The Voyager 1 spacecraft is now about 25 AU beyond the heliospheric termination shock and soon it should encounter the outer boundary of the heliosphere, the heliopause. This is set to be at 120 AU in the modulation model used for this study. This implies that Voyager 1, and soon afterwards also Voyager 2, should be able to measure the heliopause spectrum, to be interpreted as the lowest possible local interstellar spectrum, for low energy galactic electrons (1 MeV to 120 MeV). This could give an answer to a long outstanding question about the spectral shape (energy dependence) of the galactic electron spectrum at these low energies. These in situ electron observations from Voyager 1, until the year 2010 when it was already beyond 112 AU, are used for a comparative study with a comprehensive three dimensional numerical model for the solar modulation of galactic electrons from the inner to the outer heliosphere. A locally developed steady state modulation model which numerically solves the relevant heliospheric transport equation is used to compute and study modulated electron spectra from Earth up to the heliopause. The issue of the spectral shape of the local interstellar spectrum at these low energies is specifically addressed, taking into account modulation in the inner heliosheath, up to the heliopause, including the effects of the transition of the solar wind speed from supersonic to subsonic in the heliosheath. Modulated electron spectra from the inner to the outer heliosphere are computed, together with radial and latitudinal profiles, focusing on 12 MeV electrons. This is compared to Voyager 1 observations for the energy range 6–14 MeV. A heliopause electron spectrum is computed and presented as a new plausible local interstellar spectrum from 30 GeV down to 10 MeV. The comparisons between model predictions and observations from Voyager 1 and at Earth (e.g. from the PAMELA mission and from balloon flights) and in the inner heliosphere (e.g. from the Ulysses mission) are made. This enables one to make conclusions about diffusion theory applicable to electrons in the heliosphere, in particular the rigidity dependence of diffusion perpendicular and parallel to the local background solar magnetic field. A general result is that the rigidity dependence of both parallel and perpendicular diffusion coefficients needs to be constant below P < 0.4 GV and only be allowed to increase above this rigidity to assure compatibility between the modeling and observations at Earth and especially in the outer heliosphere. A modification in the radial dependence of the diffusion coefficients in the inner heliosheath is required to compute realistic modulation in this region. With this study, estimates of the intensity of low energy galactic electrons at Earth can be made. A new local interstellar spectrum is computed for these low energies to improve understanding of the modulation galactic electrons as compared to previous results described in the literature. / Thesis (M.Sc. (Physics))--North-West University, Potchefstroom Campus, 2012.

The Voyager 1 spacecraft is now about 25 AU beyond the heliospheric termination shock and soon it should encounter the outer boundary of the heliosphere, the heliopause. This is set to be at 120 AU in the modulation model used for this study. This implies that Voyager 1, and soon afterwards also Voyager 2, should be able to measure the heliopause spectrum, to be interpreted as the lowest possible local interstellar spectrum, for low energy galactic electrons (1 MeV to 120 MeV). This could give an answer to a long outstanding question about the spectral shape (energy dependence) of the galactic electron spectrum at these low energies. These in situ electron observations from Voyager 1, until the year 2010 when it was already beyond 112 AU, are used for a comparative study with a comprehensive three dimensional numerical model for the solar modulation of galactic electrons from the inner to the outer heliosphere. A locally developed steady state modulation model which numerically solves the relevant heliospheric transport equation is used to compute and study modulated electron spectra from Earth up to the heliopause. The issue of the spectral shape of the local interstellar spectrum at these low energies is specifically addressed, taking into account modulation in the inner heliosheath, up to the heliopause, including the effects of the transition of the solar wind speed from supersonic to subsonic in the heliosheath. Modulated electron spectra from the inner to the outer heliosphere are computed, together with radial and latitudinal profiles, focusing on 12 MeV electrons. This is compared to Voyager 1 observations for the energy range 6–14 MeV. A heliopause electron spectrum is computed and presented as a new plausible local interstellar spectrum from 30 GeV down to 10 MeV. The comparisons between model predictions and observations from Voyager 1 and at Earth (e.g. from the PAMELA mission and from balloon flights) and in the inner heliosphere (e.g. from the Ulysses mission) are made. This enables one to make conclusions about diffusion theory applicable to electrons in the heliosphere, in particular the rigidity dependence of diffusion perpendicular and parallel to the local background solar magnetic field. A general result is that the rigidity dependence of both parallel and perpendicular diffusion coefficients needs to be constant below P < 0.4 GV and only be allowed to increase above this rigidity to assure compatibility between the modeling and observations at Earth and especially in the outer heliosphere. A modification in the radial dependence of the diffusion coefficients in the inner heliosheath is required to compute realistic modulation in this region. With this study, estimates of the intensity of low energy galactic electrons at Earth can be made. A new local interstellar spectrum is computed for these low energies to improve understanding of the modulation galactic electrons as compared to previous results described in the literature. / Thesis (M.Sc. (Physics))--North-West University, Potchefstroom Campus, 2012.

