Digital Commons Network^™

Bridging Relational And Institutional Accountability: A Mixed Methods Study Of Implementing Sámi Ethical Research Guidelines In Finland’S Public Health Sector, Anna Charlotta Kihlstrom

Theses and Dissertations

The Ethical Guidelines for Research Involving Sámi People in Finland represent a critical step toward ethical Indigenous research; however, a gap remains between these principles and their implementation. This study responds to a research priority identified by the Sámi Social Affairs and Health Committee and examines how ethical research guidelines can be operationalized in the collaboration between the Sámi Parliament and the Finnish Institute for Health and Welfare (THL).

An exploratory sequential mixed methods design was employed, grounded in an Indigenous research paradigm and relational accountability. Extensive community engagement was carried out as a foundational part of the research methodology. …

Commissioning & Daily Qa Of Converted Linac For Electron Flash, Tomaj Javidtash

Theses and Dissertations

Ultra-high dose rate (FLASH) radiotherapy has demonstrated promising normal tissue sparing in preclinical studies; however, the lack of standardized dosimetry, commissioning, and quality assurance (QA) methodologies remains a major barrier to its reproducible and safe implementation. In particular, conventional clinical commissioning and QA protocols are not directly applicable at FLASH dose rates due to challenges associated with detector response, dose-per-pulse effects, and beam control limitations.

This thesis presents the commissioning of a converted Varian 21EX linear accelerator for electron FLASH operation within the Division of Medical Physics at the Virginia Commonwealth University (VCU) Department of Radiation Oncology. Comprehensive beam characterization …

Mitochondrial Insoluble Aggregates In Aging And Alzheimer’S Disease Models: Cross-Species Proteomic Integration, Identification Of Conserved Candidates, And Pharmacological Disruption Of Eef-2 Interactions, Sonu Pahal

Theses and Dissertations

Protein aggregation within mitochondria emerges early in both aging and Alzheimer’s disease (AD) and contributes to progressive loss of proteostasis. Insoluble mitochondrial aggregate fractions from Caenorhabditis elegans revealed extensive enrichment of metabolic and translational proteins that also appear in human Alzheimer hippocampal aggregates. Comparative analysis across age and genotype identified a conserved subset of aggregation-prone proteins, several of which cluster around elongation factor 2 (eEF-2), a regulator of ribosomal translocation and energy coupling. Cross-species integration defined a network in which eEF-2 links chaperones, metabolic enzymes, and RNA-binding proteins that co-aggregate in both human Alzheimer material and nematode models. Functional tests …

Acute Exposure Of American Oyster (Crassostrea Virginica) To Selected Antidepressant Drug: Histological, Biochemical, And Immunohistochemical Assessments, Md. Faisal Amin

Theses and Dissertations

The rapid increase in pharmaceutical use has brought significant health benefits to humans. Studies have shown that many pharmaceuticals, such as antidepressants, are often detected in surface waters, groundwater, and even drinking water. These pharmaceuticals in aquatic environments threaten marine life seriously. Marine bivalves are vital source of seafood for people worldwide. In this study, we examined the effects of short-term exposure to fluoxetine, an antidepressant used to treat depression, at low (0.5 μg/L) and high (5 μg/L) doses over a one-week period on American oysters (Crassostrea virginica) under controlled laboratory conditions. Histological analysis revealed atrophy in the gills and …

The Social Standing Versus The Mind Standing Of Older Adults In Egypt: Cross-Sectional Analysis Of The Relationship Between Social Capital And Cognitive Functions, Shaza H. Shinaishen Dr

Theses and Dissertations

Introduction: Egypt's population, much like that of other countries, is expected to age considerably over the course of the coming decades. Although biological and socioeconomic predictors of cognitive function have been studied widely, personal level social capital remains unexplored, especially in LMICs.

Purpose: This study primarily investigates the relationship between individual social capital and cognitive functioning among older adults aged 65 years and older in Egypt using the structural and cognitive components of social capital, including group membership, civic engagements, and caregiving roles.

