VictorJuiz/thesis huggingface dataset:
Molecular imaging and proteomics approaches towards elucidating oxidative neuronal signaling pathways

Hydrogen peroxide (H2O2) has long been considered a toxic byproduct of cellular metabolism and a causative agent of disease, particularly of neurodegenerative diseases such as Alzheimer's and Parkinson's. While high concentrations of this reactive molecule are undoubtedly deleterious, a more nuanced view of its biological activity has developed over the last two decades as evidence of a beneficial signaling role and deliberate H2O2 production by mammalian tissues has emerged. Indeed, there is even evidence that H2O2 plays a signaling role in the brain despite its potential to wreak havoc in this sensitive organ. This dissertation addresses this surprising result and demonstrates well-regulated physiological production and transport of H2O2 by brain neurons and its reactivity with potential cellular signaling targets. Specifically, fluorescent probes for H2O2 are used in live cultured neurons to demonstrate that this molecule is produced by the membrane-bound NADPH oxidase 2 (Nox2) enzyme in cortical neurons in response to activation of N-methyl-D-apartic acid receptors (NMDARs). Furthermore, intercellular transmission of H2O2 is demonstrated in a Nox2 knockout-rescue system. A signaling role for this endogenous H2O2 is proposed, inasmuch as the Nox2-sensitive oxidation of protein cysteinyl residues contingent on NMDAR stimulation is detected, and the affected proteins are identified. Finally, the H2O2-mediated modulation of neuronal actin dynamics is demonstrated to be Nox2-dependent as well, suggesting a role for redox signaling in neuronal plasticity.

Advisor: Chang, Christopher J
Localization of E. coli Chemoreceptor Arrays

The bacterial chemotaxis system, a ubiquitous signaling network found in most bacteria, is comprised at its core of a large chemoreceptor cluster found specifically at the cell pole. Despite a wealth of structural and biochemical information on the system's components, it is not clear how the chemoreceptor cluster is reliably targeted to the pole. By bending growing E. coli in agar micro-chambers, we have found that chemoreceptor cluster localization is highly sensitive to membrane curvature within non-polar regions of the cell. Furthermore, the strength of the curvature sensitivity we measured is sufficient to explain reliable polar cluster targeting. We propose that entropic spreading between the transmembrane domains of chemoreceptor trimers of dimers leads to the conical complex observed in structural studies, whose shape in turn induces energetically unfavorable deformations in the membrane. We used the entropic spreading model to engineer curvature sensitivity into a series of synthetic protein complexes that we designed out of long, alpha-helical transmembrane proteins that bind to multivalent protein scaffolds. By altering the connectivity of a complex, we were able to control whether complexes were found preferentially in regions of positive or negative membrane curvature. Entropic spreading presents a novel, and potentially widespread mechanism for membrane curvature sensing and generation.

Advisor: Liphardt, Jan
Constituting a Self through an Indian Other. A Study of Select Works by Stefan Zweig and Hermann Hesse

This study explains how “India” can sometimes be used in German-language literature in non-Orientalist terms. As I closely analyze Stefan Zweig's Die Augen des ewigen Bruders: Eine Legende, his essay “Die indische Gefahr für England,” and Hermann Hesse's Siddhartha all within a postcolonial theoretical framework, I argue that these texts that either take place in India or contend with Indian themes are less about India than about coming to terms with self-identity. With Zweig's work, I demonstrate how India is used as a means toward self-reflection and self-critique. Accordingly, I turn to Zweig's fraught relationship to the Austro-Hungarian Empire as well as interest in internationalism to verify, through historical and biographical analysis, how these texts that are ostensibly about an Other are inexorably a means of constituting a Self. Since with Zweig's texts I establish that “Indienliteratur” can be read in postcolonial terms, I move in a different direction with my reading of Hesse's “German-Indian” story by not taking recourse to locating its cultural identity. I borrow analytical developments I make previously on the relationship between individual and community/national identity in order to engage with identity on a philosophical scale. I examine how Siddhartha, a text that condemns every kind of teaching, paradoxically helped teach individualistic identity formation in the era of U.S. Counterculture.

