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African Sleeping Sickness In British Uganda And Belgian Congo, 1900-1910: Ecology, Colonialism, And Tropical Medicine, Dana Bivens

Theses and Dissertations

This thesis deconstructs the social, ecological, and colonial elements of the 1900-1910 Human African Trypanosomiasis (African Sleeping Sickness) epidemic which affected British Uganda and Belgian Congo. This paper investigates the epidemic’s medical history, and the subsequent social control policies which sought to govern the actions of the indigenous population. In addition, this paper argues that the failure to understand and respect the region’s ecological conditions and local knowledge led to disease outbreaks in epidemic proportions. Retroactive policies sought to inflict western medical practices on a non-western population, which resulted in conflict and unrest in the region. In the Belgian Congo, …

Peracetic Acid: A Practical Agent For Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds, William R. Trahan

Theses and Dissertations

Advanced biomaterials and sophisticated processing technologies aim to fabricate tissue-engineering scaffolds that can predictably interact within a biological environment at a cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed prior to clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone (PCL), a low melting polymer, and …

Incorporation Of Molecular Diagnostics Into Medical Laboratory Science Curriculum: Clinical Facilities Expectations. An Asynchronous, Iterative, Online Delphi Study., Barbara Kraj

Theses and Dissertations

The medical laboratory science (MLS) profession is in need for published molecular diagnostics competency-based standards and curriculum. To assess their expectations of new MLS graduates, professionals performing and supervising performance of clinical molecular assays were surveyed to rate the importance of relevant cognitive and psychomotor learning objectives. A modified, asynchronous, iterative online Delphi process was utilized for assessment of consensus on the importance of the objectives. The survey was delivered through online REDCap application. Program directors of 221 MLS programs accredited by the National Accrediting Agency for Clinical Laboratory Science (NAACLS) were asked to forward the first Delphi survey to …

Modification And Evaluation Of A Brain Computer Interface System To Detect Motor Intention, Christopher V. Hagerty-Hoff

Theses and Dissertations

It is widely understood that neurons within the brain produce electrical activity, and electroencephalography—a technique used to measure biopotentials with electrodes placed upon the scalp—has been used to observe it. Today, scientists and engineers work to interface these electrical neural signals with computers and machines through the field of Brain-Computer Interfacing (BCI). BCI systems have the potential to greatly improve the quality of life of physically handicapped individuals by replacing or assisting missing or debilitated motor functions. This research thus aims to further improve the efficacy of the BCI based assistive technologies used to aid physically disabled individuals. This study …

Characterization Of Leukocyte-Platelet Rich Fibrin, A Novel Biomaterial, Fadi K. Hasan

Theses and Dissertations

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and are successfully used in oral surgery. Several commercial systems exist that generate various forms of platelet concentrates including Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF). The alpha- granules of entrapped platelets release a variety of peptide growth factors that promotes healing. Usually PRP is a suspension that can be injected into the site of injury or used as a gel with the addition of thrombin (PRP-gel). In contrast Choukroun’s L-PRF is a dense fibrin based biomaterial enriched with platelets and growth factors. The physical state of …

Interplay Between Artemis And Tdp1 In Sensitivity To Radiomimetic Agents, Ajinkya S. Kawale

Theses and Dissertations

DNA double-strand breaks containing unligatable termini are potent cytotoxic lesions leading to cell death or growth arrest. Artemis, which is associated with the Non-Homologous End Joining (NHEJ) pathway, is the major end processing nuclease that resolves unligatable termini, especially the 3′ blocks, by nucleolytic trimming. Tyrosyl-DNA Phosphodiesterase 1 (TDP1) is an enzyme which is biochemically competent in 3′-phosphoglycolate processing. The purpose of this study is to investigate if TDP1 is an end-processing enzyme involved in the NHEJ pathway. Clonogenic Survival assays using shRNA-mediated TDP1 knockdown and Artemis knockout (Artemis-/-) in HCT116 cells showed increased sensitivity to Neocarzinostatin (NCS) and Calicheamicin, …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Phenotypic Characterization Of Pnpase Knockdown In C. Elegans, Laura A. Lambert

Theses and Dissertations

The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction..

