VictorJuiz/thesis huggingface dataset:
Regulation of Transcriptional Interference by the Swi/Snf Complex

Alternative transcription start sites can affect transcript isoform diversity and translation levels. In a recently described form of gene regulation, coordinated transcriptional and translational interference results in transcript isoform-dependent changes in protein expression. Specifically, a long undecoded transcript isoform (LUTI) is transcribed from a gene-distal promoter, interfering with expression of the gene-proximal promoter. Though it contains the coding sequence of the downstream gene, translation of the LUTI is restricted by uORFs present in its 5′ leader sequence. While transcriptional and chromatin features associated with LUTI expression have been described, the mechanism underlying LUTI-based transcriptional interference is not well understood. Using an unbiased genetic approach followed by integrated genomic analysis, we uncovered that the Swi/Snf chromatin remodeling complex is required for co-transcriptional nucleosome remodeling that leads to LUTI-based repression. We identified 12 genes with tandem promoters that rely on Swi/Snf function for transcriptional interference during protein folding stress, including LUTI-regulated genes./nWe further explored Swi/Snf repressive activity by performing kinetic and molecular assays for the LUTI-regulated gene histidine triad nucleotide-binding 1 (HNT1), revealing that Swi/Snf recruitment and repressive function at the HNT1 locus depends on transcription initiation and elongation of HNT1LUTI. This prompted our further investigation into a role for Swi/Snf in transcription elongation, leading to the finding that Swi/Snf performs co-transcriptional nucleosome remodeling at its target loci independently of its canonical role in transcriptional activation. We conclude this co-transcriptional remodeling function by Swi/Snf may function to promote transcription elongation at canonical gene targets but serves a repressive function at target genes with tandem promoters and transcriptional readthrough. To our knowledge, this is the first evidence of Swi/Snf's direct involvement in gene repression via a cis transcriptional interference mechanism.

Advisor: Ünal, Elçin
Precise Pulse Discrimination for Space-Based Timing Front Ends

The conversion of trigger events to their digital equivalent is a central component of any timing-based front end, with applications found in mass spectrometry, single channel analyzers, and a huge variety of 3D mapping and ranging systems.At the same time, ever-tightening size, weight, and power budgets for space launches with a skyrocketing (no pun intended) number of launches in the last decade have made application-specific integrated circuit solutions increasingly appealing. However, conventional analog methods of pulse discrimination introduce timing walk or are limited to a narrow range of pulse shapes, while early-stage digitization requires impractically high sample rates for the events in question./nThis work presents the analysis, design, and measurement of an integrated constant fraction discriminator with theoretically zero timing walk and a programmable, constant trigger fraction which does not depend on input pulse shape.The specific silicon presented here was designed for the Solar Probe Analyzer for Ions as part of its time-of-flight mass spectrometer to determine the ion composition of space plasmas. This dissertation discusses the front end requirements for a radiation hardened pulse discriminator in the context of SPAN-Ion. We then address the architectural modifications used to achieve a pulse shape-independent constant trigger fraction, as well as the analog and digital hardening techniques required to detect, correct, and/or mitigate radiation-induced effects. Finally, this work presents the first attempt at an integrated pulse-shaping front end for SPAN-Ion, concluding with simulation results from a more recent chip and a discussion of future work both for SPAN-Ion and for further code base development.

Advisor: Pister, Kristofer
Control of Meiotic Entry by Dual Inhibition of the Key Mitotic Transcription Factor SBF

Transcription factors induce dynamic changes in gene expression to drive cellular differentiation. During the mitotic G1/S of budding yeast when the cell irreversibly commits to divide, transcription factors SBF(Swi4-Swi6) and MBF(Mbp1-Swi6) play essential roles by activating the expression of the G1/S transcriptome. While SBF and MBF act in parallel to mediate the mitotic G1/S transition, their regulation and function in meiosis have remained elusive. Here we characterize both the functional impact of SBF activation on meiotic entry and the molecular mechanisms restricting SBF activity in meiosis./nWe first elucidated the functional significance of SBF activity restriction in meiosis and found that elevation of Swi4 protein levels was sufficient to activate SBF, resulting in mis-expression of SBF targets in meiosis. Further experimentation led us to discover that untimely SBF activation caused downregulation of early meiotic genes and delayed meiotic entry. Meiotic entry delays were caused by reduction in the function of Ime1, a master transcriptional regulator of meiosis. Among the SBF targets, G1 cyclins were the main driver of meiotic delays. We further found that G1 cyclins blocked the interaction between Ime1 and its cofactor Ume6./nWe next investigated how SBF activity is restricted during meiosis and identified two parallel mechanisms: repression of the SBF-specific Swi4 subunit through LUTI-based regulation and inhibition of SBF by Whi5, a homolog of the Rb tumor suppressor. Our study provides insight into the role of SWI4LUTI in establishing the meiotic transcriptional program and demonstrates how the LUTI-based regulation is integrated into a larger regulatory network to ensure timely SBF activity.

Advisor: Ünal, Elçin
Enhancing Visual Media Through Reflection and Recomposition

Visual media like vector graphics and presentations are essential to human communication. Artists, designers, and presenters use an iterative reflection and recomposition process to progressively refine their work. Here, reflection describes gathering and absorbing feedback or information after some visual media is created, while recomposition describes adapting and transforming some existing visual media. The key to supporting these stages is providing users with rich, flexible data representations that adhere to their domain and task. Additionally, user interfaces for interacting with this data must balance raw transformative power and the author's creative control. This dissertation supports these media reflection and recomposition processes, and presents techniques for leveraging automatic styling and feedback systems in visual media creation processes./nThe goal is to broaden the focus on generative creation tools to the more extensive iterative cycle designers employ (i.e., reflection and recomposition). The first aspect focuses on collecting and refining presentation feedback with SlideSpecs. SlideSpecs is a system for collecting, aggregating, and understanding presentation feedback to assist author refinements. Next, this dissertation will present VST and VLT, a pair of automation-powered design tools for transferring and mixing vector graphics styles and layouts. These tools enable mixing higher-level design properties and rules across vector graphics by generating and leveraging cross-design correspondences. These approaches acknowledge the richness of authors' flexibility and control when shaping their media. With this framing, I demonstrate the benefits and requirements for extending this richness throughout the iterative design cycle.

Advisor: Hartmann, Björn
Male Bias in Generic Statements: A Contrastive Analysis of English and German Role Nouns

Language users frequently encounter generic personal statements, which refer to a person or group of people whose gender is irrelevant or unknown (e.g., “A doctor must go to medical school.”). Though intended as gender-neutral, generic terms have been found to elicit an assumption of a male referent – i.e., a male bias. Whereas male bias studies in English have typically analyzed generic-used pronouns, German studies have overwhelmingly focused on plural nouns. As a result, male bias in English and German singular nouns is less understood. Furthermore, it remains unclear whether English and German language users are equally likely to read a singular generically intended noun as male. My dissertation remedies this gap by analyzing how linguistic differences between English and German impact the likelihood of interpreting a generically intended singular noun as male. Specifically, in my project, I contrast how the two languages impart gender information, both as a result of inherent properties – e.g., grammatical and lexical gender – as well as linguistic practices, such as the generic masculine (GM) – the “generic” use of male-specific terms – and the adoption of GM alternatives. I argue that singular generic nouns are more likely to elicit a male bias in German due to grammatical gender, higher rates of gender-specific personal nouns, and increased use of gender-specific terms in generic contexts. By contrasting English and German singular nouns, this project sheds new light on the potential sources of male bias in generic language.

Advisor: Shannon, Thomas F
From the Line of Scrimmage to the Picket Line: Student-Athlete Protest in an Age of Protest, 1968-1972

My dissertation focuses on black student-athlete protest in the 1960s and how universities managed, conceptualized and disciplined student-athletes similarly to how employers disciplined labor throughout the 19th and 20th centuries. My project uses four case studies at four universities: University of Wyoming, Syracuse University, the University of California-Berkeley and Oregon State University. My research into protests by athletes at these universities discovered that these universities employed strategies that were remarkably similar to techniques employers often used to control and discipline labor in the late 19th and early twentieth centuries. These disciplinary measures indicate that by the 1960s, college sport was a last bastion of 19th century workplace norms, and culture. My research highlights important questions we should ask about the relationship between student-athletes and universities: the historical complexities of how student-athletes were managed, conceptualized and ultimately treated as labor should be of paramount importance for how we think about student protest and black radicalism in the 1960s, as well as how we think about student-athletes today.This dissertation hopes to link the experiences of student-athletes to the history of capitalism. Athletic departments, with many university’s blessings, were structured like, and often operated similar to corporations throughout the 20th century. A critical part of this incorporation was how the university and coaches decided to classify and manage student-athletes. Throughout the twentieth century, Student-athletes worked for their respective universities off the field, and were subject to rules that other employees had, with none of the protections that traditional laborers had. Debates over how student-athletes’ labor, how were controlled and managed stretch back to the 19th century. In order to link sport and labor together, coaches and universities argued that they would teach student-athletes the essential links between sport and work. In order to do this, they borrowed tactics that employers used from the 19th century to the mid twentieth century to restrict labor movement. Universities also provided coaches with near complete authority for on field and off field matters like housing, restricted the wages of student-athletes for on and off the field labor, and consolidated disciplinary policies to athletic departments. The development of athletic departments in the 1920s and 1930s were consolidations of power from students to administrators, and from administrators to coaches. These processes all coalesced around student-athletes, transforming them into a hybrid of student and labor, with all of the burdens and none of the protections.

