VictorJuiz/thesis huggingface dataset:
Integrating geological and geophysical data to study the mechanics of multifault earthquakes with reference to the 1992 M 7.3 Landers, California earthquake [electronic resource]

Earthquakes that rupture multiple faults are larger than those predicted from individual fault lengths, making understanding such events critical to seismic hazard mitigation. This research explores stress transfer across extensional steps between nearby faults to address the influence of fault geometry on fault interactions. While mapped surface data often are restricted to the realm of the geologist, and subsurface data, such as aftershocks, often are restricted to the realm of the geophysicist, integration of these data in forward boundary element method models proves advantageous in constraining the 3D geometry of the multiple strike-slip faults that ruptured in the 1992 M 7.3 Landers, California earthquake. Further forward modeling reveals that this fault geometry influences inferences of fault interactions across an extensional step along the southern-central rupture. Estimates of potential step width made with planar faults indicate direct transfer of slip across the step, while conclusions from models incorporating non-planar fault geometries indicate that slip along a crossing fault located within the step is critical to slip transfer. In general, models incorporating planar approximations to more realistic non-planar fault geometries do not capture the behavior of non-planar faults and are more sensitive to changes in model parameters, including friction and the tectonic driving stress orientation. The tectonic driving stress orientation exerts the greatest influence over non-planar fault behavior, but is poorly constrained near Landers and in many regions around the world. A new approach to inverting earthquake data for the tectonic stress state that honors the mechanical relationships among this stress, fault slip, and the stress and displacement fields surrounding the faults following slip is presented and applied in the Landers region.

Keywords: Geological and Environmental Sciences.
Advisor: Pollard David D. primary advisor. Thesis advisor
Beroza Gregory C. (Gregory Christian) advisor. Thesis advisor
Hilley George E. advisor. Thesis advisor
Integrative methods for the analysis of genome wide association studies [electronic resource]

Genome Wide Association Studies (GWAS) have identified over 4,500 common variants in the human genome that are statistically associated with diseases and other phenotypical traits. Most identified associations, however, only have a small effect on disease risk, and their relevance in a clinical setting remains the subject of extensive debate. In this thesis I present three integrative analysis directions that extend on GWAS by developing new methods, by using genotyping data to ask new questions, and by integrating additional types of data to generate functional hypotheses about the biological processes underlying associations. First, I introduce a new classifier-based methodology that identifies similarities in the genetic architecture of diseases. This method can successfully identify both known and novel relationships between common diseases. Second, I show how control individuals from a GWAS can be used to detect genetic differences between the pseudoautosomal regions of chromosomes X and Y in the general population. Finally, I present an approach that integrates experimental data generated by the ENCODE consortium in order to identify functional Single Nucleotide Polymorphisms (SNPs). These functional SNPs are associated with a phenotype, either directly or through linkage disequilibrium, and overlap a functional region of the genome such as a transcribed region or a transcription factor binding site. Up to 80% of all associations previously reported in a GWAS can be mapped to a functional SNP.

Advisor: Batzoglou Serafim primary advisor. Thesis advisor
Butte Atul J. advisor. Thesis advisor
Dill David L. advisor. Thesis advisor
Interaction of polyglutamine fibrils with the mammalian cell surface [electronic resource]

Neurodegeneration is currently as inexorable in its progression as it is devastating in its scope. Current therapies are largely ineffective, in large part because the etiology of disease is still undetermined. In all of these diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, the presence of a particular form of protein aggregate -- the amyloid fibril -- has led investigators to propose that this structure is a large facet of disease pathogenesis. Though this aggregate has been observed for centuries, how amyloid or amyloid precursors contribute to disease is still unknown. In mammalian prion diseases, amyloid is also central to pathology and transmission. In these cases, the amyloid fibril is an infectious unit, transmitted from individual to individual through consumption of contaminate brain or fecal matter or through contaminated surgical instruments. Recently, we and others have observed that amyloid fibrils derived from neurodegenerative-disease-related proteins like tau, [alpha]-synuclein, and polyglutamine can be transmitted from cell-to-cell in a manner similar to prion disease. These observations raise many questions regarding the mechanism of transmission and the contribution of this phenomenon to disease progression. This study analyzed the interaction of polyglutamine fibrils with the mammalian cell surface. We identified several factors that drastically influence the binding and internalization of polyglutamine fibrils. We show that fibrillar structure and the electrostatic composition of the fibril influences its binding to the cell surface. Furthermore, we demonstrate that polyglutamine fibrils bind to distinct binding sites on the surface, and that a particular class of sites seems to consist of proteins involved in cell adhesion. Finally, we describe a novel bioassay to determine genes involved in aggregate uptake on a genome-wide scale. The findings from this work increase our understanding of how this phenomenon occurs, and by extension will provide a foundation from which to understand whether the prion-like transmission of amyloid fibrils in neurodegeneration contributes to disease progression.

Keywords: Biology.
Advisor: Kopito Ron Rieger
Cegelski Lynette advisor. Thesis advisor
Mudgett Mary Beth
Nelson W. J. (W. James) advisor. Thesis advisor
Interests abroad and actions at home [electronic resource] : the politics of U.S. bilateral trade balances

Despite the implications for the distribution of the gains and losses from trade, bilateral trade balances have been under-examined as both structural and institutional variables. The existing literature has failed to examine any evidence to explain why some bilateral trade balances have become politicized while others have been ignored by the government through changes in both the security relationships and economic position of the United States. This thesis addresses this omission by studying the bilateral trade balances of the United States from 1946 to the present, using a core dataset of all trade balances between the United States and its trading partners, a set of over 150 countries. This comprehensive data reveals significant bilateral variation in the politicization of bilateral trade balances in the realm of trade policy, supporting the hypothesis that variations in the size of the bilateral trade balance result in variations in political responses. This thesis makes several contributions to the literature. First, I demonstrate the importance of reconceptualizing the measurement of bilateral trade balances using the bilateral terms-of-trade. Secondly, I present evidence demonstrating the relationship between the size of bilateral trade balances and politicization. To study government action on bilateral trade balances, I analyze anti-dumping cases, showing that U.S. foreign direct investment is an important predictor of government action against bilateral trade deficits. I then analyze the impact of bilateral trade balances upon mass politicization, using an original measure of media attention. Finally, I present qualitative evidence of the variations in politicization by examining the history of trade conflicts between the United States and Japan. Overall, I demonstrate that bilateral trade balances are important to understanding variations in the politicization of trade.

Keywords: Political Science.
Advisor: Goldstein Judith primary advisor. Thesis advisor
Krasner Stephen D.
Rivers Douglas
The intersection of right and good in Kant's metaphysics of morals [electronic resource]

My dissertation focuses on the ways that erroneous beliefs contributing to conclusions about what we morally ought to do can and cannot be legitimately employed within a Kantian context. I approach this issue through questions about Kant's theory of conscience and the role of conscience in moral decision-making. According to the standard reading of Kant's ethics, there is a single set of objectively correct duties for all agents. On my reading, by way of contrast, an agent's duties are determined to some extent by his/her beliefs about the world. In other words, I give a defense of a kind of limited pluralism within Kant's ethics. I do this by arguing for three main claims. First, I argue (in chapters 1 and 2) that in Kant's ethics agents with similar core values but different beliefs about how the world works will arrive at very different (but nonetheless reasonable) conclusions about what they ought to do in particular situations. Second, I argue (in chapters 3 and 4) that according to Kant an agent who acts according to his/her conscience is behaving permissibly. And third, I argue (in chapters 5 and 6) that for Kant juridical duties are fundamentally different from ethical duties, so an ethical pluralism could be represented in a single (Kantian) state despite the fact that there are limits as to what counts as reasonable. In this way, I hope to show that even within Kant's system of objective value, because agents might have different beliefs about how the world works, there is no determinable set of judgments for a set of circumstances that exists independently of those agents' beliefs and intentions. To put this another way (to bring out where I diverge from the now-standard reading of Kant's ethics), I am arguing that the results of Kant's moral standard, the Categorical Imperative (CI), are radically underdetermined without information about an agent's beliefs about how the world works. One can determine whether something is permissible for an ideal agent (with only true beliefs); one can determine whether something is permissible for some given, fallible agent; but one cannot determine whether something is permissible simpliciter, for it is indeterminate. In slogan form, the underlying idea of this is that for Kant permissibility does not exist in a vacuum. We can make judgments about permissibility only for a given context, and part of that context includes information about an agent and his/her beliefs about how the world works.

