VictorJuiz/thesis huggingface dataset:
Non-parametric goodness-of-fit testing and applications [electronic resource]

The current state of statistical practice is dominated by the use of model-based methods. A natural basic question is whether the model fits the data. This is a central question and has been studied for over a century. There is a vast literature available; however, a majority of the literature is focused on the univariate case. Far less work has been done on the general case and the theory is very sparse. This thesis introduces a general methodology, based on (non-commutative) Fourier analysis, to construct tests of goodness of fit for distributions on relatively general spaces. The procedure is developed for a simple null hypothesis and has been carried out for several examples, including the normal distribution, the uniform distribution, and the uniform distribution on high-dimensional spheres. The method is used to construct two families of tests of uniformity on the compact classical groups. Carrying out the program for the compact groups involves a substantial use of the representation theory of Lie groups, including derivation of new group theoretic formulas. These tests are used to numerically study the mixing-time of a recently introduced Markov chain Monte Carlo sampler on the orthogonal group. The method is extended to the composite null hypothesis of parametric families of distributions. The asymptotic properties are studied and computational aspects are discussed. This has been carried out for several examples: testing for multivariate normality, testing for the beta family, testing for the gamma family, testing for the chi-square family, and testing for the exponential family. Motivated by an application in material sciences, the method has been successfully carried out for several parametric families of distributions on the group of three dimensional rotations. The power function against local alternatives is studied in details and various properties are established. In particular, these tests are asymptotically admissible. The tests have been tried out on several examples and show favorable performance compared to existing methods.

Keywords: Statistics.
Advisor: Diaconis Persi primary advisor. Thesis advisor
Chatterjee Sourav advisor. Thesis advisor
Siegmund David
Nonparametric methods for functional genomics and applications to immune aging [electronic resource]

Rapid advances in DNA sequencing technology have facilitated the development of assays interrogating numerous attributes of cellular identity, including chromatin structure, DNA methylation, and DNA/protein interactions. As recent work has demonstrated the roles of transcription factor (TF) binding and chromatin organization as "leading indicators" of disease and development, considerable effort has been devoted to cataloging the various epigenomic markers of cell state, increasingly within the context of large, multi-institutional projects. However, the analysis methodologies in widespread use largely date to the early days of microarrays and RNA-seq, and are designed for small-scale functional genomics studies based on gene expression data. Such methods require the user to explicitly encode, in the form of a linear model, the structure of the experimental design. This constraint forces the investigator to decide, a priori, which experimental covariates are expected to affect the gene expression measurements, and how those covariates interact with one another. Additionally, because these methods are intended for use with gene expression data, they incorporate parametric assumptions that are particular to that data type and are not necessarily applicable to epigenomic data. In this dissertation, I present my work addressing these analytical shortcomings and discuss the use of epigenomic data for functional genomics: First, I introduce a statistical technique for associating principal components (PCs) with experimental covariates, enabling assumption-free quantification of confounding and correction for nuisance variables. Second, I describe an extension to the association between PCs and covariates, allowing for nonparametric differential analysis. Third, I demonstrate the application of functional genomics to chromatin structure data, establishing putative molecular mechanisms associated with CD8 T cell differentiation and aging in humans. Altogether, this dissertation facilitates and demonstrates the application of the functional genomics paradigm to the broad scope of assay types enabled by recent advances in high-throughput sequencing technologies.

Keywords: Biomedical Informatics.
Advisor: Greenleaf William James primary advisor. Thesis advisor
Kundaje Anshul
Pritchard Jonathan (Jonathan K.) advisor. Thesis advisor
Nothing Tastes As Sweet As Screen Time: Understanding the Rules Parents Have for Media Use

The use of media as a means of entertainment, distraction, or as an education tool for children is commonplace. While some believe that technology is generally improving life, there exists only a small amount of research on how devices are impacting the development of the young children who spend so much time with their screens. As we begin to examine the effects of such devices on children an important question to answer is what regulations parents currently enact around how their children are allowed to use technology. In this study, I seek to determine how parents create technology regulations, or “screen time rules,” and how well they perceive the effectiveness of these rules? This work represents a first look at what constitutes “screen time rules” and how parents and caregivers across the country construct them.

