Engineering Commons^™

Shape Memory Alloy Capsule Micropump For Drug Delivery Applications, Youssef Mohamed Kotb

Theses and Dissertations

Implantable drug delivery devices have many benefits over traditional drug administration techniques and have attracted a lot of attention in recent years. By delivering the medication directly to the tissue, they enable the use of larger localized concentrations, enhancing the efficacy of the treatment. Passive-release drug delivery systems, one of the various ways to provide medication, are great inventions. However, they cannot dispense the medication on demand since they are nonprogrammable. Therefore, active actuators are more advantageous in delivery applications. Smart material actuators, however, have greatly increased in popularity for manufacturing wearable and implantable micropumps due to their high energy …

Vertical Federated Learning Using Autoencoders With Applications In Electrocardiograms, Wesley William Chorney

Theses and Dissertations

Federated learning is a framework in machine learning that allows for training a model while maintaining data privacy. Moreover, it allows clients with their own data to collaborate in order to build a stronger, shared model. Federated learning is of particular interest to healthcare data, since it is of the utmost importance to respect patient privacy while still building useful diagnostic tools. However, healthcare data can be complicated — data format might differ across providers, leading to unexpected inputs and incompatibility between different providers. For example, electrocardiograms might differ in sampling rate or number of leads used, meaning that a …

Decellularization Strategies Of Naturally Derived Biomaterials For Tissue Engineering Applications, Julia Elizabeth Hohn

Theses and Dissertations

In 2017, over 3.5 million peripheral vascular surgeries were performed worldwide with over 400,000 vascular repair or replacement surgeries being performed in the United States each year alone. As the number of vascular repair surgeries, including both coronary and peripheral bypass grafting procedures, continues to increase each year, these statistics indicate an urgent need for more effective and readily available replacement materials. Regenerative medicine and tissue engineering (TE) approaches, including the design, fabrication, and validation of suitable biomaterials in vitro that direct the repair and regeneration of damaged tissues, have been proposed to alleviate this problem. While advanced biomaterials have …

In Vitro And In Vivo Studies Of Mediator Kinase, Lili Wang

Theses and Dissertations

This project addresses the molecular and in vivo activities of transcriptionregulating module CKM, comprised of CDK8 (or CDK19) kinases, Cyclin C, MED12 and MED13. Our lab has found that CDK8/19 potentiates NFkB-induced transcription. In this study, we confirmed that both CDK8 and CDK19 regulate gene expression in kinasedependent manner. CDK8 and CDK19 are not required for NFkB-induced transcription, which also occurs in HEK293-dKO (CDK8 and CDK19 double knockout) cells, but such transcription becomes CDK8/19-dependent upon re-expression of CDK8 or CDK19 in dKO. Surprisingly. pre-treatment with a CDK8/19 inhibitor decreases the effect of CDK8/19 on NFkB-induced transcription.

In another set of …

Methods For Inference And Analysis Of Gene Networks From Rna Sequencing Data, Himangi Srivastava

Theses and Dissertations

RNA (Ribonuceic Acid) sequencing technology is a powerful technology used to give re- searchers essential information about the functionality of genes. The transcriptomic study and downstream analysis highlight the functioning of the genes associated with a specific biological process/treatment. In practice, differentially expressed genes associated with a particular treatment or genotype are subjected to downstream analysis to find some critical set of genes. This critical set of genes/ genes pathways infers the effect of the treatment in a cell or tissue. This disserta- tion describes the multiple stages framework of finding these critical sets of genes using different analysis methodologies …

The Effect Of Low Dose Penicillin On Tumor Development In ApcMin/+ Mice, Kinsey Ann Sierra Meggett

Theses and Dissertations

Antibiotics have been our most effective weapon against bacterial infections since their discovery in the early 1900s. Their use has been critical in reducing mortality rate from infectious diseases. However, in the last few decades, the overuse of antibiotics, beginning at an early age and into adulthood, has become a growing concern globally. Penicillin is one of many extensively used antibiotics in early childhood that has been used to treat childhood infections. Recent studies showed that exposure to low dose penicillin can have adverse effects leading to chronic illness such as diabetes, allergies, inflammation, and susceptibility to obesity, with the …

