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Assessing The Role Of Polyphenols As A Vascular Protectant Against Drug Induced Vascular Injury, Anson Jacob Oommen Jan 2019

Assessing The Role Of Polyphenols As A Vascular Protectant Against Drug Induced Vascular Injury, Anson Jacob Oommen

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Vascular injury is identified during pre-clinical toxicity testing within certain pharmacological classes of drug candidates and induces degenerative and hyperplastic changes in endothelial (ECs) and vascular smooth muscle (VSMCs) cells. This drug-induced vascular injury has been show as a side-effect caused by various classes of drugs, including, antibacterial (e.g., azithromycin), anti-malarial (e.g., quinoline), anti-viral (e.g., anti-hepatitis C virus interferons) and nonsteroidal anti-inflammatory drugs (e.g., ibuprofen), and affects normal cardiovascular function and can further lead to various cardiovascular conditions like arrhythmia, cardiac arrest, high blood pressure, and even heart attack. The search for agents capable of reducing ...


Computational Simulation Of A Femoral Nail Fracture, Stephen Charles Whatley Jan 2019

Computational Simulation Of A Femoral Nail Fracture, Stephen Charles Whatley

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Every year in the United States roughly 300,000 people over the age of 65 suffer from a hip fracture. Ninety five percent of which are the result from a fall. The resulting hip fracture can be classified into several categories of fracture. Depending on the damage the patient could be implanted with a femoral nail device to assist in their recovery. These devices can, however, have complications during recovery. In some cases, these nails can have a failure rate as high as 10%. When failure occurs, extensive investigations are needed to determine the causes of failure. These investigations involve ...


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 ...


Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn Jan 2019

Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn

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This study evaluated the combined effects of an exercise intervention and nutritional supplement on biomarkers of stress and resilience, and the relationships of those markers with physical and cognitive performance. 130 healthy Active-Duty Air Force (AF) personnel were recruited to participate in a double-blind, placebo controlled 12-week exercise and nutritional intervention. Serum was collected at basal and high stress conditions pre- and post-intervention to track the following biomarkers: cortisol, dehydroepiandrosterone-sulfate (DHEA-S), norepinephrine (NE), neuropeptide Y (NPY), and serotonin. The exercise intervention significantly attenuated the cortisol response and peak stress cortisol levels. The nutritional intervention decreased peak stress NE. The selected ...


Characterization Of In-Vivo Damage In Implantable Cardiac Devices And The Lead Residual Properties, Anmar Mahdi Salih Jan 2019

Characterization Of In-Vivo Damage In Implantable Cardiac Devices And The Lead Residual Properties, Anmar Mahdi Salih

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Approximately, 92.1 million patients in the US suffer from cardiovascular diseases with an estimated healthcare cost of over $300 billion; out of which at least one million patients have Cardiac Implantable Electronics Devices (CIED). CIED represented by pacemakers, Implantable Cardioversion Defibrillator (ICD), and Cardiac Resynchronization Therapy (CRT) are exposed to in-vivo damage. These damages are complex and composed on multiple levels and present challenges while assessing their combined extent. Since 2004, more than one hundred recalls were reported for cardiac devices. ICD devices had the majority with 40.8% recalls, pacemaker recall percentage was 14.5%, CRT recall percentage ...


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 ...


M1 To M2 Macrophage Induction Using Retinoic Acid And Mesenchymal Stem Cells Loaded On An Electrospun Pullulan/Gelatin Scaffold To Promote Healing Of Chronic Wounds, Kaivon Assani Jan 2018

M1 To M2 Macrophage Induction Using Retinoic Acid And Mesenchymal Stem Cells Loaded On An Electrospun Pullulan/Gelatin Scaffold To Promote Healing Of Chronic Wounds, Kaivon Assani

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Modulation of macrophage polarization is required for effective tissue repair and regenerative therapies. Conversion of macrophages from inflammatory M1 to fibrotic M2 phenotype could help in diseases such as chronic wound which are stuck in inflammatory state. During the inflammatory phase, macrophages are of the inflammatory phenotype (M1) and distribute pro-inflammatory cytokines including TNF-a and IL1[beta] which are microbicidal and recruit/activate cells. In normal wound healing macrophages then switch to a fibrotic phenotype (M2) promoting wound closure by angiogenesis, and matrix deposition. Chronic wounds are a major biological and financial burden to both patients and the health care ...


