VictorJuiz/thesis huggingface dataset:
Chemical tools to interrogate and inhibit bacterial exotoxins

Antibiotic resistance is a significant emerging health threat. Exacerbating this problem is the overprescription of antibiotics as well as a lack of development of new antibacterial agents. A paradigm shift towards the development of non-antibiotic agents that target the virulence factors of bacterial pathogens is one way to begin to address the issue of resistance. Of particular interest are compounds targeting bacterial toxins that protect against toxin-induced pathology without harming healthy commensal microbial flora. Development of successful anti-toxin agents would likely decrease the use of antibiotics, thereby reducing selective pressure that leads to resistance mutations. In addition, anti-toxin agents are not only promising for therapeutic applications, but also can be used as tools to study the role of toxins in bacterial pathogenesis. This work highlights strategies to combat two pathogenic bacteria by specifically targeting and neutralizing virulence factors that cause human disease. Toxin B (or TcdB) is elaborated by the bacterium Clostridioides (formerly Clostridium) difficile, an opportunistic bacterial pathogen that is a prevalent cause of nosocomial infections. Botulinum neurotoxins (BoNTs) from Clostridial spp. are the causative agents of botulism, a life-threatening flaccid paralysis caused by toxin internalization with or without an accompanying bacterial infection. Both TcdB and BoNTs are multidomain proteins that contain a protease domain. TcdB contains a cysteine-protease domain important for autoprocessing and BoNT contains a zinc-dependent metalloprotease domain that cleaves host proteins important for the propagation of neuronal action potentials. We hypothesized that cell-permeant, small-molecule inhibitors of the protease domains of these toxins would mitigate bacterial pathology in the host. Using activity-based probes to screen for covalent modifiers of reactive active site and active- site adjacent cysteines of TcdB and BoNT, we identified a preference for selenide-based small-molecule inhibitors for both toxins. We show that the parent selenide, ebselen, inhibits TcdB and BoNT by forming an irreversible covalent selenium-cysteine bond. Biochemical, cell-based, and animal model studies revealed nanomolar protection by ebselen and its analogs against toxin-induced pathology for BoNT and TcdB. Together, these data identify a class of selenide small-molecules that are cell-permeant, non-toxic and active against multiple bacterial toxins that can also be used to study the roles of these toxins in bacterial pathogenesis. Further, these compounds are ideal candidates for potential development as broad-spectrum antivirulence agents

Advisor: Bogyo Matthew
Grimes Kevin
Lowe Anson W.
The chemistry, kinetics, and implications of oxygen defects in Li-excess oxides

Li-excess layered oxides are a promising class of positive electrode materials with the potential to simultaneously improve both the energy density and cost of Li-ion battery systems. However, these materials suffer from several adverse electrochemical properties resulting from a host structure that becomes unstable at low lithium contents. In this dissertation, a comprehensive view of the role of oxygen defects in Li-excess oxides will be developed. First, the coupling of oxygen and lithium defects will be rationalized from thermodynamic principles. Using X-ray spectroscopy and ptychography, the continuous loss of oxygen from Li-excess materials over cycling will then be demonstrated. Surprisingly, a variety of characterization techniques indicate that the oxygen-deficient bulk structure contains persistent oxygen vacancies, offering a unified framework for understanding previous observations of transition metal reduction and cation disordering with cycling. I will then investigate other factors which affect the oxygen release process, including the lithium content and the particle morphology. Overall, the results presented in this dissertation inform the design and utilization of Li-excess oxides and illuminate promising chemical, structural, and morphological approaches for mitigating oxygen release in layered oxide materials

Keywords: Materials Science and Engineering.
Advisor: Chueh William
Lindenberg Aaron Michael
Salleo Alberto
China’s Evolving Taiwan Policy: Bargaining on the Brink and Elite Threat Perceptions

This paper assesses change and continuity in China’s Taiwan policy since the 17th century. Using policy documents, speeches, newspapers, and secondary sources as evidence, it advances the hypothesis China’s policy towards Taiwan is an evolving function of elite threat perception and military capabilities relative to other international actors. Case studies include the Qing’s decision to invade the island, the Qing’s response to Japanese occupation of Taiwan in 1874, Mao’s changing Taiwan policy in the 1950’s, Deng’s outlook toward Taiwan, and policy post-1989.

Keywords:  Center for East Asian Studies
East Asian Studies, China, Taiwan, Policy
Text
Thesis
Advisor: Mastro Oriana
Chinese Fintech Companies And Their “Going Out” Strategies

In the late 1990s, Chinese President Jiang Zemin launched the strategy of Chinese companies’ “Going Out” into foreign markets as part of China’s “Opening-up and Reform.” These companies were largely state-owned enterprises (SOEs) and generally concentrated in the primary industry. Fast forward three decades and China is arguably undergoing a new form of “Going Out,” albeit of a different nature. This current phase is largely a bottom-up and private-led movement, driven by China’s most rapidly growing and innovative companies—its private technology companies. This paper outlines the ascendance of China’s fintech companies, primarily Ant Group and Tencent, since their incipience in the early 2000s. It analyzes these companies’ motivations and strategies for global expansion and considers their current and prospective influence on financial digitization across the globe. Finally, it assesses the distinct opportunities and challenges that China’s fintech companies face—both domestically and abroad—as they strive to grow up and go out.

Keywords:  Stanford Global Studies
Stanford
CEAS
China
Fintech
Innovation
Technology
Thesis
Advisor: Li Hongbin
Chinese Influence in South America: Dimensions of Power in Argentina and Chile

How does China attempt to wield influence in South America? China's economic and political influence has risen rapidly over the past decade. Beijing's growing power has taken overt forms like its rising stature in international institutions, as well as more subtle forms in the media and legislatures of countries all over the world. This thesis analyzes several country case studies to assess how Beijing is exercising power in South America. More broadly, it illuminates how China’s hard, sharp, and soft power can interact as mechanisms of control. I find that China has consistently used coercive and manipulative tactics to build its influence abroad. These findings can help inform policymakers who seek to understand how China is actively expanding its global influence, particularly in those countries with which it has significant trading relationships.

Keywords: China
Latin America
Chile
Argentina
Thesis
Advisor: Diamond Larry
Chinese Investment Strategy Across Latin America

Why do certain Latin American countries receive substantially more Chinese investment than others? Since 2005, the People’s Republic of China’s investment in Latin America has grown, as evidenced by its upward trend of investment with the region now receiving nearly 10% of total Chinese investment, or $200bn. Scholars, analysts, and policymakers argue that growing Chinese investments, notably ones from its Belt and Road Initiative, are intended for global influence through corruption and debt diplomacy. Using the American Enterprise Institute’s China Global Investment Tracker, this thesis assesses the conventional wisdom by identifying the drivers of Chinese investment across Latin American nations. Specifically, it explains why Argentina, Brazil, Ecuador, Peru, and Venezuela receive high levels of Chinese investment compared to regional peers like Colombia and Mexico. The data suggests that Latin American corruption is not an influential factor in Chinese investment destinations, instead, the potential for commodity exports like soybeans, petroleum, and copper appears more important. The United States government must understand that Beijing’s intentions in the region – which are geared around securing commodity exports – and compete accordingly rather than maligning the PRC’s actions in Latin America without providing a competitive alternative.

Keywords:  Center for International Security and Cooperation
Center for International Security and Cooperation
Stanford University
Freeman Spogli Institute
Thesis
Advisor: Zegart Amy
Fingar Thomas
Trinkunas Harold
Circuit techniques for compact and lightweight high-voltage DC power supplies

High voltage power supplies are essential in scientific, medical, environmental, security, and robotics fields. The size and weight of the circuit often limit the portability of the system and the range of applications. Smaller, faster, and more efficient power supplies will enable new scientific and commercial advances. My thesis presents circuit techniques to improve the performance of high voltage dc generators. A traditional way of generating a high dc voltage involves a step-up transformer built with a bulky magnetic core and a Cockcroft-Walton voltage multiplier, assembled on an FR4 printed circuit board and sometimes potted in insulating epoxy. Recently, many advances are being made in wide-bandgap semiconductor devices, sub-millimeter size passive components, and high-frequency circuit design methodologies. Those technological developments enable new techniques to design a high voltage power supply. This dissertation presents several new ways to build a high voltage dc generator: a planar PCB transformer that simplifies high-voltage isolation transformer design, a new voltage multiplier topology that exhibits less output voltage drop than the traditional Cockcroft-Walton multiplier, and foldable converters assembled on a flexible PCB to miniaturize kilovolts-level power supplies down to the sub-centimeter scale. My dissertation includes the motivation for investigating each of those circuit techniques and relevant power supply designs as well as application examples. I experimentally validate that by using those techniques appropriately, one can build a smaller and lighter power supply that exceeds traditional boundaries of high voltage generator performance

Keywords: Electrical Engineering.
Advisor: Rivas-Davila Juan
Lee Thomas H.
Murmann Boris
A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation

The role of the DNA sequence in protein-coding genes has been widely established due to the obvious functional relevance and well-defined relationships between DNA variation and protein sequence. However, most disease-associated variants are not in protein-coding sequences. This has led to much investigation of non-coding variation as it relates to protein-coding gene regulation. Critically, non-coding regulatory elements within DNA are intricately linked to cell type-specific protein-coding gene expression. This dissertation contributes to the goal of uncovering the underlying cis-regulatory logic of non-coding DNA sequences driving cell type-specific gene expression in homeostasis and disease. Cell type-specific non-coding cis-regulatory elements are known to drive important gene expression programs. However, it is still unclear what combinatorial DNA sequences underlie cell type-specific gene regulatory mechanisms. The objective of this dissertation is to progress our understanding of cis-regulatory logic through integration of genome-wide regulatory maps followed by modeling of combinatorial DNA motif logic in cis-regulatory modules regulating cell type-specific gene expression programs and focused identification of functional regulatory DNA motif combinations (DMCs) in homeostasis and complex disease. In Chapter 2, I generate epigenomic and transcriptomic profiles of 15 primary human cell types and perform integrated analysis to define cell type-specific open chromatin peak-long range looped-expressed target gene transcripts (PLTs). I then incorporate disease-associated single nucleotide variants (SNVs) from the NHGRI GWAS catalog and Genotype-Tissue Expression (GTEx) data to link SNVs enriched in cell type-specific PLTs to putative target genes. In Chapter 3, I model the genomic information necessary to derive cis-regulatory modules linked to cell type-specific gene expression programs and nominate transcription factor (TF) DMCs underlying cell type-specific regulatory logic. Finally, in Chapter 4, I validate DMC logic in four primary human cell types and identify cancer-specific regulatory logic in human squamous cell carcinoma and melanoma cells. The findings and approaches described in this dissertation add to the existing annotation of functional combinatorial TF motif logic and help build a framework for future studies of cis-regulatory logic

Keywords: Genetics.
Advisor: Khavari Paul A.
Baker Julie (Professor of genetics)
Chang Howard Y. (Howard Yuan-Hao)
Montgomery Stephen
Climate, agriculture, and economic development : theories and methods for agricultural productivity analysis

Increasing agricultural productivity is a cornerstone of the global sustainable development agenda. Using resources more efficiently can reduce the environmental impacts of food systems and create economic opportunities for the world's poor, the majority of whom earn their living from agriculture. However, there remain fundamental uncertainties about how to effectively direct investments for agricultural development, and the role agricultural productivity growth plays in economic development more generally. One key source of uncertainty is global climate change, which is predicted to disproportionately affect agriculture in developing countries. In my dissertation, I investigate the relationship between climate, agricultural productivity, and development in three chapters. In my first chapter, I develop an original method for quantifying how measurement errors in agricultural survey data affect patterns of productivity observed among smallholder farmers. Applying this method to data from four countries in Sub-Saharan Africa, I show that measurement errors inflate the apparent differences between high- and low-productivity farmers and attenuate how persistent farmers' productivity appears over time. Both these distortions have implications for the evaluation of potential development interventions. In my second chapter, I propose an original econometric framework for measuring the impacts of climate change that correctly incorporates the statistical relationship between climate and weather and distinguishes between impacts resulting from changing weather patterns and those resulting from climate-induced changes in non-weather inputs to production, such as ecosystem services. Applying this framework to data from the U.S., I show that changes in non-weather factors represent a large share of historical climate impacts on agricultural land productivity. My third chapter examines the palm oil processing sector in West Africa. In it, I argue theoretically that, despite producing little oil per unit of fruit processed, small-scale `artisanal' firms can increase the aggregate efficiency of the processing sector when there is significant seasonality in palm fruit yields. I then provide evidence in support of this theory using data from an original survey of oil palm farmers in Ghana. Overall, my dissertation advances new tools for agricultural productivity analysis in the context of climate change, and highlights how climate can shape the organization of agricultural industries

Advisor: Kolstad Charles D. 
Naylor Rosamond
Burke Marshall
Emerick Kyle 
Plambeck Erica L.
Close-microphone cross-talk cancellation in ensemble recordings with statistical estimation

While recording an ensemble of musicians, microphone cross-talk, or "bleed", is considered a nuisance by audio engineers. When two microphones pick up the same signal with a time delay, comb filtering artifacts are present. An expensive solution to the microphone bleed problem is to use acoustic isolation panels between musicians. Obviously, this is not feasible in a live setting. Simpler solutions include using directional microphones with specific polar patterns to pick up radiation from a desired direction and using the close-miking technique where microphones are placed at a distance of 5 - 50 cm from the sound source. Interference can become significant in such cases due to the effect of nearby strong reflective surfaces. The complexity lies in the fact that there is usually an arbitrary number and distribution of instruments and microphones, and results are influenced by the room acoustics of the studio where the ensemble is recorded. In this thesis, I propose statistically optimal estimators to cancel microphone bleed offline in the mixing and production stage. First, a calibration stage is proposed, where one instrument is played at a time and recorded by all the microphones. This single-input, multiple-output (SIMO) system is used to estimate an approximate relative transfer function matrix, which represents the acoustic path from each source to each microphone and encodes the room response, as well as the mic directivity and source radiation patterns. A convex cost function is derived in the time-frequency domain that simultaneously optimizes the sources and the relative transfer function matrix, which is assumed to be time-invariant. It is shown that minimizing this cost function gives the Maximum Likelihood (ML) estimate when the microphone signals are assumed to be normally distributed. The ML estimator is extended to include apriori statistics of the sources, and the Maximum Aposteriori Probability (MAP) estimator is derived. The proposed methods are evaluated against a state-of-the-art Multichannel Wiener Filter based algorithm on a simulated dataset of string quartet recordings in a shoebox room, and on a drum-kit recorded in the CCRMA recording studio. The results show that cross-talk cancellation is achieved while maintaining the perceptual quality of the separated sources

Keywords: Music.
Advisor: Chafe Chris
Smith Julius O. (Julius Orion)
Abel Jonathan (Jonathan Stuart)
Coarse-grained chromatin models for meiotic homolog pairing

The process of homolog recombination in Prophase I is a key step in sexual reproduction, and errors in this process can lead to chromosome nondisjunction and are a major contributor to birth defects. However, while we know that pairing involves the coordination of many independent loci on each chromosome, the mechanism by which these loci are robustly brought together is still unknown. While the polymer physics of bare DNA is well described by the wormlike chain model, Eukaryotic chromatin is far from bare, and the presence of histones, transcription factors and other proteins that drastically alter the structure of chromatin are likely to have a profound effect on the polymer physics of chromatin in early meiosis. Therefore, in order to compare in vivo data of homolog pairing dynamics to an analytical theory, we develop a theory for kinked wormlike chains, to incorporate the geometric effects of, for example, nucleosomes on the polymer physics of chromatin. We show that there exists an "effective" wormlike chain (with a rescaled persistence length) that describes the mesoscopic structure of nucleosome-laden chromatin. Using a novel statistical method for analyzing Markov renewal processes in finite time windows, we then compare trajectories of individual homologous loci during early meiosis in S. cerevisiae to our expectations based on first-principles polymer theory, using both analytical and simulation results. We show that homologous locus pairing is largely a transient process, and that no active forces bringing together the loci to reproduce our experimental data. This is consistent with homolog pairing being a purely thermally-driven process, despite its importance to the successful completion of meiosis. Further, our model demonstrates that it only takes a handful of homologous linkages per chromosome to reproduce the physics of fully "paired" chromosomes, illustrating how a single tethered locus can drastically restrict the diffusion of DNA tens to hundreds of kilobases away

Advisor: Spakowitz Andrew James
Boettiger Alistair
Bryant Zev David 
Qin Jian (Professor of Chemical Engineering)
A collaborative bioarchaeology of African diaspora and enslavement in colonia Cañete, Peru

In 2009, the Peruvian government apologized to its citizens of African descent for the exclusion enacted against them from the colonial period to the present. While this gesture initiated a long-awaited process of addressing the history of enslavement and its lasting impacts for Afro-descendant communities, it has yet to be translated into meaningful reform. Afro-Peruvian histories—including histories of captivity, exploitation, and racialized violence—continue to be largely absent in academic curricula and public discourse. Such silencing has direct implications on contemporary sociopolitics in Peru, as Afro-Peruvian communities continue to face structural inequalities and marginalization in their everyday lives. This dissertation addresses these issues by considering how community-engaged archaeology can serve as both a tool to cultivate a closer understanding of histories of African enslavement in Peru, and a space where descendant communities can pursue a politics of belonging in contemporary scholarship and heritage discourse. As a case study, it focuses on research at Hacienda La Quebrada (1741-1849), a historic sugar plantation in the central coastal valley of Cañete, Peru. Through bioarchaeological, historical, and ethnographic work at the former plantation and in the communities that live around the site today, this project asks: What were the everyday conditions of living for enslaved Africans and Afro-descendants at La Quebrada, and how did these conditions shape their overall life-histories? How do members of the local descendant community and other Afro-Peruvian stakeholders in the region remember and relate to these histories? Finally, how can the findings of interdisciplinary archaeological research contribute to efforts to revalorize African diaspora histories and cultural heritage in Cañete today? By addressing these questions, this dissertation demonstrates how community-engaged archaeology can work to confront the subalternization of African descendant communities in hegemonic narratives of history, heritage, and national identity. Its collaborative approach to studying the lived experiences of enslavement shows how archaeology can critically address histories of colonial violence while simultaneously reinforcing empowering narratives that foreground the contributions of African descended peoples to Peruvian society and culture. At the same time, by empowering communities to study and retell their pasts in accordance with their own worldviews, and by working together to commemorate these histories through public heritage work, this project ultimately contributes to larger efforts for recognition, inclusivity, and the pursuit of community rights in Peruvian archaeology

Keywords: Anthropology.
Advisor: Voss Barbara L.
Bauer A. J. (Andrew Joseph)
Hodder Ian
Rick John W.
Tung Tiffiny A.