[pt] O presente trabalho teve como objetivo central, a modelagem termodinâmica computacional de escórias contendo TiO2 através do modelo termodinâmico quase-químico estatístico de Kapoor-Frohberg- Gaye. Neste contexto, os seguintes pseudo-binários foram investigados: Al2O3-TiO2, MgOTiO2, MnO-TiO2 e FeO-TiO2. Os resultados das otimizações demonstraram a possibilidade de emprego do referido modelo para uma descrição quantitativa do comportamento termodinâmico destes sistemas. Tanto os diagramas de fases quanto os dados de atividade química foram avaliados e satisfatoriamente descritos pelo modelo. Adicionalmente, ficou evidente a necessidade de correção dos modelos de energia de Gibbs (G) dos óxidos mistos presentes em cada um dos sistemas. As correções determinaram, para a faixa de temperatura onde os dados termodinâmicos foram otimizados, desvios relativos em G inferiores a 1%, sendo perfeitamente aceitáveis, levando-se em consideração comparações entre valores de energia de Gibbs disponíveis na literatura. Os resultados do presente trabalho foram comparados com os obtidos por Erickson e Pelton (1992). Nesta última referência os autores empregaram o modelo de Pelton e Blander (1986), em essência muito similar ao modelo utilizado no presente trabalho. As comparações evidenciaram que os dois modelos podem fornecer uma descrição quantitativa equivalente para o comportamento termodinâmico experimental. / [en] The present work has the main goal of modeling liquid oxide mixtures (slags) by using the Kapoor-Frohberg-Gaye modified quasi- chemical model. In this context the thermodynamic behavior of the following systems was studied: Al2O3-TiO2, MnO-TiO2, MgO-TiO2 and FeO-TiO2. The optimization results confirmed that the Kapoor-Frohberg-Gaye model can in fact be used for the quantitative description of the thermodynamics of all the investigated systems. Phase diagrams and chemical activity data were assessed and satisfactorily described by the model. It was evident that the Gibbs energy (G) of the mixed oxides had to be modified. However, the relative energy corrections for the Gibbs energy was equal or less then 1%, for the temperature range between where the thermodynamic data was optimized, which is quite acceptable, taking into account comparisons of Gibbs energy values from the current literature. Comparisons were done with the results from Erickson e Pelton (1992), which used a modified quasi-chemical model proposed by Pelton e Blander (1986), very similar to the model used in the present work. The comparison shows that the two models can offer an equivalent quantitative description of the experimental thermodynamics.

Flavin adenine dinucleotide (FAD) is a coenzyme that participates in the redox process of flavoenzymes. Attempts to characterize the catalytic pathways of these enzymes have relied in part on the use of FAD chemical models. The efforts described in this dissertation focus on the chemical model approach to investigate the mechanism of the monoamine oxidase (MAO) catalyzed oxidation of the cyclic tertiary allylamine 1-methyl-4-(2-methyl-1H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (TMMP), which is a close analog of the parkinsonian-inducing designer drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAO-B catalyzes the conversion of MPTP and its derivatives into active neurotoxins in the brain that subsequently mediate neurogenerative processes that mimic the events leading to idiopathic Parkinson\'s disease. Monoamine oxidase inhibitors are currently used to treat early stages of Parkinson\'s disease. Two FAD chemical models are examined in this project: 5-ethyl-3-methyllumiflavinium perchlorate (5Et3MLF+ClO4-) and 3-methyllumiflavin (3MLF). The flavinium salt 5Et3MLF+ClO4- is an activated form of 3MLF. These FAD chemical models have been used to examine the MAO catalyzed oxidation. MAO-B is expressed in the brain and is known to be involved in the conversion of TMMP into the neurotoxic metabolite 1-methyl-4-phenyl pyridnium (MMP+). MAO-B is responsible for the alpha-carbon oxidation of TMMP to yield 1-methyl-4-(2-methylpyrrol-2-yl)-2,3-dihydropyridinium (DHP+), which then undergoes a second 2-electron oxidation to MMP+. Previous findings demonstrated that 3MLF and 5Et3MLF+ClO4- promoted the oxidation reaction of primary and secondary amines but not tertiary amines. However, the cyclic tertiary allylamine TMMP has not been examined experimentally. Therefore, the alpha-carbon oxidation of TMMP in the presence of the FAD chemical models is reported in this dissertation. The effect of dioxygen and water on the activity of these FAD models is also investigated. / Ph. D.