A Novel Model To Study Adipose-Derived Stem Cell Differentiation, Austin N. Worden

Theses and Dissertations

The use of three-dimensional (3D) culture systems (hydrogels) and adipose-derived stem cells (ADSCs) in regenerative medicine to advance early-stage investigation and modeling of the mechanisms of diseases, treatments, targets, etc. has recently increased. ADSCs, specifically, are utilized due to their innate programming during embryogenesis and in adult tissues in addition to their ability to differentiate into mesodermal, endodermal, and ectodermal cell-specific lineages. Of importance is that these advancements do not involve a model specimen (i.e. mice or rats) and simulate the numerous conflicting signals a migrating cell is exposed to in vivo such as chemokines, extracellular matrix (ECM), growth factors, …

Role Of Estrogen In Regulating Diet-Induced Obesity In Females, Ahmed Aladhami

Theses and Dissertations

Menopause puts a female at risk for several chronic diseases, including an increased risk of obesity. Estrogens are major sex hormones of females that dramatically decrease during menopause. Several murine studies have established the crucial role of estrogen and estrogen receptor alpha (ERα) on energy homeostasis, glucose metabolism, and insulin action. However, previous works have produced contradicting findings, hence, further work is needed to optimize better outcomes. Therefore, my dissertation focuses on optimizing and characterizing different estrogen-deficient models, as well as using novel double transgenic inducible and tissue-specific models that overexpress aromatase (estrogen producing enzyme) and estrogen receptor isomers alpha …

Study Of The Effect Of B-Cell-Intrinsic Mhcii Antigen Presentation On Germinal Center B Cell Evolution Using The Brainbow Mouse Model, Nia Hall

Theses and Dissertations

Major histocompatibility complex class II (MHCII) are molecules that are essential for B cell activation, as well as clonal competition among activated B cell clones during germinal center (GC) reactions. However, it is unknown to what extent MHCII drives the selection of some clones over others. This is of particular importance since MHCII is highly polymorphic with the ability to indirectly alter gutmicrobiome composition by altering the immunoglobulin A (IgA) repertoire. To study this, we utilized a novel triple-transgenic mouse model to assess how B-cellintrinsic MHCII influences GC responses and GC clonal diversity, with an eyeforward to understanding the relevance …

Impact Of Acetylcholine On Internal Pathways To Basal Amygdala Pyramidal Neurons, Tyler Daniel Anderson-Sieg

Theses and Dissertations

The basolateral nuclear complex of the amygdala (BNC) – consisting of the lateral (LA), basolateral (BL), and basomedial nuclei (BM) – detects salient environmental stimuli (cue-detection) and motivates appropriate behavioral responses to their implied meaning (cue-guided behavior) via a precise pattern of internal circuitry. Glutamatergic signals representing environmental stimuli enter the LA and split into parallel streams that activate pyramidal neurons (PNs) in the anterior and posterior BL (BLa and BLp), which putatively mediate negative and positive emotions, respectively. The BL is the most densely innervated target of the cholinergic basal forebrain (CBF) and ACh transients (phasic ACh) in cortex …

Impaired Metabolic Flexibility In A Mouse Model Of Leigh Syndrome, Richard Sterling Mccain Jr

Theses and Dissertations

Metabolic dysfunction burdens tissues with high energy demands, particularly the brain. Leigh syndrome is a mitochondrial encephalopathy stemming from genetic defects in the electron transport chain. Leigh syndrome patients develop lactic acidosis, ataxia, bilateral necrotizing lesions in the brainstem and basal ganglia, lesion microgliosis, and eventually death due to respiratory failure. The NADH dehydrogenase [ubiquinone] iron-sulfur protein 4 (NDUFS4) knockout mouse is an established model of Leigh syndrome due to impaired assembly of mitochondrial Complex I that develops motoric deficits and necrotizing lesions in the brainstem vestibular nuclei and olfactory bulb. In addition to the Complex I-derived bioenergetics defect, altered …

