Avec une prévalence en constante augmentation, le diabète de type II est devenu un réel enjeu de santé publique. Cette pathologie se caractérise par une hausse de la production hépatique de glucose, reflet d'une néoglucogenèse accrue qui évoluera en hyperglycémie chronique. Le foie est donc un tissu-cible privilégié pour lutter contre les déséquilibres du métabolisme glucidique. Une nouvelle drogue dérivée de la Metformine et dénuée d'effets secondaires, le E008, a été synthétisée par Merck-Santé pour normaliser la glycémie des sujets diabétiques. Le double objectif de notre travail a consisté à (i) étudier les modifications des flux métaboliques au niveau hépatique dans un modèle nutritionnel de rats développant un syndrome métabolique, (ii) analyser les effets de ce nouveau composé médicamenteux et tenter d'élucider ses mécanismes d'action. Le régime enrichi en graisses entraîne une hausse de la néoglucogenèse associée à des perturbations de la fonction mitochondriale : hausse des radicaux libres, inhibition de la respiration, variation du potentiel rédox. Un dénominateur commun à ces évènements pourrait être une altération mutuelle de la composition des lipides membranaires et des quinones. L'administration du nouvel agent antidiabétique E008 à des rats sous régime gras permet de réduire leur production hépatique exacerbée de glucose, en modifiant le contrôle des voies métaboliques. De plus, il induit une inhibition subtile de la respiration cellulaire en agissant à la fois sur la chaîne respiratoire et sur le système phosphorylant (complexe I inhibé et expression réduite de l'ANT). Son action est également liée à une activation de la protéine kinase AMP dépendante (AMPK), par altération des rapports des nucléotides adényliques.

Nous présentons dans cette thèse un travail portant sur l'étude de l'ancrage, de la structure et de la dynamique du réseau de vortex dans des supraconducteurs de type II (Nb-Ta, Pb-In, YBCO). Notre contribution porte d'abord sur l'étude des mécanismes d'ancrage et de désancrage du réseau de vortex dans des cristaux non maclés d'YBCO par des mesures de transport continu, de suceptibilité alternative et d'aimantation. Nous mettons en évidence le rôle prédominant de la surface dans la phase "solide" qui se répercute dans la valeur du courant critique mesurée, et la conservation de la cohérence des vortex dans la phase "liquide". Des mesures d'écho de spin et de Diffraction de Neutrons aux Petits Angles (DNPA) ont été réalisées sur le réseau de vortex dans des échantillons de Nb-Ta et Pb-In. La vitesse du réseau de vortex, ainsi que sa distribution ont été mesurées et analysées. Une mise en ordre dynamique du réseau de vortex a été observée dans Pb-In par les mesures de DNPA. La perfection du réseau de vortex et l'effet du courant de transport sont analysés grâce à l'étude des pics de Bragg. L'étude de la courbure des vortex révèle que leur ancrage est également localisé en surface dans ces échantillons. Enfin, la déformation du réseau de vortex dans YBCO maclé est étudiée par des mesures de DNPA en statique.

