Biomedical Engineering and Bioengineering Commons^™

Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay

Theses and Dissertations

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold …

Novel 3d Bench Top Model For Vascular Calcification Research, Ursla-Marie K. Offiah

Theses and Dissertations

Cardiovascular disease is the leading cause of non-communicable disease in the whole world killing 17 million people in 2012. Among the many vascular diseases is vascular calcification (VC) which is the mineral build up in the walls of blood vessels. Medial calcification is the plaque buildup in the medial layer of the blood vesicle that is characterized by arterial stiffness and high blood pressure. Current calcification research involves two dimensional (2D) lab methods such as flat petri dishes to investigate the mechanism that causes and inhibits vascular calcification. Research has shown that the use of three-dimensional (3D) models can be …

Ethanol-Induced Impacts On Nervous System Development And Dopamine Transporter Characterization In Schmidtea Mediterranea Planaria, Brennen Covely

Theses and Dissertations

Fetal alcohol spectrum disorders (FASD) are diagnosed in 2-5% of newborns, but the biology underlying FASD is poorly understood and challenging to study with existing model organisms. A new model for FASD research is Schmidtea mediterranea (Smed) planaria. Smed have a remarkable ability to regenerate their central nervous system (CNS), and possess a well-studied, simple genome. Previous studies have shown that ethanol exposure delays this regeneration, yet this relationship is not fully understood. Here, we show that alcohol exposure affects Smed in a dose-dependent manner, eliciting characteristic withdrawal-like behaviors and impacting cognitive function. Interestingly, prior exposure does not alter subsequent …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

The Effect Of Pulsed Field Dc Electrophoresis And Field Amplified Sample Stacking On The Microchip Electrophoretic Separation Of Organic Dyes, Travis Geoffrey Stewart

Theses and Dissertations

The utility of field amplified sample stacking and pulsed field electrophoresis toward improving electrophoretic outcomes was studied with regards to the electrophoretic separation of three organic dyes rhodamine B, 2’,7’-dichlorofluorescein, and fluorescein salt in microchip electrophoresis conditions. In this study, there were four experimental groups: nonstacking nonpulsed, nonstacking pulsed, sample stacking nonpulsed, and sample stacking pulsed.

Electrophoretic outcomes were evaluated by examining the electrophoretic separations under an epifluoresence detection method, plotting the signal intensities vs. time, and comparing separation resolutions and signal-to-noise ratios between experimental groups. From this it was shown that sample stacking nonpulsed conditions yielded the best outcome …

Role Of Epigenome In Regulation Of Inflammation By Ahr Ligands 2,3,7,8-Tetrachlorodibenzo-P-Dioxin And 6-Formylindolo[3,2-B] Carbazole, Alkeiver Cannon

Theses and Dissertations

Autoimmune Hepatitis (AIH) is a chronic inflammatory disease of the liver mediated by immune cells and characterized by a variety of parameters including circulating autoantigens, elevated immunoglobulin G (IgG) and aminotransferases, and interface hepatitis. Unfortunately, despite treatment with broadly immunosuppressive drugs, the disease progresses to cirrhosis and end-stage liver disease in several cases. In order to develop a more specific treatment, the mechanisms governing the liver injury resulting from inflammation and autoimmunity need to be elucidated.

For decades, activation of Aryl Hydrocarbon Receptor (AhR) was excluded from consideration as a therapeutic approach due to the potential toxic effects of AhR …

Neurochemical, Molecular, And Behavioral Effects Of Intranasal Insulin, Jennifer Marie Erichsen

Theses and Dissertations

Age-related cognitive decline (ARCD) is one of the most dreaded aspects of growing old and a public health concern. Unfortunately, there is currently no treatment that effectively ameliorates ARCD. In recent decades, intranasal insulin (INI) has demonstrated promising memory enhancements for rodents and individuals with Alzheimer’s disease, both in basic science research laboratories and multi-center clinical trials. Other studies have shown INI improves memory and cognition in healthy rodents and humans, indicating that INI may hold promise as a successful ARCD therapeutic. However, there is a glaring lack of evidence regarding how INI produces these effects. The goal of these …

Role Of Ahr In The Epigenetic Regulation Of Immune Cells In Lungs During Acute Respiratory Distress Syndrome, Bryan Latrell Holloman

