Biomedical Engineering and Bioengineering Commons^™

Interaction Of Due-B And Treslin During The Initiation Of Dna Replication, Sumeet Poudel

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The initiation of DNA replication is a highly regulated and coordinated process. To ensure that the entire genome is replicated only once per cell cycle, many replication proteins are assembled on the chromatin in a step-wise and cell cycle dependent manner. This process is controlled by interaction of replication proteins, post-translational modifications of the replication factors, control of cellular localization of the proteins, or replication factor degradation after their function terminates. Two kinases, CDK (cyclin dependent kinase) and DDK (Dbf4/Drf1 dependent kinase), play important roles during the initiation stage of DNA replication. The c-myc DNA unwinding element-binding protein (DUE-B) is …

Comparison Of Vascular Pulsatility In The Native Beating Heart Versus Direct Mechanical Ventricular Actuation Support Of The Fibrillating Heart, Nathan Victor Wright

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Most conventional cardiac assist devices today employ continuous flow blood pumps to supplement function in the dysfunctional heart. Continuous flow pumps are predominantly preferred to the original pulsatile pumps due to the smaller size (greater implantability) and higher efficiency they achieve. However, interest in the impact of vascular pulsatility on human health has arisen from the growing evidence of higher complications with nonpulsatile devices compared to pulsatile devices. Direct cardiac compression (DCC) offers a unique solution to the pulsatility issue through the application of force directly to the heart's surface. It is believed that employing the existing pump architecture of …

Evidence That Myo-Inositol Plus Ethanolamine Elevates Plasmalogen Levels And Lends Protection Against Oxidative Stress In Neuro-2a Cells, Isaie Sibomana

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Plasmalogens are glycerophospholipids abundant in brain and heart tissues. Evidence suggests that they have antioxidant properties. Studies from our laboratory showed that rats treated with myo-inositol plus ethanolamine (ME) have elevated ethanolamine plasmalogens (PE-Pls) in brain and are protected against phosphine-induced oxidative stress. We hypothesized that ME elevates PE-Pls levels and protects against oxidative stress through oxidation of its vinyl ether bond. We tested this hypothesis in Neuro-2A cell culture and assessed the effects of treatments with myo-inositol (M), ethanolamine (Etn), or a combination (ME) on the: (1) effects on phospholipid (PL) classes, especially Etn PLs; (2) effects on cell …

Design And Evaluation Of A Fiber Optic Shape Tracker For Use As A Navigational Aid In Endovascular Guidewires And Catheters, Benjamin Stewart Rinehart

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Endovascular intervention is the current gold-standard for screening and treating aortic aneurysms and complications caused by peripheral vascular disease (PAD). A typical endovascular procedure begins with inserting an endovascular guidewire into the femoral artery via incision. A catheter is then threaded over the guidewire and both tools are then navigated to the treatment site. The navigation is guided solely by fluoroscopy (x-ray) imagery that is performed throughout the duration of the procedure. Not only does this method provide limited 2-D guidance, but also exposes the patient and medical staff to high levels of radiation. This thesis research focuses on the …

Refining A Post-Stroke Pharmacological And Physical Treatment To Reduce Infarct Volume Or Improve Functional Recovery, Using Gene Expression Changes In The Peri-Infarct Region To Examine Potential Mechanisms In Male And Female Rats, Moner A. Ragas

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Stroke, a life-threatening medical condition, is the fifth-leading cause of death in the United States with an estimated annual cost of treatments above $70 billion. A combination of innovative approaches was used in our lab to optimize the pre-clinical stroke research design by choosing the most appropriate animal model and methodologies to increase the translational capability of the stroke research. The first study, modeled after ongoing clinical trials using fluoxetine, refined the appropriate timing of fluoxetine and ascorbic acid delivery if a rat was on simvastatin for 7 days pre-stroke and throughout the remainder of the study. Administration of fluoxetine …

Co-Transplantation Of Endothelial Progenitor Cells And Neural Progenitor Cells For Treating Ischemic Stroke In A Mouse Model, Jinju Wang

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Ischemic stroke (IS) is a major cause of death and disability with limited and less effective therapeutics. Transplantation of stem cells, such as neuronal progenitor cells (NPCs) and endothelial progenitor cells (EPCs), is promising for treating IS. It is well known that neurogenesis and angiogenesis are critical for cerebral repair following ischemic injury. However, whether co-transplantation of EPCs and NPCs has synergistic effects remains unclarified. In addition, the PI3K/Akt pathway participates in modulating a widely range of cellular functions such as anti-apoptotic and anti-oxidant. The signal pathways responsible for the effects of grafted NPCs and EPCs are also waiting for …

