This thesis presents the development of a triaxial cell and a proposal for methodology for estimating horizontal tension edometric condition by conducting laboratory tests on samples unsaturated compacted soil in OMC. The development of triaxial cell permits the use of voltages or controlled deformation. Moreover, the machine allows independent application increments of axial and radial stresses, thereby facilitating implementation assay in any way triaxial stresses. The proposed methodology simplifies estimate lateral tension through comparison of axial stress-strain curves of the test edomÃtrico conventional triaxial and consolidation tests under different paths tensions with the constant relationship between the axial and radial increments. In this case, the value of K0 would be corresponding to the constant trajectory in which the triaxial test curve edomÃtrico overlaps the curve of the test in terms of stress and axial deformations. They were tests performed with different soil types and the results were- roughly consistent with estimates from correlations empirical, thus allowing validate the proposal presented in this research. also It was studied the change of horizontal stress during the collapse flood conditions in edomÃtricas. In these tests it was found that during the breakdown voltage can horizontal remain virtually constant or even decreasing. / Esta dissertaÃÃo apresenta o desenvolvimento de uma cÃlula triaxial e uma proposta de metodologia para estimativa de tensÃo horizontal em condiÃÃo edomÃtrica, atravÃs da realizaÃÃo de ensaios de laboratÃrio em amostras nÃo saturadas de solo compactadas na umidade Ãtima. O desenvolvimento da cÃlula triaxial possibilita a aplicaÃÃo de tensÃes ou deformaÃÃes controladas. AlÃm disso, o equipamento permite a aplicaÃÃo independente de incrementos de tensÃes axiais e radiais, facilitando dessa forma a execuÃÃo de ensaio triaxial sob qualquer caminho de tensÃes. A metodologia proposta simplifica a estimativa da tensÃo lateral atravÃs da comparaÃÃo das curvas tensÃo-deformaÃÃo axial entre o ensaio edomÃtrico convencional e ensaios de adensamento triaxiais sob diferentes caminhos de tensÃes com a relaÃÃo constante entre os incrementos axial e radial. Nesse caso, o valor de K0 seria o correspondente à trajetÃria constante na qual a curva do ensaio triaxial se sobrepÃe a curva do ensaio edomÃtrico em termos de tensÃes e deformaÃÃes axiais. Foram realizados ensaios com diferentes tipos de solo e os resultados mostraram-se aproximadamente concordantes com as estimativas realizadas a partir de correlaÃÃes empÃricas, permitindo dessa forma validar a proposta apresentada nessa pesquisa. TambÃm foi estudada a variaÃÃo da tensÃo horizontal durante o colapso por inundaÃÃo em condiÃÃes edomÃtricas. Nesses ensaios verificou-se que, durante o colapso, a tensÃo horizontal pode permanecer praticamente constante ou atà mesmo diminuir.

The use of agricultural waste, such as rice husk (RH), for the production of cheap and eco-friendly polymer composites has emerged as a promising field of interest. The aim of this work was the preparation of high-density polyethylene (HDPE)-based composites reinforced with rice husk and an organic pro-oxidant (EG) for the production of seedlings tubes. Photodegradation and degradation tests in simulated soil were performed for 90 and 180 days in order to study the decomposition of these composites. The SEM and OM images suggest that degradation of the composites samples was more extensive than the pure HDPE samples, probably because the composites present intense light absorption in the UV range, facilitating the degradation process even before biodegradation begins. In addition, after introducing RH particles in the polymeric matrix, the mechanical tensile and flexural properties, experienced significant changes, suggesting that the RH particles were homogeneously dispersed throughout the polymer matrix. In addition, it was possible to identify microorganisms with polyethylene biodegradation activity, such as Aspergillus niger, Penicillium spp., Trichoderma spp., Rhizopus spp. The results have demonstrated that HDPE, RH, and EG are attractive