Biomedical Engineering and Bioengineering Commons^™

Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows

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G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways via interaction with external stimuli. [1-5] Despite sharing similar structure and cellular mechanism, GPCRs participate in a uniquely broad range of physiological functions. [6] Due to the size and functional diversity of the GPCR family, these receptors are a major focus for pharmacological applications. [1,7] Current state-of-the-art pharmacology and toxicology research strategies rely on computational methods to efficiently design highly selective, low toxicity compounds. [9], [10] GPCR-targeting therapeutics are associated with low selectivity resulting in increased risk of adverse effects and toxicity. Psychoactive drugs that are active at Class A GPCRs used …

The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi

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ΔNp63α, a member of the p53 family of transcription factors, plays a critical role in normal development and human disease. Loss of ΔNp63α expression is associated with increased cancer invasiveness and metastasis. The small GTPase Rac1 is a master regulator of cell motility, and increased Rac1 activity upregulates cell invasion in multiple human cancers. Increased cancer cell invasion associated with ΔNp63α knockdown and Rac1 activation suggests a novel mechanism by which ΔNp63α regulates tumor invasiveness through Rac1. Accordingly, we sought to delineate the effects of ΔNp63α on Rac1 phosphorylation, activation and subcellular localization. We identified a novel ΔNp63α/miR-320a/PKCᵧ signaling pathway …

Minimally Invasive Repair Of Elongated Chordae Tendineae In The Mitral Valve, Walid Abuhashim, Diana Albaba, Austin Ghiates, Rebecca Leiter, Mary Robakowski

Williams Honors College, Honors Research Projects

In the United States, about 4 million people have been estimated to suffer from severe mitral valve regurgitation [5]. Due to the high risks involved, about half of those patients are ineligible for surgery to repair the valve, because of their poor health [6]. Elongation of the chordae tendineae has been found to be one of the significant causes of regurgitation. To address this, the team has developed a device called “Chord Fastener”, which will restore proper function to the valve via shortening of the chordae tendineae [1]. Via this shortening mechanism, the device will reduce mitral valve regurgitation and …

Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger

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Recent experimental findings in the Rich lab suggest there are important gaps in our understanding of muscle excitability in various disease states. To generate and test hypotheses as well as to determine whether our current understanding of various aspects of muscle excitation can fully explain experimental findings, an accurate model of muscle excitation was needed. Previous studies have modeled excitation of muscle, but in each case, important aspects were omitted. One reason for this is that little effort has been made to accurately simulate muscle action potentials. In this thesis I present progress made towards generation of a model of …

Quantifying Mafenide Release From 3d Printed Phenylalanine-Coumarin Copolyester Scaffolds, Jacob Seeh

Williams Honors College, Honors Research Projects

This project addressed burn wound healing through controlled release of the antibacterial drug mafenide encapsulated by a copolyster into 3D printed scaffolds. Scaffolds were printed at 25^oC and 0.77-1 bar in a cross-hatch pattern with uniform thickness, distance between parallel layers, and diameter then photo-crosslinked. The number of scaffolds available for testing was limited by the amount of polymer that could be synthesized. A high-performance liquid chromatography method was developed specifically for this experiment and used to determine daily release of mafenide from the scaffold into a 2-mL phosphate buffer solution. During the first 24 hours a large …

Tubing/Lines Entanglement Reduction In Healthcare Settings, Abigail Kraft, Amy Beskitt, Grace Elerick, Zachery Steck

Williams Honors College, Honors Research Projects

Intravenous (IV) lines used in various healthcare settings pose a risk to patients and their caretakers. A few common risks include IV lines becoming torn out and coming into contact with open wounds. We propose to solve this problem by designing a device that prevents IV and wire entanglement without obstructing patient care. Our objectives in identifying a solution include increasing patient comfort, mobility, and ease of transfer. By solving this issue, other potential benefits include reducing time spent on non-essential tasks and reducing number of personnel needed to transport patients. We intend to validate our product with healthcare employees …

