VictorJuiz/thesis huggingface dataset:
Dynamics of enteroviral polyprotein cleavages and implications for antiviral drug development

Enteroviruses are a group of positive stranded RNA viruses that primarily infect the enteric tract, but many species have also been associated with neurological complications, especially acute flaccid myelitis. While poliovirus, the most well studied member of this group, is on its way to eradication, there are other Enteroviruses currently circulating and causing disease, and outbreaks of vaccine associated polio still occur. Therefore, novel treatments are needed. Unfortunately, antiviral treatment is often thwarted by the emergence of drug resistant variants due to the high mutation rates of RNA viruses. One potential avenue for overcoming the problem of resistance is to choose targets that produce dominant inhibitors when interacting with the antiviral drug. Previous work in the lab showed that viral proteases that cleave themselves from the viral polyprotein obligately intra-molecularly can produce such dominant inhibitors by causing uncleaved viral precursor proteins to accumulate. In this work, I explore the potential for enteroviral proteases to produce dominant inhibitors. Chapter 1 summarizes relevant background information, including enterovirus biology, polyprotein processing, and the concept of dominant drug targets. In chapter 2, I identify intra-molecular cleavages in the poliovirus, EV-A71, and EV-D68 polyprotein processing cascades. In chapter 3, I determine the efficacy of existing antivirals for intra- vs inter- molecular cleavages, demonstrating that some antivirals can very effectively inhibit even rapid intra-molecular cleavages. In chapter 4, I show that blocking 2A protease cleavage in multiple enterovirus species can lead to suppression of wildtype viral growth in mixed populations, supporting the hypothesis that inhibiting 2A cleavage could lead to the production of dominant inhibitors. In chapter 5, I attempt to identify the mechanism by which 2A mutant genomes exert a dominance phenotype over more fit wildtype viral genomes. Finally, in chapter 6, I discuss remaining open questions and new research directions stemming from this work. The findings detailed here not only contribute to our understanding of basic enterovirus biology, but also illustrate a paradigm through which novel antiviral treatment approaches can be developed.

Keywords: Medicine.
Genetics.
Advisor: Kirkegaard Karla
Carette Jan
Fire Andrew
Sherlock Gavin
Dynamics of rotating structures in a magnetized plasma discharge

Azimuthally propagating instabilities, in the form of regions of higher plasma density, are sometimes seen propagate in Hall thrusters and other magnetized discharges. These structures, termed spokes, have been linked to an increase in axial electron mobility and are thought to play a role in breathing mode oscillations. The goal of this work is to understand the physics behind the spokes and study the conditions for their formation and propagation. Two small ring-shaped magnetized discharges (5 mm and 19 mm in diameter) form inside two configurations, that differ only in size, of a device designed to promote the exclusive growth of the same spokes observed in Hall thrusters while being much easier to operate. Two main diagnostic techniques are used: high-speed imaging, through a transparent layer of Indium Tin Oxide (ITO) constituting the anode, and anode segmentation current measurements, obtained by segmenting the anode into electrically isolated regions. Both diagnostic techniques reveal the presence of spokes azimuthally propagating along the discharge ring in the frequency range 100 kHz to 10 MHz when operating with argon gas. A theoretical framework is developed to model the propagation of the spokes as a saturated instability wave. The linear perturbation analysis of the equations leads to an analytical form of the wave dispersion relation which reveals the instability conditions and is shown to be in agreement with experimental results. Experimentally, operating conditions are varied to characterize how the propagation of these plasma structures is influenced by the various parameters. Discharge current and distance between electrodes are found to be the parameters to which their propagation is most sensitive. A spectral analysis of the segmented anode currents reveals the presence of a threshold current under which the direction of propagation of the spokes reverses. A theoretical model suggests this rotation inversion to be caused by the large density gradients that are promoted by low currents and can lead to an inversion of the local electric field

Keywords: Engineering.
Mechanical Engineering.
Advisor: Cappelli Mark A. (Mark Antony)
Hara Ken
Raitses Yevgeny
Early childhood educational opportunities under the Kentucky Education Reform Act

In this dissertation, I examine how two major social programs in Kentucky -- state-funded preK and Family Resource and Youth Service Centers -- impact children's outcomes across the state, including racial, ethnic, and economic equity through elementary school. In each chapter, I will analyze how early childhood opportunities relate to outcomes including Kindergarten-readiness, including cognitive, language, physical, and socioemotional skills; uptake of preventative health care including early health check-ups, vision screenings, and immunizations; unexcused absences, chronic absence, and discipline in Kindergarten or through elementary school; and performance on statewide standardized math and ELA assessments in Grades 3--5. To do this, I leverage what may be the first statewide, student-level dataset that will permit the linking across preK settings, Kindergarten-readiness, and school outcomes through Grade 3. I look at eight cohorts from the Kentucky Longitudinal Data System from 2013-2014 through 2019-2020, including demographic, academic, health, and service records of approximately 300,000 unique students in preK, comprising 2.3 million student-year observations from preK through Grade 5. This dissertation provides evidence that thirty years after the Kentucky Education Reform Act established state-funded preK and Family Resource and Youth Service Centers, the programs have impacts on equity and outcomes from Kindergarten through Grade 5.

