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Sample records for stage cox model

  1. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    Probabilistic properties of Cox processes of relevance for statistical modelling and inference are studied. Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties...... and point process operations such as thinning, displacements, and superpositioning. We also discuss how to simulate specific Cox processes....

  2. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    2005-01-01

    Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties and point process operations such as thinning, displacements, and super positioning. We also discuss how...... to simulate specific Cox processes....

  3. Identifying nonproportional covariates in the Cox model

    Czech Academy of Sciences Publication Activity Database

    Kraus, David

    2008-01-01

    Roč. 37, č. 4 (2008), s. 617-625 ISSN 0361-0926 R&D Projects: GA AV ČR(CZ) IAA101120604; GA MŠk(CZ) 1M06047; GA ČR(CZ) GD201/05/H007 Institutional research plan: CEZ:AV0Z10750506 Keywords : Cox model * goodness of fit * proportional hazards assumption * time-varying coefficients Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.324, year: 2008

  4. An Additive-Multiplicative Cox-Aalen Regression Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; Cox regression; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; Cox regression; survival analysis; time-varying effects...

  5. Extensions and Applications of the Cox-Aalen Survival Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

    Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects......Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects...

  6. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  7. A Box-Cox normal model for response times

    NARCIS (Netherlands)

    Klein Entink, R.H.; Fox, J.P.; Linden, W.J. van der

    2009-01-01

    The log-transform has been a convenient choice in response time modelling on test items. However, motivated by a dataset of the Medical College Admission Test where the lognormal model violated the normality assumption, the possibilities of the broader class of Box–Cox transformations for response

  8. Cox's regression model for dynamics of grouped unemployment data

    Czech Academy of Sciences Publication Activity Database

    Volf, Petr

    2003-01-01

    Roč. 10, č. 19 (2003), s. 151-162 ISSN 1212-074X R&D Projects: GA ČR GA402/01/0539 Institutional research plan: CEZ:AV0Z1075907 Keywords : mathematical statistics * survival analysis * Cox's model Subject RIV: BB - Applied Statistics, Operational Research

  9. A Box-Cox normal model for response times.

    Science.gov (United States)

    Klein Entink, R H; van der Linden, W J; Fox, J-P

    2009-11-01

    The log-transform has been a convenient choice in response time modelling on test items. However, motivated by a dataset of the Medical College Admission Test where the lognormal model violated the normality assumption, the possibilities of the broader class of Box-Cox transformations for response time modelling are investigated. After an introduction and an outline of a broader framework for analysing responses and response times simultaneously, the performance of a Box-Cox normal model for describing response times is investigated using simulation studies and a real data example. A transformation-invariant implementation of the deviance information criterium (DIC) is developed that allows for comparing model fit between models with different transformation parameters. Showing an enhanced description of the shape of the response time distributions, its application in an educational measurement context is discussed at length.

  10. Multivariate Product-Shot-noise Cox Point Process Models

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

    We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the process...... can be obtained in closed analytical forms and approximate simulation of the process is straightforward. We use the proposed process to model interactions within and among five tree species in the Barro Colorado Island plot....

  11. Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

  12. Extended cox regression model: The choice of timefunction

    Science.gov (United States)

    Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

    2017-07-01

    Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

  13. A Monte Carlo Investigation of the Box-Cox Model and a Nonlinear Least Squares Alternative.

    OpenAIRE

    Showalter, Mark H

    1994-01-01

    This paper reports a Monte Carlo study of the Box-Cox model and a nonlinear least squares alternative. Key results include the following: the transformation parameter in the Box-Cox model appears to be inconsistently estimated in the presence of conditional heteroskedasticity; the constant term in both the Box-Cox and the nonlinear least squares models is poorly estimated in small samples; conditional mean forecasts tend to underestimate their true value in the Box-Cox model when the transfor...

  14. ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.

    Science.gov (United States)

    Huang, Jian; Sun, Tingni; Ying, Zhiliang; Yu, Yi; Zhang, Cun-Hui

    2013-06-01

    We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. However, the presented oracle inequalities are sharper since the compatibility and cone invertibility factors are always greater than the corresponding restricted eigenvalue. In the Cox regression model, the Hessian matrix is based on time-dependent covariates in censored risk sets, so that the compatibility and cone invertibility factors, and the restricted eigenvalue as well, are random variables even when they are evaluated for the Hessian at the true regression coefficients. Under mild conditions, we prove that these quantities are bounded from below by positive constants for time-dependent covariates, including cases where the number of covariates is of greater order than the sample size. Consequently, the compatibility and cone invertibility factors can be treated as positive constants in our oracle inequalities.

  15. Functional form diagnostics for Cox's proportional hazards model.

    Science.gov (United States)

    León, Larry F; Tsai, Chih-Ling

    2004-03-01

    We propose a new type of residual and an easily computed functional form test for the Cox proportional hazards model. The proposed test is a modification of the omnibus test for testing the overall fit of a parametric regression model, developed by Stute, González Manteiga, and Presedo Quindimil (1998, Journal of the American Statistical Association93, 141-149), and is based on what we call censoring consistent residuals. In addition, we develop residual plots that can be used to identify the correct functional forms of covariates. We compare our test with the functional form test of Lin, Wei, and Ying (1993, Biometrika80, 557-572) in a simulation study. The practical application of the proposed residuals and functional form test is illustrated using both a simulated data set and a real data set.

  16. Ensembling Variable Selectors by Stability Selection for the Cox Model

    Directory of Open Access Journals (Sweden)

    Qing-Yan Yin

    2017-01-01

    Full Text Available As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010, a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region Λ in lasso and the parameter λmin properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify Λ and λmin. Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

  17. Multi-omics facilitated variable selection in Cox-regression model for cancer prognosis prediction.

    Science.gov (United States)

    Liu, Cong; Wang, Xujun; Genchev, Georgi Z; Lu, Hui

    2017-07-15

    New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge. There is also a shortage of computational tools for predicting cancer prognosis by using supervised learning methods. The current standard approach is to fit a Cox regression model by concatenating the different types of omics data in a linear manner, while penalty could be added for feature selection. A more powerful approach, however, would be to incorporate data by considering relationships among omics datatypes. Here we developed two methods: a SKI-Cox method and a wLASSO-Cox method to incorporate the association among different types of omics data. Both methods fit the Cox proportional hazards model and predict a risk score based on mRNA expression profiles. SKI-Cox borrows the information generated by these additional types of omics data to guide variable selection, while wLASSO-Cox incorporates this information as a penalty factor during model fitting. We show that SKI-Cox and wLASSO-Cox models select more true variables than a LASSO-Cox model in simulation studies. We assess the performance of SKI-Cox and wLASSO-Cox using TCGA glioblastoma multiforme and lung adenocarcinoma data. In each case, mRNA expression, methylation, and copy number variation data are integrated to predict the overall survival time of cancer patients. Our methods achieve better performance in predicting patients' survival in glioblastoma and lung adenocarcinoma. Copyright © 2017. Published by Elsevier

  18. Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Arendt Thomas

    2005-11-01

    Full Text Available Abstract Neuronal expression of cyclooxygenase-2 (COX-2 and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD. The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia cells are shown to secrete substances that can induce expression of COX-2 and cell cycle proteins in vitro. Using post mortem brain tissue we have investigated whether activation of microglia and astrocytes in AD brain can be correlated with the expression of COX-2 and phosphorylated retinoblastoma protein (ppRb. The highest levels of neuronal COX-2 and ppRb immunoreactivity are observed in the first stages of AD pathology (Braak 0–II, Braak A. No significant difference in COX-2 or ppRb neuronal immunoreactivity is observed between Braak stage 0 and later Braak stages for neurofibrillary changes or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is significantly decreased in Braak stage C compared to Braak stage A for amyloid deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the later Braak stages and is significantly increased in Braak stage V-VI compared to Braak stage 0 for neurofibrillary changes. In addition, a significant negative correlation is observed between the presence of KP1, CR3/43 and GFAP immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia. In contrast to in vitro studies, post mortem data do not support a causal relation between the activation of microglia and astrocytes and the expression of neuronal COX-2 and ppRb in the pathological cascade of AD.

  19. Turbine stage model

    International Nuclear Information System (INIS)

    Kazantsev, A.A.

    2009-01-01

    A model of turbine stage for calculations of NPP turbine department dynamics in real time was developed. The simulation results were compared with manufacturer calculations for NPP low-speed and fast turbines. The comparison results have shown that the model is valid for real time simulation of all modes of turbines operation. The model allows calculating turbine stage parameters with 1% accuracy. It was shown that the developed turbine stage model meets the accuracy requirements if the data of turbine blades setting angles for all turbine stages are available [ru

  20. Bond and CDS Pricing via the Stochastic Recovery Black-Cox Model

    Directory of Open Access Journals (Sweden)

    Albert Cohen

    2017-04-01

    Full Text Available Building on recent work incorporating recovery risk into structural models by Cohen & Costanzino (2015, we consider the Black-Cox model with an added recovery risk driver. The recovery risk driver arises naturally in the context of imperfect information implicit in the structural framework. This leads to a two-factor structural model we call the Stochastic Recovery Black-Cox model, whereby the asset risk driver At defines the default trigger and the recovery risk driver Rt defines the amount recovered in the event of default. We then price zero-coupon bonds and credit default swaps under the Stochastic Recovery Black-Cox model. Finally, we compare our results with the classic Black-Cox model, give explicit expressions for the recovery risk premium in the Stochastic Recovery Black-Cox model, and detail how the introduction of separate but correlated risk drivers leads to a decoupling of the default and recovery risk premiums in the credit spread. We conclude this work by computing the effect of adding coupons that are paid continuously until default, and price perpetual (consol bonds in our two-factor firm value model, extending calculations in the seminal paper by Leland (1994.

  1. Cox proportional hazards models have more statistical power than logistic regression models in cross-sectional genetic association studies

    NARCIS (Netherlands)

    van der Net, Jeroen B.; Janssens, A. Cecile J. W.; Eijkemans, Marinus J. C.; Kastelein, John J. P.; Sijbrands, Eric J. G.; Steyerberg, Ewout W.

    2008-01-01

    Cross-sectional genetic association studies can be analyzed using Cox proportional hazards models with age as time scale, if age at onset of disease is known for the cases and age at data collection is known for the controls. We assessed to what degree and under what conditions Cox proportional

  2. Structured spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable fo...... dataset consisting of 2796 days and 5834 spatial locations of fires. The model is compared with a spatio-temporal log-Gaussian Cox point process model, and likelihood-based methods are discussed to some extent....

  3. Measures to assess the prognostic ability of the stratified Cox proportional hazards model

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures...

  4. Estimation in the positive stable shared frailty Cox proportional hazards model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Pipper, Christian Bressen

    2005-01-01

    model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large...

  5. SECOND ORDER LEAST SQUARE ESTIMATION ON ARCH(1 MODEL WITH BOX-COX TRANSFORMED DEPENDENT VARIABLE

    Directory of Open Access Journals (Sweden)

    Herni Utami

    2014-03-01

    Full Text Available Box-Cox transformation is often used to reduce heterogeneity and to achieve a symmetric distribution of response variable. In this paper, we estimate the parameters of Box-Cox transformed ARCH(1 model using second-order leastsquare method and then we study the consistency and asymptotic normality for second-order least square (SLS estimators. The SLS estimation was introduced byWang (2003, 2004 to estimate the parameters of nonlinear regression models with independent and identically distributed errors

  6. A new semi-supervised learning model combined with Cox and SP-AFT models in cancer survival analysis.

    Science.gov (United States)

    Chai, Hua; Li, Zi-Na; Meng, De-Yu; Xia, Liang-Yong; Liang, Yong

    2017-10-12

    Gene selection is an attractive and important task in cancer survival analysis. Most existing supervised learning methods can only use the labeled biological data, while the censored data (weakly labeled data) far more than the labeled data are ignored in model building. Trying to utilize such information in the censored data, a semi-supervised learning framework (Cox-AFT model) combined with Cox proportional hazard (Cox) and accelerated failure time (AFT) model was used in cancer research, which has better performance than the single Cox or AFT model. This method, however, is easily affected by noise. To alleviate this problem, in this paper we combine the Cox-AFT model with self-paced learning (SPL) method to more effectively employ the information in the censored data in a self-learning way. SPL is a kind of reliable and stable learning mechanism, which is recently proposed for simulating the human learning process to help the AFT model automatically identify and include samples of high confidence into training, minimizing interference from high noise. Utilizing the SPL method produces two direct advantages: (1) The utilization of censored data is further promoted; (2) the noise delivered to the model is greatly decreased. The experimental results demonstrate the effectiveness of the proposed model compared to the traditional Cox-AFT model.

  7. Selection of the optimal Box-Cox transformation parameter for modelling and forecasting age-specific fertility

    OpenAIRE

    Shang, Han Lin

    2015-01-01

    The Box-Cox transformation can sometimes yield noticeable improvements in model simplicity, variance homogeneity and precision of estimation, such as in modelling and forecasting age-specific fertility. Despite its importance, there have been few studies focusing on the optimal selection of Box-Cox transformation parameters in demographic forecasting. A simple method is proposed for selecting the optimal Box-Cox transformation parameter, along with an algorithm based on an in-sample forecast ...

  8. A simple approach to power and sample size calculations in logistic regression and Cox regression models.

    Science.gov (United States)

    Vaeth, Michael; Skovlund, Eva

    2004-06-15

    For a given regression problem it is possible to identify a suitably defined equivalent two-sample problem such that the power or sample size obtained for the two-sample problem also applies to the regression problem. For a standard linear regression model the equivalent two-sample problem is easily identified, but for generalized linear models and for Cox regression models the situation is more complicated. An approximately equivalent two-sample problem may, however, also be identified here. In particular, we show that for logistic regression and Cox regression models the equivalent two-sample problem is obtained by selecting two equally sized samples for which the parameters differ by a value equal to the slope times twice the standard deviation of the independent variable and further requiring that the overall expected number of events is unchanged. In a simulation study we examine the validity of this approach to power calculations in logistic regression and Cox regression models. Several different covariate distributions are considered for selected values of the overall response probability and a range of alternatives. For the Cox regression model we consider both constant and non-constant hazard rates. The results show that in general the approach is remarkably accurate even in relatively small samples. Some discrepancies are, however, found in small samples with few events and a highly skewed covariate distribution. Comparison with results based on alternative methods for logistic regression models with a single continuous covariate indicates that the proposed method is at least as good as its competitors. The method is easy to implement and therefore provides a simple way to extend the range of problems that can be covered by the usual formulas for power and sample size determination. Copyright 2004 John Wiley & Sons, Ltd.

  9. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-12-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM.

  10. Structured Spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    2010-01-01

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable fo...... data set consisting of 2796 days and 5834 spatial locations of fires. The model is compared with a spatio-temporal log-Gaussian Cox point process model, and likelihood-based methods are discussed to some extent....

  11. Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

    Science.gov (United States)

    Liu, K; Mazumdar, S; Stone, R A; Dew, M A; Houck, P R; Reynolds, C F

    2001-01-01

    When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

  12. Default risk modeling beyond the first-passage approximation: Extended Black-Cox model

    Science.gov (United States)

    Katz, Yuri A.; Shokhirev, Nikolai V.

    2010-07-01

    We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm’s ability to avoid default even if company’s liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company’s default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity.

