Hipopituitarismo congênito é caracterizado por deficiência hormonal múltipla devido a mutações de fatores de transcrição envolvidos na embriogênese hipofisária. As células-tronco estão presentes na hipófise e são caracterizadas por dar origem a uma célula progenitora e uma célula indiferenciada por divisão assimétrica. Estão envolvidas na hipófise em processos de alta demanda metabólica em diferentes fases da vida. Em estudos prévios, observou-se o acúmulo dos marcadores de células-tronco Sox2 e Nr2e1 no camundongo Ames, que apresenta mutação no gene Prop1. O Sox2 é o marcador consenso de células-tronco na hipófise enquanto que o Nr2e1, nunca antes caracterizado na hipófise, é essencial para a manutenção de células-tronco e neogenese no cérebro. A perda de função deste gene pode causar agressão e falta de instinto materno em camundongos. Com isso, o objetivo desse projeto foi utilizar o animal modelo zebrafish para avaliar o papel repressor do gene prop1 e caracterizar o gene nr2e1 bem como, confirmar se o mesmo está envolvido com a diferenciação terminal na hipófise, e sua interferência no comportamento do animal mutado. O zebrafish se encaixa adequadamente nesse projeto pois é de fácil manutenção, econômico e com rápido desenvolvimento. No presente estudo criou-se 2 modelos de zebrafish utilizando-se a técnica de edição genômica conhecida como CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) para nocautear os genes prop1 e nr2e1. Esta técnica permite uma interrupção específica e substituição de bases no genoma, resultando em uma alta especificidade, baixa toxicidade celular e é herdável. O zebrafish homozigoto com mutação no gene nr2e1 se desenvolve e reproduz como o animal controle, porém apresenta um comportamento mais exploratório quando comparado com o animal selvagem e o heterozigoto. A imunofluorescência para o anticorpo Sox2 no animal mutado mostrou se diferente do selvagem, pois apresenta um aumento da expressão temporal e o mesmo não se colocaliza com o Nr2e1. A imunofluorescência feita com os hormônios não se mostrou diferente entre o mutado e o selvagem. Conclui-se diante dos achados de normalidade do desenvolvimento, fertilidade, ausência de co-localização com o gene Sox2 e presença de hormônios como Tsh, Fsh e Gh, que o gene nr2e1 não é crucial na diferenciação terminal na hipófise porém o animal mutado apresenta um comportamento diferente do animal selvagem. Os resultados da caracterização do zebrafish com mutação no gene prop1 ainda estão em andamento devido a dificuldade de se estabelecer essa linhagem / Congenital hypopituitarism is characterized by multiple hormone deficiencies due to mutations in transcription factors involved in pituitary embryogenesis. Stem cells, which by definition can each give rise to a progenitor and an undifferentiated cell by asymmetric division, are present in the pituitary gland and are important during periods of high metabolic demand in different phases of life. In previous studies, the accumulation of the stem cell markers Sox2 and Nr2e1 was observed in the Ames mouse, which harbors a mutation in Prop1. Sox2 is the consensus stem cell marker in the pituitary gland, while the role of Nr2e1 in the pituitary development has not been characterized although it is essential for neural stem cell maintenance and neogenesis in the brain and its loss of function causes pathological aggression and lack of maternal instinct in mice. In this project, the zebrafish animal model was used to characterize the role of nr2e1, to confirm whether this gene can be involved in the pituitary terminal differentiation, and to determine the effects of this gene on animal behavior. The zebrafish is a particularly appropriate model for use in this project because it is easy to maintain, is economical, and has a rapid metabolism and growth rate. In the present study, we created 2 zebrafish models by knocking out prop1 and nr2e1 using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) genome-editing technique. This technique enables highly specific gene/reading frame interruption and/or base substitution in the genome, with low cellular toxicity and high heritability. Zebrafish with homozygous nr2e1 mutations develop and reproduce similarly to wild-type zebrafish, but present a more exploratory behavioral pattern compared to wild-type and heterozygous zebrafish. Based on immunofluorescence, Sox2 expression was higher in the mutant zebrafish than in the wild type and was not co-localized with Nr2e1 expression. Hormone expression did not differ between wild-type and mutant zebrafish. We conclude that nr2e1 is not crucial in the terminal differentiation of the hormone-forming pituitary gland; however, it induces a distinct behavioral phenotype at the larval stage. Analyses of zebrafish harboring a prop1 mutation are ongoing owing to issues with the establishment of the lineage

The main aim of this contribution is to introduce the potential that modern information technologies open to authors converting a teaching material from a printed to an electronic version. The authors come out of their own experience and propose options that are suitable especially for creation of study materials in mathematics education. Among others the contribution presents the use of flash animations, java scripts and Computer Algebra Systems.

