This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

Ces travaux de thèse s’inscrivent dans le cadre d’une collaboration entre les laboratoires G2ELAB et IMEP-LAHC en lien avec le projet BQR WiSiTUDe (Grenoble-INP). Le but de cette thèse concerne la conception, modélisation et caractérisation du gate driver intégré pour transistors de puissance à base d’un transformateur sans noyau pour le transfert isolé d'ordres de commutation. La thèse est composée de deux grandes parties : - Une partie de la conception, la modélisation et la caractérisation du transformateur intégré dans deux technologies CMOS 0.35 µm bulk et CMOS 0.18 µm SOI. - Une partie de la conception, la simulation et la mise en œuvre de deux circuits de commande intégrée dans ces deux technologies. Ainsi, l’aspect du système du convertisseur de puissance sera étudié en proposant une nouvelle conception couplée commande/puissance à faible charge. Les résultats de ce travail de thèse ont permis de valider les approches proposées. Deux modèles fiables (électrique 2D et électromagnétique 3D) du transformateur ont été établis et validés via une réalisation CMOS 0.35 µm standard. De plus, un driver CMOS bulk, intégrant l’ensemble du transformateur sans noyau avec plusieurs fonctions de pilotage de la commande rapprochée a été caractérisé et validé. Finalement, un gate driver générique a été conçu en technologie CMOS SOI, intégrant dans une seule puce les étages de commande éloignée, l’isolation galvanique et la commande rapprochée pour transistors de puissance. Ce gate driver présente nombre d’avantages en termes d’interconnexion, de la consommation de la surface de silicium, de la consommation énergétique du driver et de CEM. Les perspectives du travail de thèse sont multiples, à savoir d’une part l’assemblage 3D entre le gate driver et le composant de puissance et d’autre part les convertisseurs de multi-transistors. / This thesis work focuses on the design, modelling and the implementation of integrated gate drivers for power transistors based on CMOS coreless transformer. The main objectives of thesis are the design, modeling and characterization of coreless transformer in two technologies CMOS 0.35 µm bulk and CMOS 0.18 µm SOI, as well as the design and the characterization of two integrated gate drivers in these two technologies. The results of thesis allow us to validate our proposal models for coreless transformer: 2D electrical model and 3D electromagnetic model. Moreover, one CMOS bulk isolated gate driver which monolithically integrates the coreless transformer, the secondary side control circuit for power transistors has been fabricated and validated for both high side and low side configuration in a Buck converter. Finally, a CMOS SOI isolated gate driver is designed; integrates in one single chip the external control, the coreless transformer and the close gate driver circuit for power transistors. This one-chip solution presents a numerous advantages in term of interconnect parasitic, energy consumption, silicon surface consumption, and EMI with a high level of galvanic isolation. The perspectives of this SOI gate driver are multiple, on the one hand, are the 3D assemblies between gate driver/power transistors and on the other hand, are the multiple-switch converter.

Objective: Description of the clinical, biochemical and genetic features of a Polish patient with familial glucocorticoid deficiency. Methods: Detailed clinical investigation, hormonal analysis and sequencing of the coding region of the melanocortin 2 receptor (MC2R) gene in this patient. Results: We report on a 3-month-old boy with familial glucocorticoid deficiency who presented at the age of 3 months with skin hyperpigmentation, muscle weakness, mild jaundice and constipation. Hormonal analyses revealed high ACTH and TSH serum concentrations, low serum cortisol concentration along with normal blood electrolytes. On hydrocortisone supplementation, the disease symptoms disappeared and the child recovered completely. His physical and mental development progresses normally. Genetic analysis disclosed a novel compound heterozygous MC2R mutation p.Leu46fs and p.Val49Met. Conclusion: The heterozygous p.Leu46fs mutation adds to the small number of MC2R nonsense mutations and is the first frameshift mutation within the first transmembrane domain of the receptor. According to molecular modeling the Val49Met mutation results in a structural change of the first transmembrane domain and in a potential novel interaction of the transmembrane domains I and VII. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The imaginary part of the retarded self energy is of particular interest as it contains a lot of physical information about particle interactions. In higher order loop diagrams the calculation become extremely tedious and if we have to do the same at finite temperature, it includes an extra dimension to the difficulty. In such a condition we require to switch between bases and select the best basis for a particular diagram. We have shown in our calculation that in higher order loop diagrams, at #12;finite temperature, the R/A basis is most convenient on summing over the internal vertices and very efficient on calculating some particular diagrams while the result is most easily interpretable in the Keldysh basis for most other complex diagrams.

