Etude de la Commande et de l'Observation d'une Nouvelle Structure de Conversion d'Energie de type SMC (Convertisseur Multicellulaire Superposé)

Ce manuscrit apporte une contribution à la commande et à l'observation du convertisseur multicellulaire superposé (SMC). Cette nouvelle structure de conversion d'énergie, brevetée en 2001, présente des caractéristiques très intéressantes qui lui confèrent un intérêt certain pour les applications industrielles de forte puissance. Les présents travaux ont pour objet principal d'améliorer le fonctionnement des convertisseurs SMC et de montrer leur compétitivité pour ce domaine d'application. Cet enjeu est atteint de deux manières différentes mais complémentaires : en positionnant le SMC dans le domaine basse tension/forte puissance, une gamme de tension réduite par rapport à son domaine de prédilection ; en développant des techniques d'observation des tensions internes de la structure, afin de réduire son coût et d'assurer son fonctionnement optimal et sécurisé. La première partie de ce mémoire est consacrée à la présentation du fonctionnement, de la commande et des propriétés associées aux principales structures multiniveaux. Il s'agit de montrer l'intérêt que représente la topologie SMC dans les systèmes de conversion de puissance vis-à-vis des autres convertisseurs de cette famille. Nous effectuons ensuite une étude comparative des pertes, performances et coûts des topologies d'onduleurs 2 et 3 niveaux à base d'IGBT pour une application basse tension/forte puissance. L'enjeu consiste à légitimer l'utilisation du SMC à ce niveau de tension par rapport aux topologies classiques et multiniveaux concurrentes. La deuxième partie de ce manuscrit est dédiée à l'observation fine en temps réel des tensions internes de la structure SMC. Le contrôle actif de ces dernières revêt en effet un caractère important, car il conditionne la survie du convertisseur en garantissant une répartition équilibrée des contraintes en tension sur les semi-conducteurs de puissance. Cet équilibrage actif nécessite la connaissance de ces grandeurs à l'échelle de la période de découpage. La suppression des capteurs différentiels nécessaires permettrait donc de réduire de manière significative le coût global de ces structures dans le cadre d'applications industrielles. Nous présentons ainsi trois méthodes d'estimation : un reconstructeur de tension, une structure d'observation basée sur une simulation numérique en temps réel du système associée à une mesure de tension et un observateur à modes glissants. Ces techniques sont toutes validées par simulation sur des structures multicellulaires superposées à 3 cellules de commutation. L'observateur à modes glissants est également validé expérimentalement pour un onduleur SMC 7 niveaux triphasé 15kVA. Son implantation est réalisée à l'aide d'une carte numérique associant un DSP et un FPGA. ABSTRACT : This PhD Thesis deals with the control and the observation of Stacked Multicell Converters (SMC). Developed and validated within the LEEI at the beginning of years 2000, the SMC topology benefits from outstanding dynamic performances that dedicates it to medium voltage and high power applications. This manuscript tends to optimise the operation of this particular converter and to confirm its competitiveness with respect to other multilevel structures. This objective is achieved by different but complementary issues: legitimating the SMC for low voltage and high power applications and observing the flying capacitor voltages of the converter so as to reduce the topology cost and guarantee its safe and optimal operation. The first part of this thesis details the operation, the control strategy and the properties of the main multilevel topologies, in order to underline the SMC advantages for power conversion systems. A comparative study of the losses, performances and costs of IGBT-based 2 and 3-level topologies is then carried out for a particular low voltage and high power application. The main objective is to legitimate the use of the SMC converter even for this voltage range, compared to other classical and multilevel competitive structures. The second part is dedicated to the real-time observation of the SMC flying capacitor voltages. This topology indeed relies on flying capacitors so as to equally share the voltage constraint on several power switches. Balancing those internal voltages is a major issue, since it determines the lifetime of the converter. Removing the differential sensors required by the active control would result in a significant reduction of the topology cost for industrial applications. Three estimation methods are therefore introduced: a voltage reconstruction, a digital real time simulation of the converter combined with a voltage measurement and a sliding mode observer. Those techniques are validated by simulation for a 7-level Stacked Multicell Converter. The sliding mode observer is also confirmed experimentally with our 15kVA three-phase 7-level SMC prototype. Its implementation is realised using a digital board that combines a DSP and a FPGA

Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning

Kallmann Syndrome: Mutations in the Genes Encoding Prokineticin-2 and Prokineticin Receptor-2

Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases. In a cohort of 192 patients we took a candidate gene strategy and identified ten and four different point mutations in the genes encoding the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2), respectively. The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state. In addition, one of the patients heterozygous for a PROKR2 mutation was also carrying a missense mutation in KAL1, thus indicating a possible digenic inheritance of the disease in this individual. These findings reveal that insufficient prokineticin-signaling through PROKR2 leads to abnormal development of the olfactory system and reproductive axis in man. They also shed new light on the complex genetic transmission of Kallmann syndrome

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in CYP11A1 Gene

Context: The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first rate-limiting step of steroidogenesis. CYP11A1 mutations are associated with primary adrenal insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY patients.Objective: To define the pathogenicity mechanism for the p.Glu314Lys variant, previously reported, and found in four additional patients with CYP11A1 deficiency.Subjects and Methods: DNA of four patients presenting with delayed PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing. Three CYP11A1 mutations were characterized in vitro and in silico, and one by mRNA analysis on testicular tissue.Results: All patients were compound heterozygous for the previously described p.Glu314Lys variant. In silico studies predicted this mutation as benign with no effect on splicing but mRNA analysis found that it led to incomplete exon 5 skipping. This mechanism was confirmed by minigene experiment. The protein carrying this mutation without exon skipping should conserve almost normal activity, according to in vitro studies. Two other mutations found in trans, the p.Arg120Gln and p.Arg465Trp, had similar activity compared to negative control, consistent with the in silico studies.Conclusions: We provide biological proof that the p. Glu314Lys variant is pathogenic due to its impact on splicing and seems responsible for the moderate phenotype of the four patients reported herein. The present study highlights the importance of considering the potential effect of a missense variant on splicing when it is not predicted to be disease causing

Infection à enterovirus en pédiatrie

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hyperthyroïdie de l'enfant et de l'adolescent (revue de la littérature, arbres décisionnels, illustration par des cas limougeaux récents)

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mutations activatrices du récepteur sensible au calcium (aspects moléculaires, phénotypiques et implications thérapeutiques à travers une large étude collaborative)

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Syndrome d'activation macrophagique (à propos de deux cas pédiatriques)

Le syndrome d'activation macrophagique (SAM) est une entité anatomo- clinique née de la redéfinition récente des pathologies à prolifération histiocytaire. Il s'agit de l'ensemble des manifestations cliniques, biologiques et anatomopathologiques des histiocytoses hémophagocytaires. A partir de données de la littérature et de la description de deux cas pédiatriques, nous avons tenté de résumer les connaissances actuelles concernant le SAM chez l'enfant. Ce syndrome est évoqué devant une fièvre prolongée associée à une hépatosplénomégalie et une pancytopénie, suspecté devant une hypertriglycéridémie et une hypofibrinogénémie, affirmé par la mise en évidence d'une infiltration tissulaire par des macrophages hémophagocytaires. Les étiologies sont : lymphohistiocytose familiale, maladies inflammatoires, déficits immunitaires congénital et acquis, et infections virales, bactériennes, et parasitaires. Le traitement à visée pathogénique doit être débuté précocement simultanément aux thérapeutiques symptomatiques et étiologiques. Grâce à un diagnostic et un traitement précoce, le pronostic peut être amélioré.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge périnatale de la coarctation de l'aorte dans les régions Limousin et Midi-Pyrénées

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF