Vestígios arqueofaunísticos resgatados em sítios arqueológicos de Mato Grosso e Mato Grosso do Sul revelaram a existência pretérita de grupos humanos caçadores-coletores generalistas, nestes Estados. Inseridos neste contexto, estão os sítios arqueológicos Maracaju 1, MS e Santa Elina, MT, caracterizados por serem abrigos sob rocha, que apresentam painéis com inscrições rupestres, e por uma quantidade de remanescentes arqueofaunísticos, associados a outros vestígios da cultura material. Diante do exposto, o presente trabalho teve por objetivos (1) compreender, sob a perspectiva da arqueofauna, os padrões de subsistência das populações humanas pretéritas que ocuparam Maracaju 1, MS e Santa Elina, MT, dois abrigos em bioma de Cerrado; (2) delinear as atividades (específicas ou não) realizadas pelos grupos humanos que ocuparam estes abrigos; e, diante disso, (3) inferir a função destes abrigos para as populações pretéritas locais. Para tanto, estes registros zooarqueológicos foram estudados por meio de métodos e técnicas multidisciplinares (e.g. Taxonomia e Tafonomia experimental). Diante dos resultados deste trabalho, foi possível inferir que a caça e as atividades de subsistência, nas ocupações atribuídas aos caçadores-coletores, em Maracaju 1, ocorreram de modo sucessivo e, provavelmente, sazonal. Esta característica de ocupação fortaleceu a hipótese do elevado grau de mobilidade e das ocupações mais horizontalizadas na paisagem, característica desses grupos humanos. Do mesmo modo, a explicação mais parcimoniosa para o contexto zooarqueológico de Santa Elina, é a de que as ocupações humanas tiveram um caráter, provavelmente sazonal e ocorreram durante as alocações de recursos ligadas a outros eventos culturais, evidenciados pelos registros rupestres e pelos vestígios arqueológicos resgatados neste sítio. / Archaeofaunistic remains rescued in archaeological sites from Mato Grosso and Mato Grosso do Sul have shown the existence of generalists past hunter-gatherers groups in these states. Embedded in this context, there are the archaeological sites Maracaju 1, MS and Santa Elina, MT, characterized by being rock shelters, with rock art, and a quantity of archaeofaunistic remains, along with other traces of material culture. Facing the above, this work aimed to (1) understand, from the perspective of archaeofauna, the subsistence patterns of the people who occupied Maracaju 1, and Santa Elina, two shelters in the Cerrado biome, (2) outlining the activities (specific or not) done by human groups who occupied these shelters, and face it, (3) deduce the function of these shelters for local people. To reach that, these zooarchaeological records were studied using multidisciplinary methods and techniques (e.g. Taxonomy and Experimental taphonomy). Facing these results, it was possible to infer that hunting and subsistence activities, in occupations attributed to hunters-gatherers in Maracaju 1, occurred in successive and probably seasonal context. This occupation characteristic has strengthened the hypothesis of the high degree of mobility and more horizontalised occupations in the landscape, characteristic of these human groups. Similarly, the most parsimonious explanation for the zooarchaeological context of Santa Elina, is that the human occupation, probably had a seasonal character and occurred during the resources allocation related to other cultural events, evidenced by the rock art and the archaeological remains rescued in this site.

