VictorJuiz/thesis huggingface dataset:
Building a wiring diagram of the human genome

How cells utilize the same DNA to accomplish different functions is a central problem in cell biology. This process is thought to be controlled in large part by hundreds of thousands of small non-coding DNA elements, like enhancers, that turn protein-coding genes on and off across vast genomic distances. The dominant model invoked to explain how these interactions occur is through the formation of DNA loops that bring elements that lie far apart along the DNA polymer into spatial proximity. However, the wiring diagram of enhancer-gene looping, and the mechanisms by which these interactions form, are poorly understood. In this dissertation, I present my graduate work on (i) the comprehensive mapping of DNA looping between regulatory elements genome-wide; (ii) the dynamics of DNA looping in vivo; and (iii) the molecular mechanisms underlying the formation of DNA loops between regulatory elements. First, we develop in situ Hi-C, a DNA-DNA proximity ligation assay in the setting of intact nuclei, which we use to create kilobase resolution 3D maps of the human genome. These maps reveal a partitioning of the genome into roughly 10,000 loops. The loops are bound by the DNA-binding protein CTCF and the cohesin complex at convergently oriented CTCF-bound DNA motifs. Second, in order to explain this "convergent rule", we propose a model of loop formation by DNA extrusion, where the cohesin complex binds at a single locus and tracks in opposite directions along the DNA, extruding a loop, until it halts at barriers including inward-oriented CTCF-bound motifs. We test key predictions of the extrusion model. We show that it correctly predicts the detailed consequences that CRISPR genome-editing of CTCF motifs will have on loops. It also correctly predicts the effects of degrading cohesin: namely, rapid dissolution of loops genome-wide. We show that extrusion is ATP-dependent and moves at speeds of ~0.5-1kb/s. These models and estimates have since been validated, in detail, by numerous laboratories. Finally, we develop intact Hi-C, DNA-DNA proximity ligation in the setting of intact chromatin, which is much more sensitive to the presence and the position of loops. Using intact Hi-C, we comprehensively identify all loci capable of forming loops in the genome, including tens of thousands of enhancers, which we systematically link to their targets and connect to transcriptional consequences. By combining our comprehensive loop anchor annotations with perturbations of anchor associated proteins, we identify a novel mechanism for promoter-enhancer loop formation when cohesin loop extrusion is arrested at RNA polymerase II binding sites. Taken together, this work establishes a mechanistic basis for the formation of regulatory DNA loops in the human genome. It also lays the foundation for the generation of a comprehensive catalog of distal regulatory interactions in an organism

Advisor: Kornberg Roger D.
Greenleaf William James
Kundaje Anshul
Aiden Erez
Building an Intelligent Goal-setting Coach: Transformer-based Evaluation and Suggestion of Written Goals

The structured practice of writing learning goals has been shown to be beneficial for both cognitive and noncognitive skill development (Evans and Hardy, 2013; Ridley et al., 2010). Furthermore, these effects are increased when the goals follow the SMART framework, meaning they are Specific, Measurable, Attainable, Relevant, and Time-bound (Lawlor, 2012). However, the implementation of such programs in schools is challenged by teachers’ lack of availability to provide feedback (Rao, 2021). Therefore, the goal of this project is to use Natural Language Processing to automate two parts of the coaching process– evaluation and suggestion– to save teachers time when implementing a goal-setting program. Firstly, for evaluation, because attainability and relevancy vary based on the writer, I focus on the other three facets, and experiment with four models to evaluate written goals for whether they are Specific, Measurable, and/or Time-bound. Specifically, I experiment with the following systems: one that uses separate vanilla RNNs with linear classification heads for each task, one that uses a single vanilla RNN base that feeds into three task-specific output heads, a system with three separate BERT models with fine-tuned linear classification heads, and finally, a single fine-tuned BERT model base with three output heads, utilizing hard parameter sharing. From these experiments, I conclude that the single BERT base model with three output heads is most advantageous because of its performance and its parameter cost savings and reduced training time. Secondly, as a proof of concept for suggestion, I utilize GPT-3 with few-shot learning and demonstrate the ability for the model to adapt goals to make them Time-bound, with a success rate of 82%. Lastly, I contribute a novel dataset of 1,000 written personal goals, each labeled for whether they are Specific, Measurable, and/or Time-bound. These three pieces hopefully add to the development of automated goal-setting coaching, to expand possibilities for program implementation in schools.

