VictorJuiz/thesis huggingface dataset:
Tracing the Farallon plate through seismic imaging with USArray

The Farallon plate system has been subducting off the western United States since at least the middle Mesozoic. This plate has undergone virtually every subduction process during this time including a long episode of flat-slab subduction, generation of microplates, and formation of oceanic plateaus. The shallow remains of this plate are two small microplates, the Gorda and Juan de Fuca, in the Pacific Northwest. The anomalous nature of these two small plates and the missing deeper evidence of subduction has motivated this study./nThe USArray seismic experiment has provided unprecedented spatial sampling of the seismic wavefield in the continuous United States. Utilizing this dataset, new imaging methods have been implemented and older imaging methods have been revitalized. This study first uses ambient seismic noise in the Pacific Northwest to extract short period Rayleigh waves which are sensitive to lithospheric scale structure. Phase velocities from this model are then combined with teleseismic delay times of body waves and surface waves to image the structure of the continuous United States from the surface through the mantle transition zone. The resolving power of this model allows tracing of the Farallon plate from the trench to the lower mantle./nThe seismic velocity structure of the continuous United States is broadly composed of a slow western half and fast eastern half separated by the Rocky Mountain Front. The low velocity of the western U.S. contains several high velocity anomalies. While previous work has focused on individual anomalies and suggested they represent lithospheric instabilities, a larger regional view indicates that these are the western remnants of the Farallon plate. Below the thick cratonic lithosphere of the eastern U.S., the Farallon plate contains significant topography due to a subducted heterogeneity of the oceanic plate and a viscosity contrast through the mantle transition zone. The velocity models presented herein provide a cohesive picture of Farallon subduction for the past 150 Ma.

Advisor: Allen, Richard M
Dual Upstream Open Reading Frames Control Translation of a Herpesviral Polycistronic mRNA

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. KSHV expresses a number of transcripts with the potential to generate multiple proteins, yet relies on the cellular translation machinery that is primed to synthesize only one protein per mRNA. Here we report that the viral transcript encompassing ORF35-37 is able to direct synthesis of both ORF35 and ORF36, while the 3'-proximal ORF37 is translated from a monocistronic transcript under separate transcriptional regulation. While ORF36 encodes the KSHV protein kinase and functions to phosphorylate and activate the anti-viral prodrug ganciclovir, ORF37 expresses SOX (shutoff and exonuclease), a viral protein responsible for promoting widespread degradation of host mRNAs. Surprisingly, ORF36 is robustly translated as a downstream cistron from the ORF35-37 polycistronic transcript in a cap-dependent manner. Two short, upstream open reading frames (uORFs) were identified within the 5' UTR of the polycistronic mRNA. While both uORFs function as negative regulators of ORF35, unexpectedly, translation of the downstream ORF36 gene occurs by a termination-reinitiation mechanism after translation of both uORF1 and uORF2. The sequence of the viral uORFs appears unimportant, and they instead function to position the translation machinery to favor translation of the downstream major ORF. Furthermore, the newly developed KSHV genetic system was used to introduce a mutation into the viral genome to disrupt uORF2 and this single nucleotide change leads to a dramatic drop in infectious viral titer. Positional conservation of uORFs within a number of related viruses suggests that this may be a common γ-herpesviral adaptation of a host translational regulatory mechanism. Thus, KSHV uses a host strategy generally reserved to repress translation to instead allow for the expression of an internal gene.

Advisor: Glaunsinger, Britt A
Perturbative Methods in Path Integration

This dissertation addresses a number of related questions concerning perturbative "path" integrals. Perturbative methods are one of the few successful ways physicists have worked with (or even defined) these infinite-dimensional integrals, and it is important as mathematicians to check that they are correct./nChapter 0 provides a detailed introduction./n/nWe take a classical approach to path integrals in Chapter 1. Following standard arguments, we posit a Feynman-diagrammatic description of the asymptotics of the time-evolution operator for the quantum mechanics of a charged particle moving nonrelativistically through a curved manifold under the influence of an external electromagnetic field. We check that our sum of Feynman diagrams has all desired properties: it is coordinate-independent and well-defined without ultraviolet divergences, it satisfies the correct composition law, and it satisfies Schrödinger's equation thought of as a boundary-value problem in PDE./n/nPath integrals in quantum mechanics and elsewhere in quantum field theory are almost always of the shape ∫ f es for some functions f (the "observable") and s (the "action"). In Chapter 2 we step back to analyze integrals of this type more generally. Integration by parts provides algebraic relations between the values of ∫ (-) es for different inputs, which can be packaged into a Batalin–Vilkovisky-type chain complex. Using some simple homological perturbation theory, we study the version of this complex that arises when f and s are taken to be polynomial functions, and power series are banished. We find that in such cases, the entire scheme-theoretic critical locus (complex points included) of s plays an important role, and that one can uniformly (but noncanonically) integrate out in a purely algebraic way the contributions to the integral from all "higher modes," reducing ∫ f es to an integral over the critical locus. This may help explain the presence of analytic continuation in questions like the Volume Conjecture./n/nWe end with Chapter 3, in which the role of integration is somewhat obscured, but perturbation theory is prominent. The Batalin–Vilkovisky homological approach to integration illustrates that there are generalizations of the notion of "integral" analogous to the generalization from cotangent bundles to Poisson manifolds./nThe AKSZ construction of topological quantum field theories fits into this approach; in what is usually called "AKSZ theory," everything is still required to be symplectic./nUsing factorization algebras as a framework for (topological) quantum field theory, we construct a one-dimensional Poisson AKSZ field theory for any formal Poisson manifold M. Quantizations of our field theory correspond to formal star-products on M. By using a ``universal'' formal Poisson manifold and abandoning configuration-space integrals in favor of other homological-perturbation techniques, we construct a universal formal star-product all of whose coefficients are manifestly rational numbers.

