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Co-Factors In Fgf Signaling, Christopher Yanucil Jan 2020

Co-Factors In Fgf Signaling, Christopher Yanucil

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The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …


Epigenetic Regulation In Cancer And Development, Theodore Busby Jan 2020

Epigenetic Regulation In Cancer And Development, Theodore Busby

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Feedback loops between cellular cues and changes in gene expression mediate the interactions between a multitude of regulatory events that promote development and cancer. Vesicular trafficking is an important process in carrying out signaling events by transporting receptors and ligands to and from the cell surface. GBF1 and BIG1 are large guanine-exchange factors (GEFs) that activate GTPase mediated shuttling of cargo through the Golgi apparatus. This dissertation demonstrates that GBF1 localizes to the cytoplasmic membrane in glioblastoma multiform cells to maintain cell shape and promote migration. Reports have shown that BIG1translocates to the nucleus is hepatocyte carcinoma cell lines in …


Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo Jan 2020

Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo

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Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …


Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson Jan 2020

Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson

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In the US, nearly 40% of adults have obesity. Further, obesity is known toincrease the risk for development, recurrence, and mortality associated with multiple types of cancer. However, despite such high prevalence, the impact of excess body weight on anti-tumor immunity and response to immunotherapeutics remains poorly and incompletely understood. In order to address these deficiencies, we have utilized multiple approaches to study obesity-associated perturbations in the immunogenetic, soluble protein, and cellular profiles of mice bearing mammary tumors and treatment naive human subjects with clear cell renal cell carcinoma (ccRCC). In a pre-clinical murine model of breast cancer, we find …


Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman Jan 2020

Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman

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The central noradrenergic (NA) system is critical for maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer’s disease (AD). In fact, the locus coeruleus (LC), the major source of norepinephrine (NE) in brain, is the first site of pathological tau accumulation in human AD associated with axon loss throughout forebrain, including hippocampus. The dentate gyrus (DG) is heavily innervated by LC-NA axons, where released norepinephrine (NE) acts on β adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex (EC) to facilitate long-term synaptic plasticity and memory formation. These synapses show …


Microrna Regulation Of Post-Injury Cardiac Remodeling And Heart Failure, John Clark Henderson Jan 2020

Microrna Regulation Of Post-Injury Cardiac Remodeling And Heart Failure, John Clark Henderson

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Doxorubicin (DOX), an anthracycline, is a widely used chemotherapy agent against various forms of cancer; however, it is also known to induce dose-dependent cardiotoxicity leading to adverse outcomes. Investigating the underlying molecular signaling might have clinical implications. MicroRNAs (miRNAs) have been shown to mediate many diseases and are used as biomarkers for chemotherapy; but currently their role in the regulation of DOX-induced cardiotoxicity is not well understood. Our previous study has shown upregulation of miRNA-377 in the cardiomyocytes (CMs) after cardiac ischemia-reperfusion injury in mice. In this dissertation, we discovered that miR-377 was upregulated in the myocardium after DOX treatment, …


Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong Jan 2020

Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong

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IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …


Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson Jan 2020

Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson

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Although several racial/ethnic minority women groups (e.g., Latina, Black, Asian-American, and Native-American women) have lower breast cancer incidence than white women, they are more likely to die from breast cancer. One possible explanation for this discrepancy is racial/ethnic differences in mammography use. Mammography has been shown to contribute to the discovery of tumor proliferation earlier which translates to less breast cancer complications like greater risk of breast cancer-related mortality. Previous studies on racial/ethnic differences in mammography adherence (e.g., annual and biannual mammography adherence) have been inconclusive, and they generally overlook important contextual factors, namely neighborhood quality and geographic location (e.g., …


Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly Jan 2020

Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly

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Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …


A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder Jan 2020

A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder

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Cardiometabolic diseases are becoming increasingly prevalent in modern society due to low activity lifestyles and poor nutrition. Inorganic dietary nitrate (diNO3) has shown to potentially improve cardiometabolic health in a number of different populations but remains to be corroborated in humans with type 2 diabetes (T2D). This preliminary analysis aimed to determine the effects of consuming an acute, concentrated dose of diNO3 containing beetroot juice (BRJ) on hemodynamic and glycemic responses in humans with T2D while controlling for pharmacological influences. Three participants with a clinical diagnosis of T2D were recruited into this study. Pulsewave Velocity (PWV) was used to assess …


Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel Jan 2020

Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel

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Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …


The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier Jan 2020

The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier

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Previously, abnormal nucleoli were noted as indicators of cancerous lesions andused as a pathologic readout of neoplasia. Nucleolar hypertrophy and increased nucleolar number have been correlated with increased breast cancer (BC) mortality rates. Although various functions of the nucleolus have been investigated, it remains widely understudied in the context of cancer. The nucleolus was initially thought to be solely the site of ribosome biogenesis. However, over half of the proteins found in the nucleolus are associated with other biological functions. It is evident that the nucleolus plays major roles in stress response, DNA repair, and critical cellular aspects that influence …


Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke Jan 2020

Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke

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Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …


An Augmented Framework For Validating Neural Network Predictions Based On Statistical Modeling, William Stonewall Monroe Jan 2020

An Augmented Framework For Validating Neural Network Predictions Based On Statistical Modeling, William Stonewall Monroe

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The Parkinson's Progression Markers Initiative (PPMI) dataset (which includes several types of imaging datasets) was created to generate biomarkers for diagnosing the presence and severity of Parkinson’s Disease (PD). Unlike some conditions, PD is not intuitively diagnosed directly from brain imaging. As such, it is vital to understand as well as classify PD. Deep learning techniques are becoming increasingly prevalent in medical imaging workflows. In some cases, deep learning outperforms human diagnostic ability. However, the black-box nature of many machine learning models can be troubling, particularly in a medical context since the results could imply alternate treatments and a human …


Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota Jan 2020

Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota

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The tumor suppressor Merlin is encoded by Neurofibromin 2 (NF2) gene. Merlin is predominantly located in the cell cortex where regulates cell proliferation by mediating cell contact-dependent growth inhibition. Metastatic breast cancer tissues presented with a remarkable loss of Merlin protein, revealing clinical relevance of Merlin. In order to examine the cellular effect of Merlin deficiency, breast cancer cell lines were silenced for NF2. Additionally, to assess the impact of Merlin loss at the organismal level, a mammary-specific NF2 knockout mouse mammary tumor model was engineered. Merlin deficiency induced a metabolic shift from mitochondrial oxidative phosphorylation to aerobic glycolysis. Furthermore, …


Mendicant Enterprise And Human Rights In New Spain, Elliot Nicholson-Cox Jan 2020

Mendicant Enterprise And Human Rights In New Spain, Elliot Nicholson-Cox

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In 1521, the destruction of Aztec leadership created a disjointed network of native communities in what is now Mexico but would come to be known as New Spain. Until 1572 New Spain was an open and contested space for political, economic, and religious dominance among various Spanish factions. This dominance was predicated upon an evangelical mission in service to the conversion of native people from “pagans” to Christians. Religious education and evangelization by mendicant friars may have, either as a deliberate or consequential outcome, promoted or enforced collaboration and minimized direct and violent conflict during this period. Some religious friars …


Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan-Russell Jan 2020

Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan-Russell

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Endogenous antioxidant responses defend the lung against oxygen toxicity. In premature neonates, oxygen toxicity and impaired antioxidant defenses contribute to the development of bronchopulmonary dysplasia (BPD), the leading cause of long-term morbidity among premature infants. In adults, oxygen toxicity and impaired antioxidant defense contributes to the pathogenesis of acute lung injury (ALI). Acute Respiratory Distress Syndrome (ARDS), a severe form of ALI, can cause permeant lung damage and mortality. Our lab has established that pharmacologic thioredoxin reductase-1 (TXNRD1) inhibition attenuates lung injury in murine BPD and ALI models. The protective effects of TXNRD1 inhibition are mediated by the activation of …


The Non-Protostegid Cretaceous Marine Turtles Of Alabama And Their Bearing On The Evolution Of Extant Chelonioids, Andrew Gentry Jan 2020

The Non-Protostegid Cretaceous Marine Turtles Of Alabama And Their Bearing On The Evolution Of Extant Chelonioids, Andrew Gentry