Theses and Dissertations

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) arises from pulmonary inflammatory diseases that stem from direct and indirect activation of immune cells. Severe complications from ALI/ARDS arise when inflammatory mediators initiate an overzealous immune response leading to the destruction of lung epithelial cell barriers, which causes systematic oxygen deprivation. Infiltrating innate immune cells drive the immune response during the acute phase of a lung injury. However, I3C, a naturally occurring AhR ligand found in cruciferous vegetables such as broccoli, collard greens, and kale, plays a crucial role in suppressing inflammatory mediators through its immunomodulatory functionality, which regulates both …

Optimizing Left Ventricular Assist Device Hemodynamics Via Patient Specific Computational Analysis, Jasmine Josefina Martinez

Theses and Dissertations

The best treatment for patients with end stage heart failure is a heart transplant but given the scarcity of donor hearts, a promising alternative treatment has become left ventricular assist devices (LVAD). However, complications such as right heart failure, stroke, and adverse hemodynamic outcomes continue to occur. This thesis will cover investigations into continuous flow LVAD treatment optimization techniques to improve patient outcomes. Optimization techniques explored include an in-house developed optimization algorithm that is completed in three phases on a computational lumped parameter model that is representative of the cardiovascular system using an electrical circuit analogy. This three-phase optimization technique …

Electro-Mechanical Data Fusion For Heart Health Monitoring, Kemal Yakut

Theses and Dissertations

Heart disease is a major public health problem and one of the leading causes of death worldwide. Therefore, cardiac monitoring is of great importance for the early detection and prevention of adverse conditions. Recently, there has been extensive research interest in long-term, continuous, and non-invasive cardiac monitoring using wearable technology. Here we introduce a wearable device for monitoring heart health. This prototype consists of three sensors to monitor electrocardiogram (ECG), phonocardiogram (PCG), and seismocardiogram (SCG) signals, integrated with a microcontroller module with Bluetooth wireless connectivity. We also created a custom printed circuit board (PCB) to integrate all the sensors into …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

A Comparative Study On The Functionality Of Porcine Dura As A Tissue-Engineered Dura Mater Graft For Clinical Applications, Ashma Sharma

Theses and Dissertations

Damage to dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. In this study we explore the mechanics, structure, and immunological capacity of xenogeneic dura mater to be considered as a replacement for human dura. A comparative analysis is done between native porcine dura and a commercially available bovine collagen-based dura graft. Native porcine dura mater was decellularized and subjected to mechanical …

Electromechanical Fatigue Properties Of Dielectric Elastomer Stretch Sensors Under Orthopaedic Loading Conditions, Andrea Karen Persons

Theses and Dissertations

Fatigue testing of stretch sensors often focuses on high amplitude, low-cycle fatigue (LCF) behavior; however, when used for orthopaedic, athletic, or ergonomic assessments, stretch sensors are subjected to low amplitude, high-cycle fatigue (HCF) conditions. As an added layer of complexity, the fatigue testing of stretch sensors is not only focused on the life of the material comprising the sensor, but also on the reliability of the signal produced during the extension and relaxation of the sensor. Research into the development of a smart sock that can be used to measure the range of motion (ROM) of the ankle joint during …

Computer Vision And Machine Learning Applications In Cellular Images And Clinical Data, Guochang Ye

Theses and Dissertations

With the progressive development of artificial intelligence (AI), automated analysis has been explored for substituting tedious manual methods in cellular image analysis. Additionally, medical information not included in the conventional statistical methods is now being reconsidered with AI-based personalized medicine. The adaptivity and flexibility of AI ensure its efficiency and accuracy. In this work, computer vision and machine learning (ML) methods under the scope of AI are explicitly investigated and applied to cellular images and clinical data for cytological analysis and to provide diagnosis-based assistance/predictions. Firstly, novel computer vision algorithms achieve cell detection and differentiation estimation on phase-contact microscopic images …

Effects Of Orthopedic Implant And Host Bone Properties On Stress-Shielding Induced Osteopenia, Scott Jason Jan Baskerville

Theses and Dissertations

Stress shielding is a term commonly used in literature to describe a bone density reducing phenomenon which occurs due to long-term exposure of bone tissue to sub-homeostatic levels of mechanical stimuli. A number of mechanobiological models ranging in complexity and purpose have been developed with the general overall intent of predicting bone remodeling behavior under a set of prescribed conditions. A previously developed heuristic model is expanded in the present work through model calibration with physiological data and the development of a reduced bone-implant-construct (BIC) mechanical model configurable for patient factors such as age, gender, and associated bone properties. The …

