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

Le développement d'un système a pour objectif de répondre à des exigences. Aussi, le succès de sa réalisation repose en grande partie sur la phase de spécification des exigences qui a pour vocation de décrire de manière précise et non ambiguë toutes les caractéristiques du système à développer.Les spécifications d'exigences sont le résultat d'une analyse des besoins faisant intervenir différentes parties. Elles sont généralement rédigées en langage naturel (LN) pour une plus large compréhension, ce qui peut mener à diverses interprétations, car les textes en LN peuvent contenir des ambiguïtés sémantiques ou des informations implicites. Il n'est donc pas aisé de spécifier un ensemble complet et cohérent d'exigences. D'où la nécessité d'une vérification formelle des spécifications résultats.Les spécifications LN ne sont pas considérées comme formelles et ne permettent pas l'application directe de méthodes vérification formelles.Ce constat mène à la nécessité de transformer les spécifications LN en spécifications formelles.C'est dans ce contexte que s'inscrit cette thèse.La difficulté principale d'une telle transformation réside dans l'ampleur du fossé entre spécifications LN et spécifications formelles.L'objectif de mon travail de thèse est de proposer une approche permettant de vérifier automatiquement des spécifications d'exigences utilisateur, écrites en langage naturel et décrivant le comportement d'un système.Pour cela, nous avons exploré les possibilités offertes par un modèle de représentation fondé sur un formalisme logique.Nos contributions portent essentiellement sur trois propositions :1) une ontologie en OWL-DL fondée sur les logiques de description, comme modèle de représentation pivot permettant de faire le lien entre spécifications en langage naturel et spécifications formelles; 2) une approche d'instanciation du modèle de représentation pivot, fondée sur une analyse dirigée par la sémantique de l'ontologie, permettant de passer automatiquement des spécifications en langage naturel à leur représentation conceptuelle; et 3) une approche exploitant le formalisme logique de l'ontologie, pour permettre un passage automatique du modèle de représentation pivot vers un langage de spécifications formelles nommé Maude. / The main objective of system development is to address requirements. As such, success in its realisation is highly dependent on a requirement specification phase which aims to describe precisely and unambiguously all the characteristics of the system that should be developed. In order to arrive at a set of requirements, a user needs analysis is carried out which involves different parties (stakeholders). The system requirements are generally written in natural language to garantuee a wider understanding. However, since NL texts can contain semantic ambiguities, implicit information, or other inconsistenties, this can lead to diverse interpretations. Hence, it is not easy to specify a set of complete and consistent requirements, and therefore, the specified requirements must be formally checked. Specifications written in NL are not considered to be formal and do not allow for a direct application of formal methods. We must therefore transform NL requirements into formal specifications. The work presented in this thesis was carried out in this framework. The main difficulty of such transformation is the gap between NL requirements and formal specifications. The objective of this work is to propose an approach for an automatic verification of user requirements which are written in natural language and describe a system's expected behaviour. Our approach uses the potential offered by a representation model based on a logical formalism. Our contribution has three main aspects: 1) an OWL-DL ontology based on description logic, used as a pivot representation model that serves as a link between NL requirements to formal specifications; 2) an approach for the instantiation of the pivot ontology, which allows an automatic transformation of NL requirements to their conceptual representations; and 3) an approach exploiting the logical formalism of the ontology in order to automatically translate the ontology into a formal specification language called Maude.

Mitochondrial dysfunction is a phenomenon observed in models of Traumatic Brain Injury (TBI). Loss of mitochondrial bioenergetics can result in diminished cellular homeostasis leading to cellular dysfunction and possible cellular death. Consequently, the resultant tissue damage can manifest as functional deficits and/or disease states. Therapeutic strategies to target this mitochondrial dysfunction have been investigated for models TBI and have shown promising effects. For this project, we tested the hypothesis that mitoNEET, a novel mitochondrial membrane protein, is a target for pioglitazone mediated neuroprotection. To test this, we used a severe Controlled Cortical Impact (CCI) injury model in mitoNEET null and wild-type mice. We then dosed these animals with pioglitazone or NL-1, which is a compound that has a similar structure to pioglitazone allowing us to hone in one the importance of mitoNEET binding. Wild-type animals treated with the mitoNEET ligands, both pioglitazone and NL-1, had improved mitochondrial function, tissue sparing and functional recovery, compared to mitoNEET null animals. In addition to this specific hypothesis tested, our experiments provided insight casting doubt on the central dogma that mitochondrial dysfunction following TBI is the result of vast oxidative damage and consequential irreversible mitochondrial loss. The data from these studies show that when mitoNEET is targeted with pioglitazone at 12 hours’ post-injury, mitochondrial dysfunction can be reversed. Additionally, when bypassing proteins upstream of Complex I with an alternative biofuel, such as beta-hydroxybuterate (BHB), TBI related mitochondrial dysfunction is once again reversed. This leads to novel hypothesis for future work which posits mitoNEET as a redox sensitive switch; when mitoNEET senses changes in redox, as seen in TBI, it inhibits mitochondrial respiration. When targeted with an agonist/ligand or bypassed with a biofuel TBI mitochondrial dysfunction can be reversed. These studies support the role of mitoNEET in the neuropathological sequelae of brain injury, supporting mitoNEET as a crucial target for pioglitazone mediated neuroprotection following TBI. Lastly, these studies propose a mechanism of TBI related mitochondrial dysfunction which can reversed with pharmacological agents.