<p><i>Francisella tularensis</i> is a Gram-negative intracellular pathogen causing the zoonotic disease tularemia. <i>F. tularensis</i> can be found almost all over the world and has been recovered from several animal species, even though the natural reservoir of the bacterium and parts of its life cycle are still unknown. Humans usually get infected after handling infected animals or from bites of blood-feeding arthropod vectors. There are four subspecies of <i>F. tularensis</i>: the highly virulent <i>tularensis</i> (Type A) that causes a very aggressive form of the disease, with mortality as high as 60% if untreated, the moderately virulent <i>holarctica</i> (Type B) and <i>mediasiatica</i>, and the essentially avirulent subspecies <i>F. novicida</i>. So far, our knowledge of the molecular mechanisms that would explain these differences in virulence among the subspecies is poor. However, recent developments of genetic tools and access to genomic sequences have laid the ground for progress in this research field. Analysis of genome sequences have identified several regions that differ between <i>F. tularensis</i> subspecies. One of these regions, RD19, encodes proteins postulated to be involved in assembly of type IV pili (Tfp), organelles that have been implicated in processes like twitching motility, biofilm formation and cell-to-cell communication in pathogenic bacteria. While there have been reports of pili-like structures on the surface of <i>F. tularensis</i>, these have not been linked to the Tfp encoding gene clusters until now. Herein, I present evidence that the <i>Francisella</i> pilin, PilA, can complement pilin-like characteristics and promote assembly of fibers in a heterologous system in <i>Neisseria gonorrhoeae. pilA</i> was demonstrated to be required for full virulence of both type A and type B strains in mice when infected via peripheral routes. A second region, RD18, encoding a protein unique to <i>F. tularensis</i> and without any known function, was verified to be essential for virulence in a type A strain. Interestingly, the non-licensed live vaccine strain, LVS (Type B), lacks both RD18 and RD19 (<i>pilA</i>) due to deletion events mediated by flanking direct repeats. The loss of RD18 and RD19 is responsible for the attenuation of LVS, since re-introducing them <i>in cis</i> could restore the virulence to a level similar to a virulent type B strain. Significantly, these deletion events are irreversible, preventing LVS to revert to a more virulent form. Therefore, this important finding could facilitate the licensing of LVS as a vaccine against tularemia.</p>

<p><strong>Background: </strong>To suffer from diabetes type II affects peoples new situation of life and therefore even their experiences of quality of life. <strong>Aim: </strong>The aim with this study was to describe how people with diabetes's type II experiences their quality of life. <strong>Method:</strong> The method that was used was a literature study with describing and deductive approach, where people’s experiences have come forth on the basis of Rustoens (1993) definition of quality of life. In total we analyzed 16 scientific articles that were categorized in four themes through a systematic content analysis (Evans, 2003) which resulted in four themes and nine subthemes. Orems (2001) theory of self-care has been used as the theoretical frame of reference. <strong>Result: </strong>In the result, it appear that people with diabetes's type II experiences quality of life differently on the basis of those four different themes, being active, to have fellowship, to have ego and to have a base spirit of happiness. The different themes conduct in different ways to create a good quality of life among people with diabetes type II. <strong>Conclusion:</strong> People with diabetes type II have a need to increase their knowledge and understanding to cope with the disease. A continuous contact with health-care and belonging to a group was important. From without the four different themes the individual can self choose to see its own needs to be able to obtain good quality of life.</p>

In this work we investigated fabrication of semiconductor nanomaterials and evaluated their potential for photo-chemical and photovoltaic applications. We investigated different II-VI semiconductor nanomaterial systems; (i) ZnO oriented nanowire arrays non-epitaxially grown from a substrate; and (ii) colloidal CdE (E=Te,Se,S) quantum structures synthesized by solution-based thermal decomposition of organo-metallic precursors. We have studied the synthesis of vertically aligned ZnO nanowire arrays (NWA), by a wet chemical process on various substrates. We have extended this method wherein nanofibers of poly-L-lactide act as a substrate for the radially oriented growth of ZnO nanowires. By combining the large surface area and the flexibility of the PLLA-ZnO hierarchical nanostructure we have shown the proof-of-principle demonstration of a ‘continuous-flow’ water treatment system to decompose known organic pollutants in water, as well as render common waterborne bacteria non-viable. We have studied synthesis of colloidal quantum dots (QD), and show size, morphology and composition tailored nanocrystals for CdE (E=S, Se, Te) compositions. We have studied the influence of crystal growth habits of the nanocrtsyals on the final morphology. Furthermore we have synthesized core-shell, CdSe-CdS QDs with spherical and tetrahedral morphologies by varying the reaction conditions. We show that these core-shell quantum dots show quasi-type II characteristics, and demonstrate with I-V measurements, the spatial localization of the charge carriers in these hetero-nanocrystals. For this purpose, we developed hybrid materials consisting of the core-shell quantum dots with electron acceptors (ZnO nanowires) and hole acceptors (polymeric P3HT nanofibers). In addition we have also compared the synthesis reaction when carried out with conventional heating and microwave-mediated heating. We find that the reaction is enhanced, and the yield is qualitatively better when using microwave induced heating. / QC 20120525

