Doctor of Philosophy

dissertationOver 40 years ago, the first computer simulation of a protein was reported: the atomic motions of a 58 amino acid protein were simulated for few picoseconds. With today's supercomputers, simulations of large biomolecular systems with hundreds of thousands of atoms can reach biologically significant timescales. Through dynamics information biomolecular simulations can provide new insights into molecular structure and function to support the development of new drugs or therapies. While the recent advances in high-performance computing hardware and computational methods have enabled scientists to run longer simulations, they also created new challenges for data management. Investigators need to use local and national resources to run these simulations and store their output, which can reach terabytes of data on disk. Because of the wide variety of computational methods and software packages available to the community, no standard data representation has been established to describe the computational protocol and the output of these simulations, preventing data sharing and collaboration. Data exchange is also limited due to the lack of repositories and tools to summarize, index, and search biomolecular simulation datasets. In this dissertation a common data model for biomolecular simulations is proposed to guide the design of future databases and APIs. The data model was then extended to a controlled vocabulary that can be used in the context of the semantic web. Two different approaches to data management are also proposed. The iBIOMES repository offers a distributed environment where input and output files are indexed via common data elements. The repository includes a dynamic web interface to summarize, visualize, search, and download published data. A simpler tool, iBIOMES Lite, was developed to generate summaries of datasets hosted at remote sites where user privileges and/or IT resources might be limited. These two informatics-based approaches to data management offer new means for the community to keep track of distributed and heterogeneous biomolecular simulation data and create collaborative networks

Rapid-Response Urban CFD Simulations Using a GPU Computing Paradigm on Desktop Supercomputers

In the event of chemical or biological (CB) agent attacks or accidents, first-responders need hazard prediction data to launch effective emergency response action. Accurate and timely knowledge of the wind fields in urban areas is critically important to identify and project the extent of CB agent dispersion to determine the hazard-zone. In their 2008 report (GAO-08-180), U.S. Government Accountability Office has reported that first responders are limited in their ability to detect and model hazardous releases in urban environments. The current set of modeling tools for contaminant dispersion in urban environments rely on empirical assumptions with diagnostic equations (Wang et al. 2003, Williams et al. 2004). The main advantage of these models is their relatively fast turn-around times, although their predictive capabilities can be limited. As part of the Joint Effects Model (JEM), funded by the Department of Defense, urban transport and dispersion models have been evaluated for their rapid-response capabilities. As discussed in Heagy et al. (2007), majority of the urban transport and dispersion models considered in the evaluation study fell short of satisfying the JEM key performance parameter of maximum 10-minutes run-time on a desktop computer, and the models that were able to satisfy the performance parameter were employed at low resolutions

One-day symposium “The Hollywood Turn: Viewing, Theorizing, Deconstructing American Cinema Anew”

American cinema as an object of study continues to occupy a special place in academic circles. Far from resulting in a consensual body of texts and concepts, research in this field now encompasses a multitude of approaches, ranging from historical and cultural to socio-economic perspectives and, following the development of new audiovisual technologies, a growing interest for its status as a vast repertoire of continuously remediated images and icons. In keeping with this long tradition of st..

Évaluation d’un nouveau modèle de pratique de la physiothérapie en première ligne pour les patients souffrant de pathologies musculosquelettiques

