Cette thèse porte sur l'étude des effets quantiques en dynamique moléculaire (DM). La DM est une méthode numérique qui permet l'étude des propriétés de la matière condensée. Cependant, la méthode étant basée sur la mécanique classique, les effets quantiques associés à la dynamique des noyaux, tels que l'énergie de point zéro ou l'effet tunnel, ne sont pas pris en compte. Ces effets quantiques nucléaires peuvent cependant jouer un rôle majeur, en particulier aux basses températures et/ou dans les systèmes contenant des atomes légers comme l'hydrogène. La dynamique moléculaire par intégrales de chemins (PIMD) est souvent utilisée, dans ce cas, pour tenir compte de la nature quantique des noyaux. Cette approche fournit des résultats quantiques exacts, mais son coût en temps de calcul élevé limite son domaine d'application. La méthode du bain thermique quantique (QTB) a été proposée comme une alternative à la PIMD. L'approche QTB est particulièrement intéressante car son coût en temps de calcul est équivalent à celui de la DM standard permettant ainsi l'étude de systèmes complexes et de plus grande taille.La première partie de cette thèse est consacrée à l'étude de la méthode QTB. Nous avons étudié le comportement de la méthode sur différents systèmes modèles afin d'étudier ses limites. En particulier, le problème du "zero point energy leakage" est étudié en détail et nous montrons que l'augmentation du coefficient de friction du QTB permet de limiter ce problème. Nous avons également développé une combinaison de la méthode QTB avec la méthode PIMD. Cette méthode combinée QTB-PIMD permet de réduire le coût en temps de calcul des simulations PIMD standards.Dans une deuxième partie, nous avons utilisé ces méthodes pour étudier la conduction de l'hydrogène dans des matériaux pérovskites. Nous nous intéressons d'abord à l'impact des effets quantiques sur la diffusion de l'hydrogène dans BaZrO3, un matériau d'électrolyte potentiel pour piles à hydrogène. L'hydrogène étant l'élément le plus léger, un impact important des effets quantiques est attendu. Nous trouvons que les effets quantiques sont effectivement importants à basse température, mais leur impact sur la diffusion reste faible aux températures de fonctionnement typiques des piles à hydrogène. Enfin, nous avons étudié les mécanismes de diffusion de l'hydrogène dans GdBaCo2O5.5. Nous mettons en évidence une diffusion anisotrope dans ce matériau et deux mécanismes principaux de diffusion. / This thesis deals with the study of quantum effects in molecular dynamics (MD). MD is a powerful numerical method to investigate the properties of condensed matter systems. However, since the method is based on classical mechanics, quantum effects associated with the dynamics of the nuclei, such as zero-point energy or tunnelling, are not taken into account. These nuclear quantum effects can, however, play a major role in particular at low temperatures and/or in systems containing light atoms such as hydrogen. In these cases, a standard way to account for the quantum nature of the nuclei is to use path integral molecular dynamics (PIMD). This method provides exact quantum results however its high computational cost limits its range of applicability. The quantum thermal bath (QTB) method has been proposed as an alternative to PIMD. The QTB method is particularly appealing because of its computational cost that is equivalent to standard MD thus allowing to study large and complex systems.The first part of this thesis is devoted to the study of the QTB method. We have studied the behavior of the method in selected model systems in order to investigate its limitations. We have focused, in particular, on the zero-point energy leakage problem and found that increasing the friction coefficient of the QTB can significantly limit this problem. We also have developed another way to use the QTB method by combining it with PIMD. This combined QTB-PIMD method allows, in particular, to decrease the computational cost of standard PIMD simulations.In a second part, we have used these methods to study hydrogen conduction in perovskite materials. We have first investigated the impact of quantum effects on the diffusion of hydrogen in BaZrO3, a potential electrolyte material for hydrogen fuel cells. Since hydrogen is the lightest element, we expect quantum effects to have a significant impact on its dynamics. We find that quantum effects are indeed significant at low temperatures although their impact on the diffusion remains low at the typical working temperatures of hydrogen fuel cells. Finally, we have investigated the diffusion mechanisms of hydrogen in GdBaCo2O5.5. We evidence that the diffusion is anisotropic in this material and two main diffusion mechanisms.