Keywords: Philosophy
Advisor: Wood Allen W. primary advisor. Thesis advisor
Anderson R. Lanier advisor. Thesis advisor
Cohen Joshua
Friedman Michael advisor. Thesis advisor
Investigating Wnt/ss-catenin signaling in stem cells and progenitors of the developing and adult mouse brain [electronic resource]

In order for a tissue to be properly sized and patterned, enormous care must be taken to ensure that cell proliferation and differentiation are tightly regulated. The embryonic brain must execute a temporally and spatially defined developmental scheme, resulting in the production of millions of cells of multiple lineages. These cells and their resultant functional architecture must be maintained in the homeostatic adult mouse brain. These processes are in part controlled by external signaling factors, which include Wnts, and their transcriptional programs. However, the degree to which and exact mechanisms by which cell fate choices--including self-renewal, proliferation, and differentiation--are controlled by Wnt/ss-catenin signaling are unknown. Here, I describe studies to investigate these questions. First, I show the identification of a novel target of Wnt/sscatenin signaling, Pou6f1, which mediates neural differentiation and proliferation in embryonic neural progenitor cells. Next, I illustrate the use of a lineage tracing approach using a Wnt/ss-catenin target gene, Axin2, to identify and trace sites of Wnt/ss-catenin responsiveness in the developing and adult mouse brain and central nervous system. Using this same Axin2CreERT2 mouse, I describe the functional consequences of loss of sscatenin from Axin2-expressing cells. Axin2CreERT2 labels numerous radial glial cell populations throughout the central nervous system, three of which serve as functional stem/progenitor populations. Loss of ss-catenin from adult Axin2+ populations results in tissue architecture defects and increased proliferation, presumably because Wnt serves as a self-renewal signal. These studies demonstrate the importance of Wnt/ss-catenin signaling for mediating multiple cell fate choices during the development and homeostasis of the mouse central nervous system, and suggest mechanisms by which neural stem/progenitor populations could be manipulated for therapeutic outcomes.

Keywords: Developmental Biology.
Advisor: Nusse Roel
Palmer Theo advisor. Thesis advisor
Talbot William
An investigation of liquefying hybrid rocket fuels with applications to solar system exploration [electronic resource]

Developments in hybrid propulsion technology over the past several decades have made these motors attractive candidates for a variety of applications. In the past, they have been overlooked due to the low regression rate of classical hybrid fuels or in favor of the heritage and commercial availability of liquid or solid propulsion systems. The slow burning rate translates into either a reduced thrust level or the requirement for a complicated, multi-port fuel grain to increase the available burning surface area. These major disadvantages can be mitigated through the use of liquefying hybrid fuels, such as paraffin. Typically, this increase is enough to achieve desired thrust levels with a simple, single port design. Benefits unique to the paraffin-based hybrid design makes it a competitive and viable option for solar system exploration missions. Two specific examples are included to illustrate the advantages of hybrids for solar system exploration. A hybrid design for a Mars Ascent Vehicle as part of a sample return campaign takes advantage of paraffin's tolerance to low and variable temperatures. Hybrid propulsion systems are well suited for planetary orbit insertion because of their ability to throttle, stop and restart at high thrust levels. The high regression rates of liquefying hybrid fuels are due to a fuel entrainment mass transfer mechanism. The design, assembly and results of an experiment to visualize this mechanism are presented. A combustion chamber with three windows allows visual access to the combustion process. A flow conditioning system is employed to create a uniform oxidizer flow at the entrance to the combustion chamber. Experimental visualization of entrainment mass transfer will enable the improvement of combustion models and therefore future hybrid designs.

Keywords: Aeronautics and Astronautics
Advisor: Cantwell Brian primary advisor. Thesis advisor
Alonso Juan José
Christensen R. M. (Richard M.) advisor. Thesis advisor
Hubbard Scott
Issue representation in the 107th-111th congresses [electronic resource]

In order to assess the quality of our democracy, it is important to understand how often, and in what circumstances, legislators follow the will of their constituents. But scholars still have only a limited understanding about the degree to which legislators follow their constituents' preferences on individual issues. In this dissertation, I develop new techniques to accurately measure the policy preferences of the American public at a variety of geographic levels, including states, congressional districts, and state legislative districts. I use this approach to evaluate the degree to which members of the United States House represent the preferences of their constituents on a wide range of issues. I find that representatives are highly responsive to issue-specific public opinion, but they are more responsive to their partisan sub-constituencies than independents. Next, I examine whether vigorous electoral competition improves the link between legislators and their constituents. I find that legislators are more responsive to their constituents in electorally competitive districts. Moreover, they are less responsive to their partisan sub-constituency. Finally, I examine whether there is a stronger link between legislators and their constituents on the most salient, important issues. I find that greater issue salience does not increase legislators' responsiveness to their average constituent. Instead, representatives are more responsive to their partisan sub-constituency on salient issues. In addition, legislators' roll calls are more likely to be congruent with the opinion of a majority of their partisans on salient issues. Taken together, this dissertation deepens our understanding of representative democracy in the United States.

