stellar surfaces. From these time series, one computes power spectra which contain a wealth of information. In particular, for solar-like pulsators, we are able to observe the signal of granulation as well as the eigenmodes of stellar oscillations, both of which are a direct consequence of the convection in the star's envelope. Asteroseismology allows us to probe the interior of stars much like an ultrasound. Furthermore, with the large spatial photometric surveys CoRoT and Kepler, a new scope for seismology appeared. Indeed, it is possible to characterise to first order the oscillation spectra of solar-like pulsators with few indices or parameters, called seismic indices. Using simple relations, they allow us to estimate fundamental parameters of these stars. Asteroseismology is by consequence a very powerful tool for the study of stellar populations.In the perspective of the development of the Stellar Seismic Indices (SSI - The opening of the SSI database is planned for the summer of 2016, see http://ssi.lesia.obspm.fr/).) database, the purpose of my thesis was to develop an automatic method able to extract simultaneously the seismic indices and the parameters characterizing the granulation signature of solar-like pulsators. This method, called MLEUP, was optimized for red giants because for the few hundred main-sequence solar-like pulsators observed by CoRoT and Kepler, several tens of thousands of red giants have been observed by these same missions. MLEUP has a major advantage over most existing methods: it relies on the use red-giant stellar oscillation universal pattern (UP) to fit the oscillation spectra. This allows us to analyse the unsmoothed spectrum and fit simultaneously both granulation and oscillations with the maximum likelihood estimate (MLE).As a first step, MLEUP was tested on Monte Carlo simulations in order to quantify its performances. These simulations have revealed that MLEUP achieves very good performances, with low biases and dispersions. As a second step, we applied MLEUP to more than 36,500 stars observed by CoRoT and Kepler, thereby yielding seismic indices and granulation parameters for more than 13,500 stars. Those results have already been used in several works and are expected to be used in many more.

Si l'évolution des étoiles simples est relativement bien comprise, l'étude des étoiles binaires, qui représentent la majorité des étoiles, nécessite encore des progrès majeurs, particulièrement en ce qui concerne leurs différents modes d'interactions. Dans ces systèmes, la composition de surface d'une étoile peut être altérée non seulement par l'accrétion d'éléments synthétisés au sein de l'étoile compagnon, mais également par des processus de mélanges internes induits par les forces de marées et d'un transport du moment angulaire. Plusieurs classes d'étoiles post-transfert de masse (les étoiles à baryum, CH et S) possèdent effectivement des compositions de surface caractérisées par la présence d'éléments lourds, tel que le baryum. Ces systèmes sont présumés se former au sein de systèmes binaires incluant une étoile de la branche asymptotique des géantes (appelé étoile AGB). Ces dernières sont des étoiles remarquables qui représentent l'unique site d'une nucléosynthèse particulière. En effet, elles constituent les contributeurs essentiels de la production de fluor ou de baryum. Les étoiles AGB sont également caractérisées par une importante perte de masse par vent qui éjecte progressivement leur enveloppe enrichie en ces éléments. Au sein d'un système binaire, une partie de ce vent est accréditée par l'étoile compagnon et pollue ainsi sa surface, laissant une signature spectrale distincte qui subsistera longtemps après que l'étoile AGB ait disparu. Ce scénario est suggéré comme étant responsable de la formation d'une grande variété d'étoiles chimiquement particulières, tels que les étoiles à baryum.<p>Cependant, plusieurs propriétés clés de ces systèmes, en particulier leurs distributions de périodes orbitales et d'excentricités, demeurent inexpliquées depuis des décennies. L'incapacité de nos modèles à reproduire ces propriétés orbitales met en évidence notre compréhension limitée des mécanismes d'interaction qui gouvernent l'évolution des systèmes binaires. Plus particulièrement, des mécanismes qui génèrent des orbites excentriques au sein des étoiles à baryum et des systèmes analogues sont requis. Nous examinons ainsi la possibilité qu'à sa naissance l'étoile naine blanche subisse un kick ou que la présence d'un disque entourant le système binaire soit à l'origine des fortes excentricités observées chez les étoiles à baryum. Ces deux mécanismes permettent pour la première fois depuis l'étude de ces systèmes d'apporter une solution à ces problèmes. Il est montré comment comprendre les signatures induites par un compagnon étoile AGB et les corréler avec les propriétés orbitales du système binaire est essentiel pour tester et améliorer notre connaissance de l'évolution des étoiles binaires; l'objectif de ce travail.<p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Florence Delay et Jacques Roubaud ont réécrit sous la forme de dix pièces, la légende arthurienne, avec ses origines, ses aventures et sa double fin, terrestre et céleste. Pour écrire Graal Théâtre, les auteurs ont eu la double démarche des clercs médiévaux : fidélité et liberté. La légende arthurienne a connu quelques transformations. Le personnage du géant fait partie du renouveau « delayroubaldien ». Les géants médiévaux ont subi une rénovation complète. Le géant brutal, à la limite de l’animalité, ayant pour seule arme une massue, a disparu. Dans Graal Théâtre, il cède la place à de grands chevaliers faés. Pour Florence Delay et Jacques Roubaud, il n’y a plus de distinction entre grands chevaliers et géants. Mais le géant dans Graal Théâtre n’est pas un chevalier comme les autres. Il fait généralement partie de l’Autre Monde. Il participe au merveilleux arthurien : il détient certains pouvoirs comme l’invisibilité et la quasi-immortalité, il possède des châteaux merveilleux. De plus, sa grande taille incite à se méfier de lui. Parfois ami, souvent ennemi, quelquefois les deux, le géant est un personnage ambivalent. Dans les romans médiévaux, le personnage du géant mettait en valeur la chevalerie. Dans Graal Théâtre, le géant met en avant les failles du système chevaleresque. La fonction du géant n’est plus de mourir mais bel et bien de vivre à travers les siècles comme un cri de révolte. Le géant n’est plus un témoin du passé mais bien un personnage moderne. / Florence Delay and Jacques Roubaud have re-written the Arthurian legend with its origins, its adventures and its two endings – the earthly and the celestial - as ten plays. In order to write Graal Théâtre, the authors used the dual process adhered to by medieval clerics: accuracy and freedom. The Arthurian legend has undergone some changes. The character of the giant is a part of the Delay-Roubaud renewal. The medieval giants have undergone a complete renovation. The savage giant, almost animal, and whose only weapon was a club, has disappeared. In Graal Théâtre his place is taken by faé knights. For, according to Florence Delay and Jacques Roubaud, there is no longer a distinction between great knights and giants. But the giants in Graal Théâtre are not just any knight. They are usually from the Other World. They are part of the Arthurian supernatural: they have certain powers such as invisibility and near-immortality and they own magical castles. Besides, their great height makes us mistrust them. Sometimes friends, sometimes enemies and sometimes both, the giants are ambivalent characters. In medieval stories, the giants were used to highlight chivalry. In Graal Théâtre the giants call attention to the faults in the system of chivalry. The function of the giants is no longer to die, but to live through the centuries, like a call to revolution. The giants are no longer witnesses to the past, but real modern characters.

