The role of T-type calcium channels (TTCCs) in the heart is unclear. TTCCs are transiently expressed throughout the neonatal heart during a period of rapid cardiac development. A few weeks postnatally, TTCCs are no longer found in ventricular myocytes (VMs) and calcium influx via TTCCs (ICa,T) is only detected in the SA node and Purkinje system. However, pathologic cardiac stress is associated with re-expression of TTCCs in VMs. Whether ICa,T in this setting promotes cardiac growth or exacerbates cardiac function is a topic of debate. The focus of this thesis work was to examine the effect of TTCC re-expression in the normal and diseased myocardium. Our experiments were performed in a transgenic mouse model with inducible, cardiac-specific expression of α1G TTCCs. While both the α1G and α1H TTCC subtypes re-appear during cardiac disease, we specifically evaluated the effects of α1G TTCCs since mRNA levels of this TTCC subtype are markedly elevated during cardiac pathology. We found that transgenic mice with α1G overexpression had robust ICa,T with biophysical properties similar to those published in previous studies. α1G mice had a small increase in cardiac function and showed no evidence of cardiac histopathology or increased mortality. These findings were in contrast to the phenotype of transgenic mice with augmented L-type calcium channel (LTCC) activity secondary to overexpression of the β2a regulatory subunit. While the magnitude of calcium influx in α1G and β2a VMs was similar, we found that cardiac contractility of β2a mice was significantly greater than α1G mice. Also, β2a mice had significant cardiac fibrosis, myocyte death, and premature lethality compared to the benign phenotype of α1G mice. We showed that the phenotypic differences are likely related to the differential spatial localization of T- and LTCCs. Whereas α1G TTCCs were principally localized to the surface sarcolemma, LTCCs were primarily found in the transverse tubules in close proximity to the sites of sarcoplasmic reticulum calcium release. We evaluated the effect of TTCC expression during cardiac disease by inducing myocardial infarction (MI) in α1G mice. Acutely (1-week post MI), α1G mice showed similar worsening of cardiac function and mortality rates compared to control post-infarct mice. However, α1G hearts had smaller infarct sizes which correlated with increased Akt and NFAT activation in α1G than control hearts. After chronic heart failure, i.e. 7- weeks post-infarction, α1G hearts had significant hypertrophic response as determined by increased HW/BW ratio, myocyte cross-sectional area, as well as NFAT and Akt activity. Finally, α1G mice had a small survival benefit than control mice, which while statistically non-significant, suggests that TTCC re-expression does not exacerbate cardiac function as hypothesized by some investigators. We conclude that TTCCs play a minimal role in cardiac function and activate pro-survival signaling pathways in the myocardium. / Physiology

In this dissertation, I explored the effects of developmental hypoxia on heart contractility in three separate species of ectotherms: the common snapping turtle (Chelydra serpentina), the American alligator (Alligator mississippiensis), and the zebrafish (Danio rerio). I began with the common snapping turtle and tested whether the utilization of the sarcoplasmic reticulum was altered in response to developmental hypoxia. In the next two chapters, developmental hypoxia of the American alligator was explored studying how the cardiac tissue was affected, specifically in physiological stressors, sarcoplasmic reticulum utilization and sensitivity to pharmacological increases in contractility. The last chapter explored how zebrafish heart contractility was altered in response to chronic hypoxia from egg to adult. Findings from these chapters suggest that while developmental hypoxia did alter cardiac contractility, it did not alter the response of the heart to physiological stressors such as increased heart rate or under hypoxia. Overall, these findings contribute to increasing the current understanding of how developmental hypoxia alters the cardiovascular system but with an emphasis on the cardiac tissue level.

