Introdução: Esclerose múltipla (EM) é uma doença de caráter geralmente progressivo na qual a inflamação e a desmineralização da substância branca do sistema nervoso central resultam em vários sinais e sintomas neurológicos. É considerada uma doença de incapacidade, sendo que os pacientes podem apresentar distúrbios de marcha e sintomas motores que afetam a Qualidade de Vida (QV). Os imunomoduladores (betainterferons (ß-INF) 1A, 1B e acetato de glatirâmer (AG)) reduzem a frequência e a gravidade dos surtos e se espera que proporcione uma melhora sintomática, diminuição da frequência e gravidade das recorrências, consequentemente o número de internações. Estes medicamentos, dentre outros, são fornecidos pelo Ministério da Saúde (Protocolos Clínicos e Diretrizes Terapêuticas – EM). É uma doença de alta relevância, no Brasil ainda existem poucos trabalhos de avaliação da QV desta patologia e o MSQOL-54 é um questionário específico bastante utilizado pela comunidade científica internacional. Objetivos: O objetivo principal foi a tradução e validação do MSQOL-54 para o português do Brasil e o secundário de avaliar QV na coorte gaúcha de EM. Métodos: Os pacientes com em tratamento foram recrutados de uma amostra de conveniência de pacientes atendidos no Hospital das Clínicas de Porto Alegre e da Secretaria do Estado (SES-RS). Para coleta de dados foram utilizados: Formulário Sociodemográfico, MSQOL-54-Português, WHOQOL-Bref, Escala de Depressão de Beck e a Escala Expandida do Estado de Incapacidade (EDSS). Exceto o EDSS que foi aplicado por um neurologista, os demais questionários foram aplicados por pesquisadores treinados. Para análise de reprodutibilidade o MSQOL-54-Português foi aplicado em dois momentos distintos (teste-reteste). Resultados: Os 100 pacientes que participaram do estudo levaram em média 19 minutos para responder o MSQOL-54. O coeficiente alfa de Cronbach dos Componentes Saúde Física (CSF) e Mental (CSM) foi 0,85 e 0,80; respectivamente e entre as 12 escalas a variação foi de 0,63-0,94. O BDI teve boa correlação com CSF e CSM (MSQOL-54 Português), moderada (r=-0,61) e forte (r=-0,78), respectivamente. O WHOQOL-Bref apresentou correlação moderada com o CSF em quase todos seus domínios, forte com o CSM e com os demais, (r=-0,252), na função cognitiva (r=0,214) e no LDF (r=-0,220). O EDSS teve uma correlação moderada no domínio saúde física (r=-0,545), fraca no CSF fraca com a LDM (=-0,240) e com a função cognitiva (=-0,198). O resultado da comparação entre as médias dos escores das escalas do MSQOL-54 dos indivíduos em tratamento com ß-INF ou AG, somente o domínio função social apresentou diferença significativa, pacientes que utilizaram o ß-INF apresentaram escore médio mais elevado em relação ao AG. Conclusão: Os resultados permitem considerar satisfatória a adaptação do MSQOL-54-Português, tendo sido eficaz a avaliação da QV relacionada à saúde dos pacientes com EM. Em comparação com o artigo original em inglês a validação do MSQOL-54 na versão brasileira pode ser aceita. / Background: Multiple sclerosis (MS) is a disease of progressive character generally in which the inflammation and the demineralization of the white matter from the central nervous system result in several signals and neurological symptoms. It is considered as an incapacitating disease, in which patients may present motion disorders and motor symptoms that affect the Quality of Life (QL). The immunomodulatory drugs (interferons beta (ß-INF) 1A, 1B and glatiramer acetate (GA)) reduce the frequency and the severity of the surges and it is expected that they provide a symptomatic improvement, decreasing frequency and severity the recurrences, and consequently the number of hospitalizations. It is a disease of high relevance, in Brazil there are still few evaluation studies on the QL of this pathology and the MSQOL-54 is a specific questionnaire much used by international scientific community. Objectives: The main objective is to evaluate QL in the cohort of MS from Rio Grande do Sul region. 1) Performing the cultural adaptation of MSQOL-54 translated for Portuguese and validating it. 2) Evaluating the outcome of QL under the different alternatives of MS treatment. Methods: The patients under treatment were recruited from a convenience sample of patients attended at Hospital das Clínicas de Porto Alegre (HCPA) and from the State’ Secretariat. For the data collection, it was used: a sociodemographical form, Portuguese MSQOL-54 questionnaires, WHOQOL-Bref, Beck’s Depression Inventory and the Expanded Disability Status Scale (EDSS). Except to the EDSS, which was applied by a neurologist, the other forms were applied by trained researchers. For the reproducibility analysis, the MSQOL-54 was applied in two distinct moments. Results: The 100 patients who participated in the study took an average of 19 minutes to answer the MSQOL-54. Cronbach’s alpha coefficients of the components “physical health” (PHC) and “mental health” (MHC) were of 0.85 and 0.80 respectively and among the 12 scales the variation was from 0.63 up to 0.94. BDI had good correlation with PHC and MHC (MSQOL-54 Portuguese), moderate (r=-0.61) and strong (r=-0.78) respectively. WHOQOL-Bref presented moderate correlation with PHC in almost all domains, a strong one with MHC and a moderate one with the others. EDSS had a moderate correlation in physical health domain (r=-0.545), weak in PHC (r=-0.252), in the cognitive function (r= 0.214) and in PPL (r=-0.220). In diagnosis time the correlation was weak with LDM (=-0.240) and with the cognitive function (=-0.198). Considering that in June 2012 there were 947 patients registered in the States Secretariat who received these drugs’ there direct monthly cost with MS drugs US$ 1,075,016.70. Not considering deaths or new cases, the annual cost was US$ 12,900,200.00. Conclusion: The results indicate that the adaptation of MSQOL-54 Portuguese is satisfactory, being effective the quality of life evaluation related to the health of patients with MS. In comparison with the original essay in English, the validity of MSQOL-54 in Brazilian version can be accepted.

