Automated Conversion Of Multicellds Digital Cell Lines And Isa-Tab Filesets., Connor Joseph Burns

Electronic Theses and Dissertations

Biological simulation tools are a valuable asset to bridge the gap between biological experimentation and biological theory. As systems thinking has become more regularly applied to biological materials and processes, these materials and processes have been characterized in multi-disciplinary, computational manners. This characterization has yielded an ability to create more realistic simulation tools that can provide in silico experiments for a wider range of scenarios. One prominent simulation tool is PhysiCell, an open-source physics-based multicellular simulation program which utilizes input Digital Cell Lines or Digital Snapshots from the MultiCellular Data Standard (MCDS) project.

This project aims to allow data exchange …

Cfd Analysis Of Acoustofluidic Channels And The Effects On Biologic Delivery., Zachary T. Long

Electronic Theses and Dissertations

T-cell transformation is an ever-expanding treatment for several types of cancer, with a potential to be adapted to other disorders in which the immune system plays a key role in the pathophysiology. Currently, all FDA approved chimeric antigen receptor (CAR) T-cell cancer therapies rely on transformation via viral transduction. However, viral transduction is plagued by poor consistency and the potential to create adverse immune reactions when T-cells are reintroduced into a patient. Other transformation methods are being explored, with an alternative called acoustofluidic sonoporation showing promise. In these procedures, cells are passed through a channel, of the millimeter scale, while …

Simulation Of Fracture Strength Improvements Of A Human Proximal Femur Using Finite Element Analysis., Waleed Ebraheem Alim

Electronic Theses and Dissertations

The most common hip fracture in the elderly occurs as a result of a fall to the side with impact over the greater trochanter resulting in a fracture of the proximal femur. The fracture usually involves the femoral neck or the intertrochanteric region. It has recently been determined that the fracture crack of a hip fracture typically initiates on the superior-lateral cortex of the femoral neck and then propagates across the femoral neck, resulting in a complete fracture. The strength of the superior-lateral cortex of the femoral neck is likely determined by the combined properties of the generally thin cortex …

Machine Learning Approaches For Lung Cancer Diagnosis., Ahmed Mahmoud Ahmed Shaffie

Electronic Theses and Dissertations

The enormity of changes and development in the field of medical imaging technology is hard to fathom, as it does not just represent the technique and process of constructing visual representations of the body from inside for medical analysis and to reveal the internal structure of different organs under the skin, but also it provides a noninvasive way for diagnosis of various disease and suggest an efficient ways to treat them. While data surrounding all of our lives are stored and collected to be ready for analysis by data scientists, medical images are considered a rich source that could provide …

Development And Applications Of In-Vitro And In-Silico Models Of The Cardiovascular System To Study The Effects Of Mechanical Circulatory Support., Moustafa Meki

Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. With ongoing interest in CVDs treatment, preclinical models for drug/therapeutic development that allow for fast iterative research are needed. Owing to the inherent complexity of the cardiovascular system, current in-vitro models of the cardiovascular system fail to replicate many of the physiological aspects of the cardiovascular system. In this dissertation, the main concern is with heart failure (HF). In advanced HF, patients may receive Left Ventricular Assist Devices (LVADs) as a bridge to transplant or destination therapy. However, LVADs have many limitations, including inability to adapt to varying tissue demand …

Imparting 3d Representations To Artificial Intelligence For A Full Assessment Of Pressure Injuries., Sofia Zahia

Electronic Theses and Dissertations

During recent decades, researches have shown great interest to machine learning techniques in order to extract meaningful information from the large amount of data being collected each day. Especially in the medical field, images play a significant role in the detection of several health issues. Hence, medical image analysis remarkably participates in the diagnosis process and it is considered a suitable environment to interact with the technology of intelligent systems. Deep Learning (DL) has recently captured the interest of researchers as it has proven to be efficient in detecting underlying features in the data and outperformed the classical machine learning …

