VictorJuiz/thesis huggingface dataset:
Synthesis, Characterization, and Stoichiometric and Catalytic Reactivity of Metalloproteins Binding Noble Metals in Place of Native Metals

Catalysis by enzymes and transition metal complexes enables the modern synthetic/nstrategies used to prepare bulk and fine chemicals. However, despite their exquisite selectivity and potential for evolution, metalloenzymes are rarely used in synthetic chemistry, in part due to the limited scope of reactions catalyzed by natural metalloenzymes. To expand the scope of substrates and the range of transformations with which metalloenzymes react, two distinct approaches have been followed. One approach designs promiscuous enzymes by directed evolution. An advantage of this method is that it exploits native, selective substrate binding sites. An alternative strategy creates artificial enzymes by affixing an abiological transition metal complex within a protein scaffold by cysteine bioconjugation or biotin-labeling. Although this method has been used successfully to impart abiological activity onto enzymes, a significant drawback is that the native binding pocket of the protein scaffold is occupied by the bulky metal complex that is introduced, excluding the substrate from its natural binding site./nAt the intersection of these two approaches lies a third strategy that is rarely followed: the/nsimple substitution of the native metal of a natural enzyme with an abiological metal. This strategy has the potential to create enzymes containing any metal of interest, while retaining the natural, evolvable substrate-binding site of the protein scaffold. We have sought new and superior approaches to the preparation, characterization, and application of diverse catalysts of this class, formed from both proteins that bind metals using organic cofactors and proteins that bind metals directly using amino acid side chains./nDespite challenges confronting their preparation, characterization, and application, our studies have revealed that diverse members of this class of artificial metalloenzymes can indeed be prepared efficiently and characterized as comprehensively as one would characterize natural enzymes and small molecule metal complexes. Moreover, the stoichiometric and catalytic reactivity of the noble metal sites within these proteins can be controlled by mutagenesis of the native substrate-binding site surrounding the abiological metal. With these studies as a foundation, we and others can now seek the creation of nearly limitless combinations of noble metals and protein scaffolds that can catalyze reactions with activities and selectivities not possible for either enzyme or transition metal catalysts alone.

Advisor: Hartwig, John F
Appeals to Authenticity: Discourses on the True Self and the Politics of Identity Construction

This dissertation examines how appealing to a “true self” may have social and political value, even if such a self does not exist. Across contemporary life, individuals invoke notions of an inner self that has been maimed by oppressive norms and practices, or that would be harmed if it assimilated, conformed, or otherwise departed from who it was. From transgender individuals seeking to become the gender they feel they truly are, to indigenous groups seeking exemptions from equality laws, a variety of groups today cast their political claims in terms of authenticity. However, in the past quarter century, such appeals have been criticized by scholars from across the humanities and social sciences, who fault authenticity for stipulating regulatory notions of group identity, stigmatizing those who fall outside its norms, and relying on untenable notions of selfhood and self-knowledge. Some have even called for abandoning the term./nThe dissertation responds to these critiques and argues for a renewed appreciation of authenticity in political life. Through an engagement with Jean-Jacques Rousseau, Michel Foucault, Judith Butler, and writings from American social movements from the sixties and today, I formulate a framework for appealing to the term that departs its problematic ontological grounds and is attuned to its political risks. Each chapter responds to a particular challenge facing such appeals, from the status of the “self” they imply, to their claims of genuine self-knowledge, to the risks of exclusion, and to the ways they can blur the public/private line. In addressing these critiques, I show that there are good reasons to continue to value authenticity: appeals to the term may enable marginalized groups to counter oppressive representations of themselves, mobilize individuals around visions of selfhood and community, facilitate critiques of social norms, and animate practices of resistance.

Advisor: Brown, Wendy
Population and Individual Stem Cell Dynamics in the Olfactory Epithelium

