Energy-based acoustic quantities provide vital information about acoustic fields and the characterization of acoustic sources. Recently, the phase and amplitude gradient estimator (PAGE) method has been developed to reduce error and extend bandwidth of energy-based quantity estimates. To inform uses and applications of the method, analytical and experimental characterizations of the method are presented. Analytical PAGE method bias errors are compared with those of traditional estimation for two- and three-microphone one-dimensional probes. For a monopole field when phase unwrapping is possible, zero bias error is achieved for active intensity using three-microphone PAGE and for specific acoustic impedance using two-microphone PAGE. A method for higher-order estimation in reactive fields is developed, and it is shown that a higher-order traditional method outperforms higher-order PAGE for reactive intensity in a standing wave field. Extending the applications of PAGE, the unwrapped phase gradient is used to develop a method for directional sensing with improved bandwidth and arbitrary array response.

The carbonate radical anion (CO3•-, CR) is an important reactive oxygen species produced in vivo by one-electron oxidation of CO2 or bicarbonate, constituents of the major physiological buffer. It was demonstrated for the first time by using an HPLC-based analysis of low-molecular products of DNA damage that CRs react with DNA 2΄-deoxyribose by the hydrogen abstraction mechanism. CRs exhibit a ~ 800-fold preference for one-electron oxidation of guanine over hydrogen abstraction from DNA sugar, in sharp contrast with •OH. CRs also have, as compared to •OH, an increased preference for the H1΄ abstraction, which is the most thermodynamically favorable due to the highest stability of the respective deoxyribosyl radical but kinetically the slowest due to low solvent accessibility, by the expense of the decreased preference for the H5΄ abstraction. All these findings are in agreement with the characteristics of CR as a potent oxidant and selective hydrogen abstractor.

8-oxo-7,8-dihydroguanine (8oxoG) is one of the most important base lesions formed during oxidative damage of DNA. The aim of the present research was to investigate the effects of DNA concentration, G content, and the nature of oxidizing species on the kinetics of 8oxoG in model DNA solutions by using HPLC. The experimentally obtained yields of 8oxoG were typically in the range of 2-2.5% of total concentration of guanine. The ratios of the rate constant of hole diffusion in DNA to the rate constant of conversion of the hole into 8oxoG (kd/kr) were calculated from the experimental data using the diffusion model of charge transfer in DNA to be in the range of 200-300, in agreement with previously reported kd/kr ratios in the duplex DNA oligonucleotides (GGA)n or (GGTT)n. Our current diffusion model cannot satisfactorily explain the absence of the G content dependence of the 8oxoG yields, which indicates that a more advanced model is required.

Methamphetamine (METH) is a highly addictive substance that is highly prevalent in today’s society, with over 1 in 20 adults over 26 having taken it at least once. While it is known that METH, a common psychostimulant, acts on both the mesolimbic dopamine (DA) and nigrostriatal DA systems by affecting proteins involved in DA reuptake and vesicular packaging, the specific mechanism of what is known as METH neurotoxicity remains obscure, but has been shown to involve oxidative stress. Studies have shown that reactive oxygen species act on the same proteins that METH affects. Oxidative species have also been known to catalyze the formation of melanins in dopaminergic cells. We explore this link more fully here. In an in vitro system, oxidative species (including Fe3+, an inorganic catalyst for oxidative stress), enhance the rate of melanization of DA. Methamphetamine increased oxidative stress in an in vivo model. Additionally, METH enhanced phasic (stimulated) DA release and caused an electrically-independent efflux of DA. Lidocaine abolished phasic DA release, but did not affect METH-induced DA efflux, indicating action-potential dependent and independent mechanisms behind METH’s effects. The sigma-1 receptor antagonist BD 1063 significantly attenuated METH’s effect on DA release. Depletion of intracellular calcium (Ca2+) reserves also attenuated METH-enhancement of DA release. We investigated the role of oxidative species in METH-induced DA efflux. Reduced glutathione (the substrate for glutathione peroxidase) and 4-hydroxy-TEMPOL (a superoxide dismutase mimetic) blocked METH’s effect on DA release, suggesting that a reactive oxygen species (ROS), most likely superoxide, is necessary for METH-induced DA efflux. Finally, oxidative stress as well as acute METH impairs the vesicular monoamine transporter 2 (VMAT2) by S-glutathionylation modification of Cys-488, highlighting VMAT2 as a likely regulator of METH’s effects on electrically independent DA release. These findings help outline a model in which METH induces DA release in the NAc through a signaling cascade involving the sigma receptor and ROS signaling molecules.

