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Use Of Microscale Hydrophobic Surface Features For Integration Of 3d Cell Culture Into Multi-Functional Microfluidic Devices, Soroosh Torabi

Theses and Dissertations--Mechanical and Aerospace Engineering

3D cell culture and microfluidics both represent powerful tools for replicating critical components of the cell microenvironment; however, challenges involved in integration of the two and compatibility with standard tissue culture protocols still represent a steep barrier to widespread adoption. Here we demonstrate the use of engineered surface roughness in the form of microfluidic channels to integrate 3D cell-laden hydrogels and microfluidic fluid delivery. When a liquid hydrogel precursor solution is pipetted onto a surface containing open microfluidic channels, the solid/liquid/air interface becomes pinned at sharp edges such that the hydrogel forms the “fourth wall” of the channels upon solidification. …

Multiscale Finite Element Modeling Of Active Contraction In Striated Muscle, Charles Kurtis Mann

Theses and Dissertations--Mechanical and Aerospace Engineering

Greater than one in three American adults have at least one type of cardiovascular disease, a major cause of morbidity. Computational cardiac mechanics has become an important part of the research effort to understand the heart’s response to mechanical stimuli and as an extension, disease progression and potential therapies. To this end, the present work aims to extend these efforts by implementing a cell level contractile model in which active stress generation in muscle tissue is driven by half-sarcomere mechanics. This is accomplished by enhancing the MyoSim model of actin and myosin in order to produce a multiscale model. This …

Study Of Stress-Based Fiber Reorientation Law In A Finite Element Model Of Cardiac Tissue, Alexus Lori Rockward

Theses and Dissertations--Mechanical and Aerospace Engineering

Myofiber organization in the heart plays an important role in achieving and maintaining physiological cardiac function. In many cardiac disease states, myofibers and particularly cardiomyocytes are disorganized in chaotic patterns, a phenotype known broadly as myocardial disarray. In familial hypertrophic cardiomyopathy (HCM), this disorganization in the form of myocyte disarray is thought to contribute to impaired cardiac function and the development of arrhythmia during disease progression. However, the mechanisms regarding fiber reorientation in the heart are yet still unclear, and few adaptative laws have been created to explore these mechanisms. A stretch-based law was developed with the aim of achieving …

Redesigning Products To Optimize Sustainable Performance In Multi-Generational Closed-Loop Production For Advancing The Circular Economy, Buddhika Minendra Hapuwatte

Theses and Dissertations--Mechanical and Aerospace Engineering

Sustainable manufacturing and the circular economy concepts promote efficient and effective resource use to minimize the adverse economic, environmental, and social impacts of alarmingly increasing consumption rates. Product design is the key to implement these transformations in manufacturing. However, the currently available sustainable and circular design methods are not comprehensive and inadequate—especially for multi-generational products. Therefore, designing sustainable products optimized for circular and closed-loop production systems is a challenging task. The 6Rs concept introduced ‘Redesign’ to modify a product’s engineering specifications and allow sustainable utilization of the end-of-use resources from previous generations, thus closing the production loop. Therefore, the objective …

Cell And Biofilm Adhesion Strength Quantified By The Laser Spallation Technique Yields A Novel Biocompatibility Metric, The Adhesion Index, James Boyd

Theses and Dissertations--Mechanical and Aerospace Engineering

Implant associated infections are one of the leading causes of hospital acquired infections in the United States. Medical orthopedic implant devices are designed to improve adhesion of relevant cells within our body. In the case of orthopedic implants, osteoblast cells will adhere and allow for proper integration with the body’s bones. However, virulent bacteria will also adhere onto medical implants and proliferate into biofilms. Bacterial biofilms become extremely difficult to eradicate clinically as antibiotics are not as effective, resulting in severe infections or loss of implant. The aim of this research is to quantify the adhesion strength differential between relevant …

Effective Modulus Of Cracked Bodies: A Finite Element Analysis, Alan Thomas Varughese

Theses and Dissertations--Mechanical and Aerospace Engineering

This thesis considers how cracks in an elastic body can alter the body’s elastic properties. In the present study the elastic property of note is the elastic or young’s modulus. It is desired to investigate to what extent the number and orientation of cracks can cause a reduction in the elastic modulus. Because of the complex nature of the elastic fields resulting from multiple cracks interacting together in a finite geometry an analytical solution is not possible or considered. Rather the Finite Element Method is used to determine the elastic response to a body with many cracks. This provides a …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Precision Drug Delivery For Vancomycin Efficacy And Safety In Critically Ill Patients, Alexander Flannery

Theses and Dissertations--Clinical and Translational Science

Vancomycin is the most commonly prescribed antibiotic for hospitalized patients. Despite this fact and decades of clinical use, clinicians remain challenged to meet dosing targets of this narrow therapeutic index drug as well as minimize the risks of therapy, primarily nephrotoxicity. These concerns are magnified in critically ill patients given their severity. Accordingly, in a series of five clinical studies, we sought to identify optimal methods of vancomycin administration in critically ill patients to maximize efficacy and minimize nephrotoxicity via three techniques: use of continuous versus intermittent infusion, use of first-dose pharmacokinetic calculations to guide dosing, and use of loading …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …

Comparison Of Implant-Retained Overdenture And Conventional Complete Denture In The Edentulous Mandible: A Survey Study To Measure Patients' Satisfaction And Quality Of Life In Dental School Clinical Environment, Ahmad Kutkut

Theses and Dissertations--Clinical and Translational Science

Patient satisfaction and quality of life are integral parts of assessing the quality of oral health care. Current aging population trends suggest a growing need to understand the effects of edentulism on oral health and quality of life. As the proportion of aged Americans expands, there will be an increased need to understand treatment options and patient communication strategies. In addition, as new treatment options and innovative technologies emerge, it will be essential to understand patients' concerns and identify best practices associated with denture treatments' individual fit and function. Advanced denture treatments can now be fabricated using CAD/CAM digital denture …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

The Trust-Based Classroom: An Analysis Of Current Trends In Social And Emotional Learning And The Development Of A New Trust-Based Approach To Art Education, Ellen Prasse

Theses and Dissertations--Art and Visual Studies

Many current social and emotional learning (SEL) programs cite building trust as a key factor to an effective SEL program. Despite these references, however, they often lack an emphasis on teaching methods of building trust between students and their peers, the teacher, and the environment. Instead they focus on a specific aspect of teaching like the procedural practices of Responsive Classroom or communication and open-mindedness as in Open Circle. Explicitly building trust, however, could create an art classroom atmosphere conducive to high quality learning. This paper analyzes current trends in social and emotional learning and outlines the characteristics of the …

Remote Supported Communication For Adults With Chronic Aphasia: A Serendipitous Study, Allie Hopper

Theses and Dissertations--Communication Sciences and Disorders

Supported communication is defined as anything that improves access to or participation in communication events or activities (King, Simmons-Mackie, & Beukelman, 2012). This thesis describes the results of a study that took place when a training program to provide graduate students in Communication Sciences and Disorders (CSD) with “hands on” experience in providing supported communication to persons with chronic aphasia (PWA) was interrupted by the outbreak of Coronavirus-19 and switched to a remote delivery format to fulfil service and training obligations to the PWA and the CSD graduate students respectively. The study (1) describes the actions taken to covert a …

Genetic Mouse Models Of Liver Disease: Potential Roles Of Zhx2 (Afr1) And Afr2 In Damage And Regeneration, Courtney P. Turpin

Theses and Dissertations--Pharmacology and Nutritional Sciences

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

The Role Of Microtubule-Associated Protein Tau In Neuronal Excitability And Epileptogenesis, Ryan A. Cloyd

Theses and Dissertations--Physiology

Tauopathies, including Alzheimer’s disease (AD), are devastating diseases with an immense burden on society which is predicted to increase in coming decades. In addition to progressive loss of memory and cognitive function, patients with tauopathies have a 6-10 fold increase in lifetime risk for seizures, and many are diagnosed with epilepsy. The presence of epileptiform activity on electroencephalogram (EEG) recordings from patients with AD predicts faster cognitive decline compared to patients without abnormal EEG readings. Electrophysiological measurements in murine models of AD have identified neuronal hyperexcitability. Furthermore, reducing tau phosphorylation or expression confers seizure resistance in animal epilepsy models. Although …

Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr

Theses and Dissertations--Physiology

Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily relies on animal models. The purpose of this project is to develop and study novel mammalian models of SCI to provide insights for the development and effective implementation of SCI therapies.

Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but …

Metabolic And Electrophysiological Effects Of Fibroblast Growth Factor 19 In The Dorsal Vagal Complex, Jordan Wean

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC) is an important homeostatic regulatory center located in the hindbrain that alters vagal parasympathetic activity in response to central, viscerosensory, and humoral cues. Within the DVC, second-order sensory neurons in the nucleus tractus solitarius (NTS) integrate ascending vagal sensory input with descending regulatory inputs from higher brain areas and respond to circulating hormones and glucose. In turn, the NTS projects to the dorsal motor nucleus of the vagus (DMV) which is comprised of cholinergic motor neurons and regulates gastric motility, hepatic glucose production, and pancreatic hormone release functions, among others.

Fibroblast growth factor 19 (FGF19) …

Development Of A Robust Linac-Based Radiosurgery Program For Multiple Brain Metastases & Estimation The Radiobiological Response Of Indirect Cell Kill, Allison Palmiero

Theses and Dissertations--Radiation Medicine

Accurate and precise delivery of Stereotactic Radiosurgery (SRS) using Gamma Knife (GK) unit by Leksell is a gold standard for multiple intracranial lesions. SRS provides less brain toxicity compared to whole brain radiotherapy techniques historically used. However, these treatments are limited in availability and are accompanied by long treatment times with painful, intolerable headframe fixation. With advancements in linear accelerator (Linac) based SRS, multiple brain lesions can be treated separately with individual isocenters or, more recently, altogether with a single isocenter multi-target (SIMT) volumetric modulated arc therapy (VMAT) technique. SIMT methods reduce the challenges of treating patients with GK by …

Profiling Social Media Tourists Using Literature During 2015-2019: Criminal Profiling Method, Jijun Chen

Theses and Dissertations--Retailing and Tourism Management

With the continuous development of mobile commerce and the Internet, social media has deeply penetrated people’s lives and fundamentally changed the way of searching, reading and using travel-related information. With this backdrop, this research studied social media tourists (SMTs) who share or acquire information related to the hospitality and tourism on social media platforms. Based on 271 empirical articles retrieved from major databases and top hospitality and tourism journals in the recent five years from 2015 to 2019, this research developed a profiling framework about SMTs using criminal profiling method. The findings showed the possibility of using the criminal profiling …

Evaluating The Performance Of Reusable Level 2 Isolation Gowns, Susan I. Dabbain

Theses and Dissertations--Retailing and Tourism Management

The purpose of this research was to evaluate the performance of commercially available reusable Level 2 isolation gowns over the product’s lifecycle by assessing the ability to protect at an AAMI Level 2. The performance of the gowns was evaluated to determine if they met the required specifications of the AAMI and ASTM standards. Seventy-two commercially available Level 2 reusable gowns from six sample groups were evaluated. The results of testing the barrier and durability performance were compared to the specification of ANSI/AAMI PB70:2012 and ASTM F3352 – 19. Gowns were evaluated initially, and after 5, 10, 25, 50, and …

Seeing Double With Cannabis: Heteroploid Populations In Bipolaris Gigantea, Causal Agent Of Bipolaris Leaf Spot, Desiree Szarka

Theses and Dissertations--Plant Pathology

Bipolaris leaf spot (BLS) disease emerged with the reintroduction of hemp as a crop in the United States following more than 60 years of prohibition. The causal agent was identified as Bipolaris gigantea (=Drechslera gigantea), a known minor pathogen of monocots which causes devastating disease on hemp. BLS has been confirmed throughout Kentucky and reported in 15 states. Morphology and growth characteristics of isolates from eight counties across Kentucky were similar with the exception of some isolates producing protoperithecial-like structures. Phylogenetic and whole genome analysis indicated that some isolates were haploid, containing a single allele at each gene …

Maturation Of Equine Proximal Sesamoid Bones In Thoroughbred Horses, Angela Maria Mangine

Theses and Dissertations--Veterinary Science

Proximal sesamoid bone (PSB) injuries account for approximately 50% of all fatal catastrophic musculoskeletal injuries in Thoroughbred racehorses. In addition, PSB fractures are not uncommon in Thoroughbred foals and yearlings as a result of energetic or intense free exercise. The ability to interpret some PSB pathology assessments, however, is more difficult given the limited information published on the normal development and maturation of these paired sesamoid bones. In addition, the level of normal variation in PSB morphological and structural parameters within the Thoroughbred population as a function of age, body size, gender, and inter-animal variation are not well documented, complicating …

Structural Adaptation Of Equine Proximal Sesamoid Bones To High-Speed Exercise, Kathryn Mary Babiarz

Theses and Dissertations--Veterinary Science

Proximal sesamoid bone (PSB) fractures are one of the most commonly reported catastrophic musculoskeletal injuries (CMI) in Thoroughbred racing. Despite the seriousness of these injuries, an understanding of the structural changes that occur normally within PSBs in response to the biomechanical forces of high-speed exercise and how they relate to pathological events leading to fracture remain limited. To address this critical knowledge gap, PSBs from Thoroughbred horses were analyzed with both computed tomography (CT) and microcomputed tomography (µCT) to assess their morphological and structural parameters. Comparisons were made using samples from the left and right forelimbs of Thoroughbreds of both …

An Assessment Of The Carrier State And A Novel Marker Of Leptospira And Abortion In Central Kentucky Horses, Gloria Louise Gellin

Theses and Dissertations--Veterinary Science

Leptospirosis is a reemerging zoonotic infection of worldwide importance and affects all mammals. The bacterium is transmitted to animals and humans by urine, fetal membranes and body fluids. Leptospira shedding in the urine contaminates both soil and water, exposing both humans and animals to the bacterium. Leptospirosis in horses can cause abortion and is one of the etiologies of equine recurrent uveitis which can lead to blindness. Equine leptospiral abortion in Central Kentucky is primarily caused by serovar Pomona, with occasional cases attributed to serovar Grippotyphosa. There are a few reports in the literature attributing abortion to serovar Bratislava in …

Muscle Mass And Immune Function In The Senior Horse, Alisa Christina Herbst

Theses and Dissertations--Veterinary Science

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has …

Vole Population Dynamics In Cover Crops Transitioning To Soybeans With Integrated Pest Management By Habitat Modification, Jena L. Nierman

Theses and Dissertations--Forestry and Natural Resources

The use of cover crops has been a wildly used method in rotational row crop production. Cover crops have minimized soil runoff and aided in maintaining nutrients in agricultural fields. Increased use of cover crops has seen a corresponding increase in the amount of damage done to soybeans by voles. Currently, there are no mitigation methods that successfully decrease vole populations in agricultural fields. The use of habitat manipulation as an integrated pest management solution has not been studied as a practical solution for vole population management. During 2019 and 2020, I tested the impacts of various cover crop termination …

The Impacts Of Imazapic On Garlic Mustard And Non-Target Forest Floor Vegetation In Central Kentucky’S Hardwood Forests, Pavan Kumar Podapati

Theses and Dissertations--Forestry and Natural Resources

Alliaria petiolata is an invasive biennial herb that poses a substantial threat to various ecosystems across the United States. Imazapic herbicide can control A. petiolata infestations, but there is limited peer-reviewed data on impacts of pre-emergent imazapic spraying to forest floor communities. This research examined the impacts of pre-emergent imazapic (0.84 kg/ha) with Pentra-Bark® surfactant on ground cover of A. petiolata and the spring perennials Claytonia virginica and Erigenia bulbosa. Experimental populations in randomized blocks within two forest stands in central Kentucky received the following treatments at 0.84 kg ai/ha: imazapic with Pentra-Bark®, glyphosate with Pentra-Bark®, Pentra-Bark® alone, and …

Extraction Of Micro- And Nano-Plastic Particles From Water Using Hydrophobic Natural Deep Eutectic Solvents, Jameson R. Hunter

Theses and Dissertations--Biosystems and Agricultural Engineering

The production of plastic and the amount of waste plastic that enters the environment increases every year. Synthetic polymers will gradually break down into particles on the micro- and nano-scale. The micro- and nano-plastics pose a significant ecological harm by transporting toxic chemicals and causing inflammation and cellular damage when ingested. Two common plastics are polyethylene terephthalate (PET) and Polystyrene (PS), and a newer bioplastic polylactic acid (PLA) that has become a popular alternative. Deep eutectic solvents are a recently discovered solvent composed of a hydrogen bond donor and hydrogen bond acceptor and have been proposed as a cheaper alternative …

Assessing The Use Of Lidar And Uav Technology For Monitoring Growing Alfalfa, Stuart Tucker Sheffield

Theses and Dissertations--Biosystems and Agricultural Engineering

Alfalfa is a popularly grown crop because of its value as a nutritious feed source for livestock. The efficient production of an alfalfa crop relies on the monitoring of certain parameters, like height, quality, and yield. Traditionally, producers have used manual measurements of alfalfa plant height to estimate the nutritive quality and yield of a growing alfalfa crop. Manual measurements of plant height are often labor intensive and provide low resolution data that is not acceptable for full field scale assessment of growing alfalfa. The two studies presented in this thesis offer detailed insight into the rapid and accurate monitoring …