VictorJuiz/thesis huggingface dataset:
The evolution and demography of X-linked and GWAS SNPs [electronic resource]

Population geneticists have used genome-wide single nucleotide polymorphism (SNP) datasets to investigate the demographic history of humans and to identify regions of the human genome subject to selection. While some general statements can be made about genome as a whole, every genomic locus has its own evolutionary history. The work contained in this dissertation is aimed at elucidating this history for two particular SNP subsets. The first two chapters explore the effects of selection on the X chromosome. Chapter 1 presents evidence that the X chromosome is more frequently a target of selection than the autosomes and identifies regions of the chromosome where selection may have acted. Chapter 2 explores the evolutionary history of one of these regions in depth through haplotype analyses. Chapter 3 investigates the role of selection in the evolution of SNPs with phenotypic associations and finds evidence for selection on SNPs associated with pigmentation, blood pressure, autoimmune disease, and infectious disease susceptibility. Overall, this work as a whole reinforces the conclusion that natural selection acts unevenly throughout the genome and presents evidence for selection on two subsets of genome-wide SNP datasets: X-linked SNPs and SNPs with phenotypic associations.

Keywords: Genetics
Advisor: Feldman Marcus W. primary advisor. Thesis advisor
Altman Russ advisor. Thesis advisor
Bustamante Carlos (Carlos D.) advisor. Thesis advisor
Tang Hua (Geneticist) advisor. Thesis advisor
Examining an unexpected protective role of amyloid-beta in experimental autoimmune encephalomyelitis [electronic resource]

[Beta]-amyloid-42 (A[beta]42) and [beta]-amyloid-40 (A[beta]40), major components of senile plaque deposits in Alzheimer's disease (AD), are considered neurotoxic and pro-inflammatory. In Multiple Sclerosis (MS), A[beta]42 is upregulated in brain lesions and damaged axons. Here we found, unexpectedly, that treatment with either A[beta]42 or A[beta]40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. A[beta]42 and A[beta]40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive Th1 or Th17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo A[beta]2 and A[beta]40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major pro-inflammatory cytokines and chemokines were reduced in the blood following A[beta] peptide treatment. Protection conferred by A[beta] treatment did not require its delivery to the brain: adoptive transfer with lymphocytes from donors treated with A[beta]42 attenuated EAE in WT recipient mice and A[beta] deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with A[beta]-treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of A[beta] there is exacerbated clinical EAE disease progression. Since A[beta]42 and A[beta]40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.

Keywords: Neurology.
Advisor: Steinman Lawrence primary advisor. Thesis advisor
Han May Htwe advisor. Thesis advisor
Utz Paul advisor. Thesis advisor
Wyss-Coray Anton advisor. Thesis advisor
Experimental determination of rate constants for reactions of the hydroxyl radical with alkanes and alcohols [electronic resource]

Over one quarter of the energy usage in the United States currently occurs in the transportation sector. Improvements in energy conversion efficiency and sustainability in transportation applications, therefore, can substantially contribute to improved energy security in our future. The design of advanced high-efficiency energy conversion devices for transportation applications can be facilitated with complex computer models of combustion processes. The development of these models requires a large experimental database to ensure accuracy of the computational predictions. This thesis discusses how experimental studies are utilized to create a database of rate constants for elementary reactions; these rate constants are integral components of any computational model of combustion chemistry. During a combustion process, the reaction of the hydroxyl (OH) radical, a highly reactive chemical intermediate, with a combustible fuel molecule is a major fuel consumption pathway under many combustion conditions. Thus, the rate constants for these types of reactions must be accurately known to develop a computational model that correctly describes the combustion chemistry. This thesis presents an experimental method for measuring rate constants in the reaction family of OH + Fuel -> Products using a shock tube reactor, laser diagnostics, and tert-butylhydroperoxide (TBHP) as an OH radical precursor. Important rate constant parameters describing subsequent reactions of TBHP decomposition are also studied. Current transportation fuels of interest in the combustion community include molecules in the alkane and butanol classes. Alkane molecules are a major component of many petroleum-derived fuels such as gasoline and jet fuel. Isomers of the butanol molecule are gaining popularity as a potential renewable alternative to gasoline because of their high energy density and the many known methods of production from biomass and agricultural byproducts. The rate constant measurement method is applied to the reaction of OH with three alkane molecules (n-pentane, n-heptane, and n-nonane) and four isomers of butanol (n-butanol, iso-butanol, sec-butanol, tert-butanol), and the results are reported in this thesis. Comparison of the rate constant results to estimation methods in the literature are presented, and, for several of the isomers of butanol studied, the measured data are also used to validate and/or suggest refinements to existing detailed kinetic mechanisms.

