In this document, we present ou study about the conception and realization of VMOS and Schottky and JBS Diodes on Silicon Carbide. This work allowed us optimize and fabricate diodes using Tungsten as Schottky barrier on both Schottky and JBS diodes of different blocking capability between 1.2kV and 9kV. Moreover, our study of the VMOS, by considering the overall fabrication process, has permitted to identify the totality of the problems we are facing. Thusly we could ameliorate the devices and try new designs as the VIEMOS or the monolithic integration of temperature and current sensors.

Dans le contexte des transports plus électriques, les parties mécaniques tendent à être remplacées par leurs équivalents électriques plus petits. Ainsi, le composant lui-même doit supporter un environnement plus sévère et de lourdes contraintes (haute tension, haute température). Les composants silicium deviennent alors inappropriés. Depuis la commercialisation des premières diodes Schottky en 2001, le carbure de silicium est le matériau reconnu mondialement pour la fabrication de dispositifs haute tension avec une forte intégration. Sa large bande d'énergie interdite et son fort champ électrique critique permettent la conception de transistors à effet de champ avec jonction (JFET) pour les hautes tensions ainsi que les diodes associées. Les structures étudiées dépendent de nombreux paramètres, et doivent ainsi être optimisées. L'influence d'un paramètre ne pouvant être isolée, des méthodes mathématiques ont été appelées pour trouver la valeur optimale. Ceci a conduit à la mise en place d'un critère d'optimisation. Ainsi, les deux grands types de structures de JFET verticaux ont pu être analysés finement. D'une part, la recherche d'une structure atteignant les tensions les plus élevées possible a conduit à l'élaboration d'un procédé de fabrication complexe. D'autre part, un souci de simplification et de stabilisation des procédés de fabrication a permis le développement d'un composant plus simple, mais avec une limite en tension un peu plus modeste.

Human α-N-Acetylglucosaminidase (Naglu) is a lysosomal acid hydrolase implicated in tthe rare metabolic storage disorder known as mucopolysaccharidosis type IIIB (MPS IIIB; also Sanfilippo syndrome B). Absence of this enzyme results in cytotoxic accumulation of heparan sulphate in the central nervous system, causing mental retardation and a shortened lifespan. Enzyme replacement therapy is not currently effective to treat neurological symptoms due to the inability of exogenous Naglu to access the brain. This laboratory uses a Spodoptera frugiperda (Sf9) insect cell system to express Naglu fused to a synthetic protein transduction domain with the intent to facilitate delivery of Naglu across the blood-brain barrier. The project described herein may be broken down into three main sections. Firstly, the impact of two cryptic splice sites on Naglu expression levels was analyzed in both transiently expressing Sf9 cultures and stably selected cell lines. Secondly, the effectiveness of the native Naglu secretion-signaling peptide in the Sf9 system was examined. Finally, purification of a Naglu fusion protein from suspension culture medium was performed using hydrophobic interaction chromatographic techniques. The ultimate goal of this research is to develop an efficient system for economical, large-scale production of a human recombinant Naglu fusion protein that has the potential to be successfully used for enzyme replacement therapy to treat MPS IIIB. / Graduate

