VictorJuiz/thesis huggingface dataset:
Molecular Dynamics of Mechanosensing and Mechanotransduction at the Focal Adhesions

Focal adhesions are critical to cellular processes such as cell migration and cell-substrate adhesion. Focal adhesion formation can be mechanically regulated: forces either from outside the cell or from contracting actin filaments can induce rapid growth and maturation of the focal adhesions. One hypothesis explored here contends that force-induced focal adhesion formation results from mechanosensing by individual protein components. Molecular dynamics computational simulations are developed to evaluate mechanosensing by talin and vinculin. In Part 1 of this dissertation, two force-induced conformational changes are suggested for talin's activation: (i) the cryptic vinculin-binding sites (VBS) can be activated by stretch of an individual talin rod domain, and (ii) talin can adopt multiple dimer orientations in response to forces applied from outside the cell. The mechanisms of vinculin activation are then explored in Part 2. The trajectory of a vinculin conformational changes that would render it activated is predicted along with the structure of an activated vinculin. Domain 1 (D1) is predicted to separate from the vinculin tail (Vt) during activation. In this context, the PIP2 from the cell membrane is shown to preferentially bind basic residues on the vinculin surface and recruit vinculin to membrane proximal regions, potentially allowing for vinculin phosphorylation. The impact of phosphorylation on the vinculin structure is simulated and it is suggested that phosphorylation could prime vinculin for activation by reducing the strength of inter-domain interactions stabilizing the auto-inhibited vinculin conformation. In Part 3 of this dissertation, the interaction of activated vinculin with its binding partners is simulated. It is demonstrated that a talin VBS can only link vinculin prior to activation but can completely bind vinculin following activation. Vinculin activation by movement at D1 is shown to be necessary and sufficient for linking vinculin to actin filaments. Furthermore, simulation of F-actin caping by vinculin suggests that a second vinculin conformational change, releasing Vt from all vinculin head domains, facilitates effective capping of the actin filament. Three vinculinbinding sites on F-actin are predicted. These simulations demonstrate that indeed both talin and vinculin can exhibit molecular mechanosensing.

Advisor: Mofrad, Mohammad R. K.
Writing the Storyteller: Folklore and Literature from Nineteenth-Century France to the Francophone World

Nineteenth-century modernity, according to Walter Benjamin and other critics, kills storytelling. Instead of treating this as a real disappearance, I consider how writers continually reinvent this death to work through historically specific questions about tradition, memory, and cultural transmission. In nineteenth-century France, for example, the recurrent belief in the end of tradition prompted movements for folklore collection--like Napoléon III's decree for the preservation of poésies populaires--as well as broad reflections about the future of cultural expressivity. Nodier, Nerval, Mérimée, and Champfleury, all combined literary creation with folklore study for the eclipse of oral tradition was, paradoxically, the very foundation of modern literature as it was coming to be defined. Thus, Nerval appends to his Sylvie a folklore collection so as to mark the distance between the written and the oral, reaffirming literary modernity while mourning tradition. Though far-removed from folklore, Barbey d'Aurevilly's short stories and fragmented frames that impede narrative transmission also question the very possibility of storytelling. In addition to such formal innovations, writers also revisited earlier storytelling topoi. In the early eighteenth century, when Antoine Galland introduced Les Mille et une nuits to the West, Schéhérazade's life-or-death storytelling stood as commentary on the tyranny of audience demands as the patronage system was breaking down. But nineteenth-century writers returned to this ancient storytelling sultana to think about the demands of newspaper editors, growing readerships, and the transformation of literature into mass market entertainment. Finally, interest in folklore fades on the mainland, but debates about preservation of traditions and ownership of cultural goods--debates once linked to France's colonial projects--become central to post-colonial Francophone literature. Patrick Chamoiseau and other proponents of créolité spotlight the paradox of preserving Creole storytellers' legacies in writing--or in French. Assia Djebar even intersperses her bloody tale of a modern Algerian Schéhérazade with fragments from Galland's eighteenth-century text, foregrounding the question of what happens to the voice and to stories after a storyteller dies. In short, folklore has a long history of being a reference point for thinking about the very notions of literature or modernity that supposedly spell its demise. Literary depictions of storytelling tell a story less about oral culture than about literature itself. And concern about who is no longer telling stories often reveals a deeper cultural anxiety about who is now writing or reading stories.