This work focuses on the safe and stable operation of an autonomous power system interconnecting an AC source with various types of power electronic loads. The stability of these systems is a challenge due to the inherent nonlinearity of the circuits involved. Traditionally, the stability analysis in this type of power systems has been approached by means of small-signal methodology derived from the Nyquist stability criterion. The small-signal analysis combined with physical insight and the adoption of safety margins is sufficient, in many cases, to achieve a stable operation with an acceptable system performance. Nonetheless, in many cases, the margins adopted result in conservative measures and consequent system over designs. This work studies the system stability under large-perturbations by means of three different tools, namely parameter space mapping, energy functions, and time domain simulations. The developed parameters space mapping determines the region of the state and parameter space where the system operation is locally stable. In this way stability margins in terms of physical parameters can be established. Moreover, the boundaries of the identified stability region represent bifurcations of the system where typical nonlinear behavior appears. The second approach, based on the Lyapunov direct method, attempts to determine the region of attraction of an equilibrium point, defined by an operation condition. For this a Lyapunov function based on linear matrix inequalities was constructed and tested on a simplified autonomous system model. In Addition, the third approach simulates the system behavior on a computer using a detailed system model. The higher level of model detail allows identifying unstable behavior difficult to observe when simpler models are used. Because the stability of the autonomous power system is strongly associated with the characteristics of the energy source, an improved voltage controller for the generator is also presented. The generator of an autonomous power system must provide a good performance under a wide variety of regimes. Under these conditions a model based controller is a good solution because it naturally adapts to the changing requirements. To this extent a controller based on the model of a variable frequency synchronous generator has been developed and tested. The results obtained show a considerable improvement performance when compared to previous practices. / Ph. D.

The soft x-rays (wavelengths less than 30 nm) emitted by the sun are responsible for the production of high energy photoelectrons in the D and E regions of the ionosphere, where they deposit most of their energy. The photoelectrons created by this process are the main drivers for dissociation of nitrogen ($N_2$) molecules in the altitude range below 200 km. The dissociation of $N_2$ is one of main mechanisms responsible for the production of nitric oxide (NO) at these altitudes. These processes are important to understand because NO plays a critical role in controlling the temperatures of various regions of Earth's atmosphere. In order to estimate the dissociation rate of $N_2$ we need its dissociation cross-sections. The dissociation cross-sections of $N_2$ due to inelastic collisions with electrons is primarily es- timated from the cross-sections of its excitation states (using predissociation factors) and dissociative ionization channels. Predissociation is the transition without emission of radi- ation from a stable excited state to an unstable excited state of a molecule that leads to dissociation. Unfortunately, the lack of cross-section data, particularly at high electron en- ergies and of higher excited states of N 2 and N 2 + , introduces uncertainty in the dissociation cross-section and subsequently the dissociation rate calculation, which leads to uncertainties in the NO production rate. We have updated a photoelectron model with thoroughly-revised electron impact cross- section data of all major species and experimentally determined predissociation factors. The dissociation rates of $N_2$ using this model are compared to the dissociation rates obtained using another existing (Solomon and Qian [2005]) model. A parameterized version of the updated dissociation rates are used in a one-dimensional global average thermospheric/ ionospheric model, ACE1D (Atmospheric Chemistry and Energetics), to obtain the updated production rates of NO. In the final chapter, we use the ACE1D model to show that the energies deposited by the solar soft x-rays in the lower thermosphere at altitudes between 100 -150 km affect the temperature of the Earth's thermosphere at altitudes well above 300 km. By turning off the input solar flux in the different wavelength bins of the model iteratively, we are able to demonstrate that the maximum change in exospheric temperature is due to changes in the soft solar x-ray bins. We also show, using the thermodynamic heat equation, that the molecular diffusion via non-thermal photoelectrons is the main source of heat transfer to the upper ionosphere/thermosphere. Moreover, these temperature changes and heating effects of the solar soft x-rays are comparable to that of the much stronger He II 30.4nm emission. Finally, we show that the uncertainties in the solar flux irradiance at these soft x-rays wavelengths result in corresponding uncertainties in the modeled exospheric temperature, and these uncertainties increase substantially with increased solar activity. / Doctor of Philosophy / The radiation from the sun covers a wide range of the electromagnetic spectrum. The soft x-rays with wavelengths less than 30 nm are the most energetic and variable part of the spectrum, and would have detrimental effects on humans were they not absorbed by the atmosphere. The absorption of soft x-rays by the Earth's atmosphere at altitudes near 100- 150 km creates ionized and energized particles. These energetic changes can affect and even damage the satellites in low Earth orbit, and can cause radio communication blackouts and radiation storms (large quantities of energetic particles, protons and electrons accelerated by processes at and near the Sun). Therefore, we need to have good models that can quantify these changes in order to correctly predict their effects on our atmosphere, and help to mitigate any harmful effects. The soft x-rays and the extreme ultraviolet (EUV) are responsible for ionization of the major neutral species, $N_2$ , $O_2$ and O, in the Earth's atmosphere, which leads to the production of ions and energetic photoelectrons. These high energy photoelectrons can cause further ion- ization, excitation and dissociation. We study the dissociation of $N_2$ by these photoelectrons to create neutral N atoms. The N atoms created via this process combine with the $O_2$ in the atmosphere to produce nitric oxide (NO), which is one of the most important minor constituents because of its role in regulating atmospheric heating/cooling. The production of NO peaks near 106 km altitude, where most of the energy of the soft x-rays are deposited. However, they also affect the temperature of the upper atmosphere well above this altitude. This is because the energy of the photoelectrons is conducted to the upper atmosphere by collisions of electrons and ions with ambient neutral atoms and molecules, thus increasing their temperature. In this study, we use modeling of soft x-ray irradiance, photoelectron ionization, excitation and dissociation rates and atmospheric neutral temperature to quantify the effects of soft x-rays on the Earth's atmosphere.

