Indiana University-Purdue University Indianapolis (IUPUI) / Dicalcium phosphate dihydrate (DCPD) cements have been used for bone repair due to its excellent biocompatibility and resorbability. However, DCPD cements are typically weak and brittle. To overcome these limitations, the sodium citrate used as a setting regulator and the coating of poly-L-lactide acid (PLLA) technique have been proposed in this study. The first purpose of this thesis is to develop composite PLLA/DCPD scaffolds with enhanced toughness by PLLA coating. The second purpose is to examine the biocompatibility of the scaffolds. The final purpose is to investigate the degradation behaviors of DCPD and PLLA/DCPD scaffolds. In this experiment, DCPD cements were synthesized from monocalcium phosphate monohydrate (MCPM) and 𝛽-tricalcium phosphate (𝛽 –TCP) by using deionized water and sodium citrate as liquid components. The samples were prepared with powder to liquid ratio (P/L) at 1.00, 1.25 and 1.50. To fabricate the PLLA/DCPD composite samples, DCPD samples were coated with 5 % PLLA. The samples were characterized mechanical properties, such as porosity, diametral tensile strength, and fracture energy. The mechanical properties of DCPD scaffolds with and without PLLA coating after the in vitro static degradation (day 1, week1, 4, and 6) and in vitro dynamic degradation (day 1, week 1, 2, 4, 6, and 8) were investigated by measuring their weight loss, fracture energy, and pH of phosphate buffer solution. In addition, the dog bone marrow stromal stem cells (dBMSCs) adhesion on DCPD and PLLA/DCPD composite samples were examined by scanning electron microscopy. The cell proliferation and differentiation in the medium conditioned with DCPD and PLLA/DCPD composite samples were studied by XTT (2,3-Bis(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt), and alkaline phosphatase (ALP) assay, respectively. The addition of sodium citrate and PLLA coating played a crucial role in improving the mechanical properties of the samples by increasing the diametral tensile strength from 0.50 ± 0.15 MPa to 2.70 ± 0.54 MPa and increasing the fracture energy from 0.76 ± 0.18 N-mm to 12.67 ± 4.97 N-mm. The DCPD and PLLA/DCPD composite samples were compatible with dBMSCs and the cells were able to proliferate and differentiate in the conditioned medium. The degradation rate of DCPD and PLLA/DCPD samples were not significant different (p > 0.05). However, the DCPD and PLLA/DCPD composite samples those used sodium citrate as a liquid component was found to degrade faster than the groups that use deionized water as liquid component

Indiana University-Purdue University Indianapolis (IUPUI) / Peripheral arterial disease is caused by plaque buildup in the peripheral arteries. Standard treatments are available when the blockage is proximal and focal, however when distal and diffuse the same type of the treatment options are not beneficial due to the diseased locations. Restoration of blood flow and further salvaging of the limb in these patients can occur in a retrograde manner through the venous system, called retroperfusion or arteriovenous reversal. Retroperfusion has been explored over the last century, where early side to side artery to venous connections had issues with valve competency prohibiting distal flows, edema buildup, and heart failure. However, more recent clinical studies create a bypass to a foot vein to ensure distal flows, and though the results have been promising, it requires a lengthy invasive procedure. It is our belief that the concerns of both retroperfusion approaches can be overcome in a minimally invasive/catheter based approach in which the catheter is engineered to a specific resistance that avoids edema and the perfusion location allows for valves to be passable and flow to reach distally. In this approach, the pressure flow relations were characterized in the retroperfused venous system in ex-vivo canine legs to locate the optimal perfusion location followed by in-vivo validation of canines. Six canines were acutely injured for 1-3 hours by surgical ligation of the terminal aorta and both external iliac arteries. Retroperfusion was successfully performed on five of the dogs at the venous popliteal bifurcation for approximately one hour, where flow rates at peak pressures reached near half of forward flow (37±3 vs. 84±27ml/min) and from which the slope of the P/F curves displayed a retro venous vasculature resistance that was used to calculate the optimal catheter resistance. To assess differences in regional perfusion, microspheres were passed during retroperfusion and compared to baseline microspheres passed arterially prior to occlusion in which the ratio of retroperfusion and forward perfusion levels were near the ratio of reversed and forward venous flow (0.44) throughout the limb. Decreases in critical metabolites during injury trended towards normal levels post-retroperfusion. By identifying the popliteal bifurication as a perfusion site to restore blood flow in the entirety of the distal ischemic limb, showing reversal of injury, and knowing what catheter resistances to target for further chronic studies, steps towards controlled retroperfusion and thus more efficient treatment options can be made for severe PAD patients.