Keywords: Education.
Advisor: Obradovic Jelena
reardon sean
Sanders Lee
An E-cadherin and PAR-3-based symmetry breaking mechanism translates stable cell/cell contacts into coordinate tissue polarity in C. elegans intestinal epithelial cells

Tissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. One of the most prevalent animal tissues are epithelia, which polarize along a characteristic apico-basolateral axis and are critical for protecting internal organs from the external environment. The mechanisms which 'break symmetry' and inform the orientation and execution of apico-basolateral polarity axes across diverse epithelia remain poorly understood. To address these questions, I explored symmetry breaking in the developing Caenorhabditis elegans intestine, a simple epithelial tube which gains its polarity as a sixteen-celled primordium when apical proteins polarize along a central embryonic midline. After introducing general principles of epithelial polarity (Chapter 1) and development of the worm intestine (Chapter 2), I describe essential roles I found for the polarity scaffold PAR-3 and the transmembrane adhesion protein HMR-1/E-cadherin in epithelial symmetry breaking (Chapter 3). C. elegans intestinal cells break their symmetry as an 8-celled primordium when they localize PAR-3 and HMR-1 into large puncta I term Local Polarity Complexes (LPCs). By pairing detailed imaging approaches with powerful genetic tools to remove LPC components specifically in the intestine, I discovered that PAR-3 and HMR-1 function as an interdependent module to build LPCs during, but that these factors diverge in function to elaborate tissue polarity. In Chapter 4, I describe how asymmetric information is transmitted to intestinal cells to mark the first meaningful polarity cue within the tissue. I found that LPCs mature exclusively at homotypic (intestine/intestine) contacts and are largely absent from heterotypic (intestine/neighbor) contacts. Through careful analysis of high temporal resolution developmental movies and acute perturbations with chemical inhibitors, I showed that symmetry breaking is mediated by inherent differences in contact stability: LPCs can form at all intestinal surfaces but are systematically removed from heterotypic contacts via neighbor rearrangements and oriented cell division. This work reveals a novel 'molecule-agnostic' symmetry breaking paradigm for an internally developing epithelium. Finally, I demonstrate the existence of backup mechanisms which eventually polarize intestinal primordia which lack HMR-1 (Chapter 5), and describe a proof-of-concept forward genetic screening approach to reveal interactors working in concert with or parallel to HMR-1

Keywords: Humanities and Sciences.
Biology.
Advisor: Feldman Jessica L.
Oro Anthony
Shen Kang
Simon Michael (Biology professor)
Ecological determinants and effects of manganese oxidation state and bioavailability

Soil organic matter (SOM) contains more than three times as much C as the atmosphere does. Even a small tip of the balance between SOM formation and SOM decomposition can have disproportionate effects on CO2 concentrations in the atmosphere, therefore on climate. Manganese (Mn) is a biologically essential redox-active metal that remains a largely unexplored but possibly critical element controlling soil C stocks. As Mn undergoes reduction-oxidation reactions, it assumes a reactive, intermediate oxidation state that can oxidize organic C. The significance of Mn redox cycling to ecosystem C storage remains poorly resolved. I combine field measurements from a rainfall gradient and laboratory experiments to elucidate how rainfall shape Mn redox cycling, how Mn redox cycling interacts with SOM in natural soils, and how foliar Mn versus soil Mn influences grass-litter decomposition. This is the first systematic investigation of rainfall's effect on Mn oxidation state within the rhizosphere and on the role of Mn in grassland C stability. Given the existential threat that climate change poses, we need to understand the soil processes that affect this massive, labile C pool. Rainfall gradients are a powerful tool to evaluate how and where Mn potentiates OM decomposition. In Chapter 2, I determine that rainfall defines patterns in Mn oxidation state and redox cycling along a Hawaiian rainfall gradient. In Chapter 3, I analyze the influence of Mn on soil C stability in situ on a grassland rainfall gradient and in vitro using an incubation experiment; the results show that Mn bioavailability does not destabilize organic C in a grassland soil. In Chapter 4, I examine the roles of soil Mn versus foliar Mn on grass-litter decomposition on a rainfall gradient and in laboratory incubations; both experiments demonstrate that Mn, whether foliar- or soil-derived, does not control litter decomposition in a grassland. This research can inform models to revise projections on the capacity of soils to sequester C in the face of climate change

