Digital Commons Network^™

Long-Term Efficacy And Safety Of Cardiac Genome Editing For Catecholaminergic Polymorphic Ventricular Tachycardia, Oliver M Moore, Yuriana Aguilar-Sanchez, Satadru K Lahiri, Mohit M Hulsurkar, J Alberto Navarro-Garcia, Tarah A Word, Joshua A Keefe, Dean Barazi, Elda M Munivez, Charles T Moore, Vaidya Parthasarathy, Jaysón Davidson, William R Lagor, So Hyun Park, Gang Bao, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model.

AIM: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for

METHODS …

Artificial Intelligence In Stock Analysis And Portfolio Building, Sean M. Lynch

Honors Theses and Capstones

The emergence of artificial intelligence (AI) investment analysts, often referred to as “robo-advisors”, has the potential to change traditional portfolio management. These systems access vast amounts of data and make portfolio management decisions and stock market predictions. In this study, I compared AI-generated portfolios with portfolios that were created manually. Surprisingly, the human-generated portfolios outperformed the AI portfolios. However, the prompt used in the AI application affects these results. The subset of AI portfolios that were created with specific objectives specified in the prompts outperformed those that were created with more generic prompts. Overall, this research sheds light on the …

Implementation Of The Dutch Biking System In The United States Subject: Portsmouth Nh, Linda K. Freeman

Honors Theses and Capstones

This thesis explores the feasibility of implementing the Dutch Biking System in the United States, focusing on Portsmouth NH as a potential candidate for such infrastructure development. By analyzing the history of bicycles, the Dutch biking system, and the American biking system, the study aims to establish the need for enhanced biking infrastructure in the U.S. The research outlines a comprehensive implementation plan based on cost considerations and project scope, with a long-term vision spanning several decades. Key stakeholders, including civil engineers, communications specialists, and data analysts, play crucial roles in designing, promoting, and evaluating the biking infrastructure. The study …

Working Memory And Math Skills In Children With And Without Adhd, Fatou Gaye, Nicole B. Groves, Elizabeth S.M. Chan, Alissa M. Cole, Emma M. Jaisle, Elia F. Soto, Michael J. Kofler

Department of Psychology Faculty Scholarship and Creative Works

Objective: Children with attention-deficit/hyperactivity disorder (ADHD) frequently demonstrate deficits in working memory and in multiple domains of math skills, including underdeveloped problem-solving and computation skills. The Baddeley model of working memory posits a multicomponent system, including a domain-general central executive and two domain-specific subsystems—phonological short-term memory and visuospatial short-term memory. Extant literature indicates a strong link between neurocognitive deficits in working/short-term memory and math skills; however, the extent to which each component of working/short-term memory may account for this relation is unclear. Method: The present study was the first to use bifactor (S·I-1) modeling to examine relations between each working/short-term …

Monitoring And Control Of Coal Dust Exposure Using Low-Cost Pm Sensors And Computational Fluid Dynamics, Nana Kobina Amoako Amoah

Doctoral Dissertations

"Overexposure to respirable coal mine dust has been linked to causing serious health problems including coal workers pneumoconiosis (CWP) and chronic massive fibrosis. The prevalence of these health problems has been on the increase since the 2000s due to increased exposure levels with roof bolter operators having the highest exposure levels. The currently used PDM3700 is too expensive, heavy and bulky which limits their use only for regulatory monitoring failing to measure miners’ personal exposure levels. Also, since roof bolter operators are more prone to elevated coal dust levels, the canopy air curtain (CAC) was developed to protect then high …

A Human-Centered Framework For Oncological Healthcare System Modeling Applied To Mobile Radiation Delivery, Alex Price

