VictorJuiz/thesis huggingface dataset:
Double displacement reactions [electronic resource] : novel strategies for nucleic acid detection
Keywords: Chemistry

This thesis describes the design, synthesis, and evaluation of two new classes of self-ligating oligonucleotide probes: Double Displacement and Sandwich probes. These probes are an extension of previous work in our laboratory with quenched autoligation (QUAL) probes, which produce a fluorescent signal by a template-dependent SN2 displacement of a fluorescence quencher, increasing the emission of a conjugated fluorophore. These probes are used to detect complementary RNA sequences in vitro and in cells, making them useful diagnostic agents for differentiating between different cell types based on their genetics. Both new classes of probes improve and expand on previous QUAL approaches by requiring two displacement reactions to fully unquench a nearby fluorophore. Three potential Double Displacement architectures, all possessing two fluorescence quencher/leaving groups (dabsylate groups) at the 5' end of a fluorescently-labeled oligonucleotide, were synthesized and evaluated for templated reaction with nucleophile probes both in vitro and in intact bacterial cells. All three DD probe designs provided substantially better initial quenching than a single quencher control. In isothermal templated reactions in vitro, Double Displacement probes yielded considerably lower background signal than previous single-displacement probes; investigation into the mechanism revealed that one dabsylate acts as a sacrificial leaving group, reacting nonspecifically with water, but yielding little signal because another quencher group remains. Templated reaction with the specific nucleophile probe is required to activate a signal. The best-performing probe architecture was demonstrated in a two-color, FRET-based two-allele discrimination system in vitro, and was shown to be capable of discriminating between two closely related species of bacteria differing by a single nucleotide at a ribosomal RNA target site. Sandwich probes also require two displacements to fully unquench an oligonucleotide-conjugated fluorophore, Unlike Double Displacement probes, these molecules have one fluorescence quencher at each end of the oligonucleotide, each of which is unquenched by a flanking nucleophile oligonucleotide. These probes also show improved initial quenching, excellent single nucleotide polymorphism discrimination and template-dependent activation in intact bacterial cells. Both of these new classes of template reactive oligonucleotide probes advance the field of reagent-free oligonucleotide ligation reactions and show promise for applications in detecting cellular RNA.
A duration analysis of sovereign debt [electronic resource]
Keywords: Economics

A two-state duration model with recurrent events is developed to investigate the determinants of time to default and time to settlement jointly for a relatively large sample of developing countries in the post-war period. It explicitly addresses state dependence in sovereign debt-servicing behavior and explores a possible link between default and debt settlement. The maximum likelihood estimation results suggest that the default and settlement hazards have different determinants: the default hazard is largely predicted by macroeconomic fundamentals, whereas the settlement hazard is linked more with intuitional factors and default history. Controlling for country-specific unobserved heterogeneities is important for consistent estimation of the covariate effects and the results also indicate significant efficiency gains from the joint estimation. The time-aggregation issue is discussed further with numerical examples under various assumptions for the baseline.
Dynamic constitutional stability [electronic resource]
Keywords: Political Science.

This dissertation has four objectives. Building on the contributions of Friedrich Hayek and Douglass North, it demonstrates the importance of organizational learning and "adaptive efficiency" (North 2005) in accounting for the stability of institutions -- especially in periods of rapid change. Second, it applies this perspective to what I call the problem of dynamic constitutional stability, or why some constitutions are better at responding to change and crisis, and thus surviving, than others. Third, it argues that creating dynamic stability by building a constitution capable of responding to change was the central concern of Federalists in designing the Federal Constitution of 1787. Fourth, it offers a new institutional framework to consider classic questions of constitutional and statutory interpretation and the role of the judiciary in the American constitutional system.
Dynamic contrast-enhanced breast MRI [electronic resource]
Keywords: Electrical Engineering

T1-weighted dynamic contrast-enhanced (DCE) breast MRI has shown high sensitivity in detecting tumors, but has suffered from low specificity. Accuracy of tumor detection and characterization is enhanced by high temporal and spatial resolution, high signal-to-noise ratio (SNR), reliable fat suppression, and reduction of flow artifacts. This thesis presents imaging techniques for improving DCE breast MRI in terms of imaging speed and image quality. It first demonstrates that slab-phase modulation of the two breast slabs improves parallel imaging quality in terms of SNR and aliasing artifacts. Second, it presents temporal acceleration scheme by using parallel imaging to achieve high temporal resolution. Thorough patient study results are also included. Third, it shows that fat suppression can be improved by applying independent shimming to each breast through in vivo experiments. Finally, it demonstrates that partial saturation can eliminate flow artifacts efficiently in RF-spoiled gradient-echo sequences. This technique would be helpful to quantification of kinetic parameters from DCE-MRI.
Dynamic games and mechanisms with serially dependent private information [electronic resource]
Keywords: Economics

