Le TD2 est caractérisé par un état inflammatoire de bas grade qui compromet la sécrétion et l‘action de l‘insuline. L‘installation de cette inflammation semble être la conséquence de l‘intoxication aux polluants environnementaux tels que les POP (Polluants Organiques Persistants) et/ou le changement de la flore intestinale, induit par un régime riche en graisse (HFD). L‘intestin est l‘un des premiers tissus exposés aux bactéries pathogènes et à certains POP. Cet organe est aussi le premier impliqué dans la régulation de l‘homéostasie glucidique. Il est donc raisonnable de supposer qu‘une inflammation chronique de l‘intestin puisse avoir des conséquences sur le développement du TD2. Nos objectifs généraux étaient donc : d‘évaluer le rôle de l‘inflammation entérocytaire dans le développement du diabète TD2 et de clarifier l‘effet du Resvératrol (RSV) sur cette maladie. Nos résultats suggèrent que l'inflammation intestinale est impliquée dans l‘établissement d‘un TD2. Cette inflammation pourrait intervenir en libérant des cytokines inflammatoires, en diminuant le taux de GLP-1 et en favorisant le passage des facteurs diabétogènes, de l‘intestin vers les tissus cibles de l‘insuline. L‘induction ou la diminution de l‘inflammation intestinale par des facteurs inflammatogènes (BaP) ou anti-inflammatoires (RSV) sont respectivement associées à l‘aggravation ou à l‘amélioration de l‘état diabétique.Nous avons également montré que le RSV pourrait améliorer l‘état diabétique en normalisant la flore intestinale modifiée par un régime HFD et en augmentant la concentration de GLP-1.. De plus, une co-administration du RSV avec le sitagliptine, un inhibiteur de l‘enzyme DPP4, dégradant le GLP-1, montre une potentialisation de l‘effet du RSV par le sitagliptine: Ces résultats ouvrent la porte pour l‘utilisation de RSV dans la prévention et le traitement du TD2. / The TD2 is characterized by a low-grade inflammatory state that impairs the secretion and action of insulin. Environmental pollutants such as POP (Persistent Organic Pollutants) and the change in gut flora induced by a high fat diet (HFD), are suspected to play an important role in the installation of this inflammation.The intestine is one of the first tissues exposed to pathogenic bacteria and some POP. This organ is also the first take part in the regulation of glucose homeostasis. So, it is reasonable to assume that chronic inflammation of the bowel may affect the development of TD2. Our objectives were: to assess the role of inflammation in the enterocyte development of diabetes TD2 and clarify the effect of Resveratrol (RSV) on the disease.Our results suggest that intestinal inflammation is involved in the establishment of a TD2. This inflammation could affect TD2 through releasing inflammatory cytokines, reducing the concentration of GLP-1 and promoting the passage of diabetogenic factors from the intestine to target tissues of insulin. The induction or reduction of intestinal inflammation by factor inflammatory (BaP) or anti-inflammatory (RSV) are respectively associated with worsening or improvement of the diabetic state.We also showed that the RSV could improve the diabetic state by normalizing the intestinal flora modified by diet and HFD, by increasing the concentration of GLP-1. In addition, co-administration of sitagliptin with RSV, an inhibitor of the enzyme DPP4,which degrade GLP-1, shows a potentiation of the effect of RSV in the sitagliptin: These results open the door for the use of RSV in the prevention and treatment of TD2.Keywords: Resveratrol, type 2 diabetes

