Digital Commons Network^™

Dynamics Of Karyotype Evolution, Elena Kuzmin, Toby M Baker, Peter Van Loo, Leon Glass

Faculty, Staff and Student Publications

In the evolution of species, the karyotype changes with a timescale of tens to hundreds of thousand years. In the development of cancer, the karyotype often is modified in cancerous cells over the lifetime of an individual. Characterizing these changes and understanding the mechanisms leading to them has been of interest in a broad range of disciplines including evolution, cytogenetics, and cancer genetics. A central issue relates to the relative roles of random vs deterministic mechanisms in shaping the changes. Although it is possible that all changes result from random events followed by selection, many results point to other non-random …

Modeling Acute Myocardial Infarction And Cardiac Fibrosis Using Human Induced Pluripotent Stem Cell-Derived Multi-Cellular Heart Organoids, Myeongjin Song, Da Bin Choi, Jeong Suk Im, Ye Na Song, Ji Hyun Kim, Hanbyeol Lee, Jieun An, Ami Kim, Hwan Choi, Joon-Chul Kim, Choongseong Han, Young Keul Jeon, Sung Joon Kim, Dong-Hun Woo

Faculty, Staff and Student Publications

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating …

Investigation Of Inherited Noncoding Genetic Variation Impacting The Pharmacogenomics Of Childhood Acute Lymphoblastic Leukemia Treatment, Kashi Raj Bhattarai, Robert J Mobley, Kelly R Barnett, Daniel C Ferguson, Baranda S Hansen, Jonathan D Diedrich, Brennan P Bergeron, Satoshi Yoshimura, Wenjian Yang, Kristine R Crews, Christopher S Manring, Elias Jabbour, Elisabeth Paietta, Mark R Litzow, Steven M Kornblau, Wendy Stock, Hiroto Inaba, Sima Jeha, Ching-Hon Pui, Cheng Cheng, Shondra M Pruett-Miller, Mary V Relling, Jun J Yang, William E Evans, Daniel Savic

Faculty, Staff and Student Publications

Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Jak2v617f Reversible Activation Shows Its Essential Requirement In Myeloproliferative Neoplasms, Andrew J Dunbar, Robert L Bowman, Young C Park, Kavi O'Connor, Franco Izzo, Robert M Myers, Abdul Karzai, Zachary Zaroogian, Won Jun Kim, Inés Fernández-Maestre, Michael R Waarts, Abbas Nazir, Wenbin Xiao, Tamara Codilupi, Max Brodsky, Mirko Farina, Louise Cai, Sheng F Cai, Benjamin Wang, Wenbin An, Julie L Yang, Shoron Mowla, Shira E Eisman, Amritha Varshini Hanasoge Somasundara, Jacob L Glass, Tanmay Mishra, Remie Houston, Emily Guzzardi, Anthony R Martinez Benitez, Aaron D Viny, Richard P Koche, Sara C Meyer, Dan A Landau, Ross L Levine

Faculty, Staff and Student Publications

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic …

Proton Therapy Mediates Dose Reductions To Brain Structures Associated With Cognition In Children With Medulloblastoma, Julianna Sienna, Lisa S Kahalley, Donald Mabbott, David Grosshans, Anna Theresa Santiago, Arnold Dela Cruz Paulino, Thomas E Merchant, Gohar S Manzar, Hitesh Dama, David C Hodgson, Murali Chintagumpala, Mehmet Fatih Okcu, William E Whitehead, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Uri Tabori, Julie M Bennett, Anirban Das, Tim Craig, Derek S Tsang

Faculty, Staff and Student Publications

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy.

Methods and materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores.