Fluorescent Nanocomposite Of Embedded Ceria Nanoparticles In Crosslinked Pva Electrospun Nanofibers, Nader Shehata, Soha Gaballah, Effat Samir, Aya Hamed, Marwa Saad

Biology Faculty Publications

This paper introduces a new fluorescent nanocomposite of electrospun biodegradable nanofibers embedded with optical nanoparticles. In detail, this work introduces the fluorescence properties of PVA nanofibers generated by the electrospinning technique with embedded cerium oxide (ceria) nanoparticles. Under near-ultra violet excitation, the synthesized nanocomposite generates a visible fluorescent emission at 520 nm, varying its intensity peak according to the concentration of in situ embedded ceria nanoparticles. This is due to the fact that the embedded ceria nanoparticles have optical tri-valiant cerium ions, associated with formed oxygen vacancies, with a direct allowed bandgap around 3.5 eV. In addition, the impact of …

Analysis Of Vocal Fold Kinematics Using High Speed Video, Harikrishnan Unnikrishnan

Theses and Dissertations--Electrical and Computer Engineering

Vocal folds are the twin in-folding of the mucous membrane stretched horizontally across the larynx. They vibrate modulating the constant air flow initiated from the lungs. The pulsating pressure wave blowing through the glottis is thus the source for voiced speech production. Study of vocal fold dynamics during voicing are critical for the treatment of voice pathologies. Since the vocal folds move at 100 - 350 cycles per second, their visual inspection is currently done by strobosocopy which merges information from multiple cycles to present an apparent motion. High Speed Digital Laryngeal Imaging(HSDLI) with a temporal resolution of up to …

A Fractal-Based Mathematical Model For Cancellous Bone Growth Considering The Hierarchical Nature Of Bone, Stephanie Marie Suhr

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The hierarchical structure of bone alone is not comprehensive enough to provide morphological explanation of how the size and arrangement of the trabeculae within cancellous bone affect load distribution, particularly concerning deterioration of bone in elderly patients. The collagen network and hydroxyapatite play a large role in defining the shape of trabeculae in cancellous bone despite that the arrangement and size is seemingly random. The growth of plates and rods in cancellous bone is mainly due to loading and stress lines within the bone, but mathematical predictive models can be developed using fractal analysis to show how bone may grow …

Early Assessment Of Burn Severity In Human Tissue With Multi-Wavelength Spatial Frequency Domain Imaging, Chien Sing Poon

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Burn injuries such as thermal burns, which are caused by contact with flames, hot liquids, hot surfaces, and other sources of high heat as well as chemical burns and electrical burns, affects at least 500,000 people in the United States, to which 45,000 of them require medical treatment and 3,500 of them result in death. It has also been reported that in the United States alone, fire results in a death approximately every three hours and an injury every 33 minutes. Early knowledge about burn severity can lead to improved outcome for patients. In this study, the changes in optical …

Optical Redox Imaging Of Metabolic Activity, Syed Anwar Hyder Zaidi

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Fluorescence imaging can be used to determine tissue metabolism, which is an indication of the cellular functionality. Metabolic contrast is useful for the early detection of several medical conditions such as cancer, diabetes, lung diseases etc. This study aims to use fluorescence imaging to quantify NADH and FAD, which are cellular metabolic indicators. A parameter known as Redox ratio, can be used to study metabolic state of several tissue types and disease states. To quantify the Redox ratio, three fluorescence imaging systems were optimized to measure the fluorescence signal from NADH and FAD. The first system was a camera based …

A Theoretical Study Of Polymer Based Drug Delivery Systems, Ebtisam Abdullatif Aldaais

Theses and Dissertations

Polymer nanostructured materials for drug delivery applications have witnessed tremendous progress in recent years due to their vast potential. One-end-grafted polymers can form grafted micelles with specific mechanical properties. Biological conditions can alter these properties resulting in the protection or release of drugs. Charged surfactants can also form micelles in an aqueous solution, which can also be manipulated through special conditions. On the micellar surface, self-organized polyelectrolytes can be stimulated to extend their attached ligands and thus increase the probability of binding to targeted receptors. This thesis focuses on modeling polymer-based drug delivery systems by studying the physical interactions between …

In Vitro Visualization Of Pediatric Sized Mechanical Heart Valve Performance Using Aortic Root Model In Mock Circulatory Loop, Sarah Lederer

