Absence epilepsy is a neurological disorder that commonly occurs in children. Some studies have shown that absence seizures predominantly originate either in the thalamus or the cerebral cortex. Some cerebellar nuclei (CN) neurons project to these brain areas, as explained further in Fig. 2.6 in Chapter 2. Also, some CN neurons have been observed to show modulation during the absence seizures. This indicates that they somehow participate in the seizure and hence are referred to as "participating neurons" in this thesis. In this research, I demonstrate how machine learning techniques and computer simulations can be applied to investigate the properties and the input conditions present in these participating neurons. My investigation found a sub-group of CN neurons, with similar interictal spiking activity, spiking activity between the seizures, that are most likely to participate in seizures. To investigate the input conditions present in the CN neurons that produce this type of interictal activity, I used a morphologically realistic conductance based model of an excitatory CN projection neuron [66] and optimised the input parameters to this model using an Evolutionary Algorithm (EA). The results of the EA revealed that these participating CN neurons receive a synchronous and bursting input from Purkinje cells and bursting input with long intervals(approx. 500ms) from mossy fibre. The same interictal activity can also be produced when the Purkinje cell input to the CN neuron is asynchronous. The excitatory input in this case also had long interburst intervals but there is a decrease in excitatory and inhibitory synaptic weight. Surprisingly, a slight change in these input parameters can change the interictal spiking pattern to an ictal spiking pattern, the spiking pattern observed during absence seizures. I also discovered that it is possible to prevent a participating CN neuron from taking part in the seizures by blocking the Purkinje cell input.

In the past decade, the field of NMR spectroscopy has seen the emergence of ever more powerful superconducting magnets, which has opened the door for the observation of many traditionally challenging or non-receptive nuclei. In this dissertation, a variety of ionic solids with organic coordination environments are investigated using quadrupolar solid-state NMR experiments with an ultrahigh-field magnet (21.1 T). Two general research directions are presented including a 79/81Br solid-state NMR study of a series of 6 triphenylphosphonium bromides for which single-crystal X-ray structures are reported herein. A second research direction is also presented wherein alkaline-earth metal (25Mg, 43Ca, and 87Sr) solid-state NMR is used to characterize a systematic series of 16 aryl and alkyl carboxylates. In both studies, the quadrupolar nuclei studied are deemed “exotic” due to their unreceptive nature to NMR spectroscopic analysis including low natural abundances, large quadrupole moments, or low resonance frequencies. A variety of coordination modes to alkaline-earth metals, including N-atom coordination, are characterized herein for the first time using alkaline-earth metal solid-state NMR. In all cases, the electric field gradient (EFG) and chemical shift (CS) tensors are characterized and correlated to structural features such as interatomic distances measured from the crystal structure of the compound under study. In all of the projects undertaken herein, the gauge-including projector-augmented-wave density functional theory (GIPAW DFT) method is used, which allows for the prediction and rationalization of the experimental EFG and CS tensor parameters based on the input crystal structure. In the case of 43Ca solid-state NMR experiments reported in this dissertation, a linear correlation between the calculated and experimental 43Ca quadrupolar coupling constants, CQ, is used as a calibration curve for GIPAW DFT calculations performed on the 18 structural models currently available for the vaterite polymorph of CaCO3. Vaterite cannot be fully characterized by X-ray diffraction alone; therefore an NMR crystallography protocol is used in order to identify the model that best accounts for 43Ca solid-state NMR experiments performed on vaterite. It is expected that the conclusions from this dissertation can be used for future studies involving structural refinement and elucidation of solid materials containing challenging quadrupolar nuclei.