The Role Pde11a4 Signaling And Compartmentalization In Social Behavior, Kaitlyn Pilarzyk

Theses and Dissertations

People tend to be social by nature. Being socially connected not only helps people live longer and healthier lives, but being an engaged and contributing member of society strengthens our communities overall. Maintaining intact social behaviors is key to maintaining this wellbeing, with disruptions negatively affecting both mental and physical health. Indeed, social isolation and feelings of loneliness can significantly increase a person’s risk of premature death, heart disease, and stroke as well as depression, anxiety, suicide, and dementia. Maintaining the ability to create and store social memory with age is, therefore, key to maintaining proper social behaviors. Unfortunately, individuals …

Role Of Ahr Ligands In Immune Modulation To Suppress Inflammation Through The Regulation Of Microrna And Gut Microbiome, Osama Azeldeen Abdulla

Theses and Dissertations

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and an environmental sensor that is highly conserved evolutionarily. It was first discovered in the early 1970s for its ability to bind with high affinity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental pollutant and induce a xenobiotic-metabolizing enzyme known as aryl hydrocarbon hydroxylase (AHH). AhR was shown to regulate TCDD-mediated toxicity against a variety of tissues including the immune system. More recently, AhR has been characterized as key regulator of the immune system, specifically the differentiation of T cells. Also, several AhR ligands have been characterized in addition to TCDD such as …

Developing And Comparing Sensor For Movement Analysis And Biofeedback, Umaiyaal Vasudevaraja

Theses and Dissertations

Background: Recent advances in the field of wearable technology are now at a peak in the sports field and the medical field. The validity, reliability, and application of such systems are still under research and yet to be revealed.

Purpose: This study aims to design and constructing the Inertial Measurement Unit (IMU) hardware with the required software to collect accelerometer data for potential use in human movement studies and test the efficacy of the collected IMU accelerometer data by comparing it with the motion capture data.

Methods: In this study, the IMU sensor is coupled with the Arduino, loaded with …

17 Β-Estradiol And Phytoestrogens Attenuate Apoptotic Cell Death In Hiv-1 Tat Exposed Primary Cortical Cultures, Sheila Marie Adams

Theses and Dissertations

Despite the advent of highly active antiretroviral therapy (HAART), neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). The poor CNS delivery of anti-retrovirals allows continued virus production and renders neurons susceptible to the toxic effects of released viral proteins. The neurotoxic potential of HIV-1 viral protein Tat has been shown to include excitotoxicity, oxidative stress, and mitochondrial dysfunction leading to subsequent cell death. Thus, Tat is thought to have a key role in the pathogenesis of HIV-associated neurodegeneration. Estrogens are universally considered to be neuroprotective, as such; estrogens have positive implications in the treatment …

Expansion Microscopy: A New Approach To Microscopic Evaluation, Ashley Ferri

Theses and Dissertations

Optical microscopy resolution is limited by the wavelengths of light and the series of microscope lenses and other optical components used to create a magnified image of cell structures in a sample. Often the cell structures are smaller or closer together than the resolution limits of a light microscope. In 2015 the Boyden group at the Massachusetts Institute of Technology (MIT) created a sample preparation technique, expansion microscopy which involves embedding biological samples in a crosslinked, swellable, hydrogel polymer that allows for uniform physical separation of cell components so that they can subsequently be resolved by light microscopy. Using the …

Helicobacter’S Effects On Colitis/Colon Cancer And The Response To Indole 3-Carbinol, Rasha Raheem Abdulhamza Alkarkoushi

Theses and Dissertations

Enterohepatic Helicobacter (EHH) species are gram-negative bacteria, which are poorly studied. Several studies suggest that EHH species contribute to inflammatory bowel disease IBD in humans. IBD and colorectal cancer (CRC) has emerged as a public health challenge worldwide. Indole-3-carbinol (I3C) is one of the natural dietary indoles abundant in Brassica (cruciferous) vegetables. The aryl hydrocarbon receptor (AhR) plays an essential role as a regulator by controlling the balance between Tregs and Th17 cells. The activation of AhR by ligands derived from food or intestinal microbiota is an essential control mechanism in that balance. Moreover, many studies showed indoles achieving chemo-preventive …