Prenatal assessment of fetal health is routinely offered throughout pregnancy to ensure that the most effective management can be provided to maintain fetal and maternal well-being. Currently, invasive testing is used for definitive diagnosis of fetal aneuploidy, which is associated with a 1% risk of iatrogenic fetal loss. Developing non-invasive prenatal testing (NIPT) is a key area of research and methods to increase the level of cell-free fetal DNA (cffDNA) within the maternal circulation have been discussed to improve accuracy of such tests. In this study, three strategies; co-amplification at lower denaturation temperature polymerase chain reaction (COLD-PCR), inverse-PCR and Pippin Prep™ gel electrophoresis, were analysed to identify a novel approach to selectively enrich shorter cffDNA fragments from larger maternal cell-free DNA (cfDNA). The sensitivity of droplet digital PCR (ddPCR) against real-time PCR (qPCR) was compared for fetal sex and RHD genotyping. In addition RHD zygosity testing was carried out for non-maternal samples. Consequently, Pippin Prep™ gel electrophoresis was combined with ddPCR analysis for the NIPD of Down Syndrome (DS) in pseudo-maternal samples. The results revealed that the Pippin Prep™ gel electrophoresis enrichment approach successfully demonstrated 2-fold to 5-fold increases in the cffDNA fraction. However, further optimisation assays of COLD-PCR and inverse-PCR using actual maternal samples were required. The spike experiments for DS detection revealed that with the present assay IV overrepresentation of the chromosome 21 target could be significantly detected for samples with ≥15% ‘cffDNA fraction’. In conjunction with the Pippin Prep™ enrichment method, this would have enabled assessment of all 10 maternal samples. Alternatively, fetal sex and RHD genotyping results determined that ddPCR provides a more sensitive platform compared to qPCR approaches, particularly for samples that express low cffDNA fractions (<2%). The ddPCR platform also proved to be a rapid and accurate system for the determination of RHD zygosity. This study highlights that ddPCR could be used as opposed to qPCR for accurate determination of fetal sex and RHD status. While sequencing approaches currently provide the most sensitive platforms for NIPT of fetal aneuploidy, high costs (>£400) prevent universal application. The combination of cffDNA enrichment with ddPCR analysis could provide a cheaper and more widely available platform for NIPD. However, further large scale validation studies using actual maternal samples are required.

Cette recherche traite de la réactivité des parlementaires français vis-à-vis de leur circonscription.Ce faisant, notre thèse investit l’aspect dyadique de la représentation politique qui a été largementignoré par la littérature française et offre ainsi un nouveau regard sur la variété des activités desdéputés français tant à Paris qu’en circonscription. En s’inspirant des écrits du néoinstitutionnalismedes choix rationnels, notre thèse vise à mettre en lumière les déterminantsinstitutionnels de la réactivité vis-à-vis de la circonscription ainsi que les logiques qui sous-tendentles pratiques de représentation. En surmontant le descriptivisme de beaucoup d’études à ce sujetet à l’aide de solides matériaux empiriques, nous montrons que le territoire d’élection affectegrandement le comportement des députés tant dans le contenu que sur la forme des activités. Lacirconscription et les attentes différenciées des citoyens agissent de manière systématique sur lamanière dont les députés mènent leur mandat. / This research deals with French MPs responsiveness. This dissertation studies the dyadicrepresentation in the French Assemblée nationale which was largely neglected by scholars. It givesthus a new insight on the diversity of French MPs activities both in Paris and in their district.Following the arguments of the rational choice new institutionalism, our dissertation aims tohighlight the institutional determinants of MPs responsiveness toward their district and the logicsthat underlie their practices of representations. By overcoming the descriptiveness of many studiesand thanks to original and solid empirical data, we show that the characteristics of the districtstrongly affect both the kind and the content of MPs activities. The district and the various citizens’expectations systematically affect the way French MPs conceive their mandate.

Studien tillverkar en modell av en värdeflödesanalys hos ett tillverkningsföretag för att se hur värdeskapande företaget är. Studien tar även fram förbättringsförslag på hur företaget kan bli mer värdeskapandeoch effektiva i sitt arbete.

Nous présentons dans ce document, notre étude de la conception et la réalisation de VMOS et de diodes Schottky et JBS en carbure de silicium. Ce travail nous a permis d'optimiser et de fabriquer des diodes utilisant une barrière Schottky en Tungsten de différentes tenues en tension entre 1,2kV et 9kV. De plus, notre étude du VMOS nous a permis d'identifier la totalité des problèmes auxquels nous faisons face. Ainsi, nous avons pu améliorer ces composants tout en essayant de nouveaux designs tels que le VIEMOS et l'intégration monolithique de capteurs de temperature et de courant. / In this document, we present ou study about the conception and realization of VMOS and Schottky and JBS Diodes on Silicon Carbide. This work allowed us optimize and fabricate diodes using Tungsten as Schottky barrier on both Schottky and JBS diodes of different blocking capability between 1.2kV and 9kV. Moreover, our study of the VMOS, by considering the overall fabrication process, has permitted to identify the totality of the problems we are facing. Thusly we could ameliorate the devices and try new designs as the VIEMOS or the monolithic integration of temperature and current sensors.