This dissertation consists of three essays. In "A Folk Theorem with Markovian Private Information" (with Juan F. Escobar) we consider repeated Bayesian two-player games in which the players' types evolve according to an irreducible Markov chain, type transitions are independent across players, and players have private values. The main result shows that, with communication, any Pareto efficient payoff vector above a minmax value can be approximated arbitrarily closely in a perfect Bayesian equilibrium as the discount factor goes to one. In the second essay, "Dynamic Mechanism Design: Incentive Compatibility, Profit Maximization, and Information Disclosure" (with Alessandro Pavan and Ilya R. Segal), we examine the design of dynamic screening mechanisms for environments in which the agents' types follow a stochastic process, decisions may be made over time, and the decisions may affect the type process. We derive a formula for an agent's equilibrium payoff in an incentive-compatible mechanism, which generalizes Mirrlees's envelope formula of static mechanism design. When specialized to quasi-linear environments, the formula yields a dynamic revenue-equivalence result and an expression for dynamic virtual surplus, which is instrumental for the design of profit-maximizing mechanisms. We also provide sufficient conditions for incentive compatibility. We apply the results to derive optimal dynamic contracts for a number of novel settings. The final essay, "Ironing without Control, " extends a method for solving a class of optimization problems, encountered frequently in mechanism design, where a functional is maximized over the set of nondecreasing functions. For example, the approach can be used to solve principal-agent models with adverse selection.
Econometric analysis of policy effect [electronic resource]
Keywords: Management Science and Engineering

The generalized method of moments (GMM) is a general approach to tackle problems of endogeneity which is very common in econometric studies. However, the asymptotic theory of GMM provides a poor approximation to finite sample performance of its estimators and associated test statistics largely due to the weak or a large number of moment conditions. The focus of this dissertation is to propose a new approach for moment restriction models that has advantages over previous approaches when some moment restrictions are weakly informative or when a particular subvector rather than the whole parameter vector is of interest. Our method consists of two stages and is denoted by 2SMMS (two-stage model and moment selection). First, we would like to eliminate from consideration those models that do not approximate well the true model. Second, among those models and moment restrictions which are not eliminated, we would like to choose the model and moment restriction combination which provides the best estimate of the parameter vector of interest. Theoretical analysis shows that under regularity conditions our procedure chooses the correct model that has the largest number of moment restrictions and the smallest number of unknown parameters, whose covariance matrix is the smallest according to some prescribed measures. Our new procedure is also illustrated in a simulation study and an empirical study, which show that ours improve significantly upon Andrews and Lu's (2001).
The economics of market thickness [electronic resource]
Keywords: Economics

This work investigates the differences between thin and thick markets, both on the demand side and on the supply side. The first chapter deals with the effects of market thickness in a list-order market, a market where sellers list goods for sale and determine the ask price, and buyers choose among the goods listed for sale but can not negotiate the prices. We focus on the supply side in this market, and show that in thicker markets, markets in which both buyers and sellers arrive more frequently, sellers raise their prices. This finding indicates that a thick market is not necessarily more efficient that a thin market, at least in the sense that the final allocation of goods might leave a larger share of potentially beneficial trades unfulfilled. The second and third chapters deal with the effects of online news on the political media market. The introduction of the Internet as a publishing medium for news changed the cost structure on the supply side of the political news market: the lower cost of content production and publishing turned niche issues and views into viable markets. The second chapter develops a theory that explains why people who seek news online tend to be, on average, more non-centrist than people who do not and provides some empirical evidence that this is indeed the case. The third chapter investigates whether the introduction of broadband Internet swayed people's views away from center, but finds no evidence for such influence. It seems that by lowering content production costs on the supply side, the markets for news with non-centrist slant became thicker on the supply side, but made no impact on the demand side.
Educational robotics [electronic resource] : transformative or trendy?
Keywords: Education.

This study investigated the use of robotics activities to teach introductory computer programming. Two conditions, one using physical programmable robots and one us- ing a virtual programmable agent, were used to teach parallel curricular sequences in secondary technology classes. Addressing open questions and inconsistent findings in existing literature, the study examined the comparative effect of each condition on both cognitive and affective outcomes. Instrumentation included assessment items, affective scale measures, semi-structured interviews and queries of participants' back- ground (e.g., prior experience) and demographic information. In general, no main effects of condition were found on cognitive or affective measures. However, signifi- cant effects of gender and other background variables suggest robotics activities used in a general classroom setting may serve to reinforce rather than disrupt existing patterns of differential success and engagement.
Effective schools addressing the achievement gap [electronic resource] : case studies and cross case analysis of three schools in San Francisco
Keywords: Education.

