Medicine and Health Sciences Commons^™

Codont5: A Multi-Task Codon Language Model For Species-To-Species Translation, Ashley N. Babjac

Doctoral Dissertations

DNA (DeoxyriboNucleic Acid) carries the genetic information for the biological processes and function of all organisms. It is composed of nucleotides, which can be grouped into 3-mer triplets called codons. It is well known that codons encoding the same amino acid, referred to as "synonymous" codons, are selected with differing frequencies between organisms. Prior research has revealed there are codons used with much higher frequency than others, causing to them being "preferred" in highly expressed genes. This has led to the development of multiple computational models that do a good job predicting gene expression in some protein-coding genes; however, their …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

An Evaluation Of Methods To Reduce Inframammary Surface Dose In Prone Breast Irradiation, Seth Alvarado

Doctoral Dissertations

In cases of breast radiation treatments via external beam radiation therapy, the incidence of radiation dermatitis has been reported. In prior studies, this acute radiation side-effect has been correlated with the immobilization devices in cases of prone breast irradiation. They attribute this to the bolus effect that occurs with the interaction of the incident photon beam at different projections causing an increase in measured surface dose. The type of radiation planning technique, and patient positioning during the undertaking of these techniques, have also shown to influence this bolus effect. This study focuses on these factors in treatment planning in order …

A Computational Study Of Sleep And The Hemispheres Of The Brain, Tera Ashley Glaze

Doctoral Dissertations

"Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy -- the brain. Presented here is the …

Post-Concussion Experiences Of Collegiate Student-Athletes, Kaitlin Iris Singer

Doctoral Dissertations

Sports-related concussions are a major public health concern affecting a significant number of collegiate student-athletes. Medical and public health research has addressed every aspect of concussion management processes including concussion education, medical diagnosis, recovery, and returning to sport and classroom. This research has led to several best-practices for concussion management. Since 2010, the NCAA has mandated that its member institutions maintain concussion management policies and procedures. However, the current recommendations, based primarily on medical research, have been found in quantitative studies of the behaviors and practices of athletic trainers, coaches, and student-athletes to be ineffective. To date, no studies have …

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

Inhibition Of The Pi3k/Akt Signaling Pathway Increases Efficacy Of Doxorubicin And Its Derivative Ad198 In Bladder And Oral Cancers, Dmitriy Smolensky

Doctoral Dissertations

Doxorubicin (Dox) is a successful chemotherapy to treat various cancers, including bladder and oral cancers. Many patients initially respond to Dox-based regimens, however often cancers become resistant. A novel derivatives of Dox, e.g. N-benzyladriamycin-14-valerate (AD198), have been developed to overcome Dox-induced drug resistance and cardiotoxicity. The purpose of this thesis was to determine the efficacy of AD198 and Dox in bladder and oral cancers in vitro.

Part-I of this dissertation focuses on the bladder cancer, including discussing risk factors, diagnosis, staging, and current treatment options, following by a description of altered molecular mechanisms responsible cancer progression. This section also focuses …

Characterization And Development Of Amyloid-Reactive Peptides As Tracers For Quantitative Molecular Imaging, Emily Brooke Martin

Doctoral Dissertations

Amyloidosis is a degenerative protein misfolding disorder that leads to the extracellular accumulation of amyloid deposits containing protein fibrils, heparan sulfate proteoglycans, glycoproteins and apolipoproteins. To date, at least 27 proteins have been identified as components of pathologic amyloid fibrils. In systemic forms of the disease, amyloid deposits can evade the immune system and expand throughout various tissues. As the deposits grow, tissue architecture is disrupted, leading to organ dysfunction and death.

In the US, there are ~3500 newly diagnosed patients with amyloidosis annually. The deposition of light chains as amyloid (AL amyloidosis) is the most common form of visceral …

Safety And Immunoreactivity Of A Xenogeneic Dna Plasmid Vaccine Expressing Human Tyrosinase In Tumor-Bearing Horses, Luis Miguel Lembcke Perez Prieto

Doctoral Dissertations

Melanomas are among the most common skin tumors in horses (second only to sarcoids), with prevalence rates reaching as high as 80% in adult gray horses. Despite the wide availability of measures of local control, there are currently no systemic therapies that can effectively prevent spread, or treat metastatic or locally advanced/non-resectable melanoma in horses. A form of gene immunotherapy based on a plasmid DNA construct containing a xenogeneic form of the antigen tyrosinase have been developed and optimized for targeting cancer in both humans and dogs; and have demonstrated significant immunoreactivity and clinical benefit in the treatment of melanocytic …