Made available in DSpace on 2016-04-26T18:10:29Z (GMT). No. of bitstreams: 1 Dissertacao Ana Amelia Corazza Genioli.pdf: 7329161 bytes, checksum: a2cf5caeb757cf7a4ee164b547abe878 (MD5) Previous issue date: 2005-09-01 / Through the reading of theoretical texts and contemporary works of art this research examines three aspects of the concept of frontiers or borders: frontiers between individuals and territory between individuals and communities and frontiers inside the art system itself The methodology used did not focus on one specific area of knowledge instead it covered several areas under the auspices of the theory of communication (Sodré 2002 Greiner e Katz 2005 e Sebeok 1991) artistic research (Miwon Kwon 2002) and some topics discussed under the aegis of cognitive science (Lakoff e Johnson 1987) as well as the theory of culture (Bhabha 1998 Shohat e Stam 1998) The first chapter investigates the concept of space transformed into place through the mediation of the individual and how in artwork determinate elements can designate categories The works themselves inform through signs which are the product of the artist s expression in a certain ambient that will be understood by the spectator or participant through the mechanisms that organize communicational systems It also analyses situations where the media itself is transformed into ambience The two following chapters concern situations outside the individual focus and also contextualize situations of frontiers from the point of view of individuals in communities It presents strategies of resistance to discourses given a priori based on narratives of in-between places and the comprehension of plural and partial identities The third chapter also analyses artwork and theory concerning the relativisation of systems and the fouth chapter concerns the work of three artists that consider the limits set by the art system itself The focus of this work has been developed from the tensions conflicts and ambiguities referring to the notion of frontier established by cultural constructs From the undestanding of the process of construction of these senses emerges the necessity for new options that will propose alternative concepts including concepts concerning curatorial work as disscussed at the end of this dissertation The questioning of cultural frontiers affects the curatorial experience as it highlights the relational nature of a group of work their signifying components and their context as open sense a continuum that gravitates between political posture and artist creation / Através de leituras de textos teóricos e trabalhos de arte contemporânea esta pesquisa aborda o sentido de bordas ou fronteiras acerca de três focos específicos: as fronteiras entre indivíduo e território entre indivíduos e comunidades e por fim as fronteiras do próprio sistema de arte Para tanto foi utilizada uma metodologia que não se restringiu a uma determinada área de conhecimento recorrendo a fontes diversas a partir de teorias da comunicação (Sodré 2002 Greiner e Katz 2005 e Sebeok 1991) pesquisas artísticas (Miwon Kwon 2002) e alguns tópicos discutidos no âmbito das ciências cognitivas (Lakoff e Johnson 1987) e das teorias da cultura (Bhabha 1998 Shohat e Stam 1998) O primeiro capítulo trata do espaço que se transforma em lugar pela mediação do sujeito Observa-se em trabalhos de arte como determinados elementos podem designar categorias e como a obra, ela mesma informa através de sinais que são produtos da expressão do artista em trânsito com o ambiente e que serão compreendidos pelo espectador ou participante através de mecanismos que organizam os sistemas de comunicação São abordadas ainda algumas situações em que a própria mídia se transforma em ambiência Os dois capítulos seguintes abordam situações fora do foco individual mas que também contextualizam uma situação de fronteiras a partir da reflexão acerca de indivíduos em comunidades São apresentadas estratégias de resistência a discursos dados a priori a partir de narrativas de entre-lugares e a compreensão da existência de identidades plurais e parciais No terceiro capítulo são ainda analisadas obras de arte e teorias concernentes à relativização dos sistemas e o quarto capítulo gira finalmente em torno de três artistas que problematizam através de seus trabalhos de arte os limites que o sistema de arte propõe A problemática deste trabalho desenvolve-se portanto a partir das tensões conflitos e ambigüidades referentes à própria noção de fronteira estabelecida pelos constructos culturais A partir da compreensão do processo de construção destes sentidos parece surgir a necessidade de novas opções que tragam conceitos alternativos inclusive no que diz respeito às experiências curatoriais O sentido de questionamento das fronteiras culturais projeta-se para a experiência curatorial na medida em que evidencia a natureza relacional das obras seus componentes sígnicos e o seu contexto como algo que tenha um sentido aberto um continuum entre vida política e criação artística

