Intracardiac pathways mediating the parasympathetic control of various cardiac functions are incompletely understood. Several intracardiac ganglia have been demonstrated to potently influence cardiac rate [the sinoatrial (SA) ganglion], atrioventricular (AV) conduction (the AV ganglion), or left ventricular contractility (the cranioventricular ganglion). However, there are numerous ganglia found throughout the heart whose functions are poorly characterized. One such ganglion, the posterior atrial (PA) ganglion, is found in a fat pad on the rostral dorsal surface of the right atrium. We have investigated the potential impact of this ganglion on cardiac rate and AV conduction. We report that microinjections of a ganglionic blocker into the PA ganglion significantly attenuates the negative chronotropic effects of vagal stimulation without significantly influencing negative dromotropic effects. Because prior evidence indicates that the PA ganglion does not project to the SA node, we neuroanatomically tested the hypothesis that the PA ganglion mediates its effect on cardiac rate through an interganglionic projection to the SA ganglion. Subsequent to micro-injections of the retrograde tracer fast blue into the SA ganglion, >70% of the retrogradely labeled neurons found within five intracardiac ganglia throughout the heart were observed in the PA ganglion. The neuroanatomic data further indicate that intraganglionic neuronal circuits are found within the SA ganglion. The present data support the hypothesis that two interacting cardiac centers, i.e., the SA and PA ganglia, mediate the peripheral parasympathetic control of cardiac rate. These data further support the emerging concept of an intrinsic cardiac nervous system.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released within the heart during myocardial ischemia. The present study was done to determine the regional localization and abundance of CGRP receptors in the guinea pig heart. CGRP binding sites in 20 μm frozen sections of heart were labeled using [125I]CGRP. Non-specific binding was determined in the presence of 1 μM unlabeled CGRP or CGRP8-37. Significant amounts of specific CGRP binding were identified in atrial and ventricular myocardium, all portions of the conducting system, coronary arteries, the aorta and pulmonary trunk and intracardiac ganglia. Specific binding of CGRP to the left atrium was two-fold higher than binding to the right atrium (0.667±0.052 v 0.340 ± 0.029 fmol/mg tissue, n = 5, CGRPs8-37 group). In contrast to the atria, a lower and uniform density of CGRP receptors occurred in contractile tissue of the ventricular myocardium (e.g. 0.239 ± 0.013 fmol/mg left ventricle, n = 5). The highest concentration of CGRP receptors in guinea pig cardiac tissue occurred at the bundle of His and the bundle branches (0.752 ± 0.087 and 0.71.3 ± 0.138 fmol/mg tissue, respectively, n = 5). CGRP receptors were localized to coronary vessels throughout the heart and to the ascending aorta and pulmonary trunk. Lastly, intracardiac ganglia exhibited moderate levels of specific [125I]CGRP binding (0.475 ± 0.043 fmol/mg, n = 5). These findings support the concept that CGRP can have direct effects on atrial and ventricular function as well as coronary flow. The high density of CGRP receptors in the distal conducting system and the presence of CGRP receptors in intracardiac ganglia further suggest that CGRP could have important effects on cardiac conduction velocity and parasympathetic regulation of the heart.

The world is facing a major challenge when it comes to proper energy utilization. The increasing energy demand, the depleting fossil fuel resources and the growing environmental and ecological concerns are factors that drive the need for creative solutions. Renewable energy resources such as solar sit in the center of these solutions. Due to their intermittent nature, development of energy storage systems is crucial. This dissertation focused on the latent thermal energy storage systems that incorporate phase change materials (PCM). The main goal was to enhance the heat transfer rates in these systems to address the low melting (energy storage stage) and solidification (recovery stage) rates that are caused by the PCMs’ low thermal conductivity values. The application of multiple PCMs (m-PCMs) with varying melting temperatures in several arrangements was investigated. The effects of applying m-PCMs on the conduction heat transfer and on the natural convection heat transfer in both horizontally and vertically oriented heat exchangers were studied. This was followed by an optimization study of the PCMs’ melting temperatures and the working fluid flow rate. Further heat transfer enhancement using metal fins was also investigated. Numerical models were developed and validated. Results are reported and discussed. Significant enhancement in both complete melting time and energy storage capacity was obtained by the m-PCMs in series arrangement. This enhancement is more pronounced in the vertically oriented system. The working fluid flow rate was found to have a limited effect during the melting stage. However, it seems to be crucial in the solidification stage.

