VictorJuiz/thesis huggingface dataset:
Forces generated by T cells augment antigen signaling [electronic resource]
Keywords: Biophysics.

Activation of T cells through TCR binding to antigen is a highly sensitive process. Recent evidence suggests triggering of the T cell receptor (TCR) integrates both binding kinetics and mechanical forces. To both measure and apply mechanical forces in real-time during T cell activation, I triggered T cells using a novel application of atomic force microscopy (AFM). Using cantilevers coated with antigen, I was able to deliver mechanical and chemical stimulation to T cells. T cells generate patterns of pushing and pulling forces during activation through rapid turnover of actin as well as myosin contractility. I demonstrate how the strength and duration of phases of force generation are regulated by the action of actin capping and severing proteins. In particular, I highlight the role of cofilin in generating pull forces and how it's activity can be regulated by Ca2+ levels. Loss of cell-generated forces through disruption of the cytoskeleton abrogated signaling. Emulation of these lost forces through movement of the AFM cantilever rescued signaling in these F-actin inhibited T cells. In addition, reducing the forces felt by T cells through force clamping of the cantilever decreased the sensitivity of T cells to low antigen concentrations. My work, taken with other findings, show that T cells generate forces during activation and a combination of these mechanical forces and biochemical ligation is required for optimal T cell activation. These studies suggest a mechanical—biochemical feedback loop in which TCR-triggered T cells generate forceful contacts with antigen-presenting cells to amplify signaling through TCR-pMHC engagements.
Fourier collocation methods for unsteady flows [electronic resource]
Keywords: Mechanical Engineering.

Fully resolved CFD simulations of unsteady aerodynamics are still too expensive to be deployed during the engineering design process. Most aerodynamic-design studies, however, only require knowledge of the steady-state flow field, not the transient behavior that precedes it. Collocation methods in time, such as the time-spectral method and the harmonic-balance method, obviate the need to model transients by directly solving for the steady state --- offering significant cost savings. They do so by using Fourier and Fourier-like basis functions to represent the flow field at a handful of points in time. The harmonic-balance method assumes the underlying spectrum is tonal, i.e. dominated by a finite set of known frequencies. This dissertation presents the discovery of "inadmissible frequency sets, " which cause the harmonic-balance method to fail unconditionally. A mathematically grounded strategy for avoiding such inadmissible sets is also proffered. Selecting harmonic-balance time instances using this new approach is shown to eliminate the presence of corrupted solutions and allows the method to admit all possible frequency sets. This dissertation will also address the use of collocation methods in time to model flow fields where the oscillatory character of the steady state is unknown a priori. Specifically, a new algorithm that allows the harmonic-balance method to be used with unknown frequency content will be discussed. In addition, two new algorithms will be presented that allow the time-spectral method, which is used to model periodic flows, to be used in cases where the underlying periodicity is either unknown or naturally occurring due to stable limit-cycle oscillations.
France and the Internationalization of Security: A Conceptual History of Security During the Interwar Years (1919-1933)
Keywords:  Fisher Family Honors Program in Democracy
France
security
interwar
1920s
French
Thesis

During the interwar period in France (1919-1933), the meaning of “security” evolved from a very narrow summation of French desires for territorial guarantees against Germany, to a broad conception that concerned a wide array of values and crossed national and regional boundaries. This can be explained by new domestic concerns in France, and the internationalization of the concept through the League of Nations. In France, overwhelming territorial and military anxieties after the war necessitated the emergence of a new language of security to convey these fears. In the wake of war, the language of security predominantly referred to tangible guarantees. Fears over French national decline and the falling birth rate, however, brought the French family and cultural attitudes into the realm of security concerns. As the French government shaped policy to tackle cultural concerns as well as military affairs, cultural and military issues became conflated in a more expansive definition of national security. Internationally, the language of security was slowly adopted into the discourse of the League of Nations through several negotiations over the Treaty of Mutual Guarantee (1923), the Geneva Protocol (1924), and the Locarno Treaty (1925). This encouraged nations to develop their own specific national security policies. By the start of the 1930s, security had become both more specific—as each nation shaped their own security policy—and gained a plurality of meanings, as it was used to refer to regions as well as nations, and to all national values—be they military, cultural, economic, or political.
From Ansel Adams to Instagram: Tracing Inflection Points in the American Relationship with Nature via the National Parks
Keywords: Program in Science Technology and Society
Stanford University
STS
National parks
Nature and technology
Thesis