UBC's Drs. Walter Hardy, Doug Bonn and Ruixing Liang were awarded the 2006 Brockhouse Canada Prize for Interdisciplinary Research in Science and Engineering. A partnership between Dr. Helen Burt's reseach laboratory and Angiotech Pharmaceuticals has earned the 2006 NSERC Synergy Award for Innovation.

Indiana University-Purdue University Indianapolis (IUPUI) / A gearless hydraulic wind energy transfer system utilizes the hydraulic power transmission principles to integrate the energy of multiple wind turbines in a central power generation location. The gearless wind power transfer technology may replace the current energy harvesting system to reduce the cost of operation and increase the reliability of wind power generation. It also allows for the integration of multiple wind turbines to one central generation unit, unlike the traditional wind power generation with dedicated generator and gearbox. A Hydraulic Transmission (HT) can transmit high power and can operate over a wide range of torque-to-speed ratios, allowing efficient transmission of intermittent wind power. The torque to speed ratios illustrates the relationship between the torque and speed of a motor (or pump) from the moment of start to when full-load torque is reached at the manufacturer recommended rated speed. In this thesis, a gearless hydraulic wind energy harvesting and transfer system is mathematically modeled and verified by experimental results. The mathematical model is therefore required to consider the system dynamics and be used in control system development. Mathematical modeling also provided a method to determine the losses of the system as well as overall efficiency. The energy is harvested by a low speed-high torque wind turbine connected to a high fixed-displacement hydraulic pump, which is connected to hydraulic motors. Through mathematical modeling of the system, an enhanced understanding of the HTS through analysis was gained that lead to a highly efficient hydraulic energy transmission system. It was determined which factors significantly influenced the system operation and its efficiency more. It was also established how the overall system operated in a multiple wind turbine configuration. The quality of transferred power from the wind turbine to the generator is important to maintaining the systems power balance, frequency droop control in grid-connected applications, and to ensure that the maximum output power is obtained. A hydraulic transmission system can transfer large amounts of power and has more flexibility than a mechanical and electrical system. However high-pressure hydraulic systems have shown low efficiency in wind power transfer when interfaced with a single turbine to a ground-level generator. HT’s generally have acceptable efficiency at full load and drop efficiency as the loading changes, typically having a peak around 60%. The efficiency of a HT is dependent on several parameters including volumetric flow rate, rotational speed and torque at the pump shaft, and the pressure difference across the inlet and outlet of the hydraulic pump and motor. It has been demonstrated that using a central generation unit for a group of wind turbines and transferring the power of each turbine through hydraulic system increases the efficiency of the overall system versus one turbine to one central generation unit. The efficiency enhancement depends on the rotational speed of the hydraulic pumps. Therefore, it is proven that the multiple-turbine hydraulic power transfer system reaches higher efficiencies at lower rotational speeds. This suggests that the gearbox can be eliminated from the wind powertrains if multiple turbines are connected to the central generation unit. Computer simulations and experimental results are provided to quantify the efficiency enhancements obtained by adding the second wind turbine hydraulic pump to the system.

