Biomedical Engineering and Bioengineering Commons^™

Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl

Browse all Theses and Dissertations

Ras proteins are small GTPases that regulate cell proliferation, differentiation and survival at the plasma membrane (PM). There are three Ras isoforms ubiquitously expressed in mammalian cells: H-, N- and K-Ras. Constitutively active Ras mutations are found in ~19% of all human cancers, with ~75% of those being in K-Ras. There are K-Ras inhibitors in clinic but they only target the oncogenic K-RasG12C mutant, which only makes up a small sub-set of K-Ras-driven cancers. Thus, there still exists a need for a pan anti-K-Ras drug. Ferrocene derivatives are a class of compounds that have been shown to inhibit the growth …

Brain Morphometry From Neuroimaging As A Biomarker For Alzheimer's Disease, Nonyelum Benedicta Aniebo

Browse all Theses and Dissertations

Alzheimer’s disease (AD) is the seventh leading cause of death globally with an estimated 6.5 million Americans aged 65 and above living with Alzheimer’s dementia in 2022 and at a projected national cost of $321 billion. AD is characterized by a progressive and irreversible neurodegenerative dysfunction with clinical symptoms such as deterioration in cognition and memory loss. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a multi-site, public-private global research initiative that supports both investigation and development of treatments that slow or terminate AD progression. The study included 60 participants, comprising 30 AD and 30 control cohorts respectively. All participants were …

Longitudinal Oxygen Imaging In 3d (Bio)Printed Models, Ryan Curtis O'Connell

Graduate Theses, Dissertations, and Problem Reports

Electron paramagnetic resonance (EPR), and its molecular imaging modality, is a powerful tool to noninvasively map various biological and chemical markers within objects of interest. Reliable data acquisition is a major impeding factor for longitudinal hands-off measurements. Measurements are especially challenging in biomedical applications, as live objects are not static. Frequent changes occur that require constant fine recalibration of the EPR detection system, called the resonator. To enable longitudinal imaging, a technology permitting automatic digital control of resonator coupling, tuning, and EPR data acquisition was developed. Automation was achieved through the utilization of a microcontroller and digital peripheral components such …

Machine Learning And Deep Learning Approaches For Gene Regulatory Network Inference In Plant Species, Sai Teja Mummadi

Dissertations, Master's Theses and Master's Reports

The construction of gene regulatory networks (GRNs) is vital for understanding the regulation of metabolic pathways, biological processes, and complex traits during plant growth and responses to environmental cues and stresses. The increasing availability of public databases has facilitated the development of numerous methods for inferring gene regulatory relationships between transcription factors and their targets. However, there is limited research on supervised learning techniques that utilize available regulatory relationships of plant species in public databases.

This study investigates the potential of machine learning (ML), deep learning (DL), and hybrid approaches for constructing GRNs in plant species, specifically Arabidopsis thaliana, …

Neonatal Intraocular Injection And Delivery System, Nina Treacher, Cory Ramsey, Marie Kosco, Jackson Carrell

Williams Honors College, Honors Research Projects

The proposed project is a way to deliver liquid medicine into the neonatal eye to prevent retinal detachment with lower risk for bacterial infection and drug misplacement. Currently, ophthalmologists use diabetic needles to introduce medication to the neonate eye. They estimate the injection location with hand-held calipers. This may allow the medicine to be misplaced from poor needle placement and introduce preventable error. The goal is to improve the delivery system ophthalmologists currently use by investigating ways to alter or enhance commonly used injection systems to make the procedure safer and more effective.

Frostflex, Isaac Edmondson, Caleb Edmondson, Joey Esker, Nadine Salem

Williams Honors College, Honors Research Projects

Research has shown that the majority of heat lost during physical exercise leaves the body through the hands, feet, and the face. Our design project seeks to develop cooling glove technology to increase the rate at which heat leaves the body during recovery from physical exertion. The goal of this project was to investigate different ways in which heat absorption through various mediums can be manipulated and scaled into an adaptable, flexible design in which athletes of all levels, from recreational to professional, can improve their physical performance with the use of our gloves. Deliverables include a functional prototype, product …

Side Cutting Biopsy Needle For Endoscopes, Cade Smarr, Ella B. Brinkman, Christine Skakun, Vincent Grosso

Williams Honors College, Honors Research Projects

Develop a side cutting biopsy needle that fits through the working channel of the endoscope similar to stereotactic needle with syringe suction to overcome the small biopsy samples due to instrument size limitations. The problem users are facing is that the biopsy samples through the endoscope are small secondary to instrument size limitations. The idea for this problem is to develop a side cutting biopsy needle that fits through the working channel of the endoscope similar to stereotactic needle, syringe suction.