Computer Algebra Systems (CAS), a powerful mathematical software currently available on hand held calculators, is becoming increasingly available to assist secondary students learn school mathematics. This study investigates how two teachers taught introductory differential calculus to their Year 11 classes using multiple representations in a CAS-supported curriculum. This thesis aims to explore the impact of the teaching on students’ understanding of the concept of derivative. / Understanding of the concept of derivative was gauged using an innovative Differentiation Competency Framework that was developed to describe understanding of the concept of derivative. It consists of eighteen competencies for formulation and interpretation of derivatives with, and without, translation between different representations. It clarified the objectives of the curriculum, purpose for using particular CAS activities, and also guided the construction of individual test items on the Differentiation Competency Test that enabled individual and class learning about the concept of derivative to be identified. / The Framework also helped identify each teacher’s privileging characteristics and facilitated analysis of the learning in relation to the teaching. / This study found that using multiple representations was important in developing understanding of the concept of derivative but that the graphical and the symbolic representations were the most useful and important to emphasize and link. / Analysis of the teaching actions showed that the teachers used CAS in ways that were consistent with their teaching approach and preferred use of representations and that a conceptual teaching method and student-centred style supported understanding of the concept of derivative. / Teaching is directly linked to learning and each class developed a different understanding of the concept of derivative that related to the combined effect of their teacher’s privileging characteristics: calculus content, teaching approach, and use of CAS. This study also shows that if a CAS-supported curriculum is to be successfully implemented, it needs to acquire institutional status including a corresponding change in assessment to legitimize new teaching practices.

Hipopituitarismo congênito é caracterizado por deficiência hormonal múltipla devido a mutações de fatores de transcrição envolvidos na embriogênese hipofisária. As células-tronco estão presentes na hipófise e são caracterizadas por dar origem a uma célula progenitora e uma célula indiferenciada por divisão assimétrica. Estão envolvidas na hipófise em processos de alta demanda metabólica em diferentes fases da vida. Em estudos prévios, observou-se o acúmulo dos marcadores de células-tronco Sox2 e Nr2e1 no camundongo Ames, que apresenta mutação no gene Prop1. O Sox2 é o marcador consenso de células-tronco na hipófise enquanto que o Nr2e1, nunca antes caracterizado na hipófise, é essencial para a manutenção de células-tronco e neogenese no cérebro. A perda de função deste gene pode causar agressão e falta de instinto materno em camundongos. Com isso, o objetivo desse projeto foi utilizar o animal modelo zebrafish para avaliar o papel repressor do gene prop1 e caracterizar o gene nr2e1 bem como, confirmar se o mesmo está envolvido com a diferenciação terminal na hipófise, e sua interferência no comportamento do animal mutado. O zebrafish se encaixa adequadamente nesse projeto pois é de fácil manutenção, econômico e com rápido desenvolvimento. No presente estudo criou-se 2 modelos de zebrafish utilizando-se a técnica de edição genômica conhecida como CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) para nocautear os genes prop1 e nr2e1. Esta técnica permite uma interrupção específica e substituição de bases no genoma, resultando em uma alta especificidade, baixa toxicidade celular e é herdável. O zebrafish homozigoto com mutação no gene nr2e1 se desenvolve e reproduz como o animal controle, porém apresenta um comportamento mais exploratório quando comparado com o animal selvagem e o heterozigoto. A imunofluorescência para o anticorpo Sox2 no animal mutado mostrou se diferente do selvagem, pois apresenta um aumento da expressão temporal e o mesmo não se colocaliza com o Nr2e1. A imunofluorescência feita com os hormônios não se mostrou diferente entre o mutado e o selvagem. Conclui-se diante dos achados de normalidade do desenvolvimento, fertilidade, ausência de co-localização com o gene Sox2 e presença de hormônios como Tsh, Fsh e Gh, que o gene nr2e1 não é crucial na diferenciação terminal na hipófise porém o animal mutado apresenta um comportamento diferente do animal selvagem. Os resultados da caracterização do zebrafish com mutação no gene prop1 ainda estão em andamento devido a dificuldade de se estabelecer essa linhagem / Congenital hypopituitarism is characterized by multiple hormone deficiencies due to mutations in transcription factors involved in pituitary embryogenesis. Stem cells, which by definition can each give rise to a progenitor and an undifferentiated cell by asymmetric division, are present in the pituitary gland and are important during periods of high metabolic demand in