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The non-protostegid marine turtle fossils recovered from the Late Cretaceous of Alabama may represent some of the most recent common ancestors of modern marine turtles. Despite their evolutionary significance, almost no formal studies have been conducted on these animals for more than 60 years. Many of these species are known from incomplete holotypes which has led to decades of systematic ambiguity and made specific referrals of recently collected fossil material exceedingly challenging. The aim of this study is to review and describe the specimens of Cretaceous marine turtles collected from Alabama to determine if this material can be used to …


Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin Jan 2020

Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin

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Asthma patients are increasingly presenting with asthma that is more difficult to control and treat than in years past. A subset of these patients who are sensitive to fungal species are described as having severe asthma with fungal sensitization (SAFS). Given the severity of disease, there is ever increasing interest in identifying the immune processes underlying SAFS disease pathology and the development of novel therapeutics to improve management. While sensitivity to multiple fungal species has been described in SAFS, none is more common than Aspergillus fumigatus. Here, we describe two previously unrecognized contributors to the amelioration of disease pathology in …


Quantifying Operational Impacts Of Various Work Zone Setups, Traffic Composition, And Driving Behaviors, A B M Tausif Ullah Chy Jan 2020

Quantifying Operational Impacts Of Various Work Zone Setups, Traffic Composition, And Driving Behaviors, A B M Tausif Ullah Chy

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The presence of work zones due to pavement repair and rehabilitation is very common in highway facilities. Lane closures associated with work zones result in capacity reduction, which in turn often leads to increased congestion at such locations. Properly set work zones can minimize the adverse operational impacts. This thesis documents part of a study at the University of Alabama at Birmingham that investigated and compared the performance of freeway facilities in the presence of work zones under various Temporary Traffic Control (TTC) and lane closure scenarios while taking under consideration traffic composition and driving behaviors. The study site was …


Novel Methods For Establishing The Capacity For Nociception And Cognition In The Zebrafish Danio Rerio, Chris Taylor Jan 2020

Novel Methods For Establishing The Capacity For Nociception And Cognition In The Zebrafish Danio Rerio, Chris Taylor

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Here we demonstrate the utility of a zebrafish-based model of nociception to serve as a novel screening tool for analgesic drugs. Zebrafish swimming behavior was measured following administration of various algogens used in rodent research. All compounds reduce distance traveled, thought to be an expression of nociception. Furthermore, we undertook to investigate the contribution of sex and feeding history on the acetic acid-evoked nociceptive response in zebrafish. Data suggest that male fish were more sensitive to pain than females, and that females recovered from pain faster than males. Dietary restriction increased pain sensitivity in zebrafish. We then tested the viability …


C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez Jan 2020

C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez

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C-reactive protein (CRP) is an evolutionarily conserved pattern recognition molecule that was first characterized for its participation in the acute phase response to bacterial infection. In the last 90 years, knowledge of CRP biology in innate immunity has expanded significantly. CRP is known to bind and activate the classical pathway of complement, to opsonize bacteria and inflamed tissue, and to modulate myeloid cell functions. CRP is normally present in the blood at low levels with its biosynthesis and serum concentration rapidly rises upon systemic inflammation. For example, high levels of serum CRP are found following acute kidney injury (AKI) in …


Quest Towards The Development Of Human Cardiac Tissue Equivalents Made From Human Induced Pluripotent Stem Cell Derived Cardiac Cells, Wesley Labarge Jan 2020

Quest Towards The Development Of Human Cardiac Tissue Equivalents Made From Human Induced Pluripotent Stem Cell Derived Cardiac Cells, Wesley Labarge

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The human heart is one of the more complex organs in the body to study and understand given the structural and functional characteristics it possesses. These characteristics work in synchrony to transfer oxygen-rich blood to vital organs throughout the body and oxygen-deficient blood back to the lungs for oxygenation. Furthermore, it can be reasoned that when these complexities are compounded with disease states which negatively affect the structure and function of the heart, determining the best treatments while also limiting adverse side effects becomes increasingly more challenging. While the goal of having patient-specific therapies has not completely been realized, the …


Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby Jan 2020

Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby

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Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …


Single Cell Proteins Affect Growth Performance And Body Composition Of Pacific White Shrimp Litopenaeus Vannamei, Yuan Yuan Jan 2020

Single Cell Proteins Affect Growth Performance And Body Composition Of Pacific White Shrimp Litopenaeus Vannamei, Yuan Yuan

