Introduction: Excitability in cardiomyocytes is dependent on the subthreshold current required to raise transmembrane potential to the activation threshold and subsequent recruitment of voltage gated sodium channels to trigger an action potential. Conduction in cardiomyocytes is dependent on the robustness and speed of action potential propagating through tissue. Both are equally important for normal heart function and claim to be linear correlated (i.e if conduction decreases, excitability decreases) Cardiac sodium channels are densely expressed in the intercalated disc within the perinexus, which is two orders of magnitude narrower than bulk extracellular interstitium. The biphasic relationship between conduction and perinexus is well-researched and consistent between computations models. We hypothesized a biphasic relationship between Excitability and perinexal width (Wp). In addition, we hypothesize that the relationship between excitability and conduction is not linear but dependent on the original width of the perinexus. Methods/and Results: Ex vivo guinea pig hearts were epicardially paced and optically mapped to assess ventricular conduction and excitability. Strength-duration curves were constructed for pacing stimuli to measure rheobase (inversely correlated to excitability). Computation models incorporating ephaptic coupling and sodium channel localization to cleft widths between cardiomyocytes demonstrate these findings. Conclusion: Models and experiments reveal that the excitability and perinexus relationship is biphasic where narrowing and widening perinexus decreases conduction and excitability thus showing a linear relationship between excitability and conduction. However, the excitability and conduction become overly complex in the transition phase from release of self-attenuation to reduced self-activation. Therefore, targeting ephaptic coupling and monitoring plasma ions may be a novel strategy for increasing the efficacy and efficiency of cardiac pacemakers. / Doctor of Philosophy / The heart is a muscular organ that uses electrical impulses to function. The heart is made of cells called cardiomyocytes that allow for electricity to flow through the cells. They are connected via different junctions such as gap junctions, adherens, etc. Any loss of electrical coordination leads to irregular heartbeats which can lead to heart death. There are two ways to study electrical coordination, excitability, how easy is for the current to start in the tissue, and conduction, how easy can that current travel through the tissue. Since the 1900s researchers have stated that if excitability decreases conduction decreases. In other words, if you need more current to start the heart (excitability decreases) then that current will travel slower through the tissue (conduction decreases) thus increasing one chances of irregular heartbeats. However, the understanding of how conduction works has changed but not of excitability. For example, originally current was thought to travel through channels called gap junctions. If you have limited availability of gap junctions, current increases (aka excitability decreases) and conduction decreases. However, other species such as frogs, fishes have limited number of gap junctions and can survive. Therefore, a new mechanism was proposed called ephaptic coupling. There is space next to the gap junctions called perinexus which is rich in a channel called Na channels, which is the main driving force for excitability and conduction. The lab has shown that if you change that space between cells, you can change the conduction response. In other words, if you decrease the space between the cells, conduction will not change therefore reducing the chances of irregular heartbeats. Therefore, my project is to understand if by changing this space between cells, is excitability and conductions are still correlates of each other. Using mathematical and animal models, this dissertation shows excitability and conduction have a very complicated relationship.

Shock wave interactions such as those that occur during atmospheric re-entry, can produce extreme thermal loads on aerospace structures. These interactions are reproduced experimentally in hypersonic wind tunnels to study how the flow structures relate to the deleterious heat fluxes. In these studies, localized fluid jets created by shock interactions impinge on a test cylinder, where the temperature due to the heat flux is measured. These measurements are used to estimate the heat flux on the surface as a result of the shock interactions. The nature of the incident flux usually involves dynamic transients and severe nonuniformities. Finding this boundary flux from discrete unsteady temperature measurements is characterized by instabilities in the solution. The purpose of this work is to evaluate existing methodologies for the determination of the unsteady heat flux and to introduce a new approach based on an inverse technique. The performance of these methods was measured first in terms of accuracy and their ability to handle inherently ``unstable'' or highly dynamic data such as step fluxes and high frequency oscillating fluxes. Then the method was expanded to estimate unsteady and nonuniform heat fluxes. The inverse methods proved to be the most accurate and stable of the methods examined, with the proposed method being preferable. / Ph. D.