Advisor: Rosenthal, Caitlin
Phases of information encoding in many-body quantum states

Intermediate-scale quantum devices operate controllably and can maintain quantum entanglement in systems of up to a few hundred qubits. From a many-body perspective, these devices exhibit a novel interplay of entangling unitary evolution, measurements, and decoherence, which is expected to give rise to new emergent phenomena. In this dissertation, we study the collective phenomena associated with information encoding and focus on two broad classes of systems: (i) monitored quantum circuits that consist of unitary evolution and measurements; (ii) topologically ordered states subject to local decoherence./nMonitored random quantum circuits have been shown to undergo a measurement-induced phase transition in the steady state when increasing the measurement rate. In the first part of the dissertation, we develop a theoretical framework that maps the quantum information dynamics in monitored circuits to equilibrium statistical mechanics models. We show that the measurement-induced transition can be formulated as a transition in the capacity of the circuit to encode quantum information and further as symmetry-breaking transitions in statistical-mechanical models. Within this framework, we also identify new phases of information flow in monitored circuits, both when symmetry is imposed on circuit elements and when the circuit is at finite times./nTopologically ordered states in quantum codes can store quantum information in the presence of local decoherence up to a finite threshold. In the second part of this dissertation, we study the effect of decoherence on general quantum ground states with topological order. We develop a theoretical framework based on effective field theory to identify the possible phases induced by decoherence and characterize their capacity to encode quantum information. We further propose information-theoretical quantities to define topological order in the ensuing decoherence-induced mixed states.

Advisor: Altman, Ehud
Excavating the genome mine of Pseudomonas putida KT2440

Pseudomonas putida is an important chassis strain for the valorization of lignin. While we know much about this host and have developed numerous tools to engineer it, we still lack a complete understanding of its accessory genes that may be important for a variety of metabolisms and stress responses. Using a functional genomics method called barcode abundance sequencing (BarSeq), thousands of conditionally essential genes can be assayed in a pooled manner to elucidate their functions. With these assays novel metabolisms and novel gene functions can be identified and used to inform genetic engineering efforts. To validate the practicality of this method, we first assayed the aromatic metabolic pathways of Pseudomonas putida KT2440, and then applied the initial step of hydroxycinnamate catabolism toward the synthesis of a curcuminoid. Following this success, we sought to characterize the other diverse metabolisms of P. putida. Fatty acids and alcohols are highly sought after bioproducts for use as fuels and commodity chemicals; however, P. putida is known to metabolize most of these compounds. We therefore used BarSeq to elucidate the metabolism of 23 of these compounds with applications ranging from surfactants to plastic monomers. The results of these assays could then be used to inform engineering efforts for the production of these molecules and their derivatives. Given the diversity of metabolisms, next we sought to analyze the nitrogen metabolisms of P. putida as these again have applications as commodity chemicals. To this end, 52 different nitrogen-containing compounds were assayed via BarSeq as sole nitrogen sources. These molecules have many overlapping gene requirements in their metabolism, thus requiring a method for effectively analyzing and interpreting the data. The machine learning method known as t-stochastic neighbor embedding (tSNE) was employed to generate an interactive map of clustered genes with the distances between genes determined by the similarity of each gene’s BarSeq data.

Advisor: Keasling, Jay D
Refugee Legacies, Media Objects, and Collective Memory: Evolutions of Diasporic Consciousness among Sri Lankan Tamils in Canada

