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Chacterization of Influenza Antibody-Antigen Complexes Using Hydrogen-Deuterium Exchange Mass Spectrometry and Computational Modeling
No full textInfluenza viruses pose a major threat to public health due to their diversity and rapid evolution. Recently, a novel class of Abs was discovered that targets the trimeric interface (TI) of the HA head with remarkable breadth and affinity, making the HA TI a promising target for immunogen design. In this thesis, we investigated the interactions of protective H7-specific monoclonal Abs targeting the TI-2 site—the second major TI antigenic site in the HA head—to identify shared structural determinants essential for eliciting these broadly reactive Abs, ultimately informing rational influenza vaccine design. Using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and computational modeling, our study characterized the binding of three TI-2 Abs (H7-214, H7-241, and H7-247). We identified key structural determinants critical for TI-2 site recognition: the N208–S216 β-strand and the G196–V202 loop. Our epitope mapping studies also suggested that the HA TI-2 antigenic landscape comprises multiple distinct yet overlapping epitopes rather than a single fixed binding site. This work advanced our understanding of TI regions as a valuable focus for influenza immunity and identified key structural features within the HA TI-2 site as targets for developing a broadly protective pan-H7 vaccine. Additionally, my project proposed a hybridized approach that combines computational docking with HDX-MS epitope mapping for structural prediction of Ab-Ag complexes, known as RosettaHDX. Sparse data from HDX-MS can restrict the conformational space to relevant structures, while computational docking provides atomic-level resolution models. By incorporating HDX data as both distance restraints and a scoring term in the RosettaDock algorithm, RosettaHDX successfully generated near-native models (interface root-mean-square deviation ≤ 4 Å) for all nine benchmark complexes, producing an average of 3.6 times more near-native models than Rosetta alone. To our knowledge, no other platform has benchmarked HDX-MS data in docking. Additionally, we are the first to devise a predictive metric based on docking results with HDX to identify allosteric peptides. With HDX-MS data acquisition taking as little as one week per epitope mapping experiment, our established method enables more reliable predictions of Ab-Ag complexes in relatively short timeframes. This method could be a valuable tool for structure-based therapeutic and vaccine development, particularly in high-pressure, time-sensitive situations such as pandemics or public health emergencies
Calculated Words: The Hidden Math of Eighteenth-Century Literature
No full textBy tracing the historical forces of geometry and Newtonian physics and calculus, a vein of otherwise latent critical analysis opens for approaches to the English literature of the eighteenth century. In Calculated Words, mathematical principles serve both as a method of studying literature and as an object of study within literature. By first tracing the mathematical tendencies present throughout the history of literary criticism, I establish a precedent for the work that comprises each chapter, work that ranges from tracing the influence of Newtonian calculus’s interest in minutiae on early novelistic technique in Samuel Richardson’s Sir Charles Grandison (1753) to examining how the limits of geometrical knowledge make social and literary formulations more difficult to figure in the work of Adam Smith and Henry Fielding. Finally, despite the benefits that incorporating scientific and mathematic advancements into our thinking offers, I conclude by emphasizing the continuing importance of local, interpersonal relationships and understandings of the world
School Choice and Urban Socio-Spatial Boundaries
No full textExpansive school choice programs are often implemented for the perceived ability for students to overcome geographic disparities in access to high-quality education, though it remains to be seen if these programs are in fact connecting communities that were separated through racial segregation and addressing the educational inequities associated with it. These initiatives take place in complex environments, and historical context makes it important to acknowledge how they impact the communities they serve. This study pairs census data with administrative data from a large urban school district in the southeastern United States to examine how the implementation of an expansive school choice program impacted geographic and demographic patterns in where students enroll. Findings indicate that affluent and marginalized areas of the city maintain school segregation even when students opt into choice schools, challenging assumptions about how school choice could impact broader community processes
Exploring Mechanisms behind Phase Formations of Metal Chalcogenide Nanoparticles
