O controle neural da pressão arterial é essencial para a manutenção da homeostase do organismo. Este controle é realizado principalmente por núcleos bulbares e hipotalâmicos. Um dos principais sistemas de neurotransmissão envolvidos no controle da pressão arterial é o catecolaminérgico. Células noradrenérgicas e adrenérgicas estão presentes em todos os centros bulbares reguladores da pressão arterial, enquanto seus receptores, principalmente o receptor α2 adrenérgico (α2r), estão presentes nas mesmas regiões além de estarem presentes também nos núcleos hipotalâmicos. Estes receptores, quando ativados nestes núcleos, geram respostas cardiovasculares e atuam em conjunto com outros sistemas de neurotransmissão neste controle. Dentre estes sistemas de neurotransmissão, merecem destaque os sistemas angiotensinérgico e glutamatérgico, não apenas por estarem presentes nestes núcleos, mas também por atuarem no controle da pressão arterial. Contudo, pouco se sabe sobre como o sistema catecolaminérgico interage com estes sistemas. Desta forma, estudamos neste projeto a influência do sistema glutamatérgico e angiotensinérgico sobre o sistema catecolaminérgico no bulbo de ratos. Através de culturas de células bulbares, demonstramos que a ativação de receptores glutamatérgicos do tipo NMDA é capaz de elevar os níveis proteicos do α2R e que os receptores ionotrópicos do tipo não-NMDA precisam estar desbloqueados para tal. Em ratos adultos, microinjeções repetidas inibem a resposta bradicárdica induzida pela ativação dos α2rR no NTS. Contudo, o knockdown dos receptores AT1 de angiotensina restaura a resposta bradicárdica. A partir destes resultados, foi demonstrado que o sistema glutamatérgico é capaz de modular o sistema catecolaminérgico, enquanto o knockdown do receptor AT1 de angiotensina no NTS acentua a resposta bradicárdica dos α2R do NTS. Estes resultados sugerem que os sistemas de neurotransmissão bulbares interagem de diferentes formas e a compreensão deste controle pode vir a ser de grande valia para a compreensão de como se dá o controle da pressão arterial pelo sistema nervoso / The neural control of blood pressure is essential for the maintenance of the homeostasis of the organism. This control is performed mainly by nuclei in the medulla oblongata and in the hypothalamus. One of the main neurotransmitter system involved in this control is the catecholaminergic. Noradrenergic and adrenergic cells are present in all medullary nuclei involved in the arterial pressure regulation, while its receptors, especially the α2 adrenoceptor, are present in the same region plus hypothalamic nuclei. These receptors, upon activation in these nuclei, generate cardiovascular response, and act with other neurotransmission systems in this control. Among these systems, the glutamatergic and angiotensinergic deserve attention not only for also being present in the same nuclei, but for also acting in the control of the arterial pressure. Both angiotensinergic and glutamatergic systems interact with the catecholaminergic system throughout the nervous system. However, little is known about how the catecholaminergic system interacts with these systems in the modulation of blood pressure. Therefore, we studied in this project the influence of the glutamatergic and angiotensinergic systems over the catecholaminergic system in the medulla oblongata of rats. Through cell cultures of the medulla oblongata, we demonstrated that the activation of glutamatergic NMDA receptors is capable of elevating the proteic levels of α2-adrenoceptors, and that non-NMDA receptors need to be unblocked for such. In adult rats, repeated microinjections inhibit the bradycardic response elicited by the α2 adrenoceptors in the NTS. However, the angiotensin AT1 receptors knockdown restored the bradycardic response. Through the chronic knockout of angiotensinergic AT1 receptors in the NTS, we observed bradycardic response elicited by the activation of α2 adrenoceptors in the NTS of the knock-down rats. These results suggest that the medullary neurotransmission systems interact in different ways, and the comprehension of this control may be of great value for the comprehension of how the neural control of the blood pressure works

Les Glycosaminoglycannes (GAGs) sont une famille de polysaccharides principalement localisés au niveau de la matrice extracellulaire et de la membrane plasmique. Ils peuvent interagir avec des facteurs de croissance et des cytokines pour réguler leurs activités, participer à des transports protéiques à travers la membrane cellulaire, moduler les activités de certaines enzymes telles que les cathepsines (enzymes lysosomales). Toutes ces activités démontrent que les GAGs jouent des rôles primordiaux dans la régulation de la croissance, la différenciation, l'adhésion, l'inflammation et la mort cellulaire.L'implication de ces polysaccharides dans la régulation de l'apoptose via la voie mitochondriale n'a toujours pas été déterminée. Ici, nous démontrons dans un modèle cellulaire de fibroblastes de peau en culture primaire, soumis à un stress oxydatif par de l'H2O2, qu'un mimétique des GAGs, l'OTR4120, est capable de protéger la membrane du lysosome, de réduire le taux de ROS intracellulaires et d'inhiber la chute