VictorJuiz/thesis huggingface dataset:
The contribution of RNA to heterochromatin [electronic resource]
Keywords: Biochemistry.

Accurate chromosome segregation is essential for proper cell division and normal organismal development in all eukaryotes. Chromosome segregation errors generate aneuploid cells that cause human genetic disease and characterize most human cancers. Our long term goal is to understand the cellular mechanisms that ensure accurate chromosome segregation. During cell division, pairs of replicated chromosomes must remain linked until anaphase in order to properly segregate to daughter cells. The primary sites for cohesion between sister chromatids exist at the heterochromatic outer regions of the centromere, called pericentric heterochromatin. Disruption of this heterochromatin domain disturbs cohesion, resulting in chromosome segregation errors and aneuploidy. The concept of non-coding RNAs directing chromatin modifications is a growing paradigm in cell biology and substantial evidence implicates non-coding RNAs in the formation of human pericentric heterochromatin. Unraveling the RNA-dependent mechanisms of pericentric heterochromatin formation has clear implications in human disease; dysfunctional regulation of pericentric transcription characterizes numerous cancers in mouse and humans and is thought to contribute to genomic instability. We discovered that RNA remains physically attached to human mitotic chromosomes, and is enriched at pericentric regions. We found that SUV39H1 and SUV39H2, two histone methyltransferases critical for heterochromatin formation, directly bind RNA in vitro and associate with RNA transcribed from pericentric regions in vivo. We found that treatment of mitotic chromosomes with single-stranded ribonuclease decreases SUV39H1 localization to pericentric regions, suggesting an RNA-dependent mechanism for SUV39H1 targeting. To determine to role of direct RNA binding by SUV39H1, we mapped the minimal RNA binding domain of SUV39H1 to its chromodomain, and identified mutants that severely disrupt direct RNA binding in vitro. RNA binding-deficient SUV39H1 mutants display a marked impairment of localization to pericentric regions in vivo, and are generally less stably associated with chromatin. These results suggest a novel role for non-coding RNA in the targeting of SUV39H1 to pericentric heterochromatin. We propose a model in which both direct RNA binding, in addition to histone binding, differentially contribute to the affinity of SUV39H1 for pericentric heterochromatin, ensuring faithful heterochromatic silencing of a chromatin domain that is vital for proper chromosome segregation.
Contributions to fault detection and diagnosis with high-dimensional data [electronic resource]
Keywords: Statistics.

Motivated by applications to root-cause identification of faults in multistage manufacturing processes which involve a large number of tools or equipments at each stage, we consider multiple testing in regression models whose outputs represent the quality characteristics of a multistage manufacturing process. Because of the large number of input variables that correspond to the tools or equipments used, this falls in the framework of regression modeling in the modern era of big data. On the other hand, with quick fault detection and diagnosis followed by tool rectification, sparsity can be assumed in the regression model. We introduce a new approach to address the multiple testing problem and demonstrate its advantages over existing methods. We also illustrate its performance in an application to semiconductor wafer fabrication that motivated this development. The problem of detection and diagnosis of abrupt changes in a stochastic system on the basis of sequential observations has many applications, some of which are discussed in this thesis. In statistical process control (SPC), the past decade witnessed the emergence of a new direction in quality control because of the availability of big data, making use of contemporaneous developments in the statistics literature on high-dimensional data analysis. It has been noticed that in multivariate and high-dimensional applications, only a sparse subset of quality characteristics or other variables of interest undergoes abnormal changes that lead to deviations from the state of statistical control. The past decade also witnessed major developments in surveillance over sensor networks, cyber-security and information systems. We give a general theory for sequential fault detection in these stochastic models and also modify and extend it to the much less developed problem of fault diagnosis. This fault diagnosis, or change isolation problem, is to determine upon detection of change in a system which one in a set of possible changes has actually occurred. In this connection, we also develop a parallel theory of sequential multiple hypothesis testing.
Control of salmonella transmission by the intestinal microbial community [electronic resource]
Keywords: Microbiology and Immunology.