Methods: A cross-sectional survey on 363 older individuals in different geographical and demographic segments of Egypt using …

Fountain, Sadaf Azadehfar

Theses and Dissertations

This thesis investigates the intersections of water, power, identity, and architecture through the lens of colonial and postcolonial landscapes, focusing particularly on Persian gardens and fountain sculptures. Drawing on historical, cultural, and symbolic frameworks, the study explores how water systems embody both practical and spiritual roles, positioning water as a force of control, resistance, and regeneration. Central to this work are analyses of arches and garden designs, which serve as architectural metaphors for cosmic harmony, community gathering, and contested space. Through a combination of visual analysis, historical research, and personal artistic practice—including ceramic sculptures and multimedia installations—this thesis traces the …

Toxiverse: An Online Comprehensive Chemical Profiling, Modeling, And Data Analysis Platform, Yitao Shen

Theses and Dissertations

Massive chemical data is now publicly available through publications and various online databases. However, most online databases only provide data unsuitable for modeling purposes and limited machine learning (ML) modeling for those data. As a public chemical toxicity evaluation tool to resolve these issues, the Toxicology Universe (ToxiVerse) portal hosts curated chemical structures and toxicological/pharmaceutical data of 26,000 compounds which can be used directly for modeling purposes. Furthermore, users can upload chemical datasets to extract all involved bioassays for compounds inside as biological profiles. ToxiVerse also features automatic QSAR modeling of uploaded datasets using multiple chemical descriptors and algorithms provided …

Establishing A Conventional Linac-Based Electron Flash Beam, Justin Defrancisco

Theses and Dissertations

Problems: A rediscovered radiotherapy technique, FLASH, involves increasing the dose rate to >40 Gy/s. For a given dose, FLASH is shown to decrease the normal tissue complication probability without affecting the tumor control probability. More preclinical studies are necessary to confirm and enable these desirable properties on humans. Current preclinical investigations have diverse constraints, requiring FLASH apparatuses with flexible parameters and accurate control. However, there are limited FLASH platforms available, the existing ones are costly. Our institution is not in possession of any such infrastructure. Even if available, dosimetry and beam control in FLASH are extremely lacking. There is …

Inorganic Arsenite [I-As (Iii)] Represses Human Renal Progenitor Cell Characteristics And Induces Neoplastic-Like Transformation, Md Ehsanul Haque

Theses and Dissertations

Studies on populations exposed to inorganic arsenic (iAs) have shown an association between this particular exposure and the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to long-term alterations that might lead to CKD or RCC. This study’s hypothesis is that renal exposure to iAs might alter the renal cells responsible for the repair and regeneration of nephrons damaged by iAs exposure or other renal toxicants. The kidney possesses a minority epithelial cell population that co-express PROM1 and CD24 that …

Discovering Therapeutic Strategies In Colorectal Cancer Via Synthetic Lethal Genetic Screens On Patient-Derived Organoid Models, Sana Khalili

Theses and Dissertations

Precision medicine is a revolutionary approach of targeting genetic alterations that are present only in tumor cells to find vulnerabilities that can be targeted with therapy. Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens can reveal all genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs.

In this dissertation, I comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. I identified all somatic mutations, all expressed genes, and conducted a genome-wide CRISPR dropout screen to elucidate …

Using Phylogenomics And Environmental Metabarcoding To Understand The Distribution And Evolutionary Histories Of Amoebae, Robert E. Jones

Theses and Dissertations

Protists are defined as eukaryotic organisms that are not animals, land plants, or fungi and make up the vast majority of eukaryotic diversity. Unfortunately, they are often overlooked and under sampled. Some rationales behind this are that they are often microscopic, most rarely the cause of human disease, and are often difficult to get into culture. Molecular phylogenetics has revolutionized our understanding of the evolutionary history of eukaryotes and without a clear picture of protist evolution our understanding would be severely hindered. Phylofisher is an easy-to-use phylogenomic software package, with an accompanying database and various utilities, intended for deep phylogenomic …

Investigating The Protein Interactome Of Escherichia Coli To Understand Metabolic Regulation When Proteins Bind: A Systems Biology Study., Shomeek Chowdhury

Theses and Dissertations

Proteins bind other proteins and work together as machines to perform many biological functions. Metabolic enzymes governing the life-sustaining metabolic reactions and therefore, metabolism are proteins which also binds other proteins. In this dissertation work, I have explored proteins when they interact with metabolic enzymes, play any role in regulating the cell’s metabolism. I study this phenomenon in Escherichia coli whose protein-protein interaction data is readily available in public databases with proper reference to the experimental study. Another good reason is the predictions we make in this computational study can be tested and validated in E. coli as it is …

Monte-Carlo Method For Identifying Aberrantly Expressed Genes In Cancer, Matthew M. Beltran

