VictorJuiz/thesis huggingface dataset:
An information-theoretic analysis of the ON/OFF pathway split in the Drosophila visual system
Keywords:  Department of Physics
Drosophila
visual system
pathway splitting
efficient coding
information theory
Thesis

Many animals exhibit sensory systems that split into multiple parallel pathways at an early processing stage. For example, the visual system of the fruit fly Drosophila melanogaster is split into separate ON and OFF pathways to facilitate the detection of increments and decrements in light intensity, respectively. Although previous studies have considered the computational features of similar ON/OFF pathway architectures, they have invariably focused on sensory systems that utilize a digital code consisting of action potentials. In contrast, the Drosophila visual system consists largely of cells that fire graded potentials and therefore rely on an analog rather than digital code. In this study I have sought to address the hypothesis that an analog ON/OFF pathway architecture of the sort exemplified by the Drosophila visual system is advantageous for the efficient coding of sensory stimuli. By evaluating the information-theoretic properties of an analog model sensory system consisting of parallel ON/ON or ON/OFF pathways, I demonstrate that the latter configuration requires a lower average signal amplitude to convey the same amount of information about a given stimulus. Furthermore, I show that empirical estimates of the information capacity of the split ON/OFF pathway in flies are consistent with the predictions of my rudimentary model. These results suggest that pathway splitting has similarly beneficial implications for sensory systems based on analog codes as for systems based on digital codes.
Analysis and application of linkage disequilibrium in population and statistical genetics
Keywords: Biology.

Linkage disequilibrium (LD) is the non-random association of alleles at different genetic loci. This dissertation consists of three projects that relate to the analysis and application of LD on various topics within population and statistical genetics. Various measures of LD have been proposed in the literature, each with different arguments favoring its use. Chapter 2 employs a theoretical approach to examine mathematical properties of five different measures of LD. These results help place the use of various LD statistics into their proper contexts, and provide a mathematical basis for comparing their values. Next, the presence of LD in genomes can be leveraged for a number of different applications in statistical genetics. Chapter 3 examines one such example in genetic imputation. Specifically, we ask the question of how to optimally select a subset of a study sample for sequencing when choosing an internal reference panel for imputation, in order to maximize the eventual imputation accuracy. We compare two algorithms—maximizing phylogenetic diversity (PD) and minimizing average distance to the closest leaf (ADCL)—and conclude that while both algorithms give better imputation results as compared to randomly selecting haplotypes to be included in the reference panel, imputation accuracy is the highest when minimizing ADCL is used as the method for panel selection. Finally, LD in genomes can produce genetic signatures that may be suggestive of certain demographic processes. Genetic linkage results in the preservation of homozygous segments in the genome that are produced as the result of genomic sharing, which can then be detected as runs of homozygosity (ROH). Chapter 4 analyzes the distribution of ROH lengths in a sample of worldwide Jewish and non-Jewish populations, and employs a model-based clustering method to classify the ROH in a given population into three classes (short, intermediate, and long) based on length. Furthermore, for a subset of the Jewish populations in this study, we were able to obtain estimates of demographic rates of consanguinity (as indicated by the rates of close-relative unions). We find that the level of consanguinity in those populations is predictive of long ROH, thus finding genetic signatures of mating patterns that existed in a population's history. Making use of theoretical, computational, and statistical approaches, these chapters together provide a wide-ranging account of different aspects of LD, as related to their respective applications within the field.
Analysis of Structure in Feed-Forward Spiking Neural Networks and Applications to Neuromorphic Control of High Degree-Of-Freedom Robotic Manipulators
Keywords:  Department of Computer Science
Neuromorphic Computing
Spiking Neural Networks
Robotics
Task Space Control
Jacobian Matrix
Factorizations
Discrete Fourier Transform
Stanford Department of Computer Science
Thesis

Computing task jacobians (differential maps from the joint space to the operational space of a robotic manipulator) through the use of spiking neural networks (SNNs) has significant applications to power-efficient robot control. However, the complexity of such differential maps increases substantially with the dimensionality of their inputs, rending the problem of SNN function-fitting nontrivial for high-DOF redundant manipulators. In this thesis, we present a function factorization scheme and neural architecture that overcomes some of the challenges associated with fitting. We perform systematic structural analysis of SNNs under this architecture, and show that such a scheme can accurately decode complex multidimensional functions. In particular, we show that task jacobians can be decoded accurately over the full (discretized) joint space of a redundant manipulator using the factorized neural architecture. Specifically, we were able to achieve an RMS error of less than 0.03 per component over the joint space of a six degree-of-freedom manipulator. This level of decode accuracy represents substantial improvement over prior work in this area. Because the SNN implementations we developed were based on Izhikevich neuron models, the results of this thesis can potentially be applied to controlling robots accurately using low-power neromorphic chips.
Analysis of the Fourier Mode Phase Distribution in the CMB as a Test of Inflation Theory
Keywords:  Department of Physics
Cosmic Microwave Background
Inflation Theory
Thesis