Les Noyaux Actifs de Galaxies (AGN) se situent au centre de galaxies extrêmement lointainesdont la luminosité provient de l’interaction d’un trou noir central supermassif et d’undisque d’accrétion. Il en résulte l’éjection à des vitesses relativistes de jets de matière collimatés.L’interférométrie à très longue base (VLBI) permet, grâce aux très grandes résolutionsatteintes, d’observer finement la structure de ces jets et de déterminer très précisément laposition astrométrique des objets. En raison de leur distance, les AGN ne présentent pas demouvements propres, ce qui les rend idéaux pour la construction de systèmes de référenceultra-précis et très stables.Des instabilités en position de quelques centaines de microsecondes d’arc, généralementimputées aux variations de la structure des jets, sont toutefois souvent observées sur des échellesde temps de quelques mois à quelques années. Le travail présenté ici étudie le lien entre les deuxphénomènes de façon statistique. Sur la base d’observations VLBI régulières conduites entre1994 et 2003, nous comparons l’évolution de la position astrométrique et de la structure des jetspour un échantillon de 68 AGN sur une période de 10 ans. Les résultats de l’étude indiquent quela corrélation entre les deux phénomènes existe mais n’est pas aussi forte qu’attendue. Le travailest complété par une simulation des effets causés sur la trajectoire des jets par la précessiondu disque d’accrétion ainsi que par la présence d’un système binaire de trous noirs. Appliquéeau cas de la source 1308+326, l’étude montre que l’amplitude de ces effets est compatible avecles oscillations de la trajectoire observées en VLBI. / Active Galactic Nuclei (AGN) are located in the center of extremely distant and bright galaxies. Their luminosity comes from the interaction between a super-massive central blackhole and an accretion disk, producing a relativistic collimated jet of matter. Thanks to the extremely high resolution achieved by Very Long Base line Interferometry (VLBI), the jet structure may be studied in detail, while the astrometric position of the AGN is determined with ahigh accuracy. Because of their location at cosmological distances, no proper motions are detected for those objects, making them ideal fiducial points for building highly-precise celestial reference frames.Instabilities up to a few hundreds of micro arc seconds are yet often observed in astrometricpositions on time scales from months to years. This is generally thought to be caused by theevolution of source structure. The study presented here investigates the correlation between the two phenomena on a statistical basis. Based on regular VLBI observations conducted between1994 and 2003, astrometric position variations and source structure evolution are compared fora sample of 68 AGN over a period of 10 years. The results indicate that a correlation between the two phenomena does exist but it is not as strong as expected. Additionally, a simulation of the effects caused by the precession of the accretion disc and the potential presence of abinary black hole in the center of the AGN is presented. Applied to the source 1308+326, the simulation shows that the magnitude of the effects is consistent with the oscillations of the jet trajectory observed on VLBI scale.

Nesse trabalho, foi feito o tratamento e a análise de cubos de dados de 8 núcleos ativos de galáxias próximos, no óptico e no infravermelho. O tratamento e a análise de todos os cubos de dados foram feitos utilizando-se uma série de metodologias específicas, muitas das quais foram desenvolvidas nos últimos anos pelo grupo de trabalho do autor. A análise de todos os cubos de dados foi feita com quatro objetivos principais: análise da fenomenologia geral nos arredores do AGN com a Tomografia PCA; análise das populações estelares, da emissão térmica de poeira e do featureless continuum nos arredores do AGN com uma síntese espectral feita com o software Starlight; análise da cinemática estelar e do gás ao redor do buraco negro central e, em alguns casos, simulação com o objetivo de se determinar a massa do buraco negro; análise dos mecanismos de excitação e ionização do gás ou da emissão de hidrogênio molecular. / In this work, we have treated and analyzed data cubes of 8 nearby active galactic nuclei, in the optical and in the infrared. All data cube treatment and analysis were performed using a series of specific methodologies, many of which were developed in the last few years by the author\'s working group. The analysis of all data cubes was performed with four main objectives: analysis of the general phenomenology of the AGN environment, using PCA Tomography; analysis of the stellar populations, of the thermal emission from dust and of the featureless continuum in the vicinity of the AGN, with a spectral synthesis performed with the Starlight software; analysis of the stellar and gas kinematics around the central black hole and, in some cases, simulations with the purpose of determining the mass of the black hole; analysis of the excitation and ionization mechanisms of the gas or of the emission from molecular hydrogen.