Keywords: Humanities and Sciences.
Biology.
Advisor: Vitousek Peter Morrison
Casciotti Karen Lynn
Chadwick Oliver A.
Fendorf Scott
Peay Kabir
Ecologies of care : migrant women, precarious housing, and the politics of eradication in Chile

This dissertation is an ethnographic and historical study of the politics of migrant life in Chile. It draws on participant observation, interviews, participatory mapping, archival research, and media analysis to track changing configurations of migration, vulnerability, and protection in the northern border city of Antofagasta. Migrant encampments in Antofagasta are at high risk for fires and climate-change induced mudslides, and concentrate disproportionate levels of poverty and crime. As predominantly Black and Indigenous migrant women make precarious spaces livable, their lives and livelihoods become entangled with dangerous environments. I argue that the "ecologies of care" that result from this spatial transformation are in tension with state projects that allegedly protect vulnerable populations by "eradicating" environments where poverty, crime, and risk take place. Drawing on this case, my research proposes a perspective on the politics of migrant life that goes beyond theoretical frameworks of rights and citizenship, foregrounding instead everyday spatial practices through which migrant women engage the state. A place- and person-based, community-engaged ethnography, this dissertation integrates anthropological, decolonial, and feminist theories of violence and vulnerability with ecological approaches to health, inequality, and care

Keywords: Humanities and Sciences.
Anthropology.
Advisor: Garcia Angela
Ferguson James
Fullwiley Duana
Han Clara
Hansen Thomas Blom
The ecology and evolution of social learning by predators

Social learning may help foragers find food, but can cause competition. I first examined the evolution of social learning by predators in predator prey models, examining the ecological implications of three types of social learning: (1) unbiased social learning, in which social learners randomly choose a behavior from their demonstrators, (2) conformist social learning, in which learners are more likely to adopt the behavior used by most demonstrators, and (3) success-biased social learning, in which social learners copy successful demonstrators. Unbiased and conformist social learning caused diet preferences and hence increased competition in the predator population, but success-biased social learning did not. I then examined the evolution of cooperative hunting when transmitted vertically (from parents to offspring) or horizontally between members of the same generation. When rare, cooperative hunting may allow predators to escape competition for prey caught alone, which we call the small prey, and may allow them to access "big prey" which cannot be caught alone, but a lonely cooperator cannot catch food unless it can transmit its behavior to another predator. The cooperative hunting model found that vertical transmission of cooperative hunting is only sufficient for the evolution of cooperative hunting if predators stay near relatives. Otherwise, horizontal cultural transmission is essential for cooperative hunting. Ecological factors such as high availability of big prey and low availability of small prey further selected for cooperative hunting.

Keywords: Humanities and Sciences.
Biology.
Advisor: Feldman Marcus
Rosenberg Noah
Tuljapurkar Shripad
Economic Dependence on Japan and China’s Response to Anti-Japan Demonstrations from 1985 to 2012

It has been more than 50 years since Japan and China normalized their diplomatic relationship in 1972. Now, China and Japan are the world’s second and third-largest economies which play an essential role in the peace, stability, and prosperity of the region. However, until now, both countries have not realized a long-term stable relationship.
One of the serious challenges to improving the bilateral relationship is Chinese public sentiment toward Japan. After the normalization of diplomatic relations, there were several anti-Japan demonstrations in China:1985, 2005, and 2012. The 1985 case occurred in response to the Japanese Prime Minister (PM) Nakasone visited the Yasukuni Shrine. The 2005 case occurred in response to Japan’s bid for a permanent Security Council seat in the United Nations (UN). The 2012 case occurred in response to the “nationalization” of the Senkaku Islands by the Noda administration. In each case, there was Chinese public anger that affected both the Japanese and the Chinese governments. However, the actions of the Chinese government varied. Only in some cases did the Chinese government tolerate the demonstrations, and only in some cases did the CCP strategically use public sentiment to increase its domestic and diplomatic interests, once the anti-Japan demonstrations broke out. The question is why China responded differently.
While there have been a number of studies on these demonstrations, as I will discuss below, this thesis will try to shed additional light on why the Chinese Communist Party (CCP) adopted different attitudes towards anti-Japan protests over time. The central research question is under what circumstances does the CCP government repress or tolerate the anti-Japan protests.
In contrast to much of the existing on these protests, I will focus on China’s economic dependence on Japan, which has changed dramatically over the last 40 years. China, when the first anti-Japan demonstrations broke out in 1985 is very different from the one when the more recent demonstrations occurred in 2012. China went from being a poor developing country in 1978 to overtaking Japan to become the world’s second-largest economy in 2010. This change in economic status may be one possible reason why China’s reactions changed over time. I will examine whether the CCP’s management of the anti-Japan demonstrations over time is correlated with changes in the nature of China’s economic relationship with Japan.

