Os estimadores de estado são ferramentas primordiais para monitoramento em tempo real dos sistemas elétricos de potência, principalmente por permitir a execução de funções básicas relacionadas à segurança destes sistemas. No entanto, nos sistemas de distribuição, por possuírem uma série de particularidades e pelo reduzido número de medidas disponíveis em tempo real, os estimadores de estado convencionais desenvolvidos para sistemas de transmissão não são capazes de oferecer boas estimativas para determinação do estado da rede. Neste contexto, o Estimador de Demanda Trifásico em Tempo Real (EDTTR) desenvolvido neste trabalho, fundamentado nos métodos de estimação de demanda, tem como foco principal proporcionar maior precisão ao monitoramento da rede primária de alimentadores de distribuição radiais, ao contemplar as características intrínsecas do modelo da rede. O EDTTR consiste em dois estágios principais: o primeiro é caracterizado pela estimação off-line das demandas dos transformadores de distribuição por meio do processo de agregação de cargas, considerando informações dos consumidores. O segundo estágio é realizado em tempo real, utiliza um algoritmo eficiente de Varredura Direta Inversa para a solução do fluxo de carga, auxiliado da estrutura de dados chamada Representação Nó-Profundidade para armazenar a topologia da rede. Neste estágio também ocorre o ajuste recursivo das estimativas obtidas no Estágio 1 com base nas poucas medidas disponíveis em tempo real. No intuito de melhorar a representação da rede primária, o EDTTR desenvolvido possibilita o tratamento dos transformadores de distribuição conectados em Delta-Yn. Esta proposição permite uma caracterização do modelo das cargas mais fiel, sendo capaz de superar problemas de convergência, além de contribuir para a qualidade do processo de estimação. Desenvolveu-se, também, uma plataforma de testes que permite a análise do impacto de fatores que deterioram o processo de estimação de demandas, como: a má classificação dos consumidores, o comportamento dos mesmos, que na prática não é exatamente igual ao da classe de carga a ele atribuída, a possibilidade de perdas não técnicas, erros grosseiros e falhas de comunicação nos medidores do alimentador. O EDTTR foi validado em simulações utilizando um alimentador real da cidade de Ribeirão Preto com base em dados fornecidos pela distribuidora CPFL Paulista. / The state estimators are primordial tools for electric power systems real time monitoring. These tools allow the execution of basic functions related to systems security. However, conventional state estimators, developed for transmission systems, can not provide good estimates to the state of distribution systems. This is due to two main factors, the few real time measures available in distribution systems, and the intrinsic complexity of them. In this context, the developed Real Time Three-Phase Load Estimator (EDTTR), based on load estimation methods, aims to provide better estimates to the monitoring of the primary network of radial distribution feeders, considering all the intrinsic sets of the system model. The EDTTR consists of two main stages: the first is characterized by the off-line load estimation of the distribution transformers by a load aggregation process, which uses consumers information as input data. In the second stage the off-line estimates obtained in Stage 1 are recursively refined in real-time basing on the available measurements. This procedure is executed by a computationally efficient backward/forward sweep load flow algorithm based on the data structure called Node-depth Encoding. The developed EDTTR allows the treatment of distribution transformers connected in Delta-Yn improving the primary network representation. A test platform is also developed that enables the analysis of the impact of factors that deteriorate the demand estimation process, such as the poor classification of consumers, the poor representativeness of the load class for certain consumers, the possibility of non-technical losses, and of gross errors and communication faults in the feeder meters. The developed EDTTR performance was tested in simulations that uses a real feeder from Ribeirão Preto city, based on system data provided by CPFL Paulista utility.

As doenças cardiovasculares (DCV) são responsáveis pela maioria das mortes ocorridas em todo o mundo. Os riscos para o desenvolvimento destas patologias podem ser amenizados, em parte, por meio de uma dieta rica em alimentos de origem vegetal. Neste sentido, os frutos nativos brasileiros, como os pertencentes à família Myrtaceae, podem contribuir para melhorar a qualidade da alimentação, pois apresentam altos teores de compostos bioativos, entre eles, os fenólicos (CBF). Pouco se sabe sobre os efeitos dos polifenóis destes frutos para redução do risco de desenvolvimento das DCV. Sendo assim, este trabalho buscou avaliar a bioacessibilidade dos CBF presentes em polpas de cambuci e jabuticaba e seus efeitos in vitro sobre mecanismos de ação relacionados às DCV. Para tanto, extratos ricos em polifenóis foram obtidos a partir de extrações em fase sólida (C18 e PA) das polpas de ambos os frutos, submetidas ou não à simulação da digestão gastrointestinal. Estes extratos tiveram seus efeitos inibitórios sobre a atividade da Enzima Conversora de Angiotensina I (ECA) e a agregação plaquetária induzida por adenosina difosfato avaliados in vitro. De acordo com os resultados obtidos, a digestão in vitro foi capaz de liberar os CBF da matriz alimentar. Tal bioacessibilidade parece ter sido importante apenas para a inibição da agregação plaquetária, uma vez