  13. Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation

    DEFF Research Database (Denmark)

    Yang, Ye; Christensen, Ole Fredslund; Sorensen, Daniel

    2011-01-01

    of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box–Cox transformations. Litter size data in rabbits and pigs that had previously been analysed...... in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box–Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis...... in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected...

  14. The tariff for fire and theft car insurance: analysis with a Cox model

    OpenAIRE

    Bruno Scarpa

    2013-01-01

    In this paper we analyze the problem of identification of a tariff for a Fire & Theft Car policy for Insurance Companies. Usually companies obtain this tariff by empirical estimate of the pure rate by evaluating the impact of some personalization variables. In this paper we propose the usage of a semi-parametric Cox model, where the response variable is not the waiting time until an event, but the degree of damage because of theft or fire of a car. The proposed model allows to easily tackle t...

  15. The tariff for fire and theft car insurance: analysis with a Cox model

    Directory of Open Access Journals (Sweden)

    Bruno Scarpa

    2013-05-01

    Full Text Available In this paper we analyze the problem of identification of a tariff for a Fire & Theft Car policy for Insurance Companies. Usually companies obtain this tariff by empirical estimate of the pure rate by evaluating the impact of some personalization variables. In this paper we propose the usage of a semi-parametric Cox model, where the response variable is not the waiting time until an event, but the degree of damage because of theft or fire of a car. The proposed model allows to easily tackle typical problems in data available to the companies, like the presence of franchises, which are treated as censored data.

  16. A class of Box-Cox transformation models for recurrent event data.

    Science.gov (United States)

    Sun, Liuquan; Tong, Xingwei; Zhou, Xian

    2011-04-01

    In this article, we propose a class of Box-Cox transformation models for recurrent event data, which includes the proportional means models as special cases. The new model offers great flexibility in formulating the effects of covariates on the mean functions of counting processes while leaving the stochastic structure completely unspecified. For the inference on the proposed models, we apply a profile pseudo-partial likelihood method to estimate the model parameters via estimating equation approaches and establish large sample properties of the estimators and examine its performance in moderate-sized samples through simulation studies. In addition, some graphical and numerical procedures are presented for model checking. An example of application on a set of multiple-infection data taken from a clinic study on chronic granulomatous disease (CGD) is also illustrated.

  17. A random effects meta-analysis model with Box-Cox transformation.

    Science.gov (United States)

    Yamaguchi, Yusuke; Maruo, Kazushi; Partlett, Christopher; Riley, Richard D

    2017-07-19

    In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and prediction intervals from the normal random effects model. The

  18. A random effects meta-analysis model with Box-Cox transformation

    Directory of Open Access Journals (Sweden)

    Yusuke Yamaguchi

    2017-07-01

    Full Text Available Abstract Background In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. Methods We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. Results A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and

  19. BOX-COX transformation and random regression models for fecal egg count data

    Directory of Open Access Journals (Sweden)

    Marcos Vinicius Silva

    2012-01-01

    Full Text Available Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants fecal egg count (FEC is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used to achieve normality before analysis. However, the transformed data are often not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6,375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (covariance components. We also proposed using random regression models (RRM for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4 adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.

  20. Box-Cox Transformation and Random Regression Models for Fecal egg Count Data.

    Science.gov (United States)

    da Silva, Marcos Vinícius Gualberto Barbosa; Van Tassell, Curtis P; Sonstegard, Tad S; Cobuci, Jaime Araujo; Gasbarre, Louis C

    2011-01-01

    Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.

  1. Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation.

    Science.gov (United States)

    Yang, Ye; Christensen, Ole F; Sorensen, Daniel

    2011-02-01

    Over recent years, statistical support for the presence of genetic factors operating at the level of the environmental variance has come from fitting a genetically structured heterogeneous variance model to field or experimental data in various species. Misleading results may arise due to skewness of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box-Cox transformations. Litter size data in rabbits and pigs that had previously been analysed in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box-Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected by the presence of asymmetry in the distribution of data. We recommend that to avoid one important source of spurious inferences, future work seeking support for a genetic component acting on environmental variation using a parametric approach based on normality assumptions confirms that these are met.

  2. Expectation Maximization Algorithm for Box-Cox Transformation Cure Rate Model and Assessment of Model Misspecification Under Weibull Lifetimes.

    Science.gov (United States)

    Pal, Suvra; Balakrishnan, Narayanaswamy

    2018-05-01

    In this paper, we develop likelihood inference based on the expectation maximization algorithm for the Box-Cox transformation cure rate model assuming the lifetimes to follow a Weibull distribution. A simulation study is carried out to demonstrate the performance of the proposed estimation method. Through Monte Carlo simulations, we also study the effect of model misspecification on the estimate of cure rate. Finally, we analyze a well-known data on melanoma with the model and the inferential method developed here.

  3. Statistical power to detect violation of the proportional hazards assumption when using the Cox regression model.

    Science.gov (United States)

    Austin, Peter C

    2018-01-01

    The use of the Cox proportional hazards regression model is widespread. A key assumption of the model is that of proportional hazards. Analysts frequently test the validity of this assumption using statistical significance testing. However, the statistical power of such assessments is frequently unknown. We used Monte Carlo simulations to estimate the statistical power of two different methods for detecting violations of this assumption. When the covariate was binary, we found that a model-based method had greater power than a method based on cumulative sums of martingale residuals. Furthermore, the parametric nature of the distribution of event times had an impact on power when the covariate was binary. Statistical power to detect a strong violation of the proportional hazards assumption was low to moderate even when the number of observed events was high. In many data sets, power to detect a violation of this assumption is likely to be low to modest.

  4. Maximum likelihood estimation for Cox's regression model under nested case-control sampling

    DEFF Research Database (Denmark)

    Scheike, Thomas Harder; Juul, Anders

    2004-01-01

    -like growth factor I was associated with ischemic heart disease. The study was based on a population of 3784 Danes and 231 cases of ischemic heart disease where controls were matched on age and gender. We illustrate the use of the MLE for these data and show how the maximum likelihood framework can be used......Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazards...... model. The MLE is computed by the EM-algorithm, which is easy to implement in the proportional hazards setting. Standard errors are estimated by a numerical profile likelihood approach based on EM aided differentiation. The work was motivated by a nested case-control study that hypothesized that insulin...

  5. New Inference Procedures for Semiparametric Varying-Coefficient Partially Linear Cox Models

    Directory of Open Access Journals (Sweden)

    Yunbei Ma

    2014-01-01

    Full Text Available In biomedical research, one major objective is to identify risk factors and study their risk impacts, as this identification can help clinicians to both properly make a decision and increase efficiency of treatments and resource allocation. A two-step penalized-based procedure is proposed to select linear regression coefficients for linear components and to identify significant nonparametric varying-coefficient functions for semiparametric varying-coefficient partially linear Cox models. It is shown that the penalized-based resulting estimators of the linear regression coefficients are asymptotically normal and have oracle properties, and the resulting estimators of the varying-coefficient functions have optimal convergence rates. A simulation study and an empirical example are presented for illustration.

  6. Interpretable inference on the mixed effect model with the Box-Cox transformation.

    Science.gov (United States)

    Maruo, K; Yamaguchi, Y; Noma, H; Gosho, M

    2017-07-10

    We derived results for inference on parameters of the marginal model of the mixed effect model with the Box-Cox transformation based on the asymptotic theory approach. We also provided a robust variance estimator of the maximum likelihood estimator of the parameters of this model in consideration of the model misspecifications. Using these results, we developed an inference procedure for the difference of the model median between treatment groups at the specified occasion in the context of mixed effects models for repeated measures analysis for randomized clinical trials, which provided interpretable estimates of the treatment effect. From simulation studies, it was shown that our proposed method controlled type I error of the statistical test for the model median difference in almost all the situations and had moderate or high performance for power compared with the existing methods. We illustrated our method with cluster of differentiation 4 (CD4) data in an AIDS clinical trial, where the interpretability of the analysis results based on our proposed method is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. A staged service innovation model

    NARCIS (Netherlands)

    Song, L.Z.; Song, Michael; Benedetto, Di A.C.

    2009-01-01

    Drawing from the new product development (NPD) literature, service quality literature (SERVQUAL), and empirically grounded research with 53 service innovation decision makers, we develop a staged service innovation model (SIM) for decision makers. We tested the model using empirical data from 329

  8. A nonlinear isobologram model with Box-Cox transformation to both sides for chemical mixtures.

    Science.gov (United States)

    Chen, D G; Pounds, J G

    1998-12-01

    The linear logistical isobologram is a commonly used and powerful graphical and statistical tool for analyzing the combined effects of simple chemical mixtures. In this paper a nonlinear isobologram model is proposed to analyze the joint action of chemical mixtures for quantitative dose-response relationships. This nonlinear isobologram model incorporates two additional new parameters, Ymin and Ymax, to facilitate analysis of response data that are not constrained between 0 and 1, where parameters Ymin and Ymax represent the minimal and the maximal observed toxic response. This nonlinear isobologram model for binary mixtures can be expressed as [formula: see text] In addition, a Box-Cox transformation to both sides is introduced to improve the goodness of fit and to provide a more robust model for achieving homogeneity and normality of the residuals. Finally, a confidence band is proposed for selected isobols, e.g., the median effective dose, to facilitate graphical and statistical analysis of the isobologram. The versatility of this approach is demonstrated using published data describing the toxicity of the binary mixtures of citrinin and ochratoxin as well as a new experimental data from our laboratory for mixtures of mercury and cadmium.

  9. Neoplasms escape selective COX-2 inhibition in an animal model of breast cancer.

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

    Cyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.

  10. QSAR Modeling of COX -2 Inhibitory Activity of Some Dihydropyridine and Hydroquinoline Derivatives Using Multiple Linear Regression (MLR) Method.

    Science.gov (United States)

    Akbari, Somaye; Zebardast, Tannaz; Zarghi, Afshin; Hajimahdi, Zahra

    2017-01-01

    COX-2 inhibitory activities of some 1,4-dihydropyridine and 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives were modeled by quantitative structure-activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R 2 ) of 0.972 and 0.531 for training and test groups, respectively. The quality of the model was evaluated by leave-one-out (LOO) cross validation (LOO correlation coefficient (Q 2 ) of 0.943) and Y-randomization. We also employed a leverage approach for the defining of applicability domain of model. Based on QSAR models results, COX-2 inhibitory activity of selected data set had correlation with BEHm6 (highest eigenvalue n. 6 of Burden matrix/weighted by atomic masses), Mor03u (signal 03/unweighted) and IVDE (Mean information content on the vertex degree equality) descriptors which derived from their structures.

  11. Maximum likelihood estimation for Cox's regression model under nested case-control sampling

    DEFF Research Database (Denmark)

    Scheike, Thomas; Juul, Anders

    2004-01-01

    Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazard...

  12. Cox-2 Plays a Vital Role in the Impaired Anxiety Like Behavior in Colchicine Induced Rat Model of Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Susmita Sil

    2016-01-01

    Full Text Available The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space of cAD by inhibiting it with three different doses (10, 20, and 30 mg of etoricoxib (a cox-2 blocker in two time points (14 and 21 days. The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain.

  13. Prognosis for medically treated elderly patients with coronary artery disease. Analysis by the cox model

    International Nuclear Information System (INIS)

    Furuno, Takashi; Yamasaki, Fumiyasu; Yabe, Toshikazu; Matsumura, Yoshihisa; Kitaoka, Hiroaki; Doi, Yoshinori

    1997-01-01

    The prognostic importance of age among well-known prognostic factors such as extent of coronary artery lesions, cardiac function, and myocardial ischemia was evaluated in 147 elderly patients with coronary artery disease aged 65 years or older who underwent dipyridamole perfusion scintigraphy and coronary angiography. After excluding 32 patients who initially underwent percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG), 115 patients who were initially treated medically were analysed by the Cox model for cardiac events during a mean follow-up period of 29±22 months. Among the 114 patients who were available for follow-up, nine patients (7.9%) had cardiac events, including five cardiac deaths and four non-fatal cardiac events (requiring PTCA or CABG). When the 114 patients were divided into three age-groups; 53 patients aged 65-69 years, 42 aged 70-74 years and 19 aged 75 years or older, the incidence of cardiac death was highest in those aged 75 years or older. Univariate analysis showed that age of 70 years or older (hazards ratio 15.15, p=0.004), scintigraphic diffuse slow washout (hazards ratio 8.77, p=0.002), and triple-vessel or left main trunk disease (hazards ratio 6.36, p=0.05) were important prognostic factors. Multivariate analysis showed that scintigraphic diffuse slow washout (hazards ratio 6.33, p=0.05), and triple-vessel or left main trunk disease (hazards ratio 11.94 p=0.05) were statistically significant as independent prognostic factors. However, when age of 70 years or older was included in the analysis, it showed higher hazards ratio (21.21, p=0.03) than that of scintigraphic diffuse slow washout (7.36) or triple-vessel or left main trunk disease (5.30). Age of 70 years or older may be a significant prognostic factor in elderly patients with coronary artery disease which has an equivalent importance to the extent of coronary lesions. (author)

  14. Survival analysis of clinical mastitis data using a nested frailty Cox model fit as a mixed-effects Poisson model.

    Science.gov (United States)

    Elghafghuf, Adel; Dufour, Simon; Reyher, Kristen; Dohoo, Ian; Stryhn, Henrik

    2014-12-01

    Mastitis is a complex disease affecting dairy cows and is considered to be the most costly disease of dairy herds. The hazard of mastitis is a function of many factors, both managerial and environmental, making its control a difficult issue to milk producers. Observational studies of clinical mastitis (CM) often generate datasets with a number of characteristics which influence the analysis of those data: the outcome of interest may be the time to occurrence of a case of mastitis, predictors may change over time (time-dependent predictors), the effects of factors may change over time (time-dependent effects), there are usually multiple hierarchical levels, and datasets may be very large. Analysis of such data often requires expansion of the data into the counting-process format - leading to larger datasets - thus complicating the analysis and requiring excessive computing time. In this study, a nested frailty Cox model with time-dependent predictors and effects was applied to Canadian Bovine Mastitis Research Network data in which 10,831 lactations of 8035 cows from 69 herds were followed through lactation until the first occurrence of CM. The model was fit to the data as a Poisson model with nested normally distributed random effects at the cow and herd levels. Risk factors associated with the hazard of CM during the lactation were identified, such as parity, calving season, herd somatic cell score, pasture access, fore-stripping, and proportion of treated cases of CM in a herd. The analysis showed that most of the predictors had a strong effect early in lactation and also demonstrated substantial variation in the baseline hazard among cows and between herds. A small simulation study for a setting similar to the real data was conducted to evaluate the Poisson maximum likelihood estimation approach with both Gaussian quadrature method and Laplace approximation. Further, the performance of the two methods was compared with the performance of a widely used estimation

  15. Causal Mediation Analysis for the Cox Proportional Hazards Model with a Smooth Baseline Hazard Estimator.

    Science.gov (United States)

    Wang, Wei; Albert, Jeffrey M

    2017-08-01

    An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.

  16. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Mousavi Nia

    2017-03-01

    Full Text Available Background: Nepeta dschuparensis Bornm (NP is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2 and interleukin-1β (IL-1β protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. Methods: Twenty-six male rats were randomly divided into 3 groups: 1 sham (n=6: no middle cerebral artery occlusion (MCAO procedure, 2 control (n=10: MCAO procedure and treatment with normal saline, and 3 NP extract (n=10: MCAO procedure and treatment with the NP extract (20 mg/kg, i.p. at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1β and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01. Results: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1β and COX-2 protein levels too (P<0.01. Conclusion: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1β and COX-2.

