Cet ouvrage porte sur la réaction du clergé canadien face à l’invasion américaine de 1775-1776. Alors que l’historiographie considère généralement que les prêtres de la colonie restèrent fidèles au gouvernement britannique à cette occasion, trois curés se détachèrent au contraire de cette image de loyalisme : Eustache Chartier de Lotbinière (1716-1785), Pierre-René Floquet (1716-1782) ainsi que Pierre Huet de La Valinière (1732-1806). Soupçonnés par les autorités ecclésiastiques et coloniales d’entrenir des sympathies pour les révolutionnaires américains, ces hommes furent frappés par diverses sanctions, affectant durablement le déroulement de leur carrière. / This dissertation examines the reaction of Canadian clergy to the American invasion of 1775-1776. While historians have generally considered that the priests of the colony remained loyal to the British Government on this occasion, three priests stand in contrast to this image of loyalty: Eustache Chartier de Lotbinière (1716-1785), Pierre-René Floquet (1716 -1782), Joseph Huguet (1725-1783) and Pierre Huet de La Valinière (1732-1806). Suspected by church and colonial authorities to have shown sympathy to the American revolutionaries, these men were struck by various sanctions that permanently affected the development of their careers.

Les leucémies aigues myéloïdes (LAM) sont des hémopathies malignes de mauvais pronostic dont les thérapies actuelles ne permettent d’obtenir des taux de survie à 5 ans chez les adultes que d’environ 40%. Par conséquent, il est nécessaire d’approfondir nos connaissances concernant les mécanismes d’oncogenèse pour développer de nouvelles approches thérapeutiques. Malgré leur hétérogénéité clinique et biologique, les LAM ont certaines caractéristiques communes comme l’activation de la voie de signalisation mTORCl qui est détectée dans la plupart des échantillons de LAM. MTORCl contrôle la survie, la croissance et la prolifération cellulaire, notamment via le contrôle de la traduction des ARNm et donc de la synthèse protéique. Au cours de ce travail, nous montrons qu’il existe, dans les LAM, une dérégulation de mTORCl qui explique les limites des effets anti-leucémiques observés avec la rapamycine (un inhibiteur allostérique de mTORCl) et qui est médiée en partie par l’activité de la sérine thréonine kinase Pim2, qui contrôle la phosphorylation de la cible de mTORCl, la protéine 4E-BP1. Cependant, cibler directement la traduction produit des effets anti-leucémiques importants, ce que nous avons montré en utilisant une molécule inhibant spécifiquement le complexe d’initiation de la traduction, le 4EGI-l. EIF4E est essentiel à l’initiation de la traduction et nous avons montré sa surexpression au niveau protéique dans la plupart des échantillons de LAM au diagnostic par comparaison à des cellules hématopoïétiques normales CD34+. Bien que son niveau d’expression n’ait pas de valeur pronostique intrinsèque, ce résultat suggère un potentiel important au blocage de la traduction dans la plupart des cas de LAM. Dans la perspective d’inhiber mTORCl, nous avons activé la voie LKBl/AMPK par la metformine, ce qui a induit des effets anti-leucémiques in vitro et in vivo via une modification du métabolisme cellulaire avec en particulier une inhibition de la synthèse de protéines oncogéniques. La metformine n’étant pas un candidat en thérapeutique dans les LAM du fait d’un index thérapeutique trop étroit, de nouvelles molécules modulant la voie LKBl/AMPK sont en cours de développement. Enfin, nous avons étudié le rôle de la sérine thréonine kinase Pim2, qui contrôle la traduction protéique et la survie dans les cellules de LAM Flt3-ITD+. Nous avons de plus montré que la sur-expression de Pim2 constitue un nouveau mécanisme de résistance aux inhibiteurs de Flt3 et représente donc une cible thérapeutique prometteuse dans cette catégorie de LAM. L’étude de la voie mTORCl et de la traduction permet donc d’envisager de multiples perspectives thérapeutiques dans les LAM dont certaines sont déjà en cours de développement clinique. / Acute myeloid leukemia (AML) are hematological malignancies with adverse prognosis in which therapies only gives 40% survival within 5 years in adults. Hence, it is important to increase our knowledge regarding oncogenesis to further develop new therapeutic approaches. Despite their clinical and biological heterogeneity, AML have in common the constitutive activation of mTORC1 signaling which is detected in most AML samples. MTORC1 controls cell survival, growth and proliferation, in particular through control of mRNA translation and protein synthesis. During this work, we show, in AML, that mTORC1 is deregulated which explain the poor effects observed with rapamycin (a mTORC1 allosteric inhibitor) and is partially mediated by the serine/threonine kinase Pim-2 which controls the mTORC1 target 4E-BP1. Nevertheless, directly targeting translation, using a specific translation initiation inhibitor named 4EGI-1, have important anti leukemic effects. EIF4E is described as essential in translation initiation and we show its protein overexpression in most AML samples at diagnosis compared with normal hematopoietic CD34+ cells. Whereas eIF4E level expression has no prognostic impact, this result suggests an important potential for treatment targeting translation initiation in AML. In our purpose of inhibiting mTORC1, we were able to activate LKB1/AMPK signaling pathway with metformin, which induces anti leukemic effects in vitro and in vivo through in particular oncogenic protein translation inhibition. Metformin is not a good AML therapeutic candidate because of a narrow therapeutic index, new compound targeting LKB1/AMPK are in development. Finally, we studied the role of the serine/threonine kinase Pim-2 and show that it controls protein translation and FLT3-ITD+ AML cells survival. Furthermore, we show that Pim-2 overexpression is a new mechanism of Flt3 inhibitors resistance and represent a new promising therapeutic target in this AML subtype. Overall, mTORC1 and protein translation study in AML show multiple therapeutics perspective, some of them are already in clinical development.

