VictorJuiz/thesis huggingface dataset:
Regulating Trafficking of Nociceptive Transient Receptor Potential Channels

Transient receptor potential (TRP) channels are a family of receptor proteins regulating pain sensation. TRP receptors are activated by a variety of noxious stimuli, such as capsaicin (chili peppers), heat, and mechanical stress. Chronic TRPV1 stimulation leads to desensitization of the receptor, a process which is mediated by calcium/calmodulin dependent kinases. This attribute, however, has yet to been leveraged for treatment of chronic pain diseases. Here, we identify a potential C-terminal phosphorylation site that is involved in regulating level of TRPV1 expression at the cell surface. In dorsal root ganglion cells, confocal microscopy and western blot show that de-phosphorylation of threonine 705 through creation of a T705A mutation is sufficient to induce significantly increased expression at the plasma membrane. Mimicking constitutive phosphorylation through a T705E mutant at that site induces the receptor to be retained on intracellular membranes. TRPV4 - another member of the TRPV family - also has a similar trafficking switch region that contains two adjacent threonines T739 and T740, both potentially involved in regulating TRPV4 surface expression. Confocal and western blot data show that removing the potential T740 phosphorylation site is sufficient to significantly increase surface trafficking. However, the phosphomimetic mutation reduced but did not eliminate surface expression.

Keywords:  Department of Biology
Biology
TRPV1
capsaicin
opioid
Thesis
Advisor: Gross Eric
Cyert Martha
Reimagining Strategic Philanthropy: From Principal-Agent Problems to Bottom-Up Learning in Foundations

Foundations are beginning to dwarf the U.S. government as agents of global development, both in terms of financial resources and influence. There is, however, little research on the top-down nature of foundations’ role in development. This study interviewed staff at 17 foundations, either actively working against or failing to address this top-down nature, about the factors contributing to hierarchical dynamics in philanthropy, as well as mechanisms to reduce resulting power imbalances. The results indicate that foundations face various principal-agent problems of social coordination in their work. The strategic philanthropy framework attempts to address these problems by shifting more control to the principal, thereby intensifying top-down hierarchies. In contrast, participating foundations had redefined strategic grantmaking as working against top-down hierarchies and emphasizing investing in and learning from partnerships with grantee organizations. These foundations used bottom-up organizational learning to incorporate grantee knowledge and expertise into their decision-making and move towards more participatory grantmaking. Bottom-up learning was, however, lacking in the officer-board and grantee-board relationships, limiting foundations’ abilities to fully utilize the knowledge they were acquiring from their grantees. Overall, bottom-up learning and its ability to create participatory grantmaking was strongest in community foundations.

Keywords: strategic philanthropy
principal-agent problem
bottom-up learning
top-down development
Thesis
A relational architecture for graph, linear algebra, and business intelligence querying

Modern analytics workloads extend far beyond the SQL-style business intelligence queries that relational database management systems (RDBMS) were designed to process efficiently. As a result, RDBMSs often incur orders of magnitude performance gaps with the best known implementations on modern analytics workloads such as graph analysis and linear algebra queries. The relational model is therefore largely forsaken on such workloads, resulting in a flurry of activity around designing specialized (low-level) graph and linear algebra packages. In this dissertation we present a new type of relational query processing architecture that overcomes these shortcomings of traditional relational architectures. To do this we present a new in-memory query processing engine called EmptyHeaded. EmptyHeaded uses a new, worst-case optimal (multiway) join algorithm as its core execution mechanism, making it fundamentally different from nearly every other relational architecture. With EmptyHeaded, we show how the crucial optimizations for graph analysis, linear algebra, and business intelligence workloads can be captured in such a novel relational architecture. The work presented in this dissertation shows that, unlike traditional RDBMSs, this new type of relational query processing architecture is capable of delivering efficient performance in multiple application domains.

Advisor: Olukotun Oyekunle Ayinde 
Ré Christopher 
Zaharia Matei
The relationship between bacterial stress responses and cell shape : from the molecular to the macroscopic

