Development of shear databases attracted a great deal of attention in the shear research community within the last decade. Although a few shear databases have already been developed by several research groups, there is no comprehensive shear database that is focused on prestressed concrete members. This thesis aims to develop a shear database for prestressed concrete members with an intensive literature review. This literature review resulted in a database that contained a total of 1,696 tests reported in North America, Japan, and Europe from 1954 to 2010. The database was used to evaluate shear design provisions available in North America, Japan, and Europe. The variations in measured versus calculated shear strength using twelve shear design equations were analyzed. The analysis results indicated that design expressions based on the Modified Compression Filed Theory (MCFT) produced the best performance to estimate the shear strength of prestressed concrete members with sufficient shear reinforcement. The MCFT-based design expressions, however, provided unconservative strength estimations for members that failed in shear but exhibited signs of horizontal shear damage and/or anchorage zone distress. The ACI 318-08 detailed method was found to be less conservative than the MCFT-based design expressions. Additionally, on the basis of a careful examination of test results included in the database, a new limit for the minimum shear reinforcement was proposed. The database was also used to investigate the shear behavior of prestressed concrete members. This investigation revealed that there was no evidence of size effect in the shear strength of prestressed concrete members with sufficient shear reinforcement. Additionally, it was found that prestress force and shear reinforcement increased the shear strength although there was an upper limit on the effectiveness of shear reinforcement. / text

Endothelial cells (ECs) form the inner lining of all blood vessels in the body, and coat the outer surfaces of heart valves. Because ECs are anchored to extracellular matrix proteins and are positioned between flowing blood and underlying interstitium, ECs are constantly exposed to hemodynamic shear, and act as a semi-permeable barrier to blood-borne factors. In vitro cell culture flow (ICF) systems have been employed as laboratory tools for testing endothelial properties such as adhesion strength, shear response, and permeability. Recently, advances in microscale technology have introduced microfluidic systems as alternatives to conventional ICF devices, with a multitude of practical advantages not available at the macroscale. However, acceptance of microfluidics as a viable platform has thus far been reserved because utility of microfluidics has yet to be fully demonstrated. For biologists to embrace microfluidics, engineers must validate microscale systems and prove their practicality as tools for cell biology. Microfluidic devices were designed, fabricated, and implemented to study properties of two EC types: aortic ECs and valve ECs. The objective was to streamline experimentation to reveal phenotypic traits of the two types and in the process demonstrate the usefulness of microfluidics. The first task was to develop a protocol to isolate pure populations of valve ECs because reported methods were inadequate. Dispase and collagenase in combination for leaflet digestion followed by clonal expansion of cell isolates was optimal for obtaining pure valve EC populations. Using a parallel microfluidic network, we discovered that valve ECs adhered strongly and spread well only on fibronectin and not on type I collagen. In contrast, aortic ECs adhered strongly on both proteins. Both aortic and valve ECs were then exposed to shear and analyzed for cell orientation. Morphological analyses showed aortic and valve ECs both aligned parallel to flow when sheared in a macroscale flow chamber, but aortic ECs aligned perpendicular to flow when sheared in a microchannel. Finally, a microfluidic membrane device was designed and characterized as a potential tool for measuring albumin permeability through sheared endothelial monolayers. Overall, these studies revealed novel EC characteristics and phenomena, and demonstrated accessibility of microfluidics for EC studies.

