The tautomerase superfamily is composed of a group of proteins characterized by two key features: the N-terminal proline and a beta-alpha-beta-motif. This superfamily has been divided into five families represented by 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), cis-3-chloroacrylic acid dehalogenase (cis-CaaD), malonate semialdehyde decarboxylase (MSAD), and macrophage migration inhibitory factor (MIF). Cg10062 is a homologue of cis-CaaD, but has several distinct biochemical properties from cis-CaaD. For example, Cg10062 can be irreversibly inhibited by (R)- or (S)-oxirane-2-carboxylate, whereas cis-CaaD can only be irreversibly inhibited by (R)-oxirane-2-carboxylate. FG41MSAD is a homologue of MSAD, with comparable decarboxylase activity but missing Arg-73 known to be crucial for the MSAD activity. In order to understand the unique biochemical characteristics of Cg10062 and FG41MSAD, we have solved five crystal structures. These crystal structures have established a solid structural basis for understanding the mechanisms of their activities. The eukaryotic protein phosphatases are composed of a group of proteins that are responsible for reversible phosphorylation. The eukaryotic protein phosphatases have been divided into three families, the phosphoprotein phosphatase (PPP) family, the protein phosphatase Mg2+- or Mn2+-dependent (PPM) family and the protein Tyr phosphatase (PTP) family. PDP1 is a member of PPM family. PDP1 is also an important component of the large pyruvate dehydrogenase complex (PDC) which catalyzes the decarboxylation of pyruvate to yield acetyl-CoA with the accompanying reduction of NAD+. In order to understand the mechanism in which it dephosphorylates its target protein we have solved the structure of the catalytic domain of PDP1. Analysis of these structures in the light of their evolutionary contexts enables us to appreciate the unity and diversity of the biological systems at the chemical level and help us solve interesting problems, such as the possible physiological functions for some members within the tautomerase superfamily. / text

Quand deux couches fluides immiscibles sont soumises à des vibrations verticales, des ondes stationnaires apparaissent à l'interface si l'amplitude de ces oscillations est suffisamment grande. Des travaux récents ont mis en évidence que les motifs observés étaient étonnamment variés, ce qui a largement contribué à l'intéerêt que revet aujourd'hui le problème de Faraday. Nous avons réalisé la première simulation numérique complète tridimensionnelle des ondes de Faraday. Les algorithmes employés sont une méthode de projection dédiée à la résolution des équations de Navier-Stokes et une méthode de Front-Tracking consacrée au traitement de l'interface. Les courbes neutres et les modes propres temporels sont en accord avec la théorie de Floquet. Nous avons ensuite simulé le problème de Faraday dans des conditions d'apparition de motifs carrés et hexagonaux. Les spectres spatio-temporels des motifs simulés sont en accord avec l'expérience. Cependant, les hexagones se déstabilisent vers une alternance régulière de motifs de différentes symétries, suggérant la présence d'une orbite homocline. Nous avons élaboré un algorithme forçant la symétrie hexagonale pour déterminer le point fixe de cette orbite. Nous avons enfin réalisé une étude numérique de l'instabilité de dérive dans l'expérience de Faraday bidimensionnelle périodique. Un déplacement horizontal de motifs initialement immobiles avait été expérimentalement constaté lorsque les oscillations dépassaient un seuil secondaire. Les simulations ont confirmé ce résultat. Des diagrammes de bifurcation mettant en évidence des instabilités supplémentaires ont été tracés et complétés par une analyse spectrale spatio-temporelle.