Keywords: Child
Development
Technology
Screen Time
Regulations
Devices
Thesis
Advisor: Hancock Jeff
A novel gamma-delta T cell subset prevents malarial parasitemic recurrence [electronic resource]

Malaria carries a heavy morbidity and mortality burden worldwide. Despite overwhelming evidence that gamma-delta T cells play an important role during malaria, the precise functional and phenotypic characteristics of these cells remain the least understood facets of the adaptive immune response during Plasmodium infection. We report that gamma-delta T cells were highly expanded and activated after the resolution of acute parasitemia in the Plasmodium chabaudi model of murine malaria, with a similarly activated gamma-delta T cell profile late after P. falciparum infection in human volunteers. Using single-cell paired-chain T cell receptor (TCR) sequencing, we determined that gamma-delta T cells were clonally expanded, were restricted to the TRAV15N-1 (Vdelta6.3) V-region, and had convergent complementarity-determining region 3 (CDR3) sequences, implying an antigen-specific gamma-delta T cell response. Whole trancriptome analysis of the expanded gamma-delta T cell population revealed an unexpected transcriptional profile that could promote recruitment and polarization of the myeloid compartment (Spp1 [osteopontin], Csf1 [M-CSF], Ccl3) -- suggesting a novel function for gamma-delta T cells. Never before shown in gamma-delta T cells, M-CSF protein was present in ~70% of the expanded gamma-delta T cells. Both gamma-delta T cells and M-CSF were found to be necessary for preventing parasitemic recrudescence following resolution of acute parasitemia. These findings indicate the presence of a novel subset of gamma-delta T cells that fill a specialized protective role in the late stage of malaria.

Advisor: Davis Mark primary advisor. Thesis advisor
Boothroyd John C. advisor.
Boyd Scott
Chien Yueh-Hsiu
Schneider David (David Samuel)
Novel oligodeoxyfluoroside derivatives - sub-nanometer fragments of graphene assembled on DNA, and a DNA-based photoswitch [electronic resource]

This thesis describes the design and creation of novel Oligodeoxyfluorosides (ODFs), which are assemblies of fluorescent chromophores held together by DNA backbone. In the first chapter, we showcase our DNA-based carbon dots, which are made from sub-nanometer fragments of graphene assembled on the DNA backbone. These polyaromatic hydrocarbon stacks fluoresce in a wide range of colors spanning the visible spectrum, and were demonstrated to be useful for the multi-chromatic bioimaging of live cells, requiring only single wavelength excitation for multiplex imaging. These carbon dot mimics were found to exhibit most of the properties of carbon dots, and constitute an unprecedented 'bottom-up' approach to synthesizing low polydispersity carbon-dots with precisely known chemical structures. In the second chapter, we investigate the mechanism of a unique photoswitchable bisphenylalkynylpyrene containing ODF sequence, SSVV, that was found in a previous study to change emission color from green to blue upon UV irradiation. We propose a UV induced [2+2+2] cyclization of the bis-alkyne moiety with ambient oxygen as the origin of the color-change reaction, in which spatial separation of stacked pyrene units cause selective loss of excimer emission. In the third chapter, we investigate the effect of ODF sequence length on their optical properties and analyte sensing abilities. The emission profiles of ODFs are known to be sensitive to their immediate chemical environments, and have been utilized in previous studies for fluorescence sensing of varied analytes. Our study found diminished quantum yields as ODF sequence length increases, and no enhancements to the emission response on analyte exposure with longer sequences. Our fourth and final chapter describes our attempt to utilize the DNA backbone for the controlled assembly of Aggregation Induced Emission (AIE) dyes, with the expectation that we could elicit the AIE effect in a precise manner by varying the number of dye stacked against each other. However, this approach to realizing AIE was largely unsuccessful. Also included is a preface chapter containing an introduction to Oligodeoxyfluorosides, and summaries to each of the aforementioned chapters.

Keywords: Chemistry.
Advisor: Kool Eric T. primary advisor. Thesis advisor
Boxer Steven G. (Steven George)
Santiago Juan G. advisor. Thesis advisor
Novel phenomena in topological states of matter [electronic resource]

Topological states of matter exhibit properties that are protected by certain topological invariants and are invariant under perturbations. Depending on whether they have an excitation gap or not, these topological states can be classified into gapped and gapless phases. In this thesis, we first discuss the novel properties and recent developments of two kinds of gapped topological states in two-dimensions (2D): the quantum anomalous Hall (QAH) insulator and the chiral topological superconductor (TSC), which can be realized in thin films of 3D topological insulators. In particular, we identify the presence of a zero Hall conductance plateau and a unique half plateau of two-terminal conductance in the QAH state and the chiral TSC state, respectively, both of which are confirmed by experiments. In the second part, we present two novel kinds of gapless topological states of matter characterized by linking numbers: the 5D Weyl semimetal and the 3D time reversal invariant superconductor with linked nodal lines, which show interesting bulk-boundary correspondences and topological responses.

