VictorJuiz/thesis huggingface dataset:
Inhibition of the T-cell Kinase ZAP-70

The adaptive immune system responds to foreign antigens to produce a highly specific immune response. T-cells, a type of white blood cell of the adaptive immune system, can either directly kill infected cells or aid in sending signals that regulate the immune response. The T-cell receptor is expressed on the surface of T-cells and recognizes foreign antigens presented by antigen presenting cells. Unlike transmembrane receptor tyrosine kinases, the T-cell receptor does not contain its own kinase activity. Rather, the T-cell receptor recruits a number of non-receptor tyrosine kinases upon extracellular antigen binding to trigger intracellular signaling cascades. Zeta-chain associated protein of 70-kDa (ZAP-70) is one such non-receptor tyrosine kinase that is recruited to regions of the T-cell receptor known as Immuno-receptor Tyrosine-based Activation Motifs (ITAMs). Clinical observations, as well as chemical genetic studies, suggest that ZAP-70 is a possible target for T-cell inhibition./nSmall molecule inhibitors of ZAP-70 may prove to be therapeutically useful for the treatment of autoimmune disease or for organ transplant rejection. Because no such molecules exist today, we hope to exploit the structural insights gleaned from the recently solved autoinhibited structure of ZAP-70 to discover an allosteric inhibitor. In this dissertation, I describe a method of inhibiting the interaction between ZAP-70 and the T-cell receptor. I performed a high throughput screen for inhibitors of ZAP-70:ITAM binding and identified a collection of hit compounds. Inhibition by these compounds was verified in an orthogonal assay and was dose-dependent. I found that the compounds targeted the tandem-SH2 domains of ZAP-70 and were thiol-reactive. I go on to show that covalent cysteine modification underlies the inhibition of ZAP-70 and that individual compounds are specific for different cysteine residues.

Advisor: Kuriyan, John
Essays in Environmental Economics

Policy makers are increasingly choosing market-based policies over command and control options. In this dissertation, I explore two instances of policy choices in environmental economics: a relatively novel market-based approach to handle congestion in transportation policy; and, government provision and control in the arena of water policy./nThe first chapter estimates the traffic volume and travel time effects of the recently implemented road congestion pricing on the San Francisco-Oakland Bay Bridge. I employ both a difference-in-differences and regression discontinuity approach to analyze previously unexploited data for the two years spanning the price change and obtain causal estimates of the hourly average treatment effects of the policy. I find evidence of peak spreading in traffic volume and significant decreases in travel time during peak hours. I also find suggestive evidence of substitution to a nearby bridge that is not subject to congestion pricing. In addition, I show significant decreases in travel time variability. Using my results, I calculate own- and cross-price elasticities for trips due to the toll change and include back-of-the-envelope calculations for the welfare effects of the policy./nThe second chapter I explore the impact of government water delivers in California's Central Valley. California's agricultural sector receives large quantities of irrigation water from the federal and state water projects. In recent years, there have been significant restrictions on these deliveries due to droughts and regulation to protect endangered species. This chapter empirically tests the hypothesis that higher deliveries to water districts in a given county lead to higher agricultural employment and cropped area and provides point estimates of this effect and uncertainty around the estimates. The results show robust evidence of a statistically and economically significant impact of irrigation water deliveries on employment and area. This effect is robust to different definitions of employment, alternate control groups, and different windows of data.

Advisor: Auffhammer, Maximilian
Logic Informed

I develop an informational conception of logic as a science fundamentally concerned not with truth but with information. Facts about logical validity, on this conception, tell us about the structure of the bodies of information that we generate, encounter, absorb, and exchange as we interact with one another and learn about our world. I also investigate the normative role of logic in our epistemic practices. In particular, I argue against the widespread idea that there are rational requirements to have logically coherent beliefs that are not merely epiphenomenal on evidential norms.

