Résumé de la thèse:Le syndrome néphrotique idiopathique (SNI) est la forme la plus fréquente de néphropathies glomérulaires et résulte d'altérations touchant les podocytes. La progression de la maladie est associée à une déplétion podocytaire et l'apparition de glomérulosclérose. Malgré de nombreuses études moléculaires et des avancées scientifiques indiscutables sur les formes génétiques, la pathogénie du SNI reste une énigme.Nous avons trouvé que la protéine c-mip est spécifiquement induite dans les podocytes des patients atteints de SNI.Nous avons montré que les souris transgéniques c-mip développent une protéinurie néphrotique qui n'est associée ni à des lésions inflammatoires glomérulaires ou interstitielles, ni à des dépôts de complexes immuns circulants ou de complément. Les études in vitro et in vivo ont démontré que c-mip se lie à Fyn et bloque la liaison de Fyn avec la néphrine et N WASP. Il en résulte une inhibition de la voie de signalisation de la néphrine et l'incapacité de N-WASP à recruter Nck, ce qui altère l'organisation du cytosquelette podocytaire et contribue au développement de la protéinurie masssive.D'autre part, nous avons montré que Wt1 se lie au promoteur de c-mip et bloque sa transactivation. Au cours du SNI acquis, les résultats obtenus in vitro et dans les souris transgéniques suggèrent que c-mip inhibe la transcription du gène de Wt1 médiée par NF-κB, interagit avec Wt1 via son domaine LRR et favorise la dégradation de Wt1 par le protéasome.Nous avons également trouvé que c-mip interfère avec l'activation de la voie NF-κB en destabilisant la sous-unité RelA, tandis que la sous-unité p50 est préservée. Les résultats in vitro et dans le modèle murin suggèrent que c-mip est dotée de propriétés pro-apoptotiques.Ces travaux montrent que la protéine c-mip joue un rôle crucial dans la physiopathologie du SNI et constitue une cible thérapeutique de choix. / SummaryPodocyte damages are the initiating event in the pathogenesis of idiopathic nephrotic syndrome (INS). Progression of podocyte disease is associated with cellular depletion and appearance of glomerulosclerosis. The molecular pathophysiology of this disease remains an enigma.We showed that c-mip (c-maf inducing protein) is up-regulated in podocytes during the active phase of INS.We generated c-mip transgenic mice overexpressing c-mip specifically in podocytes. These mice developed morphological and biochemical alterations similar to INS. We demonstrated that c-mip switches off podocyte proximal signaling by preventing the interaction between Fyn and nephrin, resulting in the inhibition of nephrin phosphorylation in vitro and in vivo. Moreover, we found that the in vivo interactions of Fyn with Nck and N WASP are inhibited, which may account for disorganization of the cytoskeleton and the effacement of foot processes.We showed that, under physiological conditions, Wt1 inhibits the transcriptional induction of c-mip. Conversely, we demonstrated that, under pathological conditions, c-mip inhibits NF κB mediated-Wt-1 transcription, interacts in vitro and in vivo with Wt1 via its LRR domain, and targets Wt1 to proteasome degradation.We also observed that the induction of c-mip in patients with INS is correlated with a downregulation of RelA in podocytes. We showed that c-mip alters NF-κB signaling by destabilizing the RelA protein, while p50 is preserved. Morever, the results established in stably transfected podocytes and in transgenic mice suggest that c-mip is a proapoptotic protein.Collectively, these data postulate that c-mip functions as a negative regulator and plays a central role in podocytes disorders during INS.

The 11 year solar-cycle component of climate variability is assessed in historical simulations of models taken from the Coupled Model Intercomparison Project, phase 5 (CMIP-5). Multiple linear regression is applied to estimate the zonal temperature, wind and annular mode responses to a typical solar cycle, with a focus on both the stratosphere and the stratospheric influence on the surface over the period ∼1850–2005. The analysis is performed on all CMIP-5 models but focuses on the 13 CMIP-5 models that resolve the stratosphere (high-top models) and compares the simulated solar cycle signature with reanalysis data. The 11 year solar cycle component of climate variability is found to be weaker in terms of magnitude and latitudinal gradient around the stratopause in the models than in the reanalysis. The peak in temperature in the lower equatorial stratosphere (∼70 hPa) reported in some studies is found in the models to depend on the length of the analysis period, with the last 30 years yielding the strongest response. A modification of the Polar Jet Oscillation (PJO) in response to the 11 year solar cycle is not robust across all models, but is more apparent in models with high spectral resolution in the short-wave region. The PJO evolution is slower in these models, leading to a stronger response during February, whereas observations indicate it to be weaker. In early winter, the magnitude of the modelled response is more consistent with observations when only data from 1979–2005 are considered. The observed North Pacific high-pressure surface response during the solar maximum is only simulated in some models, for which there are no distinguishing model characteristics. The lagged North Atlantic surface response is reproduced in both high- and low-top models, but is more prevalent in the former. In both cases, the magnitude of the response is generally lower than in observations.

