Les explications politiques de la fin de la monarchie de Juillet demandent à être reconsidérées. L’historiographie, s’appuyant sur les témoignages des acteurs qui l’ont combattue a insisté sur le refus du roi d’accorder la réforme électorale et parlementaire, refus appuyé par le cabinet ministériel dirigé par Guizot et par la Chambre des députés. La Charte de 1830 définissait le cadre d’un régime où le roi avait sa place et où le gouvernement devait chercher l’appui et le concours des chambres parlementaires. Dans ces conditions, le pouvoir exécutif devait obtenir l’assentiment des assemblées pour mener sa politique. Le refus de la réforme s’explique alors par l’obtention d’une majorité parlementaire acquise au gouvernement par des moyens peu avouables (élections manipulées, corruption, pressions de toutes sortes sur les députés) et la présence massive de députés fonctionnaires a priori dociles et obéissants. Était-ce vraiment le cas ? La dernière Chambre des députés élue en 1846 voit une victoire ministérielle incontestable plus fondée sur les effets du suffrage censitaire que par des manipulations. Le comportement de cette majorité durant cette courte législature révèle en fait que le cabinet s’occupa plus de composer avec les dissensions qui sont apparues en son sein que d’essayer de la diriger et de la dominer. En réalité, on en vient à se demander si Guizot, loin d’imposer son point de vue aux députés ministériels n’était pas en fin de compte le porte-parole de leurs aspirations conservatrices. / The political explanations for the downfall of the July monarchy require re-examination. Relying on testimonies from the politicians who battled against it, historiography gives preference to the king’s refusal of parliamentary and electoral reform, a refusal that was backed by the ministerial cabinet under the direction of Guizot and the Chamber of deputies. The Charter of 1830 laid the foundations of a regime with a place for the king, and where the government had to solicit the assistance and cooperation of the assemblies. In these conditions, in order to conduct its policies, the executive branch had to first obtain the consent of the assemblies. The refusal of reform is thus attributed to the government’s winning the parliamentary majority by dubious means (corruption, rigged elections, and putting deputies under pressure of all sorts) and the immense presence of bureaucrats who were assumed obedient and docile. Was this really the case? The monarchy’s last Chamber of deputies, elected in 1846, reached an incontestable ministerial victory, due more to the effects of censitary suffrage than rigging. The behavior of this majority over the short course of this term of office actually reveals that the cabinet was more concerned with dissent from within than it was with trying to lead and dominate it. By this one is led to wonder if Guizot, far from imposing his point of view on ministerial deputies, wasn’t actually the spokesperson for their conservative aspirations.

The chromosomal translocation of t(14;18)(14q32;18q21) is a characteristic aberration of follicular lymphoma and Diffuse Large B cells lymphoma. By PCR, it was proved that the rearrangement of chromosomes 14 and 18 leads to an overexpression of BCL2, an anti-apoptotic protein, which is one of the factors responsible for the maturation of the diseases. The translocation involves the promoter region of IGH gene and the transcriptional unit of BCL2 gene. Previous studies carried out in Dr Tosi’s lab showed a looping out of the BCL2 gene from its chromosome territory in 15% of the nuclei analysed. This looping out could be possibly responsible for the transcriptional activity of the gene. A further relevant finding concerns the spatial distribution of the genes involved in the translocation in the interphase nuclei. In the Pfeiffer cell line, harbouring the t(14;18) rearrangement, the translocated BCL2 gene was positioned in the cell nuclei according to a bimodal distribution. One could speculate that the distribution in the periphery and in the centre of the nuclei could divide the Pfeiffer cell line in two different subpopulations, consequently from the transcriptional activity. These preliminary data set the ground for more experimental work to test whether genes associated with the nuclear interior were transcriptionally active as opposed to the genes positioned towards the nuclear periphery, transcriptionally inactive. The work here presented focuses on this investigation using RNA-DNA FISH (Fluorescence in situ hybridization). My work enabled the detection of IGH, BCL2 and t(14;18) genes along with their transcripts inside of the nuclei of Pfeiffer cell line. Contrary to what had been hinted by previous work, my results showed multiple nuclear positions of transcriptionally active IGH/BCL2 translocation. The result will need to be further supported by software analysis in order to define its specific nuclear position and to ensure the perfect localization of the genes inside each nucleus.