Thesis (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Progressive familial heart block I (PFHBI) is an inherited autosomal dominant cardiac conduction disorder which segregates in a large South African (SA) pedigree, two smaller SA families and a Lebanese family. It specifically affects conduction in the ventricles and is of unknown cause. Clinically, PFHBI is detected on electrocardiogram (ECG) by evidence of bundle-branch disease, i.e., as right bundle branch block, left anterior or posterior hemiblock, or complete heart block with broad QRS complexes. The PFHBI-causative gene was mapped to a lOcM region on chromosome 19ql3.3 using linkage analysis, and the locus was subsequently reduced to 7cM by genetic fine mapping. The present study involved a multi-strategy approach to search for the PFHBI gene. The objectives were the further reduction of the PFHBI locus by genetic fine mapping using published and novel markers, searching for short gene transcripts from publicly available databases and the generation of an integrated map of the locus to which genes were mapped. Prioritised genes were screened for PFHBI-causing mutations and, in addition, the PFHBI locus was searched for the presence of a G protein-encoding gene (PI 15- RhoGEF), a connexin (Cx) gene and any genes containing a CTG repeat expansion motif, since these genes are plausible PFHBI candidate genes. Genotyping and fine genetic mapping using known and novel polymorphic dinucleotide (CA)n and novel tetranucleotide (A3G)n repeat markers across the PFHBI locus were performed. Publicly available databases, such as LLNL (Livermore, USA), and GENEMAP (NCBI) were searched for ESTs which, in turn, were extended using clustering programmes, such as UNIGENE (NCBI) and STACK (SANBI), and the resulting consensus sequences were subsequently BLAST-searched against the protein databases. Using the available data, an integrated physical and genetic map of the PFHBI locus was generated and, as the HGP progressed, a number of novel genes were placed thereon. Subsequently, genes were prioritised on the basis of position, function and expression profile. Genetic fine mapping reduced the PFHBI locus from 7cM to 4cM. The EST approach yielded 38 ESTs, of which 24 ESTs matched proteins, such as activating transcription factor 5 (ATF5), actin-binding protein (KPTN) and zinc finger protein 473 (ZFP473) (May 2003). All the map data generated experimentally and computationally were placed on the PFHBI map. The PI 15-RhoGEF was excluded as a PFHBI candidate gene and although homologous sequences to connexin 37 (Cx37) was located on both chromosome 19 radiation hybrid clones (RHG12 and ORIM-7), it was not identified on the DNA clones spanning the PFHBI locus. No evidence of an expansion of a CTG repeat motif sequence in PFHBI-affected individuals was found. Five highly prioritised candidate genes, namely, 5CZ2-associated X protein (BAX), potassium voltage-gated channel Shaker-related subfamily member 7 (KCNA7’), potassium inwardly-rectifying channel, subfamily J, member 14 (KIR2.4), lin-7 homolog B {LIN-7B) and glycogen synthase 1 (GSYI) were selected for mutation screening. No disease associated mutations were identified in the exonic and flanking intronic regions of these genes. In summary, this study reduced the PFHBI locus substantially and generated a detailed map of the region. A number of attractive candidate genes were excluded from causing PFHBI; however, several plausible candidate genes are still present at this gene-rich locus and remain to be screened. Identifying the PFHBI-causative gene and associated mutation will provide a platform for further studies to understand the pathophysiology, not only of PFHBI, but also of other more commonly occurring conduction disturbances. / AFRIKAANSE OPSOMMING: Progressiewe