Feasibility Study To Measure The Impact Of A Specialized Core Exercise On Metabolic Efficiency And Stability During Walking For Above Knee Amputees, Shaye M. Tiell, Sabrina R. Segretario, Serena M. Myers, Emily G. Tully

Williams Honors College, Honors Research Projects

The objective of this study is to determine the feasibility of improving the gait of above-knee (AK) amputees by performing daily core exercises aimed to provide an efficient and stable walking pattern. The goal of the exercise is to strengthen core muscles and form temporary neural connections in the brain aimed at improving metabolic efficiency and stability. We will be implementing the Wright Balance Core 360 Exercise Technique for completion by our subjects. Motion capture technology will be utilized in conjunction with a metabolic oxygen consumption analyzer to collect stability and metabolic efficiency data while amputees walk on a treadmill. …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

Intermittent Theta Burst Stimulation: Application To Spinal Cord Injury Rehabilitation And Computational Modeling, Neil Mittal

Theses and Dissertations

Loss of motor function from spinal cord injuries (SCI) results in loss of independence. Rehabilitation efforts are targeted to enhance the ability to perform activities of daily living (ADLs), but outcomes from physical therapy alone are often insufficient. Neuromodulation techniques that induce neuroplasticity may push the limits on recovery. Neuromodulation by intermittent theta burst transcranial magnetic stimulation (iTBS) induces neuroplasticity by increasing corticomotor excitability, though this has most frequently been studied with motor targets and on individuals not in need of rehabilitation. Increased corticomotor excitability is associated with motor learning. The response to iTBS, however, is highly variable and unpredictable, …

Silk Hydrogels Incorporated With Melanin, Anne Lutz

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Melanin is a naturally produced pigment found within the human body. Melanin is known for its ability to protect against Ultra Violet light, but also its ability to allow for mechanical protection. Making melanin a good addition to biomedical devices such as hydrogels. Silk hydrogels are weak in their load bearing capabilities but are known for their biocompatibility, biodegradability, and porosity. This makes the silk hydrogel a good material to incorporate melanin into in order to improve the mechanical properties. For the silk solution to form a solid, there must be a presence of both a catalyst and an oxidizer …

Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt

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Objectives: Heart failure (HF) refractory to medical management can be effectively treated with mechanical support. However, available devices are frequently associated with complications due to blood contact. Direct cardiac compression (DCC) devices augment LV systolic pump function by externally compressing the heart surface. Direct Mechanical Ventricular Actuation (DMVA) is a unique DCC method providing not only systolic but, importantly, diastolic support. However, DCC in general remains a relatively poorly understood modality. The purpose of this study was to examine DMVA’s effect on restoration of physiologic function in the failing heart. Methods: Global ischemic HF was induced with 5 mins of …

Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda

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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …

Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows

Browse all Theses and Dissertations

G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways via interaction with external stimuli. [1-5] Despite sharing similar structure and cellular mechanism, GPCRs participate in a uniquely broad range of physiological functions. [6] Due to the size and functional diversity of the GPCR family, these receptors are a major focus for pharmacological applications. [1,7] Current state-of-the-art pharmacology and toxicology research strategies rely on computational methods to efficiently design highly selective, low toxicity compounds. [9], [10] GPCR-targeting therapeutics are associated with low selectivity resulting in increased risk of adverse effects and toxicity. Psychoactive drugs that are active at Class A GPCRs used …

Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy

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The carotid bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Elucidating the “signal” that couples carotid body sensory type I cell (CBSC) hypoxic mitochondrial inhibition with potassium channel closure has proven to be an arduous task; to date, a multitude of oxygen-sensing chemotransduction mechanisms have been described and altercated (Varas, Wyatt & Buckler, 2007; Gao et al, 2017; Rakoczy & Wyatt, 2018). Herein, we provide preliminary evidence supporting a novel oxygen-sensing hypothesis suggesting CBSC hypoxic chemotransductive signaling may in part …

Tibial Strains And Tray-Bone Micromotions After Total Knee Arthroplasty: Computational Studies Evaluating The Tibial Fixation, Huizhou Yang