Mouthpiece For Patients With Neuromuscular Disorders, Rebekah Starkey, Carissa Thompson, Michael Dickens, Andrew Pero

Williams Honors College, Honors Research Projects

Neuromuscular Disorders (NMDs) impact people throughout the world. An early hallmark of these disorders includes some degree of facial muscle weakness. Respiratory testing is important to evaluate the progression of these patients’ NMDs. However, these tests require that the patient purses their lips around a mouthpiece to create a tight seal. This is a difficult task for one with facial muscle degeneration. This often leads to results that fail to reflect the patient’s true respiratory ability and prevents their physician from providing the appropriate degree of care. The objective of this project was to develop a face mask or mouthpiece …

Embok 5.0 - Industry 4.0/5.0 Manifest And Latent Dimensions Mapping To The Asem Embok, T. Steven Cotter

Engineering Management & Systems Engineering Faculty Publications

Industry 3.0 automation emerged replacing human labor with high volume processes and robotics. Industry 4.0, cyber-physical systems, and Industry 5.0, mass customization and cognitive systems, are in the early stages of emergence. Research into the impact of Industry 4.0 and 5.0 is focused at the strategic or organizational levels or on the technological challenges. Research into the impact of Industry 4.0 and 5.0 on engineering management has been limited to their impact on project management. This leaves open the question of the directions in which ASEM should evolve the Engineering Management Body of Knowledge (EMBOK) under the emergence of Industry …

Enhancing Dental Aligners With Direct 3d Printing Manufacturing, Erin Clark, Lauren Ickes, Tyler Madison

Williams Honors College, Honors Research Projects

Replacement of thermoforming with direct 3d printed aligners, molding appliances for dental and alveolar movement. Currently the process involved requires 3d printing models and plastic thermoforming, trimming and polishing to fabricate the end product. If possible a product that could be 3d printed that had stress retention, crack resistance, and stain resistance properties delivered in thickness between .030 and .040 inches.

Exploring Ph Gradient Phenomena In Non-Linear Electrokinetic Microfluidic Devices, Azade Tahmasebi

Dissertations, Master's Theses and Master's Reports

Electrokinetic microfluidics is a versatile technology utilized within lab on a chip (LOC) devices for diagnostic and analytical applications; advantages include reduced resource demands, flexibility, and simplicity of use. Dielectrophoresis (DEP) is a precision nonlinear electrokinetic tool utilized within microfluidic microdevices to induce polarization and control bioparticle motions for applications that range from hemoglobin separations to cancer cell isolation and detection. Despite promising results, undesired side phenomena can occur in electrokinetic systems which impede reproducibility and accuracy. These unfavorable phenomena have not been comprehensively explored in the literature. Prior preliminary research suggests the fundamental phenomena originate from microelectrodes utilized in …

An Experimentally Validated Computational Model For The Degradation And Fracture Of Magnesium-Based Implants In A Chemically Corrosive Environment, Mark M. Ousdigian

Dissertations, Master's Theses and Master's Reports

In the orthopedic and cardiovascular fields there is a growing interest for biodegradable implants, which can be naturally degraded in the body environment over time so that no extraction surgery is required. These implants must be designed to maintain their strength until the fracture has healed in the body, which could be influenced by many factors such as -the patient’s age, activities, body weight, pre-existing conditions etc. Hence, an ideal implant design should be done on a patient-by-patient basis. In the present work, a computational model is developed to predict the degradation and fracture of magnesium-based implants in a stress-coupled …

Collagen V Promotes Fibroblast Contractility, And Adhesion Formation, And Stability, Shaina P. Royer-Weeden

Dissertations, Master's Theses and Master's Reports

Ehlers-Danlos syndrome, classical type, (cEDS) is a hereditary connective tissue disorder causing excessive elasticity and fragility of the connective tissue and problems with wound healing. Most cases of cEDS are caused by haploinsufficiency for collagen V. Collagen V regulates collagen fibril diameter. In cEDS fibroblast migration is impaired and integrin expression is altered.

