VictorJuiz/thesis huggingface dataset:
A Gene Ontology Approach to Autism Spectrum Disorders Through the Window of Hypoxia

Autism spectrum disorders (ASDs) are fundamentally social and behavioral disorders with a range of comorbidities and social and financial impacts. Recent studies have estimated ASDs to have a heritability of around 50%, while indicating that there is also a significant environmental component. It is clear that neither genes nor environment in isolation can explain the etiology of autism. Large-scale genomics studies have identified a set of genes that have been shown to have a high association with ASDs. In addition, recent studies have identified certain environmental factors associated with an increased risk for developing ASDs, with pre- and perinatal hypoxia as one of the more salient factors. However, the interaction between genes and environment through the lens of hypoxia has yet to be evaluated.
This study aimed to find and characterize the intersection between genes associated with autism and the genes associated with the cellular response to hypoxia. Every gene in a database of autism-associated genes was interrogated, through a thorough literature search and comparison with a set of microarray data, for evidence of its regulation by hypoxia. This process created a set of genes associated with both autism and the hypoxia response. A statistical test for overrepresentation indicated that hypoxia-regulated genes were overrepresented in the ASD database; the proportion of ASD genes also responsive to hypoxia was roughly twice what would be expected by chance. Functional and network analyses then showed that specific biological functions were overrepresented in the ASD/Hypoxia gene set, indicating that the number of hypoxia-regulated genes among all ASD genes, were indeed greater than would be expected by chance, and fell into specific networks and pathways. This lays the groundwork for functional characterization of variations in these genes in a population affected with autism as well as a neurotypical population. With a better understanding of how variations in certain genes can affect an individual’s response to a potential hypoxic event, researchers and medical professionals alike can open up better therapeutic avenues for children and adults affected by ASDs.

Keywords:  Department of Biology
Biology
Psychiatry and Behavioral Sciences
Neurobiology
Genetics
Thesis
Advisor: O'Hara Ruth
Hallmayer Joachim
Fernald Russell
A Generation Without Memories: Understanding Pinochet's Dictatorship Among Chilean University Students

Through this project, I investigated perceptions and understandings of Augusto Pinochet’s dictatorship (1973-1989) among university students in Chile, a generation that did not live through the dictatorship yet still interacts with those who did. The main framework for the analysis is that of generations, drawing primarily on Karl Mannheim’s essay “The Sociological Problem of Generations” (1923) and engaging with his ideas of generational location and generation units. As memory is an important discourse surrounding the dictatorship in current Chilean society, I also engage with literature about memory, including Pierre Nora and Andreas Huyssen. In performing this research, I spent summer, 2016 in Santiago, Chile, interviewing students from La Universidad de Chile and La Universidad Católica while also sitting in on a class at La Universidad de Chile and exploring sites of memory. I argue that, not experiencing the dictatorship directly but still having their lives shaped by those who did, university students experience a unique generational location, one that divides itself into generational units due to the controversy over the dictatorship and political spaces of their universities. These students still engage in the discourse of memory surrounding the dictatorship, particularly emphasizing that it can’t be forgotten. However, their temporal distance from the dictatorship creates an emotional distance as well, something that enables them to acknowledge the dictatorship while still focusing on important current issues. The generation of university students therefore illuminates Chile’s process of reconciliation and moving forward while still interacting with the past and the polarization it created.

Keywords: generations
memory
chile
pinochet
students
Stanford Department of Anthropology
Thesis
A Model of Firm Formality and Tax Evasion

Rampant informality in developing economies proves to be a major obstacle to public revenue collection, limiting investment in crucial public infrastructure. The model presented in this paper sheds light on inter-firm mechanisms that motivate firms to either transact formally or transact informally and evade taxes. The formulation allows us to predict comparative statics on a variety of parameters, including the effective tax rate, the likelihood of audit, the penalties levered against firms caught transacting informally, and the distribution of firm sizes in the economy. Empirical support for each of these predictions is discussed. In particular, the model provides theoretical underpinnings for predicting the effect of multinational entry and trade liberalization on the size of the informal sector—two questions which have hitherto been largely neglected in the literature.

