18525 research outputs found
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Integrating Large-Scale Human Genetic and Regulatory Genomic Data to Functionally Annotate ctcf Binding Variation
No full textCCCTC binding factor (CTCF) regulates gene expression through DNA binding at thousands of genomic loci. Genetic variation in these CTCF binding sites (CBSs) are important drivers of phenotypic variation, yet extracting those that are likely to have functional consequences in whole genome sequencing (WGS) remains challenging. Through this dissertation, I explore conceptual frameworks to identify and prioritize CBS variants in gnomAD, a WGS database consisting of 76,156 individuals. First, I integrate computational and experimental predictions of CTCF binding into an empirical false-positive measure that can be applied to the score distribution of a precision-weight matrix. I then synthesize CTCF’s binding patterns at 1,063,878 genomic loci across 214 biological contexts into a summary of binding activity. This measure correlates with both conserved nucleotides and sequences that contain high-quality CTCF binding motifs. Finally, I use binding activity to evaluate high confidence allelic binding predictions for 1,253,329 SNVs in gnomAD that disrupt a CBS. I find a strong, positive relationship between the mutability adjusted proportion of singletons (MAPS) metric and the loss of CTCF binding at loci with high in vitro activity. Together, this body of work nominates thousands of rare, noncoding variants that disrupt CTCF binding for further functional studies while providing a blueprint for synthesizing large-scale genomic data to better prioritize noncoding variation in human disease studies
Formal Safety and Cyber-Security in Mixed-Autonomy Traffic
No full textThis work studies formal safety and cyber-security in mixed-autonomy traffic flows. Mixed-autonomy traffic flows have a mix of human drivers and automated vehicles (AVs). This work considered three emergent problems in this context. 1) Are adaptive cruise control (ACC) vehicles string-stable? Through experimentation on commercially available ACCs we found them to not be string stable. 2) Are ACCs stealthy vectors of attack against traffic? Through building a high fidelity simulation testing environment we found that ACCs may be used to attack traffic flows in a stealthy manner. 3) Can control barrier functions (CBFs) guarantee the safety of AVs in live traffic? Through experimentation we found that CBFs do not provide formal safety in real world contexts, but can practically be used to supervise otherwise unsafe AV algorithms
Electronic Subsystem Modeling in Radiation Environments Using the SEAM Platform
No full textSpaceborne systems are continuously exposed to harsh radiation environments, including total ionizing dose (TID) effects, single-event effects (SEEs), and transient disruptions. These radiation-induced phenomena can significantly compromise the functionality, reliability, and safety of critical subsystems. As systems become increasingly integrated and component-level testing grows more difficult and costly, developing effective assurance strategies is essential to mitigate these risks.
Mathematically-based simulation platforms, such as SPICE and TCAD, often require detailed physical parameters and material properties that may not be readily available from device manufacturing companies, particularly for complex subsystems incorporating commercial off-the-shelf (COTS) components or legacy modules. This poses challenges for accurately modeling radiation effects in systems whose internal design details are not fully accessible, such as star trackers.
To address these challenges, this thesis investigates subsystem-level modeling in radiation environments using the Systems Engineering and Assurance Modeling (SEAM) platform. SEAM provides a structured, qualitative approach to building system models, functional models, Goal Structuring Notation (GSN) models, and fault trees. It enables systematic analysis of radiation vulnerabilities and the development of mitigation strategies. Operating at a high level of abstraction compared to mathematically based low-level tools, SEAM supports fault propagation analysis and vulnerability prediction even with limited design data.
Two case studies demonstrate the methodology: a temperature control subsystem in a CubeSat’s Command and Data Handling (CDH) board and critical electronic modules from the PyCubed satellite platform, including its microprocessor and modular radio. Through detailed subsystem modeling, fault analysis, and assurance case construction, this work illustrates how SEAM can help engineers identify failure modes and improve radiation tolerance.