  17. Synergism between COX-3 inhibitors in two animal models of pain.

    Science.gov (United States)

    Muñoz, J; Navarro, C; Noriega, V; Pinardi, G; Sierralta, F; Prieto, J C; Miranda, H F

    2010-04-01

    The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test. The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice. Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain. These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.

  18. Inference of median difference based on the Box-Cox model in randomized clinical trials.

    Science.gov (United States)

    Maruo, K; Isogawa, N; Gosho, M

    2015-05-10

    In randomized clinical trials, many medical and biological measurements are not normally distributed and are often skewed. The Box-Cox transformation is a powerful procedure for comparing two treatment groups for skewed continuous variables in terms of a statistical test. However, it is difficult to directly estimate and interpret the location difference between the two groups on the original scale of the measurement. We propose a helpful method that infers the difference of the treatment effect on the original scale in a more easily interpretable form. We also provide statistical analysis packages that consistently include an estimate of the treatment effect, covariance adjustments, standard errors, and statistical hypothesis tests. The simulation study that focuses on randomized parallel group clinical trials with two treatment groups indicates that the performance of the proposed method is equivalent to or better than that of the existing non-parametric approaches in terms of the type-I error rate and power. We illustrate our method with cluster of differentiation 4 data in an acquired immune deficiency syndrome clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

    2015-08-01

    Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

  20. Comparison of exact, efron and breslow parameter approach method on hazard ratio and stratified cox regression model

    Science.gov (United States)

    Fatekurohman, Mohamat; Nurmala, Nita; Anggraeni, Dian

    2018-04-01

    Lungs are the most important organ, in the case of respiratory system. Problems related to disorder of the lungs are various, i.e. pneumonia, emphysema, tuberculosis and lung cancer. Comparing all those problems, lung cancer is the most harmful. Considering about that, the aim of this research applies survival analysis and factors affecting the endurance of the lung cancer patient using comparison of exact, Efron and Breslow parameter approach method on hazard ratio and stratified cox regression model. The data applied are based on the medical records of lung cancer patients in Jember Paru-paru hospital on 2016, east java, Indonesia. The factors affecting the endurance of the lung cancer patients can be classified into several criteria, i.e. sex, age, hemoglobin, leukocytes, erythrocytes, sedimentation rate of blood, therapy status, general condition, body weight. The result shows that exact method of stratified cox regression model is better than other. On the other hand, the endurance of the patients is affected by their age and the general conditions.

  1. Application and validation of Cox regression models in a single-center series of double kidney transplantation.

    Science.gov (United States)

    Santori, G; Fontana, I; Bertocchi, M; Gasloli, G; Magoni Rossi, A; Tagliamacco, A; Barocci, S; Nocera, A; Valente, U

    2010-05-01

    A useful approach to reduce the number of discarded marginal kidneys and to increase the nephron mass is double kidney transplantation (DKT). In this study, we retrospectively evaluated the potential predictors for patient and graft survival in a single-center series of 59 DKT procedures performed between April 21, 1999, and September 21, 2008. The kidney recipients of mean age 63.27 +/- 5.17 years included 16 women (27%) and 43 men (73%). The donors of mean age 69.54 +/- 7.48 years included 32 women (54%) and 27 men (46%). The mean posttransplant dialysis time was 2.37 +/- 3.61 days. The mean hospitalization was 20.12 +/- 13.65 days. Average serum creatinine (SCr) at discharge was 1.5 +/- 0.59 mg/dL. In view of the limited numbers of recipient deaths (n = 4) and graft losses (n = 8) that occurred in our series, the proportional hazards assumption for each Cox regression model with P DKT (P = .043), and SCr 6 months post-DKT (P = .017). All significant univariate models for graft survival passed the Schoenfeld test. A final multivariate model retained SCr at 6 months (beta = 1.746, P = .042) and donor SCr (beta = .767, P = .090). In our analysis, SCr at 6 months seemed to emerge from both univariate and multivariate Cox models as a potential predictor of graft survival among DKT. Multicenter studies with larger recipient populations and more graft losses should be performed to confirm our findings. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  2. Artificial neural networks versus proportional hazards Cox models to predict 45-year all-cause mortality in the Italian Rural Areas of the Seven Countries Study

    Directory of Open Access Journals (Sweden)

    Puddu Paolo

    2012-07-01

    Full Text Available Abstract Background Projection pursuit regression, multilayer feed-forward networks, multivariate adaptive regression splines and trees (including survival trees have challenged classic multivariable models such as the multiple logistic function, the proportional hazards life table Cox model (Cox, the Poisson’s model, and the Weibull’s life table model to perform multivariable predictions. However, only artificial neural networks (NN have become popular in medical applications. Results We compared several Cox versus NN models in predicting 45-year all-cause mortality (45-ACM by 18 risk factors selected a priori: age; father life status; mother life status; family history of cardiovascular diseases; job-related physical activity; cigarette smoking; body mass index (linear and quadratic terms; arm circumference; mean blood pressure; heart rate; forced expiratory volume; serum cholesterol; corneal arcus; diagnoses of cardiovascular diseases, cancer and diabetes; minor ECG abnormalities at rest. Two Italian rural cohorts of the Seven Countries Study, made up of men aged 40 to 59 years, enrolled and first examined in 1960 in Italy. Cox models were estimated by: a forcing all factors; b a forward-; and c a backward-stepwise procedure. Observed cases of deaths and of survivors were computed in decile classes of estimated risk. Forced and stepwise NN were run and compared by C-statistics (ROC analysis with the Cox models. Out of 1591 men, 1447 died. Model global accuracies were extremely high by all methods (ROCs > 0.810 but there was no clear-cut superiority of any model to predict 45-ACM. The highest ROCs (> 0.838 were observed by NN. There were inter-model variations to select predictive covariates: whereas all models concurred to define the role of 10 covariates (mainly cardiovascular risk factors, family history, heart rate and minor ECG abnormalities were not contributors by Cox models but were so by forced NN. Forced expiratory volume and arm

  3. Evaluation of protocol change in burn-care management using the Cox proportional hazards model with time-dependent covariates.

    Science.gov (United States)

    Ichida, J M; Wassell, J T; Keller, M D; Ayers, L W

    1993-02-01

    Survival analysis methods are valuable for detecting intervention effects because detailed information from patient records and sensitive outcome measures are used. The burn unit at a large university hospital replaced routine bathing with total body bathing using chlorhexidine gluconate for antimicrobial effect. A Cox proportional hazards model was used to analyse time from admission until either infection with Staphylococcus aureus or discharge for 155 patients, controlling for burn severity and two time-dependent covariates: days until first wound excision and days until first administration of prophylactic antibiotics. The risk of infection was 55 per cent higher in the historical control group, although not statistically significant. There was also some indication that early wound excision may be important as an infection-control measure for burn patients.

  4. Cancer survival analysis using semi-supervised learning method based on Cox and AFT models with L1/2 regularization.

    Science.gov (United States)

    Liang, Yong; Chai, Hua; Liu, Xiao-Ying; Xu, Zong-Ben; Zhang, Hai; Leung, Kwong-Sak

    2016-03-01

    One of the most important objectives of the clinical cancer research is to diagnose cancer more accurately based on the patients' gene expression profiles. Both Cox proportional hazards model (Cox) and accelerated failure time model (AFT) have been widely adopted to the high risk and low risk classification or survival time prediction for the patients' clinical treatment. Nevertheless, two main dilemmas limit the accuracy of these prediction methods. One is that the small sample size and censored data remain a bottleneck for training robust and accurate Cox classification model. In addition to that, similar phenotype tumours and prognoses are actually completely different diseases at the genotype and molecular level. Thus, the utility of the AFT model for the survival time prediction is limited when such biological differences of the diseases have not been previously identified. To try to overcome these two main dilemmas, we proposed a novel semi-supervised learning method based on the Cox and AFT models to accurately predict the treatment risk and the survival time of the patients. Moreover, we adopted the efficient L1/2 regularization approach in the semi-supervised learning method to select the relevant genes, which are significantly associated with the disease. The results of the simulation experiments show that the semi-supervised learning model can significant improve the predictive performance of Cox and AFT models in survival analysis. The proposed procedures have been successfully applied to four real microarray gene expression and artificial evaluation datasets. The advantages of our proposed semi-supervised learning method include: 1) significantly increase the available training samples from censored data; 2) high capability for identifying the survival risk classes of patient in Cox model; 3) high predictive accuracy for patients' survival time in AFT model; 4) strong capability of the relevant biomarker selection. Consequently, our proposed semi

  5. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  6. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  7. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introducea general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive...

  8. Pharmacological interaction between oxcarbazepine and two COX inhibitors in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vučković, Sonja M; Poznanović, Goran; Ugrešić, Nenad D; Prostran, Milica Š; Bošković, Bogdan

    2011-01-01

    Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The combination of different drugs activates both central and peripheral pain inhibitory pathways to induce additive or synergistic antinociception, and this interaction may allow lower doses of each drug combined and improve the safety profile, with lower side-effects. This study aimed to examine the effects of oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model of inflammatory hyperalgesia, and determine the type of interaction between drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in a fixed-dose fractions of the ED₅₀ and the type of interaction was determined by isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120 mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose-dependent anti-hyperalgesia in carrageenan-injected rats. ED₅₀ values (mean±SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17±3.65, 47.07±10.27 and 13.05±1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations induced significant and dose-dependent anti-hyperalgesia. Isobolographic analysis revealed that oxcarbazepine exerts a synergistic interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs in combination. In contrast, there was an additive interaction with etodolac. Synergistic interaction of oxcarbazepine with ibuprofen and its additive interaction with etodolac provide new information about the combination pain treatment and could be explored further in patients with inflammatory pain. Adverse effect analysis of the combinations is necessary to verify possible clinical use of the mixtures. Copyright

  9. Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol-lowering drugs.

    Science.gov (United States)

    Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G; Shah, Arvind K; Lin, Jianxin

    2013-10-15

    In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the deviance information criterion is used to select the best transformation model. Because the model is quite complex, we develop a novel Monte Carlo Markov chain sampling scheme to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol-lowering drugs where the goal is to jointly model the three-dimensional response consisting of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) (LDL-C, HDL-C, TG). Because the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately; however, a multivariate approach would be more appropriate because these variables are correlated with each other. We carry out a detailed analysis of these data by using the proposed methodology. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol lowering drugs

    Science.gov (United States)

    Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G.; Shah, Arvind K.; Lin, Jianxin

    2013-01-01

    In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data (IPD) in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the Deviance Information Criterion (DIC) is used to select the best transformation model. Since the model is quite complex, a novel Monte Carlo Markov chain (MCMC) sampling scheme is developed to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol lowering drugs where the goal is to jointly model the three dimensional response consisting of Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). Since the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately: however, a multivariate approach would be more appropriate since these variables are correlated with each other. A detailed analysis of these data is carried out using the proposed methodology. PMID:23580436

  11. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods : the example of antidepressant use and the risk of hip fracture

    NARCIS (Netherlands)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

    2016-01-01

    BACKGROUND: Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and

  12. Flexible mixture modeling via the multivariate t distribution with the Box-Cox transformation: an alternative to the skew-t distribution.

    Science.gov (United States)

    Lo, Kenneth; Gottardo, Raphael

    2012-01-01

    Cluster analysis is the automated search for groups of homogeneous observations in a data set. A popular modeling approach for clustering is based on finite normal mixture models, which assume that each cluster is modeled as a multivariate normal distribution. However, the normality assumption that each component is symmetric is often unrealistic. Furthermore, normal mixture models are not robust against outliers; they often require extra components for modeling outliers and/or give a poor representation of the data. To address these issues, we propose a new class of distributions, multivariate t distributions with the Box-Cox transformation, for mixture modeling. This class of distributions generalizes the normal distribution with the more heavy-tailed t distribution, and introduces skewness via the Box-Cox transformation. As a result, this provides a unified framework to simultaneously handle outlier identification and data transformation, two interrelated issues. We describe an Expectation-Maximization algorithm for parameter estimation along with transformation selection. We demonstrate the proposed methodology with three real data sets and simulation studies. Compared with a wealth of approaches including the skew-t mixture model, the proposed t mixture model with the Box-Cox transformation performs favorably in terms of accuracy in the assignment of observations, robustness against model misspecification, and selection of the number of components.

  13. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis - A Cox model analysis.

    Science.gov (United States)

    Delbarre, Angélique; Amor, Bernard; Bardoulat, Isabelle; Tetafort, Aymeric; Pelletier-Fleury, Nathalie

    2017-01-01

    This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-valueshyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee replacement and show that patients treated with hyaluronic acid have similar direct medical costs for ambulatory care compared to patients treated with corticosteroids only.

  14. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  15. RESEARCH OF EARLY STAGES OF MODELING

    Directory of Open Access Journals (Sweden)

    Andrey Borisovich Nikolaev

    2017-05-01

    Full Text Available In represented article the questions of estimate of accuracy of an average integral characteristics of random process in the course of imitation modeling is considered. For the purposes of analytical treatment of initial stage of modeling a conditionally nonstationary Gaussian process is analyzed as stationary Gaussian process with boundary prehistory. A model of approximant autocorrelation function is recommended. Analytical expression for variance and mathematical expectation of average integral estimation are obtained. Statistical estimation efficiency criterion, the probability of belonging to correct parameter interval is introduced. Dependences of closeness in estimation statistics clearing interval at transient behavior are researched for various types of processes.

  16. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis – A Cox model analysis

    Science.gov (United States)

    Amor, Bernard; Bardoulat, Isabelle; Tetafort, Aymeric; Pelletier-Fleury, Nathalie

    2017-01-01

    Due to the growing worldwide prevalence of knee osteoarthritis, the optimal management of this issue is critical for reducing its burden. Objectives This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. Materials and methods Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. Results A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-valueshyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. Conclusion This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee

  17. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  18. Determining the effect of worker exposure conditions on the risk of hearing loss in noisy industrial workroom using Cox proportional hazard model.

    Science.gov (United States)

    Aliabadi, Mohsen; Fereidan, Mohammad; Farhadian, Maryam; Tajik, Leila

    2015-01-01

    In noisy workrooms, exposure conditions such as noise level, exposure duration and use of hearing protection devices are contributory factors to hearing loss. The aim of this study was to determine the effect of exposure conditions on the risk of hearing loss using the Cox model. Seventy workers, employed in a press workshop, were selected to study their hearing threshold using an audiometric test. Their noise exposure histories also were analyzed. The results of the Cox model showed that the job type, smoking and the use of protection devices were effective to induce hearing loss. The relative risk of hearing loss in smokers was 1.1 times of non-smokers The relative risk of hearing loss in workers with the intermittent use of protection devices was 3.3 times those who used these devices continuously. The Cox model could analyze the effect of exposure conditions on hearing loss and provides useful information for managers in order to improve hearing conservation programs.

  19. Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

    Science.gov (United States)

    Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

    2013-05-01

    Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

  20. Estimating inverse probability weights using super learner when weight-model specification is unknown in a marginal structural Cox model context.