Ce travail de thèse a été axé sur l’étude de la réponse immunitaire T chez des patients atteints d’artérite à cellules géantes (ACG) et de pseudo-polyarthrite rhizomélique (PPR). Plusieurs études cliniques successives interrégionales ont permis d’inclure de nombreux patients (57 ACG et 27 PPR) des Centres Hospitaliers (CH) Universitaires et des CH de l’interrégion Est. Les échantillons sanguins ont été étudiés dans le laboratoire de l’unité INSERM U1098. Tout d’abord, nous avons confirmé l’implication des lymphocytes Th17 dans la pathogénie de l’ACG et avons montré pour la première fois leur implication au cours de la PPR. De plus, notre étude des lymphocytes T (LT) CD4+CD161+ a permis de mieux comprendre les mécanismes de plasticité entre les réponses Th1 et Th17 au cours de ces deux pathologies. Nous avons complété ces travaux par l’étude de la réponse T régulatrice en montrant qu’il existe un déficit quantitatif en Treg au cours de l’ACG et la PPR. Dans la suite de ce travail, nous avons mis en évidence, chez des patients atteints de polyarthrite rhumatoïde, que le blocage de la voie de signalisation de l’IL-6 par un anticorps monoclonal dirigé contre le récepteur de l’IL-6 permet de corriger le déséquilibre de la balance Th17/Treg, en diminuant la réponse Th17 et en augmentant simultanément la réponse T régulatrice, à l’inverse des corticoïdes qui diminuent le pourcentage de Th17 sans corriger le déficit en Treg. Enfin, dans la dernière partie de ce travail, nous avons montré pour la première fois que les LT CD8+ étaient également impliqués dans la pathogénie de l’ACG et la PPR. Ces résultats ont permis de progresser dans les connaissances physiopathologiques de l’ACG et la PPR en évoluant d’un modèle articulé autour d’un déséquilibre de la balance Th1/Th2 vers celui d’un déséquilibre de la balance Th17/Treg et permettent de proposer des thérapeutiques mieux ciblées pour l’ACG et la PPR. / The aim of this thesis was to investigate the T-cell immune response in the course of giant-cell arteritis (GCA) and polymyalgia rheumatica (PMR). Several studies conducted by our team allowed us to obtain blood samples from many patients affected by GCA (n=57) and PMR (n=28). Immunological studies were performed in INSERM U1098, University Of Burgundy, Dijon, France. We firstly demonstrated the implication of Th17 and CD4+CD161+ T cells in the pathogenesis of these two diseases, thus extending the knowledge in the plasticity mechanisms arising between Th1 and Th17 cell-immune responses in GCA and PMR. Furthermore, we investigated the regulatory T cell immune response in these two affections, demonstrating that although being functional, the percentage of circulating Treg was decreased in GCA and PMR patients. As interleukin-6 (IL-6) had been shown to control the Th17/Treg balance, we studied Th17 and Treg frequencies in rheumatoid arthritis patients treated with an anti-IL-6 receptor antibody (tocilizumab). We showed that the blockade of the IL-6 pathway was able to correct the Th17/Treg imbalance by decreasing the number of Th17 cells and simultaneously increasing that of Treg. Finally, we demonstrated for the first time the implication of CD8+ T cells in the pathogenesis of GCA and PMR. This thesis allowed us to progress in the knowledge of the pathogenesis of GCA making the pathogenesis model progress from a Th1/Th2 to a Th17/Treg imbalance model. Altogether, these data deciphering the immune response in the pathogenesis of GCA and PMR bring new knowledge which will lead to better targeted therapies.

The main objective of the diploma thesis is to evaluate the Internet activities of mountain resorts in the Giant Mountains and then submit recommendations aimed at improving the marketing on-line communication within these resorts, which can increase the awareness and interest of the public to visit the mountain resorts in the Giant Mountains. Due to the on-line questionnaire survey is then possible to determine the current interest and attendance of each mountain resort based on respondents' answers. Individual goals of the diploma thesis are mainly detailed characteristics of marketing including its on-line form, current forms of marketing communication mix etc.