The lymphatic system is an extensive vascular network responsible for the transport of fluid, immune cells, proteins and lipids. It is composed of thin-walled vessels, valves, nodes and ducts, which work together to collect fluid, approximately 4 L/day, from the interstitium transporting it back to the systemic network via the great veins. The failure to transport lymph fluid results in a number of disorders and diseases. Lymphedema, for example, is a pathology characterized by the retention of fluid in limbs creating extreme discomfort, reduced mobility and impaired immunity. In general, there are two types of edema: primary edema, being those cases that are inherited (i.e. genetic predisposition), and secondary edema, which develop post-trauma or injury of the lymphatic vessels. With the onset of breast cancer and radiation therapies, the prevalence of secondary edema is on the rise. Clinical studies have shown that up to 80% of women who undergo nodal-dissection surgery develop lymphedema in their arms within 3-5 years of the surgery. Unfortunately, there is no cure or remedy for lymphedema stemming from our lack of understanding of the lymphatic system. The goal of this study was to evaluate lymph flow both experimentally and analytically to better understand the mechanisms regulating lymph transport. In particular we investigated the effects of pressure, volume loads and valve resistance on lymphatic function in the rat mesentery. Our experimental results were then used to develop computational and constitutive models to emulate the dynamic behavior of lymph transport. Collectively, the data illustrate the mechanics of lymphatic contractility and lymph flow. In particular, lymph flow and pumping significantly increased post edemagenic stress in the rat model. Furthermore, lymphangions exhibited highly nonlinear pressure-diameter responses at low pressures between 3-5 cmH2O. These experimental results strongly suggest the regulation of lymph flow via changes in pressure, shear stress and vessel diameter. Furthermore, the computational and constitutive models from this study provide great insight into lymphatic function characterizing the mechanical properties of a single pumping unit (i.e. lymphangion). These models will serve as valuable tools to further lymphatic research.

Traditional blowing agents (e.g., hydrochlorofluorocarbons) in plastic foaming processes has been phasing out due to environmental regulations. Plastic foaming industry is forced to employ greener alternatives (e.g., carbon dioxide, nitrogen), but their foaming processes are technologically challenging. Moreover, to improve the competitiveness of the foaming industry, it is imperative to develop a new generation of value-added plastic foams with cell structures that can be tailored to different applications. In this context, the objective of this thesis is to achieve a thorough understanding on cell nucleation and growth phenomena that determine cell structures in plastic foaming processes. The core research strategy is to develop innovative visualization systems to capture and study these phenomena. A system with accurate heating and cooling control has been developed to observe and study crystallization-induced foaming behaviors of polymers under static conditions. The cell nucleation and initial growth behavior of polymers blown with different blowing agents (nitrogen, argon and helium, and carbon dioxide-nitrogen mixtures) have also been investigated in great detail. Furthermore, two innovative systems have been developed to simulate the dynamic conditions in industrial foaming processes: one system captures a foaming process under an easily adjustable and uniform extensional strain in a high temperature and pressure environment, while the other achieves the same target, but with shear strain. Using these systems, the extensional and shear effects on bubble nucleation and initial growth processes has been investigated independently in an isolated manner, which has never been achieved previously. The effectiveness of cell nucleating agents has also been evaluated under dynamic conditions, which have led to the identification of new foaming mechanisms based on polymer-chain alignment and generation of microvoids under stress. Knowledge generated from these researches and the wide range of future studies made possible by the visualization systems will be valuable to the development of innovative plastic foaming technologies and foams.

Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found to be co-localized with increased osteoclastic bone resorption. Osteoclasts are recruited to remodel sites of apoptosis or bone microdamage; however, it is unclear whether the apoptotic or neighbouring healthy osteocytes are responsible for targeted bone remodeling. I hypothesized that apoptotic osteocytes are: (a) directly responsible for initiating bone remodeling by recruiting osteoclast precursors and directing osteoclast differentiation, and (b) indirectly responsible by signaling to nearby healthy osteocytes that, in turn, regulate osteoclastogenesis. In this in vitro study, apoptotic osteocytes were found to increase osteoclast precursor migration and osteoclast formation. Inhibition of the osteoclastogenic protein, receptor activator of nuclear factor kappa B ligand (RANKL), in conditioned medium abolished the osteoclastogenic effect of apoptotic osteocytes. Healthy osteocytes surrounded by apoptotic regions were modeled by applying apoptotic osteocyte conditioned medium to healthy osteocytes. These cells also promoted osteoclastogenesis, and had increased expression of macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Inhibition of these factors abrogated the pro-osteoclastic effect of healthy osteocytes conditioned by apoptotic osteocytes. These findings support the hypothesis that apoptotic osteocytes directly and indirectly, by signaling to nearby healthy osteocytes, initiate osteoclastogenesis. One limitation of our and other conventional in vitro models is the lack of real-time cell communication and physiologically-relevant mechanical environment. Using a microfluidics approach, a miniature fluid shear delivery system was created for in vitro osteocyte cultures. The purpose of this microsystem was to increase control of the cell microenvironment for subsequent integration into scalable screening platforms or co-culture systems for studying osteocyte mechanobiology under physiological loading conditions. Fluid shear stress was periodically applied without external pumping using a deflecting elastomer membrane, where up to 2 Pa of oscillating shear stress was possible by manipulating membrane dimensions. Osteocyte culture, viability and calcium response were demonstrated in the microdevice. Further studies should attempt to characterize calcium signaling in osteocytes which, using a conventional macro-scale system, was found to dependent on cell-cell communication.