Doctor of Philosophy (PhD) / The Australian cotton industry has developed high yielding and high quality fibre production systems and attributes a significant contribution of this achievement to highly innovative breeding programs, specifically focused on the production of premium quality lint for the export market. Breeding programs have recently shifted attention to the development of new germplasm with superior stress tolerance to minimise yield losses attributed to adverse environmental conditions and inputs such as irrigation, fertilisers and pesticides. Various contributors to yield, such as physiology, biochemistry and gene expression have been implemented as screening tools for tolerance to high temperatures under growth cabinet and laboratory conditions but there has been little extension of these mechanisms to field based systems. This study evaluates tools for the identification of specific genotypic thermotolerance under field conditions using a multi-level ‘top down’ approach from crop to gene level. Field experiments were conducted in seasons 1 (2006) and 3 (2007) at Narrabri (Australia) and season 2 (2006) in Texas (The United States of America) and were supplemented by growth cabinet experiments to quantify cultivar differences in yield, physiology, biochemical function and gene expression under high temperatures. Whole plants were subjected to high temperatures in the field through the construction of Solarweave® tents and in the growth cabinet at a temperature of 42 oC. The effectiveness of these methods was then evaluated to establish a rapid and reliable screening tool for genotype specific thermotolerance that could potentially improve the efficiency of breeding programs and aid the development to high yielding cultivars for hot growing regions. Cotton cultivars Sicot 53 and Sicala 45 were evaluated for thermotolerance using crop level measurements (yield and fibre quality) and whole plant measurements (fruit retention) to determine the efficacy of these measurements as screening tools for thermotolerance under field conditions. Sicot 53 was selected as a relatively thermotolerant cultivar whereas Sicala 45 was selected as a cultivar with a lower relative thermotolerance and this assumption was made on the basis of yield in hot and cool environments under the CSIRO Australian cotton breeding program. Yield and fruit retention were lower under tents compared with ambient conditions in all 3 seasons. Yield and fruit retention were highly correlated in season 1 and were higher for Sicot 53 compared to Sicala 45 suggesting that fruit retention is a primary limitation to yield in a hot season. Thus yield and fruit retention are good indicators of thermotolerance in a hot season. Temperature treatment and cultivar differences were determined for fibre quality in seasons 1 and 3; however, quality exceeded the industry minimum thereby indicating that fibre quality is not a good determinant of thermotolerance. Physiological determinants of plant functionality such as photosynthesis, electron transport rate, stomatal conductance and transpiration rate were determined for cultivars Sicot 53 and Sicala 45 under the tents and an index of these parameters was also analysed to determine overall plant physiological capacity in the field. Physiological capacity was also determined under high temperatures in the growth cabinet using a light response curve at various levels of photosynthetically active radiation (PAR). Photosynthesis and electron transport rate decreased, whilst stomatal conductance and transpiration rate increased under the tents as well as under high temperatures in the growth cabinet. Photosynthesis and electron transport rate were higher for Sicot 53 but stomatal conductance and transpiration rate were higher for Sicala 45 under the tents. No cultivar differentiation was evident for plants grown under high temperatures in the growth cabinet. Temperature treatment and cultivar differences in physiological function were greater in a hot year (season 1), thereby indicating the importance of cultivar selection for thermotolerance in the presence of stress. Electron transport rate was correlated with yield in season 1, thus suggesting the suitability of this method for broad genotypic screening for thermotolerance under field conditions. Biochemical processes such as membrane integrity and enzyme viability were used to determine cultivar specific thermotolerance under high temperature stress in the laboratory, field and growth cabinet. Electrolyte leakage is an indicator of decreased membrane integrity and may be estimated by the relative electrical conductivity or relative cellular injury assays. The heat sensitivity of dehydrogenase activity, a proxy for cytochrome functionality and capacity for mitochondrial electron transport, may be quantified spectrophotometrically. Cellular membrane integrity and enzyme viability decreased sigmoidally with exposure to increasing temperatures in a water bath. Membrane integrity was higher for Sicot 53 compared with Sicala 45 under the tents and under high temperatures in the growth cabinet. No temperature treatment or cultivar differences were found for enzyme viability under the tents; however, enzyme viability for Sicala 45 was higher in the growth cabinet compared with Sicot 53. Relative electrical conductivity was strongly correlated with yield under ambient field conditions and under the tents, suggesting impairment of electron flow through photosynthetic and/or respiratory pathways, thus contributing to lower potential for ATP production and energy generation for yield contribution. Thus, the membrane integrity assay was considered to be a rapid and reliable tool for thermotolerance screening in cotton cultivars. Gene expression was examined for cultivars Sicot 53 and Sicala 45 grown under high (42 oC) temperatures in the growth cabinet. Rubisco activase expression was quantified using quantitative real-time polymerase chain reaction analysis and was decreased under high temperatures and was lower for Sicala 45 than Sicot 53. Maximum cultivar differentiation was found after 1.0 h exposure to high temperatures and hence, leaf tissue sampled from this time point was further analysed for global gene profiling using cDNA microarrays. Genes involved in metabolism, heat shock protein generation, electron flow and ATP generation were down-regulated under high temperatures in the growth cabinet and a greater number of genes were differentially expressed for Sicala 45, thereby indicating a higher level of heat stress and a greater requirement for mobilisation of protective and compensatory mechanisms compared with Sicot 53. Cultivar specific thermotolerance determination using gene profiling may be a useful tool for understanding the underlying basis of physiological and biochemical responses to high temperature stress in the growth cabinet. There is future opportunity for profiling genes associated with heat stress and heat tolerance for identification of key genes associated with superior cultivar performance under high temperature stress and characterisation of these genes under field conditions. This research has identified cultivar differences in yield under field conditions and has identified multiple physiological and biochemical pathways that may contribute to these differences. Future characterisation of genes associated with heat stress and heat tolerance under growth cabinet conditions may be extended to field conditions, thus providing the underlying basis of the response of cotton to high temperature stress. Electron transport rate and relative electrical conductivity were found to be rapid and reliable determinants of cultivar specific thermotolerance and hence may be extended to broad-spectrum screening of a range of cotton cultivars and species and under a range of abiotic stress. This will enable the identification of superior cotton cultivars for incorporation into local breeding programs for Australian and American cotton production systems.

