Le virus du papillome humain (HPV) est l’infection sexuellement transmise la plus fréquente au monde. Plusieurs études ont établi son implication dans l’étiologie de pratiquement tous les cancers du col de l’utérus, une maladie qui constitue un problème de santé majeur dans les pays pauvres. Le HPV est également responsable de 90% des cancers de l’anus, 40-50% des cancers du pénis, de la vulve et du vagin, et 30% des cancers de la tête et du cou. L’objectif général de cette thèse est de combler les lacunes relatives aux connaissances sur la distribution génotypique du HPV dans les lésions néoplasiques cervicales utérines et de la tête et du cou, plus particulièrement en Afrique. Les objectifs spécifiques sont les suivants: 1) analyser la distribution génotypique du HPV dans les cancers du col de l’utérus et faire une analyse comparative de cette distribution dans cinq pays africains en fonction de la prévalence du VIH; 2) évaluer la présence du HPV dans les cancers de la tête et du cou au Sénégal; 3) faire une revue de la littérature et une méta-analyse sur la distribution du HPV dans les cancers de la tête et du cou dans toutes les régions du monde. Pour le premier et le second objectifs, qui découlent d’un large projet international coordonné par l’Institut Catalan d’Oncologie pour l’Organisation Mondiale de la Santé (OMS), une étude transversale multicentrique a été menée au Mali et au Sénégal pour collecter des blocs de paraffine de patientes diagnostiquées entre 2001 et 2010 du cancer invasif du col et des cancers de la tête et du cou. Pour le troisième objectif, une revue exhaustive de la littérature a permis d’identifier tous les articles qui ont été publiés sur les cancers de la tête et du cou dans tous les pays du monde et d’effectuer une méta-analyse sur la prévalence de l’ADN du HPV selon le site du cancer et la région géographique. Notre analyse montre que les principaux types de HPV ciblés dans les vaccins prophylactiques (HPV16/18) représentent la majorité des types de HPV détectés dans le cancer invasif du col de l’utérus en Afrique subsaharienne. Par contre, le HPV45 vient au second rang dans certains pays d’Afrique, dont le Mali et le Sénégal. Nos données suggèrent également que le VIH aurait un rôle dans la contribution relative du HPV18 et HPV45 dans le développement du cancer du col de l’utérus. Au Sénégal, notre étude montre que la prévalence du HPV dans les cancers de la tête et du cou est très faible et ne semble pas jouer un rôle important dans l’oncogenèse. Finalement, la méta-analyse a mesuré la prévalence des HPV dans les cancers de la cavité orale, de l’oropharynx, du larynx et de l’hypopharynx, et confirme l’importante contribution relative du HPV16 dans ces cancers. Globalement, cette thèse permet de mieux comprendre l’impact potentiel des vaccins prophylactiques sur l’incidence des cancers associés au HPV. / Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Several studies have shown its involvement in the etiology of virtually all cancers of the cervix, which is a major health problem in poor countries. HPV is also responsible for 90% of anal cancers, 40-50% of penile, vulvar and vaginal cancers, and 30% of head and neck cancers. The overall objective of this thesis is to fill the gaps in knowledge on the genotype distribution of HPV in anogenital and head and neck neoplasia, especially in sub-Saharan Africa. The specific objectives are to: 1) analyze HPV genotype distribution in cervical cancer and compare this distribution in five African countries according to HIV prevalence; 2) evaluate the presence of HPV in cancers of the head and neck in Senegal; 3) review the literature on the distribution of HPV in cancers of the head and neck in all regions of the world and perform a meta-analysis. For the first and second objectives, which were derived from a larger international project coordinated by the Catalan Institute of Oncology for the World Health Organization (WHO), a cross-sectional multicentric study was conducted to collect paraffin-embedded blocks of invasive cervical cancer and head and neck cancer diagnosed between 2001 and 2010 in Mali and Senegal. For the third objective, a comprehensive search of the literature was conducted to identify all articles published to date on head and neck cancer. A meta-analysis was performed to estimate the prevalence of HPV DNA according to cancer site and geographical region. Our analysis shows that the main HPV types targeted in the prophylactic vaccines (HPV16/18) accounted for the majority of the HPV types found in invasive cervical cancer in sub-Saharan Africa. Our data also suggests that HIV may play a role in the contribution of HPV18 and HPV45 to the development of cervical cancer. However, HPV45 ranks second in many African countries, notably in Mali and Senegal. In Senegal, our study shows that HPV DNA prevalence in head and neck cancer is very low and is not importantly involved in the oncogenesis. Finally, the meta-analysis measured the prevalence of HPV in cancers of the oral cavity, oropharynx, larynx and hypopharynx, and confirmed the significant relative contribution of HPV16 in these cancers. Overall, this thesis contributes to a better understanding of the potential impact of HPV prophylactic vaccines on the incidence of HPV-associated cancers.