Phase-contrast magnetic resonance imaging (PC-MRI) is a powerful tool for measuring blood flow and has a wide range of cardiovascular applications. Simulation of PC-MRI from numerical flow data would be useful for addressing the data quality of PC-MRI measurements and to study and understand different artifacts. It would also make it possible to optimize imaging parameters prior to the PC-MRI measurements and to evaluate different methods for measuring wall shear stress. Based on previous studies a PC-MRI simulation tool was developed. An Eulerian-Lagrangian approach was used to solve the problem. Computational fluid dynamics (CFD) data calculated on a fix structured mesh (Eulerian point of view) were used as input. From the CFD data spin particle trajectories were computed. The magnetization of the spin particle is then evaluated as the particle travels along its trajectory (Lagrangian point of view). The simulated PC-MRI data were evaluated by comparison with PC-MRI measurements on an in vitro phantom. Results indicate that the PC-MRI simulation tool functions well. However, further development is required to include some of the artifacts. Decreasing the computation time will make more accurate and powerful simulations possible. Several suggestions for improvements are presented in this report.

Traditional blowing agents (e.g., hydrochlorofluorocarbons) in plastic foaming processes has been phasing out due to environmental regulations. Plastic foaming industry is forced to employ greener alternatives (e.g., carbon dioxide, nitrogen), but their foaming processes are technologically challenging. Moreover, to improve the competitiveness of the foaming industry, it is imperative to develop a new generation of value-added plastic foams with cell structures that can be tailored to different applications. In this context, the objective of this thesis is to achieve a thorough understanding on cell nucleation and growth phenomena that determine cell structures in plastic foaming processes. The core research strategy is to develop innovative visualization systems to capture and study these phenomena. A system with accurate heating and cooling control has been developed to observe and study crystallization-induced foaming behaviors of polymers under static conditions. The cell nucleation and initial growth behavior of polymers blown with different blowing agents (nitrogen, argon and helium, and carbon dioxide-nitrogen mixtures) have also been investigated in great detail. Furthermore, two innovative systems have been developed to simulate the dynamic conditions in industrial foaming processes: one system captures a foaming process under an easily adjustable and uniform extensional strain in a high temperature and pressure environment, while the other achieves the same target, but with shear strain. Using these systems, the extensional and shear effects on bubble nucleation and initial growth processes has been investigated independently in an isolated manner, which has never been achieved previously. The effectiveness of cell nucleating agents has also been evaluated under dynamic conditions, which have led to the identification of new foaming mechanisms based on polymer-chain alignment and generation of microvoids under stress. Knowledge generated from these researches and the wide range of future studies made possible by the visualization systems will be valuable to the development of innovative plastic foaming technologies and foams.

Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found to be co-localized with increased osteoclastic bone resorption. Osteoclasts are recruited to remodel sites of apoptosis or bone microdamage; however, it is unclear whether the apoptotic or neighbouring healthy osteocytes are responsible for targeted bone remodeling. I hypothesized that apoptotic osteocytes are: (a) directly responsible for initiating bone remodeling by recruiting osteoclast precursors and directing osteoclast differentiation, and (b) indirectly responsible by signaling to nearby healthy osteocytes that, in turn, regulate osteoclastogenesis. In this in vitro study, apoptotic osteocytes were found to increase osteoclast precursor migration and osteoclast formation. Inhibition of the osteoclastogenic protein, receptor activator of nuclear factor kappa B ligand (RANKL), in conditioned medium abolished the osteoclastogenic effect of apoptotic osteocytes. Healthy osteocytes surrounded by apoptotic regions were modeled by applying apoptotic osteocyte conditioned medium to healthy osteocytes. These cells also promoted osteoclastogenesis, and had increased expression of macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Inhibition of these factors abrogated the pro-osteoclastic effect of healthy osteocytes conditioned by apoptotic osteocytes. These findings support the hypothesis that apoptotic osteocytes directly and indirectly, by signaling to nearby healthy osteocytes, initiate osteoclastogenesis. One limitation of our and other conventional in vitro models is the lack of real-time cell communication and physiologically-relevant mechanical environment. Using a microfluidics approach, a miniature fluid shear delivery system was created for in vitro osteocyte cultures. The purpose of this microsystem was to increase control of the cell microenvironment for subsequent integration into scalable screening platforms or co-culture systems for studying osteocyte mechanobiology under physiological loading conditions. Fluid shear stress was periodically applied without external pumping using a deflecting elastomer membrane, where up to 2 Pa of oscillating shear stress was possible by manipulating membrane dimensions. Osteocyte culture, viability and calcium response were demonstrated in the microdevice. Further studies should attempt to characterize calcium signaling in osteocytes which, using a conventional macro-scale system, was found to dependent on cell-cell communication.

The importance of shear stress in vascular biology and pathophysiology has been highlighted by the focal development patterns of atherosclerosis, abdominal aortic aneurysms, and heart valve disease in regions exposed to disturbed flow leading to low or oscillatory shear stress at the wall of the blood vessel or the surface of the valve leaflet. The novel and significant finding of this study is that mouse aortic endothelial cell exposure to pro-atherogenic oscillatory shear stress (OS) (+/- 5 dynes/cm2) increased their production of cathepsins, the family of lysosomal cysteine proteases that are potent elastases and collagenases leading to protease degradation and remodeling of the extracellular matrix structural components. Conversely, atheroprotective unidirectional laminar shear stress (LS) (15 dynes/cm2) decreased elastase and gelatinase activities of endothelial cells through a shear stress mediated reduction in cathepsins K, L, and S activity. Their endogenous inhibitor, cystatin C, was found to be inversely regulated by shear stress; LS increased its secretion by endothelial cells while OS decreased it. Binding of free cystatin C in the conditioned media to carboxymethylated papain coated agarose beads led to an increase in cathepsin activity since the available cathepsin was not inhibited. To verify these findings in human samples, immunohistochemical analysis of cystatin C and cathepsin K was performed on human coronary arteries. Cathepsin K stained strongly in the endothelial layer of vessels with degraded internal elastic lamina while cystatin C staining intensity was strongest overlying minimally diseased vessels. Additional roles for cathepsins K, L, and S were found in endothelial cell alignment in response to unidirectional laminar shear stress, endothelial cell migration, and programmed cell death. We conclude that there is an inverse regulation of cathepsins and cystatin C in endothelial cells by LS and OS and identify the cathepsin family of proteases as potential targets for therapeutic intervention of cardiovascular disease development at sites of disturbed flow.

A 3-axis acoustic Doppler Velocimeter (ADV) with high sampling rate was used to measure the bed shear stress and turbulence under wave-current interaction conditions in this study. Experimental sites include laboratory tank, Love River in Kaohsiung and Howan coastal waters in Pingtung. Bed shear stress is estimated primarily by the inertial dissipation method, also by the turbulent kinetic energy method and eddy correlation method. Results of the laboratory experiments indicate that the bed shear stress increases as both the flow speed and wave height increase, and the flow speed is a more important factor. Field experiments can be divided into several types. The first type is under slow flows and calm waves. Love River is a typical condition of this type with turbid waters and a low flow speed. During the experimental period the ADV correlations reach 90% or more. Because the river flow is quite small, no significant bed shear stress is produced and u* is mostly less than 1 cm/s. As a result the deposition effect is much larger than erosion, thus a very thick layer of mud is formed on the riverbed. The observations in Howan in April 2010 also reveal the condition of slow flows and small waves, and the bed shear stress is also quite small. Due to the factors of clean coastal waters and weak turbulence in this season, the quality of ADV signals is poor. The second type is under large flows and small waves, as shown from the observations of Howan in April 2011, during which the maximum speed reached 25 cm/s and wave heights less than 20 cm. In this experiment the shear stress is large, the u* are mostly greater than 0.8 cm/s and the value of the drag coefficient is 0.0021; the ADV signals have good quality and the inertial sub-range is well defined. The third type is under weak flows and large waves. The observations of Howan in July 2011 show significant rainfall and maximum wave heights of 90 cm. In this case the u* are mostly centered around 1 cm/s. The acoustic backscatter intensity is positively correlated with the turbidity and wave height. Sizable bed shear stress induced by the orbital velocity of waves contributes a significant part to the total bed shear stress.