京都大学 / 0048 / 新制・論文博士 / 博士(工学) / 乙第13071号 / 論工博第4148号 / 新制||工||1659(附属図書館) / 33222 / (主査)教授 北川 進, 教授 松田 建児, 教授 阿部 竜 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Dissertation (PhD)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Heart failure due to cardiomyopathy or cardiac conduction disease is a major cause of mortality and morbidity in both developed and developing countries. Although defined as separate clinical entities, inherited forms of cardiomyopathies and cardiac conduction disorders have been identified that present with overlapping clinical features and/or have common molecular aetiologies. The objective of the present study was to identify the molecular cause of progressive familial heart block type II (PFHBII), an inherited cardiac conduction disorder that segregates in a South African Caucasian Afrikaner family (Brink and Torrington, 1977). The availability of family data tracing the segregation of PFHBII meant that linkage analysis could be employed to identify the chromosomal location of the disease-causative gene. Human Genome Project (HGP) databases have provided additional resources to facilitate the identification of positional candidate genes. Clinical examinations were performed on individuals of the PFHBII-affected family, and, where available, clinical records of subjects examined in a previous study by Brink and Torrington (1977) were re-assessed. Retrospective data suggested redefining the classification of PFHBII. Subsequently, linkage analysis was used to test described dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and cardiac conduction-causative loci on chromosomes 1, 2, 3, 6, 7, 9, 11, 14, 15 and 19 for their involvement in the development of PFHBII. Once a locus was mapped, bioinformatics tools were applied to identify and prioritise positional candidate genes for mutation screening. The retrospective and prospective clinical study redefined PFHBII as a cardiac conduction and DCM-associated disorder and simultaneously allowed more family members to be traced.Fortuitously, candidate loci linkage analysis mapped the PFHBII locus to chromosome 1q32, to a region that overlapped a previously described DCM-associated disorder (CMD1D), by the generation of a maximum pairwise lod score of 3.13 at D1S3753 (theta [θ]=0.0) and a maximum multipoint lod score of 3.7 between D1S3753 and D1S414. However, genetic fine mapping and haplotype analysis placed the PFHBII-causative locus distal to the CMD1D locus, within a 3.9 centimorgan (cM) interval on chromosome 1q32.2-q32.3, telomeric of D1S70 and centromeric of D1S505. Bioinformatics analyses prioritised seven candidate genes for mutation analysis, namely, a gene encoding a potassium channel (KCNH1), an extracellular matrix protein (LAMB3), a protein phosphatase (PPP2R5A), an adapter protein that interacts with a cytoskeletal protein (T3JAM), a putative acyltransferase (KIAA0205) and two genes encoding proteins possibly involved in energy homeostasis (RAMP and VWS59). The PFHBII-causative mutation was not identified, although single sequence variations were identified in four of the seven candidate genes that were screened. Although the molecular aetiology was not established, the present study defined the underlying involvement of DCM in the pathogenesis of PFHBII. The new clinical classification of PFHBII has been published (Fernandez et al., 2004) and should lead to tracing more affected individuals in South Africa or elsewhere. The identification of a novel disease-causative locus may point toward the future identification of a new DCM-associated aetiology, which, in turn, might provide insights towards understanding