Indiana University-Purdue University Indianapolis (IUPUI) / The thesis includes two application studies of computational fluid dynamics. The first is new and efficient drug delivery to the posterior part of the eye, a growing health necessity worldwide. Current treatment of eye diseases, such as age-related macular degeneration (AMD), relies on repeated intravitreal injections of drug-containing solutions. Such a drug delivery has significant cant drawbacks, including short drug life, vital medical service, and high medical costs. In this study, we explore a new approach of controlled drug delivery by introducing unique porous implants. Computational modeling contains physiological and anatomical traits. We simulate the IgG1 Fab drug delivery to the posterior eye to evaluate the effectiveness of the porous implants to control the drug delivery. The computational model was validated by established computation results from independent studies and experimental data. Overall, the results indicate that therapeutic drug levels in the posterior eye are sustained for eight weeks, similar to those performed with intravitreal injection of the same drug. We evaluate the effects of the porous implant on the time evaluation of the drug concentrations in the sclera, choroid, and retina layers of the eye. Subsequent simulations were carried out with varying porosity values of a porous episcleral implant. Our computational results reveal that the time evolution of drug concentration is distinctively correlated to drug source location and pore size. The response of this porous implant for controlled drug delivery applications was examined. A correlation between porosity and fluid properties for the porous implants was revealed in this study. The second application lays in the computational modeling of the oscillating

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<div>As aging proceeds, the occurrence of cardiovascular diseases increases independent of other risk factors. At atherosclerotic sites, the rise in the senescent cell population was also observed. Patients with Hutchinson Gilford Progeria Syndrome (HGPS) also showed accelerated aging syndromes and extensive atherosclerosis progression, which was due to missense mutations on the LMNA gene that led to the production of progerin, an aberrant lamin A isoform instead of regular lamin A protein. Lamins act as structural and functional components in nuclear lamina, and recent findings suggested that the ectopic expression of mutant lamin A or lamin A precursor (prelamin A) not only caused defects in cell mechanics but also disturbed mechanotransduction pathways involving lamin A, both of which may contribute to vascular dysregulation. Moreover, the observation of the accumulation of prelamin A in normal aged vascular cells further suggests shared dysregulations involving lamin A in the vascular system between aged people and HGPS patients.</div><div>In the vascular system, endothelial cells were well regulated by hemodynamic forces in vivo to maintain vascular homeostasis. Endothelial dysfunction, including impaired vasodilation and increased permeability, was regarded as the initial marker of atherosclerosis. Despite recent advancements and discussions about the potential mechanisms of progerin-induced vascular disorders, how progerin triggers endothelial dysfunction in a mechanical environment as an early event during atherosclerotic lesion formation has not been studied intensively.</div><div>To help answer the gap question, we first set our goal to understand the effect of laminar flow at arterial levels on endothelial lamins as part of the aging process. Spatial and temporal changes in lamin A/C expression were observed as cell passage went up without flow present. As shear stress was applied, lamin A/C expressions were modulated on both transcriptional and translational levels, which were also dependent on PDL. To further examine how progerin was involved in EC functions with a particular focus on the flow effects, we next generated a stable endothelial cell line that expressed progerin as our EC aging model. Endothelial wound repair under laminar flow at different rates was characterized, and differential cell proliferation activities, as well as migration deficiencies in progerin-expressing ECs during the process, were also recognized. Furthermore, we also showed the overactivated mTORC2 pathway and unusual actin polymerization activities in these cells after flow application. Our results reported changes in cell migration by progerin with flow application for the first time and provided potential candidate pathways that were disturbed by progerin under arterial flow, which may help explain the high occurrence of atherosclerotic lesions in HGPS vasculature, even at straight portion. The reported progerin-induced wound recovery defects in endothelial cells in the presence of physiological flow may also suggest a mechanism of how progerin disturbs endothelial integrity and functions under mechanical stimuli in the development of vascular pathologies.</div><div>Further extended studies may help to understand the roles of progerin in initiating atherosclerosis, which will aid in the development of potential therapies for those suffering from prelamin A-associated accelerated aging syndromes.</div>