La present tesi tracta d’aprofundir en el coneixement dels orígens del pactisme valencià. És per això que analitza de forma exhaustiva les diverses negociacions politicofiscals que tingueren lloc entre la monarquia i la comunitat política del regne de València des de mitjan segle XIII fins a la dècada de 1360. Així, tot plegat, estudia la trajectòria d’unes transformacions estretament imbricades entre si: d’una banda, el progressiu desenvolupament de la pràctica parlamentària fins a esdevenir la principal forma de resolució de greuges entre els estaments i el monarca, i, d’una altra banda, l’evolució de la fiscalitat reial i local fins a donar lloc a uns sistemes fiscals generals i municipals que quedaren controlats pels dirigents estamentals. D’aquesta manera, mitjançant l’anàlisi d’aquells canvis, es determinen amb major detall les fases i les característiques del procés de configuració del pactisme al territori valencià. / The purpose of this thesis is to deepen the knowledge on the origins of Valencian pactism. In order to achieve that, it analyzes exhaustively the various political/fiscal negotiations that took place between the monarchy and the political community of the kingdom of Valencia from the mid-thirteenth century until the 1360’s. It is, therefore, a study on the history of transformations closely imbricated in each other: on the one hand, the gradual development of the parliamentary practice until it became the main way for resolving grievances between the king and the estates of the realm and, on the other hand, the evolution of the royal and local taxation to general and local fiscal systems that were controlled by the heads of the estates. Thus, by means of analyzing these changes, the different stages and characteristics of the configuration process of pactism in the kingdom of Valencia can be more precisely determined.

L’ oncoprotéine E6 - qui joue un rôle crucial dans le processus d’oncogenèse induit par les papillomavirus a longtemps résisté à toute analyse. Depuis 1995 l’équipe Oncoprotéines a concentré ses efforts sur cette problématique. Ce qui a permis la résolution par RMN de la structure du domaine C-terminal de E6 en 2006. C’est dans ce cadre que j’ai commencé ce Doctorat en 2008, avec objectif de continuer la quête de données structurales sur E6 tout en acquérant des informations sur ses modes d’interaction avec ses cibles cellulaires. Les travaux de cette thèse ont permis l’obtention de la structure cristallographique de E6 (HPV16) en complexe avec un peptide de E6AP, en utilisant une approche originale capable de produire des protéines E6 stables et solubles. Cette structure constitue la première information structurale publiée sur des protéines E6 entières, attendue depuis plus de 20 ans par la communauté scientifique. J’ai effectué également durant cette thèse une analyse du système d’interaction de la protéine E6 basée sur une large étude d’interaction entre les protéines E6 (7 types) et 93 peptides porteurs de motif LxxLL. / The oncoprotein E6 which plays a crucial role in the process of carcinogenesis induced by HPV, has withstood all tests for a long time. Since 1995 the team « oncoproteins » has focused on this issue. This allowed the resolution of structure of C-terminal domain of E6 by NMR analysis, in 2006. In this context, i started my PhD in 2008 with aim to continue the pursuit of structural data on E6 while also acquiring information about its modes of interaction with its cellular targets. The work of this thesis has enabled us to obtain the crystal structure of E6 (HPV16) in complex with a peptide of E6AP, using an original approach capable of producing stable and soluble proteins E6. This structure represents the first structural information on full-length E6, awaited for over 20 years by the scientific community. I also performed during this thesis an analysis of the interaction system of the E6 protein based on a large study of interaction between proteins E6 (7 types) and 93 peptides bearing LxxLL motif.