que a capacidade inibitória destes compostos sobre a atividade da ECA não melhorou depois da digestão in vitro. Quanto aos resultados obtidos pelos extratos provenientes das colunas PA e C18, observa-se que as maiores concentrações de taninos nestes últimos não foram suficientes para melhorar a capacidade antiagregante, mas foram importantes para aumentar a inibição da atividade da ECA. Comparando-se as respostas apresentadas pelos dois frutos, os CBF presentes no cambuci exibiram, predominantemente, potenciais anti-hipertensivo e antiagregantedo maiores do que os da jabuticaba. Neste contexto, o consumo de cambuci e jabuticaba, bem como a utilização de seus polifenóis purificados, podem ser adjuvantes para a redução dos riscos relacionados ao desenvolvimento das DCV. / The cardiovascular diseases (CVD) are the leading cause of death worldwide. The risk of development of these disorders can be reduced, partially, by a vegetal-based diet. In this way, the Brazilian native fruits from Myrtaceae family may contribute to improve the diet quality, once they have high quantity of bioactive compounds, such as the phenolic (PC). The knowledge about the cardioprotective effects of consuming these fruit polyphenols is limited, so this study aimed to evaluate the bioaccessibility of the cambuci and jaboticaba PC and their in vitro potential on CVD-related mechanisms. First, gastrointestinal digestion simulation of each fruit pulp was done, and then the polyphenols rich extracts were obtained by solid phase extractions, before and after the pulps digestion. The polyphenols rich extracts had their phenolic concentrations determined and were used to evaluate the capacity of PC in inhibit the Angiotensin Converting Enzyme (ACE) activity and the platelet aggregation induced by ADP. The results were expressed as IC50, considering the total phenolic content per milliliter of reaction. According to the results, the in vitro digestion process was able to release the polyphenols from the food matrix. Therefore, the bioaccessibility had no significant effect on ACE activity, but decreased the IC50 values of platelet aggregation. In relation to the extracts from PA and C18 columns, the higher tannin concentration In comparison to the IC50 values presented by PA extracts, the higher concentrations of tannins in the last one were not enough to improve the antiaggregant effect, but were important to increase the inhibition of ACE activity. Cambuci polyphenols presented higher antihypertensive and antiaggregant potentials than the jaboticaba compounds. In this respect, the ingestion of cambuci and jaboticaba and the use of their purified polyphenols can be of particular importance in reducing the risk for the CVD development.

Given the ever increasing reliance of today’s society on ubiquitous wireless access, the paradigm of dynamic spectrum access (DSA) as been proposed and implemented for utilizing the limited wireless spectrum more efficiently. Orthogonal frequency division multiplexing (OFDM) is growing in popularity for adoption into wireless services employing DSA frame- work, due to its high bandwidth efficiency and resiliency to multipath fading. While these advantages have been proven for many wireless applications, including LTE-Advanced and numerous IEEE wireless standards, one potential drawback of OFDM or its non-contiguous variant, NC-OFDM, is that it exhibits high peak-to-average power ratios (PAPR), which can induce in-band and out-of-band (OOB) distortions when the peaks of the waveform enter the compression region of the transmitter power amplifier (PA). Such OOB emissions can interfere with existing neighboring transmissions, and thereby severely deteriorate the reliability of the DSA network. A performance-enhancing digital pre-distortion (DPD) technique compensating for PA and in-phase/quadrature (I/Q) modulator distortions is proposed in this dissertation. Al- though substantial research efforts into designing DPD schemes have already been presented in the open literature, there still exists numerous opportunities to further improve upon the performance of OOB suppression for NC-OFDM transmission in the presence of RF front-end impairments. A set of orthogonal polynomial basis functions is proposed in this dissertation together with a simplified joint DPD structure. A performance analysis is presented to show that the OOB emissions is reduced to approximately 50 dBc with proposed algorithms employed during NC-OFDM transmission. Furthermore, a novel and intuitive DPD solution that can minimize the power regrowth at any pre-specified frequency in the spurious domain is proposed in this dissertation. Conventional DPD methods have been proven to be able to effectively reduce the OOB emissions that fall on top of adjacent channels. However more spectral emissions in more distant frequency ranges are generated by employing such DPD solutions, which are potentially in violation of the spurious emission limit. At the same time, the emissions in adjacent channel must be kept under the OOB limit. To the best of the author’s knowledge, there has not been extensive research conducted on this topic. Mathematical derivation procedures of the proposed algorithm are provided for both memoryless nonlinear model and memory-based nonlinear model. Simulation results show that the proposed method is able to provide a good balance of OOB emissions and emissions in the far out spurious domain, by reducing the spurious emissions by 4-5 dB while maintaining the adjacent channel leakage ratio (ACLR) improvement by at least 10 dB, comparing to the PA output spectrum without any DPD.