Au Québec, l’amélioration de l’accès aux soins de première ligne est basée sur le développement des Groupes de Médecine de Famille (GMF). Depuis 2014, les GMF sont incités à diversifier leur offre de service en incluant de nouvelles professions (physiothérapie, nutrition, inhalothérapie ou kinésiologie). Actuellement, peu de données sont disponibles sur leurs pratiques au sein d’un GMF. L’objectif du mémoire était d’évaluer la pratique de la physiothérapie en première ligne pour les patients souffrant de pathologies musculosquelettiques, au GMF Universitaire de l’Hôpital Maisonneuve-Rosemont de Montréal (GMF-U HMR). Une 1ère étude rétrospective (revue de 100 dossiers) visait à décrire la clientèle ayant consulté en physiothérapie au GMF-U HMR et son parcours de soins. Une 2nde étude, prospective, évaluait la fonction et la qualité de vie de patients lors d’une évaluation initiale en physiothérapie et à 3 mois, à l’aide de questionnaire autorapportés. La satisfaction envers l’évaluation et le processus de soins en physiothérapie et la perception des patients de l’efficacité des équipes de soins étaient évaluées. La clientèle du service de physiothérapie du GMF-U HMR était d’âge varié, de profil socio-économique faible et consultait pour des troubles musculosquelettiques de toutes localisations. Les 52 participants exprimaient une diminution de leur qualité de vie et des incapacités fonctionnelles modérées. Les soins de physiothérapie visaient l’autonomisation du patient (i.e. éducation thérapeutique et exercices à domicile, principalement). À 3 mois, l’évolution de la qualité de vie était significative. L’évolution de la fonction était significative pour les participants souffrant du membre supérieur. Les participants exprimaient de hauts niveaux de satisfaction envers la prise en charge en physiothérapie et une haute perception d’efficacité de l’équipe soignante. Ce projet suggère de l’intérêt de la physiothérapie auprès de la clientèle du GMF-U HMR. D’autres études sont nécessaires à travers les GMF du Québec afin de confirmer ces observations faites auprès de la clientèle du GMF-U HMR.In Quebec, improving the access to primary care is based on the development of family medicine groups (FMGs). Since 2014, FMGs have diversified their service offerings into new professions (physiotherapy, nutrition, respiratory therapy or kinesiology). This choice of professional is specific to each FMGs but there is little data available to support this choice. The objective of the dissertation was to evaluate the practice of physiotherapy in primary care for patients with musculoskeletal disorders at University FMGs of Montreal Maisonneuve-Rosemont Hospital (UFMGs HMR). A first retrospective study (review of 100 files) aimed to describe the clientele who consulted in physiotherapy at the GMF-U HMR and its care pathway. A second, prospective study assessed the function and quality of life of patients during an initial assessment in physiotherapy and at 3 months, using self-reported questionnaire. Satisfaction with assessment and process of physiotherapy care and patient perception of the effectiveness of care teams was also assessed. The clientele of the UFMGs HMR physiotherapy department was of varied age, of low socio-economic profile and consulted only for musculoskeletal disorders of all locations. participants expressed a decrease in their quality of life and moderate functional disability. Physiotherapy care was aimed at patient empowerment (i.e. therapeutic education and home exercise, mainly). At 3 months, the evolution of the quality of life was significant. The evolution of function was significant for participants suffering from the upper limb. Participants expressed high levels of satisfaction with the management of physiotherapy and a high perception of the effectiveness of the health care team. This project suggests the interest of physiotherapy with UFMGs HMR clients. Further studies are needed across Quebec FMGs to confirm these observations made to the GMF-U HMR clientele

Implementation of a Cartesian Grid Incompressible Navier-Stokes Solver on Multi-GPU Desktop Platforms Using CUDA

Today’s Graphics Processor Units (GPU) are powerful computation platforms used not only for graphic rendering but also for multi-purpose computation. Now reaching a teraflops of peak performance and over a 100 GB/sec of bandwidth, GPUs outperform the latest CPUs and provide a new high-performance computing platform. New languages such as CUDA and Brook+ allow developers to target the programmable unit of the GPUs without a graphics programming background. Scientists and engineers in various fields have started benefiting from the last generations of GPUs. In this thesis, the implementation of a Navier-Stokes solver for incompressible flow around urban-like domains is presented. Transport and dispersion of contaminants in urban environments is an area of intense research. The computational fluid dynamic (CFD) models necessary to provide realistic simulations require heavy computation, usually only possible on CPU clusters. This thesis presents the base for an urban dispersion model implementation on desktop platforms, using one or multiple GPUs as coprocessors. The governing equations implemented for this thesis are common to many problems in CFD where flow motion is involved. Using a single Tesla C870 GPU card, the CUDA implementation of the lid-driven cavity problem runs 33 times faster than a serial C code running on a single core of an AMD Opteron 2.4GHz processor. A speedup of 100 was reached by associating the Tesla S870 quad-GPU system to a quad-core CPU machine. Computations for both GPU and CPU are single precision. A more complex application including obstacle capability was developed to model building effects in the domain. Using the quad-GPU system, the flow-field in a domain of 1.28 km × 1.28 km × 320 m was computed. A low Reynolds number flow-field projection of 22 minutes (1000 time steps) could be simulated in 3 minutes. Results show that an urban dispersion is feasible on this type of platform and that models can be run within minutes to provide emergency responses. More generally, it shows that complex CFD problems can benefit from multi-GPU desktop architectures

Renal Cell Carcinoma: Focus on Safety and Efficacy of Temsirolimus

Metastatic renal cell carcinoma has harboured a poor prognosis for decades with immunotherapy being the only available therapy with high toxicity and modest effect. Dependance of renal cell carcinoma oncogenesis on the mTOR pathway has led to clinical development of temsirolimus in this setting. This sirolimus derivative has shown clinical efficacy in monotherapy for poor-risk renal cell carcinoma leading to an overall survival of 10.8 months in the pivotal phase III trial of this agent. Its specific adverse events consist of metabolic dysregulation (hyperlipemia, hyperglycemia), mucositis, rash and pneumonitis which can be severe and need careful monitoring and management. In this review, we will discuss of the clinical development of this molecule, its efficacy, its safety profile and future perspectives