Development Of An Anatomically And Electrically Conductive Brain Phantom For Transcranial Magnetic Stimulation, Hamzah A. Magsood

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for diagnostics, prognostic, and treatments of various neurological diseases. However, the lack of anatomically realistic brain phantoms has made the experimental verification of stimulation strength in the form of induced electric fields/voltages in the brain tissues an impediment to developing new TMS coils, stimulators, and treatment protocols. There are significant technological, safety, and ethical limitations to test the potential TMS treatment procedures or develop enhancements and refine them on humans or animals. This work aims to bridge the gap by introducing and developing an innovative manufacturing and fabrications process to produce a …

On-Demand Electrically Induced Decomposition Of Thin-Film Nitrocellulose Membranes For Wearable Or Implantable Biosensor Systems, Benjamin M. Horstmann

Theses and Dissertations

Implantable or subcutaneous biosensors used for continuous health monitoring have a limited functional lifetime requiring frequent replacement and therefore may be highly discomforting to the patient and become costly. One possible solution to this problem is use of biosensor arrays where each individual reserve sensor can be activated on-demand when the previous one becomes inoperative due to biofouling or enzyme degradation. Each reserve biosensor in the array is housed in an individual Polydimethylsiloxane (PDMS) well and is protected from exposure to bodily fluids such as interstitial fluid ( ISF) by a thin-film nitrocellulose membrane. Controlled activation is achieved by decomposing …

Tissue-Specific Roles Of Transforming Growth Factor Beta Ligands In Cardiac Outflow Tract Malformations And Calcific Aortic Valve Disease, Nadia Al-Sammarraie

Theses and Dissertations

Congenital heart defects and adult calcific aortic valve disease are two of the leading causes of morbidity and mortality worldwide. To date, there is no medical cure and surgical intervention is the main option of treatment. The cardiac outflow tract is the major site for these abnormalities, which are triggered by genetic and/or environmental factors that alter development and/or homeostasis. Recently, significant roles of TGFβ signaling in development of cardiovascular disorders have become more evident in humans, however, the specific requirement of individual TGFβ ligands on the pathogenesis of OFT malformations and diseases remains elusive. In the present work, three …

Effect Of Tcdd, An Environmental Contaminant, On Activation Of Ahr Leading To Induction Of Myeloid Derived Suppressor Cells (Mdscs) And The Ability Of Resveratrol, A Botanical, To Neutralize This Effect, Wurood Hantoosh Neamah

Theses and Dissertations

Aryl hydrocarbon receptor (AhR), is a ligand-activated transcription factor that integrates environmental, dietary, microbial and metabolic cues to control various cellular processes, such as the cell cycle, epithelial barrier function, cell migration and immune function. AhR was discovered as the receptor that binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leads to numerous of toxicological outcomes. In the current study, we discovered a critical role played by AhR, following activation by TCDD, in modulating a variety of immunological functions through regulation of epigenetic and microbial pathways. Our data demonstrated that AhR activation triggers MDSC mobilization from bone marrow to peritoneal …

Role Of Epigenetic, Molecular And Cellular Pathways In The Regulation Of Inflammation, William James Becker

Theses and Dissertations

Dysregulated inflammation is at the heart of countless human diseases. Graft rejection is the process by which an organ from an incompatible donor is rejected by the recipient whose immune cells attack the foreign tissue. Colitis is an inflammatory disorder caused by undue chronic inflammation in the colon and rectum that can progress to cancer. Colitis incidence is on the rise, especially in developing nations and Asia; and the list of patients who need organ transplants grow by the day. Therapies for both graft rejection and colitis are limited to immunosuppressive drugs that leaves patients vulnerable to infection, heart disease, …

Epigenetic And Purinergic Regulation Of Mast Cells Mediator Release, Zahraa Abdulmohsin Mohammed

