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

Metabolites consumed and produced by microorganisms for mass and energy conservation may cause changes in a microorganism’s environment. The microorganisms are unable to tolerate a particular environment for a long period. They may leave their old existence to find a new environment to sustain life. Essentially, organisms need to maintain their metabolic processes to survive in the new environment. Limitations of experimental studies to explore cell functions and regulations in detail result in insufficient information to explain processes of metabolic expressions under environments of organisms. Consequently, mathematical modeling and computer simulations have been conducted to combine all possible cellular metabolic fluxes into single or multiple connected networks. Metabolic modeling based on linear programming (LP) subjected to constraints with an optimization approach is often applied metabolic reconstruction. The LP objective function is maximized to obtain an optimal value of biomass flux. Optimal solutions in LP problems can be used to explain how metabolites function in metabolic reactions. As an LP problem may have many optimal solutions, this study proposes a method for enumerating all alternate optimal solutions to evaluate important reactions of metabolic pathways in microorganisms. The algorithm for generating alternate optimal solutions is implemented in MetModelGUI, a Java-based software for creating and analyzing metabolic reconstructions. The algorithm is applied to models of five microorganisms: Trypanosoma cruzi, Thermobifida fusca, Helicobacter pylori, Cryptococcus neoformans and Clostridium thermocellum. The results are analyzed using principal component analysis, and insight into the essential and non-essential pathways for each organism is derived

Le fer est un micronutriment important pour la croissance et le développement des plantes. Il agit comme cofacteur pour plusieurs enzymes et il est important pour des processus tels que la photosynthèse et la respiration. Souvent, le Fe dans le sol n’est pas bio-disponible pour la plante. Les plantes ont développé des stratégies pour solubiliser le Fe du sol pour le rendre disponible et assimilable pour elles. Il y a deux stratégies, la première est caractéristique des dicotylédones et la seconde est caractéristique des monocotylédones. Le modèle utilisé dans cette étude est une culture cellulaire de Solanum tuberosum. Une partie de la recherche effectuée a permis la mesure d’activité et d’expression relative de certaines enzymes impliquées dans le métabolisme énergétique et la fourniture de précurseurs pour la synthèse d’ADN : la Nucléoside diphosphate kinase, la Ribonucléotide reductase, la Glucose 6-phosphate déshydrogénase et la 6-Phosphogluconate déshydrogénase dans les cellules en présence ou en absence de Fe. Chez certains organismes, la déficience en Fe est associée à une perte de croissance qui est souvent liée à une diminution de la synthèse d’ADN. Chez les cultures de cellules de S. tuberosum, les résultats indiquent que la différence de biomasse observée entre les traitements n’est pas due à une variation de l’activité ou l’expression relative d’une de ces enzymes. En effet, aucune variation significative n’a été détectée entre les traitements (+/- Fe) pour l’activité ni l’expression relative de ces enzymes. Une autre partie de la recherche a permis d’évaluer l’activité des voies métaboliques impliquées dans la stratégie 1 utilisée par S. tuberosum. Cette stratégie consomme des métabolites énergétiques: de l’ATP pour solubiliser le Fe et du pouvoir réducteur (NAD(P)H), pour réduire le Fe3+ en Fe2+. Des études de flux métaboliques ont été faites afin d’étudier les remaniements du métabolisme carboné en déficience en Fe chez S. tuberosum. Ces études ont démontré une baisse du régime dans les différentes voies du métabolisme énergétique dans les cellules déficientes en Fe, notamment dans le flux glycolytique et le flux de C à travers la phosphoenolpyruvate carboxylase. En déficience de Fe il y aurait donc une dépression du métabolisme chez S. tuberosum qui permettrait à la cellule de ralentir son métabolisme pour maintenir sa vitalité. En plus des flux, les niveaux de pyridines nucléotides ont été mesurés puisque ceux-ci servent à réduire le Fe dans la stratégie 1. Les résultats démontrent des niveaux élevés des formes réduites de ces métabolites en déficience de Fe. L’ensemble des résultats obtenus indiquent qu’en déficience de Fe, il y a une baisse du métabolisme permettant à la cellule de s’adapter et survivre au stress. / Iron is an important micronutrient for plant growth and development. It participates as a cofactor for several enzymes and is important for processes such as photosynthesis and respiration. Often soil Fe is not bioavailable to the plant. Plants have developed strategies to solubilize the Fe in the soil to make it available and easy to assimilate. There are two strategies, the first is characteristic of dicotyledones and the second is characteristic of monocotyledones. The model used in these studies is a cell culture of Solanum tubersoum. A first part of the research involved the study of expression and activity of enzymes required in energy metabolism and the provision of precursors for DNA synthesis: Nucleoside dehydrogenase, Ribonucleotide reductase, Glucose 6-phohate dehydrogenase and 6-Phosphogluconate dehydrogenase. In several organisms, Fe deficiency induces a loss of biomass which is often associated with a decrease in DNA synthesis. In S. tuberosum cell cultures, the results indicate that the loss of biomass observed in Fe deficiency is not linked to a change in the activity or relative expression of these enzymes. Indeed, no significant changes were detected between treatments (+/- Fe) for activity or relative expression. In another part of the research, we evaluated the activity of the metabolism pathways involved in strategy 1, which is used by S. tuberosum. This strategy consumes energetic metabolites: ATP to solubilize Fe and reducing power (NAD(P)H) to reduce the Fe3+ to Fe2+. Metabolic flux studies were done to investigate the alterations of carbon metabolism during Fe deficiency in S. tuberosum. These studies demonstrated that in Fe deficient cells, there is a decrease in the fluxes of some pathways of energy metabolism. Particularly, in the glycolytic flux and the anaplerotic flux of PEPC. Under Fe deficiency there would be a depression of metabolism in S. tuberosum which would allow the cell to slow its metabolism to maintain its vitality. In addition to the fluxes, the levels of pyridine nucleotides were measured since they serve to reduce Fe in the strategy 1. The results show an increase in the reduced forms of these metabolites during Fe deficiency. All results together point out that during Fe deficiency the metabolism decreases, allowing the cell to survive and adapt to the stress.

