Contribution of tachykinin and kinin receptors in central autonomic control of blood pressure and behavioural activity in hypertensive rats

This work aims at studing the role of tachykinin NK-3 receptor (R) and kinin B1R in central autonomic regulation of blood pressure (BP) and to determine whether the B1R is overexpressed and functional in rat models of hypertension by measuring the effect of a B1R agonist on behavioural activity. Assumptions: (1) NK-3R located in the ventral tegmental area (VTA) modulates the mesolimbic dopaminergic system and has a tonic activity in hypertension; (2) B1R is overexpressed in the brain of hypertensive rats and has a tonic activity, which contributes to hypertension via a dopamine mechanism; (3) the inhibition of NK-3R and B1R with selective antagonists, reduces central dopaminergic hyperactivity and reverses hypertension. A model of genetic hypertension and a model of experimental hypertension were used: spontaneously hypertensive rats (SHR, 16 weeks) and Wistar-Kyoto (WKY) rats infused for 14 days with angiotensin II (Ang II) (200 ng / kg / min, subcutaneous (s.c.) with Alzet mini pump). The age-matched untreated WKY rats served as common controls. In the first study (article # 1), the cardiovascular response in SHR was evaluated following intracebroventricular (i.c.v.) and/or intra-VTA injection of an agonist (senktide) and antagonists (SB222200 and R-820) of NK-3R. These responses have also been characterized using selective dopamine antagonists DA-D1R (SCH23390), DA-D2R (raclopride) or non-selective dopamine DA-D2R (haloperidol). Also the VTA has been destroyed by ibotenic acid. The pressor response induced by senktide and the anti-hypertensive response induced by SB222200 or R-820 were more pronounced by intra-VTA. These responses were prevented by pre-treatment with raclopride and haloperidol. The lesion of the VTA has prevented the pressor response relayed by senktide (i.c.v.) and the anti-hypertensive effect of R-820 (i.c.v.). In addition, SB222200 (intra-VTA) prevented the pressor response of senktide (i.c.v.) and conversely, senktide (i.c.v.) prevented the antihypertensive effect of SB222200 (intra-VTA). The second study (article # 2) showed that the B1R antagonist (SSR240612) administered by gavage or i.c.v. reverses hypertension in both models. This anti-hypertensive effect was prevented by raclopride and haloperidol. In contrast, the two B1R antagonists (R-715 and R-954) injected s.c., which do not cross the blood-brain barrier reduced weakly blood pressure in hypertensive rats. In the third study (article # 3), the i.c.v. injection of a selective kinin B1R agonist Sar[DPhe8][des-Arg9]BK caused behavioural responses in SHR and Ang II-treated rats and had no effect in control WKY rats . The responses elicited by B1R agonist were blocked by an antagonist of NK-1 (RP67580), an antagonist of NMDA glutamate receptor (DL-AP5), an inhibitor of nitric oxide synthase (NOS) (L -NNA) as well as raclopride and SCH23390.The responses were modestly affected by the inhibitor of inducible NOS (iNOS). The B1R mRNA (measured by RT-PCR) was significantly increased in the hypothalamus, the VTA and the nucleus accumbens of hypertensive animals (SHR and treated with Ang II) compared with control rats. These neuropharmacological studies suggest that: (1) the NK-3R from the VTA is involved in the maintenance of hypertension in SHR by increasing DA transmission in the midbrain; (2) the B1R in SHR and Ang II-treated rats contributes to hypertension via a central mechanism involving DA-D2R; (3) the central B1R increases locomotor activity and nocifensive behaviours via the release of substance P (NK-1), DA and nitric oxide in both rat models of hypertension. Thus, the brain tachykinin NK-3R and kinin B1R represent potential therapeutic targets for the treatment of hypertension. The modulation of the mesolimbic/mesocortical dopaminergic pathway by these receptors suggests their involvement in other physiological functions (pleasure, motor activity, coordination of the response to stress) and pathophysiology (anxiety, depression).

Lewis’ Theory of Counterfactuals and Essentialism

La logique contemporaine a connu de nombreux développements au cours de la seconde moitié du siècle dernier. Le plus sensationnel est celui de la logique modale et de sa sémantique des mondes possibles (SMP) dû à Saul Kripke dans les années soixante. Ces dans ce cadre que David Lewis exposera sa sémantique des contrefactuels (SCF). Celle-ci constitue une véritable excroissance de l’architecture kripkéenne. Mais sur quoi finalement repose l’architecture kripkéenne elle-même ? Il semble bien que la réponse soit celle d’une ontologie raffinée ultimement basée sur la notion de mondes possible. Ce mémoire comporte quatre objectifs. Dans un premier temps, nous allons étudier ce qui distingue les contrefactuels des autres conditionnels et faire un survol historique de la littérature concernant les contrefactuels et leur application dans différent champs du savoir comme la philosophie des sciences et l’informatique. Dans un deuxième temps, nous ferons un exposé systématique de la théorie de Lewis telle qu’elle est exposée dans son ouvrage Counterfactuals. Finalement, nous allons explorer la fondation métaphysique des mondes possible de David Lewis dans son conception de Réalisme Modal.