familiele hartblok I (PFHBI) is ‘n autosomaal dominant oorerflike kardiale geleidingstoomis wat in ‘n groot Suid-Afrikaanse (SA) familie, twee kleiner SA families en ‘n Lebanese familie segregeer. Dit affekteer hoofsaaklik die geleiding in die ventrikels en die oorsaak daarvan is onbekend. Klinies word PFHBI op elektrokardiogram (EKG) geidentifiseer as a bondeltak-siekte, naamlik, as regter bondeltakblok, linker anterior of posterior hemiblok, of volledige hartblok met wye QRS komplekse. Die PFHBI-veroorsakende geen is voorheen deur koppelingsanalise tot ‘n lOcM gebied op chromosoom 19ql3.3 gekarteer, en daaropvolgens is die lokus verklein tot 7cM deur genetiese fyn kartering. Die huidige studie behels ‘n veelvuldige-strategie benadering in die soektog na die PFHBI geen. Die doel van die studie was die verdere verkleining van die PFHBI lokus deur gebruik te maak van beide gepubliseerde en nuwe genetiese merkers, die identifisering van kort geentranskripte (ESTs) uit publieke databanke en die generasie van ‘n geintegreerde kaart van die lokus. Geprioritiseerde gene is geanaliseer vir die PFHBI-veroorsakende mutasie en, daarby, is die PFHBI lokus deursoek vir die teenwoordigheid van ‘n G proteien-enkodeeringsgeen (PIJ5-RhoGEF), ‘n konneksien (Kx) geen en enige gene wat ‘n uitgebreide CTG-herhalingsmotief bevat, aangesien hierdie gene as sterk PFHBI kandidaatgene geag is. Genotipering en fynkartering deur die gebruik van bekende asook nuwe polimorfiese dinukleotied- [(CA)n] en nuwe tertranukleotied- [(A3G)n] herhalingsmerkers wat die PFHBI lokus oorbrug, is uitgevoer. Publieke databanke, soos LLNL (Livermore, USA), en GENEMAP (NCBI) is ondersoek vir ESTs wat vervolgens verleng is deur gebruik te maak van groeperende programme soos UNIGENE (NCBI) en STACK (SANBI) en die gevolglike konsensus volgordes is daama met behulp van BLAST geanaliseer teen die protei'endatabanke. Die bekomde data is vervolgens gebruik om ‘n geintegreerde fisiese en genetiese kaart van die PFHBI lokus te produseer en, soos die mens genoomprojek gevorder het, is nuwe gene daarop geplaas. Daarna is gene geprioritiseer vir mutasie analise gebaseer op posisie, funksie en uitdrukkingsprofiele. Genetiese fynkartering het die PFHBI lokus van 7cM tot 4cM verklein. Die EST benadering het 38 ESTs gei'dentifiseer, waarvan 24 ESTs proteien gelyke gehad het, bv aktiverende transkripsie faktor 5 (ATF5), aktien-verbindingsprotei'en (KPTN) en sink-vingerproteien 473 (ZFP473) (Mei 2003). A1 die karterings data wat eksperimenteel en rekenaar-gewys gegenereer is, is op die PFHBI kaart geposisioneer. Die P115-RhoGEF is uitgeskakel as ‘n PFHBI kandidaatgeen en alhoewel ’n volgorde met homologie aan konneksien37 (Kx37) gevind is op albei chromosoom 19 radiasiehibried klone (RGH12 and ORIM-7), is dit nie gei'dentifiseer in die DNS klone wat die PFHBI lokus oorbrug nie. Geen bewyse van uitbreiding van CTG herhalingsmotiewe is gevind in PFHBIaangetasde persone nie. Vyf hoogs-geprioritiseerde kandidaat gene, naamlik, BCL2-geassosieerde X proteien (BAX), kalium spanningsbeheerde kanaal, subfamilie J, lid 14 (KIR2.4), lin-7 homoloog B (LIN-7b) en glikogeen sintase 1 (GYS1), is geselekteer vir mutasie-analise. Geen siekteveroorsakende mutasie is egter gei'dentifiseer in die eksoniese of die naasliggende introniese gebiede van hierdie gene nie. Ter opsomming, hierdie studie het die PFHBI lokus verklein en het ‘n omvattende kaart van die gebied gegenereer. Verskillende kandidaat gene is uitgesluit as die oorsaak van PFHBI, alhoewel daar nog heelwat goeie kandidaat gene in hierdie geen-ryke lokus is wat geanaliseer behoort te word. Die identifiseering van die PFHBI-veroorsakende mutasie sal ‘n platform bied vir verdere studies om die patofisiologie van nie alleen PFHBI nie, maar ook meer algemene geleidingstoomisse, te verstaan.

