Digital Commons Network^™

Utilizing Hemoglobin Binding Kinetics And X-Ray Crystallography In Sickle Cell Disease Drug Development, Ahmed Alghamdi

Theses and Dissertations

ABSTRACT

UTILIZING HEMOGLOBIN BINDING KINETICS AND X-RAY CRYSTALLOGRAPHY IN SICKLE CELL DISEASE DRUG DEVELOPMENT

By Ahmed Alghamdi, M.Sc. in Medicinal Chemistry

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Medicinal Chemistry at Virginia Commonwealth University.

Virginia Commonwealth University, 2024.

Director: Dr. Martin K. Safo Professor, Department of Medicinal Chemistry

Introduction: Sickle Cell Disease (SCD) is characterized by severe hemolytic anemia, recurrent painful crises, and chronic organ damage, posing significant challenges to patients' quality of life and longevity. While current FDA-approved therapies offer symptomatic relief, they do not address the underlying molecular …

The Patient Experience Of Language Discordance And Interpreter Services In The Emergency Department, Keri L. Baker

Theses and Dissertations

Background: Clear communication is critical to the interaction of a patient and medical provider. For non-English speaking patients, language discordance, described as the lack of proficiency in a shared language, with the medical team results in a poor patient experience and poor patient outcomes. The predominant solution to language discordance is the use of interpreter services, however these services are underused in the emergency department (ED). Studies examining underuse of interpreter services have primarily focused on the clinician and little is known about the patient’s influence on the use of interpreter services.

Methods: Semi-structured interviews were conducted with 12 Spanish-speaking …

Mechanistic Analysis Of Four-Way Dna Junctions And Cytokine-Binding Aptamers For Therapeutic Interventions, Roaa S. Mahmoud

Theses and Dissertations

DNA is inherently dynamic and topologically diverse and can fold into many different structures. Besides the canonical Watson-Crick structure, other higher-order structures such as G-quadruplexes (G4), i-motifs (iM), and four-way DNA junctions are possible. Although these high-order DNA structures are known to form transiently, they are important due to the crucial roles they play in many cellular processes including DNA replication, recombination, and repair. Among these DNA structures, 4-way junctions (also known as Holliday junctions, HJ) which are formed during the repair of double-strand DNA breaks (DSBs) and interact with proteins have garnered significant attention due to their central role …

Redesign, Evaluation, And Validation Of A Commercially Viable High-Resolution Melt Based Mixture Screening Tool, Chastyn Smith

Theses and Dissertations

Analysis of evidentiary samples containing DNA from multiple contributors (“mixtures”) is a time intensive process for a forensic analyst and one where the contributor nature of a sample is not revealed until the end of the traditional forensic workflow. Often, at this stage, retesting or additional testing of mixture samples may not be possible, particularly if the DNA collection device did not preserve the DNA well enough; consequently leaving only trace amounts of a contributor’s DNA present. Thus, a new collection device that would allow for the increased preservation/integrity of evidentiary samples as well as a method that would allow …

Polyvictimization In Context: Identifying Patterns Of Peer, Dating, And Community Violence Among Black Early Adolescents, Carine Leslie

Theses and Dissertations

Early adolescents exposed to multiple forms of victimization (“polyvictimization”) may experience a number of detrimental psychosocial outcomes. Some person-centered research has identified victimization subgroups among adolescents but have not examined the overlap of peer, dating, and community victimization among Black early adolescents living in economically disadvantaged urban communities. Thus, this study empirically identifies victimization profiles in a sample of Black early adolescents to ascertain the patterns and correlates of polyvictimization. The present study aimed to (a) identify subgroups of Black early adolescents based on their frequency of peer, dating, and community victimization using latent profile analyses, and (b) evaluate the …

An Ecocritical Approach To Fyodor Abramov's Story "What Do The Horses Cry About", Badegül Can Emir

Khazar Journal of Humanities and Social Sciences

Human's destructive behaviors toward the environment also harm animals. Fyodor Abramov's story, “What Do The Horses Cry About”. focuses on this issue. While this story reflects the world through the eyes of an animal, it reveals people's changing behaviors towards animals. The study tries to read the changing attitude of man toward nature in the modern age on the axis of Fyodor Abramov's story called “What Do The Horses Cry About”. On the other hand, it tries to understand how the relationship between the human and other living things has penetrated the fiction of the story. It shall be emphasized …

