VictorJuiz/thesis huggingface dataset:
Regulation of calcineurin through interactions at a critical substrate binding site [electronic resource]

Cells respond to changing conditions by communicating through signal transduction pathways. Calcineurin, the Ca2+/calmodulin-activated serine/threonine protein phosphatase, mediates the cellular response to Ca2+ by regulating phosphorylation in diverse cellular contexts. Calcineurin plays key roles in development, neuronal signaling, and immunity by targeting a variety of substrates. Calcineurin substrates contain conserved motifs that bind to docking sites on the surface of the enzyme and contribute to substrate specificity. Our studies reveal that these docking surfaces are important not only for substrate recognition, but are vital for substrate engagement and positioning, and their accessibility is a requirement for functional dephosphorylation. We present research that defines one such surface, the LxVP docking pocket. Additionally, we elucidate the mechanism of inhibition by the viral protein inhibitor A238L, which inhibits calcineurin by occupying both critical substrate recognition sites while leaving the catalytic center fully accessible. Finally, we investigate the calcineurin variant CNbeta1, and discover the distinct molecular strategy by which autoinhibition and activation occurs in this isozyme. This work contributes to our knowledge of calcineurin regulation and substrate recognition, and lays the groundwork for understanding the complex signal transduction networks controlled by this important phosphatase.

Keywords: Biology.
Advisor: Cyert Martha S.
Frydman Judith advisor. Thesis advisor
Herschlag Daniel advisor. Thesis advisor
Stearns Tim advisor. Thesis advisor
Regulation of the INO80 chromatin remodeling complex in response to TORC1 inhibition

Eukaryotic cells have large genomes that are tightly wrapped around protein cores called histones to fit in the small nuclear compartment. However, cells also need chromatin remodeling complexes to unwind the genetic material. The yeast INO80 chromatin remodeling complex regulates the expression of genes that are involved in metabolic pathways, such as glycolysis and oxidative phosphorylation. Broadly, this research considers the relationship between the metabolism of the cell and the activity of chromatin modifying enzymes. Specifically, this research was designed to elucidate the regulation of the INO80 chromatin remodeling complex in response to nutrient stress in the yeast Saccharomyces cerevisiae. In particular, we focused on the TOR signaling pathway, which is a nutrient-responsive regulator of cell growth. Previous studies found that treatment with rapamycin or depletion of amino acids, both of which reduce TORC1 activity in the pathway, caused degradation of Ino80, the catalytic core of the INO80 complex. However, it is unknown if this also disrupts the stability of other subunits of the INO80 complex. Using Western blot analysis of epitope-tagged proteins, we analyzed the stability of the INO80 complex subunits in response to TORC1 inhibition. We find that rapamycin treatment results in specific degradation of Ino80 but no other subunits. In addition, we replicated an assay to track TORC1 activity. This study contributes to our understanding of the response of chromatin remodelers under nutrient stress, a cellular condition that can be found in disease like diabetes and cancer.

Keywords:  Department of Biology
Biology
chromatin
signaling pathway
TOR
cell metabolism
Thesis
Advisor: Morrison Ashby
Dixon Scott
Residents’ struggles continue as officials learned their lessons from San Jose flood

Four months after a major flood hit the city of San Jose, many residents are still struggling to get back in their homes, get their cars replaced, or mentally recover from the flood's impacts. While city and water district officials have learned their lessons in disaster preparation, crisis communication, and managing recovery efforts, some residents still live with friends or family members, or in hotels and temporary apartments.
The flood led to the evacuation of 14,000 people, with 1,400 of them directly affected by temporary displacement or other damages to private and/or business properties. This story and accompanying video takes a closer look at how residents are dealing with the situation. It also examines the role of the Santa Clara Valley Water District and city officials of San Jose.

Keywords:  Department of Communication
San Jose Flood
100-year flood
City of San Jose
Santa Clara Valley Water District
Clean-Up
Department of Communication
MA Thesis
Journalism
Thesis
Advisor: Migielicz Geri
Revenue management with side information [electronic resource]

Companies launch new products periodically without accurate prior knowledge of the true demand. One method to learn the demand function is price experimentation, where companies adaptively modify prices to learn the hidden demand function and use that to estimate the revenue-maximizing price. Nevertheless, proper price experimentation is a challenging problem due to the potential revenue loss during the learning horizon that can be substantially large. In fact, optimally balancing the trade-off between randomly selecting prices to expedite the learning versus selecting prices that maximize the expected earning has been subject of recent research in the operations management literature. A generic problem is to consider that a firm sells products over multiple periods without knowing the demand function. The firm sequentially sets prices to earn revenue and to learn the underlying demand function simultaneously. We establish a model to illustrate that this problem is closely related with bandits problem, which is a specific case of reinforcement learning. In addition, with accumulated data assisting to predict the true demand function, the price experimentation policy has some surprising feature. We demonstrate that, under certain conditions in the rich data environment, the challenging price experimentation problem could be solved by the ubiquitously used greedy pricing policy.