Advisor: Paige, Nicholas
Odorant Detection by Biological Chemosensor Arrays

The antennules of many marine crustaceans enable them to rapidly locate sources of odorant in turbulent environmental flows. The antennules are typically flicked through the water, causing the animal to take spatially and temporally discrete odorant samples. A substantial gap in knowledge concerns how the physical interaction between chemosensory appendages and the chemical filaments forming a turbulent plume affects odorant detection and filters the information content of the plume. The research presented here is focused on using numerical models to simulate the flow of odorant-laden water around arrays of chemosensory aesthetascs, and the transport of odorant molecules to their surfaces, during a plume sampling event. The time-varying odorant flux signals generated during these events are of key interest, since they are the lens through which a plume tracking agent will perceive its odor environment./nSimulations of infinitely long arrays of sensory hairs indicate that there are likely to be design tradeoffs between maximizing the sharpness of an odorant flux signal versus the total amount of odorant mass detected. It is also clear that the duration of odorant flux during a sampling event similar to a flick downstroke is not long enough to enable detection of 0.6 mm wide odorant filaments by crustaceans such as lobsters, or by engineered chemical sensors currently available. This suggests that the return stroke and interflick pause may be critical if these animals are to detect fine-scale plume structures./nModels of hair arrays with a finite number of hairs reinforce the above conclusions, but because this more realistic geometry allows water to flow around the array of hairs in addition to through, it reveals additional behaviors that the infinite array simplification cannot capture. Fundamentally different trends in metrics describing the sharpness of the flux signal are observed for rapidly flicking, sparse arrays of hairs versus slowly moving, densely packed arrays. These surprising transitions are not well predicted by simple parameters describing only the fluid velocity field, pointing out the importance of explicitly modeling or observing odorant transport in addition to the flow of water./nA tomographic scan of a real aesthetasc array morphology, that of the spiny lobster P. argus, reveals substantial variation and deviation from any simple, idealized geometry, and 3D effects are likely to be important to its odorant sampling dynamics. Nonetheless, numerical simulations of an idealized version of P. argus morphology indicate that on average, odor-laden water is effectively channeled into the aesthetasc array as compared to a simple straight row of hairs. A simple row, however, still achieves greater odorant flux in most regards, again emphasizing differences in properties of the flow versus properties of passive scalar transport. Crustacean antennules might therefore best serve as starting iterations instead of optimal solutions for the design of engineered chemical sensor arrays for use on plume tracking robots.

Advisor: Stacey, Mark T
Applications of Magnetic Resonance to Current Detection and Microscale Flow Imaging

Magnetic resonance has evolved into a remarkably versatile technique, with major applications in chemical analysis, molecular biology, and medical imaging. Despite these successes, there are a large number of areas where magnetic resonance has the potential to provide great insight but has run into significant obstacles in its application. The projects described in this thesis focus on two of these areas. First, I describe the development and implementation of a robust imaging method which can directly detect the effects of oscillating electrical currents. This work is particularly relevant in the context of neuronal current detection, and bypasses many of the limitations of previously developed techniques. The approach rests on a resonant interaction between an applied radiofrequency field and an oscillating magnetic field in the sample and, as such, permits quantitative, frequency-selective measurements of current density with sensitivity near the threshold required for the detection of neuronal currents. The second part of this thesis focuses on novel methodology and applications for remotely detected magnetic resonance. Remote detection separates the encoding and detection steps of a traditional magnetic resonance experiment in both time and space, allowing for high-resolution time-of-flight imaging of very small volumes of flowing nuclei. Following a discussion of the recent developments in methodology and hardware design, I present a series of remotely detected imaging experiments within microporous bead packs and organic polymer monoliths. These techniques allow for the acquisition of high-resolution images which correlate velocity, spin relaxation, and time-of-flight in previously inaccessible microscale systems.

Advisor: Pines, Alexander
Clues in the Quest for the Invisible Universe

The particle nature of dark matter is one of the most longstanding mysteries of particle physics. In this dissertation I study several potential clues, both experimental and theoretical, in the quest to understand this invisible component of the universe. In the last few years, data collected by the PAMELA, ATIC, FERMI and H.E.S.S. experiments has revealed several unexpected features in the fluxes of electron and positron cosmic rays. I investigate an interpretation of these anomalies in terms of dark matter annihilating in our galaxy through a ``cascade'' into electrons or muons. I find good ability to reproduce the data whilst evading other experimental constraints. Inspired by these anomalies, I also investigate a simple framework for dark matter, with many similarities to QCD and well motivated in the context of dynamical solutions to the hierarchy problem. In this framework dark matter decays to standard model particles through a cascade, and I again find that it can provide an excellent fit to cosmic-ray data whilst evading other constraints. I consider the implications at the LHC and in future gamma-ray measurements./nMore generally, astrophysical and cosmological considerations have a strong interplay with models of physics Beyond the Standard Model and their implications for collider experiments. I investigate the cosmology of the ``Goldstini'' framework in this context. I find that the tensions seen in standard gravitino cosmology are relaxed, and that either gravitinos or goldstinos may be dark matter. I also find that such cosmologically preferred theories may also have the most striking signatures at colliders. The LHC has the potential to observe a ``smoking gun'' signal, in which the Goldstini framework is unambiguously confirmed.