Marital quality is linked to health benefits for men and women. Although women have less risk factors than men for cardiovascular disease prior to menopause, their risk increases substantially after menopause. The purpose of this study was to assess the impact of marital quality and vasomotor symptoms on cardiovascular risk factors including C-reactive protein (CRP) and carotid intima-media thickness (cIMT) in women before, during, and after the menopausal transition. The final sample consisted of 92 married women between the ages of 40 and 60 years. Hypotheses were tested using hierarchical regression and general linear modeling. Results suggest that greater marital quality reduces the negative effect of a lower level of vasomotor symptoms on cIMT but not CRP. Contrary to hypotheses, marital quality did not predict CRP or cIMT and vasomotor symptoms were not correlated with CRP or cIMT. While analyses did not support an interaction between menopausal status and lower marital quality on vasomotor symptoms or CRP, there was limited support for an interaction between menopausal status and lower marital quality on cIMT (p = .057) suggesting that for postmenopausal women higher marital quality is related to lower levels of cIMT. Overall, findings suggest that it is important to consider the impact of psychosocial aspects of a middle aged woman's life (i.e., marital quality) in conjunction with biological stressors when assessing cardiovascular risks in women during the menopausal transition.

Orientador: Antonio Roberto Balbo / Banca: Leonardo Nepomuceno / Banca: Marcelo Suetake / Banca: Washington Alves de Oliveira / Banca: Daniela Renata Cantane / Resumo: O problema multiobjetivo de despacho econômico e ambiental com efeito de pontos de carregamento de válvula e com perdas de potência ativa, é um problema de otimização multiobjetivo, não convexo e não-diferenciável. Por apresentar tais características, normalmente, é resolvido na literatura, através de abordagens heurísticas de otimização. Com a inserção da representação da transmissão (fluxo de potência) ao problema multiobjetivo, o mesmo torna-se mais complexo de ser solucionado. Devido a estas dificuldades, são escassas as abordagens determinísticas de otimização para solução destes tipos de problemas, uma vez que elas necessitam do cálculo de derivadas parciais, enquanto que, as heurísticas não necessitam. Portanto, os principais objetivos deste trabalho são: propor uma abordagem determinística para a solução dos problemas em destaque e comparar com outros métodos disponíveis na literatura, principalmente os métodos heurísticos e meta-heurísticos. A abordagem determinística proposta tem as seguintes características: tratar a natureza multiobjetivo dos problemas através da estratégia de Restrições Canalizadas Progressivas (RCP); utilizar uma técnica de suavização de funções para lidar com a não diferenciabilidade e, por fim, utilizar um método de rescalamento não-linear, baseado na função barreira logarítmica modificada, com procedimento previsor-corretor e estratégia de correção de inércia para resolver os subproblemas resultantes da estratégia RCP. A metodologia proposta ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The multiobjective economic and environmental dispatch problem with valve-point loading effects and losses is a multiobjective, non-convex and non-differentiable optimization problem. Due to these characteristics, it has been solved in the literature mainly by heuristic approaches. The addition of the network representation to the multiobjective problem makes it more complex to be solved. Due to these difficulties, there are few deterministic optimization approaches for solving these problems. While deterministic optimization approaches require the calculation of partial derivatives, heuristic approaches do not. Therefore, the main objective of this work is to propose a deterministic approach to solve these problems and compare it with other methods available in the literature, especially the heuristic and metaheuristic methods. The proposed deterministic approach has the following characteristics: the multiobjective nature of the problems is handled through the Progressive Bounded Constraint (PBC) strategy, a smoothing function technique is employed to deal with the cost function non-differentiability and, finally, the non-linear rescaling method, based on the modified logarithmic barrier function, with predictorcorrector procedure and inertia correction strategy, is applied to solve the single objective subproblems resulting from the PBC method. The proposed methodology is applied to the test systems with 2, 6, 10, 19 and 40 generators for the multiobjective dispatch proble... (Complete abstract click electronic access below) / Doutor