Observations of the cosmic microwave background (CMB) have provided a wealth of information about the contents, evolution, and beginnings of the universe. One key component of the CMB is its temperature anisotropies, which support a fundamental assumption of inflation theory: that these fluctuations are quantum-mechanical in origin and have stretched to the size of the observable universe. This leads to the prediction that the phases of the Fourier mode decomposition of the CMB in a co-moving gauge are randomly distributed. Assuming a robust model for reconstructing the inflationary potential, we provide a method for extracting this phase distribution from CMB modes. We further provide preliminary analysis of this distribution.
Analyzing Autonomous Car Crashes in California
Keywords:  Department of Communication
self-driving cars
autonomous vehicles
California
Department of Communication and Journalism at Stanford University
Thesis

While twelve states explicitly allow autonomous vehicles (AVs) to be tested on their public roads, California still remains a pivotal location in the United States to test and study AVs. Testing is only likely to increase because in 2018 the state’s Department of Motor Vehicles changed its regulations to allow AVs to drive on public roads without humans present. This report builds on prior research to analyze the AV accident reports produced by seven companies from September 2014 through May 2018. The crashes were analyzed through six different lenses: accident frequency, speed, relative velocity, crash type, vehicular damage, and injuries. The data shows both the possible strengths and weaknesses of self-driving cars and suggests areas where improvement can be achieved, both in AV performance and transparency. Lastly, the report provides a brief analysis of the varying state laws that apply to AVs.
Analyzing Hydraulic Fractures Using Time-Lapse Electric Potential Data
Keywords:  Energy Resources Engineering
School of Earth Energy &amp; Environmental Sciences
Energy Resources Engineering
Stanford University
Thesis

Hydraulic fracturing is the process of injecting fluids at high pressure to create conductive channels in low permeability reservoirs so that oil and gas can flow through. Hydraulic fracturing will continue to play a key role in the future of oil and gas production, and characterizing the fractures is an important task to improve the understanding and utilization of the process. As an approach to augment and improve on the existing methods, resistivity measurements can be used to characterize subsurface features. The lithology, pore fluid chemistry, and water content affect the spatial distribution of resistive and capacitive characteristics of the subsurface. Fractures created by hydraulic fracturing are saturated with water and show reduced resistivity, which provides the opportunity to extract fracture characteristics by monitoring the change in resistivity distribution in the subsurface as a function of time.
The purpose of this work was to investigate a fracture characterization approach by making use of electrical potential data. We focused mainly on using electric field simulation and inverse analysis to examine subsurface electric field behavior due to fracture creation. We considered a new borehole method designed specifically for hydraulic fracture characterization, which modifies a single-borehole survey method and utilizes a permanent resistivity array. This method can attain higher resolution by implementing electrodes in or near boreholes and monitoring the electric potential distribution near the horizontal fracture zone.
The electric potential distribution in steady-state flow through a porous medium is analogous to the electrical potential distribution in an electrically conductive medium. By solving the flow equation and the Poisson equation for electrical field numerically, we can determine the fluid distribution and electric potential distribution at every time interval. The time-lapse electrical data generated by the simulator was considered as measured data and subsequently used for analyzing fracture characteristics. Inverse analysis was used in this work to find fracture parameters such as fracture length, orientation, and more. By deploying our simulator as the forward model, we used an objective function to capture the difference between measured data and data generated by the forward guess. Then we used a gradient-free nonlinear optimization scheme to minimize the objection function in order to achieve the best guess of targeted parameters.
The preliminary results of this work show that time-lapse electrical data is capable of capturing flow dynamics during fracturing process and has the potential to further assist fracture characterization.
Angular momentum conservation law in light-front quantum field theory and extended conformal symmetry of Abelian gauge theory in D ≠ 4
Keywords: Physics.