Advisor: Kudszus, Winfried
William Hazlitt and the Uses of Knowledge

Abstract/nWilliam Hazlitt and the Uses of Knowledge/nby/nPatricia Anne Pelfrey/nDoctor of Philosophy in English/nUniversity of California, Berkeley/nProfessor Steven Goldsmith, Chair/nWhile Romantic literature provides ample evidence of the pleasures of knowledge, it also reveals strong counter-examples of knowledge as overwhelming, enervating, and potentially impoverishing. What inspired this reaction, and how was it channeled through Romantic writings?/nWilliam Hazlitt is a particularly representative figure in the search for an answer to the question of why knowledge became a problem for Romantic writers because of his highly articulate awareness of the distinction between knowledge as an engine of social progress and its potentially negative role in the development of individuals. Using a range of Hazlitt's essays--from his early metaphysical treatise on identity to The Spirit of the Age--as well as the writings of Thomas Love Peacock, Percy Bysshe Shelley, and Thomas De Quincey, this dissertation analyzes the conflicted Romantic response to knowledge and its result, a variety of efforts to define the norms and values that should govern its organization, diffusion, and control. It makes two principal arguments./nThe first is that Romantic ambivalence derived from a complex of ideas and anxieties about the potentially damaging effects of certain kinds of education and learning on the brain, damage that could diminish cognitive vigor and distort the inner experience of identity. The collision between this image of the individual disempowered by knowledge and Enlightenment faith in its role as the engine of collective progress was intensified by the sheer quantity of ideas, information, opinions, theories, and discoveries that daily inundated the British reading public and critics alike. Discussions about education and learning became entangled in assumptions about the nature of the self and attitudes toward social and intellectual progress, all in the context of the need to bring order into a universe of knowledge that seemed to be expanding at a breakneck pace./nThe dissertation's second argument is that Romantic ambivalence is valuable in giving us a perspective from a time when acceptance of the uncontrollable character of knowledge was not yet complete. The Romantic idea that there could be something inevitable, perhaps disturbingly inevitable, about the growth of knowledge has fallen out of consciousness in most discussions of knowledge today. Its unceasing proliferation is widely celebrated, perhaps especially the evolving media and communication advances that have made learning a global enterprise. Useful knowledge has become the paradigm of all knowledge, rendering it immune from questions about what could or should be done about its less than beneficial outcomes. The contrast between Samuel Taylor Coleridge's On the Constitution of Church and State (1829) and Clark Kerr's The Uses of the University (1963), discussed in the final chapter, sheds light on the distance between Romantic attitudes and our own.

Advisor: Goldsmith, Steven
Neighborhood Safety and Diabetic Health: Examining the Associations between Neighborhood Safety and Cardiometabolic Risk Factors

Incidence and prevalence of chronic diseases such as diabetes are increasing in the U.S. Effective diabetes management is essential to ensure healthy outcomes and avoid severe diabetes sequelae including blindness, myocardial infarction, and early mortality. Research and interventions on diabetes management have primarily targeted changes in individual level risk factors related to physical activity, diet, and medication adherence. Features of neighborhoods, such as neighborhood safety may also be risk factors for poor diabetic management. Research has associated neighborhoods with diabetes incidence and prevalence but few studies focus diabetic populations. To this end, the overall goal of these analyses is to examine how neighborhood safety is associated with diabetic health./nMethods: Chapter 1 provides an introduction and overview to the diabetes and neighborhood safety literature. Three analyses investigating research aims related to neighborhood safety and diabetic management and health will be conducted over three chapters, as follows: Chapter 2: Perceived Neighborhood Safety and Crime in Relation to Cardiometabolic Risk Factors among type II diabetics, Chapter 3: Examining associations between police recorded crime and stress among type II diabetics, and Chapter 4: Examining associations between police recorded crime and obesity among type II diabetics. Chapter 5 provides a summary of findings, implications, and recommendations./nThis study will use data from the Diabetes Study of Northern California (DISTANCE), one of the largest, racially and ethnically diverse U.S. cohorts of diabetics followed in a managed care health system. This cohort was established to study social determinants of diabetes and is ideally suited to explore how neighborhood safety, using measures of perceived and objective crime, influence stress and cardiometabolic risk factors such as glycemic control and body mass index./nDiscussion and Significance: Diabetics are at risk for a multitude of diabetic complications and early mortality. Understanding how neighborhood level risk factors affect diabetic health may help alleviate diabetes sequelae. Contextual risk factors such as neighborhood crime and safety may be amenable to policy changes and may lead to additional effective interventions for diabetics.