materials for the design of polymeric composites for the production of seedlings tubes with excellent mechanical properties, being, also, easily decomposed in the environment once discarded. / O uso de resíduos agrícolas, como a casca de arroz (CA), para a produção de compósitos poliméricos baratos e eco-amigáveis surge como um campo de interesse promissor. O objetivo deste trabalho foi a preparação e caracterização de compósitos à base de polietileno de alta densidade (PEAD) com casca de arroz e um oxibiodegradante orgânico (EG) para a produção de tubetes florestais. Os testes de fotodegradação e degradação em solo simulado foram realizados por 90 e 180 dias, a fim de estudar a decomposição desses compósitos. As imagens de microscopia eletrônica de varredura e microscopia óptica sugerem que a degradação das amostras dos compósitos foi mais extensa do que a amostra de PEAD puro, provavelmente porque os compósitos apresentam intensa absorção de luz na faixa UV, facilitando o processo de degradação mesmo antes da biodegradação. Além disso, após a introdução de partículas de casca de arroz na matriz polimérica, as propriedades mecânicas de tração e flexão, experimentaram mudanças significativas, sugerindo que as partículas de CA foram dispersas homogeneamente em toda a matriz de polímero. Além disso, foi possível a identificação de microrganismos com atividade de biodegradação do polietileno, como Aspergillus níger, Penicillium spp., Trichoderma spp., Rhizopus spp. Os resultados demonstraram que o compósito de PEAD, CA e EG são materiais atraentes para a produção de tubetes com excelentes propriedades mecânicas, sendo, também, facilmente decompostos no ambiente, após serem descartados. / São Cristóvão, SE

Made available in DSpace on 2016-03-15T19:36:57Z (GMT). No. of bitstreams: 1 Alexandre Pastro Alves.pdf: 1203203 bytes, checksum: a4482af4edaf66d6d70071a940528a5a (MD5) Previous issue date: 2009-02-04 / Fundo Mackenzie de Pesquisa / Nanocomposites are polymeric hybrid materials where inorganic substances of nanometric dimensions are dispersed in a polymeric matrix. The fillers present area of raised surface, promoting better dispersion in the polymeric matrix and therefore an improvement of the physical properties of the composite that depends on the homogeneity of the material. The nanocomposites preparation with polymeric matrix allows in many cases to find a relation enters a low cost, due to the use of lesser amount of filler, and a raised performance level. In this work nanocomposites were obtained with pseudobohemite synthesized by sol-gel process and high density polyethylene with different concentrations of pseudobohemite. The nanocomposites were prepared by intercalation for fusing and characterized by thermal and mechanical tests. The results showed an increase in the values of hardness, tensile strength and compression strength, and an increase in the temperature of thermal distortion (HDT) and in the glass transition temperature (Tg) evidencing the interaction of nanofiller with the polymeric matrix. / Nanocompósitos poliméricos são materiais híbridos onde substâncias inorgânicas de dimensões nanométricas estão dispersas em uma matriz polimérica. As cargas apresentam área de superfícial elevada, promovendo melhor dispersão na matriz polimérica e por isso uma melhoria das propriedades físicas do compósito que depende da homogeneidade do material. A preparação de nanocompósitos com matriz polimérica permite em muitos casos encontrar uma relação entre um baixo custo, devido à utilização de menor quantidade de carga, e um elevado nível de desempenho. Neste trabalho foram obtidos nanocompósitos com pseudoboemita sintetizada pelo processo sol-gel e polietileno de alta densidade com diferentes concentrações de pseudoboemita. Os nanocompósitos foram preparados por intercalação por fusão e caracterizados por meio de ensaios térmicos e mecânicos. Os resultados mostraram um aumento nos valores de dureza, de resistência à tração e resistência à compressão, um aumento na temperatura de distorção térmica (HDT) e na temperatura de transição vítrea (Tg) evidenciando a interação da nanocarga com a matriz polimérica.