Doctor of Philosophy (PhD) / The Australian cotton industry has developed high yielding and high quality fibre production systems and attributes a significant contribution of this achievement to highly innovative breeding programs, specifically focused on the production of premium quality lint for the export market. Breeding programs have recently shifted attention to the development of new germplasm with superior stress tolerance to minimise yield losses attributed to adverse environmental conditions and inputs such as irrigation, fertilisers and pesticides. Various contributors to yield, such as physiology, biochemistry and gene expression have been implemented as screening tools for tolerance to high temperatures under growth cabinet and laboratory conditions but there has been little extension of these mechanisms to field based systems. This study evaluates tools for the identification of specific genotypic thermotolerance under field conditions using a multi-level ‘top down’ approach from crop to gene level. Field experiments were conducted in seasons 1 (2006) and 3 (2007) at Narrabri (Australia) and season 2 (2006) in Texas (The United States of America) and were supplemented by growth cabinet experiments to quantify cultivar differences in yield, physiology, biochemical function and gene expression under high temperatures. Whole plants were subjected to high temperatures in the field through the construction of Solarweave® tents and in the growth cabinet at a temperature of 42 oC. The effectiveness of these methods was then evaluated to establish a rapid and reliable screening tool for genotype specific thermotolerance that could potentially improve the efficiency of breeding programs and aid the development to high yielding cultivars for hot growing regions. Cotton cultivars Sicot 53 and Sicala 45 were evaluated for thermotolerance using crop level measurements (yield and fibre quality) and whole plant measurements (fruit retention) to determine the efficacy of these measurements as screening tools for thermotolerance under field conditions. Sicot 53 was selected as a relatively thermotolerant cultivar whereas Sicala 45 was selected as a cultivar with a lower relative thermotolerance and this assumption was made on the basis of yield in hot and cool environments under the CSIRO Australian cotton breeding program. Yield and fruit retention were lower under tents compared with ambient conditions in all 3 seasons. Yield and fruit retention were highly correlated in season 1 and were higher for Sicot 53 compared to Sicala 45 suggesting that fruit retention is a primary limitation to yield in a hot season. Thus yield and fruit retention are good indicators of thermotolerance in a hot season. Temperature treatment and cultivar differences were determined for fibre quality in seasons 1 and 3; however, quality exceeded the industry minimum thereby indicating that fibre quality is not a good determinant of thermotolerance. Physiological determinants of plant functionality such as photosynthesis, electron transport rate, stomatal conductance and transpiration rate were determined for cultivars Sicot 53 and Sicala 45 under the tents and an index of these parameters was also analysed to determine overall plant physiological capacity in the field. Physiological capacity was also determined under high temperatures in the growth cabinet using a light response curve at various levels of photosynthetically active radiation (PAR). Photosynthesis and electron transport rate decreased, whilst stomatal conductance and transpiration rate increased under the tents as well as under high temperatures in the growth cabinet. Photosynthesis and electron transport rate were higher for Sicot 53 but stomatal conductance and transpiration rate were higher for Sicala 45 under the tents. No cultivar differentiation was evident for plants grown under high temperatures in the growth cabinet. Temperature treatment and cultivar differences in physiological function were greater in a hot year (season 1), thereby indicating the importance of cultivar selection for thermotolerance in the presence of stress. Electron transport rate was correlated with yield in season 1, thus suggesting the suitability of this method for broad genotypic screening for thermotolerance under field conditions. Biochemical processes such as membrane integrity and enzyme viability were used to determine cultivar specific thermotolerance under high temperature stress in the laboratory, field and growth cabinet. Electrolyte leakage is an indicator of decreased membrane integrity and may be estimated by the relative electrical conductivity or relative cellular injury assays. The heat sensitivity of dehydrogenase activity, a proxy for cytochrome functionality and capacity for mitochondrial electron transport, may be quantified spectrophotometrically. Cellular membrane integrity and enzyme viability decreased sigmoidally with exposure to increasing temperatures in a water bath. Membrane integrity was higher for Sicot 53 compared with Sicala 45 under the tents and under high temperatures in the growth cabinet. No temperature treatment or cultivar differences were