Dissertationen zum Thema „Insular State“

Mestrado em Gestão / MBA
A investigação visou, passados dez anos, uma avaliação técnica das privatizações em Cabo Verde no sentido de, através de respostas a várias questões, nomeadamente, sobre i) o seu papel na opção estratégica de desenvolvimento do país e a coerência com os objectivos, modefo, programa, ritmo e processo adoptados, ii) a evolução das empresas privatizadas em termos da performance económico - financeira e iii) o impacto dessa evolução na macroeconomia e competitividade do País, se formular uma tese sobre "As privatizações num País pequeno, insular e arquipelágico: o caso de Cabo Verde ". Nesse âmbito, o trabalho apresenta uma parte dedicada às questões de natureza teórica e análise da literatura e outra para as questões de natureza aplicada. Mais especificamente, para cumprir com a formulação do problema, desenvolveu-se, em termos teóricos, i) a análise conceptual prevalecente na dinâmica das privatizações a nível internacional , questionando as diversas lógicas e fins, ii) a revisão da literatura sobre o desempenho económico - financeiro das empresas privatizadas e em tenvos aplicados, iii) a mensuracão dos resultados das privatizações a nível do desenvolvimento económico - social de Cabo Verde, iv) a avaliação dos resultados também a nível das empresas privatizadas para, a partir daí, v) tirar as conclusões, tomando três referências de comparação, a situação da empresa antes da respectiva privatização, estudos da Price Waterhouse sobre as empresas públicas cabo-verdianas antes das Privatizações e estudos internacionais sobre empresas privatizadas. O estudo empírico baseou - se numa amostra de 11 empresas privatizadas entre 1993 e 1999 e conclui que, apesar do pouco tempo decorrido, há evidências claras de i) uma redução significativa do peso do Estado na economia, ii) uma contribuição muito positiva para os indicadores macroeconómicos do país e iii) melhorias significativas no pós - privatização dos indicadores de rendibilidade, eficiência operativa, vendas e endividamento, com poucas excepções como no caso da ELECTRA (empresa de electricidade e água), justificado pelo impacto da profunda reestruturação estratégica de que foi alvo antes da privatização.
This dissertation makes a technical assessment of Cape Verde privatizations in order to conclude about "Privatization in a small, insular and archipelago country - the Cape Verde Republic case", by the answer to a lot of questions, namely, i) the role of privatization in the strategic development option of Cape Verde and the coherence of the adopted model, program, cadence and process, ii) the evolution of the economic and financial performance of the privatized firms and iii) the impact of this evolution on the macroeconomic performance and competitiveness of the country. For that, the work is based on one part dedicated to theoretical analysis and literature research and another one to applied questions. Specifically, to find an answer to the proposed problem, it is developed, in a theoretical approach, i) a concept analysis prevailing in the dynamic of the international privatizations, ii) a literature research concerning the result on the privatized firms performance , in the applied questions, iii) the measurement of the privatization impact in the Cape Verde economic development, iv) the measurement of the privatization impact in the firms level and, finally, v) conclusions, using three references, namely, the firm situation before privatization, Price Waterhouse research about Cape Verde State Owned Enterprises before privatizations and international studies about privatized firms. The empirical research was based on a sample of 11 cape - verdeans State Owned Enterprises privatized between 1993 and 1999 and the conclusion is, in spite of the short elapsed time, there are clear evidences of i) meaningful reduction of State weight in the cape -verdean economy, ii) a positive contribution from the privatized enterprises to the macroeconomic ratios of the country and iii) improvements in the post - privatization ratios of profitability, operating efficiency, outputs and leverage, with few exceptions like ELECTRA (water and electricity enterprise), justified by the strategic alteration before privatization.

Tese de Doutoramento em Ciências Sociais na especialidade em Desenvolvimento Socioeconómico
A tese investiga a temática da resiliência económica de Pequenos Estados Insulares. Tomando como estudo de caso, São Tomé e Príncipe, pretende-se analisar e compreender os desafios das políticas macroeconómicas na construção da resiliência económica de uma pequena economia insular e compreender por que razão as políticas macroeconómicas implementadas neste país não têm contribuído para promover a sua resiliência económica. A investigação fundamentada na análise da bibliografia sobre a temática, nos indicadores sociais e económicos e na perceção de alguns policymakers obtida através de entrevistas de elite semiestruturadas permite-nos considerar que em São Tomé e Príncipe não foram criadas, pelos governos, as condições básicas para a construção da sua resiliência económica. Da investigação emergiram um conjunto de fatores que levam a considerar que a falta de uma visão estratégica para o crescimento económico e o desenvolvimento no médio/longo prazos, as políticas macroeconómicas não têm merecido a devida relevância no contexto das políticas públicas, ao contrário do que se observou em outros países com características similares. A fragilidade institucional aliada à falta de sentido de interesse geral condicionam o contributo das políticas macroeconómicas na promoção do crescimento económico sustentável, em particular e a promoção de mudanças para o desenvolvimento, em geral.
The thesis investigates the theme of the economic resilience of Small Island States. Taking São Tomé and Príncipe as a case study, we intend to analyze the contribution / challenges of macroeconomic policies in building the economic resilience of a small island economy to understand why policies implemented in this country have not contributed to promote its economic resilience. The research, based on the analysis of the literature on the subject, social and economic indicators as well as the perception of policymakers obtained through semistructured interviews allow us to consider that in São Tome and Príncipe the government has not created sustainable essential conditions for building the country’s economic resilience. From this research emerged a set of factors that allow to consider that due to lac of strategic vision for economic growth and development in medium/long terms, macroeconomic policies have not been given due relevance in the context of public policies, in contrast of what has been observed in other countries with similar characteristics. The institutional weakness along with lack of the sense of general interest have conditioned the contribution of macroeconomic policies in promoting sustainable economic growth, in particular, and the promotion of changes for development, in general.
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Increasing numbers of people world-wide develops the disease type 2 diabetes. Development of type 2 diabetes is characterized by a shift from an insulin sensitive state to an insulin resistant state in peripheral insulin responding organs, which originates from the development of insulin resistance in the adipose tissue. Insulin resistance in combination with reduced pancreatic insulin secretion lead to overt type 2 diabetes. In this thesis, the insulin signaling network in primary adipocytes was analyzed. Key proteins and mechanisms were studied to gain deeper knowledge of signaling both in the insulin sensitive state and in the insulin resistant state produced by rapid weight gain as well as in type 2 diabetes. The surface of the adipocyte is dotted with invaginations in the cell membrane called caveolae that act as important metabolic and signaling platforms in adipocytes, and also harbor the insulin receptor. In paper I we show that insulin stimulation of primary adipocytes results in a rapid phosphorylation of the insulin receptor and caveolin-1, and that internalization of the proteins is mediated by endocytosis of caveolae. Weight gain due to overfeeding and obesity has been associated with the development of insulin resistance in insulin sensitive tissues such as the adipose tissue. In paper II we show that short-term overfeeding for one month of lean subjects results in an insulin resistant state. At the end of the study, the subjects had developed a mild systemic insulin resistance. Moreover, in isolated subcutaneous adipocytes we found several alterations of the insulin signaling pathway that mimicked alterations found in isolated subcutaneous adipocytes from subjects with type 2 diabetes. In paper III we present a first dynamic mathematical model of the insulin signaling network in human adipocytes that are based on experimental data acquired in a consistent fashion. The model takes account of insulin signaling in both the healthy, insulin sensitive state and in the insulin resistant state of type 2 diabetes. We show that attenuated mTORC1-mediated positive feedback to control of phosphorylation of IRS1 at Ser307 is an essential component of the insulin resistant state of type 2 diabetes. A future application of the model is the identification and evaluation of drug targets for the treatment of insulin resistance and type 2 diabetes. In paper IV we examine the protein kinase that catalyzes the insulin stimulated mTORC1- mediated feedback to IRS1. We find that the phosphorylation of IRS1 at Ser307 is not likely to be catalyzed by the kinases S6K1, mTOR or PKB. However, a catalyzing protein kinase for the in vitro phosphorylation of IRS1 at Ser307 was found to be associated with the complex mTORC1. In conclusion, this thesis provide new insights and characterize mechanisms of the intrinsically complex insulin signaling network of primary adipocytes, both in insulin sensitive and insulin resistant states.

Cette thèse se concentre sur le développement de solutions énergétiques basées sur les énergies renouvelables pour répondre à la demande croissante et aux prix fluctuants des énergies fossiles. En partenariat avec le LERMAB de l'Université de Lorraine et LEMA de l'Université des Comores, l'étude propose des systèmes hybrides combinant solaire, éolien et diesel avec une gestion optimisée du stockage d'énergie pour les milieux ruraux aux Comores. Utilisant des logiciels comme Homer Energy, Trnsys et Polysun, l'étude dimensionne ces systèmes en exploitant le potentiel solaire (5 kWh/m²/jour) et éolien (plus de 6 m/s) des Comores pour une distribution continue et décarbonée de l'énergie par la SONELEC. Deux solutions hybrides sont développées dans cette thèse. La première, destinée à un village rural, intègre éolien, solaire photovoltaïque et un générateur diesel d'appoint. Elle produit un excédent de 660 087 kWh/an, soit 74,2% de surplus d’énergie, avec un coût de 0,29 dollar/kWh, inférieur à celui de la SONELEC. La production est dominée par le solaire (82%), suivi de l’éolien (18%), et le diesel est réduit à presque 0 %, assurant une part de 100% renouvelables et zéro émission de gaz. Le système PV-Éolien-Diesel-Batterie optimise les ressources locales et inclut des batteries pour une alimentation stable malgré les fluctuations. La deuxième solution, validée à l'IUT de Longwy, concerne les habitats individuels avec des systèmes PV/T pour l'énergie électrique et l'eau chaude sanitaire. Combinant des panneaux photovoltaïques et des collecteurs thermiques, ces systèmes permettent une double production d'électricité et de chaleur. Un modèle de collecteur hybride PV/T, conçu et validé par des études expérimentales au Lermab, couvre 70% des besoins en eau chaude sanitaire et 80% des besoins en énergie électrique, avec un rendement total de 40%. Performants toute l'année, ils restent efficaces même dans des conditions climatiques variables. Cette recherche propose une politique énergétique durable pour les Comores, visant à réduire la dépendance au diesel, améliorer la qualité de vie et stimuler l'économie locale. Elle met en avant l'importance des mécanismes de financement, la formation des communautés locales et l'intégration de systèmes hybrides avec collecteurs PV/T pour une efficacité énergétique optimale
This thesis focuses on the development of renewable energy solutions to address the growing demand and fluctuating prices of fossil fuels. In collaboration with LERMAB of the University of Lorraine and LEMA of the University of Comoros, the study proposes hybrid systems combining solar, wind, and diesel with optimized energy storage management for rural areas in Comoros. Using software such as Homer Energy, Trnsys, and Polysun, the study designs these systems by leveraging the solar potential (5 kWh/m²/day) and wind potential (over 6 m/s) of Comoros for continuous and decarbonized energy distribution by SONELEC. Two hybrid solutions are developed in this thesis. The first, intended for a rural village, integrates wind, solar photovoltaic, and a backup diesel generator. It produces an excess of 660,087 kWh/year, representing a 74.2% energy surplus, with a cost of dollar 0.29/kWh, lower than that offered by SONELEC. Production is dominated by solar (82%), followed by wind (18%), with diesel minimized to nearly 0%, ensuring a 100% renewable share and zero gas emissions. The PV-Wind-Diesel-Battery system optimizes local resources and includes batteries to ensure stable power supply despite fluctuations. The second solution, validated at the IUT of Longwy, targets individual homes with PV/T systems for electrical energy and hot water. Combining photovoltaic panels and thermal collectors, these systems allow for dual production of electricity and heat. A hybrid PV/T collector model, designed and validated by experimental studies at LERMAB, covers 70% of hot water needs and 80% of electrical energy needs, with a total efficiency of 40%. Effective year-round, these systems remain efficient even in variable climatic conditions. This research proposes a sustainable energy policy for Comoros, aiming to reduce dependence on diesel, improve quality of life, and stimulate the local economy. It highlights the importance of financing mechanisms, training of local communities, and the integration of hybrid systems with PV/T collectors for optimal energy efficiency