the associated molecular pathophysiologies of heart failure. / AFRIKAANSE OPSOMMING: Hartversaking as gevolg van kardiomiopatie of kardiale geleidingsiekte is ‘n hoof-oorsaak van mortaliteit and morbiditeit in beide ontwikkelde en ontwikkelende lande. Alhoewel gedefinieer as verskillende kliniese entiteite is oorerflike vorms van kardiomiopatie en kardiale geleidingsstoornisse geïdentifiseer met oorvleuelende kliniese eienskappe en/of molukulêre oorsake. Die doelwit van hierdie studie was om die molukulêre oorsaak van progressiewe familiële hartblok tipe II (PFHBII), ‘n oorerflike kardiale geleidingsstoornis, wat in ‘n Suid-Afrikaanse Kaukasiër familie segregeer (Brink en Torrington, 1977), te identifiseer. Die beskikbaarheid van familie data, beteken dat koppelingsanalise gebruik kan word om die chromosomale posisie van die siekte-veroorsakende geen te identifiseer. Menslike Genoom Projek (MGP) databanke het addisionele hulpbronne beskikbaar gestel om die identifikasie van posisionele kandidaat gene te vergemaklik. Kliniese ondersoeke is uitgevoer op PFHBII-geaffekteerde familielede, en waar beskikbaar is kliniese rekords van persone, wat in ‘n vorige studie deur Brink en Torrington (1977) geassesseer was, herontleed. Retrospektiewe data-analise het die kliniese herdefinisie van PFHBII voorgestel. Daarna is koppelingsanalise gebruik om dilateerde kardiomiopatie (DKM), hipertrofiese kardiomiopatie (HKM) en kardiale geleidingssiekte-veroorsakende loki op chromosoom 1, 2, 3, 6, 7, 9, 11, 14, 15 en 19 te ondersoek vir hul moontlike bydrae tot die ontwikkeling van PFHBII. Toe die lokus gekarteer was, is bioinformatiese ondersoeke gebruik om posisionele kandidaat gene te identifiseer en prioritiseer vir mutasie analise. Die retrospektiewe en prospektiewe kliniese ondersoek het PFHBII herdefinieer as ‘n geleidingsstoornis en DKM-verbonde siekte, en terselfde tyd het dit gelei tot die opsporingvan nog familielede. Toevallig het kandidaat loki-analise die PFHBII lokus op chromosoom 1q32 gekarteer, na ‘n gebied wat met ‘n voorheen-beskyfde DKM-verbonde stoornis (CMD1D) oorvleuel, met die opwekking van ‘n makisimum paargewyse lod-getal van 3.13 by D1S3753 (theta [θ] = 0.0) en ‘n maksimum multipunt lod-getal van 3.7 tussen D1S3753 en D1S414. Genetiese fynkartering en haplotipe-analise het die PFHBII-veroorsakende lokus afwaards van die CMD1D lokus geplaas, in ‘n 3.9 centimorgan (cM) gebied op chromosoom 1q32.2-q32.3, telomeries van D1S70 en sentromeries van D1S505. Bioinformatiese analise het daarnatoe gelei dat sewe kandidaat gene vir mutasie analise geprioritiseerd is, naamlik, gene wat onderskeidelik ‘n kalium kanaal (KCNH1), ‘n ekstrasellulêre matriksproteïen (LAMB3), ‘n proteïen fosfatase (PPP2R5A), ‘n aansluiter proteïen wat met ‘n sitoskilet proteïen bind (T3JAM), ‘n asieltansferase (KIAA0205) en twee gene moontlik betrokke in energie homeostase (RAMP en VWS59) enkodeer. Die PFHBII-veroorsakende geen is nie geïdentifiseer nie, alhoewel enkele volgorde-wisselings geïdentifiseer is in vier van die sewe geanaliseerde kandidaat gene. Alhowel die molekulêre oorsaak van die siekte nie vasgestel is nie, het die huidige studie die onderliggende betrokkenheid van DKM in die pathogenese van PFHBII gedefinieer. Die nuwe kliniese klassifikasie van PFHBII is gepubiliseer (Fernandez et al., 2004) en sal lei tot die identifisering van nog geaffekteerde persone in Suid Afrika of in ander lande. Die identifikasie van ‘n nuwe siekte-verbonde lokus mag lei tot die toekomstige identifikasie van ‘n nuwe DKM-verbonde genetiese oorsaak wat, opsig self, dalk insig kan gee in die molekulêre patofisiologie van hartversaking.