The effects of collagen V on collagen gel ultrastructure and how it alters its mechanical properties were measured using scanning electron microscopy (SEM) and rheology respectively. Fibroblast contractility and adhesion dynamics were investigated to better understand the role of fibroblast disfunction in wound healing in cEDS. To …

The Effects Of Dental Hygiene Instrument Handles On Muscle Activity Production, Jessica R. Suedbeck, Daniel Russell, Cortney Armitano Lago, Emily A. Ludwig

Dental Hygiene Faculty Publications

Purpose The objective of this study was to compare the effects of ten commercially available instrument handle designs’ mass and diameter on forearm muscle activity during a simulated periodontal scaling experience.

Methods A convenience sample of 25 registered dental hygienists were recruited for this IRB-approved study. Ten commercially available instruments were categorized into four groups based on their masses and diameters: large diameter/light mass, small diameter/light mass, large diameter/heavy mass, and small diameter/heavy mass. Participants were randomized to four instruments with one from each group. Participants scaled with each instrument in a simulated oral environment while muscle activity was collected …

Pulsed Electric Field Ablation Of Esophageal Malignancies And Mitigating Damage To Smooth Muscle: An In Vitro Study, Emily Gudvangen, Uma Mangalanathan, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Andrei G. Pakhomov

Bioelectrics Publications

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca²⁺ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

Editorial: Pulsed Electric Field Based Technologies For Oncology Applications, Siqi Guo, Gregor Sersa, Richard Heller

Bioelectrics Publications

No abstract provided.

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Extracellular Vesticles In Acute Respiratory Distress Syndrome: Understanding Protective And Harmful Signaling For The Development Of New Therapeutics, Matthew Bavuso, Noel Miller, Joshua M. Sill, Anca Dobrian, Ruben M. L. Colunga Biancatelli

Bioelectrics Publications

Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by increased lung permeability, hyper-inflammatory state, and fluid leak into the alveolar spaces. ARDS is a heterogeneous disease, with multiple direct and indirect causes that result in a mortality of up to 40%. Due to the ongoing Covid-19 pandemic, its incidence has increased up to ten-fold. Extracellular vesicles (EVs) are small liposome-like particles that mediate intercellular communication and play a major role in ARDS pathophysiology. Indeed, they participate in endothelial barrier dysfunction and permeability, neutrophil, and macrophage activation, and also in the development of a hypercoagulable state. A more …

On The Chronological Understanding Of The Homogeneous Dielectric Barrier Discharge, Xinpei Lu, Zhi Fang, Dong Dai, Tao Shao, Feng Liu, Cheng Zhang, Dawei Liu, Lanlan Nie, Chunqi Jiang

Bioelectrics Publications

Dielectric barrier discharges (DBD) are widely utilised non-equilibrium atmospheric pressure plasmas with a diverse range of applications, such as material processing, surface treatment, light sources, pollution control, and medicine. Over the course of several decades, extensive research has been dedicated to the generation of homogeneous DBD (H-DBD), focussing on understanding the transition from H-DBD to filamentary DBD and exploring strategies to create and sustain H-DBD. This paper first discusses the influence of various parameters on DBD, including gas flow, dielectric material, surface conductivity, and mesh electrode. Secondly, a chronological literature review is presented, highlighting the development of H-DBD and the …

Modeling Of Transport In Anatomic Respiratory Airways: Applications In Targeted Drug Delivery And Airborne Pathogenic Transmissions, Mohammad Mehedi Hasan Akash

Electronic Theses and Dissertations

This thesis aims to explore the potential of improving the efficacy of drugs for treatment of viral infections by targeting the nasopharynx, which is commonly the first site of infection for many viral pathogens. Currently, intranasal sprays are used, but the standard protocol (“Current Use” or CU) results in suboptimal drug deposition at the nasopharynx. To address this issue, an “Improved Use” or, IU protocol has been proposed, which involves pointing the spray bottle at a shallower angle and aiming slightly towards the cheeks. The IU delivery is also robust to perturbations in spray direction, which highlights the practical utility …