This thesis asks what technological and corresponding ideological innovations caused the American relationship with nature to shift over time. It uses the national parks as an isotope, akin to a dye that measures the changes in attitude and cultural norms. While convention approaches nature as a static entity, I argue that the American relationship with nature is dynamic. Specifically, my thesis explores four inflection points, and explains how the American understanding of “nature” pivoted at each of these points —the creation of the National Park Service and zone photography, the construction of the Interstate Highway System and invention of Winnebagos, the utilization of satellite imagery to capture Earth from space, and the popularization of social media—with an increased emphasis placed on the investigation of social media. I rely upon analysis of relevant environmental literature and a survey (n=564) to draw conclusions about the manner in which our interactions in the parks have transformed. Primary research and analysis of the literature show an increasingly democratic association to the natural world and an enhanced but not universal appreciation for the ecological impacts of nature in the present day. There appears to be a tradeoff between democracy and the sublime in the national park experience.
From opportunity to strategy [electronic resource] : how executives create a system of interdependent strategic decisions
Keywords: Management Science and Engineering.

Strategy formation, the process by which executives decide on the unique set of activities to create and capture value, can be the difference between a firm capitalizing on a promising new opportunity or wasting a lot of resources on the new space only to watch a competitor succeed. Prior research on strategy formation has shown that it can be particularly difficult for executives in entrepreneurial settings due to the high levels of novelty and complexity that executives must tackle. As a result, effective strategy formation processes should combine the benefits of learning from experience and forming integrated understandings, yet prior research has not focused on how to effectively form strategy when both novelty and complexity are an issue. This leaves us unable to identify which processes lead to winning strategies in entrepreneurial settings. Moreover, prior work has been at too high a level to discern what the executives' roles in forming effective complex systems of activities are given the cognitive limitations they face. This dissertation addresses these gaps with three tightly linked studies. The first study is a literature review and agenda setting piece that categorizes prior work into a novel framework around the fundamental tension between novelty and complexity. The second study is an inductive case study of six two-side market ventures as they struggle to find coherent strategies to capture new opportunities. The third study builds on this by leveraging simulation methods to compare the strategic formation process discovered in the case study with other complex problem solving processes and explore the environmental conditions that make each most useful. Together, the studies of this dissertation offer rich theory regarding how executives can form successful strategies for their firms in entrepreneurial settings, paying particularly close attention to how they handle interdependence in their strategic decisions. Overall, this research contributes to the literatures on strategy, entrepreneurship, and organizational theory.
From water to wine [electronic resource] : the transnational emergence of Angola's middle class in the South Atlantic
Keywords: Anthropology.

This dissertation explores the transnational emergence of an Angolan middle class in the Southern Atlantic. It looks at how short term migration between Angola and Brazil facilitates class mobility, as (largely young) Angolans access education and training not available at home and return with new skills. It considers the effect of these migrations on democratization and peace in Angola, some 15 years after the civil war ended. Based on 18 months of ethnographic fieldwork in both Angola and Brazil, the dissertation develops the idea of 'capitalismo selvagem' ('jungle capitalism') as a way of approaching everyday life after a transition from socialist to capitalist economic norms, and that practice of 'trickster economics' as a strategy of surviving and thriving. It gives attention to scent, and to the use of perfume in Angola and across the Southern Atlantic, arguing that the olfactory plays an important role in helping individuals place one another sociology-econmically, and also allows people to access one aspect of aspirational lives. Drawing on fieldwork undertaken whilst a music teacher in a private primary school, as well as as a university lecturer and member of the Angolan Scouts, the thesis considers how different kinds of social capital are acquired and performed, many of which locate individuals in a sphere that is internationally legible as being that of the 'global middle class'. Structures of and for intellectual work in the nascent higher education sector, strategies for community improvement and development, and the consolidation of everyday life in peace, are all areas that are ethnographically and theoretically developed. The dissertation also argues for attention to that which is beautiful in countries such as Angola where many outsiders seem to focus so much on suffering and deprivation. Whilst it is important not to overlook the very real challenges that people face, this work argues that everyday happiness is just as valuable a subject of scholarly enquiry.
The front asymptotics for the non-local KPP equation [electronic resource]
Keywords: Mathematics.

