897 resultados para DNA Sequence, Hidden Markov Model, Bayesian Model, Sensitive Analysis, Markov Chain Monte Carlo


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Abstract interpreters rely on the existence of a nxpoint algorithm that calculates a least upper bound approximation of the semantics of the program. Usually, that algorithm is described in terms of the particular language in study and therefore it is not directly applicable to programs written in a different source language. In this paper we introduce a generic, block-based, and uniform representation of the program control flow graph and a language-independent nxpoint algorithm that can be applied to a variety of languages and, in particular, Java. Two major characteristics of our approach are accuracy (obtained through a topdown, context sensitive approach) and reasonable efficiency (achieved by means of memoization and dependency tracking techniques). We have also implemented the proposed framework and show some initial experimental results for standard benchmarks, which further support the feasibility of the solution adopted.

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Some of the rules for how members of the calmodulin (CaM) superfamily bind to target peptides are revealed by the crystal structure of the regulatory domain of scallop myosin. The structure shows that the IQ motif of the heavy chain in this invertebrate myosin imposes constraints on both the positioning and conformation of the individual lobes of the light chains. In contrast, analysis of the contact residues in the targets bound by Ca(2+)-CaM reveals how the structure of CaM accommodates a broader range of sequences consonant with this protein's functional diversity.

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It has become clear that many organisms possess the ability to regulate their mutation rate in response to environmental conditions. So the question of finding an optimal mutation rate must be replaced by that of finding an optimal mutation schedule. We show that this task cannot be accomplished with standard population-dynamic models. We then develop a "hybrid" model for populations experiencing time-dependent mutation that treats population growth as deterministic but the time of first appearance of new variants as stochastic. We show that the hybrid model agrees well with a Monte Carlo simulation. From this model, we derive a deterministic approximation, a "threshold" model, that is similar to standard population dynamic models but differs in the initial rate of generation of new mutants. We use these techniques to model antibody affinity maturation by somatic hypermutation. We had previously shown that the optimal mutation schedule for the deterministic threshold model is phasic, with periods of mutation between intervals of mutation-free growth. To establish the validity of this schedule, we now show that the phasic schedule that optimizes the deterministic threshold model significantly improves upon the best constant-rate schedule for the hybrid and Monte Carlo models.

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Background: Intra-urban inequalities in mortality have been infrequently analysed in European contexts. The aim of the present study was to analyse patterns of cancer mortality and their relationship with socioeconomic deprivation in small areas in 11 Spanish cities. Methods: It is a cross-sectional ecological design using mortality data (years 1996-2003). Units of analysis were the census tracts. A deprivation index was calculated for each census tract. In order to control the variability in estimating the risk of dying we used Bayesian models. We present the RR of the census tract with the highest deprivation vs. the census tract with the lowest deprivation. Results: In the case of men, socioeconomic inequalities are observed in total cancer mortality in all cities, except in Castellon, Cordoba and Vigo, while Barcelona (RR = 1.53 95%CI 1.42-1.67), Madrid (RR = 1.57 95%CI 1.49-1.65) and Seville (RR = 1.53 95%CI 1.36-1.74) present the greatest inequalities. In general Barcelona and Madrid, present inequalities for most types of cancer. Among women for total cancer mortality, inequalities have only been found in Barcelona and Zaragoza. The excess number of cancer deaths due to socioeconomic deprivation was 16,413 for men and 1,142 for women. Conclusion: This study has analysed inequalities in cancer mortality in small areas of cities in Spain, not only relating this mortality with socioeconomic deprivation, but also calculating the excess mortality which may be attributed to such deprivation. This knowledge is particularly useful to determine which geographical areas in each city need intersectorial policies in order to promote a healthy environment.

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"Performing organization: Oklahoma State University, College of Business Administration , Stillwater."