Doctoral Dissertations

"Healthcare systems engineering is challenging due to the complexity, geographic expansiveness, inertial properties, and the heterogeneous sub-systems, with varying vested interests. Additionally, humans comprise many of the forms and functions, and are independent, with resistance and uncertainty in their decision-making that adds complexity. Human-centered systems modeling approaches are therefore needed to capture this unique aspect of a healthcare system and to enhance understanding of emergent healthcare properties. This dissertation focuses on integrating systems modeling within healthcare and emphasizes the importance of incorporating human decision-making. Moreover, the incorporation of a human-centered approach yields particularly valuable insights into the decision-making processes that …

Modeling And Analysis Of Dc-Dc Converters For Power Distribution Networks Design, Junho Joo

Doctoral Dissertations

"Accurate modeling of power distribution networks (PDN) including voltage regulator module (VRM) is critical for high-performance digital systems including low- to high-power applications such as laptops and mobile platforms. As a consolidated end-to-end power source, PDN can be divided into several parts: the VRM to regulate the external voltage source, printed circuit board (PCB) PDN, package PDN, and on-chip PDN. A transient current drawn from the on-die circuitry will produce an instantaneous voltage drop at the bump. The time domain behavior of such a drop and the subsequent recovery is called voltage droop which is strongly associated with the VRM …

In-Depth Characterization Of The Selective Oxidation Products Of Hafnium Carbide, Jonathan Allen Scott

Doctoral Dissertations

"Materials capable of withstanding oxidative environments at temperatures >2000°C are necessary for hypersonic applications. Hafnium carbide (HfC) shows a combination of properties that lends itself toward these applications; however, its oxidation behavior is poorly understood. At 1300°C, HfC was found to oxidize via the following mechanism: 1) Initial oxidation of both C and Hf present in the system, 2) Formation of an interconnected pore network, whose size is related to the volume of gases being generated during the oxidation process, 3) Growth of the oxide scale to become sufficiently protective, 4) Formation of an initially amorphous “HfO₂C” at …

University Of New Hampshire Library Annual Report Fy 2023: Leading Change, University Of New Hampshire Library

Annual Reports and Statistics

No abstract provided.

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 …

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 …

Validation Of A Screening Tool For Sleep Apnea In Children, Brandon Khor

Theses and Dissertations

Objective: The aims of this study were to (1) determine the ability of a pediatric obstructive sleep apnea (POSA) questionnaire to identify high-risk patients through confirmation with an at-home sleep apnea test (HSAT) and (2) to evaluate the correlation between high-risk patients as identified by the questionnaire (PM-STOP-Bang) and an already validated POSA screening tool.

Methods: Orthodontic patients aged 12-17 who met the inclusion criteria were consecutively enrolled in the study (n=16). At the initial orthodontic appointment, the clinician filled out the PM-STOP-Bang questionnaire. Subsequently, participants were invited to complete a one-night HSAT (WatchPat, WP-Itamar-Medical, Caesarea, Israel), which recorded diagnostic …

The Relationship Between Material Circumstances And Primary Care Utilization After Enrollment In Virginia’S Medicaid Expansion, Hannah Shadowen

Theses and Dissertations

Health and health equity encompass not only healthcare but individual level material circumstances like food and housing, neighborhood level conditions like local consequences of residential segregation, and state and federal policies like Medicaid expansion. However, we are just beginning to understand how state level health insurance policy changes operate in the relationship between material circumstances, healthcare use, and health outcomes. This work focuses on newly enrolled Virginia Medicaid expansion members by using both claims data and survey data collected at the point individuals enrolled in Medicaid expansion and a year after Medicaid coverage.