Results: The mean dose and dose to …

Survival Disparities In Non-Hispanic Black And White Cervical Cancer Patients Vary By Histology And Are Largely Explained By Modifiable Factors, Calen W Kucera, Nicole P Chappell, Chunqiao Tian, Michael T Richardson, Christopher M Tarney, Chad A Hamilton, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christine Rojas, Collin A Sitler, Lari Wenzel, Ann Klopp, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Timothy D O'Connor, Craig D Shriver, Nicholas W Bateman, Thomas P Conrads, Neil T Phippen, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

A Radiotherapy Community Data-Driven Approach To Determine Which Complexity Metrics Best Predict The Impact Of Atypical Tps Beam Modeling On Clinical Dose Calculation Accuracy, Fre'etta Mae Dayo Brooks, Mallory Carson Glenn, Victor Hernandez, Jordi Saez, Hunter Mehrens, Julianne Marie Pollard-Larkin, Rebecca Maureen Howell, Christine Burns Peterson, Christopher Lee Nelson, Catharine Helen Clark, Stephen Frasier Kry

Faculty, Staff and Student Publications

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy.

METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes …

Empowering Collaborative Application Development: A Robust Framework For Ad-Hoc Distributed Systems, Imran Abbas Khawaja, Kamran Abid, Uzma Farooq, Zaki Malik

Faculty Publications

The amalgamation of ubiquity, mobility, computing prowess, storage, and communication of the portable electronic devices including smartphones, wearable devices, tablets have significantly altered the fabric of human existence. The software applications for these mobile devices possess the capability to disseminate and receive information, thereby enable the development of applications that may execute in collaborative manner. However, in situations with ad-hoc connectivity unavailability of infrastructure and communication breakdown are common, which inhibit information sharing across the devices, and hence affect the applications running in the collaborative spaces. Further the applications developers face challenges while developing reliable collaborative applications that can seamlessly …

The Generational Identity Crisis: A Novel, Hankun Chen

Dartmouth College Master’s Theses

This thesis is a novel set in 2032 China, where people are experiencing huge social declines and identity crises, and additionally, a technology to digitize consciousness is gaining popularity. The protagonist of the novel lose contact with his friend in the digital world, and he receives an anonymous indestructible jar one day with a label that keeps changing to direct him to different locations. In his search for his friends and the secret of the jar, he realizes that the clues are all related to things he is familiar with from the old days. During that adventure, which occurs to …

Uc Transcript 2024-05-01, Northern Illinois University

University Council Archives

No abstract provided.

Innovations In Publicly Funded Workforce Training Programs, Chris Ackley

School of Professional Studies

This paper explores the aspects of the current public workforce system and detail persistent challenges as well as promising practices in the field from both Rhode Island and other locations. The author will present a series of recommendations for state and local leaders in the field as well as affiliated training providers and nonprofit practitioners. These proposals are designed to strengthen the overall system and create more opportunity for upward mobility, especially among individuals who have historically not had equitable access to postsecondary educational attainment which provides access to economic advancement.

The State Of Special Education In Virginia, Caroline R. Aramini

School of Professional Studies

This capstone research paper discusses the current state of special education in Virginia. Some of the problems faced by the state include a checkered history of noncompliance with federal mandates, cultural hindrances related to special educator attrition and retention, and resource constraints. A history of special education and disability in education in America is provided to better contextualize solutions found in the research. Recommendations are proposed to address deficiencies, including increased economic compensation for special educators and transformation of the school culture through different strategies. These suggestions are designed to improve the current issues and address the problematic patterns displayed …

Iraqi Education Past And Present: The Role Of Policymakers And Their Ideological Background, Hadi T. Pir

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The history of Iraqi education unmistakably illustrates how policymakers have consistently operated within the same worldview since 1920. Despite apparent differences among Iraqis in terms of race, religion, sect, geography, and social and tribal norms, a shared worldview has emerged, which I term the Traditional Iraqi Paradigm (TIP). This shared worldview comprises a set of interconnected postulates. The divergence among Iraqi groups lies not in the postulates themselves but in how they translate these postulates into actions and behaviors. These translations have become historical, institutional, and psychological aspects of reality contributing to the political, social, and educational differences, conflicts, and …

Improving Visual Inspection Skills In Special Education Teachers, George G. Toman

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The Conservative Dual Criteria (CDC) method is known to improve decision-making accuracy in users when interpreting graphed data. The effectiveness of this method with in-service special education teachers, however, has not been investigated. The present study examined the effects of a virtual training package designed to improve the data-based decision-making skills of in-service special education teachers. Specifically, the virtual training consisted of a training video on the CDC method, access to a decision-making guide, and a brief training assessment. Five in-service special education teachers received training in the CDC method via the online learning management system, Canvas. A multiple baseline …