Effect Of Dimensionality On In Vitro Growth Environment And Mesenchymal Stem Cell Function, Fatema Tuj Zohora Jan 2018

Effect Of Dimensionality On In Vitro Growth Environment And Mesenchymal Stem Cell Function, Fatema Tuj Zohora

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The use of the standard two dimensional (2D) cell culture has laid down the fundamentals of molecular and cell biology. However, recent advances in cell-based regenerative medicine raises the concern on deconstructing cellular behaviors in more physiologically relevant three dimensional (3D) microenvironments. Differences in cell response in 2D versus 3D systems arise from the perturbations in gene expression patterns that stem from how cells sense their underlying 2D or surrounding 3D matrices and adjust their phenotypes accordingly. Thus, cells are no longer considered as a solitary entity of genome but a context arises from a combinatorial interactions of cell-ECM, cell-cell ...


Novel Auto-Calibrating Neural Motor Decoder For Robust Prosthetic Control, Andrew Earl Montgomery Jan 2018

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 by cellular neurophysiology knowledge of how motor neurons are activated by synaptic inputs to generate action potentials. Our results show that this neural motor decoder is fast (i.e., decoding time < 10 ms), reliable (i.e., accurate decoding of inputs varying in waveform, magnitude, and speed), and robust (i.e., accurate decoding of varying activation schemes) in controlling the prosthesis. Additionally, this decoder was successful in automatically adapting, in real-time, to dynamic changes in the synaptic input signals and decoding its magnitude and rate of activation; thus, minimizing the need for frequent daily calibrations by the amputee.


Divergent Scaling Of Miniature Excitatory Post-Synaptic Current Amplitudes In Homeostatic Plasticity, Amanda L. Hanes Jan 2018

Divergent Scaling Of Miniature Excitatory Post-Synaptic Current Amplitudes In Homeostatic Plasticity, Amanda L. Hanes

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Synaptic plasticity, the ability of neurons to modulate their inputs in response to changing stimuli, occurs in two forms which have opposing effects on synaptic physiology. Hebbian plasticity induces rapid, persistent changes at individual synapses in a positive feedback manner. Homeostatic plasticity is a negative feedback effect that responds to chronic changes in network activity by inducing opposing, network-wide changes in synaptic strength and restoring activity to its original level. The changes in synaptic strength can be measured as changes in the amplitudes of miniature post-synaptic excitatory currents (mEPSCs). Together, the two forms of plasticity underpin nervous system functions such ...


Coupling Of Mechanical And Electromagnetic Fields Stimulation For Bone Tissue Engineering, Alyaa I. Aldebs Jan 2018

Coupling Of Mechanical And Electromagnetic Fields Stimulation For Bone Tissue Engineering, Alyaa I. Aldebs

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Alternative bone regeneration strategies that do not rely on harvested tissue or exogenous growth factors and cells are badly needed. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. A major hurdle has been recreating the bone tissue microenvironment using the appropriate combination of cells, scaffold and stimulation to direct differentiation. This project presents a bone regeneration formulation that involves the use of human adipose-derived mesenchymal stems cells (hASCs) and a 3D scaffold based on a self-assembled peptide hydrogel doped with superparamagnetic nanoparticles (NPs). Osteogenic differentiation of ...


A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili Jan 2018

A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili

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Two challenging problems in the clinical study of cancer are the characterization of cancer subtypes and the classification of individual patients according to those subtypes. Further, understanding the role of differential gene expression in the development of and molecular response to cancer is a complex problem that remains challenging, in part due to the sheer number of genes and gene products involved. Traditional statistical approaches addressing these problems are hindered by within-class heterogeneity and challenges inherent in data integration across high-dimensional data. In addition, many current machine learning methods do not lend themselves to biological interpretation. We have developed a ...


