Syftet med detta examensarbete är att undersöka mellanstadieelevers förståelse av idiomatiska uttryck samt huruvida de känner igen idiomatiska uttryck till sin form och jämföra detta inom ämnena svenska och engelska. Vidare ämnar detta examensarbete att undersöka om det finns någon åldersprogression sett till elevernas förståelse av idiomatiska uttryck samt undersöka hur lärare arbetar med idiom. För att undersöka dessa frågor har en enkätundersökning samt intervjuer med lärare genomförts. Enkätundersökningen genomfördes på två olika skolor i Mellansverige, där totalt 196 elever från årskurs 4–6 deltog. Intervjuerna genomfördes på respektive skola med totalt fem legitimerade lärare. Undersökningen visar att förståelsen för idiomatiska uttryck, generellt sett, är relativt låg där elevernas förståelse för svenska idiom är högre än förståelsen för engelska idiom. Progressionen gällande engelska idiom följer en mer linjär utvecklingskurva medan progressionen gällande svenska idiom avtar efter årskurs fem. I ämnet svenska uppvisar eleverna en större förståelse för idiomens form, hur ett uttryck är uppbyggt, än betydelsen av dessa medan i ämnet engelska uppvisar eleverna motsatt resultat, det vill säga, större förståelse för idiomens betydelse än form. Resultatet visar att lärare i både ämnet svenska och ämnet engelska arbetar med idiomatiska uttryck i liten utsträckning. I ämnet svenska arbetar lärarna sporadiskt med idiom, i stort sett endast när det uppkommer i skönlitterära texter som eleverna läser och de få gånger det förekommer i läromedel. I ämnet engelska är arbetet med idiomatiska uttryck något mer planerat och strukturerat. / The purpose of this study is to investigate and compare middle school student’s understanding of Swedish and English idiomatic expressions. Furthermore, this study aims at investigating whether there is any age progression in the understanding of idioms and examine how teachers work with idiomatic expressions. The study was conducted at two different schools and a total of 196 students from year group 4 - 6 participated in a questionnaire survey and a total of five legitimized teachers was interviewed. The study shows that the overall understanding of idiomatic expressions is relatively low. However, the understanding of Swedish idioms is higher than the understanding of English idioms. The progression of English idiom comprehension follows a more linear development curve, while the progression of Swedish idiom comprehension decreases after year five. In Swedish, students show a greater understanding of the idiomatic form, how an expression is structured, rather than the actual meaning of the expression. In English idiomatic comprehension, the study shows that the students have a greater understanding when it comes to the meaning of the expression rather than the form. The result of the interviews shows that teachers, in both subjects, works with idiomatic expressions to a small extent. Swedish teachers work sporadically when idioms occur in fictional texts or when they appear in other educational materials. English teachers, on the other hand, work with idiomatic expressions in a more planned and structured way.

Les gliomes sont les principales tumeurs primitives du cerveau affectant environ 4000 nouveaux patients par an en France. La moitié des gliomes est détectée au stade avancé de glioblastome (grade IV) tandis que 15% des tumeurs sont diagnostiquées au stade II de gliomes diffus dit de bas grade. Ces tumeurs affectent des patients jeunes et présentent des mutations caractéristiques, notamment une mutation pour l’enzyme IDH1 communément retrouvée dans les glioblastomes secondaires. Ces tumeurs de bas grade sont traitées par une chirurgie, idéalement en condition éveillée mais du fait de leur nature diffuse, la partie résiduelle progressera inexorablement vers un stade III ou IV avec une survie globale entre 5 ans et 15 ans après diagnostique. La progression tumorale est hautement variable et non prédictible d’un patient à l’autre. Des foyers de progression tumorale chez 20% des patients atteints de gliome diffus de bas grade ont été identifiés. Ces foyers montrent une densité cellulaire plus élevée ainsi qu’un Ki67 augmenté. Mon travail de thèse aura consisté à étudier les modifications cellulaires et moléculaires associées à ces foyers de progression tumorale. À partir du profil ARN des foyers et des territoires adjacents, j’ai pu mettre en évidence par des techniques haut-débit la baisse d’expression significative de gènes dans les foyers notamment de AGXT2L1/ETNPPL, carboxypeptidase E, EDNRB, SFRP2. J’ai émis l’hypothèse que SFRP2 et ETNPLL pourraient s’opposer à la prolifération cellulaire et que leur diminution dans les foyers ouvrirait la voie à la transformation tumorale. Une corrélation inverse entre la quantité d’ETNPPL enzyme et la survie de patients atteints d’hépatocarcinomes a été publiée. En limitant la quantité de précurseurs de phospholipides dans la cellule, ETNPPL pourrait agir comme un