PNPase is also known to transport small RNAs into the …

The Role Of Noxa/Mcl-1 In Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, June Young Lee

Theses and Dissertations

Head and neck cancer is the sixth leading type of cancer with 90 percent of head and neck cancer arising from squamous cell lining on the epithelium of the oral and nasal cavity, pharynx, and salivary gland. Even with tremendous achievements on chemotherapeutic drugs and therapies, the long-term prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) has shown little improvement over the last three decades. Cisplatin is one of widely used chemotherapeutic drugs for multiple

cancers, including head and neck cancer, but the prolonged use of this drug is limited by its toxicity and by the …

Behavioral Responses Of Male Parasitic Wasps To Plant Cues: A Comparison Of Two Host-Plant Complex Sources Of Cotesia Congregata (Say), Megan Ayers

Theses and Dissertations

Prior exposure to plants cues can enhance assortative mating in insects. We hypothesized that, as previously reported for females, males of Cotesia congregata would display inherent responses to plant cues that could be modified by postemergence experience and further, that males originating from two different host-plant complexes (HPCs) would display different behavioral responses to these HPCs. In no-choice contact assays with a non-host plant, searching responses of males and females increased sharply at Day 2 and remained stable through Day 4. In no-choice assays with potential host plants, males searched longer on catalpa than tobacco; responses were not modified by …

Responses Of The Catalpa Sphinx, Ceratomia Catalpae, And Its Primary Parasitoid, Cotesia Congregata, To Varying Levels Of Iridoid Glycosides In Catalpa, Jessica L. Bray

Theses and Dissertations

The catalpa sphinx, Ceratomia catalpae, is a specialist on Catalpa trees, which produce iridoid glycosides (IGs). Whereas some trees are defoliated every year, others escape herbivory. Caterpillar populations are either heavily parasitized by the braconid wasp, Cotesia congregata, or remain unparasitized. We hypothesized that these patterns could be explained by variable IG concentrations among trees and insect responses to these chemicals. IG concentrations varied among trees. Percent defoliation was positively related to IG concentration. In comparisons of insect responses to relatively high or low IG concentrations, moths preferred to oviposit on trees with high IG concentrations. Caterpillars did …

The Effect Of Dexamethasone On Il-33-Mediated Mast Cell Activation, Oksana I. Chernushevich

Theses and Dissertations

Dexamethasone has been shown to inhibit IgE-mediated mast cell activation, and the present research investigated its role in suppressing IL-33-mediated mast cell activation. We have found that micromolar concentrations of Dexamethasone are capable of suppressing IL-33-mediated mast cell cytokine production, on several genetic backgrounds, and in not only bone marrow derived mast cells, but also peritoneal mast cells. Intracellular staining demonstrated that Dexamethasone significantly reduces expression of the IL-33 receptor, T1/ST2, in mast cells; however, the cytokine suppression is independent of T1/ST2 downregulation. At the same time, Dexamethasone pretreatment significantly reduced ERK phosphorylation, but our data suggests that inhibition occurs …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Identification Of Candidate Genes For Craniosynostosis, Karen Rymer

Theses and Dissertations

Craniosynostosis is a disorder characterized by the premature fusing of cranial sutures in an infant. Premature closure of these sutures can lead to detrimental consequences on the development of a child. The two broad categories of craniosynostosis are classified as syndromic and nonsyndromic. Nonsyndromic craniosynostosis involves only the fusion of one or more sutures, whereas syndromic craniosynostosis involves other abnormalities throughout the body of the affected individual. Two of the families analyzed in this study were of the syndromic nature, and known FGFR mutations were discovered. However, phenotypical features documented in association with these mutations differed from our individuals. Two …

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …

A Cross-Sectional Analysis Of Health Impacts Of Inorganic Arsenic In Chemical Mixtures, Paul Hargarten

Theses and Dissertations

Drinking groundwater is the primary way humans accumulate arsenic. Chronic exposure to inorganic arsenic (iAs) (over decades) has been shown to be associated with multiple health effects at low levels (5-10 ppb) including: cancer, elevated blood pressure and cardiovascular disease, skin lesions, renal failure, and peripheral neuropathy. Using hypertension (or high blood pressure) as a surrogate marker for cardiovascular disease, we examined the effect of iAs alone and in a mixture with other metals using a cross-sectional study of adults in United States (National Health and Examination Survey, NHANES, 2005-2010) adjusting for covariates: urinary creatinine level (mg/dL), poverty index ratio …

