VictorJuiz/thesis huggingface dataset:
The structure & [and] limits of finitism [electronic resource]

In the years since Hilbert announced his now famous proof theory and the years following Gödel's Incompleteness Theorems much important work has been done in the subject that has cemented its fate as one of the pillars of metamathematics. To be sure, many of the directions that proof theory has taken since the 1920s can be found as germs in Hilbert and the Hilbert School's writings from the period - Kreisel's unwinding program a classic example of the metamathematical analysis of a proof to extract its mathematical content, Kohlenbach's program to extract the computational content of a proof using proof-theoretic techniques, Feferman's conservativity results, a spectacular example that shows the proof-theoretic relationships between formal theories, and so many more. But the one direction that precipitated the whole of proof theory - namely, to provide an epistemic foundation for a mathematical theory by providing it with a consistency proof from the point of view of a theory strictly weaker than it, a finitistic theory in the Hilbert School's language - has remained mostly unearthed. Our first chapter studies Hilbert's early years and shows that there are more resources for the pursuit of Hilbert's Program than the tradition typically recognizes. We then turn to the structure and limits of finitist reasoning, where it is argued that by progressing through the recursive functions systematically, finitists are able to reason about higher recursions and that such reasoning provides a platform that might make the execution of Hilbert's Program's consistency proof possible, albeit for weaker formal systems than originally envisaged. In the final chapter we study some possibilities with respect to the consistency problem for finitists and show that there are some ways in which the question is left open. Hence, the goal of our dissertation is to excavate the old stones and to provide some insight into the question of limits for finitists and their associated consistency problem.

Keywords: Philosophy.
Advisor: Lawlor Krista primary advisor. Thesis advisor
Ryckman Thomas primary advisor. Thesis advisor
Burgess Alexis
Sieg Wilfried
Structure and function of the M2 and M3 muscarinic acetylcholine receptors [electronic resource]

G protein-coupled receptors (GPCRs) constitute the largest single family of transmembrane receptors in humans, and play important roles in the regulation of normal human physiology and the pathogenesis of disease. The muscarinic acetylcholine receptors are a subfamily of GPCRs, and mediate the parasympathetic effects of acetylcholine, in addition to playing critical roles in cognition, memory, and maintenance of metabolic homeostasis. The muscarinic receptors have long served as an important model system for understanding GPCR function in general. Moreover, muscarinic receptors are important targets in the treatment of disease, and are also responsible for many of the side effects of commonly used therapeutic drugs targeting other receptors. To better understand these important receptors, I employed X-ray crystallography to determine the structures of the M2 and M3 muscarinic receptors in inactive, antagonist-bound conformations. Next, I used these structures for computational ligand screening, leading to the identification of over a dozen new muscarinic ligands. Finally, I determined the structure of the M2 muscarinic receptor in an active conformation stabilized by an antibody fragment. Similarly, a second structure of the M2 receptor bound to a positive allosteric modulator was resolved, offering structural insights into the allosteric modulation of GPCRs by drug-like molecules. Taken together, this work provides a framework for the interpretation of the extensive and growing body of biological and pharmacological data regarding muscarinic receptor function, and lays a foundation for future studies of muscarinic receptor biology.

Keywords: Structural Biology.
Advisor: Kobilka Brian K. primary advisor. Thesis advisor
Brünger Axel T. advisor. Thesis advisor
Garcia K. Christopher advisor. Thesis advisor
Structure design of silicon anodes for high energy lithium batteries [electronic resource]

More than two centuries old, battery technology has never attracted so much attention as it is today from all over academia, industry, government, and general public. Its extended application in our daily life, from portable electronic devices, electric vehicles, to power grid storage is driving the urgent need for major breakthroughs, in energy density, cycle life, and cost. One of the materials of choice is silicon. Silicon anodes have an order of magnitude higher capacity than state-of-the-art graphite anodes, providing great promise for use not only in Li-ion, but also in next generation high energy Li-S and Li-O2 batteries. However, Si anodes of conventional structure have very short cycle life, because the volume change of Si upon cycling leads to fracture and unstable interfaces. In this dissertation, I employed nanoscale materials design to overcome these problems, by rationally making accurate void space available inside the structure, and limiting the surfaces that are exposed to the electrolyte. The first-generation "yolk-shell" anode prevents fracture, stabilizes the interface, and significantly extends cycle life at small mass loading. Then I designed a second-generation "pomegranate" anode that has reduced interface side-reaction, increased energy density, and enhanced electrode-level conductivity. This design performs excellently even at mass loading as high as commercial batteries. Moreover, its fabrication is highly scalable. Next, I developed a method that produces the key source material for the above designs, Si nanoparticles, from rice husks, an agricultural byproduct with extremely high annual yield, and low cost. Finally, a prelithiation method has been developed for silicon anodes so that it could be paired with high-energy sulfur cathodes to make a full battery. Such a combination can give almost 400% the energy of state-of-the-art Li-ion batteries, enabling the next generation of battery technology.