Unlike the majority of the nervous system, the olfactory epithelium (OE) continuously produces new neurons throughout adulthood. Under homeostatic conditions, OE neurogenesis is fueled by the ongoing divisions of globose basal cells (GBCs), but following severe injury that destroys all mature cell types, the normally quiescent horizontal basal cells (HBCs) regenerate the entire tissue, including GBCs, neurons, and sustentacular cells. Moreover, conditional knockout (cKO) of the transcription factor, p63, induces HBCs to differentiate at steady-state (Fletcher et al. 2011). However, the cellular and transcriptional dynamics underlying HBC self-renewal and differentiation remain poorly characterized. To maintain tissue homeostasis, an appropriate balance of stem cell self-renewal and differentiation is achieved via invariantly asymmetric divisions in invertebrates (Doe and Bowerman 2001), and a mixture of symmetric and asymmetric divisions during vertebrate development (Lechler and Fuchs 2005; Morrison et al. 1995). While regulators of these types of mitoses are conserved in adult tissues, adult stem cell divisions are often modulated by the surrounding tissue, a phenomenon known as population asymmetry (Simons and Clevers 2011). Lineage tracing of stem cells can provide insights into population asymmetry in adult tissues (Ritsma et al. 2015; Bonaguidi et al. 2011), and single-cell RNA sequencing has recently emerged as a powerful tool for probing the transcriptional changes that occur in cycling and regenerating tissues (Trapnell et al. 2014; Shin et al. 2015). This dissertation explores mechanisms of HBC self-renewal and differentiation at steady-state and during regeneration using lineage tracing and single-cell RNA-seq. The following was determined: (1) Symmetric HBC divisions are balanced by population asymmetry, independent of spindle orientation and cell polarity biases in dividing HBCs, producing activated HBCs; (2) At steady-state, p63cKO HBCs differentiate directly into sustentacular cells without dividing, and give rise to proliferative neural progenitors that generate numerous neurons; (3) During regeneration, all HBCs are recruited into an activated state and enter the cell cycle prior to renewing or differentiating; and (4) The sustentacular lineage develops prior to the neuronal lineage and via fewer changes in transcriptional state. These results provide novel insights into the dynamics that regulate HBC renewal and differentiation, as well as avenues for further exploration of OE stem cell subtypes, and provide a methodological model for investigating adult stem cells in other tissues.

Advisor: Ngai, John
Exploring carbon-carbon bond formation in nature for the production of biorenewable fuels and chemicals

Microorganisms have enormous potential as catalysts for the conversion of renewable organic material into useful chemicals, such as fuels and polymers. But engineering metabolic pathways in microorganisms requires a greater understanding of the enzymes available to catalyze each reaction of a sequential biosynthetic scheme. Fundamental to the construction of organic molecules is the formation of carbon-carbon bonds. This dissertation describes our work to identify and characterize enzymes from non-canonical carbon metabolism pathways in nature. In particular, we focus on two fermentation pathways found in eukaryotic facultative anaerobes: branched acid fermentation in the roundworm Ascaris suum and wax ester fermentation in the single-celled algae Euglena gracilis. These pathways are based on thiolase enzymes, which catalyze carbon-carbon bond formation through Claisen condensation. Our investigation has led to a greater understanding of the factors that determine substrate and product selectivity in thiolases and thiolase-based pathways and has provided insight into the physiology of E. gracilis. We further demonstrate the use of A. suum enzymes to engineer pathways in bacteria for the production of α-methyl organic acids. Our results help to expand the synthetic capabilities of engineered microorganisms.

Advisor: Chang, Michelle C. Y.
Electron Devices Based on Transition Metal Dichalcogenides

Integrated circuits consists of building blocks called transistors. A transistor is a switch that enables logic operations to perform computing. Since the invention of the first integrated circuit, transistors have been scaled down in their dimensions to increase the density of transistors per unit area to enable more functionality. Transistor scaling is continued by introducing novel device structures and materials at each technology node. Due to the challenges such as short channel effects and the power consumption issues, novel materials are investigated as a candidate for next generation transistors. In this thesis, 2-dimensinal layered semiconductors, namely transition metal dichalcogenides (TMDCs) are studied to assess their electronic material properties as a candidate channel material for next generation electronic devices./nChapter one, introduces the challenges in the state of the art MOSFET devices. Then the motivation for the use of TMDCs in MOSFETs is explained. In chapter two, doping of the TMDCs is studied to be able to probe the intrinsic electronic properties of the devices fabricated using these materials. Contact resistance can be decreased by doping and TMDC MOSFETs with near-ideal performance metrics are demonstrated. In chapter three the CMOS integration of the devices using TMDCs are examined. Logic operations are conducted by fabricating WSe2 n-FETs and p-FETs on the same flake. Then vertical 3-dimensional integration of n-FETs and p-FETs are demonstrated using the same gate. These transistors are connected as a CMOS inverter and logic operations are performed. Chapter four presents the band structure engineering study using TMDCs. Mono-multilayer MoS2 junctions are found to have a type-I heterojunction. Optoelectronic properties of this junction are investigated and the junction is shown to have a photoresponse that dominates the photoresponse coming from the contacts. In chapter five, the tunneling devices using TMDCs are studied. Dual-gated heterojunctions and homojunctions are studied. Gate-tunable diode characteristics of these structures are shown. Then p-TFETs are examined using black phosphorus homojunction devices.

