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Evaluation And Modulation Of The Circadian Clock In Human Keratinocytes And Epidermal Skin, William Harold Cvammen Iv Jan 2024

Evaluation And Modulation Of The Circadian Clock In Human Keratinocytes And Epidermal Skin, William Harold Cvammen Iv

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The circadian clock is a fundamental biological mechanism that regulates various physiological processes, including DNA repair, to synchronize with the day-night cycle. In human skin, exposure to ultraviolet (UV) light poses a significant challenge, inducing DNA damage that must be efficiently repaired to maintain genomic integrity and prevent carcinogenesis. This study delved into the complex interplay between the circadian clock, UV light exposure, DNA repair, and modulation of circadian transcriptional machinery in human skin. Initially, we examined the transcriptomic profile of the circadian clock in humans through in silico-based approaches and in vivo studies, revealing that core clock gene expression …


Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe

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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …


Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume

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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …


Monitoring Blood Flow In Animal Models Using A Camera-Based Technique, Dharminder Singh Langri Jan 2023

Monitoring Blood Flow In Animal Models Using A Camera-Based Technique, Dharminder Singh Langri

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Blood flow dynamics plays a critical role in maintaining tissue health, as it delivers nutrients and oxygen while removing waste products. It is especially important when there is a disruption in cerebral autoregulation due to trauma, which can induce ischemia or hyperemia and can lead to secondary brain injury. Thus, there is a need for noninvasive techniques that can allow continuous monitoring of blood flow during intervention. Optical techniques have become increasingly practical for measuring blood flow due to their non-invasive, continuous, and relatively lower-cost nature. This research focused on developing a low-cost, scalable optical technique for measuring blood flow …


Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl Jan 2023

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

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


Contributors To Pathologic Depolarization In Myotonia Congenita, Jessica Hope Myers Jan 2023

Contributors To Pathologic Depolarization In Myotonia Congenita, Jessica Hope Myers

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Myotonia congenita is an inherited skeletal muscle disorder caused by loss-of-function mutation in the CLCN1 gene. This gene encodes the ClC-1 chloride channel, which is almost exclusively expressed in skeletal muscle where it acts to stabilize the resting membrane potential. Loss of this chloride channel leads to skeletal muscle hyperexcitability, resulting in involuntary muscle action potentials (myotonic discharges) seen clinically as muscle stiffness (myotonia). Stiffness affects the limb and facial muscles, though specific muscle involvement can vary between patients. Interestingly, respiratory distress is not part of this disease despite muscles of respiration such as the diaphragm muscle also carrying this …


Novel Natural Language Processing Models For Medical Terms And Symptoms Detection In Twitter, Farahnaz Golrooy Motlagh Jan 2022

Novel Natural Language Processing Models For Medical Terms And Symptoms Detection In Twitter, Farahnaz Golrooy Motlagh

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This dissertation focuses on disambiguation of language use on Twitter about drug use, consumption types of drugs, drug legalization, ontology-enhanced approaches, and prediction analysis of data-driven by developing novel NLP models. Three technical aims comprise this work: (a) leveraging pattern recognition techniques to improve the quality and quantity of crawled Twitter posts related to drug abuse; (b) using an expert-curated, domain-specific DsOn ontology model that improve knowledge extraction in the form of drug-to-symptom and drug-to-side effect relations; and (c) modeling the prediction of public perception of the drug’s legalization and the sentiment analysis of drug consumption on Twitter. We collected …


Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah Jan 2022

Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah

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Breast cancer is the most prevalent cancer in women. Approximately 75% of breast cancers are estrogen receptor alpha positive (ER+) and are treatable with endocrine therapies and/or CDK inhibitors. However, endocrine therapy (ET) resistance and metastasis are major obstacles in advanced ERα+ breast cancer (ER+ BCa) therapeutics. Upregulated oncogenic ERα activity plays critical role in progression of ER+ BCa. One essential mechanism of regulating ERα signaling is the ubiquitination-dependent proteasomal degradation of ERα. Owing to its direct effect on ERα degradation, fulvestrant is a first-line FDA-approved ET for metastatic and locally advanced breast cancer and a second-line drug for treatment …


The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward Jan 2022

The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward

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Gene expression in mammalian cells requires complex nuclear choreography, and there is increasing evidence that spatiotemporal organization of chromatin and nuclear compartments plays an important role in gene expression. In this dissertation, I examined the function of SON, a splicing factor with a known role in nuclear organization, in chromatin-mediated gene expression. SON association with a transcriptionally inactive U2OS 2-6-3 reporter gene array provided a useful model to study SON’s chromatin dynamics. I demonstrated that SON associates with the inactive but not the activated array, and that SON’s RNA binding domains are not necessary for that association. Second, I discovered …


Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker Jan 2022

Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker

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Diffuse midline glioma, K27M-mutant (DMG) are intractable brain tumors, primarily occurring in the pediatric and adolescent population. Patients have a median survival of less than one year after diagnosis. A lack of therapeutic targets has been a barrier to improvement in patient survival. Irradiation therapy improves symptoms while chemotherapy and surgical intervention, for the most part, have not yet demonstrated utility for treatment. DMG are characterized by a histone H3 mutation that results in the genome-wide loss of epigenetic-repressive marks on K27 and is associated with the misexpression of genes, like Cancer/Testis antigens. A member of this group, transketolase-like 1 …