Development Of A Pediatric Cardiac Assist Maglev Pump For Use With A Universal Driver System., Landon Heath Tompkins

Electronic Theses and Dissertations

Heart failure (HF) remains the leading cause of death, affecting 26 million adults worldwide and 6.5 million adults in the United States. Pediatric HF patients have been a historically underserved population with few options for mechanical circulatory support (MCS) therapy, a leading treatment as an alternative to heart transplantation. To address this clinical need, the Inspired Universal MagLev System is being developed; a low cost, universal magnetically levitated extracorporeal MCS system with interchangeable single-use pumps that will ultimately provide adult and pediatric patients ventricular and respiratory assist therapies. The Inspired Pediatric VAD is the first single-use pump application for this …

The Use Of Nanoparticles And Electrospun Fibers For Intravaginal Delivery To Treat Viral And Bacterial Infections And Electrophysiological Measurements Of Synthetic Chloride Channels., Farnaz Minooei

Electronic Theses and Dissertations

Female reproductive viral and bacterial infections affect millions of women worldwide. Given the diversity and magnitude of these unmet reproductive health challenges, topical administration of antiretrovirals (ARVs) and antibiotics have emerged as promising approaches to maintain and restore reproductive health. However, currently available intravaginal dosage forms often suffer from low user adherence and the need for frequent, daily administration to achieve therapeutic effect. To address these challenges, the broad goal of this research was to focus on the development of new localized nanoparticle (NP) and electrospun fiber dosage forms to prolong the delivery and enhance the efficacy of active agents …

An Exercise Device Used To Achieve Bone Formation Metrics For The Strengthening Of The Proximal Femur., Sean P. Coyle

Electronic Theses and Dissertations

Lateral falls often lead to hip fracture particularly in the elderly who have low bone mineral density. These fractures frequently lead to indirect mortality soon after injury. Normal use over the course over a lifetime leads to optimized adaptation of the bone in the proximal femur according to normal loading. A lateral fall generates non-normal, lateral loading at the proximal hip where the bone has not adapted to withstand such loading. The resulting fracture is generated by reversed strains on the bone tissue in the femoral neck in the hip in contrast to vertical, quotidian loading. Modern practices for preventing …

Mathematical Characterization Of A Microfluidic Ultrasound Driven Transfection Device., Chris J. Holton

Electronic Theses and Dissertations

The objective of this thesis is to develop a mathematical model characterizing the behavior of a microfluidic sonoporation device in order to understand how standing wave conditions influence molecular delivery to cells and determine whether the model predicts device performance. A prior model based on an ultrasonic separation cell that uses standing waves to separate particles is adapted for translation to the microfluidic device. This study generates data on acoustic pressure profiles across the cell as well as identifying optimal driving frequencies. This model is validated and the equations and methods for developing this model are translated to the microfluidic …

Evaluation Of Tracing Techniques In The Rat Spinal Cord Using A Custom Matlab Application., Rachel M. Zalla

Electronic Theses and Dissertations

The objective of this research project is to evaluate the efficiency of traditional chemical tracing compared to dual-viral tracing for labeling long ascending propriospinal neurons (LAPNs) in the uninjured rat spinal cord, and to develop a MATLAB program which will accurately quantify this labeling.

To evaluate chemical tracing, Fluoro-Ruby (FR) was injected at the level of the axon terminals, and the number of ipsilateral labeled cell bodies at lumbar level was quantified. Similarly, two dual-viral systems were evaluated, by either injecting retro-AAV-Cre or HiRet-Lenti-Cre unilaterally in combination with a Cre-dependent adeno-associated virus. The HiRet-Lenti and FR groups labeled significantly greater …

Simulation Of A Continuum Tumor Model Using Distributed Computing., Dylan A Goodin