Dans le but d’améliorer les performances des nageurs professionnels, nous avons développé, en collaboration avec la Fédération Française de Natation, un système automatique de suivi à base des séquences vidéo. Pour ce faire, nous proposons un nouveau système de prise de vue 8K adapté au milieu aquatique et permettant un calibrage du bassin. Celui-ci établit le lien entre les coordonnées pixels et métriques permettant, entre autres, d’extraire le couloir concerné pour effectuer les différents traitements. Afin d’initialiser le suivi, il est nécessaire de localiser le nageur. Pour cela, nous proposons d’utiliser une approche a contrario pour détecter le mouvement, puis l’approche Scaled Composite JTC pour localiser précisément la tête du nageur. Ensuite, nous implémentons et adaptons les techniques de suivi de la littérature, notamment celles basées sur la corrélation NL-JTC, les histogrammes de couleur, les motifs binaires locaux (LBP) et les histogrammes de gradient orienté (HOG). Suite aux différentes limitations de ces techniques, nous proposons de nouvelles approches optimisées basées principalement sur la fusion de données. Tout d’abord, nous développons l’approche multipiste constituée de plusieurs pistes de suivi, où chacune représente l’une des techniques de suivi citées précédemment. Ensuite, un choix basé sur l’histogramme de couleur est effectué afin de choisir la meilleure décision parmi celles offertes par chaque piste. Cette approche a significativement amélioré les résultats mais ceux-ci restent insuffisants pour l’étude des performances. Dans ce sens, nous proposons une nouvelle approche par fusion dynamique qui consiste à fusionner le plan de corrélation NL-JTC et le plan de scores couleurs dans le but d’extraire une description plus riche de la cible (forme + couleur). Cette approche a montré de très bons résultats dans le cas où la cible à suivre est visible mais reste très sensible aux occultations de celle-ci. Afin de résoudre cette difficulté, nous améliorons l’approche proposée en suivant simultanément la tête et le maillot de bain du nageur. Cette approche multizone permet, grâce à un critère de décision complexe, de retrouver la zone occultée à l’aide de la zone visible. Enfin, une étude de performances a été menée et les résultats obtenus ont permis de valider ce système. En particulier, nous nous sommes intéressés aux mesures de vitesse cyclique, intra-cyclique et instantanée, afin d’étudier et améliorer les performances des nageurs. / Swimming Federation), an automatic tracking approach using video sequences. To do this, we propose a new 8K shooting system adapted to the aquatic environment and allowing a pool calibration. This establishes the link between pixel and metric coordinates, which allows among others, to extract the concerned lane to carry out the different treatments. In order to initialize the tracking, it is necessary to localize the swimmer. For this, we propose to use an a contrario approach to detect movement, then the Scaled Composites JTC approach to precisely localize the swimmer’s head. Afterwards, we implement and adapt several tracking techniques well-known in the literature, namely those based on the NL-JTC correlation, color histograms, Local Binary Patterns (LBP) and histograms of oriented gradient (HOG). Given the various limitations of these techniques, we propose new optimized approaches based primarily on data fusion. First, we develop a multitracking approach consists of several tracks, where each track represents one of the tracking techniques mentioned above.Then, a choice based on the color histogram is made to select the best decision among those offered by each track. This approach has significantly improved the results, but it remains insufficient for the performance analysis. Therefore, we propose a new dynamic fusion approach that combines NL-JTC correlation plane and color scores plane in order to generate a richer description of the target (form + color). This approach has shown very good results in the case where the target is visible but it is still sensitive to occlusions. To solve this problem, we improve this proposed approach by tracking simultaneously the head and the swimsuit of the athlete. This multi related targets approach enables, through a complex decision criterion, to find the occluded zone based on the visible one. Finally, a performance study is conducted and the results have validated the system. In particular, we were interested in cyclical, intra-cyclical and instantaneous speed measurements, to study and improve the swimmers’performance.