Keywords: Business.
Advisor: Bayati Mohsen primary advisor. Thesis advisor
Harrison J. Michael
Xu Kuang advisor. Thesis advisor
Revitalizing Public Life: Social Interaction in Seattle's Community Gardens

Sociologist Robert Putnam, in his classic work Bowling Alone, describes how the retreat from public life has become a problem in large cities. With Putnam’s ideas in mind, this thesis investigates social life in Seattle’s community gardens. Gardens promote urban public life through engaging a diverse array of participants, gardeners struggle to navigate the program’s rules related to its two, sometimes contradictory, goals: inclusion and community creation. While much has been written about community gardens, there is an ethnographic gap in which scholars have not learned closely from the gardeners themselves. To address this gap, I studied four garden sites using participant observation, semi-structured interviews, and informal conversation. Interacting with gardeners, I learned how they relate to each other through the shared experience of gardening as well as organizing against a common enemy manifested as vandalism and theft by non-gardeners. My findings pose questions such as: Why should local government prioritize creating programs that engage people in public space? How does a group strike a balance between inclusion of all and cohesion of some? How can public spaces best serve the full range of residents? This thesis concludes with a discussion of how Seattle’s community gardening program is one of many initiatives through which Seattle models local progressivism directly in conflict with national political and economic trends.

Keywords:  Department of Anthropology
anthropology
urban studies
sociology
community gardening
seattle
Thesis
Advisor: Garcia Angela
Ebron Paulla
Rigid and flexible multimode fiber endoscopes [electronic resource]

Endoscopes are medical instruments that transmit images through long, thin optical conduits. An endoscope built using a single multimode optical fiber (MMF) as the optical conduit has roughly two orders of magnitude better spatial resolution than current, commercial endoscopes built using fiber bundles. Despite the potential of MMF endoscopes, research is necessary to improve the signal-to-noise ratio (SNR), imaging time, field of view, and flexibility before they can become a practical technology. Chapters 2 and 3 describe and experimentally demonstrate a complete method of imaging through a rigid MMF endoscope. The advantages of this method are that arbitrary sampling patterns can be used to sample the object to be imaged, and spatial resolution is increased by a factor of 4 over comparable MMF imaging methods. In this method, a sequence of random field patterns is input to the MMF, generating a sequence of random intensity patterns at the output, which are used to sample an object; reflected power values are returned through the MMF, and linear optimization is used to reconstruct an image using a method we term optimization-based reconstruction. The point-spread function and noise performance under different SNR and noise regimes are mathematically derived. Chapters 4 and 5 describe and present experimental results for a complete method of imaging through a flexible MMF endoscope. This is achieved by the addition of a partial reflector to the distal end of the MMF, which allows measurement of the mode coupling of the transmitted light through the MMF using the reflected light arriving back at the proximal end of the MMF. We simulate imaging through such a flexible MMF endoscope with 1588 spatial modes and show that an image can be obtained even after the MMF is arbitrarily bent. We experimentally verify the first part of this method by finding that the perturbation of the light reflected from the partial reflector is indeed highly correlated with the perturbation of the light transmitted through the MMF, and use it to form spots at the distal end of a flexible MMF with quality 10-15% higher than if the perturbation of the MMF is ignored.

Keywords: Electrical Engineering.
Advisor: Kahn Joseph M. (Joseph Mardell) primary advisor. Thesis advisor
Fan Shanhui
Miller D. A. B. advisor. Thesis advisor
The rise of Shanxi merchants [electronic resource] : empire, institutions, and social change in Qing China, 1688-1850

