VictorJuiz/thesis huggingface dataset:
Human health and environmental sustainability in pathogenic landscapes : feedbacks and solutions
Keywords: Biology.

Feedbacks between human health, well-being, and environmental sustainability are increasingly well recognized, but evidence on actionable solutions to leverage these feedbacks and improve their outcomes is limited. And yet, the recently adopted United Nations Sustainable Development Goals compel decision makers to achieve health for all people while reducing poverty and conserving nature. This dissertation attempts to fill this urgent research gap and empirically assess feedbacks between human health and the environment from two perspectives: (i) environmental drivers of disease in changing landscapes, and (ii) consequences of human health and well-being on environmental change and conservation outcomes. But first, using synthesis science, we describe the environmental components of the world's most burdensome human parasitic and infectious diseases, then assess a specific type of ecosystem service -- natural enemies of human infections -- as a sustainable tool to reduce some communicable diseases. Then, we assess feedbacks between human health and environmental sustainability through two data-rich case studies. First, in the Senegal River Basin, a region hyperendemic for schistosomiasis disease, we assess ecological associations and spatial scales of human disease risk. In this region, schistosomiasis disease, which is transmitted to humans by freshwater snail hosts, can be caused by two species of schistosome parasites (and their two unique snail hosts). The World Health Organization currently recommends that snail control be implemented in endemic areas to curb transmission. However, snail control methods rarely take into consideration the unique transmission dynamics of co-endemic species, which could interfere with control outcomes for one or both species. So here we ask a critical question: what is the spatial scale and ecological correlates of schistosomiasis risk, considering two distinct schistosome species in a co-endemic landscape? We find specific, yet divergent, ecological correlates and spatial scales of risk for each species. Ultimately, these findings can be used to design ecological levers for health (like snail control) that best reflect the unique transmission ecology the targeted species. Second, in rural Borneo, we assess the impact of a 10-year, on-the-ground intervention aiming to improve human health care access in order to curb illegal logging in protected forests, and ask: Is healthcare an effective lever for conservation? Using earth observation, household surveys, and clinic data records, we find that the intervention provided health care access for more than 28,000 patients and averted > 27km2 forest loss (~70% reduction compared to controls), thus improving human health and well-being, and simultaneously preserving globally important forest carbon. In conclusion, this dissertation shows that, by recognizing and embracing complex mechanisms driving health-environment feedbacks, we can identify effective ecological levers for human health, and health levers for conservation
The hustle ethic and the spirit of platform capitalism
Keywords: Sociology.

These three papers broadly seek to understand the causes and consequences of stratification beliefs, particularly for Black Americans in the contemporary United States. I begin by contextualizing the present economic moment as one shaped by "platform capitalism, " a new form of exploitation brought about by the digital revolution. I argue that this form of economic relations develops the "hustle ethic, " or a toolkit for individuals to manage inequality through extreme optimism, faith in the transformative power of digital tools, and a reliance on one's personal capacity to overcome structural barriers. Using social media data from the app Clubhouse, I demonstrate what the hustle ethic looks like for various groups across lines of race, class, and gender. In the following papers, I observe the hustle ethic as enacted by low-income communities of color. I argue that the present economic situation creates a vacuum of knowledge about how unequal society is, even among the most vulnerable. Through ethnographic research conducted over 18 months in Inglewood, California, I show how schools, government agencies, and social media share misinformation with Black and Brown workers, which causes them to miss the few viable social mobility opportunities that exist. Instead, institutions send disadvantaged workers towards hustle ethic rhetoric and a propensity towards risky entrepreneurial ventures. In the third paper, I consider the role of grit, or hard work and persistence, which is a core tenant of the hustle ethic and particularly emphasized to low-income communities of color as a social mobility route in and of itself. I argue that grit alone without a strategic occupational strategy yields limited benefits to Black workers; grit is no match for systemic racism. Still, through 87 in-depth interviews with Black and Brown workers, I show that these opportunity seekers show an immense amount of grit in the face of inequality
I Want You to Teach My Children: The Effect of Teacher Quality on Parental School Choice in the Mexican State of Zacatecas
Keywords: Parental school choice
teacher quality
demand for schools
Mexico
Stanford Graduate School of Education International Education Policy Analysis
Thesis