Após o seqüenciamento completo do genoma humano, a busca e caracterização do conjunto completo de genes humanos constitui-se no principal desafio nesta área de investigação, sendo o passo limitante para o progresso na exploração dos dados contidos no seqüenciamento deste genoma. O projeto de transcriptoma denominado \"Transcript Finishing Initiative\" (TFI) surgiu neste contexto, com o objetivo principal de gerar fragmentos parciais de transcritos humanos, que não haviam sido descritos previamente e determinar sua seqüência, para iniciar a caracterização de novos genes humanos. A estratégia utilizada foi q alinhamento de todas as seqüências ORESTES e ESTs disponíveis com a seqüência pública do genoma humano e o agrupamento j c1usterização destas com base nas coordenadas deste genoma. Algumas das regiões que não eram cobertas por estas seqüências foram, então, completadas, por RT-PCR, utilizando-se primers ancorados nos clusters vizinhos. Cada par de clusters de ESTs selecionado para validação experimental foi designado como uma Unidade do \"Transcript Finishing\" (TFU), tendo sido validadas experimentalmente, pelo grupo TFI, Um total de 211 TFUs foram validadas, sendo que 197 seqüências consenso foram submetidas ao Genbank (CF272536-CF272733). Atualmente, apenas um pequeno número destas seqüências ainda são considerados genes novos, sem que haja um cDNA depositado em banco de dados; contudo para um número considerável destas TFUs não existe qualquer caracterização sobre sua função. Na tentativa de contribuir para melhor caracterização dos genes identificados no projeto TFI, e tendo, como base, a linha de pesquisa do laboratório, que busca genes diferencialmente expressos envolvidos em transformação maligna/tumorigênese, o presente trabalho propôs a utilização das seqüências TFUs para estudar sua possível associação com tumores de glia humanos e outros tipos de tumores (de próstata e de mama). Para tanto, as TFUs foram analisadas \"in silico\" para estabelecer seu grau de ineditismo como um novo gene ou um gene sem função conhecida, e, para análise de sua expressão diferencial entre tecidos normais e tumorais de cérebro, próstata e mama. Para validar estas análises computacionais na bancada, foram gerados macro- e microarranjos de DNA utilizando-se as TFUs disponíveis como clones físicos ou amplicons, para o rastreamento com sondas das linhagens celulares A172 e T98G de glioblastomas. Os resultados das análises destes dados foram confirmados por PCR quantitativo tanto nas linhagens como em amostras clínicas de astrocitomas que apresentam diversos graus de malignidade. Como resultado, foi possível organizar um Banco de Clones Físicos de TFUs, além de identificar e selecionar uma TFU (168), cuja expressão correlaciona diretamente com o grau de malignidade dos tumores de glia. Esta seqüência corresponde a um novo gene, já que não existe a seqüência de cDNA completo nos bancos de dados. Em vista disto, a TFU168 foi selecionada para estudos funcionais posteriores, que já estão em andamento, através da obtenção de suaseqüência completa de cDNA para ensaios de superexpressão e do silenciamento gênico através de RNAi. / Upon complete sequencing of the human genome, identification and characterization of the complete set of human genes constitutes the major challenge in this research field, constituting the limiting step for progress in exploration of the informations contained in the genome sequencing data. The Transcript Finishing Initiative (TFI) transcriptome project arose in this context, aiming at the generation, sequencing and characterization of partial new human transcripts and genes. The strategy adopted was the alignment of the alI the available ORESTES and EST sequences data with the public human genome sequence and their clusterization based on the coordinates of this genome. Thus, some of the regions which were not cover by ESTs and ORESTES (gaps) were then completed by RT-PCR using primers anchored in the neighboring clusters. Each pair of EST clusters selected for experimental validation was named Transcript Finishing Unit (TFU). A large number (211) of TFU s were validated and 197 -consensus sequences were submitted to the Genbank (CF272536-CF272733). At present, only a few of these sequences are considered as new genes without a full-Iength cDNA sequence deposited in the data bank, however, no functional characterization is yet available for a large number of these sequences. In an attempt to contribute to further characterization of these genes identified in the TFI project and keeping in mind the main interest of our laboratory, which is the identification of differentially expressed genes in tumor versus normal tissue, the present work aims at utilizing these TFUs to find differentially expressed genes associated with human glial tumors and with other kinds of tumors. To this end, these sequences were first subjected to in silico analysis in order to establish their degree of ineditism (new sequences and/or sequences with unknown function) and their expression profile between normal and tumoral tissues of brain, mammary gland and prostate. To validate this computational analysis, DNA macro- and microarrays were generated with the TFU sequences and screened with cDNA probes obtained from the A172 and T98G glioblastomas cell lines. The results of these screenings were confirmed by quantitative PCR both in cell lines and in tumor samples of different degrees of malignancy. The results obtained in this work allowed the organization of a TFUs Physical Clones Bank and the identification and selection of one sequence (TFU 168), whose expression is directly re1ated to the degree of tumor malignancy. This sequence constitutes a new gene, since no complete cDNA sequence is available in the data banks. Therefore, TFU168 was selected for further functional studies by obtaining its full-Iength cDNA sequence to be used for over expression by silencing this gene using RNAi.