Les océans expliquent une part importante de la variabilité des pluies de mousson en Afrique de l’ouest. Quels sont les mécanismes physiques de ces interactions océan– atmosphère ? Comment sont-elles reproduites par les modèles de climat ? Ces deux questions sont ici abordées, en séparant d’emblée les échelles de temps interannuelles et décennales, et en confrontant les simulations réalisées pour le 4e rapport du Groupe intergouvernemental d’experts sur l’évolution du climat (GIEC) aux données observées du xxe siècle. À l’échelle interannuelle, les anomalies de température à la surface du Pacifique équatorial, du golfe de Guinée, et de la Méditerranée sont statistiquement liées aux anomalies des pluies d’Afrique de l’ouest. La question de la stationnarité de ces liens au cours du xxe siècle est brièvement abordée. Les mécanismes physiques sont ensuite appréhendés dans les réanalyses atmosphériques et dans les simulations couplées du GIEC. Pour comprendre le comportement du modèle du Centre national de recherches météorologiques (CNRM), différentes expériences de sensibilité sont réalisées en prescrivant à l’océan une tension de vent réanalysée, sur le Pacifique tropical ou sur tout globe. Une simulation atmosphérique avec des températures de surface prescrites est aussi utilisée pour discuter du rôle du couplage océan–atmosphère. Étant donné le caractère saisonnier de la mousson africaine, le phasage temporel de la variabilité océanique doit être considéré avec attention. Dans les modèles couplés, les biais de l’El Niño–Southern Oscillation (ENSO) et de l’Atlantic Niño conduisent en effet à des interactions océan–mousson différentes de celles observées. À terme, une meilleure compréhension et simulation de la variabilité océanique et de ses influences pourrait permettre d’améliorer les scores de prévision saisonnière sur l’Afrique de l’ouest / The oceans explain an important part of the variability of monsoon rainfall overWest Africa. What are the physical processes of those ocean–atmosphere interactions? How are they simulated by climate models? Both issues are addressed, by considering the interannual and decadal time-scales separately, and comparing the simulations performed for the Intergovernmental Panel on Climate Change (IPCC) to the 20th Century observation record. At the interannual time-scale, sea surface temperature anomalies in the equatorial Pacific, the Gulf of Guinea, and the Mediterranean, are statistically linked to the West African monsoon rainfall. The stationnarity of those links is assessed over the 20th Century. The physical processes are then studied in the atmospheric reanalyses and in the IPCC coupled simulations. To understand the behaviour of the Centre national de recherches météorologiques (CNRM) model, various sensitivity experiments are carried out, with a reanalyzed wind-stress prescribed to the ocean model, over the tropical Pacific or over the global ocean. An atmospheric simulation with prescribed sea surface temperatures is also used, to discuss the role of the ocean–atmosphere coupling. Given the seasonality of the West African monsoon, attention has to be paid to the phaselocking of the oceanic variability. In the coupled models, the biases of the El Niño–Southern Oscillation (ENSO) and of the Atlantic Niño lead indeed to ocean–monsoon interactions that are different from those observed. A better understanding and simulation of the oceanic variability and its influences could in fine enhance the seasonal forecasting skills over West Africa