Since the 1980s, Sri Lanka’s ethnic conflict has caused the mass migration of over a million ethnic Tamils from their homeland, creating a transnationally interconnected Sri Lankan Tamil diaspora deeply engaged in homeland politics. This study focuses on the Tamil-Canadian diaspora, the largest Sri Lankan Tamil community outside of Sri Lanka. It seeks to explore the way particular histories of war, refugee migration, and a sustained relationship with media technologies and objects have shaped the Sri Lankan Tamil diaspora’s collective memory and diasporic consciousness. Through paying particular attention to second-generation Tamil-Canadians, this study investigates how this generation interacts with, are influenced by, and ultimately tries to contribute to this community’s evolving diasporic consciousness./nBuilding an interdisciplinary methodology, this study blends together digital ethnography, participant observation, media and visual culture analysis, as well as in-depth interviews to consider various interrelated questions about the forces that shape the identity, collective memory, and political subjectivities of this diasporic community. This study argues that it is useful to approach this community and others like it through the framework of what it means to study a refugee diaspora. The refugee diaspora framework asks us to consider how diasporic communities that migrate to escape war are wholly shaped by the particular conditions of their violent dispersal and the continuities that stem from it. These continuities extend far beyond the legal term, ‘refugee’ and have lasting effects on the diasporic imaginings of future generations. This study also argues that the collective memory of this transnational diaspora is one that is maintained by both politicized narratives forwarded by community organizations and more amorphous and embodied memories and traumas carried by individuals and families. This collective memory is then continually mediated through what this study calls a visual landscape of identity, which is made up of the media technologies, media objects, local realities, imagined homelands, and inherited traumas that the Tamil-Canadian diaspora engages with. Finally, this study argues that in their place-making projects, the second-generation of this diaspora is learning how to contribute to an evolving sense of diasporic consciousness through integrating their unique experiences, perspectives, and political subjectivities into the tapestry of Tamil identity woven by the generations before them.

Advisor: Siu, Lok
Um, Khatharya
Contributions to the Statistical Foundation of Data-driven Control

we demonstrate several techniques to prove safety guarantees for robust control problems with statistical structure; that is, for data-driven dynamical modeling or verification problems where uncertainty is modeled by probability. These guarantees are probabilistic in nature, in accordance with the statistical nature of the uncertainty, and can be derived with limited model assumptions. Indeed, some of the techniques require no more than measurability. We focus on two data-driven control problems: estimation of forward reachable sets from data, and robust control of time- and frequency-domain models defined by a Gaussian process regression model. In the former, we apply scenario optimization and statistical learning theory to obtain probabilistic guarantees of accuracy and confidence with minimal system knowledge. In the latter, we apply the theory of suprema of Gaussian processes to establish high-probability regions of attraction, L2 gain bounds, and integral quadratic constraints for the uncertain system.

Advisor: Arcak, Murat
Evaluating and Optimizing Distributed Energy Resources

Climate change is one of the most urgent problems faced by humanity, and rising sea levels, extreme weather events and desertification pose a severe threat to human life as we know it. Greenhouse gas emissions resulting from human activities have caused long-term global warming, and are primarily caused by the burning of fossil fuels to generate energy, e.g., for electricity, heat or transport. It is essential that we move to cleaner sources of energy across the board to prevent further greenhouse gas emissions, and this move is driven by three main trends./nFirst, the rise of distributed energy resources through rooftop solar, backup batteries and electric vehicles has led to the creation of a new class of consumers which have electricity production capability. These resources tend to be variable, and are owned and operated independently. Second, the move to variable clean energy production will lead to power system operators having an increased need for demand side flexibility in order to accommodate the supply-side variability. Flexible consumers can bid in their flexibility into markets for profit, or use it to reduce their emissions impact. Third, the increasing share of electric vehicles will led to an intersection of the transportation and power networks, where electric vehicles will be able to use their batteries as `mobile' storage in the power network./nThis dissertation addresses some key challenges associated with each of these trends, and proposes solutions for them.

Advisor: Spanos, Costas J
Poolla, Kameshwar
Evil, Vicious, and Nice: "Myssruled" Women’s Bodies in Late Medieval English Courts of Law

This dissertation argues that pre-Reformation policing of women’s sexuality in England was much more tolerant than recent scholarship has contended, and that women were adept in using the resources available to them in terms of their networks within the community to navigate the ecclesiastical and civil courts. The project is animated by an often-overlooked gap between the official rhetoric about women’s sexuality and practical jurisprudence, i.e., the day-to-day records of indictments, prosecutions, and outcomes. Most women brought to court for sexual misbehavior escaped punishment. Previous scholarship has explained this apparently lax system as evidence of the ineffectiveness of mechanisms of social control before the Elizabethan rise of the state. My original research shows that this was not the case. When women got off, the system was working as intended./nChapter 1 examines the language of the court records of women accused of sexual misbehavior, utilizing Latin and English language court records to demonstrate that authorities had a nuanced understanding of women’s sexual misbehavior that was obfuscated by the conventions of late medieval legal Latin. Chapter 2 engages with the scholarly debate about women’s sexual reputations and argues that women at the lower end of the social hierarchy were less concerned with their reputations than they were with using the social capital of their male friends to maintain their place, however debased, in their communities. Chapter 3 looks at the late medieval justice system through the lens of restorative justice and argues that this system reflected a focus on restoration rather than retribution. Chapter 4 looks at the elaborate shaming punishments prescribed for women convicted of sexual misbehavior in the context of the culture of performance during the period. Finally, a coda suggests how this research can offer new approaches to feminist medieval historians.

Advisor: Shagan, Ethan