du potentiel de membrane mitochondrial et ainsi d'empêcher la libération du cytochrome c et l'activation des activités caspases-9 et -3 sans affecter la voie extrinsèque de l'apoptose. Les héparanes sulfates et les chondroïtines sulfates au contraire de l'héparine, ont montré un effet protecteur de l'apoptose en inhibant les protéines clefs de ce processus de mort cellulaire. Ainsi, les GAGs naturels et l'OTR4120 sont capables s'opposer à l'apoptose, en inhibant l'activité de la cathepsine D libérée dans le cytosol, empêchant ainsi l'activation de la voie intrinsèque de l'apoptose via la mitochondrie. Ces résultats ouvrent de nouveaux horizons notamment dans certaines maladies où le stress oxydatif est impliqué comme c'est le cas de certaines maladies neurodégénératives comme la maladie de Parkinson.La cause de la maladie de Parkinson (MP) qui affecte les neurones dopaminergiques demeure encore mystérieuse, bien que différentes preuves soutiennent les hypothèses impliquant des dysfonctionnements mitochondriaux et une accumulation d'α-synucléine comme étant les événements majeurs dans cette physiopathologie. Récemment, la cathepsine D a été impliquée dans des processus de mort cellulaire et montrée comme étant surexprimée dans des modèles de la MP. De plus, apparait être l'une des principales enzymes responsables de la dégradation de l'α-synucléine. Puisque les glycosaminoglycannes (GAGs) sont capables de réguler l'activité de la cathepsine D dans des cellules en culture dans une condition de stress, nous avons cherché à démontrer si GAGs pouvaient être localisés à un niveau intracellulaire, où ils pourraient interagir avec la cathepsine D et s'ils étaient capables de réguler l'accumulation/dégradation de l'α-synucléine. Ainsi nous avons mis en place un modèle cellulaire de la MP induit par le MPP+. Nous avons observé que l'expression génétique des enzymes de la biosynthèse des GAGs (HS2ST, HS6ST et CHST8) a été modifiée dans les cellules stressées par la neurotoxine et que leurs taux mesurés par leurs sulfates étaient augmentés plus précisément au niveau des HS. Au contraire, l'absence de GAGs sulfatés induit par le chlorate de sodium, un inhibiteur de la PAPs (donneur de sulfates), a permis d'augmenter l'activité de l'activité cathepsine D et également d'inhiber l'accumulation ou d'induire la dégradation de l'α-synucléine. Pour la première fois, il a été montré que les GAGs sont capables d'agir sur l'activité cathepsine D à l'intérieur de la cellule et de réguler l'accumulation/dégradation de l'α-synucléine. / Pas de résumé anglais

L'objet de cette thèse est le spectre de puissance à une dimension du flux transmis dans les forêts Lyman-alpha. Les forêts Lyman-alpha sont un motif d'absorption observé dans les spectres de quasars correspondant à l'absorption de la lumière du quasar par les nuages d'hydrogène le long de la ligne de visée. C'est un outil cosmologique puissant car il sonde des échelles relativement petites de l'ordre de quelques Mpc. Il est aussi sensible à de petits effets non-linéaires tel que celui produit par des neutrinos massifs.Premièrement, nous avons développé deux méthodes indépendantes pour mesurer le spectre de puissance. La première est fondée sur une transformée de Fourier et la seconde sur une fonction de vraisemblance. Les deux méthodes sont indépendantes et ont des incertitudes systématiques différentes. La détermination du niveau de bruit dans les données spectrales a fait l'objet d'un traitement particulier, du fait de son impact significatif sur le spectre de puissance calculé. Nous avons appliqué ces méthodes à 13821 spectres de quasars provenant de la 9e publication de données de l'expérience BOSS sélectionnés à partir d'un échantillon de plus de 60000 spectres sur des critères comme le rapport signal sur bruit et la résolution spectrale. Les deux spectres de puissance mesurés sont en bon accord sur les douze domaines de décalage vers le rouge (<z>=2.2 à <z>=4.4) et sur l'ensemble des échelles (0.001 (km/s)^−1 à 0.02 (km/s)^−1). Nous avons soigneusement déterminé les incertitudes systématiques d'origine instrumentale et méthodologique de notre mesure.Ensuite, nous présentons un ensemble de simulations cosmologiques N-corps incluant de la matière noire, du gaz baryonique et des neutrinos visant à modéliser les régions de basse densité sondées par les forêts Lyman-alpha. Les simulations sont conçues pour répondre aux exigences de précision des données BOSS et eBOSS. Elles comportent 768^3 ou 192^3 particules de chaque type et explorent des volumes allant de (25 Mpc/h)^3 pour les simulations haute résolution à (100 Mpc/h)^3 pour les simulations grand volume. En utilisant une technique de raboutage, nous atteignons une précision équivalente à une simulation comportant 3072^3 particules de chaque type dans un volume de (100 Mpc/h)^3. Nous montrons que cette technique est précise à 2% sur des échelles allant de quelques Mpc jusqu'à quelques dizaines de Mpc. Nous explorons l'effet sur le spectre de puissance de 4 paramètres cosmologiques (n_s, sigma_8, Omega_m ,H_0), 2 paramètres astrophysiques (T_0, gamma) décrivant la relation température/densité du milieu intergalactique et de la somme des masses des neutrinos. En faisant varier ces paramètres