found for enzyme viability under the tents; however, enzyme viability for Sicala 45 was higher in the growth cabinet compared with Sicot 53. Relative electrical conductivity was strongly correlated with yield under ambient field conditions and under the tents, suggesting impairment of electron flow through photosynthetic and/or respiratory pathways, thus contributing to lower potential for ATP production and energy generation for yield contribution. Thus, the membrane integrity assay was considered to be a rapid and reliable tool for thermotolerance screening in cotton cultivars. Gene expression was examined for cultivars Sicot 53 and Sicala 45 grown under high (42 oC) temperatures in the growth cabinet. Rubisco activase expression was quantified using quantitative real-time polymerase chain reaction analysis and was decreased under high temperatures and was lower for Sicala 45 than Sicot 53. Maximum cultivar differentiation was found after 1.0 h exposure to high temperatures and hence, leaf tissue sampled from this time point was further analysed for global gene profiling using cDNA microarrays. Genes involved in metabolism, heat shock protein generation, electron flow and ATP generation were down-regulated under high temperatures in the growth cabinet and a greater number of genes were differentially expressed for Sicala 45, thereby indicating a higher level of heat stress and a greater requirement for mobilisation of protective and compensatory mechanisms compared with Sicot 53. Cultivar specific thermotolerance determination using gene profiling may be a useful tool for understanding the underlying basis of physiological and biochemical responses to high temperature stress in the growth cabinet. There is future opportunity for profiling genes associated with heat stress and heat tolerance for identification of key genes associated with superior cultivar performance under high temperature stress and characterisation of these genes under field conditions. This research has identified cultivar differences in yield under field conditions and has identified multiple physiological and biochemical pathways that may contribute to these differences. Future characterisation of genes associated with heat stress and heat tolerance under growth cabinet conditions may be extended to field conditions, thus providing the underlying basis of the response of cotton to high temperature stress. Electron transport rate and relative electrical conductivity were found to be rapid and reliable determinants of cultivar specific thermotolerance and hence may be extended to broad-spectrum screening of a range of cotton cultivars and species and under a range of abiotic stress. This will enable the identification of superior cotton cultivars for incorporation into local breeding programs for Australian and American cotton production systems.

La problématique de génération de champs magnétiques quasi-statiques intenses constitue un défi pour la physique de l’interaction laser-plasma. Proposé il y a 30 ans, l’utilisation de cibles "boucles" irradiées par laser se distinguent par leur design compact ne nécessitant aucune génération de courant pulsé en plus de la puissance laser et ont dévoilé récemment leur grand potentiel.Ce travail de thèse s’attache à la caractérisation des phénomènes physiques et au développement de cette technique. On a ainsi montré la génération de forts champs magnétiques quasi-statiques par interaction laser-matière (500 J, durée laser de 1 ns et intensité ~10^17 W/cm^2) atteignant une amplitude de plusieurs centaines de Teslas pendant 2 à 3 ns. L'évolution temporelle et la distribution spatiale des champs magnétiques ont été mesurés par trois diagnostics indépendants : sondes B-dot, rotation de Faraday et défléctométrie de protons. La caractérisation des mécanismes physiques sous-jacents ont aussi fait appel à des diagnostics de rayonnements X de la région irradiée par laser ainsi qu’à des mesures d’ombroscopie optique du fil de la boucle en expansion.Une application de ces champs au guidage magnétique d’électrons relativistes dans la matière dense a permis d'ouvrir de nouvelles perspectives au transport de hautes densités d’énergies dans la matière. En effet, en laissant suffisamment de temps pour que le champ magnétique pénètre dans la cible dense, une amélioration d’un facteur 5 de la densité d’énergie portée par les électrons après 50 µm de propagation a été mise en évidence.En outre, des décharges de courants intenses consécutives à l'irradiation par impulsion laser courtes (50 J, durée laser < 1 ps et intensité ~10^19 W/cm^2) ont été observées. Une imagerie protonique de la décharge a permis de mesurer la propagation d’une onde électromagnétique à des vitesses proches de la vitesse de la lumière. Cette onde d’une durée de ~ 40 ps a été utilisée comme lentille électromagnétique pour focaliser et sélectionner sur une bande étroite d'énergie un faisceau de protons de plusieurs MeV (jusqu’à 12 MeV) passant dans la boucle.Les résultats de ces différentes mesures et applications expérimentales ont été par ailleurs confrontées à des simulations et à des modèles analytiques.Les applications de cette