Cellular Migration As A Function Of Magnetic Field Intervention, Amy Marie Vecheck

Theses and Dissertations

This work aims to assess cellular migration in three-dimensional structures as a function of Zeeman resonance. By using Zeeman resonance to initialize intersystem crossing of electrons, also known as the Radical Pair Mechanism, bioenergetics processes would be modulated. Processes such as oxygen consumption rate and extracellular acidification rate are indicative of cellular respiration and glycolysis and can be altered based on the orientation of the magnetic field applied: parallel and perpendicular, respectively. This study focused on the parallel orientation and looked to used Zeeman resonance to increase flavin adenosine dinucleotide, which results in preventing the breakdown of F-actin. Cellular viability …

Influence Of Mouthguard Design On Sports Performance And Injury Prevention, Mohammad Ahmed

Theses and Dissertations

Contact sports are associated with some invisible injuries after the incident when symptoms do not appear until weeks after. This can be dangerous as players may continue to engage in the sport and risk further injury. Athletic mouthguards are used to reduce the risk of injury, but there is insufficient data to quantify the effectiveness of mouthguard design on sports performance and injury prevention. In this work, the thickness and material selection of the mouthguard design were characterized in terms of airway resistance, electromyography muscle activation, and energy absorption. First, the effect of thickness on the condyle and temporal bone …

Bio-Ionic Liquid Functionalized Hydrogels Towards Smart Tissue Regeneration, Vaishali Krishnadoss

Theses and Dissertations

A blend of scaffolds, biologically active molecules, and cells are required to assemble functional constructs to repair and regenerate damaged tissue or organ via tissue engineering. The scaffold supports cell growth and proliferation and acts as a medium for diverse cellular activities. Even though hydrogel's high-water content and flexible nature make it a pronounced applicant as a scaffold, they exhibit significant technical limitations such as the absence of cell-binding motifs, lack of oxygen, conductivity, adhesive properties, growth of cells in a 3-dimensional (3D) microenvironment. In this thesis, a novel material platform is evaluated and studied to address the concerns mentioned …

Image Processing Algorithms For Detection Of Anomalies In Orthopedic Surgery Implants, Alexander William Wiese

Theses and Dissertations

Orthopedic implant procedures for hip implants are performed on 300,000 patients annually in the United States, with 22.3 million procedures worldwide. While most such operations are successfully performed to relieve pain and restore joint function for the duration of the patient's life, advances in medicine have enabled patients to outlive the life of their implant, increasing the likelihood of implant failure. There is significant advantage to the patient, the surgeon, and the medical community in early detection of implant failures.The research work presented in this thesis demonstrates a non-invasive digital image processing technique for the automated detection of specific arthroplasty …

Engineering And Optimization Of An Aav Based Viral Vector To Limit The In-Vitro Expression Of Sars-Cov-2 Spike-Protein, Ronald Anderson Smithwick

Theses and Dissertations

Severe Acute Respiratory Syndrome Corona Virus-2, also known as SARS-CoV-2, is a newly emerged respiratory viral pathogen. The outbreak of SARS-CoV-2 started in Wuhan, China, in late 2019 and rapidly transformed into a pandemic. Several vaccines have been developed and are available to the public on an unprecedented timeline, protecting individuals from a severe infection and saving precious lives. However, none of the vaccines can provide a sterile immunity, and the SARS-CoV-2 transmission cycle continues. Additionally, because of the mutation-prone RNA genome and immunological selection pressure, SARS-CoV-2 is rapidly mutating, especially the Spike(S) protein, and new viral strains are arising …

Interrogating The Role Of Ing4 In Hematopoietic Stem Cells And Cancer, Zanshé Thompson

Theses and Dissertations

We recently identified the tumor suppressor, Ing4, as a critical regulator of hematopoietic stem cell (HSC) homeostasis. The mis-regulation of Ing4 in human cancers has also been shown to lend malignant cells specific advantages that support carcinogenesis and tumor progression. This activity is, in part, due to Ing4 mediated regulation of overlapping signaling pathways that regulate stem cell activity and cancer cells, including NF-B and c-Myc. In a two-part study, we have investigated the role of Ing4 in murine hematopoiesis and human malignancies. While the specific mechanisms of stem cell self-renewal, maintenance, and differentiation are poorly characterized, we have determined …