A estimulação magnética transcraniana (EMT) aplicada com diferentes orientações da bobina causa variações na amplitude e na latência dos potenciais evocados motores (PEM) dos músculos da mão. No entanto, as propriedades dos PEM são afetadas também pelos sistemas de detecção, e.g. localização e tamanho dos eletrodos de aquisição, e pela anatomia do músculo analisado, e.g. arquitetura dos tecidos muscular e adiposo. Neste estudo, verificamos como variam a distribuição espacial, a amplitude pico a pico, a latência, a velocidade de condução da fibra muscular e a frequência mediana do espectro de potência dos PEM em função da orientação da bobina de EMT. Utilizamos uma matriz bidimensional de eletrodos de superfície (grade com 13 linhas e 5 colunas) para aquisição do sinal de eletromiografia de superfície (EMGs) do músculo abdutor curto do polegar (ACP) em oito orientações da bobina de EMT em relação à linha sagital, que conecta o ínio ao násio. Duas abordagens distintas foram adotadas para comparação da amplitude em função da orientação da bobina: na primeira abordagem, calculamos a amplitude pico a pico média dos PEM compreendidos em uma região ativa do músculo localizada espacialmente a partir da matriz de EMGs, na segunda abordagem extraímos a amplitude do PEM no sinal diferencial de dois grupos de eletrodos simulando um sistema de EMGs em configuração bipolar, comumente utilizado nos procedimentos em EMT. Em ambos os métodos, identificamos amplitudes máximas para orientações da bobina em ângulos de 45° e 90°, corroborando os achados da literatura. A latência, frequência mediana e velocidade de condução dos PEM não apresentaram variações significativas com a orientação da bobina. Os mapas de distribuição espacial dos PEM indicam uma atividade muscular localizada na porção distal do músculo ACP para todos os ângulos de aplicação da EMT, demonstrando que os eletrodos convencionais de EMGs podem não estar idealmente localizados sobre a região do músculo ativada pela EMT. Por fim, identificamos que um sistema de neuronavegação pode facilitar a localização da estrutura cerebral a ser estimulada e aumentar a precisão no posicionamento da bobina. Adicionamos uma ferramenta para cálculo da orientação da bobina em função da linha sagital média de cada sujeito ao neuronavegador InVesalius Navigator, a ser utilizado nos próximos experimentos. / Transcranial magnetic stimulation (TMS) pulses with different coil orientations causes changes in amplitudes and latencies of motor evoked potentials (MEP) in muscles of the hand. Nonetheless, the properties of MEP are also affected by the systems of detection, e.g. placement and size of acquisition electrodes; and by the target muscle anatomy, e.g. architecture of fat and muscles tissues. In this study, we assessed the effect of TMS coil orientation on MEP spatial distribution, peak-to-peak amplitude, latency, conduction velocity of muscle fiber and median frequency, from the abductor pollicis brevis (APB) muscle. A grid of electrodes (13 lines and 5 columns) was used to detect the surface electromyography (sEMG) signals from the APB at eight different TMS coil orientations in respect to the midsagital line, connecting the inium and nasium. Two distinct approaches were adopted to compare the amplitude according to the coil orientation: first, we calculated the mean amplitude of MEP in the electrodes of the matrix over an active region of the muscle. Second, we extracted the amplitude of MEP in a single differential signal from two groups of matrix electrodes simulating a conventional sEMG bipolar configuration, commonly used in TMS experiments. In both cases, the maximum MEP amplitudes were induced at coil orientations of 45° and 90°, confirming the past findings in literature. However, we could not identify significant differences in latency, median frequency and conduction velocity of MEP according to different stimulus orientation. Maps of spatial distribution showed a localized muscle activity at the distal portion of the APB muscle for all the coil orientations, indicating that conventional bipolar sEMG electrodes may not be rightly placed over the active portion of the muscle recruited by TMS. Finally, we considered that a neuronavigation system could facilitate the localization of brain internal structures to apply TMS stimulus and improve the accuracy of coil handling and positioning over the stimulation point. Thereafter, we developed a computational tool to the InVesalius Navigator, to track the TMS coil position and orientation in respect to the subjects midsagital line to be used in future experiments.