Advisor: Reshetikhin, Nicolai
Engineering Escherichia coli for molecularly defined electron transfer to metal oxides and electrodes

Both organisms and human-made technological devices use the flow of charge as the basic currency of information and energy. The soft materials properties and waxy cell membranes generally do not interface electrically with solid materials. Creating an interface that permits electrical communication between living and non-living systems would enable new opportunities in fields such as biosensing, bioenergy conversion, and biocomputing. Thus my dissertation focuses on creating a blueprint for the bidirectional flow of electrons between living and non-living systems that is transferrable to a multitude of cell lines. I take a biologically-focused approach to connect the living and non-living worlds: use synthetic biology to introduce a new electron transfer pathway into E. coli. This strategy takes advantage of the respiratory capability of the dissimilatory metal reducing bacterium Shewanella oneidensis MR-1. Shewanella uses a network of multiheme cytochromes that are able to transfer charge across the inner and outer membranes of the bacteria via the heme moiety in the cytochromes. This pathway enables Shewanella to route electrons along a well-defined path from the cell interior to an extracellular inorganic material acting as a terminal electron acceptor during anaerobic respiration. By genetically engineering the cell to build and maintain the bioelectronic connections, the cells can autonomously assemble and repair these connections. This work describes the first time the outer membrane spanning and double membrane spanning Shewanella electron transfer pathway was heterologously expressed in Escherichia coli. Additionally, these engineered E. coli strains are shown to reduce soluble iron, solid iron oxide, and anodes. This work not only serves as a landmark for the expression of complex membrane associated pathways, but it also demonstrates proof of concept that this pathway could be transferrable to other cell lines. This dissertation represents the first step towards engineering bidirectional communications with electrodes, and it opens up an array of opportunities for studying the biochemical and enzymatic properties of these unique proteins as well as the potential for novel hybrid technologies.

Advisor: Groves, John T
Probing E-cadherin-Mediated Cell Adhesion Using Supported Lipid Bilayers

The E-cadherin cell adhesion protein is important for embryo development and cell-cell junction stability, and furthermore plays a role in tumor suppression. It binds apposing cells by forming trans-dimers, which can additionally be stabilized by cis-interactions. However, given the low affinity of the trans-dimer, questions persist about the mechanisms that drive the assembly of such biologically important junctions. One recent theory describes the cooperation of trans and cis-affinity in stabilizing contacts of freely diffusing E-cadherin. Another theory is instead based on the force dependence of different trans-dimer configurations. Not to be overlooked, any such hypothesis must also consider the influence of actin dynamics in forming stable junctions. A synthetic cell membrane platform was used to address these concerns by creating a controlled environment for observing E-cadherin interactions on the planar surface of a supported lipid bilayer. This allowed for the precise adjustment of physicochemical attributes and direct observation of E-cadherin mediated assembly, which uncovered new aspects of adhesion regulation./nThe behavior of cells with E-cadherin has been studied previously using lipid bilayers, but such experiments have lacked even a minimal physical characterization of the membrane surface and direct imaging of cell interactions. In this study, an E-cadherin bilayer platform was characterized with respect to fluidity and density. With the introduction of the epithelial cell line MKN28, cells were observed to interact and transport the E-cadherin, causing enrichment of the protein above initial bilayer surface densities. Immunostaining these cell-bilayer interfaces exposed an architecture similar to those found in vivo, suggesting the formation of mature E-cadherin mediated adhesions./nThe current system led to the observation that cells assembled junctions on a low-mobility protein surface much more frequently than with a fluid bilayer (adhesions assembled in 54% of cells vs. 1%). Limiting protein fluidity in other ways, such as using nano-patterned diffusion barriers, non-fluid bilayers, and cross-linking antibodies, only showed enrichment events with 1 - 3% of the cells added. The reason for this unusual behavior comes from the physical response between the surface and the cell's retraction of filopodia during junction formation. Cells on both fluid and low-mobility surfaces exhibited active membrane protrusions, but only on the low-mobility surface was protein enrichment observed underneath retracting filopodia./nThis discovery shows that E-cadherin adhesions are formed by an active process, which is dependent on the force and densities resulting from interactions with the low-mobility lipid surface. These lipid bilayer studies address the theories of adhesion assembly, with results suggesting that the decreased diffusion of E-cadherin on the low-mobility lipid surface provides the stability and resistance needed for the formation of robust, force-dependent junctions.