This thesis investigates two independent aspects of spacetime symmetries. The first part of my thesis is about the angular momentum conservation law in light-front quantum field theory. We prove the light-front Poincare invariance of the angular momentum conservation law and the helicity sum rule for relativistic composite systems. We show that the light-front wavefunction (LFWF), which describes the internal structure of a bound state, is in fact frame independent, in contrast to instant form wavefunctions. In particular, we demonstrate that j3, the intrinsic angular momentum projected onto the light-front direction, is independent of the bound state's 4-momentum and the observer's Lorentz frame. The frame independence of j3 is a feature unique to the front form. The angular momentum conservation law leads directly to a nonperturbative proof of the constraint A(0)=1 and the vanishing of the anomalous gravitomagetic moment B(0)=0. Based on the conservation of angular momentum, we derive a selection rule for orbital angular momentum which can be used to eliminate certain interaction vertices in QED and QCD. We also generalize the selection rule to any renormalizable theory and show that there exists an upper bound on the change of orbital angular momentum in scattering processes at any fixed order in perturbation theory. The second part of my thesis investigates an extended conformal symmetry for Abelian gauge theory in general dimensions. Maxwell theory in d \neq 4 spacetime dimensions is an example of a scale-invariant theory which does not possess conformal symmetry -- the special conformal transformation (SCT) explicitly breaks the gauge invariance of the theory. We construct a non-local gauge-invariant extension of the SCT, which is compatible with the BRST formalism and defines a new symmetry of the physical Hilbert space of the Maxwell theory for any dimension d \geqslant 3. We prove the invariance of Maxwell theory in d \geqslant 3 by explicitly showing that the gauge-invariant two-point correlation functions, the action, and the classical equation of motion are unchanged under such a transformation.
Animal empires [electronic resource] : the perfection of nature between Europe and the Americas, 1492-1630
Keywords: History.

Animal Empires: The Perfection of Nature Between Europe and the Americas, 1492-1615 demonstrates how Renaissance patrons, naturalists, and husbandmen developed useful but dangerous ideas to make sense of natural diversity -- nobility, race, and species -- during the consolidation of the sixteenth-century Spanish Empire. Using the three major techniques at their disposal-relocation, cultivation and training, and selective breeding-elites began a colossal experiment. They sought to create an improved version of Christian nature both in European courts and then, on a larger scale than ever before imagined, in the Americas. Case studies focus on breeding theories and practices in Mantua, Naples, Madrid, Peru, and the Valley of Mexico. Starting in the heart of Renaissance Italy and ending high in the Andes, this project integrates disparate fields of investigation -- ranging from Renaissance aesthetics and animal studies to the histories of the Spanish Empire and of biology -- to reveal an ideal of nature grandly envisioned and prosaically enacted through imperial conquest.
Antibody-adjuvant conjugates elicit robust myeloid activation and durable anti-tumor immunity
Keywords: Bioengineering.

Despite the presence of antigen-presenting myeloid cells in the tumor microenvironment during tumorigenesis, the immune system generally fails to mount an effective anti-tumor response. Recent findings in the Engleman lab revealed that simultaneous intra-tumoral delivery of tumor-binding antibodies and certain immune stimuli can induce myeloid cell uptake, processing and presentation of a wide range of tumor antigens to T cells, resulting in tumor-eradicating immunity in syngeneic mouse models. We aimed to understand the cellular and molecular mechanisms underlying this approach and further develop it for potential clinical use by designing and constructing antibody-adjuvant conjugates (AACs). Unlike separately administered components, such conjugates have the potential to deliver precise antibody-adjuvant ratios to the tumor microenvironment following intra-tumoral or systemic delivery. In vitro experiments revealed that AACs are able to potently activate human primary myeloid cells, leading to increased co-stimulatory receptor expression and production of pro-inflammatory cytokines, superior to that induced by the mixture of components. Furthermore, stimulation with the AAC induces dendritic cell differentiation and prolonged cellular survival. CyTOF-based analysis of intracellular signaling in human primary PBMCs revealed a unique signaling signature of the AACs compared to the mixture of components, suggesting a novel biological mechanism by which the AACs stimulate myeloid cells in a toll like receptor (TLR) and Fc receptor (FcR) dependent manner. Finally, we demonstrated in vivo activity in a murine tumor model, in which treatment with an AAC led to tumor clearance. These results provide a strong basis for AACs as a therapeutic technology platform as well as rationale for evaluating the safety and efficacy of these AACs in clinical trials.
Anxiety of emptiness : self and scripture in early medieval Chinese Buddhism, with a focus on Sengrui 僧叡
Keywords: Religious Studies.

This dissertation interprets a body of textual material from the earliest stratum of Chinese formulations of "buddha-nature" thinking. Buddha-nature discourse is widely acknowledged as one of the key themes in the doctrinal aspect of Chinese Buddhism from the earliest times up to the modern debates around "Critical Buddhism." Scholarship has focused mainly on its later manifestations (esp. the Dasheng qixin lun and after), leaving its beginnings relatively understudied. In this thesis, I go back to these beginnings, and trace some early, arguably the earliest, evidence for this phenomenon to the surviving writings of the early fifth century exegete Sengrui. I position this evidence in the broader cultural context of late fourth--early fifth century Chinese Buddhism's changing conceptions of scriptural authority. I argue specifically that in this body of primary material, "buddha-nature" serves as a metaphysical warrant for an ideal of universal canonicity: a nonconceptual luminosity of mind that validates the textual, hence quintessentially conceptual, totality of scripture, in an historical moment when Buddhism in China for the first time must define itself as a coherent religious entity.
AP-1 transcription factor is a barrier to nuclear reprogramming to pluripotency [electronic resource]
Keywords: Genetics.