Insulin resistance is the major metabolic defect in obesity and Type 2 diabetes. Increased lipid accumulation is strongly associated with insulin resistance. A significant component of insulin resistance is thought to be a reduced ability of insulin to activate the cascade of phosphorylation events that lead to the metabolic effects of this hormone. The broad aims of this thesis were to examine the effect of high-fat diets containing different fat subtypes on in vivo insulin signalling, under conditions normally used to detect whole body insulin resistance, and to compare the effects of acute and chronic lipid oversupply on insulin signalling in vivo. Time-course and dose-response effects of insulin stimulation on site-specific phosphorylation of key signalling proteins were studied in rat tissues in vivo, to establish an appropriate experimental system to examine the onset of activation of the insulin signalling pathway. It was determined that short insulin infusions with concurrent glucose infusion, similar to the beginning of a euglycaemic-hyperinsulinaemic clamp, significantly increased the phosphorylation of major intermediates of the insulin signalling pathway in important tissues of insulin action (skeletal muscle [RQ], liver [LIV] and white adipose tissue [EPI]). These experiments provided a platform to study insulin signalling under the same conditions used to study lipid-induced insulin resistance. The provision of diets enriched in polyunsaturated or saturated fatty acids (FA) resulted in the corresponding enrichment of these fat subtypes in rat plasma and tissues. However, the effects on insulin signalling were essentially the same. Both fat diets induced defects in sitespecific phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (PKB) in RQ and LIV, but not EPI. This suggests that the amount of fat in the diet, rather than enrichment in a particular fat subtype, had a greater impact on the development of signalling defects and that the response to high-fat feeding was tissue-specific. A 3hr elevation of circulating FA (using a lipid/heparin infusion), to a level that is relevant in clinical Type 2 diabetes, impaired insulin-stimulated PKB phosphorylation with no significant effect on IRS-1 phosphorylation. This suggests that there may be differences in the way acute and chronic exposure to increased FA impair insulin signalling. The phosphorylation defects observed in both chronic and acute studies did not seem to be associated with activation of major stress signalling pathways (JNK and NFkB), which have been suggested to have a role in lipidinduced insulin resistance. In conclusion, these studies demonstrate that impaired IRS-1 and PKB phosphorylation do have a role in the reduced insulin action observed with lipid oversupply in vivo, because the changes were detected under similar conditions as those used to determine whole body insulin resistance.

Introduction: Insulin resistance is the hall mark of a number of pathological conditions and is thought to play a major role in the cardiovascular risk associated with them. This thesis critically evaluates two insulin resistant conditions - polycystic ovary syndrome (PCOS) and type 2 diabetes (T2DM) - where there are many unresolved issues. During the course of these studies, the effect of weight loss and medications in modifying cardiovascular risk in these conditions was evaluated. Methods: The first studies focused on a randomised open labelled parallel study of metformin and rimonabant in obese patients with PCOS. Subsquently, an extension to this study was undertaken where patients who were on rimonabant were changed over to metformin, whereas those on metformin were continued on metformin for another 3 months. As part of this study the effect of rimonabant and metformin on incretin hormones in patients with PCOS was studied. The next studies focused on a randomised double blind placebo controlled study on the pleotrophic effect of atorvastatin in patients with PCOS. Subsequent metformin therapy after atorvastatin treatment was undertaken. This study led to the investigation of the effect of simvastatin and atorvastatin on biological variation of lipids in patients with T2DM that has got implications in treating to lipid targets. A corollary to this study was whether the biological variation of LDL calculated using Friedewald formula differed from that of direct LDL. Results: In the first series of studies, after 12 weeks of rimonabant there was a significant reduction in anthropometric and metabolic parameters as well as biochemical hyperandrogenemia in patients with PCOS. There was no change in any of these parameters in the metformin treated group. In three months extension arm to this study, metformin maintained the weight loss as well as enhanced the metabolic and biochemical parameters achieved by treatment with rimonabant, compared to 6 months of metformin treatment alone. There was a significant and reversible increase in glucose-dependent insulinotropic polypeptide (GIF) levels after 3 months of rimonabant treatment. There were no changes in GIF or glucagon-like peptide-1 (GLP-1) levels with metformin. In the second series of studies it has shown that atorvastatin was effective in reducing inflammation, biochemical hyperandrogenemia and metabolic parameters in patients with polycystic ovary syndrome after a 12 week period compared to placebo. The subsequent effect of three months metformin treatment was augmented by atorvastatin pre-treatment compared to placebo pre-treatment. In the subsequent study it was shown that the coefficient of variation (CV) of TC, LDL, HDL and TG on simvastatin was significant but comparable to atorvastatin in patients with T2DM. However, subsequent directly measured LDL cholesterol was shown to be an order of magnitude more stable when taking equivalent doses of atorvastatin rather than simvastatin. Conclusion: Both weight loss using rimonabant and atorvastatin were effective in reducing biochemical hyperandrogenemia and metabolic profile in patients with PCOS. The effect of rimonabant might be partly mediated through modulating GIF levels.

Un pilier d'une vie sociale fructueuse est la capacité de prédire correctement les actions des autres et de percevoir leurs états émotionnels. Des études d'interaction sociale chez les primates ont montré qu'ils sont capables de déduire ce que les autres peuvent entendre ou voir, et de prédire leurs émotions et intentions. Il a été montré qu'ils peuvent manifester différents degrés de comportements prosociaux, allant de la coopération jusqu'à des comportements altruistes et empathiques. Des études d'imageries fonctionnelles chez l'homme ont identifié l'insula antérieur (AI) comme une région cérébrale clé dans le traitement de l'empathie.Spécifiquement, cette région apparait comme l'aire intégratrice des activités liées à la douleur ressentie et observée, suggérant que l'empathie pourrait impliquer un modèle « miroir » des propriétés affectives et sensorielles de la douleur d'autrui. Cependant, les bases neuronales de ce processus n'ont pas encore été découvertes. Dans le but d'examiner le rôle de l'AI dans le traitement de l'empathie, nous avons enregistré l'activité des neurones dans l'AI de deux singes pendant qu'ils sont engagés dans une tâche sociale leur permettant de délivrer un stimulus aversif ou appétitif à leur partenaire, à lui-même ou à personne. Les résultats comportementaux ont montré que les singes prennent en compte le bien-être de leur partenaire. Les données neuronales rapportent différentes populations neuronales répondant aux stimuli aversif ou appétitif et ceux délivrés à soi ou à autrui. Notamment, la population neuronale répondant au stimulus aversif a montré trois profils d'activité : une représentation neuronale de l'expérience désagréable du partenaire, une représentation neuronale de sa propre sensation désagréable et une minorité de neurones montrant des propriétés miroirs entre soi et autrui. Nos résultats suggèrent un modèle neuronal de l'empathie représentant des propriétés distinctes entre l'expérience vécue et observée
A cornerstone of a successful social life is the ability to correctly predict others’ actions and empathically perceive their emotional states. Studies on primates’ social interaction have shown that thanks to their keen cognitive abilities monkeys are able to deduce what others can hear or see, and to predict others’ emotions and intentions. It has been shown that primates are able to display different degrees of prosocial behavior, from cooperation to even altruism and empathically driven behavior. Studies using fMRI techniques inhumans have identified the anterior insula (AI) as a key brain region in the processing of empathy. More precisely, this region emerged as the overlapping area activated for both experienced and observed pain,leading to the idea that empathy for pain may involve a mirror-matching model of the affective and sensory features of others' pain. However, the neuronal basis of this process has yet to be uncovered. In an attempt toextend and to investigate the role of the AI in the process of empathy we have recorded single cell activity inthe AI of two monkeys while they were engaged in a social task where based on the performed trials positiveor negative reinforcements could be delivered to self, another monkey, or nobody. Behavioral results showed that monkeys take into account the welfare of their partners even when this has no impact on their ownwelfare. Our neuronal findings report that distinct population of neurons respond differentially to outcomesfor self and other, and to appetitive and aversive outcomes. Interestingly the neuronal population responding to the aversive outcome showed mainly three profiles of activity: neuronal representation of conspecifics’unpleasant experience, neuronal representation of own unpleasant experience and a minority of neurons showing mirroring properties between self and other. Thus, our results suggest a neuronal model of empathy that accounts for the distinctive features between feeling and empathizing

