Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

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Telomeres are fundamental structures found at the end of all eukaryotic chromosomes that function to protect the end of chromosomes from end-to-end fusion, erosion and subsequent telomere dysfunction. Telomerase and alternative lengthening of telomere (ALT) mechanisms maintain the telomeres by compensating natural telomeric loss. ALT is found to be present in 15% of human tumours lines and it may be expressed at low levels in the normal mouse tissues. However, the exact mechanism behind ALT depression and/or activation in the mammalian cells is not fully understood. Previous studies have highlighted the role of BRCA1 in telomere dysfunction. Also, it has recently been shown that BRCA1 co-localises at telomeres in the ALT + human cells through BLM and Rad50. However, it is still unclear whether BRCA1 plays a direct role on telomere length maintenance and integrity. The aim of this project was to examine the role of BRCA1 in telomere maintenance associate with ALT in BRCA1 defective mammalian cells. Therefore to achieve this, we have set up series of experiments to look at, (a) hallmarks of ALT activity at the cytological level, (b) measuring of ALT activity using biochemical and immunocytochemistry techniques and (c) understanding the role of BRCA1 in DNA damage response mechanism and telomere dysfunction. Firstly, we found elevated levels of recombination at telomeres in the two human BRCA1 carrier cell lines and mouse embryonic stem cell with deficiency in Brca1-/-. Secondly, our data showed that human and mouse BRCA1 defective cells are significantly more sensitive to ionizing radiation in line with the DNA repair function of BRCA1. Moreover, we found persistent DNA damage at telomeres in the BRCA1 defective environment when after exposure of cells to ionizing radiation. Thirdly, we found evidence of ALT activity in some mouse cell lines, and elevated ALT in mouse cells defective in Brca1. Finally, we examined some other ALT markers using immunofluorescence. Our data indicate differences between human and mouse cells in regulating ALT. Taken together data presented in this thesis revealed that (i) BRCA1 plays a major role in telomere maintenance and defective BRCA1 mammalian cells show evidence of telomere dysfunction and telomere length shortening in line with previous publish data, (ii) BRCA1 defective mouse cells have elevated levels of ALT, (iii) the mouse lymphoblastoid LY-S cells have complete absence of ALT.

Made available in DSpace on 2014-12-17T14:36:07Z (GMT). No. of bitstreams: 1 RodrigoCB.pdf: 553723 bytes, checksum: 35e31c5f14b7f8f8ee92436ce29c4b27 (MD5) Previous issue date: 2008-03-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / La dissertation pr?tend consid?rer l'h?t?ronymie, experiment?e par le po?te Fernando Pessoa, comme une strat?gie cognitive pour ?quivaloir l'autre dans le champs de l'?ducation et minimiser des persistantes antinomies dans le processus de l'apprentissage tel que sentiment et pens?e, ?motion et raison. Ainsi, telle strat?gie se constitue en un des fondements possibles de la m?thode complexe au tisser de mode dialogique et r?cursive la relation de l'alt?rit? que se constitue les identit?s plurielles dans l'?ducation lan?ant des bases d`une science de la sensacions pour l'exercice d'une p?dagogie de la feinte / A disserta??o pretende considerar a heteron?mia, vivenciada pelo poeta Fernando Pessoa, como uma estrat?gia cognitiva para equacionar o outro no campo da educa??o e minimizar persistentes antinomias no processo de aprendizagem tal como sentimento e pensamento, emo??o e raz?o. Assim, tal estrat?gia se constitui num dos fundamentos poss?veis do m?todo complexo ao tecer de forma dial?gica e recursiva a rela??o de alteridade nas quais se moldam as identidades plurais na educa??o, lan?ando bases de uma ci?ncia das sensa??es para o exerc?cio de uma pedagogia do fingimento

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Denna uppsats utför en jämförande analys mellan två snarlika memes, vaporwave och fashwave, för att se närmare på hur deras gemensamma drag används för att kommunicera både högerextrema och icke-högerextrema budskap. Alltså: Vad är det för skillnader mellan memesen, och vad är det i vaporwave estetiska framtoner som gör den retoriskt attraktiv för en högerextrem variant i form av fashwave? Vad tillför dessa till framförandet av det högerextrema budskapet? Med en teoretisk grund i doxologi och konceptet "det imaginära" och med Roland Barthes semiologiska begreppsapparat som metodiskt redskap visar uppsatsen på att de centrala dragen hos båda memesen har likheter och skillnader. Att fashwave tar sig an vaporwaves suggestiva och mångtyda natur och spetsar till den till ett tydligt, riktat högerextremt budskap. Den doxologiska mångfalden som återfinns i memen vaporwave försvinner, och fashwave knyts således an till en högerextrem doxa. Det som tillföres i framförandet av det högerextrema budskapet är en farkost för att kunna sprida sig utåt, att högerextremister kan presenteras utåt som en modern rörelse med en uppfattad konträr placering emot de man uppfattar som "det andra". Och det är mot detta andra, som självbilden skapas.