autour d'un modèle central choisi en accord avec les résultats de Planck, nous avons construit une grille de simulations, permettant non seulement l'étude de l'effet de chaque paramètre individuellement mais aussi l'effet de chaque paire de paramètres. Nous obtenons ainsi un développement au deuxième ordre complet, incluant les termes croisés, autour de notre modèle central. Nous avons vérifié la validité de ce développement avec des simulations indépendantes obtenues soit avec des paramètres différents soit une graine différente pour la génération des conditions initiales. Une comparaison entre le spectre de puissance mesuré à partir des données dans la première partie et celui obtenu à partir de nos simulations montre un excellent accord.Enfin, même s'il reste des biais potentiels et des erreurs systématiques à étudier dans nos simulations, nous avons réalisé des ajustements en combinant notre mesure du spectre de puissance à d'autres sondes cosmologiques comme les mesures du fond diffus cosmologique par le satellite Planck. Ces résultats préliminaires sont très encourageants car ils mènent à des contraintes sur les paramètres cosmologiques parmi les plus précises à ce jour, en particulier sur la sommes des masses des neutrinos avec une limite supérieure à 0.1 ev. / The framework of the studies presented in this thesis is the one-dimensional power spectrum of the transmitted flux in the Lyman-alpha forests. The Lyman-alpha forest is an an absorption pattern seen in the spectra of high redshift quasars corresponding to the absorption of the quasar light by the hydrogen clouds along the line of sight. It is a powerful cosmological tool as it probes relatively small scales, of the order of a few Mpc. It is also sensible to small non-linear effects such as the one induced by massive neutrinos.First, we have developed two independent methods to measure the one-dimensional power spectrum of the transmitted flux in the Lyman-alpha forest. The first method is based on a Fourier transform, and the second on a maximum likelihood estimator. The two methods are independent and have different systematic uncertainties. The determination of the noise level in the data spectra was subject to a novel treatment, because of its significant impact on the derived power spectrum. We applied the two methods to 13,821 quasar spectra from SDSS-III/BOSS DR9 selected from a larger sample of over 60,000 spectra on the basis of their high quality, large signal-to-noise ratio, and good spectral resolution. The power spectra measured using either approach are in good agreement over all twelve redshift bins from <z>=2.2 to <z>=4.4, and scales from 0.001 (km/s)^−1 to 0.02 (km/s)^−1. We carefully determined the methodological and instrumental systematic uncertainties of our measurements.Then, we present a suite of cosmological N-body simulations with cold dark matter, baryons and neutrinos aiming at modeling the low-density regions of the IGM as probed by the Lyman-alpha forests at high redshift. The simulations are designed to match the requirements imposed by the quality of BOSS and eBOSS data. They are made using either 768^3 or 192^3 particles of each type, spanning volumes ranging from (25 Mpc/h)^3 for high-resolution simulations to (100 Mpc/h)^3 for large-volume ones. Using a splicing technique, the resolution is further enhanced to reach the equivalent of simulations with 3072^3 = 29 billion particles of each type in a (100 Mpc/h)^3 box size, i.e. a mean mass per gas particle of 1.2x10^5 solar masses. We show that the resulting power spectrum is accurate at the 2% level over the full range from a few Mpc to several tens of Mpc. We explore the effect on the one-dimensional transmitted-flux power spectrum of 4 cosmological parameters (n_s, sigma_8, Omega_m ,H_0), 2 astrophysical parameters (T_0, gamma) related to the heating rate of the IGM and the sum of the neutrino masses. By varying the input parameters around a central model chosen to be in agreement with the latest Planck results, we built a grid of simulations that allows the study of the impact on the flux power spectrum of these seven relevant parameters. We improve upon previous studies by not only measuring the effect of each parameter individually, but also probing the impact of the simultaneous variation of each pair of parameters. We thus provide a full second-order expansion, including cross-terms, around our central model. We check the validity of the second-order expansion with independent simulations obtained either with different cosmological parameters or different seeds for the initial condition generation. Finally, a comparison to the one-dimensional Lyman-alpha forest power spectrum obtained in the first part with BOSS data shows an excellent agreement.Eventually, even if there are still some potential biases and systematic errors that need to be studied in our simulation, we performed cosmological fits combining our measurement of the one-dimensional power spectrum and other cosmological probes such as the CMB results provided by Planck. These preliminary results are very encouraging as they lead to some of the tighest cosmological constraints as of today, especially on the sum of the neutrino masses with an upper limit of 0.1 eV.

