VictorJuiz/thesis huggingface dataset:
Understanding tumor suppression through the p53 target gene network

TP53 encodes the potent tumor suppressor, p53. TP53 is mutated in nearly half of sporadic human cancers, and inheritance of a mutant TP53 allele in the germline causes Li-Fraumeni Syndrome, which highly predisposes those affected to developing cancer early and often in their lives. Cementing the importance of p53 in tumor suppression are the data from p53 null mice, which succumb within months to mostly thymic lymphomas with 100% penetrance. Despite its unequivocal importance in tumor suppression, the precise mechanisms of p53-mediated tumor suppression remain incompletely understood. p53 is a stress-inducible transcription factor. In response to various cellular stresses, p53 accumulates in the cell, binds to DNA in a sequence-specific manner, and activates expression of target genes. Various pieces of evidence support this transcriptional activation p53 as being critical for tumor suppression. Notably, genetically engineered mouse models of cancer demonstrate that inactivation of both p53 transactivation domains (TAD) renders p53TAD1,2 comparable to p53 null alleles in tumor suppression. The p53 target gene network encompasses hundreds of genes that regulate diverse cellular processes. Our understanding of which p53 target genes and which biological processes are key to p53-mediated tumor suppression remains incomplete. Factors that complicate answering these questions are that study of p53 target genes has largely focused on in vitro studies using acute p53-activating stresses and that p53 might suppress tumorigenesis in a context-specific manner. To address this question of which p53 target genes are most important for tumor suppression, we have developed a sensitive, in vivo, combinatorial screening platform. Using a comprehensive sgRNA library targeting 272 target genes of p53, we identified Zmat3 and Cdkn1a as potent and cooperative effectors of p53-mediated tumor suppression. Using meta-analyses of published p53-dependent gene expression studies in human cell lines as well as CRISPR/Cas9 screening data compiled in the Cancer Dependency Map, we demonstrated that ZMAT3 and CDKN1A are near-universal, evolutionarily conserved target genes of p53 that serve as brakes to enhanced cellular fitness in pooled sgRNA enrichment screens. Finally, using RNA-seq, differential splicing analysis, and shotgun proteomics, we link Zmat3 and Cdkn1a loss with dysregulation of signal transduction and cell division respectively, suggesting that, through these two target genes, p53 engages parallel cellular processes in tumor suppression. These studies illuminate important modules of p53-mediated tumor suppression, an understanding that could contribute to the improved diagnosis and treatment of p53-deficient tumors in the clinic

Keywords: Medicine.
Advisor: Attardi Laura
Dixon Scott James
Jackson Peter K. (Peter Kent)
Lu Sydney
Unequal Provision of Educational Accommodations: Impacts of a Nationwide SAT Policy Change on Receipt of Accommodations

Educational accommodations are provided to support students with disabilities in the classroom. Previous research shows that students of privileged backgrounds obtain accommodations at higher rates than minority and low-income students, although research is inconclusive with respect to why these disparities exist. In this paper, I present causal evidence on the impact of an exogenous change in the incentive to obtain an accommodation. In 2016, the College Board introduced a policy stating that the accommodations provided in a student's 504 plan would automatically carry over to the SAT. By streamlining the receipt of accommodations for the SAT via 504 plans, this policy created a new incentive to seek a 504 plan, as 504 plans could now confer desirable advantages on a high-stakes college admissions test. To estimate the effect of this policy change, I employ a difference-in-differences approach using administrative data from over 9,000 public schools in the United States. I find that the policy change significantly increased 504 plan receipt among white students at wealthy high schools, but not among comparable subgroups like minority students at wealthy schools or white students at high-poverty schools. These findings shed light on some of the motivations that may lie behind accommodations-seeking, and demonstrate how current practices of accommodations provision may inadvertently perpetuate educational inequality.

Keywords: Educational sociology, disability, accommodations
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Thesis
Uniaxial heterostrain in twisted bilayer graphene above the magic angle

Twisted bilayer graphene is an experimentally rich platform, hosting a variety of exotic states of matter with an unprecedented degree of tunability. I present measurements of a twisted bilayer graphene device twisted to 1.4 degrees, well above the magic angle at which correlations dominate. Despite the lack of correlated states, the device shows several unexpected behaviors in magnetotransport: regions in density of large quadratic magnetoresistance concurrent with an apparently non-Diophantine Landau fan diagram. I show that uniaxial heterostrain of only a few tenths of a percent neatly explains these unusual magnetotransport measurements. It is presently difficult to control such small amounts of strain in experiments. If we can control it, then heterostrain becomes a powerful tuning knob to control the band structure of twisted bilayer graphene, much like twist angle.