different phases of life. In previous studies, the accumulation of the stem cell markers Sox2 and Nr2e1 was observed in the Ames mouse, which harbors a mutation in Prop1. Sox2 is the consensus stem cell marker in the pituitary gland, while the role of Nr2e1 in the pituitary development has not been characterized although it is essential for neural stem cell maintenance and neogenesis in the brain and its loss of function causes pathological aggression and lack of maternal instinct in mice. In this project, the zebrafish animal model was used to characterize the role of nr2e1, to confirm whether this gene can be involved in the pituitary terminal differentiation, and to determine the effects of this gene on animal behavior. The zebrafish is a particularly appropriate model for use in this project because it is easy to maintain, is economical, and has a rapid metabolism and growth rate. In the present study, we created 2 zebrafish models by knocking out prop1 and nr2e1 using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) genome-editing technique. This technique enables highly specific gene/reading frame interruption and/or base substitution in the genome, with low cellular toxicity and high heritability. Zebrafish with homozygous nr2e1 mutations develop and reproduce similarly to wild-type zebrafish, but present a more exploratory behavioral pattern compared to wild-type and heterozygous zebrafish. Based on immunofluorescence, Sox2 expression was higher in the mutant zebrafish than in the wild type and was not co-localized with Nr2e1 expression. Hormone expression did not differ between wild-type and mutant zebrafish. We conclude that nr2e1 is not crucial in the terminal differentiation of the hormone-forming pituitary gland; however, it induces a distinct behavioral phenotype at the larval stage. Analyses of zebrafish harboring a prop1 mutation are ongoing owing to issues with the establishment of the lineage

Das RNA-guided adaptive Immunsystem CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) immunisiert prokaryotische Zellen gegenüber mobilen genetischen Elementen (MGEs). Bei der Adaption wird eine kurze Nukleinsäurensequenz (prespacer) von den MGEs gewonnen, verarbeitet und schließlich als spacer in das CRISPR-Array integriert. Cas1 und Cas2, die Hauptbestandteile der Adaption, bilden einen Integrase-Komplex, welcher neue spacer in das CRISPR-Array integriert. Der molekulare Mechanismus für die Adaptiondes Typ II-A Systems, welches cas9, cas1, cas2, csn2 und tracrRNA codiert, ist bis heute nicht vollständig verstanden. Daher untersuchten wir die Anforderungen der verschiedenen Cas-Proteine für den Adaptionsprozess. Wir verifizierten die Adaptions-Aktivität von Typ II-A Systemen des Streptococcus thermophilus LMD-9 anhand von Adaptionsstudien nach Phagen-Infektion. Dabei beobachteten wir höhere Akquisitionsraten im CRISPR3-Lokus im Vergleich zum CRISPR1-Lokus. Unsere Plasmid-basierte Adaptionsstudie bestätigte die Notwendigkeit von Cas9, zusätzlich zu Cas1, Cas2 und Csn2 bei der Adaption. Der yeast two-hybrid und der pull-down Ansatz zeigten sowohl spezifische Interaktionen zwischen den Cas-Proteinen, als auch Interaktionen zwischen Cas-Proteinen sowie DNA-Reparatur Proteinen. Die Regionen der Cas1 und Cas9 Interaktion wurden durch SPOT peptide assay identifiziert. Zusammenfassend weist unsere Studie darauf hin, dass Cas-Proteine sowohl mit Proteinen innerhalb, als auch außerhalb des CRISPR-Cas Systems interagieren, und bietet somit eine Basis für die Erforschung der möglichen Funktionen von DNA-Reparatur Proteinen in CRISPR-Cas Systemen und vice versa. / The RNA guided adaptive immune system CRISPR (clustered regularly interspaced short palindromic repeats) Cas (CRISPR-associated) immunizes prokaryotic cells against mobile genetic elements (MGEs). During spacer acquisition stage, a short nucleic acid sequence (prespacer) is acquired from the MGEs, processed and finally integrated into the CRISPR array as a spacer, which serves as genetic memory to defend against the invasion of the cognate MGEs. The molecular mechanism for the spacer acquisition of the type II A systems, which encode cas9, cas1, cas2, csn2 and tracrRNA, is still not fully understood. Therefore, we investigated the requirement of the different Cas proteins for spacer acquisition. We verified the acquisition activity of the type II A systems of Streptococcus thermophilus LMD 9 via spacer acquisition studies by phage challenge. We observed higher acquisition rates in the CRISPR3 locus compared to the CRISPR1 locus. Our plasmid-based spacer acquisition study confirmed in addition to Cas1, Cas2 and Csn2 the requirement of Cas9 for spacer acquisition. Yeast two hybrid and pull down approaches revealed specific interactions among the Cas proteins, as well as interactions between Cas and DNA repair proteins. The interaction regions of Cas1 with Cas9 were identified by SPOT peptide assay. Altogether, our study suggests that Cas proteins interact with proteins within and beyond the CRISPR Cas systems, and it provides a basis for the investigation of the potential roles of DNA repair proteins in the CRISPR Cas systems and/or vice versa.