Making Czech Art Song Accessible For Novice Singers, Rachel Jane Sweeney Green

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Czech art song is often overlooked by vocal instructors while assigning music for the novice singer. The repertoire of Czech art song is vast, yet seldom used in vocal studios in America. Though some consider the language difficult, when approached in the correct manner it is easy for a novice to sing in Czech. This document advocates for Czech art song to be assigned and selected for the novice singer. Each chapter serves as a tool to understand and navigate Czech repertoire. The last chapter provides five examples of Czech art song selected because they align with the guidelines of …

Occupational Therapy’S Role In Developmental Programming At Early Childhood Education And Childcare Centers: A Qualitative Study, Alexis N. Foehrkolb, Jenna Lenhart, Hayley Woods, Madison Wetzel, Breanna Adkins, Sueann R. Woods

Graduate Student Scholarship

This research study aimed to discover what strategies of developmental programming are integrated into early childhood curriculum, whether occupational therapy had a role in the formation of the guidelines, and the importance of early intervention on child development. A case study with ethnographic methods was used, including observations and interviews, to gain an understanding of how sociocultural phenomena affect rural childcare centers in Morgantown, West Virginia. Data was collected and coded into 14 themes, and then analyzed by student researchers. Results from interview data found that daycare teachers are given the choice to follow provided lesson plans or individualize their …

The Governance Of Director Compensation, Lily Fang, Sterling Huang

Research Collection School Of Accountancy

The average total compensation of directors in U.S.-listed companies was $342,030 in 2020, 5.06 times the median household income. Directors set their own pay, giving rise to potential self-dealing. We argue and document that in the presence of self-dealing, external mechanisms such as legal standards act as effective means of governance. Following a landmark Delaware court ruling that subjected director pay to a more stringent legal standard, Delaware-incorporated firms reduced director compensation relative to non-Delaware firms and experienced positive and non-transient stock price reactions. Our results indicate that proper governance of director compensation enhances firm value.

The Expression Of Recombinant Cas9 Proteins In E. Coli Bl21(De3) Strains, Morgan Reese

Graduate Theses and Dissertations

Abstract Extensively used for genome editing, CRISPR-Cas9 is a relatively new tool that has made a major impact in the genomic engineering landscape. Due to this, the production of CRISPR proteins that are not commercially available can limit research applications. Here, we present methods for optimizing laboratory scale production of CRISPR proteins including Cas9. The method uses IPTG to induce gene expression of the specified Cas9 and nickel column purification to isolate proteins. CRISPR proteins are validated for purity by SDS-PAGE gel, western blot, and for activity by in vitro digestion. We thoroughly validate and compare the effectiveness of BL21(DE3) …

Temporal Trends And Dental Metric Variation In The Macaca Sylvanus Lineage, Cristina Stan

Graduate Theses and Dissertations

The extensive collection of fossil macaques from Europe, spanning from the Late Miocene to the Late Pleistocene period, is believed to be of the species Macaca sylvanus. However, there has been a prolonged discussion regarding the classification of these specimens into a single taxonomic group as the existing dental sample exhibits a large amount of morphological and metric variation. Specifically, researchers have attempted to identify multiple subspecies based on chronological data of the paleontological locality and, secondly, based on dental metric variation. In this study, I assess temporal trends in the fossil record of Macaca sylvanus and compare overall variation …

Inviting The Public Into Wildlife Research: Does Participation In Research Projects That Facilitate Interactions With Local Species Change Feelings Of Connection?, Seth Gibbons

All Dissertations

For many reasons, humans are less connected to nature. Research shows that people who feel more connected to nature are more likely to have pro-environmental intentions. One possible way to strengthen the human-nature connection is to involve the public in wildlife research, exposing them to local wildlife in a way that highlights science. This dissertation investigates two such projects, the 2019 Clemson Barred Owl Project and the Trout in the Classroom (TIC) program, to understand the effects of interacting with local species through wildlife research.

Interviews were conducted with participants and the lead researcher of the Clemson Barred Owl Project …

“How Are High School Counselors Prioritizing The Information Relevant To Stem Career Preparation In Their Communication With Stem-Interested African American Students?”, Wysheka Austin

All Dissertations

Although African Americans and other minoritized groups have gradually increased in the number of students graduating with a Science, Technology, Engineering, and Mathematics (STEM) degree over the years, these groups remain underrepresented in STEM. Among the many factors contributing to the lack of representation is “college readiness,” which includes academic preparation and awareness of the necessary steps needed for college admission and career preparation [5]. South Carolina policy only considers academic preparation in their assessment of college readiness. To measure academic preparation of any student, the state relies on standardized test scores and advanced course taking without regard to subject. …

Novel Vector Assignment Approach For Inherent Strain Modeling Of Laser Powder Bed Fusion Manufacturing, Lucas M. Morand

All Dissertations

The expansion of the design space due to additive manufacturing (AM) has been a large motivator for the success of this family of processes. Despite the complexity of the physics in metal laser powder bed fusion AM causing significant stresses and strains in finished parts, the design advantages and subsequent performance improvements continue to drive the expansion of AM. Because the trial-and-error approach to AM part development is cost prohibitive, simulation of prints has become crucial. However, full thermo-mechanical simulation is susceptible to the same pitfall of time and computational cost in order to attain part-scale results. The development of …

Time Resolved X-Ray Spectroscopy Of Highly Charged Ar, Nd, And Pr, Timothy Burke

All Dissertations

Highly Charged Ions (HCIs) may be considered ideal mini-laboratory in which one can study the physics of matter and light in an environment of high internal electric field that can not be recreated with standard lab equipment. The remaining electron(s) exist in the extremely large electric field of the nucleus and therefore measurements of electronic transitions in these systems provide stringent tests of our understanding of physics in extreme conditions. Quantum electrodynamics (QED) despite being a powerful theory exhibits large discrepancies for systems under extreme conditions. The work here investigates the atomic properties within non-Maxwellian plasmas. The HCI plasmas studied …

Development Of Advanced Simulator-Based Metrics For Suturing Skills Assessment And Feedback, Simar Singh

All Dissertations

Vascular surgery demands highly skilled suturing to manipulate and connect delicate vasculature. However, inadequate methods for open suturing skills training necessitate efficient and objective methods to develop skills. To address this need, medical training simulators for objective surgical skills training are gaining popularity for their formative assessment.

This research details the development of a system to classify suturing performance and provide feedback on a suturing skills measurement and feedback platform (called the SutureCoach). The SutureCoach simulator offers a comprehensive assessment of skill through sensors measuring needle driver motions, membrane forces and torques, subcutaneous suture needle movement, and hand motions. We …

Mesenchymal Stromal Cell Response To Degenerated Intervertebral Disc-Like Ph, Kyle Cannon

All Dissertations

Intervertebral disc degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. There are currently no clinical treatment options for IVDD that alleviate the symptoms of IVDD while simultaneously promoting repair of IVD tissue. One treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, the microenvironment of the degenerating IVD places significant stress on both native IVD cells and implanted cells. There are several questions that need to be addressed which may help further inform the development of efficacious intradiscal MSC therapies for IVDD. These questions include: 1) Do MSCs …

Development Of Earthquake Hazard Prediction Software For South Carolina And Its Applications, Vishnu Saketh Jella

All Dissertations

This dissertation presents the development of earthquake hazard generation software, CarolinaShake and CarolinaADRS, for the state of South Carolina and its applications in the field of earthquake engineering. South Carolina is a seismically active state in the eastern United States, and there is a need to accurately quantify the earthquake hazard and incorporate it into the design of infrastructure systems. To achieve this objective, the South Carolina Department of Transportation (SCDOT) is actively supporting the initiatives to update its seismic design policies and procedures of civil infrastructure systems. As part of those initiatives, first, CarolinaShake, a Windows-based graphical user interface …

Identifying Temporomandibular Disorder Morphological Risk Factors Via Explainable Deep Learning And Multiscale Biomechanical Modeling, Shuchun Sun

All Dissertations

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis and development of targeted prevention and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analysis of disease datasets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and …