PCOS is the commonest endocrine disorder amongst women associated with insulin resistance and adverse metabolic outcomes e.g. T2DM, dyslipidemia. TlDM, another metabolic disorder, on the other hand, results from auto immune destruction of insulin- producing pancreatic ~-cells, leading to hyperglycemia and its deleterious effects. The metabolic syndrome is associated with accumulation of visceral AT, which produces cytokines termed 'adipokines' implicated in the pathogenesis of diabetes and atherosclerosis. Circulating and AT omentin-l, an insulin sensitizing adipokine, were decreased in women with PCOS; metformin treatment (6 months) increased circulating omentin-l levels. Insulin and glucose decreased omentin-l production in AT; insulin also decreased circulating omentin-l in vivo. Furthermore, in vitro migration and angiogenesis were increased by serum from PCOS women compared to controls; these effects were attenuated by metformin treatment plausibly through the regulation of omentin-l levels via NF-KB (a pro-inflammatory nuclear transcription factor) and Akt pathways. CRP and VEGF induced in vitro migration and angiogenesis was decreased by omentin-l. In another study, there was a decrease in circulating omentin-l together with an increase in circulating adiponectin (fasting and postprandial), in TlDM subjects. Also, circulating and AT ASAA, a pro-inflammatory adipokine, which antagonizes insulin action, were increased in women with PCOS; metformin treatment (6 months) decreased circulating ASAA levels. Glucose increased ASAA production in AT. ASAA production by macrophages may account for these observations. Finally, circulating HMW and total adiponectin, an anti-inflammatory and insulin sensitizing adipokine, were higher in the morning and lower at night; corresponding NF-KB activities in serum treated endothelial cells were lower in the morning and higher at night. Hyperinsulinemic induction decreased HMW and total adiponectin levels but increased NF-N B activity in serum treated endothelial cells. These studies provide novel insights into the biology of adipokines, inflammation and insulin action pertinent to dysmetabolic states such as PCOS and diabetes.

Mestrado em Desenvolvimento e Cooperação Internacional
This dissertation attempts to review the critical theoretical issues concerning Small States and Small Insular Developing States, while aiming to answer some crucial related questions and to distinguish between these two notions. Additionally we attempt to spotlight some issues related to the development of Cape Verde having in consideration a possible comparison with two of the most successful African SIDS, namely Mauritius and Seychelles. A brief analysis of the social and economical situation of the three countries is made, seeking to underline their key development elements and assessing their economical and social structure. This dissertation mainly aims at assessing what Cape Verde can apprehend from the Mauritian and Seychellois experience, in an attempt to draw some useful conclusions to its development.
Esta dissertação procura rever as questões teóricas essenciais que dizem respeito aos Pequenos Estados e aos Pequenos Estados Insulares em Desenvolvimento e, simultaneamente, responder a algumas questões relacionadas com este âmbito. Adicionalmente, pretendem-se destacar algumas questões relacionadas com o desenvolvimento de Cabo Verde, tendo em consideração uma possível comparação com dois dos SIDS Africanos mais bem sucedidos, nomeadamente as Maurícias e as Seicheles. Com este intuito, é efectuada uma breve apreciação da situação económica e social destes países, numa tentativa de sublinhar os seus elementos fundamentais e de analisar a sua estrutura económica e social. Esta dissertação tem como seu objectivo fundamental a apreciação do que Cabo Verde poderá apreender da experiência de desenvolvimento das Maurícias e das Seicheles, numa tentativa de elaborar conclusões frutuosas para Cabo Verde.

Insulin resistance in diabetes (DMII) can result from membrane lipid (PM) changes. Membrane lipids play a major role in hormonal signal transduction and in appropriate amounts of such molecules may lead to either decreased, or increased membrane fluidity. Therefore, in this study we determined whether PM differences exist between African Americans (BL) and Caucasians (W) and if differences contribute to impaired insulin binding (IB) in DMII. Methodology: Subjects were recruited from Caucasian Control (CC) (n=10), African American Control (AC) (n=10), Caucasian Diabetics (CD) (n=5), African American Diabetics (AD) (n=10) groups. The diabetics were type II diabetics on daily insulin injections (age and sex-matched in both racial groups). The evaluations consisted of: three day dietary record, serum total cholesterol (TC), triglyceride (TRG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), glucose (Glu), hemoglobin A1C (A1C), insulin (Ins) levels and RBC membrane lipid composition including, fatty acids, phospholipids (PL), cholesterol (CH) and RBC insulin binding (IB), RESULTS: Cholesterol intake did not show any correlations with any blood constituents, membrane lipids or membrane properties. The macronutrient intake did not show a significant correlation with blood lipid levels, membrane properties and the anthropometric measurements as expected. The triglyceride levels were higher in diabetics (P <0.01). The lipoprotein evaluation indicated significant differences in VLDL (P <0.01), LDL (P <0.05) and HDL (P <0.0001) levels between control and diabetic subjects. There were no racial differences seen among the four groups. Diabetics had higher CH and it correlated with Glu (r= 0.65, P<0.05) and IB (r= -0.61, P <0.05). The CH/PL revealed strong correlation between LDL (r=0.42, P <0.01) and HDL (r= -0.56, P <0.05). The PM trans fatty acid levels (TFA) were highest in AD (P <0.01), but no correlations with IB & Glu. The PM saturated/polyunsaturated ratio (S/P) was higher in diabetics (P <0.05) correlating with insulin level (r= 0.42, P <0.01) & IB (r= -0.45, P <0.05), but no correlations with serum lipids occurred. The PL analysis showed no significant group differences for phosphatidyl inositol (PI) levels; however, significant racial differences were observed in phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). The W showed higher PE levels than BL and lower PC. The RBC rheological (PE/PS) properties (deformability) was lower in diabetics and AC than CC. The saturated nature of RBC [(SPH+PC)/(PE+PS)] was the lowest in CC (P< 0.056). The combination of increased S/P, and increased saturated nature, decreased PE/PS, increased CH/PL indicate decreased membrane fluidity and decreased RBC deformability, which might contribute to decreased IB in DMII. Differences in PE and PC levels between BL and W possibly indicate a racial difference in cause of insulin resistance. The racial differences in developing DMII need to be recognized so the therapeutic agents can target the exact problem in the metabolic pathway to correct the insulin resistance.

Recent advancements in gate stack engineering has led to the development of aggressively scaled, high mobility, high-k dielectric based NMOSFETs with metal gates. Most of the current literature on the subject also stressed on the need for a high temperature process step to attain the high mobility under minimal change of effective oxide thickness. However, the physical origin of high mobility is not well understood. In this work, fundamental insight into the necessity of the high temperature process step is provided. Novel experimental strategies are developed to understand the impact of interface states and bulk traps separately and exclusively on channel mobility. It is conjectured that the interface states at the SiO2/(100) bulk-Si interface are identical in nature (as far as coupling with the channel electrons is concerned) to those at the high-k/SiO2/(100) bulk-Si interface. Thus, the response of interface states on channel electrons in high-k insulator based NMOSFETs is properly calibrated by a novel thermal desorption of hydrogen experiment on SiO2/(100) bulk-Si NMOSFETs to yield a highly accurate parameterized equation. The value of interface state response parameter determined by the aforementioned experiment is compared with theoretical predictions, and independently determined projections from electrical stress measurements. The impact of transient charging on transport in the channel is investigated. It is conclusively shown that remote charge has minimal impact on mobility in the channel. The role of nitrogen induced fixed oxide charge is studied on a set of Hf-silicate samples. Role of soft optical phonon scattering and the beneficial impact of metal gates on soft optical phonon limited mobility are thoroughly investigated both theoretically and experimentally. Conclusions are drawn on the fundamental limit of mobility attainable in high-k dielectric based NMOSFETs.

Alzheimer's Disease (AD) is by far the most common cause of dementia affecting more than 35 million people worldwide. Despite considerable research, there is still no cure for this neurodegenerative disease and available treatments are only symptomatic. In the controversial literature about AD, a predominant idea refers to the crucial role of amyloid-beta protein (Abeta) in the pathogenesis of the disease; in fact, the feature in the brain of AD patients is the presence of extracellular plaques mainly composed of Abeta. Nevertheless, Abeta is physiologically produced in healthy individuals. Due to its biophysical properties, under certain conditions, Abeta may self-aggregate into multiple forms, ranging from 4 kDa monomers and including higher-order oligomers, protofibrils, and mature fibrils. For many years, the fibrillar Abeta assemblies, similar to what seen in amyloid plaques, have been considered mainly responsible for neurodegenation associated with AD. However, the quantity and temporal progression of amyloid plaques do not correlate well with the clinical evolution of the disease. There is now extensive evidence that soluble Abeta oligomers disrupt synaptic transmission and plasticity in AD. Moreover, new studies strengthen evidence that people with sporadic AD make normal amounts of Abeta, and that the toxic buildup is due to altered peptide disposal. These data are in line with the finding previously reported by our group that Abeta in its non-toxic monomeric state has a broad neuroprotective effect in vitro. This effect depends on the stimulation of type-1 insulin-like growth factor (IGF-I) receptors and/or other receptors of the insulin superfamily. The aim of this PhD thesis was to decipher Abeta activities, focusing on the relationship between the structure/aggregation state and the neurotoxic/biological activity. In paper I we have addressed the issue of Abeta toxicity, whereas the properties of the non-toxic form of Abeta, the monomer, have been considered in paper II and III. In paper I, the neurotoxic activity of Abeta was investigated in a particular model in which anabolic-androgenic steroid (AAS) sensitize neurons to the toxicity of Abeta oligomers. We found that, concentrations of the AAS that were not neurotoxic by themselves were able to increase neuronal susceptibility to the apoptotic stimulus provided by Abeta. In paper II and III, we have demonstrated that the Abeta, in its non-toxic monomeric state, activates type I IGF receptors and mimics the metabolic actions of IGFs in neurons and peripheral cells. In neurons, endogenous Abetarelease was required to uphold glucose uptake during activation, and exogenously added Abeta monomers caused the translocation of type-3 glucose transporters to the plasma membrane with ensuing glucose uptake. We suggest that pathological aggregation of Abetamonomers, as occurring in AD, might impair neuronal ability to cope with transient needs in energy provision.