thèse se déploient sur des aspects comme :- la fusion par confinement inertiel, en guidant des faisceaux d'électrons relativistes jusqu'au cœur de la capsule de combustible, tout en confinant les particules qui y déposent leur énergie ainsi que celles créées par les réactions de fusion nucléaire;- l'astrophysique et la planétologie de laboratoire, en générant des sources secondaires de particules énergétiques ou de rayonnement afin de porter la matière dense a de très hautes températures (matière tiède et dense), ou en magnétisant des plasmas pour reproduire des phénomènes astrophysiques à plus petite échelle au laboratoire;- et enfin le contrôle de faisceaux de particules chargées dans le vide pour le développement de sources laser dans le cadre d'applications s'effectuant à distance de la source notamment en science, dans l'industrie, ou même en médecine. / The problem of strong quasi-static magnetic field generation is a challenge in laser-plasma interaction physics. Proposed 30 years ago, the use of the laser-driven capacitor-coil scheme, which stands out for its compact design while not needing any additional pulsed power source besides the laser power, only recently demonstrated its potential.This thesis work aims at characterizing the underlying physics and at developing this scheme. We demonstrated the generation of strong quasi-static magnetic fields by laser (500 J, 1 ns-duration and ~10^17 W/cm^2 intensity) of several hundreds of Teslas and duration of 2-3 ns. The B-field space- and time-evolutions were characterized using three independent diagnostics: B-dot probes, Faraday rotation and proton-deflectometry). The characterization of the underlying physical processes involved also X-ray diagnostics of the laser-irradiated zone and optical shadowgraphy of the coil rod expansion.A novel application of externally applied magnetic fields to guide relativistic electron beam in dense matter has been carried out and the obtained results set the ground for improved high-energy-density transport in matter. Indeed, allowing sufficient time for the dense target magnetization, a factor 5 improvement of the electron energy-density flux at 50µm-depth was evidenced.Besides, the generation of high discharge currents consecutive to short laser pulse irradiation (50 J, <1 ps-duration and ~10^19 W/cm^2 intensity) was also pointed out. Proton imaging of the discharge permitted to measure the propagation of an electromagnetic wave at a velocity close to the speed of light. This wave, of ~40ps-duration, was used as an electromagnetic lens to focalize and energy-select a narrow energy range within a multi-MeV proton beam (up to 12 MeV) passing through the coil.All-above experimental measurements and application results were thoroughly compared to both computer simulations and analytic modeling.The applications of this thesis work in a near future will concern:- inertial confinement fusion, by guiding relativistic electron beams up to the dense core nuclear fuel, and by confining particles depositing their energy in it, or even those resulting from the fusion reactions;- laboratory planetology and astrophysics, by generating secondary sources of energetic particles and radiation to reach the warm-dense-matter state or by magnetizing plasmas to reproduce astrophysical phenomena in scaled experiments;- and finally, the control of charged particle beams in vacuum, useful in particular for the development of laser-driven sources for distant applications in science, industry or even medecine.

Introdução: Diversas evidências apontam para um papel da disfunção mitocondrial no Transtorno de Humor Bipolar (THB), mas pouco se sabe sobre isso no THB de início recente. Na mitocôndria a atividade da cadeia transportadora de elétrons (CTE) atua juntamente com o ciclo do ácido cítrico na produção de energia, mas não está claro se estão alteradas no THB. O DNA mitocondrial (DNAmt) codifica diversas proteínas da CTE e está associado ao estresse oxidativo, mas nunca foi avaliado em pacientes no THB in vivo. O estresse oxidativo está associado ao THB e à disfunção mitocondrial, mas não se sabe muito das atividades das enzimas antioxidantes no THB de início recente. O óxido nítrico (NO) é uma molécula com efeitos neuromoduladores, mas com um papel no THB ainda não elucidado. O lítio é um tratamento padrão-ouro no THB, tendo mostrado efeitos neuroprotetores. Apesar disso, pouco se conhece do efeito do lítio na CTE, nas enzimas do ciclo do ácido cítrico, no conteúdo de DNAmt e na regulação de NO em humanos. Também não está claro o papel antioxidante do lítio no THB. Metódos: Pacientes com THB em depressão (n=31), não medicados em sua maioria (84%), foram tratados por 6 semanas com lítio. Antes e depois do tratamento, verificaram-se em leucócitos as atividades dos complexos I-IV da CTE, atividades das enzimas citrato sintase, succinato desidrogenase e malato desidrogenase e também o conteúdo de DNAmt; em plasma foram analisados os níveis de NO, substâncias reativas ao ácido tiobarbitúrico (TBARS) e as atividades de catalase (CAT), glutationa peroxidase (GPx), superóxido dismutase (SOD) e razão de SOD/CAT. Os pacientes com depressão bipolar