Biomedical Engineering and Bioengineering Commons^™

Direct Material Property Determination: One-Dimensional Formulation Utilising Full-Field Deformation Measurements, Sreehair Rajan-Kattil, Michael A. Sutton, Subramani Sockalingam, Frank Thomas, Tusit Weerasooriya, Stephen Alexander

Faculty Publications

A direct approach is described to determine the elastic modulus distribution in a nominally heterogeneous material subject to tensile/compression loading and primarily experiencing deformations in the axial direction. The formulation is developed for uniaxial applications using basic theoretical constructs, resulting in a computational framework that has a matrix form [A] {E} = {R}, where the [A] matrix components are known functions of measured axial strains and axial positions, {R} components are known functions of axial body forces, applied loads and reactions and {E} components are the unknown elastic moduli at discrete locations along the length of the specimen. For a …

Investigating The Impact Of Endothelial Dysfunction And Aging On Vascular Remodeling Using Mouse Models, Liya Du

Theses and Dissertations

Endothelial dysfunction, characterized by a reduction in the bioavailability of nitric oxide (NO), is a major factor in the initiation and progression of atherosclerosis, an age-related chronic inflammatory process in the arterial wall and the leading cause of mortality and morbidity globally. A better understanding of alterations in vascular structure and function associated with endothelial dysfunction can facilitate the early detection of atherosclerosis and the development of potential pharmaceutical interventions. This study aims to clarify the impact of endothelial dysfunction in conjunction with aging on the microstructure of aortic extracellular matrix (ECM) and to elucidate the relationship between microstructural adaptation …

Histomechanical Compatibility Of Coronary Artery Bypass Grafts, Colton J. Kostelnik

Theses and Dissertations

Coronary artery disease is a localized form of atherosclerosis that can severely restrict blood flow to the heart often requiring a surgical intervention known as coronary artery bypass grafting (CABG) to reestablish perfusion to this essential circulation. To some extent, the selection of the autograft tissue is at the surgeon’s discretion with factors such as stenosis location and the existing tissue’s pathological state contributing to a choice that could be deterministic in surgical outcomes. Many post-operative complications and premature graft failures originate from graft-target tissue incompatibilities and altered blood flow patterns. We hypothesize that mechanical mismatching between the graft material …

Liquid-Phase Effects On Adsorption Processes In Heterogeneous Catalysis, Mehdi Zare, Mohammad S. Saleheen, Nirala Singh, Mark J. Uline, Muhammad Faheem, Andreas Heyden

Faculty Publications

Aqueous solvation free energies of adsorption have recently been measured for phenol adsorption on Pt(111). Endergonic solvent effects of ∼1 eV suggest solvents dramatically influence a metal catalyst's activity with significant implications for the catalyst design. However, measurements are indirect and involve adsorption isotherm models, which potentially reduces the reliability of the extracted energy values. Computational, implicit solvation models predict exergonic solvation effects for phenol adsorption, failing to agree with measurements even qualitatively. In this study, an explicit, hybrid quantum mechanical/molecular mechanical approach for computing solvation free energies of adsorption is developed, solvation free energies of phenol adsorption are computed, …

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 …

Therapeutic Payload Delivery To The Myocardium: Evolving Strategies And Obstacles, Tarek Shazly, Arianna Smith, Mark J. Uline, Francis G. Spinale

Faculty Publications

No abstract provided.

Antiviral Polymers: A Review, Ali Akbari, Ashkan Bigham, Vahid Rahimkhoei, Sina Sharifi, Esmaiel Jabbari

Faculty Publications

Polymers, due to their high molecular weight, tunable architecture, functionality, and buffering effect for endosomal escape, possess unique properties as a carrier or prophylactic agent in preventing pandemic outbreak of new viruses. Polymers are used as a carrier to reduce the minimum required dose, bioavailability, and therapeutic effectiveness of antiviral agents. Polymers are also used as multifunctional nanomaterials to, directly or indirectly, inhibit viral infections. Multifunctional polymers can interact directly with envelope glycoproteins on the viral surface to block fusion and entry of the virus in the host cell. Polymers can indirectly mobilize the immune system by activating macrophages and …