Keywords: Edtech
Transformers
Goal Setting
Text
Thesis
Building integrated and structured memory representations during goal-directed learning

Acquiring knowledge from the events in our lives that can be drawn upon in the future is central to the human experience. Interactions between the medial temporal lobe and neocortex allow us to both recall specific episodes from the past and abstract relationships across experiences when memories share common elements. Over learning, dynamic memory processes integrate new experiences with existing memory representations, building structured knowledge about the world. As the emergence of structured knowledge is crucial for planning and decision-making, delineation of the neural and psychological processes underlying integration and abstraction are necessary to advance understanding of how memory guides behavior. In this dissertation, I illustrate how technical advances in the behavioral and neural sciences are transforming the study of memory. I describe a novel, multi-day experimental paradigm that combines virtual navigation, functional neuroimaging, and neural pattern similarity analyses to investigate how humans build structured knowledge through immersive, goal-directed navigation. I begin by presenting behavioral evidence for structured knowledge formation as participants learn to navigate in local and global virtual environments and discuss how study participants differ in the building of such knowledge. In subsequent chapters, I characterize experience-driven changes in memory representations in the medial temporal, frontal, and parietal lobes across learning in local and global navigation tasks. I find that learning restructures human memory representations to reflect experienced transitions within the virtual environment. I also find evidence that the hippocampus begins to build a representational structure extending beyond directly experienced transitions, and that the nature and characteristics of hippocampal representations relate to participants' subsequent navigation performance. Together, this work sheds light on how the brain comes to represent the external world and builds memories that support flexible, goal-directed behavior

Advisor: Giocomo Lisa
Wagner Anthony David 
Gardner Justin
McClelland James L.
Williams Leanne M.
Building versatile reinforcement learning agents with offline data

Recent advances in machine learning using deep neural networks have shown significant successes in learning from large datasets. However, these successes concentrated on computer vision and natural language processing while the progress in sequential decision-making problems is still limited. Reinforcement learning (RL) methods are designed to solve such problems, but, in contrast, struggle to scale to many real-world applications, because they rely on costly and potentially unsafe online trial-and-error and require the inefficient process of learning each skill individually from scratch. In this thesis, we will present works on designing RL agents that are trained directly from offline data and capable of mastering multiple skills, addressing the aforementioned challenges. In the first part of this thesis, we first introduce an algorithm that learns performant policies from offline datasets and improves the generalization ability of offline RL agents via expanding the offline data using rollouts generated by learned dynamics models. We then extend the method to high-dimensional observation spaces such as images and show that the method enables real-world robotic systems to perform manipulation tasks. In the second part of the thesis, to avoid the issue of learning each task from scratch in prior RL works while maintaining the benefit of offline learning, we discuss how we enable RL agents to learn a variety of tasks from diverse offline data via sharing data across tasks. Moreover, we show that sharing data requires labeling the reward of data from other tasks, which relies on heavy reward engineering and is also labor-intensive. To tackle these issues, we describe how we can effectively leverage diverse unlabeled data in offline RL, bypassing the challenge of reward labeling. Finally, we conclude with listing future directions such as effective pre-training schemes with heterogeneous unlabeled offline datasets, online fine-tuning after offline pre-training and lifelong learning with offline datasets

Advisor: Finn Chelsea
Ermon Stefano
Sadigh Dorsa
Bullying & State Law: Examining Associations Between Anti-Bullying Statutes & School Safety Outcomes for Students

Bullying has increasingly become recognized as a serious social issue that impacts youth well-being. It has been linked with PTSD and is shown to be a significant risk indicator for suicide attempt. As a result, many state legislatures have addressed this issue through some form of anti-bullying legislation. However, there is wide variability in terms of the types and strength of anti-bullying provisions that are included in each state’s statutes. This study analyzes state statutes for the presence and strength of various anti-bullying legal provisions. It then examines associations between these provisions and the probability of a high school student being bullied, cyberbullied, and missing school due to safety concerns. The study provides a snapshot of the landscape of state anti-bullying laws as of September 2018, as well as some evidence regarding the types of legal provisions that appear most effective in terms of protecting students from bullying and other detrimental outcomes. This study finds that a protective definition of bullying, inclusion of all types of bullying, staff reporting requirements, counseling requirements, prohibitions on retaliation, publicly available data, and training for school staff are significantly associated both with a decreased probability of a student being bullied as well as cyberbullied.