O estradiol (E2) é requerido para a luteólise de fêmeas bovinas e injeções de E2 estimulam a liberação de prostaglandina F2&alpha; (PGF2&alpha;). É possível que o E2 estimule a síntese e/ou a atividade de moléculas envolvidas na cascata geradora de PGF2&alpha;, como enzimas e receptores para outros ligantes. O cálcio é um conhecido cofator para a proteína quinase C e fosfolipase A2, enzimas envolvidas na produção PGF2&alpha;. O objetivo geral desse estudo foi investigar os mecanismos endócrinos e moleculares estimulados pelo E2 durante a luteólise. No experimento 1, vacas holandesas não lactantes foram tratadas com 3mg de E2 nos dias 13 (n=2), 15 (n=2), 17 (n=3) e 19 (n=5) do ciclo estral e a produção de PGFM (metabólito plasmático da PGF2&alpha;) mensurada por radioimunoensaio. Concluiu-se que a administração de E2 no 17&ordm; dia do ciclo estral constitui um modelo experimental adequado para determinar os mecanismos envolvidos na síntese de PGF2&alpha;. O experimento 2, foi realizado para investigar o papel do E2 na cascata produtora de PGF2&alpha;. Novilhas cruzadas de corte, cíclicas, não lactantes, foram pareadas no dia 17 de um ciclo estral sincronizado, injetadas com 0 (n=6) ou 3mg de E2 (n=7) e abatidas 2 horas após. Explantes endometriais foram tratados com os seguintes estimuladores da síntese de PGF2&alpha;: ionóforo de cálcio (CI), melitina ou ocitocina. Explantes foram incubados em quadruplicata e amostras de meio foram coletadas imediatamente e 60 minutos após o início da cultura. As concentrações de PGF2&alpha; foram mensuradas por radioimunoensaio. Explantes endometriais tratados in vitro com CI tiveram um incremento na síntese de PGF2&alpha; de 48,41% quando foram previamente tratados com o E2 (P&le;0,01). No experimento 3, células endometriais bovinas (células BEND) foram tratadas com 0, 10-7, 10-6 ou 10-5M CI por 12h em triplicata, em três experimentos independentes. As concentrações de 10-6 e 10-5M de CI estimularam a produção de PGF2&alpha; em comparação às outras concentrações (P&le;0,05). No experimento 4, células BEND receberam 0 ou 10-13M E2 e 0 ou 10-6M CI em um arranjo fatorial 2 x 2, durante 12h em triplicata, em três experimentos independentes. A produção de PGF2&alpha; foi de 33,1; 32,5; 92,4 e 145,6 (EPM: 21,8) pg/mL para células não tratadas, tratadas com E2, CI e E2 + CI, respectivamente. Houve uma tendência do tratamento com CI estimular a produção de PGF2&alpha; (P&le;0,08), entretanto, na presença de E2 o CI estimulou significativamente a síntese de PGF2&le; (P&le;0,01). Conclui-se que em fêmeas bovinas o E2 potencializou os efeitos do CI na síntese de PGF2&alpha; endometrial. Propõe-se que o E2 ativa a síntese de enzimas que, estimuladas pelo cálcio, atuam na síntese de PGF2&alpha; endometrial / Estradiol (E2) is required for luteolysis in bovine female and E2 injections stimulate prostaglandin F2&alpha; (PGF2&alpha;) release. It is possible that E2 stimulates synthesis and/or activity of molecules in the cascade of PGF2&alpha; production, such as enzymes and receptors to other ligands. Calcium is a known cofactor for protein kinase C and phospholipase A2, enzymes involved in PGF2&alpha; production. The main goal of this study was to investigate endocrine and molecular mechanisms stimulated by E2 during luteolysis. In experiment 1, non-lactating Holstein cows were treated with 3mg E2 on days 13 (n=2), 15 (n=2), 17 (n=3) or 19 (n=5) of the day estrous cycle and production PGFM (a PGF2&alpha; plasma metabolite) was evaluated by radioimmunassay. It was concluded that E2 administration on day 17 of the cycle was an adequate