Facilitative And Competitive Interactions Among Dune Grass Species In Monoculture And Polyculture Communities, Anne M. Sciolino

Theses and Dissertations

Coastal dunes are natural barriers between land and sea and are imperative to the protection and preservation of inland ecosystems and human infrastructure. However, due to global warming, seal level rise, and coastal development, coastal dunes are under constant threat of destruction. Restoration efforts have been implemented to rebuild the protective function of dunes through the planting of dune building grasses. Dune grasses build and maintain these vital sand dunes. However, little is known about facilitative and competitive relationships among the grasses. In order to maximize restoration efforts, research is needed to better understand the biotic interactions among restorative grass …

Correlates Of Coffee And Energy Drink Use Among Individuals With Severe Alcohol Use Disorder, Enkelejda Ngjelina

Theses and Dissertations

Research on caffeine consumption among college students and young adults has primarily focused on caffeinated energy drinks (EDs) and their combination with alcohol, demonstrating a strong association with heavy and problematic alcohol use. However, little attention has been directed toward older adults. Furthermore, studies have shown that regular ED consumers are more likely to meet the criteria for alcohol dependence compared to their peers. Despite this association, little is known about ED consumption among individuals with Alcohol Use Disorder (AUD), particularly those undergoing treatment, and even less is understood about other caffeine sources such as coffee. This study aimed to …

Systemic Contributors To Health Equity: A Conceptual Framework And Moderation Analysis, Rachel Regal

Theses and Dissertations

This dissertation presents a line of research exploring systemic factors that influence health and health equity across the lifespan. A linking document prefaces two-manuscripts as follows. Manuscript 1, A Model for Enhanced Trauma-Informed Care: An Asset-Based, Transdisciplinary Approach to Health Equity, presents a synthesis of literature on multisystem resilience, social determinants of health, and adverse / positive childhood experiences to build an alternative framework to promote healing and health equity using an asset-based approach within enhanced trauma-informed systems of care and educational models. By adopting this enhanced framework, the counseling field and others can be responsive to emerging trends and …

Roleplaying Builds Character: Avatar Performance In Dungeons & Dragons As An Art-Form For Self-Development., Maria F. Pagola Garcia

Theses and Dissertations

This paper examines the impact of the performance and embodiment of Dungeons & Dragons characters on their player’s self-development and self-confidence. Focusing on the game’s 5th edition, this narrative inquiry study is concerned with the applications of D&D as an artistic tool to build both community in formal and informal spaces of art education and individual players’ self-development through the avatars being portrayed during game time.

Ten adult participants ranging from age 23-28 were selected using a mix of direct recruitment and voluntary response. They filled out a digital survey introducing themselves and their main D&D characters, then a 45-minute …

The Genetic Architecture Of Cervical Change During Pregnancy: From Modeling To Mechanism — Does The Cervix Mediate Maternal Risk For Spontaneous Preterm Birth?, Hope M. Wolf

Theses and Dissertations

This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. …

Feasibility Of Using Somatosensory Input On Pediatric Patients Receiving Dental Treatment, Liara D. Vinson

Theses and Dissertations

Purpose: The aim of this randomized, cross-over designed feasibility study is to evaluate patient anxiety, patient cooperation, and patient acceptance of a vibrating weighted vest used during the restorative treatment compared to when no device is used.

Methods: Children aged 5 to 15 years, needing at least two appointments for restorative treatment requiring local anesthesia under basic behavior guidance techniques were recruited. Patients were randomly allocated to wearing a vibrating weighted vest at one of the appointments. At both appointments, behavior was evaluated using Frankl scores and anxiety was evaluated at the beginning and at the end of …

Immobilization Of Alpha-Amylase On Chitosan-Coated Iron Oxide Nanomagnetic Nanoparticles, Maysam H. Jalil, Ahmad Asoodeh

