The deformation behaviour and twinning mechanisms of commercially pure titanium alloys were investigated using complementary diffraction techniques and crystal plasticity modelling. The main motivation for conducting this investigation was to improve understanding of the deformation of titanium to help achieve the long term aim of reducing manufacturing and design costs. The deformation behaviour was characterised with tension, compression and channel die compression tests for three important variables: orientation; temperature from 25 C to 600 C; and composition for two contrasting alloys, CP-G1 and CP-G4. The experimental data used to characterise the behaviour and determine the mechanisms causing it were: textures determined by X-ray diffraction; twin area fractions for individual modes determined using electron back-scatter diffraction; and lattice strains measured by neutron diffraction. A strong effect of the orientation–stress state conditions on the flow curves (flow stress anisotropy) was found. The propensity for prism hai slip was the dominant cause of the behaviour – samples that were more favourably oriented for prism hai slip had lower flow stresses. Twinning was the most significant secondary deformation mode in the CP-G1 alloy but only had a minor effect on flow stress anisotropy in most cases. In the CP-G4 alloy twinning generally did not play a significant role indicating that hc + ai slip modes were significant in this alloy. Differences in the flow stress anisotropy between the two alloys were found to occur largely in the elasto-plastic transition and initial period of hardening. Modelling results indicated that larger relative resolved shear stress values for secondary deformation modes in the higher purity alloy increased the initial anisotropy. Decreasing flow stresses with increasing temperature were largely caused by a decrease in the critical resolved shear stress (CRSS) values for slip, but also by a decrease in the Hall-Petch parameter for slip. The propagation of twinning was found to be orientation dependent through a Schmid law in a similar way to slip – it was activated at a CRSS and hardened so that an increasing resolved shear stress was required for it to continue operating. The CRSS values determined for the individual twin modes were – 65MPa, 180MPa, 83MPa for {1012}, {1122} and {1011} twinning, respectively. Further, twinning was found to be temperature insensitive except when the ability to nucleate twins posed a significant barrier (for {1011} twinning). Also, the CRSS for {1012} twinning was clearly shown to increase with decreasing alloy purity. A thorough method for determining crystal plasticity modelling parameters based on experimental data was formulated. Additionally, twinning was modelled in a physically realistic manner influenced by the present findings using the visco-plastic self-consistent (VPSC) model. In particular: the activity of twinning decreased in a natural way due to greater difficulty in its operation rather than through an enforced saturation; and hardening or softening due to changes in orientation and dynamic Hall-Petch hardening were important. The rigorous modelling procedure gave great confidence in the key experimental findings.

Atherosclerosis is an inflammatory disease which develops focally in regions of the vasculature where there is dysfunction of endothelial cells modulated in part by shear stress from flowing blood. To address the clinical crisis of atherosclerosis, tissue engineering has focused on development of a living blood vessel substitute for use as a vascular graft in bypass surgery. Despite substantial progress in understanding the biological basis and developing clinical treatments for cardiovascular disease, critical challenges remain. As a novel strategy to improve understanding of basic human vascular biology and develop superior tissue engineered grafts, this dissertation combines the scientific and clinical approaches by using a tissue engineered blood vessel as a more physiologic in vitro model to study endothelial cell biology. Through the use of transcriptional profiling, results demonstrate significant changes in endothelial cell gene expression using the tissue engineered blood vessel model. Furthermore, the presence of a more physiologic substrate alters the cellular response to shear stress which is a critical mediator of vascular pathology. A case study of endothelial cell function in this system focuses on cell-cell communication through gap junctions. Endothelial cell connexins which form gap junctions are shown to be differentially regulated by substrate and shear stress. Moreover, gap junction communication between endothelial cells is modulated by the mechanical environment. Studies using RNA interference to knockdown expression of individual connexin isotypes demonstrate integrated regulation of connexins yet unique roles in endothelial cell function. Collectively, results exemplify the sensitivity of endothelial cell phenotype to substrate and shear stress and underline the importance of using more physiologic models in the study of basic cell biology.

A new lattice-Boltzmann finite-element method is used to simulate large numbers of deformable red blood cells and platelets in suspension for the investigation of stress-mediated platelet-deposition mechanisms in blood. The coupled lattice-Boltzmann finite-element method provides the novel ability to simulate hundreds of realistic and deformable red blood cells and produce continuum-scale physics at physiologic hematocrit and low arterial-shear rates. The new method is developed and shown to produce single red blood cell deformation consistent with experimental results in flow chambers. Simulations of 77 to 216 cells in unbounded shear flow produce bulk and micro-rheological behavior consistent with experimental results in viscometers and tubes, including shear-thinning behavior at various shear rates. Investigation of the local stress environment in blood indicates that, although the majority of platelets experience a time-averaged shear stress equal to the suspension stress, 25% of platelets experience a localized shear stress greater than twice the suspension stress. The lattice-Boltzmann finite-element method developed in this work has been shown capable of investigating the fundamental gap between cell-level processes and continuum-level function. The complex stress environment in whole blood has been described for simple shear flow and the methodology may be extended to more complex flow geometries and incorporate platelet-adhesion models for adhesion studies. Thus, this research fits into the greater objective of prediction and control of platelet deposition in clinical and engineering applications. Furthermore, the ability to bridge the gap between cell-level processes and continuum-level function is useful in other important cardiovascular areas including leukocyte adhesion, platelet aggregate embolization, and artheriogenesis.

Turbulent mixed convection is a complicated flow where the buoyancy and shear forces compete with each other in affecting the flow dynamics. This thesis deals with the near wall dynamics in a turbulent mixed convection flow over an isothermal horizontal heated plate. We distinguish between two types of mixed convection ; low-speed mixed convection (LSM) and high-speed mixed convection (HSM). In LSM the entire boundary layer, including the near-wall region, is dominated by buoyancy; in HSM the near-wall region, is dominated by shear and the outer region by buoyancy. We show that the value of the parameter (* = ^ determines whether the flow is LSM or HSM. Here yr is the friction length scale and L is the Monin-Obukhov length scale. In the present thesis we proposed a model for the near-wall dynamics in LSM. We assume the coherent structure near-wall for low-speed mixed convection to be streamwise aligned periodic array of laminar plumes and give a 2d model for the near wall dynamics, Here the equation to solve for the streamwise velocity is linear with the vertical and spanwise velocities given by the free convection model of Theerthan and Arakeri [1]. We determine the profiles of streamwise velocity, Reynolds shear stress and RMS of the fluctuations of the three components of velocity. From the model we obtain the scaling for wall shear stress rw as rw oc (UooAT*), where Uoo is the free-stream velocity and AT is the temperature difference between the free-stream and the horizontal surface.A similar scaling for rw was obtained in the experiments of Ingersoll [5] and by Narasimha et al [11] in the atmospheric boundary layer under low wind speed conditions. We also derive a formula for boundary layer thickness 5(x) which predicts the boundary layer growth for the combination free-stream velocity Uoo and AT in the low-speed mixed convection regime.

L'hypertension artérielle (HTA) est l'une des pathologies les plus fréquentes et les plus préoccupantes des pays occidentaux. Elle est souvent associée au surpoids, à des maladies rénales, cardiaques et aussi à un dysfonctionnement du système endocrinien. Les désordres vasculaires compliquant l'HTA induite par le traitement par l'érythropoïétine recombinante (r-HuEPO) chez les patients ayant une maladie rénale chronique ou en lien avec une perturbation du système rénine-angiotensine-aldostérone (SRAA), associent une augmentation de la rigidité artérielle, une dysfonction endothéliale, un déséquilibre endothéline-1/monoxyde d'azote (ET-1/NO) et un état inflammatoire. L'inflammation vasculaire contribue à la physiopathologie de l'HTA par l'augmentation du stress oxydatif et l'activation des cellules immunitaires. Plusieurs études ont suggéré que le système immunitaire est impliqué dans le développement des maladies cardiovasculaires. Cependant le rôle des lymphocytes T régulatrices (Treg) dans l'HTA ou d'autres formes de maladies cardio-vasculaires, reste encore largement inconnu. Bien que la majorité des études ont montré que l'HTA induite par l'r-HuEPO est associée à une dysfunction endothéliale et à un déséquilibre du rapport (ET-1/NO), les mécanismes exacts restent à être identifier.Plusieurs études ont montré que l'exercice physique d'endurance prévient l'HTA chez les patients ou les modèles animaux. L'objectif de la première partie du travail est d'étudier l'impact du shear stress et de l'exercice sur les désordres vasculaires et l'HTA induits par l'r-HuEPO, en présence d'un déséquilibre endothélial (ET-1/NO). Pour ce faire, trois environnements ont été utilisés (in vitro (cellules en culture), in vitro (artères mésentériques (AM)) et in vivo (souris transgéniques sur-exprimant l'ET-1 au niveau de l'endothélium). Nos résultats montrent que l'association L-NAME/r-HuEPO est responsable d'une vasoconstriction flux-dépendante et une augmentation accrue du shear stress correspondant (plus de 25 dyn/cm2). Le Bosentan, inhibiteur non sélectif des récepteurs de l'ET-1, empêche la vasoconstriction flux-dépendante engendrée par la combinaison L-NAME/rHu-EPO, sans pour autant corriger la vasodilatation; Le traitement des souris transgéniques eET-1 avec l'r-HuEPO augmente la pression artérielle systolique, la concentration plasmatique en ET-1, le stress oxydatif, l'infiltration des monocytes et des macrophages aortiques (MOMA-2), le taux des cytokines pro-inflammatoire INF-γ, TNF-α et IL-6 et exacerbe la dysfonction endothéliale. L'exercice physique prévient tous les effets délétères engendrés par l'administration de l'r-HuEPO. Il est à noter aussi que l'exercice augmente le taux du Foxp3 dans la rate et le cortex rénal. Quant à la deuxième partie, il s'agissait de tester l'effet du transfert adoptif des Treg sur l'HTA et les désordres vasculaires induits par l'administration d'angiotensine II ou d'aldostérone à des souris. Nos résultats montrent que le transfert adoptif des Treg prévient l'HTA induite par l'Ang II, l'altération de la vasodilatation endothélium-dépendante, prévient l'augmentation de la rigidité des AM, diminue le stress oxydatif et les taux plasmatiques des cytokines proinflammatoires (INF-γ, TNF-α et IL-6), ainsi que l'infiltration aortique et rénale des macrophages. Le transfert adoptif des Treg prévient partiellement l'augmentation de la pression artérielle systolique induite par l'Aldo, prévient l'altération de la vasodilatation endothelium dépendante et le remodelage hypertrophique des AM, diminue le stress oxydatif et l'infiltration des cellules immunitaires inflammatoires. Le transfert adoptif des cellules T effectrices (Teff) exacerbe la majorité des effets de l'Aldo. Nos résultats justifient, d'une part, l'importance de l'exercice comme outil préventif de l'HTA induite par l'r-HuEPO, et d'autre part, présentent les Treg comme élément essential dans la modulation de l'HTA et des désordres cardiovasculaires.

During high flow rates, the acceleration of flow and turbulence around bridge foundations lead to scouring, defined as the removal of bed sediments. Due to the interparticle physico-chemical forces of clay particles, erodibility and transport mechanisms for fine sediments are different from those for coarse sediments, and the capability to predict the erosion resistance of fine sediments is still in question. In this study, silt-clay soil mixtures with different kaolin contents were prepared by mixing ground silica and Georgia kaolin with tap water. Geotechnical tests were carried out to obtain the physical properties of the specimens. The critical shear stress and yield stress of the soil mixtures were determined through hydraulic flume experiments and rheometer tests, respectively. Particle associations of the soil specimens were observed using the technique of scanning electron microscopy (SEM). From the laboratory work and data analysis, relationships among the critical shear stress, yield stress, and the soil physical properties were developed from multiple regression analysis. Specifically, values of the critical shear stress, yield stress, and their dimensionless form can be predicted by the soil properties including bulk density, clay content, and water content. Finally, a single relationship is obtained to predict the Shields parameter as a function of the corresponding dimensionless yield stress in this study. The results can be used to provide a methodology for engineering applications requiring the value of critical shear stress such as estimating fine sediment bed stability and assessing the erosion risk of river beds in proximity to bridge foundations and other flow obstructions.

This thesis presents a detailed, two-dimensional analysis of the performance of multi-element guard-heated hot-film wall shear stress microsensors for turbulent flows. Previous studies of conventional, single-element sensors show that a significant portion of heat generated in the hot-film travels through the substrate before reaching the fluid, causing spectral and phase errors in the wall shear stress signal and drastically reducing the spatial resolution of the sensor. Earlier attempts to reduce these errors have focused on reducing the effective thermal conductivity of the substrate. New guard-heated microsensor designs proposed to overcome the severe deficiencies of the conventional design are investigated in this thesis. Guard-heaters remove the errors associated with substrate heat conduction, by forcing zero temperature gradient at the edges and bottom face of the hot-film, and hence, block the indirect heat transfer to the flow. Air and water flow over the sensors are studied numerically to investigate design, performance and signal strength of the guard-heated sensors. Our results show, particularly for measurements in low-conductivity fluids such as air, that edge guard-heating needs to be supplemented by a sub-surface guard-heater, to make substrate conduction errors negligible. With this two-plane guard-heating, a strong non-linearity in the standard single-element designs can be corrected, and spectral and phase errors arising from substrate conduction can be eliminated. / Graduate / 0548 / etrati@uvic.ca

Using a modular approach, a vascularized tissue construct is created by embedding functional cells within submillimeter-sized collagen cylinders (modules) while the outside surfaces are seeded with endothelial cells (EC). The void spaces created by randomly packing modules into a container form EC-lined perfusion channels. Upon implantation, the tissues are remodeled by and integrated into the host and experience, to some degree, immune and inflammatory responses. This work utilized microfluidic techniques to study and model the tissue remodeling in vitro in the absence of the host response. When the construct’s tortuous perfusion channels were reproduced in poly(dimethylsiloxane) microfluidic devices and lined with EC, perfusion at higher flow rates reduced EC activation and maintained the desired quiescent EC phenotype. When applying these results to collagen constructs, higher flow rates were not achievable due to the weak mechanical properties of collagen. To increase the collagen’s mechanical strength, a semi-synthetic collagen/poloxamine-methacrylate hydrogel was examined but due to its heterogeneous surface composition, there was inadequate EC attachment and the material was deemed unsuitable for this application. Proceeding with lower flow rates, tissues assembled within microfluidic perfusion chambers from EC-seeded collagen modules showed that over the course of 24 hours, perfusion did not significantly increase activation but instead increased KLF2 expression, a transcription factor involved in the establishment of EC quiescence, and disrupted VE-cadherin bonds between adjacent EC. However, after 1 week of perfusion, the majority of EC were lost. To ameliorate this loss, mesenchymal stromal cells (MSC) were embedded within the modules in order to take advantage of their anti-apoptotic and immunomodulation effects. The MSC temporarily mitigated the loss of the EC but did not prevent it. They did, however, take on a phenotype similar to smooth muscle cells and migrated towards the EC. Perhaps this indicates that the combination of EC, MSC and perfusion drives the creation and assembly of pseudo vessels. Together, the microfluidic techniques used in this study to assemble and perfuse modular tissues revealed new insights into the remodeling process and exposed critical issues surrounding the adaptation of the EC to the combination of perfusion, remodeling and changing flow fields.

Using a modular approach, a vascularized tissue construct is created by embedding functional cells within submillimeter-sized collagen cylinders (modules) while the outside surfaces are seeded with endothelial cells (EC). The void spaces created by randomly packing modules into a container form EC-lined perfusion channels. Upon implantation, the tissues are remodeled by and integrated into the host and experience, to some degree, immune and inflammatory responses. This work utilized microfluidic techniques to study and model the tissue remodeling in vitro in the absence of the host response. When the construct’s tortuous perfusion channels were reproduced in poly(dimethylsiloxane) microfluidic devices and lined with EC, perfusion at higher flow rates reduced EC activation and maintained the desired quiescent EC phenotype. When applying these results to collagen constructs, higher flow rates were not achievable due to the weak mechanical properties of collagen. To increase the collagen’s mechanical strength, a semi-synthetic collagen/poloxamine-methacrylate hydrogel was examined but due to its heterogeneous surface composition, there was inadequate EC attachment and the material was deemed unsuitable for this application. Proceeding with lower flow rates, tissues assembled within microfluidic perfusion chambers from EC-seeded collagen modules showed that over the course of 24 hours, perfusion did not significantly increase activation but instead increased KLF2 expression, a transcription factor involved in the establishment of EC quiescence, and disrupted VE-cadherin bonds between adjacent EC. However, after 1 week of perfusion, the majority of EC were lost. To ameliorate this loss, mesenchymal stromal cells (MSC) were embedded within the modules in order to take advantage of their anti-apoptotic and immunomodulation effects. The MSC temporarily mitigated the loss of the EC but did not prevent it. They did, however, take on a phenotype similar to smooth muscle cells and migrated towards the EC. Perhaps this indicates that the combination of EC, MSC and perfusion drives the creation and assembly of pseudo vessels. Together, the microfluidic techniques used in this study to assemble and perfuse modular tissues revealed new insights into the remodeling process and exposed critical issues surrounding the adaptation of the EC to the combination of perfusion, remodeling and changing flow fields.

Investigations into the turbulent flows in uniform and nonuniform open channels by previous researchers have demonstrated the requirement and importance of understanding the turbulence structures and energy losses due to irregularity in non- uniform open channels. Responding to this requirement, the turbulent flow in one special non-uniform open channel has been studied both experimentally and numerically. This non-uniform open channel was designed so that its width and bed level vary while its cross-sectional area below the water surface keeps constant. An upstream uniforzn open channel is attached to the non-uniform open channel to establish fully developed turbulent flow conditions. A downstream uniform channel is also attached for control of water depth and downstream flow condition. The experimental study consisted of measurements of turbulent velocity field with a LDV (Laser Doppler Velocimetry) and measurements of boundary shear stress (BSS) with Roving Preston tubes in the experimental channel. Turbulent velocity components in the longitudinal and vertical directions were measured with the LDV in forward scattering mode and the laser beams were focused from the channel side wall into the water. Turbulent velocity components in the longitudinal and transverse directions were measured with the LDV in back scattering mode and the laser beams are focused from above the water surface into the water. Both the forward scattering mode measurements and the back scattering mode measurements were taken at two cross sections in the upstream uniform open-channel and at twelve cross sections in the nonuniform open channel. Obtained data include mean longitudinal velocity U, transverse velocity V, vertical velocity W, turbulence intensities u^2, v^2, w^2, and Reynolds shear stresses -uv and -uw. The chief results of these measurements are: 1) There is no separation of flow in the nonuniform open channel. 2) As flow passes from wider and shallower section to narrower and deeper section, it responds as though it experiences contraction in horizontal planes and expansion in vertical planes. The reverse occurs as flow passes from narrower and deeper section to wider and shallower section; 3) The secondary currents in the nonuniform open channel are combinations of the effects of pure contraction and expansion of channel boundaries and the effects of the vortex kind secondary currents; 4) Turbulence intensities in the non-uniform open channel show similar distribution patterns to that in the uniform open-channel but their magnitudes change due to the change of channel shape; 5) Negative values of the Reynolds shear stresses, -uw, appear at the free surface and may extend to a large depth below the free surface in the nonuniform open channel. Boundary shear stresses in the experimental channel were measured with Roving Preston tubes. The use of the Roving Preston tubes was preceded with calibrations of themselves in air pipe flow and calibrations of a special pressure transducer in air and in water. Delicate measurement procedures were designed for measurements of BSS in the nonuniform open channel. The BSS were measured at one cross section in the uniform open-channel and at twelve cross sections in the nonuniform open channel. The chief results of these measurements are: 1) The irregularity of the nonuniform open channel significantly affects the distribution of the BSS but the total shear force has little change; 2) The effect of the secondary currents on the BSS is very similar to the effect of secondary currents on the ESS in uniform open channel; 3) The irregularity in the non-uniform open channel does not cause extra energy loss since there is no flow separation. The numerical study made use of a FEM (finite element method) commercial package FIDAP to simulate the turbulent flows in the experimental channel. These simulations are carried out with Speziale's eddy-viscosity anisotropic k-E model, the standard k-E model, and the RNG model. With each model, simulations were undertaken for four consecutive uniform channels of 5 m length so that fully developed turbulent flow conditions were established before entering into the simulation of flow in the non- uniform channel. In all simulations the free surfaces were fixed. Simulation results include U, V, W, k, and E. For turbulent flow in the uniform channel, only Speziale's model is capable of predicting qualitatively correct secondary currents. For turbulent flow in the non-uniform open channel, all three models gave similar simulation results. The calculated distribution patterns of U and W are in agreement with measurements except near the free surface but differences exist in magnitude. None of the three models was capable of modelling the transverse velocity V in the nonuniform open channel correctly. Further simulations are necessary with movable free surface and better boundary condition for the energy dissipation rate s in order to achieve better agreement with the experimental values, especially near the free surface.