No / A novel dispersive system operating at 1064-nm excitation and coupled with transfer electron InGaAs photocathode and electron bombardment CCD technology has been evaluated for the analysis of drugs of abuse and explosives. By employing near-IR excitation at 1064-nm excitation wavelength has resulted in a significant damping of the fluorescence emission compared to 785-nm wavelength excitation. Spectra of street samples of drugs of abuse and plastic explosives, which usually fluoresce with 785-nm excitation, are readily obtained in situ within seconds through plastic packaging and glass containers using highly innovative detector architecture based upon a transfer electron (TE) photocathode and electron bombarded gain (EB) technology that allowed the detection of NIR radiation at 1064nm without fluorescence interference. This dispersive near-IR Raman system has the potential to be an integral part in the armoury of the forensic analyst as a non-destructive tool for the in-situ analysis of drugs of abuse and explosives. Copyright (c) 2015 John Wiley & Sons, Ltd.

In der vorliegenden Arbeit untersuchen wir verschiedene Aspekte von Herzrhythmen, von einzelnen Zellen bis zu den gesamten menschlichen Vorhöfen. Das Hauptprojekt ist die Entwicklung eines realistischen und effizienten Modells für die Erregungsausbreitung in den menschlichen Vorhöfen. Im ersten Kapitel untersuchen wir stimulierte Herzellen und den Verlust vom 1:1-Rhythmus für steigende Frequenzen. Weiter untersuchen wir Wellenausbreitung in Gewebe mit besonderen elektrophysiologischen Eigenschaften, die mit chronischen Erkrankungen der Vorhöfe in Verbindung stehen. Dann wenden wir uns Ionenmodellen zu, die ein zentraler Teil des Vorhofmodells sind. Wir untersuchen die Auswirkungen einer Verletzung der Ladungserhaltung, die in allen Ionenmodellen vorliegt, die die Konzentrationen der Ionen als Variablen enthalten, und erklären, warum diese Auswirkungen meist vernachlässigbar sind. Wir entwickeln weiter eine Methode, Ionenmodelle zu vereinfachen und dabei ihre für die Wellenausbreitung wichtigen Eigenschaften nur minimal zu verändern. Diese Methode wenden wir auf ein realistisches Ionenmodell für menschliches Vorhofgewebe an und kombinieren es mit anatomischen Daten, um das gewünschte realistische Vorhofmodell zu erhalten. Schließlich benutzen wir dieses Modell, um mögliche Mechanismen der Enstehung von Herzrhythmusstörungen zu untersuchen. / In this thesis, we study heart rhythms at different levels, from single cells to the entire human atria. The main project of this thesis is the development of a realistic and efficient model of wave propagation in the human atria. We start by studying paced single cells and their loss of 1:1 rhythmicity for increasing frequency. We go on to study wave propagation in tissue with special electrophysiologic properties, related to chronical disease of the atria. Then we treat ionic models, which are a central part of our atrial model. We discuss a recently discovered mathematical degeneracy present in all models of cardiac cells that include intracellular ion concentrations and we explain why this degeneracy has only a negligible effect on wave propagation. We develop a method to reduce the complexity of ionic models while closely retaining their wave propagation properties. Then we apply this method to a realistic ionic model of the human atria and combine it with anatomical data to get the desired model. We use this model to explore possible mechanisms for the genesis of arrhythmias.

