Aerodynamic database error filtering via high order singular value decomposition

Esta Tesis presenta un nuevo método para filtrar errores en bases de datos multidimensionales. Este método no precisa ninguna información a priori sobre la naturaleza de los errores. En concreto, los errrores no deben ser necesariamente pequeños, ni de distribución aleatoria ni tener media cero. El único requerimiento es que no estén correlados con la información limpia propia de la base de datos. Este nuevo método se basa en una extensión mejorada del método básico de reconstrucción de huecos (capaz de reconstruir la información que falta de una base de datos multidimensional en posiciones conocidas) inventado por Everson y Sirovich (1995). El método de reconstrucción de huecos mejorado ha evolucionado como un método de filtrado de errores de dos pasos: en primer lugar, (a) identifica las posiciones en la base de datos afectadas por los errores y después, (b) reconstruye la información en dichas posiciones tratando la información de éstas como información desconocida. El método resultante filtra errores O(1) de forma eficiente, tanto si son errores aleatorios como sistemáticos e incluso si su distribución en la base de datos está concentrada o esparcida por ella. Primero, se ilustra el funcionamiento delmétodo con una base de datosmodelo bidimensional, que resulta de la dicretización de una función transcendental. Posteriormente, se presentan algunos casos prácticos de aplicación del método a dos bases de datos tridimensionales aerodinámicas que contienen la distribución de presiones sobre un ala a varios ángulos de ataque. Estas bases de datos resultan de modelos numéricos calculados en CFD. ABSTRACT A method is presented to filter errors out in multidimensional databases. The method does not require any a priori information about the nature the errors. In particular, the errors need not to be small, neither random, nor exhibit zero mean. Instead, they are only required to be relatively uncorrelated to the clean information contained in the database. The method is based on an improved extension of a seminal iterative gappy reconstruction method (able to reconstruct lost information at known positions in the database) due to Everson and Sirovich (1995). The improved gappy reconstruction method is evolved as an error filtering method in two steps, since it is adapted to first (a) identify the error locations in the database and then (b) reconstruct the information in these locations by treating the associated data as gappy data. The resultingmethod filters out O(1) errors in an efficient fashion, both when these are random and when they are systematic, and also both when they concentrated and when they are spread along the database. The performance of the method is first illustrated using a two-dimensional toymodel database resulting fromdiscretizing a transcendental function and then tested on two CFD-calculated, three-dimensional aerodynamic databases containing the pressure coefficient on the surface of a wing for varying values of the angle of attack. A more general performance analysis of the method is presented with the intention of quantifying the randomness factor the method admits maintaining a correct performance and secondly, quantifying the size of error the method can detect. Lastly, some improvements of the method are proposed with their respective verification.

RNA virus error catastrophe: Direct molecular test by using ribavirin

RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA viruses may be susceptible to error catastrophe, where they undergo a sharp drop in viability after a modest increase in mutation frequency. We recently showed that the important broad-spectrum antiviral drug ribavirin (currently used to treat hepatitis C virus infections, among others) is an RNA virus mutagen, and we proposed that ribavirin's antiviral effect is by forcing RNA viruses into error catastrophe. However, a direct demonstration of error catastrophe has not been made for ribavirin or any RNA virus mutagen. Here we describe a direct demonstration of error catastrophe by using ribavirin as the mutagen and poliovirus as a model RNA virus. We demonstrate that ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. A 99.3% loss in viral genome infectivity is observed after a single round of virus infection in ribavirin concentrations sufficient to cause a 9.7-fold increase in mutagenesis. Compiling data on both the mutation levels and the specific infectivities of poliovirus genomes produced in the presence of ribavirin, we have constructed a graph of error catastrophe showing that normal poliovirus indeed exists at the edge of viability. These data suggest that RNA virus mutagens may represent a promising new class of antiviral drugs.

Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation

High affinity antibodies are generated in mice and humans by means of somatic hypermutation (SHM) of variable (V) regions of Ig genes. Mutations with rates of 10−5–10−3 per base pair per generation, about 106-fold above normal, are targeted primarily at V-region hot spots by unknown mechanisms. We have measured mRNA expression of DNA polymerases ι, η, and ζ by using cultured Burkitt's lymphoma (BL)2 cells. These cells exhibit 5–10-fold increases in heavy-chain V-region mutations targeted only predominantly to RGYW (R = A or G, Y = C or T, W = T or A) hot spots if costimulated with T cells and IgM crosslinking, the presumed in vivo requirements for SHM. An ∼4-fold increase pol ι mRNA occurs within 12 h when cocultured with T cells and surface IgM crosslinking. Induction of pols η and ζ occur with T cells, IgM crosslinking, or both stimuli. The fidelity of pol ι was measured at RGYW hot- and non-hot-spot sequences situated at nicks, gaps, and double-strand breaks. Pol ι formed T⋅G mispairs at a frequency of 10−2, consistent with SHM-generated C to T transitions, with a 3-fold increased error rate in hot- vs. non-hot-spot sequences for the single-nucleotide overhang. The T cell and IgM crosslinking-dependent induction of pol ι at 12 h may indicate an SHM “triggering” event has occurred. However, pols ι, η, and ζ are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction.

Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli

DNA polymerase V, composed of a heterotrimer of the DNA damage-inducible UmuC and UmuD\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{^{\prime}}}}\end{equation*}\end{document} proteins, working in conjunction with RecA, single-stranded DNA (ssDNA)-binding protein (SSB), β sliding clamp, and γ clamp loading complex, are responsible for most SOS lesion-targeted mutations in Escherichia coli, by catalyzing translesion synthesis (TLS). DNA polymerase II, the product of the damage-inducible polB (dinA ) gene plays a pivotal role in replication-restart, a process that bypasses DNA damage in an error-free manner. Replication-restart takes place almost immediately after the DNA is damaged (≈2 min post-UV irradiation), whereas TLS occurs after pol V is induced ≈50 min later. We discuss recent data for pol V-catalyzed TLS and pol II-catalyzed replication-restart. Specific roles during TLS for pol V and each of its accessory factors have been recently determined. Although the precise molecular mechanism of pol II-dependent replication-restart remains to be elucidated, it has recently been shown to operate in conjunction with RecFOR and PriA proteins.

Mutants in the Exo I motif of Escherichia coli dnaQ: defective proofreading and inviability due to error catastrophe.

The Escherichia coli dnaQ gene encodes the proofreading 3' exonuclease (epsilon subunit) of DNA polymerase III holoenzyme and is a critical determinant of chromosomal replication fidelity. We constructed by site-specific mutagenesis a mutant, dnaQ926, by changing two conserved amino acid residues (Asp-12-->Ala and Glu-14-->Ala) in the Exo I motif, which, by analogy to other proofreading exonucleases, is essential for the catalytic activity. When residing on a plasmid, dnaQ926 confers a strong, dominant mutator phenotype, suggesting that the protein, although deficient in exonuclease activity, still binds to the polymerase subunit (alpha subunit or dnaE gene product). When dnaQ926 was transferred to the chromosome, replacing the wild-type gene, the cells became inviable. However, viable dnaQ926 strains could be obtained if they contained one of the dnaE alleles previously characterized in our laboratory as antimutator alleles or if it carried a multicopy plasmid containing the E. coli mutL+ gene. These results suggest that loss of proofreading exonuclease activity in dnaQ926 is lethal due to excessive error rates (error catastrophe). Error catastrophe results from both the loss of proofreading and the subsequent saturation of DNA mismatch repair. The probability of lethality by excessive mutation is supported by calculations estimating the number of inactivating mutations in essential genes per chromosome replication.

A simple test of the vicarious trial-and-error hypothesis of hippocampal function.

Vicarious trial-and-error (VTE) is a term that Muenzinger and Tolman used to describe the rat's conflict-like behavior before responding to choice. Recently, VTE was proposed as a mechanism alternative to the concept of "cognitive map" in accounts of hippocampal function. That is, many phenomena of impaired learning and memory related to hippocampal interventions may be explained by behavioral first principles: reduced conflicting, incipient, pre-choice tendencies to approach and avoid. The nonspatial black-white discrimination learning and VTE behavior of the rat were investigated. Hippocampal-lesioned and sham-lesioned animals were trained for 25 days (20 trials per day) starting at 60 days of age. Each movement of the head from one discriminative stimulus to the other was counted as a VTE instance. Lesioned rats had fewer VTEs than sham controls, and the former learned much more slowly or never learned. After learning, VTE frequency declined. Male and female rats showed no significant differences in VTE behavior or discrimination learning.

Neural basis of lexical-semantic processing and integration of symbolic gestures with words

Three studies investigated the relation between symbolic gestures and words, aiming at discover the neural basis and behavioural features of the lexical semantic processing and integration of the two communicative signals. The first study aimed at determining whether elaboration of communicative signals (symbolic gestures and words) is always accompanied by integration with each other and, if present, this integration can be considered in support of the existence of a same control mechanism. Experiment 1 aimed at determining whether and how gesture is integrated with word. Participants were administered with a semantic priming paradigm with a lexical decision task and pronounced a target word, which was preceded by a meaningful or meaningless prime gesture. When meaningful, the gesture could be either congruent or incongruent with word meaning. Duration of prime presentation (100, 250, 400 ms) randomly varied. Voice spectra, lip kinematics, and time to response were recorded and analyzed. Formant 1 of voice spectra, and mean velocity in lip kinematics increased when the prime was meaningful and congruent with the word, as compared to meaningless gesture. In other words, parameters of voice and movement were magnified by congruence, but this occurred only when prime duration was 250 ms. Time to response to meaningful gesture was shorter in the condition of congruence compared to incongruence. Experiment 2 aimed at determining whether the mechanism of integration of a prime word with a target word is similar to that of a prime gesture with a target word. Formant 1 of the target word increased when word prime was meaningful and congruent, as compared to meaningless congruent prime. Increase was, however, present for whatever prime word duration. In the second study, experiment 3 aimed at determining whether symbolic prime gesture comprehension makes use of motor simulation. Transcranial Magnetic Stimulation was delivered to left primary motor cortex 100, 250, 500 ms after prime gesture presentation. Motor Evoked Potential of First Dorsal Interosseus increased when stimulation occurred 100 ms post-stimulus. Thus, gesture was understood within 100ms and integrated with the target word within 250 ms. Experiment 4 excluded any hand motor simulation in order to comprehend prime word. The effect of the prior presentation of a symbolic gesture on congruent target word processing was investigated in study 3. In experiment 5, symbolic gestures were presented as primes, followed by semantically congruent target word or pseudowords. In this case, lexical-semantic decision was accompanied by a motor simulation at 100ms after the onset of the verbal stimuli. Summing up, the same type of integration with a word was present for both prime gesture and word. It was probably subsequent to understanding of the signal, which used motor simulation for gesture and direct access to semantics for words. However, gesture and words could be understood at the same motor level through simulation if words were preceded by an adequate gestural context. Results are discussed in the prospective of a continuum between transitive actions and emblems, in parallelism with language; the grounded/symbolic content of the different signals evidences relation between sensorimotor and linguistic systems, which could interact at different levels.