Keywords: Public Policy Program
Bullying
Cyberbullying
Anti-Bullying Laws
Bullying in schools > Law and legislation
Anti-Bullying Legal Factors
Bullying > Law and legislation
State Anti-Bullying Laws
State Bullying Laws
Bullying Protective Factors
YRBSS
Stanford University
Humanities and Sciences
Public Policy Program
Text
Thesis
Advisor: Koski William
The business of living : socialism at the grassroots in Guangzhou, 1953-1989

This dissertation examines the transformation of China's socialist economy at the grassroots, from the implementation of state command in the early 1950s through the first decade of post-Mao reforms in the 1980s. It focuses on food and livelihoods—two of the most important themes of everyday life for ordinary people—in the city of Guangzhou. By examining the interface between local state and society in these two areas over the course of three decades, across the mythical divide of 1978 that marked the start of Reform and Opening, this dissertation seeks to shed light on the relationship between Mao-era command economy and post-Mao reforms, explore the origins and process of 1980s marketization, and understand the political valence and transformation of social contract that accompanied economic change. In doing so, this dissertation seeks to contribute a locally-grounded framework to our understanding of how the China of Mao became the China we know today

Keywords: History.
Advisor: Mullaney Thomas S. (Thomas Shawn)
Sommer Matthew Harvey
Weiner Amir
By and For Ourselves: Gay Men of Color and the Fight Against HIV/AIDS in San Francisco, 1970-1998

In the 1980s and 1990s, HIV/AIDS represented an existential threat to the thriving gay community of San Francisco–and particularly for gay men of color, who were being diagnosed with the disease at higher rates than their white counterparts. As mainstream AIDS service organizations like the San Francisco AIDS Foundation—the first and largest in the city—came to serve a primarily white gay clientele, gay AIDS activists of color realized that their racial exclusion from the gay community affected the ability of such mainstream gay organizations to reach gay people of color. The growing threat of AIDS to queer communities of color and the lack of resources for them in these mainstream AIDS groups led to the formation of groups led by and designed for queer men of color in the mid-1980s. Taking into account how both their race and sexual orientation influenced their lives, gay people of color prioritized cultural competence—which emphasized considering the culture and experiences of the group that were trying to reach when developing HIV prevention materials. As the epidemic dragged into the 1990s, these activists created new interventions based in an “empowerment” model that often went beyond HIV prevention to bear witness to their unique experiences as both gay and nonwhite. In this thesis, I add to the nascent scholarship on the AIDS crisis by considering how the intersections of race/ethnicity and sexual orientation influenced the AIDS services that gay men of color created.

Keywords: Gay activists
AIDS (Disease)
HIV infections > Prevention
California > San Francisco
National Task Force on AIDS Prevention (NTFAP)
National Latino/a Lesbian and Gay Organization (LLEGO)
GAPA Community HIV Project (GCHP)
Black and White Men Together (BWMT)
African American gay men
Hispanic American gay men
Asian American gay men
Native American gay men
Filipino Task Force on AIDS
Comunidad Unida en Respuesta al SIDA (CURAS)
Pomo Afro Homos
Tongues Untied
Racism
Intersectionality (Sociology)
American Indian AIDS Institute (AIAI)
Gay Men of Color Consortium (GMOCC)
Love Like This Theater
Text
Thesis
CALCOCO2, a positively selected gene in bats has differential effects on host susceptibility to bacterial infection

Bats are the likely reservoirs for many zoonotic pathogens, including Nipah, Marburg, SARS, and Ebola viruses, that can be lethal to humans but cause little disease in bats. Meta-analysis of several genes under positive selection in 18 bat species identified CALCOCO2, an intracellular autophagy receptor that targets invading microbes for destruction. An antimicrobial function of CALCOCO2 during Salmonella Typhimurium infection has been characterized in human epithelial cell lines, leading to our investigation of its effect on infections in bat cells. The objective of this work is to characterize signatures of positive selection in Chiropteran CALCOCO2 sequences, determine its function in bat cell lines, and investigate molecular mechanisms by which it impacts microbial replication. Phylogenetic analyses predict an evolutionary history of CALCOCO2 that implies long-term selective pressure on this gene. In Chapter 2, I analyze the evolution of CALCOCO2 in bats, and determine which regions display signatures of interesting evolution. Our investigation of sequence conservation and divergence highlights hotspots of polymorphism localizing to CALCOCO2 domains and motifs that regulate xenophagy initiation and completion. Chapter 3 investigates the role of CALCOCO2 in the context of Salmonella infection in bats. Depletion of CALCOCO2 via si-RNA and CRISPR-generated CALCOCO2 knockouts cells reveal a surprising pro-bacterial role of CALCOCO2 in cells from two evolutionarily distant bat species. This pro-bacterial role is not due to a differential ability of bat CALCOCO2 to detect Salmonella, and is downstream of bacterial entry. In Chapter 4, I explore the molecular mechanism underlying this pro-bacterial effect by infecting WT and KO cell lines with Salmonella inducing different levels of membrane damage, and monitoring the kinetics of autophagic membrane recruitment to bacteria. Remarkably, CALCOCO2 contributes to early SCV integrity in both human and bat cell lines, and facilitates long-term association of autophagic membranes to Salmonella only in Egyptian fruit bat cell. Collectively, this work provides evidence for microbially-driven positive selection on regulation of selective autophagy in bats, and sheds light on a genetic signature that might enable bats to tolerate dangerous pathogens without succumbing to infection