Les études astrochimiques de la formation stellaire sont particulièrement importantes pour la compréhension de l'évolution de l'Univers, du milieu interstellaire diffus à la formation des systèmes stellaires. Les récentes avancées en matière de modélisation chimique permettent d'apporter de nouveaux résultats sur le processus de formation stellaire et les structures mises en jeu. L'objectif de ma thèse était donc d'apporter un regard neuf sur la chimie de la formation stellaire en utilisant les récentes avancées sur le modèle chimique Nautilus. J'ai pour cela étudié l'évolution de la chimie du soufre durant la formation stellaire pour tenter d'apporter de nouvelles réponses au problème de déplétion du soufre. J'ai d'abord effectué une révision du réseau chimique soufré et étudié son effet sur la modélisation du soufre dans les nuages denses. En comparant aux observations, j'ai montré que le modèle textsc{Nautilus} était capable de reproduire les abondances des espèces soufrées dans les nuages denses en utilisant comme abondance élémentaire de soufre son abondance cosmique. Ce résultat m'a permis d'apporter de nouveaux indices sur les reservoirs de soufre dans ces objets. Puis j'ai effectué une étude complète de la chimie du souffre dans les coeurs chauds en me concentrant sur les effets sur la chimie de la composition pre-effondrement. J'ai également étudié les conséquences des différentes simplifications couramment faites pour la modélisation des coeurs chauds. Mes résultats montrent que la composition pre-effondrement est un paramètre majeur de l'évolution chimique des coeurs chauds, fournissant de nouveaux indices pour expliquer la variété de compositions en espèces soufrées observée dans ces objets. De plus, ma recherche a mis en évidence la nécessité d'uniformiser les modèles de chimie utilisés pour les coeurs chauds. Enfin, j'ai développé une méthode efficace pour inverser les paramètres initiaux d'effondrement de nuages denses en me basant sur une base de données de modèles physico-chimiques d'effondrement, ainsi que sur l'observation d'enveloppes de protoétoiles de Classe 0. A partir d'un échantillon de 12 sources, j'ai pu en déduire des probabilités concernant les possibles paramètres initiaux d'effondrement de la formation d'étoiles de faible masse. / Astrochemical studies of star formation are of particular interest because they provide a better understanding of how the chemical composition of the Universe has evolved, from the diffuse interstellar medium to the formation of stellar systems and the life they can shelter. Recent advances in chemical modeling, and particularly a better understanding of grains chemistry, now allow to bring new hints on the chemistry of the star formation process, as well as the structures it involves. In that context, the objective of my thesis was to give a new look at the chemistry of star formation using the recent enhancements of the Nautilus chemical model. To that aim, I focused on the sulphur chemistry throughout star formation, from its evolution in dark clouds to hot cores and corinos, attempting to tackle the sulphur depletion problem. I first carried out a review of the sulphur chemical network before studying its effects on the modeling of sulphur in dark clouds. By comparison with observations, I showed that the textsc{Nautilus} chemical model was the first able to reproduce the abundances of S-bearing species in dark clouds using as elemental abundance of sulphur its cosmic one. This result allowed me to bring new insights on the reservoirs of sulphur in dark clouds. I then conducted an extensive study of sulphur chemistry in hot cores and corinos, focusing on the effects of their pre-collapse compositions on the evolution of their chemistries. I also studied the consequences of the use of the common simplifications made on hot core models. My results show that the pre-collapse composition is a key parameter for the evolution of hot cores which could explain the variety of sulphur composition observed in such objects. Moreover, I highlighted the importance of standardizing the chemical modeling of hot cores in astrochemical studies. For my last study, I developed an efficient method for the derivation of the initial parameters of collapse of dark clouds via the use of a physico-chemical database of collapse models, and comparison with observations of Class 0 protostars. From this method, and based on a sample of 12 sources, I was able to derive probabilities on the possible initial parameters of collapse of low-mass star formation.

Les Architectures Orientées Services (SOA) sont adoptées aujourd'hui par de nombreuses entreprises car elles représentent une solution flexible pour la construction d'applications distribuées. Une Application Basée sur des Services (SBA) peut se définir comme un workflow qui coordonne de manière dynamique l'exécution distribuée d'un ensemble de services. Les services peuvent être sélectionnés et intégrés en temps réel en fonction de leur Qualité de Service (QoS), et la composition de services peut être dynamiquement modifiée pour réagir à des défaillances imprévues pendant l'exécution. Les besoins des architectures orientées services présentent des similarités avec la nature: dynamicité, évolutivité, auto-adaptabilité, etc. Ainsi, il n'est pas surprenant que les métaphores inspirées par la nature soient considérées comme des approches appropriées pour la modélisation de tels systèmes. Nous allons plus loin en utilisant le paradigme de programmation chimique comme base de construction d'un middleware. Dans cette thèse, nous présentons un middleware "chimique'' pour l'exécution dynamique et adaptative de SBA. La sélection, l'intégration, la coordination et l'adaptation de services sont modélisées comme une série de réactions chimiques. Tout d'abord, l'instantiation de workflow est exprimée par une série de réactions qui peuvent être effectuées de manière parallèle, distribuée et autonome. Ensuite, nous avons mis en oeuvre trois modèles de coordination pour exécuter une composition de service. Nous montrons que les trois modèles peuvent réagir aux défaillances de type panne franche. Enfin, nous avons évalué et comparé ces modèles au niveau d'efficacité et complexité sur deux workflows. Nous montrons ainsi dans cette thèse que le paradigme chimique possède les qualités nécessaires à l'introduction de la dynamicité et de l'adaptabilité dans la programmation basée sur les services.