The Genetic Architecture Of Water-Use Efficiency Within And Between Two Natural Populations Of Foxtail Pine, Douglas E. Harwood

Theses and Dissertations

The goal of this project was to determine the genetic architecture of water-use efficiency (WUE) for foxtail pine, which included genomic loci, and effect sizes of this trait. Foxtail pine is a subalpine endemic conifer that inhabits two distinct regional populations separated by 500 km in the mountains of California. In order to achieve this goal, a robust linkage map containing thousands of genetic markers was created using four megagametophyte arrays ranging in size from approximately 70 to 95 megagametophytes. Quantitative trait loci (QTL) discovered for WUE were mapped along the linkage map using linear mixed models and five half-sibling …

Enhanced Nanopore Detection Via Diffusion Gradients And Optical Tweezers, Kyle T. Brady

Theses and Dissertations

Nanopore-based resistive pulse sensing represents an important class of single-molecule measurements. It provides information about many molecules of interest (i.e. DNA, proteins, peptides, clusters, polymers, etc.) without the need for labeling. Two experiments that are especially well suited for studying with nanopore sensors are DNA sequencing and DNA-protein force measurements. This thesis will describe progress that has been made in both areas.

DNA sequencing has become an active area of research for stochastic single-molecule sensing, with many researchers striving for the ultimate goal of single-molecule de novo DNA sequencing. One intriguing method towards that goal involves the use of a …

Engineering Of Polyamidoamine Dendrimers For Cancer Therapy, Leyuan Xu

Theses and Dissertations

Dendrimers are a class of polymers with a highly branched, three-dimensional architecture comprised of an initiator core, several interior layers of repeating units, and multiple active surface terminal groups. Dendrimers have been recognized as the most versatile compositionally and structurally controlled nanoscale building blocks for drug and gene delivery. Polyamidoamine (PAMAM) dendrimers have been most investigated because of their unique structures and properties. Polycationic PAMAM dendrimers form compacted polyplexes with nucleic acids at physiological pH, holding great potential for gene delivery.

Folate receptor (FRα) is expressed at very low levels in normal tissues but expressed at high levels in cancers …

Synthesis Of Unnatural Amino Acids For Genetic Encoding By The Pyrrolysyl-Trna/Rna Synthetase System, William A. Knight

Theses and Dissertations

The complexity of all biomolecules in existence today can be attributed to the variation of the amino acid repertoire. In nature, 20 canonical amino acids are translated to form these biomolecules, however, many of these amino acids have revealed posttranslational modifications (i.e. acetylation, methylation) after incorporation. Amino acids that exhibit PTM are known for their involvement in cellular processes such as DNA repair and DNA replication; these PTMs are commonly found on histones within the chromatin complex. Utilization of in vivo site-specific incorporation has recently reported functionality of post-translationally modified amino acids.1 xii Here we report the synthesis and in …

Regulation Of Eps8 Dependent Pathways By Src In Head And Neck Squamous Cell Carcinoma, Dhwani Patel

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that begins in the epithelial cells that line the mucosal surfaces of the head and neck, including the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity, and salivary glands. Head and neck cancer is the sixth most common type of cancer with a 5-year survival rate of 60% for all cases. Over the past few years, a subset of cells with stem-like properties, called cancer stem cells, are believed to have tumor-initiation capabilities and are responsible for maintaining on-going tumor growth. Previous data from our lab suggested that …

Polycultural Interactions: Fuzzy Identity, Xi Lu

Theses and Dissertations

“Robin D.G. Kelley coined the term polyculturalism as an alternative to multiculturalism, ‘since the latter often implies that cultures are fixed, discrete entities that exist side by side—a kind of zoological approach to culture.’ ”

Polyculturalism assumes the whole world’s cultures are interactive and fluid instead of independent and static, and individuals’ relationship to cultures are complex and cannot be categorized. Yet an individual constitutes multiple cultures, and individual identity embraces the various forms of culture in all aspects of one’s life.