Estudo semântico-lexical do códice oitocentista Memoria sobre o Plano de Guerra Offensiva e Deffensiva da Capitania de Matto Grosso

Esta tese, com o intuito de contribuir para uma reflexão em torno da história da formação da língua portuguesa no Brasil, propõe como objetivo geral realizar um estudo do léxico no município de Cáceres-MT, tendo como base a discussão sobre manutenção, tendência à manutenção, desuso, tendência ao desuso e neologismo semântico de unidades lexicais extraídas de um manuscrito oitocentista. Os objetivos específicos são os seguintes: (i) compreender a história social da Capitania de Mato Grosso e do município de Cáceres, a partir das informações constantes no manuscrito Memoria, e aspectos que envolvam as condições de produção do documento e a biografia do autor; (ii) levantar o léxico do manuscrito, com recorte nos substantivos e adjetivos para servir de base na seleção das unidades lexicais a serem testadas in loco, e investigar a acepção registrada no documento das unidades lexicais, caracterizando, assim, o léxico do período oitocentista; (iii), fazer um cotejo lexicográfico abrangendo dicionários gerais dos séculos XVIII ao XXI; (iv) testar e identificar, a partir do corpus oral constituído por meio de pesquisa de campo na região urbana cacerense, o grau de manutenção, tendência à manutenção, desuso, tendência ao desuso e neologismo semântico em relação às unidades lexicais e suas respectivas acepções registradas no manuscrito. Dessa forma, toma-se como corpus de língua escrita de análise o manuscrito oitocentista Memoria sobre o plano de guerra offensiva e deffensiva da Capitania de Matto Grosso e, a partir das unidades lexicais selecionadas e extraídas dele, realizou-se a pesquisa de campo para o recolhimento do corpus de língua oral. Antes dessa recolha, tendo como base teórico-metodológica as disciplinas de Dialetologia e de Geolinguística, selecionou-se a localidade (município de Cáceres - MT) e os informantes (total de dezesseis); elaborou-se o questionário semântico-lexical, considerando fundamentalmente a proposta apresentada pelo Comitê Nacional do Projeto ALiB (2001); e realizou-se a pesquisa de campo e as transcrições das entrevistas. Para análise de natureza semântico-lexical dos corpora, recorreu aos estudos lexicográficos e lexicológicos. Tomando por base os resultados do estudo realizado, constatou-se que na realidade linguística do informante cacerense encontram-se unidades que já integravam o léxico oitocentista da língua portuguesa escrita no Brasil, ou seja, há uma memória semântico-lexical que se mantém no sistema lexical, provavelmente, devido às condições sócioculturais do município de Cáceres, Mato Grosso, cuja população, em grande parte, por quase duzentos anos, viveu na área rural. Todavia, vislumbrou-se um certo equilíbrio entre a manutenção do léxico oitocentista sem deixar de lado a inovação e o mecanismo polissêmico constitutivo do léxico.

Mean-value identities as an opportunity for Monte Carlo error reduction

In the Monte Carlo simulation of both lattice field theories and of models of statistical mechanics, identities verified by exact mean values, such as Schwinger-Dyson equations, Guerra relations, Callen identities, etc., provide well-known and sensitive tests of thermalization bias as well as checks of pseudo-random-number generators. We point out that they can be further exploited as control variates to reduce statistical errors. The strategy is general, very simple, and almost costless in CPU time. The method is demonstrated in the twodimensional Ising model at criticality, where the CPU gain factor lies between 2 and 4.

Clinical validation of an algorithm to correct the error in the keratometric estimation of corneal power for normal eyes

To validate clinically an algorithm for correcting the error in the keratometric estimation of corneal power by using a variable keratometric index of refraction (nk) in a normal healthy population.