Advisor: Groves, Jay T
Political Realism and Political Philosophy in Jean-Jacques Rousseau's Social Contract

This thesis places Jean-Jacques Rousseau in the "realist" or raison d'état tradition of political thought. While highly critical of the conceptualization of political sovereignty among earlier social contract theorists such as Hugo Grotius and Thomas Hobbes and also very condemnatory of the popular eighteen-century discourse of reason of state, Rousseau preserves some of the most important insights in the theory of state and political sovereignty of earlier authors, in particular the value, status, and justification of political life. This thesis thus looks at both the continuity and the disruption or corrections that Rousseau represents in the tradition of political realism./nThe first part of the dissertation looks at Rousseau's reflections on international politics, political economy, and the role of government. It examines Rousseau's criticism of the seemingly triumphant theory and practice of realpolitik and mercantilism in the eighteenth-century and how this criticism derives from his overriding concern with political equality and liberty in the Social Contract./nThe second part of the dissertation details the necessary link between Rousseau's conceptualization of the political and his epistemology and linguistic anthropology. Rousseau's linguistics accounts for both his emphasis on equality as the condition of the political and his anxiety over the fragility of the political. Rousseau must confront a gap between the concept of the political as a just and equitable form of civil association and the utter impossibility of the literality of the political condition. Rousseau's theory of government and his resentment of mercantile administration must be read in light of this gap between the concept and literality of the political.

Advisor: Brown, Wendy
Identification and characterization of genes involved in the biosynthesis of the plant cell wall polysaccharide xyloglucan

Xyloglucan (XyG) represents the most abundant hemicellulose in the primary cell wall of many dicot and non-graminaceous monocot plant species. Found throughout the land plant lineage, the structure of this polysaccharide varies by species, tissue, and developmental stage. Some proteins responsible for the biosynthesis and metabolism of XyG have been previously identified but additional genes remain to be uncovered. In the work presented here, several genetic and genomic approaches were used to identify previously unknown genes involved in XyG biosynthesis and metabolism. A forward genetic screen of mutagenized Arabidopsis thaliana resulted in the identification of the Altered Xyloglucan 9 (AXY9) gene, coding for a protein of unknown function, as part of an apparently plant-specific pathway for the acetylation of polysaccharides. The AXY9 protein may be part of a system for shuttling activated acetyl groups across the Golgi membrane for use by polysaccharide-specific acetyltransferases. A transcriptional profiling approach used on developing XyG-rich Tropaeolum majus seeds revealed a galactosyltransferase that acts on XyG, as demonstrated by mutant analysis in A. thaliana. By utilizing comparative genomics, two putative XyG arabinofuranosyltransferase genes were discovered from tomato, which are able to act in vivo to arabinosylate XyG. Expression of these genes rescued mechanical and morphological phenotypes of an A. thaliana mutant deficiency for XyG galactosylation, providing insight into the function of XyG substitution. To provide a testing platform for candidate genes involved in XyG biosynthesis and to investigate the activities of these genes independently from endogenous plant proteins, an attempt was made to reconstruct the XyG biosynthetic pathway in a heterologous host. This effort resulted in the production of a glucan backbone and the UDP-xylose donor substrate required for the xylosyltransferases, but a XyG polysaccharide was not detected.