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

Les microsystèmes sont des réacteurs extraordinaires pour mettre en œuvre des réactions chimiques car ils apportent un rapport de contact entre phases très supérieur à celui en ballon, la possibilité d’hypertrempe thermique tant au chauffage qu’au refroidissement et enfin l’absence d’interaction des réactifs avec les produits. Les dimensions micro-ou nanométriques de ces réacteurs sont très largement compensées par la possibilité de parallélisation à grande échelle de ces réacteurs qui permet une montée en échelle de la production sans nouveau développement. Nous avons choisi comme réaction test l’alkylation des acides benzoïques substitués par l’iodure de méthyle en présence d’une éponge à proton (TMGN). Cette réaction a été choisie car elle suit une cinétique parfaitement du second ordre. Nous avons ainsi pu montrer que cette réaction suit la relation de Hammett, déterminer le paramètres de réactivité  pour cette réaction et en opérant à température variable mesurer l’énergie et l’entropie d’activation. Nous avons également réalisé des expériences préparatives sur des substrats bifonctionnels simples et mis en évidence la sélectivité en système microfluidique. Une étude comparative de la basicité des superbases organiques comparée à la vitesse d’alkylation par l’iodure de méthyle a effectué pour mieux cerner le rapport basicité, nucléophilie de ces bases qui est peu étudié. Parallèlement l’alkylation d’un polyphénol complexe la quercétine et de substrats à haute valeur ajoutée tels que le Trolox, l’acide clofibrique et l’acide podocarpique à l’aide de systémes microfluidiques ont été étudié à l’échelle de la millimole. / Microfluidic devices have extensively been used in chemical synthesis, due to providing high surface area between phases, ease of heating or cooling and the absence of interaction between products and reactants. Microreactors can be used in parallel for scale-up purposes without any additional designing step. Here, we have studied the alkylation of substituted benzoic acids by iodomethane at the presence of a proton sponge (TMGN). This reaction was chosen because it follows second-order kinetics. The Hammett reaction constant was obtained for this reaction and by studying the reaction kinetics in different temperatures, the activation parameters were obtained. Using this set-up and using bi-functional substrates the reaction selectivity in microsystem was also investigated. By this microreactor kinetics of N-alkylation of several organic superbases by iodomethane was also studied. Finally, the microreactor system enabled small scale synthesis of several natural compounds. The alkylation of quercetin, Trolox, clofibrique acid and podocarpic acid by iodomethane at the presence of TMGN was conducted at the scale of millimole.