Electronic Theses and Dissertations

Mathematical modeling aims to provide a theoretical framework for understanding tissue dynamics and for establishing treatment response for diseased tissues, such as tumors. Previously published continuum models have successfully represented idealized two-dimensional and three-dimensional tissue for short periods of time. A recently published continuum model of cancer increases model complexity and describes three-dimensional tissue that, due to the required complexity of the geometric multigrid solver, can only be feasibly applied to millimeter-scale simulations. Furthermore, the computational cost for such models has hindered their application in the laboratory and in the clinic. With computational demands greatly outpacing current openMP-based approaches on …

Feasibility Study Of Intelligent Lvad Control For Optimal Heart Failure Therapy., John A. Karlen Iii

Electronic Theses and Dissertations

Background: Left ventricular assist devices (LVAD) are operated at constant speeds (rpm), consequently, pump flow is passively determined by the pressure difference between the LV and aorta. Since the diastolic pressure gradient (~70 mmHg) is much larger than the systolic gradient (~10 mmHg), the majority of pump flow occurs during systole. This limitation results in sub-optimal LV volume unloading, LV washing, and diminished vascular pulsatility that may be associated with increased risk for clinically-significant adverse events, including stroke, bleeding, arteriovenous malformations, and aortic insufficiency. To address these clinical adverse events, an intelligent control strategy using pump speed modulation was developed …

Suture-Less Trocar Site Closure Clip, Hares A. Patel

Electronic Theses and Dissertations

Introduction: Following laparoscopic surgery, there is a need, in many cases, to close trocar sites to prevent hernias. Currently, devices that exist on the market are suture based, but the lack of standardization in the suturing techniques together with the time-consuming nature of the procedure leads to the need for improvement in trocar site closure products. Trocar closure sites do not need to be fully closed on the fascial layer; rather, sufficiently blocking the hole at the abdominal wall can significantly reduce post-operative herniation. A retrospective study on trocar site herniation (TSH) after laparoscopic surgery indicates a TSH incidence …

A Deep Learning Approach To Detect Diabetic Retinopathy In Fundus Images., Winston R. Furtado

Electronic Theses and Dissertations

Background: Diabetic retinopathy is a disease caused due by complications of diabetes mellitus which can lead to blindness. About 33% of the US population with diabetes also show symptoms for diabetes retinopathy. If not treated, diabetic retinopathy worsens over time by progressing through two main pathological stages of non-proliferative and proliferative and four clinical stages. While the diagnostic accuracy of detecting diabetic retinopathy through machine learning have shown to be successful for OCT images, the accuracy of ultra-widefield fundus images have yet to be fully reported. This paper describes a method to non-invasively detect and diagnose diabetic retinopathy from ultra-widefield …

Modeling And Simulation Methodologies For Spinal Cord Stimulation., Saliya Kumara Kirigeeganage

Electronic Theses and Dissertations

The use of neural prostheses to improve health of paraplegics has been a prime interest of neuroscientists over the last few decades. Scientists have performed experiments with spinal cord stimulation (SCS) to enable voluntary motor function of paralyzed patients. However, the experimentation on the human spinal cord is not a trivial task. Therefore, modeling and simulation techniques play a significant role in understanding the underlying concepts and mechanics of the spinal cord stimulation. In this work, simulation and modeling techniques related to spinal cord stimulation were investigated. The initial work was intended to visualize the electric field distribution patterns in …

Rotary Pump Speed Modulation To Produce Pulsatile Flow And Ventricular Volume Unloading., Connor Joseph Smith

Electronic Theses and Dissertations

Background: Continuous-flow (CF) left ventricular assist devices (LVADs) have gained widespread clinical acceptance as a treatment option for advanced heart failure (HF); however, they have also been associated with an increased risk of adverse events, including gastrointestinal bleeding, aortic insufficiency, and hemorrhagic stroke. It has been hypothesized that the increase in adverse event incidence may be due in part to diminished vascular pulsatility and high shear stress when CF-LVADs are operated at fixed speeds. Previous studies have shown that pump speed modulation generates greater levels of pulsatility in rotary pumps than when operated at fixed speeds. The objective of this …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