Os núcleos da rafe são agrupamentos celulares cujo principal tipo é o serotoninérgico. Em anuros adultos a estimulação elétrica e química da rafe bulbar não causa alteração na ventilação, enquanto que em mamíferos, dependendo da localização exata desta estimulação, a ventilação pode ser inibida ou estimulada. Ainda em mamíferos, os núcleos bulbares da rafe participam da resposta cardiorrespiratória à hipóxia (5% O2) e hipercarbia (5% CO2), enquanto que em anfíbios isto ainda não foi investigado. Portanto, o objetivo do presente trabalho foi investigar a participação dos núcleos da rafe nas respostas cardiorrespiratórias à hipóxia e hipercarbia em sapos (Rhinella schneideri). Para isso, primeiramente os núcleos da rafe foram localizados e identificados na espécie estudada. Imunorreatividade para proteínas Fosrelacionadas foi utilizada para verificar se estes núcleos são ativados ou inibidos durante o estímulo hipóxico e hipercárbico, e, adicionalmente, o papel dos núcleos magno e pontino da rafe nas respostas cardiorrespiratórias à hipóxia e hipercarbia foi investigado por meio da lesão nãoseletiva com ácido ibotênico. A ventilação pulmonar foi medida diretamente pelo método pneumotacográfico e a pressão arterial por canulação da artéria femoral. Os resultados demonstram que os núcleos bulbares da rafe são inibidos após o estímulo hipóxico e hipercárbico. A hipóxia causou aumento da ventilação pulmonar e da frequência cardíaca nos grupos veículo e lesado. A hipercarbia causou aumento da ventilação pulmonar em ambos os grupos. A lesão nãoseletiva dos núcleos magno e pontino da rafe não teve efeito na ventilação basal (durante normóxia normocárbica) e nas respostas cardiorrespiratórias à hipóxia e hipercarbia, sugerindo que estes núcleos não participam do controle da ventilação em condições basais ou durante a hipóxia e hipercarbia em sapos. / The raphe nuclei are brainstem cell groups and the main cell type is serotonergic. In adult anurans electrical or chemical stimulation of the medullary raphe has no effect on ventilation, whereas in mammals depending on the specific site of stimulation, an excitatory or inhibitory response is elicited. In mammals the medullary raphe participate in the ventilatory and cardiovascular response to hypoxia and hipercarbia while in amphibians there are no data available. Thus the present study was designed to investigate whether the raphe nuclei of toads (Rhinella schneideri) participate in the ventilatory and cardiovascular response to hypoxia (5% O2) and hipercarbia (5% CO2). First the raphe nuclei were located and identified. Fosrelated immunoreactivity was used to verify whether the raphe nuclei are activated or inhibited by hypoxia or hypercarbia. In addition, the role of raphe magnus and pontis in the respiratory and cardiovascular responses to hypoxia and hypercarbia were investigated by nonselective lesioning with ibotenic acid. Pulmonary ventilation was directly measured by pneumotachographic method and the arterial pressure by a femoral catheter. The results indicate that the medullary raphe nuclei are inhibited after hypoxic and hypercarbic stimulus (2,5h). Hypoxia caused hyperventilation and increase in the cardiac frequency in the vehicle and lesioned groups. Hypercarbia caused hyperventilation in both groups. Chemical lesions in the raphe magnus and pontis did not affect ventilatory or cardiovascular variables under resting conditions (normoxic normocárbica) or during the response to hypoxia or hipercarbia.