Made available in DSpace on 2014-12-17T14:13:48Z (GMT). No. of bitstreams: 1 AcariliaES_TESE.pdf: 9221805 bytes, checksum: 71876e327362584aeb9dcac7d3652c4d (MD5) Previous issue date: 2013-04-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit? S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB / Esta tese teve como objetivo o desenvolvimento de novos sistemas de libera??o para duas mol?culas distintas. Na primeira parte, micropart?culas ? base de xilana e Eudragit? S-100 foram produzidas para encapsular ?cido 5-aminosalic?lico visando ? libera??o c?lonespec?fica. A xilana foi extra?da de sabugos de milho e caracterizada quanto ?s suas propriedades f?sico-qu?micas, reol?gicas e toxicol?gicas. Em seguida, dois m?todos de microencapsula??o foram utilizados: reticula??o interfacial polim?rica e secagem por aspers?o. Os sistemas produzidos foram caracterizados quanto ? morfologia, tamanho m?dio e distribui??o, estabilidade t?rmica, cristalinidade, taxa de encapsula??o e libera??o do f?rmaco in vitro. Foram obtidas micropart?culas com adequadas caracter?sticas f?sicas e rendimentos satisfat?rios atrav?s dos dois m?todos, embora os sistemas aspergidos tenham apresentado maior estabilidade t?rmica e sejam considerados mais interessantes devido a sua maior estabilidade t?rmica e aus?ncia de agentes t?xicos. No entanto, ajustes precisam ser feitos para melhorar a encapsula??o e libera??o do f?rmaco. Na segunda parte, microemuls?es do tipo ?leo em ?gua (MEs O/A) com base em triglicer?deos de cadeia m?dia (MCT) foram produzidas visando ao carreamento de anfotericina B (AmB) e aumento da sua solubilidade. Foram obtidas MEs O/A sem e com AmB com got?culas em torno de 80 e 120 nm, respectivamente, e ?ndices de polidispers?o de 0,25 e 0,31, respectivamente. A taxa de incorpora??o da AmB foi alta e dependente do volume da fase dispersa. A viabilidade celular n?o foi afetada at? 25 μg/mL da AmB. Portanto, MEs O/A a partir de MCT podem ser promissores sistemas de libera??o para AmB

Made available in DSpace on 2015-02-24T19:48:44Z (GMT). No. of bitstreams: 1 SilvanaPPG_TESE_pag119_final.pdf: 4384081 bytes, checksum: f4e3889e03bd2b77ef4e8f1b271723a8 (MD5) Previous issue date: 2012-08-06 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Northeast relief was described by the Pediplanation Model. This action discards the theoretical basis of post-Cretaceous tectonic evolution of the landscape. Through this model the Massif Pereiro - MP, Borborema Province, was established as part of the Tablelands Area Residual Sertanejos. The present work aims to establish the post- Cretaceous morphotectonic evolution of the MP by geomorphological and geological mapping using Geographic Information System, Remote Sensing and dating of sediments by Single Aliquot Regenerative-dose (SAR). The MP is contained in the core semi-arid, annual precipitation of 600-800 mm / year. The MP is NE-SW, is limited by Shear Zone Jaguaribe (ZCJ) and Portalegre Shear Zone (ZCPa), the same attitude, and crossed by several other shear zones. These shear zones show evidence of brittle Cenozoic reactivation, mostly as normal faults and shallow crustal level. The Quaternary sedimentation around the MP focuses on fault escarpments in a general pattern cascade, where ages decrease from the summits of the steep foothills. The ages of 51 sediment samples indicate a correlation with global climate following pulses: Last Interestadial-UI, the Last Glacial Maximum - LGM and the transition Pleistocene / Holocene, while the latter focus on 18 of 51 samples dated. This study also finds evidence of a new quaternary basin, here called Merejo Basin. Through these results it is concluded that no evidence of post-Cretaceous tectonic evolution of morphological MP, as their retreat along the fault scarps, invariably following the trend of the shear zones. The erosion of cliffs in large time scale is controlled by weakness zones generated by faults on the other hand the erosion of cliffs in short time, with the formation of deposits and colluvial horizons pedogenizados, has climate control. It was also found that in the study area there is a preponderance of past and current tectonic erosion processes