Three non-peripherally substituted liquid crystalline bisphthalocyanine (Pc) compounds have been studied to examine the role of central metal ions lutetium (Lu), and gadolinium (Gd) and substituent chain lengths, i.e. octyl (C8H17) and hexyl (C6H13), in determining the physical properties. For the octyl substituted Pc molecules, the head-to-tail or Jaggregates within the as-deposited spun films produced a redshift of the optical absorption Q bands in relation to their 0.01 mgml-1 solutions. Annealing at 80˚C produced a well-ordered discotic liquid crystalline (LC) mesophase causing additional redshifts irrespective of the metal ion in case of C8LuPc2 and C8GdPc2. Formation of face-to-face or H-aggregated monomers led to blueshifts of the Q bands with respect to solution spectra for C6GdPc2, both as-deposited and annealed films. Stretching and bending vibrations of pyrrole, isoindole, and metal-nitrogen bonds in Pc rings showed Raman bands at higher energy for smaller metal ion. However, no change was observed for the difference in chain lengths. As-deposited C8LuPc2 and C6GdPc2 produced comparable Ohmic conductivity, of the value 67.55 Scm-1 and 42.31 Scm-1, respectively. C8GdPc2 exhibited two orders of magnitude less conductivity than the other two due to the size effect of the central ion and side chain length. On annealing, an increase of Ohmic conductivity was noticed in the isostructural octyl substituted phthalocyanines on contrary to a reduced conductivity in hexyl substituted one. An optical band shift of the C8LuPc2 and C8GdPc2 thin films occurred on oxidation by bromine vapour. Oxidations of Pc-coated ITO were also achieved by applying potential at 0.88 V and 0.96 V electrochemically for the C8LuPc2 and C8GdPc2 compounds, respectively. To explore the applications of these compounds in biosensing, in situ interaction studies between bromine oxidised compounds and biological cofactors nicotinamide adenine dinucleotide (NADH) and L-ascorbic acid (vitamin C) were carried out using optical absorption spectroscopy. Thin films of a non-peripherally octyl substituted LC lead phthalocyanine was exposed to 99.9 % pure hydrogen sulfide gas to produce hybrid nanocomposites consisting of lead sulphide quantum dots embedded in the analogous metal free phthalocyanine matrix. Trapping of charge carriers caused hysteresis in the current-voltage characteristics of the film on interdigitated gold electrodes. The charge hopping distance was found to be 9.05 nm, more than the percolation limit and responsible for forming two well-defined conducting states with potential application as a memristor.

<p>Experiments shows that the conductance of a quantum point contact is quantized in steps of  2e²/h, where e is the charge of the electron and h is Planck’s constant, and thereby Ohm’s law is not valid for nanostructures. By using the approximation method finite difference, the transmission for one-dimensional contacts and one- and two-dimensional potentials are investigated. In the case of two-dimensional contacts and a two-dimensional potential the Green’s function method is used. It turns out that if electrons are treated as waves, the transmission and the conductance just differ by the constant 2e²/h, which in this thesis is interpreted numerically in Matlab by using the Green’s function method.</p>

In this thesis investigations into chemically modified graphene structures are presented. Chemical functionalization of graphene is the chemical attachment of molecules or atoms to the graphene surface via covalent or Van der Waals bonds, this process offers a unique way to tailor the properties of graphene to make it useful for a wide range of device applications. One type of chemical functionalization presented in this thesis is fluorination of graphene which is the covalent attachment of fluorine to the carbon atoms of graphene and the resultant material is fluorographene which is a wide band-gap semiconductor. For low fluorine coverage the low temperature electron transport is through localized states due to the presence of disorder induced sub-gap states. For high fluorine coverage the electron transport can be explained by a lightly doped semiconductor model where transport is through thermal activation across an energy gap between an impurity and conduction bands. On the other hand, at low temperatures the disorder induced sub-gap density of states dominates the electrical properties, and the conduction takes place via hopping through these localized states. In this thesis it is also shown that electron beam irradiation can be used to tune the coverage of fluorine adatoms and therefore control energy gap between the impurity and conduction bands. Futhermore, electron beam irradiation also offers a valuable way to pattern conductive structures in fluorinated graphene \textit{via} the irradiation-induced dissociation of fluorine from the fluorinated graphene. This technique can be extended to the patterning of semiconducting nano-ribbons in fluorinated graphene where the spatial localization of electrons is just a few nm. The second type of chemical functionalization presented in this thesis is the intercalation of few layer graphene with ferric chloride which greatly enhances the electrical conductivity of few layer graphene materials making them the best known transparent conductors.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

BACKGROUND: His bundle pacing (HBP) is a relatively new treatment modality for patients experiencing issues with the cardiac conduction system. The treatment is thought to be an advantageous therapy compared with the standard treatment because it uses the native conduction pathway instead of introducing a non-physiological correction pathway which has been documented to increase the risk of heart failure. First carried out in humans in 2000 (Deshmukh, Casavant, Romanyshyn, & Anderson, 2000), HBP has been shown to be superior to right ventricular pacing and equivalent to cardiac resynchronization therapy. Because of the relative recency of the application of this technique in humans, there is a need for more studies to understand the long-term effectiveness and to guide training for new clinicians. 