Ce travail vise à étudier pourquoi et comment des néologismes arabes résultent de la traduction du français vers l'arabe. En effet, partant d'une perspective interprétative de la traduction, le nombre de néologismes produits par celle-ci est censé être limité. La production de ceux-ci est censée être encore moins lorsqu'il s'agit de la traduction générale (par opposition à la traduction spécialisée). Or, examinant des textes généraux contemporains traduits du français vers l'arabe, nous remarquons une production néologique non négligeable. La présente étude se propose, ainsi, d'analyser les raisons de l'émergence de tels néologismes dans les textes traduits en arabe contemporain et d'examiner les moyens de formation de ces néologismes arabes ainsi que l'influence de la langue source; en l'occurrence le français, dans cette formation. Les textes, faisant l'objet de cette étude, sont des documents officiels de l'ONU datant de 2005-2006. Ces textes sont publiés par l'ONU et destinés, entre autres, au grand public. / The aim of this thesis is to figure out both the reasons as well the ways of producing new Arabic words, or rather neologisms, as a result of French-Arabic translation. According to the interpretive concept of translation, the amount of neologisms resulted by translation is supposed to be limited. Especially when it comes to general translation, the predicted chance of producing such neologisms is extremely low. Nevertheless, going over few general contemporary Arabic texts translated from French shows how hard it is to ignore these newly produced neologisms Thus, this research discusses the reasons of the existence of such a phenomenon called Neologism in texts translated into contemporary Arabic. Furthermore, it analyzes the different ways of forming those neologisms in Arabic and how the source language (French language) influences this forming. This study is based on texts and documents published by the UN (2005- 2006) and addressed to laymen.

Il est communément admis que la traduction est liée à l'interprétation, ce dont témoignent des formules telles que « comprendre c'est traduire » ou « interpréter pour traduire ». Cette thèse se donne pour objectif de parcourir les principales articulations du nœud entre interprétation et traduction et d'évaluer les chances de le desserrer. Pour ce faire, deux axes sont retenus. D'une part, l'opposition entre le bon sens et les paradoxes qui recoupe l'opposition entre les théories traditionnelles et critiques de la traduction. D'autre part, une lecture des réflexions sur la traduction au regard de certaines notions mises en avant par des penseurs assimilés à ce qui a pu être appelé la « théorie française », puis reprises en critique littéraire.Les hypothèses de George Steiner concernant la traduction et les principes de la Théorie Interprétative de la Traduction développée à l'ÉSIT sont ainsi étudiés et confrontés aux propositions d'Henri Meschonnic et d'Antoine Berman. Pour approfondir l'enquête et tenter de délimiter la portée du modèle herméneutique du sens en traduction, les travaux notamment de Saussure, Benveniste, Derrida, Deleuze, Ricœur ou Barthes jusqu'à ceux, plus récents, d'Agamben, Rancière et Huyghe sont convoqués.Dans ce sillage, la thèse invite enfin à considérer la traduction comme une technè ouverte et indéterminée et suggère d'aborder le lien entre traduction et interprétation du point de vue des réflexions sur la répétition et la représentation qu'ont pu inspirer le personnage du copiste et sa place croissante en littérature depuis Flaubert. / It is commonly accepted that translation and interpretation are linked, as is reflected in phrases such as “understanding as translation” and “interpret to translate”. The objective of this thesis is to examine the main threads of the knot that joins interpretation and translation, and to evaluate the chances of untangling these threads.Two approaches were used to do this. The first approach examines the conflict between common sense and the paradoxes raised by comparing traditional and critical theories of translation. The second approach considers reflections on translation in the light of certain notions advanced by thinkers associated with what can be called the “French theory” and then adopted in literary criticism.Thus, George Steiner’s hypotheses concerning translation and the principles of the Interpretative Theory of Translation developed at the ÉSIT are assessed and contrasted with propositions put forward by Henri Meschonnic and Antoine Berman. Works by de Saussure, Benveniste, Derrida, Deleuze, Ricœur, and Barthes, as well as by more recent authors such as Agamben, Rancière, and Huyghe, are appraised in order to develop this analysis further, and to try and define the range of the hermeneutic model of meaning in translation.The results of these analyses suggest that translation should be considered an open and indeterminate techne, and that the link between translation and interpretation can be addressed via reflections on the repetition and the representation inspired by the character of the copyist and its growing place in literature since Flaubert.