Endothelial cells (ECs) form the inner lining of all blood vessels in the body, and coat the outer surfaces of heart valves. Because ECs are anchored to extracellular matrix proteins and are positioned between flowing blood and underlying interstitium, ECs are constantly exposed to hemodynamic shear, and act as a semi-permeable barrier to blood-borne factors. In vitro cell culture flow (ICF) systems have been employed as laboratory tools for testing endothelial properties such as adhesion strength, shear response, and permeability. Recently, advances in microscale technology have introduced microfluidic systems as alternatives to conventional ICF devices, with a multitude of practical advantages not available at the macroscale. However, acceptance of microfluidics as a viable platform has thus far been reserved because utility of microfluidics has yet to be fully demonstrated. For biologists to embrace microfluidics, engineers must validate microscale systems and prove their practicality as tools for cell biology. Microfluidic devices were designed, fabricated, and implemented to study properties of two EC types: aortic ECs and valve ECs. The objective was to streamline experimentation to reveal phenotypic traits of the two types and in the process demonstrate the usefulness of microfluidics. The first task was to develop a protocol to isolate pure populations of valve ECs because reported methods were inadequate. Dispase and collagenase in combination for leaflet digestion followed by clonal expansion of cell isolates was optimal for obtaining pure valve EC populations. Using a parallel microfluidic network, we discovered that valve ECs adhered strongly and spread well only on fibronectin and not on type I collagen. In contrast, aortic ECs adhered strongly on both proteins. Both aortic and valve ECs were then exposed to shear and analyzed for cell orientation. Morphological analyses showed aortic and valve ECs both aligned parallel to flow when sheared in a macroscale flow chamber, but aortic ECs aligned perpendicular to flow when sheared in a microchannel. Finally, a microfluidic membrane device was designed and characterized as a potential tool for measuring albumin permeability through sheared endothelial monolayers. Overall, these studies revealed novel EC characteristics and phenomena, and demonstrated accessibility of microfluidics for EC studies.

The spatial and temporal structure of the flow, vorticity and stress over equilibrium orbital-scale sand ripples are investigated at turbulence-resolving scales with a wide-band coherent Doppler profiler (MFDop) in an oscillating tray apparatus. The oscillation period and horizontal excursion were 10 s and 0.5 m. Velocity profiles were acquired with 3 mm vertical resolution and at a 42 Hz sampling rate. Ripple wavelength and amplitude were 25 cm and 2.2 cm. The MFDop measurements are used to investigate the development of the lee vortex as a function of phase, and the co-evolution of turbulent kinetic energy, Reynolds stress and turbulence production. Shear stress is determined from the vertically-integrated vorticity equation and using the double-averaging approach. Friction factors obtained from the two methods are comparable and range from 0.1 to 0.2.

The factors influencing habitat selection by juveniles of species within the family Unionidae (i.e., unionids), between post-larval detachment from a fish host and burrowing into the substratum, are largely unknown. Bed shear stress (τw) has been proposed as a critical factor. A laboratory wall jet apparatus generated τw to assess the response of juvenile Epioblasma triquetra, Villosa iris, Lampsilis fasciola, and Ligumia nasuta. The relationships between juvenile unionids, τw, and chemical and physical parameters were also examined in the field. There was a significant relationship between unionid resuspension and τw in the laboratory (resuspension when τw > 0.26 Pa), and adhesion behaviour required greater critical τw. Near-bed velocity and D50 grain size predicted sphaeriid clam density (a proxy for juvenile unionids) in the field. Laboratory experiments confirmed predictions that juvenile unionids cannot establish beyond a critical τw, demonstrating the importance of hydrodynamics in dispersal and for developing unionid conservation measures. / NSERC and Species At Risk Research Fund Ontario (MNR) to J.D.A.