The Submission Of A Section 513(G) Request For Information, Morgan Ashley Lano

Theses and Dissertations

The Food and Drug Administration designates all medical devices into one of three general classes contingent on their intended use, indications for use, and potential risk to the user. This classification dictates the further path the device must take to be approved for the commercial market. Section 513(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360c(g)) is submitted in order to gain the agency’s unofficial classification and suggested regulatory requirements. The Coagulation Companion (MicroVide) is a device designed to fluorescently quantify a key enzyme involved in the coagulation cascade, plasmin, in pediatric patients. clot formation and degradation …

Advanced Materials For Skin Regeneration, Ingrid Safina

Theses and Dissertations

Massive skin loss, over 20% of the total body surface area, is challenging to heal (Rowan et al. 2015). Ideally, autologous skin grafts have the ability to support complete skin reconstruction. However, skin grafting faces major limitations, such as shortage of donor sites and secondary injury. Alternatively, advanced materials can be used to produce skin constructs that could potentially serve as skin substitutes (Stanton and Billmire 2002). Herein, we used two polymeric materials: graphene and polyurethane (PU) to produce films that support skin cells in their growth and maturation. The surface properties of these materials were modified to enhance their …

Universal Design In Bci: Deep Learning Approaches For Adaptive Speech Brain-Computer Interfaces, Srdjan Lesaja

Theses and Dissertations

In the last two decades, there have been many breakthrough advancements in non-invasive and invasive brain-computer interface (BCI) systems. However, the majority of BCI model designs still follow a paradigm whereby neural signals are preprocessed and task-related features extracted using static, and generally customized, data-independent designs. Such BCI designs commonly optimize narrow task performance over generalizability, adaptability, and robustness, which is not well suited to meeting individual user needs. If one day BCIs are to be capable of decoding our higher-order cognitive commands and conceptual maps, their designs will need to be adaptive architectures that will evolve and grow in …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Dna Condensation State Regulates Nuclear Lamina Strain And Cellular Adaptation To Physiological Forces, Brooke E. Danielsson

Theses and Dissertations

The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell, as well as from forces generation within the cell. In recent years, the nucleus has been proposed to act as a cellular mechanosensor, with changes to nuclear shape and architecture playing an important role in how the cell responds to physiological forces. Aberrant forms of the nuclear envelope protein lamin A/C, as well as epigenetic modifications to chromatin, has been shown to modify nuclear stiffness and viscosity, therefore effecting nuclear mechanics and mechanotransduction. Altered nuclear mechanics is associated …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Innovative Techniques Of Neuromodulation And Neuromodeling Based On Focal Non-Invasive Transcranial Magnetic Stimulation For Neurological Disorders, Ivan C. Carmona-Tortolero

Theses and Dissertations

This dissertation aims to develop alternative technology that improves the current range of application of transcranial magnetic stimulation (TMS), on a scale that would permit defining specific non-invasive treatments for Parkinson’s disease and other neurological disorders. This is accomplished through three specific objectives. 1) The design of a neurostimulation system that increases the focality in TMS to regions of narrow target areas and variable depths in the brain cortex. 2) The assessment of the feasibility of novel high-frequency neuromodulation techniques that would allow increasing the focality in deeper areas beyond the cortical surface. 3) The development of a computational model …

Improving The Early Detection Of Cardiovascular Toxicity Secondary To Radiotherapy For Lung Cancer Via Patient-Specific Quantitative Magnetic Resonance Imaging, Alireza Omidi

Theses and Dissertations

Purpose: To assess the cardiopulmonary-induced dose variation on the left ventricle (LV) and evaluate the spatiotemporal evolution of cardiac/aortic function following radiotherapy (RT).

Methods: 8 lung cancer patients who were scheduled to receive RT were recruited for this study. Each patient underwent one 4D-CT at baseline. MRI scans including cine GRE, T1/T2, LGE, and 4D-flow were acquired at baseline, 3-months and 6-months post-RT to evaluate the cardiac/aortic function. Finally, image registration was used to assess the cardiopulmonary-induced dose variation on the LV.

Results: Mean RT-dose was minimum during inspiration and systole (at expiration). No significant differences were found in the …