Les minéralisations uranifères de type roll-front du bassin de Chu-Sarysu (Kazakhstan) affectent des formations silico-clastiques continentales d'âge début paléogène. Les formations sont constituées d'une alternance de sables arkosiques et d'argiles provenant de l'altération de granites peralumineux et de roches volcaniques calco-alcalines, mais aussi de roches paléozoïques du Massif du Karatau. Toutes les formations ont une fraction argileuse dominée par les smectites, associées à de la palygorskite, ce qui pourrait indiquer des alternances de périodes humides et chaudes et de périodes sèches. L'ensemble des séries a été soumis à un enfouissement faible qui n'a pas beaucoup évolué depuis les derniers dépôts, comme l'indique, le caractère immature des matières organiques (MO), la présence smectite néoformées automorphes non interstratifiées et la présence pérenne de pyrites framboïdales liée à une activité bactérienne qui est attestée par les extrêmes fluctuations de [delta]34S des pyrites. La cimentation des sables minéralisés par la calcite est locale et est à mettre en relation avec la percolation de fluides météoriques de basse température. La minéralisation est fortement corrélée aux MO, et aux pyrites, notamment dans les faciès de levées en sommet de séquence de chenal, et en association avec les macro-débris végétaux disséminés au sein des sables de chenaux. Les phosphocoffinites sont plus tardives. Ces gisements ressemblent à ceux analogues du Wyoming, mais en différent par la taille des front redox, l'hétérogénéité de la répartition des minéralisations à petite échelle, et l'existence probable d'une préconcentration non négligeable liée aux matières organiques / Roll front ore U-ore deposits in the Chu-Sarysu basin (Kazakhstan) occur in paleogene, continental silicoclastic formations. Sedimentary sequences include unconsolidated arkosic sands and clay lenses, formed by detrital minerals issued from granites and calkalcaline volcanites but also from paleozoïc series from Karatau. All formations are characterized by a fine grain clay fraction dominated by smectites, associated with palygorskite which could be the result of alternated humid and dry periods. All series underwent a rather shallow burial which is indicated by the immature feature of the organic matter, the presence of newly formed unaltered smectites, and the presence of pyrite framboïds which are formed by bacterial sulphate reduction, indicated by the wide range of delta34S of pyrites. Sands are locally cemented by calcite which precipitated from meteoric fluids at low temperature. U-ores are spatially and genetically related to sulphides and organic matter, especially in levee facies at the top of the sedimentary sequence and in association with organic macro-clasts disseminated within the sand channels. Phospho-coffinites occur latter on. These deposits show similarities with those of Wyoming but differ by the size of the roll fronts front redox, the heterogeneity of the U-ores at small scale, and a probable significant pre-concentration associated with organic matter

5 Abstract Type 1 diabetes (T1D) is a serious organ-specific autoimmune disease characterised by irreversible destruction of pancreatic β-cells by immune system. This process results in an absolute insulin deficiency. Both genetical predisposition and environmental factors influence the development of the disease. β-cell destruction is mediated by cellular components of an immune system. Proinflammatory Th1 response is considered as most pathological. Autoimmune destruction of β-cells can be identified by the detection of specific serum autoantibodies a long time before the T1D clinical onset. Currently, there is no efficient cure available to prevent or at least to delay the destructive insulitis. This diploma thesis describes the influence of synthetic diabetogenic autoantigens GAD65 and IA2 on the cytokine response of peripheral blood mononuclear cells (PBMC) obtained from T1D patients with regards to their antibody profile. The study has been carried out on patients with confirmed T1D diagnosis who tested positive for anti-GAD65 and/or anti-IA2 autoantibodies. By using flow cytometry we measured the cell type ratio in PBMC samples. The cells have been stimulated by three different concentrations of antigens and their IFNγ and IL-17 production has been detected by ELISPOT assay. In the case of both...