No full textOur understanding of nanoparticle phase control is currently limited by our knowledge of the mechanisms responsible. How molecular precursors interact with each other, the solvent, and the ligand, and how they decompose thermally can all have an effect on the resulting phase of the product. Through the use of various analytical techniques like nuclear magnetic resonance (NMR), in-situ gas phase Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM), we shed light on the interactions that can occur between ubiquitous reagents in nanosynthesis. In the first project, we demonstrate that thiourea can interact with oleic acid during the synthesis of metal sulfide nanoparticles to produce ammonium thiocyanate, a more reluctant sulfur source, leading to the formation of metastable and sulfur poor nanoparticles, a trend seen across four different metals (Cu2+, Ni2+, Co2+, and Fe3+). In the second project, we use selenourea for the synthesis of iron selenides, and, for the first time, show that chalcogen allotropes can act as phase-determining intermediates in the synthesis of metal chalcogenides. In the presence of oleylamine, selenourea can decompose into red selenium, leading to the formation of Fe7Se8. In the presence of oleic acid, grey selenium forms instead and leads to the formation of FeSe2. In the third project, we make progress towards the synthesis of colloidal chromium telluride nanoparticles. With the use of the fast reacting didodecyl ditelluride, we show that commonly used chromium (III) halide precursors yield only unreactive Te(0). We attempt to overcome this synthetic challenge with the synthesis of a more reactive chromium (II) iodide. Finally, in the fourth project, we use the steric effects of N-heterocyclic derived selenoureas to influence not only the phase of iron selenide nanoparticles but also their morphology. We find that as the sterics of the N-heterocyclic derived selenourea increase, the nanoparticle size decreases, and the shape becomes more irregular. With these reports, we hope to deconvolute the mechanisms affecting phase control and to add onto our synthetic tool-box for repeatable and reliable synthesis of nanoparticles
From Purpose to Commitment: The Role of Transformational Leadership in a Nonprofit Organization
No full textLeadership and Learning in Organizations capstone projectThe Make-A-Wish Foundation is a global nonprofit organization that grants life-changing wishes to children with critical illnesses. This study aimed to understand how leaders at Make-A-Wish Mid-South understood, practiced, and behaved in their roles, to provide strategies to further leadership development initiatives. We drew on James Burns’ (1978) theory of transformational leadership, which was further defined by Bernard Bass (1985), and Peng et al.’s (2020) moderated mediation model of transformational leadership and affective commitment to inform our project questions and conceptual framework. To answer our project questions, we asked employees to voluntarily participate in an online quantitative survey and qualitative interview. A review of quantitative survey and qualitative interview responses confirmed that centralization moderates the relationship between transformational leadership and affective commitment
Optimized Back-Biasing Strategy to Improve TID Tolerance in Conventional-Well 22nm FDSOI Transistors
No full textIn a 22nm FDSOI CMOS technology architecture, back-biasing for total-ionizing-dose (TID) effects mitigation accelerates transistor degradation by increasing the rate of buried oxide (BOX) trapped charge accumulation. Conventional dynamic back-biasing maintains a constant threshold voltage shift (ΔVth) by continuously increasing the magnitude of back-gate voltages as total dose increases, unintentionally accelerating BOX charge accumulation. An optimized strategy instead delays compensatory back-biasing until the threshold voltage approaches its operational limit, minimizing early charge accumulation and reducing long-term degradation. Experimental results across various device sizes demonstrate that this approach lowers TID-induced threshold voltage shifts at larger doses. For example, in an 80/32 nm NMOS device, the optimized method reduced pre-annealing and post-annealing ΔVth increases due to back-biasing to 2% and <1%, compared to 17% and 12% when conventional back-biasing is used. This strategy effectively mitigates TID-induced degradation, enhancing device reliability at higher radiation doses
Their Spirits You Can't Digest: Race, Ritual, and the Return of the Animal
No full textTheir Spirits You Can’t Digest: Race, Ritual, and the Return of the Animal reconstructs a literary and environmental history of human-animal relationships in the rural US South to demonstrate how figurations of animality shape, and are shaped by, the material embodied experiences of violence that engender racial identities across species. The dissertation moves from the theological registers of the symbolic to the legal and material questions of land, agriculture, and (dis)possession. This interplay of agrarian practice, religious narrative, and legal discourse positions live animals as props and the southern landscape as the stage for both performing and disrupting rituals of race-making. These rituals, I argue, persist into the present in the form of festivals of animal slaughter held annually across the South, a practice I ethnographically document. Analyzing African American literature alongside agrarian legal archives and visual ethnography, Their Spirits You Can’t Digest contests the violence of Enlightenment humanism, guiding readers in encounters with southern