Keywords:  Department of Economics
Stanford Department of Economics
Thesis
Advisor: Jackson Matthew
“A Secret System of Caves and Conduits”: Patterns of Thought in W. H. Auden’s Poetry About the Natural World

This paper analyzes recurring themes and patterns of thought in the nature poetry of W. H. Auden. This topic, typically neglected in most Auden criticism, focuses on the themes from Auden's nature poetry that persist throughout his poetic career. Divided into three sections--poetry about mines and mining, poetry about the body and the natural landscape, and poetry about places unknown--this paper argues that a more complete reading of Auden occurs when one examines his work in light of the subject, the natural world, rather than in a chronological way, as in most criticism. In combining the critical approaches of Edward Mendelson and John Fuller, this paper hopes to examine an atypical topic in a unique manner. In conclusion, Auden's poetry about the natural world keeps returning to the same concerns and anxieties. Though Auden is a poet characterized in part by the way that his poetry changes throughout his life, this paper examines how these recurring themes appear repeatedly in Auden's poetry about the natural world.

Keywords:  Department of English
W. H. Auden
Auden
nature
poetry
nature poetry
English
landscape
mines
Rookhope
Department of English
natural world
Thesis
Advisor: Jenkins Nicholas
Greene Roland
A structure–function analysis of the C. elegans γ-TuSC protein GIP-1

The microtubule cytoskeleton is spatially reorganized from the centrosomes to new subcellular sites during cell differentiation in many cell types, yet the importance of possessing distinct microtubule organizing centers (MTOCs) and the mechanisms governing MTOC reassignment remain poorly understood. Centrosomal and non-centrosomal microtubules are nucleated by a conserved nucleating complex, the γ-tubulin small complex (γ-TuSC), which is comprised of GIP-1/GCP3, GIP-2/GCP2, and TBG-1/γ-tubulin. Tissues of the nematode C. elegans display dualistic MTOC localization, in which γ-TuSC proteins are capable of localizing to both MTOCs, but do so at distinct times in development. This makes C. elegans an ideal system for studying the process of MTOC reassignment. We have proposed a model of MTOC reassignment whereby regulation of γ-TuSC protein localization dictates the sites of functional MTOCs. The gip-1 locus is predicted to encode multiple isoforms, presenting the possibility that differential expression of GIP-1 isoforms may play a role in this process. We therefore set out to investigate the role of GIP-1 in the developing C. elegans intestine. In this tissue, MTOC proteins are translocated from the centrosomes to the future apical cell membrane following their final round of divisions, resulting in a relatively simple dichotomy of MTOC function. Because a complete loss of functional MTOCs leads to an early arrest in embryonic development, we adapted an endogenous protein degradation pathway to deplete GIP-1 exclusively in the developing intestine around the time of MTOC reassignment. We found that GIP-1 is required for normal apical localization of GIP-2 and TBG-1, but not for apical localization of microtubules or the polarity protein PAR-3. Embryos depleted of intestinal GIP-1 have fewer and abnormally enlarged intestinal nuclei as compared to control embryos. Using a structure–function approach to identify GIP-1 domains required for MTOC localization and function, we have identified two domains (GIP-1[N], GIP-1a[G+C]) that localize to centrosomes but not apical membranes. Together, these results demonstrate that GIP-1 is vital for normal mitosis in the early embryonic intestine, and highlight the presence of redundant microtubule nucleating and anchoring mechanisms in this tissue. Furthermore, we provide the first evidence that GIP-1 may localize to centrosomal and apical membrane MTOCs through distinct protein domains. Future efforts focused on understanding the consequences of GIP-1 depletion for microtubule dynamics will greatly inform our understanding of the role of GIP-1 in regulating the microtubule cytoskeleton. With aberrant microtubule organization linked to some epithelial cancers and invasive cell behavior, understanding this basic cellular process may inform future efforts to inhibit cancer proliferation and metastasis.

Keywords:  Department of Biology
biology
caenorhabditis
elegans
cytoskeleton
microtubule
microtubule organizing center
MTOC
γ-TuRC
γ-TuSC
γ-Tubulin
gip-1
GCP3
gip-2
GCP2
Thesis
Advisor: Feldman Jessica
Stearns Tim
The academic resilience of Latinas in STEM fields [electronic resource]

