Medicine and Health Sciences Commons^™

Producing A Subunit Vaccine For Porcine Epidemic Diarrhea Virus, Zayn Khamis

Electronic Thesis and Dissertation Repository

Porcine epidemic diarrhea virus (PEDv) causes disease and mortality to piglets worldwide. Most vaccines used to combat the disease have been ineffective live attenuated virus vaccines. The goal of this project was to produce a plant-made subunit vaccine based off the membrane protein of the virus. This is the first time this protein has been produced in plants. An elastin-like polypeptide fusion membrane protein accumulated up to 0.8 mg/g of fresh leaf weight when transiently expressed in Nicotiana benthamiana. Virus-like particles were also produced for the first time for PEDv, and were able to form with just the membrane …

The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie

Masters Theses

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

The Effects Of Tranexamic Acid On Mortality Rate In Trauma Patients Compared To Trauma Patients With No Tranexamic Acid Treatment, Bradley Earl Tolar

Doctoral Projects

Traumatic injury is the leading cause of death for many age groups. Traumatic accidents caused over 130,000 deaths in the United States in 2014. This DNP project studied the effects of Tranexamic acid on mortality rate in trauma patients. After the completion of a needs assessment at a local level II trauma center, a literature review was performed. The literature showed a decrease in mortality rate when patients were administered Tranexamic acid within 3 hours of injury with statistically significant statistics. Also, the data from the literature showed no correlation between vascular occlusive events and Tranexamic acid use in trauma …

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …

Stability And Kinetics Of Dna Pseudoknots: Formation Of T∗A•T Base-Triplets And Their Targeting Reactions, Calliste Steffensmeier

Theses & Dissertations

Pseudoknots have been found to play important roles in the biology of RNA. These stem-loop motifs are considered to be very compact and the targeting of their loops with complementary strands is accompanied with lower favorable free energy terms. We used a combination of spectroscopic (UV, CD and fluorescence), calorimetric (DSC, PPC and ITC) and kinetic (SPR) techniques to investigate: 1) Local base-triplet formation in pseudoknots; 2) energetic contributions for the association of pseudoknots with their complementary strands; and 3) the kinetic rates as a function of targeting strand length.

We investigated a set of DNA pseudoknots with sequence: d(TCTCT …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

Quef And Quef-Like: Diverse Chemistries In A Common Fold, Adriana Bon Ramos

Dissertations and Theses

The tunneling fold (T-Fold) superfamily is a small superfamily of enzymes found in organisms encompassing all kingdoms of life. Seven members have been identified thus far. Despite sharing a common three-dimensional structure these enzymes perform very diverse chemistries.

QueF is a bacterial NADPH-dependent oxidoreductase that catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ₀) to a primary amine (preQ₁) in the queuosine biosynthetic pathway. Previous work on this enzyme has revealed the mechanism of reaction but the cofactor binding residues remain unknown. The experiments discussed herein aim to elucidate the role of residues lysine 80, …

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts …

Circumventing Cisplatin Resistance In Ovarian Cancers Through Reactivation Of P53 By Non-Cross-Resistant Platinum Analogs, Michelle Martinez-Rivera

Dissertations & Theses (Open Access)

Abstract

CIRCUMVENTING CISPLATIN RESISTANCE IN OVARIAN CANCERS THROUGH REACTIVATION OF P53 BY NON-CROSS-RESISTANT PLATINUM ANALOGS

Michelle Martinez-Rivera, B.S.

Advisory Professor: Zahid H. Siddik, Ph.D.

Cisplatin (cis-Pt), an anticancer platinum (Pt) drug, is used widely in the treatment of several malignancies, such as ovarian cancer. This Pt compound induces DNA damage, which results in p53 activation through post-translational modifications, mainly phosphorylation, culminating in execution of programmed cell-death. However, despite initial therapeutic response to cis-Pt, clinical resistance to this drug emerges leading to disease progression. Pt-resistance phenotypes have been associated with dysfunction in the p53 signaling pathway. Therefore, an effort to understand …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii

Dissertations

The studies presented in section 1 (Chapters I-IV) focus on the design and development of nucleic acid four-way junctions (4WJs) to target a member of the high mobility group (HMG) proteins, the proinflammatory cytokine high mobility group box 1 protein (HMGB1). In the present study, hybrid PNA-DNA 4WJs based on a model DNA 4WJ were constructed to improve the thermal stability of 4WJs while maintaining strong binding affinity toward HMGB1. An electrophoretic mobility shift assay (EMSA) was used to examine the binding affinity of an isolated DNA binding domain of HMGB1, the HMGB1 b-box (HMGB1b), toward a set of PNA-DNA …

An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison

Dissertations & Theses (Open Access)

AN AUTOMATED SYRINGE PUMP SYSTEM FOR IMPROVING THE REPRODUCIBILITY OF DYNAMIC HYPERPOLARIZED MRI PHANTOMS

Harlee Grace Harrison, B.S.

Advisory Professor: James Bankson, Ph.D.

Magnetic Resonance Imaging (MRI) is a powerful tool in the diagnosis of cancer due to its ability to provide good soft tissue contrast and image resolution without the use of ionizing radiation. The use of hyperpolarized pyruvate as a contrast agent for tumor metabolism during MR scans has the potential to provide information about tumor metabolism in vivo that is not available from traditional imaging measurements or any other method. Hyperpolarization is achieved through dynamic nuclear polarization. …

Effects Of Prenatal Exposure To Bisphenol A On Fetal Lung Development, Ayten Hijazi

Electronic Thesis and Dissertation Repository

Prenatal exposure to bisphenol A (BPA), one of the most prevalent endocrine disrupting chemicals, is associated with lung dysfunction and diseases in later life. However, it is unknown if this association has a fetal origin. In this thesis, a series of in vivo and in vitro experiments were conducted to determine the effects of prenatal exposure to BPA on fetal lung development, and define the underlying molecular mechanisms. Environmentally relevant doses of BPA were administered to pregnant mice via diet from embryonic day (E) 7.5 to 18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of …

Union College Smokers: Hurting Themselves But Helping Others? Mixed Research On The Relationship Between Smoking And Volunteering, Cameron Robertson

Honors Theses

This mixed methodology research project analyzes the relationship between smoking cigarettes and volunteer participation rates utilizing an empirical analysis of 2006 and 2010 Current Population Surveys (CPS), as well as a qualitative analysis on the perception and behaviors of Union College student smokers. Existing studies have indicated a negative association between smoking cigarettes and social participation, yet little research has been done on the specific relationship between smoking status and volunteer participation. Utilizing CPS supplements on tobacco use and volunteering, this empirical analysis finds that smoking cigarettes has a significant association with decreased volunteer participation rates. This research also includes …

Traveling With Stowaways: The Human Microbiome And Travel, Alisha N. Hughes

Global Honors Theses

The human microbiome is a research field that is fairly new and thus, not yet fully understood. However, past research has revealed that the human host and the microorganisms interact with each other. To comprehend how influential the connection between host and its stowaways is, the following text will first offer general information on the human microbiome, before moving on to a pilot case study proposal. With the use of similar case studies, this proposal aims to investigate how the human microbiome changes when the host travels and analyzes the changes and their affects on the individual’s health. The paper’s …

Do Rats Consume Ethanol To Regulate A Negative Emotion Induced By A Successive Negative Contrast Procedure?, Andrew Dieterich

Seton Hall University Dissertations and Theses (ETDs)

According to the self-medication hypothesis, individuals may consume drugs or alcohol, or engage in other behaviors in order to reduce a negative emotional state (Khantzian, 1985; Gross, 2013; Crum et al., 2013). Rats experiencing a negative state induced by various stressors (Bertholomey et al., 2010), or a decrease or loss in reward value of a sucrose solution (Manzo et al., 2015; Manzo et al., 2014) demonstrate increased consumption of alcohol. I used successive (SNC) and anticipatory negative contrast (ANC) procedures to further examine this hypothesis and the previous findings (Manzo et al., 2015), that rats increase consumption and preference for …

Addiction: Physiology In Performance, Opioid Pharmacology In Character Development For The Theater, Lacey M. Smith