on the morphological evolution / O relevo do Nordeste foi descrito por meio do modelo de pediplana??o. Esta base te?rica descarta a atua??o da tect?nica p?s-cret?cea na evolu??o da paisagem. Atrav?s deste modelo o Maci?o do Pereiro MP, Prov?ncia Borborema, foi definido como parte do Dom?nio dos Planaltos Residuais Sertanejos. O presente trabalho tem por objetivo estabelecer a evolu??o morfotect?nica p?s-cret?cea do MP, atrav?s da cartografia geol?gica e geomorfol?gica com uso de Sistema de Informa??o Geogr?fica, Sensoriamento Remoto e data??o de sedimentos por Single Aliquot Regenerative-dose (SAR). O MP est? contido no n?cleo semi?rido, de precipita??o anual entre 600 a 800 mm/ano. O MP tem dire??o NE-SW, ? limitado pela Zona de Cisalhamento de Jaguaribe (ZCJ) e Zona de Cisalhamento Portalegre (ZCPa), de mesma atitude, e atravessado por v?rias outras zonas de cisalhamento. Estas zonas de cisalhamento apresentam evid?ncias de reativa??o fr?gil cenozoica, na sua maioria como falhas normais e de n?vel crustal raso. A sedimenta??o quatern?ria em torno do MP se concentra em escarpas de falhas, em um padr?o geral em cascata, onde as idades diminuem das cimeiras aos sop?s das escarpas. As idades de 51 amostras de sedimentos indicam correla??o com seguintes pulsos clim?ticos globais: ?ltimo Interestadial- UI, o ?ltimo M?ximo Glacial - UMG e a transi??o Pleistoceno/Holoceno, sendo que nesta ?ltima concentram-se 18 das 51 amostras datadas. O presente trabalho tamb?m encontra evid?ncias de uma nova bacia quatern?ria, aqui denominada de Bacia Merejo. Atrav?s destes resultados conclui-se que h? evidencia de tect?nica p?s-cret?cea na evolu??o morfol?gica do MP, pois as suas escarpas recuam paralelamente ?s falhas, seguindo invariavelmente o trend das zonas de cisalhamento. A eros?o das escarpas em grande escala de tempo ? controlada pelas zonas de fraqueza geradas pelos falhamentos, por outro lado ? eros?o das escarpas em curtos espa?os de tempos, com a forma??o dos dep?sitos coluvionares e horizontes pedogenizados, possui controle clim?tico. Concluise ainda que na ?rea de estudo haja a preponder?ncia da tect?nica pret?rita e atual sobre os processos erosivos na evolu??o morfol?gica

Made available in DSpace on 2015-03-03T15:47:46Z (GMT). No. of bitstreams: 1 LeonardoCTB_DISSERT.pdf: 2119704 bytes, checksum: 5bdd21de8bfa668bba821593cdd5289f (MD5) Previous issue date: 2011-02-07 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Multi-objective combinatorial optimization problems have peculiar characteristics that require optimization methods to adapt for this context. Since many of these problems are NP-Hard, the use of metaheuristics has grown over the last years. Particularly, many different approaches using Ant Colony Optimization (ACO) have been proposed. In this work, an ACO is proposed for the Multi-objective Shortest Path Problem, and is compared to two other optimizers found in the literature. A set of 18 instances from two distinct types of graphs are used, as well as a specific multiobjective performance assessment methodology. Initial experiments showed that the proposed algorithm is able to generate better approximation sets than the other optimizers for all instances. In the second part of this work, an experimental analysis is conducted, using several different multiobjective ACO proposals recently published and the same instances used in the first part. Results show each type of instance benefits a particular type of instance benefits a particular algorithmic approach. A new metaphor for the development of multiobjective ACOs is, then, proposed. Usually, ants share the same characteristics and only few works address multi-species approaches. This works proposes an approach where multi-species ants compete for food resources. Each specie has its own search strategy and different species do not access pheromone information of each other. As in nature, the successful ant populations are allowed to grow, whereas unsuccessful ones shrink. The approach introduced here shows to be able to inherit the behavior of strategies that are successful for different types of problems. Results of computational experiments are reported and show