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 …

Decellularized Articular Cartilage Microgels As Microcarriers For Expansion Of Mesenchymal Stem Cells, Esmaiel Jabbari, Azadeh Sepahvandi

Faculty Publications

Conventional microcarriers used for expansion of human mesenchymal stem cells (hMSCs) require detachment and separation of the cells from the carrier prior to use in clinical applications for regeneration of articular cartilage, and the carrier can cause undesirable phenotypic changes in the expanded cells. This work describes a novel approach to expand hMSCs on biomimetic carriers based on adult or fetal decellularized bovine articular cartilage that supports tissue regeneration without the need to detach the expanded cells from the carrier. In this approach, the fetal or adult bovine articular cartilage was minced, decellularized, freeze-dried, ground, and sieved to produce articular …

The Lognometer: A New Normalized And Computerized Device For Assessing The Neurodevelopment Of Fine Motor Control In Children, Christian O'Reilly, Rejean Plamondon, Nadir Faci

Publications

Motor skills are fundamental for the development of children. Neurodevelopmental tests currently used by professionals for measuring motor control maturity exhibit several limitations. To address some of these, we have designed the Lognometer, a tablet-based device that can run computerized neuromotor tests. To normalize this tool against a representative population, we collected handwritten triangles from 780 children. We used the Sigma-Lognormal model and a prototype-based parameter estimation algorithm to analyze these movements. To ensure clinical acceptance, we developed an explainable solution relying on statistical regression. We evaluated how well the proposed lognormal decomposition captures the motor control maturation between 6 …

Comparing Symbolic And Connectionist Algorithms For Correlating The Age Of Healthy Children With Sigma-Lognormal Neuromuscular Parameters, Zigeng Zhang, Christian O'Reilly, Rejean Plamondon

Publications

It is important to accurately evaluate the motor control maturity to help physicians diagnose delayed or abnormal motor development in children. Traditionally, it has been challenging to design assessment methods that are practical and accurate at the same time. This study aims to develop an effective algorithm to predict motor control maturity based on the Kinematic Theory of rapid human movements. We used handwritten pen strokes made on an electronic tablet by 513 children (5.5 to 13 years of age). We considered two types of movements: a single stroke and a triangle drawing test. For the analysis, Sigma-Lognormal parameters were …

Rapid Ac Electrokinetic Micromixer With Electrically Conductive Sidewalls, Fang Yang, Wei Zhao, Cuifang Kuang, Guiren Wang

Faculty Publications

We report a quasi T-channel electrokinetics-based micromixer with electrically conductive sidewalls, where the electric field is in the transverse direction of the flow and parallel to the conductivity gradient at the interface between two fluids to be mixed. Mixing results are first compared with another widely studied micromixer configuration, where electrodes are located at the inlet and outlet of the channel with electric field parallel to bulk flow direction but orthogonal to the conductivity gradient at the interface between the two fluids to be mixed. Faster mixing is achieved in the micromixer with conductive sidewalls. Effects of Re numbers, applied …

The Immune Modulatory Role Of Endocannabinoid Anandamide To Suppress Inflammation Through Regulation Of Microrna And Microbiome, Muthanna Ali Sultan

Theses and Dissertations

Cannabinoids are group of compounds that exerts their anti-inflammatory action through activation of CB1 and CB2 receptors and other minor receptors. In the current study, we investigated the effect of Anandamide (AEA) on Acute Respiratory Distress Syndrome (ARDS) induced by exposure to Staphylococcus Enterotoxin B (SEB) intranasally. We found that C57BL/6 mice treated with AEA showed improvement in the clinical functions of the lungs, accompanied by a decrease in the infiltration of inflammatory cells in the lung tissue, and a decrease in the secretion of pro-inflammatory cytokines. Furthermore, AEA regulated the miRNA profile of the mononuclear cells in the lungs …

