Digital Commons Network^™

Polydrug Use Among People Who Use Opioids, National Survey On Drug Use And Health 2002 To 2017., Diana Kuo Stojda

Electronic Theses and Dissertations

Introduction: Mortality due to overdose has been increasing since 2010 in the U.S., with an increase in the reported use of heroin and co-use of heroin and prescription opioids. Trends and correlates of polydrug use need to be analyzed to propose policies to reduce overdose risk. The overall objective of this study is to characterize high-risk polydrug groups among people who use opioids (PWUO) to understand the patterns of co-used substances and overdose risk factors. Methods: Publicly available data from the 2002-2017 National Survey on Drug Use and Health were analyzed to obtain weighted prevalence rates and trends …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Zika Virus-Induced Lysis Of Cervical Cancer Cells, Harini Krishnapura

Electronic Theses and Dissertations

Cervical cancer is the fourth most frequent cancer in women with an estimated 570,000 new cases globally in 2018. Treatment of advanced cervical cancer is often unsuccessful leading to high cancer-related mortality rates, especially in under-resourced countries. Recently, a possible role for the cell surface glycoprotein CD24 in host cell specificity of Zika virus was reported. As an extension of this work, Zika viruses have been proposed as oncolytic therapy for the treatment of neuroblastoma and other CD24 positive tumors. To determine the permissiveness of cervical cancer cells to Zika virus infection and its association with CD24, we assessed cytopathic …

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

Synthesis And Evaluation Of 1,2,4-Oxadiazolidinones: The Search For A Potential Non-Β-Lactam Β-Lactamase Inhibitors., Chimdi Eke Kalu

Electronic Theses and Dissertations

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, their effectiveness is drastically threatened by bacterial β-lactamases. β-lactamases is responsible for the resistance to most antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance; however, in this study 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring scaffold in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized by treating nitrones …

Generalizations Of The Arcsine Distribution, Rebecca Rasnick

Electronic Theses and Dissertations

The arcsine distribution looks at the fraction of time one player is winning in a fair coin toss game and has been studied for over a hundred years. There has been little further work on how the distribution changes when the coin tosses are not fair or when a player has already won the initial coin tosses or, equivalently, starts with a lead. This thesis will first cover a proof of the arcsine distribution. Then, we explore how the distribution changes when the coin the is unfair. Finally, we will explore the distribution when one person has won the first …

Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao

Electronic Theses and Dissertations

Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection leads to a phenomenon of inflammaging, in which chronic infection or inflammation induces an immune aged phenotype with T cell dysfunction. Thus, HCV or HIV infection has been deemed as a model to study the mechanisms of T cell infammaging and viral persistence in humans. In this dissertation, T cell homeostasis, DNA damage and repair machineries were investigated in patients with chronic HCV or HIV infection at risk for inflammaging. We found a significant depletion in CD4 T cells, which was correlated with their apoptosis in chronically HCV/HIVinfected patients, compared …

Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen

Electronic Theses and Dissertations

In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect …

New Insights Into Mycofactocin Biosynthesis, Structure And Function, Richard Selorm Ayikpoe

Electronic Theses and Dissertations

Mycofactocin is a putative ribosomally synthesized and post-translationally modified peptide (RiPP)-derived redox cofactor. Its biosynthesis is accomplished through the dedicated actions of the products of six conserved genes, mftABCDEF. The mycofactocin pathway is one of the most widely distributed RiPP systems in bacteria however, this distribution is heavily skewed towards the Mycobacteria genus including human pathogenic variants such as M. tuberculosis and M. ulcerans. Gene expression studies have demonstrated the essentiality of the pathway in the ability of M. tuberculosis to utilize the host's cholesterol as sole carbon source during latency. However, the biosynthesis, structure and physiological function …

Examining The Role Of Reproductive Interference In The Decline Of Native Green Treefrogs Following Cuban Treefrog Invasions, Joseph Kennedy

Electronic Theses and Dissertations

Reproductive interference occurs when the mating behaviors of one species negatively impact the fitness of another species. It is of increasing interest in invasive species biology because the introduction of alien species often leads to novel sexual interactions with native taxa, which can contribute to their decline. I examined whether reproductive interference plays a role in the decline of native green treefrogs (Hyla cinerea) following invasions of Cuban treefrogs (Osteopilus septentrionalis) in the southeastern United States. The impetus for this study revolves around similarities in spectro-temporal features of Cuban treefrog courtship calls and green treefrog aggressive calls. The significance of …