Electronic Theses and Dissertations

Cemented and cementless fixation in total knee arthroplasty (TKA) have been successfully used for decades. As the number of younger and more active patients treated with TKA continues to increase, long-term implant survivorship is of increasing importance. One of the most common complications and hence the reason for revision is mechanical loosening (23.1% of all revised TKA). The loosening mechanisms have been proposed for different fixation types. For cemented fixation, bone remodeling after surgery is regulated by the changes in strain energy density (SED). The recruitment of osteoclasts and osteoblasts is controlled by SED-related signals. Insufficient stimuli can promote bone …

Exploring Rapid Solidification And Equal Channel Angular Pressing In The Fabrication Of Mg-Based Alloys For Medical Applications, Emily Tom

Dissertations, Master's Theses and Master's Reports

The development of magnesium bioresorbable implants has become increasingly popular due to the increased need for temporary implants and magnesium’s excellent biocompatibility and suitable elastic modulus. Even though magnesium is an excellent candidate, when alloyed with other metals magnesium’s corrosion rate becomes too rapid for bioresorbable medical applications. The investigation into novel processing techniques to control the formation of precipitates to improve mechanical strength and ductility as well as corrosion rates has become of interest. This work investigates the combination of two nonequilibrium processing techniques, rapid solidification (RS) and equal channel angular pressing (ECAP), and the effects it has on …

Machine Learning Approach For Vigilance State Classification In Mice, Anik Muhury

Theses and Dissertations--Electrical and Computer Engineering

Sleep has a significant impact on cognitive abilities such as memory, reaction time, productivity, and creative thinking; however, there are many aspects of this important activity that are not clearly understood. Over the last century, researchers have developed technology and animal models to assist in the study of sleep. Manual sleep scoring is time consuming, reduces productivity, and is impacted by human scorer subjectivity. On the other hand, automatic sleep stage categorization can enhance consistency and reliability, aiding professionals in identifying sleep related health problems.

In recent times various studies reported significant achievements for automatic vigilance detection and overcome the …

Accurate Measurement Of Healthy Joint Kinematics To Inform Diagnosis And Treatment, Vasiliki Kefala

Electronic Theses and Dissertations

The description of human motion has a primary importance in different scientific areas such as medicine, sports, physical therapy. Kinematics specifically studies pure motion without reference to the causes of motion such as forces. Understanding the kinematics of human movement is of critical importance in medicine and biology. Motion measure­ment can be used in order to to evaluate functional performance of limbs under normal and abnormal conditions. Kinematic knowledge is also important for diagnosis and surgi­cal treatment of joint disease and the design of implants to rehabilitate function. Accurate joint kinematics is essential to protect articular functionality. An alteration may …

Dislocation Mechanics Of Total Hip Arthroplasty: A Combined Experimental And Computational Analysis, Michael Scinto

Electronic Theses and Dissertations

While total hip arthroplasty is considered a successful procedure, dislocation remains a serious complication as recurrent dislocations may require additional surgeries. Knowledge on dislocation events as they occur in vivo are limited, therefore researchers rely on experimental and computational methods. A custom MATLAB script and an experimental procedure utilizing a six-degree of freedom actuator were developed to further understand how various surgical considerations affect dislocation mechanics in total hip arthroplasty. Computationally, it was determined that impingement free range of motion is limited during internal rotation in flexion and during external rotation in extension. Experimentally, our results suggest that the posterior …

Biocybersecurity: A Converging Threat As An Auxiliary To War, Lucas Potter, Orlando Ayala, Xavier-Lewis Palmer

Engineering Technology Faculty Publications

Biodefense is the discipline of ensuring biosecurity with respect to select groups of organisms and limiting their spread. This field has increasingly been challenged by novel threats from nature that have been weaponized such as SARS, Anthrax, and similar pathogens, but has emerged victorious through collaboration of national and world health groups. However, it may come under additional stress in the 21st century as the field intersects with the cyberworld-- a world where governments have already been struggling to keep up with cyber attacks from small to state-level actors as cyberthreats have been relied on to level the playing field …