Obesity and type 2 diabetes are the most prevalent metabolic diseases affecting over 50% of people in the western world. Although the pathogenesis of type 2 diabetes is not fully understood, growing evidence links this disease to a state of chronic inflammation, which occurs in metabolically active tissue such as the liver, adipose tissue and skeletal muscle and results in the secretion of inflammatory cytokines, of which interleukin-6 (IL-6) is one. It is generally accepted that elevations in the plasma and/or tissue of this family of cytokines have a negative effect on whole body glucose homeostasis. While there is compelling evidence for the negative effects of resistin and TNF-á on insulin sensitivity, the role of IL-6 in the etiology of insulin resistance is not fully understood. The notion of negative effects of IL-6 in metabolic processes is further confounded by the marked elevations of IL-6 which occur in conjunction with the beneficial activity of exercise. We firstly sought to examine the effect of the lipolytic hormone adrenaline on IL-6 expression and release in order to establish whether IL-6 acts independently of adrenaline in the regulation of fat metabolism. Reporting the absence of an effect of adrenaline on IL-6, we then investigated the role of IL-6 on metabolic processes in humans at rest and during exercise in circumstances where lipolysis was inhibited. Marked increases in IL-6 circulating protein and tissue gene expression were observed with exercise and further so with fatty acid suppression. In a mouse model of IL-6 depletion marked insulin sensitivity was observed, which was reversed with IL-6 treatment. In a mouse model with normal endogenous IL-6 levels IL-6 treatment also impaired glucose tolerance. Contrastingly, in a rat model both chronic and acute IL-6 treatment improved glucose tolerance In summary, studies from this thesis suggest that, rather than being causally related to insulin resistance, the cytokine IL-6 increases lipolysis, fat oxidation, and glucose metabolism in insulin sensitive tissues in humans. This does not appear to be the case in the mouse, where contrasting actions are observed, perhaps due to differences in the reliance of various parameters for metabolic processes between the species.

Les isolants topologiques 3D sont un nouvel état de la matière décrit par un volume iso-lant électriquement et recouvert par des états de surface métalliques. Une jonction Joseph-son topologique (TJJ) formée autour de ces états de surface peut théoriquement contenirun mode lié d’Andreev ayant une périodicité doublée par rapport aux modes liés d’An-dreev conventionnels 2p périodiques. Le mode d’Andreev 4p périodique serait la briqueélémentaire de l’ordinateur quantique topologique. Ainsi, nous étudions la dynamique dece mode particulier lors de mesures de Shapiro sur des jonctions Josephson fabriquées surdes isolants topologiques à base de bismuth.A?n d’identi?er les e?ets d’un mode 4p-périodique dans une mesure de Shapiro, nousutilisons un model phénoménologique permettant de simuler la caractéristique courant-tension d’une TJJ lors de telles mesures. Nous prédisons deux signatures du mode 4p-périodique et estimons leur robustesse face aux e?ets de chau?age par e?et Joule et face àun modèle d’empoisonnement thermiquement activé du mode 4p-périodique.Par des mesures de Shapiro, nous étudions la dynamique des TJJ basées sur le matériausimple qu’est le Bi2Se3. L’observation des deux mêmes signatures précédemment anticipéespar nos simulations, à savoir un ordre d’apparition non conventionnel des pas de Shapiroainsi que la persistance d’un supercourant à la fermeture du plateau de Shapiro n = 0prouve la présence d’un mode 4p-périodique.Notre étude s’est également portée sur un autre isolant topologique le BiSbTeSe2. Nousavons e?ectué sa croissance par cristallisation liquide-solide et avons mis en évidence,par des mesures d’interférométrie supraconductrice une supraconductivité de surface sanstransport électronique par le volume
Three dimensional topological insulators (3D TI) are a new state of matter composedof an electrically insulating bulk covered by metallic surface states. Theoretically, a topo-logical Josephson junction composed of these surface states can host an Andreev Boundstate (ABS) that has twice the periodicity of the conventional 2p periodic ABSs. The4p periodic ABS is expected to be the building block of topological quantum computing.Therefore, we study the dynamic of this particular ABS by performing Shapiro measure-ment on Josephson junctions built with bismuth based 3D TI.To identify the e?ects of a 4p periodic ABS in a Shapiro measurement, we use a phe-nomenological model that simulates the voltage-current characteristics of a TJJ. We predicttwo signatures of the 4p periodic ABS and estimate their robustness against Joule heatingand thermally activated quasiparticle poisoning of the 4p periodic mode.We study the Josephson junctions dynamics by performing Shapiro measurements onjunctions built on Bi2Se3. We observe the two previously anticipated signatures, whichare the non-conventional appearance order of the Shapiro steps and the remaining of asupercurrent at the closing of the Shapiro step n = 0. They prove the presence of a 4pperiodic ABS.We also study the topological insulator BiSbTeSe2 that we have grown by using themelting growth method. By superconducting interferometric measurements, we show asuperconducting surface transport without bulk electronic conduction

This thesis studies the physics of multilayer heterostructures grown from topological insulators (TIs), primarily bismuth selenide and antimony telluride, and other topologically trivial materials. This is done by extending a standard low-energy 3D TI Hamiltonian and varying its associated material parameters across the simulation domain. New results arising from the position-dependent TI interface model are found. For the first time, this method is incorporated into a density-functional theory (DFT) solver in order to study the self-consistent charge density in multilayer TI heterostructures due to the interface states. The thesis is structured as follows. The introduction (Ch. 1) presents a pedagogical review of the theory of 3D TIs and low-energy Hamiltonians used to study them, as well as typical methods in solid state physics that are made use of throughout the thesis. Chapter 2 presents the position-dependent Hamiltonian, showing new evidence for topological features of bulk states including varying degrees of band mixing and inversion; also, interface state tunnelling is shown to be affected by atomic layer orbital overlap, and incomplete localisation of surface states is demonstrated for antimony telluride. Chapter 3 presents a new DFT model of TI heterostructure interfaces and shows how conduction through TI interface states can be controlled with an electric field. Chapter 4 covers the extension of the model in Ch. 1 to 2D cross-sections of TI wires and heterostructures, showing for the first time evidence of localisation of conduction almost entirely within the inner interfaces of a 2D heterostructure wire. Chapter 5 presents our work with magnetic fields, demonstrating evolution of interface and bulk states with changing magnetic field and Landau level, as well as presenting new evidence for more complex spin structures in bismuth selenide arising from Landé factor signs. Our conclusions are presented in Chapter 6.