Disease transmission is a multifaceted process mediated by the interactions between the pathogen and host. Salmonella enterica serovars are important human pathogens that cause disease ranging from food poisoning to persistent systemic infections, such as typhoid fever. Transmission occurs via the fecal-oral route, and epidemiological analyses have revealed heterogeneity in host transmission capabilities. A minority of hosts are persistent carriers of disease that are responsible for a large majority of new infections. These carriers are thus termed supershedders, but relatively little is known about the factors that dictate pathogen transmission. The focus of this dissertation work is to identify critical principles and determinants that govern Salmonella transmission. Chapter 1 introduces what is known about S. Typhimurium colonization and supershedding in a mouse model of typhoid fever. The role of the host immune response and intestinal microbiota in modulating infection are highlighted. In Chapter 2, ecological theories are applied to predict S. Typhimurium transmission dynamics. There is intense Salmonella intraspecies competition to colonize transmission niches in the cecum and colon. Salmonella interacts with trillions of commensal microbes within these distal gut sites, and another goal of this study is to investigate how the intestinal microbiota influences supershedding. Host diet can drastically alter the microbiota, and Chapter 3 details the development of a supershedder microbiota induced by a high cholesterol diet. Differences in host genetic backgrounds also influence microbiota composition, and in Chapter 4, we demonstrate that supershedding can be conferred by fecal microbiota transplantation. This body of work reveals that the host microbiota controls levels of Salmonella excreted in feces, as well as host tolerance to infection. Chapter 5 reflects on the importance of the microbiota in influencing Salmonella transmission, and considers the implications on best treatment practices and disease control.
Controlling light at the nanoscale for broadband metamaterials, efficient solar cells, and subwavelength 3D imaging [electronic resource]
Keywords: Materials Science and Engineering.

The iridescent wings of a butterfly, the vivid colors of a stained glass window, the mesmerizing rainbow in a soap bubble - all of these beautiful optical phenomena are made possible by the interaction of light with nanoscale materials. Beyond brilliant colors, rational control of the unique and often surprising ways in which light interacts with materials at extremely small length scales has enabled novel optical phenomena, devices, and characterization techniques. In this thesis, we discuss three such applications of nanophotonic engineering: metamaterials, solar cells, and nanoscale optical tomography. First, we describe the design of a metamaterial - a composite material with a tunable refractive index spanning positive, zero, and negative values - that operates over a broad spectral range. While metamaterials have made possible previously unthinkable phenomena including invisibility cloaking and sub-diffraction-limited imaging, designing a metamaterial with a broad operational bandwidth at visible frequencies is an outstanding challenge. Here we demonstrate theoretically a broadband metamaterial presenting negative indices across hundreds of nanometers in the visible and near-infrared, more than doubling previous record bandwidths. Second, we discuss optical methods for increasing photocurrent from solar cells by making use of low energy subbandgap photons. Upconversion - the process of converting low energy light to high energy light - promises to be an economical solution to this problem, but existing upconverting materials require substantial improvements to become viable. Here we describe the realistic improvements achievable with an upconverter enhanced solar cell and propose a nanophotonic system to improve the efficiency of the upconversion process itself. Last, we introduce a new method for probing light-matter interactions with nano\-meter scale resolution in three dimensions. Our technique, called cathodoluminescence tomography, extends sub-diffraction limited imaging from two to three spatial dimensions, while also revealing spectral information across visible and near infrared frequencies. This new imaging capability could be used, for example, to probe the distribution of defect states in photovoltaics, or locate recombination centers in light emitting diodes.
Controlling light transmission with nanostructured metallic surfaces [electronic resource] : applications in polarimetry, transparent electrodes, and anti-reflective coatings
Keywords: Electrical Engineering.

Metallic structures such as antennas and waveguides are widely used to concentrate and guide electromagnetic radiation into electronic circuits at radio and microwave frequencies. Because of their high conductivity, metals are also used for the wiring in electronic circuitry. At near infrared and visible frequencies, however, metals have been underutilized. In this spectral range, dielectric elements such as lenses and waveguides are used to manipulate electromagnetic radiation. Recent progress in nanotechnology has opened up opportunities to make and characterize metallic structures at the nano scale, which are requirements for use of metals in this spectral range. Miniaturized metallic devices could potentially replace some of their bulky dielectric counterparts at near IR and visible frequencies, while simultaneously performing an additional electronic function. This would enable new optical applications that are not possible with dielectrics alone. This dissertation presents our work on controlling light transmission with nanostructured metallic films for three applications, all of which are typically the domain of dielectrics: polarimeters, anti-reflective coatings, and transparent electrodes. In all three applications, the nanostructured metallic film simultaneously performs optical (light transmission) and electronic (charge extraction) functions. We perform full-field electromagnetic simulations to characterize and optimize these metallic nanostructures. We also experimentally show the applicability of these designs for real devices through integration with semiconductor photodetectors and performing photocurrent and reflection measurements. The demonstrated devices extend the reach of metal optics to a wide range of optoelectronic applications including displays, touch screens, solar cells, and polarimetric imagers and sensors.
Culturally Immersive Programming for Native American/Alaska Native Students: Benefits, Impacts, and Implications Based Upon a Survey of NERDS (Native Education Raising Dedicated Students)
Keywords: Native American/Alaska Native
Youth
Culture
Cultural Programming
Education
NERDS
Attitudes
Thesis