Keywords: Mechanical Engineering
Advisor: Hanson Ronald primary advisor. Thesis advisor
Bowman Craig T. (Craig Thomas)
Golden David
Experimental study of vacuum microplasma spraying [electronic resource]

Vacuum plasma spraying (VPS) is an industrial process for depositing coatings of metal or ceramic in order to impart surface properties to an underlying part, or to build freestanding parts. High-value coatings of high melting point, oxidation-sensitive materials for applications such as aerospace components or biomedical implants are enabled by the vacuum process. Commercially available VPS systems operate at arc power levels of 40--120 kW and with deposition rates of 25¬--50 g/min. In recent years, the plasma spray community has developed interest in scaling down such systems to reduce the cost of small-scale applications and/or for novel applications enabled by lower deposition rates. The work of this dissertation is the first published account of vacuum microplasma spraying (VMPS), operating at arc power levels of 1--2 kW and deposition rates of 0.1--1 g/min. The dissertation documents the design, construction, and testing of the VMPS system, by means of decomposition into subprocesses. For subprocess 0 (powder delivery to the plasma jet), the work entailed development of a novel powder feeder. For subprocess 1 (arc discharge and nozzle flow), a supersonic plasma nozzle with internal powder injection was developed and tested. Flow, calorimetric, and pressure measurements in the nozzle are presented and incorporated into a thermodynamic model for the plasma generated by the arc discharge. For subprocess 2h (plasma--particle heat transfer), a novel "surrogate particle" heat transfer measurement was developed and used to evaluate heat transfer rates to sprayed particles. In conjunction with finite element modeling of convection and radiation to the particle, these experimental data were used to estimate required residence time for sprayed particles of various metals. For subprocess 2m (plasma--particle momentum transfer), a planar laser Mie scattering system was employed for imaging and tuning of particle trajectories, and a particle image velocimetry (PIV) system was used to determine particle velocities and residence times. Final recommendations include the use of smaller particle diameters in order to enhance melting behavior in these low-power plasma jets. The system is capable of depositing challenging, high-value metals and ceramics. With expected improvements from particle size reduction, it is prepared for advanced applications.

Keywords: Mechanical Engineering
Advisor: Cappelli Mark A. (Mark Antony) primary advisor. Thesis advisor
Edwards Christopher
Prinz F. B. advisor. Thesis advisor
An experimental test of the effect of norm-referenced and criterion-referenced feedback on just world beliefs, motivation, and performance [electronic resource] : does social disadvantage matter?

The just world beliefs, self-reported commitment to long-term academic goals, time spent studying, and change in performance after receiving norm-referenced, criterion-referenced, and control feedback were compared. Students from two high schools in Northern California serving lower middle and upper middle class populations respectively took a difficult math test and were provided with failure feedback based on either a norm-referenced, criterion-referenced, or non-referenced standard. Participants were offered an opportunity to study before they took a second difficult math test. For socially disadvantaged students (as indicated by mother's highest level of education), norm-referenced feedback resulted in significantly less time studying for the second test. In addition, a significant interaction between level of social disadvantage and type of feedback on change in performance is revealed. In particular, norm-referenced feedback is found to have a significant negative effect on the change in performance of disadvantaged students and a significant positive effect on the change in performance of advantaged students. While feedback type did not significantly affect student just world beliefs, a relationship between just world beliefs and time spent studying that is moderated by level of social disadvantage is revealed. The results add to the literature by generalizing findings from previous research to a different population and to different measures of just world beliefs and motivation suggesting a potential developmental component to the relationship between just world beliefs and motivation. The research also sheds new light on how norm-referenced feedback differentially affects student outcomes depending on level of social disadvantage.

Keywords: Education.
Advisor: Haertel Edward primary advisor. Thesis advisor
Carter Prudence L.
Cohen Geoffrey L. (Geoffrey Lawrence) advisor. Thesis advisor
Exploiting non-linear Arrhenius dependence of diode IV curves to determine Schottky barrier band diagrams [electronic resource]

Accurate extraction of Schottky barrier height is imperative to the development of low resistance contacts. An analytical model for current density is found that accurately accounts for conduction in the thermionic emission (TE), thermionic field emission (TFE), and field emission (FE) regimes. Use of this model in non-linear regression allows more information to be extracted from diode current-voltage-temperature (IVT) curves than previously possible. The proposed model uses the Arrhenius non-linear dependence experimental diode IV curves to regress the Schottky barrier height ([phi]B0), steepness factor (E00), and Fermi level ([xi]), enabling band diagrams of the measured interfaces to be determined. This model is tested against both simulated interfaces using the transmission matrix method (TMM) and experimental data. This complete picture of band information allows material interface behavior to be understood more completely, ultimately facilitating more efficient contact engineering.