Growth Regulation Of Pancreatic Cancer Cells And Their Normal Cells Of Origin By Nicotinic Acetylcholine Receptors, Mohammed Hussein Al-Wadei

Doctoral Dissertations

Pancreatic cancer is the fourth leading cause of cancer mortality with a five-year survival rate of less than 5 %. It shows no symptoms until it has reached an advanced stage upon which it has metastasized to distant organs limiting therapeutic options. Several studies have identified smoking, alcohol, diabetes and pancreatitis as risk factors for pancreatic cancer. While smoking is a well-documented risk factor for this malignancy, there still remains a controversy on whether alcohol can act as a risk factor itself or cooperatively enhances the effects of other risk factors.

Previous reports provide evidence that nicotinic acetylcholine receptors (nAChRs) …

Toward Personalized Medicine: The Potential Role Of Rna Interference In Plasma Cell Dyscrasia, Jonathan E Phipps

Doctoral Dissertations

A major contributor to mortality in patients with plasma cell dyscrasias (PCDs); i.e., multiple myeloma, light chain deposition disease and AL amyloidosis is the deposition as insoluble aggregates of monoclonal immunoglobulin light chain proteins (LC) in the kidneys and other organs. Currently anti-plasma cell chemotherapies are used to reduce LC synthesis, and slow deposition. While effective, these treatments are toxic, non-specific, expensive, and might not be appropriate in all cases, making the identification of an alternate means of reducing toxic LC species desirable. To this end, we have investigated whether RNA interference (RNAi) could achieve these goals.

Human (RPMI 8226, …

Immunologic Risk Prediction Model For Kidney Graft Function, Christina Diane Bishop

Doctoral Dissertations

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, …

Role Of Il-17 And Th17 Cells In Hsv Induced Ocular Immunopathology, Amol Sahebrao Suryawanshi

Doctoral Dissertations

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4⁺ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4⁺ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains …

Mechanism Of Phospholipid Induction Of Cell Migration, Dongwei Wu

Doctoral Dissertations

Lysophosphatidic acid (LPA) is a potent bioactive lipid component of oxidized low density lipoproteins (oxLDL). High concentrations of LPA have been detected in human atherosclerotic plaques. Our data has shown that LPA highly induces smooth muscle cell (SMC) migration. Cyr61, a matricellular protein, which also accumulates in human atherosclerotic plaques, has been implicated in the injury-induced neointimal formation. Smooth muscle cell migration is a key event in the development of atherosclerosis, and it contributes to the progressive growth of atherosclerotic lesions. Data generated by this study demonstrate that LPA markedly induces Cyr61 expression in mouse aortic smooth muscle cells (MASMC). …

Development Of An Autonomous Mammalian Lux Reporter System, Daniel Michael Close

Doctoral Dissertations

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of …

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez '98

Doctoral Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows:

Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype.

Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …

The Regulation Of Neuropeptide Corazonin And Its Functional Analyses In Drosophila Melanogaster, Seung-Hoon Choi

Doctoral Dissertations

Neuropeptides regulate diverse physiological processes, including homeostatic metabolism, behavior, reproduction, and development. The neuropeptide Corazonin (Crz), was first isolated from American cockroach, P. americana, as a potent cardioactive substance, and has been shown to exert diverse functions in different insects. In Drosophila, Crz expression is limited to three groups of neurons; totaling only 26 neurons out of ~10,000 neurons in a third instar larval central nervous system (CNS). In adults, Crz is expressed in 6-8 pairs of protocerebral neurons and 2 pairs of male specific abdominal ganglion. To gain insight into such tight regulatory mechanisms of …

The Effects Of 17- Beta Estradiol On G-Protein Inwardly Rectifying Potassium Channels (Girks) In Breast Cancer, Michael W. Hance

Doctoral Dissertations

Breast cancer is a leading cause of cancer death and in 2009, the American Cancer Society estimates that over 192,000 new cases of breast cancer will be diagnosed, and over 40,000 women will die from breast cancer. Estrogen (E2) is required for normal female development and reproduction, but long-term exposure is carcinogenic and considered a risk factor for breast cancer. Membrane ion channels are essential for cell proliferation and are suggested to have a role in cancer, especially potassium channels. In the present study, we investigate the effects of estrogen and the estrogen antagonist ICI182780 on G-protein inwardly rectifying potassium …