Advisor: Javey, Ali
Social Inequality and the Body: Diet, activity, and health differences in a prehistoric Muisca population (Sabana de Bogotá, Colombia, AD 1000-1400)

This project uses multiple methods to explore how the biosocial variables of age, sex, and status intersect with social inequalities in a prehistoric Colombian population. The archaeological site of Tibanica in the Sabana de Bogotá, Colombia (AD 1000-1400) is an ideal place to examine the biocultural aspects of intersectionality, as it is a settlement of a complex chiefdom society. Inequality may be tied to age groups, differences between the sexes, or between those who are archaeologically recognized as higher/lower status based on mortuary practices. This project studies three loci where identities and inequality may be expressed and evidenced in the body: food consumption patterns, physical labor, and skeletal health. Human skeletons present the opportunity to study how these variables that are both biologically real and socially constituted, may relate to unequal power access within any society. 199 human skeletons were studied using stable isotope analysis (13C, 15N) of tooth and bone samples (n=199) to reconstruct individual dietary histories, cross-sectional geometry analysis of femur (n=63) and humerus (n=33) bones to study human activity patterns, and bone remodeling in the metacarpal to examine overall bone loss and health (n=75). Dietary and activity data indicate significant differences between women and men over the lifetime, suggesting that different spheres of identity and activities were delineated by sex and age. Stable isotope data show differential access to particular foods, with both sexes consuming significant amounts of maize, but females consumed less maize and more C3-type foods than males. Cross-sectional geometry data revealed that male work emphasized lower body strength, probably related to agricultural work, while female activities required a strong upper body, likely related to food preparation and childcare activities. Skeletal health data indicate that in older age both women and men lost cortical bone in the hand, but women were more severely affected earlier in life, possibly due to skeletal responses to pregnancy and/or lactation. While historical and archaeological research of the Muisca has focused on the importance of social rank within a hierarchical chiefdom society, this dissertation suggests that a very salient aspect of everyday experience for the Muisca may have begun with social difference of another kind: between the sexes. These results demonstrate the capacity for bioarchaeological studies to provide unique data that can reveal complex social relationships that may not be observed through other lines of evidence, challenging assumptions about ancient peoples, and directing us to new lines of inquiry.

Advisor: Agarwal, Sabrina C
Nuclear level density and gamma-ray strength function of 243Pu

The level density and $\gamma$-ray strength function of $^{243}$Pu have been determined using the Oslo method.\/nA 12~MeV deuteron beam from the University of Oslo cyclotron was used to populate excited states in the quasi-continuum of $^{243}$Pu using the $^{242}$Pu$(d,p)$ reaction. The distribution of primary $\gamma$-rays as function of the excitation energy has been extracted from particle-$\gamma$ coincidence data. Based on the Brink-Axel asumption that the primary $\gamma$-ray spectrum is proportional to the product of the $\gamma$-ray transmission coefficient (which only depends on the transition energy) times the level density at the excitation energy of the final state. The $\gamma$-ray strength function is calculated from the $\gamma$-ray transmission coefficient assuming pure dipole radiation. Both, the level density and $\gamma$-ray strength function, are normalized using available experimental data from libraries. \/nThe level density of $^{243}$Pu follows closely the constant-temperature level density formula. An enhancement of the $\gamma$-ray strength function is seen at low energies that is similar to that previously measured in other actinides. This structure is interpreted as the M1 scissors resonance. Its centroid $\omega=2.42(5)\:\mathrm{MeV}$ and its total strength $B=10.1(15)\:\mu_N^2$ are in excellent agreement with sum-rule estimates./nThe measured level density and $\gamma$-ray strength function were then used to calculate the $^{242}$Pu$(n,\gamma)$ cross section within the Hauser-Feshbach formalism.

Advisor: Vujic, Jasmina
Reducing Faulty Executions of Distributed Systems

When confronted with a buggy execution of a distributed system—which are commonplace/nfor distributed systems software—understanding what went wrong requires/nsignificant expertise, time, and luck. As the first step towards fixing the underlying bug,/nsoftware developers typically start debugging by manually separating out events that are/nresponsible for triggering the bug (signal) from those that are extraneous (noise)./nIn this thesis, we investigate whether it is possible to automate this separation process./nOur aim is to reduce time and effort spent on troubleshooting, and we do so by/neliminating events from buggy executions that are not causally related to the bug, ideally/nproducing a “minimal causal sequence” (MCS) of triggering events./nWe show that the general problem of execution minimization is intractable, but we/ndevelop, formalize, and empirically validate a set of heuristics—for both partially instrumented/ncode, and completely instrumented code—that prove effective at reducing execution/nsize to within a factor of 4.6X of minimal within a bounded time budget of 12 hours./nTo validate our heuristics, we relay our experiences applying our execution reduction/ntools to 7 different open source distributed systems.