Keywords:  Stanford Global Studies
Anti-Japan demonstrations
Japan-China relations
Economic dependence
1985 to 2012
Text
Thesis
Advisor: Oi Jean
The economic impacts of energy and climate technology in the global south

We are in a race against time to mitigate the worst impacts of climate change. Fortunately, the speed and scale of climate technology innovation and deployment is increasing in some wealthy countries. But, most of the Global South is being left behind, in terms of mitigation, adaptation and entrepreneurial opportunity. This lack of infrastructure and technology deployment is particularly true in Sub Saharan Africa (SSA), home to 1.2b people. This current situation is troublesome given that most people in the Global South, and especially SSA, contributed very little to climate change but are bearing the immediate brunt of its impacts. To help address the lack of progress, I designed my dissertation in two parts - to explore the past effects of energy development and prospective impacts of climate technology adoption. Specifically, I study how electricity development and increased access affects wealth and public health; and second, the potential impacts of electric vehicle deployment on reducing climate emissions and air pollution and increasing government revenue. Following the introduction of the dissertation, I start by briefly discussing the lack of research and investment in climate technology in the Global South, in which I illustrate why this lacking attention is so unfortunate, noting the historic social justice component\citep{Ratledge:2022b}. Then, in the first full chapter, we use satellite imagery and machine learning to impute wealth at the community level and measure the impact of Uganda's grid expansion on household wealth\citep{Ratledge:2022a}. This research is novel in terms of imputing data at scale in SSA, developing a first of its kind time series of electric grid evolution, and applying this data in causal analysis. I extend the exploration of electrification in my next chapter by tracking childhood mortality in SSA post night time light (NTL) luminosity. I find childhood mortality rates decrease and wealth increases post NTL visibility, providing additional insight into how and when communities can escape the well-documented `poverty trap' that plagues communities across the Global South. In the last chapter I simulate electric vehicle roll out in Kenya and find that Kenya could save hundreds of millions of dollars in emissions costs and simultaneously increase government revenue by a quarter billion dollars over the next ten years. Together, my research creates a clearer understanding of both the historic effects of electrification in SSA and quantifies the potential impacts of climate technology deployment, where the benefits are substantial and deserve greater attention and investment

Keywords: Sustainability.
Advisor: Burke Marshall
Reichelstein Stefan
Caldeira K. (Ken)
Field Christopher B.
Economies of weaving : women, labor, and textiles at Morgantina from the bronze age to the republican era

Textiles were everywhere in antiquity and their production was remarkably labor intensive. Textile labor was also one of the only productive activities which was explicitly gendered as women's work. In this dissertation, I investigate how women's labor was mobilized and allocated for textile manufacture, focusing in particular on the household as a central locus of production and consumption. The archaeological site of Morgantina in east-central Sicily serves as my primary case study. The site is especially apt for this analysis because of its unique collection of over 2,000 textile tools, well-documented excavation history dating back almost 70 years, and long span of habitation. Textile tools have been recovered in contexts dating to all major periods at the site from the Early Bronze Age (ca. 2400--1600 BC) through the Republican era (2nd and 1st centuries BC). The wide chronological span of these artifacts affords the opportunity to connect long-term changes with broader sociopolitical and economic phenomena. This study makes three main contributions. First, I utilize the vast archive of notebooks and drawings from previous excavations at Morgantina to date a sizable number of textile tools recovered at the site. The result is a sequence of artifacts spanning two millennia which both demonstrates broad continuities in the technologies used for spinning and weaving, and also identifies important moments of innovation. Second, I offer a new methodology for studying textile tools which combines the close analysis of archaeological context with recently developed techniques for reconstructing production possibilities. Lastly, I draw on these historical and methodological insights to track changes in the socioeconomic organization of textile manufacture. My findings call into question pervasive narratives in the field of economic history which focus on population growth and urbanization as the prime movers of craft specialization. In place of these narratives, I foreground an array of neglected factors—such as gender, the structure of the household, dependence on enslaved labor, the use of coinage, and political formations—which were pivotal in promoting and constraining specialization in antiquity.

Keywords: Humanities and Sciences.
Classics.
Advisor: Saller Richard
Trimble Jennifer
Ceserani Giovanna
GlebaMargarita
WalthallDenton Alex