L’Imagerie par Résonance Magnétique Nucléaire des noyaux exotiques (X), autres que l’Hydrogène, permet d’explorer in vivo le métabolisme et la physiologie en conditions normales ou pathologiques mais aussi d’étudier la pharmacologie de manière non-invasive. Toutefois, ces explorations souffrent de la moindre sensibilité en IRM de ces noyaux et de leur plus faible concentration dans les tissus. Le Sodium-23 (23Na) est le second noyau le plus visible en RMN dans les tissus cérébraux et sa distribution, dans les compartiments intra- et extracellulaires, est strictement régulée notamment par la pompe Na+/K+-ATPase. Les stocks d’adénosine triphosphate (ATP) et de phosphocréatine (PCr), réservoirs d’énergie pour l’activité enzymatique, doivent être perpétuellement reconstitués pour assurer le bon fonctionnement cellulaire. C’est pourquoi étudier les distributions cérébrales de ces deux métabolites phosphorylées en plus de celle du sodium permettrait de définir des indicateurs quantitatifs de la viabilité et du métabolisme cellulaire. Enfin, le lithium est le traitement de référence pour la prévention de la crise maniaque chez le patient bipolaire. Pour autant, de nombreuses questions se posent, encore aujourd’hui, quant à sa distribution cérébrale et à son mécanisme d’action thérapeutique. Durant ces trois années de thèse, nous nous sommes intéressés, en particulier, aux problématiques d’imagerie rapide par échantillonnage non-Cartésien, de reconstruction de ces images et de quantification du 23Na, du Phosphore-31 (31P) et du Lithium-7 (7Li). Nous avons développé une méthode permettant la correction des différents biais d’acquisition à travers la cartographie du champ statique B0 et des profils de transmission (B1+) et de réception (B1-) des antennes utilisées. De plus, la quantification des temps de relaxation longitudinale (T1) et transverse (T2) permet de compenser les effets de ces mécanismes de relaxation sur le signal RMN pour obtenir des mesures de concentrations robustes et fiables. En raison d’un moment quadripolaire important, l’emploi de séquence à temps d’écho ultra-court (UTE) est indispensable en IRM du 23Na en combinaison avec des schémas non-Cartésiens d’encodage spatial. Des méthodes de reconstruction dédiées aux acquisitions non-Cartésiennes ont été évaluées et comparées en termes de qualité d’image mais aussi de robustesse des stratégies de sous-échantillonnage. Enfin, une approche multi-gradient-écho (MGE), alternative aux approches de Multiple Filtrage Quantique (MQF), a été implémentée afin d’approcher la quantification dans les différents compartiments cellulaires. Ces développements ont donné lieu à des applications cliniques en Sodium à 3T chez des volontaires sains en collaboration avec le service de Neurologie de l’Hôpital Universitaire d’Aix la Chapelle en Allemagne. Une application clinique en IRM 23Na à 3T est actuellement en cours chez des patients atteints par la maladie d’Alzheimer à Aix la Chapelle. Des preuves de concept en recherche clinique, à 7T à NeuroSpin, ont été réalisées en IRM du 31P chez des sujets sains et en 7Li chez des patients bipolaires sous traitement lithium en collaboration avec l’hôpital Fernand Widal à Paris et son centre expert Bipolaire. / Nuclear Magnetic Resonance Imaging of exotic (X) nuclei, other than Hydrogen, allows to probe in vivo metabolism and cellular physiology in normal or pathological conditions. Moreover, X-MRI can be used in pharmacology studies. However, X-MRI suffers from the relatively low sensitivities and in vivo concentrations of these nuclei. Sodium nuclei (23Na) is the second most NMR visible nuclei in brain tissues and its distribution in both intra- and extra-cellular compartments is tightly regulated by, in particular, the Na+/K+ ATPase pump. Stocks of Adenosine Triphosphate (ATP) and Phosphocreatine (PCr), main sources of cellular energy are perpetually maintained to ensure proper cellular function. This is why, study of spatial distributions of these two phosphorylated metabolites along with Sodium could yield insights about cellular viability and metabolism. Finally, Lithium is the reference treatment to prevent the onset of maniac events for patients suffering from bipolar disorders. Nevertheless, many questions are still unanswered about its spatial distribution in brain tissues and its underlying therapeutic mechanism. During these three years of PhD, we implemented efficient Acquisition and