foram comparados com 28 controles saudáveis. Resultados: Em comparação com controles, os pacientes com THB tiveram um aumento de GPx (p < 0,001) e CAT (p=0,005) e uma diminuição de SOD/CAT (p=0,001), sem outras diferenças nos demais biomarcadores. Pacientes com THB I mostraram uma diminuição de citrato sintase (p=0,02) e uma discreta diminuição do conteúdo de DNAmt (p=0,05) em comparação com o THB II; o conteúdo de DNAmt esteve ligeiramente diminuído no THB I comparado com controles (p=0,05). Do início ao fim do tratamento com lítio houve aumento da atividade do complexo I da CTE (p=0,02), diminuição de TBARS (p=0,02) e SOD (p=0,03) e aumento de NO (p=0,02), sem haver alteração de outros parâmetros. Depois do tratamento, o TBARS se mostrou diminuído em respondedores comparados a não respondedores (p=0,02) e diminuído no THB II em comparação com o THB I (p=0,04). Discussão: No THB de início recente, houve poucas alterações em biomarcadores. Os achados sugerem aumento de CAT e GPx na depressão bipolar de início recente e uma diminuição de conteúdo mitocondrial no THB I comparado com o THB II, que devem ser confirmadas por outros estudos. Os resultados reforçam um papel neuroprotetor do lítio, sugerindo que a droga aumente a atividade do complexo I da CTE mitocondrial e aumente os níveis de NO na depressão bipolar. Além disso, o lítio reforçou o seu papel antioxidante e modulador das enzimas antioxidantes no THB / Background: Several evidences point to a role for mitochondrial dysfunction in Bipolar Disorder (BD), but few is known about it on short-term BD. In mitochondria the electron transport chain (ETC) acts jointly with citric acid cycle to produce energy, but it is not clear if they are altered in BD. Mitochondrial DNA (mtDNA) encodes several ETC proteins and is associated with oxidative stress, but it was never evaluated in BD in vivo. Oxidative stress is associated with BD and with mitochondrial dysfunction, but few is known about the activities of antioxidant enzymes in short-term BD. Nitric oxide (NO) is a molecule with neuromodulatory effects, but with an unclear role in BD. Lithium is a gold-standard treatment for BD, which has shown neuroprotective effects. However, few is known about lithium effect on ETC, citric acid cycle, mtDNA content, and NO regulation in humans. Also, lithium\'s antioxidant role in BD is unclear. Methods: Patients with BD depression (n=31) unmedicated in majority (84%) received lithium treatment for 6 weeks. Before and after treatment, in leukocytes the activities of ETC complex I-IV, citrate synthase, succinate dehydrogenase, and malate dehydrogenase, and mtDNA content were evaluated; in plasma, NO levels, thiobarbituric acid reactive substances (TBARS), the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and SOD/CAT ratio were evaluated. Bipolar depression patients were compared with 28 healthy controls. Results: When compared with controls, BD patients showed an increase in GPx (p < 0.001) and CAT (p=0.005) and a decrease in SOD/CAT (p=0.001), but showed no difference for other biomarkers. Patients with BD I showed a decrease in citrate synthase (p=0.02) and a slight decrease in mtDNA content (p=0.05) when compared to BD II; mtDNA content was slightly decreased in BD I compared to controls (p=0.05). From baseline to endpoint, there was an increase in ETC complex I activity (p=0.02), a decrease in TBARS (p=0.02) and SOD (p=0.03) and an increase in NO (p=0.02), without change in other parameters. After treatment, TBARS was decreased in responders compared to non-responders (p=0.02) and decreased in BD II compared to BD I (p=0.04). Discussion: In short-term BD few alterations were observed on biomarkers. The findings suggest increase on CAT and GPX in short-term bipolar depression and mitochondrial content decrease in BD I when compared to BD II, which deserve other studies for confirmation. The results reinforce a lithium\'s neuroprotective role and suggest that lithium increases ETC complex I activity and NO levels in bipolar depression. Moreover, lithium reinforced its role as antioxidant and as a modulator of antioxidant enzymes in BD

Une compréhension sans cesse plus pointue des processus élémentaires de transferts de charges et d’énergie, qui sont à la base même de nombreux processus biologiques, permet non seulement l’élaboration mais aussi l’amélioration de la mise au point de molécules photoactives utiles dans différentes applications. C'est le cas (i) de systèmes moléculaires et supramoléculaires destinés à mimer efficacement la photosynthèse, ou encore (ii) de molécules photoactives capables d’interagir avec des macromolécules biologiques et d’induire une transformation de ces biomolécules. C’est dans ce cadre général que s’inscrit l’élaboration de nouveaux complexes polyazaaromatiques de Ru(II) capables d’interagir avec la double hélice d’ADN et de photoréagir avec sa base la plus réductrice, la guanine, par transfert d’électron photoinduit. C’est sur la base de ces processus que des nouveaux agents antitumoraux photoactivables ont pu être développés. L’utilisation de complexes de Ru(II) dans le design d’entités supramoléculaires polymétalliques