frein en s’opposant à la prolifération et de fait, sa diminution dans les foyers de transformation des gliomes pourrait lever cette inhibition. Mes travaux auront été innovants tant dans leur approche comparative des différents compartiments tumoraux pour chaque patient étudié et auront révélés ETNPPL comme corrélé à la gliomagenèse et potentielle cible thérapeutique. / Gliomas are the main primary brain tumours affecting around 4000 new patients in France each year. Half of gliomas are detected in the advanced stage of glioblastoma (grade IV) while 15% of tumours are diagnosed in stage II (diffuse low-grade gliomas-DLGG). These tumors affect young patients and bear characteristic mutations, including a mutation for the enzyme IDH1 commonly found in secondary glioblastomas. These low-grade tumours are treated by surgery, ideally in awake condition but due to their diffuse nature, the residual part will progress inexorably to stage III or IV with overall survival between 5 and 15 years after diagnosis. Tumor progression is highly variable and unpredictable from one patient to another. Foci of tumor progression have been identified in 20% of patients with DLGG. These foci show a higher cell density and an increased Ki67. My thesis work consisted in studying the cellular and molecular changes associated with tumor progression. From the RNA profile of the foci and adjacent territories, I was able to highlight through high-throughput techniques significant decrease in gene expression in the foci, particularly of AGXT2L1/ETNPPL, carboxypeptidase E, EDNRB, SFRP2. I hypothesized that SFRP2 and ETNPLL could oppose cell proliferation and that their decrease would pave the way for tumor transformation. An inverse correlation between the amount of ETNPPL and the survival of patients with hepatocarcinoma has been published. By limiting the amount of phospholipid precursors in the cell, ETNPPL could act as a brake against proliferation and indeed, its decrease in glioma transformation foci could remove this inhibition. My PhD work will have been innovative in the comparative approach of the different tumors’ compartments for each patient studied and will have revealed ETNPPL as correlated to gliomagenesis and as potential therapeutic target.

O presente trabalho tem como objetivo geral analisar a progressão textual e a estrutura temática em resenhas produzidas por alunos no Ensino Superior, a partir dos pressupostos teórico da Linguística Sistêmico-funcional (HALLIDAY, 1978; HALLIDAY e MATTHIESSEN, 2004, 2014; MARTIN e ROSE, 2007; ROSE e MARTIN, 2012) aliados à Linguística Textual, a partir dos estudos de referenciação, numa perspectiva sociointeracionista (MONDADA, 2001; MONDADA e DUBOIS, 2003; MARCUSCHI, 1983 e 2008; KOCH et al.,2005; KOCH e ELIAS, 2010; KOCH, 2014; CAVALCANTE, 2011, 2012 e 2013; CAVALCANTE et al., 2014; e CIULLA, 2008). O que motivou este estudo foram as dificuldades enfrentadas por alunos, ao produzirem textos que exijam um rigor acadêmico, e o interesse por entender como o estudo dos processos de organização temática e referencial podem subsidiar o trabalho com a escrita acadêmica. Para tanto, os dados foram analisados a partir da metafunção textual, considerando os quatro estratos contextuais que envolvem o texto: o contexto de cultura e sua realização em gêneros, o contexto de situação por meio das variáveis de registro de campo, relações e modo, o estrato semântico-discursivo por meio da análise dos sistemas discursivos de identificação e periodicidade, e dos processos de referenciação, a fim de observar como os alunos constroem a progressão textual e as funções textual-discursivas mais recorrentes na composição do gênero resenha; e por fim, o estrato lexicogramatical analisado por meio da identificação da estrutura temática e estrutura da informação. Trata-se de um estudo de cunho qualitativo-interpretativo Os sujeitos de pesquisa foram alunos da Universidade Estadual do Rio grande do Sul (UERGS), frequentando o primeiro semestre em nível de graduação. O corpus é constituído por 10 (dez) textos do gênero resenha. Os resultados mostram que os padrões de estrutura temática estão diretamente relacionados à composição dos gêneros e ao conhecimento que os alunos possuem em relação à lexicogramática, aos aspectos semântico-discursivos e estruturais do texto. A análise do estrato discursivo-semântico permitiu olhar para a metafunção textual e entender como se dá o processo de progressão textual, a partir dos processos de progressão temática e progressão referencial. Pelos tipos de referências e estrutura temática presentes nos textos, pode-se concluir que os alunos têm conhecimento destas estratégias de construção textual, no entanto é evidente a necessidade de tornar este conhecimento explícito, de modo que suas produções evoluam em termos de qualidades discursivas. Por fim, como contribuição desta tese, espera-se despertar o interesse para a temática abordada, bem como oferecer subsídios teóricos e práticos para o planejamento