La mondialisation néo-libérale s’accompagne d’un renforcement de divers droits de propriété intellectuelle, selon des rythmes et des modalités variées. Ces évolutions, parfois conçues comme un nouveau mouvement d’enclosure, sont contestées dès les années 1980. L’ensemble de ces contestations, que l’on peut appeler « le Libre », se fonde sur l’idée que les biens informationnels doivent rester ou redevenir des biens communs. Le Libre, traversé de nombreuses lignes de tension voire de fracture, porte dans son nom même la trace de son origine historique : le mouvement des logiciels libres. C’est dire si cette mouvance est consubstantielle du développement des technologies de l’information et de la communication. Elle ne saurait cependant être cantonnée au domaine du numérique, pour autant qu’une telle catégorie se révèle opératoire. En effet, si ses objectifs comme son fonctionnement montrent un usage avancé et réflexif de dispositifs numériques, ils montrent aussi un engagement marqué dans des pratiques et des représentations spatiales diversifiées qui vont parfois jusqu’à l’ancrage local fort. La problématique de cette thèse se situe donc au nœud qui tient ensemble le double paradoxe d’une mouvance qui gagne en reconnaissance sociale et en légitimité politique sans qu’il existe de consensus quant à l’identité de ses acteurs, ses objectifs ou ses limites d’une part ; d’ancrage fort d’individus dont les pratiques techniques laisseraient supposer la mise en œuvre d’espaces de représentation bien plus mobiles et mondialisés d’autre part. Cette problématique interroge donc le moment technique de l’individuation des espaces géographiques. En employant une méthode comparatiste sur nos terrains québécois et aquitains, nous tenterons de faire émerger quelques caractéristiques des lieux du monde contemporain. C’est pourquoi le concept géographique de lieu sera discuté et enrichi tout au long de cette thèse. / Neo-liberal globalization brings a reinforcement of several intellectual property rights, under a variety of ways and rhythms. These developments, sometimes understood as a new enclosure movement, are challenged since the eighties. All these challenges, that we chose to call “the Libre”, is based on the idea that informational goods must belong to the commons. The “Libre”, crossed by lots of tension or even dividing lines, is marked in its very name by its historical beginnings : the Free Software movement. In other words, the “Libre” movement is part and parcel of the development of information and communication technologies. However, it can’t be restricted to the digital world, provided that such a category is operational. Indeed, if its objectives as its functioning show an advanced and reflexive use of digital apparatus, they also show a clear commitment in diverse spatial practices and representations that can reveal strong local anchorages. Therefore, problematics of this research lies at the knot that ties together the double paradox of a movement that is gaining social recognition and political legitimacy without any consensus about who are its actors, its objectives or its limits on one hand; of locally anchored individuals whose technical practices that would suggest more mobile and global spaces of representation on another hand. Thus, these problematics questions the technical moment of individuation of geographical spaces. Using a comparatist method on our Quebec and Aquitaine fieldwork, we will attempt to detect some characteristics of places of the contemporary world. This is why the geographical concept of place will be extensively discussed and enriched all along this thesis.

Este trabalho apresenta os resultados preliminares de levantamento arqueológico realizado na RDS Amanã, Estado do Amazonas. Situada na região do médio curso do rio Solimões e baixo Japurá, a RDS Amanã está na fase de preparo do seu plano de gestão. A respeito do Patrimônio Arqueológico existente na reserva Amanã 32 sítios arqueológicos formados por terra preta, cerâmica e material lítico polido foram identificados em etapas de levantamento realizadas entre 2006 e 2008. Levando em consideração o tamanho, densidade e variabilidade dos vestígios arqueológicos, assim como, a intensidade dos processos pós-deposicionais os sítios Boa Esperança e Bom Jesus do Baré foram escolhidos para realização de mapeamentos e escavação. O objetivo principal desse mestrado é apresentar o contexto arqueológico da reserva Amanã a partir de uma perspectiva comparativa com pesquisas arqueológicas que ocorrem em outros locais da Amazônia. Mais especificamente com a cronologia estabelecida para as ocupações ceramistas na Amazônia Central e áreas adjacentes, como Baixo Amazonas e médio Rio Caquetá/Japurá. A partir de dados relativos ao tamanho, composição, formato e estratigrafia dos sítios, assim como analise cerâmica e datações é formulada uma cronologia preliminar para o lago Amanã. / The main goal of this dissertation is to introduce the archaeological context of the Amanã Sustainable Development Reserve, situated near the middle course of the Amazon and the lower course of the Japurá Rivers, in the state of Amazonas; its management plan is currently under preparation. This context is then compared to the archaeology of other areas of Amazonia. Preliminary results of the archaeological survey carried out between 2006 and 2008 will be presented, during which time 32 archaeological sites were identified. These are composed of anthropogenic dark earth, pottery and ground lithics. The Boa Esperança and Bom Jesus do Baré archaeological sites were selected for mapping and excavation due to their size, density and the variability of archaeological material they contain. An initial chronology for the Amanã Lake is put forward, based on data related to site size, composition, form and stratigraphy. This is then contrasted to ceramicist occupations identified in the Central Amazon and adjacent areas (the Lower Amazon and middle Caquetá/Japurá). Such a comparative approach is employed as a tool to allow the insertion of the Amanã Lake in the wider scenario, in this way allowing for a contribution to debates and discussions that are important to Amazonian Archaeology, such as the origin and dispersal of ceramic traditions. The data will further provide information to be utilized with local inhabitants for the future development of research, public archaeology and the reserve\'s management activities.