Advisor: Mujahid, Mahasin
The Home, the Map and the Garden: Literary Space as Monumental Space in Kofman, Perec and Rodoreda

This dissertation explores how three authors, Sarah Kofman, Georges Perec and Mercè Rodoreda, create textual monuments to divisive historical events. I look most closely at Kofman's Rue Ordener, rue Labat, Perec's W ou le souvenir d'enfance and Rodoreda's El carrer de les Camèlies. We can think of these texts as textual monuments because they emphasize the spatial aspect of their narratives and because they are concerned with memory./nThe first chapter of the dissertation considers how, in Rue Ordener rue Labat, Sarah Kofman is able to write a memoir that recognizes the specificity of her experience while at the same time letting the reader into the story. I employ Emmanuel Levinas' concept of the intersubjective space of the home to understand how Kofman, at both the level of content and structure, allows the reader to co-create the textual space./nIn the second chapter I turn to Georges Perec's W ou le souvenir d'enfance. Perec, unable to recall his childhood memories, instead creates a memoir structured by the "fragile intersection" of several texts. The textual monument he creates is not monolithic, but rather takes its form from the multiple paths between nodes of meaning./nThe third chapter considers Mercè Rodoreda's novella, El carrer de les Camèlies. Rodoreda uses the motifs of the garden and the cemetery to advocate for a textual monument that valorizes what Gilles Deleuze and Félix Guattari would call "rhizomatic" connections between people and symbols, rather than a monument that concentrates on roots and the past./nThe Conclusion considers the important common features of the three texts, namely the idea that memory is constructed by a person in the present and that this construction, while it can be experienced as tragic for the person remembering, can also be liberating. Future work in this area would seek to establish a relationship between poststructuralist theory, narratology and the emphasis on space common to both textual and physical monuments in the twentieth century.

Advisor: Alter, Robert
Improving RR Lyrae Distance Indicators Through Instrumentation, Observation, and Calibration

Due to technological limitations and peculiarities of Nature, classes of astronomical distance indicators are applicable only in specific distance ranges. The Cosmic Distance Ladder is the framework by which we link together distance indicators, climbing from one rung to the next, in order to measure physical distance on an absolute scale. The object of this dissertation is one category of distance indicators, called RR Lyrae pulsating variable stars, which has commanded substantial scientific study for more than a century./nRR Lyrae stars are low mass (M ~ 0.7 Msol), old (age > 1010 yr) Population II objects that are found mixed in with any stellar population of requisite age. They are unstable to radial harmonic oscillations (pulsations) because of their specific mass, metallicity content, and interior composition. It has been empirically determined, and theoretically justified, that the pulsation periods of individual RR Lyrae stars are correlated with their intrinsic luminosity; hereafter referred to as the RR Lyrae period--luminosity relation. Thus, if one can measure the period of a star (a relatively straightforward task given sufficient observations), then one can use that star as a standard candle and infer its distance./nThe work in this dissertation is aimed at improving our understanding of the period--luminosity relation of RR Lyrae stars, and particularly at improving the precision of RR Lyrae distance measurements. By leveraging (and advancing) new observational facilities, gathering an abundance of new classical observations, and developing new statistical methods to combine a wealth of multi-wavelength data, this goal has been accomplished. In this dissertation I describe the involved methodology and report distances to a calibration sample of 134 RR Lyrae stars with a median fractional distance error of 0.66 per cent./nIn the following chapters I describe the arc of this research. First, I present an instrumentation development project that contributed to a new simultaneous multi-band imaging camera which is well-suited to study RR Lyrae stars and accumulate the invaluable near-infrared photometry necessary for highly-precise distance measurements. Then, I present a series of RR Lyrae period--luminosity relation studies that iteratively combine more and more data (increasing both in calibration sample size and number of wavebands) while simultaneously developing the necessary statistical models and computational methods. Finally, as an application of the results of these earlier investigations, I combine catalog data with new, longer-wavelength observations of the Large Magellanic Cloud (LMC) to measure the three-dimensional shape of the distribution of RR Lyrae stars in the LMC and derive a new distance measurement to the LMC of 50.2482 ± 0.0546 (statistical) ± 0.4628 (systematic) kpc, which is a fractional distance error of 1.03 per cent.

Advisor: Bloom, Joshua S
Labs of Democracy: Using Regional Variation to Understand Fiscal Policy Issues