This study seeks to understand the ways in which a culturally immersive, extracurricular program affects Native American /Alaska Native (NA/AN) youth attitudes towards education. Furthermore, this study analyzes how NA/AN youth identities are tied to issues of curriculum, representation, and community involvement. A survey was conducted of 37 NA/AN youth participating in a program entitled Native Education Raising Dedicated Students (NERDS) to examine how they felt represented, engaged, and respected in educational settings. While most previous research has focused on the implementation and pedagogical roots of culturally responsive teaching, this research instead evaluates how students have been affected during their involvement in a culturally responsive program called NERDS. Findings of this research show that there was no measured difference between the attitudes of new and veteran NERDS students. Participating students also stated that their involvement in NERDS allowed them opportunities to connect with and take pride in their NA/AN identity. The survey demonstrates that while NA/AN youth believe NERDS to be a positive representation of NA/ANs, they also feel that they are not represented in what is taught and read during school. The successful influence of the NERDS program offers a promising culturally responsive model for schools seeking to better serve NA/AN students.
Curativity - Exhibit Your Story
Keywords: Learning
Design &amp; Technology
Learning
Design
Technology
Museum
Project-Based Learning
PBL
field trip
elementary school
informal learning
Constructionism
maker
makerspace
Stanford Graduate School of Education
Thesis

A museum has three integral goals – to entertain, support learning, and build dialogue
amongst its visitors and between visitors and the content on display (Simon, 2010).
Informal learning experiences in settings such as museums, zoos, and aquariums can
be powerful drivers of affective and cognitive growth in learners young and old
(DeWitt & Storksdieck, 2008). Specifically, grade school field trips are some of the
most memorable and exciting portions of a student’s educational career. However,
without purposeful pre-visit preparation, students are not oriented to the physical
space of the museum prior to arrival and may not be able to access the concepts
presented in the museum in a single visit (Hein, 1998). In Curativity, we present a new
way to prepare students for learning through a shared project-based experience
before a field trip excursion so that students see field trips, and museums in turn, as
experiences and places that are fun, educational, and accessible.
The dark Camus [electronic resource]
Keywords: French and Italian.

This dissertation explores a seldom-recognized dimension and seeks to complexify our understanding of an author renowned for his "solar" humanism. I begin with a reflection on the shifting, sometimes contradictory role of darkness in Camus's writings. Here I discuss texts like "Le Renégat" and La Chute to contrast more didactic, or typically "Camusian" works like La Peste and L'Homme Révolté in which battling images and metaphors of light and darkness clearly evoke the greater struggle between Good and Evil. The departing question, therefore, is what are we to make of this eternal dualism in Camus when it becomes blurred, and even inverted (the most renowned, and bewildering example of which is Meursault's murder in L'Etranger "à cause du soleil)"? By analyzing works from three distinct periods in Camus's career -- earliest essays, wartime, and last writings -- I argue that Camus suffered from the reputation he himself constructed as a, if not the "belle âme" of his generation. I subsequently trace the varying presence and intensity of his undoubted Shadow: an instinctive, irrational, sometimes violent, and ultimately, deeply cynical response to his equal calls for language, love, justice and measure under the sun.
Data mining for demand management [electronic resource] : segmentation, targeting, and analytics visualization
Keywords: Electrical Engineering.

As power generation gets more distributed, and electricity markets become more deregulated throughout the world, utilities have been trying to find a way to match consumption with generation. Recently, advanced metering infrastructure (AMI) has been deployed wide-spread including smart meters, and smart meters make two-way communication possible between the meter and the central system. They provide concrete information about customer electricity consumption and create a unique opportunity to investigate and understand customer consumption behavior much better than before. Integrating the needs of utilities and potential benefits to customers, the ultimate target of the studies in this dissertation is building a data-driven demand management system which is based on smart meter data analytics. Thus, we develop scalable methodologies of data analytics using data mining, machine learning techniques. The methodologies developed in this dissertation include learning customer consumption patterns, segmenting customers by relevant features, selecting the proper customers for various energy programs and implementing a data analytics system.
Deconvoluting the immune repertoire [electronic resource]
Keywords: Bioengineering.