de propostas de intervenção no contexto acadêmico, constituindo-se em uma importante ferramenta para o trabalho com a escrita e análise textual/discursiva no Ensino Superior. / The present thesis has as a general objective analyze the textual progression and thematic structure in reviews produced by students in Higher Education, based on the theoretical assumptions of Systemic Functional Linguistics (HALLIDAY, 1978; HALLIDAY and MATTHIESSEN, 2004, 2014; MARTIN and ROSE , 2007; ROSE and MARTIN, 2012) allied to Textual Linguistics, supported by the referential studies, in a socio-interactionist perspective. (MONDADA, 2001; MONDADA and DUBOIS, 2003; MARCUSCHI, 1983 and 2008; KOCH et al.,2005; KOCH and ELIAS, 2010; KOCH, 2014; CAVALCANTE, 2011, 2012 and 2013; CAVALCANTE et al., 2014; and CIULLA, 2008). What motivated this study were the difficulties faced by students, when they produced texts with academic rigor demand, and the interest to understand how the study of the processes of referential and thematic organization and can support the work with academic writing. For this, the data were analyzed from the textual metafunction, considering four contextual strata that involve the text: the context of culture and its realization in genres, the context of situation across the variables of field, tenor and mode, the semantic-discursive stratum through the analysis of the discursive systems of identification and periodicity, and of the processes of reference, in order to observe how the students build textual progression the textual discourse functions, which are more used in the composition of review genre; and finally, the lexicogrammatical stratum analyzed through the identification of the thematic structure and information structure. This is a qualitative-interpretative study The investigation subjects were students of the Universidade Estadual do Rio Grande do Sul (UERGS), attending the first semester at undergraduate level. The corpus is constituted by 10 (ten) texts of the review genre. The results show that the patterns of thematic structure are directly related to the composition of the genres and to the knowledge that the students have in relation to the lexicogrammar, to the semantic-discursive and structural aspects of the text. The analysis of the discursive-semantic stratum allowed us to look at the textual metafunction and to understand how the process of textual progression occurs, from the processes of thematic progression and referential progression. For the types of references and thematic structure present in the texts, it can be concluded that the students are aware of these strategies of textual construction, however it is evident the necessity to become this knowledge explicit, in such a way that their productions develop in terms of discursive qualities. In conclusion, as a contribution of this thesis, it is hoped to awaken the interest for the approached topic, as well as to offer theoretical and practical subsidies for the planning of intervention proposals in the academic context, constituting an important tool for working with writing and textual/discursive analysis in Higher Education.

Submitted by Maike Costa (maiksebas@gmail.com) on 2016-03-30T11:36:15Z No. of bitstreams: 1 arquivo total.pdf: 1989591 bytes, checksum: c1b3f2740144367fd7ef458d0603ba20 (MD5) / Approved for entry into archive by Viviane Lima da Cunha (viviane@biblioteca.ufpb.br) on 2016-03-30T15:42:56Z (GMT) No. of bitstreams: 1 arquivo total.pdf: 1989591 bytes, checksum: c1b3f2740144367fd7ef458d0603ba20 (MD5) / Made available in DSpace on 2016-03-30T15:42:56Z (GMT). No. of bitstreams: 1 arquivo total.pdf: 1989591 bytes, checksum: c1b3f2740144367fd7ef458d0603ba20 (MD5) Previous issue date: 2015-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work presents a research on the Induction Principles and the Recurrences, its history, mathematical concepts and applications used. Were developed some statements of Induction Principle and the Recurrences using some basic concepts from Number Theory, Combinatorics, Geometry and Set Theory that can be explored in high school. Was submitted a few activities that can be applied in the classroom of the high school in the development of mathematical concepts such as Arithmetic Progression, Geometric Progression, Geometry, Combinatorial Analysis and Numeric Sets among other topics. / Este trabalho apresenta uma pesquisa sobre os Princípios de indução e Recorrências, sua história, conceitos matemáticos utilizados e aplicações. Foram desenvolvidas algumas demonstrações do Princípio de indução e Recorrências, utilizando-se alguns conceitos básicos de Teoria dos Números, Análise Combinatória, Teoria dos Conjuntos e Geometria que podem ser explorados no Ensino Médio. Foram apresentadas algumas atividades que podem ser aplicadas em sala de aula do Ensino Médio no desenvolvimento de conceitos matemáticos como Progressão Aritmética, Progressão Geométrica, Geometria, Combinação e Conjuntos Numéricos entre outros temas.