Theses and Dissertations

Gene expression provides insight into the functional variations on the cellular level that shape biological phenomena. Several recent sequencing technologies have produced an abundance of expression profiles spurring entirely new disciplines of biological study. With this myriad of data, the new task is deciding how to assess and extract meaningful insights. Identifying genes with expression changes in disease conditions is often the first step in finding potential biomarkers for diagnosis, and targets for pharmaceutical treatments. Parametric statistical tests at the individual gene level have been the conventional approach for finding differentially expressed genes. These tests exhibit high statistical power but …

The Development Of An Effective Synthetic Pathway To The Hiv Protease Inhibitor Darunavir And Its Structural Derivatives For Sar Studies Via An Asymmetric Glycolate Aldol Addition Reaction Approach, Emmanuel Ayim

Theses and Dissertations

The Centers for disease control and Prevention (CDC) published an article describing the disease that would later become known as HIV/AIDS in 1981. There were no treatments for this new disease, and by the time patients began exhibiting detectable symptoms, it would be too late to provide any meaningful treatments. Through the efforts made by the scientific community and social activism, new classes of drugs appeared for the treatment of this disease. These drugs are highly effective when combined with other therapeutic agents that suppress the proliferation of the virus. These combined therapies have helped alleviate the previously insurmountable risks …

Developing Microfluidic Devices For Biomolecule Analysis, Jacob Brent Nielsen

Theses and Dissertations

Microfluidics can take laboratory processes and miniaturize them, which led to the term lab-on-a-chip. Microfluidic devices are fabricated with a variety of materials and methods, each offering distinct advantages for bioanalysis. This dissertation describes two methods to create these devices, with the use of four different materials to achieve different assay needs. In the first application in this dissertation, hot-embossed cyclic olefin copolymer was used to create microdevices to electrophoretically separate seven preterm birth biomarkers. One biomarker, thrombin-antithrombin III, cannot be purchased commercially so I developed methods for its assembly in the lab. Dot blots and mass spectrometry were used …

Mutations In Lamin And How It Causes Multiple Tissue-Specific Disorders, Bismark Acquah

Theses and Dissertations

Lamins are the major components of the nuclear lamina where they provide a platform for the binding of proteins to the chromatin and confer mechanical stability (Dittmer and Misteli.,2011). Mutations in the human LMNA gene result in at least 15 distinct disorders ranging from muscular dystrophies to neurological disorders to lipodystrophies (Vytopil et al.,2003). Interestingly, some mutant forms of lamin protein aggregate, which may be toxic to the cells. However, it is unknown how specific mutations in lamin give rise to tissue-specific disease. I hypothesize that certain tissues are susceptible to specific lamin mutations due to the inability of tissue-specific …

Design And Synthesis Of Donor-Acceptor-Donor Xanthene-Based Near Infrared I And Shortwave Infrared (Swir) Dyes For Biological Imaging, Chathuranga Rathnamalala

Theses and Dissertations

Small molecule organic dyes with absorption and emission in the near infrared region (NIR) attracted much attention for various applications such as dye sensitized solar cells, fluorescent guided surgery, stimuli responsive bioimaging and photodynamic therapy. Dyes with high absorption and emission in the NIR region are beneficial for stimuli responsive bioimaging due to the deeper penetration of NIR light, less cell damage, high resolution, and low background autofluorescence from biomolecules. Of the many small molecule dyes, xanthene-based dyes exhibit outstanding photophysical properties and good stimuli response for use in bioimaging applications. However, absorption and emission of the xanthene dyes lie …

Developing Genotypic And Phenotypic Systems For Early Analysis Of Drug-Resistant Bacteria, Yesman Akuoko

Theses and Dissertations

Antimicrobial resistance in bacteria is a global health challenge with a projected fallout of 10 million deaths annually and cumulative costs of over 1 trillion dollars by 2050. The currently available tools exploited in the detection of bacteria or their DNA can be expensive, time inefficient, or lack multiplex capabilities among others. The research work highlighted in this dissertation advances techniques employed in the phenotypic or genotypic detection of bacteria and their DNA. In this dissertation, I present polymethyl methacrylate-pressure sensitive adhesive microfluidic platforms developed using a time-efficient, inexpensive fabrication technique. Microfluidic devices were then equipped with functionalized monoliths and …

Coordination Environment And Thermodynamics Of Colloidal Quantum Dots In Polar Solvents, Nuwanthaka Prasad Jayaweera Millaniyage