Os mecanismos da infertilidade relacionada à endometriose ainda não foram esclarecidos, embora diversos estudos proponham um efeito deletério desta doença sobre a qualidade oocitária (QO). No entanto, a análise de oócitos em pacientes com endometriose não é rotineiramente exequível, uma vez que os oócitos humanos raramente são doados para pesquisa e sua aplicação em técnicas invasivas impede sua utilização em procedimentos de reprodução assistida. Neste contexto, as evidências sugerem que as células cumulus (CC) podem ser utilizadas como biomarcadores indiretos capazes de prever a QO. Desta forma, através de um estudo inédito, objetivamos determinar o perfil diferencial de transcritos em CC de mulheres inférteis, com e sem endometriose avançada, submetidas à estimulação ovariana controlada para injeção intracitoplasmática de espermatozoides. Para tanto, realizamos um estudo caso-controle, que analisou via sequenciamento de nova geração de RNA (RNA-Seq), 3 grupos (controle, endometriose III/IV sem endometrioma e endometriose III/IV com endometrioma), com 3 pools de 3 pacientes cada. Dentre os principais genes desregulados identificados nas comparações entre os grupos com endometriose avançada e mulheres sem a doença foram evidenciados transcritos com expressão alterada envolvidos na via de fosforilação oxidativa, genes relacionados aos processos da acetilação e conjugação de ubiquitina, além de genes associados a via de biossíntese do colesterol e do estradiol. Esses resultados demonstram que as CC de mulheres inférteis com endometriose avançada apresentam alterações moleculares possivelmente relacionadas ao desenvolvimento folicular e oocitário. Através do enriquecimento dos principais genes desregulados, nossos dados indicam as potenciais vias alteradas nesse processo que podem interferir na aquisição da competência gamética e por sua vez, mediar o comprometimento da fertilidade dessas pacientes. / The endometriosis related infertility mechanisms still remain to be elucidated, although several studies propose a deleterious effect of this disease on oocyte quality. However, the oocyte analysis in patients with endometriosis is not routinely feasible, since human oocytes are rarely donated to researches and their application in invasive techniques precludes their use in reproduction procedures. In this context, evidences suggest that cumulus cells (CC) could be used as indirect biomarkers capable of predicting oocyte quality. Thus, through an unprecedented study, we aimed to determine the differential transcripts profile in CC of infertile women with and without advanced endometriosis and its different stages, undergoing controlled ovarian stimulation for intracytoplasmic sperm injection. Therefore, we performed a case-control study, which analyzed by RNA next generation sequencing (RNA-Seq), 3 groups (control, endometriosis III/IV without endometrioma and endometriosis III/IV with endometrioma), with 3 pools of 3 patients each. The comparison of top deregulated genes among groups of advanced endometriosis and control patients show us altered genes associated with oxidative pathways, acetylation and ubiquitination process, aside from genes related to cholesterol and estradiol regulation. These data elucidated that CC of infertile woman with advanced endometriosis carried essential molecular alteration linked with follicular and gametic development. Through enrichment of the top deregulated genes, we can point out the potential pathways altered in this process toward oocyte commitment and infertility in these patients.