Improved basic understanding, predictability, and controllability of vortex-dominated and unsteady aerodynamic flows are important in enhancement of the performance of next generation helicopters. The primary objective of this research project was improved understanding of the fundamental vorticity and turbulent flow physics for a dynamically stalling airfoil at realistic helicopter flight conditions. An experimental program was performed on a large-scale (C = 0.45 m) dynamically pitching NACA 0012 wing operating in the Texas A&M University large-scale wind tunnel. High-resolution particle image velocimetry data were acquired on the first 10-15% of the wing. Six test cases were examined including the unsteady (k>0) and steady (k=0) conditions. The relevant mechanical, shear and turbulent time-scales were all of comparable magnitude, which indicated that the flow was in a state of mechanical non-equilibrium, and the expected flow separation and reattachment hystersis was observed. Analyses of the databases provided new insights into the leading-edge Reynolds stress structure and the turbulent transport processes. Both of which were previously uncharacterized. During the upstroke motion of the wing, a bubble structure formed in the leading-edge Reynolds shear stress. The size of the bubble increased with increasing angle-of-attack before being diffused into a shear layer at full separation. The turbulent transport analyses indicated that the axial stress production was positive, where the transverse production was negative. This implied that axial turbulent stresses were being produced from the axial component of the mean flow. A significant portion of the energy was transferred to the transverse stress through the pressure-strain redistribution, and then back to the transverse mean flow through the negative transverse production. An opposite trend was observed further downstream of this region.

This research is part of the extension of the SRICOS-EFA method for predicting the maximum scour depth history around the bridge abutment. The basic objective is to establish the equation for predicting the maximum bed shear stress around the abutment at the initial condition of scouring. CHEN3D (Computerized Hydraulic ENgineering program for 3D flow) program is utilized to perform numerical simulations and predict bed shear stress before scouring. The Chimera technique incorporated in CHEN3D makes the program capable of simulating all kinds of complex geometry and moving boundary. CHEN3D program has been proven to be an accurate method to predict flow field and boundary shear stress in many fields and used in bridge scour study in cohesive soils for more than ten years. The maximum bed shear stress around abutment in open rectangular channel is studied numerically and the equation is proposed. Reynolds number is the dominant parameter, and the parametric studies have been performed based on the dimensional analysis. The influence of channel contraction ratio, abutment aspect ratio, water depth, abutment shape, and skew angle has been investigated, and the corresponding correction This research is part of the extension of the SRICOS-EFA method for predicting the maximum scour depth history around the bridge abutment. The basic objective is to establish the equation for predicting the maximum bed shear stress around the abutment at the initial condition of scouring. CHEN3D (Computerized Hydraulic ENgineering program for 3D flow) program is utilized to perform numerical simulations and predict bed shear stress before scouring. The Chimera technique incorporated in CHEN3D makes the program capable of simulating all kinds of complex geometry and moving boundary. CHEN3D program has been proven to be an accurate method to predict flow field and boundary shear stress in many fields and used in bridge scour study in cohesive soils for more than ten years. The maximum bed shear stress around abutment in open rectangular channel is studied numerically and the equation is proposed. Reynolds number is the dominant parameter, and the parametric studies have been performed based on the dimensional analysis. The influence of channel contraction ratio, abutment aspect ratio, water depth, abutment shape, and skew angle has been investigated, and the corresponding correction factors have been proposed. The study of the compound channel configuration is conducted further to extend the application of the proposed equation. Numerical simulations of overtopping flow in straight rectangular channel, straight compound channel and channel bend have been conducted. The bridge deck is found to be able to change the flow distribution and the bed shear stress will increase significantly once overtopping. The influence of the channel bend curvature, abutment location in the channel bend, and the abutment shape is also investigated. The corresponding variation of the bed shear stress has been concluded. The scour models, including the erosion rate function, roughness effect, and the turbulence kinetic energy, have been proposed and incorporated into the CHEN3D program. One flume test case in NCHRP 24-15(2) has been simulated to determine the parameters for the roughness and the turbulence kinetic energy. The prediction of the maximum scour depth history with the proposed model is in good agreement with the measurement for most cases. The influence of overtopping flow on the abutment scour development is also studied and the corresponding correction factor is proposed.