that the proposed approach is able to produce significantly better approximation sets than other methods / Problemas de otimiza??o combinat?ria multiobjetivo apresentam caracter?sticas peculiares que exigem que t?cnicas de otimiza??o se adaptem a esse contexto. Como muitos desses problemas s?o NP-?rduos, o uso de metaheur?sticas tem crescido nos ?ltimos anos. Particularmente, muitas abordagens que utilizam a Otimiza??o por Col?nias de Formigas t?m sido propostas. Neste trabalho, prop?e-se um algoritmo baseado em col?nias de formigas para o Problema do Caminho mais Curto Multiobjetivo, e compara-se o algoritmo proposto com dois otimizadores encontrados na literatura. Um conjunto de 18 inst?ncias oriundas de dois tipos de grafos ? utilizado, al?m de uma metodologia espec?fica para a avalia??o de otimizadores multiobjetivo. Os experimentos iniciais mostram que o algoritmo proposto consegue gerar conjuntos de aproxima??o melhores que os demais otimizadores para todas as inst?ncias. Na segunda parte do trabalho, uma an?lise experimental de diferentes abordagens publicadas para col?nias de formigas multiobjetivo ? realizada, usando as mesmas inst?ncias. Os experimentos mostram que cada tipo de inst?ncia privilegia uma abordagem algor?tmica diferente. Uma nova met?fora para o desenvolvimento deste tipo de metaheur?stica ? ent?o proposta. Geralmente, formigas possuem caracter?sticas comuns e poucos artigos abordam o uso de m?ltiplas esp?cies. Neste trabalho, uma abordagem com m?ltiplas esp?cies competindo por fontes de comida ? proposta. Cada esp?cie possui sua pr?pria estrat?gia de busca e diferentes esp?cies n?o tem acesso ? informa??o dada pelo ferom?nio das outras. Como na natureza, as popula??es de formigas bem sucedidas tem a chance de crescer, enquanto as demais se reduzem. A abordagem apresentada aqui mostra-se capaz de herdar o comportamento de estrat?gias bem-sucedidas em diferentes tipos de inst?ncias. Resultados de experimentos computacionais s?o relatados e mostram que a abordagem proposta produz conjuntos de aproxima??o significativamente melhores que os outros m?todos

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-03T22:09:09Z No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-04T20:35:03Z (GMT) No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) / Made available in DSpace on 2016-02-04T20:35:03Z (GMT). No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) Previous issue date: 2015-02-26 / Esta tese trata de duas pesquisas no campo da modelagem molecular, com diferentes naturezas conceituais, por?m, baseadas em semelhantes princ?pios te?ricos da f?sica qu?ntica e da qu?mica computacional. No primeiro estudo, com o intuito de esclarecer os aspectos estruturais e energ?ticos da estabilidade da tripla-h?lice do col?geno humano, foram quantificadas as energias de intera??o entre os res?duos de amino?cidos que comp?em o pept?deo homotrim?rico T3-785, por interm?dio de c?lculos de Mec?nica Qu?ntica na luz da Teoria do Funcional da Densidade (DFT) e do m?todo de Fracionamento Molecular com Capuzes Conjugados (MFCC). Assim, as for?as de atra??o e repuls?o de cada um dos 90 res?duos que comp?em o sistema foram assinadas e as regi?es com alta/baixa estabilidade identificadas e comparativamente analisadas. Os dados obtidos aprofundaram as discuss?es sobre a estabilidade conformacional do col?geno. Na segunda pesquisa, propriedades de transporte eletr?nico de dois modelos biol?gicos foram exploradas. Nesse sentido, 27 miRNAs associados ao autismo e pept?deos formados pelas sequ?ncias (Thr-Ala)n e (Ala-Lys)n tiveram suas curvas de corrente-voltagem (I x V) calculadas. Os c?lculos computacionais foram parcialmente executados pelo m?todo qu?ntico DFT e, fundamentalmente, dentro de um modelo tight-binding, em conjunto com a t?cnica de matriz de transfer?ncia. No caso dos miRNAs, os resultados sugerem que um tipo de biosensor pode ser desenvolvido para distinguir diferentes tipos de autismo. J? os pept?deos analisados, demonstraram-se como bons candidatos para a constru??o de um diodo molecular. Ambos os resultados podem fundamentar e estimular pesquisas experimentais com essas biomol?culas no campo da nanoeletr?nica.