Diabetes mellitus is not only a very serious disease, causing discomfort and pain to millions across the world, but with the aging of the population and the prevalence of a sedentary lifestyle, it is assuming the proportion of a real epidemic, becoming a public health and social emergency. In answer to this call, research on diabetes has been intensely carried out in the past decades and the knowledge and understanding of its etiology have been significantly improved. However, investigation is still ongoing, many important questions are still unanswered, and the causes eliciting the pathogenesis and progression of the diseases are not yet fully understood. During all these years of research, sophisticated tools have been developed to study the glucose-insulin metabolic system in vivo, and cope with the inaccessibility to direct measurement of some of the key phenomena underlying the glycemic control. Such tools, as complex test protocols and model-based approaches used to interpret the experimental data, have proven powerful weapons of investigation, but, considering the epidemic proportion of the disease, there is great demand for approaches that are less invasive, less expensive and therefore more suitable for large clinical studies. Mathematical and statistical techniques that collectively go under the name of “population approaches” have already been developed and are largely employed for pharmacokinetics and pharmacodynamics studies in drug development. However, in spite of their interesting potential, they have not found significant application yet in the context of metabolism research. Thus, investigation is required to probe the feasibility and relevance of such approaches in the study of diabetes. The research presented here addresses these issues, and is aimed at applying these sophisticated techniques to the modeling of glucose metabolism, first assessing the applicability of these approaches and tailoring them to the problem under investigation, then employing them to the analysis of data from population studies. First, a simulated but physiologically plausible dataset is created based on previous real data and employed as a benchmark to assess the applicability of population approaches to the Intra Venous Glucose Tolerance Test (IVGTT) minimal model of glucose disappearance. Various population algorithms have been proposed in the literature, therefore a thorough comparison of the available methodologies is performed, and a sparse data situation is replicated to test the robustness of these methods in such cases. The results select the First-Order Conditional Estimation as method of choice and show its robustness to poor sampling. Then, a larger real dataset is employed and analyzed with the same techniques, this time assessing the quality of the results with a Monte Carlo sampling approach to profile the likelihood function. Then the population model is optimized, to provide a base model for the following covariate analysis. In fact, at the time of the experiments, demographic data about the subjects has been collected, and the purpose of the covariate analysis is to determine whether some of these variables are significantly correlated with the model parameters and can be successfully used to explain part of the differences among the subjects. After a first exploratory regression analysis, different models are tested, integrating the most significant covariates directly as predictors into the model. In agreement with previous findings in literature, basal insulinemia, age and visceral abdominal fat are shown to be good predictors of insulin sensitivity and their introduction in the model is able to account for about a third of the between-subject variability of the values of this parameter. The use of covariates enhances the explanatory power of the model and opens the way for devising new lighter experimental protocols. One of the main benefits of the population approaches, in fact, consists in their ability to borrow information across the population and use it to improve the individual parameter estimates. As a result, the experimental protocols can be less demanding, both in invasiveness and economic cost, allowing in this way a broader use in large clinical studies. The results presented here, in fact, show that population approaches are very robust and able to cope with sparse data situations. In addition, the use of covariates in the model enhances even further the power of such techniques and makes them very appealing approaches to the study of glucose-insulin metabolism. In addition, a population approach is proposed to solve the problem of the estimation of the Disposition Index (DI) of glucose tolerance in a population. Since both insulin sensitivity and beta-cell response must be taken into account to assess the actual efficiency of the glucose disposal system, the DI was proposed to condense the information conveyed by both these parameters in a single value. Traditionally, approaches based on a geometrical fit are used to determine the value of DI in a population of subjects characterized by the same degree of glucose tolerance. However, all these methods rely on the assumption that all the subjects in the population share exactly the same value of DI and are therefore not able to account for the population variability, which is inevitably inherent to biological data. In this work, a NonLinear Mixed-Effects Approach is proposed to analyze the distribution of the insulin sensitivity and beta-cell response indices across a population, and then obtaining the information on the DI from the population features thus estimates. Comparisons on simulated datasets between the newly proposed method and its competitors prove that a proper model of the variability structure is essential to avoid severe bias in the estimates.
Il diabete mellito è non solo una patologia molto seria, che causa disagi e sofferenze a milioni di persone nel mondo, ma, anche a causa dell’affermarsi di uno stile di vita sedentario e dell’invecchiamento della popolazione, negli ultimi decenni ha raggiunto proporzioni epidemiche, diventando una vera e propria emergenza sanitaria e sociale. Per fronteggiare questo problema, molte risorse sono state dedicate all’attività di ricerca scientifica, che ha permesso una più profonda conoscenza dell’eziologia del diabete. Tuttavia, il diabete è a tutt’oggi ancora inguaribile e molte questioni rimangono aperte, fra cui la completa comprensione dei fattori che causano e fanno progredire la malattia. Anni di ricerca hanno permesso di sviluppare molti sofisticati strumenti per studiare il sistema metabolico glucosio-insulina in vivo e poter così fronteggiare il problema dell’inaccessibilità diretta di alcuni dei fenomeni chiave che controllano la glicemia. Tali strumenti, fra cui protocolli di studio e approcci basati su modello usati per interpretare i dati sperimentali, si sono rivelati armi molto potenti nelle mani dei ricercatori, ma le proporzioni epidemiche della malattia e il parziale cambiamento delle strategie e obiettivi della ricerca hanno sollevato l’esigenza di poter disporre di metodologie meno invasive, più economiche, e quindi più adatte ad essere applicate ad estesi studi clinici. Alcuni strumenti matematici e statistici che sono collettivamente conosciuti con il nome di “approcci di popolazione” sono già stati sviluppati e vengono largamente impiegati in studi di farmacocinetica e farmacodinamica, per lo sviluppo di farmaci. Tali approcci si prefiggono come obiettivo primario di stimare la distribuzione dei parametri di un modello all’interno di una popolazione e pertanto si avvalgono, per la stima individuale, delle informazioni disponibili sull’intero gruppo di soggetti. Sono particolarmente adatti a situazioni in cui il campionamento intensivo in un singolo soggetto non è possibile, e quando l’interesse del ricercatore è focalizzato sulla variabilità inter-individuale. Tuttavia, nonostante le loro interessanti potenzialità, gli approcci di popolazione non sono ancora apprezzati all’interno dell’ambiente di ricerca sulle malattie metaboliche, e la loro applicazione in tali studi è stata molto limitata. Pertanto è necessaria dell’attività di ricerca per saggiare l’effettiva fattibilità e rilevanza dell’utilizzo di tali approcci nello studio del diabete. La ricerca qui presentata risponde a queste esigenze, proponendosi come obiettivo l’applicazione di queste sofisticate tecniche ai modelli di metabolismo del glucosio, prima testandone la fattibilità e adattandole al problema in esame, e poi impiegandole nell’analisi di dati raccolti in studi di popolazione. Poiché in letteratura sono stati proposti molti diversi algoritmi, come primo passo, un dataset simulato è stato utilizzato per effettuare un confronto delle metodologie quando applicate al modello minimo del glucosio per il Test di Tolleranza IntraVenosa al Glucosio (IVGTT). First-Order Conditional Estimation (FOCE) si è rivelato come l’algoritmo più soddisfacente, in quanto ha fornito i risultati più accurati e robusti in caso di scarsità o rumorosità dei campioni. Successivamente, per validare i risultati trovati su dati reali, l’analisi è stata ripetuta su un dataset più esteso, relativo a 204 soggetti sani testati con IVGTT. Per poter saggiare la bontà delle soluzioni fornite dai vari algoritmi, è stato impiegato un sistema di stima della likelihood function basato su campionamento Monte Carlo. Questa analisi, non solo ha permesso di confermare la scelta di FOCE come metodo preferenziale, ma si è anche rivelata come un potente strumento per valutare la precisione delle stime dei parametri di popolazione. Successivamente, è stato messo a punto e ottimizzato un modello di popolazione, conservando nella matrice di covarianza solo i termini di correlazione fra i parametri SI-P2 e SG-VOL. Questo modello è servito come base per la successiva integrazione di covariate nel modello. Al momento dell’esecuzione degli esperimenti, infatti, sono stati raccolti alcuni dati sui pazienti, fra cui altezza, peso, sesso, età, glicemia e insulinemia basali, informazioni sul grasso corporeo. È stata effettuata una analisi per determinare quali fra queste variabili potessero essere usate per spiegare parte della variabilità nei valori dei parametri del modello minimo fra i diversi soggetti. Il risultato è un modello che integra queste informazioni direttamente nelle sue equazioni, mentre i coefficienti di regressione per ognuno dei predittori diventano veri e propri parametri del modello e il loro valore viene ottimizzato insieme agli altri parametri di popolazione. L’analisi effettuata ha trovato come buoni predittori per SI e P2 l’ età, l’insulinemia basale e il grasso addominale, che in ambo i parametri riescono a spiegare una buona fetta della variabilità inter-individuale. Sia l’impiego di metodologie di popolazione, sia l’introduzione delle covariate nel modello, permettono di aumentarne il potere predittivo, e sono in grado di usare informazioni indipendenti dai soli dati sperimentali. Questo permette di mettere a punto dei protocolli di studio meno invasivi, meno costosi, e pertanto più adatti ad un impiego su larga scala: ulteriore ricerca potrebbe avere come obiettivo l’ottimizzazione di una sampling schedule ridotta, che si avvantaggi dell’utilizzo degli approcci di popolazione. Ad ogni modo, il dataset utilizzato in questa analisi comprende solo soggetti sani, ed è quindi caratterizzato da una quantità limitata di variabilità di popolazione. Pertanto, sarebbe necessario ripetere l’analisi su altri dataset, per poter confermare questi risultati, in particolare sulle covariate. Inoltre, in una sezione successiva, un metodo di popolazione è stato applicato anche ad un altro problema diverso, la stima del Disposition Index (DI) del glucosio. Questo è un indice calcolato combinando sensitività e responsività all’insulina, che serve per testare l’effettiva efficacia del sistema di controllo della glicemia. Ci sono due versioni proposte per la formula, una semplificata, che consiste semplicemente nel prodotto (da cui il nome di Legge Iperbolica), e una con un parametro aggiuntivo ad esponente della sensitività all’insulina. Per poter calcolare il DI medio in una popolazione, e per poter saggiare quale delle due formule sia effettivamente più adatta, in letteratura si trovano alcuni approcci basati su un fit geometrico. Tuttavia, alcune approssimazioni sono utilizzate per semplificare il fit, e sono molte le questioni metodologiche spesso sottovalutate. Pertanto viene presentato qui un nuovo metodo Total Least Squares (TLS) che affronta il problema senza l’impiego di approssimazioni. Grazie ad alcune simulazioni, si è effettuato un paragone fra i vari metodi disponibili, e il nuovo algoritmo è risultato migliore rispetto ai predecessori. Tuttavia, tutti gli algoritmi basati su fit si fondano sull’ipotesi che i soggetti appartenenti alla popolazione abbiano lo stesso valore di DI, e l’unica fonte di incertezza nei dati sia dovuta alla stima degli indici di secrezione e sensitività. Questa ipotesi sembra una forte semplificazione e, in effetti, l’analisi di un dataset reale sembra confermare la presenza di variabilità di popolazione nei valori del DI. Ulteriori simulazioni hanno confermato che tutti metodi basati su fit, TLS compreso, falliscono quando la variabilità di popolazione è presente. Pertanto, è stato ideato un altro metodo basato su approcci di popolazione e, in particolare, su NonLinear Mixed-Effects Models (NLMEM), che è in grado di separare la variabilità nei dati, poiché fondato su ipotesi meno restrittive. Tale algoritmo stima i parametri della distribuzione di probabilità congiunta degli indici di secrezione e sensitività, e poi estrae le informazioni sul DI dalla matrice di covarianza. NLMEM si è rivelato equivalente a TLS quando non c’è variabilità di popolazione, ma di gran lunga più affidabile quando le ipotesi per il fit geometrico non sono rispettate, pertanto si è deciso di utilizzarlo sul dataset reale per testare la validità della legge iperbolica. Anche se una validazione su altri dataset è auspicabile per validare i risultati qui presentati, il modello con il parametro aggiuntivo sembra spiegare i dati in maniera più soddisfacente, e il valore del parametro sembra dipendere dalla coppia di parametri usata per la definizione del DI, più che dalla popolazione in esame (anziani piuttosto che giovani). Inoltre, nello studio qui proposto, il punto di partenza sono stati i valori degli indici di secrezione già calcolati, insieme con la loro precisione, grazie ad un metodo tradizionale; un approccio ancora più potente consisterebbe nell’utilizzare un modello di popolazione per stimare contemporaneamente sia gli indici di secrezione che sensitività, sia i parametri della loro distribuzione di popolazione, da cui ricavare le informazioni sul DI. Riassumendo, in questo lavoro si sono messi in luce i vantaggi dell’applicazione di approcci di popolazione nello studio nel diabete. Le potenzialità sono molte, dal miglioramento delle stime dei parametri individuali grazie all’uso dei prior di popolazione o di covariate e la relativa possibilità di mettere a punto protocolli di studio più leggeri, fino all’analisi di situazioni in cui la struttura gerarchica della variabilità è un aspetto cruciale.

Objective: Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population. Design: A cross-sectional, epidemiological study. Methods: IGF-I levels were measured with an automated chemiluminescence assay system in 6282 patients from the DETECT study. Weight, height, and waist and hip circumference were measured according to the written instructions. Standard deviation scores (SDS), correcting IGF-I levels for age, were calculated and were used for further analyses. Results: An inverse U-shaped association of IGF-I SDS with BMI, waist circumference, and the ratio of waist circumference to height was found. BMI was positively associated with IGF-I SDS in normal weight subjects, and negatively associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of 22.5–25 kg/m2 in men (+0.08), and at a BMI of 27.5–30 kg/m2 in women (+0.21). Multiple linear regression models, controlling for different diseases, medications and risk conditions, revealed a significant negative association of BMI with IGF-I SDS. BMI contributed most to the additional explained variance to the other health conditions. Conclusions: IGF-I standard deviation scores are decreased in obesity and underweight subjects. These interactions should be taken into account when analyzing the association of IGF-I with diseases and risk conditions.