Keywords: Electrical Engineering
Advisor: Saraswat Krishna primary advisor. Thesis advisor
Miller D. A. B. advisor. Thesis advisor
Wong Hon-Sum Philip
Extensions and applications of persistence based algorithms in computational topology [electronic resource]

In this thesis, we discuss various extensions and applications of the seminal idea of persistent homology applied to metric datasets. In the first part, we discuss the computation of certain classes of maps between chains on simplicial complexes. It turns out that the parameterization of appropriately functorial maps may be found by computing the homology of the hom-complex of two chain complexes. We also discuss the selection of geometrically meaningful maps through optimization procedures. In particular, one would be interested in computing maps between chains on the complexes that are bisimplicial - meaning that the images and preimages of simplices contain either zero or one simplices. We also develop a relaxation of this problem that can be framed as a linear program. The theory of zigzag persistence has opened new doors in topological data analysis. Hypothetical applications were discussed in a paper by Carlsson and de Silva. In the second part we discuss in detail algorithms and the implementation of these applications, and demonstrate their use on various datasets. The applications include topological bootstrapping, parameter thresholding, and the comparison of witness complexes. In the third part we discuss some theoretical and algorithmic results on the probabilistic nature of random matroids, random subgraphs and random subcomplexes. First, we discuss some background information regarding sampling matroids, and provide some connections to existing literature on computational complexity and combinatorics. We close with a discussion regarding the randomized computation of the Tutte polynomial of certain dense graphs as well as the extension of these results to sampling the higher skeleta of simplicial complexes.

Advisor: Carlsson Gunnar
Guibas Leonidas J. advisor. Thesis advisor
Müllner Daniel
Extracellular molecular interactions in celiac disease [electronic resource]

This dissertation is aimed to explore two critical extracellular interactions in the pathogenesis of celiac disease: thioredoxin mediated extracellular tissue transglutaminase (TG2) activation and binding interaction between gluten peptides and HLA-DQ2. The mechanism of activation of TG2 in the extracellular matrix remained a fundamental mystery in biology as well as in celiac disease pathogenesis. Earlier investigations have highlighted the role of a disulfide bond formed by vicinal Cys residues in maintaining calcium-bound TG2 in an inactive state. We characterized the redox potential of this disulfide bond to be approximately -190 mV, which is very oxidative for a disulfide bond in proteins. We then identified a physiological factor human thioredoxin (Trx) for the activation of oxidized TG2. With a kcat/KM of 1.6 [mu]m-1min-1. Trx was a highly specific activator of oxidized human TG2. Both recombinant Trx and interferon-[gamma] stimulated Trx released from monocytes can activate extracellular TG2 around the fibroblasts. In addition to explaining how TG2 can be activated by dietary gluten in the small intestinal mucosa of celiac sprue patients, our findings reveal a new strategy for inhibiting the undesirable consequences of TG2 activity in this widespread and lifelong disease. Inspired by the finding of Trx mediated TG2 activation, we then sought to develop small molecule disulfide inhibitors targeting extracellular Trx. We performed a careful structural-activity relationship study based on an imidazolyl isobutyl disulfide compound. Two rounds of inhibitor screening suggested that aromatic ring part mainly contributes to ligand binding, and a new lead compound was identified with ~26 fold increased inhibition selectivity. Potential inhibitor binding site was also predicted near Cys73 by docking model and Trx mutant results. Our findings provide novel tools to study Trx-TG2 interaction in celiac disease as well as a promising therapeutic candidate. Understanding the binding interaction between HLA-DQ2 and antigenic peptides lies at the center of antigen presentation in celiac disease. We use capillary electrophoresis-fluorescence detection to investigate competition and displacement of endogenous peptides by an immunogenic gluten peptide (the 20-mer) for binding to HLA-DQ2. Remarkably, this immunogenic peptide could displace CLIP peptides from DQ2 binding site under neutral but not acidic pH condition. This unique property of gluten peptide supports a direct loading mechanism of antigen presentation in the extracellular environment.

Keywords: Chemistry
Advisor: Khosla Chaitan
Cui Bianxiao advisor. Thesis advisor
Herschlag Daniel
Fabrication and characterization of nanoscale resistance change memory [electronic resource]