How do we respond to our environment? How much does our environment drive our very form, our physical shape? These are fundamental questions that biology must grapple with on all scales of life. Understanding how the shape of an organism is formed, how it is maintained, and how it interacts with external stresses is key to understanding its strengths, limitations, and what it could become. My thesis examines a portion of the complex relationship between organism and environment by studying the physical changes bacteria undergo in both friendly and hostile environments, using the well-studied model organism Escherichia coli. In Chapter one, I will introduce the relevant bacterial physiology necessary for understanding cellular growth and division. I will also define the structural and molecular determinants of cell shape in bacteria, and then examine what is known about how environmental conditions impact cell shape. In chapter two, I will start at the protein level, examining a key protein in the cell division machinery, FtsZ, and its relationship to inhibitors that induce cell death. In chapter three, four and five, I will move to larger cellular structures and discuss how genetic or external perturbations effect the integrity of the bacterial cell wall, the key macromolecule in cell shape determination. In chapter six, I will move from single molecules to molecular networks: I will examine a stress response pathway, the Rcs pathway, and its connection with perturbations to cell width and its influence on cell length. I will show how these observations again relate to the interaction and regulation of the cell wall synthesis machinery governed by cytoskeletal proteins MreB and FtsZ, respectively. In chapter seven, I move finally from single cell behavior to the behavior of cell populations under stress. Specifically, I will utilize previous work examining the relationship between increased cell size and fitness as the basis for generating a cell shape mutant library. I then used this library in a high-throughput chemical genomics screen to further characterize the types of stressful environments in which size plays a key role in fitness, revealing evolutionary pressures on cell shape. I will conclude in chapter eight by re-examining the fundamental questions posed at the beginning of this chapter and reflect on how this work moves us a step forward in illuminating the complex and varied ways in which organisms interact and are changed by their environment.

Keywords: Bioengineering.
Advisor: Huang Kerwyn Casey
Altman Russ 
Covert Markus 
Liphardt Jan
The relationship of surface deformation to groundwater storage and quality in the San Joaquin Valley, California

Land subsidence due to groundwater pumping in the San Joaquin Valley of California is known to cause many negative side effects, including a loss of groundwater storage. The general theory behind surface deformation, which includes subsidence and rebound, due to changes in the groundwater system, is well established. Surface deformation occurs as a direct result of changes in water level in an aquifer system, and can be permanent or recoverable, depending on the stress history of the aquifer system. An advanced satellite method known as Interferometric Synthetic Aperture Radar (InSAR) can be used to measure surface deformation with ~cm accuracy, at a resolution of ~100 m and measurements every 10 to 40 days. In spite of our ability to measure surface deformation with this method, and the existing theory describing the relation of deformation to changes in water level, it remains challenging to relate this deformation to changes in the aquifer system because so much information is required to do so accurately. The goal of this thesis is to develop methods to improve our ability to monitor and model groundwater storage and quality by incorporating InSAR with geological, geophysical and water quality datasets. This includes developing methods that estimate how much observed deformation is permanent, methods that predict deformation given water level changes, and methods that relate deformation to arsenic contamination. By integrating multiple datasets with InSAR, we are able to extract more useful hydrogeological information that provides water managers with tools to map and model deformation due to changes in the groundwater system, as well as its impacts on groundwater storage and quality. Our key findings are that 1) in the San Joaquin Valley, 54-98% of the subsidence that occurred from 2007-2010 throughout our study area was permanent, 2) by combining InSAR data with airborne electromagnetic (AEM) data, we are able to model surface deformation over time and improve estimates of the subsurface hydrostratigraphy, as well as hydrologic, geomechanical and rock physics parameters, 3) our modeling indicates that the land has subsided by as much as 3 m since 1990 in one specific location within our study area, and 4) land subsidence resulting from overpumping is linked to arsenic contamination in the San Joaquin Valley aquifer system.

Keywords: Geophysics.
Advisor: Knight Rosemary (Rosemary Jane)
Fendorf Scott 
Zebker Howard A.
Remaining Authentic on Digital Media using an Existential Framework

Unlike any other generation before them, digital natives are constant users of various social media platforms. These social media platforms include sites such as Facebook, Instagram, and Twitter, which all have the power to influence the users identity and self-perception. Despite the pervasive use of these social media platforms, individuals still appears quite indifferent and uncritical of the effects that social media may be having on society. This literature review will examine previous research that has been conducted on the relationship between digital natives and social media use, specifically as it pertains to achieving authenticity of self. Though examining the works of various philosophers and research studies from different scholars, the meaning of authenticity before and after the invent of social media will be discussed. Further, this thesis will examine how technology use such as social media, increases authenticity of individuals in the technological age. The ways in which technology has hindered authentic expression of self will also be explored. The main questions that will be structure the thesis include: What do past philosophers believe classifies a human being as an authentic member in society? How has the concept of authenticity evolved with the invent of the internet and social media? What is social media’s effect on the human experience, specifically on the individual’s ability to act authentically online?

