Thesis (Ph. D.)--University of Adelaide, Dept. of Applied Mathematics, 1987. / Includes bibliographical references (leaves 184-190).

Thesis (MEng) - Industrial Research Institute Swinburne, Swinburne University of Technology, 2003. / Thesis submitted for the degree of Master of Engineering by Research, Industrial Research Institute Swinburne, Swinburne University of Technology, 2003. Typescript. Includes bibliographical references (p. 159-169).

Thesis (Ph. D.)--Michigan State University. Dept. of Electrical and Computer Engineering, 2008. / Title from PDF t.p. (viewed on July 22, 2009) Includes bibliographical references (p. 294-312). Also issued in print.

Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2010. / Committee Co-Chair: Ajit Yoganathan; Committee Co-Chair: Ari Glezer; Committee Member: Rudy Gleason. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph.D.)--University of Iowa, 2006. / Includes separate files for thesis supplements. Supervisor: H.S. Udaykumar. Includes bibliographical references (leaves 182-195).

Canine myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs affecting all breeds, and it shares many similarities with the equivalent human disease. From the only transcriptomic report for canine MMVD published in 2006, serotonin signalling was identified as a contributing factor and has been widely studied since. Two transcriptomic profiling studies in human MMVD have also identified oxidative stress response and bone morphogenic protein signalling contributing to disease pathology. All studies at the transcriptional level have identified a variety of biological functions in MMVD suggesting dynamic extracellular matrix (ECM) remodelling processes are on-going. Moreover, cellular changes found in MMVD are somewhat reminiscent of the events seen in early heart valve, suggesting possible re-activation of signalling pathways of which those driving development and endothelial-to-mesenchymal transition (EndoMT) are particularly interesting. EndoMT, in which endothelial cells change their identity to mesenchymal phenotype and migrate into the cardiac jelly underneath the endothelium, is a crucial mechanism in valvulogenesis. Whether or not gene regulation of EndoMT and valve development also plays a role in MMVD is unknown. In this study, the MMVD cellular changes in the Cavalier King Charles Spaniel (CKCS), a breed with the highest prevalence, earliest onset, and rapid progression of the disease, was investigated. Secondly, transcriptional profiling was conducted using the latest canine microarray chips, a single affected breed (CKCSs), stringent sample quality control and statistical thresholds, with quantitative polymerase chain reaction (Q-PCR) for data validation. After transcriptional mapping, multi-platform in silico analysis was conducted to identify relationship between differentially expressed genes and their relevant biological functions. Next, a comparison study using immunohistochemistry was performed on different severities of myxomatous valves to localize the proteins of interest. Finally, to model the transcriptional factors and their downstream targets, mitral valve endothelial cell (MVEC) clones were derived from the canine normal mitral valves for future in vitro studies. Cellular changes of MMVD between CKCS and non-CKCS populations showed no difference in their distribution, number and phenotypic markers. Global genomic expression analysis identified similar (inflammation, up-regulation of serotonin receptor and bone morphogenic protein) and novel biological functions (epithelial-to-mesenchymal transition) compared to the previous study in 2006. Key transcriptional factors and genes associated with EndoMT including SNAI1, TAGLN, ACTA2, ACTG2, HAS2, and CTNNB1 were found up-regulated, and NID1, LAMA2, CDH5 were down-regulated in the MMVD group. In myxomatous mitral valves, increased expression of HAS2 in myofibroblasts, SNAI1 expression in endothelial cells, and co-expression of CDH5 and α-smooth muscle actin (α-SMA) also suggested the presence of EndoMT compared to normal valves. Nevertheless, there is also evidence of EndoMT in normal valves (α-SMA positive endothelial cells) which might suggest contribution to life-long valve re-modelling. In addition, there was a decreased expression of microRNAs associated with modulation of extracellular matrix transcripts, including miR-23, miR-29, and miR-218, indicating epigenetic regulation in MMVD. Based on the cellular changes, MMVD in CKCS appears to be representative of MMVD in all breeds and the early-onset of MMVD in that breed does not lead to different end-stage pathology. Novel biological functions such as EndoMT, were identified by transcriptional profiling, and by using powerful bioinformatic tools providing insight into understanding gene regulation in MMVD. Furthermore, a relationship between developmental biology processes and MMVD pathogenesis was established, with a likely important role for epigenetics in disease pathogenesis.