Saccular aneurysms are the abnormal plastic deformation of veins and arteries that can lead to lethal thrombus genesis or internal hemorrhaging. Medication and surgery greatly reduce the mortality rates, but treatment is limited by predicting who will develop aneurysms. A common location for saccular aneurysm genesis is at the main middle cerebral artery (MCA) bifurcation. The main MCA bifurcation is comprised of the M1 MCA segment, parent artery, and two M2 segments, daughter arteries. Studies have found that the lateral angle (LA) ratio of the MCA bifurcation is correlated with aneurysm formation. The LA ratio is defined as the angle between the M1 and the larger M2 divided by the angle between the M1 and the smaller M2. When the LA ratio is equal to 1, perfectly symmetrical, no aneurysms are found at the MCA bifurcation. When the LA ratio is greater than 1.6, aneurysms are commonly found at the MCA bifurcation. In the research described here, varying MCA bifurcation angles were compared to uncover any changes to fluid flow and wall shear stress that could stimulate aneurysm growth. Eight pre-aneurysm MCA bifurcation models were created in SolidWorks® using 120 degrees, 90 degrees, and 60 degrees as the angle between the M1 and the larger M2. LA ratios of 1, 1.6 and 2.2 were then used to characterize the other branch angle (60 degrees with a LA ratio of 1 was excluded). These models were imported into COMSOL Multiphysics® where the laminar fluid flow module was used to simulate non-Newtonian blood flow. Fluid flow profiles showed little to no change between the models. Shear stress changed when the LA ratio was increased, but the changed varied between the 120, 90 and 60 degree models. 120 degree models had a 3.87% decrease in max shear stress with a LA ratio of 2.2 while the 90 degree models had 7.5% decrease in max shear stress with a LA ratio of 2.2. Each daughter artery had distinct areas of high shear stress when the LA ratio equaled 1. Increasing the LA ratio or decreasing the bifurcation angle caused the areas of shear stress to merge together. Increasing LA ratio caused shear stress to decrease and spread around the MCA bifurcation. The reduction in max wall shear stress for high LA ratios supports current aneurysm genesis hypothesizes, but additional testing is required before bifurcation geometries can be used to predicted aneurysm genesis.

Previous studies have shown that soil erodibility and critical shear stress are highly influenced by weathering processes such as freeze-thaw cycling and wet-dry cycling. Despite over forty years of research attributing changes in soil properties over time to climate-dependent variables, little quantitative information is available on the relationships between streambank erodibility and critical shear stress and environmental conditions and processes that enhance streambank erosion potential. The goal of this study was to investigate temporal changes in streambank erodibility and critical shear stress due to surface weathering. Soil erodibility and critical shear stress were measured monthly in situ using a multi-angle submerged jet test device. Environmental and soil data were also collected directly at the streambank surface to determine freeze-thaw cycles, soil moisture, soil temperature, bulk density, soil erodibility, critical shear stress, and other atmospheric conditions that could impact bank erosion potential. Statistical tests, including a nonparametric alternative to ANOVA and multiple comparison tests, were used to determine if temporal changes in soil erosion potential were greater than spatial differences. Regression analyses were also utilized to identify the factors contributing to possible changes in soil erodibility, critical shear stress, and bulk density. The nonparametric alternative to ANOVA in combination with Dunn's nonparametric multiple comparison test showed soil erodibility was significantly higher (p=0.024) during the winter (November - March) and the spring/fall (April - May, September - October). Regression analyses showed 70 percent of soil erodibility variance was attributed to freeze-thaw cycling alone. Study results also indicated that bulk density is highly influenced by climate changes since gravimetric water content and freeze-thaw cycles combined explain as much as 86 percent of the variance in bulk density measurements. Results of this study show significant amounts of variation in the resistance of streambank soils to fluvial erosion can be attributed to subaerial processes, specifically changes in soil moisture and temperature. These results have potential implications for streambank modeling and restoration projects that assume constant values for soil erodibility. Watershed models and restoration designs should consider the implications of changing soil erodibility during the year in model development and stream restoration designs. / Master of Science

The interaction between fluid dynamics and biofilm growth plays a key role in both medical and industrial applications. Biofilms, or bacteria that are embedded in a protective matrix of extracellular polymeric substances, settle on interfaces such as on implanted devices or ship hulls. These biofilms canthen cause infectious diseases or significantly increase drag. In this thesis, we investigate the influence of flow, specifically shear stress, on the development of biofilm. The first paper presents a new facility to investigate biofilm growth in laminar flow cells over extended periods of up to several weeks. Optical coherence tomography is used to obtain three-dimensional scans of the biofilm structure at regular intervals. From these time series, we derive a simple model that relates the growth of an individual microcolony to the growth of the full biofilm depending on the wall shear stress. Additionally, we show that biofilm streamers, thin, flexible filaments that extend into the bulk flow, can form on sharp biofilm structures in laminar flow, even if the substratum is a flat surface. The second contribution is a report detailing preliminary studies on biofilm experiments. We investigate the formation of biofilm in the shear layer behinda backward-facing step. The results indicate a maximum shear stress, beyond which biofilm growth is inhibited. We also provide guidelines for the design of experimental setups for the investigation of the influence of fluid dynamics on biofilm and vice-versa. / Samspelet mellan fluiddynamik och biofilmtillväxt spelar en nyckelroll i både medicinska och industriella tillämpningar. Biofilmer, eller bakterier som är inbäddade i en skyddande matris av extracellulära polymera substanser, sätter sig på ytor som på implanterade enheter eller fartygsskrov. Dessa biofilmer kan sedan orsaka infektionssjukdomar eller avsevärt öka vattenmotståndet. I den här avhandlingen undersöker vi hur flöde, speciellt skjuvspänning, påverkar utvecklingen av biofilm. I den första artikeln presenteras en ny uppställning för att undersöka biofilmstillväxt i flödesceller med laminärt flöde under längre perioder på upp till flera veckor. Optisk koherenstomografi används för att få tredimensionella skanningar av biofilmstrukturen vid regelbundna intervall. Från dessa tidsserier härleder vi en enkel modell som relaterar tillväxten av en enskild mikrokoloni till tillväxten av hela biofilmen beroende på väggskjuvspänning. Dessutom visar vi att biofilm filament som sträcker sig in i bulkflödet, kan bildas på skarpa biofilmstrukturer i laminärt flöde, även om substratum är en plan yta.  Det andra bidraget är en rapport som beskriver preliminära studier av biofilmsexperiment. Vi undersöker bildandet av biofilm i skjuvskiktet bakom ett bakåtvänt steg. Resultaten indikerar en maximal skjuvspänning, bortom vilken biofilmstillväxt hämmas. / <p>QC 240314</p>