Parkinson's disease (PD) is a progressive neurodegenerative and movement disorder that involves specific loss of dopaminergic neurons in the substantia nigra of the brain. Exact causes of PD are unknown. However, cells affected in PD are centers of dopamine (DA) synthesis, storage, and metabolism, which implicate DA as an endogenous neurotoxin that contributes to PD. Furthermore, DA is known to undergo oxidation to radicals and quinones. These reactive species exert deleterious effects on cells through a variety of mechanisms that are relevant to the pathogenesis of PD. Another potential mechanism of toxicity for DA is metabolism to 3,4-dihydroxyphenylacetaldehyde (DOPAL). This reactive metabolite is significantly more toxic than the parent DA. DOPAL has several demonstrated mechanisms of toxicity, including formation of protein-adducts via reaction with amine-type cellular nucleophiles. However, known toxicity mechanisms do not fully account for DOPAL's high toxicity. Oxidation of DOPAL to a reactive quinone or radical could help explain its high toxicity. Therefore, the hypothesis of this work is that DOPAL is capable of undergoing oxidation that leads to increased protein modification and nucleophilic reactivity. Experimentally, oxidation of DOPAL results in formation of a semi-quinone radical and an ortho-quinone, as confirmed by electron paramagnetic resonance spectroscopy and nuclear magnetic resonance spectroscopy, respectively. In agreement with the stated hypothesis, oxidation of DOPAL enhanced its ability to induce protein cross-linking of a model protein (glyceraldehyde 3-phosphate dehydrogenase) as indicated by polyacrylamide gel-electrophoresis. Also, the presence of anti-oxidants (ascorbate, N-acetyl cysteine) attenuated the reactivity of DOPAL with the model aminenucleophile N-acetyl lysine. These results indicate that DOPAL oxidation enhances both protein cross-linking and nucleophilic reactivity. This work resulted in several other important findings. DOPAL is shown to undergo carbonyl-hydration in aqueous media, and spontaneous oxidation of DOPAL results in formation of superoxide. Furthermore, DOPAL is shown to be susceptible to oxidation by cyclooxygenase-2, an enzyme known to be involved in PD. This provides a potential mechanism for formation of the oxidized products identified here. As DA metabolism and oxidation occur in cells affected by PD, the experimental results demonstrated here are likely relevant for understanding the pathogenesis of PD.

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In this dissertation, several volt-var optimization methods have been proposed to improve the expected performance of the distribution system using distributed renewable energy sources and conventional volt-var control equipment: photovoltaic inverter reactive power control for chance-constrained distribution system performance optimisation, integrated distribution system optimization using a chance-constrained formulation, integrated control of distribution system equipment and distributed generation inverters, and coordination of PV inverters and voltage regulators considering generation correlation and voltage quality constraints for loss minimization. Distributed generation sources (DGs) have important benefits, including the use of renewable resources, increased customer participation, and decreased losses. However, as the penetration level of DGs increases, the technical challenges of integrating these resources into the power system increase as well. One such challenge is the rapid variation of voltages along distribution feeders in response to DG output fluctuations, and the traditional volt-var control equipment and inverter-based DG can be used to address this challenge. These methods aim to achieve an optimal expected performance with respect to the figure of merit of interest to the distribution system operator while maintaining appropriate system voltage magnitudes and considering the uncertainty of DG power injections. The first method is used to optimize only the reactive power output of DGs to improve system performance (e.g., operating profit) and compensate for variations in active power injection while maintaining appropriate system voltage magnitudes and considering the uncertainty of DG power injections over the interval of interest. The second method proposes an integrated volt-var control based on a control action ahead of time to find the optimal voltage regulation tap settings and inverter reactive control parameters to improve the expected system performance (e.g., operating profit) while keeping the voltages across the system within specified ranges and considering the uncertainty of DG power injections over the interval of interest. In the third method, an integrated control strategy is formulated for the coordinated control of both distribution system equipment and inverter-based DG. This control strategy combines the use of inverter reactive power capability with the operation of voltage regulators to improve the expected value of the desired figure of merit (e.g., system losses) while maintaining appropriate system voltage magnitudes. The fourth method proposes a coordinated control strategy of voltage and reactive power control equipment to improve the expected system performance (e.g., system losses and voltage profiles) while considering the spatial correlation among the DGs and keeping voltage magnitudes within permissible limits, by formulating chance constraints on the voltage magnitude and considering the uncertainty of PV power injections over the interval of interest. The proposed methods require infrequent communication with the distribution system operator and base their decisions on short-term forecasts (i.e., the first and second methods) and long-term forecasts (i.e., the third and fourth methods). The proposed methods achieve the best set of control actions for all voltage and reactive power control equipment to improve the expected value of the figure of merit proposed in this dissertation without violating any of the operating constraints. The proposed methods are validated using the IEEE 123-node radial distribution test feeder.