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Dans le cadre de cette thèse, il s’agit de voir l’influence de la composition du fluide sur le flux extrait. En effet l’eau utilisée pour le refroidissement des bandes d’acier en sortie de laminoir est recyclée et est potentiellement polluée par des résidus d’huile provenant de la lubrification des cylindres de laminoir. Nous avons conçu un dispositif expérimental original qui consiste à chauffer sur sa face supérieure un disque en Nickel à des températures de l’ordre de 600°C grâce à un dispositif d’induction électromagnétique et ensuite à le refroidir par un jet impactant. La face non refroidie est accessible à une mesure par thermographie infrarouge. Ces conditions de mesures nous ont permis d’estimer le flux extrait sur la face supérieure (lieu du refroidissement) à partir des mesures de température par thermographie infrarouge sur la face inférieure à l’aide d’un modèle de conduction inverse spécifiquement développé. Les résultats ont permis de montrer que la présence d’huile, si elle dégrade le flux maximal extrait dans certaines zones, conduit à une cinétique globale du refroidissement supérieure à celle de l’eau pure. / In this work, we are interested in the influence of the fluid’s composition on the cooling flux. In fact water used for cooling is recycled and can be potentially polluted by residues oil from the lubrication of rolling cylinder. We have designed an original experimental device which consists of heating a Nickel disk on its upper face at temperatures of 600°C through electromagnetic induction and then cooling it by jet impingement. The reverse face is available by infrared thermography measurements. These conditions allowed us to estimate the heat flux on the upper face (the cooling area) by infrared thermography measurements with a specific inverse heat conduction model. The results showed that the presence of oil, if it degrades the maximum cooling flux in some areas, led to a better overall cooling than that obtained with pure water.

by Tong Kwok Wang. / Parallel title in Chinese characters. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 71-74. / Acknowledgement / Abstract / Chapter 1. --- Introduction / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Properties --- p.5 / Chapter 1.3 --- Background of this research --- p.10 / Chapter 1.4 --- The Present Experiment --- p.11 / Chapter 2. --- Theory / Chapter 2.1 --- Conduction Mechanism --- p.15 / Chapter 2.2 --- Temperature Dependence of Thermal Conductivity --- p.16 / Chapter 2.3 --- Phonon Conductivity and phonon mean free path --- p.20 / Chapter 3. --- Experimental / Chapter 3.1 --- Thermal Diffusivity by Laser Photothermal Radiometry --- p.22 / Chapter 3.2 --- Resistivity Measurement --- p.30 / Chapter 3.3 --- Sample Preparation --- p.36 / Chapter 3.4 --- Data Analysis --- p.37 / Chapter 4. --- Results and Discussion / Chapter 4.1 --- Thermal Conductivity --- p.41 / Chapter 4.2 --- Electronic Thermal Conductivity --- p.47 / Chapter 4.3 --- Phonon Thermal Conductivity --- p.52 / Chapter 4.4 --- Phonon Mean Free Path --- p.58 / Chapter 5. --- Conclusion and Suggestions for Further Work --- p.68 / References --- p.71 / Appendixes --- p.75

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Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering. / Microfiche copy available in Archives and Engineering. / Includes bibliographical references. / M.S.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 17, 2007) Vita. Includes bibliographical references.

A steady state, axial flow thermal conductivity test apparatus was designed and constructed to operate between room temperature and approximately 4 Kelvin, and to be compatible with existing electronic instrumentation and a continuous flow cryostat. The test design included a radiation shield that had its temperature profile matched to that of the sample to minimize radiation heat transfer losses. The cryostat was used to provide the controllable, low temperature test environment in which the test apparatus would operate. A special wiring bundle was constructed to ensure proper connection of the test device to the required electronic instrumentation, which was controlled from a computer by custom written software. Once assembled, the thermal conductivity of a high purity copper sample was measured over the temperature range from 45 to 300 Kelvin and compared to literature recommended values. The test was performed a second time to check repeatability of the measurements over a range of temperature. Next, the thermal conductivity of a high purity niobium sample was measured and compared to literature recommended values. This test was also performed twice. When completed, these tests had demonstrated the accuracy and repeatability of the measurement of thermal conductivity by the test apparatus over the range of temperatures specified and over a range of conductivities. Finally, the thermal conductivity of a sample of the bulk metallic glass Vitreloy 1 was measured over the same temperature range. As far as was known, this was the first time the thermal conductivity of this particular material had been tested below 400 Kelvin. / Graduation date: 2003