The blood is a complex fluid that contains, in addition to water, cells, macro-molecules and a large number of smaller molecules. The physical properties of the blood are therefore the result of non-linear interactions of its constituents, which are influenced by the local flow field conditions. Hence, the local blood viscosity is a function of the local concentration of the blood constituents and the local flow field itself. This study considers the flow of blood-like fluids in generalised 90-degree bifurcating pipes and patient-specific arterial bifurcations relevant to the large aortic branches in humans. It is shown that the Red Blood Cell (RBC) distribution in the region of bifurcations may lead to large changes in the viscosity, with implications on the concentrations of the various cells in the blood plasma. This in turn implies that the flow in the near wall regions is more difficult to estimate and predict than that under the assumption of a homogeneous fluid. The rheological properties of blood are complex and are difficult to measure, since the results depend on the measuring equipment and the inherent flow conditions. We attempt to model the viscosity of water containing different volume fractions of non-deforming RBC-like particles in tubes. The apparent viscosities of the mixtures obtained from these model experiments have been compared to the predictions of the different rheological models found in the literature. The same rheological models have also been used in the different simulations, where the local RBC concentration and local shear rate are used in the viscosity models. The flow simulations account for the non-linearity due to coupling between the flow and fluid rheology. Furthermore, from a physiological perspective, it is shown that oscillatory wall shear stresses are affected by changes in RBC concentration in the regions of the bifurcation associated with atherogenesis. The intrinsic shear thinning rheological property of the blood, in conjunction with stagnation in separated flows, may be responsible for elevated temporal wall shear stress gradients (TWSSG) influencing endothelial cell behaviour, which has been postulated to play a role in the development of atherosclerosis. The blood-like fluid properties along with variations in the RBC concentration could also lead to variations in the developing flow structures in the larger arteries that could influence the work the heart has to bear. / <p>QC 20131206</p>

The lymphatic system is crucial for normal physiologic function, performing such basic functions as maintaining tissue fluid balance, trafficking immune cells, draining interstitial proteins, as well as transporting fat from the intestine to the blood. To perform these functions properly, downstream vessels (known as collecting lymphatics) actively pump like the heart to dynamically propel lymph from the interstitial spaces of the body to the blood vasculature. However, despite the fact that lymphatics are so important, there exists very little knowledge regarding the details of this active pumping. Specifically, it is known that external mechanical loading such as fluid shear stress and circumferential stress due to transmural pressure affect pumping response; however, anything other than simple, static relationships remain unknown. Because mechanical environment has been implicated in lymphatic diseases such as lymphedema, understanding these dynamic relationships between lymphatic pumping and mechanical loading during normal function are crucial to grasp before these pathologies can be unraveled. For this reason, this thesis describes several tools developed to study lymphatic function in response to the unique mechanical loads these vessels experience both in vitro and ex vivo. Moreover, this work investigates how shear stress sensitivity is affected by transmural pressure and how the presence of dynamic shear independently affects lymphatic contractile function.

The amount and type of cohesive sediment found in gravel river beds can have important implications for the health of aquatic biota, surface/groundwater interactions and water quality. Due to landscape disturbances in the Elbow River watershed, increased sediment fluxes have negatively impacted fish habitat, water quality and water supply to the City of Calgary. However, little is known about the source of cohesive sediment and its interaction with gravel deposits in the Elbow River. This research was designed to: 1) quantify the transport properties (critical shear stress for erosion, deposition, porosity, settling velocity, density) of cohesive sediment and 2) evaluate the potential for coarse gravel to entrap cohesive sediment in the Elbow River. A 5m annular flume was used to conduct erosion and deposition experiments using plane and coarse bed conditions. The critical shear stress for deposition and erosion of the Elbow River cohesive sediments was 0.115Pa and 0.212Pa, respectively. The settling velocity of the cohesive sediment had an inverse relationship between floc size and settling velocity for larger flocs, due to a decrease in floc density with increased size. Cohesive sediment moved from the water column into the gravel bed via the coupling of surface and pore water flow. Once in the gravel bed, cohesive sediments were not mobilized from the bed because the shear produced by the flume was less than the critical shear to mobilize the gravel bed. Using a model developed by Krishnappan and Engel (2006), an entrapment coefficient of 0.2 was determined for the gravel bed. Entrapment coefficients were plotted against substrate size, porosity and hydraulic conductivity, demonstrating a relationship between entrapment coefficient and these variables. It was estimated that 864kg of cohesive sediment is stored in the upper 0.08m of a partially submerged point bar in the Elbow River. Accordingly, when flow conditions are sufficient to mobilize the gravel bed and disturb the amour layer, cohesive materials may be entrained and transported into the Glenmore Reservoir, where it will reduce reservoir capacity and may pose treatment challenges to the drinking water supply.