Keywords: Microbiology and Immunology.
Advisor: Hadly Elizabeth Anne
Kirkegaard Karla
Carette Jan
Sawyer Sara
Calling for the Vote: A Descriptive Analysis of Calls to the Election Protection Hotline During 2020

In my thesis, I explore the present-day actualization of voting rights. After the dismantling of the preclearance requirement of the Voting Rights Act of 1965 (VRA) with the Supreme Court’s decision in Shelby County v. Holder (2013), what are the contemporary challenges to accessing the franchise, and do those challenges impact communities unevenly? Do historically marginalized communities experience increased burdens in exercising their rights? Is it more challenging for individuals to vote in counties that were previously subject to preclearance but no longer need approval to alter voting procedures? Utilizing a novel data source, Election Protection Hotline data, I analyze the nearly 200,000 reports of voting challenges and questions that the Lawyers’ Committee for Civil rights received during the calendar year of 2020. With a three-pronged research design, first, I offer a state-level descriptive investigation of calls to the Hotline in ten states that met a threshold based on Google Trends results. Second, I focus specifically on four states to compare county-level census demographic information from the American Communities Survey (ACS) and Hotline call volume by county relative to the population. Specifically, I use regression analysis to see how race, median household income, and unemployment rate affect call volume. Finally, I exploit the pre-Shelby County county-to- county variation in preclearance coverage in North Carolina to compare the frequency of calls in localities that were previously covered by preclearance with places that were not covered, investigating the consequences of the Shelby County majority opinion for voters. My results indicate that counties with a larger Black or African American population reported more voting challenges to the Election Protection Hotline. My research also shows that individuals reported more challenges voting in counties that are no longer constrained by the VRA, suggesting that preclearance remains a vital tool to protect minority voting rights and prevent democratic backsliding.

Keywords: Political Science
Bonica, Adam
Voting Rights Act of 1965 (United States)
Election law
Elections
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Thesis
Caregiver and Child Health Under Lockdown: Impacts of the COVID-19 Pandemic on Caregiver Outcomes, Caregiving Behaviors, and Health Services Utilization in Rural China

The COVID-19 pandemic has exacerbated societal and health inequities globally. In rural China, in particular, disparities in caregiver and child health already existed and may have shifted, in part due to the uniquely strict lockdown mandates. Caregiver outcomes, caregiving behaviors, and perinatal health services utilization seemingly changed immediately for the many under-resourced communities in rural China. By studying the outcomes and behaviors of families with children born before lockdowns and those with children born during lockdowns, I identify the profound impacts of the COVID-19 pandemic on communities in rural China. I find that paternal but not maternal migration significantly slowed during the pandemic and related lockdowns, which may have contributed to the significantly improved mental health outcomes in caregivers – most often mothers and grandmothers in rural China – through heightened social support. Caregiving behaviors of household and nutrition expenditures and infant feeding practices generally remained the same, other than a significant increase in spending on infant micronutrient supplements. Perinatal health services utilization suffered significantly in some areas, particularly in postnatal care, yet significantly improved in other areas, such as in aspects of prenatal care. This research has implications in public health initiatives and global health policies to improve quality of life for the most vulnerable populations. Contributing knowledge through academic research to the literature on caregiver and child health is essential to promoting equity and transforming lives.

Keywords: Rural China
Public health
COVID-19 (Disease)
Health services accessibility
Mental health
China
Infants > Health and hygiene
Infants > Development
Infants > Nutrition
Caregiver and Child Health
Maternal health services
Caregivers > Health and hygiene
Caregivers > Mental health
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Thesis
Advisor: Rozelle Scott
Darmstadt Gary