Made available in DSpace on 2016-04-25T19:21:07Z (GMT). No. of bitstreams: 1 Dissertacao Gilberto Cabral da Silva.pdf: 1528100 bytes, checksum: 1cb9f67fd62cfb84861765c173eda720 (MD5) Previous issue date: 2005-08-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This Work intends an epistemological approach of David Hume s Dialogues Concerning Natural Religion by French philosopher Clément Rosset s category of tragic philosophy . We propose a new interpretative possibility of Hume s thought in the Dialogues, different form the naturalism and beyond the simple skepticism . The concept of tragic philosophy allows one to think the Dialogues Concerning Natural Religion as a work of tragic philosophy, in which the concept of nature is completely dissolved by the skeptic arguments. / Esta dissertação pretende uma abordagem epistemológica dos Diálogos sobre a Religião Natural de David Hume por meio da categoria de filosofia trágica , trabalhada pelo filósofo francês Clément Rosset. Propomos uma nova possibilidade interpretativa do pensamento de David Hume, diferente do naturalismo e além do simples ceticismo. O conceito de filosofia trágica permite pensar os Diálogos sobre a Religião Natural como uma obra de filosofia trágica, na qual é efetuada, através dos argumentos céticos, a completa dissolução do conceito de natureza .

Ce mémoire porte sur les fondements naturels du jugement moral et l'objectif principal de ce travail est de faire ressortir l'importance de revoir nos conceptions philosophiques sur ce sujet. C'est en nous appuyant sur deux principaux modèles philosophiques, le sentimentalisme et le rationalisme, que nous identifions les éléments constitutifs du jugement moral. L'étude de ces modèles se réfère aux travaux de David Hume et Emmanuel Kant et permet de souligner que la définition du rôle des émotions et de la raison dans la formation du jugement moral diffère dans chacune de ces conceptions. Ensuite, c'est en nous appuyant sur le modèle intuitionniste social proposé par Jonathan Haidt que nous étudions l'influence humienne sur la conception contemporaine du jugement moral. La problématique soulevée se trouvant essentiellement dans une dichotomie entre les définitions que proposent les modèles sentimentaliste et rationaliste en ce qui a trait aux rôles respectifs des émotions et de la raison, nous tentons d'éclairer le problème en exposant différentes études neuroscientifiques sur la question afin de reconsidérer les définitions présentées. Pour ce faire, nous nous intéressons à la question morale d'un point de vue phylogénique et ontogénique. D'abord, en étudiant les fondements génétiques, les bases neuronales, les fondements émotionnels et les mécanismes fondamentaux, ensuite en étudiant les déterminants sociaux et culturels. Finalement, nous concluons avec l'idée que les théories philosophiques contemporaines peuvent tirer certains bénéfices en considérant les observations scientifiques récentes au sujet des fondements du jugement moral. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Jugement moral, sentimentalisme, rationalisme, intuitionnisme social, neurosciences.