Reconstruction protocols for 23Na, 31P and 7Li MRI using Ultra-Short Echo-Time (UTE) sequences and non-Cartesian sampling combined with dedicated quantification pipelines to obtain accurate and robust concentration measurements in the brain. In particular, our proposed method accounts for signal bias due to the heterogeneities in coil transmission (B1+) and reception (B1-). Additionally, longitudinal (T1) and transverse (T2) relaxation times were assessed and the NMR signal was corrected for their respective weighting. Our quantification pipeline was validated in vitro for 23Na MRI. Various Fourier space sampling schemes along with under-sampling strategies and reconstruction methods were evaluated and compared. Finally, a multiple-gradient-echo (MGE) acquisition was implemented to explore cellular compartmentalization as an alternative to Multiple Quantum Filtering (MQF) approaches. These developments were applied at 3T in a clinical research setting for 23Na MRI on healthy volunteers in collaboration with the Neurology department of Aachen University Clinic, opening the way for an ongoing study of Alzheimer’s disease patients. Proof-of-concept studies were conducted at 7T at NeuroSpin for 31P MRI on healthy volunteers and for 7Li MRI in bipolar patients to study brain lithium distribution in collaboration with Hospital Fernand Widal in Paris.

abstract: I describe the first continuous space nuclear path integral quantum Monte Carlo method, and calculate the ground state properties of light nuclei including Deuteron, Triton, Helium-3 and Helium-4, using both local chiral interaction up to next-to-next-to-leading-order and the Argonne $v_6'$ interaction. Compared with diffusion based quantum Monte Carlo methods such as Green's function Monte Carlo and auxiliary field diffusion Monte Carlo, path integral quantum Monte Carlo has the advantage that it can directly calculate the expectation value of operators without tradeoff, whether they commute with the Hamiltonian or not. For operators that commute with the Hamiltonian, e.g., the Hamiltonian itself, the path integral quantum Monte Carlo light-nuclei results agree with Green's function Monte Carlo and auxiliary field diffusion Monte Carlo results. For other operator expectations which are important to understand nuclear measurements but do not commute with the Hamiltonian and therefore cannot be accurately calculated by diffusion based quantum Monte Carlo methods without tradeoff, the path integral quantum Monte Carlo method gives reliable results. I show root-mean-square radii, one-particle number density distributions, and Euclidean response functions for single-nucleon couplings. I also systematically describe all the sampling algorithms used in this work, the strategies to make the computation efficient, the error estimations, and the details of the implementation of the code to perform calculations. This work can serve as a benchmark test for future calculations of larger nuclei or finite temperature nuclear matter using path integral quantum Monte Carlo. / Dissertation/Thesis / Doctoral Dissertation Physics 2020

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第21568号 / 理博第4475号 / 新制||理||1642(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 青木 慎也, 教授 田中 貴浩, 准教授 髙山 史宏 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第22246号 / 理博第4560号 / 新制||理||1655(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 永江 知文, 教授 田中 貴浩, 教授 萩野 浩一 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

This diploma thesis deals with cavitation flow in the microscale, which remains an area with a lack of sufficient description of this phenomenon. At the same time, microfluidics is a field experiencing a dramatic rise in numerous biochemical applications, which underlines the relevance of researches of this type. In theoretical part of the thesis, cavitation was described in detail. In the practical part, a microfluidic device with a cavitation orifice was designed and manufactured. The ANSYS program was used for this design. An experiment was performed with the designed microchip, the aim of which was to observe a cavitating flow on the orifice. This measurement took place at the microfluidic laboratory at Victor Kaplan Department of Fluid Engineering. Due to the failure of the experiment, a CFD model of two-phase cavitation flow was built. The conclusions of the thesis were compiled from the findings of measurement and the results of modeling.