Text-to-speech synthesis enables the speech-impeded user of an augmentative and alternative communication system to partake in any conversation on any topic, because it can produce dynamic content. Current synthetic voices do not sound very natural, however, lacking in the areas of emphasis and emotion. These qualities are furthermore important to convey meaning and intent beyond that which can be achieved by the vocabulary of words only. Put differently, speech synthesis requires a more comprehensive analysis of its text input beyond the word level to infer the meaning and intent that elicit emphasis and emotion. The synthesised speech then needs to imitate the effects that these textual factors have on the acoustics of human speech. This research addresses these challenges by commencing with a literature study on the state of the art in the fields of natural language processing, text-to-speech synthesis and speech prosody. It is noted that the higher linguistic levels of discourse, information structure and affect are necessary for the text analysis to shape the prosody appropriately for more natural synthesised speech. Discourse and information structure account for meaning, intent and emphasis, and affect formalises the modelling of emotion. The OCC model is shown to be a suitable point of departure for a new model of affect that can leverage the higher linguistic levels. The audiobook is presented as a text and speech resource for the modelling of discourse, information structure and affect because its narrative structure is prosodically richer than the random constitution of a traditional text-to-speech corpus. A set of audiobooks are selected and phonetically aligned for subsequent investigation. The new model of discourse, information structure and affect, called e-motif, is developed to take advantage of the audiobook text. It is a subjective model that does not specify any particular belief system in order to appraise its emotions, but defines only anonymous affect states. Its cognitive and social features rely heavily on the coreference resolution of the text, but this process is found not to be accurate enough to produce usable features values. The research concludes with an experimental investigation of the influence of the e-motif features on human speech and synthesised speech. The aligned audiobook speech is inspected for prosodic correlates of the cognitive and social features, revealing that some activity occurs in the into national domain. However, when the aligned audiobook speech is used in the training of a synthetic voice, the e-motif effects are overshadowed by those of structural features that come standard in the voice building framework. / PhD (Information Technology), North-West University, Vaal Triangle Campus, 2014

Analysis of functional connectivity of simultaneously recorded multiple spike trains is one of the major issues in the neuroscience. The progress of the statistical methods to the analysis of functional connectivity of multiple spike trains is relatively slow. In this thesis two statistical techniques are presented to the analysis of functional connectivity of multiple spike trains. The first method is known as the modified correlation grid (MCG). This method is based on the calculation of cross-correlation function of all possible pair-wise spike trains. The second technique is known as the Cox method. This method is based on the modulated renewal process (MRP). The original paper on the application of the Cox method (Borisyuk et al., 1985) to neuroscience data was used to analyse only pairs and triplets of spike trains. This method is further developed in this thesis to support simultaneously recorded of any possible set of multiple spike trains. A probabilistic model is developed to test the Cox method. This probabilistic model is based on the MRP. Due to the common probabilistic basis of the probabilistic model and the Cox method, the probabilistic model is a convenient technique to test the Cox method. A new technique based on a pair-wise analysis of Cox method known as the Cox metric is presented to find the groups of coupled spike trains. Another new technique known as motif analysis is introduced which is useful in identifying interconnections among the spike trains. This technique is based on the triplet-wise analysis of the Cox method. All these methods are applied to several sets of spike trains generated by the Enhanced Leaky and Integrate Fire (ELIF) model. The results suggest that these methods are successful for analysing functional connectivity of simultaneously recorded multiple spike trains. These methods are also applied to an experimental data recorded from cat’s visual cortex. The connection matrix derived from the experimental data by the Cox method is further applied to the graph theoretical methods.

"Mémoire présenté à la Faculté des études supérieures en vue de l'obtention du grade de maître en droit option Droit des biotechnologies". Ce mémoire a été accepté à l'unanimité et classé parmi les 10% des mémoires de la discipline. / La science génétique tend de plus en plus à identifier des maladies génétiques et à associer des comportements humains au bagage génétique. Or, ces applications peuvent servir à exclure et stigmatiser des individus. Cela crée parfois ce qu'on appelle de la discrimination génétique. Le domaine de l'emploi est particulièrement propice à voir surgir cette forme de discrimination. Nous voulons ici déterminer dans quelle mesure les chartes des droits de la personne canadienne et québécoise protègent les travailleurs contre la discrimination génétique. Nous regardons d'abord si la lutte contre la discrimination génétique est compatible avec les objectifs de la règle anti-discrimination. Ensuite, nous examinons la prohibition de la discrimination basée sur le handicap afin de voir si celle-ci peut empêcher la discrimination génétique des travailleurs. Finalement, nous tentons de voir si les caractéristiques génétiques pourraient constituer un motif analogue de discrimination prohibé par la Charte canadienne. / Increasingly, the genetic science tends to identify sorne genetic diseases and to associate the human behaviors to the genetic code. This uses can serve to exclude and stigmatize the individuals. This sometimes creates what is called the genetic discrimination. The workplace is particularly favorable to see emerging this form of discrimination. We try to determine in what way the human rights charters protect the workers against the genetic discrimination. First, we scrutinize if the struggle against the genetic discrimination is well-suited with the objecti ves of the principles of the non-discrimination. Secondly, we examine if the prohibition of the disability discrimination could prevent the genetic discrimination against the workers. Finally, we try to establish if the genetic characteristics could constitute an analogous ground of discrimination prohibited by the Canadian Charter.