Paper 1 asks if newly enrolled Medicaid …

Walleye (Sander Vitreus) Do Not Exhibit An Aggregative Predatory Response To Larval White Sturgeon (Acipenser Transmontanus) In The Upper Columbia River In Lake Roosevelt, Washington, Seth A. Barr

EWU Masters Thesis Collection

Seasonal prey abundance can drive predatory fishes to aggregate in areas of high prey density. This project aimed to determine whether Walleye (Sander vitreus) exhibit an aggregative predation response to larval White Sturgeon (Acipenser transmontanus) drifts in the Lake Roosevelt system which is a reservoir of the Columbia River in Washington State. Populations of sturgeon are threatened worldwide, and are in need of conservation research. Walleye are a popular nonnative piscivorous game fish that were accidentally or illegally introduced to Lake Roosevelt in the 1950’s. Walleye in this study were obtained by gillnetting during White Sturgeon pre-spawn, peak spawn, and …

Constitutional Liberalism Through Thick And Thin: Reflections On Frank Michelman’S Constitutional Essentials, James E. Fleming, Linda C. Mcclain

Faculty Scholarship

In his new book, Constitutional Essentials, Frank Michelman provides a splendid elaboration and defense of “the constitutional theory of political liberalism” implicit in John Rawls’s classic work, Political Liberalism. In this essay, we make some observations about what a difference 30 years makes, comparing the political and constitutional climate in which Rawls wrote and published Political Liberalism in 1993 with the climate in which Frank wrote and published this exegesis of it. We focus on (1) changes in our circumstances of pluralism, including the accentuation of polarization and unreasonable views, and (2) the simultaneous breakdown of trust in the Supreme …

Merppa: Middle East Review Of Public Policy And Administration., Laila El Baradei

Faculty Journal Articles

No abstract provided.

Interplay Of Antibody Responses To Closely Related Viruses And Autoimmunity, Chun-Yang Lin

Theses and Dissertations (ETD)

Antibodies produced by B cells are crucial for eliminating infectious pathogens and preventing secondary infection. However, antibodies may also bind to self-antigens and contribute to autoimmune disease. While pathogen infections have been associated with development of autoimmune diseases, the precise contributions of viral infections to autoimmunity remain elusive. The presence of autoreactive antibodies is associated with an increased risk of developing autoimmune disease. Thus, analyzing the impact of viral infection and vaccination on the development of autoreactive antibodies will provide essential insight into mechanisms that contribute to autoimmune disease.

Examining How Non-Antifungal Medications Impact Host-Fungal Interactions, Parker Ryan Reitler

Theses and Dissertations (ETD)

Invasive fungal infections (IFIs) are estimated to kill 1.5 million people each year with mortality rates remaining high (around 30-70%), despite the availability of three major classes of antifungal drugs. Furthermore, millions more suffer debilitating infections of the mucosal membranes or destructive subcutaneous mycoses. One of the most common IFIs is invasive candidiasis, mostly commonly caused by Candida albicans infections, with mortality rates of approximately 30%. In addition, the population of susceptible individuals and the incidences of both mucosal and systemic mycoses continue to rise due to the widespread use of broad-spectrum antibacterial agents, cancer chemotherapies, and the immune suppressive …

Anatomical And Physiological Characterization Of Striatal Activation Of The Cerebral Cortex, Yuhan Wang

Theses and Dissertations (ETD)

Purpose. The striatum receives excitatory glutamatergic input from nearly all parts of the cerebral cortex, and its output is delivered by direct pathway medium spiny neurons (dMSNs) expressing D1 type dopamine (DA) receptors (D1Rs) and indirect pathway MSNs (iMSNs) expressing D2 DA receptors (D2Rs). Loss of DA results in the imbalance between the activities of dMSNs and iMSNs in Parkinson’s disease (PD), leading to ab-normal interactions between the cerebral cortex and striatum. Thus, understanding the inter-actions between the cortex and striatum is important. The monosynaptic corticostriatal cir-cuit has been extensively studied. In contrast, due to the poly-synaptic nature of the …

The Impact Of Candida Albicans Glycogen On Fitness, Virulence And Host Response, Jian Miao

Theses and Dissertations (ETD)