Keywords:  Department of Communication
Authenticity
Social Media
True Self
Thesis
Advisor: Hancock Jeff
Liu Sunny
"Reporters for RAN translation of C9ORF72 amyotrophic lateral sclerosis and the role of hnRNP A1"

The translation of expanded DNA repeats lacking an AUG start codon has been implicated in amyotrophic lateral sclerosis (ALS), a progressive and universally fatal neurodegenerative disease. While the RNA transcripts and proteins produced by repetitive regions of the C9ORF72 gene have been characterized as toxic and correlate with disease, how these repeats are able to circumvent the conventional mechanisms of translation remain unknown. The field has begun to uncover genes responsible for driving this form of translation, but a model for the non-canonical mechanism remains unresolved, as is an understanding of how it contributes to ALS and other repeat-associated diseases. We have developed a GFP reporter with which we are able to visualize these abnormal translation products, called dipeptide repeat (DPR) proteins, using fluorescence microscopy. Using shRNA knockdown, we have investigated the role of hnRNP A1 in this possible disease pathway of ALS. We also saw a possible but equivocal reduction in DPR protein product when hnRNP A1 was knocked down in HEK293T cells with shRNAs. Given the prominence of repeat expansions in ALS and other neurodegenerative diseases—Huntington Disease, several spinocerebellar ataxias (SCA), and Fragile X-associated tremor/ataxia syndrome (FXTAS)—understanding how these sequences are translated and finding the genes responsible can reveal therapeutic targets for treating these diseases.

Keywords:  Department of Biology
Biology
School of Medicine
Molecular Genetics
Thesis
Advisor: Gitler Aaron
Fraser Hunter
Representation learning methods for computational social science

The combination of machine learning and massive social datasets has the potential to revolutionize our ability to predict and understand human behavior. However, machine learning on large social datasets is difficult because these datasets tend to be multimodal, dynamic, and involve graph-structured relationships (e.g., social networks between users)---while traditional machine learning tools are largely designed for static datasets comprised of simple Euclidean vectors or grids. In this dissertation, we address this challenge and describe new methods for machine learning on massive, graph-structured social datasets. The technical focus of this dissertation is on techniques for graph representation learning, i.e., representation learning with graph-structured or relational data. We show how we can use graph representation learning to model social systems in a data-driven way---by learning social representations or embeddings directly from raw data, rather than relying on painstaking and brittle feature engineering. We introduce techniques to learn social representations of individuals, communities, words, and generic social media content, and we highlight the utility of such embeddings in a large number of applications, including using social representations to uncover new laws of language evolution and to power a social recommender system serving millions of users. The key contributions of this dissertation are twofold: First, we describe new representation learning algorithms that are specifically designed to accommodate the relational complexities of social data. Second, we show---through numerous applications---how learned social representations can facilitate new kinds of social science and new kinds of social applications.

Advisor: Jurafsky Dan
Leskovec Jurij 
Ré Christopher
Resource allocation and decision making for groups

Social choice theory concerns the design and analysis of methods for aggregating possibly conflicting individual preferences to reach a collective decision in a satisfactory manner. The discipline dates from Condorcet's voting paradox in the 18th century, and its paradigm was significantly influenced by Arrow's seminal work in the 1950s. While classical social choice theory focuses on the existence and non-existence of aggregation methods that satisfy certain axioms, over the past two decades computer scientists have studied the discipline from a computational perspective, leading to an active research area of computational social choice. This dissertation presents results of the classical flavor as well as those applying complexity concepts and algorithmic techniques. In the first part, we consider resource allocation settings. We depart from the usual framework in which each recipient of a bundle of items is represented by a single preference, and assume instead that each interested party consists of agents who may have different preferences on the items. We study the problem of assigning a small subset of indivisible items to a group of agents so that the subset is agreeable to all agents, and derive bounds on the size of such a set under various informational and computational assumptions. We also investigate fairness guarantees in the allocation of indivisible items among groups. While the problem is more challenging than in the traditional setting with individual agents, we show that it is nevertheless possible to obtain positive results using asymptotic analysis and approximation. In the second part, we study decision making problems, where our goal is to choose the "best" alternatives from a given set of alternatives. We demonstrate that the bipartisan set, a method for selecting the best alternatives from a tournament proposed in the 1990s, is the unique method that satisfies a number of desirable properties. In addition, we consider issues related to choosing winners in sports competitions. We show that if tournament organizers have the freedom to determine the bracket of a single-elimination tournament, they can often make their favorite player win the tournament. We also tackle the problem of scheduling asynchronous round-robin tournaments, in which all games take place at different times, and propose schedules that perform well with respect to measures concerning the quality and fairness of the tournament.