Nanoparticles For Targeted Drug Delivery To Cancer Stem Cells: A Review Of Recent Advances, Yavuz Nuri Ertas, Keyvan Abedi Dorcheh, Ali Akbari, Esmaiel Jabbari

Faculty Publications

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized …

Regulation Of Inflammatory Processes By Tryptamine, Cannabidiol And 2,3,7,8-Tetrachlorodibenzo-P-Dioxin, Nicholas Dopkins

Theses and Dissertations

Host immunity is a complicated system of pro-inflammatory and anti-inflammatory processes that respond to exogenous and endogenous threats to regulate host physiology, inhibit carcinogenesis, and protect from infections. Sustained deviance from normal immunological function occurs due to a variety of factors both endogenous and exogenous, with some factors that can dysregulate host immunity including: genetics, microbiota composition, toxin exposure, age, gender, and smoking. The etiology of inflammatory disorders is both convoluted and complex due to the sheer number of facets regulating host immunity. To better contribute to understanding how immunological dysregulation occurs we focused on how three anti-inflammatory compounds (tryptamine, …

Anatomical Correlates Of Age-Related Basal Forebrain Dysfunction, Brandy Lynn Somera

Theses and Dissertations

The basal forebrain (BF) is comprised of several nuclei including the substantia innominata, medial septum, nucleus basalis and diagonal band of broca which are involved in cognitive functions including attention, motivation, and arousal. BF neurons are particularly vulnerable to dysfunction and degeneration in aged humans and, more dramatically, in diseases such as Alzheimer's disease (AD). Age-related BF dysfunction may reflect diminished afferent regulation as well as an altered local glial environment. Our lab has previously shown reduced orexin/hypocretin innervation of BF in aging, a phenomenon that may link afferent dysfunction with altered microglial homeostasis. There is little research examining these …

An In Vitro Approach To Vascular Therapeutic Testing, Shahd Ali Hasanain

Theses and Dissertations

Aortopathies refer to a broad class of pathological conditions affecting the aorta and are a major cause of morbidity and mortality in the US. Specifically, aortic aneurysms and aortic dissections have diverse etiologies that are initiated by alterations in the tissue’s extracellular-matrix (ECM) proteins, namely collagen and elastin, thereby predisposing the aortic wall to weaken and rupture. Pentagalloyl glucose (PGG) has recently emerged as a non-surgical treatment to reduce the risk of dissection or rupture. PGG is a known antioxidant and anti-inflammatory which has been shown to have ECM-restorative qualities that enhance collagen and elastin’s functional properties. Prior studies using …

Pseudomyxoma Peritonei Derived Cancers: A Novel Study On Growth And Growth Suppression Utilizing Common Colorectal Cancer Agents, Raymond Kennith Bogdon

Theses and Dissertations

Pseudomyxoma peritonei is a devastating gastrointestinal disease characterized by the production of mucinous ascites within the peritoneal cavity. Historically, this condition is discovered in the advanced state due to the lack of adequate screening tests and typically presents as an enlarged abdomen and with symptoms of gastrointestinal distress. Treatment for this disease is a combination of cytoreductive surgery and heated intraperitoneal perfusion chemotherapy, but a successful operation does not guarantee full remission of this malignancy. This study focuses on 3 untested variants of PMP cancer, and 2 mucinous colorectal adenocarcinomas that had invaded into the peritoneal cavity. Clinical presentation of …

On Using The Bmcsl Equation Of State To Renormalize The Onsager Theory Approach To Modeling Hard Prolate Spheroidal Liquid Crystal Mixtures, Donya Ohadi, David S. Corti, Mark J. Uline

Faculty Publications

Modifications to the traditional Onsager theory for modeling isotropic–nematic phase transitions in hard prolate spheroidal systems are presented. Pure component systems are used to identify the need to update the Lee–Parsons resummation term. The Lee–Parsons resummation term uses the Carnahan–Starling equation of state to approximate higher-order virial coefficients beyond the second virial coefficient employed in Onsager’s original theoretical approach. As more exact ways of calculating the excluded volume of two hard prolate spheroids of a given orientation are used, the division of the excluded volume by eight, which is an empirical correction used in the original Lee–Parsons resummation term, must …