Abstract The principal aim of this study was to explore associations between systemic inflammatory status and periodontal inflammation and tissue destruction. The study population consisted of 61 patients with chronic periodontitis, 30 periodontally healthy control subjects, and 80 subjects with type 1 diabetes mellitus (T1DM). The T1DM subjects were periodontally treated and re-examined eight weeks after completion of the treatment. The periodontal measures included plaque, probing depth (PD), bleeding on probing (BOP) and attachment level (AL). The serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interleukin (IL)-10, as well as the gingival crevicular fluid (GCF) level of matrix metalloproteinase (MMP)-8 were analyzed using commercially available ELISA assays, and serum high density lipoprotein (HDL) level using direct enzymatic methods. Serum IL-6 level associated significantly with the extent of inflamed periodontal pockets in T1DM subjects. Moreover, serum IL-6 modulated local periodontal inflammation in T1DM patients; periodontal healing turned out to be poorer in subjects with a high level of serum IL-6 than in those with a low level. Serum TNF-α/IL-10 ratio was three times higher in chronic periodontitis patients than in periodontally healthy control subjects. In T1DM subjects a significant inverse association between serum HDL level and the extent of inflamed periodontal pockets was found; subjects with a low serum HDL level presented 50% more inflamed periodontal sites than subjects with a high serum HDL level. A significant association between GCF MMP-8 level in shallow crevices and the extent of periodontal attachment loss in chronic periodontitis patients was observed. In conclusion, we focused on analyzing associations between systemic inflammatory status and periodontal conditions. According to our results, periodontal inflammation/infection is associated with systemic inflammatory status using serum IL-6, TNF-α/IL-10 ratio and HDL as indicators. Also, a high level of MMP-8 in GCF in shallow crevices could be indicative of higher susceptibility to periodontal infection and tissue destruction. / Tiivistelmä Tutkimuksen tavoitteena oli tarkastella hampaiden kiinnityskudosten tulehduksen (pardodontiitti) ja siihen liittyvän inflammaation yhteyttä systeemiseen tulehdustilaan. Tutkimusaineistoon kuului 61 yleistervettä potilasta, joilla oli kohtalaisesti tai pitkälle edennyt parodontiitti, 30 yleistervettä yksilöä, joiden hampaiden kiinnityskudokset olivat terveet/lähes terveet (kontrolliryhmä), sekä 80 tyypin 1 diabetes mellitus (T1DM) potilasta, joilla esiintyi vaihtelevasti parodontiittia. T1DM potilaiden parodontiitti hoidettiin, ja heidät tutkittiin uudelleen kahdeksan viikon kuluttua hoidon päättymisestä. Tutkittavilta tarkastettiin plakin määrä, ientaskujen syvyys, ienverenvuoto ja hampaiden kiinnityskudoksen menetys. Systeemistä tulehdustilaa mitattiin käyttäen seerumin interleukiini (IL)-6, tuumorinekroosifaktori (TNF)-α ja interleukiini (IL)-10 tasoja. Lisäksi määritettiin ientaskunesteen matriksimetalloproteinaasi (MMP)-8 taso. Kaikki edellä mainitut tulehduksen välittäjäainetasot määritettiin käyttäen ELISA-menetelmää. T1DM potilaiden seerumin IL-6 pitoisuuden ja tulehtuneiden ientaskujen määrän välillä vallitsi positiivinen yhteys. Lisäksi havaittiin, että seerumin korkea IL-6 taso heikensi parodontiitin paranemista. T1DM potilailla havaittiin käänteinen yhteys seerumin HDL-pitoisuuden ja tulehtuneiden ientaskujen määrän välillä. Tutkittavilla, joilla seerumin HDL-taso oli matala (<1.35 mmol/l), oli 50 % enemmän tulehtuneita ientaskuja kuin niillä, joilla HDL-taso oli korkea (≥1.35). Parodontiitti-ryhmässä seerumin TNF-α/IL-10 suhde oli kolminkertainen verrattuna kontrolliryhmän vastaavaan ilmentäen voimakkaampaa matala-asteista tulehdusta parodontiitti-potilailla. Matalista (<4 mm) ientaskuista kerätyn ientasunesteen MMP-8 pitoisuuden ja parodontiitin vaikeusasteen välillä vallitsi merkittävä postiivinen yhteys parodontiitti-potilailla. Yhteenvetona, systeemisen tulehdustilan ja hampaiden kiinnityskudosten välillä vallitsee kaksisuuntainen yhteys; toisaalta parodontiitti lisää matala-asteista systeemistä tulehdustilaa ja toisaalta kohonnut systeeminen tulehdustila lisää alttiutta parodontiittiin ja siihen liittyvään inflammaatioon. Lisäksi ientaskunesteen korkea MMP-8 pitoisuus matalissa ientaskuissa voi merkitä lisääntynyttä alttiutta parodontiumin alueen tulehdukselle ja kudostuholle.