OBJECTIVES: The objectives of this study were to (1) define the utility of three-dimensional mapping as a guiding tool for lead placement in HBP, (2) investigate the electroanatomical imaging of the atrioventricular (AV) septum, bundle of His, and other areas of the conduction system, (3) apply these observations to guide optimal pacing lead placement in the clinical setting, and (4) describe the correction of right and left bundle branch blocks by HBP. METHODS: Patients with pacemaker indication due to diseased conduction system were identified and recommended to undergo His bundle lead implantation. The lead was navigated into the heart by fluoroscopy and progressing the catheter through the axillary, subclavian, and cephalic veins. During the procedure, electroanatomical mapping was conducted by a quadripolar catheter to guide lead placement. His cloud, non-selective capture, and selective capture areas were marked and used to generate a 3D model layering the patient conduction system onto the physical anatomy. Pacemapping was then utilized to identify the most suitable area for disease correction.
Results: HBP mapping data were available in 24 patients. Several different responses to pacemapping were observed in the area of the AV septum including selective HBP (S-HBP), non-selective HBP (NS-HBP) (with upper, lower, and common variants), and right bundle branch (RBB) capture. Capture areas were superimposed onto the 3D model in real time and used to guide lead implantation for purposes of correcting various forms of conduction disease. The use of electroanatomical mapping (EAM) reduced the need for fluoroscopic guidance compared with the non-EAM-assisted procedure. Four common patterns were observed while mapping: (1) pattern 1, selective capture surrounded by upper and lower non-selective regions of capture; (2) pattern 2, selective capture surrounded by a common non-selective region of capture; (3) pattern 3, two separate non-selective capture areas with no selective capture; (4) pattern 4, common non-selective capture area with no selective capture. There was no correlation between capture threshold voltage and location of non-selective capture. Also, no correlation was found between capture threshold voltage and presence of common non-selective versus upper and lower non-selective capture areas. Patients with left bundle branch block (LBBB) and RBBB had similar His capture anatomy and were correctable by NS-HBP. CONCLUSIONS: HBP guided by electroanatomical mapping should be considered as a standard approach during pacemaker implantation. Because the underlying conduction anatomy is variable among patients, the use of EAM can direct lead positioning at a more physiologic location. In addition, EAM-guided implantation can reduce the need for fluoroscopy.