Keywords: Humanities and Sciences.
Physics.
Advisor: Goldhaber-Gordon David
Feldman Ben
KastnerMarc
Uniform Transition Tree-Structured Critically Sampled Filterbanks

Critically sampled filterbanks are useful in applications like audio coding that involve processing the time-varying spectral characteristics of signals. Critically sampled filterbanks can be implemented with a tree-structure. The odd-numbered subbands of a critically sampled filterbank exhibit frequency inversion, causing subbands to be unordered in frequency past the first layer. We show how subbands can be swapped at each layer to maintain their ordering. Self-similar filterbanks, using the same filters at each layer of the tree, have nonuniform transition widths and long impulse responses. We explore using filters with wider transition widths at deeper layers, and we demonstrate that this technique can be used to implement an efficient uniform transition filterbank. We compare this uniform transition filterbank with a self-similar filterbank in an audio codec, showing that the uniform transition filterbank achieves a smaller maximum transition width at a lower impulse response length.

Keywords: Electrical Engineering
Electrical engineering
Signal processing
Filterbanks
Audio coding
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Thesis
Advisor: Schafer Ron
Mujica Fernando
Bosi Marina
Unity and Struggle Beyond Borders: An Examination of Anti-Hindutva Activism in the United States

This thesis is an endeavor to study the organized resistance against Hindutva in the United States, exploring the development of contradictions between Hindutva and anti-Hindutva movements, as well as explaining current contentions within the anti-Hindutva movement. I start by tracing the historical development of global Hindutva, from its origins in India towards its current manifestations in the United States. Then, through a combination of analysis of semi-structured interviews from representatives from three anti-Hindutva organizations (Ambedkar King Study Circle, Hindus for Human Rights, and Indian American Muslim Council), as well as the examination of digital documents and reports, I explore the current landscape of anti-Hindutva activism in the United States. In particular, I consider how the issues of Hindu majoritarianism and caste discrimination have mobilized South Asian American and Indian American communities to oppose Hindutva both in India as well as within the United States. I specifically argue that the current anti-Hindutva movement has increasingly resisted against the expression of Hindutva politics within the United States through analyzing two key incidents - the protests against the appearance of a bulldozer at an Indian Independence Day rally in August 2022 at Edison, NJ, and the February 2023 passing of an ordinance against caste discrimination in Seattle. I also explore contentions within the anti-Hindutva movement in the United States, explaining how the relationship between caste and Hindutva has led some anti-Hindutva organizations to emphasize the distinction Hindutva from Hinduism, while others have offered a deeper critique of caste violence that opposed Hindutva, but also investigates the Brahmanical origins of caste and its relationship to Hinduism. Despite certain disagreements about the relationship of caste, Hindutva, and Hinduism, I maintain that critical unities between organizations have featured prominently in the successful actions against Hindutva in the United States. I also note how these solidarities have extended beyond just the issues of Hindutva, arguing that the fight against Hindutva in the United States has become increasingly connected to other struggles for liberation, from anti-capitalist struggles to the battle against racism.

Keywords: Religion
Caste
Transnationalism
South Asian Americans
Activism
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Thesis
Universal optical instrumentation for exoplanet atmospheres

Any astronomical inferences rely fundamentally on a model of the universe which incorporates relevant physical processes of the system in question. These models enable experimentation in otherwise inaccessible environments by providing a fictitious copy of the universe in which researchers can control the initial conditions or governing equations to disentangle cause and effect. An increasing number of experiments rely on astrophysical objects as essential components in the instrumentation, with various physical mechanisms forming the operating principle through which inferences are ultimately drawn. This has blurred the preexisting conventions which distinguish the human constructed instrumentation from the environment in which they operate as well as the objects under investigation. A complete understanding of astrophysical instrumentation will require a hierarchical modeling strategy which incorporates all relevant physical processes over all scales to connect observations to inferences. Analysis of optical propagation through the turbulent atmosphere of the Earth demonstrates a fundamental limitation to single-deformable-mirror adaptive optics systems such as the Gemini Planet Imager as a result of scintillation. At the other end of the optical path, turbulent mixing in exoplanetary atmospheres can result in chemical abundances of molecules such as carbon monoxide which depart from equilibrium expectations, changing the near-infrared colors of the planet. Lastly, explorations of novel instrumentation such as a starshade and the solar gravitational lens may enable unprecedented observations of other worlds