The growing literature about parental school choice tries to look at determinants of parental school choice, such as distance to household, peer effects, infrastructure, and tuition. This paper contributes to this literature by investigating the role of teachers. In particular, it discusses how an educational reform in Mexico that changed the way teachers are hired affects parental school choice. I show descriptive evidence that teachers hired after the reform have significantly better grades on a standardized exam. Using the percentage of teachers hired through the merit-based system at schools in the northern state of Zacatecas, I estimate a conditional logit model to determine the impact of this new merit-based hiring system on parental school choice. In order to address identification concerns, I use a simulated instrumental variable: teacher vacancies per school. I find no evidence of the chance of parents choosing a school changing if the percentage of teachers hired through the merit-based system increases.
The idea of Greek (pre)history : archaeological knowledge production and the making of "Early Greece, " c. 1950-1980
Keywords: Classics.

This dissertation interrogates the relationships between archaeological practice and broader intellectual trends surrounding the study of the Late Bronze Age (LBA) -- Early Iron Age (EIA) transition in Greece, and, in doing so, presents a case study of mechanisms of archaeological knowledge production in Greek archaeology. In contrast to current historiographical treatments of the LBA-EIA transition, I frame my inquiry around disciplinary "negotiations, " rather than "divides, " and systematically include archival materials to trace the development of scholarly networks, research agendas, and practices. I demonstrate that the LBA-EIA transition was a focalization of the larger debate concerning the relationship between prehistoric and historic Greece, which arose in the late 19th century, and that the study of early Greece has been affected by changing understandings of culture and continuity. As cultural evolutionism and race gradually lost ground as indicators of cultural continuity in the post-WWII period, the interpretation of the archaeological record of the LBA-EIA transition was treated with a new empiricism but at the same time was increasingly beholden to historicizing narratives and models. While innovations in archaeological method have contributed to the study of early Greece, the reception and idealization of Western and Classical civilization have continued to remain in the background of the LBA-EIA transition
Identification of host-targeting antiviral drug combinations and targets
Keywords: Chemical Engineering.

Despite remarkable progress in the last fifty years in the fight against infectious disease, diverse viruses continue to pose major global health challenges. There is a critical need for rapidly deployable, broad-spectrum antiviral therapies. Generally, antiviral therapies are either direct-acting antivirals (DAAs) or host-targeted therapies. This thesis focuses on exploring the potential of and mechanisms underlying two distinct host-targeting antiviral strategies. Firstly, we explore combination therapies comprising inhibitors of de novo pyrimidine biosynthesis—a host-targeting antiviral strategy that has been shown to be effective in vitro against > 30 diverse DNA and RNA viruses. To improve their efficacy under physiologically relevant conditions, we combine inhibitors of the de novo pyrimidine biosynthesis with inhibitors of nucleoside salvage and transport. Using the salvage inhibitor cyclopentenyl uracil (CPU), we successfully demonstrate antiviral activity of this combination in the context of dengue infection. Furthermore, we demonstrate that the efficacy of direct-acting antivirals such as RNA-dependent RNA-polymerase (RdRp) inhibitors can be enhanced via modulation of pyrimidine biosynthesis. This proof-of-concept paves the way for dual virus and host-targeting strategies. Additionally, we perform a genome-wide analysis of human targets of the macrolide antibiotic josamycin. Macrolide antibiotics are commonly prescribed for their ability to inhibit bacterial protein synthesis. However, it is increasingly recognized that they also possess non-canonical anti-viral and other therapeutic activities in mammalian cells. To better understand their modes of action in mammalian cells, we performed a genome-wide shRNA screen in K562 cancer cells to identify genes that modulate sensitivity to josamycin. We report diverse mammalian targets including mitochondrial translation, glycolysis and the mitogen activated protein kinase (MAPK) cascade. This work demonstrates the utility of genome-wide approaches for drug target identification and uncovers human targets of this antibiotic class in an unbiased fashion
Identification of proteins at the parasitophorous vacuole membrane of Toxoplasma gondii
Keywords: Microbiology and Immunology.