experimental model to determine mechanisms involved in endometrial PGF2&alpha; synthesis. Experiment 2 was designed in order to investigate the role of E2 in the enzymatic cascade of PGF2&alpha; production. Cyclic, cross-bred beef heifers were paired on day 17 of a synchronized estrous cycle, injected with 0 (n=6) or 3mg of E2 (n=7) and slaughtered after two hours. Endometrial explants were treated with stimulators of the cascade of PGF2&alpha; synthesis, i.e., calcium ionophore (CI), melittin or oxytocin. Explants were incubated in quadruplicate and medium samples were collected immediately and 60min after to begin culture. The concentrations PGF2&alpha; were measured by radioimmunoassay. Endometrial explants in vitro treatment with CI production the PGF2&alpha; was 48,41% higher in from cows treated with E2 (P&le;0,01). In experiment 3, bovine endometrium cells (BEND cells) were treated with 0, 10-7, 10-6 or 10-5M CI for 12h in triplicate, in three independent experiments. The 10-6 and 10-5M concentrations of CI stimulated production of PGF2&alpha; in comparison to other concentrations (P&le;0,05). In experiment 4, BEND cells received 0 or 10-13M E2 and 0 or 10-6M CI in a 2 x 2 factorial arrangement, for 12h in triplicate cultures in three independent experiments. Production of PGF2&alpha; was 33.1, 32.5, 92.4 and 145.6 (pooled SEM: 21.8) pg/mL for cells treated with nothing, E2, CI and E2 + CI, respectively. Treatment with CI alone tended to stimulate PGF2&alpha; production (P&le;0,08), however, in the presence of E2, CI significantly stimulated PGF2&alpha; synthesis (P&le;0,01). It was concluded that in bovine female the E2 improved the CI effects in endometrial PGF2&alpha; synthesis. It proposes that E2 active the enzyme synthesis that, calcium stimulated, actuate in endometrial PGF2&alpha; synthesis

The first three, pure, single-isomer, 6-O-sulfo a-cyclodextrins, the sodium salts of hexakis(6-O-sulfo)-a-CD (HxS), hexakis(2,3-di-O-methyl-6-O-sulfo)-a-cyclodextrin (HxDMS) and hexakis(2,3-di-O-acetyl-6-O-sulfo)-a-cyclodextrin (HxDAS) have been synthesized, analytically characterized and utilized as chiral resolving agents in capillary electrophoresis. The purity of each synthetic intermediate and of the final product was determined by HPLC-ELSD and indirect UV-detection capillary electrophoresis. The structural identity of each intermediate and final product was verified by 1D and 2D NMR, and mass spectrometry.HxS, HxDMS and HxDAS have been used to separate a series of neutral, basic, ampholytic and acidic enantiomers in pH 2.5 and pH 9.5 aqueous and acidic methanol background electrolytes using capillary electrophoresis. Rapid separations with satisfactory peak resolution values were obtained for most of the analytes, indicating that HxS, HxDAS and HxDMS can serve as chiral resolving agent for a wide range of analytes. The observed separation patterns follow the predictions of the CHArged Resolving agent Migration (CHARM) model. The separation patterns observed with HxS, HxDAS and HxDMS as chiral resolving agent were compared with those of (1) b-cyclodextrin analogues, such as, heptakis(6-O-sulfo)-b-cyclodextrin (HS), heptakis(2,3-di-O-acetyl-6-O-sulfo)-b-cyclodextrin (HDAS) and heptakis(2,3-di-O-methyl-6-O-sulfo)-b-cyclodextrin (HDMS); (2) g-cyclodextrin analogues, such as, octakis(6-O-sulfo)-g-cyclodextrin (OS), octakis(2,3-di-O-acetyl-6-Osulfo)- g-cyclodextrin (ODAS) and octakis(2,3-di-O-methyl-6-O-sulfo)-g-cyclodextrin (ODMS). The effects of the structure of the analytes, and those of the pH and the solvent of the background electrolyte were also studied.