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Objective: Antidepressant drugs and cognitive-behavioural therapy (CBT) are effective treatment options for depression and are recommended by clinical practice guidelines. As part of the Assessing Cost-effectiveness - Mental Health project we evaluate the available evidence on costs and benefits of CBT and drugs in the episodic and maintenance treatment of major depression. Method: The cost-effectiveness is modelled from a health-care perspective as the cost per disability-adjusted life year. Interventions are targeted at people with major depression who currently seek care but receive non-evidence based treatment. Uncertainty in model inputs is tested using Monte Carlo simulation methods. Results: All interventions for major depression examined have a favourable incremental cost-effectiveness ratio under Australian health service conditions. Bibliotherapy, group CBT, individual CBT by a psychologist on a public salary and tricyclic antidepressants (TCAs) are very cost-effective treatment options falling below $A10 000 per disability-adjusted life year (DALY) even when taking the upper limit of the uncertainty interval into account. Maintenance treatment with selective serotonin re-uptake inhibitors (SSRIs) is the most expensive option (ranging from $A17 000 to $A20 000 per DALY) but still well below $A50 000, which is considered the affordable threshold. Conclusions: A range of cost-effective interventions for episodes of major depression exists and is currently underutilized. Maintenance treatment strategies are required to significantly reduce the burden of depression, but the cost of long-term drug treatment for the large number of depressed people is high if SSRIs are the drug of choice. Key policy issues with regard to expanded provision of CBT concern the availability of suitably trained providers and the funding mechanisms for therapy in primary care.

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2000 Mathematics Subject Classification: Primary 60J80, Secondary 62F12, 60G99.

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Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: (1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (E LUMO) via QSAR modelling and analysis; (2) to validate the models by using internal and external cross-validation techniques; (3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl ) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: (1) Linear or Multi-linear Regression (MLR); (2) Partial Least Squares (PLS); and (3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: (1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; (2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; (3) E LUMO are shown to correlate highly with the NCl for several classes of DBPs; and (4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

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The Monte Carlo method is accurate and is relatively simple to implement for the solution of problems involving complex geometries and anisotropic scattering of radiation as compared with other numerical techniques. In addition, differently of what happens for most of numerical techniques, for which the associated simulations computational time tends to increase exponentially with the complexity of the problems, in the Monte Carlo the increase of the computational time tends to be linear. Nevertheless, the Monte Carlo solution is highly computer time consuming for most of the interest problems. The Multispectral Energy Bundle model allows the reduction of the computational time associated to the Monte Carlo solution. The referred model is here analyzed for applications in media constituted for nonparticipating species and water vapor, which is an important emitting species formed during the combustion of hydrocarbon fuels. Aspects related to computer time optimization are investigated the model solutions are compared with benchmark line-by-line solutions

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Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: 1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (ELUMO) via QSAR modelling and analysis; 2) to validate the models by using internal and external cross-validation techniques; 3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: 1) Linear or Multi-linear Regression (MLR); 2) Partial Least Squares (PLS); and 3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: 1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; 2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; 3) ELUMO are shown to correlate highly with the NCl for several classes of DBPs; and 4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