Mit dieser Arbeit ist weltweit zum ersten Mal die molekulare Dynamik von vereinzelten,d.h. einander nicht berührenden Polymerketten experimentell bestimmt worden. Die Grundlagen dafür sind einerseits die breitbandige dielektrische Spektroskopie mit ihrer außerordentlich hohen experimentellen Empfindlichkeit und andererseits die Weiterentwicklung einer speziellen Probenanordnung, bei der hochleitfähige Silizium-Elektroden durch elektrisch isolierende Siliziumdioxid-Nanostrukturen in einem vordefinierten Abstand gehalten werden und so den Probenkondensator bilden. Im Rahmen dieser Arbeit wurde die Höhe der Nanostrukturen (und damit des Elektrodenabstands) auf nur 35 nm reduziert. Damit gelang der Nachweis, dass selbst vereinzelte kondensierte Polymer-Knäuel - im Rahmen der Messgenauigkeit - dieselbe Segmentdynamik (bzw. denselben dynamischen Glasübergang), gemessen in ihrer mittleren Relaxationsrate, wie die makroskopische Schmelze („bulk“) aufweisen. Nur ein kleiner Anteil der Segmente zeigt eine langsamere Dynamik, was auf attraktive Wechselwirkungen mit dem Substrat zurückzuführen ist, wie komplementäre Untersuchungen mittels Infrarot-Spektroskopie zeigen. Zudem bieten diese Experimente die Möglichkeit, nach der dielektrischen Messung die mit Nanostrukturen versehene obere Elektrode zu entfernen und die Verteilung der vereinzelten Polymerketten, deren Oberflächenprofile und Volumen mit dem Rasterkraftmikroskop zu bestimmen. Erst damit gelingt der Nachweis, dass die Polymer-Knäuel im Mittel aus einer einzelnen Kette bestehen. Die Kombination dieser drei unabhängigen Messmethoden liefert ein schlüssiges und detailliertes Bild, gekennzeichnet dadurch, dass attraktive Oberflächenwechselwirkungen die Glasdynamik nur über ca. 0,5nm direkt beeinflussen. In einem zweiten Teil trägt die Arbeit mit der Untersuchung dünner Polymerschichten im Nanometer-Bereich zu einer international geführten, kontroversen Diskussion um die Frage, ob sich im Falle solcher räumlichen Begrenzungen der dynamische und kalorimetrische Glasübergang ändern, bei. Dabei zeigt mit den präsentierten dielektrischen und ellipsometrischen Messungen eine Kombination aus einer Methode, die im Gleichgewichtszustand misst und einer, die den Übergang in den Nichtgleichgewichtszustand bestimmt, dass sich sowohl Polystyrol-Schichten verschiedener Molekulargewichte bis zu einer Dicke von nur 5 nm als auch Polymethylmethacrylat-Schichten auf unterschiedlichen (hydrophilen und hydrophoben) Substraten bis zu einer Dicke von 10 nm weder in ihrem dynamischen noch ihrem kalorimetrischen Glasübergang von der makroskopischen Schmelze unterscheiden.

Aescin is a mixture of several acidic triterpenoid saponin glycosides found in the extracts of the horse chestnut tree. Horse chestnut, Aesculus Hipoocastanum, is one of the 25 domestic species of Aesculus that are mostly large, ornamental shade trees. Although known to be poisonous, the nuts of the horse chestnut are used by Amerindians, after detoxification. Horse chestnuts are said to have several traditional medicinal usages including even cancer. In this study the biochemical, genotoxic, and cytotoxic effects of aescin was studied using isolated lymphocytes, whole blood lymphocytes and HL-60 promyeloid leukemia cell lines. Cytotoxicity of aescin was examined by trypan blue viability staining of the cells in culture treated with varying aescin concentrations. It was observed that aescin was cytotoxic at all concentrations, for all cell types studied, except whole blood lymphocytes, where it was not cytotoxic at 10-9 and 10-10 M concentrations. Genotoxicity of aescin was examined by sister chromatid exchange and micronucleus. The genotoxic effect of Aescin was observed to be more significant over isolated lymphocytes compared to other cell lines. On the otherhand, aescin at 10-8 M and lower concentrations were observed to be non-genotoxic over whole blood lymphocytes whereas this concentration was considerably toxic for isolated lymphocytes and for HL-60 cell lines. Apoptotic properties of aescin were determined by DNA fragmentation, cytochrome c release and negative NAPO staining. All the Aescin concentrations tested resulted in apoptosis over HL-60 cell lines, whereas necrosis was not observed. However, isolated lymphocytes showed both apoptosis and necrosis upon treatment with 10-6 M to 10-8 M aescin, exhibiting apoptosis only at 10-9 M and 10-10 M. Biochemical effects of aescin were investigated by following GST and NAT enzyme activities. An increase in GST enzyme activity was observed over all cell lines treated with increasing aescin concentrations for 72 hours. Whereas NAT activity was decreased upon treatment with aescin in similar manner.

No description available.