Advisor: Nomura, Yasunori
An Investigation of Human Inductive Biases in Causality and Probability Judgments

People often makes inductive inferences that go beyond the data that are given. In order to generate these inferences, people must rely on inductive biases - constraints on learning that guide conclusion from limited data. This thesis presents a survey of three topics concerning people's inductive biases./nThe first part of this thesis examines people's expectations about the strengths of causes in elemental causal induction - learning about the relationship between a single cause and effect. These expectations are formalized as prior probabilities in a Bayesian model. We estimate people's prior beliefs concerning the variables involved in such causal systems using the technique of iterated learning and demonstrate that a Bayesian model using the priors which are produced by this experiment performs well in predicting human behavior./nThe second part attempted to capture people's inductive biases in causal relationships by expressing them in logical rules, and assign prior probabilities in a way that favors simplicity. Experimental data shows that it captured how people responded to causal reasoning tasks and helped explain the biases towards simpler representations./nThe final part of this thesis investigated the differences in inductive biases between people from North American and Chinese cultures concerning judgment discrimination - how people differentiate choices of higher and lower values. We found cultural differences in a wide range of domains. The findings demonstrate the extents to which cultural influences contribute to judgment discrimination. These results were attributed to the differences in inductive biases of the two cultures./nThese investigations combined to demonstrate the strong and broad influence of inductive biases on human reasoning, learning, judgments, and decision making. They suggest the importance of understanding these inductive biases in our attempt to understand human cognition.

Advisor: Peng, Kaiping
Griffiths, Thomas L
Design and Transient Analysis of Passive Safety Cooling Systems for Advanced Nuclear Reactors

The Pebble Bed Advanced High Temperature Reactor (PB-AHTR) is a pebble fueled, liquid salt cooled, high temperature nuclear reactor design that can be used for electricity generation or other applications requiring the availability of heat at elevated temperatures. A stage in the design evolution of this plant requires the analysis of the plant during a variety of potential transients to understand the primary and safety cooling system response. This study focuses on the performance of the passive safety cooling system with a dual purpose, to assess the capacity to maintain the core at safe temperatures and to assist the design process of this system to achieve this objective. The analysis requires the use of complex computational tools for simulation and verification using analytical solutions and comparisons with experimental data./nThis investigation builds upon previous detailed design work for the PB-AHTR components, including the core, reactivity control mechanisms and the intermediate heat exchanger, developed in 2008. In addition the study of this reference plant design employs a wealth of auxiliary information including thermal-hydraulic physical phenomena correlations for multiple geometries and thermophysical properties for the constituents of the plant. Finally, the set of performance requirements and limitations imposed from physical constrains and safety considerations provide with a criteria and metrics for acceptability of the design. The passive safety cooling system concept is turned into a detailed design as a result from this study./nA methodology for the design of air-cooled passive safety systems was developed and a transient analysis of the plant, evaluating a scrammed loss of forced cooling event was performed. Furthermore, a design optimization study of the passive safety system and an approach for the validation and verification of the analysis is presented. This study demonstrates that the resulting point design responds properly to the transient event and maintains the core and reactor components at acceptable temperatures within allowable safety margins. It is also demonstrated that the transition from steady full-power, forced-cooling mode to steady decay-heat, natural-circulation mode is stable, predictable and well characterized.

Advisor: Peterson, Per F
School District Policymaking Responses to Demographic Change in New Immigrant Destinations