The use of new tools for mathematics at school wins increasingly Importance. It follows from this that they are consquences as well as on aims and contents of mathematics at school us like on methods in the lessons. It is not unusual, that students and parents and also university professors are to be feared, that the calculation competence is decreasing with the use of CAS. In the lesson should be showed a possible way to developing such competences in the beginning phase of the learning process in Algebra. The examples refer to a level of school mathematics for students in the middle school age. The methods tell apart phases with and without CAS and shows a didactic principles of mathematics lessons in the case of use of CAS handheld technology.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Malgré le fait que les traitements basés sur l'exposition et la prévention de réponse ont clairement démontré leur efficacité avec le Trouble Obsessionnel- Compulsif (TOC), les résultats cliniques avec cette combinaison sont loin d'être optimaux. La thérapie cognitive pour le TOC est prometteuse. Les quatre études présentées ici ont pour but d'approfondir la compréhension des variables cognitives associées au TOC. La première étude appuie empiriquement le lien entre la surestimation du danger, la responsabilité et le perfectionnisme et les symptômes obsessionels-compulsifs (OC). La deuxième étude démontre que la correction des croyances idéographiques sans aucune forme d’exposition ou de prévention de réponse représente un traitement efficace avec les vérificateurs compulsifs. La troisième étude suggère qu'au moins un des mécanismes impliqués dans le traitement cognitif et le traitement comportemental impliquerait la précédence d'un changement cognitif sur la diminution de symptômes. Utilisant la même méthodologie, la quatrième étude démontre les liens bidirectionnels entre les états émotionnels indépendants, les cognitions et les symptômes. De plus, cette étude suggère que le processus de changement entre ces trois variables pourrait être différent chez les patients qui répondent bien ou non au traitement. Ces quatre études fournissent un appui empirique aux modèles théoriques formulés pour expliquer le TOC. Elles comportent également des implications cliniques considérables.

S’inscrivant dans le domaine des sciences de l’orientation, ce mémoire contribue de façon originale au développement des connaissances sur la construction identitaire. Il s’intéresse au problème de développement et de vitalité des communautés francophones en situation minoritaire au Canada, et ses répercussions sur la construction identitaire des jeunes. Une recherche qualitative sous forme d’enquête par récits biographiques a permis d’analyser plus spécifiquement les parcours individuels et le rapport à l’identité acadienne de vingt-deux jeunes francophones originaires du nord du Nouveau-Brunswick lors d’une expérience de mobilité géographique dans la poursuite d’études universitaires. Les résultats démontrent que les tensions existentielles sont toujours présentes, qu’elles varient d’une personne à l’autre et qu’elles sont plus marquantes lors des périodes critiques de la vie. La synergie des tensions crée une (re)construction identitaire perpétuelle qui diffère pour chaque individu selon sa représentation du milieu, son sentiment d’appartenance et son besoin d’autonomie. / Stemming from the field of Guidance and Counselling, this research brings a new understanding and furthers our knowledge on the topic of identity construction. It studies the problem of development and vitality encountered by the francophone communities living in a minority situation in Canada, and how it affects the identity construction of youths. A qualitative research performed through studies of life stories gave access to a more specific analysis of individual journeys and their relationship to acadian identity for twenty-two young francophones of northern New Brunswick during their geographical mobility for the pursuit of university studies. Results show that existential tensions are still present, that they vary between individuals and that they are more significant during the various critical life stages. This synergy of tensions creates a perpetual identity (re)construction that differs between individuals according to their own understanding of their milieu, their sense of belonging and their need for autonomy.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2007-2008. / Ce mémoire a comme objectifs principaux de déterminer l'effet sur la production de l'incitatif pression des pairs sous deux modes de paiement différents, le paiement fixe et le paiement à la pièce, ainsi que d'évaluer l'impact des modes de paiement sur la qualité. Pour évaluer ces effets, nous avons réalisé une expérience en laboratoire dont la tâche consistait à de la saisie de données sur ordinateur. Pour mesurer l'effet des variables sur la production, une régression MCO et une régression quantile au niveau de la médiane sont utilisées. Les résultats démontrent que l'effet de l'incitatif pression des pairs subit un effet d'éviction ''crowding out effect'' lors de l'ajout de l'incitation extrinsèque paiement à la pièce. De plus, on observe que la compétition induite par la pression des pairs a un effet uniquement chez les hommes et que la relation entre le niveau de pression et la productivité est non linéaire. Cette relation signifie qu'au-dessus d'un certain niveau de pression la productivité diminue. Pour l'analyse de la qualité, l'estimation est réalisée avec le modèle binomial négatif. Nos résultats confirment qu'une réponse à l'incitatif paiement à la pièce occasionne un échange "trade off" entre qualité et productivité. Nos résultats démontrent de plus que l'absence d'un contrôle de qualité engendre un biais lors de l'inférence.