A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis Jan 2017

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 ...


Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin Jan 2017

Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin

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We know that animals are tuned to survive different environmental conditions or else life would not exist. Unfortunately, this is often forgotten or ignored when designing experiments. As Marsh Tenney articulated, "The physiologist keeps the whole always in mind. He accepts the tactical necessity of reductionism to understand parts, but, once done, for him it is only the beginning, never the end” (from Remmers, 2005). In an era when it is all too common to take environmental complexity out of the organism to understand physiology, my work puts some of that complexity back in the study of organisms. I take ...


Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash Jan 2017

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the ...


Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri Jan 2017

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 ...


Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash Jan 2017

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the ...


Identifying The Impact Of Noise On Anomaly Detection Through Functional Near-Infrared Spectroscopy (Fnirs) And Eye-Tracking, Ryan Dwight Gabbard Jan 2017

Identifying The Impact Of Noise On Anomaly Detection Through Functional Near-Infrared Spectroscopy (Fnirs) And Eye-Tracking, Ryan Dwight Gabbard

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Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance (ISR) operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts' decision making process. In this study the effects of different noise stimuli on analysts' performance and workload in anomaly detection were investigated by simulating a noisy work environment. Functional near infrared spectroscopy (fNIRS) was utilized to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbD) concentration changes in the prefrontal cortex (PFC), as well as behavioral measures which include eye-tracking, reaction time, and accuracy rate. It was found that HbO for some of ...


Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades Jan 2017

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs is controversial. Determining the direction of NKCC1- mediated fluxes is ...


Identification Of Novel Ligands And Structural Requirements For Heterodimerization Of The Liver X Receptor Alpha, Shimpi Bedi Jan 2017

Identification Of Novel Ligands And Structural Requirements For Heterodimerization Of The Liver X Receptor Alpha, Shimpi Bedi

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LXRs, LXRa (NR1H3) and LXRß (NR1H2), are ligand-activated transcription factors that are members of the nuclear receptor superfamily. Oxysterols and nonsteroidal synthetic compounds bind directly to LXRs and influence the expression of LXR dependent genes. The use of murine models and LXR-selective agonists have established the important role of LXRs as sterol sensors that govern the absorption, transport, and catabolism of cholesterol. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver to aid in the removal of excess cholesterol. Not surprisingly, LXR dysregulation is a feature of several human diseases ...


Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak Jan 2017

Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak

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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to ...


Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite Jan 2017

Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite

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Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor under various stressors will promote phenotypic cellular changes, known as epithelial-to-mesenchymal transition (EMT), which allows cells to begin to invade surrounding tissue, enter the circulatory system, and eventually seed a distant metastatic site. The phospholipase D (PLD) enzymes are critical regulators of cell signaling pathways necessary for cell migration. While the importance of PLD enzymes in cancer cell invasion is well known, clinically applicable methods of PLD inhibition are not yet available. The best-studied ...


Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent Jan 2017

Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent

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Neurotoxicity is one of the most significant side effects diminishing clinical efficacy and patient quality of life during and following chemotherapy. Oxaliplatin (OX) is a platinum based chemotherapy agent used in the treatment of colorectal cancer. Colorectal cancer currently ranks as the 4th most common cancer, and the majority of patients receive OX as a part of their adjuvant therapy. OX based adjuvant therapies significantly improve 5 year survival rates, however in many cases patients must stop treatment early because of the neurotoxic side effects. OX causes two clinically distinct forms of neurotoxicity. Acutely, within hours and for days following ...


Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades Jan 2017

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs is controversial. Determining the direction of NKCC1- mediated fluxes is ...