Objective: Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population. Design: A cross-sectional, epidemiological study. Methods: IGF-I levels were measured with an automated chemiluminescence assay system in 6282 patients from the DETECT study. Weight, height, and waist and hip circumference were measured according to the written instructions. Standard deviation scores (SDS), correcting IGF-I levels for age, were calculated and were used for further analyses. Results: An inverse U-shaped association of IGF-I SDS with BMI, waist circumference, and the ratio of waist circumference to height was found. BMI was positively associated with IGF-I SDS in normal weight subjects, and negatively associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of 22.5–25 kg/m2 in men (+0.08), and at a BMI of 27.5–30 kg/m2 in women (+0.21). Multiple linear regression models, controlling for different diseases, medications and risk conditions, revealed a significant negative association of BMI with IGF-I SDS. BMI contributed most to the additional explained variance to the other health conditions. Conclusions: IGF-I standard deviation scores are decreased in obesity and underweight subjects. These interactions should be taken into account when analyzing the association of IGF-I with diseases and risk conditions.

Extreme environments pose major obstacles for electronics in the form of extremely wide temperature ranges and hazardous radiation. The most common mitigation procedures involve extensive shielding and temperature control or complete displacement from the environment with high costs in weight, power, volume, and performance. There has been a shift away from these solutions and towards distributed, in-environment electronic systems. However, for this methodology to be viable, the requirements of heavy radiation shielding and temperature control have to be lessened or eliminated. This work gained new understanding of the best practices in analog circuit design for extreme environments. Major accomplishments included the over-temperature -180 C to +120 C and radiation validation of the SiGe Remote Electronics Unit, a first of its kind, 16 channel, sensor interface for unshielded operation in the Lunar environment, the design of two wide-temperature (-180 C to +120 C), total-ionizing-dose hardened, wireline transceivers for the Lunar environment, the low-frequency-noise characterization of a second-generation BiCMOS process from 300 K down to 90 K, the explanation of the physical mechanisms behind the single-event transient response of cascode structures in a 45 nm, SOI, radio-frequency, CMOS technology, the analysis of the single-event transient response of differential structures in a 32 nm, SOI, RF, CMOS technology, and the prediction of scaling trends of single-event effects in SOI CMOS technologies.

The development and characterization of experimental setups for angle-resolved photoelectron spectroscopy (ARPES) and spin- and angle-resolved photoelectron spectroscopy (SARPES) is described. Subsequently, the two techniques are applied to studies of the electronic band structure in topologically non-trivial materials. The laser-based ARPES setup works at a photon energy of 10.5 eV and a typical repetition rate in the range 200 kHz to 800 kHz. By using a time-of-flight electron energy analyzer electrons emitted from the sample within a solid angle of up to ±15 degrees can be collected and analyzed simultaneously. The SARPES setup is equipped with a traditional hemispherical electron energy analyzer in combination with a mini-Mott electron polarimeter. The system enables software-controlled switching between angle-resolved spin-integrated and spin-resolved measurements, thus providing the possibility to orient the sample by mapping out the electronic band structure using ARPES before performing spin-resolved measurements at selected points in the Brillouin zone. Thin films of the topological insulators (TIs) Bi2Se3, Bi2Te3 and Sb2Te3 are grown using e-beam evaporation and their surface states are observed by means of ARPES. By using a combination of low photon energies and cryogenic sample temperatures the topological states originating from both the vacuum interface (surface) and the substrate interface are observed in Bi2Se3 films and Bi2Se3/Bi2Te3 heterostructures, with total thicknesses in the ultra-thin limit (six to eight quintuple layers), grown on Bi-terminated Si(111) substrates. Band alignment between Si and Bi2Se3 at the interface creates a band bending through the films. The band bending is found to be independent of the Fermi level (EF) position in the bulk of the substrate, suggesting that the surface pinning of EF in the Si(111) substrate remains unaltered after deposition of the TI films. Therefore, the type and level of doping of the substrate does not show any large influence on the size of the band bending. Further, we provide experimental evidence for the realization of a topological crystalline insulator (TCI) phase in the narrow-band semiconductor Pb1−xSnxSe. The TCI phase exists for temperatures below the transition temperature Tc and is characterized by an inverted bulk band gap accompanied by the existence of non-gapped surface states crossing the band gap. Above Tc the material is in a topologically trivial phase where the surface states are gapped. Thus, when lowering the sample temperature across Tc a topological phase transition from a trivial insulator to a TCI is observed. SARPES studies indicate a helical spin structure of the surface states both in the topologically trivial and the TCI phase.

QC 20130507

Galvos smegenų insultas dėl aukštų mirtingumo ir ilgalaikio neįgalumo rodiklių išlieka viena didžiausių visuomenės sveikatos problemų daugelyje pasaulio šalių, tarp jų ir Lietuvoje. Didelei daliai sergančiųjų galvos smegenų insultu išlieka judėjimo, apsitarnavimo, pažinimo funkcijų sutrikimų, kurie blogina jų gyvenimo pilnatvę. Ligonių, ištiktų galvos smegenų insulto, funkcinės būklės atsigavimas yra skirtingas, todėl labai svarbu nustatyti veiksnius, kurie gali turėti įtakos reabilitacijos efektyvumui. Darbo tikslas: įvertinti veiksnius, turinčius įtakos ligonių, patyrusių galvos smegenų insultą, reabilitacijos efektyvumui antrajame reabilitacijos etape ir nustatyti jų prognozinę vertę. Darbo uždaviniai: 1. Įvertinti galvos smegenų insultą patyrusių asmenų klinikinę ir bendrą funkcinę būklę bei susijusių su motorika ir pažinimo funkcijomis gebėjimų sutrikimus ir jų kitimą antrajame reabilitacijos etape. 2. Įvertinti kompleksinės reabilitacijos efektyvumą antrajame reabilitacijos etape priklausomai nuo ligonių amžiaus, lyties, insulto pobūdžio, galvos smegenų pažeidimo lokalizacijos ir insulto sunkumo. 3. Nustatyti veiksnius, turinčius įtakos reabilitacijos efektyvumui ir jų prognozinę vertę. Mūsų atliktas tyrimas parodė, kad vyresnis amžius, kairiojo galvos smegenų pusrutulio pažeidimas ir sunkesnė neurologinė būklė antrojo reabilitacijos etapo pradžioje turi reikšmingos įtakos funkcinės būklės sunkumui antrojo reabilitacijos etapo pabaigoje. Įrodyta, kad sunkūs motorikos... [toliau žr. visą tekstą]
Stroke is one of the most relevant public health issues due to high mortality and long-lasting disability rates around the world and in Lithuania. As a consequence, stroke patients stay with such functional disorders as motoric, self-care, and cognitive dysfunctions, that impair their life satisfaction. Complex rehabilitation improves functional status in stroke patients. However, the recovery of functional status in stroke patients is different even if stroke diagnosis is the same. Aim of the study: to establish factors, influencing the effectiveness of second stage rehabilitation, and to evaluate their predictive value in stroke patients. Goals of the study: 1. to evaluate clinical and functional status, motoric and cognitive dysfunctions and its dynamics during second stage rehabilitation in stroke patients; 2. to establish the effectiveness of complex second stage rehabilitation depending on patients' age, gender, type of stroke, damage localization, and severity of stroke; 3. to establish the factors, influencing the effectiveness of rehabilitation and to evaluate their predictive value in stroke patients. Our study demonstrated, that older age, damage in left brain hemisphere, and severity of neurologic condition as measured at baseline all are related with subsequent functional status at the end of second stage rehabilitation. The study investigated, that low rehabilitation effectiveness during second stage rehabilitation on general functional status is predicted... [to full text]

Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of obesity-related inflammation and insulin resistance in adipose tissue. However, the mechanisms responsible for induction of ER stress are presently unclear. Proper ER redox state is crucial for oxidative protein folding and secretion and impaired protein folding in ER leads to induction of unfolded protein response and ER stress. However, while ER redox state is more oxidizing compared to the rest of the cell, its regulation is poorly understood. In order to determine the effects of ER redox state on development of ER stress and insulin resistance, several fluorescence-based sensors have been developed. However, these sensors have yielded results that are inconsistent with each other and with earlier non-fluorescence-based studies. In this study we attempted to develop and characterize a sensitive tool to study the ER redox state in adipocytes in real-time by targeting a new generation of redox-sensitive green fluorescent protein (roGFP) to ER. The roGFP1-iL sensor targeted to the ER is termed ‘eroGFP1-iL’ by convention. The ER-targeting eroGFP1-iL construct contains the signal peptide from adiponectin and the ER retention motif KDEL and has a midpoint reduction potential of -229 mV in vitro in oxidized and reduced lipoic acid. Despite having a midpoint reduction potential that is 50 mV higher than the previously determined midpoint reduction potential of the ER, eroGFP1-iL was found capable of detecting both oxidizing and reducing changes in the ER. In an attempt to determine the mechanisms by which roGFP1-iL detects oxidizing changes, we found that, first, glutathione mediated the formation of disulfide-bonded roGFP1-iL dimers with an intermediate excitation fluorescence spectrum resembling a mixture of oxidized and reduced monomers. Second, glutathione facilitated dimerization of roGFP1-iL, which in effect shifted the equilibrium from oxidized monomers to dimers, thereby increasing the molecule’s reduction potential compared with a dithiol redox buffer like lipoic acid. From this study, we concluded that the glutathione redox couple in ER significantly raised the reduction potential of roGFP1-iL in vivo by facilitating its dimerization while preserving its ratiometric nature, which makes it suitable for monitoring oxidizing and reducing changes in ER with high reliability in real-time. The ability of roGFP1-iL to detect both oxidizing and reducing changes in ER and its dynamic response in glutathione redox buffer between approximately -190 and -130 mV in vitro suggest a range of ER redox potential consistent with those determined by earlier approaches that did not involve fluorescent sensors. Our primary aim in developing eroGFP1-iL as a redox-sensing tool was to be able to assess whether redox changes represent an early initiator of ER stress in obesity-induced reduction in high molecular weight (HMW) adiponectin in circulation. Hypoxia is a known mediator of redox changes. We found that oligomerization of HMW adiponectin was impaired in the hypoxic conditions observed in differentiated fat cells. The redox-active antioxidant ascorbate was found capable of reversing hypoxia-induced ER stress. Lastly, we demonstrated that changes in ER redox condition is associated with ER stress response and is implicated in the mechanism of action of the insulin-sensitizing agent troglitazone and desensitizing agent palmitate. Using the redox sensing property of eroGFP1-iL, palmitate was found to be an effective modulator of redox changes in the ER and troglitazone was found to cause oxidizing changes in the ER. The action of palmitate in causing aberrant ER redox conditions was associated with aberrant HMW adiponectin multimerization. Palmitate-induced ER stress was ameliorated by troglitazone. Taken together, the data suggest a potential role of ER redox changes in ER stress and impaired protein folding in adipocytes.