Toxoplasma gondii is an obligate intracellular parasite that replicates within a parasitophorous vacuole inside a host cell. The membrane encompassing this vacuole, the parasitophorous vacuole membrane (PVM), is extensively modified by Toxoplasma through the addition of various effector proteins. These effectors enable a variety of host-parasite interactions to occur at this interface that both support and inhibit the growth of the parasites. Despite the importance of the variety of known host-parasite interactions occurring at the PVM, only a small number have thus far been identified due to a poor understanding of the proteins present at this interface. Given this, the work described in this dissertation addresses two important research topics. First, the study presented in Chapter 2 uses affinity purification of the Toxoplasma PVM protein MYR1 followed by mass spectrometry to identify and functionally characterize additional proteins involved in the translocation of Toxoplasma effectors across the PVM, a critical mechanism by which Toxoplasma can influence and reshape the host environment. Second, the work presented in Chapter 3 identifies host and parasite proteins specifically present at the host cytosolic side of the PVM using recent advances in enzyme-catalyzed protein proximity labeling. This method takes advantage of the promiscuous biotin ligase miniTurbo to label proteins in its immediate vicinity. This is the first known study designed to identify all proteins on the host cytosolic side of the PVM in an unbiased way. The knowledge gained from these two approaches provides a substantial advance in our understanding of, and ability to mechanistically study, interesting and disease-relevant aspects of host-parasite biology occurring at the literal interface of Toxoplasma and the host cells it infects
Identifying frizzled receptors that are essential for intestinal stem cell maintenance
Keywords: Biology.

The mammalian small intestinal epithelium is a rapidly self-renewing tissue with a high turnover rate maintained by intestinal stem cells that reside at the base of glands called crypts. The intestinal epithelium is notably dependent on canonical Wnt/b-catenin signaling. Wnt proteins are evolutionarily conserved, secreted ligands that regulate cell-cell communication during developmental and adult tissue homeostasis. Wnt binding to its receptor Frizzled (Fzd) and co-receptors Lrp5/6 initiates canonical (i.e. Wnt/b-catenin) signaling. Our lab and others have shown that inhibition of Wnt ligands, receptors, or downstream signaling leads to the loss of intestinal crypts and Lgr5+ intestinal stem cells (ISCs) indicating that Wnt signaling is critical for ISC maintenance. To date, 19 Wnt ligands and 10 Fzd receptors have been discovered in mammals. However, due to extensive cross-reactivity among Wnt ligands and Fzd receptors, it is unclear which Fzds are functionally relevant in ISC biology. In addition, it is not known which intestinal cell types are responsible for expressing functionally important Fzd receptors for stem cell maintenance. Understanding the mechanisms of Wnt activation in ISC maintenance will allow us to finely regulate Wnt signaling to promote regeneration following intestinal epithelial damage from diseases or harsh treatments such as radiation or chemotherapy. Furthermore, since dysregulations of Wnt/b-catenin signaling are frequently found in gastrointestinal diseases including inflammatory bowel diseases and cancers, addressing these questions holds tremendous potential for translational applications. Our lab has been collaborating with Dr. Chris Garcia's lab at Stanford to better understand intestinal stem cell biology, and his lab has recently bioengineered Wnt agonists and antagonists that mediate Wnt signaling in a Fzd-subtype specific manner. Using these novel proteins as initial screening tools, I will present work identifying Fzd subtypes essential for ISC maintenance in vitro and in vivo. I will further identify cell types that express the corresponding Fzd receptors by using intestinal organoid culture systems and genetic mouse models. First, I define essential Fzds necessary for ISC maintenance using Wnt antagonists as loss-of-function probes. Next, I characterize the molecular mechanism of stem cell and crypt/villus loss induced by Wnt-Fzd complex disruption. Lastly, I deploy Wnt agonists as gain-of-function probes to evaluate the therapeutic potential of Wnt as a replacement for endogenous Wnt in ISCs and in the transplantation setting. Collectively, this dissertation thesis presents fundamental molecular insights into Wnt signaling mechanisms with the ultimate goal of understanding Fzd specificity in the intestinal stem cell compartment
Identifying mechanisms of regulation and signal integration of the heat shock response
Keywords: Biochemistry.