La protéine p53 (« Gardien du génome ») doit être altérée pour que le cancer puisse se développer. Les nombreuses thérapies anti-cancéreuses disponibles sont très efficaces mais la réponse clinique est souvent transitoire et les cancers disséminés rechutent ou progressent du fait de l'évolution de sous-populations cancéreuses résistantes au traitement, impliquant souvent TP53 qui est le gène le plus muté dans les formes agressives de nombreux cancers. Nous l’avons étudié dans la leucémie lymphoïde chronique (LLC) et les syndromes myélodysplasiques avec délétion 5q (SMD del(5q)). Grâce à l’étude rétrospective longitudinale de 40 patients atteints de SMD del(5q), nous avons généré des données de NGS ciblé et montré que le statut mutationnel de TP53 au diagnostic ne permettait pas de prédire la progression tumorale, contrairement à ce qui avait été publié précédemment (Jädersten et al., JCO 2011). Nous avons montré que c’était l’évolution clonale du gène TP53 qui était l’élément clé de la progression des SMD del(5q). Nous avons observé de nombreuses émergences de clones mutés entre le stade diagnostique et un stade ultérieur de la maladie, toujours après initiation du traitement par lénalidomide.Le lénalidomide a été approuvé comme nouveau traitement spécifique et très efficace contre l’anémie liée aux SMD del(5q), permettant à la plupart des patients d’être indépendants des transfusions sanguines. Le lénalidomide permet souvent d’éradiquer le clone tumoral porteur de l’anomalie génétique del(5q) isolée, induisant une rémission clinique. Malheureusement, cette rémission est courte avec une durée médiane de 2 ans, puis, dans environ 1 cas sur 2, survient une transformation en leucémie aiguë secondaire de pronostic péjoratif.Nous avons étudié un possible lien entre le traitement par lénalidomide et l’évolution clonale de TP53 par annotation clinico-bio-thérapeutiques des résultats de séquençage de TP53 chez les 24 patients dont les échantillons séquentiels avaient été analysés. Dans notre étude, les patients avec progression tumorale (dont 10 évolutions clonales de TP53 et 1 évolution clonale de RUNX1) avaient reçu une dose cumulée de lénalidomide supérieure à celle reçue par les patients dont la tumeur était restée stable (p = 0.036). Nous avons observé chez plusieurs patients que l’éradication de la tumeur n’était pas utile à l’amélioration de la qualité de vie des patients. La non-éradication semblait même permettre un maintien de l’équilibre clonal et une compétition entre les différents sous-clones de la tumeur, résistants ou non au lénalidomide.Nous discutons de l’évolution de l'écologie de la tumeur au cours du traitement, i.e., l’évolution de ses interactions avec son micro-environnement qui se modifie après chaque nouvelle dose de traitement. Un modèle évolutif dit théorie de la thérapie adaptative, développée récemment remet en question les protocoles conventionnels de thérapie anti-cancéreuse qui préconisent souvent d'administrer la dose maximale tolérée par le patient (Gatenby, 2009). Elle suggère que la dose minimale efficace présenterait l’avantage de ne pas éradiquer les cellules cancéreuses sensibles au traitement pour qu'elles restent en compétition avec les cellules cancéreuses résistantes et limiter la progression ou la rechute. Nous suggérons de prendre en compte également la diminution des effets indésirables pour le patient, améliorant ainsi sa qualité de vie, et enfin la diminution des dépenses de santé pour la collectivité. A ce jour, peu d’études cliniques évaluent l’intérêt de l’adoption de tels protocoles de thérapie adaptative.Néanmoins, des modèles in vivo (xénogreffes) et in silico (modèles statistiques) ont permis d’analyser la dynamique évolutive des populations tumorales en fonction du traitement reçu. Ces modèles prédisent que la survie de l’hôte peut être maximisée par la mise en place d’une thérapie adaptative. / P53 protein is named «guardian of the genome » because it must be altered to let cancer grow.TP53 is the most mutated gene in agressive cancers.Numerous systemic therapies are successful for treatment of disseminated cancers. However, clinical response is often transient, and cancer undergo relapse or progression due to emergence of resistant populations. These latter often harbour TP53 mutations. We studied TP53 in chronic lymphoid leukemia (CLL) and lower-risk myelodysplastic syndroms with del(5q), MDS del(5q). We conducted a retrospective longitudinal study in 40 patients suffering from MDS del(5q). We obtained targeted NGS data showing that TP53 mutational status at diagnosis could not predict tumor progression, by contrast with previously published data (Jädersten et al., JCO 2011). We show that TP53 clonal evolution is the key feature of tumor progression in MDS del(5q). We observed numerous mutated sub-clones emerging between diagnosis and follow-up. In our study, this emergence always followed onset of lenalidomide treatment. Lenalidomide was recently approved as a new therapy specifically improving anemia in patients with MDS del(5q). It allows most patients to