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

<p>The size and complexity of local area and wide area networks are continually growing and so do the requirements of high availability. Today we rely on the technology and it should always work. Network management is therefore getting more and more important. Network management includes: monitoring and isolating faults, measuring performance, configuring the resources, making sure the network is secured and more. </p><p>Since in the early 1990s the management has typically been done with SNMPv1 or CMIP and using the client/server model. SNMPv1 is insecure, CMIP is complex and the traditional centralized paradigm is no longer sufficient to handle the management requirements of large networks. </p><p>As the demands for security and flexibility increases, new ways to manage networks are needed. This research tries to find out how a network management system should function, what management protocol to use, how to enhance the flexibility and how to make the system more secure.</p>

abstract: The implications of a changing climate have a profound impact on human life, society, and policy making. The need for accurate climate prediction becomes increasingly important as we better understand these implications. Currently, the most widely used climate prediction relies on the synthesis of climate model simulations organized by the Coupled Model Intercomparison Project (CMIP); these simulations are ensemble-averaged to construct projections for the 21st century climate. However, a significant degree of bias and variability in the model simulations for the 20th century climate is well-known at both global and regional scales. Based on that insight, this study provides an alternative approach for constructing climate projections that incorporates knowledge of model bias. This approach is demonstrated to be a viable alternative which can be easily implemented by water resource managers for potentially more accurate projections. Tests of the new approach are provided on a global scale with an emphasis on semiarid regional studies for their particular vulnerability to water resource changes, using both the former CMIP Phase 3 (CMIP3) and current Phase 5 (CMIP5) model archives. This investigation is accompanied by a detailed analysis of the dynamical processes and water budget to understand the behaviors and sources of model biases. Sensitivity studies of selected CMIP5 models are also performed with an atmospheric component model by testing the relationship between climate change forcings and model simulated response. The information derived from each study is used to determine the progressive quality of coupled climate models in simulating the global water cycle by rigorously investigating sources of model bias related to the moisture budget. As such, the conclusions of this project are highly relevant to model development and potentially may be used to further improve climate projections. / Dissertation/Thesis / Ph.D. Mechanical Engineering 2013

The size and complexity of local area and wide area networks are continually growing and so do the requirements of high availability. Today we rely on the technology and it should always work. Network management is therefore getting more and more important. Network management includes: monitoring and isolating faults, measuring performance, configuring the resources, making sure the network is secured and more. Since in the early 1990s the management has typically been done with SNMPv1 or CMIP and using the client/server model. SNMPv1 is insecure, CMIP is complex and the traditional centralized paradigm is no longer sufficient to handle the management requirements of large networks. As the demands for security and flexibility increases, new ways to manage networks are needed. This research tries to find out how a network management system should function, what management protocol to use, how to enhance the flexibility and how to make the system more secure.

Les océans expliquent une part importante de la variabilité des pluies de mousson en Afrique de l'ouest. Quels sont les mécanismes physiques de ces interactions océan- atmosphère ? Comment sont-elles reproduites par les modèles de climat ? Ces deux questions sont ici abordées, en séparant d'emblée les échelles de temps interannuelles et décennales, et en confrontant les simulations réalisées pour le 4e rapport du Groupe intergouvernemental d'experts sur l'évolution du climat (GIEC) aux données observées du xxe siècle. À l'échelle interannuelle, les anomalies de température à la surface du Pacifique équatorial, du golfe de Guinée, et de la Méditerranée sont statistiquement liées aux anomalies des pluies d'Afrique de l'ouest. La question de la stationnarité de ces liens au cours du xxe siècle est brièvement abordée. Les mécanismes physiques sont ensuite appréhendés dans les réanalyses atmosphériques et dans les simulations couplées du GIEC. Pour comprendre le comportement du modèle du Centre national de recherches météorologiques (CNRM), différentes expériences de sensibilité sont réalisées en prescrivant à l'océan une tension de vent réanalysée, sur le Pacifique tropical ou sur tout globe. Une simulation atmosphérique avec des températures de surface prescrites est aussi utilisée pour discuter du rôle du couplage océan-atmosphère. Étant donné le caractère saisonnier de la mousson africaine, le phasage temporel de la variabilité océanique doit être considéré avec attention. Dans les modèles couplés, les biais de l'El Niño-Southern Oscillation (ENSO) et de l'Atlantic Niño conduisent en effet à des interactions océan-mousson différentes de celles observées. À terme, une meilleure compréhension et simulation de la variabilité océanique et de ses influences pourrait permettre d'améliorer les scores de prévision saisonnière sur l'Afrique de l'ouest

The work presented in the thesis focuses on systematically documenting the multi scale nature of the temporal persistence and spatial coherence of tropical rainfall. There are three parts to the thesis: The first two parts utilize satellite-retrieved rainfall at multiple observational resolutions to characterize the space-time organization of rain; the third part assesses the ability of state-of-the-art coupled models to reproduce some of the observed features. In the first part of the study, which focuses on the temporal persistence of rain, we analyze the Tropical Rainfall Measurement Mission (TRMM) satellite-based observations to compare and contrast wet and dry spell characteristics over the tropics (30 S-30 N). Defining a wet (dry) spell as the number of consecutive rainy (nonrainy) days, we find that the distributions of wet spells (independent of spatial resolution) exhibit universality in the following sense. While both ocean and land regions with high seasonal rainfall accumulation (humid regions) show a predominance of 2-4 day wet spells, those regions with low seasonal rainfall accumulation (arid regions) exhibit a wet spell duration distribution that is essentially exponential in nature, with a peak at 1 day. The behaviour that we observed for wet spells is reversed for dry spell distributions. The total rainfall accumulated in each wet spell has also been analyzed, and we find that the major contribution to seasonal rainfall for arid regions comes from very short length wet spells; however, for humid regions, this contribution comes from wet spells of duration as long as 30 days. An exhaustive sensitivity study of factors that can potentially affect the wet and dry spell characteristics (e.g., resolution) shows that our findings are robust. We also explore the role of chance in determining the 2-4 day mode, as well as the inuence of organized convection in separating reality from chance. The second part deals with the spatial coherence of tropical rain. We take two different approaches, namely, a global and local view. The global view attempts to quantify the con-ventional view of rain, i.e., the dominance of the intertropical convergence zone (ITCZ), while the local view tries to answer the question: if it rains, how far is the influence felt in zonal and meridional directions? In both approaches, the classical e-folding length for spatial decorrelation is used as a measure of spatial coherence. The major finding in the global view approach is that, at short timescales of accumulation (daily to pentad to even monthly), rain over the Equator shows the most dominant zonal scale. It is only at larger timescales of accumulation (seasonal or annual) that the dominance of ITCZ around 7 N is evident. In addition, we also find a semi-log linearity between the spatial scales, seen from afar, and timescale of accumulation, with a break in linearity around typical synoptic timescales of 5-10 days. The local view quantifies the dominance of the zonal scale in the tropical ocean convergence zones, with an anisotropy value (ratio of zonal to meridional scales) of 3-4. Over land, on the other hand, the zonal and meridional scales are comparable in magnitude, suggesting that rain tends to be mostly isotropic over continental regions. This latter finding holds true, irrespective of the spatial and temporal resolutions at which rain is observed. Interestingly, the anisotropy over ocean, while invariant with spatial resolution, is found to be a function of temporal resolution: from a value of 3-4 at daily timescale, it decreases to around 1.5 at 3-hourly resolution, suggesting that perhaps rain fundamentally might be isotropic in nature at an event scale. The final part analyses a few models from the suite of Coupled Model Intercomparison Project (CMIP5) models, to evaluate their ability to reproduce some of these aforementioned features. For all the strong biases that models are known to have, some of the observed features are captured well by the models. Specifically, on the temporal persistence front, the observed 2-4 day mode of wet (dry) spells of rain over humid (arid) regions is also seen in models. The overestimation of longer duration wet spells appears to be the primary cause of a positive bias in the number of rainy days from the models. In general, the tendency of models to not stop raining results in lower and higher number of shorter and longer duration wet spells, respectively, and consequently an overall reduction in dry spells of all durations. On the spatial coherence front, the main finding from the global view approach is that the observed semi-log linearity of the zonal spatial scale of rainfall as a function of timescale of accumulation is strikingly well-reproduced by the models. Even more remarkable is that the models are able to mimic the break in this linearity around 5 days (typical synoptic scale). What the models fail to do prominently is the transition of the dominance of equatorial rain at smaller timescales of accumulation to the dominance of ITCZ at around 7 N at higher timescales of accumulation. Based on the local view approach, we find that, in general, even though the zonal and meridional scales are overestimated, the observed isotropy of continental rain is captured very well by the models. Over the oceans, the success is less prominent, especially with the core of the ITCZ showing much larger ratios than those observed. Thus, the models seem to be able to reproduce the anisotropy for the wrong reasons, and the proposed anisotropy ratio could be a useful metric in further diagnosis of climate models.

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