Advisor: MacFarlane, John
Exploring the electronic, vibrational, and chemical sensing properties of graphene, nanotubes, nanoparticles, and other nanomaterials

Some might view the "nano revolution" as one of the most important developments of our time, as nanomaterials have been and continue to be a seemingly endless source of new and exciting physics and have found application in almost every imaginable aspect of our lives. Carbon allotropes such as graphene, which is a single atomic layer of carbon atoms in a hexagonal lattice, carbon nanotubes (CNTs), which can be thought of as graphene sheets rolled up into cylinders, and graphene nanoribbons (GNRs) have garnered massive attention in recent years due to their remarkable properties and many potential uses. This work investigates the fundamental properties and applications of certain nanomaterials such as carbon allotropes, semiconducting metal oxide (SMO) nanoparticles, and others in the exciting fields of gas sensing, nanoelectromechanical oscillation, and optical near field enhancement. It also introduces a novel GNR synthesis technique./nChapter 1 of this work is a brief introduction to the nanomaterials that will be investigated here. Chapter 2 presents experimental investigations into the interaction between gases and certain nanomaterials, including SMO nanoparticles, gold nanowires and thin films, CNTs, bare graphene, and graphene functionalized by a novel electrodeposition technique. New findings on the sensing mechanism of tungsten oxide nanoparticles for hydrogen sulfide gas are discussed. These findings suggest that previous models were incorrect or incomplete. Chapter 3 discusses sustained self-oscillations of a singly-clamped CNT under constant bias, a phenomenon which obviates the need for large external sources to drive nanomechanical oscillations. A model of the phenomenon is presented and used to guide scalable, top-down fabrication of self-oscillators. In chapter 4, a novel, clean technique for synthesizing GNRs with desired dimensions is demonstrated. It is shown that this method allows for transmission electron microscopy and electronic characterization of the GNRs during and after synthesis. A model of the underlying physical mechanism is proposed. In chapter 5, optical field enhancement near nanostructures, which has applications in optical antennae, photovoltaics, and near field optical microscopy, is modeled.

Advisor: Zettl, Alex
Ethnography Otherwise: Interventions in Writing, Photography, and Sound in Mexico and Brazil

This dissertation takes up the question of what it means to read and practice ethnography otherwise. I study works by Gertrude Duby Blom, Fernando Benítez, and Héctor García of Mexico, as well as Mário de Andrade and Darcy Ribeiro of Brazil, to develop otherwise as both a way of thinking about experimental ethnographic practices and a prompt for re-reading materials produced in an ethnographic mode. Expanding on the idea that ethnographic works are `made, not found,' the chapters draw attention to ways that ethnographies inscribe traces of the multiple parties that participate in their production, while examining a series of twentieth-century ethnographic experiments by figures on the fringes of formal anthropology--an amateur photographer who takes tens of thousands of photographs in Lacandon indigenous communities in Chiapas (Blom); a Brazilian modernista writer and musicologist who approaches fieldwork as a listening practice and positions himself as an apprentice to his informants (Andrade); an ethnologist turned novelist who stages his novel like an unruly ethnographic archive (Ribeiro); and a journalist who sets out to study and document indigenous lifeways in Mexico on an almost epic scale (Benítez)./nIf critical ethnography scholarship has theorized the inherent ambivalence of ethnographic materials often in terms of a crisis of ethnographic authority and textualization--that is, as a problem of graphing cultures into written texts--then the readings here grapple with the intentionality of ethnographic materials themselves alongside the stories of the people who produce them. These case studies suggest that re-thinking the photographs, recordings, writings, and archives that are made ethnographic involves complicating the ethnographer's position of privilege and noticing what resists or escapes her intentions. Yet they also problematize a way of reading that can reinscribe that position of privilege, a reading practice in which the ethnographer becomes the focal point of ethnographic encounters and the party principally responsible for the making and re-making of ethnographic materials. The chapters that follow bring out a series of ethno-modalities--modes of ethnographic inscription and creation--that move across photography, writing, and audio-recording to consider the messiness of fieldwork, the excess of ethnographic records and archives, and the unpredictability and unruliness of ethnographic objects in terms of what they inscribe and produce.