Theses and Dissertations

Mast cells (MCs) are well known for their implications in allergic reactions. They are also known to have multiple functions in the innate and adaptive immune system. Their activation plays an essential role in many aspects of physiological and pathological conditions. Allergies are considered chronic conditions that affect more than 60 million people in the U.S. These diseases are driven by the activation of MCs in response to IgE-mediated antigen, rendering these cells as targets for the management of allergies and asthma. Therefore, this research considers the understanding of their activation and the regulation of their response to be an …

Interdependent Mechanisms Of Stress Susceptibility, Julie Elaine Finnell

Theses and Dissertations

Social stress is a significant risk factor for the emergence of psychiatric disorders including depression and anxiety. While there are a number of commercially available therapeutic options for the treatment of these disorders, these treatments require weeks of continuous use to produce behavioral efficacy. It has also been suggested that these traditional therapies are only marginally effective in producing complete remission, suggesting that our understanding as it pertains to the mechanisms underlying stressinduced behavioral dysfunction is still in its infancy. In the last few years, inflammation has become a major focus in the field of stress and depression as clinical …

The Contribution Of Adipose Tissue From Ovariectomized Mice To Colon Cancer, Meredith Smith Carson

Theses and Dissertations

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when …

Astrocyte Sensitivity To Dopamine In Culture And Ex Vivo, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. This thesis illustrates effects of dopamine on cultured astrocytes and astrocytes in brain slices (ex vivo). In striatal cultures, extracellular dopamine triggered changes in astrocytic Ca²⁺ signaling and rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation, but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. To isolate possible mechanisms underlying these structural and functional changes, whole-genome RNA sequencing was …

Three-Dimensional Plasma Cell Survival Microniche In Multiple Myeloma, Katrina A. Harmon

Theses and Dissertations

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled proliferation of long-lived plasma cells (PCs) in the bone marrow (BM), which constitute at least 10% of BM cellularity. Normally, long-lived plasma cells make up less than 1% of BM cells. Plasma cells become neoplastic when a clonal PC population produces a monoclonal immunoglobulin protein. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is made when there is an increase in monoclonal PCs within the BM, but less than 10%, and the patient does not present with end-organ damage, which is associated with active MM. Though not considered …

Biophysical Analyses Of Left Ventricular Remodeling Secondary To Myocardial Infarction And Left Ventricular Pressure Overload, William Manuel Torres

Theses and Dissertations

Left ventricular (LV) remodeling is nominally an adaptive process that restores biomechanical function following myocardial injury and/or sustained alterations in loading conditions. This remodeling can materialize as changes in myocardial geometry, composition, and mechanical properties. When these changes fail to restore LV biomechanical function, remodeling is termed maladaptive. It is generally accepted that maladaptive LV remodeling underlies the progression to heart failure in various forms of heart disease. The central hypothesis of this study is that we can leverage echocardiographic imaging techniques to non-invasively quantify changes in biomechanical function and mechanical properties in a serial manner throughout the progression towards …

Three-Dimensional Plasma Cell Survival Microniche In Multiple Myeloma, Katrina A. Harmon

Theses and Dissertations

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled proliferation of long-lived plasma cells (PCs) in the bone marrow (BM), which constitute at least 10% of BM cellularity. Normally, long-lived plasma cells make up less than 1% of BM cells. Plasma cells become neoplastic when a clonal PC population produces a monoclonal immunoglobulin protein. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is made when there is an increase in monoclonal PCs within the BM, but less than 10%, and the patient does not present with end-organ damage, which is associated with active MM. Though not considered …

Beneficial Effects Of Resveratrol Against Colitis And Colorectal Cancer Mediated By The Host Microbiome, Epigenome, And Immune Response, Haider Rasheed Daham Alrafas

Theses and Dissertations

Resveratrol, a natural polyphenol compound found in red wine, the skins of grapes, and other plant products, has been used as a traditional medicine for thousands of years throughout human history, but current research has revealed this natural component is capable of modulating a variety of immunological, microbial, and epigenetic mechanisms to improve overall health and well-being of hosts that consume it. Colitis, an inflammatory bowel disease characterized by chronic inflammation in the colon and rectum, which has been associated with colon cancer. This cancer incidence is rising in younger adults in the US. Thus, newer approaches to prevent colitis …