Le point de départ de ce travail est l’importance de l’Interprétation Consécutive (IC), en particulier de l’Interprétation Consécutive Monologique (ICM) dans le milieu universitaire, où elle est requise et a son espace préservé et valorisé. En considérant que cette modalité d’interprétation apporte des défis pour son exécution, même aux interprètes les plus expérimentés, il faut établir la juste dimension et la valorisation des ressources qui sont utiles aux sous-compétences traductives qui font partie du rôle de l’interprète. La Prise de Notes (PN) est une des ressources qui aident l’utilisation de la mémoire dans cette modalité d’interprétation. Ainsi, ce travail se propose d’investiguer la PN, une fois qu’il comprend qu’il s’agit d’une étape décisive pour la réussite de l’interprétation. Pour cela, cette recherche se penche sur les études d’auteurs importants de ce domaine, dans le but de connaître la méthodologie de la PN qu’ils proposent et mieux comprendre la spécificité et la place de la PN dans l’IC. Pour atteindre ce propos, ce travail présente une révision théorique sur la PN, en proposant un répertoire sur elle et revise les Compétences en Traduction recommendées par Hurtado Albir en comparant ses résultats avec la pratique des interprètes. La prétention du rapprochement entre théorie et pratique est d’attribuer la juste importance à la PN et d’aider à équiper l’interprète pour qu’il ait de meilleurs résultats dans son rôle. L’analyse réalisée souligne l’importance d’une préparation de l’interprète pour le travail en IC, qui se sert de la PN comme une aide à la mémoire, en qualifiant encore plus le rôle du professionnel. / O ponto de partida deste trabalho é a relevância da Interpretação Consecutiva (IC), em particular da Interpretação Consecutiva Monológica (ICM) no meio universitário, onde ela é requisitada e tem seu espaço preservado e valorizado. Considerando que essa modalidade de interpretação traz desafios para a sua execução, mesmo para os intérpretes mais experientes, faz-se necessário o correto dimensionamento e a valorização de recursos que auxiliam as subcompetências tradutórias envolvidas na atuação do intérprete. A Tomada de Notas (TN) é um dos recursos que auxilia o uso da memória nessa modalidade de interpretação. Assim, este trabalho propõe-se a investigar a TN, por entender que se trata de uma etapa decisiva para o êxito da interpretação. Para isso, esta pesquisa se debruça sobre os estudos de importantes autores da área, com o propósito de conhecer a metodologia de TN que propõem e compreender melhor a especificidade e o lugar da TN na IC. Para alcançar esse propósito, este trabalho apresenta uma revisão teórica sobre a TN, propondo um repertório sobre ela, e revisa as Competências Tradutórias preconizadas por Hurtado Albir, confrontando seus resultados com a prática de intérpretes. A pretensão dessa aproximação entre teoria e prática é atribuir a devida importância à TN e auxiliar a instrumentalizar o intérprete para que este alcance melhores resultados na sua atuação. A análise realizada aponta para a importância de uma preparação do intérprete para a atuação em IC, que se sirva da TN como um auxílio à memória, qualificando ainda mais a atuação do profissional.