L'acide désoxyribonucléique (ADN) et l'acide ribonucléique (ARN) sont des polymères de nucléotides essentiels à la cellule. À l'inverse de l'ADN qui sert principalement à stocker l'information génétique, les ARN sont impliqués dans plusieurs processus métaboliques. Par exemple, ils transmettent l’information génétique codée dans l’ADN. Ils sont essentiels pour la maturation des autres ARN, la régulation de l’expression génétique, la prévention de la dégradation des chromosomes et le ciblage des protéines dans la cellule. La polyvalence fonctionnelle de l'ARN résulte de sa plus grande diversité structurale. Notre laboratoire a développé MC-Fold, un algorithme pour prédire la structure des ARN qu'on représente avec des graphes d'interactions inter-nucléotidiques. Les sommets de ces graphes représentent les nucléotides et les arêtes leurs interactions. Notre laboratoire a aussi observé qu'un petit ensemble de cycles d'interactions à lui seul définit la structure de n'importe quel motif d'ARN. La formation de ces cycles dépend de la séquence de nucléotides et MC-Fold détermine les cycles les plus probables étant donnée cette séquence. Mon projet de maîtrise a été, dans un premier temps, de définir une base de données des motifs structuraux et fonctionnels d'ARN, bdMotifs, en terme de ces cycles. Par la suite, j’ai implanté un algorithme, MC-Motifs, qui recherche ces motifs dans des graphes d'interactions et, entre autres, ceux générés par MC-Fold. Finalement, j’ai validé mon algorithme sur des ARN dont la structure est connue, tels que les ARN ribosomaux (ARNr) 5S, 16S et 23S, et l'ARN utilisé pour prédire la structure des riborégulateurs. Le mémoire est divisé en cinq chapitres. Le premier chapitre présente la structure chimique, les fonctions cellulaires de l'ARN et le repliement structural du polymère. Dans le deuxième chapitre, je décris la base de données bdMotifs. Dans le troisième chapitre, l’algorithme de recherche MC-Motifs est introduit. Le quatrième chapitre présente les résultats de la validation et des prédictions. Finalement, le dernier chapitre porte sur la discussion des résultats suivis d’une conclusion sur le travail. / Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are polymers of nucleotides essential for the survival of the cell. Contrary to DNA, whose main role is to store genetic information, RNA is involved in multiple metabolic processes. For example, RNA is involved in the transfer of information from DNA to protein, the processing and modification of other RNAs, the regulation of gene expression, the end-maintenance of chromosomes, and the sorting of proteins within the cell. This functional versatility of RNA comes from its structural diversity. Our laboratory developed MC-Fold, an algorithm that predicts RNA structures by representing them with nucleotide interaction graphs. The nodes in these graphs represent the nucleotides, and the edges the interactions between them. Our laboratory also observed that a limited number of interaction cycles can define the structure of any RNA motif. The formation of these cycles is determined by the nucleotide sequence and MC-Fold determines the most likely cycles based on that sequence. In this Master Degree project, I first built a database of structural and functional RNA motifs, bdMotifs, based on their constituent cycles. Then, I implemented an algorithm, MC-Motifs, which detects motifs within interaction graphs generated either by MC-Fold or by any other method. Finally, I validated my algorithm on known RNA structures such as the 5S, 16S and 23S ribosomal RNA (rRNA) and predicted structure of riboswitches. The Master thesis is divided into five chapters. The first chapter presents the chemical structure of RNA, its cellular functions and the structural folding of the polymer. In the second chapter, the database bdMotifs is described. In the third chapter, the MC-Motifs algorithm is introduced. In the fourth chapter, I present the results of MC-Motifs. Finally, in the last chapter, I discuss theses results and I give a conclusion on the project.

An examination of the persistent death motif in Twain's literature reveals a strong fusion of his art, personal experience and philosophical conclusions. Death imagery dramatizes Twain's pessimistic view of an estranged humanity existing without purpose or direction in an incomprehensible universe. Twain shows in his works that religious and social beliefs only obscure the fact that the meaning of death is beyond man's intellectual and perceptual powers. In Twain's view the only certainty about death is that it is a release from the preordained tragedies of existence. Illusions, primordial terrors, and mystifying dreams shape man's disordered reality, Twain concludes, and therefore death is as meaningless as life.