Utilizamos nesta pesquisa 40 corações de cães adultos, 17 machos e 23 fêmeas, de idades variadas, que não portavam macroscopicamente nenhuma afecção cardíaca. Os corações tiveram as artérias coronárias injetadas, separadamente, com Neoprene Látex 450, corado com pigmento vermelho, e posteriormente dissecados. Em todas estas preparações verificamos que na vascularização dos ventrículos predominava a artéria coronária esquerda que fornecia os ramos interventriculares paraconal e subsinuoso. Já, a região ocupada pelo nó sinoatrial ficava mais frequentemente (17 vezes 42,5%) na dependência do ramo proximal atrial esquerdo ou de colateral deste vaso, oriundo do ramo circunflexo esquerdo, ou deste vaso associado ao ramo distal atrial direito (8 vezes 20%), procedente do ramo circunflexo direito. Com menor frequência (14 vezes 30%), a área tomada pelo nó sinoatrial, encontramos apenas colaterais do ramo circunflexo direito, mais exatamente somente o ramo distal atrial direito (10 vezes 25%), apenas o ramo proximal atrial direito (3 vezes 7,5%) ou ainda exclusivamente o ramo intermédio atrial direito (1 vez 2,5%). Em um único caso (1 vez 2,5%) no território do nó sinoatrial observamos apenas colateral do ramo circunflexo esquerdo, isto é o ramo distal atrial esquerdo. A análise destes resultados permite concluir, que nesta espécie não existe qualquer tipo de relação entre o tipo de vascularização dos ventrículos e a irrigação do nó sinoatrial. / In this research we analyzed 40 hearts of adult dogs, males and females with different ages, which had no cardiac disease. The hearts had the coronary arteries inject using Neoprene Latex 450, stained by red pigment and then were dissected. In the ventricular vascularization the left coronary artery was predominant and it gave rise to the branches paraconal interventricular and subsinuous. The region occupied by the sinoatrial node was most frequently (17 times 42.5%) in the dependence of the left atrial proximal branch or in the collateral of that vessel, coming from the left circumflex branch, or this vessel associated to the right atrial distal branch (8 times 20%). With less frequency (14 times 30%), in the area occupied by the sinoatrial node, we found only the collaterals of the right circumflex branch, rather only the right atrial distal branch (10 times 25%), only the right atrial proximal branch (3 times 7.5%) or exclusively through the right atrial intermediary branch (1 time 2.5%). In just one case (Once 2.5%) in the area of the sinoatrial node we observed only the collateral of the left circumflex branch, i.e. the left atrial distal branch. According to our results we concluded that in this specie there are no relation between the type of vascularization of the ventricles and the irrigation of the sinoatrial node.

Nesta dissertação relatamos os resultados de medidas elétricas realizadas, a maioria delas, em folhas de 25&#956m de polivinilidene de flúor (PVDF), e em menor número em folhas de tetrafluoretileno-hexafluorpropileno (Teflon FEP). Correntes de polarização sob variadas tensões e de despolarização foram medidas a várias temperaturas e com temperatura variável. O PVDF sofre modificações, possivelmente estruturais, sob aquecimento acima de 100&#176C quando um campo elétrico parece produzir uma limpeza elétrica, resultando uma condutividade menor. As polarizações são do tipo t-n, indicando, no caso do PVDF uma distribuição em freqüências e para o FEP tratado termicamente a 200&#176C, uma em energia. Apesar das amostras de PVDF fornecerem resultados pouco reprodutíveis, pode-se concluir que para os campos empregados o comportamento é razoavelmente linear na polarização e superlinear para a condutividade. Observou-se também um comportamento anômalo da corrente, no PVDF, sob a ação prolongada de campo aplicado, mesmo para as menores tensões. Para o FEP o comportamento da corrente para os diversos campos usados foi bastante irregular embora as polarizações e as subseqüentes despolarizações coincidissem na maioria dos casos / We present here the results of electrical measurements performed, most of them, in 25&#956m foils of polyvinylidene fluoride (PVDF), and fewer in flois of tetrafluorethilene-hexafluorpropilene (Teflon FEP). Polarization currents under varied applied voltages and the corresponding depolarizations were measured at constante temperature and during heating and cooling. The PVDF exhibits modifications, possibly its structure changes, if heated above 100&#176C; in this case an electric field seems to clean the sample since its conductivity strongly decreases thereafter. The polarizations are of the t-n type, poiting to a distribution of frequencies inPVDF and of energies in FEP previously annealed at 200&#C. Although the results are poorly reproducible, some conclusions could be drawn for the PVDF: the polarization is nearly linear with the field but the conductivity shows a super linear dependence. An anomalous behavior of the current was observed at long time under tension, even the smallest use here. In the case of FEP, the magnitude of the current in relation with the voltage hás shown an irregular behavior, although polarization and the corresponding depolarization do indeed coincide in most cases