animals that reveal unexpected alliances and emancipatory possibilities. As my dissertation recovers alternative models of being and recognition that persist in spite of and against these violences, it also recasts the South from its role as the nation’s internal and deviant other to fertile ground for cultivating critical ecologies of place-making and trans-species engagement. I turn to the Black South—its writers and everyday people—to track encounters with animals that upset rituals of race-making as they reimagine interspecies relations anew. Indeed, Their Spirits You Can’t Digest uncovers a long environmental history where African American relationships with animals—on plantations with dogs, in courtrooms with hogs, and at festivals with snakes—present not just a shared state of vulnerability and precarity but rather redefine what it means to be or have a self. As I show, Black southerners crafted regional identities and communities through a praxis that neither relied on animal abjection nor sought inclusion into the political category of the human. Through these more-than-human engagements, I demonstrate how southerners often refused the terms of humanization altogether, creating their own spectacles that recast animals from living symbols of oppression to partners of co-liberation
Reconstructing the Demolished Onscreen: Representations of Eviction Conflicts (chaiqian) in Contemporary Chinese Cinema
No full textDepartment of Asian Studies Honors Thesi
Optimized federated-learning-based techniques for IoT in edge computing
No full textThe Internet of Things (IoT) generates vast amounts of data from billions of interconnected devices, creating unprecedented opportunities for machine learning applications. However, traditional centralized learning approaches face significant limitations in IoT environments, including privacy concerns, bandwidth constraints, and data sovereignty issues. Federated Learning (FL) emerges as a promising solution that enables collaborative model training across distributed edge devices while keeping data locally stored, thus preserving privacy and reducing communication overhead.
This work addresses four critical challenges in federated learning for IoT systems: (1) Communication Efficiency - reducing bandwidth requirements through optimized synchronization strategies in resource-constrained networks; (2) Data Heterogeneity and Multimodality - handling non-identically distributed (non-i.i.d.) data across devices and managing missing modalities in multimodal IoT environments; (3) System Heterogeneity - addressing computational resource variations and unpredictable client participation patterns; and (4) Lifelong Learning - managing concept drift in evolving data distributions and mitigating the straggler problem in dynamic IoT deployments.
The research focuses on optimizing FL strategies to maintain or improve performance under realistic constraints, moving beyond idealized assumptions to address the practical challenges of implementing federated learning in large-scale, heterogeneous IoT networks. By tackling these fundamental issues, this work aims to enable more efficient and robust federated learning systems that can effectively leverage the collective intelligence of distributed IoT devices while respecting privacy and resource constraints
Lessons Learned in the Age of Political Polarization: A Case Study of Five Independent Schools
No full textLeadership Policy and Organizations Department capstone projectWe are living in an age of political polarization and nowhere has it played out more publicly in the United States than within education where schools, classrooms, and campuses have become the battlegrounds for deep divisions around any number of controversial topics, the mismanagement of which can have steep consequences for educational institutions and their leaders. Being informed by years of quantitative research on the topic within the independent school sector, this qualitative research study provides a front row seat to the inner workings of five independent schools and their experiences leaning into the important work of managing political polarization. The findings are groundbreaking and extremely informative for all those who lead in educational spaces and beyond including 1) how political polarization is impacting the experiences of students, teachers, and school leaders in independent schools, 2) ways in which schools are changing their programs or policies in response to the recent social and political environment, and 3) how schools are meeting the needs of students, teachers, and school leaders. Beyond insightful and captivating stories from the experiences of these schools, this paper includes the introduction of the Helvey Power-Expression Paradigm, which is the first of its kind, a visual representation of the inverse relationship of power differentials that exist between school leaders, teachers, and students within a school community and the impact that has on each of their freedom of expression in schools. Finally, the research suggests three recommendations to the National Association of Independent Schools (NAIS), culminating in a proposed Principles of Good Practice: Leading Through an Era of Political Polarization.Peabody College of Education and Human DevelopmentDepartment of Leadership Policy and Organization