Since the early 1990s, immigrants from Latin America and Asia have been arriving in parts of the United States that have had little recent experience with immigration. How school district leaders respond to these demographic changes has significant consequences for students, families and communities. Yet, there is little research on why and how school district leaders are coming to enact some policies, and not others, in response to their changing demographics. This study examines policymaking in two Midwestern, urban school districts experiencing the arrival of growing numbers of immigrant families, increasing ethnic-racial diversity, and rising levels of poverty. The study offers a unique perspective on school district policymaking by bringing together theoretical insights from urban regime analysis and interpretive policy analysis to connect the economic and political dynamics in school districts with district administrators' on-the-ground policymaking. Drawing on interviews, observation, and archival research, I trace policymaking in each district between 2000 and 2010./nI find school district administrators perceived the need to change their school districts to be responsive to new pupils. While middle-class parents' threat of exiting the districts confined administrators' attempts to do so, some school staff members', parents' and community leaders' organizing efforts created possibilities for district policymaking. Working with these limitations and possibilities, district administrators advanced policies that sought to respond to the new students in their schools. They did so by adding programs to the existing structure of schooling rather than restructuring schooling to meet the needs of new entrants and by framing policies to generate agreement from local stakeholders. The resulting policies were influenced by community actors but also shaped by district leaders' self-interests and particular concerns. This study illuminates school district decision-makers' interpretations of educational problems and policy solutions, their strategic actions, as well as their negotiations and compromises with community actors as central factors in school district policymaking in new immigrant destinations. Furthermore, this study contributes to urban regime analysis by offering greater insight into the processes of framing and interaction between community actors and school district administrators that produce important policy outcomes

Advisor: Coburn, Cynthia E
Tools for Single-Molecule Sequence Detection and Manipulation

The ability to strongly and sequence-specifically attach modifications such as fluorophores and haptens to double-stranded DNA is critical to a variety of single-molecule experiments. We present a practical guide to labeling internal sequences of double-stranded (ds) DNA molecules for single-molecule experiments. Since single-molecule experiments are diverse in their requirements, we focus on six approaches and consider the merits and drawbacks of each. By presenting a set of criteria relevant to single-molecule experiments (e.g. labeling yield, compatibility with cofactors), the guide provides a simple reference for selecting a labeling approach for given experimental constraints. We study one of these approaches, Peptide Nucleic Acids (PNAs), in detail. Slide stretching is used to optimize DNA-PNA binding and microfluidic trapping and stretching in a cross-slot demonstrates fluorescence-based sequence detection using PNAs on a long, roughly 50 kb, untethered DNA molecule. Optical tweezer experiments on DNA-bound PNAs further demonstrate that PNAs are versatile and robust sequence-specific tethers. Lastly, we assess the feasibility of studying DNA-protein interactions between stained DNA and fluorescently-labeled protein at the single-molecule level in the microfluidic cross-slot using the motor protein SpoIIIE.

Advisor: Muller, Susan J
The Transformation of Second-Order Linear Systems into Independent Equations

Linear second-order ordinary differential equations arise from Newton's second law combined with Hooke's law and are ubiquitous in mechanical and civil engineering. Perhaps the most prominent example is a mathematical model for small oscillations of particles around their equilibrium positions. However, second-order systems also find applications in such diverse areas as chemical engineering, structural dynamics, linear systems theory or even economics. Very large second-order systems appear, for example, in mathematical modeling of complex structures by finite-element methods./nIn general, any system of second-order equations is coupled. Each equation is linked to at least one of its neighbors and the solution of one of the equations requires the solution of all equations. The "classical decoupling problem" is concerned with the elimination of coordinate coupling in linear dynamical systems. The decoupling transforms the system of equations into a collection of mutually independent equations so that each equation can be solved without solving any other equation. In "The Theory of Sound" in 1894, Lord Rayleigh already expounded on the significance of system decoupling. Since then, the problem has attracted the attention of many researchers./nMathematically, the system of differential equations is defined by three coefficient matrices. The equations are coupled unless all three matrices are diagonal. The "classical decoupling problem" is thus equivalent to the problem of simultaneous con- version of the coefficient matrices into diagonal forms. Current theory emphasizes simultaneous diagonalization of the coefficient matrices by equivalence or similarity transformations. However, it has been shown that no time-invariant linear trans- formations will decouple every second-order system. Even partial decoupling, i.e. simultaneous conversion of the coefficient matrices into upper triangular forms, is not ensured with time-invariant linear transformations./nThe purpose of this work is to present a general method and algorithm to de- couple any second-order linear system (possessing symmetric and non-symmetric co- efficients). The theory exploits the parameter "time," characteristic of a dynamical/nsystem. The decoupling is achieved by a real, invertible, but generally nonlinear map- ping. This mapping simplifies to a real, linear time-invariant transformation when the coefficient matrices can be simultaneously diagonalized by a similarity transformation. A state-space reformulation of the mapping is also derived. In homogeneous systems the configuration-space decoupling transformation is real, linear and time-invariant when cast in state space. In non-homogeneous systems, both the configuration and associated state transformations are nonlinear and depend continuously on the excitation. The theory is illustrated by several numerical examples. Two applications in earthquake engineering demonstrate the utility of the decoupling approach.

Advisor: Ma, Fai