    Science.gov (United States)

    Karim, Mohammad Ehsanul; Platt, Robert W

    2017-06-15

    Correct specification of the inverse probability weighting (IPW) model is necessary for consistent inference from a marginal structural Cox model (MSCM). In practical applications, researchers are typically unaware of the true specification of the weight model. Nonetheless, IPWs are commonly estimated using parametric models, such as the main-effects logistic regression model. In practice, assumptions underlying such models may not hold and data-adaptive statistical learning methods may provide an alternative. Many candidate statistical learning approaches are available in the literature. However, the optimal approach for a given dataset is impossible to predict. Super learner (SL) has been proposed as a tool for selecting an optimal learner from a set of candidates using cross-validation. In this study, we evaluate the usefulness of a SL in estimating IPW in four different MSCM simulation scenarios, in which we varied the specification of the true weight model specification (linear and/or additive). Our simulations show that, in the presence of weight model misspecification, with a rich and diverse set of candidate algorithms, SL can generally offer a better alternative to the commonly used statistical learning approaches in terms of MSE as well as the coverage probabilities of the estimated effect in an MSCM. The findings from the simulation studies guided the application of the MSCM in a multiple sclerosis cohort from British Columbia, Canada (1995-2008), to estimate the impact of beta-interferon treatment in delaying disability progression. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Deema A. Al-Turki

    2017-01-01

    Full Text Available New series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100 mM relative to celecoxib, the standard reference. (±-3-(4-Phenoxy-phenyl-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent.

  2. Uncertainty estimation of a complex water quality model: The influence of Box-Cox transformation on Bayesian approaches and comparison with a non-Bayesian method

    Science.gov (United States)

    Freni, Gabriele; Mannina, Giorgio

    In urban drainage modelling, uncertainty analysis is of undoubted necessity. However, uncertainty analysis in urban water-quality modelling is still in its infancy and only few studies have been carried out. Therefore, several methodological aspects still need to be experienced and clarified especially regarding water quality modelling. The use of the Bayesian approach for uncertainty analysis has been stimulated by its rigorous theoretical framework and by the possibility of evaluating the impact of new knowledge on the modelling predictions. Nevertheless, the Bayesian approach relies on some restrictive hypotheses that are not present in less formal methods like the Generalised Likelihood Uncertainty Estimation (GLUE). One crucial point in the application of Bayesian method is the formulation of a likelihood function that is conditioned by the hypotheses made regarding model residuals. Statistical transformations, such as the use of Box-Cox equation, are generally used to ensure the homoscedasticity of residuals. However, this practice may affect the reliability of the analysis leading to a wrong uncertainty estimation. The present paper aims to explore the influence of the Box-Cox equation for environmental water quality models. To this end, five cases were considered one of which was the “real” residuals distributions (i.e. drawn from available data). The analysis was applied to the Nocella experimental catchment (Italy) which is an agricultural and semi-urbanised basin where two sewer systems, two wastewater treatment plants and a river reach were monitored during both dry and wet weather periods. The results show that the uncertainty estimation is greatly affected by residual transformation and a wrong assumption may also affect the evaluation of model uncertainty. The use of less formal methods always provide an overestimation of modelling uncertainty with respect to Bayesian method but such effect is reduced if a wrong assumption is made regarding the

  3. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.

  4. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

    We introduce a new class of Cox cluster processes called generalised shot-noise processes (GSNCPs), which extends the definition of shot noise Cox processes (SNCPs) in two directions: the point process which drives the shot noise is not necessarily Poisson, and the kernel of the shot noise can...... be random. Thereby a very large class of models for aggregated or clustered point patterns is obtained. Due to the structure of GSNCPs, a number of useful results can be established. We focus first on deriving summary statistics for GSNCPs and next on how to make simulation for GSNCPs. Particularly, results...... for first and second order moment measures, reduced Palm distributions, the -function, simulation with or without edge effects, and conditional simulation of the intensity function driving a GSNCP are given. Our results are exemplified for special important cases of GSNCPs, and we discuss the relation...

  5. Stage-specific predictive models for breast cancer survivability.

    Science.gov (United States)

    Kate, Rohit J; Nadig, Ramya

    2017-01-01

    Survivability rates vary widely among various stages of breast cancer. Although machine learning models built in past to predict breast cancer survivability were given stage as one of the features, they were not trained or evaluated separately for each stage. To investigate whether there are differences in performance of machine learning models trained and evaluated across different stages for predicting breast cancer survivability. Using three different machine learning methods we built models to predict breast cancer survivability separately for each stage and compared them with the traditional joint models built for all the stages. We also evaluated the models separately for each stage and together for all the stages. Our results show that the most suitable model to predict survivability for a specific stage is the model trained for that particular stage. In our experiments, using additional examples of other stages during training did not help, in fact, it made it worse in some cases. The most important features for predicting survivability were also found to be different for different stages. By evaluating the models separately on different stages we found that the performance widely varied across them. We also demonstrate that evaluating predictive models for survivability on all the stages together, as was done in the past, is misleading because it overestimates performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

    Science.gov (United States)

    Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

    2014-09-01

    Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

  7. Decomposition of Variance for Spatial Cox Processes.

    Science.gov (United States)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-03-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees.

  8. Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups

    DEFF Research Database (Denmark)

    Christensen, E; Altman, D G; Neuberger, J

    1993-01-01

    BACKGROUND: The precision of current prognostic models in primary biliary cirrhosis (PBC) is rather low, partly because they are based on data from just one time during the course of the disease. The aim of this study was to design a new, more precise prognostic model by incorporating follow......-up data in the development of the model. METHODS: We have performed Cox regression analyses with time-dependent variables in 237 PBC patients followed up regularly for up to 11 years. The validity of the obtained models was tested by comparing predicted and observed survival in 147 independent PBC...... patients followed for up to 6 years. RESULTS: In the obtained model the following time-dependent variables independently indicated a poor prognosis: high bilirubin, low albumin, ascites, gastrointestinal bleeding, and old age. When including histological variables, cirrhosis, central cholestasis, and low...

  9. Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model.

    Science.gov (United States)

    Yang, Ying; Gao, Ling

    2017-06-01

    Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed. Western blotting and immunohistochemical staining were performed to determine cyclooxygenase 2 (COX-2) expression in hippocampus. The results showed that a rat model of STZ-induced diabetes was successfully established and that celecoxib treatment significantly improved the associated nephropathy and inflammation. Moreover, spatial memory and hippocampal long-term potentiation (LTP) were impaired in diabetic model (P memory deficit and hippocampal LTP in the diabetic rats. To understand the underlying mechanisms, the expression of some important pathways involved in memory impairment was determined. We found that brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase (p-TrkB) were decreased in diabetic rats but were effectively reversed by celecoxib treatment. As evidenced by western blotting and immunohistochemical staining, the expression of COX-2 in hippocampus was significantly upregulated in diabetic rat (P memory deficits via probable downregulation of hippocampal COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a

  10. Stages of Change or Changes of Stage? Predicting Transitions in Transtheoretical Model Stages in Relation to Healthy Food Choice

    Science.gov (United States)

    Armitage, Christopher J.; Sheeran, Paschal; Conner, Mark; Arden, Madelynne A.

    2004-01-01

    Relatively little research has examined factors that account for transitions between transtheoretical model (TTM) stages of change. The present study (N=787) used sociodemographic, TTM, and theory of planned behavior (TPB) variables, as well as theory-driven interventions to predict changes in stage. Longitudinal analyses revealed that…

  11. Using Swiss Webster mice to model Fetal Alcohol Spectrum Disorders (FASD): An analysis of multilevel time-to-event data through mixed-effects Cox proportional hazards models.

    Science.gov (United States)

    Chi, Peter; Aras, Radha; Martin, Katie; Favero, Carlita

    2016-05-15

    Fetal Alcohol Spectrum Disorders (FASD) collectively describes the constellation of effects resulting from human alcohol consumption during pregnancy. Even with public awareness, the incidence of FASD is estimated to be upwards of 5% in the general population and is becoming a global health problem. The physical, cognitive, and behavioral impairments of FASD are recapitulated in animal models. Recently rodent models utilizing voluntary drinking paradigms have been developed that accurately reflect moderate consumption, which makes up the majority of FASD cases. The range in severity of FASD characteristics reflects the frequency, dose, developmental timing, and individual susceptibility to alcohol exposure. As most rodent models of FASD use C57BL/6 mice, there is a need to expand the stocks of mice studied in order to more fully understand the complex neurobiology of this disorder. To that end, we allowed pregnant Swiss Webster mice to voluntarily drink ethanol via the drinking in the dark (DID) paradigm throughout their gestation period. Ethanol exposure did not alter gestational outcomes as determined by no significant differences in maternal weight gain, maternal liquid consumption, litter size, or pup weight at birth or weaning. Despite seemingly normal gestation, ethanol-exposed offspring exhibit significantly altered timing to achieve developmental milestones (surface righting, cliff aversion, and open field traversal), as analyzed through mixed-effects Cox proportional hazards models. These results confirm Swiss Webster mice as a viable option to study the incidence and causes of ethanol-induced neurobehavioral alterations during development. Future studies in our laboratory will investigate the brain regions and molecules responsible for these behavioral changes. Copyright © 2016. Published by Elsevier B.V.

  12. A Semimetal Model of the Normal State Susceptibility and Transport Properties of Ba(Fe1-xCox)2As2 Superconductors

    Science.gov (United States)

    Sales, Brian; Sefat, Athena; McGuire, Michael; Mandrus, David

    2010-03-01

    A simple two-band 3D model of a semimetal is constructed to see which normal state features of the Ba(Fe1-xCox)2As2 superconductors can be qualitatively understood within this framework. The model is able to account in a semiquantitative fashion for the measured magnetic susceptibility, Hall, and Seebeck data, and the low temperature Sommerfeld coefficient for 0 general conclusion from the model is that the magnetic susceptibility of most semimetals should increase with temperatures. This is indeed found to be the case for two well-known semimetals Bi and TiSe2. Research supported by the US DOE, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering.

  13. Stages as models of scene geometry.

    Science.gov (United States)

    Nedović, Vladimir; Smeulders, Arnold W M; Redert, André; Geusebroek, Jan-Mark

    2010-09-01

    Reconstruction of 3D scene geometry is an important element for scene understanding, autonomous vehicle and robot navigation, image retrieval, and 3D television. We propose accounting for the inherent structure of the visual world when trying to solve the scene reconstruction problem. Consequently, we identify geometric scene categorization as the first step toward robust and efficient depth estimation from single images. We introduce 15 typical 3D scene geometries called stages, each with a unique depth profile, which roughly correspond to a large majority of broadcast video frames. Stage information serves as a first approximation of global depth, narrowing down the search space in depth estimation and object localization. We propose different sets of low-level features for depth estimation, and perform stage classification on two diverse data sets of television broadcasts. Classification results demonstrate that stages can often be efficiently learned from low-dimensional image representations.

  14. Geometric anisotropic spatial point pattern analysis and Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Toftaker, Håkon

    . In particular we study Cox process models with an elliptical pair correlation function, including shot noise Cox processes and log Gaussian Cox processes, and we develop estimation procedures using summary statistics and Bayesian methods. Our methodology is illustrated on real and synthetic datasets of spatial...

  15. A two stage data envelopment analysis model with undesirable output

    Science.gov (United States)

    Shariff Adli Aminuddin, Adam; Izzati Jaini, Nur; Mat Kasim, Maznah; Nawawi, Mohd Kamal Mohd

    2017-09-01

    The dependent relationship among the decision making units (DMU) is usually assumed to be non-existent in the development of Data Envelopment Analysis (DEA) model. The dependency can be represented by the multi-stage DEA model, where the outputs from the precedent stage will be the inputs for the latter stage. The multi-stage DEA model evaluate both the efficiency score for each stages and the overall efficiency of the whole process. The existing multi stage DEA models do not focus on the integration with the undesirable output, in which the higher input will generate lower output unlike the normal desirable output. This research attempts to address the inclusion of such undesirable output and investigate the theoretical implication and potential application towards the development of multi-stage DEA model.

  16. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    Science.gov (United States)

    2013-01-01

    Background COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. Methods LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT). Results LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (pdiclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer. PMID:23289871

  17. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

    2005-01-01

    We introduce a class of cox cluster processes called generalised shot noise Cox processes (GSNCPs), which extends the definition of shot noise Cox processes (SNCPs) in two directions: the point process that drives the shot noise is not necessarily Poisson, and the kernel of the shot noise can...

  18. Dynamic Modeling and Very Short-term Prediction of Wind Power Output Using Box-Cox Transformation

    Science.gov (United States)

    Urata, Kengo; Inoue, Masaki; Murayama, Dai; Adachi, Shuichi

    2016-09-01

    We propose a statistical modeling method of wind power output for very short-term prediction. The modeling method with a nonlinear model has cascade structure composed of two parts. One is a linear dynamic part that is driven by a Gaussian white noise and described by an autoregressive model. The other is a nonlinear static part that is driven by the output of the linear part. This nonlinear part is designed for output distribution matching: we shape the distribution of the model output to match with that of the wind power output. The constructed model is utilized for one-step ahead prediction of the wind power output. Furthermore, we study the relation between the prediction accuracy and the prediction horizon.

  19. Predictors of time to relapse in amphetamine-type substance users in the matrix treatment program in Iran: a Cox proportional hazard model application.

    Science.gov (United States)

    Moeeni, Maryam; Razaghi, Emran M; Ponnet, Koen; Torabi, Fatemeh; Shafiee, Seyed Ali; Pashaei, Tahereh

    2016-07-26

    The aim of this study was to determine which predictors influence the risk of relapse among a cohort of amphetamine-type substance (ATS) users in Iran. A Cox proportional hazards model was conducted to determine factors associated with the relapse time in the Matrix treatment program provided by the Iranian National Center of Addiction Studies (INCAS) between March 2010 and October 2011. Participating in more treatment sessions was associated with a lower probability of relapse. On the other hand, patients with less family support, longer dependence on ATS, and those with an experience of casual sex and a history of criminal offenses were more likely to relapse. This study broadens our understanding of factors influencing the risk of relapse in ATS use among an Iranian sample. The findings can guide practitioners during the treatment program.

  20. STAGES OF A STRATEGIC MANAGEMENT MODEL

    OpenAIRE

    Mihaela – Lavinia CIOBANICA

    2014-01-01

    In the literature dedicated to strategic management there is no unitary vision of the authors regarding the sequence of actions that give content to the respective process and what their stages are. With all existing differences, the visions of different authors nevertheless observe the unitary logic of developing a series of actions. These actions begin with the competitive environment analysis in which the organization operates and with the establishment of its strategic mission and th...

  1. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

    Science.gov (United States)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

    2016-03-01

    Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

  2. STAGES OF A STRATEGIC MANAGEMENT MODEL

    Directory of Open Access Journals (Sweden)

    Mihaela – Lavinia CIOBANICA

    2014-06-01

    Full Text Available In the literature dedicated to strategic management there is no unitary vision of the authors regarding the sequence of actions that give content to the respective process and what their stages are. With all existing differences, the visions of different authors nevertheless observe the unitary logic of developing a series of actions. These actions begin with the competitive environment analysis in which the organization operates and with the establishment of its strategic mission and they end with the performance evaluation after the strategy has been applied and, if appropriate, with the reconsidering of this strategy and the making of the necessary corrections to it. Such a basic structure of the process is adopted in most organizations that practice the strategic management. But noticeable differences appear in the degree of the formalization of the process and in the involvement of different managerial levels in the designing and detailing of its components.