Keywords: Humanities and Sciences.
Physics.
Advisor: Dubra Alfredo
Macintosh Bruce
Romani Roger W. (Roger William)
Universal properties of the intrinsic microbial response to temperature fluctuations

The impact of temperature on growth is typically considered only under heat- or cold-shock conditions that elicit specific regulation. Over intermediate temperatures, the growth rate of all cells varies according to the Arrhenius law of thermodynamics; growth rate dynamics during transitions between temperatures remain mostly unstudied. Using a device that enables single-cell tracking during switches across a wide range of temperatures (0 °C to 47 °C), we show that many bacteria respond to temperatures upshifts on a characteristic time scale of ~1.6 doublings at the higher temperature, regardless of initial/final temperature or nutrient source. We rule out transcriptional, translational, and membrane reconfiguration as potential mechanisms, and instead discover that an autocatalytic enzyme network incorporating temperature-sensitive Michaelis-Menten kinetics recapitulates all temperature-shift dynamics and successfully predicts the altered temperature responses observed under simple-sugar and low-nutrient growth conditions. These findings suggest that the temperature sensitivity of metabolite flux dictates responses to temperature fluctuations.

Keywords: Humanities and Sciences.
Advisor: Huang Kerwyn Casey
Cremer Jonas
Sattely Elizabeth
Univirtual Academy

The use of Immersive Virtual Reality (IVR) platforms is increasingly being considered as a vehicle for remote work and in K-12 distance learning. Because collaboration skills are vital for students' holistic growth and the future job market, the need for new approaches to collaboration support in immersive digital learning environments is growing. Computer-supported collaboration scripting and comprehensive training are identified as potential ways to address group work support and improve learning outcomes in IVR-based learning environments. The project focus is on the purposeful design of the online environment fostering self-efficacy and scaffolding to achieve effective collaboration and produce socially shared regulation. The findings of this project have significant implications for teaching and learning collaboration skills in synchronous IVR-based learning environments, where students' trajectories can be divergent and unanticipated. The project seeks to prepare students for the collaborative technological future of remote teamwork by leveraging VR affordances and automated real-time pro-social prompting.
Addendum 1.0
Virtual Reality (VR) learning environments provide immersive and interactive experiences that have the potential to enhance educational outcomes. Collaborative problem-solving tasks in VR environments require effective communication and cooperation among group members. Intelligent Social Agents (ISAs) are computer-based characters programmed with human-like attributes that can interact and collaborate with users in the virtual world. This report aims to investigate the impact of ISA personality on reducing cognitive load when groups collaborate on problem-solving tasks in VR learning environments. The report combines information gathered from literature to analyze ISA personalities' potential effects and implications on cognitive load, group interactions, and learning experiences in this context.

Keywords: VR
IVR
CSCL
Collaboration
Virtual Learning Environments
Socialy Sharhed Regulation
Scaffolding
Checklists
Pro-social Prompting
Intelligent Social Agents
ISA
Cognitive Load
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Capstone
Report
Thesis
Student project report
Unlocking opportunity, advancing equity : improving college outcomes for marginalized students

Empirical evidence unambiguously asserts that a college education provides robust benefits to both individuals and societies. However, disparities in college enrollment and completion persist and limit opportunities for marginalized students to enjoy the advantages a college education affords, impeding progress toward equitable outcomes for all. The three chapters in this dissertation employ quantitative methods to evaluate policies and programs that aim to improve college access and success for marginalized students. The first chapter evaluates efforts to increase college access for rural students and revitalize rural economies. Results suggest a strong positive effect of branch campus openings on local economic activity. The second chapter estimates the differential impact of changes to the federal student loan policy on Historically Black Colleges and Universities (HBCUs) relative to other institutions. Results suggest that HBCUs are more responsive to these policy changes and experienced a disproportionately negative effect on enrollment when access to loans was restricted. The third chapter estimates the impact of a virtual college coaching intervention designed to help low-income, first-generation, and racial/ethnic minority students persist to degree completion. Results suggest that coaching has a positive effect on persistence to the second year, but that effect is not sustained beyond the intervention period. Together, these chapters provide evidence that informs efforts to unlock opportunity for all students and advance equity in college access and completion