become red-blood-cells-transfusion independent. Lenalidomide often eradicates the major tumor clone harbouring the isolated genetic abnormality deletion (5q) and allows clinical remission. Unfortunately, this remission is short (median, 2 years) and is followed, in 1 case out of 2, by a secondary acute leukemic transformation with a very poor prognosis.We studied the issue of a possible link between lenalidomide therapy and TP53 clonal evolution by annotating TP53 sequencing results with acute biological, clinical and therapeutic features in the 24 patients with sequential samples analyzed. In our study, patients with tumor progression (10 TP53 clonal evolution and 1 RUNX1 clonal evolution) were given a higher cumulative dose of lenalidomide compared to patients with stable disease (p = 0.036). Similarly to « adaptive therapy theory »(Gatenby 2009), we observed that eradication of the tumor wasn’t useful for improvement of quality of life. Absence of eradication might even allow to maintain a clonal equilibrium and a clonal competition between the distinct tumor sub-clones, resistant to lenalidomide or not, and therefore maintain stable disease.This theory of adaptive therapy questions the classical protocols of treatments against cancer, in which the maximal tolerated dose is preferred to the minimal effective dose. The latter might however slow down cancer progression or cancer relapse, with decreased side effects in patients, and decreased health costs.To date, few clinical trials (if any) questions such protocols of adaptive therapy. However, in vivo experiments (xenografts) and in silico statistical models allowed to study evolutionary dynamics of tumor sub-populations with and without therapy.The models predict that host survival can be maximized if “treatment-for-cure strategy” is replaced by “treatment-for-stability.” Specifically, the models predict that an optimal treatment strategy will modulate therapy to maintain a stable population of chemosensitive cells that can, in turn, suppress the growth of resistant populations under normal tumor conditions, Dr Gatenby said.

O presente trabalho tem como objetivo geral analisar a progressão textual e a estrutura temática em resenhas produzidas por alunos no Ensino Superior, a partir dos pressupostos teórico da Linguística Sistêmico-funcional (HALLIDAY, 1978; HALLIDAY e MATTHIESSEN, 2004, 2014; MARTIN e ROSE, 2007; ROSE e MARTIN, 2012) aliados à Linguística Textual, a partir dos estudos de referenciação, numa perspectiva sociointeracionista (MONDADA, 2001; MONDADA e DUBOIS, 2003; MARCUSCHI, 1983 e 2008; KOCH et al.,2005; KOCH e ELIAS, 2010; KOCH, 2014; CAVALCANTE, 2011, 2012 e 2013; CAVALCANTE et al., 2014; e CIULLA, 2008). O que motivou este estudo foram as dificuldades enfrentadas por alunos, ao produzirem textos que exijam um rigor acadêmico, e o interesse por entender como o estudo dos processos de organização temática e referencial podem subsidiar o trabalho com a escrita acadêmica. Para tanto, os dados foram analisados a partir da metafunção textual, considerando os quatro estratos contextuais que envolvem o texto: o contexto de cultura e sua realização em gêneros, o contexto de situação por meio das variáveis de registro de campo, relações e modo, o estrato semântico-discursivo por meio da análise dos sistemas discursivos de identificação e periodicidade, e dos processos de referenciação, a fim de observar como os alunos constroem a progressão textual e as funções textual-discursivas mais recorrentes na composição do gênero resenha; e por fim, o estrato lexicogramatical analisado por meio da identificação da estrutura temática e estrutura da informação. Trata-se de um estudo de cunho qualitativo-interpretativo Os sujeitos de pesquisa foram alunos da Universidade Estadual do Rio grande do Sul (UERGS), frequentando o primeiro semestre em nível de graduação. O corpus é constituído por 10 (dez) textos do gênero resenha. Os resultados mostram que os padrões de estrutura temática estão diretamente relacionados à composição dos gêneros e ao conhecimento que os alunos possuem em relação à lexicogramática, aos aspectos semântico-discursivos e estruturais do texto. A análise do estrato discursivo-semântico permitiu olhar para a metafunção textual e entender como se dá o processo de progressão textual, a partir dos processos de progressão temática e progressão referencial. Pelos tipos de referências e estrutura temática presentes nos textos, pode-se concluir que os alunos têm conhecimento destas estratégias de construção textual, no entanto é evidente a necessidade de tornar este conhecimento explícito, de modo que suas produções evoluam em termos de qualidades discursivas. Por fim, como contribuição desta tese, espera-se despertar o interesse para a temática abordada, bem como oferecer subsídios teóricos e práticos para o planejamento de propostas de intervenção no contexto acadêmico, constituindo-se em uma importante ferramenta para o trabalho com a escrita e análise textual/discursiva no Ensino Superior. / The present thesis has as a general objective analyze the