Does Chance hide Necessity? : a reevaluation of the debate ‘determinism - indeterminism’ in the light of quantum mechanics and probability theory

Dans cette thèse l’ancienne question philosophique “tout événement a-t-il une cause ?” sera examinée à la lumière de la mécanique quantique et de la théorie des probabilités. Aussi bien en physique qu’en philosophie des sciences la position orthodoxe maintient que le monde physique est indéterministe. Au niveau fondamental de la réalité physique – au niveau quantique – les événements se passeraient sans causes, mais par chance, par hasard ‘irréductible’. Le théorème physique le plus précis qui mène à cette conclusion est le théorème de Bell. Ici les prémisses de ce théorème seront réexaminées. Il sera rappelé que d’autres solutions au théorème que l’indéterminisme sont envisageables, dont certaines sont connues mais négligées, comme le ‘superdéterminisme’. Mais il sera argué que d’autres solutions compatibles avec le déterminisme existent, notamment en étudiant des systèmes physiques modèles. Une des conclusions générales de cette thèse est que l’interprétation du théorème de Bell et de la mécanique quantique dépend crucialement des prémisses philosophiques desquelles on part. Par exemple, au sein de la vision d’un Spinoza, le monde quantique peut bien être compris comme étant déterministe. Mais il est argué qu’aussi un déterminisme nettement moins radical que celui de Spinoza n’est pas éliminé par les expériences physiques. Si cela est vrai, le débat ‘déterminisme – indéterminisme’ n’est pas décidé au laboratoire : il reste philosophique et ouvert – contrairement à ce que l’on pense souvent. Dans la deuxième partie de cette thèse un modèle pour l’interprétation de la probabilité sera proposé. Une étude conceptuelle de la notion de probabilité indique que l’hypothèse du déterminisme aide à mieux comprendre ce que c’est qu’un ‘système probabiliste’. Il semble que le déterminisme peut répondre à certaines questions pour lesquelles l’indéterminisme n’a pas de réponses. Pour cette raison nous conclurons que la conjecture de Laplace – à savoir que la théorie des probabilités présuppose une réalité déterministe sous-jacente – garde toute sa légitimité. Dans cette thèse aussi bien les méthodes de la philosophie que de la physique seront utilisées. Il apparaît que les deux domaines sont ici solidement reliés, et qu’ils offrent un vaste potentiel de fertilisation croisée – donc bidirectionnelle.

On the design of customized risk measures in insurance, the problem of capital allocation and the theory of fluctuations for Lévy processes

Dans cette thèse, nous étudions quelques problèmes fondamentaux en mathématiques financières et actuarielles, ainsi que leurs applications. Cette thèse est constituée de trois contributions portant principalement sur la théorie de la mesure de risques, le problème de l’allocation du capital et la théorie des fluctuations. Dans le chapitre 2, nous construisons de nouvelles mesures de risque cohérentes et étudions l’allocation de capital dans le cadre de la théorie des risques collectifs. Pour ce faire, nous introduisons la famille des "mesures de risque entropique cumulatifs" (Cumulative Entropic Risk Measures). Le chapitre 3 étudie le problème du portefeuille optimal pour le Entropic Value at Risk dans le cas où les rendements sont modélisés par un processus de diffusion à sauts (Jump-Diffusion). Dans le chapitre 4, nous généralisons la notion de "statistiques naturelles de risque" (natural risk statistics) au cadre multivarié. Cette extension non-triviale produit des mesures de risque multivariées construites à partir des données financiéres et de données d’assurance. Le chapitre 5 introduit les concepts de "drawdown" et de la "vitesse d’épuisement" (speed of depletion) dans la théorie de la ruine. Nous étudions ces concepts pour des modeles de risque décrits par une famille de processus de Lévy spectrallement négatifs.

Understanding the transcriptional control of EIF4E and its dysregulation in acute myeloid leukemia: role of NF-κB

EIF4E, le facteur d’initiation de la traduction chez les eucaryotes est un oncogène puissant et qui se trouve induit dans plusieurs types de cancers, parmi lesquels les sous-types M4 et M5 de la leucémie aiguë myéloblastique (LAM). EIF4E est régulé à plusieurs niveaux cependant, la régulation transcriptionnelle de ce gène est peu connue. Mes résultats montrent que EIF4E est une cible transcriptionnelle directe du facteur nucléaire « kappa-light- chain- enhancer of activated B cells » (NF-κB).Dans les cellules hématopoïétiques primaires et les lignées cellulaires, les niveaux de EIF4E sont induits par des inducteurs de NF-κB. En effet, l’inactivation pharmaceutique ou génétique de NF-κB réprime l’activation de EIF4E. En effet, suite à l’activation de NF-κB chez l’humain, le promoteur endogène de EIF4E recrute p65 (RelA) et c-Rel aux sites évolutionnaires conservés κB in vitro et in vivo en même temps que p300 ainsi que la forme phosphorylée de Pol II. De plus, p65 est sélectivement associé au promoteur de EIF4E dans les sous-types LAM M4/M5 mais non pas dans les autres sous-types LAM ou dans les cellules hématopoïétiques primaires normales. Ceci indique que ce processus représente un facteur essentiel qui détermine l’expression différentielle de EIF4E dans la LAM. Les analyses de données d’expressions par séquençage de l’ARN provenant du « Cancer Genome Atlas » (TCGA) suggèrent que les niveaux d’ARNm de EIF4E et RELA se trouvent augmentés dans les cas LAM à pronostic intermédiaire ou faible mais non pas dans les groupes cytogénétiquement favorables. De plus, des niveaux élevés d’ARNm de EIF4E et RELA sont significativement associés avec un taux de survie relativement bas chez les patients. En effet, les sites uniques κB se trouvant dans le promoteur de EIF4E recrutent le régulateur de transcription NF-κB p65 dans 47 nouvelles cibles prévues. Finalement, 6 nouveaux facteurs de transcription potentiellement impliqués dans la régulation du gène EIF4E ont été prédits par des analyses de données ChIP-Seq provenant de l’encyclopédie des éléments d’ADN (ENCODE). Collectivement, ces résultats fournissent de nouveaux aperçus sur le control transcriptionnel de EIF4E et offrent une nouvelle base moléculaire pour sa dérégulation dans au moins un sous-groupe de spécimens de LAM. L’étude et la compréhension de ce niveau de régulation dans le contexte de spécimens de patients s’avère important pour le développement de nouvelles stratégies thérapeutiques ciblant l’expression du gène EIF4E moyennant des inhibiteurs de NF-κB en combinaison avec la ribavirine.

Antibody Based Diagnostic for Detection Of Vibrios and their Biological Control using Antagonistic Bacteria in Macrobrachium Rosenbergii Larval Rearing Systems

The main objective of the work undertaken here was to develop an appropriate microbial technology to protect the larvae of M.rosenbergii in hatchery from vibriosis. This technology precisely is consisted of a rapid detection system of vibrios and effective antagonistic probiotics for the management of vibrios. The present work was undertaken with the realizations that to stabilize the production process of commercial hatcheries an appropriate, comprehensive and fool proof technology is required primarily for the rapid detection of Vibrio and subsequently for its management. Nine species of Vibrio have been found to be associated with larvae of M. rosenbergii in hatchery. Haemolytic assay of the Vibrio and Aeromonas on prawn blood agar showed that all isolates of V. alginolyticus and Aeromonas sp., from moribund, necrotized larve were haemolytic and the isolates of V.cholerae, V.splendidus II, V.proteolyticus and V.fluvialis from the larvae obtained from apparently healthy larval rearing systems were non-haemolytic. Hydrolytic enzymes such as lipase, chitinase and gelatinase were widespread amongst the Vibrio and Aeromonas isolates. Dominance of V.alginolyticus among the isolates from necrotic larvae and the failure in isolating them from rearing water strongly suggest that they infect larvae and multiply in the larval body and cause mortality in the hatchery. The observation suggested that the isolate V. alginolyticus was a pathogen to the larvae of M.rosenbergii. To sum up, through this work, nine species of Vibrio and genus Aeromonas associated with M.rosenbergii larval rearing systems could be isolated and segregated based on the haemolytic activity and the antibodies (PA bs) for use in diagnosis or epidemiological studies could be produced, based on a virulent culture of V.alginolyticus. This could possibly replace the conventional biochemical tests for identification. As prophylaxis to vibriosis, four isolates of Micrococcus spp. and an isolate of Pseudomonas sp. could be obtained which could possibly be used as antagonistic probiotics in the larval rearing system of M.rosenbergii.

Tailoring the microwave dielectric properties of BaRE2Ti4O12 and BaRE2Ti5O14 ceramics bycompositional variations

Ceramic dielectric resonators in the BaO-RE2O3-TiO2 (RE=rare earth) system have been prepared by the conventional solid state ceramic route. The dielectric properties have been tailored by substitution of different rare earth oxides and by bismuth oxide addition. The dielectric constants increased with Bi addition whereas the Q decreased. The temperature coeffecient of the resonant frequency improved with bismuth addition.