Depuis la découverte des cheminées hydrothermales, de multiples travaux ont été menés afin d’en étudier la diversité microbienne. Les inventaires moléculaires réalisés ont ainsi mis en évidence une grande diversité d’espèces qui contraste avec la faible proportion (1 %) d’espèces isolées par approche culturale. Une nouvelle approche d’immobilisation cellulaire par inclusion dans une matrice de polymères (gellane et xanthane) a ainsi été développée pour permettre l’étude de ces communautés thermophiles anaérobies marines. Le système, basé sur la formation d’une émulsion entre une solution de polymères inoculée et de l’huile, permet le piégeage de cellules dans des billes de gel de 1 à 2 mm de diamètre. Les conditions optimales d’immobilisation ont été obtenues pour une émulsion réalisée à 80 °C sous agitation (150 tr/min) à partir d’une solution de gellane (2,5 %) et de xanthane (0,25 %) avec 12 g/L de NaCl et 4 g/L de citrate de sodium, bullée à l’azote et réduit au Na2S avant inoculation. Les billes ont montré une bonne résistance mécanique après 5 semaines d’incubation à des pH compris entre 5,4 et 8, des températures allant jusqu’à 90 °C et des concentrations en NaCl et soufre allant jusqu’à respectivement 80 et 5 g/L. Des cultures en batch de Thermosipho sp. AT1272 et Thermococcus kodakarensis KOD1 immobilisées ont permis d’obtenir des concentrations allant jusqu’à 107 cellules/g de billes et 108 cellules/mL de fraction liquide. Une culture en continu réalisée en bioréacteur gas-lift pendant 41 jours à partir d’une communauté synthétique immobilisée composée de 8 souches (hyper)thermophiles a démontré la capacité de l’immobilisation cellulaire à protéger les cellules face à un stress oxique et à les maintenir (3 des 8 souches) dans le bioréacteur jusqu’à ce que les conditions de culture soient propices à leur croissance. La réactivité de la communauté immobilisée face aux changements environnementaux (température) a également été démontrée. Enfin, la culture en continu réalisée pendant 64 jours d’un échantillon immobilisé de diffuseur du site Rainbow a permis la croissance de plusieurs espèces bactériennes et archéennes (Oceanithermus sp., Thermococcus sp.) dont une partie n’a été détectée que dans les billes (Sulfurimonas sp., Nitratifractor sp., Vibrio sp.) par clonage-séquençage. L’ensemble de ces résultats ont permis de valider l’utilisation d’un protocole d’immobilisation par inclusion dans une matrice de polymères pour l’étude des communautés hydrothermales, de leur diversité et de leur dynamique. / Since the discovery of hydrothermal vents, multiple studies have been conducted in order to study microbial diversity. Molecular inventories realized have thus demonstrated a great diversity of species that contrasts with the low proportion (1%) of species isolated by culture approach. A new cell immobilization approach by inclusion in a polymer matrix (gellan and xanthan) has been developed for the study of these thermophilic anaerobic marine communities. The system, based on the formation of an emulsion between an inoculated polymer solution and oil, allows the entrapment of cells in gel beads with a diameter between 1 and 2 mm. The optimal immobilization conditions were obtained for emulsion performed at 80 °C with stirring (150 rpm) with a polymer solution composed of gellan (2.5%) and xanthan (0.25%) with 12 g/L of NaCl and 4 g/L of sodium citrate, bubbled with nitrogen and reduced with Na2S before inoculation. The beads showed a good mechanical stability after a 5-week incubation at pH between 5.4 and 8, temperatures up to 90 °C and NaCl and sulfur concentrations up to respectively 80 and 5 g/L. Batch cultures of immobilized Thermosipho sp. AT1272 and Thermococcus kodakarensis KOD1 yielded concentrations up to 107 cells/g of beads and 108 cells/mL of liquid fraction. A continuous culture performed in a gas-lift bioreactor for 41 days of an immobilized synthetic community composed of 8 (hyper)thermophilic strains demonstrated the capacity of cell immobilization to protect cells from oxique stress and to maintain them (3 of 8 strains) in the bioreactor until having suitable culture conditions for their growth. The reactivity of the immobilized community to environmental change (temperature) was also demonstrated. Finally, the continuous culture performed for 64 days of an immobilized diffuser sample from Rainbow site allowed the growth of several bacterial and archaeal species (Oceanithermus sp., Thermococcus sp.), part of which was detected only in the beads (Sulfurimonas sp., Nitratifractor sp., Vibrio sp.) by cloning-sequencing. All these results have validated the use of an immobilization protocol by inclusion in a polymer matrix for the study of hydrothermal communities, of their diversity and their dynamics.

Esta pesquisa tem como objetivo investigar a proposição do hipertexto didático sobre poéticas cênicas contemporâneas como ponto de partida em processos de aprendizagem e de criação do teatro, utilizando como principal aporte metodológico a abordagem da pesquisaação fundamentada por Michel Thiollent. A revisão bibliográfica resultou na elaboração de um hipertexto didático (MARTINS, 2006), a ser publicado na internet, sobre o Teatro da Vertigem (São Paulo), produzindo um material hipertextual e multimodal para uso pedagógico, que articula textos teóricos, análises críticas, registros de espetáculos e processos, depoimentos dos artistas, descrição e análise de procedimentos de criação e fragmentos de dramaturgia. A realização e a análise de dois experimentos de aprendizagem e encenação realizados na cidade de Campo Limpo Paulista (SP), com um grupo de iniciantes em teatro e outro formado por atores amadores na faixa etária de 18 a 42 anos, permitiu a sistematização de princípios e procedimentos metodológicos de ensino e aprendizagem do teatro contemporâneo. O jogo teatral a partir de modelos estéticos (KOUDELA, RYNGAERT, PUPO, MARTINS) e procedimentos da abordagem colaborativa desenvolvida por ARAÚJO, são os eixos norteadores das práticas de criação propostas nos experimentos realizados a partir do hipertexto didático criado pelo coordenador e ampliado pelos participantes. A seleção das referências teóricas se deu a partir da perspectiva de teóricos do teatro contemporâneo como LEHMANN, FERRAL, FERNANDES, ARAÚJO, PAVIS e SARRAZAC. Os resultados obtidos poderão contribuir para o debate acerca de abordagens metodológicas que integrem estudos teóricos e históricos com práticas colaborativas de criação da cena e que possam interessar para professores, coordenadores de oficinas e encenadores envolvidos na reflexão a cerca dos processos de aprendizagem e criação da cena contemporânea. / This work investigates the proposition of hypertext courseware on contemporary scenic poetic elements as a starting point for theater creation and learning processes, having primarily relied, as a methodological input, on Michel Thiollent\'s action-research approach. The bibliographical review has resulted in hypertext courseware (MARTINS, 2006), to be published on the internet, about Teatro da Vertigem (São Paulo), having thus generated a multimode, hypertext material for educational use, which puts together theoretical texts, critical reviews, records of spectacles and processes, testimonials of artists, a description and analysis of creation processes and procedures, and figments of theater practice. The conduction and analysis of two learning and staging experiments held in the city of Campo Limpo Paulista (São Paulo, Brazil), comprising a group of theater novices and another group made up of amateur actors aged 18 to 42, allowed me to systematize some learning principles and methodologies of the contemporary theater. The theater game based on esthetic frameworks (KOUDELA, RYNGAERT, PUPO, MARTINS) as well as on collaborative approach procedures devised by ARAÚJO are the guiding pillars for the creation practices proposed during the experiments based on the educational hypertext as devised by the coordinator and further expanded by the players. Selection of theoretical references has drawn on such contemporary theater theorists as LEHMANN, FERRAL, FERNANDES, ARAÚJO, PAVIS, and SARRAZAC. The results may contribute to debates over the methodological approaches that bring together theoretical and historical studies, on one part, and collaborative staging practices, which might be useful for teachers, workshop coordinators and stage directors involving in a reflection over the contemporary theater creation and learning processes.