textual progression and thematic structure in reviews produced by students in Higher Education, based on the theoretical assumptions of Systemic Functional Linguistics (HALLIDAY, 1978; HALLIDAY and MATTHIESSEN, 2004, 2014; MARTIN and ROSE , 2007; ROSE and MARTIN, 2012) allied to Textual Linguistics, supported by the referential studies, in a socio-interactionist perspective. (MONDADA, 2001; MONDADA and DUBOIS, 2003; MARCUSCHI, 1983 and 2008; KOCH et al.,2005; KOCH and ELIAS, 2010; KOCH, 2014; CAVALCANTE, 2011, 2012 and 2013; CAVALCANTE et al., 2014; and CIULLA, 2008). What motivated this study were the difficulties faced by students, when they produced texts with academic rigor demand, and the interest to understand how the study of the processes of referential and thematic organization and can support the work with academic writing. For this, the data were analyzed from the textual metafunction, considering four contextual strata that involve the text: the context of culture and its realization in genres, the context of situation across the variables of field, tenor and mode, the semantic-discursive stratum through the analysis of the discursive systems of identification and periodicity, and of the processes of reference, in order to observe how the students build textual progression the textual discourse functions, which are more used in the composition of review genre; and finally, the lexicogrammatical stratum analyzed through the identification of the thematic structure and information structure. This is a qualitative-interpretative study The investigation subjects were students of the Universidade Estadual do Rio Grande do Sul (UERGS), attending the first semester at undergraduate level. The corpus is constituted by 10 (ten) texts of the review genre. The results show that the patterns of thematic structure are directly related to the composition of the genres and to the knowledge that the students have in relation to the lexicogrammar, to the semantic-discursive and structural aspects of the text. The analysis of the discursive-semantic stratum allowed us to look at the textual metafunction and to understand how the process of textual progression occurs, from the processes of thematic progression and referential progression. For the types of references and thematic structure present in the texts, it can be concluded that the students are aware of these strategies of textual construction, however it is evident the necessity to become this knowledge explicit, in such a way that their productions develop in terms of discursive qualities. In conclusion, as a contribution of this thesis, it is hoped to awaken the interest for the approached topic, as well as to offer theoretical and practical subsidies for the planning of intervention proposals in the academic context, constituting an important tool for working with writing and textual/discursive analysis in Higher Education.

La progression tumorale, qui conduit à la formation de métastases, est le résultat de profondes modifications des différents niveaux de régulation de l'expression des gènes comme la transcription ou l'épissage alternatif. Au cours de ma thèse, j'ai étudié le rôle de DDX5 et DDX17, deux ARN hélicases qui, au cours de la progression tumorale, sont impliquées dans la régulation transcriptionnelle, l'épissage alternatif et la biogénèse des microARNs. Pour cela, j'ai utilisé deux modèles de progression tumorale : le modèle murin 4T1, composé de cellules cancéreuses qui présentent des propriétés métastatiques différentes, et les cellules humaines MCF10A qui, après traitement au TGF-beta, sont capables de réaliser la transition épithélio-mésenchymateuse, un processus de trans-différenciation qui contribue à la formation des métastases. Dans le modèle 4T1, j'ai montré que Ddx17 et Ddx5 contribuent à l'invasivité des cellules tumorales en contrôlant des programmes transcriptionnels et d'épissage alternatif. Plus précisément, j'ai démontré que Ddx5 et Ddx17 favorisent l'agressivité des cellules cancéreuses en régulant l'épissage des variants de l'histone macroH2A1 qui, à leur tour, contrôlent l'expression de gènes impliqués dans la progression tumorale. Dans le modèle MCF10A où la transition épithélio-mésenchymateuse peut être induite sous TGF-beta, j'ai montré que DDX5 et DDX17 orchestrent dynamiquement des programmes transcriptionnels et d'épissage. Le travail effectué pendant ma thèse met en évidence l'importance des ARN hélicases DDX5 et DDX17 comme régulateurs clés de la progression tumorale, et souligne le rôle de l'épissage alternatif lors de la progression tumorale. De plus, ce travail met l'accent sur l'importance d'intégrer les différents niveaux de régulation de l'expression des gènes (transcription, épissage, microARN) pour une compréhension globale de la progression tumorale / Tumor progression leading to the formation of metastases result from deep modifications of gene expression programs at several levels, including transcription and splicing. During my PhD, I investigated the role in tumor progression of DDX5 and DDX17, two highly