Metal oxides are a very important class of materials with a wide range of photovoltaic applications. Transparent conducting oxides (TCOs) are the primary front contact materials used in thin film solar cells. Identification of methods for reducing the resistivity of these materials would have significant benefits. Development of p-type TCOs would provide alternative back contact materials and could enable further development of technologies such as bifacial, window and multijunction cells. A series of studies into these areas is presented in this work. Aluminium doped zinc oxide (AZO) is a well-known n-type TCO consisting entirely of Earth-abundant materials. Targets were manufactured from AZO powder, which was synthesised using a patented emulsion detonation process developed by Innovnano S.A. All films showed good optical transmission. Resistivity was found to decrease with both increasing time and temperature up to 300 degree C. Temperatures above 300 degree C were found to be detrimental to film formation, with increasing amounts of damage to the crystal structure and consequent increases in the resistivity. The effect of alloying molybdenum oxide with molybdenum nitride through reactive sputtering in a mixed oxygen-nitrogen atmosphere was investigated. All alloys were found to show p-type behaviour. Resistivity was found to improve with increased nitrogen content, in contrast to optical transmission, which reduced. A selection of compositions were deposited onto CdTe cells as back contacts. These cells showed an increase in efficiency with increasing nitrogen content. Work function was found to increase with increasing oxygen content, but all work functions were low. Resistivity was shown to correlate strongly with efficiency, caused by a corresponding increase in cell voltage. This implies that to form an ohmic contact on CdTe with p-type materials, work function may be less important than resistivity. The copper oxides are p-type, but uses are limited by the narrow band gaps. Cupric oxide was chosen for investigation and for alloying with other oxides with the aim of increasing the band gap. It was found that temperature and deposition environment have significant impacts on sputtered cupric oxide (CuO) films, with low temperatures and high oxygen environments producing the lowest resistivities. Extrinsic sodium doping was found to reduce the resistivity by up to four orders of magnitude. High oxygen content sodium-doped films were found to have carrier concentrations two orders of magnitude higher than that of indium tin oxide.

Diabetes mellitus typ 1 är en autoimmun sjukdom, vilket innebär att immunsystemet ser betacellerna i bukspottskörteln som främmande och angriper dem. Cellerna kan då inte producera insulin längre, vilket är ett livsviktigt hormon för kroppen. I Sverige insjuknar cirka två barn varje dag i diabetes mellitus typ 1. Sjukdomen påverkar barnets vardag och kommer alltid vara en styrande del genom livet. Många barn oroar sig över hypoglykemi samt andra komplikationer som är relaterade till sjukdomen. Syftet med studien är att beskriva upplevelser av hur vardagen påverkats hos barn som är diagnostiserade med diabetes mellitus typ 1. Metoden är en sammanställning av empirisk data och baseras utifrån Axelssons (2012) modell. Studien innehåller 11 artiklar som består av både kvalitativa och kvantitativa ansatser. Examensarbetet fokuserar på barn i åldern 6-14 år och artiklarna i studien belyser upplevelsen av att leva med diabetes mellitus typ 1. Resultatet visade att barnen upplevde känslor av utanförskap och att de kände sig annorlunda jämfört med sina vänner. Familjen hade en betydelsefull roll för barnen och sjukdomen påverkade även omgivningen. Resultatet presenteras utifrån fyra huvudkategorier och tio subkategorier. I diskussionen belyser vi känslan av att vara barn och leva med en kronisk sjukdom, familjens betydelse samt att förlika sig med sjukdomen. En grundläggande aspekt som framkommer i diskussionen är även vikten av adekvat och individanpassad information efter barnets utvecklingsnivå.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Raymond R. R. Rowland / Interferons (IFNs) comprise a group of antiviral cytokines; however, their expression at the porcine maternal-fetal interface and in fetal tissues has not previously been investigated. The purpose of this study was to analyze the expression of type I IFNs and their receptors in maternal and fetal tissues from sows infected with PRRSV. The approach was to use real-time RT-PCR to identify the expression of different subtypes of type I IFN genes. The results show that the constitutive gene expression of some subtypes including IFN-[alpha] and IFN-[alpha][omega] were detected in fetal lymphoid nodes (IFN-[alpha][omega]), placenta (several IFN-[alpha] subtypes and IFN-[omega]5) and particularly, thymus (multiple IFN-[alpha], IFN-[delta] and IFN-[omega]5). The results demonstrate that porcine type I IFNs are differentially expressed at the maternal-fetal interface and in fetal tissues in response to PRRSV infection.

Master of Science in Biomedical Sciences / Department of Anatomy and Physiology / Yongming Sang / Animal metabolic and immune systems integrate and inter-regulate to exert effective immune responses to distinct pathogens. The signaling pathway mediated by mechanistic target of rapamycin (mTOR) is critical in cellular metabolism and implicated in host antiviral responses. Recent studies highlight the significance of the mTOR signaling pathway in the interferon (IFN) response. Type I IFNs mediate host defense, particularly, against viral infections, and have myriad roles in antiviral innate and adaptive immunity. In addition to their well-known antiviral properties, type I IFNs also affect host metabolism. However, little is known about how animal type I IFN signaling coordinates immunometabolic reactions during antiviral defense. Therefore, understanding the interaction of mTOR signaling and the type I IFN system becomes increasingly important in potentiating antiviral immunity. Tissue macrophages (MФs) are a primary IFN producer during viral infection, and their polarization to different activation statuses is critical for regulation of immune and metabolic homeostasis. Using porcine reproductive and respiratory syndrome virus (PRRSV) as a model, we found that genes in the mTOR signaling pathway were regulated differently in PRRSV-infected porcine alveolar MФs at different activation statuses. Therefore we hypothesize that: 1) the mTOR signaling pathway involves host anti-PRRSV regulation; 2) mTOR signaling interacts with IFN signaling to modulate the antiviral response; and 3) different type I IFN subtypes (such as IFN-α1 and IFN-β) regulate mTOR signaling differently. We show that modulation of mTOR signaling regulated PRRSV infection in MARC-145 cells and porcine primary cells, in part, through regulating production and signaling of type I IFNs. In addition, expression and phosphorylation of two key components in the mTOR signaling pathway, AKT and p70 S6 kinase, were regulated by type I IFNs and PRRSV infection. Taken together, we determined that the mTOR signaling pathway, a key pathway in regulation of cell metabolism, also mediates the type I IFN response, a key immune response in PRRSV infection. Our findings reveal that the mTOR signaling pathway potentially has a bi-directional loop with the type I IFN system and implies that some components in the mTOR signaling pathway can serve as targets for augmentation of antiviral immunity and therapeutic designs.

Magíster en Ciencias, Mención Computación / Los sistemas de tipos-y-efectos (type-and-effect systems) permiten a los programadores hacer valer invariantes y restricciones sobre los efectos secundarios que se generan durante la evaluación de un programa. Los sistemas de tipos-y-efectos consideran efectos secundarios tales como estado, excepciones y E/S, entre otros. Desafortunadamente, los sistemas de tipos-y-efectos también obligan al programador a introducir anotaciones de efectos, lo que implica un esfuerzo adicional. En la práctica, los sistemas de tipos-y-efectos no son comúnmente usados. Conjeturamos que una de las razones importantes para la limitada adopción de los sistemas de efectos son las dificultades para realizar la transición desde un sistema donde los efectos secundarios son implícitos hacia una disciplina de efectos totalmente estática. Los tipos graduales (Gradual typing) permiten a los programadores combinar la flexibilidad de los lenguajes dinámicamente tipados con las garantías provistas por los sistemas de tipos estáticos. En lenguajes con tipos graduales, las anotaciones de tipos son parte del lenguaje, pero no son obligatorias. Un sistema de tipos gradual utiliza la información disponible para proveer garantías estáticas, rechazando los programas claramente incoherentes, e introduce verificaciones en tiempo de ejecución cuando la información estática no es suficiente para aceptar o rechazar definitivamente un programa. Esta tesis demuestra que las ideas de diseño detrás de los tipos graduales pueden aplicarse a los sistemas de tipos-y-efectos, tanto para aumentar la expresividad de estos sistemas así como para proveer flexibilidad para migrar programas con efectos secundarios impl ́ıcitos e irrestrictos hacia programas con una disciplina de efectos completamente estática. Se adaptaron ideas de tipos graduales para introducir verificación gradual de efectos para sistemas de tipos-y-efectos. La verificación gradual de efectos habilita al programador para decidir dónde y cuándo introducir anotaciones de efectos, agregando verificaciones en tiempo de ejecución cuando las anotaciones estáticas son insuficientes. Para evitar redefinir la verificación gradual de efectos para cada disciplina de tipos-y-efectos, introducimos verificación gradual de efectos para una plataforma genérica de tipos-y-efectos, en la que se puede instanciar cualquier disciplina de efectos monotónica, produciendo un sistema coherente. Presentamos la verificación gradual de efectos basándonos en conceptos de interpretación abstracta para construir la verificación gradual de efectos genérica. Utilizando verificación gradual de efectos genérica, introducimos tipos graduales para sistemas de tipos-y-efectos: un sistema donde las anotaciones de efectos y de tipos no son obligatorias, y donde se introducen verificaciones en tiempo de ejecución y casts cuando la información estática no es suficiente para asegurar la coherencia de un programa. De la manera definida, los tipos graduales para sistemas de tipos-y-efectos permiten migrar desde sistemas carentes de anotaciones de efectos o de tipos hacia una disciplina estática de tipos-y-efectos de manera segura.