Made available in DSpace on 2014-12-17T15:07:04Z (GMT). No. of bitstreams: 1 MariaASM.pdf: 63217 bytes, checksum: 05be60dbf83ca4b7d547db7cb4c02508 (MD5) Previous issue date: 2008-04-14 / This work has as objective generality to make a multidimensional analysis in the genre journalistic assay, communicative genre that, beyond complex and multimodal, presents hybrid characteristics. Specifically, with the intention to propose defining criteria of the cited genre, this research looks for to establish differences and similarities between the assay and other genres of the same sphere, from the description and interpretation of used multimodal resources. The analysis of the formal, schematical and rhetorical resources identified in the formatting of the journalistic assay sample that the analyses are supported in the socio-semiotic and socio-rhetorical approaches. In the formal dimension, we contemplate elements that constitute design of the text, including the forms of representation from the typography, the colors, images, as well as the aspects communicative-linguistics: the modalization indices, the communicative operators and the category time; in the schematical dimension, we present the organizational structure, considering the rhetorical movements postulates for Swales (1990) and in the rhetorical dimension we observe the categories: who writes, for who it writes, on what it writes and where writes. The adopted methodologicals postulates are of qualitative nature and the procedure is documentary, data that in we are valid them written texts of this genre as analysis object. Corpus it is constituted by a composed sample for 14 extracted texts of a set of 173 propagated journalistic assays weekly for the magazine Veja, in the period between August of 2004 and January of 2008. The analysis of the data showed that the journalistic assay, object of this study, materializes through multiple symbolic representations and multiple subjects that turn since a small episode of the daily facts of great social relevance in the present time, of historical and cultural nature, nationwide or international. Used for the first time by Montaigne in 1580, to assign, in saying of the proper author, written fast on its life and historical events, which could nor be remembered later , the term `assay' was enriched with other specifications, of form to enclose the one that if they call scientific assay today, academic assay, journalistic assay and other types of specific assays. These denominations have to see with the enrollment of the members of diverse of practices communities, in virtue of the multiplicity of activities carried through in these spheres. The conclusions the one that we arrive had been the following ones: 1. the discursive genre is not a pure entity, in virtue of the multiplicity of situations where the sorts if insert in the social actions; 2. the institutions define the configuration of one definitive genre, also its proper assignment, since for backwards of all discursive genre a voice exists to discipline - institutional voice, and in the case of the assays for analyzed us, the institutional voice if it presents, really, as a defining trace; 3. the journalistic assay, for its multiple symbolic representations, multiple subjects and for passing explicit or implicit opinions of its author, resembles it other genres, being able, therefore, to be inserted in a colony of opinionatives genres / Este trabalho tem como objetivo geral fazer uma an?lise multidimensional no g?nero ensaio jornal?stico, g?nero discursivo que, al?m de complexo e multimodal, apresenta caracter?sticas h?bridas. Especificamente, com o intento de propor crit?rios definidores do referido g?nero, esta pesquisa procura estabelecer diferen?as e semelhan?as entre o ensaio e outros g?neros da mesma esfera, a partir da descri??o e interpreta??o de recursos multimodais utilizados. A an?lise dos recursos formais, esquem?ticos e ret?ricos identificados na formata??o do ensaio jornal?stico mostra que as an?lises se enquadram nas abordagens s?cio-semi?ticas e s?cio-ret?ricas. Na dimens?o formal, contemplamos elementos que constituem o design do texto, incluindo as formas de representa??o a partir da tipografia, das cores, imagens, bem como os aspectos