In this thesis, I will demonstrate how combined functional/genomic analysis of the immune repertoire provides a clearer picture of a patient's immune response. I will show tools that I have advanced and developed for characterizing the immune system: immune repertoire library construction, long read sequencing on the Illumina platform, high throughput functional assays with antibodies cloned from single cells, and a data processing framework for combining functional and repertoire data. I will show influenza specific lineage recall over subsequent years of vaccination with trivalent influenza vaccine and identify several broadly binding anti-influenza antibody lineages. I will show how this platform can be used to identify which antibody lineages comprise segments of the mixed signal from a serum binding assay. Furthermore I will present evidence of low seroprevalence of influenza subtypes with H2, H5, H7 and H9 HA and apply this platform to identify multiple candidate antibodies for treating seasonal and pandemic influenza. Lastly I will show progress on a method for rapid DNA fabrication that could be used to quickly produce antibody genes mined from the repertoire, but has broader potential application in the field of synthetic biology.
Deep linear neural networks [electronic resource] : a theory of learning in the brain and mind
Keywords: Electrical Engineering.

Humans and other organisms show an incredibly sophisticated ability to learn about their environments during their lifetimes. This learning is thought to alter the strength of connections between neurons in the brain, but we still do not understand the principles linking synaptic changes at the neural level to behavioral changes at the psychological level. Part of the difficulty stems from depth: the brain has a deep, many-layered structure that substantially complicates the learning process. To understand the specific impact of depth, I develop the theory of gradient descent learning in deep linear neural networks. Despite their linearity, the learning problem in these networks remains nonconvex and exhibits rich nonlinear learning dynamics. I give new exact solutions to the dynamics that quantitatively answer fundamental theoretical questions such as how learning speed scales with depth. These solutions revise the basic conceptual picture underlying deep learning systems--both engineered and biological--with ramifications for a variety of phenomena. I highlight three consequences at different levels of detail. First, the theory shows that layerwise unsupervised learning is a domain general strategy for speeding up subsequent learning, which I link to critical period plasticity in sensory cortices. Second, the theory suggests that depth influences the size and timing of receptive field changes in visual perceptual learning. And third, by considering data drawn from structured probabilistic graphical models, the theory reveals that only deep (and not shallow) networks undergo quasi stage-like transitions during learning reminiscent of those found in infant semantic development. These applications span levels of analysis from single neurons to cognitive psychology, demonstrating the potential of deep linear networks to connect detailed changes in neuronal networks to changes in high-level behavior and cognition.
Default prediction for small businesses [electronic resource]
Keywords: Management Science and Engineering.

Small business loan defaults have been an active research area. Two major families of default prediction models are reduced form models and structural form models. Reduced form models focus on finding the statistical relations between default events and various economic variables, while structural form models focus on describing default event as a stopping time of some stochastic process. First we propose a reduced form model that uses massive amounts of data mined from the internet to supplement traditional economic variables in the data set. We compared the performance of reduced form models using internet covariates versus those using traditional covariates, and explored the possibility of a hybrid model using both types of covariates. Secondly, we propose a structural form model where we integrate the impact of relationship lending, a practice that has achieved success in recent years, into an incomplete information model. Numerical results are provided for both models.
Defining the Interactions Between Chromatin Remodeler INO80 and Microtubules
Keywords:  Department of Biology
biology
Stanford University
cancer biology
molecular biology
chromatin remodeler
INO80
mitosis
microtubule
tubulin
Saccharomyces cerevisiae
Thesis

Chromatin remodelers are protein complexes characterized by their role in manipulating and modifying chromatin and histones. They are known to regulate transcription and DNA damage response, but recent discoveries suggest they also regulate chromosome segregation and other aspects of mitosis, proposing a novel and undefined role for chromatin remodelers. Such is the case for INO80, a well studied 15 subunit protein complex. Preliminary data show a likely interaction between INO80 and microtubules, both of which are essential for proper chromosome segregation and correctly positioning components of the dividing cell. Thus, to maintain proper chromosome segregation and cell division, we hypothesize that the INO80 complex plays a vital role in mitosis by binding to and stabilizing microtubules. Using yeast genetics in S. cerevisiae, we found a strong association between the INO80 complex and tubulin after immunoprecipitation and separation by molecular density on a sucrose gradient. We next investigated this interaction in mutants of the various INO80 modules further to characterize each mutant’s relationship with microtubules. It was found that the N-terminal region of Ino80 was necessary for its association with tubulin. Furthermore, we investigated the DNA content of each mutant using FACS as well as its response to microtubule destabilizing agents in a fitness assay. Overall, investigating the role of chromatin remodeler INO80 in mitosis may elucidate a mechanism for developing chromosomal and other mitotic defects dependent on interactions between INO80’s subunits and microtubules. This mechanism of action may help characterize and explain the presence of mitotic defects in cancer cells.