Safety Assessment And Chemical Fingerprint Analysis Of Medicinal Plants Commonly Consumed As Herbal Teas; Rooibos (Aspalathus Linearis) And Moringa (Moringa Oleifera), Omer I. Fantoukh

Electronic Theses and Dissertations

The first chapter discusses the significance of natural products, safety challenges, and quality issues concisely. Specifically, the impact of herb-drug interaction on consumers and the quest for chemical markers for chemical fingerprinting development are provided. Rooibos tea (Aspalathus linearis) is a popular South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of CYP450 isozymes. In chapter two, the phytochemical investigation of A. linearis resulted in the isolation and characterization of 14 phenolic compounds. Safety assessment of the phytochemicals through interaction with CYP, PXR, and P gp was conducted. The …

Development Of In Vitro Point Of Care Diagnostics (Ivpcd) Based On Aptamers Integrated Biosensors, Nileshi Saraf

Electronic Theses and Dissertations

The global market for the medical diagnostic industry is worth 25 billion dollars in the United States and is expected to grow exponentially each year. Presently available methods for biodetection, such as immunoassays, chemiluminescence and fluorescent based assays are expensive, time consuming and require skilled labor with high-end instruments. Therefore, development of novel, passive colorimetric sensors and diagnostic technologies for detection and surveillance is of utmost importance especially in resource constrained communities. The present work focusses on developing novel and advanced in vitro biodiagnostic tools based on aptamer integrated biosensors for an early detection of specific viral proteins or small …

Development And Evaluation Of Vaccine Candidates For Senecavirus A, Bishwas Sharma

Electronic Theses and Dissertations

Senecavirus A (SVA) has been associated with several outbreaks of vesicular disease (VD) since 2014 in major swine-producing countries around the world. The virus causes VD that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Currently there are no commercial vaccines available for SVA. Here, we developed a live attenuated SVA strain by mutating a wild type SVA strain SD15-26 (wt SVA). The live attenuated virus, rSVA mSacII, replicated less efficiently in cell cultures in vitro and expressed lower amounts of VP1 and VP2 capsid proteins than wt SVA. Most importantly, the rSVA mSacII virus failed to induce clinical …

Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-strand RNA virus of the genus Senecavirus, family Picornaviridae. Senecavirus A is an emerging picornavirus of swine, which causes vesicular disease (VD) in pigs that is clinically indistinguishable from footand- mouth disease and other high consequence VDs of swine. There is evidence that SVA has been circulating in the US swine population since the late eighty’s, however, recently the virus emerged worldwide, and it has been associated with several VD outbreaks in pigs in many of the major swine producing countries. Despite the recent surge in the number of cases of …

Greater Sage-Grouse Survival, Breeding Ecology, Resource Selection, And West Nile Virus Prevalence On The Eastern Fringe Of Their Range, Lindsey Anne Parsons

Electronic Theses and Dissertations

The greater sage-grouse (Centrocercus urophasianus) is a sagebrush (Artemisia spp.) obligate species that has experienced population declines over the past several decades. Sage-grouse are a species of conservation concern throughout the Intermountain West and are considered a species of greatest conservation need in South Dakota. Numerous studies have documented drivers of demographic performance at the core of their distribution; however, relatively few studies have examined sage-grouse inhabiting the eastern extent of their range, in South Dakota. We sought to examine sage-grouse space use in multiple seasons, estimate survival, and determine factors affecting nest success in South Dakota …

Alternative Treatment Options For Controlling Anthelmintic-Resistant Haemonchus Contortus Populations In South Dakota Sheep Herds, Adam Sarah

Electronic Theses and Dissertations

Haemonchus contortus is a common economically important gastrointestinal nematode that obliges the survival and productivity of small ruminants, especially sheep and goats. Anthelmintic resistance is a primary challenge in ruminant health management programs in preventing and controlling the H. contortus populations; therefore, there is a great necessity in finding and developing natural plant products for use as alternatives to commercial anthelmintics for controlling H. contortus in pastured sheep and goats. This dissertation has three major aims conducted in three separate studies: the first in vivo one was to evaluate the extended effect of a springtime, combined-treatment with 3 anthelmintics having …

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

Rumen Microbial Culture Library And In Vitro Analysis Of Selected Bacterial Species On Colonization Resistance Against Bovine Enteric Pathogens, Maria Antony