L'objectif principal de ma thèse a été la caractérisation de l'histoire évolutive des voies de signalisation au travers d'une double approche: (i) l'analyse phylogénétique de leurs composés; et (ii) l'identification et la caractérisation de leurs interactions par l'analyse des interactomes d'organismes modèles. Or, bien que de nombreux outils soient disponibles pour la reconstruction d'arbres de gènes individuels, peu de méthodes ont été développées pour l'étude d'un ensemble de protéines impliquées dans un même processus cellulaire. Pourtant, au sein de la cellule, la plupart des protéines agissent en interaction avec d'autres protéines. Dans un premier temps, j'ai étudié l'histoire évolutive de la famille des PI3K (Phosphatidylinositol 3-kinases). Cette première analyse phylogénétique détaillée m'a permis de mettre en place une méthodologie applicable aux voies de signalisation. Un problème important rencontré dans cette étude a consisté en la sélection de transcrits alternatifs et ceci m'a conduit à développer un logiciel dédié nommé BATfinder (\Best Aligned Transcript finder). Dans le but d'étudier la voie de signalisation AKT/mTOR, j'ai effectué l'implémentation de la méthodologie validée avec les PI3K. Cette implémentation a pris la forme d'un pipeline automatique nommé EPINe (Easy Phylogenetics for Interaction Networks). Ce pipeline est théoriquement utilisable pour l'analyse phylogénétique de tout réseau métabolique eucaryote / The main goal of my thesis was the characterization of the evolutionary history of signalling pathways through a twofold approach: (i) the phylogenetic analysis of their components; and (ii) the identification and characterization of their interactions by the analysis of model organisms interactomes. While many tools are available for single genes tree reconstruction, only a few methods have been developed for the study of a set of proteins involved in the same cellular process. However, inside the cell, most of proteins interact with others.Initially, I studied the evolutionary history of the PI3K family (Phosphati-dylinositol 3-kinases). This first detailed phylogenetic analysis allowed me to set up a methodology suitable for signalling pathways. One of the important problems encountered in this study was the selection of alternative transcripts and this led me to develop a software called BATfinder (Best Aligned Transcript finder ). In order to study the AKT/mTOR signalling pathway, I have implemented the methodology previously validated with PI3Ks. This implementation was carried out as an automated pipeline called EPINe (Easy Phylogenetics for Interaction Networks). This pipeline is theoretically usable for the phylogenetic analysis of any eukaryotic metabolic network

Esta dissertação trata da temática da tradução juramentada, que tem sido cada vez mais objeto de pesquisa nos Estudos da Tradução, por conta de sua presença significativa, seja no âmbito acadêmico ou empresarial. A tradução juramentada, que difere das demais formas de tradução especialmente pela força imposta pela fé pública, que incide na postura e olhar adotados pelos Tradutores Públicos e Intérpretes Comerciais brasileiros, nos conduziu à hipótese de que a visibilidade do tradutor torna-se acentuada em virtude da delegação desse poder, que tem por finalidade principal a segurança jurídica das relações negociais na sociedade. A partir de um histórico escolar brasileiro do Ensino Médio, traduzido por doze tradutores públicos paulistanos para o inglês do Canadá, este trabalho tem por objetivo, com o auxílio das modalidades de tradução de Aubert (2006), mapear as estratégias de tradução e os perfis desses diferentes profissionais, oriundos de duas gerações distintas, aprovados nos dois últimos concursos realizados pela Junta Comercial do Estado de São Paulo (1978 e 1998), considerando a sua visibilidade pela fé pública. A tipologia textual documento escolar e o gênero histórico escolar foram selecionados tendo em vista sua grande frequência em tradução juramentada, motivada pelo crescente intercâmbio acadêmico-cultural entre Brasil, Canadá, Estados Unidos e demais países de língua inglesa. Para tanto, realizamos uma breve reflexão acerca dos modelos de Berman (1985), Rei (1971, 1976) e Baker (1996) e suas respectivas aplicações no tocante à tradução juramentada e, particularmente, ao estudo do objeto de pesquisa em pauta. Em seguida, descrevemos os procedimentos técnicos de tradução de Vinay e Darbelnet (1958), que serviram como base para a concepção do modelo das modalidades de tradução de Aubert (1984, 1998, 2006). Complementarmente, retratamos a evolução do modelo das modalidades de tradução, com destaque para as mudanças ocorridas e possíveis contribuições. Para tanto, adotamos no presente estudo uma metodologia com base em duas etapas. Primeiramente, realizamos o levantamento dos dados em relação às dispersões das soluções tradutórias e, em seguida, classificamos os dados em unidades lexicais para aplicação do modelo das modalidades de tradução. Por fim, descrevemos o perfil de cada tradutor e os resultados gerais por grupo, bem como o comparativo das duas gerações, com o auxílio de gráficos. A hipótese da visibilidade acentuada mostrou-se válida e necessária como garantia jurídica da boa aplicação da fé pública no cumprimento do ofício do tradutor público e intérprete comercial. / This dissertation addresses the topic of sworn translation, which has been increasingly researched in the field of Translation Studies by virtue of its relevant presence, whether in the academic or corporate areas. Sworn translation, which differs from other kinds of translations particularly for the power vested by the full faith and credit, having an effect on the attitude and view adopted by Brazilian Sworn Translators and Commercial Interpreters, led us to the hypothesis that the translators visibility is emphasized by the vesting of such power, the main purpose of which is to ensure legal certainty in business relations in society. From a Brazilian secondary school transcript translated by twelve sworn translators of the State of São Paulo into Canadian English, this work aims, with the support of Auberts translation modalities (2006), to map the translation strategies and profiles of such various professionals, from two different generations, who passed the last two public examinations held by the Board of Trade of the State of São Paulo (in 1978 and 1998), taking into account their visibility by the full faith and credit. The text typology school document and the gender school transcript were chosen because of their great frequency in sworn translation, motivated by the increasing academic and cultural exchange between Brazil and Canada, the United States, and other English-speaking countries. Therefore, we briefly reflected on Berman (1985), Rei (1971, 1976) and Bakers (1996) models and their application to sworn translation and particularly to the study of the subject matter hereof. Then, we described Vinay and Darbelnets (1958) translation procedures, which were the basis for the conception of Auberts (1984, 1998, 2006) translation modalities model. In addition, we outlined the evolution of the translation modalities model, with an emphasis on changes made and possible contributions. Thus, we adopted a two-stage methodology in this study. First, we compiled the data for the dispersion of the translation solutions, and then, classified the data into lexical units to apply the translation modalities model. Finally, we described the profile of each translator and the general results by group, as well as a comparison between the two generations, presented in graphical form. The hypothesis of high visibility was proven to be valid and necessary as a legal guarantee of the proper application of full faith and credit in fulfilling the office of sworn translator and commercial interpreter.

This interpretative phenomenological analysis (IPA) study was implemented to explore and describe the initial and long-term motivations of community volunteers within a selected homeless shelter in central Indiana. The settlement house movement of human service delivery was the conceptual framework, which provided guidance and understanding concerning why and how community members provide human services through volunteerism. The research question examined the ways in which long-term volunteers thought about and made sense of their motivations to volunteer initially and over the long term at a homeless shelter. To answer the research question, the IPA methodology was implemented with 6 long-term community volunteers at a selected shelter. This design provided rich qualitative text that was analyzed to develop themes to explain and describe how the 6 study participants made sense of their individual motivations descriptively, emotionally, religiously, and socially. The overarching conclusion was that all 6 participants shared a common theme, which was Evangelical tradition, volunteerism, and social responsibility. This new finding provides a first look at the motivations of community volunteers, previously unknown in academic literature, and indicates a key subgroup of volunteers that may be the focus of future research on assisting community shelters with recruiting and retaining community members for the effort to eradicate homelessness in the United States.