In 2008, San Francisco Unified School District had the highest average scores on state standardized achievement tests of all the large urban districts in California, but had the widest achievement gap when comparing its district average with scores of its lowest performing students. Using case study methodology, this study examines the characteristics of three elementary schools in San Francisco with larger increases in "academic productivity" (a measure of how much value a school adds beyond students initial achievement) than other schools. These schools also show signs of accelerating the outcomes for traditionally underserved students in San Francisco like African Americans, Latinos, and English Learners. The study compares the characteristics of these three effective schools in San Francisco in a cross case analysis that summarizes the prominent characteristics among these schools. In the end, this study presents suggestions for further research and hypotheses about the practices, structures, and policies that help schools in San Francisco close the achievement gap.
Efficient embedded computing [electronic resource]
Keywords: Electrical Engineering

This dissertation describes Elm, an efficient programmable system for high-performance embedded applications. Elm is significantly more efficient than conventional embedded processors on compute-intensive kernels. Elm allows software to exploit parallelism to achieve performance while managing locality to achieve efficiency. Elm implements a novel distributed and hierarchical system organization that allows software to exploit the abundant parallelism, reuse, and locality that are present in embedded applications. Elm provides a variety of mechanisms to assist software in mapping applications efficiently to massively parallel systems. To improve efficiency, Elm allows software to explicitly schedule and orchestrate the movement and placement of instructions and data. This dissertation presents an analysis of the efficiency of conventional embedded processors, and evaluates the impact that the concepts and mechanisms proposed for Elm have on processor and system efficiency.
Efficient models and algorithms for problems in genomics [electronic resource]
Keywords: Statistics

We present models and algorithms that can be applied to common problems in analysis of genomic data. These include CNV (Copy Number Variation) detection, local ancestry inference in admixed populations, and haplotype inference in panels of unrelated individuals. Chapter 2 proposes a new algorithm for the Fused Lasso Signal Approximator which was recently been proposed as an alternative to HMM's for CNV detection. Chapter 3 describes new models for local ancestry inference when high density genotype data is available, and our focus is on a higher order Autoregressive Hidden Markov Model (ARHMM). We give solutions to problems that have thus far prevented the use of higher order ARHMM's for this task, and we demonstrate the model on real and simulated data. Finally, in chapter 4 we given an approach for inferring haplotypes from unphased genotype data. We optimize a likelihood closely related to the PHASE model (which is considered one of the most accurate), and we show that the proposed approach is substantially more accurate than recent alternatives. The work in these chapters contributes to common and important tasks in analysis of genomic data for association studies.
EGO-1, an essential Caenorhabditis elegans RNA-directed RNA polymerase, modulates gene expression through the messenger RNA-templated production of short antisense effector RNAs [electronic resource]
Keywords: Genetics

The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. These genes must direct the regulation of cell proliferation, meiosis, and sex determination, as well as gamete formation and fertilization. Several genes required for small RNA biogenesis and function are also required for the proper organization and development of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for C. elegans germ-line development and efficient RNAi of germ-line expressed genes. Additionally, ego-1 mutants have been shown to exhibit defects in heterochromatin assembly on unpaired DNA and proper chromosome segregation during meiosis. Despite our understanding of the morphology of ego-1 mutant worms, it has remained unclear how the loss of a putative RdRP can cause such dramatic phenotypes in the C. elegans germline. That is, what role does EGO-1 play in promoting the development of the germline? There is strong evidence for the requirement of the C. elegans RdRP RRF-3 in producing endogenous small RNAs that target mRNA produced from specific genes. Additionally, there is evidence that EGO-1 may interact directly with chromatin. The questions become what target (or perhaps targets) is being disrupted in the ego-1 mutant and are they being disrupted at the chromatin or RNA level? Using high-throughput small RNA and messenger RNA sequencing we found that EGO-1 is required to produce small RNAs antisense to a number of germline-expressed genes through several developmental stages. We found that these genes fall into several classes including genes required for kinetochore (klp-7) and nuclear pore (npp-3) assembly, as well as the production of histone-modifying (set-21) and centromeric proteins (hcp-3). We also found several RNAi-related genes to be targets of EGO-1 (csr-1, mut-14, mut-16, prg-1, tsn-1). Finally, we show a strong correlation between the loss of small RNAs and the rise of mRNA levels in ego-1(-) animals.
Eiger's role in Drosophila melanogaster immunity [electronic resource]
Keywords: Immunology.