Master of Science / Department of Statistics / Christopher I. Vahl / Estimation of sample size is an important and critical procedure in the design of clinical trials. A trial with inadequate sample size may not produce a statistically significant result. On the other hand, having an unnecessarily large sample size will definitely increase the expenditure of resources and may cause a potential ethical problem due to the exposure of unnecessary number of human subjects to an inferior treatment. A poor estimate of the necessary sample size is often due to the limited information at the planning stage. Hence, the adjustment of the sample size mid-trial has become a popular strategy recently. In this work, we introduce two methods for sample size re-estimation for trials with a binary endpoint utilizing the interim information collected from the trial: a blinded method and a partially unblinded method. The blinded method recalculates the sample size based on the first stage’s overall event proportion, while the partially unblinded method performs the calculation based only on the control event proportion from the first stage. We performed simulation studies with different combinations of expected proportions based on fixed ratios of response rates. In this study, equal sample size per group was considered. The study shows that for both methods, the type I error rates were preserved satisfactorily.

Bakgrund: Diabetes typ 1 är en stor folksjukdom som främst drabbar yngre människor. Att drabbas av diabetes är påfrestande fysiskt och psykiskt. Det är därför ett viktigt ämne att belysa för att kunna underlätta och förbättra vården av barn och ungdomar med diabetes. Syfte: Syftet med litteraturstudien var att belysa barn och ungdomars erfarenheter av att leva med diabetes typ 1. Metod: Litteraturstudien är en sammanställning av 10 kvalitativa studier där samtliga kvalitetsgranskats, analyserats och sammanställts. Deltagarna i litteraturstudien var 6–22 år gamla. Resultat: Resultatet visade på barn och ungdomars erfarenheter av att leva med diabetes typ 1 från att få diagnosen, ta kontroll över sjukdomen, få stöd från hälsoprofessioner, familj och vänner till att lära sig leva ett förändrat men ”normalt” liv.Konklusion: Att leva med diabetes är en ständig kamp om att leva så normalt och självständigt som möjligt. Detta underlättas genom stöd och tillräcklig information från familj och vårdpersonal. Denna fördjupande kunskap och förståelse av barn och ungdomars erfarenheter av att leva med diabetes kan bidra till förbättrad diabetesvård som kan underlätta för dessa att leva ett gott liv trots diabetes. / Background: Diabetes type 1 is a large endemic disease that mainly affects younger people. Diabetes has shown to be straining physically and psychologically and is an important subject to highlight to ease and improve the care for adolescents with diabetes. Purpose: The aim with this literature study was to highlight children and adolescents experience of living with diabetes type 1. Method: The literature study is a compilation of 10 qualitative studies that has been quality reviewed, analysed and compiled. The participants in the study was 6-22 years old. Results: The result showed children and adolescents experiences of living with diabetes type 1. From being diagnosed, taking control of the disease, getting support from healthcare, family and friends to learning how to live a changed but “normal” life.Conclusions: To live with diabetes is a constant struggle to live as normal and independent as possible. This facilitates with care and information from family and health professionals. Increased knowledge and understanding of children and adolescence experience of living with diabetes may help to improve diabetes healthcare which can ease their life despite diabetes.