No description available.

The mitral valve in the heart sometimes struggles with diseases and complications, and needs to be replaced. This problem becomes more frequent with the ageing of the population in developed countries. The most common practice consists of suturing a prosthetic valve into place. However, newer methods are being devised and tested to make the surgery faster and less invasive. In particular, various types of new sutureless heart valve systems exist on the market. However, there is still a need for a tool designed for the intracardiac delivery and anchoring of a prosthetic mitral valve, as addressed here. A number of criteria and specifications were set by researchers at the Robarts Research Institute (London, ON) who came up with the design task. To address their request, ten conceptual designs of a sutureless, virtual-reality guided, self-anchoring, intracardiac system were developed to hold a prosthetic mitral valve, deliver it safely, and quickly affix it in position. The winning concept adequately met the design criteria. Two prototypes were manufactured. The attachment of a prosthetic valve to a simulated mitral valve annulus was tested with the first prototype to verify feasibility and measure leakage. The second prototype was pressure tested in a dynamic surgical phantom reproducing the circulatory conditions during surgery. While the preliminary feasibility of the concept was established, recommendations were made to develop a less bulky design.

One of the major achievements in cardiac surgery over the past 30 years has been the ability to replace severely diseased heart valves with prosthetic ones. The option of using prosthetic heart valves for the treatment of valvular diseases has improved and prolonged many lives. This is reflected in around 120,000 heart valve replacement operations carried out every year in North America alone to correct the cardiovascular problems of stenosis, insufficiency, regurgitation, etc. The development of artificial heart valves depends on reliable knowledge of the hemodynamic performance and physiology of the cardiovascular system in addition to a sound understanding, at the fundamental level, of the associated fluid mechanics. It is evident from the literature review that noninvasive measurements in a confined area of complex transient geometry, providing critical information relating to valve performance, are indeed scarce. This thesis presents results of an extensive test program aimed at measuring turbulence stresses, steady and transient velocity profiles and their decay downstream of the mitral valve. Three mechanical tilting disc-type heart valves (Björk-Shiley convexo- concave, Björk-Shiley monostrut, and Bicer-Val) and two biological tissue valves (Hancock II and Carpentier-Edwards supraannular) are studied. The investigation was carried out using a sophisticated and versatile cardiac simulator in conjunction with a highly sensitive, noninvasive, two-component three-beam laser doppler anemometer system. The study covers both the steady (valve fully open) and pulsatile (resting heart rate) flow conditions. The continuous monitoring of the parametric time histories revealed useful details of the complex flow as well as helped establish location and timing of the peak parameter values. In addition, orientation experiments are conducted on the mechanical valves in an attempt to reduce stresses by altering the position of the major orifice. The experiments suggest correlation between high stresses and orientation. Based on the the data, the following general conclusions can be made: (i) Hemodynamic test results should be presented in nondimensional form to render them independent of test facilities, flow velocities, size of models, etc. This would facilitate comparison of results by different investigators, using different facilities and test conditions. (ii) The valves tested showed very disturbed flow fields which generated high turbulent stresses presenting a possibility of thromboembolism and, perhaps, haemolysis. (iii) Implantation orientation of the valve significantly affect the mechanical prostheses flow field. The single vortex formation in the posterior orientation results in a reduction in stresses compared to the anterior configuration. (iv) The present results together with the earlier information on pressure drop and regurgitation provide a comprehensive and organized picture of the valve performance. (v) The information is fundamental to the improvement in valve design, and development of guidelines for test methodology and acceptable performance criteria for marketing of the valves. / Applied Science, Faculty of / Mechanical Engineering, Department of / Graduate

The Cu/NiFe/Cu/Co/(CoOx) spin-valves have been prepared by the ion-beam sputtering method. Their GMR ratio and the time stability have been investigated by the magnetoresistance and the MOKE measurements at room temperature. The reproducibility of the preparation of the samples have been studied as well, i.e. two identically configurations of the layers should have the same magnetotransport properties.