Establishing metrics of diversification can calibrate the observed scope of diversity within a lineage and the potential for further phenotypic diversification. There are two potential ways to calibrate differences between phenotypes. The first metric is based on the structure of the network of direct and indirect connections between elements, such as the genes, proteins, enzymes and metabolites that underlie a phenotype. The second metric characterizes the dynamic properties that determine the strength of the interactions among elements, and influence which elements are the most likely to interact. Determining how the connectivity and strength of interactions between elements lead to specific phenotypic variations provides insight into the tempo and mode of observed evolutionary changes. In this dissertation, I proposed and tested hypotheses for how the structure and metabolic flux of a biochemical network delineate patterns of phenotypic variation. I first examined the role of structural properties in shaping observed patterns of carotenoid diversification in avian plumage. I found that the diversification of species-specific carotenoid networks was predictable from the connectivity of the underlying metabolic network. The compounds with the most enzymatic reactions, that were part of the greatest number of distinct pathways, were more conserved across species’ networks than compounds associated with the fewest enzymatic reactions. These results established that compounds with the greatest connectivity act as hotspots for the diversification of pathways between species. Next, I investigated how dynamic properties of biochemical networks influence patterns of phenotypic variation in the concentration and occurrence of compounds. Specifically, I examined if the rate of compound production, known as metabolic flux, is coordinated among compounds in relation to their structural properties. I developed predictions for how different distributions of flux could cause distinct diversification patterns in the concentrations and presence of compounds in a biochemical network. I then tested the effect of metabolic network structure on the concentrations of carotenoids in the plumage of male house finches (Haemorhous mexicanus) from the same population. I assessed whether the structure of a network corresponds to a specific distribution of flux among compounds, or if flux is independent of network structure. I found that flux coevolves with network structure; concentrations of metabolically derived compounds depended on the number of reactions per compound. There were strong correlations between compound concentrations within a network structure, and the strengths of these correlations varied among structures. These findings suggest that changes in network structure, and not independent changes in flux, influence local adaptations in the concentrations of compounds. Lastly, the influence of carotenoid network structure in the evolutionary diversification of compounds across species of birds depends on how the structure of the network itself evolves. To test whether the carotenoid metabolic network structure evolves in birds, I examined the patterns of carotenoid co-occurrence across ancestral and extant species. I found that the same groups of compounds are always gained or lost together even as lineages diverge further from each other. These findings establish that the diversification of carotenoids in birds is constrained by the structure of an ancestral network, and does not evolve independently within a lineage. Taken together, the results of this dissertation establish that local adaptations and the evolutionary diversification of carotenoid metabolism are qualitatively predictable from the structure of an ancestral enzymatic network, and this suggests there is significant structural determinism in phenotypic evolution.

: In freshwater systems phosphorus (P) is the limiting element in the cause of eutrophication. In many Swedish lakes, causes of eutrophication have been attributed to more of internal loading than external since the external loading has been fairly well managed. Internal loading is linked to the mobility of sediment P, which are known to be Bioavailable P (BAP). Sediments from Lake Hällerstadsjön in Sweden was studied to know the BAP concentration and its possible release into the water column under reduced conditions. Sediments were sampled at two different depths, 0-5 cm and 5-10cm. BAP was determined by a phosphorus fractionation scheme. Sediments were incubated under oxic and anoxic conditions in the laboratory to evaluate sediment P release. Spatial variation in the distribution of P forms across the lake was also studied, in order to examine possible local patterns, particularly along a transect from the main inlet to the outlet. Fractionation analyses showed a trend of; Residual-P > NaOH-P > HCl-P > BD-P > Loosely bound P. The fractions constituting the BAP was higher at the 0-5 cm sediment depth than 5-10 cm. Sediment P flux was recorded for anoxic but not oxic sediment. BAP correlated significantly with sediment P flux (P= 0.01). Spatially, the P distribution varied both at depths and along a latitudinal transect, from the main inlet to the outlet.  Dredging of the surface sediments with high BAP content would possibly be an effective means of preventing eutrophication of the lake.

Student Number : 9608998A - MSc dissertation - School of Electrical and Information Engineering - Faculty of Engineering and the Built Environment / The history of flux compression is relatively short. One of the founders, a Russian physicist, Sakharov developed the idea of compressing a magnetic field to generate high magnetic fields and from this he also developed a generator to produce current impulses. Most of this initial work was performed in military research laboratories. The first open source literature became available in the 1960s and from there it has become an international research arena. There are two types of flux compression generators, field generators and current generators. These are discussed along with the basic theory of flux compression generators and related physics. The efficiency of generators is often quite low. However in many generators high explosives are used and because of their high energy density, the current or field strength produced is substantially greater then the initial source. This of course limits the locations possible for experimental work and subsequently limits the industrial applications of flux compression generators . This research presents a theoretical design for a non-explosive flux compression generator. The generator is designed to produce a current impulse for tests in laboratory and remote locations. The generator has the advantage of being non-destructive, therefore reducing costs, and allowing for repeatable experiments. The design also reduces the possibilities or many of the loss mechanisms.