Advisor: Shenker, Scott
Incongruent emotion experience in schizophrenia: The role of negative affect and response inhibition

We investigated the relationship between incongruent emotion experience (negative emotion reported in response to positive and neutral stimuli), state negative affect, and response inhibition (a facet of cognitive control) in people with and without schizophrenia. We also tested whether a positive mood induction (the Broad-Minded Affective Coping, or BMAC, procedure) would decrease state negative affect and subsequently decrease incongruent emotion experience in people with schizophrenia. People with schizophrenia or schizoaffective disorder (n=29) reported significantly more state and trait negative affect and more incongruent emotion experience in response to positive and neutral film clips compared to people without schizophrenia (n=26). The BMAC procedure increased positive affect but did not decrease negative affect in all participants nor did it influence reports of incongruent emotion experience in people with schizophrenia. State negative affect, but not response inhibition, predicted incongruent emotion experience in people with schizophrenia. These results indicate that incongruent emotion experience may reflect heightened state negative affect in people with schizophrenia that does not readily diminish in the face of positive experiences.

Advisor: Kring, Ann M.
Fast Algorithms for Exact Exchange

This thesis describes several new theoretical developments that facilitate/nthe computation of the exact exchange energy, a vital component of accurate/nmolecular simulations. The primary technique on which these/ndevelopments are based is the resolution of the identity approximation,/nparticularly the pair atomic resolution of the identity approximation (PARI)./nWe prove that computation of exact exchange using the PARI approximation/nis variationally stable, and provide benchmarks of the performance and accuracy/nof our implementation. We then show that the most commonly used SCF convergence acceleration algorithm, DIIS,/nenables the design of a new fast exchange algorithm that we designate as occ-RI-K./nNext, we combine the preceding occ-RI-K algorithm with the PARI approximation/nto create a linear-scaling/nexact exchange algorithm for the specific case of large weakly-interacting systems./nFinally, we discuss our development of a high-level, object-oriented software library for/nblock-sparse tensor operations. This library provides the underlying implementation/nfor all of the algorithms discussed in this thesis.

Advisor: Head-Gordon, Martin
Statistical Analysis and Modeling for Biomedical Applications

This dissertation discusses approaches to two different applied statistical challenges arising from the fields of genomics and biomedical research. The first takes advantage of the richness of whole genome sequencing data, which can uncover both regions of chromosomal aberration and highly specific information on point mutations. We propose a method to reconstruct parts of a tumor's history of chromosomal aberration using only data from a single time-point. We provide an application of the method, which was the first of its kind, to data from eight patients with squamous cell skin cancer, in which we were able to find that knockout of the tumor suppressor gene TP53 occur early in that cancer type./nWhile the first chapter highlights what's possible with a deep analysis of data from a single patient, the second chapter of this dissertation looks at the opposite situation, aggregating data from several patients to identify gene expression signals for disease phenotypes. In this chapter, we provide a method for hierarchical multilabel classification from several separate classifiers for each node in the hierarchy. The first calls produced by our method improve upon the state-of-the-art, resulting in better performance in the early part of the precision-recall curve. We apply the method to disease classifiers constructed from public microarray data, and whose relationships to each other are given in a known medical hierarchy.

Advisor: Huang, Haiyan
If you are not counted, you don't count: Estimating the size of hidden populations

Background: Despite advances in treatment and prevention services, HIV infection remains a leading cause of morbidity and mortality worldwide, identified by the 2010 Global Burden of Disease report as the fifth leading cause of global disability adjusted live years. While the epidemiologic features of HIV infection vary globally, marginalized populations, such as men who have sex with men (MSM), female sex workers (FSW), and injection drug users (IDUs) are consistently at increased risk for HIV infection relative to the general population. Targeting such marginalized, or hidden, populations has become a global priority to maximize the effectiveness of the public health response to the HIV pandemic. Members of these populations are often difficult to find, and the size of these populations is largely unknown, making it difficult to calculate epidemiologic measures of disease and to evaluate the reach and coverage of public health programs./nMethods: Through three separate analyses, this dissertation will investigate the reliability and the plausibility of population size estimation methods when applied to hidden populations. Chapter 1 systematically reviews the literature on population size estimation methods and assesses the degree to which different methods, applied to the same population, calculate similar estimates of the target population. Chapter 2 evaluates a novel size estimation method, the SS-PSE, by applying it to a Respondent-Driven Sampling study of African-American MSM in San Francisco, and comparing results to other methods. Chapter 3 applies capture-recapture models to evaluate the completeness of the Alameda County HIV surveillance system, and examines the role of sampling bias in this application./nDiscussion and Significance: The results of the analyses featured in this dissertation demonstrate that variability in population size estimates from different size estimation methods is common, though often unaddressed. Population size estimation is fundamental to public health surveillance, serving as the basis for policy decisions and quantifying the magnitude of disease. To produce reliable population size estimates, which have implications for the allocation of limited public health resources to marginalized populations, investigators should consistently apply multiple size estimation methods and carefully consider the influence of sampling bias.

Advisor: Reingold, Arthur
McFarland, William