related multifunctional DEAD box RNA helicases that are involved in transcription and splicing as well as in microRNA biogenesis. For this purpose, I used two breast cancer models of tumor progression : the 4T1 mouse model composed of cancer cells that exhibit different metastatic properties and MCF10a human cells that undergo epithelial-to-mesenchymal transition upon Tgf-beta treatment, a trans-differentiation process contributes to metastasis formation. In the 4T1 mouse model, I showed that Ddx17 and Ddx5 contribute to tumor-cell invasiveness by controlling both transcriptional and splicing programs. More specifically, I demonstrated that Ddx5 and Ddx17 promote cancer cells aggressiveness by regulating the splicing of the macroH2A1 histone which in turn impacts on the expression of genes implicated in tumor cell invasiveness. In the Tgf-beta induced epithelial-to-mesenchymal trans-differentiation model, I showed that DDX5 and DDX17 dynamically orchestrate transcription, microRNA and splicing programs. The work performed during my PhD highlights the importance of DDX5 and DDX17 RNA helicases as key regulators of tumor progression in breast cancer, and also underlines the role of alternative splicing during tumor progression. Furthermore, this work emphasizes the importance of integrating the different layers of the gene expression process (transcription, splicing, microRNA) for a comprehensive understanding of tumor progression

Le TGFbeta intervient dans la régulation de nombreux processus cellulaires comme la prolifération, la différenciation, la migration, l'apoptose, du développement embryonnaire jusqu'à la vie adulte. Le TGFbeta est aujourd'hui bien décrit pour son rôle de suppresseur de tumeur de par ses activités anti-prolifératives et pro-apoptotiques, en particulier sur les cellules épithéliales. Cependant, au cours de la progression tumorale, le TGFbeta devient un promoteur de tumeur en favorisant l'angiogenèse, l'échappement de la tumeur vis-à-vis du système immunitaire et en induisant la transition épithélio-mésenchymateuse. Après fixation du ligand TGFbeta , le complexe de récepteurs active les protéines cytoplasmiques Smad2 et Smad3 qui s'associent à Smad4 pour former le complexe transcriptionnel qui se transloque alors dans le noyau pour réguler la transcription de nombreux gènes cibles. Récemment, la protéine TIF1gamma a été décrite pour intervenir dans la régulation négative de la voie du TGFbeta , en monoubiquitinant Smad4 ou en interagissant avec Smad2/3 en compétition avec Smad4. Cette voie de signalisation devant être finement contrôlée pour cibler son action en fonction du contexte cellulaire, nous analysons ici la régulation des interactions fonctionnelles entre la voie canonique du TGFbeta et la protéine TIF1gamma. Dans cette étude, nous montrons que TIF1gamma agit comme un régulateur négatif des fonctions de Smad4 dans la voie de signalisation du TGFbeta au cours du processus de transition épithélio-mésenchymateuse et au cours de la différenciation terminale des cellules épithéliales mammaires et de la lactation. Nous étudions également la SUMOylation de TIF1gamma comme nouveau niveau de régulation de la réponse cellulaire au TGFbeta . Nous avons ainsi caractérisé les sites fonctionnels de SUMOylation de TIF1gamma et montré que cette modification post-traductionnelle inhibe la formation du complexe transcriptionnel Smad et est nécessaire pour réguler temporellement la résidence de Smad4 au niveau du promoteur de gènes cibles du TGFbeta . Nos résultats montrent le rôle important de la SUMOylation de TIF1gamma dans la régulation de la transition épithélio-mésenchymateuse induite par le TGFbeta . En conclusion, notre travail met en avant le rôle majeur de TIF1gamma dans la régulation de la réponse transcriptionnelle au TGFbeta . De plus, nous montrons que la SUMOylation de TIF1gamma est nécessaire à son activité répressive sur Smad4 / The cytokine TGFbeta regulates several cellular processes such as proliferation, differentiation, migration and apoptosis, from embryonic development to adulthood. TGFbeta is well described for its tumor suppressor role through antiproliferative and proapoptotic activities, in particular in epithelial cells. During tumor progression however, TGFbeta becomes a tumor promotor, favoring angiogenesis, immune suppression and inducing the epitheliomesenchymal transition. Binding of TGFbeta ligand to its receptors activate cytoplasmic messenger Smad2 and Smad3 to complex with Smad4 and shuttle into the nucleus to regulate TGFbetatarget genes expression. Recently, TIF1gamma has been described as a new negative regulator of TGFbeta signaling, through monoubiquitination of Smad4 or direct competition with Smad4 to bind activated Smad2/3. This signaling pathway has to be finely tuned to target an action dependent on a cellular context, which is why we analyze here the regulation of functional interactions between the TGFbeta canonical signaling and TIF1gamma. In this study, we show that TIF1gamma acts as a negative regulator of Smad4 functions in TGFbetasignaling during