Electronic Theses and Dissertations

The anaerobic habitat of the four chambers in ruminant’s foregut plays a vital role in the fermentation of the food by the active involvement of the residing microbial community. The cultivability and the potential role of rumen bacteria in the field of livestock production, host health and immunity are important to study. The developed anaerobic culturing techniques enable us to culture and screen different rumen bacteria to study the anti-pathogenic effects. Whole genome sequencing and analysis help us to understand the genome level characteristics of the rumen bacterial species individually. Since the majority of the rumen biosphere is still not …

Development Of A Novel Nanotechnology-Based Vaccine Adjuvant And Delivery System For Systemic And Mucosal Immunity, Mohammed Ali Bakkari

Electronic Theses and Dissertations

Many serious infections for which there are no existing vaccines, enter by a mucosal route such as HIV, influenza, and tuberculosis, etc. Therefore, designing safe and effective mucosal vaccines that elicit robust immune response at mucosal sites is still a major challenge without a safe mucosal adjuvant. Previously, our laboratory had discovered inulin acetate as a novel toll-like-receptor-4 agonist (adjuvant). The study in this dissertation explored the application of nanoparticles prepared with inulin acetate (InAc-NPs) as a vaccine adjuvant and delivery system for enhancing mucosal immunity. The rationale behind selecting InAc-NPs is their proven ability to activate strong systemic immunity …

Cropping Sequence Affects Subsequent Soybean Yield, Soil Microbiome And Soil Health, Izzet Bulbul

Electronic Theses and Dissertations

Rotation is an important cultural practice that farmers use to manage crop growth and diseases. Diversified crop rotations directly affect plant residue inputs that may enrich specific groups of microbes that form beneficial associations with the following crop. At two field sites, yield differences were observed in soybeans planted after the following four long-term (14 year) crop sequences: continuous corn (CC), corn (Zea mays)/corn/soybean (Glycine max) (CCS), corn/soybean/corn (CSC), soybean/corn/soybean (SCS). Soybean yields were in decreasing order, CC>CCS>CSC>SCS, and the yield differences could not be explained by soil chemical and physical properties previously …

A Sustainable Future In The Implementation Of Clinical Pharmacogenomics, Nicholas Keeling

Electronic Theses and Dissertations

Purpose: The sustainability of clinical pharmacogenomics requires further study of clinical education on the topic, its effects on clinical workflow, and the responsibilities of different providers for its delivery. Tools from the discipline of implementation science were utilized herein to help achieve the purposes of the three studies. The broad purpose of this dissertation is to advance the work of clinical pharmacogenomic implementation through a more rigorous convergence with implementation science.

Methods: Three studies constitute the whole of this dissertation. The first is a scoping review that provides a broad characterization of the methods utilized in available peer-revieliterature focusing on …

Developing Zebrafish As An In Vivo Model To Screen Compounds For Anti-Cancer Activity In Human Breast Cancer, Trisha Dhawan

Electronic Theses and Dissertations

Breast Cancer (BC) is the most frequently diagnosed cancer; 1:8 women are at risk of developing BC in her lifetime. Cancer metastasis causes the majority of deaths in BC patients. Moreover, side effects of traditional chemotherapeutic drugs (TCD) impair the quality of life of these patients. Discovery and development of safe and effective new therapies is imperative for the treatment of BC and targeting metastasis. The goal herein is to further expand the applicability of in vivo xenotransplantation of human BC cells in transgenic zebrafish to screen potential chemotherapeutics for toxicity and efficacy. For xenotransplantation, MCF-7, BT-474, and MDA-MB-231 BC …

Explication Of Moral Disgust: Assessing Physiological And Behavioral Responses To Disgust Eliciting Videos, Sarah Michelle Scott

Electronic Theses and Dissertations

Results indicate a significant self-reported disgust response among core animal reminder and contamination domains whereas the moral domains elicited both anger and disgust. Physiologically no change was measured in skin conductance; heart rate decrease in response to animal reminder contamination community and autonomy video clips. Significant behavioral avoidance was demonstrated when presented with the core and animal reminder video clips. Further when measuring facial muscle activation the levator labii was significantly activated in response to the core video clip but no others. The current study highlights the difficulty in establishing characteristic responses to disgust stimuli especially within the moral domain. …

Novel Approaches To Evaluate And Enhance Neonatal Calf Gastrointestinal Health And Development, Fernanda Trindade Da Rosa