Advisor: Pauly, Markus
Torturing Molecular Motors: Single-Molecule Studies of Viral Packaging and Flagellar Switching

Molecular motors play a central role in all known living systems. Cells use them to fight the never ending battle against entropy. Motors allow cells to organize their components in space and time to perform complex functions. In this thesis I focus on two molecular motors: the packaging motor of phi29, and the flagellar motor of Escherichia coli. These are both well-studied motors with decades of research poured into them. By leveraging past knowledge, I was able to undertake subtle studies of their function. I tortured these motors by putting them in sub-optimal operating conditions to test their limits./nFor the phage motor we were primarily interested in what sort of contacts it uses to engage and exert force on its DNA substrate. We queried the nature of these contacts by making a series of modified DNA substrates, with a focus on methylphosphonate substitutions that maintain the structure of DNA while removing the negative charge. Interestingly, we found that the negative charge of the phosphates was not required for the motor to translocate DNA, but that the charge stabilizes the interaction and makes the motor less likely to slip. We also discovered that the motor interacts more strongly with one of the DNA strands, and we used these modifications to identify a set of periodic contacts./nFor the flagellar motor I was interested in the role of proton motive force (PMF) in changing the rotational direction of the motor, which is controlled by a complex on its cytoplasmic side called the flagellar switch. The motor is powered by PMF, but does the PMF also affect the switch? We found that in fact the switch is affected by changes in PMF. This has implications for the switching mechanism. The switch is not only affected by the chemical binding signal, but is also affected by its associations with the motor and potentially its proximity to charges on the cell membrane.

Advisor: Liphardt, Jan T
An Athenian Commentary on Plato's Republic: Poetry, science and textual engagement in Proclus' In Rem.

Proclus' Commentary on Plato's Republic is the only extant ancient Greek commentary on Plato's Republic. Despite the fact that it includes discussions of most of the major parts of the book, it has received very little scholarly attention. This dissertation introduces the work in its entirety and tries to identify some of the most important contributions it can make to philosophical and philological scholarship on the Republic. I am particularly attentive to ways in which Proclus' concerns--such as responding to Epicurean critiques of Platonic myth or defending Homer--may help us see Plato's work in its cultural context./nThe first chapter focuses on introducing the work and answering basic questions about the place of the Republic in late antique Platonism, the extent of Proclus' sources and what portions of the Republic Proclus discusses. I consider the form of the commentary, arranged as various essays, in comparison with Proclus' other commentaries which proceed in a line by line manner. I respond to arguments that have claimed that the commentary is not a unified work by considering the form and extent of the essays relative to the content of the Republic./nThe second chapter argues that Proclus' commentary is not trimming the Platonic tradition to fit into the religious orthodoxy of late antiquity but rather stressing arguments and interpretative approaches that became most influential in the Renaissance. I consider several examples such as Proclus' interest in the Orphic and Pythagorean tradition, his emphasis on gender equality and the scientific aspects of his approach to natural philosophy./nThe third chapter considers some important aspects of Proclus' hermeneutics. I consider how and why Proclus sometimes disagrees with Plato. In particular, I focus on some portions of the commentary that demonstrate Proclus' approach to the dramatic aspects of the dialogues and discuss why Proclus' defence of Homer includes some observations about his Platonic hermeneutics. I consider also his responses to Aristotle's idea of catharsis and his approach to Glaucon's role in the Republic./nThe fourth chapter translates and discusses a particular portion of the sixth essay in which Proclus argues, contrary to the view Socrates expresses in the Republic, that Homer is a text which teaches the political virtue of sophrosune. I consider the historical origins of allegorizing interpretations and then distinguish between Proclus' use of allegory and his use of other interpretative methodologies. I consider in particular Proclus' defence of the idea of euphrosune and compare his approach with earlier philosophical discussions which responded to the same passage of Homer (Odyssey 9.6-10) and interrogated the passage along the lines suggested in the Republic.

Advisor: Long, Anthony
Ferrari, G.R.F.
Care and Enforcement: A study of police training for teacher education researchers

Teachers must mediate the persistent tension in American society and American education between individual freedoms and civic virtue. This creates philosophical and practical problems for teachers in classrooms who must make decisions that affect the experiences of individual students as well as the whole class. Teacher education unsuccessfully attempts to mediate this tension by conceptualizing the work of teaching as "caring" work, and in doing so, regularly obfuscates the role of teachers in constraining individual freedoms in their day-to-day work./nIn an effort to better conceptualize preparation for the difficult work of mediating the tension between individual freedoms and civic virtue in teaching, this study looks at police training to see how police are prepared to mediate the same tensions. Police unapologetically prepare candidates to constrain individual freedoms and to enforce a particular vision of social order. In an attempt make the familiar world of teacher education strange, this is a case study that uses a grounded theory approach to examine a signature pedagogy of police preparation - scenario training./nAn analysis of scenario training revealed three signature problems for which candidates were prepared: uncertainty, stress, and the high cost of error. Police were trained to contend with these problems through routines that caused them to draw on both explicit and tacit forms of knowledge. The framing of these problems, as well as the strategies that candidates were taught to contend with them, caused police preparation to privilege enforcement of social order over the protection of individual freedoms. This raises the hypothesis that teacher education, by invoking care as a framework for understanding teachers' work, privileges preparation for nurturing individual students over enforcing order in the classroom or for preparing a citizenry for the common good.

Advisor: Little, Judith Warren