Honors Thesis

Actors inquire into the physical, mental, and emotional impulses of their respective characters in the effort to develop a cohesive persona for the stage. The goal of this research is to determine whether a more thorough, scientific understanding of the physiopyschological phenomena a character experiences, specifically opioid withdrawal, will aid in the depiction of symptoms on stage. The project began with a research period and culminated in physical dissemination through theater performance. Both video, audio, and text media were utilized to establish a thorough comprehension of the physiological mechanisms in opioid addiction. Further profiling of the characteristics and symptomatic episodes …

Clinical Study Of Canine Tear Lacritin As A Treatment For Dry Eye, Katherine E. Kelly

Senior Honors Projects, 2010-2019

Keratoconjunctivitis sicca (KCS), the deficiency of tears also known as dry eye, is a prevalent disease that affects both humans and canines. The current treatment for dye eye, cyclosporine (Restatis®), only provides temporary relief, is often associated with discomfort and is inconsistently effective. Lacritin is a naturally occurring tear glycoprotein secreted from the human and canine lacrimal glands. It has been shown that lacritin stimulates basal tearing in rabbits when applied topically. This study characterized the amount and form of lacritin found in the tears of dogs with healthy and dry eyes—information which may be applied to the development of …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …

Investigating Metal Cations As Potential Inhibitors Of Iapp Aggregation: Kcl, Cacl2, And Cucl2, Megan Burke

Honors Thesis

IAPP is an amyloid protein that misfolds, causing toxic aggregation in the pancreas of Type II Diabetes patients. In this study, three metal cations (KCl, CaCl2, and CuCl2) are tested in Thioflavin T assays and atomic force microscopy (AFM) to see if they inhibit the aggregation of IAPP.

Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, Jacob M. Amburn

Chancellor’s Honors Program Projects

No abstract provided.

Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo

Forensic Science Theses

Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …

Using Poincaré And Coefficient Analyses To Assess Changes In Variability In Respiration As A Function Of Leptin Status, Sex, And Buprenorphine In Mice, Wateen Hussein Alami

Chancellor’s Honors Program Projects

No abstract provided.

Interaction Between Two E3 Ligases, Nedd8ylated Cullin And Hhari, Kheewoong Baek

Theses and Dissertations (ETD)

RBR (RING1-in between RING-RING2) is a special type of E3 ubiquitin ligase containing three zinc-binding RING (Really Interesting New Gene) domains, while adopting mechanisms of HECT (Homologous to E6-AP Carboxyl Terminus) for substrate ubiquitination. Most well known RBRs include Parkin and HOIP, which are associated with Parkinson’s disease and innate immune deficiency. However, it is not well known how the RBR proteins gain activity, as they are known to be autoinhibited. Here I show that a specific F430A, E431A, E503A triple mutation of RBR protein HHARI (Human homologue of Ariadne) and its interaction with NEDD8ylated cullin RING ligase can both …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, Roshni Patel

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast growth factors (FGFs) are family of proteins that belong to a group of growth factors that are found in mammals and play an important role in angiogenesis, differentiation, organogenesis, and tissue repair. In summary, their main functionality is involved in cell division and proliferation. Because FGFs plays such a vital role in cell proliferation, they are mainly involved in the process of wound healing and injuries. FGF binds to its ligand, heparin—a heavily sulfated glycosaminoglycan. The binding of heparin to FGF occurs through electrostatic interactions, specifically between the negatively charged sulfate groups on heparin and positively charged residues such …

Studies On The Prevalence And Control Of Parasitic Helminths In "Natural" Laying Hens, Brittany R. Weir

Animal Science Undergraduate Honors Theses

One societal trend that has been gaining much traction and popularity since the 21^st century began is “organic” and/or “natural” food products. In 1999, the global market accounted for $15.2 billion dollars worth of organic food and drink, compared to the market in 2014 where we consumed $80 billion dollars worth (Willer et. al, 2016). With “natural” production of food animals however, “natural” parasite transmission may be a consequence. To that end, this experiment examines the prevalence of helminths in 110 “natural” laying hens from three regional farms and the efficacies of fenbendazole, piperazine, and levamisole on what should …

Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., Michelle L. Mason

Biological Sciences Undergraduate Honors Theses

Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties. …