The Effectiveness Of Localized Ultrasound And Aptamer Surface Modification On Nanoemulsions For Drug Delivery To Spheroids., Daniel A. Hodge

Electronic Theses and Dissertations

Cancer is a group of diseases that affects 1.6 million and kills nearly 600,000 Americans each year. The National Cancer Institute defines it as “diseases in which abnormal cells divide without control and can invade nearby tissues” and it is often treated with one or more of the following: chemotherapy, radiation, surgery. The expense for these treatments is expected to rise to $156 billion by 2020. Localized delivery can improve effectiveness and cancer survival rates, decrease the cost of treatment, and decrease the side effects of chemotherapy. This paper addresses models for this localized delivery through nanoemulsions. Nanoemulsions are a …

Investigating The Likelihood Of Pediatric Femur Fracture Due To Falls Through Finite Element Analysis., Keyonna Mckinsey

Electronic Theses and Dissertations

Bone fracture is the second most common injury of child abuse. Studies have generally reported that femur fractures are more likely due to abuse than accidental causes in cases where the child is non-ambulatory. They have also found that household falls are commonly offered as the cause of injury in cases of abuse. In this study, a finite element (FE) pediatric femur model will be developed and used to evaluate likelihood of fracture in common household fall scenarios (bed falls and feet first falls). This will provide greater biomechanical evidence as to the likelihood of femur fracture due to common …

Investigation Of Cardiovascular Tissue Following 56fe-Radiation And Potential Countermeasure Effectiveness., Alexandra R Decarlo

Electronic Theses and Dissertations

Exposure to ionizing radiation is an important medical concern because it can lead to health problems including cancer and cardiovascular issues. In space, astronauts are exposed to ionizing radiation that is not experienced by those who remain on Earth. This radiation can cause health problems such as cardiovascular disease. One way this can happen is through the creation of reactive oxygen species, which can activate TGF-β1, contributing to fibrosis or other cardiovascular problems. Antioxidants can be a potential pharmacological mitigator of these excess reactive oxygen species because of their ability to neutralize reactive oxygen species. One such antioxidant with potential …

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, …

Longitudinal Tracking Of Physiological State With Electromyographic Signals., Robert Warren Stallard

Electronic Theses and Dissertations

Electrophysiological measurements have been used in recent history to classify instantaneous physiological configurations, e.g., hand gestures. This work investigates the feasibility of working with changes in physiological configurations over time (i.e., longitudinally) using a variety of algorithms from the machine learning domain. We demonstrate a high degree of classification accuracy for a binary classification problem derived from electromyography measurements before and after a 35-day bedrest. The problem difficulty is increased with a more dynamic experiment testing for changes in astronaut sensorimotor performance by taking electromyography and force plate measurements before, during, and after a jump from a small platform. A …

Design And Development Of A Multifunctional Surgical Device For Ground And Space-Based Surgical Applications., Brooke Elaine Barrow

Electronic Theses and Dissertations

With the possibility of longer ventures into space, NASA will face many new medical challenges. The ability to surgically treat trauma and other disorders in reduced gravity requires reliable wound access, containment, and visualization. In collaboration with Carnegie Mellon University, the University of Louisville is currently developing the AISS (Aqueous Immersion Surgical System) to increase efficiency and control of the operative field in space-based surgeries. Reliable wound access and containment is achieved by placing a transparent wound-isolation dome securely over the wound-site and pressurizing it with a saline solution. Leak-free trocars provide access ports for various surgical instruments. This system …

Materials Design With Polylactic Acid-Polyethylene Glycol Blends Using 3d Printing And For Medical Applications., Jeremiah R. Bauer