Le problème étudié dans cette thèse est celui du débruitage d'images numériques cor- rompues par un bruit blanc gaussien. Les méthodes utilisées pour récupérer une meilleure image reposent sur les patchs et sont des variantes des Non-Local Means. Les contributions de la thèse sont à la fois pratiques et théoriques. Tout d'abord, on étudie précisément l'influence des divers paramètres de la méthode. On met ensuite en lumière une lim- ite observée sur le traitement des bords par les méthodes à patchs habituelles. On donne alors une meilleure façon de combiner l'information fournie à partir des patchs pour estimer pixel par pixel. D'un point de vue théorique, on présente un cadre non asymptotique pour contrôler notre estimateur. On donne alors des résultats de type inégalités oracles pour des estimateurs vérifiant des propriétés plus restrictives. Les techniques utilisées reposent sur l'agrégation d'estimateurs, et plus particulièrement sur l'agrégation à poids exponentiels. La méthode requiert typiquement une mesure du risque, obtenue à travers un estimateur sans biais de celui-ci, par exemple par la méthode de Stein. Les méthodes de débruitage étudiées sont analysées numériquement par simulations.

The effectiveness of seismic retrofitting applied to enhance seismic performance was assessed for a five-story reinforced concrete (RC) flat-slab building structure in the central United States. In addition to this, an assessment of seismic fragility that relates the probability of exceeding a performance level to the earthquake intensity was conducted. The response of the structure was predicted using nonlinear static and dynamic analyses with synthetic ground motion records for the central U.S. region. In addition, two analytical approaches for nonlinear response analysis were compared. FEMA 356 (ASCE 2000) criteria were used to evaluate the seismic performance of the case study building. Two approaches of FEMA 356 were used for seismic evaluation: global-level and member-level using three performance levels (Immediate Occupancy, Life Safety and Collapse Prevention). In addition to these limit states, punching shear drift limits were also considered to establish an upper bound drift capacity limit for collapse prevention. Based on the seismic evaluation results, three possible retrofit techniques were applied to improve the seismic performance of the structure, including addition of shear walls, addition of RC column jackets, and confinement of the column plastic hinge zones using externally bonded steel plates. Finally, fragility relationships were developed for the existing and retrofitted structure using several performance levels. Fragility curves for the retrofitted structure were compared with those for the unretrofitted structure. For various performance levels to assess the fragility curves, FEMA global drift limits were compared with the drift limits based on the FEMA member-level criteria. In addition to this, performance levels which were based on additional quantitative limits were also considered and compared with FEMA drift limits.

The effectiveness of seismic retrofitting applied to enhance seismic performance was assessed for a five-story reinforced concrete (RC) flat-slab building structure in the central United States. In addition to this, an assessment of seismic fragility that relates the probability of exceeding a performance level to the earthquake intensity was conducted. The response of the structure was predicted using nonlinear static and dynamic analyses with synthetic ground motion records for the central U.S. region. In addition, two analytical approaches for nonlinear response analysis were compared. FEMA 356 (ASCE 2000) criteria were used to evaluate the seismic performance of the case study building. Two approaches of FEMA 356 were used for seismic evaluation: global-level and member-level using three performance levels (Immediate Occupancy, Life Safety and Collapse Prevention). In addition to these limit states, punching shear drift limits were also considered to establish an upper bound drift capacity limit for collapse prevention. Based on the seismic evaluation results, three possible retrofit techniques were applied to improve the seismic performance of the structure, including addition of shear walls, addition of RC column jackets, and confinement of the column plastic hinge zones using externally bonded steel plates. Finally, fragility relationships were developed for the existing and retrofitted structure using several performance levels. Fragility curves for the retrofitted structure were compared with those for the unretrofitted structure. For various performance levels to assess the fragility curves, FEMA global drift limits were compared with the drift limits based on the FEMA member-level criteria. In addition to this, performance levels which were based on additional quantitative limits were also considered and compared with FEMA drift limits.

The thesis focuses on creation of precaution „Plan applicable in case of exceptional/unsafe incidents taking place at TJ Tesla swimming pool located in Brno”. The theoretical chapter(s) deal with legislative framework and related bills regarding leak of dangerous substances from buildings. It also deals with protection of population within the Czech Republic with regard to separate measures applicable according to the character of incident. The practical chapter(s) deal with analysis of risks within the premises and define the character of unsafe attributes of the risk sources. The various risks are therefore modelled in order to show the possible range of unsafe effects on population. These models are necessary to define the most effective protective measures applicable while exceptional/unsafe incidents occur. The aim of the thesis is to create the specific precaution plan as well as dispute the way the incidents of unsafe substances of below the legislative limit amount could be handled.