Indiana University-Purdue University Indianapolis (IUPUI) / Type I diabetes is an autoimmune disorder characterized by the loss of insulin producing islet cell mass. While daily insulin injection provides an easy means of glycemic control, it does not prevent long-term complications associated with diabetes. Islet transplantation has been suggested as a permanent cure for type 1 diabetes. However, the recurrence of host immunity and shortage of donor islets hinder the prevalence of islet transplantation. Biomaterial strategies provide an alternative route to solving the problems associated with host immune response and shortage of donor islets. One highly recognized platform for achieving these goals are hydrogels, which are hydrophilic crosslinked polymers with tissue-like elasticity and high permeability. Hydrogels prepared from poly(ethylene glycol) (PEG) derivatives are increasingly used for a variety of tissue engineering applications, including encapsulation of pancreatic islets and serving as a material platform for pseudo-islet differentiation. PEG hydrogels formed by mild and rapid thiol-ene photo-click reactions are particularly useful for studying cell behaviors in three-dimension (3D). Thiol-ene PEG-based hydrogels can be rendered biodegradable if appropriate macromer and cross-linker chemistry is employed. However, the influence of hydrogel matrix properties on the survival, growth, and morphogenesis of cells in 3D has not been fully evaluated. This thesis aims at using norbornene-functionalized PEG macromers to prepare thiol-ene hydrogels with various stiffness and degradability, from which to study the influence of hydrogel properties on pancreatic cell fate processes in 3D. Toward establishing an adaptable hydrogel platform for pancreatic tissue engineering, this thesis systematically studies the influence of hydrogel properties on encapsulated endocrine cells (e.g., MIN6 beta-cells) and exocrine cells (PANC-1 cells), as well as human mesenchymal stem cells (hMSC). It was found that thiol-ene photo-click hydrogels provide a cytocompatible environment for 3D culture of these cells. However, cell viability was negatively affected in hydrogels with higher cross-linking density. In contrast to a monolayer when cultured on a 2D surface, cells with epithelial characteristic formed clusters and cells with mesenchymal features retained single cell morphology in 3D. Although cells survived in all hydrogel formulations studied, the degree of proliferation, and the size and morphology of cell clusters formed in 3D were significantly influenced by hydrogel matrix compositions. For example: encapsulating cells in hydrogels formed by hydrolytically degradable macromer positively influenced cell survival indicated by increased proliferation. In addition, when cells were encapsulated in thiol-ene gels lacking cell-adhesive motifs, hydrolytic gel degradation promoted their survival and proliferation. Further, adjusting peptide crosslinker type and immobilized ECM-mimetic bioactive cues provide control over cell fate by determining whether observed cellular morphogenesis is cell-mediated or matrix-controlled. These fundamental studies have established PEG-peptide hydrogels formed by thiol-ene photo-click reaction as a suitable platform for pancreatic tissue engineering

Indiana University-Purdue University Indianapolis (IUPUI) / A constant-volume combustor is used to investigate the ignition initiated by a traversing jet of reactive hot gas, in support of combustion engine applications that include novel wave-rotor constant-volume combustion gas turbines and pre-chamber IC engines. The hot-jet ignition constant-volume combustor rig at the Combustion and Propulsion Research Laboratory at the Purdue School of Engineering and Technology at Indiana University-Purdue University Indianapolis (IUPUI) was used for this study. Lean premixed combustible mixture in a rectangular cuboid constant-volume combustor is ignited by a hot-jet traversing at different fixed speeds. The hot jet is issued via a converging nozzle from a cylindrical pre-chamber where partially combusted products of combustion are produced by spark- igniting a rich ethylene-air mixture. The main constant-volume combustor (CVC) chamber uses methane-air, hydrogen-methane-air and ethylene-air mixtures in the lean equivalence ratio range of 0.8 to 0.4. Ignition delay times and ignitability of these combustible mixtures as affected by jet traverse speed, equivalence ratio, and fuel type are investigated in this study.