Hilla University College Journal For Medical Science

Amylases are widely used enzymes across various industries such as clinical chemistry, pharmaceuticals, food processing, detergents, textiles, and paper manufacturing. Immobilization can enhance their effectiveness. Nanostructured materials have become important in many fields, including magnetite nanoparticles (Fe₃O⁴) for immobilizing enzymes. The study aimed to immobilize alpha-amylase extracted from Bacillus subtilis onto iron oxide nanoparticles coated with chitosan to compare its catalytic efficacy to its free form. Iron oxide nanoparticles were synthesized and coated. The substrate underwent amylase introduction with glutaraldehyde, stabilizing formation on chitosan-iron oxide nanoparticles. XRD, FT-IR, FE-SEM, and DLS were used to analyze immobilized …

Molecular Characterization Of Bla Oxa-51 Gene Among Acinetobacter Baumannii Isolates In Babylon Province, Huda H. Al-Hasnawy, Alya A. Rahi, Baraa H. Hadi

Hilla University College Journal For Medical Science

Background: Acinetobacter baumannii, identified as an ESKAPE pathogen, is part of a group of bacteria known for their high antibiotic resistance and significant role in nosocomial infections. Objectives: The objective of the current study is to investigate the genetic sequences of the blaOXA-51 gene in A. baumannii isolates. Materials and Methods: 600 specimens were collected during the period from September 2022 to December 2022 from three hospitals in Babylon Province/ Iraq. Results: In the present study, 20 (3.33%) out of 600 isolates from (urine, Burn, blood and wound)in percentage 6(30%), 5(25%), 5(25%), and 4(20%) respectively. The identification …

Potential Antidiabetic Activity Of Ficus Carica: The Concept Of Antioxidant Properties In A Rat Model, Hawraa Abdul-Jabbar I. Shwayekh, Reyadh H. Al-Mosawi, Alaa Jafear Mahrath

Hilla University College Journal For Medical Science

Background: The benefits associated with a healthy diet can be attributed to higher concentrations of antioxidants found in fruits and vegetables such as flavonoid-polyphenolic compounds, tocopherols, and carotenoids.

Objectives: The aim of the study was to investigate the antioxidant activity of Ficus Carica and the histopathological study in striptozotocin (STZ) induced T2DM in rats and compare the effect of the plant with sitagliptin.

Materials and Methods: Forty apparently healthy male Wister rats weighing between 180 and 250 grams were used in the current investigation, which began in December 2023. To create type 2 diabetes mellitus (T2 DM), rats were fed …

Speech Regulation And Tobacco Harm Reduction, Jonathan H. Adler, Jacob James Rich

Faculty Publications

Part I of this essay describes what is currently understood about the relative health risks of ENDS [electronic nicotine delivery systems] and other vaping products, particularly as compared to combustible cigarettes.

Part II of this essay describes the current regulatory regime governing tobacco products and how this regime has been applied to ENDS and other vaping products.

Part III of this essay explains how the FDA’s regulatory regime hampers the ability of ENDS manufacturers to inform consumers about the relative risks of their products and the potential use of ENDS as smoking cessation aids.

Part IV explains why this regulation …

Tarnished Gold: The Endangered Species Act At 50, Jonathan H. Adler

Faculty Publications

This Article aims to take stock of the [Endangered Species Act] ESA’s success and failures during its first fifty years, particularly with regard to the conservation of species habitat on private land. While the ESA authorizes powerful regulatory tools for species conservation, there are serious questions as to whether such tools are the most effective means of conserving species and the habitats on which they rely. Given that most species rely upon private land for their survival, the ESA’s ability to foster private land conservation will affect the law’s overall success.

This abstract has been taken from the author's introduction.

Mechanism Of Action Of Kl-50, A Candidate Imidazotetrazine For The Treatment Of Drug-Resistant Brain Cancers, Eric D. Huseman, Anna Lo, Olga Fedorova, James L. Elia, Susan E. Gueble, Kingson Lin, Ranjini K. Sundaram, Jooneseok Oh, Jinchan Liu, Fabian Menges, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Victor S. Batista, Jason M. Crawford, Anna M. Pyle, Ranjit S. Bindra, Seth B. Herzon

Chemistry Faculty Research and Publications

Aberrant DNA repair is a hallmark of cancer, and many tumors display reduced DNA repair capacities that sensitize them to genotoxins. Here, we demonstrate that the differential DNA repair capacities of healthy and transformed tissue may be exploited to obtain highly selective chemotherapies. We show that the novel N3-(2-fluoroethyl)imidazotetrazine “KL-50” is a selective toxin toward tumors that lack the DNA repair protein O⁶-methylguanine-DNA-methyltransferase (MGMT), which reverses the formation of O⁶-alkylguanine lesions. We establish that KL-50 generates DNA interstrand cross-links (ICLs) by a multistep process comprising DNA alkylation to generate an O⁶-(2-fluoroethyl)guanine (O⁶FEtG) …