Eiger is the sole TNF family member found in Drosophila melanogaster. This signaling molecule is induced during infection and is required for an appropriate immune response to many microbes; however, little is known concerning where eiger is produced and what genes are regulated by eiger. Here we show that eiger is made in the fly's fat body during a Salmonella typhimurium infection. Using tissue specific knockdowns we found that eiger expression in the fat body is required for all of the phenotypes we observed in eiger null mutant flies. This includes reduced melanization, altered antimicrobial peptide expression and reduced feeding rates. The effect of eiger on feeding rates alone may account for the entire phenotype seen in eiger mutants infected with S. typhimurium. We further characterized the eiger response using transcriptional arrays. We found that the eiger regulates a number of genes involved in metabolism and hormonal signaling during an immune response. How these genes are involved in the immune response is not clear. Finally we examined the role of age related decline of the immune system in D. melanogaster during bacterial infection. We found that vigor and tolerance are reduced when old flies are challenged with a variety of bacterial pathogens.
Electrocatalytic dioxygen reduction by surface-immobilized molecular copper complexes [electronic resource]
Keywords: Chemistry

Surface-immobilized Cu(I) complexes with substituted 1,10-phenantrholines and related ligands are competent electrocatalysts for the 4-electron reduction of dioxygen to water. A large library of Cu(I) complexes has been adsorbed to the carbon electrodes by either physisorption or by covalent attachment directly to the carbon surface. The rate of electrocatalytic dioxygen reduction is studied using the hydrodynamic techniques rotating-disk voltammetry and rotating-ring disk voltammetry. From these studies, potential-dependent kinetic rates are established. The onset potential and kinetic rate for O2 reduction can be modulated by changing the nature of the ligand in the immobilized Cu complex, or by changing the nature by which the Cu complex is attached to the surface. Evidence is presented that the 4-electron reduction of dioxygen to water operates by a binuclear pathway that requires 2 Cu catalysts in close proximity to coordinate and reduce a single dioxygen molecule. Mechanisms are proposed for dioxygen reduction by adsorbed Cu(I) complexes that are consistent with the observed data. Electrocatalytic hydrogen peroxide reduction has also been studied briefly in an attempt to intercept the dioxygen-reduction mechanism, and the results of these studies are reported.
Electrode surface activation and nanostructuring effects on fuel cell performance [electronic resource]
Keywords: Materials Science and Engineering

Fuel cells are an attractive clean energy technology due to the low or zero emissions from operation and the potentially high efficiency. However, several challenges exist that hinder the implementation of fuel cells as a part of portable power devices. Among these challenges are the losses inherent to fuel cell operation. This work presents the results of three studies that attempt to lower activation losses on the fuel cell anode by catalysis or increased reaction area. The first study focuses on the anode electrochemistry for a novel fuel cell device that utilizes the naturally occurring charge separation in photosynthesis as the electrolyte. The second study investigates the use of an oxide ion conducting electrolyte and a PtRu anode for a direct methanol fuel cell at temperatures much lower than previously considered feasible. The third study examines the fabrication of high-surface area mixed electronic and ionic conducting anodes and their impact on fuel cell performance. The latter two studies are motivated by interest in low-temperature direct methanol fuel cells for mobile devices, while the former was an exploratory investigation into the possibility of "bioelectricity", which may more appropriately have been called a "photosynthetic fuel cell". Photosynthesis energizes electrons obtained through hydrolysis in the thylakoid space and through a series of steps, reduces the charge-carrying protein ferredoxin (Fd). The charge on Fd is used in numerous processes throughout the cell. It is well established that Fd does not readily give up its charge to a bare metal electrode. Therefore, mediators or surface modifiers must be used to capture this high-energy electron. The bioelectricity investigation studied the effects of various chemical modifiers attached to gold electrodes on the electrooxidation of reduced Fd and found that poly-L-lysine covalently bound to a monolayer of mercaptoundecanoic acid on gold resulted in reasonable oxidation kinetics. Typical solid oxide fuel cells operate at temperatures above 600°C. It was found in the second study that a PtRu anode was effective in low temperature (250-450°C) direct methanol operation using yttria-stabilized zirconia (YSZ), (Y2O3)0.08(ZrO2)0.92, as the electrolyte. In this arrangement, methanol may be used without equimolar quantities of water, in contrast to typical direct methanol fuel cells (DMFCs). Electrochemical impedance spectroscopy (EIS) measurements were analyzed in an effort to better understand the rate-limiting processes. In the third study presented in this work, the fabrication of high-surface are mixed electronic and ionic conducting (MEIC) anodes is discussed, along with the results of fuel cell characterization with MEIC anodes of high surface area. In particular, fuel cells fabricated using yttrium-doped BaZrO3 (BYZ) electrolytes are studied with high surface area Pd anodes for use with H2 and methanol fuels.