Physiotherapy and cycling training influence to patient’s independence and mobility in early stage after stroke That physical therapy is effective working with patients after cerebrovascular disease has for long been proved by research, but which methods works most effectively and should be widely applied are still in discussion. The research found that the traditional physical therapy is not sufficient quickly restore the balance and walk function. Scientists searching for new methods but not always the proposed methods are effective; there are some contradictory opinions in the literature. Actual problem for new methods searching how quicken balance and gait recovery and reduce rehabilitation period for patients after stroke still remains. We used combination of physical therapy program based on principles of Bobath and training with bicycle ergometer for patients in early period following stroke. This kind of cyclical training was chosen because it made a dynamic, bilateral action which has many similarities to walking, but is safer and can be performed when person is in early stage of motor recovery after the stroke. Also this method quickens compensatory mechanisms. We evaluated that complex physical therapy program based on Bobath method principles with cyclic training statistically significantly more influenced patients after brain infarction independence, balance and gait than the program based on Bobath method principles alone (p<0,05). Our research shows that... [to full text]
Kineziterapijos ir ciklinės treniruotės poveikis asmenų savarankiškumui ir mobilumui ankstyvuoju reabilitacijos periodu po galvos smegenų insulto Moksliniais tyrimais įrodyta, kad kineziterapija yra efektyvi reabilituojant pacientus po galvos smegenų kraujotakos sutrikimų. Atlikti įvairūs kineziterapijos efektyvumą analizuojantys tyrimai naudojant paprasčiausias kineziterapijos priemones bei sudėtingus aparatus įvairiais periodais pacientams po insulto. Tačiau ne visada siūlomi metodai buvo efektyvūs, nepakankamai nagrinėti metodai gerinantys pacientų pusiausvyros ir ėjimo funkcijas ankstyvuoju reabilitacijos periodu po insulto. Išlieka aktuali naujų metodikų paieškos problema, kaip pagreitinti pusiausvyros ir ėjimo funkcijų atsigavimą bei sutrumpinti pacientams po galvos smegenų insulto reabilitacijos periodą. Tyrimo metu taikytas Bobath‘o metodikos ir veloergometro treniruotės derinys pacientams po galvos smegenų insulto ankstyvuoju reabilitacijos periodu. Treniruotė veloergometru pasirinkta todėl, kad juo atliekamas dinaminis, bilateralinis veiksmas daug kuo panašus į ėjimą, tačiau yra saugesnis ir gali būti pradėtas taikyti ankstyvuoju periodu po insulto. Be to, šis metodas pagreitina kompensacinius mechanizmus. Įvertinta, kad kineziterapijos programa, kurios metu buvo taikoma Bobath‘o metodika ir ciklinė treniruotė, labiau veikė asmenų po galvos smegenų infarkto savarankiškumą, pusiausvyrą ir ėjimą negu programa, kurios metu buvo taikoma tik Bobath‘o metodika (p<0,05)... [toliau žr. visą tekstą]

Dissertação de Mestrado em Relações Internacionais
A relação Diplomática entre São-Tomé e Príncipe e Taiwan, estabelecida em Maio de 1997, é considerada um dos acordos mais polémicos na história da diplomacia São-Tomense. Foi assim considerada pois o acordo implicou o rompimento das relações diplomáticas de SãoTomé e Príncipe com a República Popular da China (RPC), país que apoiara a sua luta de libertação e com quem mantinha cordiais relações de cooperação. Ainda que contestada, a relação com Taiwan manteve-se por duas décadas apesar de momentos de conturbação, tendo este país implementado em São Tomé e Príncipe diversos projectos com destaque para as áreas da saúde, da agricultura e da educação. É nesse sentido, que o presente trabalho vai centrar-se sobre a relação entre os dois estados insulares, analisando os seus antecedentes, a sua evolução e o seu término para apurar até que ponto esta cooperação foi benéfica e contribuiu para o desenvolvimento do arquipélago São -Tomense.
The diplomatic relationship between Sao Tome e Principe and Taiwan that was established in May 1997 was considered one of the most controversial agreement in the diplomatic history of Sao Tome and Principe because this agreement forced the severance of the relationship between Sao Tome and Principe and Popular Republic of China, a country that had supported São Tome independence struggle and the post-colonial government. Even so the relationship lasted almost two decades although there were moments of some troubles, having Taiwan implemented several projects, particularly in the areas of health, agriculture and education. It is in this sense that the present works will focus more in the referred relationship, its background, its evolution and terms and analyze to what extent this cooperation will contribute to the development of the archipelago.
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Forty Sprague Dawley rats were randomly separated into one of three experimental groups: Run-Trained (RT), Swim-Trained (SW), or Control (CON). The runners were further separated into 2 groups: Good-runners (RT1), or Poor-runners (RT2) according to their performance on the treadmill. All of the trained groups were endurance trained at approximately 80% V02 max for two hours per day, five days per week in the appropriate mode of exercise. After nine weeks of equi-intensity training, the perimetrial fat pads were removed and the calls isolated. The adipocytes from the trained animals were significantly smaller in volume and diameter than the adipocytes from the controls. Adipocytes from all of the trained groups were significantly more sensitive to insulin than the CON group according to the definition by Kahn (60). The cells from the RT1 and SW groups were significantly more responsive to insulin than both the RT2 and CON groups. The adipocytes from the RT1 group were also significantly more responsive to insulin than the SW group. The differences in cell responsiveness to insulin were highly correlated to the average size of the cells studied. From the data presented in this study threeconclusions were drawn: 1) Both running and swimming at the reported intensity, duration, and frequency have a significant effect on the morphology and metabolism of the isolated adipocyte, 2) Adipocyte morphology, insulin sensitivity, and insulin responsiveness are dependent on the frequency, intensity, and duration of a given exercise training protocol, and 3) Each type of exercise training has its own drawbacks: with swimming, the rats may experience some hypoxia which may alter their metabolic fuel utilization, and during running not all of the animals may be capable or willing to complete the run.Ball State UniversityMuncie, IN 47306

Inledning: Uthållighetsträning definieras som den typ av träning där flertalet stora muskelgrupper används och är i behov av hjärt-kärlsystemets kapacitet för att transportera syre till musklerna. Att fasta innebär i de flesta studier att ingen typ av föda intas före träningspassen medan att inte fasta vanligtvis innebär att 90 minuter före ett träningspass intas en kolhydratrik måltid. Insulin är viktig i fett-, protein- och kolhydratmetabolismen samt i uppsamlingen av socker i blodet. Glykogen fungerar som en energireserv i skelettmusklerna. Fria fettsyror är viktiga för att ge energi till den cellulära metabolismen som ska kunna fortgå. Syfte: Syftet med denna studie var att ta reda på om kroppen påverkas på olika sätt av uthållighetsträning på fastande respektive icke-fastande mage vad gäller insulin, muskelglykogen samt fria fettsyror hos människor. Metod: Litteratursökning i OneSearch med sökorden training* AND fasted state där sex artiklar valdes ut. Cohen’s D användes för att ge studiernas resultat en effektstorlek. Konfidensintervall användes för att bestämma om studierna var statistiskt signifikanta. Resultat: Tre studier undersökte insulin där resultaten visade att samtliga grupper som inte fastade före träningspassen hade lägst koncentration av insulin i viloperioden efter eftertestet. Samtliga sex studier undersökte muskelglykogen där resultaten visade att koncentrationen av muskelglykogen var högst efter eftertestet i gruppen som fastade före träningspassen i fem av sex studier. Tre studier undersökte fria fettsyror där resultaten visade att koncentrationen av fria fettsyror var lägst i eftertestet i gruppen som fastade före träningspassen i två av tre studier. Diskussion: Träning i icke-fastat tillstånd leder till att glykogennivåerna sparas vilket i sin tur leder till att oxidationen av insulin ökar vilket resulterar i lägre koncentrationer av insulin efter eftertestet. Träning i fastat tillstånd resulterar i ökad koncentration av muskelglykogen till energiunderhåll samt högre nivåer av β-hydroxyacyl coenzym A dehydrogenas (β-HAD), citratsyntasaktiviteten (CS-aktiviteten) samt succinatdehydrogenasaktiviteten vilket leder till ökad muskulär oxidativ kapacitet. Intag av kolhydrater före ett träningspass leder till ökat glykogenbesparande vilket resulterar i lägre koncentrationer av muskelglykogen jämfört med icke-fastat tillstånd. Högre koncentration av muskelglykogen före förtestet leder till högre koncentrationer av muskelglykogen i eftertestet. Träning i fastat tillstånd resulterar i lägre koncentrationer av fria fettsyror på grund av ökad FATmax (den maximala hastigheten av fettförbränning), ökad maximal oxidativ enzymaktivitet, uppreglering av hormonkänsligt lipas (HSL), ökat proteinuttryck av fettsyra-translokas / CD36 (FAT / CD36) samt ökat membranbundet proteinbindande protein som leder till ökad fettförbränning. Koncentrationen av fria fettsyror höjdes även i en studie på grund av att insulinutsöndringen inte skulle sjunka för lågt i gruppen som fastade före träningspassen. Konklusion: Resultaten visade att i tre av tre studier var insulinkoncentrationen lägst efter eftertestet i gruppen som intog en kolhydratrik måltid före träningspassen. I fem av sex studier var koncentrationen av muskelglykogen högst efter eftertestet i gruppen som fastade före träningspassen. I två av tre studier var koncentrationen av fria fettsyror lägst efter eftertestet i gruppen som fastade före träningspassen. Dessa resultat ökar förståelsen av hur träning på fastande respektive icke-fastande mage påverkar kroppen med avseende på insulin, muskelglykogen samt fria fettsyror. Vidare forskning skulle kunna undersöka dessa tre fysiologiska markörer under sex månader för att se om resultaten blir desamma i dessa två grupper.
Introduction: Endurance training is defined as the type of exercise where most major muscle groups are used in need of the cardiovascular system’s ability to transport oxygen to the muscles. Fasting means in most studies that no type of food is taken before the workout while not fasting usually means that a carbohydrate meal is taken 90 minutes before a workout. Insulin is important in fat, protein and carbohydrate metabolism as well as in the collection of sugar in the blood. Glycogen acts as an energy reserve in the skeletal muscles. Free fatty acids are important to provide energy for the cellular metabolism that can continue. Aim of the study: The aim of the study was to find out if the body is affected in different ways by endurance training exerted in fasted respectively non-fasting state regarding insulin, muscle glycogen and free fatty acids in humans. Methods: Literature search in OneSearch with the words training* AND fasted state where six articles were selected. Cohen’s D was used to give the results of the studies an effect size. Confidence interval was used to determine if the studies were statistically significant. Results: Three studies investigated insulin, where the results showed that all groups that did not fast before the workouts had the lowest concentration of insulin during the rest period after the test. All six studies investigated muscle glycogen, where the results showed that the concentration of muscle glycogen was highest after post-test in the group that fasted before the workouts in five out of six studies. Three studies investigated free fatty acids where the results showed that the concentration of free fatty acids were lowest in the post-test in the group that fasted before the workouts in two of three studies. Discussion: Training in the non-fasting state causes the glycogen levels to be saved, which in turn leads to increased oxidation of insulin resulting in lower concentrations of insulin after the post-test. Training in the fasted state results in increased concentration of muscle glycogen for energy maintenance and higher levels of β-hydroxyacyl coenzyme A dehydrogenase (β-HAD), citrate synthase activity (CS activity) and succinate dehydrogenase activity, leading to increased muscular oxidative capacity. Intake of carbohydrates prior to a workout leads to increased glycogen saving, resulting in lower concentrations of muscle glycogen compared to non-fasted state. Higher concentration of muscle glycogen before the pretest leads to higher concentrations of muscle glycogen in the post-test. Training in fasted state results in lower concentrations of free fatty acids due to increased FATmax (maximum rate of fat burning), increased maximal oxidative enzyme activity, hormone sensitive lipase (HSL) upset, increased fatty acid translocase / CD36 protein expression (FAT / CD36) as well as increased membrane bound protein binding protein which leads to increased fat burning. The concentration of free fatty acids was also increased in a study due to the fact that insulin secretion should not fall too low in the group that fasted before the workouts. Conclusion: The results showed that in three out of three studies, the insulin concentration was lowest after the post-test in the group who took a carbohydrate meal before the workouts. In five out of six studies, the concentration of muscle glycogen was highest after the post-test in the group that fasted before the workouts. In two out of three studies, the concentration of free fatty acids was lowest after the post-test in the group that fasted before the workouts. These results increase the understanding of how exercise in the fasted state and non-fasted state affects the body with regard to insulin, muscle glycogen and free fatty acids. Further research could investigate these three physiological markers for six months to see if the results are the same in these two groups.