ling??stico-discursivos: ?ndices de modaliza??o, os operadores discursivos e a categoria tempo; na dimens?o esquem?tica, apresentamos a estrutura organizacional, considerando os movimentos ret?ricos postulados por Swales (1990) e na dimens?o ret?rica observamos as categorias: quem escreve, para quem escreve, sobre o que escreve e onde escreve. Os postulados metodol?gicos adotados s?o de natureza qualitativa e o procedimento ? documental, dado que nos valemos de textos escritos desse g?nero como objeto de an?lise. O corpus ? constitu?do por uma amostra composta por 14 textos extra?dos de um conjunto de 173 ensaios jornal?sticos veiculados semanalmente pela revista Veja, no per?odo entre agosto de 2004 e janeiro de 2008. A an?lise dos dados mostrou que o ensaio jornal?stico, objeto desse estudo, materializa- se atrav?s de m?ltiplas representa??es simb?licas e m?ltiplos temas que versam desde um pequeno epis?dio do cotidiano a fatos de grande relev?ncia social na atualidade, de natureza hist?rica e cultural, de ?mbito nacional ou internacional. Empregado pela primeira vez por Montaigne em 1580, para designar, no dizer do pr?prio autor, escritos ligeiros sobre sua vida e sobre acontecimentos hist?ricos, os quais poderiam nem ser lembrados depois , o termo ensaio foi enriquecido com outras especifica??es, de forma a abranger o que se denominam hoje ensaio cient?fico, ensaio acad?mico, ensaio jornal?stico e outros tipos de ensaios espec?ficos. Essas denomina??es t?m a ver com o engajamento dos membros de comunidades de pr?ticas diversas, em virtude da multiplicidade de atividades realizadas nessas est?ncias. As conclus?es a que chegamos foram as seguintes: 1. o g?nero discursivo n?o ? uma entidade pura, em virtude da multiplicidade de situa??es em que os g?neros se inserem nas a??es sociais; 2. as institui??es definem a configura??o de um determinado g?nero, inclusive a sua pr?pria designa??o, visto que por tr?s de todo g?nero discursivo existe uma voz disciplinar a voz institucional e, no caso dos ensaios por n?s analisados, a voz institucional se apresenta, realmente, como um tra?o definidor; 3. o ensaio jornal?stico, por suas m?ltiplas representa??es simb?licas, m?ltiplos temas e por passar opini?es expl?citas ou impl?citas do seu autor, assemelha-se a outros g?neros, podendo, portanto, ser inserido em uma col?nia de g?neros opinativos

La corruption se définit de la manière la plus large comme tout « abus de pouvoir aux fins d’un profit privé ». Sous ses différentes formes, elle apparaît intimement liée à l’exercice du pouvoir. Cette dimension politique en fait l’envers de la démocratie, ainsi qu’un phénomène criminel particulièrement difficile à identifier, poursuivre et réprimer. Au cours des dernières décennies, elle aurait acquis une nouvelle dimension mondiale, rendant nécessaire une constante adaptation des dispositifs tant préventifs que répressifs. Cependant, le système pénal anti-corruption semble tributaire des profondes tensions générées par la confrontation permanente de la logique de l’État de droit à celle du pouvoir. Les résistances politiques s’avèrent nombreuses dans la perspective de diminuer les obstacles à une pleine efficacité répressive. Le juge pénal se trouve alors placé en première ligne de ce processus dialectique. Par son audace investigatrice et sa jurisprudence compensatrice, il contribuerait de manière décisive à faire évoluer le droit et, plus largement, à redéfinir les équilibres démocratiques entre pouvoir et contre-pouvoir. Sur le plan national, la justice acquiert ainsi une autonomie, une légitimité et une indépendance inédites. À travers la lutte contre la corruption transnationale, ce droit sous haute tension doit répondre au double défi de son efficacité et de son extranéité. L’approche systémique de la lutte contre la corruption permet alors de penser la cohérence d’ensemble des dispositifs juridiques, qu’il s’agit d’aligner suivant le même but : constituer une barrière protectrice pour le bien commun / Corruption is defined, in the broadest sense as any “abuse of power for private gain”. In its various forms, this phenomenon appears to be closely linked to the exercise of power. This political dimension makes it the opposite of democracy, as well as a criminal phenomenon which is