Keywords: Chemistry.
Advisor: Cui Yi
Dai Hongjie
Moerner W. E. (William Esco)
Structure/function correlations of binuclear non-heme iron enzymes and their de novo models [electronic resource]

Binuclear non-heme iron enzymes are pervasive in nature and catalyze a variety of biologically important reactions, including reactions relevant to the biosynthesis of DNA, fatty acid metabolism, the protection of pathogens from oxidative stress, cell signaling, iron storage, and many others. Elucidating the structures of their diiron active sites and the contributions of these structures to reactivity can provide molecular level insight into catalysis. The near IR circular dichroism (CD), magnetic circular dichroism (MCD), and variable temperature variable field (VTVH) MCD spectroscopies form a powerful methodology that allows for detailed structural understanding of the diiron active sites in these enzymes. Presented are studies that focus on myo-inositol oxygenase, an enzyme with significance to human health, and de novo designed diiron proteins that model native enzymes.

Keywords: Chemistry.
Advisor: Solomon Edward I. primary advisor. Thesis advisor
Cegelski Lynette advisor. Thesis advisor
Pande Vijay advisor. Thesis advisor
Structuring climate policy in the Korean electricity sector [electronic resource] : politics, institutions and mitigative capacity building

Designing a climate policy for the Korean electricity sector is significant as well as imperative, because it is a major industry responsible for around a two-fifth of the greenhouse-gas emissions in Korea, the 8th largest nation in that respect. Now that Korea has announced a voluntary emission reduction target to limit the greenhouse-gas emissions 30 percent below its business-as-usual emission by 2020, structuring a web of climate policy tools for the electricity sector even takes on a sense of urgency to help Korea achieve such a target. Considering that the Korean government intends to achieve climate objectives with the national cap-and-trade scheme starting in 2015, I argued that such an effort will not be effective because of the opposition from the businesses and the industries. As an alternative approach I suggested what I termed "mitigative capacity building, " in the sense that it turns attention to an often neglected aspect of certain policy measures that are not totally related to climate policy per se but, when combined together, have broad implications for climate perspectives. I then assessed each policy option under the following four criteria: economic viability, technological feasibility/up-scalability, political acceptance and greenhouse-gas emission reduction potential. In the end I drew out a roadmap for the policy suggestion package, distinguishing what will be achievable in the short term from what will be possible in the medium to long term. Short-term options include: A gradual fuel switch from coal to natural gas; the renewable portfolio standards (RPS) with some changes in operation; the expansion of nuclear power; a phase-in of increases in the retail electricity price; and a focus on demand side management (DSM). Two other policy options labeled as a mid- to long-term policy tools are the smart grid and carbon capture and storage (CCS) because of the uncertainty of technological feasibility/up-scalability and the lack of economic viability at least in the foreseeable future.

Keywords: Law JSD.
Advisor: Thompson Barton H.
Hensler Deborah R.
Wara Michael
Study of a Novel Gene Mutation in Bartter-Gitelman's Syndrome

Bartter’s and Gitelman’s syndromes are a family of inherited autosomal recessive disorders in which genetic mutations inhibit diuretic-sensitive sodium transporters and result in hypotension, hypokalemia, and metabolic alkalosis. We identified a patient who exhibits a mixed phenotype between Bartter’s and Gitelman’s syndrome and has progressive chronic kidney disease. We employed a candidate gene approach to identify mutations in the CLCNKB gene, a gene often considered in patients with a mixed phenotype of this nature, in an index patient of Filipino descent. We then sought to link the mutation to disruption of ClC-Kb protein function by characterizing the mutant phenotype using in vitro studies. We identified a novel gene mutation (nt G499T, aa G167C) at a conserved site within the ion permeation pathway of the channel which, based on structural-function studies in the lower order Chloride channel family member, CLC-0, switches the ion selectivity of the channel from chloride to sodium. We assessed for and found significant differences in levels of gene expression and cell surface protein expression between the wild type and mutant G167C in cultured cells. Furthermore, we found that the mutant G167C was localized on the basolateral membrane of cells in the thick ascending limb and distal convoluted tubules from biopsies of affected family members. Based on these studies, we have described a novel mutation in the pore of ClC-Kb, and suggest that the G167C mutation contributes to the atypical presentation of Bartter-Gitelman’s syndrome, possibly leading to progressive chronic kidney disease.