Indiana University-Purdue University Indianapolis (IUPUI) / Atherosclerotic lesions of human beings are common diagnosed in regions of arte- rial branching and curvature. The prevalence of atherosclerosis is usually associated with hardening and ballooning of aortic wall surfaces because of narrowing of flow path by the deposition of fatty materials, platelets and influx of plasma through in- timal wall of Aorta. High Wall Shear Stress (WSS) is proved to be the main cause behind all these aortic diseases by physicians and researchers. Due to the fact that the atherosclerotic regions are associated with complex blood flow patterns, it has believed that hemodynamics and fluid-structure interaction play important roles in regulating atherogenesis. As one of the most complex flow situations found in cardio- vascular system due to the strong curvature effects, irregular geometry, tapering and branching, and twisting, theoretical prediction and in vivo quantitative experimental data regarding to the complex blood flow dynamics are substantial paucity. In recent years, computational fluid dynamics (CFD) has emerged as a popular research tool to study the characteristics of aortic flow and aim to enhance the understanding of the underlying physics behind arteriosclerosis. In this research, we study the hemo- dynamics and flow-vessel interaction in patient specific normal (healthy) and dilated (diseased) aortas using Ansys-Fluent and Ansys-Workbench. The computation con- sists of three parts: segmentation of arterial geometry for the CFD simulation from computed tomography (CT) scanning data using MIMICS; finite volume simulation of hemodynamics of steady and pulsatile flow using Ansys-Fluent; an attempt to perform the Fluid Structure Simulation of the normal aorta using Ansys-Workbench. Instead of neglecting the branching or smoothing out the wall for simplification as a lot of similar computation in literature, we use the exact aortic geometry. Segmen- tation from real time CT images from two patients, one young and another old to represent healthy and diseased aorta respectively, is on MIMICS. The MIMICS seg- mentation operation includes: first cropping the required part of aorta from CT dicom data of the whole chest, masking of the aorta from coronal, axial and saggital views of the same to extract the exact 3D geometry of the aorta. Next step was to perform surface improvement using MIMICS 3-matic module to repair for holes, noise shells and overlapping triangles to create a good quality surface of the geometry. A hexahe- dral volume mesh was created in T-Grid. Since T-grid cannot recognize the geometry format created by MIMICS 3-matic; the required step geometry file was created in Pro-Engineer. After the meshing operation is performed, the mesh is exported to Ansys Fluent to perform the required fluid simulation imposing adequate boundary conditions accordingly. Two types of study are performed for hemodynamics. First is a steady flow driven by specified parabolic velocity at inlet. We captured the flow feature such as skewness of velocity around the aortic arch regions and vortices pairs, which are in good agreement with open data in literature. Second is a pulsatile flow. Two pulsatile velocity profiles are imposed at the inlet of healthy and diseased aorta respectively. The pulsatile analysis was accomplished for peak systolic, mid systolic and diastolic phase of the entire cardiac cycle. During peak systole and mid-systole, high WSS was found at the aortic branch roots and arch regions and diastole resulted in flow reversals and low WSS values due to small aortic inflow. In brief, areas of sudden geometry change, i.e. the branch roots and irregular surfaces of the geom- etry experience more WSS. Also it was found that dilated aorta has more sporadic nature of WSS in different regions than normal aorta which displays a more uniform WSS distribution all over the aorta surface. Fluid-Structure Interaction simulation is performed on Ansys-WorkBench through the coupling of fluid dynamics and solid mechanics. Focus is on the maximum displacement and equivalent stress to find out the future failure regions for the peak velocity of the cardiac cycle.

Indiana University-Purdue University Indianapolis (IUPUI) / An excess of bone resorption over bone formation leads to osteoporosis, resulting in a reduction of bone mass and an increase in the risk of bone fracture. Anabolic and anti-resorptive drugs are currently available for treatment, however, none of these drugs are able to both promote osteoblastogenesis and reduce osteoclastogenesis. This thesis focused on the role of eukaryotic translation initiation factor 2 alpha (eIF2alpha), which regulates efficiency of translational initiation. The elevation of phosphorylated eIF2alpha was reported to stimulate osteoblastogenesis, but its effects on osteoclastogenesis have not been well understood. Using synthetic chemical agents such as salubrinal and guanabenz that are known to inhibit the de-phosphorylation of eIF2alpha, the role of phosphorylation of eIF2alpha in osteoclastogenesis was investigated in this thesis. The questions addressed herein were: Does the elevation of phosphorylated eIF2alpha (p-eIF2alpha) by salubrinal and guanabenz alter osteoclastogenesis? If so, what regulatory mechanism mediates the process? It was hypothesized that p-eIF2alpha could attenuate the development of osteoclast by regulating the transcription factor(s) amd microRNA(s) involved in osteoclastogenesis. To test this hypothesis, we conducted in vitro and in silico analysis of the responses of RAW 264.7 pre-osteoclast cells to salubrinal and guanabenz. First, the in vitro results revealed that the elevated level of phosphorylated eIF2alpha inhibited the proliferation, differentiation, and maturation of RAW264.7 cells and downregulated the expression of NFATc1, a master transcription factor of osteoclastogenesis. Silencing eIF2alpha by RNA interference suppressed the downregulation of NFATc1, suggesting the involvement of eIF2alpha in regulation of NFATc1. Second, the in silico results using genome-wide expression data and custom-made Matlab programs predicted a set of stimulatory and inhibitory regulator genes as well as microRNAs, which were potentially involved in the regulation of NFATc1. RNA interference experiments indicated that the genes such as Zfyve21 and Ddit4 were primary candidates as an inhibitor of NFATc1. In summary, the results showed that the elevation of p-eIF2alpha by salubrinal and guanabenz leads to attenuation of osteoclastogenesis through the downregulation of NFATc1. The regulatory mechanism is mediated by eIF2alpha signaling, but other signaling pathways are likely to be involved. Together with the previous data showing the stimulatory role of p-eIF2alpha in osteoblastogenesis, the results herein suggest that eIF2alpha-mediated signaling could provide a novel therapeutic target for treatment of osteoporosis by promoting bone formation and reducing bone resorption.