Nordihydroguaiaretic acid (NDGA), is a naturally-occurring lignan isolated from the creosote bush (Larrea tridentata). The aqueous extract of this shrub, commonly referred to as Chaparral tea, was listed in the American pharmacopeia as an ethnobotanical used to treat tuberculosis, arthritis and cancer. Other documented traditional applications of creosote bush extract include treatment for infertility, rheumatism, arthritis, diabetes, gallbladder and kidney stones, pain and inflammation among many others. In spite of the numerous pharmacological properties, NDGA use has been associated with toxicities including hepatotoxicity in humans. Previous studies in our group showed that oxidative cyclization of NDGA (a di-catechol) at physiological pH forms a dibenzocyclooctadiene that may have therapeutic benefits whilst oxidation to ortho-quinone likely mediates toxicological properties. In order to investigate the structural features responsible for pharmacological and toxicological properties, a series of NDGA analogues were designed, synthesized and characterized for the purpose of studying their oxidative metabolism. Literature procedures were modified to successfully prepare seven lignan analogues via multi-step synthesis. In our effort to understand the mechanisms of NDGA intramolecular cyclization, the prepared analogues were incubated under previously established conditions where NDGA autoxidized to yield the dibenzocyclooctadiene derivative. We also evaluated the stability of the analogues under the conditions of this study. Furthermore, we evaluated bioactivation potential of the prepared analogues with a goal of eliminating reactive metabolite liability through rational structural modification. We incubated NDGA and its analogues in rat liver microsomes (RLM) in the presence of glutathione as a nucleophilic trapping agent. Standards for comparison were generated by performing glutathione trapping experiments with chemical and enzyme oxidation systems. The potential of the dibenzocyclooctadiene lignan 2 derived from NDGA under physiological conditions to contribute to toxicological properties via reactive metabolite formation was also evaluated. Glutathione conjugates were detected by electrospray ionization-mass spectrometry (ESI-MS) scanning for neutral loss (NL) 129 Da or 307 Da in positive ion mode or precursor ion (PI) scanning for 272 Da in negative ion mode and further characterized by liquid chromatography–tandem mass spectrometry (LC–MS/MS) or in a single LC-MS run using multiple reactions monitoring (MRM) as a survey scan to trigger acquisition of enhanced product ion (EPI) data. We determined that NDGA autoxidation at pH 7.4 is dependent on substituents and/or substitution pattern on the two aromatic rings. In particular, spontaneous intramolecular cyclization to a dibenzocyclooctadiene required a di-catechol lignan, raising the possibility that o-Q formation may not be necessary for cyclization to occur. Cyclization was significantly inhibited in the presence of excess GSH which supports the involvement of free radicals as opposed to o-Q in the intramolecular cyclization process. The mono-catechol analogues A1 and A4 underwent oxidation to o-Q but no evidence of cyclization was found implying that electrophilic substitution cannot account for NDGA cyclization. The phenol-type analogues were oxidatively more stable in comparison with the catechol-type analogues at pH 7.4. The results demonstrate that electrophilic substitution makes no contribution to the intramolecular cyclization process and that a radical mediated process accurately describes the situation for NDGA. Oxidative metabolism and bioactivation studies on NDGA and its analogues revealed that reactive metabolites formation is dependent on substitution and/or substitution pattern of the aromatic rings. Cytochrome P450-mediated oxidation of NDGA and its catechol-type analogues yielded electrophilic intermediates which reacted with GSH. The GSH mono-conjugates were identified as ring adducts derived from o-Q although the position at which the GSH binds to the aromatic rings could not be determined. We also found that NL 129 or 307 scanning in positive ionization mode has potential diagnostic utility in distinguishing between aromatic and benzylic GSH conjugates although further studies may be required for validation. We found no evidence of p-QM either directly or via isomerization of o-Q intermediates suggesting that o-Q is the major reactive toxicophore responsible for reactive metabolite mediated toxicities associated with NDGA use. In addition, we demonstrated that the NDGA-derived dibenzycyclooctadiene lignan (cNDGA 2) undergoes P450-mediated oxidation to a reactive metabolite which might have toxicological implications. There was no evidence of P450-mediated oxidation to reactive metabolites for the phenol-type NDGA analogues. It is concluded that structural modification efforts should focus on phenol-type analogues to potentially enhance the safety profile of NDGA.