Digital Commons Network^™

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 …

Targeting Of Oncogenic Aaa-Atpase Trip13 Reduces Progression Of Pancreatic Ductal Adenocarcinoma, Farrukh Afaq, Sumit Agarwal, Prachi Bajpai, Sameer Al Diffalha, Hyung-Gyoon Kim, Shajan Peter, Moh'd Khushman, Subhash Chauhan, Priyabrata Mukherjee, Sooryanarayana Varambally, Upender Manne

School of Medicine Publications

Thyroid hormone receptor-interacting protein 13 (TRIP13) is involved in cancer progression, but its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. Thus, we assessed the expression, functional role, and mechanism of action of TRIP13 in PDAC. We further examined the efficacy of TRIP13 inhibitor, DCZ0415, alone or in combination with gemcitabine on malignant phenotypes, tumor progression, and immune response. We found that TRIP13 was overexpressed in human PDACs relative to corresponding normal pancreatic tissues. TRIP13 knockdown or treatment of PDAC cells with DCZ0415 reduced proliferation and colony formation, and induced G2/M cell cycle arrest and apoptosis. Additionally, TRIP13 knockdown …

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 …

Evaluation Of A Novel 3d-Printed Task Trainer For The Simulation Of Gynecological Procedures At A Medical Academic Center, Jami Monico, Karen S. Carlson

Manuscripts: Obstetrics & Gynecology

Introduction

Learning and mastering the performance of gynecological procedures in a secure and supervised simulation setting is important for learners, especially in the early phases of medical education. This project aims to assess the efficacy of an innovative gynecological task trainer for diverse simulation sessions. Following engagement with the task trainer, learners evaluated their experiences with a comprehensive questionnaire. The results of the survey were scientifically analyzed and interpreted.

Methods

The innovative gynecological task trainer was created with 3D-printed plastic, silicone, and a tabletop base. Learners engaged in simulations in which they performed gynecologic procedures using the task trainer. Subsequently, …

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 …

Longevity,Feeding Behavior, And Egg Production Of Adult House Flies (Musca Domestica) Provided With Potential Farm Foods, Anna Elise Grimenstein

Graduate Research Theses & Dissertations

House flies (Musca domestica) are cosmopolitan pests to both humans and livestock, and they can vector many diseases. House flies are especially associated with livestock facilities, as adult flies lay eggs in rotting organic matter such as manure. While it is understood that the diet an adult fly receives can affect biological parameters such as longevity and egg production, not much research has been done to address foods that are accessible to house flies in their natural habitat. The present study examined the longevity, feeding behavior, and egg production rates of adult house flies given different foods they would have …

A Wasteside Story: Establishment And Evolution Of A Wastewater Surveillance Lab, Through The Pandemic And Beyond, Syed Shahrukh Hyder

Graduate Research Theses & Dissertations

Wastewater based epidemiology is a fast growing and practical solution to monitor the spread of disease within a population. As the COVID-19 pandemic grounded the world to a standstill, methods to monitor its spread and prepare appropriate responses became vital to begin the return to normalcy. Such was the case in universities around the world where the campus and surrounding community were vital in fulfilling the educational mission in the face of a generational health crisis. The population in a midsize higher educational institute such as Northern Illinois University (NIU) is a broad mix of on-campus and off campus students, …

The Energetics Of Seasonality In Wild Diademed Sifaka (Propithecus Diadema): A Technical And Biological Validation Of Fecal Triiodothyronine Radioimmunassay, Casey Farmer

Graduate Research Theses & Dissertations

The energetic state of an animal has vital consequences for its fitness, but it can be difficult to detect through behavioral observations. The development of techniques to determine an animals’ energetic state non-invasively would allow conservation planners to rapidly assess the energy balance and conservation potential of individuals, groups, and populations. Thyroid hormones like triiodothyronine (T3) regulate and reflect metabolic state in mammals. T3 is a non-invasive biomarker that can be detected in feces and could potentially be used for this purpose. I perform the first validation of a commercially available T3 radioimmunoassay designed for humans on a wild strepsirrhine …

Assessing The Relationship Between Neighborhood Inequality And Stem Employment For Underrepresented Minorities With Stem Degrees, Brian P. Hurley

Graduate Research Theses & Dissertations

The purpose of this study is to assess whether there is a relationship between neighborhood inequality in which underrepresented minorities (URMs) with STEM degrees reside and their employment in STEM fields. The current study deploys an Intersectional Theory (IT) research framework and Bourdieu’s Theory of Practice to identify the influence of neighborhood capital on successful matriculation through the STEM pipeline as well as variables that elucidate latent inequities in the STEM pipeline which lead to unequal outcomes for URMs. Generalized Linear Multilevel Models (GLMMs) are used to answer the research questions where the individual variables of gender, race, and age …

An Exploration Of The Sense Of Belonging For African American Women Licensed Clinicians In A Voluntary Professional Counseling Organization, Raushanah Jackson

Graduate Research Theses & Dissertations

Due to historical oppression in academe, the voices of African American women have been excluded, or unjustifiably limited, in academic research and from mainstream psychological thought. This study was one aim at understanding the experiences of belonging of women of African American ancestry who were clinically licensed professional members in a volunteer member counseling organization. Centering African American women’s voices was used through a lens of critical race theory and Black Feminist Thought to illuminate the structural, representational, and sociopolitical barriers that African American women face. An Interpretive Phenomenological Analysis approach was used to center the voices of five licensed …

Pathology And Diagnosis In Inflammatory-Related Diseases: Covid-19 And Age-Related Macular Degeneration, Zane Russell Lacasse

Graduate Research Theses & Dissertations

Chronic inflammation and dysfunctional inflammatory responses are believed to be contributing factors to the severity of many diseases. Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it has been recognized that levels of inflammatory markers and the severity of coronavirus disease-2019 (COVID-19) cases are closely related. The work within this dissertation begins with establishing an alternative platform for the diagnosis of COVID-19 and explores ways to enhance the diagnostic utility of this platform. An alternative route for COVID-19 diagnosis was explored using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). The platform utilizes a non-invasive sampling technique …

Genomic Clustering And Comparative Analysis Of Sars-Cov-2 Variants And Subvariants In Year 2022, Fatemeh Nazaritiji

Graduate Research Theses & Dissertations

This study presents a bioinformatic analysis of SARS-CoV-2 genomes sampled in 2022, aimed at showing the genetic diversity and evolutionary patterns of the virus. A random selection of 1,000 genomes from a large collection of sequenced genomes was used to conduct an all-vs-all pairwise alignment, forming the basis for a genetic distance matrix utilizing thenumber of substitutions. This matrix served as a tool for clustering analysis, enabling the identification of distinct genomic variants and their relationships. Multidimensional Scaling (MDS) was employed to visualize the data in a two-dimensional space, revealing several distinct clusters that suggest the presence of diverse viral …

Mixed Mechanisms Of Multi-Site Phosphorylation, Suha Jayyousi Dajani

Graduate Research Theses & Dissertations

Multi-site phosphorylation is an important mechanism in cell biology that regulates protein function and activity. It also plays a critical role in a wide variety of cellular processes that control intra-cellular signaling. Studies on mono- and dual-site phosphorylation have been conducted theoretically and experimentally by researchers. However, there is little research on triple-site and multi-site mixed mechanism phosphorylation.

The aim of this research is to study and identify the number of positive steady states (multistationarity) in a mathematical model of a triple-site mixed mechanism, processive and distributive, phosphorylation network. This research is accomplished by means of ordinary differential equations, Jacobian …

On The Ground And From Above: A Multi-Factor Analysis Of The Direct And Indirect Drivers Of Tallgrass Prairie Small Mammal Communities, Erin Rowland-Schaefer

Graduate Research Theses & Dissertations

Tallgrass prairies are among the most globally threatened ecosystems, with only one percent of the historical extent remaining in Illinois. Prairie restoration is an essential strategy to preserve biodiversity and reestablish threatened species. Practitioners use management tools to shift the landscape context of prairie restoration sites, such as prescribed fire and land cover change. Managers can also impact the landscape connectivity and edge proximity of certain areas through the use of mowed driving lanes. The effects of these factors on small mammals, which are central in tallgrass prairie food webs and relevant to human health and restoration success, are not …