Introdução: Esclerose múltipla (EM) é uma doença de caráter geralmente progressivo na qual a inflamação e a desmineralização da substância branca do sistema nervoso central resultam em vários sinais e sintomas neurológicos. É considerada uma doença de incapacidade, sendo que os pacientes podem apresentar distúrbios de marcha e sintomas motores que afetam a Qualidade de Vida (QV). Os imunomoduladores (betainterferons (ß-INF) 1A, 1B e acetato de glatirâmer (AG)) reduzem a frequência e a gravidade dos surtos e se espera que proporcione uma melhora sintomática, diminuição da frequência e gravidade das recorrências, consequentemente o número de internações. Estes medicamentos, dentre outros, são fornecidos pelo Ministério da Saúde (Protocolos Clínicos e Diretrizes Terapêuticas – EM). É uma doença de alta relevância, no Brasil ainda existem poucos trabalhos de avaliação da QV desta patologia e o MSQOL-54 é um questionário específico bastante utilizado pela comunidade científica internacional. Objetivos: O objetivo principal foi a tradução e validação do MSQOL-54 para o português do Brasil e o secundário de avaliar QV na coorte gaúcha de EM. Métodos: Os pacientes com em tratamento foram recrutados de uma amostra de conveniência de pacientes atendidos no Hospital das Clínicas de Porto Alegre e da Secretaria do Estado (SES-RS). Para coleta de dados foram utilizados: Formulário Sociodemográfico, MSQOL-54-Português, WHOQOL-Bref, Escala de Depressão de Beck e a Escala Expandida do Estado de Incapacidade (EDSS). Exceto o EDSS que foi aplicado por um neurologista, os demais questionários foram aplicados por pesquisadores treinados. Para análise de reprodutibilidade o MSQOL-54-Português foi aplicado em dois momentos distintos (teste-reteste). Resultados: Os 100 pacientes que participaram do estudo levaram em média 19 minutos para responder o MSQOL-54. O coeficiente alfa de Cronbach dos Componentes Saúde Física (CSF) e Mental (CSM) foi 0,85 e 0,80; respectivamente e entre as 12 escalas a variação foi de 0,63-0,94. O BDI teve boa correlação com CSF e CSM (MSQOL-54 Português), moderada (r=-0,61) e forte (r=-0,78), respectivamente. O WHOQOL-Bref apresentou correlação moderada com o CSF em quase todos seus domínios, forte com o CSM e com os demais, (r=-0,252), na função cognitiva (r=0,214) e no LDF (r=-0,220). O EDSS teve uma correlação moderada no domínio saúde física (r=-0,545), fraca no CSF fraca com a LDM (=-0,240) e com a função cognitiva (=-0,198). O resultado da comparação entre as médias dos escores das escalas do MSQOL-54 dos indivíduos em tratamento com ß-INF ou AG, somente o domínio função social apresentou diferença significativa, pacientes que utilizaram o ß-INF apresentaram escore médio mais elevado em relação ao AG. Conclusão: Os resultados permitem considerar satisfatória a adaptação do MSQOL-54-Português, tendo sido eficaz a avaliação da QV relacionada à saúde dos pacientes com EM. Em comparação com o artigo original em inglês a validação do MSQOL-54 na versão brasileira pode ser aceita. / Background: Multiple sclerosis (MS) is a disease of progressive character generally in which the inflammation and the demineralization of the white matter from the central nervous system result in several signals and neurological symptoms. It is considered as an incapacitating disease, in which patients may present motion disorders and motor symptoms that affect the Quality of Life (QL). The immunomodulatory drugs (interferons beta (ß-INF) 1A, 1B and glatiramer acetate (GA)) reduce the frequency and the severity of the surges and it is expected that they provide a symptomatic improvement, decreasing frequency and severity the recurrences, and consequently the number of hospitalizations. It is a disease of high relevance, in Brazil there are still few evaluation studies on the QL of this pathology and the MSQOL-54 is a specific questionnaire much used by international scientific community. Objectives: The main objective is to evaluate QL in the cohort of MS from Rio Grande do Sul region. 1) Performing the cultural adaptation of MSQOL-54 translated for Portuguese and validating it. 2) Evaluating the outcome of QL under the different alternatives of MS treatment. Methods: The patients under treatment were recruited from a convenience sample of patients attended at Hospital das Clínicas de Porto Alegre (HCPA) and from the State’ Secretariat. For the data collection, it was used: a sociodemographical form, Portuguese MSQOL-54 questionnaires, WHOQOL-Bref, Beck’s Depression Inventory and the Expanded Disability Status Scale (EDSS). Except to the EDSS, which was applied by a neurologist, the other forms were applied by trained researchers. For the reproducibility analysis, the MSQOL-54 was applied in two distinct moments. Results: The 100 patients who participated in the study took an average of 19 minutes to answer the MSQOL-54. Cronbach’s alpha coefficients of the components “physical health” (PHC) and “mental health” (MHC) were of 0.85 and 0.80 respectively and among the 12 scales the variation was from 0.63 up to 0.94. BDI had good correlation with PHC and MHC (MSQOL-54 Portuguese), moderate (r=-0.61) and strong (r=-0.78) respectively. WHOQOL-Bref presented moderate correlation with PHC in almost all domains, a strong one with MHC and a moderate one with the others. EDSS had a moderate correlation in physical health domain (r=-0.545), weak in PHC (r=-0.252), in the cognitive function (r= 0.214) and in PPL (r=-0.220). In diagnosis time the correlation was weak with LDM (=-0.240) and with the cognitive function (=-0.198). Considering that in June 2012 there were 947 patients registered in the States Secretariat who received these drugs’ there direct monthly cost with MS drugs US$ 1,075,016.70. Not considering deaths or new cases, the annual cost was US$ 12,900,200.00. Conclusion: The results indicate that the adaptation of MSQOL-54 Portuguese is satisfactory, being effective the quality of life evaluation related to the health of patients with MS. In comparison with the original essay in English, the validity of MSQOL-54 in Brazilian version can be accepted.

Les études sur Marguerite Duras (1914-1996) sont innombrables et abondantes en France, ainsi qu’en Chine. Le présent travail a dévoilé, à la lumière des méthodes empruntées à la littérature comparée, à l’analyse textuelle, à l’écriture féminine, et à l’autobiographie, comment l’œuvre de Marguerite Duras a été reçu dans le monde littéraire contemporain chinois, en dressant un bilan de la réception de l’œuvre durassienne par le biais de la traduction, par la réception de l’écriture féminine, et par le renouvellement de l’art narratif et de la technique créative dans le monde littéraire contemporain chinois. L’étude de la réception de l’œuvre durassienne en Chine à travers l’écriture romanesque de certains écrivains contemporains chinois qu’elle a influencés permet un regard particulier et une autre compréhension possible sur Marguerite Duras. / Studies on Marguerite Duras (1914-1996) in Both China and France are innumerable and abundant. By using the critical methods of literary comparison, textual analysis, feminism and autobiographical writing, etc, this thesis intends to make a survey of the reception of Duras in Chinese Contemporary literature, focusing on the aspects of translation studies, feminine writing, and narrative creativity. Meanwhile, studies on several Chinese writers deeply influenced by Duras can provide a unique perspective and different understanding to our research on this French writer.

Dans l’aire arabofrancophone, la valeur littéraire de la fiction narrative tend souvent à se confondre avec sa dimension subversive. Le présent travail aborde cette notion problématique de subversion en tant que modalité discursive et posturale. Sont analysées les perturbations infligées aux codes linguistiques, énonciatifs et génériques à la lumière du postulat suivant lequel le bilinguisme et le biculturalisme des écrivains favorisent cette veine et la nourrissent. C’est, en effet, autour d’une double appartenance, feinte ou avérée, que se rejoignent les poétiques d’auteurs aussi éloignés que Rachid BOUDJEDRA, Albert COSSERY, Edmond Amran EL MALEH, Émile HABIBI et Paul SMAÏL. L’articulation de l’analyse textuelle à celle des postures auctoriales permet de discerner une dynamique littéraire dans laquelle ce qui s’offre a priori comme une littérature politique s’avère un avatar d’une politique de la littérature. / In the Arabo-Francophone culture, the literary value of narrative fiction often tends to intermingle with its subversive dimension. The present study deals with this problematical notion of subversion considered as a posture and a discursive modality. The disturbances inflicted on linguistic, enunciative and generic codes are analysed under the assumption that the writers' bilingualism and biculturalism favour this type of inspiration and nurture it. Indeed, the poetics of authors as different as Rachid BOUDJEDRA, Albert COSSERY, Edmond Amran EL MALEH, Émile HABIBI and Paul SMAÏL seem to meet around this double belonging, whether it is real or simply assumed. Together, text analysis and authors' postures observation enable us to discern a literary movement in which what is a priori offered as a political literature ends up being a metamorphosis of a literary policy.