Advisor: Rabasa, Jose
Low Power, Scalable Platforms for Implantable Neural Interfaces

Clinically viable and minimally invasive neural interfaces stand to revolutionize disease care for patients with neurological conditions. For example, recent research in Brain-Machine Interfaces has shown success in using electronic signals from the motor cortex of the brain to control artificial limbs, providing hope for patients with spinal cord injuries. Currently, neural interfaces are large, wired and require open-skull operation. Future, less invasive interfaces with increased numbers of electrodes, signal processing and wireless capability will enable prosthetics, disease control and completely new user-computer interfaces./nThe first part of this thesis presents a signal-acquisition front end for neural recording that uses a digitally intensive architecture to reduce system area and enable operation from a 0.5V supply. The entire front-end occupies only 0.013mm2 while including "per-pixel" digitization, and enables simultaneous recording of LFP and action potentials for the first time. The second part presents the development of a minimally invasive yet scalable wireless platform for electrocorticography (ECoG), an electrophysiological technique where electrical potentials are recorded from the surface of the cerebral cortex, greatly reducing cortical scarring and improving implant longevity. A high-density flexible MEMS electrode array is tightly integrated with active circuits and a power-receiving antenna to realize a fully implantable system in a very small footprint. Building on the previously developed digitally intensive architecture, an order of magnitude in circuit area reduction is realized with 3x improvement in power efficiency over state-of-the-art enabling a scalable platform for 64-channel recording and beyond.

Advisor: Rabaey, Jan M.
Direct, time-resolved observation of protein-scale chemical reactions in living cells

This thesis studies protein-scale molecular interactions in the plasma membrane of living mammalian cells. Particular emphasis is paid to fluorescence imaging, as these methods provide high spatial density, high temporal and spatial resolution, chemically-specific information over length scales larger than most cells. In Chapter 1 reactions between the T cell receptor (TCR) and its ligand, peptide-Major Histocompatibility Complex II (pMHC), are studied in hybrid live T cell-supported lipid bilayer (SLB) junctions. The following observations are made: (1) single molecules of pMHC can trigger signaling reactions in T cells, without association of other MHC or receptor clustering, (2) live cell pMHC-TCR kinetics are similar to solution phase measurements and are consistent with in vivo estimates of kinetic thresholds for thymic selection, (3) membrane recruitment of Zeta-chain-associated protein kinase 70 (ZAP70) occurs within seconds of pMHC:TCR engagement, (4) the pMHC:TCR:ZAP70 complex is most likely stoichiometric with a 1:1:10 ratio, is spatially distinct, and is transported as a unit towards the geometric cell center in an actin-dependent process, and (5) a stochastic reaction-diffusion simulation confirms that the interactions observed are the result of pMHC:TCR molecular binding. Together, these observations indicate that signal amplification in T cells occurs downstream of the TCR. In Chapter 2 a hybrid optical/nanofabrication technique is presented for the study of actin-TCR interactions in live T cells. Live cell photoactivated light microscopy (PALM) is used to image single molecules of actin interacting simultaneously with both pMHC-TCR in freely-diffusing membrane and pMHC-TCR in distinct square corrals of laterally fluid membrane segregated by Cr diffusion barriers. Single actin molecule behavior is similar to bulk actin behavior observed using other techniques, but the single molecule approach allows access to previously unseen protein-scale information about the actin network, such as molecular tortuosity. In Chapter 3 a fixed array of gold nanospheres are embedded in a laterally fluid supported membrane, providing a novel tool for studying processes in the plasma membrane of living cells via attachment of immobile moieties to the gold lattice and mobile moieties to the fluid supported membrane. In Chapter 4 synthetic glycoprotein mimics are inserted into the plasma membranes of living cells and their clustering behavior is monitored in the presence of the putative cross-linking galectin proteins using advanced fluorescence fluctuation spectroscopies. This approach provides a novel platform for testing the "galectin lattice" hypothesis, and for studying galectin ligand binding in a physiologically-relevant context.

Advisor: Groves, Jay T
Modeling Pulsed Laser Melting of Embedded Nanoparticles

A model of pulsed laser melting of embedded nanoparticles is introduced. Pulsed laser melting (PLM) is commonly used to achieve a fast quench rate in nanoparticles; this model enables a better understanding of the influence of PLM on the size distribution of nanoparticles, which is crucial for studying or using their size-dependent properties. The model includes laser absorption according to the Mie theory, a full heat transport model, and rate equations for nucleation, growth, coarsening, and melting and freezing of nanoparticles embedded in a transparent matrix. The effects of varying the laser parameters and sample properties are studied, as well as combining PLM and rapid thermal annealing (RTA) processing steps on the same sample. A general theory for achieving narrow size distributions of nanoparticles is presented, and widths as narrow as 12% are achieved using PLM and RTA.

Advisor: Chrzan, Daryl C
The Ritual Instructions for Altar Methods (Tanfa yize): Prolegomenon to the Study of a Chinese Esoteric Buddhist Ritual Compendium From Late-Medieval Dunhuang

This dissertation offers the first comprehensive overview of a little-studied Chinese Buddhist ritual compendium known as the Ritual Instructions for Altar Methods (Tanfa yize). Attributed to the mid-Tang translator and Buddhist mage Amoghavajara (704-774), the collection contains some forty-two individual items spanning some four fascicles. Thematically, the work can be divided into two main parts. The first contains thirty-four individually named and numbered ritual texts, appended to which is a lengthy transmission account. In addition to providing a section outline of this voluminous work, the present study provides an account of the extant Duhuang manuscript copies of the text, and considers their paleographical and codicological features in an attempt to aid in its dating and reconstruction. Specifically, this study finds that the received text circulated in the Dunhuang region during the late-medieval period, and the late tenth century more specifically.

Advisor: Sharf, Robert H.
Weak Lowness Notions for Kolmogorov Complexity

The prefix-free Kolmogorov complexity, K(σ), of a finite binary string σ is the length of the shortest self-delimiting program that outputs σ and is a measure of the information content of σ. There are two very natural ways to extend this notion to infinite binary strings (identified as the binary expansions of real numbers in the interval [0,1]): one can examine the initial segment complexity of a real, i.e. K(A|n)$ as a function of n, or one can examine the compressive power of A as an oracle, i.e. KA(σ) as a function of σ./nEach of these approaches has a notion of minimality for reals. A real is K-trivial if the complexities of its initial segments are up to a constant just the complexities of their lengths. A real is low for K if it provides no more than an additive constant advantage to compressing any string./nThis dissertation examines weakenings of these notions that arise from replacing the constant bounds with slow-growing functions. The main results are that these weaker lowness notions behave very differently from the standard ones in terms of the sets of reals defined by these notions. We also include applications of these new notions to effective dimension and mutual information.

Advisor: Slaman, Theodore A
Hydrodynamic Exchange in Estuarine Perimeter Habitats

Hydrodynamic exchange in estuaries is forced by tides, freshwater input, density forcing, and winds, and controls transport of important quantities such as salinity, sediment, nutrients, and pollutants. Previous work has characterized many aspects of estuarine transport and contributed to our understanding of transport mechanisms such as gravitational exchange, tidal dispersion processes, and residual flows due to tidal asymmetries. In general, studies of estuarine transport have focused on large-scale transport processes in the along-channel direction of the estuary, which determine the overall salinity and flow structure in estuarine environments. However, study of hydrodynamic exchange at the perimeter of estuaries has also been recognized to be important, as exchange at the perimeter is relevant for understanding questions related to environmental restoration and management and ecological habitat quality./nIn this work, hydrodynamic exchange in estuaries and perimeter habitats is studied using numerical modeling and field observations of South San Francisco Bay. First, the exchange between the estuary and a small perimeter slough is measured using salinity and temperature as tracers to calculate hydrodynamic flushing of the slough through tidal exchange, using a modified tidal prism method. This method applies quasi-Lagrangian analysis to Eulerian measurements of exchange, and the results are compared to previous results from larger-scale estuarine systems, where tidal flushing is found to be significantly affected by the scale of mixing volumes in the system. Next, Lagrangian methods of particle-tracking and Lagrangian coherent structure (LCS) analysis, developed from dynamical systems theory in order to analyze complex, chaotic flows, are applied to analyze tidal transport. The results reveal the significant effects of tidal interactions with perimeter estuarine features on Lagrangian tidal transport over the tidal cycle, where perimeter interactions are found to significantly contribute to longitudinal estuarine dispersion. Finally, the effect of wind forcing on estuarine transport is examined, using Lagrangian analysis methods applied to cases of constant wind forcing with varying wind direction relative to the main axis of the estuary. Wind forcing is found to have a significant effect on hydrodynamic exchange and connectivity between the estuary and perimeter habitats, where wind in all directions increases perimeter exchange and connectivity, with the greatest effect for winds aligned with the along-axis direction of the estuary. The results of these studies are relevant to a wide range of applications requiring analysis of connectivity near the estuarine perimeter, including sediment exchange and transport and seagrass population colonization in the context of wetland habitat restoration.