  3. Possibilities Of Opening Up the Stage-Gate Model

    Directory of Open Access Journals (Sweden)

    Biljana Stošić

    2014-12-01

    Full Text Available The paper presents basic elements of the Stage-Gate and Open innovation models, and possible connection of these two, resulting in what is frequently called an “Open Stage-Gate” model. This connection is based on opening up the new product development process and integration of the open innovation principles with the Stage-Gate concept, facilitating the import and export of information and technologies. Having in mind that the Stage Gate has originally been classified as the third generation model of innovation, the paper is dealing with the capabilities for applying the sixth generation Open innovation principles in today’s improved and much more flexible phases and gates of the Stage Gate. Lots of innovative companies are actually using both models in their NPD practice, looking for the most appropriate means of opening up the well-known closed innovation, especially in the domain of ideation through co-creation.

  4. Short term load forecasting: two stage modelling

    Directory of Open Access Journals (Sweden)

    SOARES, L. J.

    2009-06-01

    Full Text Available This paper studies the hourly electricity load demand in the area covered by a utility situated in the Seattle, USA, called Puget Sound Power and Light Company. Our proposal is put into proof with the famous dataset from this company. We propose a stochastic model which employs ANN (Artificial Neural Networks to model short-run dynamics and the dependence among adjacent hours. The model proposed treats each hour's load separately as individual single series. This approach avoids modeling the intricate intra-day pattern (load profile displayed by the load, which varies throughout days of the week and seasons. The forecasting performance of the model is evaluated in similiar mode a TLSAR (Two-Level Seasonal Autoregressive model proposed by Soares (2003 using the years of 1995 and 1996 as the holdout sample. Moreover, we conclude that non linearity is present in some series of these data. The model results are analyzed. The experiment shows that our tool can be used to produce load forecasting in tropical climate places.

  5. Energy demand in Portuguese manufacturing: a two-stage model

    International Nuclear Information System (INIS)

    Borges, A.M.; Pereira, A.M.

    1992-01-01

    We use a two-stage model of factor demand to estimate the parameters determining energy demand in Portuguese manufacturing. In the first stage, a capital-labor-energy-materials framework is used to analyze the substitutability between energy as a whole and other factors of production. In the second stage, total energy demand is decomposed into oil, coal and electricity demands. The two stages are fully integrated since the energy composite used in the first stage and its price are obtained from the second stage energy sub-model. The estimates obtained indicate that energy demand in manufacturing responds significantly to price changes. In addition, estimation results suggest that there are important substitution possibilities among energy forms and between energy and other factors of production. The role of price changes in energy-demand forecasting, as well as in energy policy in general, is clearly established. (author)

  6. Relationship between metallothioneins and metals in a natural population of the clam Ruditapes decussatus from Sfax coast: a non-linear model using Box-Cox transformation.

    Science.gov (United States)

    Hamza-Chaffai, A; Amiard, J C; Cosson, R P

    1999-06-01

    Cadmium, copper and zinc were determined concomitantly with metallothionein-like proteins (MTLPs) in the subcellular fractions of Ruditapes decussatus digestive gland. This study covered 4 months and aimed to evaluate the effect of metal pollution and other factors such as sex, size and reproductive state on MTLP levels. Copper concentrations did not vary with month, however Cd and Zn concentrations showed high levels during August. Organisms showing low cadmium concentrations presented the highest cadmium percentages in the soluble fraction (SF) containing MTLPs. However for high cadmium concentrations, the insoluble fraction (IF) was implicated in cadmium association. MTLP levels varied according to the month, the sex and the size of the organisms. A non-linear model based on the Box-Cox transformation, was proposed to describe a positive and a significant relationship between MTLPs and the studied metals. A model including sex and size showed that these two factors affected MTLP levels, but were less important than metals. Males of R. decussatus showed higher significant correlations between MTLP levels and cadmium than females. Moreover, the effect of size and reproductive state on MTLP levels was less perceptible in males than in females. As a result, MTLPs in males of R. decussatus could be proposed as suitable biomarker for detecting metal contamination.

  7. The Moxie of Kathy Cox

    Science.gov (United States)

    Johns, Stephanie

    2010-01-01

    Kathy Cox, the superintendent of schools for Georgia, believes "excellence is not an accident". She made a name for herself by winning $1 million proving she was smarter than a fifth-grader on a popular television show. This article presents a profile of Cox, her family, her role as school superintendent, and her accomplishments.…

  8. A method for extending stage-discharge relationships using a hydrodynamic model and quantifying the associated uncertainty

    Science.gov (United States)

    Shao, Quanxi; Dutta, Dushmanta; Karim, Fazlul; Petheram, Cuan

    2018-01-01

    Streamflow discharge is a fundamental dataset required to effectively manage water and land resources. However, developing robust stage - discharge relationships called rating curves, from which streamflow discharge is derived, is time consuming and costly, particularly in remote areas and especially at high stage levels. As a result stage - discharge relationships are often heavily extrapolated. Hydrodynamic (HD) models are physically based models used to simulate the flow of water along river channels and over adjacent floodplains. In this paper we demonstrate a method by which a HD model can be used to generate a 'synthetic' stage - discharge relationship at high stages. The method uses a both-side Box-Cox transformation to calibrate the synthetic rating curve such that the regression residuals are as close to the normal distribution as possible. By doing this both-side transformation, the statistical uncertainty in the synthetically derived stage - discharge relationship can be calculated. This enables people trying to make decisions to determine whether the uncertainty in the synthetically generated rating curve at high stage levels is acceptable for their decision. The proposed method is demonstrated in two streamflow gauging stations in north Queensland, Australia.

  9. On spatio-temporal Lévy based Cox processes

    DEFF Research Database (Denmark)

    Prokesova, Michaela; Hellmund, Gunnar; Jensen, Eva Bjørn Vedel

    2006-01-01

    The paper discusses a new class of models for spatio-temporal Cox point processes. In these models, the driving field is defined by means of an integral of a weight function with respect to a Lévy basis. The relations to other Cox process models studied previously are discussed and formulas for t...

  10. Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Nils Ternès

    2017-05-01

    Full Text Available Abstract Background Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions. Methods Based on a parsimonious biomarker selection in a penalized high-dimensional Cox model (lasso or adaptive lasso, we propose a unified framework to: estimate internally the predictive accuracy metrics of the developed model (using double cross-validation; estimate the individual survival probabilities at a given timepoint; construct confidence intervals thereof (analytical or bootstrap; and visualize them graphically (pointwise or smoothed with spline. We compared these strategies through a simulation study covering scenarios with or without biomarker effects. We applied the strategies to a large randomized phase III clinical trial that evaluated the effect of adding trastuzumab to chemotherapy in 1574 early breast cancer patients, for which the expression of 462 genes was measured. Results In our simulations, penalized regression models using the adaptive lasso estimated the survival probability of new patients with low bias and standard error; bootstrapped confidence intervals had empirical coverage probability close to the nominal level across very different scenarios. The double cross-validation performed on the training data set closely mimicked the predictive accuracy of the selected models in external validation data. We also propose a useful visual representation of the expected survival probabilities using splines. In the breast cancer trial, the adaptive lasso penalty selected a prediction model with 4

  11. A stage-based model of design teaching

    DEFF Research Database (Denmark)

    Beier, Sofie

    2014-01-01

    With a focus on the teaching of design students in higher education, the article will present a teaching approach model that follows the stages of the design process. The model suggests that at the Definition stage, the supervisor can focus on leading the student into a more thorough elaboration ...... apply an approach inspired by the master–apprentice relationship, where the student learns by observing the master at work....

  12. Streamlining environmental product declarations: a stage model

    Science.gov (United States)

    Lefebvre, Elisabeth; Lefebvre, Louis A.; Talbot, Stephane; Le Hen, Gael

    2001-02-01

    General public environmental awareness and education is increasing, therefore stimulating the demand for reliable, objective and comparable information about products' environmental performances. The recently published standard series ISO 14040 and ISO 14025 are normalizing the preparation of Environmental Product Declarations (EPDs) containing comprehensive information relevant to a product's environmental impact during its life cycle. So far, only a few environmentally leading manufacturing organizations have experimented the preparation of EPDs (mostly from Europe), demonstrating its great potential as a marketing weapon. However the preparation of EPDs is a complex process, requiring collection and analysis of massive amounts of information coming from disparate sources (suppliers, sub-contractors, etc.). In a foreseeable future, the streamlining of the EPD preparation process will require product manufacturers to adapt their information systems (ERP, MES, SCADA) in order to make them capable of gathering, and transmitting the appropriate environmental information. It also requires strong functional integration all along the product supply chain in order to ensure that all the information is made available in a standardized and timely manner. The goal of the present paper is two fold: first to propose a transitional model towards green supply chain management and EPD preparation; second to identify key technologies and methodologies allowing to streamline the EPD process and subsequently the transition toward sustainable product development

  13. Valuation of Indonesian catastrophic earthquake bonds with generalized extreme value (GEV) distribution and Cox-Ingersoll-Ross (CIR) interest rate model

    Science.gov (United States)

    Gunardi, Setiawan, Ezra Putranda

    2015-12-01

    Indonesia is a country with high risk of earthquake, because of its position in the border of earth's tectonic plate. An earthquake could raise very high amount of damage, loss, and other economic impacts. So, Indonesia needs a mechanism for transferring the risk of earthquake from the government or the (reinsurance) company, as it could collect enough money for implementing the rehabilitation and reconstruction program. One of the mechanisms is by issuing catastrophe bond, `act-of-God bond', or simply CAT bond. A catastrophe bond issued by a special-purpose-vehicle (SPV) company, and then sold to the investor. The revenue from this transaction is joined with the money (premium) from the sponsor company and then invested in other product. If a catastrophe happened before the time-of-maturity, cash flow from the SPV to the investor will discounted or stopped, and the cash flow is paid to the sponsor company to compensate their loss because of this catastrophe event. When we consider the earthquake only, the amount of discounted cash flow could determine based on the earthquake's magnitude. A case study with Indonesian earthquake magnitude data show that the probability of maximum magnitude can model by generalized extreme value (GEV) distribution. In pricing this catastrophe bond, we assumed stochastic interest rate that following the Cox-Ingersoll-Ross (CIR) interest rate model. We develop formulas for pricing three types of catastrophe bond, namely zero coupon bonds, `coupon only at risk' bond, and `principal and coupon at risk' bond. Relationship between price of the catastrophe bond and CIR model's parameter, GEV's parameter, percentage of coupon, and discounted cash flow rule then explained via Monte Carlo simulation.

  14. Valuation of Indonesian catastrophic earthquake bonds with generalized extreme value (GEV) distribution and Cox-Ingersoll-Ross (CIR) interest rate model

    International Nuclear Information System (INIS)

    Gunardi,; Setiawan, Ezra Putranda

    2015-01-01

    Indonesia is a country with high risk of earthquake, because of its position in the border of earth’s tectonic plate. An earthquake could raise very high amount of damage, loss, and other economic impacts. So, Indonesia needs a mechanism for transferring the risk of earthquake from the government or the (reinsurance) company, as it could collect enough money for implementing the rehabilitation and reconstruction program. One of the mechanisms is by issuing catastrophe bond, ‘act-of-God bond’, or simply CAT bond. A catastrophe bond issued by a special-purpose-vehicle (SPV) company, and then sold to the investor. The revenue from this transaction is joined with the money (premium) from the sponsor company and then invested in other product. If a catastrophe happened before the time-of-maturity, cash flow from the SPV to the investor will discounted or stopped, and the cash flow is paid to the sponsor company to compensate their loss because of this catastrophe event. When we consider the earthquake only, the amount of discounted cash flow could determine based on the earthquake’s magnitude. A case study with Indonesian earthquake magnitude data show that the probability of maximum magnitude can model by generalized extreme value (GEV) distribution. In pricing this catastrophe bond, we assumed stochastic interest rate that following the Cox-Ingersoll-Ross (CIR) interest rate model. We develop formulas for pricing three types of catastrophe bond, namely zero coupon bonds, ‘coupon only at risk’ bond, and ‘principal and coupon at risk’ bond. Relationship between price of the catastrophe bond and CIR model’s parameter, GEV’s parameter, percentage of coupon, and discounted cash flow rule then explained via Monte Carlo simulation

  15. Valuation of Indonesian catastrophic earthquake bonds with generalized extreme value (GEV) distribution and Cox-Ingersoll-Ross (CIR) interest rate model

    Energy Technology Data Exchange (ETDEWEB)

    Gunardi,; Setiawan, Ezra Putranda [Mathematics Department, Gadjah Mada University (Indonesia)

    2015-12-22

    Indonesia is a country with high risk of earthquake, because of its position in the border of earth’s tectonic plate. An earthquake could raise very high amount of damage, loss, and other economic impacts. So, Indonesia needs a mechanism for transferring the risk of earthquake from the government or the (reinsurance) company, as it could collect enough money for implementing the rehabilitation and reconstruction program. One of the mechanisms is by issuing catastrophe bond, ‘act-of-God bond’, or simply CAT bond. A catastrophe bond issued by a special-purpose-vehicle (SPV) company, and then sold to the investor. The revenue from this transaction is joined with the money (premium) from the sponsor company and then invested in other product. If a catastrophe happened before the time-of-maturity, cash flow from the SPV to the investor will discounted or stopped, and the cash flow is paid to the sponsor company to compensate their loss because of this catastrophe event. When we consider the earthquake only, the amount of discounted cash flow could determine based on the earthquake’s magnitude. A case study with Indonesian earthquake magnitude data show that the probability of maximum magnitude can model by generalized extreme value (GEV) distribution. In pricing this catastrophe bond, we assumed stochastic interest rate that following the Cox-Ingersoll-Ross (CIR) interest rate model. We develop formulas for pricing three types of catastrophe bond, namely zero coupon bonds, ‘coupon only at risk’ bond, and ‘principal and coupon at risk’ bond. Relationship between price of the catastrophe bond and CIR model’s parameter, GEV’s parameter, percentage of coupon, and discounted cash flow rule then explained via Monte Carlo simulation.

  16. A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

    2018-05-02

    The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

  17. Stage wise modeling of liquid-extraction column (RDC)

    International Nuclear Information System (INIS)

    Bastani, B.

    2004-01-01

    Stage wise forward mixing model considering coalescence and re dispersion of drops was used to predict the performance of Rotating Disk Liquid Extraction Contactors. Experimental data previously obtained in two RDC columns of 7-62 cm diameter, 73.6 cm height and 21.9 cm diameter,150 cm height were used to evaluate the model predications. Drops-side mass transfer coefficients were predicted applying Hand los-baron drop model and onley's model was used to predict velocities. According to the results obtained the followings could be concluded: (1) If the height of coalescence and re dispersion i.e.:h=h p Q p / Q could be estimated, the stage wise forward mixing with coalescence and re dispersion model will predict the column height and efficiency with the acceptable accuracy, (2) The stage wise modeling predictions are highly dependent on the number of stages used when the number of stages is less than 10 and (3) Application of continuous phase mass transfer axial dispersion coefficients (k c and E c ) obtained from the solute concentration profile along the column height will predict the column performance more accurately than the Calder bank and moo-young (for K c ) and Kumar-Heartland (for E c ) correlations

  18. A kinetic model for the first stage of pygas upgrading

    Directory of Open Access Journals (Sweden)

    J. L. de Medeiros

    2007-03-01

    Full Text Available Pyrolysis gasoline - PYGAS - is an intermediate boiling product of naphtha steam cracking with a high octane number and high aromatic/unsaturated contents. Due to stabilization concerns, PYGAS must be hydrotreated in two stages. The first stage uses a mild trickle-bed conversion for removing extremely reactive species (styrene, dienes and olefins prior to the more severe second stage where sulfured and remaining olefins are hydrogenated in gas phase. This work addresses the reaction network and two-phase kinetic model for the first stage of PYGAS upgrading. Nonlinear estimation was used for model tuning with kinetic data obtained in bench-scale trickle-bed hydrogenation with a commercial Pd/Al2O3 catalyst. On-line sampling experiments were designed to study the influence of variables - temperature and spatial velocity - on the conversion of styrene, dienes and olefins.