Chez les bactéries, la ségrégation du chromosome est initiée durant la phase de réplication. Des expériences de time lapse, utilisées pour observer que la dynamique des loci frères durant le cycle cellulaire, montrent que, chez Escherichia coli, les régions sœurs restent colocalisées pour une période significative dans les régions des macrodomaines du chromosome et pour une courte période dans les régions non-structurées. Nous nous sommes posés la question suivante: est ce que l’étape de colocalisation révèle une réelle cohésion entre les chromatides sœurs ? Pour y répondre, nous avons développé un outil génétique, alternatif aux outils de biologie cellulaire, permettant de mesurer la distance entre les chromatides sœurs de manière directe. La fréquence de recombinaison intermoléculaire médiée par la recombinase Cre entre les sites loxP positionnés sur les chromatides sœurs est mesurée pour différentes positions. De cette fréquence, nous avons pu déduire la proximité entre les chromatides sœurs. Nous révélons que les loci frères restent proche l’un de l’autre pour une courte période après la réplication. Nous appelons cette étape la cohésion moléculaire, celle-ci est dépendante du locus considéré. Nous montrons que les facteurs qui favorisent la colocalisation des foci frères n’augmentent pas nécessairement l’habilité des loci frères à recombiner. En effet, la protéine MatP, un acteur de la colocalisation des macrodomaines Ter, n’affecte pas la cohésion entre les deux copies de cette région. La Topoisomérase IV est un facteur essentiel à la ségrégation des chromosomes. En son absence, les chromosomes ne peuvent se ségréger et restent colocalisés dans la cellule. Nous révélons par le test de recombinaison que l’absence de Topoisométase IV dans les cellules provoque une augmentation des interactions entre chromatides sœurs. Au final, nous avons montré que l’étape de cohésion est différente de la colocalisation, que les mécanismes moléculaires diffèrent d’une étape à l’autre et que les liens de précaténation moduleraient la cohésion post-réplicative entre chromatides sœurs. / In bacteria, the segregation of the chromosome is initiated during the replication phase. Time lapse experiments, used to watch the dynamic of loci during cell cycle, showed, in Escherichia coli, that the sister loci remain colocalized for a significant amount of time in the macrodomain regions of the chromosome and for shorter period in the Non Structured regions. We asked the following question: does this colocalization step reveal a real cohesion between the sister chromatids? To answer, we have developed a genetic tool, alternative to cell biology tools, to measure the distance between sister chromatids directly. The frequency of intermolecular recombination mediated by Cre recombinase loxP sites located on sister chromatids was measured for various loci. From this frequency we were able to deduce the proximity of sister chromatids. We revealed that sister loci remained in close proximity for a short period following replication. We called this step molecular cohesion, it is dependent on the considered locus. We showed that factors that promote colocalisation of sister foci do not necessarily increase the ability of sister loci to recombine. Indeed, the MatP protein, an actor of macrodomain Ter colocalisation, does not affect the cohesion between the two copies of this region. The TopoIV is essential for the segregation of chromosomes. In its absence, the chromosomes can not segregate and remain colocalized in the cell. We reveal by recombinaison assy that the absence of Topoisomerase IV revealed an increase of interactions between sister chromatids. To conclude, we have shown that the cohesion step is different from the colocalisation step, the molecular mechanisms differ from one stage to another and précaténation links take part in the post-replicative cohesion between sister chromatids

La majorité des ADC qui sont actuellement en clinique et en développement sont produits par une conjugaison chimique via les résidus lysine ou cystéine, menant à un produit hétérogène pour leur ratio toxine sur anticorps (DAR). L'objet des travaux de thèse a pour but de décrire la caractérisation in vitro et in vivo de nouveaux ADC optimisés et construits à partir de l'anticorps anti-CD30 cAC10, ayant le même squelette polypetidique que Adcetris, et de comparer les résultats à ce dernier. La transglutaminase bactérienne (BTG) a été utilisée pour conjuguer de manière site-spécifique la MMAE aux glutamines aux positions 295 et 297 du cAC10, amenant à des ADCs homogènes de DAR 4, TG-ADC. Des travaux préliminaires ont permis d’établir les conditions optimales de conjugaison avec un procédé en deux étapes. Les tests de cytotoxicité ont révélé des EC50 comparables entre Adcetris