Kolmogrov-Petrovskii-Piskunov (KPP) equations are a class of non-linear parabolic equations which are used to model various biological, ecological, and physical phenomena. In particular it is used as a model for population dynamics. Originally it was studied by Kolmogrov, Petrovskii and Piskunov in 1937. This thesis investigates one type of integro-differential equation: the non-local KPP equation, used in population dynamics. For the non-local KPP equation, we prove estimates regarding the front location and in particular introduce logarithmic correction. We also do a non-rigorous analysis to show the profile convergence of solution to the travelling wave.
The function and evolution of RNA editing in Drosophila [electronic resource]
Keywords: Genetics.

Many important modifications are used to tweak genomically-encoded information as it is being transcribed and translated. One type of RNA modification, adenosine-to-inosine (A-to-I) RNA editing, is a process in which the adenosine deaminase acting on RNA (ADAR) proteins catalyze the conversion of certain adenosines to inosines, which are treated by the cellular machinery as guanosines. A-to-I RNA editing is essential for the neurological and immune well-being of many animals, and it is a widespread process: There are thousands to millions of editing sites across the transcriptomes of flies and humans, respectively. However, it is largely unknown which sites are important, what their individual functions are, and what makes particular adenosines edited. In this dissertation, Drosophila is used as a model organism to explore key questions about the function and evolution of RNA editing, and the characteristics of RNA editing substrates. First, in Chapter 2, I describe the generation and characterization of an ADAR deaminase inactive point mutant fly and find that Drosophila ADAR has both neurological and immune RNA editing-dependent functions. Secondly, in Chapters 3 and 4, I explore the characteristics of edited RNA. I describe a computational pipeline used to predict the regulatory sequences base-paired to regions that undergo RNA editing and derive rules about RNA editing substrates, through an examination of the changes in RNA sequence and structure associated with changes in RNA editing across lines of Drosophila melanogaster (Chapter 3), and across Drosophila species (Chapter 4). Furthermore, a large fraction of nonsynonymous and noncoding editing events are evolutionarily constrained and therefore likely functionally important. Finally, in Chapter 5, I explore the functions of individual RNA editing events in vivo, through the generation and characterization of RNA editing event-specific mutants. These mutants validated some RNA structure predictions from Chapter 3. Furthermore, they do not have the severe phenotypes of the Adar mutants described in Chapter 2, suggesting that the editing events perturbed here could have subtle or redundant functions. Overall, this dissertation provides insights into the function and evolution of RNA editing events and their substrates.
Functional Analysis of a Mip120 Mutant in Drosophila
Keywords:  Department of Biology
Biology
Mip120
MuvB
DREAM Complex
Myb
cancer
Thesis

The Myb (Myeloblastosis) family of proteins in humans is responsible for many forms of cancer and is implicated in a cell cycle pathway. A group of five proteins called MuvB (Multivulval Class B) interacts with Myb to form the active Myb-MuvB-Core complex. The MuvB core complex also interacts with three other proteins to form the regulatory DREAM (DP, RBF, E2F2, and Myb-interacting proteins) complex. Using Drosophila melanogaster, we analyzed a mutant of Mip120 (Myb-interacting protein 120), one member of the MuvB core complex for its ability to associate with the other members of the complex. We created a Mip120 mutant because we believe a region of Mip120 that we identified and deleted may contain a serine-threonine phosphorylation site and be involved in associating with other members of the complex. Mip120 can bind to DNA and associate with Myb and RBF (Retinoblastoma-family) but it is unclear how Mip120 associates with other members of the complexes. A Mip120 mutant with a deletion in the identified region (Mip120-del136-145) was created and overexpressed in vivo to compare phenotypes and viability with wild-type Mip120 overexpression. Co-immunoprecipitation was used to determine the ability of Mip120-del136-145 to associate to other members of the complexes. The region deleted from Mip120-del136-145 was shown to have altered lethality when overexpressed in vivo but does not affect association to complex members p55 Caf1, Mip130, and Mip40 in the presence of endogenous Mip120 in vitro. These results opens new avenues of investigation into how the Myb-MuvB-Core and DREAM complexes regulate cell proliferation and differentiation.
Functional implications of flexibility in the mammalian middle ear [electronic resource]
Keywords: Mechanical Engineering.

The middle ear in terrestrial vertebrates exists to transmit acoustic signals from the environment into the fluid-filled inner ear, where they are transduced into electrical signals that can be interpreted by the brain. In mammals, the middle ear is uniquely characterized by the presence of three distinct ossicles, which are suspended in the air-filled middle ear cavity by a combination of ligaments, tendons, and in some cases, thin bony structures. The functional benefits of the flexibility afforded by this complicated anatomy are still debated. The goal of this work is to test the role of this flexibility by using a combination of experimental and computational methods to systematically remove sources of flexibility in the mammalian middle ear chain and measure the effects of these modifications. Three main studies are discussed. First, the middle ear ossicles in human specimens were replaced with artificial prostheses, which removed both the joint flexibility and the flexibility inherent in the bones themselves. Second, the ossicular joints in the human middle ear were sequentially fused in order to examine their role in more detail. Finally, sound transmission was characterized in the mouse middle ear as a case study of a mammalian middle ear with dramatically different characteristics and sources of flexibility than the human middle ear. In all three studies, a combination of experimental 3D vibration measurements and finite element modeling was used to explore the middle ear system and modifications. Experiments and simulations were performed in both the frequency domain as well as in the time domain to understand the role of middle ear flexibility in transmitting complex impulsive sounds in addition to pure sinusoidal signals. The results showed that while modifying the human ossicular chain with prostheses had no significant effect, on average, in the frequency domain, fusing the ossicular joints caused a significant increase in peak stapes velocity in response to an impulsive stimulus. In the mouse, the flexibility of ossicular joints appears to be less important than that of the malleus bone itself. These findings have interesting implications for both clinical questions relating to pathologies that increase ossicular joint stiffness as well as the basic scientific understanding of sound transmission through the human and mouse middle ears.
Fundamental performance limits of analog-to-digital compression [electronic resource]
Keywords: Electrical Engineering.

Analog-to-digital conversion is a fundamental operation in many electronic and communication systems. The principles describing the information loss as a result of transforming from continuous-time, continuous-amplitude signals to a sequence of bits lie at the intersection of sampling theory and quantization or lossy source coding theory. Classic results in sampling theory established the Nyquist rate of a signal, or, more precisely, its spectral occupancy, as the critical sampling rate above which the signal can be perfectly reconstructed from its samples. However, these results do not incorporate the quantization precision of the samples. Since it is impossible to obtain an exact digital representation of any continuous-amplitude sequence of samples, any digital representation of an analog signal will introduce some error, regardless of the sampling rate. This raises the question as to when sampling at the Nyquist rate is necessary. In other words, is it possible to achieve the same or better performance by sampling at a rate lower than Nyquist without any further assumptions about the input signal other than a limited bitrate to describe the samples? When only quantization or limited bitrate is considered, the minimal distortion in encoding a random process subject to this bitrate limitation is described by Shannon's distortion-rate function (DRF). However, this DRF is given in terms of an optimization over a family of conditional probability distributions subject to a mutual information constraint and does not explicitly incorporate sampling and other inaccuracies arising from signal processing with a limited time-resolution. In fact, the standard achievability scheme in source coding assumes that the encoder can access the realization of the analog process, or expand it with respect to an analog basis function, without any restriction on the time resolution. Since this restriction often occurs in practice, the following question arises: Given a finite number of samples per unit time from the analog process, what is the minimal distortion in recovering it from a digital encoding of these samples subject to a bitrate constraint ? The goal of this thesis is to address the two questions posed above by characterizing the minimal distortion that can be attained in recovering a random process using the most general form of quantization applied to its samples. By explicitly incorporating sampling into the minimum distortion optimization, the characterization of the minimal distortion bridges the missing theoretical gap between sampling theory and lossy data compression theory. By taking into account signal sampling and the associated distortion, the resulting distortion function generalizes and unifies sampling theory and source coding theory.
Gender identity shapes preferences for health and environmental behaviors [electronic resource]
Keywords: Sociology.

Relative to women, men are less likely to engage in many health-promoting and pro-environmental behaviors. In this dissertation, I argue that men avoid healthy and sustainable practices in order to demonstrate their masculinity and distance themselves from feminine-typed domains. Across three papers I draw on survey and experimental methods to examine the role of masculinity maintenance and gender attitudes on health and environmental preferences. Chapter 1 provides causal evidence that men's gender identity maintenance efforts negatively affect health-related preferences through two pathways: first, unhealthy choices that express masculinity, and secondly, elevated blood pressure in response to gender identity threats. In chapter 2, I show that men's lower levels of environmental concern can be explained by differences in gender beliefs and perceptions about the masculinity and femininity of pro-environmental views. Finally, in chapter 3 I test a potential intervention strategy intended to increase men's rates of sustainable practices by drawing on masculine-typed frames that fit more closely with widely held definitions of masculinity. Overall, this research shows how men's gender identity maintenance can shape preferences for health and environmental behaviors.