Made available in DSpace on 2016-12-12T20:27:37Z (GMT). No. of bitstreams: 1 Joao Cabral.pdf: 4385545 bytes, checksum: c09296f90add051ed37bd87320b15421 (MD5) Previous issue date: 2013-03-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This Master Thesis proposes a high gain non-isolated DC-DC converter applied on the processing of PV energy. The proposed converter is a boost converter with quadratic characteristic and with central point at its output. Basic operations and electric characteristics of a PV cell are described, including the procedures to determine its parameters. A model for numeric simulation is presented. A review of the high gain non-isolated DC-DC converters topologies is presented. Shows the converter´s transfer functions and the control strategy adopted as well as the design of control circuits. The control system is consisting of three loops, an internal loop of input current control, an external loop of total output voltage control and an additional loop of voltage unbalance control. The simulation and experimental results are shown to validate the analysis developed and demonstrate the performance of the control system adopted. / Esta Dissertação de Mestrado propõe um conversor CC-CC não isolado de elevado ganho para aplicação no processamento de energia solar fotovoltaica. O conversor proposto é um boost com característica quadrática e com ponto médio na sua saída. Descrevem-se o funcionamento básico e as características elétricas de uma célula fotovoltaica, incluindo-se o procedimento da determinação dos parâmetros e da modelagem dos módulos fotovoltaicos, apresentando-se um modelo para simulação numérica. Apresenta-se uma revisão de topologias de conversores CC-CC não isolados com elevado ganho estáticos. Apresentam-se as funções de transferência do conversor e a estratégia de controle adotada bem como o projeto dos circuitos de controle. O sistema de controle composto por três malhas de controle, uma malha interna de corrente de entrada, uma malha externa de tensão total e uma malha adicional de equalização de tensão. Resultados de simulação e experimentais são apresentados para validar as análises desenvolvidas e demonstrar o desempenho do sistema de controle adotado.

Ces travaux de thèse s’inscrivent dans le cadre d’une collaboration entre les laboratoires G2ELAB et IMEP-LAHC en lien avec le projet BQR WiSiTUDe (Grenoble-INP). Le but de cette thèse concerne la conception, modélisation et caractérisation du gate driver intégré pour transistors de puissance à base d’un transformateur sans noyau pour le transfert isolé d'ordres de commutation. La thèse est composée de deux grandes parties : - Une partie de la conception, la modélisation et la caractérisation du transformateur intégré dans deux technologies CMOS 0.35 µm bulk et CMOS 0.18 µm SOI. - Une partie de la conception, la simulation et la mise en œuvre de deux circuits de commande intégrée dans ces deux technologies. Ainsi, l’aspect du système du convertisseur de puissance sera étudié en proposant une nouvelle conception couplée commande/puissance à faible charge. Les résultats de ce travail de thèse ont permis de valider les approches proposées. Deux modèles fiables (électrique 2D et électromagnétique 3D) du transformateur ont été établis et validés via une réalisation CMOS 0.35 µm standard. De plus, un driver CMOS bulk, intégrant l’ensemble du transformateur sans noyau avec plusieurs fonctions de pilotage de la commande rapprochée a été caractérisé et validé. Finalement, un gate driver générique a été conçu en technologie CMOS SOI, intégrant dans une seule puce les étages de commande éloignée, l’isolation galvanique et la commande rapprochée pour transistors de puissance. Ce gate driver présente nombre d’avantages en termes d’interconnexion, de la consommation de la surface de silicium, de la consommation énergétique du driver et de CEM. Les perspectives du travail de thèse sont multiples, à savoir d’une part l’assemblage 3D entre le gate driver et le composant de puissance et d’autre part les convertisseurs de multi-transistors. / This thesis work focuses on the design, modelling and the implementation of integrated gate drivers for power transistors based on CMOS coreless transformer. The main objectives of thesis are the design, modeling and characterization of coreless transformer in two technologies CMOS 0.35 µm bulk and CMOS 0.18 µm SOI, as well as the design and the characterization of two integrated gate drivers in these two technologies. The results of thesis allow us to validate our proposal models for coreless transformer: 2D electrical model and 3D electromagnetic model. Moreover, one CMOS bulk isolated gate driver which monolithically integrates the coreless transformer, the secondary side control circuit for power transistors has been fabricated and validated for both high side and low side configuration in a Buck converter. Finally, a CMOS SOI isolated gate driver is designed; integrates in one single chip the external control, the coreless transformer and the close gate driver circuit for power transistors. This one-chip solution presents a numerous advantages in term of interconnect parasitic, energy consumption, silicon surface consumption, and EMI with a high level of galvanic isolation. The perspectives of this SOI gate driver are multiple, on the one hand, are the 3D assemblies between gate driver/power transistors and on the other hand, are the multiple-switch converter.