the epithelio-mesenchymal transition and during terminal differentiation of mammary epithelial cells and lactation. We are also interested in studying TIF1gamma SUMOylation as additional level of regulation of cell response to TGFbeta. Thus we characterized four functional SUMOylation sites in TIF1gamma and we found that this post-translational modification inhibits the formation of Smads transcriptional complex and is needed to temporally restrict Smad4 residence on the promoter of TGFbetatarget genes. Our results show the critical role of TIF1gamma SUMOylation in the regulation of TGFbeta- induced epithelio-mesenchymal transition. As a conclusion, our study unveils the major role of TIF1gamma in the regulation of TGFbeta transcriptional responses. Moreover, we show that TIF1gamma requires SUMOylation to exert its repressive activity on TGFbetasignaling

Denna kvalitativa studie har som syfte att undersöka förskollärares tillvägagångssätt och förutsättningar gällande systematiskt kvalitetsarbete. Studien samlade in empiri med hjälp av förutbestämda intervjufrågor utformade utifrån tidigare forskning för att besvara studiens syfte och frågeställningar. Resultat som uppsatsen genererar är att respondenterna är eniga om att det systematiska kvalitetsarbetet dels är något som enligt läroplanen ska genomföras, dels är en vital faktor för utveckling av verksamheten och för barnens progression. De är också eniga om att de erhålls goda förutsättningar för att genomföra detta, bland annat av rektorer och av olika verktyg. Den insamlade empirin åskådliggör att respondenternas verksamheter är grundade i barnens intressen. Studien visar att det systematiska kvalitetsarbetet genererar hög kvalitet i verksamheterna.

Vid kommunikation av information ar det viktigt att kommunicera tydlighet i sitt meddelande. För att inte förvirra informationen för mottagaren. Informationsdesign har ett antal principer för att undvika detta problem. Om en informationsdesigner använder principerna pa rätt sätt, kan informationsdesignern kommunicera tydlighet i sitt meddelande. En utbildnings progression kan vara en viktig del i att uppnå sina examensmål som student och därfor ar det viktigt om informationen kring progressionen är tydlig. Denna studie kommer att presentera principer inom informationsdesign, principer som hjälper funktions, estetiska och kognitiva egenskaper i informationsdesign. Kartläggningen i denna studie kommer att ta hjalp av funktionsprinciperna då de visar hur man främjar en god informationsdesign i hänsyn till struktur, klarhet, enkelhet, enighet och betoning. Gestaltlagar och gestaltpsykologi kommer också att vara inkluderade. För att både informationsdesign och gestaltpsykologi behandlar människans förmaga att uppfatta information, design och objekt i människans omgivning. Metoden for studien är att utföra en kvalitativ innehållsanalys över hogskolor och universitet och i vilken utsträckning dem presenterar progression och programmens kursers förkunskaper i enlighet med funktionsprinciperna från informationsdesign. Resultatet visar att majoriteten av skolorna följer informationsdesigns funktionsprinciper och det framkommer också fall av kompletteringar till informationen i form av figur/grund från gestaltlagarna. Även fast majoriteten av skolorna använder sig av funktionsprinciperna för informationsdesign upplevdes det som en utmaning att hitta källor som tar upp vikten av progression i utbildningar. / When communicating information then it is important to communicate clarity in the message. In order not to confuse the information for the recipient. Information design has several principles to avoid this problem. If an information designer uses the principles correctly, the information designer can communicate clarity in his message. The progression of an education can be an important part o fachieving one's degree goals as a student and therefore it is important if the information about the progression is clear. This study will present principles in information design, principles that help functional, aesthetic,and cognitive properties in information design. The mapping in this study will take the help of the functional principles as they show how to promote a good information design in terms of structure, clarity, simplicity, unity, and emphasis. Gestalt laws and gestalt psychology will also be included because both information design and gestalt psychology deal with the human ability to perceive information, design, and objects in the human environment. The method for the study is to perform a qualitative content analysis of colleges and universities and the programs in accordance with the functional principles of information design. The results show that most of the schools follow the functional principles of information design and there are also cases of additions to the information in the form of figures / basics from the figures. Even though most schools use the functional principles of information design, it was perceived as a challenge to find sources that address the importance of progression in education.