Avec près d’un million de nouveaux cas par an à travers le monde, le cancer colorectal est un problème de santé publique majeur. Il est la 2ème cause de mortalité par cancer en France, ce fort taux de mortalité étant relié à un pourcentage important de récidives et de métastases. L’hétérogénéité tumorale, la dissémination, la résistance aux traitements et la récidive seraient notamment dues à une population particulière de cellules tumorales appelées cellules souches cancéreuses (CSC). Ces cellules sont dotées d’une capacité d’adaptation extraordinaire et la compréhension des mécanismes moléculaires sous-tendant cette plasticité cellulaire est un objectif majeur pour concevoir de nouvelles stratégies thérapeutiques les ciblant spécifiquement. La synthèse protéique joue un rôle clé dans la carcinogénèse : d’une part, une synthèse protéique élevée est nécessaire à la prolifération des cellules tumorales, d’autre part, la traduction sélective favorise l’expression de protéines pro-oncogéniques. Considéré pendant des années comme un acteur passif de la traduction, le ribosome semblerait jouer un rôle majeur dans la régulation de la synthèse protéique. En effet, des études récentes ont montré que la composition du ribosome était « flexible » et permettrait de favoriser la traduction de certains ARN messager (ARNm). De plus, l’expression de certaines protéines ribosomiques (PR) varie entre le tissu sain et le tissu cancéreux, parfois même entre la tumeur initiale et la métastase. Ce projet vise à déterminer de quelle manière le contrôle traductionnel intervient dans plusieurs étapes clé du cancer colorectal, en se focalisant tout particulièrement sur l’acquisition ou la perte de propriétés propres aux CSC. Cette étude permettra de mieux comprendre les mécanismes moléculaires exploités par les CSC afin de résister aux traitements et s’adapter à leur environnement. De plus, ce projet pourrait mettre en évidence un rôle exercé par certaines protéines ribosomiques dans le contrôle traductionnel, à travers la filtration des ARNm par le ribosome. A plus long terme, il pourrait déboucher sur le développement de nouveaux traitements permettant de cibler spécifiquement la machinerie traductionnelle des CSC. / Despite significant advances in diagnostics and treatment, colorectal cancer (CRC) remains a major cause of mortality worldwide and occurrence of metastasis represents the primary cause of death. Metastasis process, chemoresistance and tumor recurrence is powered by a minor subpopulation of tumor cells endowed with self‐renewal and multi‐lineage differentiation ability: the cancer stem cells (CSC).Translation of mRNA into protein is the final step in gene-expression process, which mediates the formation of the translatome from genomic information. Several mechanisms, such as signaling pathways, translation factors availability, alternative open reading frame and alternative initiation pathways account for real time translatome remodeling. Moreover, an emerging concept suggests that ribosome is heterogeneous and can be "reprogrammed". These "specialized ribosomes" would preferentially engage certain mRNA at the expense of others and therefore drive cell phenotype and favor cell adaptation. Many studies have correlated deregulation of both translation machinery composition and activity with cancer initiation and evolution. From that perspective, CSC might well represent a perfect model to test whether the translation apparatus takes an active part in tumor initiation, progression, and metastasis. Our goal is to demonstrate that protein synthesis is differentially regulated depending on cancer cell subpopulation and determine whether ribosomal heterogeneity could influence tumoral evolution and plasticity. In a long run, we envision the development of novel therapies based on specific targeting of translational control in CSC.