Les convertisseurs électroniques de puissance sont voués à fonctionner sous des conditions applicatives de plus en plus sévères tout en respectant les impératifs d’efficacité énergétique et de fiabilité. Or, les besoins industriels tendent vers un plus haut niveau d’intégration fonctionnelle tout en améliorant le rapport qualité-prix. Dès lors, la solution utilisée pour le report des puces semi-conductrices est le siège de densités de courant importantes et d’un flux thermique élevé. La présence de défauts dans cette couche d’interconnexion peut conduire à la dégradation de ses performances et au vieillissement prématuré du composant. L’objectif de nos recherches est d’évaluer la pertinence d’une méthodologie basée sur la confrontation de simulations numériques et de campagnes expérimentales. L’objectif est d’améliorer la compréhension du comportement électrothermique en régime de conduction d’un transistor MOSFET en présence d’un void dans sa brasure. Dans cette manuscrite, nous présenterons la construction d’un modèle intégrant le couplage électrothermique de la partie active qui sera confronté à la réponse de résultats expérimentaux. Puis, une étude numérique basée sur la théorie des plans fractionnaires, qui minimise le nombre de simulations, sera exploitée afin de quantifier l’impact de la taille et de la position du défaut sur la réponse électrothermique du composant et de ses liaisons électriques. Les détails de la mise en place d’une étude expérimentale analogue permettront de mettre en perspective la complémentarité de cette approche. / Power converters nowadays are required to function under harsh conditions in meeting energy efficiency and reliability requirement. Whereas, industrial specifications tend toward a higher level of power integration in respect to the cost constraint. As a result, the die attach is one of the key elements in power module packaging because of high current densities and high heat flow which are transported through. Void formation in the die attach may lead to performance degradation and premature aging of the component. This study introduces a methodology based on the comparison of numerical simulations and experimental campaigns. The obtained results help to improve our understanding on the electro-thermal behaviour of MOSFETs with solder voids. In this thesis, we depict a finite element model in which electro-thermal coupling of a MOSFET active layer is taken in to account. Simulation results will be correlated to the experimental responses. Later on, a parametric numerical study based on the response surface method (RSM) which minimizes the number of simulations and future tests will be exploited to quantify the impact of void position and size on several selective performance criteria. A future serial experimental study in respect to the same RSM design is expected in prospect, in order to fulfil the complementarity for this approach.

Un modèle de commutation de mémoires résistives (ReRAM) est présenté. Celui-ci est basé sur deux hypothèses : (1) la commutation résistive est causée par des changements qui se produisent dans la zone étroite (région active) du filament conducteur sous l'influence du champ électrique et (2) la commutation résistive est un processus stochastique, donc régi par une probabilité. La région active est représentée par un réseau de connexions verticales, chacune composée de trois éléments électriques : deux d'entre eux sont de faible résistance tandis que le troisième agit comme un disjoncteur et peut être soit de résistance faible (LR) ou élevée (HR). Dans ce modèle, le changement d'état du disjoncteur est régi par une probabilité de commutation (P$_{s}$) qui est comparée à un nombre aléatoire « p ». P$_{s}$ dépend de la chute de tension le long du disjoncteur et de la tension de seuil, V$_{set}$ ou V$_{reset}$, pour définir les processus de « set » (HR à LR) et « reset » (LR à HR). Deux mécanismes de conduction ont été envisagés : ohmique pour un état LR et pour un état de résistance élevée l'effet tunnel facilité par un piège (TAT). Le modèle a été implémenté avec le langage de programmation Python et fonctionne avec une bibliothèque C externe qui optimise les calculs et le temps de traitement. Les résultats de la simulation ont été validés avec succès en les comparant avec des courbes courant-tension (IV) mesurées sur dispositifs ReRAM réels dont l'oxyde était fait de HfO$_{2}$ et pour neuf aires différentes. La flexibilité et la facilité de mise en œuvre de ce modèle de commutation résistive en font un