La miniaturisation des pièces est une étape importante pour la progression de la microtechnologie dans plusieurs domaines (connectique, médical, optique, microsystèmes mécaniques). Pour cela, le moulage par microinjection, semble être la solution clé pour la production à grande échelle de micro-composants de polymères. Pour les polymères semi-cristallins, la cristallisation, sous fort taux de cisaillement et sous des vitesses de refroidissement élevées (about 100 K/s), induit des morphologies et des propriétés spécifiques. Elle prend donc une importance considérable dans le processus de microinjection par rapport au moulage par injection classique où les épaisseurs injectées sont généralement supérieures à 1 mm. Ces microstructures ont une grande influence sur les propriétés mécaniques du produit final. La prédiction de ces propriétés à partir de la description de la microstructure est un défi technique et scientifique. Durant cette thèse, deux polymères semi-cristallins ont été microinjectés, le polyéthylène haute densité et le polyamide 12. Les analyses obtenues par la microscopie otiques montrent que les morphologies cristallines varient entre les micro- et les macro-pièces. Tandis que la morphologie de ‘peau-cœur' est présente dans les macropièces, les micropièces présentent une morphologie plutôt particulière. Les analyses combinées de diffusion et de diffraction des rayons X (SAXS et WAXS) avec un microfaisceau synchrotron, nous ont permis de déterminer la microstructure induite par le processus de microinjection dans toute l'épaisseur des pièces. Nous avons constaté que la morphologie et les orientations cristallines induites sont très dépendantes des conditions d'injection ou de microinjection. Une diminution de l'épaisseur, de la vitesse et de la température du moule, augmente l'orientation cristalline en limitant la relaxation des chaînes de polymères. / The components miniaturization is an important step in the evolution of micro technology in several domain (connectivity, medical, optical, mechanical, microsystems). For this purpose, the micro-injection molding seems to be the key solution for the large-scale micro-polymer components production.The crystallization of the semi-crystalline polymers under high shear and cooling rates (about 100 K / s), induces specific properties and morphologies, consequently, it takes a substantial importance in the process of micro-injection compared to conventional injection molding where the usually injected thicknesses is over 1 mm. These micro-structures have a great influence on the mechanical propertie of the final product. The prediction of the final product's properties based on the illustration of the micro-structure is a technical and scientific challenge. In this thesis, two semi-crystalline polymers were micro-injected, the high density polyethylene and the polyamide 12. The obtained analyzes with the use of an optical microscope showed that the Morphology of Crystals vary between micro-and macro-pieces. While the morphology of 'peau-cœur' is present in the macro-pieces, the micro-parts have a particular morphology. The combined analysis of diffusion and X-ray diffraction (WAXS and SAXS) along with the synchrotron microbeam, has allowed us to determined the micro-structure induced by the micro-injection process throughout the thickness of the pieces.We have identified that the morphology and the induced crystal's orientation are very dependent on the conditions of injection or micro-injection. The decrease of the thickness,speed and temperature of the mold will increase the crystal orientation by limiting the relaxation of the polymer chains.