Thermotrophy Exploratory Study, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The question of whether environmental heat energy could be utilized as a source of energy for biological metabolism is the center of this exploratory research. In 1979, this author postulated a hypothesis for the existence of thermotrophs that could isothermally utilize environmental heat energy as a source of their energy on Earth. According to this hypothesis, the thermotrophs could be the first primitive forms of life in the early Earth environment. The chemotrophs and phototrophs that we currently are all well familiar with might have been evolved somehow from the primitive thermotrophs. Furthermore, all the organisms currently regarded as the …

Synthesis Of A Series Of Trimeric Branched Glycoconjugates And Their Applications For Supramolecular Gels And Catalysis, Jonathan Bietsch, Anji Chen, Dan Wang, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They …

Investigating Tgf-Β1 And Fibronectin Signaling In Low Oxygen Environments, Caitlin E. Williams

Theses and Dissertations

Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.

As dense tumors form, …

Computational Modeling Of Temporal Eeg Responses To Cyclic Binary Visual Stimulus Patterns, Connor M. Delaney

Theses and Dissertations

The human visual system serves as the basis for many modern computer vision and machine learning approaches. While detailed biophysical models of certain aspects of the visual system exist, little work has been done to develop an end-to-end model from the visual stimulus to the signals generated at the visual cortex measured via the scalp electroencephalogram (EEG). The creation of such a model would not only provide a better understanding of the visual processing pathways but would also facilitate the design and evaluation of more robust visual stimuli for brain-computer interfaces (BCIs). A novel experiment was designed and conducted where …

The Wound Healing And Antibacterial Properties Of Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles, Emily N. Wandling

Theses and Dissertations

Treatments for acute respiratory distress syndrome (ARDS) are still unavailable and the prevalence of the disease has only increased due to the Covid-19 pandemic. Mechanical ventilation regiments are still utilized to support declining lung function, but they also contribute to lung damage and increase the risk of bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSC secretome and the extracellular matrix (ECM) into a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta-potential, and mass spectrometry …

Characterization And Decoding Of Speech Activity From Intracranial Signals, Pedram Zanganeh Soroush

Theses and Dissertations

Speech is the first and foremost means of human communication. Millions of people worldwide suffer from severe speech disorders due to neurological diseases such as amyotrophic lateral sclerosis (ALS), brain stem stroke, and severe paralysis. A speech neuroprosthesis that decodes speech directly from neural signals could dramatically improve life for these individuals. Recent studies have demonstrated that it is possible to decode and synthesize various aspects of acoustic speech directly from intracranial measurements of electrophysiological brain activity. For those who have completely lost the ability to speak, the objective is to synthesize acoustic speech directly from brain activity during imagined …

Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …

Ultra-Low Intensity Post-Pulse Affects Cellular Responses Caused By Nanosecond Pulsed Electric Fields, Kamal Asadipour, Carol Zhou, Vincent Yi, Stephen J. Beebe, Shu Xiao

Electrical & Computer Engineering Faculty Publications

High-intensity nanosecond pulse electric fields (nsPEF) can preferentially induce various effects, most notably regulated cell death and tumor elimination. These effects have almost exclusively been shown to be associated with nsPEF waveforms defined by pulse duration, rise time, amplitude (electric field), and pulse number. Other factors, such as low-intensity post-pulse waveform, have been completely overlooked. In this study, we show that post-pulse waveforms can alter the cell responses produced by the primary pulse waveform and can even elicit unique cellular responses, despite the primary pulse waveform being nearly identical. We employed two commonly used pulse generator designs, namely the Blumlein …

On The Chronological Understanding Of The Homogeneous Dielectric Barrier Discharge, Xinpei Lu, Zhi Fang, Dong Dai, Tao Shao, Feng Liu, Cheng Zhang, Dawei Liu, Chunqi Jiang

Electrical & Computer Engineering Faculty Publications

Dielectric barrier discharges (DBD) are widely utilised non-equilibrium atmospheric pressure plasmas with a diverse range of applications, such as material processing, surface treatment, light sources, pollution control, and medicine. Over the course of several decades, extensive research has been dedicated to the generation of homogeneous DBD (H-DBD), focussing on understanding the transition from H-DBD to filamentary DBD and exploring strategies to create and sustain H-DBD. This paper first discusses the influence of various parameters on DBD, including gas flow, dielectric material, surface conductivity, and mesh electrode. Secondly, a chronological literature review is presented, highlighting the development of H-DBD and the …