destinées à jouer le rôle de collecteurs de lumière et permettant ainsi de mimer les systèmes d’antennes naturels s’intègre également dans cette démarche. <p><p>L’ensemble de notre travail s’est concentré sur ces deux domaines d’applications. Par l’étude de différents processus de transfert de charges/d’énergie au sein des complexes seuls (processus intramoléculaires) ou en interaction avec un environnement spécifique (processus intermoléculaires), nous avons souhaité mettre en évidence l’intérêt de l’utilisation d’un nouveau ligand plan étendu, le tpac, au sein de complexes du Ru(II). Un tel ligand permet en effet de conférer d’une part une affinité élevée des complexes résultants pour l’ADN, et d’autre part, de par sa nature pontante, de connecter des unités métalliques entre elles au sein d’entités supramoléculaires de taille importante. <p><p>Les propriétés photophysiques de quatre complexes basés sur le ligand plan étendu tpac, le [Ru(phen)2tpac]2+ (P) et son homologue dinucléaire le [(phen)2Ru tpac Ru(phen)2]4+ (PP) (à base de ligands ancillaires phen), ainsi que le [Ru(tap)2tpac]2+ (T) et son homologue dinucléaire le [(tap)2Ru tpac Ru(tap)2]4+ (TT) (à base de ligands ancillaires tap), ont été étudiées et comparées entre elles.<p><p>L’examen de ces propriétés, d’abord pour les complexes seuls en solution, en parallèle avec celles de complexes dinucléaires contenant un ligand pontant PHEHAT, a permis de mettre en évidence l’importance de la nature du ligand pontant utilisé. Ces résultats ont ainsi révélé qu’un choix judicieux du ligand pontant permet de construire des entités de grande taille capables de transférer l’énergie lumineuse vers un centre (cas du ligand PHEHAT), ou, au contraire, de relier entre elles des entités ne s’influençant pas l’une l’autre d’un point de vue photophysique (cas du ligand tpac). <p><p>Les propriétés des complexes du tpac, étudiés cette fois en présence de matériel génétique (mononucléotide GMP, ADN ou polynucléotides synthétiques), se sont révélées très différentes selon que le complexe portait des ligands ancillaires phen (P, PP) ou tap (T, TT). Seuls les complexes à base de tap sont en effet photoréactifs envers les résidus guanine. Nous avons dès lors focalisé cette partie de notre travail sur les deux complexes T et TT. Cette photoréaction, ainsi que le transfert d’électron photoinduit entre ces complexes excités et la guanine, ont pu être mis en évidence par différentes techniques de spectroscopie d’émission tant stationnaire que résolue dans le temps, ainsi que par des mesures d’absorption transitoire dans des échelles de temps de la nano à la femto/picoseconde. L’étude du comportement photophysique des complexes en fonction du pH a en outre révélé de manière très intéressante que, pour des études en présence d’ADN, la protonation des états excités des complexes devait être considérée. Les résultats de cette étude nous ont fourni des pistes quant à l’attribution des processus observés en absorption transitoire.<p><p>Le transfert d’électron a également fait l’objet d’une étude par des méthodes théoriques. Ces calculs ab initio ont permis de mettre en évidence une faible influence de l’énergie de réorganisation sur la vitesse de transfert d’électron, qui semble dépendre plus sensiblement de la non-adiabaticité du processus, mais surtout de l’énergie libre de la réaction et d’un éventuel couplage à un transfert de proton. <p><p>L’ensemble des résultats obtenus avec les complexes T et TT en présence de matériel génétique, qui, de manière assez inattendue, sont très semblables, indiquent que ces complexes présentent tous deux un grand intérêt pour le développement de nouvelles drogues antitumorales photoactivables.<p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

L'étude des phénomènes turbulents se développant en sortie du propulseur de Hall est nécessaire pour pouvoir modéliser le transport anormal (par opposition au transport diffusif) des électrons à travers les lignes de champ magnétique. Les relations de dispersion de deux instabilités pouvant être responsables de ce transport ont été mesurées à des échelles millimétriques à l'aide du diagnostic de diffusion collective de la lumière. Ce travail de thèse s'attache à en donner une description aussi bien théorique qu'expérimentale, pierre à l'édifice de la compréhension du transport dans le propulseur. Une instabilité se propageant majoritairement dans la direction azimutale du propulseur y est caractérisée comme étant l'instabilité de dérive électronique ExB et un modèle analytique décrivant la fréquence expérimentale y est dérivé et validé. De plus, le manuscrit présente une méthode de déconvolution du signal de la diffusion collective de la fonction d'appareil pour ce mode. Une fois déconvoluées, les relations de dispersion expérimentales peuvent être ajustées par la fréquence du modèle analytique, ce qui permet de mesurer expérimentalement et de manière originale la température et la densité électronique dans le jet d'ions énergétiques du plasma du propulseur. Enfin, la seconde instabilité, se développant autour de la direction axiale du propulseur, est caractérisée comme l'instabilité double faisceau