This dissertation uses a regional approach to assess the aggregate effects of cutting taxes on corporations and on taxpayers in different income groups. Determining the optimal course for economic policy critically depends on the efficiency and equity consequences of these policies./nThe first chapter of this dissertation estimates the incidence of state corporate taxes on workers, landowners, and firm owners in a spatial equilibrium model in which corporate taxes affect the location choices of both firms and workers. Heterogeneous, location-specific productivities and preferences determine the mobility of firms and workers, respectively. Owners of monopolistically competitive firms receive economic profits and may bear the incidence of corporate taxes as heterogeneous productivity can make them inframarginal in their location choices. We derive a simple expression for equilibrium incidence as a function of a few estimable parameters. Using variation in state corporate tax rates and apportionment rules, we estimate the reduced-form effects of tax changes on firm and worker location decisions, wages, and rental costs. We then use minimum distance methods to recover the parameters that determine equilibrium incidence as a function of these reduced-form effects. In contrast to previous assumptions of infinitely mobile firms and perfectly immobile workers, we find that firms are only approximately twice as mobile as workers over a ten-year period. This fact, along with equilibrium impacts on the housing market, implies that firm owners bear roughly 40% of the incidence, while workers and land owners bear 35% and 25%, respectively. Finally, we derive revenue-maximizing state corporate tax rates and discuss interactions with other local taxes and apportionment formulae./nThe second chapter investigates how tax changes for different income groups affect macroeconomic activity. Using historical tax returns from NBER's TAXSIM, I construct a measure of who received (or paid for) Romer and Romer exogenous tax changes. I aggregate these tax changes by income group and state. Variation in the income distribution across U.S. states and federal tax changes generate variation in regional tax shocks that I exploit to test for heterogeneous effects. I find that the negative relationship between tax changes and growth is largely driven by tax changes for lower-income groups and that the effect of tax cuts for the top 10% on employment growth is small.

Advisor: Auerbach, Alan J
Photonic Integrated Circuits Using III-V Nanopillars Grown on Silicon

Advancement in transistor scaling and integration technology has given electronics tremendous amount of computational power. Yet, extending integration to include photonics can augment computation with the ability to create and manipulate light. Such tight electronic-photonic integration can create exciting new opportunities, such as high speed, low energy on-chip optical interconnects, advanced optical sensors, and other unforeseen applications./nElectronic-photonic integration using traditional integration methods happens to be a difficult task, however. Photonic components, such as lasers and light emitting diodes, are typically made with III-V semiconductors since silicon, the material that electronics are built on, lacks light generation ability due to its indirect band gap. Simply combining III-V materials with silicon using conventional thin film growth technique often results in nonfunctional or subpar devices because the lattice spacing mismatch between III-V and silicon creates performance degrading defects. This problem, nevertheless, can be mitigated with nanostructure growth. Thanks to the nanoscale footprint, strain from lattice mismatch can fully relax, allowing monolithic integration of high quality III-V materials onto silicon as building blocks for high performance optoelectronic devices./nIn this dissertation, a variety of optoelectronic devices integrated onto silicon using InGaAs and InP nanopillars will be presented. High speed nano light emitting diode (nano-LED) capable of generating stimulated emission is demonstrated. Observing stimulated emission from such a nano-LED marks a great milestone towards realizing electrically driven laser on silicon. And when the nano-LED is under reverse bias, the device acts as a highly efficient avalanche photodiode yielding 100x gain at as little as 1 V reverse bias. Under solar illumination, the device shows angle insensitive response and high photovoltaic efficiency of 19.6%, the highest ever reported for an InP nanostructure solar cell grown on low cost silicon substrate. Furthermore, a more sophisticated, highly sensitive bipolar junction phototransistor is made on silicon as an integrated detector to enable low energy photonic interface to logic circuit. And to validate nanopillar as viable means to building photonic integrated circuit, a proof of concept photonic data link is built and demonstrated on silicon. With nanopillar optoelectronics, tight electronic-photonic integration is becoming a reality, opening the door to a new generation of convergent electronic devices with far-reaching photonic capabilities.

Advisor: Chang-Hasnain, Connie J
Dynamic Bayesian learning and optimization in portfolio choice models

We develop two dynamic Bayesian portfolio allocation models that address questions of learning and model uncertainty by taking model-specific shortcomings into account./nIn our first model, we formulate a multi-period portfolio choice problem in which the investor is uncertain about parameters of the model, can learn these parameters over time from observing asset returns, but is also concerned about robustness. To address these concerns, we introduce an objective function which can be regarded as a Bayesian version of relative regret. The optimal portfolio is characterized and shown to involve a ``tilted'' posterior, where the tilting is defined in terms of a family of stochastic benchmarks. We have found this model to perform at least as well as a benchmark given the true market parameters, while outperforming it when the market assets have the same trend./nOur next model extends the Black-Litterman portfolio choice model by taking several potential errors into account. We extend Black-Litterman to multiple periods, which allows for us to take into account the pairs of expert forecasts and the realized return. By doing so, we can then perform inference on these experts and discover whether they may have any bias for or against any specific assets. We can also perform similar inference on the market equilibrium distribution, which is typically represented by the capital asset pricing model (CAPM). The result is a model that is analytically intractable but may be solved numerically via Gibbs sampling. Controlled tests show our model performs favorably when Black-Litterman's model assumptions about the market equilibrium and expert views are violated. Backtests shed light on the model's ability to account for CAPM's shortcomings.

Advisor: Lim, Andrew E.B.