Terra-Lsd1 Phase Separation Promotes R-Loop Formation For Telomere Maintenance In Alt Cancer Cells, Nicholas J. Reiter

Chemistry Faculty Research and Publications

The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the …

Diatom Productivity And Nutrient Dynamics In The Ross Sea, Antarctica During Warm Events In The Neogene, Marialena Christopoulou

Graduate Research Theses & Dissertations

Increased melting of the Antarctic Ice Sheet (AIS) in recent decades, has had a significant impact on many aspects of the global ocean. Models indicate that by the end of the 21st century atmospheric carbon dioxide (CO2) concentrations may exceed 500 ppm, and the average global temperature will likely warm by more than 2°C. However, data that provide model constraints on potential feedbacks in ice-ocean-atmosphere system are limited by short-timescales (e.g., decadal- to centennial-scale) and incomplete spatial coverage. In particular, little is known about the impacts of future warming and widespread melting of AIS on marine biological productivity, silicate weathering …

Inhaling The Unseen: Exploring The Presence Of Microplastics In The Human Respiratory Tract, Kara Coffman-Rea

Graduate Research Theses & Dissertations

Microplastics (plastic pieces less than 5 mm) have emerged as a pervasive form of pollution acknowledged as a universal threat to both environmental and human health. Their small size and widespread distribution pose significant risks to marine life, terrestrial ecosystems, and ultimately human health. Microplastics have been reported in food and drink items designated for human consumption, in cosmetics and consumer goods designed for human use, and within the air we breathe, each providing an entry route for microplastics to enter the human body. Recently, microplastic particles have been detected in a variety of human tissue samples (e.g., lung tissue). …

Single-Atom Catalysts For Electrochemical Energy Conversion: Copper Single-Atom Catalyst For Oxygen Reduction Reaction And Quantification Of Site Density By Co Stripping Voltammetry, Dawatage Perera

Theses and Dissertations--Chemistry

Fuel cells are considered a promising technology for achieving cleaner and more sustainable energy production and utilization. However, one of the current major challenges is the economic viability associated with the extensive use of Pt group metal (PGM) catalysts, particularly on the cathode side. Therefore, non-PGM single-atom catalysts (SACs) have received considerable attention as alternatives for PGM catalysts in the oxygen reduction reaction (ORR), which occurs at the cathode of the fuel cell. Among various SAC structures, the non-PGM/nitrogen-doped carbon-based structure (M-N-C) stands out for its excellent ORR performance.

Chapter 2 illustrates the use of copper metal in place of …

Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye

Theses and Dissertations--Chemistry

Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs, cancer continues to be a leading cause of death in the United States. Metallodrugs, especially Au complexes, have played a prominent role in the search for the next generation of chemotherapeutic agents. Herein, I report on the synthetic strategies towards the rational design of stable Au (Au)-based agents, study their reactivity in biological environment, and offer insights into the cytotoxic mechanism of action in cancer. Chemotherapeutic Au compounds exist mainly in +I or +III oxidation states. Repurposing of the Au(I) FDA approved auranofin for the treatment of diseases …

Synthesis, Functionalization, And Application Of Polymeric Membrane Blends Of Polysulfone, Poly-Ether Ether-Ketone, And Natural Fiber Additive Biochar For Optimal Water Treatment., Abelline Katusiime Fionah

Theses and Dissertations--Chemistry

According to the Center for disease control (CDC), an estimated 1.7 to 2.2 million persons die from waterborne diseases annually. The majority of individuals dying from diseases resulting from unsafe drinking water, such as diarrhea and gastroenteritis, are children. This has in turn created a global water crisis. Different methods have been developed to treat contaminated water in response to the global water crisis such as adsorption, filtration, ozonolysis, catalysis, etc. Of the methods available, filtration via polymeric membranes has been one of the most successfully applied. A membrane is a thin semi-permeable barrier (often made of a polymer) used …