Keywords: Education.
Advisor: Bettinger Eric
Antonio Anthony Lising
Dee Thomas S. (Thomas Sean)
Unpacking gender segregation within occupations : a study of job queues and social closure mechanisms in the medical profession

When women make inroads into men-dominated professions and occupations, how should we interpret these trends? While there has been an overall stall in the gender integration of occupations in the 21st century, the one exception is women's entrance into men-dominated managerial and professional roles. Substantial literature has focused on this significant demographic trend. However, considerably less literature has delved into understanding the gender-segregating process within occupations and between specialties and how these processes interact and intersect at both the occupational and specialty levels. The importance of filling this gap is underscored by the fact that within-occupational processes explain a significant proportion of wage inequality in the United States. This dissertation aims to fill this theoretical and empirical gap in the literature through a case study of the medical profession, which has been feminizing over the past four decades, with equal numbers of men and women now graduating from medical school. I argue that the same processes influencing gender segregation between occupations also affect gender segregation within occupations. Furthermore, I contend that supply side factors, specifically how workers rank specialties within an occupation (referred to as "the job queue"), play a crucial role in the gender-segregating process within an occupation and can be leveraged to increase women's representation in men-dominated specialties. My dissertation comprises three separate empirical studies. In the first study, I apply principles from community ecology literature to investigate how relative decreases in rewards, compared to the occupation as a whole, in a specialty significantly influence job queues within occupations, independent of absolute decreases in rewards in that specialty. In my second study, I identify and examine the defining features of social closure mechanisms that create opportunities for women to enter specialties within an occupation. Building on these findings, in my third study, I construct a typology of social closure mechanisms within an occupation. I empirically analyze how supply and demand side mechanisms mediate the relationship between the types of social closure mechanisms in an occupation and subsequent specialty choices. Together, these studies highlight that women and men rank specialty characteristics similarly, providing opportunities for social closure mechanisms within a specialty to be structured in ways that decrease gender segregation within occupations.

Keywords: Humanities and Sciences.
Sociology.
Advisor: Freese Jeremy
Correll Shelley Joyce
Pedulla David S.
Unraveling the immune response to vaccination in mice and humans

The fundamental goal of vaccinations is the induction of robust and durable protective immunity against pathogens. The emergence of the SARS-CoV-2 virus, and its rapid mutation into immune-evasive variants, underscored the necessity for vaccines to confer long-lasting and cross-protective memory responses. While current vaccination strategies for respiratory viruses such as SARS-CoV-2 and influenza virus provide moderate protection, achieving durable sterilizing immunity against these pathogens has remained a major challenge. This dissertation explores two vaccination strategies that have the potential to enhance current immunization approaches. First, we investigate the potential of vaccine adjuvants as a strategy to augment the magnitude, durability and breadth of vaccine-induced immunity. In Chapter 2, using mouse models, we perform a comparative evaluation of the immune responses induced by diverse vaccine adjuvants in combination with a candidate COVID-19 vaccine antigen. In Chapter 3, we delve deeper into the adaptive immune responses induced by an adjuvanted COVID-19 vaccine in humans, with a particular focus on the breadth of the antibody responses in the presence and absence of the adjuvant. Our findings presented in these two chapters highlight the crucial role of vaccine adjuvants in enhancing the immune response to vaccination, elucidate the diversity of different adjuvant formulations, and provide evidence for the enhancement of cross-reactive immunity by investigating the clonal dynamics of B cells over the course of vaccination in humans. Second, we examine the incorporation of T cell memory in addition to humoral immunity as a vaccination strategy to enhance protection against infection. In Chapter 4, using influenza as a model, we investigate the role of T cell memory and antibody responses in contributing to protection either individually or in combination. We find that combining T cell memory with humoral immunity provides with superior protection against infection, highlighting T cells as attractive targets of vaccination. In Chapter 5, using a novel vaccination platform utilizing circular RNA encoding antigenic sequences, we induce robust CD8 T cell responses in mice, elucidating a novel candidate platform for T cell vaccines. Collectively, the findings in this thesis significantly enhance our understanding of the adaptive immune responses induced by vaccination. Our results underscore the pivotal role of adjuvants in shaping the immune response to vaccination, and reveal the contribution of T cell memory to protection against infection, presenting two promising strategies to address current challenges in vaccinology.

Keywords: Medicine.
Microbiology and Immunology.
Advisor: Pulendran Bali
Davis Mark
Lanz Tobias
Martinez Olivia