This essay investigates the prospect of Romantic Irony’s potential resurgence in contemporary poetics and discusses its relevance and likeness with metamodernism. The internet has by now not only seeped into, but fully permeated, the process of literary production and distribution. The effect of this has been the birth of a new kind of poetic discourse which can broadly be called metamodernism, The New Sincerity or Alt-lit. This movement is characterized by its self-reflexive metacommentary, fragmentary nature and an oscillation between of irony and sincerity. Vermeulen and Akker, among others, have hinted at metamodernism’s relation to Romanticism, but research into the specifics of its tendency towards Romantic Irony is scarce. By viewing the writings of Steve Roggenbuck (a central figure in the new poetic movement), alongside the philosophy of Friedrich Schlegel, I propose a comparative framework for discussion of sincerity, irony and the instrumentalization of contemporary metamodernist writing. I demonstrate that Roggenbuck’s writing displays narratological, tropological and thematic tendencies commonly associated with both Romantic Irony and metamodernism. Apart from broader structural comparison, I attempt a comparative analysis between Roggenbuck’s poetry (2010-2015) and Thomas Carlyle’s novel “Sartor Resartus” (1833-1834) in order to provide a visualisation of the rhetorical and narratological strategies of Romantic Irony. I aim to frame Romantic Irony as a sensibility, or mode of discourse - rather than a strict system of thought - which may still be at work today. In extension, the sensibilities of Romantic Irony may shed further light into the philosophical potential of the seemingly incomprehensible and contradictory tendencies of metamodernism. By ironicizing its poetic form, literary ambition and desire for sincerity in a post-postmodern era, Roggenbuck’s poetry celebrates ambiguity and literary failure, ultimately framing irony as a constructive and potentially democratic operation.

En biologie clinique, disposer de mesures fiables et comparables, indépendamment du temps et du laboratoire, est primordial afin de permettre une prise en charge et un suivi adaptés des patients. Le moyen privilégié est d’établir la traçabilité métrologique des résultats de mesure aux unités du système international (SI), notamment par le biais de méthodes de référence et de matériaux de référence certifiés d’ordre supérieur. Ces travaux de thèse se sont attachés à caractériser deux méthodes de référence primaires candidates. Une méthode d’énumération absolue des lipoprotéines par ES-DMA pour l’évaluation du risque cardiovasculaire a été développée et caractérisée. Les résultats obtenus ont mis en évidence certaines limitations instrumentales rendant l’établissement de la traçabilité au SI difficile. Malgré les avantages certains de cette méthode pour l’analyse avancée de lipoprotéines, la fidélité et la robustesse des mesures ne sont pas suffisantes pour la considérer comme méthode de référence primaire. Une méthode de quantification de l’hémoglobine glyquée HbA1c, un biomarqueur du diabète sucré, par LC-MS/MS associée à la dilution isotopique a été mise en place et validée. La traçabilité au SI des résultats de dosage a été établie, toutefois, les incertitudes de mesures demeurent élevées et la comparabilité avec la méthode de référence IFCC reste à évaluer sur un nombre plus significatif d’échantillons et de laboratoires. Pour conclure, ces travaux ont mis en évidence les défis associés à la mise en place de nouvelles chaînes de traçabilité ainsi que les problématiques liées au développement de méthodes de référence primaires pour le dosage de biomarqueurs complexes. / Ensuring reliability and between-laboratory comparability of in-vitro diagnostic test results is essential for appropriate and internationally harmonized decision making and patient follow-up. To this end, a privileged way is to establish results metrological traceability to the international system of units (SI) through the development of primary reference methods and higher order reference materials. This thesis aimed at characterizing two candidate primary reference procedures.A method for lipoprotein absolute quantification by ES-DMA for cardiovascular diseases risk assessment was developed and characterized. Results evidenced some advantages of this method compared to other advanced lipoprotein testing assays, but some instrumental weaknesses make the establishment of results traceability to the SI difficult in the current state-of-the-art. Precision and robustness are additionally not sufficient for this method to be considered as a primary reference method.A method for the quantification of glycated hemoglobin HbA1c, a biomarker of diabetes mellitus, by LC/MS/MS associated to isotopic dilution was implemented and validated. Results traceability to the SI units could successfully be established. However, measurement uncertainties remain large and comparability with the IFCC reference method is still to be further assessed on a significant number of samples and laboratories.To conclude, this study highlighted the challenges associated with the implementation of new traceability chains and the difficulties related to the development and characterization of primary reference procedures for the quantification of complex biological markers.

Despite women's historical involvement in far phenomenon is a mismatch between analysts' expectations and far right women's be The lack of substantial research that focuses on women's narratives and recollections of their women's positions. A recent replication of this phenomenon is right women's motivations in en the movement is aligned to their interests. Additionally, I engage with women's perspectives on right and the lack of space and support for women's the subjects of women's interests in the alt right' women's perspectives in women's terms, as such an approach will provide analysts and

Embedding itself in the larger discussion on protests against measures taken by governments all over the world to mitigate the effects of the covid-19 pandemic, this work concerns itself with the role of the Holocaust in narratives found in prominent Telegram channels and chat groups of German covid-protests. Building on the existing body of research, it uses the theoretical framework of New Social Movement (NSM) theory to categorise the protests in Germany. Choosing a mixed-methods design, the phenomenon is described using narrative analysis, computer-assisted coding, and elements of network analysis. The narrative analysis and results of computer-assisted coding, find that the Holocaust is narrated as a valid comparison to pandemic politics, while some Telegram channels engage in historical revisionism. The network analysis reveals a large network of Telegram channels, strengthening the importance of the analysed channels for the protests in Germany