Francisella tularensis is a Gram-negative intracellular pathogen causing the zoonotic disease tularemia. F. tularensis can be found almost all over the world and has been recovered from several animal species, even though the natural reservoir of the bacterium and parts of its life cycle are still unknown. Humans usually get infected after handling infected animals or from bites of blood-feeding arthropod vectors. There are four subspecies of F. tularensis: the highly virulent tularensis (Type A) that causes a very aggressive form of the disease, with mortality as high as 60% if untreated, the moderately virulent holarctica (Type B) and mediasiatica, and the essentially avirulent subspecies F. novicida. So far, our knowledge of the molecular mechanisms that would explain these differences in virulence among the subspecies is poor. However, recent developments of genetic tools and access to genomic sequences have laid the ground for progress in this research field. Analysis of genome sequences have identified several regions that differ between F. tularensis subspecies. One of these regions, RD19, encodes proteins postulated to be involved in assembly of type IV pili (Tfp), organelles that have been implicated in processes like twitching motility, biofilm formation and cell-to-cell communication in pathogenic bacteria. While there have been reports of pili-like structures on the surface of F. tularensis, these have not been linked to the Tfp encoding gene clusters until now. Herein, I present evidence that the Francisella pilin, PilA, can complement pilin-like characteristics and promote assembly of fibers in a heterologous system in Neisseria gonorrhoeae. pilA was demonstrated to be required for full virulence of both type A and type B strains in mice when infected via peripheral routes. A second region, RD18, encoding a protein unique to F. tularensis and without any known function, was verified to be essential for virulence in a type A strain. Interestingly, the non-licensed live vaccine strain, LVS (Type B), lacks both RD18 and RD19 (pilA) due to deletion events mediated by flanking direct repeats. The loss of RD18 and RD19 is responsible for the attenuation of LVS, since re-introducing them in cis could restore the virulence to a level similar to a virulent type B strain. Significantly, these deletion events are irreversible, preventing LVS to revert to a more virulent form. Therefore, this important finding could facilitate the licensing of LVS as a vaccine against tularemia.

Detection of mid-wavelength infrared radiation is crucial for many industrial, military and biomedical applications. Photon detectors in the market can operate at only low temperature which increases weight, power consumption and total cost. Type-II InAs/GaSb superlattice infrared detectors are expected to have a major role in the infrared detector market with providing high quality detection characteristics at higher temperatures. Therefore, in the past decade, there has been an increasing interest in infrared detectors based on type-II InAs/GaSb superlattice technology due to their long range adjustable bandgap, low tunneling current and Auger recombination rates which bring potential of high temperature operation. Characterization of this photodiodes requires detailed investigations on different aspects. This study focuses on various optical and electrical characterization techniques for single pixel infrared detectors: responsivity characterization using FTIR and blackbody source, dark I-V and R-V characterizations, response time measurement. Characterizations of detector noise with respect to frequency and bias voltage are studied in detail. These characterization techniques are carried out in order to observe the effects of design with three different &ldquo / standard&rdquo / and a new &ldquo / N&rdquo / structure designs and also to understand the effects of surface passivation with atomic layer deposited Al2O3 layer and ordinary PECVD deposited Si3N4 and SiO2 layers. When standard photodiodes are compared, we observed that the one with the thickest active absorber region has the highest response and dark current density values. &ldquo / N&rdquo / structure design photodiode has very low dark current density while its optical performance is not as high as the standard designs. Si3N4 passivation degrades both optical and electrical performances. SiO2 and Al2O3 passivation layers improve optical and electrical characteristics of photodiodes. Theoretical and experimental dark current noise values of SiO2 passivated sample in agreement up to 0.18V reverse bias while those values of unpassivated and Si3N4 passivated samples agree only at zero bias. Temperature dependent R-V characteristics of photodiodes are analyzed and the surface limited activation energy is calculated in order to investigate the additional noise. At the end, surface recombination noise is proposed to cover the deficit on the noise calculation.