<p>Disertacija je posvećena re&scaron;avanju jednačina distributivnosti gde&nbsp;nepoznate funkcije pripadaju nekim poznatim klasama operacija agregacije&nbsp;i primeni dobijenih re&scaron;enja u teoriji korisnosti. Dobijeni rezultati se generalno mogu podeliti u tri grupe. Prvu grupu čine rezultati iz Glave 2 dobijeni re&scaron;avanjem jednačina distributivnosti između GM-operacija agregacije i&nbsp;oslabljenih uninormi, GM-operacija agregacije i oslabljenih nulanormi, kao i&nbsp;GM-operacija agregacije i operacija agregacije bez neutralnog i absorbujućeg&nbsp;elementa. Druga grupa rezultata, takođe iz Glave 2, je dobijena re&scaron;avanjem&nbsp;jednačina uslovne (oslabljene) distributivnosi neprekidne nulanorme u odnosu&nbsp;na neprekidnu t-konormu, i neprekidne nulanonorme u odnosu na uninorme iz&nbsp;<br />klasa U_min &cup;U_max. Treća grupa rezultata (Glava 3) je proistekla iz primene dobijenih rezultata o uslovoj distributivnosti nulanorme u odnosu na t-konormu&nbsp;u teoriji korisnosti.</p> / <p>This dissertation is devoted to solving distributivity equations involving some well-known classes of aggregation operators, and application&nbsp;the obtained results to utility theory. In general, the obtained results can&nbsp;be divided into three groups. The first group are results from Chapter 2 obtained by solving distributivity equations between GM-aggregation operators&nbsp;and relaxed nullnorm, GM-aggregation operators and relaxed uninorms, as&nbsp;well as GM-aggregation operators and aggregation operators without neutral&nbsp;and absorbing element. The second group are results, also from Chapter 2,&nbsp;obtained by solving conditional (relaxed) distributivity of continuous nullnorm with respect to &nbsp;continuous t-conorm, as well as continuous nullnorm&nbsp;with respect to uninorms from the classes U_min &cup; U_max. The third group are&nbsp;results (Chapter 3) arising from the application results on conditional distributivity of nullnorm with respect to t-conorm in utility theory.</p>

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2018-06-13T14:19:35Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Andre Carlos Auler.pdf: 3700376 bytes, checksum: c1ec033a97820b9055b6c86fad79d308 (MD5) / Made available in DSpace on 2018-06-13T14:19:35Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Andre Carlos Auler.pdf: 3700376 bytes, checksum: c1ec033a97820b9055b6c86fad79d308 (MD5) Previous issue date: 2018-04-25 / A acidez do solo é um importante fator que restringe a produção agrícola no mundo. Solos ácidos apresentam baixos valores de pH, elevados teores de alumínio trocável (Al3+) e baixa disponibilidade de cálcio (Ca2+), magnésio (Mg2+) e potássio (K+) trocáveis. Para corrigir os problemas causados pela acidez do solo, diversos materiais podem ser utilizados, com destaque para os carbonatos e os silicatos de Ca e Mg. Tais produtos apresentam distinções quanto a sua composição química e características físicas, o que repercute sobre sua reatividade no solo. Contudo, com o advento do plantio direto (SPD), os corretivos da acidez são aplicados sobre a superfície do solo, o que restringe a correção da acidez em subsuperfície. Neste contexto, o gesso agrícola é aplicado em associação aos corretivos da acidez. Embora o gesso agrícola não atue sobre a acidez ativa do solo, em subsuperfície ele atua reduzindo os teores de Al3+ e elevando os teores de Ca2+, o que melhora o ambiente radicular. O manejo químico do solo, por meio da aplicação de corretivos da acidez e de gesso agrícola pode alterar a estrutura do solo e os processos termodinâmicos que nela ocorrem. Neste contexto, o objetivo geral deste estudo foi avaliar os efeitos de corretivos de acidez do solo [calcário de rocha moída (CRM), escória de siderurgia (ES) e calcário calcinado (CC)], associados ou não ao gesso agrícola, sobre os atributos físicos e químicos do solo e a produtividade de culturas no SPD. Para isso, instalou-se um experimento em um LATOSSOLO VERMELHO-AMARELO Distrófico de textura argilo-arenosa, em Ponta Grossa-PR. Os tratamentos foram os três corretivos da acidez do solo CRM (3,8 Mg ha-1), ES (4,2 Mg ha-1) e CC (2,7 Mg ha-1) mais um tratamento controle (sem correção da acidez), associados ou não ao gesso agrícola (2,4 Mg ha-1). As doses dos corretivos foram calculadas para elevar a saturação por bases da camada 0-0,20 m a 70 %, com base em seus equivalentes carbonatos. A dose de gesso agrícola foi calculada com base no teor de argila do solo. Os corretivos e o gesso agrícola foram aplicados sobre a superfície do solo, em agosto de 2015. A rotação de culturas utilizada foi milho (2015/16) – trigo (2016) – soja (2016/17) - aveia preta (2017) – feijão (2017/18). Após a colheita do milho e do trigo, respectivamente aos 7 e aos 15 meses após a aplicação dos tratamentos, foram coletadas amostras indeformadas e deformadas de solo. Foram coletadas amostras indeformadas de solo em (i) monólitos, nas camadas 0-0,05; 0,05-0,10 e 0,10-0,20 m, para avaliação da agregação e da estabilidade de agregados; e em (ii) anéis volumétricos, nas camadas 0-0,05; 0,05-0,10; 0,10-0,20; 0,20-0,40 e 0,40-0,60 m, para avaliação da densidade do solo (Ds), porosidade total (Pt), macroporosidade (Ma), microporosidade (Mi) e retenção de água no solo. As amostras deformadas foram coletadas nas mesmas camadas de coleta dos anéis volumétricos, para determinação dos componentes da acidez do solo (pH, H+Al e Al3+), cátions básicos trocáveis (Ca2+, Mg2+ e K+) e teores de carbono lábil (COXP) e total (CO). A produtividade das culturas foi avaliada e utilizada para se determinar a eficiência agronômica dos corretivos e do gesso agrícola. Tanto aos 7 quanto aos 15 meses após aplicação dos tratamentos, os teores dos cátions básicos foram mais afetados que os componentes da acidez. Via de regra, a aplicação de gesso agrícola promoveu intensa lixiviação de Mg2+ e K+ nas camadas mais superficiais do solo, o que resultou no aumento da concentração dos nutrientes em profundidade. Referindo-se aos componentes da acidez, o Al3+ foi o componente mais alterado pela aplicação dos tratamentos, principalmente aos 15 meses após aplicação. Um resultado a ser destacado é que a ES com gesso aumentou os 9 teores de Al3+ em profundidade. Os teores de COXP e CO não foram afetados pelos tratamentos. As alterações nos atributos químicos do solo repercutiram sobre os atributos físicos. O diâmetro médio ponderado dos agregados e as proporções de macroagregados grandes foram mais influenciadas aos 15 meses após aplicação, em relação aos 7 meses, demonstrando a importância do tempo de reação dos materiais no solo sobre sua agregação. A Ds, a Pt e a Ma foram alteradas pelos tratamentos na camada de 0,40–0,60 m, diferentemente da Mi, que foi afetada nas camadas mais superficiais do solo (0–0,20 m). A retenção de água no solo foi sensível as alterações na estrutura do solo, principalmente quando os corretivos foram aplicados associados ao gesso agrícola. Deste modo, pode-se concluir que a dinâmica dos íons no solo pela correção da acidez e aplicação e gesso agrícola influencia os atributos físicos do solo, tanto em superfície como em profundidade. O aumento nos teores de Ca2+ e Mg2+ e a redução do Al3+ melhora a estrutura do solo, reduzindo sua Ds e aumentando sua Pt; e, a substituição de Al3+ por Mg2+ no complexo de troca do solo, decorrentes da aplicação da ES e do gesso agrícola influencia a retenção de água no solo. Sendo que a maior concentração do Mg2+ favorece a retenção. Os efeitos da correção da acidez do solo, independentemente do corretivo, e do gesso agrícola sobre a produtividade das culturas ocorre de maneira independente. Também, as culturas respondem de maneira distinta a correção da acidez e a gessagem. Todavia, o calcário calcinado foi o corretivo com maior eficiência agronômica, tanto quando aplicado isoladamente como quando associado ao gesso agrícola. / Soil acidity is an important factor that restricts agricultural production in the world. Acid soils have low pH values, high exchangeable aluminum (Al3 +) content and low availability of exchangeable calcium (Ca2+), magnesium (Mg2+) and potassium (K+). To correct the problems caused by the soil acidity, several materials can be used, with emphasis on carbonates and silicates of Ca and Mg. These products present distinctions as to their chemical composition and physical characteristics, which has repercussions on their reactivity on the soil. However, with the advent of no-till (NT), acidity correctives are applied to the soil surface, which restricts the correction of acidity in subsurface. In this context, the phosphogypsum is applied in association with acidity correctives. Although the phosphogypsum does not act on the active acidity of the soil, in subsurface it acts reducing the Al3+ contents and increasing the Ca2+ contents, which improves the root environment. The chemical management of the soil, through the application of correctives of acidity and of agricultural gypsum can alter the soil structure and the thermodynamic processes that occur in it. In this context, the general aim of this study was to evaluate the effects of soil acidity correctives [ground rock limestone (GRL), steel slag (SS) and calcined limestone (CL)], associated or not with soil physical and chemical attributes and crop productivity in NT. For this purpose, an experiment was carried out on a sandy-clay Typic Hapludox, at Ponta Grossa-PR. The treatments were the three soil acid correctives: GRL (3.8 Mg ha-1), SS (4.2 Mg ha-1) and CL (2.7 Mg ha-1), plus one control treatments (without acidity correction), associated or not with phosphogypsum (2.4 Mg ha-1). The corrective doses were calculated to raise the base saturation of the 0-0.20 m layer to 70%, based on their carbonate equivalents. The dose of phosphogypsum was calculated based on the soil clay content. Correctives and phosphogypsum were applied to the soil surface in August 2015. The crop rotation was corn (2015/16) – wheat (2016) – soybean (2016/17) – black oat (2017) – beans (2017/18). After the corn and wheat were harvested, at 7 and 15 months after the treatments, undisturbed and disturbed soil samples were collected. Undisturbed soil samples were collected in (i) monoliths, in the 0–0.05; 0.05–0.10 and 0.10–0.20 m layers, for evaluation of aggregation and aggregates stability; and in (ii) volumetric rings, in the 0–0.05; 0.05–0.10; 0.10–0.20; 0.20–0.40 and 0.40–0.60 m layers, to evaluate the soil bulk density (BD), total porosity (TP), macroporosity (Ma), microporosity (Mi) and soil water retention. The deformed samples were collected in the same collection layers of the volumetric rings to determine the soil acidity components (pH, H+Al and Al3+), exchangeable basic cations (Ca2+, Mg2+ and K+) and labile (POxOC) and total (OC) carbon contents. The yield crops was evaluated and used to determine the agronomic efficiency of the correctives and the phosphogypsum. Both at 7 and 15 months after application of treatments, the basic cations contents were more affected than the acidity components. As a rule, the application of phosphogypsum promoted intense Mg2+ and K+ leaching in the more superficial layers of the soil, which resulted in increased concentration of nutrients in depth. Referring to the components of acidity, Al3+ was the most altered component by the application of treatments, especially at 15 months after application. One result to be highlighted is that SS with phosphogypsum increased Al3+ contents in depth. The POcOC and OC contents were not affected by the treatments. The changes in the soil chemical attributes had repercussions on the physical attributes. The weight mean diameter of the aggregates and the proportions of large macroaggregates were more influenced at 15 months 11 after application, in relation to the 7 months, demonstrating the importance of the reaction time of the materials in the soil on their aggregation. BD, TP and Ma were altered by treatments in the layer of 0.40–0.60 m, while Mi was affected in the most superficial layers of the soil (0–0.20 m). The soil water retention was sensitive to changes in soil structure, especially when the correctives were applied associated with the phosphogypsum. In this way, it can be concluded that soil ion dynamics by the acidity correction and phosphogypsum application influences the physical attributes of the soil, both in surface and in depth. The increase in the Ca2+ and Mg2+ contents and the Al3+ reduction improve the soil structure, reducing its BD and increasing its TP; and, the substitution of Al3+ for Mg2+ in the soil exchange complex, due to the application of SS and phosphogypsum influences soil water retention. The higher concentration of Mg2+ favors retention. The effects of correcting soil acidity, regardless of the corrective, and the phosphogypsum on crop yield, occur independently. Also, crops respond differently to acidity correction and phosphogypsum application. However, the calcined limestone was the corrective with higher agronomic efficiency, both when applied alone and when associated with agricultural gypsum.

Les acides gras de la série n-3 et notamment l’acide docosahexaénoïque (DHA) jouent un rôle important dans la prévention des maladies cardiovasculaires. Un de ses métabolites, la protectine DX (PDX), qui est un isomère de la protectine D1 (PD1), inhibe l’agrégation des plaquettes sanguines. D’autres composés similaires appelés "poxytrins", qui possèdent aussi un triène conjugué avec une géométrie E,Z,E, ont également été synthétisés à partir d'autres acides gras polyinsaturés (AGPI) via la lipoxygénase de soja. Ces composés présentent des propriétés anti-agrégantes en inhibant la cyclo-oxygénase plaquettaire et le récepteur du thromboxane A2. Dans cette thèse, nous décrivons de nouveaux composés dihydroxylés synthétisés par la 15-lipoxygénase de soja à partir de l’acide alpha-linolénique (18:3n-3), un acide gras polyinsaturé indispensable consommé au niveau du gramme chez l’Homme adulte. Il est converti en acides gras monohydroxylés et dihydroxylés. Ces composés ont été séparés par HPLC en phase inverse et caractérisés par GC-MS après dérivation adéquate. Un acide gras monohydroxylé, majoritaire, l’acide 13(S)-octadécatriénoïque et quatre acides gras dihydroxylés ont été détectés. Ces derniers présentent tous un spectre UV caractéristique avec une absorption maximale à 270 nm et deux épaulements à 260 et 280 nm. Les spectres UV de deux d'entre eux sont superposables à celui de la PDX, ce qui suggère une géométrie E,Z,E des doubles liaisons de leur triène. La caractérisation complète de ces composés a été réalisée par RMN à haut champ et par GC-MS. Ce sont les acides 9(R),16(S)-dihydroxy-octadéca-10E,12E,14E-triénoïque, 9(S),16(S)-dihydroxy-octadéca-10E,12E,14E-triénoïque, 9(S),16(S)-dihydroxy-octadéca-10E,12Z,14E-triénoïque et 9(R),16(S)-dihydroxy-octadéca-10E,12Z,14E-triénoïque. Ils sont également synthétisés par la 15 lipoxygénase recombinante humaine de type 2. Ces composés dihydroxylés 9,16-diHOTEs ont été testés sur les plaquettes isolées à partir du sang humain. Nous avons observé que seules les molécules ayant la géométrie E,Z,E du triène conjugué inhibent l'agrégation plaquettaire induite par le collagène et inhibent la cyclooxygénase-1 (COX-1) de mouton. Les propriétés anti-inflammatoires de ces produits ont également été étudiés. Tous les isomères 9,16-diHOTEs, possédant un triène conjugué avec une géométrie E,Z,E, inhibent la COX-2 recombinante humaine et seul l’acide 9(R),16(S)-dihydroxy-octadéca-10E,12Z,14E-triénoïques inhibe la 5-lipoxygénase des leucocytes, siège de la synthèse des leucotriènes issus de l’acide arachidonique. En conclusion, les composés dihydroxlés possédant un triène conjugué E,Z,E, issus du 18:3n-3, ainsi que la PDX, inhibent l’activité des COX-1 et 2, et seraient anti-agrégants et anti-inflammatoires. Ces résultats donnent des perspectives pharmacologiques aux recommandations nutritionnelles promouvant la consommation d’acide alpha linolénique. / N-3 fatty acids, especially docosahexaenoic acid (DHA), play an important role in the prevention of cardiovascular diseases. One metabolite of DHA, protectin DX (PDX), an isomer of protectin D1 (PD1) (Chen P et al., 2009),possesses inhibits blood platelet aggregation. Similar compounds called "poxytrins", which have a conjugated triene with a E,Z,E geometry have also been synthesized from other polyunsaturated fatty acids (PUFA) by soybean lipoxygenase. They have anti-aggregating properties by inhibiting platelet cyclooxygenase and thromboxane A2 receptor (Chen P et al., 2011). In this thesis, we describe new dihydroxy compounds synthesized by the soybean 15-lipoxygenase from alpha-linolenic acid (18:3n-3), an essential PUFA that is consumed in the gram range in human adults . It is converted into monohydroxylated and dihydroxylated derivatives. These compounds were separated by reverse phase high performance liquid chromatography (HPLC) and characterized by gas chromatography-mass spectrometry (GC-MS) after appropriate derivatization. A main monohydroxylated fatty acid, 13(S)-octadecatrienoic acid (13(S)-OH-18:3) and four dihydroxylated fatty acids were detected. The last ones have all a characteristic UV spectrum with a maximum absorbance at 270 nm with two shoulder peaks at 260 and 280 nm. The UV spectra from two of them are superimposable to that of PDX, suggesting a E,Z,E geometry for their conjugated triene. The complete characterization of these compounds was performed by high field nuclear magnetic resonance (NMR) and by GC-MS. These are the 9(R),16(S)-dihydroxy-octadeca-10E,12E,14E-trienoic, 9(S),16(S)-dihydroxy-octadeca-10E,12E,14E-trienoic, 9(S),16(S)-dihydroxy-octadeca-10E,12Z,14E-trienoic and 9(R),16(S)-dihydroxy-octadeca-10E,12Z,14E-trienoic acids. They can also be synthesized by the (type 2) 15 human recombinant lipoxygenase. These dihydroxylated compounds (9,16-diHOTEs)were tested on isolated human blood platelets. We observed that only molecules containing a conjugated triene with a E,Z,E geometry are able to inhibit platelet aggregation induced by collagen, and inhibit sheep cyclooxygenase-1 (COX-1). The anti-inflammatory properties of these products were also studied. All 9,16-diHOTEs isomers having a conjugated triene with a E,Z,E geometry, inhibit human recombinant cyclooxygenase-2 (COX-2) and only 9(R),16(S)-dihydroxy-octadeca-10E,12Z,14E-trienoic acid inhibits polymorphonuclear leukocytes (PMN) 5-lipoxygenase which is involved in the leukotriene synthesis from arachidonic acid. In conclusion, the E,Z,E dihydroxlated compounds from 18:3n-3, as well as PDX, inhibiting the COX-1 and 2 activities appear to be anti-aggregatory and anti-inflammatory agents. These results provide pharmacological perspectives to nutritional recommendations promoting the intake of alpha-linolenic acid.

Le diabète de type 2 (DT2) est associé à un risque athéro-thrombotique élevé, en partie dû à l'hyperactivation plaquettaire et aux dyslipoprotéinémies. Les lipoprotéines de haute densité (HDL) possèdent des propriétés anti-athérogènes et subissent des modifications glycoxydatives lors du DT2. Notre objectif a été de déterminer les effets d'HDL glycoxydées in vitro ou de DT2 sur les plaquettes sanguines humaines et de déterminer leur contenu en lipides oxydés. Les HDL glycoxydées possèdent des proportions moindres d'acides linoléique et arachidonique dans les phospholipides (PL) et esters de cholestérol, des concentrations plus élevées de dialdéhyde malonique et des principaux acides gras hydroxylés (AGOH) dont les 9-HODE, 13- HODE et 15-HETE dans toutes les classes lipidiques, en particulier dans les PL ainsi que des concentrations très faibles de vitamine E comparativement aux HDL contrôles. Les HDL glycoxydées in vitro et de patients DT2 inhibent de façon dose-dépendante l'agrégation plaquettaire induite par le collagène via le récepteur SR-BI. Ces HDL glycoxydées diminuent la phosphorylation des p38 MAPK et cPLA2 plaquettaires. D'autre part, des HDL contrôles enrichies avec le PC(16:0/13-HODE) inhibent fortement l'agrégation comparativement aux HDL contrôles. De plus, les effets des sous-classes d'HDL, HDL 2 & 3, de DT2 et de témoins ont été testés sur l'agrégation plaquettaire. Les HDL2 de DT2 possèdent des concentrations d'AGOH plus élevées que les HDL3 de DT2 et tendent à inhiber plus l'agrégation plaquettaire. En conclusion, nos résultats montrent que les HDL glycoxydées de patients diabétiques ne perdent pas leurs propriétés anti-agrégantes, qui pourraient être médiées par certaines PL oxydés / Type 2 diabetes (T2D) is associated with a high athero-thrombotic risk, partly due to platelet hyperactivation and dyslipoproteinemia. High-density lipoproteins (HDL) possess antiatherogenic properties and undergo glycoxidation changes in T2D. Our objective was to determine the effects of glycoxidized HDL in vitro or from T2D patients on human blood platelets and to identify their oxidized lipid species. Compared to control HDL, glycoxidized HDL have lower proportions of linoleic and arachidonic acids in phospholipids (PL) and cholesteryl esters, higher concentrations of malondialdehyde and main hydroxylated fatty acid (HOFA) including 9-HODE, 13-HODE and 15-HETE in all lipid classes, especially in PL, and very low concentrations of vitamin E. In vitro glycoxidized and T2D HDL dose-dependently inhibit platelet aggregation induced by collagen via the SR-BI receptor. Glycoxidized HDL decrease the phosphorylation of platelet p38 MAPK and cPLA2. On the other hand, control HDL enriched with oxidized phospholipids i.e. PC(16:0/13-HODE) strongly inhibit platelet aggregation compared to controls. Moreover, the effects of HDL subclasses, HDL 2 & 3, from T2D patients and healthy controls were tested on platelet aggregation. T2D HDL2 have higher concentrations of HOFA than T2D HDL3 and tend to inhibit platelet aggregation to a greater extent. In conclusion, our results show that T2D glycoxidized HDL do not lose their anti-aggregatingproperties and are even more effective than control HDL. These anti-aggregatory effects could be partly due to some oxidized PL species

Os corantes ciânicos (CC) são compostos orgânicos que possuem uma estrutura facilmente variável, permitindo obter-se as características fotofísicas desejáveis. Devido a sua alta afinidade por estruturas biológicas, baixa citotoxicidade no escuro, alta solubilidade em meio aquoso e fotoatividade os CC são considerados compostos promissores para aplicações no tratamento do câncer por terapia fotodinâmica (TFD). CC possuem uma forte tendência de se agregar em meio aquoso, que modifica suas características fotofísicas, reduzindo os rendimentos quânticos de fluorescência e do estado tripleto, diminuindo assim sua eficiência em suas aplicações como sonda fluorescente e na TFD, todavia, a agregação aumenta a eficiência da conversão da sua energia de excitação em calor, que é importante para sua aplicação na terapia por hipertermia (HT). Sendo introduzido num organismo o CC se encontra no ambiente onde ele vai interagir com sais e estruturas nano-heterogêneas (membrana celular, ácidos nucléicos etc.), interações que podem influenciar na sua agregação. Nesse trabalho investigamos o fenômeno da agregação dos CC em suas interações com sistemas nano-heterogêneos naturais (DNA) e sintéticos (micelas) em função da sua própria estrutura, da estrutura destes sistemas e da composição da solução: as concentrações do corante e do sistema nano-heterogêneo e a força iônica. Entre os CC, escolhemos como modelos a Acridina Laranja (AL) e os corantes com dois cromóforos (BCD) que se diferem pelo ângulo formado entre seus cromóforos. Utilizamos técnicas espectroscópicas estacionárias e com resolução temporal de absorção óptica, fluorescência, espalhamento ressonante e dinâmico da luz e fotólise por pulso relâmpago. Descobrimos que em soluções aquosas homogêneas os sais induzem a agregação dos CC. No caso da AL, os sais suprimem sua fluorescência pelo aumento da agregação da AL e pela formação de um exciplexo entre a AL em seu estado excitado singleto e o ânion do sal. A interação dos CC com estruturas nano-organizadas é complexa. Observamos que na interação do CC com o DNA aparecem várias espécies em equilíbrio, tais como monômeros de CC livres e ligados ao DNA, agregados de CC ligados ao DNA e agregados de DNA ligados com os monômeros de CC. A ligação da AL ao DNA reduz a probabilidade do contato da AL com outras moléculas. Contudo, na presença do DNA os sais reduzem a agregação da AL devido à redução da constante de ligação da AL com o DNA. Na presença do dodecil sulfato de sódio (SDS), observamos que em baixas concentrações este estimula a agregação do CC. O aumento da concentração de SDS induz a desagregação do CC. Identificamos que os agregados dos CC com SDS apresentam uma dinâmica que pode perdurar por diversas horas. Durante esse período os agregados trocam suas formas H e J. Investigamos uma possível aplicação prática da agregação numa terapia de HT, identificando que a agregação protege o CC da fotodecomposição e aumenta a eficiência da geração de calor. Os resultados obtidos são importantes para avaliar o potencial de aplicação do CC como fotossensibilizadores em terapia fotodinâmica, fotohipertermia e sondas fluorescentes em diagnóstico por fluorescência. / Cyanine dyes (CD) are organic compounds that have an easily variable structure, thus allowing obtain desirable photophysical characteristics. Due to their high affinity to biological structures, low cytotoxicity in the dark, high solubility in aqueous medium and photoactivity the CD are promising materials for application as photosensitizers in cancer treatment by photodynamic therapy (PDT) and as fluorescence probes in fluorescence diagnostics (FD). CD have a strong tendency to aggregate in aqueous media, which modify their photophysical characteristics, reducing its fluorescence and triplet state quantum yields, thus decreasing their efficiency in applications in PDT and FD. At the same time, aggregation increases the probability of excitation energy conversion into heat, which is important for application in hyperthermia (HT) therapy. Being introduced into organism, CD will interact with salts and nano-heterogeneous structures (cell membrane, nucleic acids etc.). These interactions can affect its aggregation. In this work we have investigated the CD aggregation phenomenon at its interactions with natural (DNA) and synthetic (micelles) nano-heterogeneous systems in function of their own structure, structure of the nano-heterogeneous system and the solution characteristics like dye and nano-heterogeneous system concentrations and ionic strength. Among CD, we have chosen as models Acridine Orange (AO) and cyanine dyes with two chromophores (BCD) that differ by the angle between chromophores. Stationary and time-resolved optical absorption, fluorescence, resonant and dynamic light scattering spectroscopies and flash photolysis were used. We have found that in homogeneous aqueous solutions salts induce the CD aggregation. In the case of AO, the salts quench the AO fluorescence by increasing its aggregation and by forming an exciplex between the AO molecule in its singlet excited state and the salt anion. Interaction of CD with nano-organized systems is complex. We observed that at CD interaction with DNA there appear several species in equilibrium, such as CD monomers free and bound to DNA, CD aggregates bound to DNA and DNA aggregates bound