Box-Simulationen von rotierender Magnetokonvektion im flüssigen Erdkern Numerische Simulationen der 3D-MHD Gleichungen sind mit Hilfe des Codes NIRVANA durchgeführt worden. Die Gleichungen für kompressible rotierende Magnetokonvektion wurden für erdähnliche Bedingungen numerisch in einer kartesischen Box gelöst. Charakteristische Eigenschaften mittlerer Größen, wie der Turbulenz-Intensität oder der turbulente Wärmefluss, die durch die kombinierte Wirkung kleinskaliger Fluktuationen entstehen, wurden bestimmt. Die Korrelationslänge der Turbulenz hängt signifikant von der Stärke und der Orientierung des Magnetfeldes ab, und das anisotrope Verhalten der Turbulenz aufgrund von Coriolis- und Lorentzkraft ist für schnellere Rotation wesentlich stärker ausgeprägt. Die Ausbildung eines isotropen Verhaltens auf kleinen Skalen unter dem Einfluss von Rotation alleine wird bereits durch ein schwaches Magnetfeld verhindert. Dies resultiert in einer turbulenten Strömung, die durch die vertikale Komponente dominiert wird. In Gegenwart eines horizontalen Magnetfeldes nimmt der vertikale turbulente Wärmefluss leicht mit zunehmender Feldstärke zu, so dass die Kühlung eines rotierenden Systems verbessert wird. Der horizontale Wärmetransport ist stets westwärts und in Richtung der Pole orientiert. Letzteres kann unter Umständen die Quelle für eine großskalige meridionale Strömung darstellen, während erstes in globalen Simulationen mit nicht axialsymmetrischen Randbedingungen für den Wärmefluss von Bedeutung ist. Die mittlere elektromotorische Kraft, die die Erzeugung von magnetischem Fluss durch die Turbulenz beschreibt, wurde unmittelbar aus den Lösungen für Geschwindigkeit und Magnetfeld berechnet. Hieraus konnten die entsprechenden α-Koeffizienten hergeleitet werden. Aufgrund der sehr schwachen Dichtestratifizierung ändert der α-Effekt sein Vorzeichen nahezu exakt in der Mitte der Box. Der α-Effekt ist positiv in der oberen Hälfte und negativ in der unteren Hälfte einer auf der Nordhalbkugel rotierenden Box. Für ein starkes Magnetfeld ergibt sich zudem eine deutliche abwärts orientierte Advektion von magnetischem Fluss. Ein Mean-Field Modell des Geodynamos wurde konstruiert, das auf dem α-Effekt basiert, wie er aus den Box-Simulationen berechnet wurde. Für eine äußerst beschränkte Klasse von radialen α-Profilen weist das lineare α^2-Modell Oszillationen auf einer Zeitskala auf, die durch die turbulente Diffusionszeit bestimmt wird. Die wesentlichen Eigenschaften der periodischen Lösungen werden präsentiert, und der Einfluss der Größe des inneren Kerns auf die Charakteristiken des kritischen Bereichs, innerhalb dessen oszillierende Lösungen auftreten, wurden untersucht. Reversals werden als eine halbe Oszillation interpretiert. Sie sind ein recht seltenes Ereignis, da sie lediglich dann stattfinden können, wenn das α-Profil ausreichend lange in dem periodische Lösungen erlaubenden Bereich liegt. Aufgrund starker Fluktuationen auf der konvektiven Zeitskala ist die Wahrscheinlichkeit eines solchen Reversals relativ klein. In einem einfachen nicht-linearen Mean-Field Modell mit realistischen Eingabeparametern, die auf den Box-Simulationen beruhen, konnte die Plausibilität des Reversal-Modells anhand von Langzeitsimulationen belegt werden. / Box-simulations of rotating magnetoconvection in the Earth's fluid core. Simulations of the 3D MHD-equations have been performed using the code NIRVANA. The equations for compressible rotating magnetoconvection are numerically solved in a Cartesian box assuming conditions roughly suitable for the geodynamo. The characteristics of averaged quantities like the turbulence intensity and the turbulent heat flux that are caused by the combined action of the small-scale fluctuations are computed. The correlation length of the turbulence significantly depends on the strength and orientation of the magnetic field and the anisotropic behavior of the turbulence intensity induced by Coriolis and Lorentz force is considerably more pronounced for faster rotation. The development of an isotropic behavior on the small scales -- as it is observed in pure rotating convection -- vanishes even for weak magnetic fields, which results in a turbulent flow that is dominated by the vertical component. In the presence of a horizontal magnetic field the vertical turbulent heat flux slightly increases with increasing field strength, so that cooling of the rotating system is facilitated. Horizontal transport of heat is always directed westwards and towards the poles. The latter might be a source of a large-scale meridional flow whereas the first would be important in global simulations in case of non-axisymmetric boundary conditions for the heat flux. The mean electromotive force describing the generation of mean magnetic flux by turbulence in the rotating fluid is directly calculated from the simulations and the corresponding α-coefficients are derived. Due to the very weak density stratification, the α-effect changes its sign in the middle of the box. It is positive at the top and negative at the bottom of the convective instable layer. For strong magnetic fields we also find a clear downward advection of the mean magnetic field. Finally the quenching behavior of the α-effect in dependence of the imposed magnetic field strength is presented. A geodynamo-model is constructed, which is based on an α-effect that has been computed from the box simulations. For a highly restricted class of radial α-profiles the linear α^2-model exhibits oscillating solutions on a timescale given by the turbulent diffusion time. The basic properties of the periodic solutions are presented and the influence of the inner core size on the characteristics of the critical range that allows for oscillating solutions is shown. Reversals are interpreted as half of such an oscillation. They are rather seldom events because they can only occur if the α-profile exists long enough within the small critical range that allows for periodic solutions. Due to strong fluctuations on the convective timescale the probability of such a reversal is very small. Finally, a simple non-linear mean-field model with reasonable input parameters based on the box-simulations demonstrates the plausibility of the presented theory with a long-time series of a (geo-)dynamo reversal sequence.