Indiana University-Purdue University Indianapolis (IUPUI) / Pedestrian and vehicle interaction analysis in a naturalistic driving environment can provide useful information for designing vehicle-pedestrian crash warning/mitigation systems. Many researchers have used crash data to understand and study pedestrian behaviors and interactions between vehicles and pedestrian during crash. However, crash data may not provide detailed pedestrian-vehicle interaction information for us. In this thesis, we designed an automatic pedestrian tracking and status analysis method to process and study pedestrian and vehicle interactions. The proposed pedestrian tracking and status analysis method includes pedestrian detection, pedestrian tracking and pedestrian status analysis modules. The main contributions of this thesis are: we designed a new pedestrian tracking method by learning the pedestrian appearance and also their motion pattern. We designed a pedestrian status estimation method by using our tracking results and thus helped estimate the possibility of collision. Our preliminary experiment results using naturalistic driving data showed promising results.

Indiana University-Purdue University Indianapolis (IUPUI) / Non-invasive surface recording of bioelectric potentials continues to be an essential tool in a variety of research and medical diagnostic procedures. However, the integrity of these recordings, and hence the reliability of subsequent analysis, diagnosis, or recommendations based on the recordings, can be significantly compromised when various types of noise are allowed to penetrate the recording circuit and contaminate the signals. In particular, for bioelectric phenomena in which the amplitude of the biosignal is relatively low, such as muscle activity (typically on the order of millivolts) or neural traffic (microvolts), external noise may substantially contaminate or even completely overwhelm the signal. In such circumstances, the tissue-electrode interface is typically the primary point of signal contamination since its impedance is relatively high compared to the rest of the recording circuit. Therefore, in the recording of low-amplitude biological signals, it is of paramount importance to minimize the impedance of the tissue-electrode interface in order to consistently obtain low-noise recordings. The aims of the current work were (1) to complete the development of a set of tools for rapid, simple, and reliable full-spectrum characterization and analytical modeling of the complex impedance of the tissue-electrode interface, and (2) to characterize the interfacial impedance and signal-to-noise ratio (SNR) at the surface of the skin across a variety of preparation methods and determine a factor or set of factors that contribute most effectively to the reduction of tissue-electrode impedance and noise contamination during recording. Specifically, we desired to test an initial hypothesis that surface abrasion is the principal determining factor in skin preparation to achieve consistently low-impedance, low-noise recordings. During the course of this master’s study, (1) a system with portable, battery-powered hardware and robust acquisition/analysis software for broadband impedance characterization has been achieved, and (2) the effects of skin preparation methods on the impedance of the tissue-electrode interface and the SNR of surface electromyographic recordings have been systematically quantified and compared in human subjects. We found our hypothesis to be strongly supported by the results: the degree of surface abrasion was the only factor that could be correlated to significant differences in either the interfacial impedance or the SNR. Given these findings, we believe that abrasion holds the key to consistently obtaining a low-impedance contact interface and high-quality recordings and should thus be considered an essential component of proper skin preparation prior to attachment of electrodes for recording of small bioelectric surface potentials.