Background: To suffer from diabetes type II affects peoples new situation of life and therefore even their experiences of quality of life. Aim: The aim with this study was to describe how people with diabetes's type II experiences their quality of life. Method: The method that was used was a literature study with describing and deductive approach, where people’s experiences have come forth on the basis of Rustoens (1993) definition of quality of life. In total we analyzed 16 scientific articles that were categorized in four themes through a systematic content analysis (Evans, 2003) which resulted in four themes and nine subthemes. Orems (2001) theory of self-care has been used as the theoretical frame of reference. Result: In the result, it appear that people with diabetes's type II experiences quality of life differently on the basis of those four different themes, being active, to have fellowship, to have ego and to have a base spirit of happiness. The different themes conduct in different ways to create a good quality of life among people with diabetes type II. Conclusion: People with diabetes type II have a need to increase their knowledge and understanding to cope with the disease. A continuous contact with health-care and belonging to a group was important. From without the four different themes the individual can self choose to see its own needs to be able to obtain good quality of life.

<p>Obesity is a globally increasing disease particularly in developing countries and among children. It is mainly caused by intake of diets high in fat and the lack of physical activity. Obesity is a risk factor for diseases such as type II diabetes, high blood pressure, high cholesterol and certain cancers. Prediabetes is a condition where blood glucose levels are above normal but have not&nbsp / reached those of diabetes. It is difficult to diagnose, as there are no signs or symptoms. Some type II diabetes patients bear no symptoms at all and the disease is discovered late. Proteomics is a field that can provide opportunities for early diagnosis of diseases through biomarker discovery. The early diagnosis of diabetes can assist in the prevention and treatment of diabetes. Therefore there is a need for the early diagnosis of diabetes. Twenty Wistar rats were used. The rats were initially fed a CHOW diet, which is the standard balanced diet for rats, for 4 weeks. The rats were then divided into 2 groups of 10 where 1 group was fed CHOW and another was fed a high fat (HF) diet in order to induce obesity. The two groups were fed their respective diets for 18 weeks. Rats were weighed. Rats were placed in metabolic chambers and 24 hour urine samples were collected. Ketone levels were measured by Ketostix. Urine proteins were precipitated by acetone, quantified and separated on both the 1D SDS-PAGE and the 2D SDS-PAGE. Protein expression changes between CHOW and HF fed rats were determined and identified using MALDI-TOF mass spectrometry. Protein spots intensities increased and decreased between the CHOW and HF fed rats. Transducin (beta)-like 3 was identified as the only differentially expressed protein, which might serve as a potential biomarker for prediabetes.</p>

Let X and Y be two random variables such that Y depends on X=x. This is a very common situation in many real life applications. The problem is to estimate the location and scale parameters in the marginal distributions of X and Y and the conditional distribution of Y given X=x. We are also interested in estimating the regression coefficient and the correlation coefficient. We have a cost constraint for observing X=x, the larger x is the more expensive it becomes. The allowable sample size n is governed by a pre-determined total cost. This can lead to a situation where some of the largest X=x observations cannot be observed (Type II censoring). Two general methods of estimation are available, the method of least squares and the method of maximum likelihood. For most non-normal distributions, however, the latter is analytically and computationally problematic. Instead, we use the method of modified maximum likelihood estimation which is known to be essentially as efficient as the maximum likelihood estimation. The method has a distinct advantage: It yields estimators which are explicit functions of sample observations and are, therefore, analytically and computationally straightforward. In this thesis specifically, the problem is to evaluate the effect of the largest order statistics x(i) (i&gt / n-r) in a random sample of size n (i) on the mean E(X) and variance V(X) of X, (ii) on the cost of observing the x-observations, (iii) on the conditional mean E(Y|X=x) and variance V(Y|X=x) and (iv) on the regression coefficient. It is shown that unduly large x-observations have a detrimental effect on the allowable sample size and the estimators, both least squares and modified maximum likelihood. The advantage of not observing a few largest observations are evaluated. The distributions considered are Weibull, Generalized Logistic and the scaled Student&rsquo / s t.