Abstract The effect of alcohol intake on the pathophysiology of atherosclerotic cardiovascular disease is controversial, especially with respect to heavy alcohol intake. The pathobiology behind atherosclerosis is a complex and multiparametric phenomenon, therefore a self-organizing map (SOM), an unsupervised learning based artificial neural network technique, was applied in the present work. This study was carried out to investigate the effect of heavy alcohol intake on the pathophysiology of atherosclerosis, including several lipoproteins and adiponectin, an adipocyte-derived cytokine that may ameliorate atherosclerosis. Firstly, the effect of heavy alcohol intake on the capacity of HDL and its subclasses (HDL2 and HDL3) to mediate cholesterol efflux from macrophages was studied. Secondly, data of ultracentrifugally isolated lipoproteins were fed into SOM analysis to investigate whether this method can find diverse lipoprotein phenotypes from the heterogeneous lipoprotein data. Thirdly, the aforementioned method was applied to multivariate data of alcohol drinkers to study whether distinct metabolic profiles are associated to heavy alcohol consumption. The results revealed that HDL2, not HDL3, of heavy alcohol drinkers had an enhanced capacity to remove cholesterol from macrophages when compared with control persons. SOM analysis enhanced the ultracentrifugally based lipoprotein data and depicted several novel lipoprotein phenotypes. In addition, lipoprotein-based SOM analysis found two distinct metabolic profiles in heavy alcohol drinkers: an anti-atherogenic and a metabolic syndrome-like profile with opposite metabolic features, such as characteristics of lipoproteins, plasma concentration of adiponectin and prevalence of metabolic syndrome. These profiles also tended to differ in their CV risk. In conclusion, the enhanced cholesterol efflux capacity of HDL2 in heavy drinkers is an anti-atherogenic change linked to alcohol drinking. However, clinically it may be important to be aware that although heavy alcohol drinkers have a low LDL-C level, they differ in their other lipoprotein measures, forming distinct phenotypes with potentially different CV risks. Finally, SOM analysis of ultracentrifugally based lipoprotein data generates in silico classification of lipoprotein particles and thereby offers a new tool for lipoprotein research. / Tiivistelmä Alkoholinkäytön vaikutus ateroskleroottisen sydän- ja verisuonitaudin patofysiologiaan on kiistanalainen, etenkin runsaan alkoholinkäytön kohdalla. Koska patobiologia ateroskleroosin taustalla on monimutkainen ilmiö, tässä työssä sovellettiin menetelmänä itseorganisoituvaa karttaa, joka on ohjaamattomaan oppimiseen perustuva neuroverkkomalli. Tutkimuksen tavoitteena oli selvittää runsaan alkoholinkäytön vaikutusta ateroskleroosin patofysiologisiin merkkiaineisiin, mukaan lukien useita lipoproteiineja sekä adiponektiini, rasvasoluperäinen sytokiini, joka voi lievittää ateroskleroosia. Ensimmäisessä osatyössä tutkittiin runsaan alkoholinkäytön vaikutusta HDL:n ja sen alafraktioiden (HDL2 ja HDL3) kykyyn poistaa kolesterolia makrofageista. Toisessa osatyössä ultrasentrifuugaukseen perustuva lipoproteiiniaineisto syötettiin itseorganisoituvaan karttaan. Työssä selvitettiin löytäisikö menetelmä erilaisia lipoproteiinifenotyyppejä heterogeenisestä aineistosta. Kolmannessa osatyössä em. menetelmää sovellettiin monimuuttuja-aineistoon, joka koostui runsaasti alkoholia käyttävistä ja verrokeista. Tutkittiin, liittyykö runsaaseen alkoholinkäyttöön erilaisia metabolisia profiileja. Tulokset osoittivat, että suurkuluttajien HDL2-hiukkasen kolesterolinpoistokyky makrofageista oli suurempi kuin verrokeilla. Itseorganisoituvaan karttaan perustuva lipoproteiinien luokittelumenetelmä löysi useita uusia lipoproteiinifenotyyppejä. Lisäksi, em. menetelmä löysi suurkuluttajilta kaksi erilaista metabolista profiilia: anti-aterogeeninen ja metabolisen syndrooman kaltainen. Näillä oli vastakkaiset metaboliset piirteet, kuten lipoproteiinien ominaisuudet, adiponektiinin pitoisuus plasmassa ja metabolisen syndrooman esiintyvyys. Profiileihin liittyi mahdollisesti myös erilainen sydän- ja verisuonitautiriski. Tutkimus osoittaa, että alkoholin suurkuluttajilla havaittu parempi HDL2:n kyky poistaa kolesterolia soluista on anti-aterogeeninen muutos, joka liittyy alkoholin käyttöön. Kliinisesti voi olla merkittävää, että vaikka alkoholin suurkuluttajilla oli pieni LDL-C pitoisuus, he jakaantuivat muiden lipoproteiiniperäisten muuttujien perusteella kahteen eri fenotyyppiryhmään, joihin liittyi erilainen sydäntautiriski. Lisäksi itseorganisoituva kartta loi ultrasentrifugoinnilla eristetyille lipoproteiineille in silico -luokittelun, joten se tarjoaa uuden työkalun lipoproteiinitutkimukseen.