Isolation And Investigation Of The Exopolysaccharide From Thauera Sp. Mz1t, Michael S. Allen

Doctoral Dissertations

Thauera sp. strain MZ1T is a floc-forming bacterium isolated from the wastewater treatment plant of Eastman Chemical Company. Its overabundance in that system in the form of zoogloeal clusters was positively correlated to episodes of poor dewatering of activated sludge (Lajoie 2000). The specific cause of this problem was thought to be due to the production of large quantities of hydrophilic exopolysaccharide (EPS) by MZ1T, which entraps water in the form of a hydrated gel, and results in a sludge that is resistant to mechanical dewatering.

A method for the reproducible extraction of EPS from pure cultures of MZ1T was …

Analysis Of Aneuploidy During Mouse Spermatogenesis, April D. Pyle

Doctoral Dissertations

Successful transition through meiosis is required for production of chromosomally-balanced gametes. When chromosome segregation goes awry during meiosis, aneuploidy can occur. Unfortunately, the mechanisms behind this nondisjunction are not well understood. Therefore, this dissertation has focused on learning more about the causative factors associated with aneuploidy during spermatogenesis. Are there factors that are always associated with leading to production of aneuploid sperm? One of the main goals of this dissertation is to find mouse models to study what factors may be involved in chromosome malsegregation; such as pairing, recombination, and transition through the division phases of meiosis.

The first part …

Aquaporins And Aquaglyceroporins Of Legume Nodules: Structure, Function, And Regulation, James F. Guenther

Doctoral Dissertations

By isolating RNA from mature nodules of the legume Lotus japonicas and employing an RT-PCR approach, two new cDNAs were characterized whose open reading frames code for members of the MIP (Major Intrinsic Protein) family of membrane proteins. These two genes products were termed (Lotus Intrinsic Membrane Protein 1 and 2) LIMP1 and LIMP2. Both LIMP1 and LIMP2 display all the hallmarks of the MIP protein family including, six putative transmembrane domains based on hydropathy plots, and the invariant NPA (asparagine-proline-alanine) signature motifs located symmetrically on two loops, which connect transmembrane helix 3-4 and transmembrane helix 5-6. Based on sequence …

Bordetella Bronchiseptica: A Candidate Mucosal Vaccine Vector, Sreekumari Rajeev

Doctoral Dissertations

Bordetella bronchiseptica colonizes the upper respiratory tract of a wide variety of mammals and is involved in diseases such as kennel cough in dogs, atrophic rhinitis in pigs and upper respiratory tract infections of laboratory animals. Studies were focused on developing a heterologous antigen expression system in B. bronchiseptica and to evaluate the potential of this organism as a candidate mucosal vaccine vector. Since the role of Bordetella bronchiseptica and Pasteurella multocida toxin (PMT) in the disease atrophic rhinitis of pigs was well documented, this research was focused in the possibility of developing a refined vaccine to control this disease. …

X-Ray-Induced Specific-Locus Mutation Rates In Newborn And Young Mice, Paul Bruce Selby

Doctoral Dissertations

The specific-locus mutation frequency resulting from 300 R of acute X irradiation has been determined for the germ cells present in male mice at 0, 2, 4, 6, 8, 10, 14, 21, 28, and 35 days of age and also for female mice at 0 days of age, Sample size was much larger for the males irradiated on day 0 than for other age groups but in all groups it was large enough to insure that an extremely high rate would be noticed. At 35 days of age the testis is histologically similar to that of the adult. It was …

Some Reactions Of Phenothiazine And Certain Benzophenothiazines, John Charles Gilmer

Doctoral Dissertations

Summary

The consideration of the medical importance of phenothiazine derivatives and the known cancer chemotherapeutic value of the nitrogen mustards made the synthesis of some nitrogen mustard derivatives of the phenothiazines of particular interest. In the course of this research the N-{2-[bis-(2-chloroethyl)amino]ethyl} derivatives of phenothiazine, 7H-benzo[c]phenothiazine, 7H-dibenzo[c, h] phenothiazine, and 14H-dibenzo[a, h] phenothiazine were synthesized for anticancer evaluation. Also submitted to the Cancer Chemotherapy National Service Center for testing were the N-(2-chloroethyl) monofunctional nitrogen mustard derivatives of the first three phenothiazines mentioned above.