Advisor: Stacey, Mark T.
Search for variation of the fine-structure constant and violation of Lorentz symmetry using atomic dysprosium

We report on the spectroscopy of radio-frequency transitions between nearly-degenerate, opposite-parity excited states in atomic dysprosium (Dy). Theoretical calculations predict that these states are very sensitive to variation of the fine-structure constant, $\alpha$, owing to large relativistic corrections of opposite sign for the opposite-parity levels. The near degeneracy reduces the relative precision necessary to place constraints on variation of $\alpha$ competitive with results obtained from the best atomic clocks in the world. Additionally, the existence of several abundant isotopes of Dy allows isotopic comparisons that suppress common-mode systematic errors. The frequencies of the 754-MHz transition in $^{164}$Dy and 235-MHz transition in $^{162}$Dy were measured over the span of two years. Linear variation of $\alpha$ is found to be $\dot{\alpha}/\alpha = (-5.8\pm6.9)\times10^{-17}$~yr$^{-1}$, consistent with zero. The same data are used to constrain the dimensionless parameter $k_\alpha$, characterizing a possible coupling of $\alpha$ to a changing gravitational potential. We find that $k_\alpha = (-5.5\pm5.2)\times10^{-7}$, essentially consistent with zero and the best constraint to date./nThe same data are used to report a joint test of local Lorentz invariance and the Einstein Equivalence Principle for electrons. We present many-body calculations which demonstrate that the energy splitting of these states is particularly sensitive to violations of both special and general relativity. Lorentz violation for electrons is limited at the level of $10^{-17}$, matching or improving the best laboratory and astrophysical limits by up to a factor of 10, and gravitational redshift anomalies for electrons to the level of $10^{-8}$. With some enhancements, our experiment may be sensitive to Lorentz violation at the level of $9\times 10^{-20}$./nWe also report measurements of the differential polarizability between the nearly degenerate, opposite parity states. The differential scalar and tensor polarizabilities due to additional states were measured for the $|M| = 7,\dots,10$ sublevels in $^{164}$Dy and $^{162}$Dy and determined to be $\overline{\balpha}_{\sss BA}^{(0)} = 180\,(45)_\text{stat}\,(8)_\text{sys}$ mHz cm$^2$/V$^2$ and $\overline{\balpha}_{\sss BA}^{(2)} = -163\,(65)_\text{stat}\,(5)_\text{sys}$ mHz cm$^2$/V$^2$, respectively. The average blackbody radiation induced Stark shift of the Zeeman spectrum was measured around 300 K and found to be $-34(4)$~mHz/K and $+29(4)$~mHz/K for the $^{164}$Dy and $^{162}$Dy isotopes, respectively. We conclude that ac-Stark related systematics will not limit the precision of a search for variation of the fine-structure constant, using dysprosium, down to the level of $|\dot{\alpha}/\alpha|=2.6\times10^{-17}$~yr$^{-1}$ for a one-year experiment.

Advisor: Budker, Dmitry