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 Jan 2021

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 …


Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy Jan 2021

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 …


Noninvasive Blood Flow And Oxygenation Measurements In Diseased Tissue, Benjamin S. Rinehart Jan 2021

Noninvasive Blood Flow And Oxygenation Measurements In Diseased Tissue, Benjamin S. Rinehart

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The research presented in this dissertation focused on the application of optical imaging techniques to establish blood flow and oxygen saturation as effective biomarkers for two disease cases, Autism Spectrum Disorder (ASD) and Huntington’s Disease (HD). The BTBR mouse model of ASD was utilized to validate measurements of cerebral blood flow and oxygenation as biomarkers for autism. The R6/2 mouse model of juvenile HD was utilized to validate measurements of skeletal muscle blood flow following tetanic muscle contractions induced by electrical nerve stimulation. Next, a noncontact, camera-based system to measure blood flow and oxygen saturation maps was implemented to improve …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

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. …


Low Frequency Oscillations Of Hemodynamic Parameters As A Novel Diagnostic Measure For Traumatic Brain Injury, Andrea Gomez Carrillo Jan 2021

Low Frequency Oscillations Of Hemodynamic Parameters As A Novel Diagnostic Measure For Traumatic Brain Injury, Andrea Gomez Carrillo

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There is a need to improve methods of monitoring patients with traumatic brain injury (TBI) in hospital settings. Current monitoring techniques and diagnosis methods are expensive, invasive, do not provide continuous measures, expose the patient to radiation, are ambiguous in the information they provide, and/or cannot be implemented at the bedside. These techniques measure imperative markers of brain function including intracranial pressure (ICP), cerebral blood flow (CBF), and oxygenation in the brain, among others. Hospitals not only require a practical method for real-time monitoring of patients at the bedside, but also meaningful metrics that characterize TBIs, since the variety of …


Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger Jan 2021

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 …


Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt Jan 2021

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 …


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 Jan 2021

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 …


Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper Jan 2021

Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper

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Amyotrophic lateral sclerosis (ALS) is the most common motorneuron (MN) disease in adulthood. ALS is hallmarked by the progressive loss of MNs in the brain, brainstem, and spinal cord. Many hypotheses to explain the pathogenesis of ALS have been explored, but the exact mechanisms underlying the development of this disease remain unknown. However, abnormalities in MN excitability and glutamate excitotoxicity are the most widely studied. For decades, researchers have examined MN excitability in ALS, but the current literature is inconsistent, showing evidence of hyperexcitability, hypoexcitability, or no change in excitability of MNs in ALS. Many of these studies also focus …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

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. …


The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi Jan 2021

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 …


Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh Jan 2021

Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh

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Carbon Nanotubes (CNTs) have beneficial properties for cell scaffolding, which has translated into effective growth of bone, muscle, and cardiac cells. However, loose carbon nanotubes can cause in vivo toxicity. To reduce this risk, our team has developed biomimetic scaffolds with multiscale hierarchy where carpet-like CNT arrays are covalently bonded to larger biocompatible substrates. In this study, we have tested such scaffolds in two distinct types of biomedical applications involving glioblastoma and keratinocyte cells. The growth of glioblastoma (GBM) cells on our CNT-coated biomimetic scaffolds was evaluated to check their suitability as a potential chemotherapy-loaded implant for GBM patient treatment. …


Design Of A Novel Wearable Ultrasound Vest For Autonomous Monitoring Of The Heart Using Machine Learning, Garrett G. Goodman Jan 2020

Design Of A Novel Wearable Ultrasound Vest For Autonomous Monitoring Of The Heart Using Machine Learning, Garrett G. Goodman

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As the population of older individuals increases worldwide, the number of people with cardiovascular issues and diseases is also increasing. The rate at which individuals in the United States of America and worldwide that succumb to Cardiovascular Disease (CVD) is rising as well. Approximately 2,303 Americans die to some form of CVD per day according to the American Heart Association. Furthermore, the Center for Disease Control and Prevention states that 647,000 Americans die yearly due to some form of CVD, which equates to one person every 37 seconds. Finally, the World Health Organization reports that the number one cause of …


Hierarchical Structure, Properties And Bone Mechanics At Macro, Micro, And Nano Levels, Farah Mohammed Ridha Abdulateef Hamandi Jan 2020

Hierarchical Structure, Properties And Bone Mechanics At Macro, Micro, And Nano Levels, Farah Mohammed Ridha Abdulateef Hamandi

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This research focuses on the hierarchical structure of bone and associated mechanical properties at different scales to assess damage accumulation leading to premature failure, with or without instrumentation. In this work, an attempt was made to develop a framework of macro, micro, and nano damage accumulation models and implementing them to derive mechanical behavior of the bone. At macrolevel, retrospective evaluation of 313 subjects was conducted, and the damage of bone tissue was investigated with respect to subject demography including age, gender, race, body mass index (BMI), height and weight, and their role in initiating fracture. Experimental data utilized 28 …


Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis Jan 2020

Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis

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Tumors are heterogeneous systems, whose growth is influenced by intrinsic properties of malignant cells, external systemic factors (i.e. immune, neural, endocrine, etc.), and the dynamic interactions between tumor cells and their microenvironment. Given the inherent complexity of cancers, combined with the continual evolution of tumors and the development of treatment resistance, a precision medicine approach may not provide an optimal clinical response. Exploring a new paradigm that focuses on regulating cancer as a system may not only control tumor progression but also address the extraordinary challenges of tumor heterogeneity and disease recurrence in order to improve clinical outcomes. As a …


Ultraviolet-B Radiation Induces Release Of Bioactive Microvesicle Particles In Keratinocytes Via Platelet-Activating Factor And Acid Sphingomyelinase, Langni Liu Jan 2020

Ultraviolet-B Radiation Induces Release Of Bioactive Microvesicle Particles In Keratinocytes Via Platelet-Activating Factor And Acid Sphingomyelinase, Langni Liu

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Ultraviolet-B (UV-B) radiation is one of the most common environmental factors and is known to induce the production of bioactive agents that cause several diseases including skin cancer. UVB exposure stimulates the production of a phospholipid activator, platelet-activating factor (PAF), and its analogs in keratinocytes that activate the PAF receptor (PAF-R) resulting in acute inflammatory and delayed systematic immunosuppressive effects. However, as UVB only penetrates into the skin epidermal layer, the detailed mechanisms of how UVB exerts systematic effects remains unclear. Previously we found that UVB induces keratinocytes to release large numbers of microvesicle particles (MVPs). These small membrane-bound particles …


Computational Assessment Of Aortic Valve Function And Mechanics Under Hypertension, Saurav Kadel Jan 2020

Computational Assessment Of Aortic Valve Function And Mechanics Under Hypertension, Saurav Kadel

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Calcific aortic valve disease (CAVD), the most common valvular heart disorder, is associated with complications such as stroke, heart attack, aortic aneurysm, left ventricular hypertrophy, and ultimately death. While hypertension has been identified as a major risk factor for CAVD, the mechanisms by which it may promote calcification are still unknown. Given the sensitivity of valvular tissue to mechanical stress alterations, the hemodynamic abnormalities linked to hypertension may play a role in the development of CAVD. Further, the effects of hypertension on the left ventricular functionality and coronary flow resistance remain largely uninvestigated. Hence, the objectives of this thesis were …


Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark Jan 2019

Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark

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Barrett’s Esophagus (BE) is characterized by the appearance of an intestinal-like epithelium in the distal esophagus. The molecular mechanisms behind BE development are unknown. BE is often preceded by Gastroesophageal Reflux Disease (GERD) and predisposes patients to esophageal adenocarcinoma (EAC). Due to the high mortality rate associated with EAC, BE patients are continuously monitored through upper endoscopy with biopsy for progression to low grade dysplasia (LGD), high grade dysplasia, and EAC. This monitoring technique poses numerous risks, so alternative surveillance and diagnostic techniques for BE pathogenesis are continually studied. microRNA biomarkers in BE pathogenesis may provide alternative means of diagnosis …


Type 2 Diabetes Leads To Impairment Of Cognitive Flexibility And Disruption Of Excitable Axonal Domains In The Brain, Leonid M. Yermakov Jan 2019

Type 2 Diabetes Leads To Impairment Of Cognitive Flexibility And Disruption Of Excitable Axonal Domains In The Brain, Leonid M. Yermakov

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Type 2 diabetes is a metabolic disease affecting millions of people around the world. Cognitive and mood impairments are among its many debilitating complications, but disease mechanism(s) remain elusive. Here, we present a series of behavioral tasks that demonstrate impairment of cognitive flexibility in db/db mice, a commonly used type 2 diabetes model. Using immunohistochemistry, we demonstrate disruption of axon initial segments (AIS) and nodes of Ranvier, excitable axonal domains regulating neuronal output, in brain regions associated with cognitive and mood impairments. Finally, we present results of exercise treatment that ameliorates AIS disruption in these animals. Establishing cognitive flexibility deficits …


Monitoring Cerebral Functional Response Using Scmos-Based High Density Near Infrared Spectroscopic Imaging, Dharminder Singh Langri Jan 2019

Monitoring Cerebral Functional Response Using Scmos-Based High Density Near Infrared Spectroscopic Imaging, Dharminder Singh Langri

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Neurovascular coupling is an important concept that indicates the direct link between neuronal electrical firing with the vascular hemodynamic changes. Functional Near Infrared Spectroscopy (fNIRS) can measure changes in cerebral vascular parameters of oxy-hemoglobin and deoxyhemoglobin concentrations and thus can provide neuronal activity through neurovascular coupling. Currently many commercial fNIRS devices are available, but they are limited by the number of channels (usually having only 8 detectors), which can limit the sensitivity, contrast, and resolution of imaging. High-density imaging can improve sensitivity, contrast, and resolution by providing many measurements and averaging the signals originating from the target cerebral focus area …