Keywords:  Department of Biology
Bartter-Gitelman’s Syndrome
CLCNKB
ClC-Kb
mutation
Biology
Stanford
Thesis
Advisor: Bhalla Vivek
Nelson W. James
Study of Genes Contributing to the Evolution of Pathogenicity in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae, commonly used in preparation of food and beverage by humans, has been historically been considered to be a harmless fungus. Increasing reports in recent years, however, have cited S. cerevisiae as the cause of infection in both immunocompromised and healthy human patients. Accordingly, a major outstanding question is, what are the genetic adaptations that have resulted in increased virulence? In this project, we examined several candidate genes that may be guiding this pathogenesis by comparing allele-specific fitness levels of a clinical, pathogenic strain of S. cerevisiae to a nonclinical lab strain in vitro. The clinical strain alleles for SRX1, ATG33, and FLO11 exhibited a significant increase in growth at both 30 ̊ C and 37 ̊ C. In addition, the clinical strain alleles for CYT2 and LHS1 exhibited significantly increased fitness at 37 ̊ C relative to 30 ̊ C. These results provide evidence that these genes may be associated with increased pathogenicity, however, we plan to study these strains in vivo for further comparison.

Keywords:  Department of Biology
Biology
Yeast
Genetics
Evolution
Gene Expression
Pathogenicity
Pathogenesis
Thesis
Advisor: Fraser Hunter
Stevens David
Sunlight inactivation of enteric bacteria in coastal waters [electronic resource] : cellular and community-level responses

Fecal indicator bacteria (FIB), E. coli and Enterococcus spp., are used to indicate fecal pollution and thus the presence of pathogens in recreational waters. FIB concentrations are used to assess the risk of illness associated with water contact. When the concentration of FIB exceeds set criteria, advisories are posted or beaches are closed. The effectiveness of using FIB concentrations to predict health risks, however, has been called into question by diel fluctuations in FIB concentrations. FIB concentrations in recreational waters decrease during sunlight hours and increase after sunset. While many studies have documented these fluctuations, knowledge gaps remain about sunlight inactivation mechanisms and the effect of sunlight on the entire microbial community in contaminated waters. Understanding how sunlight affects enteric bacteria in coastal waters is critical for predicting the health risks associated with water contact. This dissertation investigates the effect of sunlight on enteric bacteria in coastal waters at both the cellular and community levels.

Keywords: Civil and Environmental Engineering.
Advisor: Boehm Alexandria primary advisor. Thesis advisor
Mitch William A. advisor. Thesis advisor
Nelson Kara L. advisor. Thesis advisor
Suppressing antiviral resistance via 'dominant drug targets' [electronic resource]

The emergence of drug resistance can compromise or eliminate the success of pharmaceutical treatments, especially when the genes that encode these drug targets display high mutation rates. One method for suppressing resistance, multi-drug therapy, is not currently applicable to diseases for which the need for treatment is immediate yet only one drug, or more often none, is available. This thesis documents the efficacy of a new paradigm in which a single compound directed against a 'dominant drug target" of an RNA virus suppresses the emergence of drug resistance in cultured cells and in mice. This approach is based on the principle that viral mutations that confer increased fitness, such as drug resistance, arise during intracellular replication. Thus, new drug-resistant viral genomes cannot express their phenotypes in the absence of drug-susceptible genomes until they complete a single infectious cycle. For the targets of most anti-viral compounds drug-resistant genomes can nevertheless be readily selected. However, for V-073, a compound that targets the highly oligomeric poliovirus capsid, no outgrowth of drug-resistant viruses was observed in cultured cells or in mice presumably due to the formation of chimeric structures that contain both drug-susceptible and drug-resistant subunits. The general principle that pharmaceutical targeting of oligomeric structures can suppress drug resistance is applicable to any situation in which drug-resistant genomes are first expressed in the presence of drug-susceptible genomes and their products. Examples include tumor variants that arise by error-prone gene amplification, DNA and RNA viruses, and any pathogens that secrete products into a common milieu. Reduction of the numbers of compounds needed for treatment will be of significant benefit medically and economically, but will require revision of decision-making processes during drug development.