This dissertation traces the rise of Shanxi merchants during the Qing era (1644- 1911). During the eighteenth and nineteenth centuries, merchants from Shanxi Province in north China formed an unprecedented, expansive business network that not only controlled long-distance trade between China proper, Mongolia, and Russia, but also created an empire-wide banking system in China for the first time. Given these accomplishments, Shanxi merchants have become synonymous with traditional Chinese entrepreneurship. My research considers how Shanxi merchants rose to prominence and why they became so successful. I argue that the history of Shanxi merchants has to be understood in the context of the political economy of the Qing imperial project. During the first half of the eighteenth century, thanks to its rapid expansion, the Manchu empire engulfed the Mongolian steppe and Xinjiang, which resulted in the opening of the nomadic market for Chinese traders for the first time in history. The activities of Shanxi merchants helped to integrate these frontier regions with China proper. These merchants developed a series of institutions based on the time-honored local traditions of north China, which were then adapted to suit the socio-economic conditions on the frontier. These institutional innovations included the creation of new forms of native-place organizations, trade guilds, new firm structures, and new banking systems. Shanxi merchants' institutional innovations had profound impacts on late imperial Chinese society. On the one hand, these new institutions on the frontier pioneered a series of changes in China proper during the nineteenth century. On the other hand, Shanxi merchants used these institutions to create a new social order with mercantile power at its helm, which was radically different from the orthodox Confucian order backed by imperial ideology. For this reason, I argue that understanding Shanxi merchants' history also challenges dominant perceptions of the spatial economy of the Qing Empire. As this study reveals, the remote and landlocked northern frontier of the empire was not a backwater but a center of economic dynamism, a source of enormous wealth, and an incubator of new institutions, organizations, and values. Drawing insights from the "New Qing History" scholarship and institutional economics, this dissertation builds on a wide range of primary sources, including Chinese-language archival materials from both Inner Mongolia and the Mongolian People's Republic, local business documents made available to me by private collectors in Shanxi, stele inscriptions collected by Japanese investigators during the first half of the twentieth century, as well as gazetteers, genealogies, and oral history interview records from Shanxi and Inner Mongolia.

Keywords: History.
Advisor: Sommer Matthew Harvey
Greif Avner
Lewis Mark
Wigen Kären
Robotic hand design for remote ocean exploration [electronic resource] : active selection of compliance and contact conditions

Mobile robots expand human reach into new and difficult environments, such as space, disaster sites, and the deep ocean. Robotic operations are typically executed via end-effectors, i.e. hands or grippers. Compliant underactuated hands are a useful solution in unstructured environments. This class of grippers trades off dexterity and simplicity to permit a range of grasp types and afford physical robustness without the complexity of a fully actuated design. This thesis presents the design, implementation, and testing of versatile and resilient compliant hands. The immediate application is the Ocean One submersible humanoid robot, which is intended to bring intuitive telepresence to marine exploration. Underwater vehicles take the place of divers, especially at unsafe depths, and expand our access to untapped marine environments. Relevant applications range from oil rig maintenance to ocean archeology and marine biology. Underwater environments present challenges that require special consideration when designing and controlling hands: slippery biofilms are commonplace, water currents can make reaching for flexible objects inaccurate, and buoyancy can make it easy to accidentally push floating objects away while trying to grasp them. Ocean One may need to acquire and hold a range of objects, from delicate sea creatures and priceless artifacts at shipwrecks to heavy structures and tools. By virtue of the kinematics and joint stiffnesses, the hands created for this work can perform precision fingertip pinches and strong wrap grasps. In addition, two mechanisms change the hand's passive behavior during grasping: (i) a dual-stiffness spring-winch transmission changes load-sharing characteristics between the fingers, and (ii) fingertip suction flow influences where contact occurs on the fingers and the amount of friction associated with each contact. These mechanisms alter the compliance and contact conditions of the underactuated hand, significantly influencing grasp behavior and enabling more versatility. Suction flow also acts as a simple and robust solution for tactile sensing, providing information about the finger-object contact conditions without the need for additional wiring or electronics at the hand. Improved dexterity of underactuated hands could allow them to function more effectively during unstructured and wet manipulation tasks.

Keywords: Mechanical Engineering.
Advisor: Cutkosky Mark R. primary advisor. Thesis advisor
Khatib Oussama advisor. Thesis advisor
Okamura Allison advisor. Thesis advisor
Robust body diffusion-weighted magnetic resonance imaging [electronic resource]

Body MRI has progressed as a detection method for many pathologic processes. It is effective in helping in the diagnosis of unknown primary malignancy, determining the skeletal spread of metastasis, and as a cancer screening and staging tool. Diffusion-weighted imaging (DWI) is an MRI sequence that relies on alteration in intra- and extracellular water content from the transmembrane water flux to generate image contrast. DWI is routinely used in brain imaging and is particularly useful for early detection of ischemia. However, extending DWI to body MRI poses additional technical challenges such as organ movement, proximity to gasses in bowels and lungs, and greater variability of tissue body water composition. Despite these challenges and associated image artifacts, DWI is used in many clinical scanning protocols. However, due to image artifacts and loss of image integrity and quality, the efficacy of using these images in a clinical setting is diminished. This thesis focuses on developing a DWI sequence for body MRI that is tailored to overcoming these technical challenges. Specifically, this work comprises of combining diffusion contrast preparation with a single-shot fast spin echo (SS-FSE) imaging pulse sequence. Despite its promised robustness, the SS-FSE sequence is subject to various constraints on signal phase, which cannot be guaranteed in the presence of diffusion weighting. This work overcomes this by using two approaches. The first approach uses a quadratic phase modulation throughout the echo train. This work improves this sequence by 1) redesigning the acquisition sampling pattern and reconstruction and 2) enhancing the signal stability in this sequence through optimizing the RF pulses used in the echo train. This sequence is rigorously validated in simulation, phantom scans, and clinical in vivo patient scans at the Lucille Packard Children's Hospital. The second approach consists of using a different SS-FSE sequence but is able to design the diffusion preparation module such that the unstable portion of the signal is eliminated prior to imaging. This sequence is also rigorously validated in simulation, in phantom scans, and in patient scans.