Mechanistic insight into nuclear reprogramming from one cell state to another is of fundamental and clinical importance. Here we use the heterokaryon cell-fusion model of nuclear reprogramming to capture the dynamic architecture of chromatin accessibility and gene expression. At the onset of reprogramming, we detect a transient, genome-wide increase in accessible sites enriched for the AP-1 transcription factor motif assayed by ATAC-seq. Inhibition of AP-1 by expression of a dominant-negative results in an increase in OCT4 expression in heterokaryons. Moreover, in human iPSC reprogramming, dominant negative AP-1 can replace exogenous OCT4 in the reprogramming cocktail. We identify c-Jun as the inhibitory AP-1 family member and show that its repressive activity is mediated through interaction with NURD complex component MBD3 in a phosphorylation dependent manner. Our findings reveal that AP-1, which is induced at the onset of reprogramming and traditionally thought to be an activator, creates a JUN-MBD3 repressor complex that inhibits nuclear reprogramming to pluripotency through direct targeting of an OCT4 distal regulatory element. These findings reveal an unexpected role for Jun as a repressive epigenetic gatekeeper of reprogramming to pluripotency.
Application of enantioselective dihalogenation to the total synthesis of terpene natural products
Keywords: Chemistry.

Halogenated natural products are ubiquitous and in many cases display promising biomedical potential. Due to the scarcity of methods for the stereoselective incorporation of halides into organic substrates and the difficulty of isolation from nature, access to most members for anticancer screening is severely limited. We were able to leverage an advancement made in our laboratory, which allows for chemo-, regio-, and enantioselective synthesis of vicinal dihalide products, toward the stereoselective total synthesis of several polyhalogenated natural products. One of these compounds, halomon, was tested on the Bassik laboratory target identification screen, which identified an interesting pathway that serves to export the drug from the cancer cell. We have further shown that enriched dihalides can act as novel forms of chiral, removable auxiliaries that enable synthesis of stereocenters that are difficult to access with traditional methods.
Applications of chemical biology and mass spectrometry for the analysis of the O-GlcNAcome and adeno-associated viruses
Keywords: Chemistry.

Proteins are involved in nearly all cellular processes and functions. Though there are some 20000 protein-coding genes in the human genome, the functional space of these proteins is expanded dramatically by post-translational modifications (PTMs). Therefore, understanding the functional significance of any given protein in a biological context necessitates the identification and characterization of the protein PTMs. Glycosylation is one of the most ubiquitous forms of protein PTM, and advances in bioanalytical and chemical technologies have begun to enable the study of glycoconjugates more thoroughly. O-GlcNAcylation has garnered significant attention due to its involvement in co-regulating protein phosphorylation and for its myriad functions in cellular signaling, gene transcription, translation, and development. In Chapter 1 of this dissertation, I present an overview of O-GlcNAcylation, detailing the various roles it plays in biology and the high level of regulation for this PTM. I discuss enzymatic substrate specificity related to O-GlcNAcylation, and I briefly introduce the interplay of this modification with various other PTMs. In Chapter 2, I present a brief overview of different technologies available for the study of the O-GlcNAcome. Additionally, I present preliminary data using many of these methods for the application of understanding the dynamics of protein O-GlcNAcylation during neural development. Chapter 3 of this dissertation focuses on the effects of perturbing normal O-GlcNAc cycling during stem cell differentiation. I discuss chemical inhibition of the enzymes controlling the addition and removal of the modification and introduce a potential workflow for achieving end-stage neuronal cells faster from pluripotent human embryonic stem cells. In Chapter 4, I describe more broadly a variety of orthogonal comparisons between two leading production mechanisms for adeno-associated virus (AAV) gene therapeutics used in the clinic. Using a combination of analytical approaches, including MS-based deep proteomic profiling, two-dimensional isoelectric focusing in combination with enzymatic modification removal, transmission electron microscopy, comparative capsid structural modeling by cryo-EM, human cytokine profiling in response to vector transduction, comparative functional transduction assessments in murine liver and skeletal muscle tissues in vivo, primary human fetal brain slices ex vivo, and a variety of primary and immortalized cell types in vitro, I detail how the therapeutics are chemically, structurally, and biologically distinct.