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Full-Text Articles in Engineering
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 …
Novel Natural Language Processing Models For Medical Terms And Symptoms Detection In Twitter, Farahnaz Golrooy Motlagh
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 …
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
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
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
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
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
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
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
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
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
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 …
Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh
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. …
Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda
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
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 …
Design Of A Novel Wearable Ultrasound Vest For Autonomous Monitoring Of The Heart Using Machine Learning, Garrett G. Goodman
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
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
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 …
Computational Assessment Of Aortic Valve Function And Mechanics Under Hypertension, Saurav Kadel
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 …
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 …
Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark
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 …
Monitoring Cerebral Functional Response Using Scmos-Based High Density Near Infrared Spectroscopic Imaging, Dharminder Singh Langri
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 …
Type 2 Diabetes Leads To Impairment Of Cognitive Flexibility And Disruption Of Excitable Axonal Domains In The Brain, Leonid M. Yermakov
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 …
Novel Auto-Calibrating Neural Motor Decoder For Robust Prosthetic Control, Andrew Earl Montgomery
Novel Auto-Calibrating Neural Motor Decoder For Robust Prosthetic Control, Andrew Earl Montgomery
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The overarching goal of this project is to develop novel neural motor decoders for prosthetic control. EMG decoders measure the activity from an intact but non-target muscle. Neural motor decoders transform the signal measured from the severed motor axons of the target muscle. A multi-scale, highly-realistic computer model of a spinal motor pool was developed (Allen & Elbasiouny, 2018) to serve as a computational platform for decoder development and testing. A firing rate-based algorithm was developed to transform the aggregate discharge of the motor pool into a command signal to control the simulated prosthetic MuJoCo hand. This algorithm was informed …
Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri
Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri
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Advancements in the nanotechnology have taken a huge leap in 21st century resulting in 1814 consumer products containing nanomaterials. About 47% of these products belong to the health and fitness sector and ~24% utilize silver nanoparticles (AgNPs). Despite the promising biomedical applications of AgNPs (e.g. bone cements, contrasting agents, and drug-carriers), lack of standardized methods for examining their nanokinetics (i.e., Absorption, Distribution, Metabolism, and Elimination (ADMEs)) limit their clinical implementation. The current work addresses this knowledge gap by developing analytical-based approaches for studying in vitro ADMEs of AgNPs. To demonstrate the versatility of these methodologies, two in vitro kidney study …
A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis
A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis
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Imperative to genomic stability is the ability of the cell to repair damaged DNA which can occur from numerous endogenous byproducts of metabolism or exogenous components from the environment. The Fanconi anemia pathway is a DNA repair mechanism used by human cells to resolve multiple forms of DNA damage including interstrand crosslinks (ICL). Fanconi anemia (FA) is an autosomal recessive inherited disorder characterized by genome instability, developmental abnormalities, cancer predisposition and bone marrow failure. FA is attributed to a mutations in at least 18 genes (FANCA-FANCT) that play a concerted role in DNA repair. FANCT is the latest discovery in …
Anterior Cruciate Ligament Biomechanics, Computational Modeling Of Mechanical Behavior And Injury Risk, Bharadwaj Cheruvu
Anterior Cruciate Ligament Biomechanics, Computational Modeling Of Mechanical Behavior And Injury Risk, Bharadwaj Cheruvu
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Knee joint involves interactions from various structures such as cartilage, bone, muscles, ligaments, tendon, as well as neural control. Anterior cruciate ligament (ACL) tears are one of the most frequent soft tissue injuries of the knee. A torn ACL leaves the joint unstable and at risk for further damage to other soft tissues manifested as pain, dislocation, and osteoarthritis. This injury is quite common in sports such as basketball, soccer and football. Females often tear their ACL 2-8 times more frequently than their male counterparts. An ACL injury can be devastating and significantly increases the athlete's risk for osteoarthritis long …