This thesis argues that the ornament of Fatehpur Sikri, imperial city of the Mughal emperor Akbar, was created by and for a transcultural audience as a subtle means of unification. Scholars have largely characterized Fatehpur Sikri as a site that epitomizes the blend of Hindu and Islamic architecture. Inherent in this description is the assumption that these visual elements are distinctly religious and mutually exclusive, identified as solely Hindu or Islamic. Yet the integration of various types of imagery is indicative of more dynamic cultural interactions. I have used photographic documentation to classify and analyze the ornamental elements present in three structures at Fatehpur Sikri. My analyses of these elements’ usage and placement, in conjunction with those from surrounding Indian structures, suggest not only a unique Akbari repertoire but provides insight as to the structures’ purposes.

Le ribozyme VS de Neurospora catalyse des réactions de clivage et de ligation d’un lien phosphodiester spécifique essentielles à son cycle de réplication. Il est formé de six régions hélicales (I à VI), qui se divisent en deux domaines, soit le substrat (SLI) et le domaine catalytique (tiges II à VI). Ce dernier comprend deux jonctions à trois voies qui permettent de reconnaître le substrat en tige-boucle de façon spécifique. Ce mode de reconnaissance unique pourrait être exploité pour cibler des ARN repliés pour diverses applications. Bien que le ribozyme VS ait été caractérisé biochimiquement de façon exhaustive, aucune structure à haute résolution du ribozyme complet n’a encore été publiée, ce qui limite la compréhension des mécanismes inhérents à son fonctionnement. Précédemment, une approche de divide-and-conquer a été initiée afin d’étudier la structure des sous-domaines importants du ribozyme VS par spectroscopie de résonance magnétique nucléaire (RMN) mais doit être complétée. Dans le cadre de cette thèse, les structures de la boucle A730 et des jonctions III-IV-V et II-III-VI ont été déterminées par spectroscopie RMN hétéronucléaire. De plus, une approche de spectroscopie RMN a été développée pour la localisation des ions divalents, tandis que diverses approches de marquage isotopique ont été implémentées pour l’étude d’ARN de plus grandes tailles. Les structures RMN de la boucle A730 et des deux jonctions à trois voies révèlent que ces sous-domaines sont bien définis, qu’ils sont formés de plusieurs éléments structuraux récurrents (U-turn, S-turn, triplets de bases et empilement coaxial) et qu’ils contiennent plusieurs sites de liaison de métaux. En outre, un modèle du site actif du ribozyme VS a été construit sur la base des similarités identifiées entre les sites actifs des ribozymes VS et hairpin. Dans l’ensemble, ces études contribuent de façon significative à la compréhension de l’architecture globale du ribozyme VS. De plus, elles permettront de construire un modèle à haute résolution du ribozyme VS tout en favorisant de futures études d’ingénierie. / The Neurospora VS ribozyme catalyzes the cleavage and the ligation of a specific phosphodiester bond, which is essential for its replication cycle. It is formed of six helical regions (I to VI) that are divided in two domains: the substrate (SLI) and the catalytic domain (stems II-VI). The latter contains two three-way junctions that allow recognition of the stem-loop substrate in a specific manner. This unique mode of substrate recognition could be exploited to target folded RNAs for diverse applications. Even though the VS ribozyme has been extensively characterized biochemically, no high-resolution structure of the complete ribozyme has been published yet and this limits our mechanistic understanding. A divide-and-conquer approach was previously initiated to study the structure of the important subdomains of the VS ribozyme by nuclear magnetic resonance (NMR), but this approach needs to be completed. In this thesis, the structures of the A730 loop, the III-IV-V junction and the II-III-VI junction were determined by heteronuclear NMR spectroscopy. Moreover, a unique NMR approach was developed for localizing divalent metal ions, whereas several isotope-labeling strategies were implemented to facilitate the study or large RNA molecules. The NMR structures of the A730 loop and the two three-way junctions reveal that these subdomains are well defined, that they are formed by several recurrent structural elements (U-turn and S-turn motifs, base triples and coaxial stacking) and that they contain several metal-binding sites. Interestingly, structural similarities were identified between the VS and hairpin ribozymes, which allowed the modeling of the VS ribozyme active site. In summary, these studies significantly contribute to a better understanding of the global architecture of the VS ribozyme. In addition, they will allow the construction of a high-resolution model of the complete VS ribozyme and facilitate future engineering studies.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.