Theses and Dissertations

Colloidal semiconductor quantum dots (QDs) have been extensively investigated due to their attractive properties such as size-tunable absorption and emission spectra, large molar extinction coefficients, and significant photostability. These properties make them promising candidates for optoelectronic, photocatalytic, and biomedical applications. Common synthetic procedures of QDs produce nanocrystals capped with long-chain fatty acid derivatives which are stabilized in high boiling point solvents. Especially for bioimaging applications, the exchange of these native hydrophobic ligands with hydrophilic ligands should be performed, while preserving the smaller hydrodynamic radius. The coordination environment and thermodynamic parameters of the ligand exchanges should be carefully investigated to engineer …

Method Development Biological Agent Personal Decontamination Effectiveness For Airman Battle Uniform Fabric Material: Ms2 Bacteriophage, Alisha Helm

Theses and Dissertations

This article presents a study that investigates the effectiveness of a common decontamination (decon) strategy used by Airmen in the United States Air Force who may find themselves in a densely populated area during an emergency evacuation. Ultimately, this study addresses the following questions: Is there a significant difference in the number of viral particles being re-aerosolized before and after the applied decon strategy, and is this difference significant enough to consider the decon strategy effective? The study entails using MS2 bacteriophage to contaminate swatches of Airman Battle Uniform (ABU) fabric. Swatches were secured to a vortex centered in the …

Civilian And Military Civil Engineer Mission In The Space Domain, Linda E. Kuster

Theses and Dissertations

Military and civil interest in space-based operations has increased dramatically in recent years due to the discovery of life sustaining properties such as water on Mars and advancements in cyber technology. Civilian sector discussions and research have centered on the establishment of permanent extraterrestrial infrastructure, while discussions from the military perspective have focused on providing reliable, resilient infrastructure, capable of withstanding cyber-based and kinetic attacks. Both perspectives account for known threats and sustainment methods required to ensure success in the space domain. With the existence of threats for the military and civilian missions, civil engineers will undoubtedly be critical to …

Effects Of Date Seed (Phoenix Dactylifera) Extract In An Animal Model Of Diabetes Mellitus, Sara Refaat

Theses and Dissertations

Diabetes mellitus is a chronic illness and a global epidemic. The commercial diabetic medicines available are expensive and have several adverse effects. Alternative natural products are still being sought for. Date seeds ( Phoenix dactylifera) are either thrown away as garbage or utilized as animal feed. The use of seed extract as an alternative therapy for diabetes offers a cost-effective and all-natural method for managing the disease. Methods Sprague dawley rats were randomly distributed into groups with a sample size of 4 rats per group. Date seed powder was boiled producing a 10% date seed extract which was administered in …

Insight Into Eleutherodactylus Coqui Resilience And Anuran Hypoxia Tolerance Utilizing Pincho, Randy Ortiz

Theses and Dissertations

The onset of high-throughput RNA-sequencing (RNA-seq) technology allowed research into transcriptomics to accelerate exponentially aided by the rapid advancement of bioinformatic pipelines. The Pincho workflow, my first research endeavor, is a transcriptomic workflow developed to create an avenue of high-quality reconstructions from RNA-seq data. High-quality reconstruction standards entail longer transcripts, more complete transcripts, and more raw data utilization. We have discovered an ideal trio of assemblers between transABySS, rnaSPAdes and TransLiG that would best reconstruct next-generation sequencing data according to these standards. We utilized Pincho to drive two distinct experiments: (1) exploring the genetic basis for the successful invasion of …

The Type Iv Pilus Secretin Bfpb: Structural Analysis And Binding Interactions, Janay I. Little

Theses and Dissertations

Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. The type IV pilus (T4P) of EPEC, known as the bundle-forming pilus (BFP), plays an important role in EPEC pathogenesis. T4Ps are a family of surface appendages that are important for adhesion, colonization, biofilm formation, virulence, twitching motility and many other functions. One essential component of the BFP system is the secretin, BfpB. Secretins are a large family of integral outer membrane proteins found in T4Ps as well as type II and type III secretion systems, and filamentous phages. Details of the secretin structure have been limited to the overall …

Understanding The Ahupua'a: Using Remote Sensing To Measure Upland Erosion And Evaluate Coral Reef Structure, Logan Kalaiwaipono Ellis