This dissertation adds to the literature on Latinas in science, technology, engineering, and mathematics (STEM) fields. Furthermore, it is one of the few studies to focus on Latinas in STEM in graduate school and in the workforce. Each of the three qualitative studies in this dissertation uses academic resilience as a framework to explore Latinas' journeys through the STEM pipeline, identifying protective factors or sources of support and the risk factors or challenges they encountered. In the first study, twenty Latina graduate students were interviewed about their experiences from early childhood through their time in graduate programs in STEM fields. The participants were master's or doctoral students at the same private elite university at the time of the interviews. The following were some of the major themes that were identified: earliest STEM experience, special teachers and mentors, community college experiences, decision to attend graduate school, familismo, graduate school faculty advisors/mentors, sense of belonging, and ethnic/cultural identity. The findings point to four potential areas for intervention. In the second study, twelve Latinas were interviewed about their academic and career trajectories in STEM fields. The participants had received their doctoral degrees or were employed in STEM fields at Research I institutions. Some of the risk factors or challenges that these women faced included: their families' gendered expectations, undocumented status, inaccessible research advisors, and cultural taxation. The protective factors or strengths and support systems that helped participants overcome these challenges included: family support, undergraduate research experiences, and access to academic mentors and diversity offices. In addition to the risk and protective factors identified, the Happenstance Learning Theory is used to describe participants' academic and career paths in STEM. The third study examined Latinas' experiences with microaggressions and discrimination in STEM fields and explored how experiences varied by skin tone and field of study. This study combined the participant samples of the first two studies and included analysis of survey data and interview responses. Survey results indicated that participants with lighter skin tones reported fewer experiences with microaggressions. In addition, women in science fields reported fewer microaggressions than the women in engineering fields. Responses to microaggressions included ignoring the events, confronting the offender, and relying upon protective factors such as external sources of support. Findings draw attention to colorism and phenotyping as barriers to success in STEM fields. Together, the three studies in this dissertation confirm previous findings about Latinas in STEM fields and identify new risk and protective factors.

Keywords: Education.
Advisor: Padilla Amado M. primary advisor. Thesis advisor
Barron Brigid advisor. Thesis advisor
Blikstein Paulo
Acting the exegete [electronic resource] : homeric quotation and interpretation in imperial literary symposia

This doctoral dissertation analyzes the surprisingly common presence of Homer in imperial literary symposia, i.e. fictionalized dinner conversations in the early Roman Empire, where characters often cite the already ancient poetry. Unlike past studies of text reuse at these dinner parties, this dissertation takes the setting seriously and treats these quotations from the standpoint of performance. Through the societally approved use of Homer the elite justifies its privileged position and establishes a hierarchy within itself, and these texts either accept this ideology or reject it through parody. Such an approach not only explains the role of Homer at table, but also why learning how to present and interpret poetry is a vital skill cross-culturally.

Keywords: Classics.
Advisor: Martin Richard P. primary advisor. Thesis advisor
Bowie Ewen advisor. Thesis advisor
Peponi Anastasia-Erasmia advisor. Thesis advisor
Active nanophotonics [electronic resource] : inverse design and strained germanium light emitters

Integration of optical devices into modern CMOS electronics processes offers a wide range of opportunities and challenges for optical design. Modern foundry processes provide an enormous amount of design freedom in feature shapes and sizes; such freedom is rarely fully exploited by traditional human-directed design methods. At the same time, fabrication considerations greatly limit the material selection available for on-chip optics, making integration of most existing light sources infeasible. The first part of this dissertation focuses on the use of strained germanium (Ge) as a Si-compatible light source. While Ge is naturally an indirect bandgap material and thus poorly suited to light emission, application of tensile strain can be used to modify the bandstructure of Ge, greatly increasing light emission efficiency. To this end, we present design and experimental analysis of an optical device which integrates 2.4% uniaxial tensile strain, a single-material pseudo-heterostructure, and a Q > 2,000 cavity in a Ge-on-insulator material system. The second part of this dissertation presents a method for computational inverse design of active optical devices. Rather than relying on a small number of human-chosen design parameters to determine the structure of the device, inverse design begins with an arbitrary structure and then adjusts all available degrees of freedom to create a working device. To illustrate the effectiveness of this method, we present inverse-design of an all-optical switch, resulting in a device that uses 22x less power, 2.5x less power density, and 8x less device area than similar devices reported in recent literature.