Tailoring the Microwave Dielectric Properties of BaRE2Ti4012 and BaRE2Ti5014 Ceramics by Compositional Variations

Ceramic dielectric resonators in the BaO-RE2O3-TiO2 (RE = rare earth) system have been prepared by the conventional solid state ceramic route. The dielectric properties have been tailored by substitution of different rare earth oxides and by bismuth oxide addition. The dielectric constants increased with Bi addition whereas the 0 decreased. The temperature coefficient of the resonant frequency improved with bismuth addition

Synchronization and control of chaos in coupled chaotic multimode Nd:YAG lasers

In this Letter we numerically investigate the dynamics of a system of two coupled chaotic multimode Nd:YAG lasers with two mode and three mode outputs. Unidirectional and bidirectional coupling schemes are adopted; intensity time series plots, phase space plots and synchronization plots are used for studying the dynamics. Quality of synchronization is measured using correlation index plots. It is found that for laser with two mode output bidirectional direct coupling scheme is found to be effective in achieving complete synchronization, control of chaos and amplification in output intensity. For laser with three mode output, bidirectional difference coupling scheme gives much better chaotic synchronization as compared to unidirectional difference coupling but at the cost of higher coupling strength. We also conclude that the coupling scheme and system properties play an important role in determining the type of synchronization exhibited by the system.

Freezing of 4He and its liquid-solid interface from density functional theory

We show that, at high densities, fully variational solutions of solidlike types can be obtained from a density functional formalism originally designed for liquid 4He . Motivated by this finding, we propose an extension of the method that accurately describes the solid phase and the freezing transition of liquid 4He at zero temperature. The density profile of the interface between liquid and the (0001) surface of the 4He crystal is also investigated, and its surface energy evaluated. The interfacial tension is found to be in semiquantitative agreement with experiments and with other microscopic calculations. This opens the possibility to use unbiased density functional (DF) methods to study highly nonhomogeneous systems, like 4He interacting with strongly attractive impurities and/or substrates, or the nucleation of the solid phase in the metastable liquid.

Semiclassical theory of shot noise in ballistic n+in+ semiconductor structures: relevance of Pauli and long range Coulomb interactions

We work out a semiclassical theory of shot noise in ballistic n+-i-n+ semiconductor structures aiming at studying two fundamental physical correlations coming from Pauli exclusion principle and long-range Coulomb interaction. The theory provides a unifying scheme which, in addition to the current-voltage characteristics, describes the suppression of shot noise due to Pauli and Coulomb correlations in the whole range of system parameters and applied bias. The whole scenario is summarized by a phase diagram in the plane of two dimensionless variables related to the sample length and contact chemical potential. Here different regions of physical interest can be identified where only Coulomb or only Pauli correlations are active, or where both are present with different relevance. The predictions of the theory are proven to be fully corroborated by Monte Carlo simulations.

Socio economic factors influencing the persistence and control of filariasis in Kerala-A case study of malayan filariasis in Cherthala

In general the behavioural sciences have contributed very little to filariasis research.Man's actions in creating vector breeding sites have been noted and discussed frequently inthe frlariasis literature. but virtually no systematic studies of these fonns of behavior have been undertaken (Dunn. 1979). Human behavioural observations and inquires into values and attitudes atfecting behavior that inhibits or promotes vector breeding are essential if any progress is to be made in developing self help programmes of vector control. Therefore, a systematic study on the socio-economic aspect of the community is warranted before undertaking any control programme against filariasis. In view of this the present study has been carried out which reveals the knowledge, attitude and practice concerning the causation, transmission, treatment and control of the disease. Socio economic factors that influence the creation and maintenance of vector breeding habitats were identified. characterization and ranking of these sociological factors will be helpful in identifying the determinants of human behavioural changes towards the containment of the disease- Information on the existing indigenous perception of the disease and the factors that hinder the control will be useful in developing a sound strategy from the human angle, which can be put to practical use.

Self-consistent theory of current and voltage noise in multimode ballistic conductors

Electron transport in a self-consistent potential along a ballistic two-terminal conductor has been investigated. We have derived general formulas which describe the nonlinear current-voltage characteristics, differential conductance, and low-frequency current and voltage noise assuming an arbitrary distribution function and correlation properties of injected electrons. The analytical results have been obtained for a wide range of biases: from equilibrium to high values beyond the linear-response regime. The particular case of a three-dimensional Fermi-Dirac injection has been analyzed. We show that the Coulomb correlations are manifested in the negative excess voltage noise, i.e., the voltage fluctuations under high-field transport conditions can be less than in equilibrium.