[pt] A barragem de Itaipu consiste em uma série de estruturas cujo comprimento total é de 7744 m. Uma dessas estruturas é a Barragem de Terra da Margem Esquerda (BTME), cuja extensão é de 1989 m. A BTME está fundada diretamente sobre o solo do local, que consiste em um perfil de intemperismo de basalto, indo desde argila, na superfície, à rocha sã. Seu comportamento é monitorado por 9 piezômetros elétricos, 26 piezômetros standpipe, 12 medidores de nível d`água e seis medidores de vazão. Os medidores de vazão foram inicialmente projetados para medir a água de percolação pelo corpo da barragem. Para tanto, a barragem dispõe de um sistema de canaletas para coletar a água que sai dos filtros internos e conduzi-la aos medidores. Contudo, só ocorre saída de água pelos filtros em pequenos trechos da barragem e não se tinha conhecimento da origem das águas medidas, pois ao longo da operação da usina, alterações foram feitas para drenar áreas alagadas e a água de drenagem foi conduzida ao sistema de canaletas. O objetivo desta dissertação é identificar a origem das águas medidas pelos medidores de vazão e entender como se dá o fluxo pela fundação e corpo da barragem de terra da margem esquerda. Para tanto, utilizou-se um modelo em elementos finitos, com o programa SEEP/W, para oito seções instrumentadas da barragem e procedeu-se correlações estatísticas entre todos os instrumentos da BTME. A principal conclusão obtida foi de que os medidores de vazão medem primordialmente água do reservatório que infiltra pelas fundações e que apenas uma parcela da água infiltrada é medida. / [en] The Itaipu dam consists of a series of different structures with a total length of 7744m. One of these structures is the Left Bank Earthfill Dam (LBED), whose length is 1989m. The LBED is founded directly in the local soil, which consists of a residual soil of basalt. The behaviour of the earthdam is monitored by 9 electric piezometers, 26 standpipe piezometers, 12 water level indicators and 6 flow meters. The flow meters were initially designed to measure the seepage through the dam body. For this purpose, the dam has a system of ditches to collect the water from the internal filters and to lead the water until a flow meter. However, there is water leaving the internal filters just in a little portion of the dam. In addition, there was no knowledge of the origin of the water that is measured in the flow meters, because many alterations were made in the operation of the dam to drain flooded areas. The drained water was conducted to the system of ditches. This work aims to identify the origin of the water measured in the flow meters and understand the seepage through the dam and its foundation. For this purpose a Finite Element Method analysis for eight instrumented sections was performed using the SEEP/W program. In addition, statistical correlations between data from all instrumentation of the LBED and rainfall were made. The main conclusion is that most of the water measured in the flow meters comes from the reservoir through the foundation. And only a little amount of the total seepage through the foundation is measured.

L’idée centrale de notre analyse sur l’économie française concerne la suprématie des taux d’intérêt et des dépenses publiques comme instruments de politique économique. Avec la forte hausse des taux d’intérêt au début des années 1980, les entreprises non financières ont commencé à demander moins de crédit, tandis que les ménages français, ainsi que d’autres économies en voie de développement en ont demandé davantage. Parallèlement à ces développements, les marchés spéculatifs ont dominé la bourse, le taux de chômage a augmenté, et un processus de libéralisation a suivi. Nous analysons les conséquences de ce processus de financiarisation et certains scénarios possibles en France, tout en utilisant un modèle de type Cowles Commission, qui est à son tour fondé sur la littérature stock-flux. Une attention particulière est donnée aux variables de répartition et fiscales. Les résultats du modèle indiquent que (étant donné que les entreprises françaises sont prises dans une trappe à liquidité) le taux d’intérêt a perdu son pouvoir comme une variable de politique. En revanche, les dépenses publiques ont une puissance expansionniste importante. / The core of our analysis of the French economy concerns the supremacy of interest rates and government spending as policy instruments in this economy. With the strong increase in interest rates at the beginning of the 1980s, non-financial firms started to demand less credit, whereas French households and other developing economies demanded more. Parallel to these developments, bulls became more abundant in stock markets, the unemployment rate soared and a full process of liberalization ensued. We analyze the consequences of this financialization process and some feasible scenarios in France by means of a Cowles Commission-type model that is in turn based on the stock-flow literature. Particular emphasis is given to distributive and fiscalvariables. The model’s results indicate that (given that French firms are caught in a liquidity trap) the interest rate has lost its power as a policy variable. In contrast, public spending has an important expansionary power.