Candida albicans is an opportunistic human fungal pathogen that presents in healthy persons colonizing the oropharyngeal, esophageal, and gastrointestinal mucosa. This polymorphic fungal pathogen remains a leading cause of both invasive and superficial mycoses. C. albicans can cause oropharyngeal candidiasis (OPC) and disseminated candidiasis when normal host immunity is disturbed, while also causing vulvovaginal candidiasis (VVC) in healthy women. Adaptation to different host niches requires rapid and coordinated changes in Candida metabolism and physiology to cope with host immune surveillance and to counteract host-imposed constraints such as glucose limitation. Although largely unexplored in C. albicans, the glycogen metabolism pathway is …

Improving Health Outcomes In Children And Adolescents With Asthma, Elizabeth Kate Coffey Moore

Theses and Dissertations (ETD)

Asthma is among the most prevalent chronic illnesses found in the United States, affecting millions of people under the age of 18 each year. The disease burden for affected children, adolescents, their families, and the healthcare system is immense. Finding ways to mitigate its impact is critical to improving the lives of affected children, adolescents, and their families. The three chapters included in this dissertation aimed to document the asthma triggers that children and adolescents are exposed to and strategies for reducing them and to demonstrate using Imogene King’s conceptual framework to guide nursing practice to care for and nursing …

Ftsk Regulates The Assembly Of The Division Machinery In The Ftsz-Less Chlamydia Trachomatis, Mckenna Katherine Harpring

Theses and Dissertations (ETD)

In evolving to obligate intracellular dependence, Chlamydia trachomatis serovar L2 (Ct), has eliminated several gene products essential for cell division in most other bacteria, including FtsZ, the central coordinator of divisome assembly. In the absence of FtsZ, we show that divisome assembly in Ct is initiated by FtsK, a chromosomal translocase. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge …

The Future Of Building: The Potential Impacts Of 3d Printing Within The Construction Industry, Alyssa Morrison

Honors Theses and Capstones

This research investigates the expanding practice of 3D printing in construction, focusing on its potential impacts and challenges it will face within the industry. Emphasizing both its sustainability and cost-saving benefits, this paper examines how 3D printing could potentially revolutionize traditional building methods. The ability to decrease greenhouse gas emissions, address the global housing shortage, and reduce material waste are addressed. Through interviews with industry professionals, as well as a thorough literature review, the research explores the factors driving interest and investment in 3D printing technology. Additionally, it analyzes common misconceptions regarding 3D printed structures and pinpoints areas for further …

Alpaca Assisted Activities In The New England Alpaca Industry: A Possible Solution To Farm Profitability And Participant Mental Health, Ashley Michele Masse

Honors Theses and Capstones

The high operating costs of the New England alpaca industry were putting the majority of alpaca farmers in this region in a state of financial loss. On a separate note, American communities were experiencing a prevalence of anxiety and depression. What if a single solution could help improve the outcome of both these challenges that seem to have little to do with each other? Alpaca Animal Assisted Activities (alpaca AAAs) was a possible solution. This study explored New England alpaca farm profitability and alpaca AAAs in a way no other research study has done before. A Farmer Survey was mailed …

How World’S Fairs Conceive Of The Future During Times Of Turmoil, Mikayla Lauren Tilden

Honors Theses and Capstones

During the 20th century, the theme of World's Fairs in the United States broke away from previous World Exposition traditions and centered around concepts of progress and the future. This thesis investigates the conception of the future and the evolution of the World's Fair themes during times of economic and political turmoil at the Chicago 1933–1934, New York 1939­­­–1940, and Seattle 1962 World’s Fairs. In each instance, the fair’s organizers felt the need to respond to world events, which caused them to shift their initial focus from a local attempt to increase prosperity, to a national commentary on global conditions.

Table Of Contents

The Judges' Book

No abstract provided.

Foreword, Edward M. Chen

The Judges' Book

No abstract provided.

Administrative Law: In Search Of The Public Interest, Jodi L. Short

The Judges' Book

No abstract provided.

Corporate Law: Suing Spacs, Emily Strauss

The Judges' Book

No abstract provided.

Environmental Law: The Negotiable Implementation Of Environmental Law, Dave Owen

The Judges' Book

No abstract provided.