La capacité des particules HDL à exercer des effets anti-athérogènes passe notamment par leur capacité à assurer le transport inverse du cholestérol (RCT). L'objectif principal de mon programme de recherche est l'étude de l'étape initiale du transport inverse du cholestérol que représente l'efflux de cholestérol du macrophage, dans le contexte des maladies métaboliques et du risque cardiovasculaire et de mortalité. J'ai étudié la relation entre l'efflux, et les conséquences sur le développement de l'athérosclérose dans un contexte métabolique particulier ; le syndrome métabolique (SM). J'ai démontré que les critères individuels du SM sont intimement liés à l'efflux et que ces deux notions sont associées de façon indépendante aux paramètres cliniques de l'athérosclérose. J'ai aussi évalué la pertinence de l'efflux de cholestérol comme biomarqueur de la mortalité. Cette étude identifie l'efflux comme prédicteur de la mortalité toutes causes confondues, indépendamment des taux de HDL-cholestérol et des facteurs de risques cardiovasculaires traditionnels, dans une population de patients traités par angioplastie coronaire primaire, suite à un infarctus du myocarde avec élévation du segment ST. Enfin, je me suis intéressée à à une situation métabolique particulière ; l'état postprandial. Mes travaux montrent que la réponse postprandiale hypertriglycéridémique physiologique observée chez des individus sans désordre métabolique ne s'accompagne pas d'altération majeure de l'efficacité du RCT ou de l'inflammation systémique. Mes travaux confirment le rôle déterminant de l'efflux dans la prévention du développement de l'athérosclérose et de la mortalité cardiovasculaire. / The contribution of high-density lipoprotein to cardiovascular benefit is closely linked to its anti-atherogenic role in the cellular cholesterol efflux. The main purpose of my project was to evaluate the efficiency of the first step of reverse cholesterol transport (RCT), which is the efflux capacity, on metabolic disorder context, on cardiovascular risk and on mortality. My research has focused on three independent and complementary parts. I have first evaluated the relationship between efflux and its consequences on atherosclerosis development in a metabolic syndrome (MetS) population. I have shown that individual criteria of MetS are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis. In a second study I identified cholesterol efflux capacity as a predictor of all-cause mortality in consecutive ST-segment elevation myocardial infarction patients treated by primary angioplasty, independent of HDL-C, traditional cardiovascular risks or cardiac risk factors. Finally I have evaluated the consequences of postprandial hypertriglyceridemia on the functionality of key steps of RCT and associated anti-inflammatory components. My work has shown that the physiological postprandial hypertriglyceridemia response is not accompanied by a major alteration in the efficiency of RCT or systemic inflammation, on individual without metabolic syndrome. In conclusion, I have confirmed the crucial role of the first step of reverse cholesterol transport in preventing the development of atherosclerosis and cardiovascular mortality.

Dyslipidemia can be a comorbidity of both insulin-resistance and atherosclerosis. Hypertriglyceridemia is common in hyperglycemia and is associated with hypoalphalipoproteinemia (low HDL) and with altered nucleotide or purinergic signaling. We therefore hypothesized that extracellular nucleotides may affect hepatic lipoprotein metabolism. Our studies confirm this view and show that nucleotides regulate cellular proteolytic pathways in liver cells and thereby control lipoprotein secretion and their metabolism by hepatic lipase (HL). Treatment of liver cells with the nucleotide, adenosine diphosphate (ADP), stimulates VLDL-apoB100 and apoE secretion, but blocks HDL-apoA-I and HL secretion. ADP functions like a proteasomal inhibitor to block proteasomal degradation and stimulate apoB100 secretion. Blocking the proteosome is known to activate autophagic pathways. The nucleotide consequently stimulates autophagic degradation in liver cells and increases cellular levels of the autophagic proteins, LC3 and p62. Confocal studies show that ADP increases cellular LC3 levels and promotes co-localization of LC3 and apoA-I in an autophagosomal degradation compartment. ADP acts through the G-protein coupled receptor, P2Y13, to stimulate autophagy and block both HDL and HL secretion. Overexpression of P2Y13 increases cellular LC3 levels and blocks the induction of both HDL and HL secretion, while P2Y13 siRNA reduce LC3 protein levels and cause up to a ten-fold stimulation in HDL and HL secretion. P2Y13 gene expression regulates autophagy through the insulin receptor (IR-β). A reduction in P2Y13 expression increases the phosphorylation of IR-β and protein kinase B (Akt) >3-fold, while increasing P2Y13 expression inhibits the activation of IR-β and Akt. Experiments with epitope-labeled apoA-I and HL show that activation of purinergic pathways has no effect on the internalization and degradation of extracellular apoA-I and HL, which confirms the view that nucleotides primarily impact intracellular protein transport and degradation. In conclusion, elevated blood glucose levels may promote dyslipidemia by stimulating purinergic signaling through P2Y13 and IR-β and perturbing the intracellular degradation and secretion of both HDL and VLDL.