Advisor: Roughgarden Tim 
Procaccia Ariel D.
Valiant Gregory
Resource, development and tradition : explaining persistence and costs of intergenerational marital norms in South Korea

This dissertation is comprised of an introduction and three independent papers that explore the themes of change and continuity in patrilineal marriage norms centered on patrilineal descent, patrilocal residence, and generational patriarchy in contemporary South Korea. Western European family with bilateral kinship and nuclear authority structure is taken as the default norm in the sociology of family literature, but extended family systems that embody a sex-generation hierarchy are much more common across the globe. Most extended family systems are based on patrilineality (recognition of descent only through the male links), which in turn is associated with patrilocality (residence with or near husband's kin) and generational patriarchy. Whether and to what extent the patrilineal family system has disintegrated or stayed resilient in the contemporary era is a critical issue to study, as it has important implications for gender inequality in most non-Western contexts. The three papers in this dissertation each address whether and how the traditionally patrilineal family system based on East Asian Confucianism has changed through the recent modernization processes in the context of South Korea. Collectively the findings demonstrate that although some features of the patrilineal family such as patrilocality have shifted towards bilateralism as a result of urbanization and the growing importance of economic resources, other structural aspects such as generational patriarchy and state support of the patrilineal family structure are not necessarily tied to economic development, and thus continue to be reproduced even after Korea has reached the economic status of a developed country. The findings have theoretical implications for studying family structure, economic development and gender inequality in other contexts with a patrilineal family system beyond Korea and East Asia.

Keywords: Sociology.
Advisor: Rosenfeld Michael J.
Correll Shelley Joyce 
Shin Gi-Wook
Restructuring the 3D chromosome for gene regulation

Chromatin looping is key to gene regulation, yet no broadly applicable methods to selectively modify chromatin loops have been described. This has prevented a comprehensive understanding of chromatin loop formation and maintenance. To address this, a novel method for chromatin loop re-organization using CRISPR-dCas9 (CLOuD9) was engineered to selectively and reversibly establish chromatin loops. The power of this technology to selectively modulate gene expression at targeted loci is demonstrated. Further, use of CLOuD9 enabled identification of the RNA helicase DDX5 as a novel chromatin structure regulation factor responsible for stabilization of de novo chromatin loops. This has particularly important implications in cancer, where destabilized chromatin structure is frequently observed. Collectively, findings from this body of work will be critical to obtaining a more comprehensive understanding of how chromatin dynamics specifically impact transcription apparatus to facilitate oncogenesis, and may further shed light on useful ways to design novel therapies for more targeted cancer treatments.

Advisor: Wang Kevin K. W. 
Bassik Michael 
Mallick Parag
Oro Anthony
Return to sender : photography, art, and the mail, 1845-1945

This dissertation examines the historical relationship between photography and the postal service in the United States, tracing the aesthetic influence of the mail on photographic practice as both forms developed across the nineteenth and twentieth centuries. Since the early decades of photography, practitioners have relied on a burgeoning international postal system in order to send photographs, materials, and information about technological developments across long distances. The official announcement of the daguerreotype photographic process in 1839 occurred just six years before the landmark Postal Act of 1845, in which the United States Congress reduced postage rates to allow the mail to be, for the first time, a viable form of communication for the majority of Americans. Central to the history of photography though rarely discussed within it, this dissertation examines how the mail proved a key agent in the evolution of the photograph from a singular and costly object to a reproducible and disseminable image. Through the work of photographers Southworth & Hawes, William Henry Jackson, Anne Brigman, Alfred Stieglitz, John Gutmann, and Francesca Woodman, "Return to Sender" considers how American photographers have conceptualized transmission and communication as aspects, and even primary goals, of their work. In so doing, this dissertation seeks to reconsider traditional histories of photography predicated on the priorities of modernist formalism, instead framing the history of the photographic medium as one of transmission and exchange.

Keywords: Art and Art History.
Advisor: Nemerov Alexander 
Calm Jonathan 
Greene Roland
Meyer Richard
Revoking work permits of spouses of tech immigrant workers will reduce Silicon Valley’s competitive advantage

Last year, President Trump signed the “Buy American and Hire American” executive order that
argued for the need to protect the interests of United States workers. One of the decisions driven by
this executive order will be the implementation of a rule that will eliminate work authorization of
spouses of H-1B — or high-skilled visa holders. The decision threatens to upend the tech industry
at a time when Silicon Valley’s big companies — which rely on H-1B visa workers — are already
facing a labor shortage. If their spouses aren’t allowed to work, other countries with less-restrictive
visa policies will attract these skilled workers, opponents of the rule change say.

Keywords:  Department of Communication
visa
immigration
reform
Trump
H-4
Department of Communication and Journalism
Thesis
Advisor: Zacharia Janine