This thesis investigates the correlations between short protein peptide sequences and local tertiary structures. In particular, it introduces a novel algorithm for partitioning short protein segments into clusters of local sequence-structure motifs, and demonstrates that these motif clusters contain useful structural information via two applications to structural prediction. The first application utilizes motif clusters to predict local protein tertiary structures. A novel dynamic programming algorithm that performs comparably with some of the best existing algorithms is described. The second application exploits the capability of motif clusters in recognizing regular secondary structures to improve the performance of secondary structure prediction based on Support Vector Machines. Empirical results show significant improvement in overall prediction accuracy with no performance degradation in any specific aspect being measured. The encouraging results obtained illustrate the great potential of using local sequence-structure motifs to tackle protein structure predictions and possibly other important problems in computational biology.

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

In a time when many pupils feel a lack of security in school, the demands on teachers steadily increase as society puts pressure on them and the school system as a whole. The idea for this essay was born out of a need to create tools for teachers to use while working with the set values that the Swedish curriculum deems central to education. In order to create such a tool, a survey was made to ascertain what books are currently popular among Swedish children in the age range of 9-12, and then, using indirect characterization and the literary concepts of theme and motif as method, the goal has been to determine whether this book is suitable for working with questions that are related to the aforementioned values. To that end, the following questions were asked: • Which books are popular in the age range of 9-12 at the time of this essay’s writing? • Which motifs can be found in the book based on values as a theme? • How are the values that the school system should mediate portrayed in these motifs? The results showed that the chosen book, PAX: Nidstången (by Åsa Larsson & Ingela Korsell), contained all of the five values that the Swedish curriculum deems central to education. The results, then, indicate that this book is a suitable tool to include while working with values in the classroom. However, the effectiveness of this tool is also dependent on the teacher him/herself, since a tool’s value is only ever as high as the competence of the one who uses it.

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

Le comportement de tout être humain sain d’esprit s’explique par une multitude de raisons. Outre la science psychologique, le droit, y compris le droit des contrats, s’intéresse à ces raisons, appelés motifs. Cet intérêt résulte du fait que le comportement des contractants n’est pas abstrait ; il révèle toujours l’existence de divers motifs. Or, le droit objectif ne peut accorder une importance juridique à tous les motifs des parties, étant donné que les motifs représentent une catégorie psychologique et que leur prise en compte illimitée mettrait en péril la sécurité juridique. La présente thèse de doctorat a pour but de proposer une analyse critique de la prise en compte des motifs des parties à partir d’une comparaison des droits français, serbe et anglais / The behaviour of every individual of sound mind is explained by a variety of reasons. Besides psychological science, Law, including contract law, is interested by those reasons, called motives. This interest results from the fact that the behaviour of contracting parties is not abstract; it always reveals the existence of a variety of motives. However, the legal rules of a given domestic system cannot attribute an importance to all motives of parties. This is so because motives represent a psychological category and taking into account in an unlimited way those motives would imperil security in law. This present doctoral thesis aims at proposing a critical analysis of the taking into account of parties’ motives through a comparative study of French, Serbian and English law.

ATP-dependent chromatin remodelers have been proposed to act sequentially, and to a certain extent non-redundantly, in the priming stages of the DNA Damage Response pathways by establishing chromatin in lesion sites ready to act as a scaffold for repair factors or to be displaced in order to allow DNA repair. Among remodeling factors proposed to play a role in DNA repair is SMARCAD1, a poorly characterized, non-canonical member of the SWR1-like family of SNF2/SWI2 superfamily of ATPases, which has recently been identified as a potential target for ATM/ATR phosphorylation at canonical and non-canonical sites upon DNA damage. The actual mechanism for SMARCAD1 recruitment and involvement in DNA remodeling is still unknown, and unlike most other chromatin remodelers, SMARCAD1 does not contain DNA- or histone-binding domains frequently accompanying such proteins. Instead, in addition to the core ATPase domain, only two CUE domains (a type of helical ubiquitin-binding domain) have been identified. This thesis presents the findings of an investigation intended to structurally characterize SMARCAD1 by dissecting and identifying its domain architecture, and examining the activity and ligand selectivity of its binding domains in the functional context of DNA damage repair. The solution NMR structure of the CUE1 domain is presented, describing a triple helix bundle consistent with other members of the family. Furthermore, a novel SUMO interacting motif was identified and through a combination of NMR titrations and phospho-proteomics analysis, shown to be constitutively phosphorylated which excludes the possibility of DNA damage dependent ATM targeting as the recruitment mechanism for DNA repair. Additionally, it is demonstrated that both CUE domains are poor binders of mono-ubiquitin, however CUE1 specifically mediates the high affinity binary interaction with the transcriptionally repressive master regulator KAP1. This interaction was shown to be independent of post-translational ubiquitylation but rather sustained through direct interaction with the dimeric RBCC domain of KAP1. Finally, mass spectrometry profiling of domain-dependent interactions (based on differential abundance relative to changes due to chemically induced DNA damage) suggests SMARCAD1 may be involved in p53 transcriptional regulation through interactions maintained with CUE1 prior to DNA damage, whereas the SIM domain selectively targets protein interactions upon DNA damage that simultaneously activate p53 transcriptional control and recruit SMARCAD1 to DNA damage repair pathways.