Keywords: Genetics.
Advisor: Kirkegaard Karla primary advisor. Thesis advisor
Fire Andrew Zachary advisor. Thesis advisor
Sherlock Gavin advisor. Thesis advisor
Stearns Tim advisor. Thesis advisor
Surface adsorption and resonance ionization spectroscopy for barium identification in neutrinoless double beta decay experiments [electronic resource]

Neutrinos are the only elementary particle that could have particle-antiparticle duality, called Majorana nature. If neutrinos do indeed have this property, it could be measured through neutrinoless double-beta decay, a hypothetical nuclear decay. The half-life of this decay is very long, thus the reduction of backgrounds is very important. In searches for neutrinoless double-beta decay in Xe-136, backgrounds in the signal region of interest can be eliminated by recovering the expected daughter nucleus of this decay, Ba-136. This work describes the development of a technique to recover these barium ions from liquid xenon using surface adsorption and identify them using Resonance Ionization Spectroscopy (RIS). Barium ions adsorb onto a surface in the liquid xenon, which we remove to a separate vacuum chamber for identification. Laser induced thermal desorption removes atoms from the surface into vacuum, then the barium is re-ionized using RIS and drifted down a time of flight mass spectrometer. RIS has been shown to be both efficient and selective, both favorable aspects for a barium tagging system. The prototype system described here offers both optical spectroscopic and mass spectroscopic confirmation of the barium daughter. Barium tagging is being developed for use in nEXO, a future neutrinoless double-beta decay experiment, and will allow the detector to probe into the normal hierarchy of neutrino masses.

Keywords: Physics.
Advisor: Gratta Giorgio primary advisor. Thesis advisor
Burchat P. (Patricia) advisor. Thesis advisor
Graham Peter (Peter Wickelgren) advisor. Thesis advisor
Survival and sustainability in small-scale Mexican fisheries [electronic resource] : a cross-scale examination of resilience in marine social-ecological systems

Small-scale fisheries are critical for securing livelihoods for millions of people around the world, yet are increasingly vulnerable to external drivers of change such as globalization and climate change. There is an imminent need to redirect management goals towards facilitating resilient small-scale fisheries capable of adapting in a constantly changing world. The purpose of this dissertation is to investigate how to faciliate resilient small-scale fisheries from both a social and ecological perspective at various scales. This research was carried out using a comparative case study approach across fishing communities and cooperatives along Bahia Magdalena and Golfo de Ulloa, Baja California Sur, Mexico, an important region for small-scale fisheries, characterized by extreme uncertainty and variability. I found that increased access to the environment through the equitable distribution of resources and rights can facilitate resilient small-scale fisheries from a social perspective. The ecological impacts of diversification across fisheries and livelihoods are likely context specific, however negative impacts can be minimized when policies recognize the multiple dimensions of small-scale fisheries, and when fishers are integrated into policy processes. Furthermore, a greater suite of economic opportunities within and outside the small-scale fisheries sector can provide alternative pathways out of poverty-overfishing cycles. Overall, this research suggests that with greater attention to access, equity, and participatory governance, small-scale fisheries in Mexico and beyond will be better equipped to sustain livelihoods and the environment in a changing world.

Keywords: Biology.
Advisor: Crowder Larry B.
Basurto Xavier
Bird Douglas W. advisor. Thesis advisor
De Leo Giulio A. advisor. Thesis advisor
Micheli Fiorenza advisor. Thesis advisor
Sustainable target value framework [electronic resource] : integrating life cycle assessment and target value design for improved energy and environmental performance of buildings

The built environment creates significant environmental and economic impacts. Buildings are the largest consumer of energy and greatest contributor to climate change in the United States—consuming approximately half of energy produced and contributing close to half of greenhouse gas emissions. Building designers, contractors, and owners have developed methods to consider costs, but currently have few methods to effectively assess and control a building's life cycle energy and environmental impacts during the design phase. Managing and reducing these impacts during design requires rapid information turnaround and decision-making. This research combines life cycle assessment (LCA) and target value design (TVD) to rapidly produce more sustainable building designs that account for life cycle impacts. The STV design process involves environmental design targets and an STV tool to quantify environmental design performance in an iterative design process. By establishing site-specific sustainability targets and using dynamically-updating life cycle assessments, this research demonstrates that buildings can be designed to perform at higher environmental standards than those designed without a target in place. Further, this work illustrates that setting specific environmental sustainability targets prior to design and providing support resources that allow designers to iteratively improve and re-evaluate designs, reduces the impact of the building design from initial to final design. In parallel with cost reductions resulting from target value design, STV design implementation results in building designs for which impacts decreased over the course of design and for which the final design met or surpassed the target in terms of environmental performance. STV implementation is also extended to demonstrate a method to measure and manage the cradle-to-gate life cycle environmental impacts by linking environmental targets with modern construction management methods, to enable building stakeholders to create buildings that actually to meet STV targets. The STV methodology offers building stakeholders unique analysis opportunities to examine the tradeoffs between design, construction, and operation decisions.

Keywords: Civil and Environmental Engineering.
Advisor: Jacobson Mark Z. (Mark Zachary) primary advisor. Thesis advisor
Lepech Michael primary advisor. Thesis advisor
Fischer Martin