<p> Preparations for an investigation of interfacial momentum transfer in two-phase two-component critical flows have been completed.</p> <p> The experiments involve the measurement of flow rates, axial pressure profiles, axial and transverse void fraction profiles, and axial wall shear stress profiles of steady-state gas-liquid critical flow in a vertical diverging nozzle. A photographic study is to be initiated to record the flow structure. The results of these experiments will be used to develop constitutive relations for interfacial momentum transfer.</p> <p> An experimental loop capable of circulating a gas-liquid mixture in a vertical test section was modified to suit the requirements of this investigation. The void fraction profiles are measured with a traversing gamma densitometer using a 20 mCi Co57 source. The wall shear stress profiles are obtained using the electrochemical method to measure the mass transfer coefficients of electrodes mounted flush with the test section wall. The liquid phase is an electrolyte and the gaseous phase can be air, nitrogen or freon. The latter is used to better approximate the densities of a steam-water flow.</p> <p> This report describes the required theory, measurement techniques, design and operation of the loop, and the experimental procedures.</p> / Thesis / Master of Engineering (MEngr)

<p> An investigation of the technique of obtaining the wall shear stress in a two-phase flow, by measuring the mass transfer coefficient at the wall with the electrochemical method, has been completed.</p> <p> The experiments involved the measurement of flow rates, pressure drops, void fractions and mass transfer coefficients, for a cocurrent upwards gas-liquid flow in a vertical tube, 13 mm in diameter. The liquid phase was an electrolyte consisting of 1.0 to 3.0 molar sodium hydroxide, and 0.005 to 0.010 equimolar potassium ferricyanide and potassium ferrocyanide. The gas phase was nitrogen. The flow regimes studied were slug, churn and annular.</p> <p> Emphasis is placed on the measurements obtained with the electrochemical method. Its application, advantages and disadvantages are detailed. A series of single-phase experiments were performed to explore the characteristics of the method and to serve as benchmarks for the two-phase experiments.</p> <p> The space-time-averaged values of the mass transfer coefficient were found to give the wall shear stresses to an accuracy of ±20%. Frequency analysis of the local fluctuating values indicate that measurements of the local mass transfer coefficient can be used for flow regime identification.</p> <p> The theoretical flow regime map of Dukler and Taitel successfully predicted the flow regimes. The correlations of Griffith and Wallis, and Lockhart and Martinelli as modified by Davis, predicted the pressure drops and void fractions to an accuracy ±15% when applied to the appropriate flow regimes. As a further exercise, the force interactions between the phases, referred to as the interfacial shear terms, were calculated from both the measured and predicted void fractions and pressure drops.</p> / Thesis / Master of Engineering (MEngr)

To better understand how platelets behave when exposed to high shear stress, computational fluid dynamic (CFD) models for single-layer (uniform and constant) viscosity flow and two-layer (two distinct regions of different viscosities) viscosity flow were developed. The single-layer model, which represents common standard practice, did not predict the pressure drop correctly; the error produced from using the single-layer model was approximately 95%. However, the two-layer model produced results that were within 6% of the experimental results. Experimental results used to validate CFD models were obtained from data gathered by researchers at University Medical Center (UMC) in Jackson, MS. Using Fluent 6.2, simulations were performed that showed the characteristics of blood flow in a long stenosis. The beginning of the development of a blood damage model was also investigated. This thesis could provide researchers with information that will eventually allow the prediction of platelet activation and hemolysis.

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