Keywords: Electrical Engineering.
Advisor: Vuckovic Jelena primary advisor. Thesis advisor
Miller D. A. B. advisor. Thesis advisor
Saraswat Krishna advisor. Thesis advisor
Adaptive model reduction to accelerate optimization problems governed by partial differential equations [electronic resource]

Optimization problems constrained by Partial Differential Equations (PDEs) are ubiquitous in modern science and engineering. They play a central role in optimal design and control of multiphysics systems, as well as nondestructive evaluation and detection, and inverse problems. Methods to solve these optimization problems rely on potentially many numerical solutions of the underlying equations. For complicated physical interactions taking place on complex domains, these solutions will be computationally expensive---in terms of both time and resources---to obtain, rendering the optimization procedure difficult or intractable. This dissertation introduces a globally convergent, error-aware trust region algorithm for leveraging inexpensive approximation models to greatly reduce the cost of solving PDE-constrained optimization problems in increasingly complex scenarios. While the trust region theory is general, in that it is agnostic to the particular form of the approximation model, provided it possesses certain properties, this work employs reduced-order models based on the method of snapshots and Proper Orthogonal Decomposition (POD). The trust region algorithm proceeds by progressively refining the fidelity of the reduced-order model while converging to the optimal solution. Thus, the reduced-order model is trained exactly along the optimization trajectory, circumventing the task of training in a potentially high-dimensional parameter space. The proposed method is shown to find the optimal aerodynamic shape of a full aircraft configuration in about half the time required by accepted methods. The proposed error-aware trust region algorithm is extended to handle the case where uncertainties are present in the governing equations. In such situations, the goal is to find a design or control that is risk-averse with respect to some quantity of interest. The objective function and constraints in these problems usually correspond to integrals of quantities of interest over the stochastic space, which will inevitably require many solutions of the underlying partial differential equation. For this reason, dimension-adaptive sparse grids are combined with reduced-order models to define an inexpensive approximation model, which is wrapped in the error-aware trust region framework to ensure convergence to the optimal risk-averse solution. This framework is demonstrated on a model problem from computational mechanics and shown to be several orders of magnitude faster than existing methods.

Advisor: Farhat Charbel primary advisor. Thesis advisor
Persson Per-Olof
Saunders Michael A. advisor. Thesis advisor
Adaptive particle filter in hidden Markov models [electronic resource] : a new approach and its applications

Hidden Markov models have been widely used in many fields, such as bioinformatics, econometrics, targets tracking and population genetics. The particle filter, also known as sequential Monte Carlo method, is a powerful tool for latent state filtering of the hidden Markov models. In this thesis, we propose a new methodological advancement, the adaptive particle filter, for the problem of joint parameter estimation and latent state filtering of hidden Markov models. The adaptive particle filter is a hybrid algorithm that combines particle filter and a new MCMC scheme, called sequential substitution, to provide an efficient estimate for function of the parameter and latent state, and further give a consistent estimator of Monte Carlo standard error. Specifically we approximate the posterior distribution of the parameters and latent states by a representative population of N parameter atoms, in which each parameter atom contains P weighted 'particles' where each particle consists of a latent state generated by particle filter. Sequentially updated by the sequential substitution MCMC scheme, the representative population converges weakly to i.i.d samples from the target posterior distribution in the limit of infinite many iterations. By representing the adaptive particle filter as a standard sequential substitution on the extended space of joint parameter atoms and latent state particles, we establish the asymptotic normality of the estimate for the functional posterior mean and the consistency of the Monte Carlo standard error estimator based on the theoretical result of sequential substitution. In addition, we propose the Markov chain restart to deal with the case of long observed time series. Markov chain restart suggests using the representative population of parameter and latent state generated by adaptive particle filters up to time t as approximation of posterior distribution; then particle filters performed for newly proposed parameter atoms at time t + △t can start from the middle of time t. Markov chain restart greatly reduces the computation cost of adaptive particle filters and enables performing more sequential substitution iterations. It also increases the acceptance rate of the MCMC update in adaptive particle filters. Furthermore we demonstrate the effectiveness of adaptive particle filter and Markov chain restart algorithm with simulation results on an example of a highly nonlinear hidden Markov model. Finally as an application in econometrics, we apply our approach on parameter estimation and latent volatility filtering for the jump-diffusion models using both asset returns and option prices.

Keywords: Statistics.
Advisor: Lai T. L. primary advisor. Thesis advisor
Walther Guenther advisor. Thesis advisor
Wong Wing Hung advisor. Thesis advisor
The adherens junctions control susceptibility to staphylococcus aureus α-toxin [electronic resource]

Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial alpha-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for alpha-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known alpha-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus alpha-toxin. We find that despite being injured by alpha-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7−/− mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential non-essential host target to reduce S. aureus virulence during epithelial infections.

Keywords: Microbiology and Immunology.
Advisor: Amieva Manuel primary advisor. Thesis advisor
Falkow Stanley advisor. Thesis advisor
Monack Denise M. advisor. Thesis advisor
Relman David A. advisor. Thesis advisor