The heat shock response (HSR) is the cell's primary response to cytosolic misfolded protein. It is conserved across eukaryotes and is essential for cell survival. How cells detect misfolded protein and modulate their HSR levels is a poorly understood process. Additionally, manipulation of HSR levels has shown significant promise in treating diseases including cancer and neurodegeneration. Many mechanisms have been proposed for how misfolded protein could alter HSR activity. However, these regulatory mechanisms often lack evidence for if or when they are ever employed. Thus, for most proteotoxic stress conditions, if one or more of these proposed mechanisms is used to activate the HSR or if HSR activation occurs through an entirely different mechanism remains unknown. In this dissertation, I describe our work to quantify the contributions of known HSR activation pathways and discover new pathways of activating the HSR. We developed a method to quantify the most prevalent model of HSR regulation: inhibition of the HSR by the Hsp90 chaperone. We found some stressors for which this model can explain much of the HSR activation, and others for which it contributed very little, suggesting alternative mechanisms of HSR activation. Additionally, I describe the development of ReporterSeq, a high throughput screen to identify genes which regulate a reporter gene's expression under multiple conditions in a time-resolved manner. Using ReporterSeq, we measured the effect of full genome knockdowns on HSR activation across 15 stress conditions. From these data, we identified new general and stress-specific genetic regulators of the HSR. Combined, these data give us a more complete idea of the regulatory mechanisms of the HSR and how they are integrated together
Identity-aware Graph Neural Networks
Keywords:  Department of Electrical Engineering
You, Jiaxuan
Computer Science
Artificial Intelligence
Deep Learning
Graph Neural Networks
School of Engineering
Machine Learning
Graph-based Machine Learning
ML: Relational Learning
ML: Representation Learning
ID-GNN
GNNs
GNN Expressive Power
Thesis

Message passing Graph Neural Networks (GNNs) provide a powerful modeling framework for relational data. However, the expressive power of existing GNNs is upper-bounded by the 1-Weisfeiler-Lehman (1-WL) graph isomorphism test, which means GNNs that are not able to predict node clustering coefficients and shortest path distances, and cannot differentiate between different d-regular graphs. Here we develop a class of message passing GNNs, named Identity-aware Graph Neural Networks (ID-GNNs), with greater expressive power than the 1-WL test. ID-GNN offers a minimal but powerful solution to limitations of existing GNNs. ID-GNN extends existing GNN architectures by inductively considering nodes’ identities during message passing. To embed a given node, ID-GNN first extracts the ego network centered at the node, then conducts rounds of heterogeneous message passing, where different sets of parameters are applied to the center node than to other surrounding nodes in the ego network. We further propose a simplified but faster version of ID-GNN that injects node identity information as augmented node features. Altogether, both versions of ID-GNN represent general extensions of message passing GNNs, where experiments show that transforming existing GNNs to ID-GNNs yields on average 40% accuracy improvement on challenging node, edge, and graph property prediction tasks; 3% accuracy improvement on node and graph classification benchmarks; and 15% ROC AUC improvement on real-world link prediction tasks. Additionally, ID-GNNs demonstrate improved or comparable performance over other task-specific graph networks.
Ideology and international conflict
Keywords: Political Science.

In recent years, the world has increasingly witnessed international conflict along ideological fault lines. Western policymakers warn that authoritarian countries like Russia and China are seeking to exploit divisions within democratic societies to promote autocratic tendencies, while for decades, authoritarian countries have accused the West of doing the same--of manufacturing domestic uprisings as a way to force liberalism upon them. Of course, these dynamics herald back to the Cold War, where international conflict was defined by ideological competition between capitalist and communist regimes, and before the Cold War, to the Concert of Europe, where conflict often involved clashes between republican and absolutist regimes. And yet, while history is filled with examples of conflicts along these kinds of ideological lines, there is no consensus in existing research on whether these cleavages have any effect on relations between states. Depending on where one looks, one can find arguments suggesting that ideology does or does not matter, or that there may be effects unique to liberalism. This dissertation advances our understanding of the relationship between ideology and international conflict by exploring how it affects a specific aspect of modern interstate conflict: disputes over the leadership and institutions of other countries. I argue that ideological cleavages increase the risk of these regime disputes in two ways. First, ideologically dissimilar states may attempt to change each other's regimes either due to normative preferences or the fear that these preferences exist. Second, they may resort to subversion to prevent political contagion from the success of alternative regimes. By contrast, ideologically-similar states face incentives to prop each other up against domestic threats and to refrain from using subversion to pursue their other foreign policy goals. I employ a variety of research techniques to provide evidence of these arguments, including cross-national statistical analyses, multi-country archival research, and automated text analysis of foreign propaganda. Using large-N quantitative data, I show that pairs of ideologically similar states are less likely to have policy and regime disputes, more likely to provide aid to each other in periods of domestic unrest, and have overall more cooperative relations than pairs of ideologically dissimilar countries. Focused case studies provide additional evidence of the theoretical mechanisms. Taken together, the results illustrate the shortcomings of "black boxing" the types of disputes states have, and they suggest that ideological ties between states are a major driver of patterns of international cooperation and competition