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Estudio filogenético de los géneros de Lithinini de Sudamérica Austral (Lepidoptera, Geometridae): una nueva clasificación. Se evalúa la taxonomía de la tribu Lithinini de Sudamérica Austral sobre la base de un análisis filogenético. Para el análisis se utilizó a Catophoenissa como grupo externo. Se usaron dos aproximaciones filogenéticas para evaluar las relaciones de parentesco: 1) criterio de parsimonia; e 2) inferencia bayesiana. El análisis de parsimonia se realizó a través del programa PAUP y el análisis bayesiano con cadenas de Markov y Monte Carlo a través del programa BayesPhylogenies. Los resultados generados a partir de la hipótesis filogenética permiten proponer una nueva taxonomía para los Lithinini de Sudamérica Austral. Los géneros validos son: Asestra Warren, Acauro Rindge, Calta Rindge, Euclidiodes Warren, Franciscoia Orfila y Schajovskoy, Incalvertia Bartlett-Calvert, Lacaria Orfila y Schajovskoy, Laneco Rindge, Maeandrogonaria Butler, Martindoelloia Orfila y Schajovskoy, Nucara Rindge, Odontothera Butler, Proteopharmacis Warren, Psilaspilates Butler, Rhinoligia Warren, Tanagridia Butler. Los principales cambios respecto de ordenamientos taxonómicos previos son: 1) Yalpa Rindge, es tratado como sinónimo junior de Odontothera. 2) El género Rhinoligia Warren es incorporado a los Lithinini; 3) Se reafirma que Siopla Rindge es sinónimo junior de Asestra, Yapoma Rindge y Duraglia Rindge son sinónimos de Euclidiodes Warren, mientras que Callemo Rindge y Guara Rindge son sinónimos de Tanagridia; 4) Los géneros Calta Rindge, Incalvertia Rindge, Odontothera Butler y Proteopharmacis Warren, sinonimizados por Pitkin, son redefinidos, revalidados e incorporados a la tribu Lithinini. Se describe una nueva especie para el género Franciscoia, F. ediliae Parra. Se incluye un catálogo con los géneros y especies de la tribu de la región, más las figuras de los adultos y genitalias de las principales especies.

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The aim of this work is to apply approximate Bayesian computation in combination with Marcov chain Monte Carlo methods in order to estimate the parameters of tuberculosis transmission. The methods are applied to San Francisco data and the results are compared with the outcomes of previous works. Moreover, a methodological idea with the aim to reduce computational time is also described. Despite the fact that this approach is proved to work in an appropriate way, further analysis is needed to understand and test its behaviour in different cases. Some related suggestions to its further enhancement are described in the corresponding chapter.

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This paper presents new methodology for making Bayesian inference about dy~ o!s for exponential famiIy observations. The approach is simulation-based _~t> use of ~vlarkov chain Monte Carlo techniques. A yletropolis-Hastings i:U~UnLlllll 1::; combined with the Gibbs sampler in repeated use of an adjusted version of normal dynamic linear models. Different alternative schemes are derived and compared. The approach is fully Bayesian in obtaining posterior samples for state parameters and unknown hyperparameters. Illustrations to real data sets with sparse counts and missing values are presented. Extensions to accommodate for general distributions for observations and disturbances. intervention. non-linear models and rnultivariate time series are outlined.

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Regulatory authorities in many countries, in order to maintain an acceptable balance between appropriate customer service qualities and costs, are introducing a performance-based regulation. These regulations impose penalties-and, in some cases, rewards-that introduce a component of financial risk to an electric power utility due to the uncertainty associated with preserving a specific level of system reliability. In Brazil, for instance, one of the reliability indices receiving special attention by the utilities is the maximum continuous interruption duration (MCID) per customer.This parameter is responsible for the majority of penalties in many electric distribution utilities. This paper describes analytical and Monte Carlo simulation approaches to evaluate probability distributions of interruption duration indices. More emphasis will be given to the development of an analytical method to assess the probability distribution associated with the parameter MCID and the correspond ng penalties. Case studies on a simple distribution network and on a real Brazilian distribution system are presented and discussed.

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Regulatory authorities in many countries, in order to maintain an acceptable balance between appropriate customer service qualities and costs, are introducing a performance-based regulation. These regulations impose penalties, and in some cases rewards, which introduce a component of financial risk to an electric power utility due to the uncertainty associated with preserving a specific level of system reliability. In Brazil, for instance, one of the reliability indices receiving special attention by the utilities is the Maximum Continuous Interruption Duration per customer (MCID). This paper describes a chronological Monte Carlo simulation approach to evaluate probability distributions of reliability indices, including the MCID, and the corresponding penalties. In order to get the desired efficiency, modern computational techniques are used for modeling (UML -Unified Modeling Language) as well as for programming (Object- Oriented Programming). Case studies on a simple distribution network and on real Brazilian distribution systems are presented and discussed. © Copyright KTH 2006.