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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.

La microscopie à balayage laser est limitée en résolution par la limite de diffraction de la lumière. Plusieurs méthodes de superrésolution ont été développées depuis les années 90 pour franchir cette limite. Cependant, la superrésolution est souvent obtenue au prix d'une grande complexité (laser de haute puissance pulsé, temps d'acquisition long, fluorophores spécifiques) ainsi que des limitations dans le type d'échantillon observé (observation en surface uniquement). Dans certains cas, comme pour l'illumination structurée et la microscopie SLAM, une amélioration en résolution plus modeste est obtenue, mais avec une complexité et des limites d'utilisation fortement réduites par rapport aux autres méthodes de superrésolution. Les mé- thodes que nous proposons ici sont des méthodes d'augmentation de résolution qui visent à minimiser les contraintes expérimentales et à garder un maximum des avantages des techniques d'imagerie conventionnelles. Dans les cas que nous avons étudiés, les méthodes proposées sont basées sur la microscopie confocale. Nous allons montrer dans un premier temps qu'il est possible d'augmenter de 20% la résolution d'un microscope confocal en changeant le faisceau laser utilisé pour l'excitation par un faisceau Bessel-Gauss tout en ayant un sténopé de la bonne taille (soit 1 Airy Unit). Les avantages de la méthode proposée résident dans sa simplicité d'installation et d'utilisation et sa compatibilité avec d'autres méthodes d'augmentation de résolution. Nous avons démontré les capacités d'augmentation de résolution des faisceaux Bessel-Gauss théoriquement puis exp érimentalement sur des échantillons de nano-sphères et de tissus biologiques obtenant ainsi une résolution de 0.39. Nous avons également montré que l'amélioration en résolution des faisceaux Bessel-Gauss donne une analyse statistique de la colocalisation avec un taux plus faible de faux positifs. Nous avons utilisé des faisceaux Bessel-Gauss de différents ordres pour améliorer la méthode de la microscopie SLAM et ainsi obtenir une résolution descendant à 0.17 (90 nm avec une longueur d'onde de 532 nm). La méthode proposée est entièrement basée sur la microscopie confocale et seul un module permettant de changer le faisceau laser doit être ajouté au montage. Dans un second temps, nous proposons une méthode permettant de bénéficier au maximum des propriétés de la déconvolution pour augmenter la résolution de la microscopie confocale. Pour cela, nous avons utilisé différents modes laser pour l'acquisition d'images et ces images sont utilisées comme données d'entrée pour la déconvolution (avec des mesures des PSF respectives). Les faisceaux laser utilisés apportent ainsi des informations complémentaires à l'algorithme de déconvolution permettant ainsi d'obtenir des images avec une résolution encore meilleure que si une simple déconvolution (utilisant le même algorithme) était utilisée sur l'image confocale. Par la suite, nous avons changé les faisceaux laser par des faisceaux Bessel-Gauss pour augmenter davantage l'ecacité de la déconvolution. Encore une fois, la méthode proposée est entièrement basée sur la microscopie confocale et seul un module permettant de changer le faisceau laser doit être ajouté au montage. Enfin, nous proposons d'aborder une méthode de reconstruction en trois dimensions par tomographie basée sur des projections obtenues en microscopie à deux photons utilisant les faisceaux Bessel-Gauss. En focalisant des faisceaux Bessel-Gauss à angle en microscopie deux photons, on obtient une série de projections utilisables pour une reconstruction tomographique. Le but est de tester la faisabilité de la méthode qui permettrait de reconstruire un volume, en nécessitant moins d'images que dans le cas d'une acquisition plan par plan, en microscopie deux photons classique. / Laser scanning microscopy is limited in lateral resolution by the diffraction of light. Superresolution methods have been developed since the 90s to overcome this limitation. However, superresolution is generally achieved at the cost of a greater complexity (high power lasers, very long acquisition times, specic uorophores) and limitations on the observable samples. In some cases, such as Structured Illumination Microscopy (SIM) and Switching Laser Modes (SLAM), a more modest improvement in resolution is obtained with a reduced complexity and fewer limitations. We propose here methods which improve the resolution while minimizing the experimental constraints and keeping most of the advantages of classical microscopy. First, we show that we can improve by twenty percent the resolution of confocal microscopy by using Bessel-Gauss beams, and by having the right pinhole size (1 Airy Unit), compared to conventional Gaussian beam based confocal microscopy. The advantages of this strategy include simplicity of installation and use, linear polarization compatibility, possibility to combine it with other resolution enhancement and superresolution strategies. We demonstrate the resolution enhancement capabilities of Bessel-Gauss beams both theoretically and experimentally on nano-spheres and biological tissue samples with a resolution of 0.39. We achieved these resolutions without any residual artifacts coming from the Bessel-Gauss beam side lobes. We also show that the resolution enhancement of Bessel-Gauss beams leads to a better statistical colocalization analysis with fewer false positive results than when using Gaussian beams. We have also used Bessel-Gauss beams of different orders to further improve the resolution by combining them in SLAM microscopy achieving a resolution of 0.17 (90 nm with a wavelength of 532 nm). In a second step, we propose a method to improve the resolution of confocal microscopy by combining different laser modes and deconvolution. Two images of the same eld are acquired with the confocal microscope using different laser modes and are used as inputs to a deconvolution algorithm. The two laser modes have different Point Spread Functions and thus provide complementary information leading to an image with enhanced resolution compared to using a single confocal image as input to the same deconvolution algorithm. By changing the laser modes to Bessel-Gauss beams, we were able to improve the effciency of the deconvolution algorithm and to obtain images with a residual Point Spread Function having a width smaller than 100 nm. The proposed method requires only a few add-ons to the classic confocal or two photon microscopes. Finally, we propose a three dimensional tomography reconstruction method using Bessel-Gauss beams as projection tools in two-photon microscopy. While focussing Bessel-Gauss beams at an angle in two photon microscopy, we can obtain a series of projections that can be used for tomography reconstruction. The aim is to test the practicality of the methods allowing to reconstruct a volume while using fewer images than plane by plane acquisitions as in classic two-photon microscopy.

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.