La mémoire Flash est actuellement extrêmement utilisée en tant que mémoire non volatile pour le stockage des données numériques dans presque tout type d'appareil électronique nomade (ordinateur portable, téléphone mobile, tablette, …). Pour dépasser ses limites actuelles (densité d'informations, endurance, rapidité), un grand nombre de recherches se développent notamment autour du concept de mémoires résistives qui repose sur la commutation entre différents niveaux de résistance, via l'application d'une tension.Les mémoires dont la variation de résistance dépend de réactions électrochimiques (ReRAM) sont potentiellement de bonnes candidates pour les mémoires non volatiles de prochaine génération; les mécanismes d'oxydo-réduction impliqués sont cependant souvent de type filamentaire, mettant notamment en jeu des migrations de cations d’éléments métalliques (provenant des électrodes), ou de lacunes d’oxygène. Ce caractère filamentaire rend difficilement atteignable la miniaturisation extrême, à l’échelle nanométrique.Dans cette thèse, une classe de matériaux particulière -utilisée dans le domaine du stockage d'énergie- est étudiée. L’objectif est d’approfondir l’origine des processus de commutation de résistance observés sur des films de LixCoO2. Nous caractérisons d'abord les propriétés structurales et électriques de tels films, ainsi que le comportement électrique des dispositifs élaborés à partir de ces films. Nous étudions ensuite les mécanismes électrochimiques qui sont à l’origine des commutations résistives, dans la configuration d’un contact micrométrique électrode/film/électrode. Nous cherchons à déterminer la validité d’un mécanisme qui avait été proposé auparavant, mais non démontré. Nous étudions également la cinétique de commutation des dispositifs, et proposons un modèle numérique permettant d’expliquer les résultats expérimentaux observés. Enfin, nous étudions l’applicabilité potentielle des dispositifs (intégrant les films de LixCoO2) aux mémoires Re-RAM au travers de leurs performances en termes d’endurance (nombre maximum de cycles d’écriture/effaçage), et de stabilité. En particulier, nous étudions l’influence de plusieurs paramètres (impulsions de tension, nature des électrodes, température et c…) sur ces performances. / Flash memory is now extensively used as non-volatile memory for digital data storage in most mobile electronic devices (laptop, mobile phone, tablet...). To overcome its current limits (e.g. low information density, low endurance and slow speed), many researches recently developed around the concept of resistive memories based on the switching between different resistance levels by applying appropriate bias voltages.Memories whose resistance variations depend on electrochemical reactions (ReRAM) are potentially good candidates towards next-generation non-volatile memories. The underlying redox mechanisms observed are however often of the filamentary type, involving in particular migration of cations of metal elements (coming from the electrodes), or oxygen vacancies. This filamentary character makes it challenging to attain extreme downscaling towards the nanometric scale.In this thesis, a particular class of materials - used in the field of energy storage - is studied. The aim is to investigate the origin of the resistance switching processes observed in LixCoO2 films. We first characterize the structural and electrical properties of such films, as well as the electrical behaviors of the devices elaborated therefrom. We then investigate the electrochemical mechanisms which are at the origin of resistive switching, in the micrometric electrode/film/electrode configuration. We try to determine the validity of a formerly proposed mechanism which was however not yet demonstrated. Furthermore, we study the experimental switching kinetics of devices, and propose a numerical model to explain the results observed. Finally, we examine the potential applicability of LixCoO2-based devices to Re-RAM memories through the study of their performances in terms of endurance (i.e. maximum number of write/erase cycles) and retention. Specifically, the influence of several parameters (such as voltage pulses, chemical nature of the electrodes, temperature etc.) on these performances is investigated.