The Dna Double Stranded Break Damage Response Of U87 Gbm Cells Following Irradiation Treatment, Emma Louisa Planck

Graduate Research Theses & Dissertations

Glioblastoma Multiforme is one of the most aggressive forms of cancer and is becoming increasingly prevalent in the population, especially among young adults. An estimated 13,140 people in the United States will be diagnosed with GBM this year and an estimated 10,000 people in the United States will succumb to the disease. The 5-year survival for GBM patients is only 7.2% with a mean survival time of only 12-18 months. Even with subsequent chemotherapy and irradiation treatments GBM has a very high treatment resistance and has a recurrence rate of roughly 70%. Treatments such as radiation therapy induce lethal DNA …

Effort Of Reproducibility: Metrics, Methods, And Models To Navigate The Landscape Of Reproducible Research, Akhil Pandey Akella

Graduate Research Theses & Dissertations

Validating scientific claims is an elaborate process that involves researchers investing considerable time and effort to discover the validity of claims. It involves repeatability, reproducibility, and replicability, where each subsequent step requires increased effort and time. With the evolving nature of computational experiments and the exponential pace at which scientific publications are disseminated, researchers find it challenging to devote time, energy, and resources to assess claims made in papers of interest. Preemptive signals for reproducible effort can be helpful to researchers in filtering academic works of interest, thereby allowing them to adjust efforts based on need. Through this research, I …

How Students On A Healthcare Track Value Learning Communication Skills, Christina M. Cline

Graduate Research Theses & Dissertations

Communication is a critical component of effective healthcare. Students interested in going into healthcare fields require training to learn how to effectively communicate. These students have a need to learn communication skills. Understanding students’ value for learning these skills is necessary for increasing the motivation to learn. In this study, a mixed method approach was used to investigate the value that students on a healthcare track had for learning communication skills. Quantitative methods were used to develop a survey measuring student value and then evaluate students’ value when completing a communication skills activity in a gross human anatomy course. Qualitative …

Academic Grouping And School Sense Of Belonging: An Interpretive Phenomenological Analysis Of Middle School Student Voices, Kevin Cox

Graduate Research Theses & Dissertations

School sense of belonging is critical for students’ academic achievement and emotional well-being. The development of a sense of school belonging is influenced by direct and indirect factors within the school environment. Categorization into low and high achievement groups based on academics is a process largely outside the direct control of a student. This study employed an interpretive phenomenological analysis of interviews conducted with 17 seventh- and eighth-grade students about their belonging experience in a Midwestern public middle school. Experiences of students academically categorized as high, typical, or low achievers were compared and described in the context of three emergent …

Evaluation Of Conservation Strategies For Blanding’S Turtles (Emydoidea Blandingii), Callie Klatt Golba

Graduate Research Theses & Dissertations

Across the globe, biodiversity is threatened due to anthropogenic changes to the environment and large numbers of freshwater species, especially turtles, are facing population declines. Resources for conservation are limited, making empirically based conservation planning of utmost importance. Effective management strategies incorporate relevant biological information to outline specific and feasible actions that will mitigate the greatest threats to a species. Blanding’s Turtles (Emydoidea blandingii) are a long-lived, semi-aquatic, freshwater species that are classified as endangered in Illinois and internationally. As with other species of concern, Blanding’s Turtles are threatened by habitat loss, fragmentation, and degradation. They are also threatened by …

A Comparison Of Academic Achievement And Psychological Symptoms In Homeschooled And Traditionally Schooled Children: Accounting For Demographic And Family Characteristics, Lauren Elizabeth Hauck

Graduate Research Theses & Dissertations

The prevalence of homeschooling is increasing, especially in the aftermath of the COVID-19 pandemic. However, methodologically strong research examining how children's well-being may differ based on their schooling type (i.e., homeschooled vs. traditionally schooled) is rare. This study is a response to a call for advancing the methodological rigor and expanding our understanding of family contributions to differences between homeschooled and traditionally schooled children’s adjustment. Thus, the study aims to determine if differences between homeschooled and traditionally schooled (i.e., attending public school) children’s academic and emotional adjustment are present after accounting for both family demographic characteristics and parenting and home …