Keywords: Political Science.
Advisor: Rodden Jonathan primary advisor. Thesis advisor
Brady David advisor. Thesis advisor
Jackman Simon
Weingast Barry R. advisor. Thesis advisor
It is all about timing and location [electronic resource] : coordination of calcium signaling controls cell migration

Terminating cell migration is critical for cancer treatment, because malignancy progresses through migrating tumor cells (metastasis) and migrating endothelial cells (neoangiogenesis.) Although cell migration requires Ca2+ for polarity and turning, it is not well understood how Ca2+ signals regulate cell migration. By studying sheet migration using endothelial cells loaded with Fura-2/AM, we identified pulsatile local Ca2+ pulses near the cell front. Each Ca2+ pulse controlled a local retraction and adhesion process in lamellipodia. Eliminating endogenous Ca2+ pulses reduced lamellipodial retraction while photo-release of Ca2+ from NP-EGTA induced front retraction and adhesion, indicating that these small Ca2+ signals were both necessary and sufficient for cyclic lamellipodia activity. Mechanistically, these local Ca2+ pulses acts through myosin light-chain kinase and myosin II to mediate actin cable retraction and to strengthen focal adhesion. We further explored the origin of these local Ca2+ signals. Removing extracellular Ca2+ did not eliminate local Ca2+ pulses, suggesting that these local signals are generated from activated inositol-3-phosphate receptors (IP3R) in the endoplasmic reticulum (ER). Inhibiting receptor tyrosine kinases (RTK) diminished local Ca2+ pulses, confirming that RTK-induced IP3R activation was the major source of these Ca2+ signals. More experiments demonstrated that diacylglycerol, the downstream regulator of RTK signaling, was also enriched in the cell front. It contributed to cell motility and polarity through protein kinase C. Therefore, polarized RTK signaling generates local Ca2+ signals and diacylglycerol in the cell front to ensure coordinated cell movement. We also investigated how Ca2+ homeostasis was maintained during cell migration. Our data showed that plasma membrane Ca2+ ATPases (PMCA) pumped Ca2+ out of the cell more actively in the front than in the back. The resulting low basal Ca2+ in the front of migrating cells maintained the sensitivity of the cell front to local Ca2+ pulses. Furthermore, to avoid depletion of Ca2+ in the front ER after it being released through IP3R, microtubules transported STIM1, a sensor of ER luminal Ca2+, toward the cell front triggering store-operated Ca2+ influx near the leading edge. Thus, cells maintain efficient migration through coordinated Ca2+ signaling systems. In summary, temporal-spatial coordination of Ca2+ signaling controls cell migration by regulating local adhesion, motility, and polarization. Our research also reveals the importance of interactions between signaling modules in migrating cells. Finally, a "synthetic immobility" screen will elucidate how different components are coordinated in cell migration, and will identify novel drug targets against cancer metastasis.

Advisor: Meyer Tobias primary advisor. Thesis advisor
Axelrod Jeffrey (Jeffrey David) advisor. Thesis advisor
Chen James
Nelson W. J. (W. James) advisor. Thesis advisor
Jet substructure for the LHC [electronic resource]

The discovery of new physics at the LHC hinges on our ability to discriminate the old (the Standard Model) from the new. The study of the substructure of jets offers a powerful set of techniques for improving the reach of new physics searches at the LHC. Moreover, jet substructure observables are a sensitive probe of QCD dynamics and motivate a variety of tests of QCD. This thesis explores several jet substructure techniques with a particular focus on applications to event discrimination. First, a jet observable is introduced that probes the color structure of pairs of subjets. This observable is incorporated into a top tagging algorithm, where it is shown to improve discrimination between top jets and QCD jets. Second, an alternative approach to jet substructure is introduced that is distinct from the prevailing methods based on the clustering trees induced by sequential jet algorithms. This approach makes use of two-particle angular correlations to identify substructure within jets. In one application, this approach is used to construct a top tagging algorithm that is competitive with existing methods. In another application, ensemble averages of angular correlations are used to study the underlying event and pile-up effects.

Keywords: Physics
Advisor: Wacker Jay primary advisor. Thesis advisor
Peskin Michael Edward
Schwartzman Ariel G. advisor. Thesis advisor