L’ATP est synthétisée par les mitochondries à partir de réactions d’oxydoréduction catalysées les complexes de la chaîne respiratoire. Ces réactions impliquent des transferts d’électrons intra-protéine. Une capacité de production de l’anion superoxyde, formé par la réaction de l’oxygène avec un électron, a été identifiée pour les complexes I et III. Les espèces actives de l’oxygène (EAOs) sont des molécules dérivées de l’anion superoxyde. Si elles ne sont pas correctement régulées par les défenses antioxydantes de la cellule, ces EAOs peuvent réagir avec les composants de la cellule et nuire à son fonctionnement : ce déséquilibre est appelé stress oxydatif. L’altération d’un ou plusieurs complexes respiratoires associée à un stress oxydatif cellulaire est un mécanisme commun à de nombreuses maladies neurodégénératives. Dans ce travail nous nous intéressons plus particulièrement à l’atrophie optique autosomique dominante de type 1 (ADOA-1). L’ADOA-1 est une maladie neurodégénérative principalement causée par des mutations du gène codant la protéine mitochondriale OPA1 impliquée dans la dynamique mitochondriale. Les tableaux cliniques et l’âge de début de la maladie sont variables. Il n’existe pas de corrélation claire entre génotypes et phénotypes permettant d’expliquer cette variabilité ni de traitement à cette pathologie. L’hypothèse d’un stress oxydatif a été proposée pour expliquer la variabilité de ces symptômes. C’est pourquoi notre objectif est d’améliorer la compréhension des mécanismes physiopathologiques impliqués dans cette maladie en développant des modèles mathématiques de la production des EAOs par la chaîne respiratoire. Nous avons utilisé deux méthodes de modélisation. Dans le premier cas, nous modélisons l’activité des complexes respiratoires et la production d’anion superoxyde par les complexes I et III par des équations de vitesse que nous construisons en trois étapes. Nous analysons d’abord les données biochimiques disponibles dans la littérature. Nous proposons ensuite des interprétations physiques à ces comportements et les traduisons sous forme de règles floues. Nous modélisons enfin ces règles en utilisant des fonctions données par le formalisme de Michaelis-Menten. Les équations de vitesse sont fonction de variables chimiques telles que la concentration des espèces chimiques impliquées dans les réactions des complexes respiratoires et ne prennent pas en compte le détail des réactions intra-protéine impliquées dans le fonctionnement des complexes. Cette méthode permet de construire un modèle simple, permettant de simuler l’activité des complexes I et III et leur production de superoxyde dans différentes conditions, et qui est facilement modifiable ou intégrable dans un modèle plus complet de la mitochondrie. Le modèle du complexe I que nous avons créé, est capable de simuler l’activité catalytique et la production des EAOs en mode direct par le complexe I pour différentes configurations et concentrations de substrats et produits. / Mitochondria are cellular organelles involved in ATP (adenosine triphosphate) supply to cells. Mitochondrial ATP is produced by the oxidative phosphorylation which involves redox reactions catalysed by the four protein complexes of the mitochondrial respiratory chain. These redox reactions require intra-protein electron transfers. The complex I and complex III of the respiratory chain are able to generate superoxide anion, which is formed by the reaction of oxygen with one electron. Reactive oxygen species (ROS) are molecules derived from the superoxide anion. ROS which are not regulated by cellular antioxidant defences can react with the components of the cells and disturb its functioning: this imbalance between ROS and antioxidant defences has been termed “oxidative stress”. Dysfunctions of one or several respiratory complexes associated to an oxidative stress is a mechanism common to numerous neurodegenerative diseases. In this work, we focus on autosomal dominant optic atrophy 1 (ADOA-1 or DOA-1). DOA-1 is a neurodegenerative pathology mainly caused by mutations in the gene OPA1 which codes for a mitochondrial protein involved in mitochondrial dynamics. The symptoms and ages of onset of the disease are variable. There is no clear correlation between genotypes and phenotypes which can explain this variability and to date, there is no established medical treatment for the disease. The hypothesis of an oxidative stress has been proposed to explain the variability of symptoms observed in patients. Indeed, the mitochondrial energetic metabolism is altered in biological models (cell cultures and animal models) of DOA-1 and low levels of antioxidant defences have been measured in cells from patients suffering from severe forms of the pathology. Hence, our objective is to improve the understanding of the physio-pathological mechanisms involved in this disease by developing mathematical models of ROS production by the respiratory chain. We use two modelling methods. The first method consists in modelling the activities of respiratory complexes and the superoxide production by complexes I and III with rate equations that we build in three steps. We first analyse the biochemical data available in the literature. We subsequently interpret this data physically and translate them in the form of fuzzy rules. We then model these rules with mathematical functions provided by the formalism of Michaelis-Menten. The rate equations depend on chemical variables such as the concentrations of chemical species involved in the reactions catalysed by the respiratory complexes. They do not include the details of intra-protein electron transfers, occurring during the catalysis performed by the complexes. This method enables us to build a simple model simulating the activities and superoxyde productions of complexes I and III in different conditions and that can easily be modified or integrated in a more comprehensive model of the mitochondrion. Our model of complex I can simulate the forward and reverse activities and ROS productions of the enzyme for different concentrations of substrates and products.