  19. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus Plenge

    2017-01-01

    This paper establishes a remarkable result regarding Palm distributions for a log Gaussian Cox process: the reduced Palm distribution for a log Gaussian Cox process is itself a log Gaussian Cox process that only differs from the original log Gaussian Cox process in the intensity function. This new...... result is used to study functional summaries for log Gaussian Cox processes....

  20. Early increased density of cyclooxygenase-2 (COX-2 immunoreactive neurons in Down syndrome

    Directory of Open Access Journals (Sweden)

    Maria Mulet

    2017-06-01

    Full Text Available Neuroinflammation is one of the hallmarks of Alzheimer’s disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer’s disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer’s disease.

  1. Perioperative Pain Relief by a COX-2 Inhibitor Affects Ileal Repair and Provides a Model for Anastomotic Leakage in the Intestine

    NARCIS (Netherlands)

    van der Vijver, R.J.; Laarhoven, C.J. van; de Man, B.M.; Lomme, R.M.L.M.; Hendriks, T.

    2013-01-01

    The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or

  2. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  3. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    International Nuclear Information System (INIS)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    2012-01-01

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  4. SEKULARISASI DALAM PANDANGAN HARVEY COX

    Directory of Open Access Journals (Sweden)

    Fauzan Fauzan

    2017-02-01

    Full Text Available Sebagian besar kaum agamawan (ortodoks memandang sekularisasi sebagai ancaman terhadap eksistensi agama. Namun sebaliknya, Harvey Cox memandang sekularisasi sebagai teologi perubahan sosial yang bertujuan mendobrak kebuntuan agama yang terbelenggu oleh ide “pemeliharaan” dan “kemapanan”. Tulisan ini membahas pandangan Harvey Cox tentang sekularisasi, konsepnya tentang Kota Sekuler (Secular City, dan Tuhan pada masyarakat sekuler. Cox melihat sekularisasi merupakan sebuah keniscayaan sejarah. Sekularisasi merupakan gerakan yang membebaskan manusia dari dogma yang membelenggu kebebasan manusia. Melalui simbol Kota Sekuler, Cox menghadirkan paradigma teologi yang lebih sesuai dengan keadaan masyarakat modern saat ini. Cox melihat bahwa Tuhan sebagaimana yang diajarkan oleh Kristiani –juga agama lain– bukanlah Tuhan yang sebenarnya. Tuhan tak lebih dari sebuah penamaan yang kehadirannya terkadang kosong dan ambigu. Semenjak penamaan dilekatkan dalam lingkungan sosio kultural tertentu, maka kata “Tuhan” tidak suci lagi. Apabila Tuhan dimaknai secara “ketat” dalam ruang tradisi yang berbeda-beda, maka akan terjadi benturan yang terkadang membutuhkan pengorbanan jiwa.

  5. Two-step two-stage fission gas release model

    International Nuclear Information System (INIS)

    Kim, Yong-soo; Lee, Chan-bock

    2006-01-01

    Based on the recent theoretical model, two-step two-stage model is developed which incorporates two stage diffusion processes, grain lattice and grain boundary diffusion, coupled with the two step burn-up factor in the low and high burn-up regime. FRAPCON-3 code and its in-pile data sets have been used for the benchmarking and validation of this model. Results reveals that its prediction is in better agreement with the experimental measurements than that by any model contained in the FRAPCON-3 code such as ANS 5.4, modified ANS5.4, and Forsberg-Massih model over whole burn-up range up to 70,000 MWd/MTU. (author)

  6. On A Two-Stage Supply Chain Model In The Manufacturing Industry ...

    African Journals Online (AJOL)

    We model a two-stage supply chain where the upstream stage (stage 2) always meet demand from the downstream stage (stage 1).Demand is stochastic hence shortages will occasionally occur at stage 2. Stage 2 must fill these shortages by expediting using overtime production and/or backordering. We derive optimal ...

  7. Numerical modelling of the HAB Energy Buoy: Stage 1

    DEFF Research Database (Denmark)

    Kurniawan, Adi

    This report presents the results of the first stage of the project "Numerical modelling of the HAB Energy Buoy". The objectives of this stage are to develop a numerical model of the HAB Energy Buoy, a self-reacting wave energy device consisting of two heaving bodies, and to investigate a number...... and a summary of the main findings is presented. A numerical model of the HAB Energy Buoy has been developed in the frequency domain using two alternative formulations of the equations of motion. The model is capable of predicting the power capture, motion response, and power take-off loads of the device...... configuration are imposed to give a more realistic prediction of the power capture and help ensure a fair comparison. Recommendations with regard to the HAB design are finally suggested....

  8. Salmonella enterica serovar Enteritidis enterocolitis during late stages of gestation induces an adverse pregnancy outcome in the murine model.

    Directory of Open Access Journals (Sweden)

    Mariángeles Noto Llana

    Full Text Available Foodborne diseases caused by Salmonella enterica serovar Enteritidis (S. Enteritidis are a significant health problem. Pregnancy, state of immunological tolerance, is a predisposing condition for the development of infections with intracellular pathogens. Salmonella species can cause pregnancy complications such as chorioamnionitis, transplacental fetal infection, pre term labor, abortions, neonatal and maternal septicemia. However, the specific mechanisms by which Salmonella infections trigger these alterations are not clear. In the present work, using a self-limiting enterocolitis murine model, we show that the ingestion of a low dose of S. Enteritidis at late stages of pregnancy (day 15 of gestation is sufficient to induce massive maternal infection. We found that Salmonella infection leads to 40% of pre term delivery, 33% of abortion and fetal growth restriction. Placental dysfunction during S. Enteritidis enterocolitis was confirmed through cellular infiltration and hypoxia markers (MPO activity and COX-1 and COX-2 expression, respectively. Apoptosis in placental tissue due to Salmonella infection was also evident at day 18 of gestation when investigated by morphometric procedure, DNA fragmentation and Fas/FasL expression. Also, the expression of IFN-γ, TNF-α, IL-17 and IL-10 was up regulated in response to Salmonella not only in placenta, but also in amniotic fluid and maternal serum. Altogether, our results demonstrate that S. Enteritidis enterocolitis during late stages of gestation causes detrimental effect on pregnancy outcome.

  9. Log Gaussian Cox processes on the sphere

    DEFF Research Database (Denmark)

    Pacheco, Francisco Andrés Cuevas; Møller, Jesper

    We define and study the existence of log Gaussian Cox processes (LGCPs) for the description of inhomogeneous and aggregated/clustered point patterns on the d-dimensional sphere, with d = 2 of primary interest. Useful theoretical properties of LGCPs are studied and applied for the description of sky...... positions of galaxies, in comparison with previous analysis using a Thomas process. We focus on simple estimation procedures and model checking based on functional summary statistics and the global envelope test....

  10. The Study on Stage Financing Model of IT Project Investment

    Directory of Open Access Journals (Sweden)

    Si-hua Chen

    2014-01-01

    Full Text Available Stage financing is the basic operation of venture capital investment. In investment, usually venture capitalists use different strategies to obtain the maximum returns. Due to its advantages to reduce the information asymmetry and agency cost, stage financing is widely used by venture capitalists. Although considerable attentions are devoted to stage financing, very little is known about the risk aversion strategies of IT projects. This paper mainly addresses the problem of risk aversion of venture capital investment in IT projects. Based on the analysis of characteristics of venture capital investment of IT projects, this paper introduces a real option pricing model to measure the value brought by the stage financing strategy and design a risk aversion model for IT projects. Because real option pricing method regards investment activity as contingent decision, it helps to make judgment on the management flexibility of IT projects and then make a more reasonable evaluation about the IT programs. Lastly by being applied to a real case, it further illustrates the effectiveness and feasibility of the model.

  11. The Study on Stage Financing Model of IT Project Investment

    Science.gov (United States)

    Xu, Sheng-hua; Xiong, Neal N.

    2014-01-01

    Stage financing is the basic operation of venture capital investment. In investment, usually venture capitalists use different strategies to obtain the maximum returns. Due to its advantages to reduce the information asymmetry and agency cost, stage financing is widely used by venture capitalists. Although considerable attentions are devoted to stage financing, very little is known about the risk aversion strategies of IT projects. This paper mainly addresses the problem of risk aversion of venture capital investment in IT projects. Based on the analysis of characteristics of venture capital investment of IT projects, this paper introduces a real option pricing model to measure the value brought by the stage financing strategy and design a risk aversion model for IT projects. Because real option pricing method regards investment activity as contingent decision, it helps to make judgment on the management flexibility of IT projects and then make a more reasonable evaluation about the IT programs. Lastly by being applied to a real case, it further illustrates the effectiveness and feasibility of the model. PMID:25147845

  12. The study on stage financing model of IT project investment.

    Science.gov (United States)

    Chen, Si-hua; Xu, Sheng-hua; Lee, Changhoon; Xiong, Neal N; He, Wei

    2014-01-01

    Stage financing is the basic operation of venture capital investment. In investment, usually venture capitalists use different strategies to obtain the maximum returns. Due to its advantages to reduce the information asymmetry and agency cost, stage financing is widely used by venture capitalists. Although considerable attentions are devoted to stage financing, very little is known about the risk aversion strategies of IT projects. This paper mainly addresses the problem of risk aversion of venture capital investment in IT projects. Based on the analysis of characteristics of venture capital investment of IT projects, this paper introduces a real option pricing model to measure the value brought by the stage financing strategy and design a risk aversion model for IT projects. Because real option pricing method regards investment activity as contingent decision, it helps to make judgment on the management flexibility of IT projects and then make a more reasonable evaluation about the IT programs. Lastly by being applied to a real case, it further illustrates the effectiveness and feasibility of the model.

  13. The protection motivation theory within the stages of the transtheoretical model - stage-specific interplay of variables and prediction of exercise stage transitions.

    Science.gov (United States)

    Lippke, Sonia; Plotnikoff, Ronald C

    2009-05-01

    Two different theories of health behaviour have been chosen with the aim of theory integration: a continuous theory (protection motivation theory, PMT) and a stage model (transtheoretical model, TTM). This is the first study to test whether the stages of the TTM moderate the interrelation of PMT-variables and the mediation of motivation, as well as PMT-variables' interactions in predicting stage transitions. Hypotheses were tested regarding (1) mean patterns, stage pair-comparisons and nonlinear trends using ANOVAs; (2) prediction-patterns for the different stage groups employing multi-group structural equation modelling (MSEM) and nested model analyses; and (3) stage transitions using binary logistic regression analyses. Adults (N=1,602) were assessed over a 6 month period on their physical activity stages, PMT-variables and subsequent behaviour. (1) Particular mean differences and nonlinear trends in all test variables were found. (2) The PMT adequately fitted the five stage groups. The MSEM revealed that covariances within threat appraisal and coping appraisal were invariant and all other constrains were stage-specific, i.e. stage was a moderator. Except for self-efficacy, motivation fully mediated the relationship between the social-cognitive variables and behaviour. (3) Predicting stage transitions with the PMT-variables underscored the importance of self-efficacy. Only when threat appraisal and coping appraisal were high, stage movement was more likely in the preparation stage. Results emphasize stage-specific differences of the PMT mechanisms, and hence, support the stage construct. The findings may guide further theory building and research integrating different theoretical approaches.

  14. Thermal properties Forsmark. Modelling stage 2.3 Complementary analysis and verification of the thermal bedrock model, stage 2.

    Energy Technology Data Exchange (ETDEWEB)

    Sundberg, Jan; Wrafter, John; Laendell, Maerta (Geo Innova AB (Sweden)); Back, Paer-Erik; Rosen, Lars (Sweco AB (Sweden))

    2008-11-15

    This report present the results of thermal modelling work for the Forsmark area carried out during modelling stage 2.3. The work complements the main modelling efforts carried out during modelling stage 2.2. A revised spatial statistical description of the rock mass thermal conductivity for rock domain RFM045 is the main result of this work. Thermal modelling of domain RFM045 in Forsmark model stage 2.2 gave lower tail percentiles of thermal conductivity that were considered to be conservatively low due to the way amphibolite, the rock type with the lowest thermal conductivity, was modelled. New and previously available borehole data are used as the basis for revised stochastic geological simulations of domain RFM045. By defining two distinct thermal subdomains, these simulations have succeeded in capturing more of the lithological heterogeneity present. The resulting thermal model for rock domain RFM045 is, therefore, considered to be more realistic and reliable than that presented in model stage 2.2. The main conclusions of modelling efforts in model stage 2.3 are: - Thermal modelling indicates a mean thermal conductivity for domain RFM045 at the 5 m scale of 3.56 W/(mK). This is slightly higher than the value of 3.49 W/(mK) derived in model stage 2.2. - The variance decreases and the lower tail percentiles increase as the scale of observation increases from 1 to 5 m. Best estimates of the 0.1 percentile of thermal conductivity for domain RFM045 are 2.24 W/(mK) for the 1 m scale and 2.36 W/(mK) for the 5 m scale. This can be compared with corresponding values for domain RFM029 of 2.30 W/(mK) for the 1 m scale and 2.87 W/(mK)for the 5 m scale. - The reason for the pronounced lower tail in the thermal conductivity distribution for domain RFM045 is the presence of large bodies of the low-conductive amphibolite. - The modelling results for domain RFM029 presented in model stage 2.2 are still applicable. - As temperature increases, the thermal conductivity decreases

  15. Survival analysis II: Cox regression

    NARCIS (Netherlands)

    Stel, Vianda S.; Dekker, Friedo W.; Tripepi, Giovanni; Zoccali, Carmine; Jager, Kitty J.

    2011-01-01

    In contrast to the Kaplan-Meier method, Cox proportional hazards regression can provide an effect estimate by quantifying the difference in survival between patient groups and can adjust for confounding effects of other variables. The purpose of this article is to explain the basic concepts of the

  16. Lévy based Cox point processes

    DEFF Research Database (Denmark)

    Hellmund, Gunnar; Prokesová, Michaela; Jensen, Eva Bjørn Vedel

    2008-01-01

    In this paper we introduce Lévy-driven Cox point processes (LCPs) as Cox point processes with driving intensity function Λ defined by a kernel smoothing of a Lévy basis (an independently scattered, infinitely divisible random measure). We also consider log Lévy-driven Cox point processes (LLCPs......) with Λ equal to the exponential of such a kernel smoothing. Special cases are shot noise Cox processes, log Gaussian Cox processes, and log shot noise Cox processes. We study the theoretical properties of Lévy-based Cox processes, including moment properties described by nth-order product densities...