Les ARNm codent pour les protéines, tandis qu'un grand nombre d'ARNs nommés longues ARNs non codants (ARNlnc) ne sont pas traduites en protéines. Les deux types d’ARNs existent en isoforms qui se distinguent à cause de l’épissage alternatif. Certains des ARNlnc jouent des rôles importants dans la croissance et différentiation cellulaire. Cependant, leurs fonctions dans la cytotoxicité de la chimiothérapie anti-cancéreuse médicamenteuse utilisant le 5-fluorouracile (5-FU) sont encore inconnues. Pendant mes travaux j'ai trouvé que le traitement par le 5-FU cause l’accumulation des ARNlnc. Ce phénomène est parfois, sous forme d’ARN double brin (ARNds) formé par une paire de transcrits chevauchant, corrélé négativement avec le niveau de la protéine codée par l'ARNm. Cette inhibition potentielle de la traduction des régulateurs du cycle cellulaire clés et les gènes essentiels en formant des l'ARNds peut éventuellement empêcher la progression du cycle cellulaire. Nos analyses prometteuses devraient inspirer des études approfondies des ARNlnc dans la cytotoxicité du 5-FU chez la levure et l’homme afin d’'améliorer la chimiothérapie. J'ai trouvé que la surexpression de RRP6, peut conduire à une résistance accrue au traitement par le 5-FU. Je démontre ensuite que l’ARNlnc MUT1312 forme des ARNds avec RRP6 qui sont négativement corrélés avec le niveau de la protéine Rrp6. Par ailleurs, la surexpression de MUT1312 pendant la mitose et associé avec une diminution d’Rrp6. Ainsi, mon étude suggère que MUT1312 soit impliqué dans la régulation de Rrp6 pendant la differentiation cellulaire. Mes recherches de MUT477/SWI4 indiquent la function importante de la méiose induite à long ARN non codantes en tant que forme d'ARN double brin potentiellement réguler la traduction. J'ai trouvé que SUT200 pourrait inhiber la transcription de CDC6 durant la méiose par read-through. Un cas comparable est MUT1465 et CLN2. J’ai fait un criblage in silico pour trouver des facteurs de transcription qui activent des MUTs durant la méiose. J’ai trouvé que la plupart des MUTs sont induites par Ndt80. MUT1465 est parmi eux : il pourrait être induite par Ndt80 ce qui inhiberait l’expression de CLN2 après l’initiation de la méiose. J’ai trouvé que la répression de certains MUTs par le complexe Ume6/Rpd3 en mitose est différemment régulée entre JHY222 et SK1. MUT100 qui ne possède pas l'élément USR1 fixé par Ume6, et qui est donc une cible indirecte, est déréprimé dans JHY22 ume6 mais pas dans SK1 ume6. Pour la régulation de l'étude de isoforme méiose, Nous avons trouvé que le complexe histone déacétylase Rpd3/Sin3/Ume6, empêche également l'induction de l'isoforme longue de BOI1 dans la mitose par liaison directe de liaison Ume6 à sa cible de URS1. Orc1 est importante pour la réplication de l'ADN. J’ai démontré que mORC1 est une cible directe de l'activateur Ndt80 et que son motif de fixation (MSE) est nécessaire pour l'induction de l’isoforme mORC1 et du gene méiotique SMA2 transcrit de façon divergente. J’ai trouvé qu'une souche incapable d’induire mORC1, contient des niveaux anormalement élevés d’Orc1 pendant la gamétogenèse, ce qui corréle mORC1 avec la baisse de la protéine Orc1. En conclusion, mes études au cours du doctorat révèlent des nouvelles cibles et ainsi offrent des nouvelles perspectives de l’amélioration de la chimiothérapie par le 5-FU. Les mécanismes incluent la formation d'un ARN double brin avec son ARNm anti-sens pour potentiellement inhiber la traduction de l'ARNm, et inhibition en aval de l'ARNm par transcription read-through d’une ARNlnc. Mon travail a également révélé un mécanisme de régulation des ARNlnc et les isoforms d’ARN pendent la croissance et la différentiation cellulaire. / RNAs are molecules with important functions in diverse cellular processes. mRNAs encode proteins, while a large number of RNAs called long noncoding RNAs (lncRNAs) are not translated into proteins. Both types of RNAs exist in various isoforms due to alternative splicing.Some of lncRNA play important roles in cell growth and differentiation. However, their functions in the cytotoxicity of the drug anticancer chemotherapy using 5-fluorouracil (5-FU) are still unknown. During my research I found that treatment with 5-FU causes accumulation of lncRNA. Acuumulated antisense lncRNA form double stranded RNA with the mRNAs , negatively correlated with the level of the protein encoded by the mRNA. This potential inhibition of translation of key cell cycle regulators and essential genes by forming dsRNA may possibly prevent the progression of the cell cycle. My results suggest that lncRNA are likely to play an important role in the cytotoxicity of 5-FU. Our promising testing should inspire in-depth studies of lncRNA in the cytotoxicity of 5-FU in yeast and humans to improve chemotherapy.Rrp6 is a 3'-5 'exoribonuclease, which plays an important role in the regulation and modification of rRNA, mRNA and lncRNA. I found that overexpression of RRP6, the homologue of the yeast EXOSC10 gene in mammals, can lead to increased resistance to treatment with 5-FU. I found that the lncRNA MUT1312 form dsRNA with RRP6 that are negatively correlated with the level of Rrp6 protein. Furthermore, overexpression of MUT1312 during mitosis and associated with a decrease of Rrp6. Thus, my study suggests that MUT1312 may involved in the regulation of Rrp6 during cell differentiation. I further explored the function of the double-stranded RNA in meiosis. My research about SWI4/MUT477 