Approaches were developed for building extraction and updating from high resolution satellite imagery. The developed approaches include two main stages: (i) detecting the building patches and (ii) delineating the building boundaries. The building patches are detected from high resolution satellite imagery using the Support Vector Machines (SVM) classification, which is performed for both the building extraction and updating approaches. In the building extraction part of the study, the previously detected building patches are delineated using the Hough transform and boundary tracing based techniques. In the Hough transform based technique, the boundary delineation is carried out using the processing operations of edge detection, Hough transformation, and perceptual grouping. In the boundary tracing based technique, the detected edges are vectorized using the boundary tracing algorithm. The results are then refined through line simplification and vector filters. In the building updating part of the study, the destroyed buildings are determined through analyzing the existing building boundaries and the previously detected building patches. The new buildings are delineated using the developed model based approach, in which the building models are selected from an existing building database by utilizing the shape parameters. The developed approaches were tested in the Batikent district of Ankara, Turkey, using the IKONOS panchromatic and pan-sharpened stereo images (2002) and existing vector database (1999). The results indicate that the proposed approaches are quite satisfactory with the accuracies computed in the range from 68.60% to 98.26% for building extraction, and from 82.44% to 88.95% for building updating.

Habilitationsschrift--Freiburg i.B. / Bibliography: p. 253-266.

Habilitationsschrift--Freiburg i.B. / Bibliography: p. 253-266.

El problema de la causalidad es, probablemente, una cuestión atingente a casi todas las áreas del saber humano. En el reconocimiento de determinadas relaciones causales se funda en gran medida toda nuestra vida cotidiana, nuestra subsistencia como especie y por supuesto nuestras ciencias.

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Orientador: Profª. Drª. Maria Isabel Limongi / Dissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Programa de Pós-Graduação em Filosofia. Defesa: Curitiba, 27/03/2013 / Inclui referências : f. 64-65 / Área de concentração: Historia da Filosofia Moderna e Comtemporânea / Resumo: Pretendo, neste trabalho, analisar a formação de conceitos na construção do sistema moral de Hume atrás de um debate entre o autor escocês e três representantes de sistemas morais distintos. Respectivamente John Locke e sua moral demonstrativa, Francis Hutcheson e a moral sentimentalista e por fim Thomas Hobbes e a moral egoísta. Hume elaborou um sistema moral inédito, mas não podemos desconsiderar que suas críticas e elogios a outros filósofos morais são fundamentais na constituição de seu projeto sobre as ações morais. Propomos neste trabalho, elencar três concepções distintas às quais Hume recorre para justificar seu ataque à tradição moral racionalista, às relações de ideias encontradas no Ensaio sobre o entendimento humano de John Locke. Focaremos esse ponto da teoria moral lockeana, pois Hume pretende provar que a moral não é passível de demonstração aos moldes da matemática, conforme pretendia Locke. Em seguida apresentaremos o elogio de Hume conferido aos sentimentalistas morais. Tomamos como representante da presente corrente Francis Hutcheson. Hume adota o moral sense e o rearranja conforme sua concepção própria. Por fim, apresentamos a moralidade em Thomas Hobbes, que é egoísta. Notamos que com essa conversa entre Hume e nossos filósofos escolhidos os papéis da razão e das paixões são recolocados de modo original para a época. Depois de expormos as teorias desses três filósofos, e de posicionarmos Hume, estruturando dessa maneira a sua edificação sobre a moralidade, pretendemos demonstrar como para a Hume a moral é regulada e podemos alcançar, a partir da própria natureza humana, juízos morais estáveis. / Abstract: I intend in this work to analyze important concepts in the construction of Hume's moral system behind a debate between the Scottish author and three representatives of different moral systems. Respectively John Locke and his moral demonstrative, Francis Hutcheson and moral sentimentalist and finally Thomas Hobbes and his selfish moral. Hume developed a novel system of morality, but we can not ignore that his criticisms and compliments the other moral philosophers are fundamental in the constitution of his Project. We propose in this paper, listing three different conceptions of which Hume uses to justify his attack on the moral rationalist tradition, on the relation of ideas found in the Essay concerning human understanding by John Locke. We will focus this point of Lockean moral theory, since Hume intends to prove that morality is not susceptible to molds demonstration of mathematics, as intended Locke. Then, we present the praise given to Hume's moral sentimentalists. We take this as representative of the current Francis Hutcheson. Hume adopts the moral sense and rearrange as your own design. Finally, we present morality in Thomas Hobbes, that is selfish. We note that this conversation between Hume and our philosophers chosen the roles of reason and the passions are replaced so original for its time. After exposing the theories of these three philosophers, and position ourselves Hume, thus structuring your edification about morality, we intend to demonstrate how Hume morality is regulated and can achieve from the very human nature, stable moral judgments.