  17. Hydrogeological conceptual model development and numerical modelling using CONNECTFLOW, Forsmark modelling stage 2.3

    Energy Technology Data Exchange (ETDEWEB)

    Follin, Sven (SF GeoLogic AB, Taeby (Sweden)); Hartley, Lee; Jackson, Peter; Roberts, David (Serco TAP (United Kingdom)); Marsic, Niko (Kemakta Konsult AB, Stockholm (Sweden))

    2008-05-15

    Three versions of a site descriptive model (SDM) have been completed for the Forsmark area. Version 0 established the state of knowledge prior to the start of the site investigation programme. Version 1.1 was essentially a training exercise and was completed during 2004. Version 1.2 was a preliminary site description and concluded the initial site investigation work (ISI) in June 2005. Three modelling stages are planned for the complete site investigation work (CSI). These are labelled stage 2.1, 2.2 and 2.3, respectively. An important component of each of these stages is to address and continuously try to resolve discipline-specific uncertainties of importance for repository engineering and safety assessment. Stage 2.1 included an updated geological model for Forsmark and aimed to provide a feedback from the modelling working group to the site investigation team to enable completion of the site investigation work. Stage 2.2 described the conceptual understanding and the numerical modelling of the bedrock hydrogeology in the Forsmark area based on data freeze 2.2. The present report describes the modelling based on data freeze 2.3, which is the final data freeze in Forsmark. In comparison, data freeze 2.3 is considerably smaller than data freeze 2.2. Therefore, stage 2.3 deals primarily with model confirmation and uncertainty analysis, e.g. verification of important hypotheses made in stage 2.2 and the role of parameter uncertainty in the numerical modelling. On the whole, the work reported here constitutes an addendum to the work reported in stage 2.2. Two changes were made to the CONNECTFLOW code in stage 2.3. These serve to: 1) improve the representation of the hydraulic properties of the regolith, and 2) improve the conditioning of transmissivity of the deformation zones against single-hole hydraulic tests. The changes to the modelling of the regolith were made to improve the consistency with models made with the MIKE SHE code, which involved the introduction

  18. Radiolabeled COX-2 Inhibitors for Non-Invasive Visualization of COX-2 Expression and Activity — A Critical Update

    Directory of Open Access Journals (Sweden)

    Torsten Kniess

    2013-05-01

    Full Text Available Cyclooxygenase-2 (COX-2 is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET and single photon emission computed tomography (SPECT since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[18F]fluorination or de[11C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field.

  19. Cell-type-specific roles for COX-2 in UVB-induced skin cancer

    Science.gov (United States)

    Herschman, Harvey

    2014-01-01

    In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

  20. Two stage neural network modelling for robust model predictive control.

    Science.gov (United States)

    Patan, Krzysztof

    2018-01-01

    The paper proposes a novel robust model predictive control scheme realized by means of artificial neural networks. The neural networks are used twofold: to design the so-called fundamental model of a plant and to catch uncertainty associated with the plant model. In order to simplify the optimization process carried out within the framework of predictive control an instantaneous linearization is applied which renders it possible to define the optimization problem in the form of constrained quadratic programming. Stability of the proposed control system is also investigated by showing that a cost function is monotonically decreasing with respect to time. Derived robust model predictive control is tested and validated on the example of a pneumatic servomechanism working at different operating regimes. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  1. Geology - Background complementary studies. Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. [Geological Survey of Sweden, Uppsala (Sweden); Skagius, Kristina [Kemakta Konsult AB, Stockholm (Sweden)] (eds.)

    2007-09-15

    During Forsmark model stage 2.2, seven complementary geophysical and geological studies were initiated by the geological modelling team, in direct connection with and as a background support to the deterministic modelling of deformation zones. One of these studies involved a field control on the character of two low magnetic lineaments with NNE and NE trends inside the target volume. The interpretation of these lineaments formed one of the late deliveries to SKB that took place after the data freeze for model stage 2.2 and during the initial stage of the modelling work. Six studies involved a revised processing and analysis of reflection seismic, refraction seismic and selected oriented borehole radar data, all of which had been presented earlier in connection with the site investigation programme. A prime aim of all these studies was to provide a better understanding of the geological significance of indirect geophysical data to the geological modelling team. Such essential interpretative work was lacking in the material acquired in connection with the site investigation programme. The results of these background complementary studies are published together in this report. The titles and authors of the seven background complementary studies are presented below. Summaries of the results of each study, with a focus on the implications for the geological modelling of deformation zones, are presented in the master geological report, SKB-R--07-45. The sections in the master report, where reference is made to each background complementary study and where the summaries are placed, are also provided. The individual reports are listed in the order that they are referred to in the master geological report and as they appear in this report. 1. Scan line fracture mapping and magnetic susceptibility measurements across two low magnetic lineaments with NNE and NE trend, Forsmark. Jesper Petersson, Ulf B. Andersson and Johan Berglund. 2. Integrated interpretation of surface and

  2. Geology - Background complementary studies. Forsmark modelling stage 2.2

    International Nuclear Information System (INIS)

    Stephens, Michael B.; Skagius, Kristina

    2007-09-01

    During Forsmark model stage 2.2, seven complementary geophysical and geological studies were initiated by the geological modelling team, in direct connection with and as a background support to the deterministic modelling of deformation zones. One of these studies involved a field control on the character of two low magnetic lineaments with NNE and NE trends inside the target volume. The interpretation of these lineaments formed one of the late deliveries to SKB that took place after the data freeze for model stage 2.2 and during the initial stage of the modelling work. Six studies involved a revised processing and analysis of reflection seismic, refraction seismic and selected oriented borehole radar data, all of which had been presented earlier in connection with the site investigation programme. A prime aim of all these studies was to provide a better understanding of the geological significance of indirect geophysical data to the geological modelling team. Such essential interpretative work was lacking in the material acquired in connection with the site investigation programme. The results of these background complementary studies are published together in this report. The titles and authors of the seven background complementary studies are presented below. Summaries of the results of each study, with a focus on the implications for the geological modelling of deformation zones, are presented in the master geological report, SKB-R--07-45. The sections in the master report, where reference is made to each background complementary study and where the summaries are placed, are also provided. The individual reports are listed in the order that they are referred to in the master geological report and as they appear in this report. 1. Scan line fracture mapping and magnetic susceptibility measurements across two low magnetic lineaments with NNE and NE trend, Forsmark. Jesper Petersson, Ulf B. Andersson and Johan Berglund. 2. Integrated interpretation of surface and

  3. GENERALISED MODEL BASED CONFIDENCE INTERVALS IN TWO STAGE CLUSTER SAMPLING

    Directory of Open Access Journals (Sweden)

    Christopher Ouma Onyango

    2010-09-01

    Full Text Available Chambers and Dorfman (2002 constructed bootstrap confidence intervals in model based estimation for finite population totals assuming that auxiliary values are available throughout a target population and that the auxiliary values are independent. They also assumed that the cluster sizes are known throughout the target population. We now extend to two stage sampling in which the cluster sizes are known only for the sampled clusters, and we therefore predict the unobserved part of the population total. Jan and Elinor (2008 have done similar work, but unlike them, we use a general model, in which the auxiliary values are not necessarily independent. We demonstrate that the asymptotic properties of our proposed estimator and its coverage rates are better than those constructed under the model assisted local polynomial regression model.

  4. Geology Forsmark. Site descriptive modelling Forsmark - stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. [Geological Survey of Sweden, Uppsala (Sweden); Fox, Aaron; La Pointe, Paul [Golder Associates Inc (United States); Simeonov, Assen [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Isaksson, Hans [GeoVista AB, Luleaa (Sweden); Hermanson, Jan; Oehman, Johan [Golder Associates AB, Stockholm (Sweden)

    2007-10-15

    The geological work during stage 2.2 has involved the development of deterministic models for rock domains (RFM) and deformation zones (ZFM), the identification and deterministic modelling of fracture domains (FFM) inside the candidate volume, i.e. the parts of rock domains that are not affected by deformation zones, and the development of statistical models for fractures and minor deformation zones (geological discrete fracture network modelling or geological DFN modelling). The geological DFN model addresses brittle structures at a scale of less than 1 km, which is the lower cut-off in the deterministic modelling of deformation zones. In order to take account of variability in data resolution, deterministic models for rock domains and deformation zones are presented in both regional and local model volumes, while the geological DFN model is valid within specific fracture domains inside the north-western part of the candidate volume, including the target volume. The geological modelling work has evaluated and made use of: A revised bedrock geological map at the ground surface. Geological and geophysical data from 21 cored boreholes and 33 percussion boreholes. Detailed mapping of fractures and rock units along nine excavations or large surface outcrops. Data bearing on the characterisation (including kinematics) of deformation zones. Complementary geochronological and other rock and fracture analytical data. Lineaments identified on the basis of airborne and high-resolution ground magnetic data. A reprocessing of both surface and borehole reflection seismic data. Seismic refraction data. The outputs of the deterministic modelling work are geometric models in RVS format and detailed property tables for rock domains and deformation zones, and a description of fracture domains. The outputs of the geological DFN modelling process are recommended parameters or statistical distributions that describe fracture set orientations, radius sizes, volumetric intensities

  5. Geology Forsmark. Site descriptive modelling Forsmark - stage 2.2

    International Nuclear Information System (INIS)

    Stephens, Michael B.; Fox, Aaron; La Pointe, Paul; Simeonov, Assen; Isaksson, Hans; Hermanson, Jan; Oehman, Johan

    2007-10-01

    The geological work during stage 2.2 has involved the development of deterministic models for rock domains (RFM) and deformation zones (ZFM), the identification and deterministic modelling of fracture domains (FFM) inside the candidate volume, i.e. the parts of rock domains that are not affected by deformation zones, and the development of statistical models for fractures and minor deformation zones (geological discrete fracture network modelling or geological DFN modelling). The geological DFN model addresses brittle structures at a scale of less than 1 km, which is the lower cut-off in the deterministic modelling of deformation zones. In order to take account of variability in data resolution, deterministic models for rock domains and deformation zones are presented in both regional and local model volumes, while the geological DFN model is valid within specific fracture domains inside the north-western part of the candidate volume, including the target volume. The geological modelling work has evaluated and made use of: A revised bedrock geological map at the ground surface. Geological and geophysical data from 21 cored boreholes and 33 percussion boreholes. Detailed mapping of fractures and rock units along nine excavations or large surface outcrops. Data bearing on the characterisation (including kinematics) of deformation zones. Complementary geochronological and other rock and fracture analytical data. Lineaments identified on the basis of airborne and high-resolution ground magnetic data. A reprocessing of both surface and borehole reflection seismic data. Seismic refraction data. The outputs of the deterministic modelling work are geometric models in RVS format and detailed property tables for rock domains and deformation zones, and a description of fracture domains. The outputs of the geological DFN modelling process are recommended parameters or statistical distributions that describe fracture set orientations, radius sizes, volumetric intensities

  6. Risk model in stage IB1-IIB cervical cancer with positive node after radical hysterectomy

    Directory of Open Access Journals (Sweden)

    Chen Z

    2016-05-01

    Full Text Available Zhilan Chen,1,2,* Kecheng Huang,1,* Zhiyong Lu,1,3 Song Deng,1,4 Jiaqiang Xiong,1 Jia Huang,1 Xiong Li,5 Fangxu Tang,1 Zhihao Wang,6 Haiying Sun,1 Lin Wang,1 Shasha Zhou,1 Xiaoli Wang,1 Yao Jia,1 Ting Hu,1 Juan Gui,7 Dongyi Wan,1 Ding Ma,1 Shuang Li,1 Shixuan Wang11Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology, Wuhan, 2Department of Obstetrics and Gynecology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 3Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, 4Department of Obstetrics and Gynecology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 5Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, 6Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Huazhong University of Science and Techonology, Wuhan, 7Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS and overall survival (OS. A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk

  7. MCEM algorithm for the log-Gaussian Cox process

    OpenAIRE

    Delmas, Celine; Dubois-Peyrard, Nathalie; Sabbadin, Regis

    2014-01-01

    Log-Gaussian Cox processes are an important class of models for aggregated point patterns. They have been largely used in spatial epidemiology (Diggle et al., 2005), in agronomy (Bourgeois et al., 2012), in forestry (Moller et al.), in ecology (sightings of wild animals) or in environmental sciences (radioactivity counts). A log-Gaussian Cox process is a Poisson process with a stochastic intensity depending on a Gaussian random eld. We consider the case where this Gaussian random eld is ...

  8. Simultaneous confidence bands for Cox regression from semiparametric random censorship.

    Science.gov (United States)

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

    Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined.

  9. Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice.

    Science.gov (United States)

    Kim, Joohwee; Vaish, Vivek; Feng, Mingxiao; Field, Kevin; Chatzistamou, Ioulia; Shim, Minsub

    2016-10-07

    Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders.

  10. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    2016-01-01

    and hard core behaviour can be achieved by applying a dependent Matérn thinning to a Cox process. An exact formula for the intensity of a Matérn thinned shot noise Cox process is derived from the Palm distribution. For the more general class of Matérn thinned Cox processes, formulae for the intensity...

  11. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    of clustering and hard core behaviour can be achieved by applying a dependent Matérn thinning to a Cox process. An exact formula for the intensity of a Matérn thinned shot noise Cox process is derived from the Palm distribution. For the more general class of Matérn thinned Cox processes, formulae...

  12. Allan Cox 1926”1987

    Science.gov (United States)

    Coe, Rob; Dalrymple, Brent

    More than 1000 friends, students, and colleagues from all over the country filled Stanford Memorial Chapel (Stanford, Calif.) on February 3, 1987, to join in “A Celebration of the Life of Allan Cox.” Allan died early on the morning of January 27 while bicycling, the sport he had come to love the most. Between pieces of his favorite music by Bach and Mozart, Stanford administrators and colleagues spoke in tribute of Allan's unique qualities as friend, scientist, teacher, and dean of the School of Earth Sciences. James Rosse, Vice President and Provost of Stanford University, struck a particularly resonant chord with his personal remarks: "Allan reached out to each person he knew with the warmth and attention that can only come from deep respect and affection for others. I never heard him speak ill of others, and I do not believe he was capable of doing anything that would harm another being. He cared too much to intrude where he was not wanted, but his curiosity about people and the loving care with which he approached them broke down reserve to create remarkable friendships. His enthusiasm and good humor made him a welcome guest in the hearts of the hundreds of students and colleagues who shared the opportunity of knowing Allan Cox as a person."

  13. Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

    Science.gov (United States)

    Shek, L L; Godolphin, W

    1988-10-01

    The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

  14. Crocetin Downregulates the Proinflammatory Cytokines in Methylcholanthrene-Induced Rodent Tumor Model and Inhibits COX-2 Expression in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Bing Chen

    2015-01-01

    Full Text Available The effect of crocetin (C20H24O4 on methylcholanthrene- (MCA- induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA, polymorphonuclear cells (PMN, interleukin-1β (IL-1β, and tumor necrosis factor-α (TNF-α were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS activation in HeLa cells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1β, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent.