to CD monomers. The aggregation of DNA molecules around AO monomers reduces the probability for AO contact with other molecules. In the presence of DNA salts reduce AO aggregation due to reduction of the AO binding constant to DNA. Sodium dodecyl sulfate (SDS) in low concentrations induces CD aggregation, while higher SDS concentrations stimulate CD disaggregation. The process of CD aggregation in the presence of SDS can continue for several hours. During this period, the form of aggregates may modify from H to J or from J to H depending on the dye structure. The irradiation of dye solutions with visible light increases the solution temperature. Aggregation protected CD from photodecomposition and increased heat generation. The results obtained may help in evaluation the potential of CD as photosensitizers in photodynamic therapy, photohyperthermia and fluorescent probes in fluorescence diagnostics.

Species conservation is typically founded upon a range of management strategies, which integrate both biological and socioeconomic data. In this thesis, population genetics, acoustic telemetry, spawning aggregation surveys and stakeholder assessments were used to address key knowledge gaps limiting effective conservation management for critically endangered Nassau grouper (Epinephelus striatus) stocks in The Bahamas. A panel of polymorphic microsatellite markers was optimised to assess the genetic population dynamics of more than 400 Nassau grouper sampled throughout the country. Microsatellite data indicate that contemporary Nassau grouper populations in The Bahamas are predominantly genetically diverse and weakly differentiated, but lack geographic population structure. Assessments of changes in effective population size (Ne) show substantive reductions in Ne within The Bahamas compared to historic values that are likely due to natural disturbances. Evidence for recent bottlenecks occurring in three islands as well as an active spawning site, along with higher inbreeding coefficients in two islands were also found, and can be attributed to more recent anthropogenic activities. Collapse of a historically important Nassau grouper fish spawning aggregation (FSA) was supported by both acoustic telemetry and spawning aggregation survey dives. Restriction-site-associated DNA sequencing (RAD-seq) of 94 Nassau grouper was used to explore intraspecific population dynamics, loci under selection and patterns of gene flow in The Bahamas. Genomic assessments of diversity were in accord with microsatellite data and examinations of gene flow support higher levels of connectivity in The Bahamas than was previously suggested. The increased resolution gained from assessments of genomic data support intraspecific population structuring that may be driven by differences in gene flow and putative loci under divergent selection. Telemetry data were successfully used to identify the origins of spawning adults, and support demographic connectivity through migrations between an active FSA in the central Bahamas and home reef habitats within the Exumas and a no-take marine protected area. Stakeholder assessments highlight the complexities of fisheries management within The Bahamas, with key stakeholders often exhibiting conflicting opinions regarding the status of Nassau grouper and the efficacy of management options. However, these groups mutually agree upon the need to better manage remaining Nassau grouper stocks within The Bahamas through science-grounded policies. Synthesis of these studies along with a review of fisheries governance in The Bahamas was used to develop a comprehensive national management plan for Nassau grouper to facilitate better conservation for remaining populations of this ecologically important marine species.

Control and analysis of protein aggregation is an increasing challenge to biopharmaceutical research and development. Therefore it is important to understand the interactions, causes and analysis of particles in order to control protein aggregation to enable successful biopharmaceutical formulations. This work investigates the role of different non-ionic surfactants on protein conformational stability, as assessed by HSDSC, and on protein size stability as assessed by Dynamic Light Scattering (DLS), HIAC and MFI. BSA and IgG2 were used as model proteins. Thermal unfolding experiments indicated a very weak surfactant-immunoglobulin IgG2 interaction, compared to much stronger interactions for the BSA surfactant systems. The DLS results showed that BSA and IgG2 with different surfactants and concentration produced different levels of particle size growth. The heat treatment and aging of samples in the presence of Tween 20, Tween 80, Brij 35 and Pluronic F-68 surfactants led to an increase in the populations of larger particles for BSA samples, whereas IgG2 systems did not notably aggregate under storage conditions MFI was shown to be more sensitive than HIAC technique for measuring sub-visible particles in protein surfactant systems. Heat treatment and storage stress showed a significant effect on BSA and IgG2 protein sub-visible particle size stability. This work has demonstrated that both proteins with different Tween 20, Tween 80, Brij 35 and Pluronic F-68 concentrations, have different level of conformational and size stability. Also aging samples and heating stress bears the potential to generate particles, but this depends on surfactant type. Poor predictive correlations between the analytical methods were determined.