This thesis evaluated supplementation with two components of flaxseed during exercise training on inflammation in older adults.<P>Experiment 1: This experiment assessed secoisolariciresinol diglucoside (SDG) supplementation during aerobic exercise training on inflammation in older adults. Methods: One hundred subjects aged 50y or older were randomized to receive either SDG or placebo before completing a 6-month walking program. Fasting concentrations of interleukin-6 and tumor necrosis factor-á, glucose, triacylglycerol (TAG), high density lipoprotein (HDL), low density lipoprotein, and total cholesterol as well as leukocyte cell count were measured every two months while body composition, resting blood pressure, and a composite Z-score of six metabolic syndrome risk factors were assessed at baseline and 6 months. Results: Men on placebo increased metabolic syndrome composite Z-score (p<0.05). TAG increased (p=0.017) in men on placebo relative to men on SDG and men on SDG decreased (p=0.045) DBP relative to men on placebo. Conclusions: SDG had no effect on inflammation while it is effective in attenuating risk factors associated with metabolic syndrome in older males but not females.<p>Experiment 2: This experiment evaluated alpha-linolenic acid (ALA) supplementation during strength exercise training on inflammation in older adults. Methods: Fifty-one healthy older adults (65.4±0.8y) were randomized to receive ALA or a placebo before completing a 12 wk strength training program. Subjects were evaluated at baseline and 12 weeks for TNF-á and IL-6, muscle strength, body composition, and muscle thickness. Results: Males supplementing with ALA decreased IL-6 concentration (p=0.003). The female placebo and male ALA group had a significant increase in knee flexor thickness (p<0.05). Chest and leg press strength, lean tissue mass, and muscle thickness significantly increased, while percent fat and total body mass decreased with training (p<0.05), with no difference between ALA and placebo. Conclusions: ALA lowers IL-6 in older men, but has minimal effect on muscle mass and strength during resistance training.<p>General Conclusion: A composite score of metabolic syndrome is attenuated in males supplementing with SDG. ALA reduces IL-6 in older men. Older men, but not older women, derive specific health benefits from increased consumption of components of flaxseed consumed during an exercise program.

This thesis evaluated supplementation with two components of flaxseed during exercise training on inflammation in older adults.<P>Experiment 1: This experiment assessed secoisolariciresinol diglucoside (SDG) supplementation during aerobic exercise training on inflammation in older adults. Methods: One hundred subjects aged 50y or older were randomized to receive either SDG or placebo before completing a 6-month walking program. Fasting concentrations of interleukin-6 and tumor necrosis factor-á, glucose, triacylglycerol (TAG), high density lipoprotein (HDL), low density lipoprotein, and total cholesterol as well as leukocyte cell count were measured every two months while body composition, resting blood pressure, and a composite Z-score of six metabolic syndrome risk factors were assessed at baseline and 6 months. Results: Men on placebo increased metabolic syndrome composite Z-score (p<0.05). TAG increased (p=0.017) in men on placebo relative to men on SDG and men on SDG decreased (p=0.045) DBP relative to men on placebo. Conclusions: SDG had no effect on inflammation while it is effective in attenuating risk factors associated with metabolic syndrome in older males but not females.<p>Experiment 2: This experiment evaluated alpha-linolenic acid (ALA) supplementation during strength exercise training on inflammation in older adults. Methods: Fifty-one healthy older adults (65.4±0.8y) were randomized to receive ALA or a placebo before completing a 12 wk strength training program. Subjects were evaluated at baseline and 12 weeks for TNF-á and IL-6, muscle strength, body composition, and muscle thickness. Results: Males supplementing with ALA decreased IL-6 concentration (p=0.003). The female placebo and male ALA group had a significant increase in knee flexor thickness (p<0.05). Chest and leg press strength, lean tissue mass, and muscle thickness significantly increased, while percent fat and total body mass decreased with training (p<0.05), with no difference between ALA and placebo. Conclusions: ALA lowers IL-6 in older men, but has minimal effect on muscle mass and strength during resistance training.<p>General Conclusion: A composite score of metabolic syndrome is attenuated in males supplementing with SDG. ALA reduces IL-6 in older men. Older men, but not older women, derive specific health benefits from increased consumption of components of flaxseed consumed during an exercise program.

