To simplify the measurement of energy-based structural metrics, a general registration process for the scanning laser doppler vibrometer (SLDV) has been developed. Existing registration techniques, also known as pose estimation or position registration, suffer from mathematical complexity, instrument specificity, and the need for correct optimization initialization. These difficulties have been addressed through development of a general linear laser model and hybrid registration algorithm. These are applicable to any SLDV and allow the registration problem to be solved using straightforward mathematics. Additionally, the hybrid registration algorithm eliminates the need for correct optimization initialization by separating the optimization process from solution selection. The effectiveness of this approach is demonstrated through simulated application and by validation measurements performed on a specially prepared pipe. To increase understanding of the relationships between structural energy metrics and the acoustic response, the use of structural energy density (SED) in active structural acoustic control (ASAC) has also been studied. A genetic algorithm and other simulations were used to determine achievable reduction in acoustic radiation, characterize control system design, and compare SED-based control with the simpler velocity-based control. Using optimized sensor and actuator placements at optimally excited modal frequencies, attenuation of net acoustic intensity was proportional to attenuation of SED. At modal and non-modal frequencies, optimal SED-based ASAC system design is guided by establishing general symmetry between the structural disturbing force and the SED sensor and control actuator. Using fixed sensor and actuator placement, SED-based control has been found to provide superior performance to single point velocity control and very comparable performance to two-point velocity control. Its greatest strength is that it rarely causes unwanted amplifications of large amplitude when properly designed. Genetic algorithm simulations of SED-based ASAC indicated that optimal control effectiveness is obtained when sensors and actuators function in more than one role. For example, an actuator can be placed to simultaneously reduce structural vibration amplitude and reshape the response such that it radiates less efficiently. These principles can be applied to the design of any type of ASAC system.

Surface mean pressures, oil flow visualization, and 3-velocity-component laser-Doppler velocimeter measurements are presented for a turbulent boundary layer of momentum thickness Reynolds number, 7300 and thickness delta over two circular based axisymmetric bumps of height H = delta and 2delta and one rectangular based symmetric bump of H = 2delta. LDV data were obtained at one plane x/H ¥ 3.26 for each case. Complex vortical separations occur on the leeside and merge into large stream-wise mean vortices downstream for the 2 axisymmetric cases. The near-wall flow (y+ < 90) is dominated by the wall. For the axisymmetric cases, the vortices in the outer region produce large turbulence levels near the centerline and appear to have low frequency motions that contribute to turbulent diffusion. For the case with a narrower span-wise shape, there are sharper separation lines and lower turbulence intensities in the vortical downstream flow. Fine-spatial-resolution LDV measurements were also obtained on half of the leeside of an axisymmetric bump (H/delta = 2) in a turbulent boundary layer. Three-dimensional (3-D) separations occur on the leeside with one saddle separation on the centerline that is connected by a separation line to one focus separation on each side of the centerline. Downstream of the saddle point the mean backflow converges to the focal separation points in a thin region confined within about 0.15delta from the local bump surface. The mean backflow zone is supplied by the intermittent large eddies as well as by the near surface flow from the side of the bump. The separated flow has a higher turbulent kinetic energy and shows bimodal histograms in local and U and W, which appear to be due to highly unsteady turbulent motions. By the mode-averaged analysis of bimodal histograms, highly unsteady flow structures are estimated and unsteady 3-D separations seem to be occurring over a wide region on the bump leeside. The process of these separations has very complex dynamics having a large intermittent attached and detached flow region which is varying in time. These bimodal features with highly correlated local u and w fluctuating motions are the major source of large Reynolds stresses local u2, w2 and -uw. Because of the variation of the mean flow angle in the separation zones, the turbulent flow from different directions is non-correlated, resulting in lower shearing stresses. Farther from the wall, large stream-wise vortices form from flow around the sides of the bump. / Ph. D.

This dissertation presents the results from an experimental study of three-dimensional turbulent tip gap flow in a linear cascade wind tunnel with 3.3% chord tip clearance with and without moving endwall simulation. Experimental measurements have been completed in Virginia Tech low speed linear cascade wind tunnel. A 24" access laser-Doppler velocimeter (LDV) system was developed to make simultaneous three-velocity-component measurements. The overall size of the probe is 24"à 37"à 24"and measurement spatial resolution is about 100 μm. With 24" optical access distance, the LDV probe allows measurements to be taken from the side of the linear cascade tunnel instead of through the bottom of the tunnel floor. The probe has been tested in a zero-pressure gradient two-dimensional turbulent boundary layer. Experimental measurements (oil flow visualization, pressure measurement, and LDV measurement) for the stationary wall captured the major flow structures of the tip leakage flow in the linear compressor cascade, such as tip leakage vortex, tip leakage vortex separation and tip separation vortex. Large velocity gradients in the tip leakage vortex separation, tip leakage vortex, and tip separation vortex regions generate large production of the Reynolds stresses and turbulent kinetic energy. One of the most interesting features of the tip leakage flow is the bimodal velocity probability histograms of the v component due to the unsteady motion of the flow in the interaction region between the tip leakage vortex and tip leakage jet. The tip separation vortex, tip leakage vortex separation, and tip leakage vortex contain most of turbulent kinetic energy and generate the highest dissipation rate. Relative motion of the endwall significantly affects the tip gap flow structures, especially in the near wall region. Compared to the stationary wall case, velocity gradients in the near wall region for the moving wall case are much smaller and lower velocity gradients in the near wall region cause the low production of Reynolds stresses and turbulent kinetic energy. Similar to the stationary wall case, high Reynolds stresses and turbulent kinetic energy values are mainly located in the vicinity of the tip leakage vortex and tip separation vortex region. The bimodal velocity probability histograms of the v component are also found at the same locations. The tip separation vortex with most of the turbulent kinetic energy generates the highest dissipation rate. The dissipation rate in the tip leakage vortex region is reduced with the decrease of turbulent kinetic energy under the moving wall effect. / Ph. D.

The International Organization for Standardization (ISO) provides no vibration-based sound power measurement standard that provides Precision (Grade 1) results. Current standards that provide Precision (Grade 1) results require known acoustic environments or complex setups. This thesis details the Vibration Based Radiation Mode (VBRM) method as one approach that could potentially be used to develop a Precision (Grade 1) standard. The VBRM method uses measured surface velocities of a structure and combines them with the radiation resistance matrix to calculate sound power. In this thesis the VBRM method is used to measure the sound power of a single-plate and multiple plate system. The results are compared to sound power measurements using ISO 3741 and good alignment between the 200 Hz and 4 kHz one-third octave band is shown. It also shows that in the case of two plates separated by a distance and driven with uncorrelated sources, the contribution to sound power of each individual plate can be calculated while they are simultaneously excited. The VBRM method is then extended to account for acoustically radiating cylindrical geometries. The mathematical formulations of the radiation resistance matrix and the accompanying acoustic radiation modes of a baffled cylinder are developed. Numberical sound power calculations using the VBRM method and a boundary element method (BEM) are compared and show good alignment. Experimental surface velocity measurements of a cylinder are taken using a scanning laser Doppler vibrometer (SLDV) and the VBRM method is used to calculate the sound power of a cylinder experimentally. The results are compared to sound power measurements taken using ISO 3741.

No description available.

Peripheral artery disease (PAD) affects more than 200 million people worldwide. PAD refers to illness due to a reduction or complete occlusion of blood flow in the artery, especially to the extremities in disease conditions, such as atherosclerosis or diabetes. Critical limb ischemia (CLI) is a severe form of PAD associated with high morbidity and mortality. Currently, no effective and permanent treatments are available for this disease. The current endovascular medications (e.g., angioplasty or stents) only relieve the clinical symptoms while the surgical therapies (e.g., bypass or endarterectomy) require grafting vessels from a healthy organ to the diseased limb of the patient. However, even with these therapeutic techniques, 30% of patients still undergo limb amputation within a year. Thus, understanding of disease mechanism and development of new therapeutic approaches are in urgent needs. Meis1 (myeloid ecotropic viral integration site 1) gene belongs to the three-amino-acid loop extension subclass of homeobox gene families, and it is a highly conserved transcription factor in all eukaryotes. Up to date, little is known about the role of Meis1 in regulating vascular remodeling under ischemic condition. In this study, we aim to investigate the role and underlying mechanism of Meis1 in the regulation of arteriogenesis and angiogenesis using hindlimb ischemia model of transgenic neonatal mice. The long-term goal is to develop a new treatment for patients with PAD. Three separate but related studies were planned to complete the proposed research aims. To better understand the role of Meis1, we reviewed, in the first chapter, all literature relevant to the recent advances of the Meis1 in normal hematopoiesis, vasculogenesis, and heart developments, which were mostly studied in zebrafish and mouse. Briefly, Meis1 is found to be highly expressed in the brain and retina in zebrafish and additional in the heart, nose, and limb in mouse during the very early developmental stage, and remains at a low level quickly after birth. Meis1 is necessary for both primitive and definitive hematopoiesis and required for posterior erythroid differentiation. The absence of Meis1 results in a severe reduction of the number of mature erythrocytes and weakens the heart beats in zebrafish. Meis1 deficiency mouse is dead as early as E11.5 due to the severe internal hemorrhage. In addition, Meis1 is essential in heart development. Knock-down of Meis1 can promote angiotensin II-induced cardiomyocytes (CMs) hypertrophy or CMs proliferation, which can be repressed by a transcription factor Tbx20. Meis1 appears to play a complicated role in the blood vessels. Although the major blood vessels are still normal when global deletion of Meis1, the intersegmental vessel cannot be formed in Meis1 morphants in the zebrafish, and the small vessels are either too narrow or form larger sinuses in Meis1 deficient mouse. The effects of Meis1 on the vascular network under normal and disease (ischemia) condition remain largely unknown, and the existing data in this field is limited. In the second chapter, we developed a method protocol to identify mice of all ages, especially neonates that we faced methodological difficulties to easily and permanently label prior to our major experiments. In this study, single- or 2-color tattooing (ear, tail, or toe or combinations) was performed to identify a defined or unlimited number of mice, respectively. Tail tattooing using both green and red pastes was suitable for identifying white-haired neonatal mice as early as postnatal day (PND) 1, whereas toe tattooing with green paste was an effective alternative approach for labeling black-haired mouse pups. In comparison, single-color (green) or 2-color (green and red) ear tattooing identified both white and black adult mice older than three weeks. Ear tattooing can be adapted to labeling an unlimited number of adult mice by adding the cage number. Thus, tattooing various combinations of the ears, tail, and toes provides an easy and permanent approach for identifying mice of all ages with minimal disturbance to the animals, which shows a new approach than any existing method to identify mouse at all ages, especially the neonatal pups used in the present study (Chapter 4). Various formation of hindlimb ischemia with ligations of femoral artery or vein or both have been reported in the literature. The ischemic severity varies dependent on mouse strains and ligation methods. Due to the tiny body size of our experimental neonatal mice (PND2), it is technically challenging to separate the femoral artery from femoral vein without potential bleeding. In the third chapter, we aimed to explore a suitable surgical approach that can apply to neonatal mice. To this end, we compared the effects of femoral artery/vein (FAV) excision vs. femoral artery (FA) excision on hindlimb model using adult CD-1 mice. We showed during the 4-week period of blood reperfusion, no statistically significant differences were found between FAV and FA excision-induced ischemia regarding the reduction of limb blood flow, paw size, number of necrotic toes, or skeletal muscle cell size. We conclude that FAV and FA excision in CD-1 mice generate a comparable severity of hindlimb ischemia. In other words, FAV ligation is no more severe than FA ligation. These findings provide valuable information for researchers when selecting ligation methods for their neonate hindlimb models. Based on these findings, we selected FAV ligation of hindlimb ischemia approach to study the function of Meis1 in vascular remodeling of neonatal mice. In the fourth chapter (the main part of my dissertation), we investigated the roles of Meis1 in regulating arteriogenesis and angiogenesis of neonatal mouse under the ischemic condition. To this end, endothelial cell-specific deletion of Meis1 was generated by cross-breeding Meis1flox/flox mice with Tie2-Cre mice. Wild-type (WT, Meis1f/f) and endothelial cell-specific knock-out (KO, Meis1ec-/-Tie2-Cre+) C57BL/6 mice at the age of PND2 were used. Under the anesthesia, the pups were subject to hindlimb ischemia by excising FAV. Laser Doppler Imager was used to measure the blood flow pre- and post-surgery up to 28 days. Toe necrosis, skeletal regeneration, and vascular distributions were examined at the end of experiments (PND28 post-ischemia). Surprisingly, during 4-week periods after ischemia, the blood flow ratios (ischemic vs. control limb) in KO mice significantly increased compared to WT on PND14 and PND28, suggesting the inhibitory effects of Meis1 on blood flow recovery under ischemic condition. Meanwhile, WT mice showed more severe necrotic limb (lower ratio of limb length and area, and higher necrotic scores at PND7) than those in the KO mice. Furthermore, significant increases in diameters of Dil-stained arterioles of the skin vessel and the vessels on the ligation site were observed in KO mice, indicating the enhanced arteriogenesis in KO mice. To investigate the underlying mechanism, RNA from the ischemia and control limb was extracted and q-PCR was used to study the potential genes involved in the mechanism. Casp3 and Casp8 were found downregulated showing less apoptosis in the KO mice. On the other hand, endothelial cells (ECs) were isolated from the lungs of 3-5 WT and KO neonates using CD31 Microbeads. CD31+ cells were plated and treated with 0, 0.5, and 1μM doxorubicin for 24 hours and analyzed with various assays. Meis1-KO ECs demonstrated higher cell viability and formed a higher number of vascular tubes than those in WT ECs following 0.5μM Dox treatment, presenting the potential ability of angiogenesis in KO-ECs. Furthermore, the increased viability in KO ECs may be due to the decreased expression or activities of Casp8 and Casp3. In conclusion, my present studies have developed a new methodology to easily and permanently identify all mice at any ages. The insignificant differences between FAV and FA ligations suggest that a relative-easy surgical approach could be used to generate hindlimb ischemic model, which potentially reduces the cost, decreases the surgical time and prevents damage of femoral nerve from surgical tools. More importantly, by using transgenic mice, we found that Meis1-KO dramatically increased blood flow and protected the ischemic hindlimb through vascular remodeling. Obviously, the molecular and cellular mechanisms underlying the above beneficial effects appear complicated and likely to involve multiple cellular remodeling processes and molecular signaling pathways to enhance arteriogenesis and angiogenesis and/or reduce cellular apoptosis through Meis1-mediated pathways. Our study demonstrated that under ischemic condition, knockout of Meis1 increases expression of Hif1a, which then activates Agt or VEGF, thus enhances arteriogenesis or angiogenesis; In addition, knockout of Meis1 activates Ccnd1, which subsequently promotes regeneration of skeletal muscle, and reduces expression of Casp8 and Casp3, thus preventing limb tissue from ischemia-induced apoptosis. Our innovative findings offer great potential to ultimately lead to new drug discovery or therapeutic approaches for prevention or treatment of PAD. / PHD / Peripheral artery disease (PAD), which affects more than 200 million people worldwide, commonly refers to the vascular diseases of legs or feet due to a reduction or even complete occlusion of blood flow to these areas. PAD is usually caused by blockage of main vessels in limbs under certain diseases, such as atherosclerosis. Unfortunately, no effective and permanent treatments are available for this disease. The current medications only relieve the clinical symptoms while the surgical therapy requires grafting vessels from a healthy organ to the diseased limb of the patient. In the present study, we aim to explore a new approach to facilitate the vessel formation in ischemic limb using Meis 1 transgenic mice. Meis 1 (myeloid ecotropic viral integration site 1) gene belongs to homeobox gene families, and it is a highly conserved transcription factor in all eukaryotes. My dissertation aims to understand how Meis 1 affects vascular remodeling in the mouse following induced hindlimb ischemia (to mimic PAD). To better understand the role of Meis 1, we first reviewed the literature studying the Meis 1 function on normal hematopoiesis, vasculogenesis, and heart development in zebrafish and mouse. The studies show that Meis 1 plays a complicated role in the blood vessels. When entirely deleting Meis 1 in the zebrafish, the intersegmental vessels cannot be formed. While in a mammal study, it is found that the major blood vessels are normal while the small vessels are either too narrow or form larger sinuses in Meis 1 deficient mouse. Thus, Mesi1 appears to play an important role in regulating vascular network, but the available information in this field is insufficient. The present projects aimed to study the roles of Meis 1 in regulating vascular remodeling following the hindlimb ischemia induced by ligation of main limb vessels (to mimic PAD). The transgenic mice with the deletion of Meis 1 (called knockout or KO mice) were generated by a Cre-loxP system (a gene manipulation method) to remove Meis 1 only in endothelial cells. The resulting KO mice were subject to the hindlimb ischemia and compared to those mice with the intact Meis 1 (called wild-type, or WT). To this end, the entire experiments contain three separate studies. In the first studies (Chapter 2), we developed an easy, but a permanent method to identify the mice at all age, especially the neonatal mice we used in the projects. Briefly, we used single- or 2-color tattooing to identify a defined or unlimited number of mice, respectively. We labeled our adult mice with ear tattooing combined with cage number and neonatal mice with toe tattooing if necessary to identify the individual animals. Next (Chapter 3), we determined the effects of femoral artery/vein (FAV) ligation vs. femoral artery (FA) ligation alone on hindlimb severities. The purpose of this study was to generate a suitable ligation model for the neonatal mice. Interestingly, no statistically significant differences were found between FAV and FA excision-induced ischemia, suggesting that FAV ligation could be applied to the neonatal hindlimb ischemia model in the rest of study. Upon the establishment of identification and ligation approaches for neonatal mice, we conducted systemic studies at both in vitro and in vivo settings to investigate the biological function of Meis 1 under ischemic condition. Briefly, two groups of Meis 1 mice at ages of postnatal day 2 were used in the study: WT (the normal mice), and endothelial specific knock-out (KO, Meis 1 gene was entirely deleted in endothelial cells). Under anesthesia, the postnatal day 2 pups were induced hindlimb ischemia, and blood flow was measured pre- and post-ischemia up to 4 weeks. Our data demonstrated that the blood flow was significantly higher in KO mice than WT mice, suggesting deletion of Meis 1 in endothelial cells can increase blood perfusion following ischemic injury. Moreover, the KO mice showed less toe damage compared with WT, thus showing protective benefit in rescuing the damaged limb. We also found that deletion of Meis 1 in endothelial cells increased cell viability and induced generation of more numbers of vessels under an induced apoptosis condition. These findings suggested that the deletion of Meis 1 in endothelial cells facilitates vessel formation and prevents the injured limbs from loss or undergoing apoptosis/necrosis, which may lead new drug discovery and development of effective therapy for treatments of PAD.

Thesis (MScEng)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: This thesis investigates the feasibility of the laser Doppler vibrometer (LDV) for use in the autonomous auscultation of the human heart. As a non-contact measurement device, the LDV could become a very versatile biomedical sensor. LDV, stethoscope, piezoelectric accelerometer (PA) and electrocardiogram (ECG) signals were simultaneously recorded from 20 volunteers at Tygerberg Hospital. Of the 20 volunteers, 17 were confirmed to have cardiovascular disease. 3 patients with normal heart sounds were recorded for control data. The recorded data was successfully denoised using soft threshold wavelet denoising and ensemble empirical mode decomposition. The LDV was compared to the PA in common biomedical applications and found to be equally accurate. The heart sound cycles for each participant were segmented using a combination of ECG data and a simplicity curve. Frequency domain features were extracted from each heart cycle and input into a k-nearest neighbours classifier. It was concluded that the LDV can form part of an autonomous, non-contact auscultation system. / AFRIKAANSE OPSOMMING: Hierdie tesis ondersoek die haalbaarheid daarvan om die laser Doppler vibrasiemeter (LDV) vir die outonome beluistering van die menslike hart te gebruik. As 'n kontaklose meettoestel kan die LDV werklik 'n veelsydige biomediese sensor word. Twintig vrywilligers by die Tygerberg Hospitaal se LDV-, stetoskoop-, piësoelektriese versnellingsmeter (PV)- en elektrokardiogram (EKG) seine is gelyktydig opgeneem. Uit die 20 vrywilligers was daar 17 bevestigde gevalle van kardiovaskulêre siektes. Die data van drie pasiënte met normale hartklanke is as kontroledata opgeneem. Geraas is suksesvol uit die opgeneemde data verwyder deur 'n kombinasie van sagtedrempelgolf en saamgestelde empiriese modus ontladingstegnieke. Die LDV was vergelyk met die PV vir algemene biomediese gebruike en daar was gevind dat dit vergelykbare akkuraatheid het. Die hartklanksiklusse van elke deelnemer is gesegmenteer deur EKG data en 'n eenvoudskromme te kombineer. Frekwensiegebiedskenmerke is uit elke hartsiklus onttrek en in 'n k-naastebuurpunt klassifiseerder ingevoer. Daar is tot die gevolgtrekking gekom dat die LDV deel van 'n outonome, kontaklose beluisteringstelsel kan uitmaak.

La compréhension du système cardiovasculaire périphérique est une clé indispensable pour le diagnostic précoce de nombreuses pathologies. Les signaux de fluxmétrie laser Doppler donnent des informations sur la microcirculation sanguine et permettent ainsi d'avoir une vue périphérique du système cardiovasculaire. Ce travail de thèse s'inscrit dans l'étude des propriétés de ces signaux physiologiques. Dans un premier temps nous présentons la technique de fluxmétrie laser Doppler et son utilité en recherche clinique. Nous détaillons ensuite l'analyse que nous avons menée afin d'obtenir des informations sur l'origine des fluctuations observées sur les signaux. L'implémentation de différents outils de traitement du signal dans les domaines temporel et fréquentiel a permis de montrer que ces fluctuations pourraient provenir, en partie, des propriétés physiologiques et/ou anatomiques de la zone étudiée. Afin d'étudier plus en détails ces fluctuations, nous avons ensuite mis en place une analyse multifractale des signaux de fluxmétrie laser Doppler. Les différents résultats obtenus ont permis de faire ressortir la possible implication des propriétés physiologiques de la zone étudiée dans la complexité des signaux de fluxmétrie laser Doppler.

<p>The human stomach normally contains high levels of bioactive nitric oxide (NO). This NO derives from salivary nitrate (NO₃^-) that is converted to nitrite (NO₂^-) by oral bacteria and thereafter non-enzymatically reduced in the acidic gastric lumen to NO. Nitrate is a common component in vegetables, and after ingestion it is absorbed in the small intestine. Interestingly, circulating nitrate is then concentrated by the salivary glands. Hence, intake of nitrate-rich vegetables results in high levels of NO in the stomach. The physiological effects of the high concentration of NO gas normally present in the gastric lumen have been hitherto unknown, and the present investigations were therefore conducted to address this issue.</p><p>NO produced in the gastric lumen after nitrate ingestion increased gastric mucosal blood flow and the thickness of the firmly adherent mucus layer in the stomach. The blood flow and mucus layer are essential defense mechanisms that protect the mucosa from luminal acid and noxious agents. Nonsteroidal antiinflammatory drugs (NSAID) are commonly prescribed and effective drugs for treating pain and inflammation, but are associated with severe gastrointestinal side effects. We demonstrated that a nitrate-rich diet protects against NSAID-induced gastric damage, as a result of the increased formation of NO in the stomach. We also showed that the gastroprotective effect attributed to nitrate depended completely on conversion of nitrate to nitrite by the bacterial flora colonizing the tongue, and that the oral microflora is therefore important in regulating physiological conditions in the stomach.</p><p>In summary, this thesis challenges the current dogma that nitrate intake is hazardous, and on the contrary suggests that dietary nitrate plays a direct role in regulating gastric homeostasis. It is likely that a sufficient supply of nitrate in the diet together with the oral microflora is essential for preventing pathological conditions in the gastrointestinal tract.</p>

L'étude des écoulements turbulents supersoniques par Vélocimétrie Laser Doppler soulève de nombreuses difficultés spécifiques. Les fréquences élevées des fluctuations de vitesse posent notamment le problème de l'inertie des particules, aggravé par la basse densité de fluide. Dans le montage bidimensionnel, le processus de validation des signaux dépend fortement de la direction de la vitesse instantanée mesurée. Ces phénomènes dont les conséquences ont été mises en évidence dans les mesures sont largement étudiées et commentés. Nous avons développé et parfois optimisé le traitement statistique des données bidimensionnelles. Le traitement de l'intervalle de temps séparant les acquisitions laisse déjà entrevoir les difficultés majeures qui s'opposent à une exploitation systématique de cette donnée temporelle.