As the current charge-based memory technologies such as DRAM and Flash Memory are facing their fundamental scaling limits, new types of memory technologies such as spin-torque-transfer RAM (STTRAM), phase-change memory (PCM), and metal-oxide resistance change memory (RRAM) have been actively explored. Among these candidates, RRAM devices utilize the resistance change property of the metal-oxide films, and have shown promising results such as fast switching speed, low programming current, and good CMOS compatibility. Despite the potential advantages, they suffer from the critical issues that must be addressed for the high-density memory application, which includes existence of forming-process, large variation in switching characteristics, and cell selection issue in cross-point structures. In this thesis, first, the process and characterization methodology for RRAM devices is demonstrated to verify the characteristics and potential issues in the nanoscale regime down to 50x50-nm^2 size. Unipolar switching memory cells using NiO thin films were fabricated by ebeam lithography process. The fabricated device characteristics and the scaling trends will be discussed. Next, two novel RRAM structures are proposed for improved cell characteristics. In the first structure, both top and bottom electrodes are processed prior to the metal-oxide deposition, and therefore, contamination-less programming region is achieved in the memory cell. Moreover, the novel structure features more confined conduction path compared to the conventional structure, which results in narrower low-resistance distribution. The process flow and characteristics of the nanoscale NiO memory cells using this structure will be demonstrated. In the second structure, an oxide-to-oxide interface is incorporated inside the memory cell in order to utilize the initial leakage and eliminate the high-voltage forming process (OTO Cell Technology). Due to this initial leakage, the as-fabricated AlOx memory cells exhibit low-resistance sates, while the conventional AlOx devices show high-resistance initial states. The new memory cell does not require the high-voltage forming process since the as-fabricated cells can be switched to high-resistance states with a regular RESET voltage. Finally, application of the forming-free OTO cells to the complementary resistive switch (CRS) scheme will be discussed using the measured cell characteristics. The CRS scheme was proposed as a potential solution to the high-density cross-point memory arrays for resistive memory. The novel memory cells with forming-free property demonstrate promising results, which enables the CRS scheme for bipolar switching RRAM cells.

Keywords: Electrical Engineering
Advisor: Wong Hon-Sum Philip
Nishi Yoshio
Saraswat Krishna advisor. Thesis advisor
Factors that influence the open circuit voltage and stability of polymer [electronic resource] : fullerene bulk heterojunction solar cells

Solution processed organic photovoltaics offer the potential of providing solar energy at a significantly lower cost than conventional solar cells due to scalable manufacturing by roll-to-roll printing, low materials costs and facile installation of light-weight modules. Recently, power conversion efficiencies of over 10% have been achieved in small area multijunction devices, and stability lifetimes of several years have been demonstrated, though these are not yet sufficient for commercialization. The development of new materials that can produce high open circuit voltage devices is critically important for improving the efficiency of multijunction organic solar cells. Polymer:fullerene solar cells with power conversion efficiencies of over 7% are demonstrated with blends of the polymer PBDTTPD and the fullerene PCBM. These devices achieve an open circuit voltage of 0.94V and internal quantum efficiencies of 88% and thus are an ideal candidate for the large bandgap junction of tandem organic solar cells. The open circuit voltage is increased above 1V when the polymer is blended with multi-adduct fullerenes, but the current and fill factor are greatly reduced. Photoluminescence, electroluminescence and photocurrent measurements indicate that excitons undergo energy transfer to the fullerene rather than dissociate to form charges at the heterojunction interface due to the small difference in energy between the fullerene bandgap and charge transfer states. Consequently new non-fullerene electron acceptor materials with larger bandgaps may be required for devices to achieve both near unity internal quantum efficiencies and open circuit voltages exceeding 1.0V. The photodegradation of polymer:fullerene blend films exposed to ambient conditions for a variety of polymer and fullerene derivative combinations is also presented. The rate of irreversible polymer photobleaching in blend films was found to consistently and dramatically increase with decreasing electron affinity of the fullerene derivative. Furthermore, blends containing fullerenes with the smallest electron affinities photobleached at a faster rate than films of the pure polymer. These observations can be explained by a mechanism where both the polymer and fullerene donate photogenerated electrons to diatomic oxygen to form the superoxide radical anion which degrades the polymer.

Keywords: Applied Physics
Advisor: Harris J. S. (James Stewart)
McGehee Michael
Salleo Alberto
Fast dynamics of aqueous biological molecules investigated with 2D IR spectroscopy [electronic resource]

Proteins are dynamic structures that are in constant fluctuations, and their ability to undergo structural changes is critical to their function. However, their fastest dynamics in thermal equilibrium have remained largely unexplored. In this work, studies that examine the dynamics of aqueous proteins using two-dimensional infrared echo spectroscopy (2D IR) are presented. In particular, investigations of fast fluctuations in proteins and peptides within the context of structural changes upon denaturation are discussed. 2D IR is a nonlinear optical spectroscopic technique that can measure ultrafast dynamics of complex molecules in the picoseconds regime, timescales ~6-10 orders of magnitude faster than nuclear magnetic resonance. In addition, the relatively low energy mid-IR laser pulses used in this study probe the relevant nuclear degrees of freedom without significantly perturbing the protein structure or dynamics. Brief descriptions of the experimental setup and methods, as well as analysis and interpretation, are given.

Keywords: Chemistry
Advisor: Fayer Michael D. primary advisor. Thesis advisor
Andersen Hans
Dai Hongjie