Background: Infants of diabetic mothers (IDM) are at increased risk for the development of obesity and metabolic syndrome (MS) in childhood. Maternal obesity, fetal macrosomy and early acceleration of postnatal growth may be additional risk factors. Objective: Aim of present study is to assess whether an increased weight gain can be detected in IDM and to define which biochemical markers of metabolism in the newborn and anthropometric parameters in the first year of life can be used to identify those IDM that are most subject to growth acceleration. Design/Methods: 56 infants of daibetic mothers both non insulin-treated (NIT-GDM) and insulin-treated (IT-GDM) have been recruited. Each newborn has been assessed for metabolic and nutritional status (Glycaemia, Electrolytes, Blood Urea Nitrogen, Retinol Binding Protein [RBP], Cholesterol, Triglycerides Total Fatty Acids) at 4+1 days of life. Anthropometric measurements (weight, length, head circumference, waist circumference, tricep skinfold) have been taken in the first year of life (at birth, 1, 3, 6 and 12 months). The most well known risk factors for obesity and MS in childhood and most frequent morbidities of GDM on fetus and newborn have been studied. Results: Premature NIT-GDM, at term NIT-GDM, premature IT-GDM and at term IT-GDM have been compared. Growth pattern has shown to be consistent with normal growth curves of the paediatric population. A greater weight gain in IT-GDM compared to NIT-GDM infants has been found. A reduced incidence of short term most frequent complications of ODM has been found in our sample, compared to literature reports. Greater values of RBP have been detected in IT-GDM infants (p=0.049). Also, RBP values appear to be positively correlated with parameters of waist circumference at 6 and 12 months and weight at 6 and 12 months (p=0.004; R2 0.19). Lipid metabolism was not found to be modified by insulin treatment, and it was not related to growth parameters at any age. Conclusions: The normality of growth parameters and the low incidence of complications in the short term are likely due to effective implementation of monitoring protocols and prevention in pregnancy and early neonatal period. The laboratory data support other findings according to which RBP can be used to identify those subjects that are at increased risk of developing MS in childhood and that are especially in need for an early nutritional intervention.

The ruthenates are perhaps one of the most diverse group of materials known up to date. These compounds exhibit a wide array of behaviors ranging from the exotic pwave superconductivity in Sr2RuO4, to the itinerant ferromagnetism in SrRuO3, and the Mott-insulating behavior in Ca2RuO4. One of the most intriguing compounds belonging to this group is Ca3Ru2O7 which is known to undergo an antiferromagnetic ordering at 56K and an insulating transition at 48K. Most intriguing, however, is the behavior displayed by this compound in the presence of an external magnetic field. For fields parallel to the a-axis, the compound undergoes a metamagnetic transition into the ferromagnetic region at 6 T. If the external field direction is changed to the b-axis then the result will be different. colossal magnetoresistance occurs and a fall in reistivity of up to three orders of magnitude is recorded at fields of 15T. Most interesting, however, is the energy gap observed for this material. A number of groups have measured such gap with different methods and found conflicting results. For this reason it was of vital importance to perform measurements on this compound and try to resolve this issue. Tunneling spectroscopy is one of the most powerful techniques which can be used to probe the electronic properties of a material. The method is best suited to measure the density of states of a material and hence the nature of the strong correlations which dictate the properties of the compound. We performed a series of tunneling spectroscopy measurements by means of planar tunnel junctions. These types of junctions were chosen because of their stability over a large temperature range and their stability in the presence of an external field. The anisotropies which showed up in the resistivity and magnetization measurements manifested also in our data. For tunneling parallel to the a-axis, we observed a gap opening at 48K with a width a peak to peak width of 2Δa ~258±15meV. As the temperature was lowered, the gap size increased reaching a maximum width of 2Δa ~ 845±38meVat 4.2K. Tunneling parallel to the b-axis, the gap has a much smaller size than the a-axis gap. At 48K the gap width is about 2Δb ~ 201±13 meV and reaches a maximum width of 2Δb ~ 366±33 meV at 4.2K. For the c-axis, the situation is different since the gap opens at 56K instead of 48K. The gap width at 56K is about 2Δc ~ 102±6meV and reaches a maximum width of 2Δc ~ 179±14 meV at 4.2K. In the presence of an external field, we noticed that the overall behavior was always the same in the ab-plane but differed in c-axis direction. In our experiment, an external field was applied along the a-axis and measurements were made at 4.2K. For aaxis tunneling, the gap width decreased to a value of 2Δa ~ 587±27 meV at 4.2 K at 7T. On the other hand, the gap width in the b-axis direction decreased to a value of 2Δb ~ 308±25 meV for the same field. For the c-axis direction, the gap decreased to a value of 2Δc ~ 112±8 meV at 7T. The DOS of the c-axis differs for fields of 6T and above. A third peak emerges inside the gap on the valence side of the DOS. This third peak seems to be a direct consequence of the metamagnetic transition at 6T observed by other groups and may be attributable to a spin-filtering effect.

Cette thèse décrit la réalisation et l’étude de réseaux bidimensionnels de résonateurs supraconducteurs en nid d’abeille. Ce travail constitue un premier pas vers la simulation de systèmes de la matière condensée avec des circuits supraconducteurs. Ces réseaux sont micro-fabriqués et sont constitués de plusieurs centaines de sites. Afin d’observer les modes propres qui y apparaissent dans une gamme de fréquence entre 4 et 8 GHz, nous avons mis au point une technique d’imagerie. Celle-ci utilise la dissipation locale créée par un laser avec lequel nous pouvons adresser chaque site du réseau. Nous avons ainsi pu mesurer la structure de bande et caractériser les états de bord de nos réseaux. En particulier, nous avons observé les états localisés qui apparaissent à l'interface entre deux isolants de Semenoff ayant des masses opposées. Ces états, dits de Semenoff, sont d'origine topologique. Nos observations sont en excellent accord avec des simulations électromagnétiques ab initio
This thesis describes the realization and study of honeycomb lattices of superconducting resonators. This work is a first step towards the simulation of condensed matter systems with superconducting circuits. Our lattices are micro-fabricated and typically contains a few hundred sites. In order to observe the eigen-modes that appear between 4 and 8 GHz, we have developed a mode imaging technique based on the local dissipation introduced by a laser spot that we can move across the lattice. We have been able to measure the band structure and to characterize the edge states of our lattices. In particular, we observe localized states that appear at the interface between two Semenoff insulators with opposite masses. These states, called Semenoff states, have a topological origin. Our observations are in good agreement with ab initio electromagnetic simulations

Topological states of matter are a novel family of phases that elude the conventional Landau paradigm of phase transitions. Topological phases are characterized by global topological invariants which are typically reflected in the quantization of physical observables. Moreover, their characteristic bulk-boundary correspondence often gives rise to robust surface modes with exceptional features, such as dissipationless charge transport or non-Abelian statistics. In this way, the study of topological states of matter not only broadens our knowledge of matter but could potentially lead to a whole new range of technologies and applications. In this light, it is of great interest to find novel topological phases and to study their unique properties. In this work, novel manifestations of topological states of matter are studied as they arise when materials are subject to additional symmetries. It is demonstrated how symmetries can profoundly enrich the topology of a system. More specifically, it is shown how symmetries lead to additional nontrivial states in systems which are already topological, drive trivial systems into a topological phase, lead to the quantization of formerly non-quantized observables, and give rise to novel manifestations of topological surface states. In doing so, this work concentrates on weakly interacting systems that can theoretically be described in a single-particle picture. In particular, insulating and semi-metallic topological phases in one, two, and three dimensions are investigated theoretically using single-particle techniques.