Ce projet étudie si les difficultés de coordination visuomotrice observées chez des enfants nés très prématurément, sans déficit majeur et maintenant d'âge scolaire, s'accompagnent de différences de fonctionnement cérébral, telles que testées par les stimulations magnétiques transcrâniennes (TMS). Davantage de difficultés visuomotrices sont mises en évidence chez ces enfants en comparaison de pairs nés à terme. Des différences dans les mécanismes de programmation motrice sont documentées en parallèle des difficultés fonctionnelles. Les principaux paramètres TMS tributaires de ces différences sont l'inhibition intracorticale (complètement absente chez les enfants prématurés), l'excitabilité de base du cortex moteur primaire ainsi que la variabilité des réponses aux stimulations. Ces différences dans les mécanismes neurophysiologiques renseignent sur l'origine cérébrale des difficultés visuomotrices observées chez les grands prématurés. Ces données TMS pourraient être des biomarqueurs dont l'évolution permettrait d'affiner le dépistage et d'adapter l'intervention pour une meilleure prise en charge des enfants prématurés.

Biological invasion has become a major threat to economy, ecology, global biodiversity and ecosystem function of aquatic ecosystems. The main aim of the thesis was to study the effects of the zebra mussel (Dreissena polymorpha), a versatile invasive species, on phytoplankton dynamics and ecosystem function of lakes. In a first attempt, I compared the density of Dreissena and the physicochemical data of ecosystems that it invaded among North American and European lakes to identify important factors in its invasion success. Secondly, I investigated the impact of zebra mussels on phytoplankton community composition in a natural lake. Thirdly, I evaluated whether zebra mussel feeding behavior were affected by the presence of predatory waterborne cues. Finally, I examined the effect of Dreissena on seston stoichiometry. A Generalized Additive Model revealed that a joint effect of surface area, mean depth, total phosphorus and calcium concentrations can explain the variability in Dreissena density. Selective grazing by zebra mussels varied in relation to seasonal phytoplankton dynamics. Risk cues released by predators affected both feeding rate and prey selection of the mussels and had cascading indirect effects on phytoplankton biomass and community structure. I found that the flux in nutrients caused by differences in zebra mussel consumption lead to a variation in phytoplankton nutrient limitation. The flexibility of zebra mussel feeding behavior and variation in susceptibility among phytoplankton groups to mussel ingestion indicate that invading zebra mussels could alter phytoplankton community composition of lakes and have important ecosystem consequences. The results of this thesis contribute to the growing evidence that predators indirectly affect resource dynamics and food web structure through their non-lethal effects on consumers. The results suggested that zebra mussel can indirectly both reduce and increase the energy transfer efficiency from primary producers to upper trophic levels in the pelagic and benthic food webs, respectively.