Keywords: Bioengineering.
Advisor: Pauly John (John M.) primary advisor. Thesis advisor
Nishimura Dwight George advisor. Thesis advisor
Pelc Norbert J. advisor. Thesis advisor
Role of Circadian Rhythms in Cued and Contextual Fear Conditioning

Disruptions in circadian timing impair spatial and recognition memory in humans and in rodents. The complete loss of circadian timing also impairs these kinds of memory. For my project, I examined the role of circadian timing on fear memory. I used Siberian hamsters because their circadian timing can be eliminated by a simple one-time manipulation of the light-dark cycle. Arrhythmic hamsters had impaired contextual fear memory but not cued fear memory. Thus, circadian arrhythmia impaired the association of the foot shock with the context of the testing chamber, but not with the association of the tone with the chamber.

Keywords:  Department of Biology
Biology
Neurobiology
Circadian Rhythms
Sleep
Learning and Memory
Fear Conditioning
Thesis
Advisor: Heller Craig
Fernald Russell
The role of common and rare variants in gene regulation across human tissues [electronic resource]

Interpreting the phenotypic impacts of the millions of variants within each individual's genome is a fundamental, unsolved problem in genetics and medicine. Thus far, efforts to profile this variation have focused on associations with molecular traits like gene expression. These association studies are becoming larger and more commonplace, though they still face major challenges regarding computation, statistical power, and potential biases in the variants they assess. This dissertation details some of the computational and statistical challenges plaguing these associations studies and offers example solutions. Chapter 2 describes a multiple-testing correction procedure for cis-expression quantitative trait locus (cis-eQTL) studies that dramatically reduces computation time while maintaining accuracy and statistical power for regulatory variant discovery. Chapter 3 explains the bias for common variation in cis-eQTL studies and outlines a general method for the discovery of gene expression outliers to detect rare regulatory variants with large effects across many tissues using the Genotype Tissue Expression dataset. Chapter 4 addresses the disadvantages of this method by developing a test for outlier gene expression which accounts for correlation structure and missing data, thereby allowing for detection of tissue-specific effects. Overall, these chapters provide a better understanding of the role of both common and rare variants and their impact on gene expression across human tissues.

Keywords: Genetics.
Advisor: Bustamante Carlos (Carlos D.) primary advisor. Thesis advisor
Montgomery Stephen
Petrov Dmitri Alex
Pritchard Jonathan (Jonathan K.) advisor. Thesis advisor
The role of myosin copy number variation (CNV) in adaptive evolution of sticklebacks [electronic resource]

Copy number variations (CNV) are a common source of genomic variation that have been linked to many diseases in humans. To look for copy number changes that may also contribute to advantageous traits during vertebrate evolution, we looked for recurrent CNVs that are positively associated with particular ecological environments in threespine stickleback fish. Freshwater sticklebacks show an expanded number of tandemly arranged myosin heavy chain 3 (MYH3) genes compared to marine fish. In a global analysis of many populations, we find that increased MYH3 copy numbers have evolved repeatedly in many recently derived postglacial freshwater locations. Interestingly, differences in copy number are maintained even in the presence of gene flow between hybridizing marine-stream species-pairs within single rivers, and between benthic and limnetic species-pairs within individual lakes. These results strongly suggest that the repeated copy number differences contribute to adaptive divergence between ecotypes. We identify a muscle regulatory enhancer within the duplicated MYH3 region, and show that elevated copy number is associated with increased MYH3 RNA levels in skeletal muscle. Finally, we provide a dynamic test of MYH3 evolution by monitoring changes in copy number following replicated experimental transplants of marine fish into freshwater lakes in Alaska. Significant MYH3 copy number changes evolve within only 5 to 7 generations following colonization of the new freshwater environments. These results provide a compelling new example of adaptive copy number changes in sticklebacks, and suggest copy number changes can provide an important source of advantageous variants when vertebrates adapt to rapidly changing environmental conditions.

Keywords: Genetics.
Advisor: Kingsley David M. (David Mark) primary advisor. Thesis advisor
Ashley Euan A. advisor. Thesis advisor
Sherlock Gavin advisor. Thesis advisor
Urban Alexander