Investigating Dynamics Of Electron Transfer Flavoprotein And Its Partner Flavodoxin Via Small Angle Neutron Scattering And Fluorine Nmr, Sharique Ahmad Khan

Theses and Dissertations--Chemistry

Anaerobic bacteria and archaea thrive in seemingly inhospitable environments because they are extremely energy efficient. Their capacity to fully utilize electrochemical energy is based in large part on their ability to conduct electron transfer bifurcation ('bifurcation') at strongly reducing potentials, thereby producing extremely potent reducing agents able to fix nitrogen and make molecular hydrogen. This chemistry is made possible by the use of a flavin as the site of bifurcation, supported by a specialized protein environment and mechanisms that control the flow of individual electrons.

Bifurcating electron transfer flavoproteins (Bf-ETFs) are versatile protein modules that provide the bifurcating capability associated …

How Saudi Undergraduate Students Perceive Teacher Support, Basic Psychological Needs, And Academic Motivation, Anas M. Alhudib

Graduate Research Theses & Dissertations

This dissertation examines the Saudi undergraduate educational environment, exploring relationships among teacher support, basic psychological needs satisfaction and frustration, academic motivation, and GPA. The study investigates whether basic psychological needs mediate the relationship between teacher support and academic motivation, utilizing a structural equation model with 312 Saudi undergraduate students. The findings reveal a positive relationship between teacher support and basic psychological need satisfaction, influencing academic motivation. Interestingly, GPA did not correlate with other variables. Various models were tested, resulting in two sets of models that underscore the significant role of basic psychological needs as mediators in shaping the relationship between …

The Relationship Of Intolerance Of Uncertainty And Inferential Confusion To Obsessive-Compulsive Symptoms In A Nonclinical Sample, Fiona Christina Ball

Graduate Research Theses & Dissertations

Intolerance of uncertainty (IU) is a transdiagnostic cognitive vulnerability that has been linked to obsessive-compulsive (OC) and generalized anxiety (GA) symptoms. Inferential confusion (IC) refers to dysfunctional reasoning which overvalues imagined possibilities and devalues sensory information. The inference-based approach (IBA) proposes that IC generates obsessional doubt which leads to OC symptoms. Conceptually, IU and IC both involve the existence of multiple possibilities, and the limits of knowledge. No prior research has studied these constructs together. The current study sought to examine the relationships among IU, IC, and OC symptoms in a nonclinical sample. IC was explored as a potential condition …

Hunting Types In North American Eocene And Oligocene Carnivores And Implications For Nimravid Extinction, Miguel Andres Castellanos

Graduate Research Theses & Dissertations

The late Eocene and Oligocene is traditionally seen as a time of great climactic shift, with open habitats beginning to appear and forests receding. This time period saw both the diversification and subsequent extinction of North American nimravids. The causes of the extinction of this early sabertooth group in the Arikareean remain unclear. One possibility for their decline is that nimravids were competitively disadvantaged in open habitats relative to contemporary, possibly more cursorial caniform predators. Here I analyze and compare the hunting styles of Eocene and Oligocene predators in correlation with their ecological implications via discriminant function analysis of the …

The Role Of Osaa Gene In Aspergillus Fumigatus Development, Secondary Metabolism And Virulence., Apoorva Dabholkar

Graduate Research Theses & Dissertations

Aspergillus fumigatus is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. Deletion of the osaA gene resulted in colony growth reduction. Conidiation is also influenced by osaA; both osaA deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of osaA are necessary for expression of the conidiation regulatory genes brlA, abaA and wetA. In addition, osaA is necessary for normal cell wall integrity. Furthermore, deletion of osaA resulted in a reduction in the ability of …

Microwave Simulations Of A Beam Position Monitor And Circuit Designs Assisting Its Beam Testing, Marc Jacob Crowell

Graduate Research Theses & Dissertations

Beam position monitors (BPMs) are non-destructive diagnostic devices widely used in particle accelerators. I will first introduce the need for precision beam position measurement in particle accelerators, and then provide an overview of various types of BPMs. For the first part of my work, I focus on the design and simulation of a button-BPM. Microwave and wakefield simulations were performed to characterize the output signals. Such a design could find a potential application at the Argonne Wakefield Accelerator (AWA) at the Argonne National Laboratory. Although no BPMs have been fabricated to this date, a future beam experiment will be needed …