This work describes the results of experimental study of the flow of soft objects (microgels) through microchannels. This work was carried with the intention of building a fundamental biophysical model for the flow of neutrophil cells in microcirculatory system. In Chapter 1 we give a summary of the literature describing the flow of cells and “model cells” in microchannels. Paramount to this we developed methods to modify microchannels fabricated in poly(dimethyl siloxane) (PDMS). Originally, these microchannels could not be used to mimic biological microenvironments because they are hydrophobic and have rectangular cross-sections. We designed a method to create durable protein coatings in PDMS microchannels, as outlined in Chapter 3. Surface modification of the channels was accomplished by a two-step approach which included (i) the site-specific photografting of a layer of poly(acrylamide) (PAAm) to the PDMS surface and (ii) the bioconjugation of PAAm with the desired protein. This method is compatible with different channel geometries and it exhibits excellent longevity under shear stresses up to 1 dyn/cm. The modification was proven to be successful for various proteins of various molecular weights and does not affect protein activity. The microchannels were further modified by modifying the cross-sections in order to replicate cardiovascular flow conditions. In our work, we transformed the rectangular cross-sections into circular corss-sections. Microchannels were modified by polymerizing a liquid silicone oligomer around a gas stream coaxially introduced into the channel, as outlined in Chapter 3. We demonstrated the ability to control the diameter of circular cross-sections of microchannels. The flow behaviour of microgels in microchannels was studied in a series of experiments aimed at studying microgel flow (i) under electrostatic interactions (Chapter 4), (ii) binding of proteins attached to the microgel and the microchannel (Chapter 5) and (iii) under the conditions of varying channel geometry (Chapter 6). This work overall present’s new methods to study the flow of soft objects such as cells, in the confined geometries of microchannels. Using these methods, variables can be independently probed and analyzed.

Endothelial cells (EC) exposed to oscillatory shear stress (OS) experience oxidative stress as a signature of atherosclerosis. Conversely, unidirectional laminar shear stress (LS) reduces reactive oxygen species (ROS) levels and inflammatory responses. Peroxiredoxins (PRX) are antioxidant enzymes that reduce hydrogen peroxide, but have yet to be investigated in response to shear stress. We hypothesized that LS, compared to OS, promotes increased expression of PRX, which in turn influences the balance of ROS in EC. In this study, we identified all six PRX family members in bovine aortic endothelial cells (BAEC). Furthermore, we revealed that PRX are regulated by shear stress in EC. When compared to OS and static culture (ST), exposure to chronic LS upregulated PRX1 levels intracellularly. LS also upregulated PRX5 relative to ST, but not OS. In addition, PRX exhibited broad subcellular localization in BAEC, but these patterns did not change in response to shear stress. To establish the functional importance of PRX1 in shear stress-dependent redox balance, we next examined the role of PRX1 in LS-mediated hydrogen peroxide regulation. Here, Amplex Red assay was used to measure ROS levels in BAEC. Depletion of PRX1 using siRNA resulted in significantly higher ROS levels following LS, OS, and ST, while PRX5 depletion did not. These findings indicated that chronic exposure to LS upregulates PRX1 expression to keep ROS levels low in EC. To identify the pathway by which atheroprotective LS stimulates PRX1 protein production, we also undertook gene expression studies. We discovered that LS upregulates Prdx1 gene in a time-dependent manner compared to OS or ST. However, this increase in expression was not due to stabilization of Prdx1 mRNA. In addition, Prdx1 promoter analysis revealed a Nrf2 transcription factor binding site 160bp upstream of the gene. Nrf2 overexpression promoted basal PRX1 protein production, while Nrf2 depletion reduced Prdx1 mRNA following exposure to LS. Collectively, our work illustrated that LS affects PRX1 by inducing the Prdx1 gene, in part via the transcription factor Nrf2. Moreover, this discovery of PRX1 as a mechanosensitive antioxidant may contribute important insights into endothelial cell biology and provide a novel therapeutic target for vascular diseases.