Influenza A is involved in hundreds of thousands of deaths globally every year resulting from viral infection-related complications. Previous efforts to subdue the virus by preventing proper function of wild-type (WT) neuraminidase (N), and M2 proteins using oseltamivir and amantadine (AMT) or rimantadine (RMT), respectively, exhibited success initially. Over time, these drugs began exhibiting mixed success as the virus developed drug resistance. M2 is a proton channel responsible for the acidification of the viral interior which facilitates release of the viral RNA into the host. M2 has a His37-tetrad that is the selective filter for protons. This protein has been demonstrated to be a feasible target for organic compounds. However, due to a mutation from serine to asparagine at residue 31 of M2, which is found in the majority of influenza strains circulating in humans, AMT and RMT block is insufficient. From simulations, it is unclear whether the insensitivity results from weak binding or incomplete block. The question of how the S31N mutation caused MT and RMT insensitivity in M2 is addressed here by analyzing the binding kinetics of AMT and RMT using the two-electrode voltage clamp electrophysiology method. The dissociation rate constant (k2) is dramatically increased compared to WT for both AMT and RMT, by 1500-fold and 17000-fold respectively. Testing of AMT at 10 mM demonstrates complete block, albeit weak, of the S31N M2 channel. At 10 mM, RMT does not reach complete block even though the binding site is saturated. When RMT is in the bound state, it is not blocking all the current, and is binding without block. These results motivated the development of novel M2 blockers using copper complexes focusing on the His37 complex in M2. I hypothesized that copper complexes would bind with the imidazole of a histidine in the His37 complex and prevent proton conductance. The His37 complex is highly conserved in the M2 channel and, therefore, would be important target for influenza therapeutics. By derivatizing the amines of known M2 blockers, AMT and cyclooctyalmine, to form the iminodiacetate or iminodiacetamide, we have synthesized Cu(II) containing complexes and characterized them by NMR, IR, MS, UV–vis, and inductively coupled plasma mass spectroscopy (ICP-MS). The copper complexes, but not the copper-free ligands, demonstrated H37-specific blocking of M2 channel currents and low micromolar anti-viral efficacies in both Amt-sensitive and Amt-resistant IAV strains with, for the best case, nearly 10-fold less cytotoxicity than CuCl2. Isothermal titration calorimetry was used to obtain enthalpies that showed the copper complexes bind to one imidazole and curve fitting to the electrophysiology data provided rate constants for binding in the M2 channel. Computational chemistry was used to obtain binding geometries and energies of the copper complexes to the His37-tetrad. The results show that the copper complexes do bind with the His37 complex and prevent proton conductance and influenza infection.

[Truncated abstract] The Swan River is a highly seasonal estuary in the south-west of Western Australia. Salinity may vary from fresh to marine at various times throughout the estuary, depending mostly on the intensity of freshwater discharge. There are occasional problematic dinoflagellate blooms which have spurred investigation of the dynamics of the phytoplankton community. The objective of this research was to examine how phytoplankton biomass and species' successions are influenced by the multiple variables in the aquatic ecosystem, and, if possible, to determine the dominant factors ... Comparisons of phytoplankton nutrient limitation simulations with experimental observations from field bioassays require further investigation, but reinforce findings that nutrients may only limit phytoplankton biomass when there is a convergence of favourable hydrological and hydrodynamic conditions. The Swan River estuary has undergone substantial hydrological modifications from pre-European settlement. Land clearing has increased freshwater discharge up to 5- fold, while weirs and reservoirs for water supply have mitigated this increase and reduced the duration of discharge to the estuary. Nutrient loads have increased approximately 20-fold from pre-European levels. The individual and collective impacts of these hydrological changes on the Swan River estuary were examined using the hydrodynamic-ecological numerical model. The simulation results indicate that despite increased hydraulic flushing and reduced residence times, increases in nutrient loads are the dominant perturbation, producing increases in the frequency and biomass of blooms by both estuarine and freshwater phytoplankton. By comparison, changes in salinity associated with altered seasonal freshwater discharge have a limited impact on phytoplankton dynamics. Reductions of nutrient inputs into the Swan River estuary from its catchment will provide a long-term improvement in water quality but manipulations of freshwater discharge have the potential to provide a provisional short-term remediation measure allowing at least partial control of phytoplankton bloom potential and eutrophication.