Morita Baylis-Hillman (MBH) reaction a carbon-carbon bond forming reaction between an α,β-unsaturated carbonyl and aldehydes or activated ketones in the presence of a nucleophilic catalyst. The MBH reaction is an atom-economical method of rapid increase of molecular complexity. The development of this process has received considerable attention in recent years. This dissertation presents the development of a new catalytic system for the symmetric and asymmetric MBH reaction. The new system for the racemic version of this reaction was accomplished employing a 1:1:1 ratio of catalytic amounts (10 mol%) of MgI2, TMEDA and DMAP and proved to be highly effective. For the asymmetric version was developed a highly enantio-selective system based on Fu’s planar chiral DMAP derivative (II) with ee´s up to 98%. Abnormal MBH adducts are obtained employing either ethyl 2,3-butadienoate or ethyl propiolate in good yields, in the presence if MgI2 and either a tertiary amine or phosphine as the nucleophile. The α,β-unsaturated carbonyls where prepared by a modified direct α- methylenation using paraformaldehyde, diisopropylammonium trifluoroacetate, and catalytic acid or base with excellent yields for several carbonyls compounds. The Negishi cross-coupling reaction is the Pd or Ni-catalyzed stereoselective cross-coupling or organozincs and aryl-, alkenyl-, or alkynyl halides. Enantioselective Negishi cross-coupling of aryl zincs and α-bromo ketones was accomplished employing a NCN Pincer complex as the catalyst with ee´s up 99%. The required pincer complexes have been prepared by the oxidative addition of pincer ligands with palladium or nickel. Additionally, It has been developed a direct and highly active, (NCN)-Pd catalytic system for the α-arylation of ketones with a variety of aryl bromides using the air and moisture stable [t-BuPheBox-Me2]PdBr (XVI) as the catalyst. The adducts are obtained in excellent yields (92% average for 20 examples) in only 1 hour using 1 mol% of catalyst loading. Perhaps more importantly, the work described here shows that XVI is highly reactive, highly selective, even on substrates bearing challenging functional groups such alkenes.

In this study, hydrolytic enzymes from sunn pest (Eurygaster integriceps) and cotton bollworm (Helicoverpa armigera) midguts were identified and characterized in terms of their optimum pH, Km and Vmax values. Hydrolytic activities were also tested for inhibition by several protease and alpha-amylase inhibitors which can be used for the development of insect resistant plants through transgenic technologies. For sunn pest midgut, a low proteolytic activity, belonging mostly to trypsin-like and leucine aminopeptidase-like proteases, and a very high alpha-amylase activity was found in sunn pest midgut, reflecting its high carbohydrate diet. Proteolytic activities could not be inhibited by natural protease inhibitors (SBTI and aprotinin) but inhibited significantly by a general serine protease inhibitor PMSF and metalloprotease inhibitors CdCl2 and CuCl2. alpha-Amylase activity of sunn pest midgut is resistant to inhibition by bean alpha-amylase inhibitor, but inhibited by chickpea, wheat and maize alpha-amylase inhibitors by 26 %, 37 % and 40 %, respectively. For cotton bollworm midgut, a very high proteolytic activity, belonging to serine and metalloprotease type, was detected. alpha-Amylase activity was lower compared to sunn pest midgut, but there were higher and diverse type of proteases, might be reflecting its wide range of host preference. Proteolytic activity was significantly inhibited by both natural protease inhibitors (SBTI and aprotinin). It was also inhibited by several synthetic protease inhibitors (PMSF, E-64, TPCK, CdCl2, CuCl2, Chymostatin). alpha-Amylase activity was inhibited by 60 % by wheat alpha-amylase inhibitor, while maize, chickpea and bean alpha-amylase inhibitors had no effect on cotton bollworm midgut alpha-amylase activity.