My research examines how polyculturalism affects aspects of communications among people who hold a multiplicity of voices. It …

Applications Of Stability Analysis To Nonlinear Discrete Dynamical Systems Modeling Interactions, Jonathan L. Hughes

Theses and Dissertations

Many of the phenomena studied in the natural and social sciences are governed by processes which are discrete and nonlinear in nature, while the most highly developed and commonly used mathematical models are linear and continuous. There are significant differences between the discrete and the continuous, the nonlinear and the linear cases, and the development of mathematical models which exhibit the discrete, nonlinear properties occurring in nature and society is critical to future scientific progress. This thesis presents the basic theory of discrete dynamical systems and stability analysis and explores several applications of this theory to nonlinear systems which model …

Determinants Of Stress And Effects On Performance In Internal Medicine Residents, Sarah Braun

Theses and Dissertations

The purpose of the present study was to assess: a) perceived stress, burnout, depression, and empathy at three time points in internal medicine residents, b) the role of gender and trait mindfulness in stress response during residency and c) to evaluate the impact these variables have on performance evaluations. Additionally, specific tasks of the residency that may contribute to the experience of stress and burnout were evaluated to test a model of job strain. Stress predicted subsequent burnout and depression. Burnout predicted subsequent depression, and stress mediated this relationship. Women reported higher mean levels of empathy and burnout than men. …

Prediction Of Protein-Protein Interactions In Escherichia Coli From Experimental Data In Treponema Pallidum, Marco A. Abreu

Theses and Dissertations

Protein – Protein interactions (PPIs) are thought to be conserved between species, although this has not been systematically investigated. This problem was explored in Escherichia coli from experimental data in Treponema pallidum by predicting PPIs, focusing on protein domains of little or unknown function. The comparison of T. pallidum to a model organism such as E. coli can not only reveal additional data about T. pallidum but also reveals how E. coli is similar to this distantly related, obligate parasite. A set of novel T. pallidum interactions, enriched for proteins of unknown function, were the basis of over 23,000 predicted …

Cute As A Button, Marta R. Finkelstein

Theses and Dissertations

Cute As A Button explores powerlessness, vulnerability, illness and addiction all wrapped up in tender buttons and a cute, cuddly creature. Using animation, sculpture, sound and an intimate space, I surround the viewer in a saccharine nightmare, one that references the dark underbelly of the cute and the sweet. The visual and aural elements are representative of the psychological and emotional states of powerlessness, which are overcome by the act of making and exploring a medium over which I can have complete control.

The Orphanage Of Things: A Narrative Of Abandonment, Malaz Elgemiabby

Theses and Dissertations

In Sudan, 110 babies are abandoned in the streets of Khartoum every month. The majority of abandoned children are born out of wedlock. Young women with illegitimate pregnancies are often ostracized by their families and society, and the lack of emotional, financial and legal support has led many to take desperate measures, including the abandonment of their children. Relinquishing mothers exist like ghosts in Sudanese society. The only evidence of the mother’s experience is her anonymous, abandoned child. In order to understand and examine this phenomenon, I used ethnographic performance art informed by design research practice (Performative Research Design). I …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

Cyclic Gmp: A Satiety Signal In C. Elegans, Ji S. Park

Theses and Dissertations

Appetite control and satiety mechanisms help animals maintain energy homeostasis; however, these mechanisms can be misregulated, leading to overweight and obesity. Caenorhabditis elegans is an excellent model system to study appetite and satiety because of its conserved behavioral aspects of satiety and conserved molecular mechanisms. ASI senses nutrition and its activity is required for the behavioral state of satiety quiescence. The purpose of this thesis project was to elucidate the function of cGMP signaling in ASI by looking at behavioral effects from the pharmacological use of sildenafil (Viagra), a PDE inhibitor, and the effects on ASI activation from mutating guanylyl …

A Continuous Process Towards The Synthesis Of Quinolones, Stevara N. Clinton

Theses and Dissertations

Abstract

The development of quinolones is described from the first quinolone to the latest fluoroquinolones. Quinolones have generated considerable interest since their discovery because of their antibacterial capabilities. Analogs incorporating the 4-quinolone ring system comprise a largely expanding group of synthetic compounds. The development of antibacterial resistance has created the need for an efficient synthesis of quinolones that can be easily adapted toward the assembly of quinolone based antibacterial drugs.

There are several reported approaches to the 4-quinolone ring system. Many of these methods use expensive starting materials, require the removal of high boiling solvents, or use high temperature conditions …