In addition, the thesis introduces structural and functional modeling approaches that capture both physical architecture and operational logic. A Key Performance Indicator (KPI)-based method is also proposed to guide fault modeling, especially in cases involving complex and extensive subsystem documentation. These methods demonstrate SEAM’s capability to support early-stage modeling and assurance case development for spaceborne subsystems under radiation exposure
Strengthening Early Literacy Through RTI: An Analysis of K-2 Intervention, Teacher Roles, and Impact of RTI in Hamilton County Schools
No full textLeadership Policy and Organizations Department capstone projectThis mixed methods study explores the implementation and early impact of the strategy employed by Hamilton County Public Schools to place an RTI teacher at each elementary school. This investment was made in an effort to improve K-2 achievement, as measured by a universal screener. Relying on 20 interviews, as well as observations and universal screener data analysis, results showed that RTI teachers were spending their time in alignment with the district vision for the role, on average, but there was wide variation between schools. RTI teachers are generally satisfied with their support, but there are opportunities for alignment around expectations and filling gaps in professional learning. While there are early results of student growth in schools implementing this RTI teacher strategy with fidelity, more research is needed. Recommendations include aligning district and school expectations, tailoring professional development, improving data systems, and monitoring the implementation of Tier I foundational skills.Peabody College of Education and Human DevelopmentDepartment of Leadership Policy and Organization
The Impact of Face-to-Face Meetings on Trust, Socio-Emotional, and Cognitive Outcomes in Remote Learning
No full textLeadership and Learning in Organizations capstone projectThis study investigates the role of face-to-face (F2F) meetings in enhancing relational trust, socio-emotional development, and academic outcomes in synchronous remote learning environments. It examines whether an initial in-person meeting between students and their teacher fosters relational trust when they then work in synchronous online learning environments. Quantitative analysis reveals that students who met their teachers prior to online instruction reported higher levels of relational trust, greater interpersonal communication, and improved class attendance. These findings support theories of relational trust as a foundation for effective learning and connection in virtual educational environments.
Contributing to a growing body of literature on online education, the findings suggest that in-person meetings can significantly influence psychological safety, participation and engagement. Hybrid models that integrate in-person meetings with synchronous virtual environments may be particularly effective in supporting high-need or vulnerable individuals. The findings offer actionable strategies for educators and program designers seeking improve socio-emotional and academic outcomes in synchronous remote learning and working environments
Designing for Transformation: A Formative Evaluation of an Executive Leadership Development Program to Foster Adaptive Leadership
No full textLeadership and Learning in Organizations capstone projectThis capstone project conducted a formative evaluation of a 900-employee, member-owned financial institution's Enterprise Leadership Development Program aimed at executives. The evaluation generated actionable insights and recommendations to enhance program design and implementation, focusing on the relevance to leadership needs, sustained support mechanisms, transformational learning, adaptive leadership principles, and a robust evaluation framework.
To deepen understanding of current leadership development dynamics, relevant theories were explored, including Transformational Learning Theory, Adaptive Leadership Framework, and the Kirkpatrick Evaluation Model. A mixed-methods approach, utilizing both qualitative and quantitative data through surveys, interviews, and document analysis, provided evidence-based insights.
Findings confirmed the program's alignment with strategic priorities while identifying opportunities for improved cross-functional collaboration and ongoing leadership growth. The evaluation highlighted the importance of personalized support, such as Individual Development Plans (IDPs), mentorship, and peer networks for effective skill application. Recommendations emphasized the need for embedded learning and digital tools to enhance accessibility, thereby providing a structured approach to reinforce leadership development, foster organizational integration, and sustain transformation. By refining program design, leaders can acquire critical competencies and effectively drive enterprise-wide change
User Response to Legal Intervention and The Efficacy of Industry Self-Regulation Regarding Digital Assets: Evidence from Genshin Impact
No full textDigital worlds have an increasing impact in the everyday lives of people around the globe, with online games acting as a vehicle for socialization, recreation, and even livelihood as individuals operate through their virtual avatars. Within these online games, the presence of loot boxes has seen increasing use as a monetization system, whether merely incidental or completely integrated into the gameplay structure. As more individuals play online games and the revenue of the video game industry increases, the problems associated with loot boxes have an increasingly outsized impact on users. Due to their chance-based nature and their design to cause addiction, legal scrutiny should be placed on the use of loot boxes as a result of their ease of access to vulnerable populations such as minors, scrutiny which has not translated into regulation in the United States. This dissertation will study loot boxes in an integrated gacha game, Genshin Impact, through a survey targeted towards the games most invested players. It will focus on three distinct areas: the rationality and responsiveness of player behavior, the response of players to different taxation schemes, and the sentiment of players towards regulation. All questions are framed in the context of the game to ensure optimal applicability and accuracy of responses, a novel approach in the literature which typically focuses on broad and general studies. The results of the study will provide evidence for the proper treatment and regulation of loot boxes in a broader context
Investigating Brain Endothelial Cell Mechanics with Engineered in vitro Models
No full textAs life expectancy in the US has increased, a growing percentage of the adult population is expected to suffer from age-related neurodegenerative diseases, such as Alzheimer’s disease (AD). Common vascular risk factors like hypertension and arterial stiffening, are associated with vascular remodeling, cerebrovascular disease, and blood-brain barrier disruption. Brain endothelial cell dysfunction is the central driver of blood-brain barrier disruption and downstream neurodegeneration. Due to the clear associations between vascular basement membrane remodeling with blood-brain barrier disruption, we sought to investigate the consequences of mechanical inputs on cellular dysfunction using an in vitro model. Previous work has shown that brain endothelial cells exhibit sensitivity to both fluid shear stress and substrate stiffness, but no studies have examined the consequences of both factors in the same model, likely due to significant engineering challenges. In this dissertation, we examine the consequences of substrate stiffness and fluid shear stress on brain endothelial cell dysfunction, in addition to providing a design for a microfluidic splitter to increase experimental throughput. We show that brain endothelial cells have reduced membrane expression of a crucial junctional support protein, ZO-1, when cultured on 30 kPa hydrogels compared to 6 kPa hydrogels in static conditions. Exposure to physiological fluid shear stress impacts cell morphology, increasing cell size and elongation across both hydrogels. Further transcriptomic analysis and quantification of intracellular protein production revealed a distinct inflammatory response of cells cultured on 30 kPa hydrogels across both static and physiological fluid shear stress. To our knowledge, this is the first model to demonstrate a direct connection between substrate identity and brain endothelial inflammation in a perfused model, supporting the need for further investigation into mechanical regulation of brain endothelial cell dysfunction. We also demonstrate successful formation of a confluent 3D brain endothelial microvessel, fabricated from a cleanroom-free 3D-printed mold. This system represents an important step to overcoming technical limitations to the use of in vitro models
Learning Beyond Utility: Fairness, Explainability, and Diversity
No full textMachine learning models have achieved great success in real-world applications but may introduce unfairness when optimized solely for utility performance (e.g., accuracy). This dissertation explores beyond-utility aspects, focusing on fairness and its intersections with explainability and diversity. First, it identifies and mitigates fairness issues in recommendations, addressing biases in online dating, interest diversity, and dataset imbalances. Second, it introduces explanation fairness to ensure fairness in both outcomes and decision-making, proposing a framework that balances utility, traditional fairness, and explanation fairness. Third, it examines the connections between fairness and diversity, extending diversity considerations to users and analyzing interactions on both the user and item sides. Overall, this dissertation advances responsible ML practices, promoting models that are both powerful and equitable
PREPARATION OF EARLY CHILDHOOD EDUCATORS TO REFER STUDENTS WITH SUSPECTED VISUAL IMAPIRMENTS FOR SPECIAL EDUCATION EVALUATION
No full textThis study explores early childhood educators’ knowledge of visual impairments in children and their understanding of the referral process for special education services. Early identification of visual impairments is essential to ensuring that children receive timely support and access to appropriate educational interventions. Despite this importance, limited research has focused on educators' awareness of early indicators of visual impairments and their ability to navigate referral procedures. This paper investigates the specific signs and symptoms that educators report recognizing in young children, such as difficulty with eye tracking, frequent squinting, sitting too close to visual materials, or delays in visual-motor integration. It also examines educators’ familiarity with the formal processes for referring a child for vision screening or special education evaluation.
To explore these issues, the study utilized a national survey targeting early childhood educators across various educational settings. The survey assessed participants’ knowledge of visual impairment indicators and their experiences with referral procedures. Additionally, it examined several factors that may influence knowledge levels, including pre-service training, access to professional development, teaching experience, and institutional resources. Quantitative analysis revealed significant correlations between increased knowledge and educators who had received formal training related to special education or vision health. Professional development opportunities and school-based support systems also contributed positively to knowledge and referral confidence.
Findings suggest that enhancing both pre-service and ongoing training in visual health can strengthen educators’ capacity to identify and respond to visual impairments. The paper concludes with recommendations for improving early childhood educator preparation and promoting early intervention for children with visual needs.Dr. Rachel Schles (Advisor