Novel Cell Killing Mechanism Of Hydroxyurea In The Fission Yeast Schizosaccharomyces Pombe And Its Implications In Improving Antifungal Therapy, Amanpreet Singh Jan 2016

Novel Cell Killing Mechanism Of Hydroxyurea In The Fission Yeast Schizosaccharomyces Pombe And Its Implications In Improving Antifungal Therapy, Amanpreet Singh

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Hydroxyurea (HU, also known as hydroxycarbamide) is a well known ribonucleotide reductase (RNR) inhibitor that depletes cellular deoxyribonucleoside triphosphates (dNTPs, the building blocks of DNA). Depleted dNTP pools inside the proliferating cells stalls ongoing DNA replication forks, leading to the activation of the well-conserved DNA replication checkpoint (also known as intra-S phase checkpoint) pathway. One of the major functions of the checkpoint pathway is to protect ongoing forks from collapsing. Stalled forks, if not protected by the checkpoint pathway, lead to DNA damage and ultimately cell death. Thus it is believed that DNA damage resulting from collapsed forks is the ...


Optical Redox Imaging Of Metabolic Activity, Syed Anwar Hyder Zaidi Jan 2016

Optical Redox Imaging Of Metabolic Activity, Syed Anwar Hyder Zaidi

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


Modeling Effects Of Diet On Human Gut Microbiota, Richard Thomas Agans Jan 2016

Modeling Effects Of Diet On Human Gut Microbiota, Richard Thomas Agans

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The human gut microbiota is integrally involved in the metabolism of nutrients contained within the human diet. Studies into human nutrition have primarily been carried out using human and animal models. These studies are extremely important in our understanding of human nutrition, however, suffer from inherent limitations including unique microbial compositions between individuals, compliance in human studies, inability to carry out mechanistic studies, and inability to interrogate proximal regions of the gut without applying invasive techniques. In vitro gut simulator systems circumvent many of these limitations in animal and human models by allowing control of gut environmental conditions, decreasing variability ...


Extension Of Multivariate Analyses To The Field Of Microbial Ecology, Vijay Shankar Jan 2016

Extension Of Multivariate Analyses To The Field Of Microbial Ecology, Vijay Shankar

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Ground-breaking advancements in molecular and analytical techniques in the past decade have enabled researchers to accumulate data at an extraordinary rate. Especially in the field of microbial ecology, the introduction of technologies such as high-throughput sequencing, quantitative microarrays, nuclear magnetic resonance and mass spectrometry has led to the interrogation of diverse and previously unexplored microbial communities at unparalleled depth. Analysis and interpretation of patterns within datasets acquired with such high-throughput methods require powerful statistical approaches. A class of such techniques called multivariate statistical analyses is an excellent choice for analysis of complex microbiota-related datasets. This field of statistics is constantly ...


Novel Therapeutic Approach For Regulating The Susceptibility Of Epitheliato Adenovirus Infection, Mahmoud Soliman Salem Alghamri Jan 2016

Novel Therapeutic Approach For Regulating The Susceptibility Of Epitheliato Adenovirus Infection, Mahmoud Soliman Salem Alghamri

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Human Adenoviruses (AdVs) are etiologic agents for respiratory tract, digestive tract, heart, and eye infections. Although most AdV infections are self-resolving, some infections progress to acute respiratory disease with up to 50% mortality, particularly in immunosuppressed people. Except for vaccines for serotypes, 4 and 7, serotypes that are prevalent in the military, no vaccines or therapeutics that specifically prevent or treat AdV infection exist. On the other hand, AdV remains the most common vector system used in gene therapy clinical trials worldwide and several AdV vectors show promise in phase III clinical trials. The majority of AdVs use the coxsackievirus ...


A Functional Analysis Of The 3’ Regulatory Region Of The Immunoglobulin Heavy Chain Gene, Andrew David Snyder Jan 2016

A Functional Analysis Of The 3’ Regulatory Region Of The Immunoglobulin Heavy Chain Gene, Andrew David Snyder

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The immunoglobulin heavy chain (IGH) locus is partially responsible for immunoglobulin (Ig) production in B cells. The human IGH locus contains two 3’ regulatory regions (3’IghRR) that each contain three enhancers, which are thought to help drive overall transcription of the locus and also influence class switching to alternative Ig isotypes. The hs1.2 enhancer within the 3’IghRR is polymorphic in humans, containing a 53 bp invariant sequence (IS) that can be repeated up to four times. In vitro, the human hs1.2 enhancer is a sensitive target of exogenous chemicals, particularly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or ...