Electronic Theses and Dissertations

Physiological adaptations of the gastrointestinal tract (GIT) epithelial cells as well as methods to manipulate early life GIT microbiota colonization during the neonatal stage, is of great importance to the dairy industry. The first objective of this research was to optimize a method based on evaluation of bovine transcripts in fecal RNA via RTqPCR using L-selectin (SELL) as a marker for polymorphonuclear leukocytes (PMNL), keratin 8 (KRT8) and fatty acid binding protein 2 (FABP2) for GIT enterocytes, and tight junctions in fecal RNA and GIT sections in dairy calves. To test the reliability of the fecal RNA method, fecal and …

The Effect Of Proteolytic Queues On Antibiotic Tolerance And Persistence Cells Population In Escherichia Coli, Alawiah Abualrahi

Electronic Theses and Dissertations

A major contributing factor to the abundance of antibiotic-resistant microorganisms and failed antibiotic treatment is survival due to antibiotic tolerance and persistence. Antibiotic tolerance is a widespread phenomenon that enables cells to survive treatment without carrying a resistance gene. This phenomenon renders antibiotic treatments less effective and facilitates antibiotic resistance. We are particularly interested in proteases, responsible for degradation of proteins, because of their known relationship to tolerance and persistence. Here, we examine the effects of proteases and antibiotic survival using queueing theory, in which one type of customer competes for processing by servers, that has traditionally been applied to …

Effects Of Commercial Feed Additives On The Gut Microbiota Of Food Animals, Prakash Poudel

Electronic Theses and Dissertations

Weaning is a stressful event of newborn animals which can lead to dysbiosis in the GIT causing invasion of pathogens, retarded growth, high incidence of diarrhea, and increased neonatal mortality. Since antibiotics use in livestock production have been regulated, various feed additives have been designed as antibiotic alternatives to use in newborn animal during weaning. This thesis investigated the dynamics of bacterial composition of GIT in weaned animals fed commercial feed additives by analysis of high throughput sequencing data generated from PCR-amplified DNA targeting V1-V3 region of 16S rRNA gene. Experiment 1 investigated the rumen environment of neonatal calves fed …

Increasing Accumulation Of Glyceollins In Soybeans Via Optimization Of The Fungal Incubation Process, Stephanie Wootton

Electronic Theses and Dissertations

Continual use of antibiotics in the feed of food animals was viewed a solution to the problem of disease outbreaks in livestock produced in confinement operations. This practice also improved animal performance, likely due to the reduction in sub-clinical infections. Unfortunately, this practice led to a new problem, the development of antibiotic resistant microbes. This increase in antibiotic resistance reduced the direct benefits of antibiotics in animal production. Moreover, as antibiotic resistance spread from animal to human pathogens, this practice created a major public health concern. This led the FDA to enact the Veterinary Feed Directive in 2017 that greatly …

Description And Alleviation Of The Stress Response In Atlantic Sharpnose Sharks (Rhizoprionodon Terraenovae), White-Spotted Bamboo Sharks (Chiloscyllium Plagiosum), And Golden Shiners (Notemigonus Crysoleucas), Lauren Nicole Fuller

Electronic Theses and Dissertations

Sharks are an essential component of many marine ecosystems; however they have experienced population declines mainly attributed to overfishing and capture of sharks as bycatch. Despite sharks often being released when captured as bycatch the act of capture can result in a stress response which may cause severe physiological perturbations. Studies have investigated the physiological impacts of capture stress on elasmobranchs but most have primarily focused on the secondary stress response. I conducted a series of studies to further describe the primary stress response through quantification of adrenocorticotropic hormone (ACTH) while also investigating methods such as sedation and limiting air …

Progress Toward The Synthesis Of 3-Methoxyflavones As Potential Antioxidants, Neuroprotective Agents, And Trifluoromethylated 19f Nmr Probes, Reem Alkhodier

Electronic Theses and Dissertations

The total synthesis of polyhydroxylated flavones have proven to be challenging, due to the presence of more than one hydroxyl group. Direct cyclization was not successful in any of the attempts. However, by using a silyl protecting group, the cyclization was feasible. Other reactions like the Friedel-Crafts acylation and selective protection of phenols were also difficult.

Design Of Thermosensitive Hydrogel For Extended-Release Of Praziquantel, Sheng Feng

Electronic Theses and Dissertations

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most comanti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications …