VictorJuiz/thesis huggingface dataset:
Reducing reference usage in detection of regulated RNA processing

RNA sequencing methods have become increasingly sensitive, high-throughput, and cost- effective, resulting in an unprecedented volume of sequencing data accessible to the public. RNA processing events, such as alternative splicing or alternative polyadenylation, leave distinct signatures in RNA-seq reads. However, RNA-seq data is critically underutilized: sequence variation from RNA processing, beyond simple annotated alternative splicing, is most often ignored. We introduce a new statistical method to detect regulated RNA processing from single- cell RNA-seq data, that does not rely on existing gene annotations. Using this method, we detect cell type-specific RNA processing differences in human lung. We also discover developmentally regulated RNA processing changes, including global 3'UTR length changes, in both human spermatogenesis and Arabidopsis thaliana root development. We also demonstrate the use of a fully reference-free statistical method for discovery of regulated sequence variation in plant RNA-seq data. By fully removing the reliance on alignment to detect regulated changes, we can discover condition- and cell type-dependent RNA processing events even when an isoform or entire gene is missing from the reference

Keywords: Medicine.
Biochemistry.
Advisor: Salzman Julia
Das Rhiju
Gao Alex
Straight Aaron
Reductive electrochemical technologies to target macroconstituents : in potable reuse, wastewater discharge, and agricultural fumigation

Most current methods of water and wastewater treatment systems involve the purchase and transport of chemicals to centralized treatment facilities. Interest in decentralized treatment systems is growing, partly because pumping water to and from treatment facilities constitutes a significant fraction of the overall energy used within the water cycle. Electrochemical treatment systems are particularly attractive for these decentralized systems, since their modular nature enables them to be placed in locations such as the basements of apartment buildings. They also have the potential to be operated remotely, thereby avoiding the need to hire highly trained operators for each treatment site. An additional advantage is the potential to generate chemical reagents on-site, avoiding the purchase and shipping of reagents to these distributed sites and the associated CO2 emissions. While electrochemical treatment technologies are a potentially powerful tool for advancing decentralized treatment, there have been three main limitations that have inhibited scale-up. First, research has focused on oxidative (anodic) systems, but these systems can oxidize chloride and other halides, which are ubiquitous, into toxic halogenated products (e.g., perchlorate). Second, expensive materials are used to fashion anodes to combat their degradation under oxidative conditions (e.g., boron-doped diamond). Third, research has often targeted oxidation of contaminants that are microconstituents (< μg/L), but competition by macroconstituents (e.g., mg/L of dissolved organic matter) results in low process efficiencies and treatment timescale in excess of the ~1 h timescales typical of full-scale water and wastewater treatment processes. In this thesis, I offer a novel approach to address these three challenges. First, I focus on reductive (cathodic) processes, thereby avoiding halide oxidation to toxic byproducts. Second, I use inexpensive materials to construct cathodes (e.g., stainless steel, carbon), which was possible because their use as cathodes avoided their oxidative degradation. Third, I focused on three applications relevant to three separate sub-fields of environmental engineering where the cathode targeted macroconstituents, enhancing process efficiency and enabling treatment over reasonable timescales. For each application, I evaluate the impact of various performance metrics (e.g., voltage/current, pH, ionic strength, and electrode materials) to determine the optimal operational conditions. Using this data and real water or matrix conditions, I develop initial cost estimates against currently used technologies to assess whether the electrochemical process is feasible and where improvements need to be made in future work on the treatment processes.

Keywords: Engineering.
Advisor: Mitch William
Criddle Craig
Luthy Richard G.
Reframing US-China strategic competition in the Indo-Pacific: the role and agency of Southeast Asian nations

The prevailing geopolitical landscape painted in the media is often as follows: the US and China are caught in a Thucydides trap in which a rising power is challenging to eclipse the incumbent, and Southeast Asia is a key theatre where this will play out. Many are reminded of the Cold War, during which Southeast Asian countries were divided along their alignment strategies. Today, they face pressure from the US and China to pick a side in international politics and they are often portrayed as a prize to be won. They appear helpless and at risk of being the collateral damage of great power rivalry. Moreover, the narratives portrayed in Western and Chinese media and/or literature are divided – both sides see themselves as the force of good for the prosperity of the region and are critical when Southeast Asian countries work with the other.
However, there is also an alternative perspective that the US-China strategic competition could provide fertile ground for Southeast Asian countries to advance their own national interests. While navigating the US-China tension can be challenging, the big powers’ eagerness to engage and win them over gives them additional leverage and more options to obtain the necessary support and assistance for their own development. The trade war and the push for decoupling may also inadvertently present new opportunities for some Southeast Asian countries. The Southeast Asian nations have always acted according to what pragmatism dictates and they will no doubt try to make the best use of the situation.
Hence, this paper seeks to explore the ways in which Southeast Asian countries could shape the dynamics of the US-China strategic competition in the Indo-Pacific region and the key drivers behind their foreign policy toward the two big powers. To this end, it delves deeper into three case study countries that lie on different points along the spectrum of US/China-leanings – namely Laos, Indonesia, and the Philippines – to illustrate the relevant factors at play. The paper can also help inform American and Chinese policymakers about the needs of Southeast Asia and the effectiveness of their current approaches. Most importantly, it hopes to reframe the conversation to focus more on the agency of the region and shed light on the Southeast Asian point of view that tends to be lacking in the current discourse.

Keywords:  Stanford Global Studies
Southeast Asia
US-China relations
US-China great power competition
Laos
Indonesia
Philippines
Stanford Global Studies
Text
Thesis
Advisor: McFaul Michael
Marciel Scot
Regulatory mechanisms of the anti-cancer cGAMP-STING pathway

Throughout our lifetimes, our bodies encounter a plethora of threats on the cellular level, including pathogen infection, cellular damage, and the development of cancer. When these threats are not properly detected, they can lead to serious health problems, including death. Thankfully, our cells are pre-programmed with an array of innate immune pathways that can quickly respond to threats by detecting specific molecular danger signals that indicate a threat is present. Of these innate immune pathways, the cGAMP-STING pathway is on the forefront of the immune response due to its ability to detect mislocalized double stranded DNA (dsDNA). Since mislocalized dsDNA is a danger signal nearly ubiquitous with cellular threats, the cGAMP-STING pathway is essential for responding to most threats, including pathogen infection, cellular damage, and cancer. Given the extensive role of the cGAMP-STING pathway in defending against threats, regulation of the pathway is crucial to ensure its proper function. In this work, I show how intercellular pathway activation is regulated through cell-type specific transporters of the pathway's agonist, cGAMP, and how intracellular pathway activation is regulated through the E3-ubiquitin ligase PELI2

Keywords: Medicine.
Biochemistry.
Advisor: Li Lingyin
Gao Alex 
Kim Peter
Re-imagining and expanding the diagnostic toolbox : towards robust and scalable molecular quantification

Why is it that our local pharmacy only has pregnancy strips and CGMs as molecular monitors? What can we actually monitor at the doctors office reliably, and why not certain biomarkers? These are questions that underlay the body of work presented in this thesis. Particularly, I focus on some of the technical challenges of measuring and monitoring molecular biomarkers. The field of precision medicine is entering a critical phase, with unprecedented access to vast computational resources and diverse data types such as CT scans, X-rays, and electronic health records. These resources, combined with powerful algorithms, have demonstrated significant potential for disease diagnosis and treatment. Unfortunately, molecular information has yet to be used in a scalable and reliable manner, although it is a critical component to understanding disease and health status. As a result, unraveling the basis and respective markers for disease and health remains a daunting task. This thesis highlights and begins addressing some fundamental problems in scaling up the quantification of molecular biomarkers. Particularly, many current solutions assume that the intrinsic affinity between the affinity reagent and the target are the limiting factor, or view background signal and noise as an annoying feature. I will share some of our recent works that take advantage of these aspects to provide more robust and scalable molecular quantification techniques including: A method to tune molecular assays to expand the range of quantification across a larger portion of the proteomic dynamic range, a mathematical framework to relax the selectivity requirements on affinity reagents for assay design, assay development for scalable small molecule measurement, and a way to spatially minimize the effect of non-specific binding. These works take a step towards improving the way and scope of biomarkers that are measured from a fundamental level and have the potential to shift molecular quantification to be more accessible for medical diagnostics.

Keywords: Engineering.
Bioengineering.
Advisor: Soh H. Tom
Covert Markus
Dunn Alexander
Reimagining youth agency and social media platforms with middle school girls and nonbinary youth

In an effort to engender a greater will and capacity among students to act on the world (Ahearn, 2002; Giddens, 1984), this Youth Participatory Design Research (YPDR) study engaged 42 middle-school girls and nonbinary youth enrolled in an American private school in the design, building, and implementing of a social media platform for young people. Analysis of pre- and post-surveys, using a validated tool for assessing agency (Vaughn et al., 2020b), indicated that agency among participants increased by a small but significant margin during the YPDR process. Youth felt an increased sense of intentionality and choice in what they learned in school, and to a lesser degree, increased self-identification as coders. In addition, qualitative analysis of their design and platform artifacts, presentation videos, interviews, and think-alouds reveals that these student designers re-imagined social media platforms to provide themselves and other youth with opportunities for agency development through making choices safely online. Youth designed novel platform features to assist users in comfortably sharing their voices by lowering the stakes of sharing, offering novel choices around anonymity, audience selection, feedback management, and using digital spaces as a bridge between in- and out-of-school work. A self-starting after-school club then spent two academic years bringing their peers' designs to life through building and implementing a social media platform in their school. They subsequently designed their own pedagogical research projects to further test and iterate on their platform, demonstrating the extent to which agency came into play in unexpected ways. Taken together, this study's results suggest that youth may simultaneously develop agency and build agency-promoting technologies for and in schools. Pedagogical approaches that have as their purpose supporting agency development and providing students with opportunities to re-design technologies that otherwise harm them, can help, while also offering teachers a framework for repurposing their classrooms as critical hubs of change.

Keywords: Education.
Advisor: Levine Sarah (Sarah R.)
Garcia Antero
Willinsky John
Reinventing the politics of literature : rediscovery, ritual, and reference as concepts of repetition in the works of Peter Handke and Lee Yangji

This dissertation examines concepts of repetition in the literary works of Austrian-Slovene writer Peter Handke (1942-) and Japanese-Korean writer Lee Yangji (1955-92). The concept of repetition is, in its everyday usage, bound to past traumas, psychological compulsions, and retributive resentments; at the same time, repetition plays a critical role in the development of motor and cognitive skills, the acquisition of new knowledge, and the deepening of understanding. Against the tendency of writers of German- and Japanese-language literature during the twentieth century to draw from socially- and psychologically-oriented understandings of repetition, the literary works of Peter Handke and Lee Yangji reimagined repetition as a portal to renewals of inheritance, rites of healing, and rearticulations of moral and aesthetic commitments. This dissertation argues that the partially overlapping, parallel processes by which Handke and Lee made their rediscoveries of their respective Slovene and South Korean minority heritages during the 1980s -- returns to roots in order to restore a sense of identity ruptured by the Second World War -- were mediated by the literary modes of translation, performance, and allusion; and moreover, these literary modes brought both writers into closer proximity to an enriching and edifying experience of repetition. This dissertation thus neither decouples politics from literature nor lays out a political agenda for literature, but rather takes repetition as a starting point for reconfiguring the political assumptions we bring to reading, writing, and language more generally

Keywords: Humanities and Sciences.
Comparative Literature.
Advisor: Berman Russell A.
Levy Indra A.
Gumbrecht Hans Ulrich
Zur Dafna
Relating outcrop and subsurface expressions of the Magallanes-Austral Basin: Provenance of the eastern Magallanes-Austral Basin from detrital zircon U-Pb sediment core ages, Southern Patagonia

Analyzing how provenance signatures of tectonically complex ancient sedimentary basins vary between the outcrop and the subsurface is crucial to understanding basin filling history. The 500+ km-long outcrop belt of the Magallanes-Austral Basin in southern Patagonia and its subsurface to the east allows us to constrain relationships between longitudinal and transverse sediment sources feeding the basin. New detrital zircon U-Pb ages (n=2558) from nine subsurface core samples from the Springhill, Piedra Clavada, and La Anita Formations along a 140 km east-west seismic reflection transect (50°S latitude; 71.5-69.5°W longitude) reveal provenance and filling history of the basin’s eastern subsurface extent. Detrital zircon ages (n=1068) were also collected from four outcrop Springhill Formation samples 140 km northwest from the transect near Lago San Martin. Maximum depositional ages (MDAs) from the Springhill Formation cores range from 154.9–146.8 Ma, which are older than correlative outcrop ages of 144.6–126.7 Ma. MDAs from the Piedra Clavada and La Anita Formations range from 93.4–91.4 Ma and 78.9–78.3 Ma, respectively, and overlap in age or are slightly younger than outcrop ages. The unimodal Late Jurassic age distribution from the Springhill Formation suggests that it almost exclusively was sourced by recycling of its underlying El Quemado Complex and highlights the underfilled nature of the Rocas Verdes Basin. By the Early Cretaceous, detritus supplied to the basin was derived from the arc, fold and thrust belt, and distal synrift volcanic sources. The occurrence of Early–Middle Jurassic ages in the Piedra Clavada Formation samples suggest either the basin was sourcing from the North Patagonia Massif to the north-northeast and from the Deseado Massif to the northeast or recycling exhumed volcaniclastic sequences in the northern margin of the basin. By the Late Cretaceous, the basin fill was more locally sourced, as suggested by the muted signal of Early–Middle Jurassic ages in La Anita Formation samples and a second mode of Late Jurassic–Early Cretaceous ages locally derived from recycling exhumed El Quemado Complex from the fold and thrust belt. We suggest that the longitudinal and local transverse drainages that sourced the Magallanes-Austral Basin outcrop belt also propagated eastward across the basin (what is now subsurface strata). Distal sourcing from the North Patagonian Massif is determined by subsidence and bypass in the Golfo San Jorge Basin and existence of Albian–Turonian fluvial transport systems capable of transporting Jurassic sediment to the Magallanes-Austral Basin.

Keywords: Malkowski, Matthew
Dobbs, Stephen
McHargue, Timothy
Detrital Zircon
Maximum Depositional Age
Magallanes-Austral Basin
Patagonia
Springhill Formation
La Anita Formation
Piedra Clavada Formation
Text
Thesis
Advisor: Graham Stephan
Relational work, post-bureaucracy, and inequality in Silicon Valley

In this dissertation, I explored the role of relational labor in Silicon Valley post-bureaucratic workplaces through two cases: the implementation of AI ethics in technology companies, and the role of employee's relational work at WeWork. I examine the growth of the field of AI ethics, also referred to as "responsible AI, " which has developed in response to criticisms following investigations of algorithms that revealed disproportionate harms on marginalized groups. I agrue that legitimacy shapes organizational similarity, or isomorphism, in the field and show that this constrains corporate practices related to ethics. Next, I examine ethics workers through the lens of institutional entrepreneurship to understand the barriers to implementing responsible AI in technology organizations. I focus on the diplomatic and interpersonal skills ethics entrepreneurs must engage in on a case-by-case basis in order to effect change, due to the lack of organizational infrastructure and support they receive. I find that ethics entrepreneurs face three major barriers to their work: the product-centered institutional environment, the difficulty of quantifying ethics in metrics-driven organizations, and frequent reorganizations of teams which make it difficult to access knowledge and maintain relationships central to their work. As a result of these barriers, ethics workers, who are often from marginalized backgrounds, take on great personal risk when raising ethics issues. Finally, I aim to understand what motivates the reaggregation of decentralized knowledge work in coworking spaces like WeWork. In recent years, coworking has exploded in popularity amongst knowledge workers. How can we understand the social and cultural forces that precipitated this shift from disaggregated to reaggregated work? I focus on the emotional labor and relationship labor performed by culture workers at WeWork, and I argue that this labor sustains decentralized capitalism. Despite the underlying spirit of techno-utopianism in Silicon Valley (Turner, 2006) and what Karppi and Nieborg (2021) describe as "an almost pathological belief in their corporation's ability to make the world a better place, " diversity in the technology industry remains stagnant or even regressive (Gee and Peck, 2015). This dissertation examines the stakes of changes to knowledge work, by outlining the consequences for workers at large but especially the implications on racial and gender inequality at work. These stakes have potential to affect not only the workplace, but also companies' products and society at large

Keywords: Humanities and Sciences.
Communication.
Advisor: Christin Angèle
Hamilton James
Turner Fred
Valentine Melissa (Melissa A.)
Relativistic jets in the era of X-ray polarimetry

Measuring X-ray polarization has been a major goal in astrophysics for the last 40 years. With the launch of NASA's Imaging X-ray Polarimetry Explorer (IXPE) in December 2021, soft X-ray polarimetry (1-10 keV) is now possible. In this thesis, I introduce an optimal signal extraction method for X-ray polarimeters based on gas pixel detectors. Using IXPE's thus improved sensitivity, I make progress towards identifying the high-energy emission processes and magnetic field geometries responsible for radiation in blazar jets. First, I develop a simulation-based inference framework for measuring X-ray polarization as a function of time, energy, and position in gas pixel detectors, proving that for a fixed model budget the framework is optimal. Second, I propose a simple geometrical jet model to study the polarization properties of leptonic blazar jets, including their observed EVPA rotations and their detection prospects with IXPE. Finally, I interpret IXPE's measurements of BL Lacertae across the synchro-Compton transition region to suggest leptonic-dominated emission processes in blazars, and of Mrk 421 to provide evidence for helical magnetic fields as the source of EVPA rotations

Keywords: Humanities and Sciences.
Physics.
Advisor: Romani Roger W. (Roger William)
Blandford Roger D.
Michelson Peter F.