et les TG-ADC. Les données d’efficacité in vivo montrent une efficacité équivalente voire légèrement supérieure pour les TG-ADC que Adcetris. L'étude de biodistribution in vivo dans un modèle avec et sans tumeur est réalisé avec un 125-I TG-ADC et est comparé à 125I-Adcetris. Le TG ADC site spécifique montre une meilleure distribution tumorale. Adcetris a une distribution non médiée par la cible, dans le foie et la rate, plus importante. En ligne avec ces résultats, la dose maximale tolérée des TG ADC est significativement plus élevée que Adcetris chez le rat. Ces résultats suggèrent que les ADC homogènes ont une meilleure pharmacocinétique et un meilleur index thérapeutique comparés aux ADC avec des DAR hétérogènes. / Most ADC that are currently in clinical use or development produced by chemical conjugation of a toxin via either lysine or cysteine residues, inevitably leading to heterogeneous products with variable drug-to-antibody ratios (DARs). Here, we describe the in vitro and in vivo characterization of novel ADCs that are based on the anti-CD30 antibody cAC10, which has the same polypeptide backbone as Adcetris, and compare the results with the latter. Bacterial transglutaminase (BTG) was exploited to site-specifically conjugate derivatives of MMAE to the glutamines at position 295 and 297 of cAC10, yielding homogeneous ADCs with a DAR of 4, TG-ADC. Preliminary works have led to define optimal conditions for conjugation, but also define a two step process. In vitro cell toxicity experiments revealed comparable EC50-values for Adcetris and TG-ADC. The efficacy data have shown slightly better efficacy for TG-ADC compared to Adcetris. Quantitative time-dependent in vivo biodistribution studies in normal and xenografted mice were performed with a selected 125I TG ADC and compared with 125I-Adcetris. Adcetris has an higher liver and spleen unspecific uptakes. In line with these results, the maximum tolerated dose of the BTG-coupled ADC (> 60 mg/kg) was significantly higher than that of ADCETRIS® (18 mg/kg) in rats. These results suggest that homogenous ADCs display improved pharmacokinetics and better therapeutic indexes compared to chemically modified ADCs with variable DARs.

This project is a development and tracking system for graduate students in the Department of Computer Science of CSUSB. This project will cover front-end web site development, back-end database design and security. This website provides secure access to information about ideas for projects, status on on-going projects, and reports of finished projects using My SQL and Apache Tomcat.

Cette thèse vise à modéliser l’entrée en résilience des organisations en contexte extrême. L’accident de Fukushima Daiichi, étudié au travers du témoignage de Masao Yoshida, directeur de la centrale lors des faits, et des rapports d’enquête, soutient la recherche en tant qu’étude de cas. Ces sources d’informations croisées avec notre cadre théorique, nous permettent de répondre à la question de recherche suivante : Dans quelles mesures pouvons-nous parler de résilience lors de l’accident de Fukushima Daiichi ? Si oui, quelle forme la résilience a-t-elle prise, quels processus ont été activés et ce plus particulièrement dans lors des premiers temps du processus général de résilience ?Une méthodologie spécifique d’analyse du matériau est produite et démontre l’utilité du témoignage de Masao Yoshida pour participer au retour d’expérience. La thèse tire un ensemble de leçons de l’accident et propose une grille d’analyse originale en regard de l’équilibre précaire entre centralisation et décentralisation que le témoignage et les rapports d’enquête mettent en lumière. Le modèle produit définit en détails la logique processuelle et émergente de l’entrée en résilience. / The aim of this research if to develop a model of entry to resilience for organizations facing extreme events. The Fukushima Daiichi nuclear power plant accident is used as a case study. The accident is analyzed through the testimony of the Site Superintendent Masao Yoshida and the investigation reports. The goal is to answer the following questions: what are the conditions to assess resilience during the Fukushima Daiichi accident? What shape did the resilience take in this context? What processes have been activated particularly during the initiation of the resilience process?A specific methodology is produced to analyze Masao Yoshida’s testimony. This methodology also proves the usefulness of such a material to develop feedbacks in industrial organizations. The thesis draws lessons from the accident and defines an evaluation grid to study the precarious equilibrium between on-site and off-site that is highlighted by the data used. The provided model defines the processual and emerging logic of entry to resilience.