Ce manuscrit présente une étude des composés multiferroïques RMnO$_3$ hexagonaux (R=Ho, Y, Yb, In, Sc). L'accent est mis sur les corrélations spin/spin statiques et dynamiques et sur le couplage entre degrés de liberté de spin et de réseau. Cette étude s'appuie sur de nombreux résultats de diffusion de neutrons aussi bien sur poudres que sur monocristaux. La diffraction permet de déterminer précisément les positions atomiques et la structure magnétique. Nous avons pu développer un modèle rendant compte de la très grande variété de comportements observés dans ces systèmes en nous basant sur la frustration des interactions d'échange interplans. La frustration des interactions magnétiques n'est pas simplement due au réseau triangulaire de Mn mais aussi aux interactions entre Mn de plans adjacents. Cette frustration est directement controlée par la position du Mn par rapport à une valeur seuil $x=1/3$ dans la maille élémentaire. Les mesures de diffusion inélastiques ont permis de valider ce modèle en vérifiant certaines prédictions à partir de mesures de dispersion d'onde de spins et d'un calcul numérique solide (signe de la constante d'échange interplan, transitions de réorientation). Elles ont également confirmé le rôle primordial des interactions RMn sur la dynamique de spin des Mn. Enfin des mesures complexes de diffusion inélastique de neutrons polarisés ont mis en évidence une hybridation entre excitations de réseau et de spin. Un modèle basé sur l'interaction de Dzyaloshiinski-Moriya est proposé pour rendre compte des observations expérimentales. Ce mode hybride est a rapprocher de l'électromagnon observé dans de nombreux systèmes, et semble être une composante inhérente à l'existence de la multiferroïcité.

Dans les milieux ionisés existe un grand nombre d’espèces chimiques. Beaucoup sont en quantité minoritaire mais jouent pourtant, par leur grande réactivité, un rôle essentiel dans les processus de transformation chimique. Cette étude s’intéresse à la structure et à la dynamique des ions moléculaires, ainsi qu’aux collisions réactives pour des systèmes intervenant dans les atmosphères planétaires et dans le milieu interstellaire, comme les réactions mettant en jeu le monoxyde de carbone. Des modélisations numériques sont nécessaires à la préparation des expériences de fusion thermonucléaire. Enrichis par les résultats expérimentaux, concernant les ions d’hydrocarbures tels que le méthane, ils fournissent une aide pour l'interprétation des phénomènes observés dans les tokamaks. L’identification des réactions physiques à l’origine de la présence de particules dans le plasma est une étape importante afin de comprendre les environnements ionisés. Les systèmes examinés à Louvain-la-Neuve sont donc choisis pour leur intérêt immédiat en astrophysique ou en physique des plasmas. Alors que la connaissance des processus d'ionisation par impact d'électrons d’espèces atomiques ou ioniques simples est bien établie, ce n’est pas encore le cas lorsque la cible primaire est un ion moléculaire. L'existence d'au moins un degré de liberté supplémentaire rend possible la dissociation de l'ion moléculaire initial en plusieurs fragments, une partie de l’énergie potentielle est alors transférée sous forme d’énergie cinétique aux produits. En conséquence, ceux-ci sont généralement distribués dans de larges gammes angulaire et énergétique. L’analyse fine des distributions permet d’étudier les détails de la collision électronique. L’expérience a pour thématique majeure la mesure des sections efficaces absolues en fonction de l’énergie des électrons projectiles incidents, pour des réactions impliquant des espèces ioniques polyatomiques. L’observation des seuils de réaction et de l’énergie cinétique des fragments permet de déterminer la zone de Franck-Condon accessible et les états moléculaires impliqués dans les processus considérés. Les travaux réalisés au laboratoire ont démontré que l'appareillage existant est bien approprié à ce type d’étude. A un niveau plus fondamental, l’examen comparatif minutieux des présentes mesures, des résultats issus d’autres expériences et des prédictions des formalismes semi-empiriques, permet d’améliorer la connaissance des phénomènes collisionnels.