Electronic Theses and Dissertations

This thesis is an examination of two material systems derived from polylactic acid (PLA) and polyethylene glycol (PEG). PLA is a polymer commonly sourced from renewable sources such as starches and sugars. It is a relatively strong, biodegradable polymer, making it ideal for use in the body. Even though it has a relative high strength, PLA is also brittle leading to the use of plasticizers to increase flexibility. One such plasticizer is PEG, which is a material that can exist at room temperature as either a thin liquid, or a hard waxy solid depending on the molecular weight. The first …

Tumor-Targeted Double Emulsions For Ultrasound-Triggered Delivery Of Molecular Therapeutics., Connor S Centner

Electronic Theses and Dissertations

Cancer is the second leading cause of death in the United States, with 1.74 million new cancer cases diagnosed and 610,000 cancer deaths expected in 2018 alone. Current treatments often result in negative systemic effects and ineffective treatment of the tumor. Drug delivery vehicles have been developed for more effective local delivery methods, but many drug delivery vehicles lack spatial and temporal control. Targeted double emulsions are a new class of drug delivery vehicles which present a promising option for a high payload and controlled delivery. The purpose of our project was to develop and characterize an aptamer-chelated double emulsion …

Optimization Of Plga And Plga-Dasatinib Particles Through A Taguchi Design Approach, Rayeanne N Balgemann

Electronic Theses and Dissertations

Proliferative vitreoretinopathy (PVR) is a disease of the retina in the human eye. Retinal pigment epithelium cells (RPE) undergo an epithelial to mesenchymal transition in response to retinal trauma. This transition gives the cells mobility and allows them to potentially infiltrate the vitreous chamber and deposit on either side of the retina. Once cell deposition has occurred, along with several other transformed cells derived from cell types such as Müller glia, these migratory cells can form a membrane contiguous with the retinal extracellular matrix and, upon contraction, cause wrinkling of the retina. If left untreated PVR can lead to traction …

Restoring Cholesterol Homeostasis In Familial Hypercholesterolemia Cell Line Model, Lubna Hindi

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that results in elevated levels of low-density lipoprotein cholesterol (LDL-C). This increase in serum cholesterol level has been shown to result in premature coronary artery disease (CAD) with devastating symptoms from a young age. Today, the prevalence of heterozygous FH (HeFH) and homozygous FH (HoFH) is estimated to be 1 in 320 and 1 in 160,000 people, respectively. FH is referred to as an underdiagnosed disease due to the large number of mutations that continues to grow. These mutations often exist in one of or a combination of three genes: low-density lipoprotein …

Material Properties Design Using Simulations And Experiments For Powder Injection Molding Of Lead Zirconate Titanate (Pzt)., Bhushan Pramod Bandiwadekar

Electronic Theses and Dissertations

Powder injection molding (PIM) process simulations can be performed to minimize the number of injection molding experiments by estimating material properties necessary for PIM simulations. In current work, lead zirconate titanate (PZT) powder-polymer binder feedstock was compounded for 45 vol. % and 52 vol. % solids loading. PIM experiments on designed micro-pillar array geometry were performed using 52 vol. % PZT. Using PIM experiments results as basis, PIM simulations were performed on designed micro-pillar array geometries to understand the effectiveness of PIM simulations with the use of estimated feedstock properties in predicting molding behavior that have micro-features. Additionally, PIM simulations …

A Novel Approach To Assess Minimally Invasive Surgical Device Failure Utilizing Adverse Event Outcome Severity And Design Complexity., Marie K. Riggs

Electronic Theses and Dissertations

Medical device failure and misuse have the potential to cause serious injury and death. Given the intricate nature of the instruments utilized specifically in minimally invasive surgery (MIS), users and manufacturers of surgical devices share a responsibility in preventing user error and device failure. A novel approach was presented for the evaluation of minimally invasive device failures, which involved assessing the severity of adverse event outcomes associated with the failures modes and investigating aspects of the devices’ design that may contribute to failure. The goals of this research were to 1) characterize the design attributes, failure modes, and adverse events …