Keywords: Physics.
Advisor: Zhang Shoucheng primary advisor. Thesis advisor
Kivelson Steven advisor. Thesis advisor
Qi Xiaoliang advisor. Thesis advisor
Novel roles for the Parkinson's disease gene PINK1 in Drosophila [electronic resource]

Parkinson's disease (PD) is the second most common neurodegenerative disorder and the second most common movement disorder in the world. It is progressive and disabling, and has no cure. An ever-increasing body of research suggests that mitochondrial dysfunction plays a key role in PD pathogenesis. For example, one cause of familial, early-onset PD is the loss of function of PINK1 (PTEN-induced putative kinase 1), a mitochondria-targeted serine/threonine kinase. In this dissertation, we ask how PINK1's loss of function affects mitochondrial health, and contributes to PD pathogenesis. We first sought to better understand the effects of PINK1's loss of function on mitochondrial transport by clarifying PINK1's relationship to a known target Miro, a motor adaptor critical for mitochondrial motility. We found that PINK1 mediates the phosphorylation of Miro at three specific sites, and that phosphorylation at these sites is critical for the health of dopaminergic neurons, synaptic growth at neuromuscular junctions, and mitochondrial motility in Drosophila. During this study, we established an in vivo method for identifying novel physiological functions of PINK1-mediated phosphorylation of its substrates, which we used in our second study. To expand our understanding of the cellular functions of PINK1, we employed an unbiased phosphoproteomic screen to identify potential novel targets. We were surprised to uncover a relationship between PINK1 and medium-chain acyl-CoA dehydrogenase (MCAD), an enzyme critical for the oxidation of fatty acids. Using methods developed in our first study, we found that PINK1 mediates the phosphorylation of MCAD at a specific serine site, and that phosphorylation at this site is critical to maintaining locomotor and morphological features in Drosophila. We also employed metabolic profiling and found that phosphorylation at this serine site is critical for the regulation of certain metabolites, and that PINK1's loss of function results in widespread disruption of metabolites in Drosophila. By uncovering novel physiological consequences of PINK1-mediated phosphorylation of Miro, we have further clarified PINK1's role in mitochondrial transport. By uncovering a novel relationship between PINK1 and MCAD, we have implicated PINK1 in metabolic homeostasis. Overall, by studying the functions of PINK1, we hope we have come one step closer to identifying biomarkers and therapeutic targets for PD, and to understanding the basis of its pathogenesis.

Advisor: Wang Xinnan
Clandinin Thomas R. (Thomas Robert)
Lu Bingwei
Reimer Richard J. advisor. Thesis advisor
Nudge strategies [electronic resource]

Whether and how people ("Choice Architects", or CAs) try to exploit the biases of other people ("Choice Makers", or CMs) to influence their choices is critical to understanding strategic interactions in social, political, and economic environments. For instance, CAs must often decide between giving CMs choice sets with positive or certain options (influencing CMs toward safer options) versus negative or risky options (influencing CMs toward riskier options). In Chapter 1, we show that individuals' nudge strategies -- decisions about how to exploit others' biases -- are distorted toward presenting choice sets with positive or certain options, across eleven experiments involving diverse samples (executives, law/business/medical students, adults) and contexts (public policy, business, medicine). These distortions primarily reflect CA decision biases (\textit{loss aversion for choice sets} and a \textit{certainty effect for choice sets}) rather than CA social preferences, and they can cause majorities to use nudge strategies that backfire. Surprisingly, people's predictions about the directional effects of nudges are generally correct. Thus, prompting people to consider their predictions can improve suboptimal nudge strategies. In Chapter 2, we expand the investigation of Chapter 1, focusing on how Choice Architects decide to use a broader set of nudges (e.g. anchors, social norms, and options described using a positive frame) to influence Choice Makers, and how CAs act in more social situations (e.g. negotiations). When people are choosing which influence tactics to use in negotiations and social interactions, how do they choose which anchor to provide, which social norm to present, and whether to use a positive or negative frame to describe an option? We investigate the nudge strategies people use in such situations and document two primary patterns. First, individuals are more likely to use optimal nudge strategies than suboptimal nudge strategies on average, suggesting that they understand the directional effects of influence tactics. Second, individuals' nudge strategies reveal ``pro-social distortions'' towards tactics that can produce positive psychological and/or economic outcomes for their counterparts. We consider and evaluate three theories of CA behavior, based on standard economic theory, pro-social preferences, and the social heuristics hypothesis. In Chapter 3, I report a novel experimental test of the loss aversion theory of Choice Architect behavior introduced in Chapter 1. I construct a measure of loss aversion for choice sets based on people's stated valuations of four influence opportunities. Consistent with loss aversion for choice sets, I find that CAs value loss-framed choice sets less than gain-framed choice sets; moreover, I estimate an average CA loss aversion coefficient of 2.42, very close to CM loss aversion coefficients that have been previously estimated using analogous methods.

Keywords: Business.
Advisor: Neale Margaret Ann
Halevy Nir
Levav Jonathan
Numerical analysis and implicit time stepping for high-order, fluid flow simulations on GPU architectures [electronic resource]

High-order discontinuous finite element methods are becoming increasingly more pop- ular for simulations of vortex dominated flows over complex geometries because they are inherently less dissipative than traditional second-order finite volume methods. In particular, the Flux Reconstruction (FR) approach has gained popularity because it not only offers less dissipation but is also eminently parallelizable on multi-core processors and accelerators. An extensive amount of research has been performed for accelerated explicit methods for FR but more realistic simulations often require high aspect ratio meshes where the maximum stable time step or CFL condition is determined by the smallest cell. This can lead to significant limitations in explicit time integration. In this dissertation, eigensolution analysis is performed to study the effect of these limitations on the stability, dissipation and dispersion properties of the nodal Discontinuous Galerkin (DG) scheme via FR for advection-diffusion. It is shown that the CFL condition for advection-diffusion is stricter than that for pure-advection or pure-diffusion individually and a suitable estimate for the maximum stable time step is proposed. The CFL condition is strongly influenced by the choice of interface fluxes and, in general, the condition for a scheme using centered values is much higher than that which has one-sided values. It is also shown that schemes with centered interface values produce less error for well resolved solutions while schemes with one- sided interface values produce less error for solutions that are under-resolved. These results are verified for one- and two-dimensional advection-diffusion of an approximate Gaussian and two-dimensional Couette flow. In addition to eigensolution analysis, a multi-GPU, implicit time stepping method ivis developed, implemented and tested in order to study the feasibility of an implicit scheme on modern hardware. It is shown that a nonlinear solver can be constructed for the Direct Flux Reconstruction (DFR) method which maintains element-locality and high arithmetic intensity with minimal communication costs on modern GPU clusters. Analytical element local Jacobians for the DFR method are derived and a Kronecker product formulation is used to reduce the time complexity from O(P^(3d−1)) to O(P^(d+1)) for Euler simulations and O(P^(3d)) to O(P^(d+2)) for Navier-Stokes where P is the degree of the Lagrange basis polynomials and d is the spatial dimension. Numerical results are obtained for the inviscid bump, inviscid NACA0012 airfoil, isentropic vortex, laminar Joukowski airfoil and three-dimensional half cylinder with a Reynolds number of 1000.

Keywords: Aeronautics and Astronautics.
Advisor: Jameson Antony
Alonso Juan José
Lele Sanjiva K. (Sanjiva Keshava)
The numerical delta method, bootstrap, model selection, and parameter inference [electronic resource]

The first chapter of this dissertation studies new inference methods for handling nondifferentiable functions of structural parameters. Such functions arise in many counterfactual analyses that policy makers use to assess the effectiveness of their policies. For example, a policy maker may want to determine for which individuals in a population a treatment is most effective. After estimating quantile treatment effects for several different quantiles, she wishes to provide standard errors for the maximum effect. The pointwise maximum function is nondifferentiable, which invalidates classical inference methods. In some cases, the function of interest may not even be directionally differentiable. In these cases, the directional delta method cannot be applied. Examples of functions that are not known to be directionally differentiable include many M-estimators with nondifferentiable objective functions, such as the maximum score estimator, the LASSO estimator, and the 1-norm Support Vector Machine (SVM) regression estimator. It is well established that the conventional bootstrap will not always consistently estimate the limiting distribution of these estimators and therefore cannot be used to conduct inference. As an alternative to the conventional bootstrap, the second chapter of this dissertation proposes a numerical bootstrap procedure which can consistently estimate the limiting distribution for a large class of estimators including those with convergence rates slower than root-n. Sometimes there are many different estimators policy makers can use to determine the effectiveness of their policies, and the question of how to select among the different estimators becomes important. The third chapter of this dissertation discusses how researchers can choose among the different estimators in a data-driven way and how to account for the variation in the estimate that arises from experimenting with different estimators. We propose to simulate the post selection distribution using subsampling by repeatedly performing model selection on each subsampled dataset and using the percentiles of the resulting subsampling distribution for inference.

Keywords: Economics.
Advisor: Hong Han primary advisor. Thesis advisor
Romano Joseph P.
Wolak Frank A. advisor. Thesis advisor