Theses and Dissertations

Under ever intensifying pressures from land use, climate change, and erosion, tropical islands are among the most vulnerable systems in the world. Terrestrial systems are weakened by intensifying land use patterns, the weakening of which is highlighted when high intensity rainfall events erode sediment and leads to sediment deposition on the marine system. The deposition of sediment on the marine system is a major stressor that can lead to weakened coral reefs and a decrease in marine resources commonly gathered for food. These interactions have led to the emergence of biocultural resource management strategies, one of which is the ahupua'a …

Fabrication And Characterization Of Force Spun Polymeric Nanofiber For Drug Delivery And Tissue Engineering Applications, Salahuddin Ahmed

Theses and Dissertations

This study focuses on the development and characterization of polymeric nanofiber for drug delivery and tissue engineering applications. In this study, poly(lactic-co-glycolic) acid (PLGA), Poly-vinyl alcohol (PVA), and Pullulan(PL) were used as the base polymers to develop the nanofiber. Bioactive components Oleanolic acid(OA), Oxymatrine(OM), and Salvianolic Acid(SA) were incorporated in PLGA, PVA, and PL, respectively, via solution mixing. The nano fiber systems were developed using the Forcespinning® method. Morphological, thermo-physical, and biological properties of the fiber mats were analyzed. The composite fiber system containing OA showed a very high drug loading efficiency. The composite fiber system containing high concentration of …

Synthesis Of Bioactive Heterocycles, Shaila Akter Shetu

Theses and Dissertations

The Discovery of a variety of heterocyclic drugs for the treatment of cancer and other diseases (e.g, neglected tropical diseases) is a medical breakthrough and inspiring for the research community as a whole. A wide range of natural, semi-synthetic, and synthetic anticancer drugs are synthesized using various methods. Among them, β -lactams stand out as a novel class of antibiotics that has different types of biological as well as anti-cancer properties. β -lactam has become a premier and active research subject towards the development of revolutionary anti-cancer drugs. In recent years, a large amount of investigations have been done to …

Importance Of Light Activation For Plant Cryptochrome And Antibacterial Drug Delivery Strategies, Merfat Ahmed Hammad

Theses and Dissertations

The goal of this project is to investigate the benefits of applying light in different systems. In the first part, the magnetoreception process that occurs in the light activated cryptochrome of Arabidopsis Thaliana was investigated. In the second part, photo-carbon monoxide releasing molecules (photo-CORMs) were investigated for their antibacterial effect to develop biomedical strategies. Overall, this has been achieved in three different studies. The first study investigated if the forward lightdriven reaction is involved in the magnetoreception process or not in cryptochrome (CRY). To accomplish this, the plant seedlings were tested for 90 minutes as follows: 5 minutes in the …

Changes In The Regulation Of The Unfolded Protein Response During Aging In Peromyscus, Elham Soltanmohammadi

Theses and Dissertations

Endoplasmic reticulum (ER) stress has been linked to various metabolic pathologies, neurodegeneration, and aging. Although various mechanistic aspects of the resulting unfolded protein response (UPR) have been elucidated, its regulation in genetically diverse populations remains elusive. In the present study we evaluated the expression of chaperones BiP/GRP78, GRP94 and calnexin (CANX) in the lungs, liver, and brain of 7 months old and 2–3 years old outbred deer mice P. maniculatus and P. leucopus. Chaperones’ _expression was highly variable between species, tissues and ages suggesting that levels of expression of individual chaperones do not change consistently during aging. Despite this variation, …

Synthesis And Anticancer Evaluation Of Novel Pyrazolo[1,5-A]Pyrimidines: Discovery Of A Novel Lead Compound With Selective Activities Against Vps34 And Jak1-Jh2 Pseudokinase, Reuben Dass

Theses and Dissertations

A library of 25 novel 3,6-disubstituted and 3-substituted pyrazolo[1,5-a]pyrimidines were synthesized using a microwave chemical reactor in 3 steps with a total reaction time of 1 hour. The products were obtained in good to excellent yields (20-93%, ave. = 62%). The synthesis began with the reaction of aryl acetonitriles with dimethylformamide-dimethylacetal (120C, 20 min), followed by treatment of the resulting 2-arylacrylonitrile with H2NNH2 • HBr (120C, 20 min). The intermediate 4-arylpyrazol-5-amine obtained was finally reacted with either 2-aryl-substituted malondialdehydes or 1,1,3,3-tetramethoxypropane (120C, 20 min) to give the final products. The products were either collected directly on a Buchner funnel or …