Theses and Dissertations

Congenital heart valve disease is one of the most common abnormalities in children, with common valve defects being aortic stenosis, mitral stenosis, and valvular regurgitation. Although adult sized mechanical heart valve (MHV) replacements are widely studied and utilized, there are currently no FDA approved prosthetic heart valves available for the pediatric population. This is due to a variety of reasons such as a limited patient pool for clinical trials, limited valve sizes, and complex health histories in children. Much like adult sized mechanical heart valves, potential complications with pediatric heart valve replacements include thrombosis, blood damage due to high shear …

Efficiency Evaluation Of A Magnetically Driven Multiple Disk Centrifugal Blood Pump, Kayla H. Moody

Theses and Dissertations

Heart failure is expected to ail over 8 million people in America by 2030 leaving many in need of cardiac replacement. To accommodate this large volume of people, ventricular assist devices (VADs) are necessary to provide mechanical circulatory support. Current VADs exhibit issues such as thrombosis and hemolysis caused by large local pressure drops and turbulent flow within the pump. Multiple disk centrifugal pumps (MDCPs) use shearing and centrifugal forces to produce laminar flow patterns and eliminate large pressure drops within the pump which greatly reduce risks that are in current VADs. The MDCP has a shaft drive system (SDS) …

In-House Fabrication Of Multi-Sized Polystyrene Microcarriers For Neural Stem Cell Expansion, Jessica Forrester

Theses and Dissertations

The clinical demand for neural stem cells drives the need for a reproducible method used to generate a large quantity of well-characterized cells to support regenerative therapies. Microcarriers are currently being used as a scaffold for stem cell culture to aid in this expansion process because they provide a larger surface area while also requiring fewer cell passages compared to monolayer culture. The main objective of this project was to investigate how human neural stem cell attachment, proliferation, and multipotency would respond to three-dimensional (3D) culture using peptide-coated microcarriers of varying diameters. In this study, multi-sized polystyrene microcarriers were fabricated …

Effects Of Antidepressants On Human Mesenchymal Stem Cell Differentiation On Clinically Relevant Titanium Surfaces, Nancy B. Ayad

Theses and Dissertations

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most frequently prescribed class of drugs worldwide and are implemented in the treatment of depression and other psychiatric disorders. SSRIs relieve depressive symptoms by modulating levels of the neurotransmitter serotonin in the brain. SSRIs block the function of the serotonin transporter, thereby increasing concentrations of extracellular serotonin. However, serotonin levels in the neurons of the brain only account for 5% while the remaining 95% is present outside the brain. Serotonin receptors and transporter are located on bone resident cells (mesenchymal stem cells (MSCs)), osteoblasts and osteoclasts, and serotonergic activity is believed to affect …

Therapeutic Potential Of Catechins And Derivatives For The Prevention Of Alzheimer’S Disease, Shelby Elaine Chastain

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative condition that affects 1 in 9 people over the age of 65, an estimated 5.4 million Americans. It is the only disease among the top 10 that cannot be prevented, cured, or treated. Based on the lack of a viable therapeutic for the prevention or cure of AD, it is vital that therapeutic research for AD continues. AD is characterized by the deposition of extracellular neuritic plaques comprised of insoluble amyloid-β (Aβ) fibrils. These plaques are formed from the amyloidogenic aggregation of Aβ monomer, generated from the cleavage of the amyloid precursor protein (APP) …

Automated Image Analysis And Spatial Computational Modeling Of Nf-Kb In Cerebrovascular Endothelial Cells, Kasey Catalfomo

Theses and Dissertations

Cerebrovascular endothelial cells play a key part in the inflammatory response of the blood-brain barrier in pathological conditions such as Alzheimer’s disease. Specifically, the NF-κB signaling pathway plays a central role. Better understanding of the factors in inflammatory disease progression can lead to more effective treatments for such devastating illnesses like Alzheimer’s, asthma, arthritis, cancer, diabetes and many more inflammatory diseases. The proposed approach analyzes spatial NF-κB distribution contained in multispectral stacked micrograph images of cerebrovascular endothelial cells indexed based on dose of the activating protein and the length of activation. Image analysis code identifies the location of nuclear boundaries …

Direct Current Stimulation Modulates Ltp And Ltd: Activity-Dependence And Dendritic Effects, Gregory Kronberg

Dissertations and Theses

Transcranial direct current stimulation (tDCS) has been reported to improve various forms of learning in humans. Stimulation is often applied during training, producing lasting enhancements that are specific to the learned task. These learning effects are thought be mediated by altered synaptic plasticity. However, the effects of DCS during the induction of endogenous synaptic plasticity remain largely unexplored. To model endogenous plasticity I induced long-term potentiation (LTP) and depression (LTD) at Schaffer collateral synapses in CA1 of rat hippocampal slices. When induction was paired with concurrent DCS, the resulting plasticity was biased towards potentiation, such that LTP was enhanced and …