No description available.

Mice infected with neurotropic variants of the murine coronavirus, mouse hepatitis virus, (strains JHMV or J2.2–V–1) develop acute and chronic CNS infections, and provide a model system to study the pathogenesis of virus–induced neuroinflammation, mechanisms of virus persistence, and anti–viral immune responses in the CNS. Using the J2.2–V–1 model of CNS infection, we addressed the role of sustained CCL2 production during viral infection using mice in which CCL2 was expressed transgenically in oligodendrocytes. Tonic CCL2 expression in the CNS resulted in delayed kinetics of virus clearance, and converted what is typically a mild, nonlethal disease to acutely lethal encephalitis, with the majority of mice succumbing to the infection. CCL2 induced a rapid and dysregulated inflammatory response that was no longer protective and was unable to efficiently clear virus from the CNS. Infected CCL2 Tg mice had increased numbers of Foxp3–expressing CD4 T cells (Tregs) and of macrophages and microglia expressing elevated levels of YM–1, a marker for alternatively activated macrophages, and nitric oxide. Our results showed that CCL2 has effects beyond serving as a chemoattractant for leukocytes, and has effects on the composition and function of inflammatory cells at sites of infection. In a separate set of experiments, I identified and characterized two additional heteroclitic variants of the JHMV epitope S598 that induced CD8 T cells with greater antigen sensitivity to the native S598 determinant relative to the cells primed by the native epitope. One of these heteroclitic epitopes elicited a T cell response with nearly complete cross–reactivity towards the native peptide. The structural data show that these heteroclitic epitopes induced modest conformational changes in the local environment of the peptide–MHCI complex. I also provide data to support the notion that heteroclitic determinants augment functional avidity by increasing surface epitope density. Collectively, these data will help guide the design of heteroclitic epitopes in the setting of vaccine development. Lastly, I examined the consequences of oxidative stress induced by viral infection on antigen presentation. The brains of JHMV–infected mice were found to have signs of oxidative stress, with significantly decreased ratios of reduced (GSH) to oxidized (GSSG) glutathione, suggesting that there is an environment that is conducive for cysteine modification with oxidized glutathione. We found that virus–induced oxidative stress resulted in the presentation of both native and S–glutathionylated forms of the JHMV epitope S510 by infected cells. A subset of the S510–specific CD8 T cells failed to recognize the modified form of the epitope, suggesting that GSH–modification of a cysteine–containing viral epitope might interfere with T cell recognition. Further, GSH-modified peptides were identified in stressed human cells, including herpes virus–transformed B cells, suggesting that the modification is not limited to mouse cells. Collectively these findings have implications for both anti–viral immunity and anti–tumor immunity, where oxidative stress has been shown to play a role during infection and tumorgenesis.

This exegesis examines the landscape of heaven depicted in the contemporary novel, The Lovely Bones by Alice Sebold. I examine the various characteristics of the heaven (or 'afterlife') depicted in Sebold's novel, with the aim of ascertaining the narrative effects of using this device. Using Ingrid Daemmrich's analysis of the paradisiacal motif in literature as a framework (Daemmrich, I 1997, Studies on Themes and Motifs in Literature: Enigmatic Bliss, The Paradise Motif in Literature, Peter Lang, New York), I reveal characteristics in The Lovely Bones that are both consistent with and challenge traditional literary representations of heaven and which therefore demonstrate that the text utilises the established literary motif of heaven for symbolism and meaning, but in a contemporary context. I explore the growing trend of contemporary literary heavens by reviewing two other literary heavens that are relevant to this scholarship. I examine where as writers and readers, we ascertain our concept of heaven (in society's religious foundations and from prior literature), and for the relevance of the key text, I briefly discuss the author's likely cultural influences. Having established the novel's lack of alignment with a religious version of heaven, I then examine the nature of and the narrative effect of, the personalised heaven depicted in the novel, The Lovely Bones. In doing so, I explore one of the new portraits of heaven in literature, an example which represents a growing trend away from portraying a classic edenic heaven shared by all humanity (and traditional to literary representations of heaven), toward a contemporary, personalised heaven that seeks to meet the wants and desires of the individual in our modern society. With reference to literature's ability to reflect back to us, our society's beliefs and values, I examine what this new portrait of heaven reveals about society. Access to the project examined in conjunction with this exegesis has been restricted due to copyright.

La régulation des évènements de prolifération et de différenciation cellulaire, lors du cycle de Plasmodium falciparum, implique un contrôle fin de l'expression des gènes. La conception d'une biopuce ciblée a permis l'identification de gènes différentiellement exprimés lors du cycle érythrocytaire de deux clones 3D7 et F12 (ne produisant pas de gamétocytes). L'implication de plusieurs protéines dans le processus de gamétocytogénèse a été proposée. L'étude d'un facteur de transcription, PfMyb1, a été engagée. Celui-ci est capable de lier spécifiquement des motifs ADN. Une baisse de la croissance des parasites traités par un ARN double brin spécifique du transcrit pfmyb1 a été observée. Les conséquences de l'extinction partielle de l'expression du transcrit et de la protéine PfMyb1, à son pic d'expression, sur le transcriptome des gènes de Plasmodium ont été étudiées. L'analyse des promoteurs, nous a permis de mieux comprendre les modalités de la régulation par ce facteur.