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The globally growing human population has increased the needs for protein based food. Single cell proteins (SCPs) as unconventional protein source, when coupled to aq-uaculture production, offer a means to ensure future protein needs can be met. To demon-strate a given type of SCP has potential as a protein source for use in aquaculture feed; a number of investigations are needed including demonstrating that the SCP is attractable and accepted by the animals, leads to equivalent survival, growth and nutritional compo-sition. This dissertation represents a series of investigations designed to evaluate the fea-sibility of using a bacterial based (MRD-Pro) and …


Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford Jan 2020

Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford

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The effective antibiotic pool is shrinking with antibiotic resistance a constant problem that threatens to make our current therapies obsolete. To combat this, new drug screening methodologies are required since the traditional drug screens are offering limited results or only improvements upon current treatments. This work expands upon the idea that transition metal toxicity can be preferentially targeted towards bacteria. Specifically, the focus is on copper dependent inhibitors that quickly work to eliminate Staphylococcus aureus. S. aureus is a particularly threatening bacteria with high strain variability, a litany of survival and virulence factors, and multiple drug resistance mechanisms that are …


Smoke Inhalation, Lung Function, And Heart Rate In Wildland Firefighters, Jordan E. Nelson Jan 2020

Smoke Inhalation, Lung Function, And Heart Rate In Wildland Firefighters, Jordan E. Nelson

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Given the close proximity to the fire front and limited use of respiratory protection, wildland firefighters are exposed to elevated levels of biomass smoke during regular occupational shifts. Due to the complex composition of biomass smoke, the relationships relating biomass smoke exposure to health outcomes has yet to be elucidated. In addition to occupational exposures, increasing intensity of wildfire events may place communities within close proximity to wildfires at risk of biomass smoke exposure. This study aimed to assess exposures to biomass smoke particles and quantify respiratory and cardiovascular health responses during active fire events using novel monitoring techniques. Personal …


A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le Jan 2019

A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le

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Membrane proteins belonging to the ATP-Binding Cassette (ABC) superfamily are responsible for transporting substrates into or out of cells. ABC transporters, such as P-glycoprotein (Pgp/ABCB1) defend cells by the active efflux of many chemically diverse cytotoxic compounds. The ABC protein, CFTR/ABCC7, is a passive chloride ion channel that provides fluid homeostasis. Pgp and CFTR of are high clinical interest since mutations in CFTR can result in Cystic Fibrosis (CF) and upregulation of Pgp in tumor cells can result in multidrug resistance (MDR). There has been a major effort to develop clinical drugs to treat CF by either repairing defects in …


Bmp2-Derived Molecules For Increasing Osteoinductivity Of Bone Grafts To Enhance Bone Regeneration, Andrew Scott Curry Jan 2019

Bmp2-Derived Molecules For Increasing Osteoinductivity Of Bone Grafts To Enhance Bone Regeneration, Andrew Scott Curry

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The “gold standard” of bone grafting materials is autograft. Unfortunately, autogenous bone must first be harvested from the patient, leading to complications such as donor site morbidity. Because of this, many surgeons rely on non-autogenous bone grafting materials. While these grafts are more available than autogenous bone, they require extensive processing which significantly reduces their osteoinductivity. Therefore, there is substantial interest in finding ways to add osteoinductive molecules to these grafts. Previously, our lab has focused on utilizing molecules derived from bone morphogenetic protein 2 (BMP2) with an attached hydroxyapatite-binding domain (polyglutamate) to anchor them onto bone grafting materials. Previous …


Quantifications Of Theranostic Polymer-Based Particles For Image-Guided Drug Delivery, Sithira Ratnayaka Jan 2019

Quantifications Of Theranostic Polymer-Based Particles For Image-Guided Drug Delivery, Sithira Ratnayaka

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Modern medicine employs many drugs in its disease treatment methods. This is because they provide the best permanent solutions to complicated ailments. However the usefulness of these drugs is mitigated by several factors, namely that of specific release. Common drug delivery mechanisms lack the specificity needed to ensure that release is limited to the diseased area, which can lead to unnecessary side effects. By utilizing medical imaging, both drug delivery devices and physiology can be observed by physicians, which can greatly increase the specificity of drug delivery. Specifically, utilizing a very inert medical imaging modality, such as ultrasound, guarantees minimum …