indicates the important function of meiosis induced long noncoding RNA as a form of double-stranded RNA potentially regulate translation. Another aspect of the function of lncRNA is to regulate the transcription of downstream mRNA. I found SUT200 could inhibit transcription of CDC6 during meiosis by read-through. A similar case is CLN2/MUT1465. I did an in silico screening to find transcription factors that activate MUTs during meiosis. I found that most MUTs are induced by Ndt80. MUT1465 is among them: it could be induced by Ndt80 which inhibit the expression of CLN2 after initiation of meiosis. I found that repression of certain MUTs by the Ume6 / Rpd3 complex in mitosis is regulated differently between JHY222 and SK1. MUT100 which does not have the Ume6 binding site URS1 element, and is therefore an indirect target is derepressed in JHY22 ume6 but not in SK1 ume6. For the study about regulation of meiosis isoform, we have found that the histone deacetylase complex Rpd3 / Sin3 / Ume6 prevents the induction of long isoform BOI1 in mitosis by direct binding Ume6 binding to its target URS1.Orc1 is important for DNA replication. I have demonstrated that mORC1 is a direct target of the Ndt80 activator and its binding motif (MSE) is required for induction of isoform mORC1 and meiotic gene SMA2 divergently transcribed. I found that a strain incapable of inducing mORC1 contains abnormally high levels of Orc1 during gametogenesis, which correlates with mORC1 declining Orc1 protein. Since eukaryotic genes often encode multiple transcripts with 5'-UTR of variable length, the findings are likely relevant to gene expression during development and disease in higher eukaryotes. In conclusion, my studies during PhD reveal new targets and thus offer new prospects for improving chemotherapy with 5-FU. Mechanisms include (1) the formation of a double strand with its antisense mRNAs to potentially inhibit translation of mRNA, and (2) downstream inhibition of mRNA transcription read-through of a lncRNA. My work also revealed a lncRNA regulatory mechanism and RNA isoforms dangling growth and cell differentiation.

Nous proposons dans cette recherche de mener un travail explorateur sur la problématique de la traduction des titres dans la presse économique destinée à la vulgarisation. De ce fait, notre but est d’aboutir à des observations empiriques et proposer une approche de traduction adaptée à ces énoncés.Nous avons exploré, dans la première partie, les fondements théoriques et pratiques en traductologie et examiné les différents éléments en œuvre dans l’activité traductionnelle. Nous avons également proposé une approche de traduction adaptée aux titres de presse et à la leur spécificité linguistique et stylistique. Ce procédé appelle à une exploration analytique de la textuelle de départ aux niveaux de la linguistique et de la stylistique afin d’établir une équivalence qui puisse configurer la formation structurale et préserver sa portée, d’une part, et transmettre ses effets rhétoriques, d’autre part. Cette approche nous permet de décider de la démarche suivie pour aboutir à l’équivalence recherchée, d’où la pratique d’une traduction bijective, injective, surjective, ou libre. Dans la partie empirique, nous avons analysé deux corpus en nous basant sur les types de traduction proposés. Le premier a été prélevé afin de juger du degré d’adéquation de chaque traduction en matière de pertinence sémantique et de fonctionnalité du parcours suivi. Le deuxième a été prélevé en raison des particularités stylistiques des titres sélectionnés afin d’établir des équivalences illustratives du modèle configuratif transmissionnel proposé.La conclusion porte sur des constatations formulées sur les procédés suivis dans les corpus choisis et sur le modèle configuratif transmissionnel proposé. / This research aims at exploring problematic issues relating to the translation of headlines in popular, economic magazines. Hence, it means to derive relevant empirical observations and propose a translation theory adapted to the headlines in question.With that objective in mind, we have allotted the initial part of our research to the theoretical and practical approaches encountered in translation studies and examined the various elements at work during the translation process. We have also proposed a model of translation adapted to headlines and their linguistic and stylistic characteristics. This approach calls for an analytical exploration of the source text at the linguistic and stylistic levels in order to establish an equivalence that reflects its structural formation and preserves its impact, on the one hand, and conveys its rhetorical effects, on the other. Such an approach is also decisive in establishing the process to follow to deliver the equivalence being sought through three types of translation: bijective, injective, surjective, or free. In the empirical part of our study, we have analyzed two selected bodies based on the types of translation proposed. The analysis of the first body was meant to evaluate the degree of adequacy of each rendition in terms of semantic relevancy and functionality. The analysis of the second body, which is made up of headlines selected for their stylistic peculiarities, was meant to establish illustrative equivalences of the configurative transmissional model we have proposed.In the concluding part of our research, we have formulated observations of all the processes studied in the selected bodies and in the proposed model.