In his keynote address to the National Council of Teachers of Mathematics research pre-session, Sloane (2006b) challenged mathematics education researchers to ‘quantify qualitative insights’. This quasi-experimental study used blended methods to investigate the development of two-digit addition and subtraction strategies. Concurrent classroom teaching experiments were conducted in two intact first grade classrooms (n = 41) in a mid-Atlantic American public school. From a pragmatic emergent perspective, design research (Gravemeijer & Cobb, 2006) was used to develop local instructional theory. An amplified theoretical framework for early base-ten strategies is explicated. Multilevel modelling for repeated measures was used to evaluate the differences in strategy usage between classes across occasions and the association of particular pedagogical practices with the emergence of incrementing and decrementing by ten (N10) or decomposition (1010) strategies (Beishuizen, Felix, & Beishuizen, 1990).The two matched classes were not different in terms of gender, poverty, race, pre-assessment performance, and special education services. After the first unit of instruction with differentiated pedagogical tools, the collection class was significantly (p = .001) more likely to use 1010 than the linear class. No difference was demonstrated during the post-assessment. Students in both classes were more likely to use N10 during the last structured interview than in the first (p < .0001). Furthermore, there was no difference between the two classes in using any advanced strategy; however, students in both classes were more likely to use an advanced strategy at the conclusion of the study than they were initially (p = .033). The order of emergence of 1010 and N10 was not associated with the ability to develop both strategies, but there was an association (p < .001) between use of an advanced strategy and success on a district-mandated written assessment of two-digit addition and subtraction.Two original instructional sequences of contextually-based investigations are presented. Protocols transcribed from videotaped lessons and dynamic assessment interviews are presented to illuminate specific constructs detected and to illustrate the pedagogical techniques. An amplified framework for early place value constructs is proposed. Recommendations for future studies, curricular changes, and the need of early intervention are discussed.

Traditionally, response to treatment in hematological malignancies is evaluated by light microscopy of bone marrow (BM) smears, but due to more effective therapies more sensitive methods are needed. Today, detection of minimal residual disease (MRD) using immunological and molecular techniques can be 100 times more sensitive than morphology. The main aim of this thesis was to compare and evaluate three currently available MRD methods in childhood acute lymphoblastic leukemia (ALL): (i) real-time quantitative PCR (RQ-PCR) of rearranged antigen receptor genes, (ii) multicolor flow cytometry (FCM) of leukemia-associated immunophenotypes and (iii) real-time quantitative PCR of fusion gene transcripts (RT-PCR). In paper I, we assessed the applicability of RQ-PCR in a population-based cohort of childhood ALL diagnosed in Sweden between 2002-2006. Clonal IG/TCR rearrangements were identified in the 96% of the 279 ALL cases. Using RQ-PCR, the quantitative range of 10-3 was reached in 93% of B-cell precursor (BCP) ALL and 86% of T-cell ALL (T-ALL) by at least one target gene. In paper II, we compared MRD detection using both RQ-PCR and FCM in the context of NOPHO ALL-2000 protocol. By applying the stratification threshold of ≥0.1% MRD late during induction therapy (day 29), we could demonstrate that both methods can predict the risk of BM relapse but not extramedullary relapse. However, the threshold of ≥0.2% MRD appears to be more optimal using RQ-PCR in BCP ALL, whilst in T-ALL, the results indicate that RQ-PCR is preferable for MRD assessment. The stability of RNA in vitro is a critical factor when using sensitive molecular techniques such as MRD detection. In paper III, we evaluated the influence on MRD detection when blood is collected in tubes with RNA stabilization reagents (PAX gene Vacutatiner®) compared to collection in EDTA-tubes (non-stabilized). We analyzed 68 matched samples from chronic myeloid leukemia patients and the results indicated that non-stabilized blood processed within 30 hours is preferable for MRD detection. In paper IV, follow-up samples from eight children with Philadelphia positive (Ph+) ALL were evaluated with the three available MRD methods. MRD measured by the fusion gene transcripts (BCR-ABL1) appeared to be the most sensitive method, however, precise quantification can be difficult and the other methods are thus complementary. In conclusion, all three applied MRD methods are useful and correlate to each other, although not necessary exchangeable in individual patients. We also conclude that MRD assessment by RQ-PCR, based on rearranged IG/TCR genes and multicolor FCM are predictive for identification of high risk childhood ALL patients.

The racialized realities faced by Black students provide an impetus to examine the controversy over Canada's first Africentric Alternative School, approved on January 29, 2008 by the Toronto District School Board. Newspaper articles, editorials and letters to the editor, as well as speeches by delegations and trustees, provide a rich snapshot of the arguments put forth in the heated political debate. Through the lens of equity and critical race theory, the diverse and divergent stances taken by both proponents and opponents of the school are analysed and understood. A conceptual framework of hidden and public transcripts (Scott, 1990) is used to distinguish arguments that reflect on the lived experiences of Black students from those that reiterate the dominant discourses of liberal democratic societies. The findings emerge as three opposing sets of themes that reveal a transcript reflective of the ongoing salience of racism within ostensibly liberal claims to racial equality.