Ultrahigh Field Magnetic Resonance Imaging – Technical Development And Translational Applications, Judy Alper

Dissertations and Theses

Magnetic resonance imaging (MRI) may be used to provide detailed images of the human body with excellent soft tissue contrast. Alongside its current widespread clinical applications for diagnosis and treatment, MRI allows researchers to measure structure and function of different tissue types in order to advance our understanding of human biology and enable new medical applications of MRI. In particular, diseases affecting nerves and vessels, such as trigeminal neuralgia, with uncertain etiology can be studied using multiple MRI modalities so that treatment planning can we more effective and patient outcomes can be improved. Ultrahigh field MRI scanners, such as those …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

The Molecular And Mechanical Mechanisms Of The Age-Associated Increase In The Severity Of Experimental Ventilator Induced Lung Injury, Joseph Ames Herbert

Theses and Dissertations

Abstract

Background

The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and mortality. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood.

Pulmonary edema is a hallmark of VILI and the severity of edema increases with age. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress (ARDS) patients, but has not been investigated in VILI. We hypothesized that age-associated increases in pulmonary edema promote age-related increases in ventilator-associated mortality. Endoplasmic reticulum (ER) …

Electrophysiology Of Basal Ganglia (Bg) Circuitry And Dystonia As A Model Of Motor Control Dysfunction, Deepak Kumbhare

Theses and Dissertations

The basal ganglia (BG) is a complex set of heavily interconnected nuclei located in the central part of the brain that receives inputs from the several areas of the cortex and projects via the thalamus back to the prefrontal and motor cortical areas. Despite playing a significant part in multiple brain functions, the physiology of the BG and associated disorders like dystonia remain poorly understood. Dystonia is a devastating condition characterized by ineffective, twisting movements, prolonged co-contractions and contorted postures. Evidences suggest that it occurs due to abnormal discharge patterning in BG-thalamocortocal (BGTC) circuitry. The central purpose of this study …

Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young

Theses and Dissertations

Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …

Improved Capability Of A Computational Foot/Ankle Model Using Artificial Neural Networks, Ruchi D. Chande

Theses and Dissertations

Computational joint models provide insight into the biomechanical function of human joints. Through both deformable and rigid body modeling, the structure-function relationship governing joint behavior is better understood, and subsequently, knowledge regarding normal, diseased, and/or injured function is garnered. Given the utility of these computational models, it is imperative to supply them with appropriate inputs such that model function is representative of true joint function. In these models, Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scans and literature inform the bony anatomy and mechanical properties of muscle and ligamentous tissues, respectively. In the case of the latter, literature reports …

Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr

Theses and Dissertations

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …

Role Of E-Cadherin Force In The Spatial Regulation Of Cell Proliferation, Abhinav Mohan

Theses and Dissertations

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. A hallmark of epithelial cells is strong cell-cell junctions. These junctions include E-Cadherin, a type of adherens junction that is critical for both barrier function and contact inhibition. Prior experiments by other groups have shown that adherens junctions are subject to mechanical tension. Externally applied forces (e.g. stretch) results in changes in E-Cadherin forces that coordinate proliferation. My current work tests the hypothesis that E-Cadherin forces mediate the spatial regulation of cell proliferation even in the absence of externally applied forces.

An Investigation Of Kinetic Visual Biofeedback On Dynamic Stance Symmetry, Trisha J. Massenzo

Theses and Dissertations

The intent of the following research is to utilize task-specific, constraint-induced therapies and apply towards dynamic training for symmetrical balance. Modifications to an elliptical trainer were made to both measure weight distributions during dynamic stance as well as provide kinetic biofeedback through a man-machine interface. Following a review of the background, which includes research from several decades that are seminal to current studies, a design review is discussed to cover the design of the modified elliptical (Chapter 2).

An initial study was conducted in a healthy sample population in order to determine the best visual biofeedback representation by comparing different …

A Computational Study Of Curvature In The Outflow Graft Of A Continuous Flow Left Ventricular Assist Device, Laura Patterson

Theses and Dissertations

Left ventricular assist devices (LVADs) are an increasingly utilized therapy for end-stage heart failure. Thrombosis within the graft from the pump to the aorta has been documented, but is poorly researched. This study examines the effect of graft geometry, as measured by radius of curvature, bend angle, and diameter, on thrombogenic flow patterns within the graft for a range of flow conditions. It also examines the effect blood properties, including viscosity and density, on these flow patterns. The results indicated that radius of curvature had a powerful effect on thrombogenic flow patterns. Flowrate and bend angle were also influential. The …