Vascular Endothelial Dysfunction And Effects On Arterial Wall Microstructure, Jeffrey Thomas Rodgers

Theses and Dissertations

Vascular endothelial cell dysfunction (ECD) is a disease characterized by the inability of the vascular endothelial cells to transmit signaling molecules, namely nitric oxide (NO), in response to changes in blood flow rate. This disease is shown to be incident in the onset of more severe vascular disease such as hypertension, atherosclerosis, and heart failure. Long-term ECD is shown to cause long-term remodeling such as decreased flow-mediated dilation, increased pulse-wave velocity, intimal-medial thickening, and increased wall stiffness due to collagen deposition. We used second harmonic generation (SHG) microscopy to analyze this change in the collagen microstructure of the arterial extracellular …

Age And Sex Dependency Of Thoracic Aortic Aneurysm Progression In A Mouse Model Of Marfan Syndrome, Nazli Gharraee

Theses and Dissertations

Aneurysm of the ascending aorta is the most common type of thoracic aortic aneurysm, and it is a life-threatening manifestation of Marfan syndrome (MFS), a connective tissue disorder caused by mutation of the FBN1 gene. Incidence of Marfan syndrome is similar for men and women; however, men suffer from more severe aortic events compared to women.

This study aims to provide a better understanding of age and sex dependency of cell and extracellular matrix alterations of the aortic wall during the progression of the aneurysm caused by Marfan syndrome. To achieve this goal, the C1041G/+ mouse model of Marfan syndrome …

Defining The Pathophysiology Of Gut Humoral Immunodeficiency, Ahmed Dawood Mohammed

Theses and Dissertations

Mucosal antibodies maintain gut homeostasis by promoting spatial segregation between host tissues and luminal microbes. Antibody-deficiency is the most common form of primary immunodeficiency observed in humans. In antibody-deficient humans, abnormal composition of the gut microbiota ('dysbiosis') is associated with chronic inflammatory responses and gastrointestinal complications. However, the mechanisms by which dysbiosis promotes inflammatory disease are poorly defined. In the studies described in this dissertation, we utilize CD19-/- mice as a model of antibody deficiency to test the hypothesis that antibody deficiency negatively impacts gut physiology under steady-state conditions. Chapter #1 is an overview of B cell development and how …

Mechanism Of Therapeutic Efficacy Of New Drugs In Glioblastoma, Firas Hameed Khathayer

Theses and Dissertations

Glioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to brain health. The deregulation of epigenetic mechanisms is considered the main agent in the developing of GBM. One of the enzymes involved in epigenetic alternation and cancer development are histone deacetylases enzyme (HDAC) by removal acetyl group from histone and create condensed chromatin that suppresses transcription gene to histone and non-histone proteins involved in tumorigenesis. Histone deacetylase inhibitors (HADCi) are the most common therapeutic methods for many types of cancer treatments. In the present study, we used relative HDAC inhibitor …

A Comparative Study Of Cannabinoids & Cb1 Receptor Gi Signaling, Haley Kristen Andersen

Theses and Dissertations

The legalization of medical marijuana has highlighted cannabinoids as a potential, opioid-free therapeutic option for pain management; however, the rise in illicit synthetic cannabinoid-induced toxicity has demonstrated the need to outline cannabinoid molecular signaling. The cannabinoid-type 1 (CB1) receptor is an endogenous G protein-gated receptor (GPCR), well-expressed in the central nervous system (CNS) associated with modulating neuronal activity. Cannabinoid agonists bind to the CB1 receptor resulting in the inhibitory G protein (Gi) complex to dissociate into two subunits, Gβγi and Gαi. The Gαi subunit inhibits adenylyl cyclase, leading to a decrease in cyclic adenosine monophosphate (cAMP). The Gβγi subunit activates …