entre les ions simplement et doublement chargés du plasma / The study of turbulent phenomena that grow at the exit plane of the Hall thruster is required to modelize the anomalous transport (in contrast to the diffusion transport) of electrons across the magnetic field lines. The dispersion relations of two instabilities that can be responsible for this transport have been mesured at millimetric scales by mean of the collective light scattering diagnostic. The aim of the thesis is to describe them theoretically as well as experimentally, improving the understanding of the Hall thruster transport. In the thesis, an instability that propagates principally azimuthally is caracterized as the ExB electron drift instability and an analytical model that describes the experimental frequency is derived and validated. In addition, the manuscript presents an original method to unfold the signal of the collective scattering diagnostic from the instrumental function of this mode. Once corrected, the experimental dispersion relations can be adjusted by the frequency given by the analytical model, allowing to measure experimentally and in an original way the electron temperature and density in the energetic ion jet of the Hall thruster plasma. The second instability that is mainly propagating in the axial direction is caracterized as the two-stream instability between the simply and doubly charged ions of the plasma

ROS are frequently associated with deleterious effects caused by oxidative stress. Despite the harmful effects of non-specific oxidation, ROS also function as signal transduction molecules that regulate various biological processes, including stem cell proliferation and differentiation. Here we show that mitochondrial ROS level determines cell fate during differentiation of the pluripotent stem cell line P19. As stem cells in general, P19 cells are characterized by a low respiration activity, accompanied by a low level of ROS formation. Nevertheless, we found that P19 cells contain fully assembled mitochondrial electron transport chain supercomplexes (respirasomes), suggesting that low respiration activity may serve as a protective mechanism against ROS. Upon elevated mitochondrial ROS formation, the proliferative potential of P19 cells is decreased due to longer S phase of the cell cycle. Our data show that besides being harmful, mitochondrial ROS production regulates the differentiation potential of P19 cells: elevated mitochondrial ROS level favours trophoblast differentiation, whereas preventing neuron differentiation. Therefore, our results suggest that mitochondrial ROS level serves as an important factor that directs differentiation towards certain cell types while preventing others.

Studium transportu náboje v Ta2O5 oxidových nanovrstvách se zaměřuje především na objasnění vlivu defektů na vodivost těchto vrstev. Soustředíme se na studium oxidových nanovrstev Ta2O5 vytvořených pomocí anodické oxidace. Proces výroby Ta2O5 zahrnuje řadu parametrů, jež ovlivňují koncentraci defektů (oxidových vakancí) v této struktuře. Vrstva oxidu Ta2O5 o tloušťce 20 až 200 nm se často používá jako dielektrikum pro tantalové kondenzátory, které se staly nedílnou součástí elektrotechnického průmyslu. Kondenzátory s Ta2O5 dielektrickou vrstvou lze modelovat jako strukturu MIS (kov – izolant – polovodič). Anodu tvoří tantal s kovovou vodivostí, katodu potom MnO2 či vodivý polymer (CP), které jsou polovodiče. Hodnoty elektronových afinit, respektive výstupních prací, jednotlivých materiálů potom určují výšku potenciálových bariér vytvořených na rozhraních kov-izolant (M – I) a izolant-polovodič (I – S). Dominantní mechanizmy transportu náboje lze určit analýzou I-V charakteristiky zbytkového proudu. Dominantní mechanizmy transportu náboje izolační vrstvou jsou ohmický, Poole-Frenkelův, Shottkyho a tunelování. Uplatnění jednotlivých vodivostních mechanismů je závislé na teplotě a intenzitě elektrického pole v izolantu. Hodnota zbytkového proud je významným indikátorem kvality daného izolantu. Ten závisí na technologii výroby kondenzátoru, významně především na parametrech anodické oxidace a na materiálu katody. I-V charakteristiky zbytkového proudu se měří v normálním a reversním módu, tj. normální mód značí kladné napětí na anodě a reversní mód záporné napětí na anodě. I-V charakteristika je výrazně nesymetrická, a proto tyto kondenzátory musí být vhodně polarizovány. Nesymetrie I-V charakteristiky se snižuje s klesající teplotou, při teplotě pod 50 K a je možno některé kondenzátory používat jako bipolární součástky. Z analýzy I-V charakteristiky lze určit řadu parametrů, jako tloušťku izolační vrstvy a koncentraci defektů v izolační Ta2O5 vrstvě a dále lze odhadnout parametry MIS modelu kondenzátoru - stanovit hodnotu potenciálových bariér na rozhraních M – I a I – S. Měření C-V charakteristik při různých teplotách v rozsahu 10 až 300 K je využíto pro určení výšky potenciálové bariéry na rozhraní I – S, závislosti kapacity na teplotě a dále pro výpočet efektivní plochy elektrod. Z výbrusu vzorků na skenovacím elektronovém mikroskopu byly určeny tloušťky dielektrika Ta2O5 pro jednotlivé vyhodnocované řady kondenzátorů.