outil puissant pour l'étude des ReRAM / A model for the switching of resistive random-access memories (ReRAM) is presented. This model is based on two hypotheses: (1) the resistive switching is caused by changes that occur in the narrow zone (active region) of the conductive filament under the influence of the electric field and (2) the resistive switching is a stochastic process governed by a switching probability. The active region is represented by a net of vertical connections, each one composed of three electrical elements: two of them are always low resistive (LR) while the third one acts as a breaker and can be low or high resistive (HR). In the model, the change of the breaker's state is governed by a switching probability (P$_{s}$) that is compared with a random number $p$. P$_{s}$ depend on the voltage drop along the breaker and the threshold voltage, V$_{set}$ or V$_{reset}$ for set (HR to LR) or reset (LR to HR) processes. Two conduction mechanism has been proposed: ohmic for the low resistive state and trap-assisted tunneling (TAT) for the high resistive state. The model has been implemented in Python and works with an external C-library that optimizes calculations and processing time. The simulation results have been successfully validated by comparing measured and modeled IV curves of HfO$_{2}$-based ReRAM devices of nine different areas. It is important to note that the flexibility and easy implementation of this resistive switching model allow it to be a powerful tool for the design and study of ReRAM memories

Indiana University-Purdue University Indianapolis (IUPUI) / Voltage-‐gated sodium channels (VGSCs) are critical for the initiation and propagation of electrical signals in neurons; consequently they are significant regulators of neuronal excitability. They are exquisitely tuned and aberrations in their activity can lead to pathophysiological conditions. This dissertation highlights the roles of two prominent brain isoforms of VGSCs, Nav1.1 and Nav1.6. These isoforms have distinct localization in the brain. Specifically, Nav1.1 is predominantly expressed in the soma and proximal axon initial segment (AIS) of GABAergic neurons, while Nav1.6 is found at the distal AIS and nodes of Ranvier of both GABAergic and excitatory neurons. Several mutations have been identified in Nav1.1 and recently mutations in Nav1.6 have been discovered in patients with distinct epileptic phenotypes that respond poorly to current anti-epileptics. There is a need to better understand mechanistically how mutations in these channel isoforms lead to epilepsy in order to identify more efficacious treatment strategies. Therefore, the aims of this dissertation were to 1) examine the differential biophysical properties of Nav1.1 and Nav1.6, 2) determine the biophysical consequences of epilepsy-­associated mutations in Nav1.1 and Nav1.6 and examine the effects of cannabinoids on wildtype and mutant channel activity and 3) test the effects of selective inhibition of Nav1.1 versus Nav1.6 on epileptiform activity. To address these aims, whole­‐cell electrophysiology and mutlielectrode array recordings were used. The results demonstrate that 1) Nav1.1 and Nav1.6 have important differences in their biophysical properties that may be important in the fine­‐tuning of neuronal excitability, 2) epilepsy-­‐associated mutations in Nav1.1 and Nav1.6 alter several biophysical properties of the channels but have differential effects on resurgent current generation suggesting a divergence in the mechanism by which they induce epileptogenesis and cannabidiol can inhibit aberrant channel activity and reduce neuronal excitability and 3) pharmacological inhibition of Nav1.6, but not Nav1.1, abolishes epileptiform activity. Overall, this dissertation provides insight into the distinct contributions of Nav1.1 and Nav1.6 to physiological and pathophysiological firing activity and their ability to be targeted for therapeutic purposes. This knowledge is critical for understanding the potential role of VGSCs in epilepsy syndromes and identifying possible drug targets for more efficacious treatment strategies.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18951号 / 工博第3993号 / 新制||工||1615(附属図書館) / 31902 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 北川 進, 教授 松田 建児, 教授 安部 武志 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20792号 / 医博第4292号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 川村 孝, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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