particularly difficult to identify, prosecute and control. In the last decades, corruption has acquired a new international dimension that seemingly requires the constant adjustment of measures and provisions of law. However, the system dedicated to anti-corruption is seemingly born out of deep tensions generated by the permanent confrontation of the logic of the rule of law with the logic of power. There remains much political resistance to addressing the enforcement gap and remove the barriers to full repressive efficiency. The criminal judge is therefore placed at the forefront of this dialectical process. Through his investigative boldness and establishment of compensatory jurisprudence, the criminal judge contributes decisively to developing the law and, more broadly, to redefine the democratic balance between power and countervailing checks and balances. Nationally, justice thus acquires unprecedented autonomy, legitimacy and independence. Through the fight against transnational corruption, this law under high pressure must meet the dual challenge of its effectiveness and its foreignness. As a result, the systemic approach to the fight against corruption suggests we might think legal provisions in their overall consistency, with respect to their final aim: provide a line of defense for the common good

Chez les mammifères, les cellules apoptotiques peuvent être complètement dégradées par des cellules phagocytaires spécialisées ou servir de vecteur d'ADN Le transfert d'oncogènes via les cellules apoptotiques aboutit à la transformation des cellules receveuses uniquement si celles-ci sont déficientes en p53. Sachant que Fniicogène E6 des papillomavirus humains (HPV) à haut risque induit la dégradation de p53, il est concevable que son transfert par la cellule apoptotique soit à l'origine d'un mécanisme alternatif de carcinogenèse associée aux HPV. Afin de confirmer cette hypothèse, l'apoptose de cellules dérivées de cancer du col de l'utérus, abriiam ou non des séquences d'HPV, a été induite. En collaboration avec l'équipe de Patrick Sandoz du laboratoire d'optique de FEMTO-ST, nous avons adapté leur inicr;système référencé en position à l'observation automatisée de Finternalisation des cellules apoptotiques. Nous avons aussi déterminé que les cellules apoptotiques son! phagocytées par les fîbroblastes quel que soit leur statut virologique. Seules les cellules apoptotiques dérivées de cellules abritant de l'ADN d'HPV transforment les cellules receveuses. L'expression de l'ADN viral, dont E6, dans les fîbroblastes transformés ainsi que la perte d'expression des protéines p53 et p21 suggère que les oncogènes d'HPV pourraient être à l'origine de la transformation. Les résultats présentés dans ces travaux mettent en évidence un nouveau mécanisme de carcinogenèse associée aux HPV via la phagocytose des cellules apoptotiques, potentiellement impliqué dans la transformation de cellules primaires et la progression des tumeurs associées aux HPV. / Apoptotic cells in mammals may be completely degraded by specialized phagocytic cells or serve as a DNA vector. The oncogene transfer via apoptotic cells leads to the transformation of récipient cells but only when they are p53 deficient. As the E6 oncogene of high-risk human papillomavirus (HPV) leads to p53 dégradation, its transfer from apoptotic cells may be the cause of an alternative mechanism of HPV-associated carcinogenesis. To confirm this hypothesis, we induced apoptosis of cervical cancer cells that may harbor HPV sequences. In collaboration with Patrick Sandoz's team at the FEMTO-ST optical laboratory, we used their position-referenced microsystem for the automated observation of apoptotic cell internalization. We also found that apoptotic cells are phagocytized by fibroblasts regardless of their virological status. Only apoptotic cells from cells harboring HPV DNA transform recipient cells. Viral DNA expression, including E6, in transformed fibroblasts and the loss of p53 and p21 protein expression suggest that HPV oncogènes may cause transformation. These results highlight a new mechanism of HPV-associated carcinogenesis via apoptotic cell phagocytosis. This mechanism may be involved in thé transformation of primary cells and the progression of HPV-associated tumors.