  15. A Dual-Stage Two-Phase Model of Selective Attention

    Science.gov (United States)

    Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

    2010-01-01

    The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

  16. Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    International Nuclear Information System (INIS)

    Aggarwal, Anshu; Al-Rohil, Rami N; Batra, Anupam; Feustel, Paul J; Jones, David M; DiPersio, C Michael

    2014-01-01

    Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Immunohistochemistry was performed to assess co-expression of α3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin α3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Although expression of integrin α3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between α3 and COX2 in both tissue microarrays (r s = 0.49, p < 0.001, n = 59) and archived samples (r s = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage. COX2 and α3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin α3β1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of α3β1

  17. Bladder cancer staging in CT urography: effect of stage labels on statistical modeling of a decision support system

    Science.gov (United States)

    Gandikota, Dhanuj; Hadjiiski, Lubomir; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

    2018-02-01

    In bladder cancer, stage T2 is an important threshold in the decision of administering neoadjuvant chemotherapy. Our long-term goal is to develop a quantitative computerized decision support system (CDSS-S) to aid clinicians in accurate staging. In this study, we examined the effect of stage labels of the training samples on modeling such a system. We used a data set of 84 bladder cancers imaged with CT Urography (CTU). At clinical staging prior to treatment, 43 lesions were staged as below stage T2 and 41 were stage T2 or above. After cystectomy and pathological staging that is considered the gold standard, 10 of the lesions were upstaged to stage T2 or above. After correcting the stage labels, 33 lesions were below stage T2, and 51 were stage T2 or above. For the CDSS-S, the lesions were segmented using our AI-CALS method and radiomic features were extracted. We trained a linear discriminant analysis (LDA) classifier with leave-one-case-out cross validation to distinguish between bladder lesions of stage T2 or above and those below stage T2. The CDSS-S was trained and tested with the corrected post-cystectomy labels, and as a comparison, CDSS-S was also trained with understaged pre-treatment labels and tested on lesions with corrected labels. The test AUC for the CDSS-S trained with corrected labels was 0.89 +/- 0.04. For the CDSS-S trained with understaged pre-treatment labels and tested on the lesions with corrected labels, the test AUC was 0.86 +/- 0.04. The likelihood of stage T2 or above for 9 out of the 10 understaged lesions was correctly increased for the CDSS-S trained with corrected labels. The CDSS-S is sensitive to the accuracy of stage labeling. The CDSS-S trained with correct labels shows promise in prediction of the bladder cancer stage.

  18. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

    Science.gov (United States)

    de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

    2009-02-01

    Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P IAS tone.

  19. Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling.

    Science.gov (United States)

    Raj, Vinit; Bhadauria, Archana S; Singh, Ashok K; Kumar, Umesh; Rai, Amit; Keshari, Amit K; Kumar, Pranesh; Kumar, Dinesh; Maity, Biswanath; Nath, Sneha; Prakash, Anand; Ansari, Kausar M; Jat, Jawahar L; Saha, Sudipta

    2018-03-23

    We attempted a preclinical study using DMH-induced CRC rat model to evaluate the antitumor potential of our recently synthesized 1,3,4-thiadiazoles. The molecular insights were confirmed through ELISA, qRT-PCR and western blot analyses. The CRC condition was produced in response to COX-2 and IL-6 induced activation of JAK2/STAT3 which, in turn, was due to the enhanced phosphorylation of JAK2 and STAT3. The treatment with 1,3,4-thiadiazole derivatives (VR24 and VR27) caused the significant blockade of this signaling pathway. The behavior of STAT3 populations in response to IL-6 and COX-2 stimulations was further confirmed through data-based mathematical modeling using the quantitative western blot data. Finally, VR24 and VR27 restored the perturbed metabolites associated to DMH-induced CRC as evidenced through 1 H NMR based serum metabolomics. The tumor protecting ability of VR24 and VR27 was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Model atmospheres for novae during the early stages

    International Nuclear Information System (INIS)

    Wehrse, R.; Hauschildt, P.H.; Shaviv, G.; Starrfield, S.; Arizona State Univ., Tempe, AZ

    1989-01-01

    Continuum and line blanketing models for the photospheres of novae in the early stages of their outbursts are presented. The expanding envelopes are characterized by a very slow increase of density with decreasing radius which leads to very large geometrical extensions and large temperature differences between the inner and outer parts. The spectra show a large IR excess and a small Balmer jump which may be either in absorption or in emission. For the parameters considered (T eff = 10 4 , 1.5 x 10 4 , 2 x 10 4 K, R = 10 11 cm, solar composition), most lines are in absorption. The effects of both modifications in the temperature structure (e.g. by heating from shock fronts) and changes in the abundances of the heavy elements on the emergent spectra are briefly discussed. 13 refs., 11 figs

  1. Modelling of the initial stage of the surface discharge development

    International Nuclear Information System (INIS)

    Gibalov, V.; Pietsch, G.

    1998-01-01

    Computer modelling of the initial stage of the surface discharge was performed by solving numerically the coupled continuity, the Poisson and Townsend ionization equations and taking into account the ionization, attachment and detachment processes. The potential distribution at the dielectric surface and at the boundaries which surround the integration region have been calculated with the charge-image method in a 3D approach. In order to eliminate numerical diffusion effects, the solution of the continuity equation was corrected using a flux correction transport routine. At the positive voltage the development of the discharge channel is determined mainly by the shape of the electrode tip. At the negative voltage the following phases of the discharge may be distinguished: the initial phase, the cathode directed streamer phase resulting in the cathode layer formation, and the propagating phase. The physical processes governing each discharge phase are described in detail. (J.U.)

  2. Two-Stage Electricity Demand Modeling Using Machine Learning Algorithms

    Directory of Open Access Journals (Sweden)

    Krzysztof Gajowniczek

    2017-10-01

    Full Text Available Forecasting of electricity demand has become one of the most important areas of research in the electric power industry, as it is a critical component of cost-efficient power system management and planning. In this context, accurate and robust load forecasting is supposed to play a key role in reducing generation costs, and deals with the reliability of the power system. However, due to demand peaks in the power system, forecasts are inaccurate and prone to high numbers of errors. In this paper, our contributions comprise a proposed data-mining scheme for demand modeling through peak detection, as well as the use of this information to feed the forecasting system. For this purpose, we have taken a different approach from that of time series forecasting, representing it as a two-stage pattern recognition problem. We have developed a peak classification model followed by a forecasting model to estimate an aggregated demand volume. We have utilized a set of machine learning algorithms to benefit from both accurate detection of the peaks and precise forecasts, as applied to the Polish power system. The key finding is that the algorithms can detect 96.3% of electricity peaks (load value equal to or above the 99th percentile of the load distribution and deliver accurate forecasts, with mean absolute percentage error (MAPE of 3.10% and resistant mean absolute percentage error (r-MAPE of 2.70% for the 24 h forecasting horizon.

  3. Mathematical modeling of a single stage ultrasonically assisted distillation process.

    Science.gov (United States)

    Mahdi, Taha; Ahmad, Arshad; Ripin, Adnan; Abdullah, Tuan Amran Tuan; Nasef, Mohamed M; Ali, Mohamad W

    2015-05-01

    The ability of sonication phenomena in facilitating separation of azeotropic mixtures presents a promising approach for the development of more intensified and efficient distillation systems than conventional ones. To expedite the much-needed development, a mathematical model of the system based on conservation principles, vapor-liquid equilibrium and sonochemistry was developed in this study. The model that was founded on a single stage vapor-liquid equilibrium system and enhanced with ultrasonic waves was coded using MATLAB simulator and validated with experimental data for ethanol-ethyl acetate mixture. The effects of both ultrasonic frequency and intensity on the relative volatility and azeotropic point were examined, and the optimal conditions were obtained using genetic algorithm. The experimental data validated the model with a reasonable accuracy. The results of this study revealed that the azeotropic point of the mixture can be totally eliminated with the right combination of sonication parameters and this can be utilized in facilitating design efforts towards establishing a workable ultrasonically intensified distillation system. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

    Directory of Open Access Journals (Sweden)

    Richard Dela Cruz

    2016-06-01

    Full Text Available Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

  5. A Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success

    Science.gov (United States)

    Luong, Ming; Stevens, Jeff

    2015-01-01

    The Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success, a theoretical stages-of-growth model, explains long-term success in IT outsourcing relationships. Research showed the IT outsourcing relationship life cycle consists of four distinct, sequential stages: contract, transition, support, and partnership. The model was…

  6. A stage-based model of manatee population dynamics

    Science.gov (United States)

    Runge, M.C.; Langtimm, C.A.; Kendall, W.L.

    2004-01-01

    A stage-structured population model for the Florida manatee (Trichechus manatus latirostris) was developed that explicitly incorporates uncertainty in parameter estimates. The growth rates calculated with this model reflect the status of the regional populations over the most recent 10-yr period. The Northwest and Upper St. Johns River regions have growth rates (8) of 1.037 (95% interval, 1.016?1.056) and 1.062 (1.037?1.081), respectively. The Southwest region has a growth rate of 0.989 (0.946?1.024), suggesting this population has been declining at about 1.1% per year. The estimated growth rate in the Atlantic region is 1.010 (0.988?1.029), but there is some uncertainty about whether adult survival rates have been constant over the last 10 yr; using the mean survival rates from the most recent 5-yr period, the estimated growth rate in this region is 0.970 (0.938?0.998). Elasticity analysis indicates that the most effective management actions should seek to increase adult survival rates. Decomposition of the uncertainty in the growth rates indicates that uncertainty about population status can best be reduced through increased monitoring of adult survival rate.

  7. Model of unplanned smoking initiation of children and adolescents: an integrated stage model of smoking behavior.

    Science.gov (United States)

    Kremers, S P J; Mudde, A N; De Vries, H

    2004-05-01

    Two lines of psychological research have attempted to spell out the stages of adolescent smoking initiation. The first has focused on behavioral stages of smoking initiation, while the second line emphasized motivational stages. A large international sample of European adolescents (N = 10,170, mean age = 13.3 years) was followed longitudinally. Self-reported motivational and behavioral stages of smoking initiation were integrated, leading to the development of the Model of Unplanned Smoking Initiation of Children and Adolescents (MUSICA). The MUSICA postulates that youngsters experiment with smoking while they are in an unmotivated state as regards their plans for smoking regularly in the future. More than 95% of the total population resided in one of the seven stages distinguished by MUSICA. The probability of starting to smoke regularly during the 12 months follow-up period increased with advanced stage assignment at baseline. Unique social cognitive predictors of stage progression from the various stages were identified, but effect sizes of predictors of transitions were small. The integration of motivational and behavioral dimensions improves our understanding of the process of smoking initiation. In contrast to current theories of smoking initiation, adolescent uptake of smoking behavior was found to be an unplanned action.

  8. Adverse Effects of COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  9. Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Edwin Roger Parra

    2013-12-01

    Full Text Available OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc and idiopathic pulmonary fibrosis (IPF patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP in SSc patients and usual interstitial pneumonia (UIP in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP, and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

  10. A Comparative Study of Cox Regression vs. Log-Logistic ...

    African Journals Online (AJOL)

    Colorectal cancer is common and lethal disease with different incidence rate in different parts of the world which is taken into account as the third cause of cancer-related deaths. In the present study, using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of patients with colorectal ...

  11. Testing the Box-Cox Parameter for an Integrated Process

    NARCIS (Netherlands)

    J. Huang (Jian); M. Kobayashi (Masahito); M.J. McAleer (Michael)

    2011-01-01

    textabstractThis paper analyses the constant elasticity of volatility (CEV) model suggested by Chan et al. (1992). The CEV model without mean reversion is shown to be the inverse Box-Cox transformation of integrated processes asymptotically. It is demonstrated that the maximum likelihood estimator

  12. Stages of driving behavior change within the Transtheoretical Model (TM).

    Science.gov (United States)

    Kowalski, Kristina; Jeznach, Anna; Tuokko, Holly Anna

    2014-09-01

    Many older adults voluntarily restrict their driving or stop driving of their own accord. Driving behavior change may occur in stages, as predicted by the Transtheoretical Model of Behavior Change (TM). This study explored the process of older driver behavior change within the TM framework using interviews/focus groups with drivers and former drivers aged 71-94 years. Within those groups of drivers, driving behavior was divided into two classes: those who changed their driving with age and those who did not. Those who changed their driving as they aged included people gradually imposing restrictions ("gradual restrictors") and those making plans in anticipation of stopping driving ("preparers"). Participants who did not change their driving included those who employed lifelong driving restrictions ("consistent") and those who made no changes ("non-changers"). Preliminary support for TM within the driving context was found; however, further exploration of driving behavior change within this framework is warranted. It is important to continue to investigate the factors that might influence driving behavior in older adults. By promoting self-regulation in individuals, it may be possible to help older adults continue to drive, thereby improving older adult's mobility and quality of life. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

  13. Retail gentrification. Staged spaces and the gourmet market model

    Directory of Open Access Journals (Sweden)

    Luz de Lourdes Cordero Gómez del Campo

    2017-12-01

    Full Text Available Retail gentrification is understood as a process in which commercial activity is transformed to meet the needs of a sector of the population with higher incomes resulting in the displacement of merchants and products, seen from the implementation of the model of the gourmet market. This process, which is seen in the interest of copying the commercial formats of successful cases from gourmet markets such as the San Miguel Market in Madrid or the Borough Market in London, is linked to an offer aimed at satisfying consumption demands produced by a sector of the population that although not being equivalent concepts, different authors identify as cultural omnivores or creative class, coinciding in that these groups have a high cultural and economic capital. In the present work it is discussed how in Mexico City in the absence of the transformation of public markets into gourmet markets and with the inauguration of the Roma Market in 2014, the staging of commercial spaces labeled as gourmet markets has intensified and they are inserted in neighborhoods where they seek to generate development and links with the community, but because of their prices and the characteristics of the products they offer, they are beyond the reach of the local population.

  14. A match-mismatch test of a stage model of behaviour change in tobacco smoking

    NARCIS (Netherlands)

    Dijkstra, A; Conijn, B; De Vries, H

    Aims An innovation offered by stage models of behaviour change is that of stage-matched interventions. Match-mismatch studies are the primary test of this idea but also the primary test of the validity of stage models. This study aimed at conducting such a test among tobacco smokers using the Social

  15. A semimetal model of the normal state magnetic susceptibility and transport properties of Ba(Fe1-xCox)2As2

    International Nuclear Information System (INIS)

    Sales, B.C.; McGuire, M.A.; Sefat, A.S.; Mandrus, D.

    2010-01-01

    A simple two-band 3D model of a semimetal is constructed to determine which normal state features of the Ba(Fe 1-x Co x ) 2 As 2 superconductors can be qualitatively understood within this framework. The model is able to account in a semiquantitative fashion for the measured magnetic susceptibility, Hall, and Seebeck data, and the low temperature Sommerfeld coefficient for 0 < x < 0.3 with only three parameters for all x. The purpose of the model is not to fit the data but to provide a simple starting point for thinking about the physics of these interesting materials. Although many of the static magnetic properties, such as the increase of the magnetic susceptibility with temperature, are reproduced by the model, none of the spin-fluctuation dynamics are addressed. A general conclusion from the model is that the magnetic susceptibility of most semimetals should increase with temperatures.

  16. Regulation of COX and LOX by curcumin.

    Science.gov (United States)

    Rao, Chinthalapally V

    2007-01-01

    Turmeric (Curcuma longa) is extensively used as a household remedy for various diseases. For the last few decades, work has been done to establish the biological activities and pharmacological actions of curcumin, the principle constituent of turmeric. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases due to its anti-inflammatory activity. Arachidonic acid-derived lipid mediators that are intimately involved in inflammation are biosynthesized by pathways dependent on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The role of LOX and COX isoforms, particularly COX-2, in the inflammation has been well established. At cellular and molecular levels, curcumin has been shown to regulate a number of signaling pathways, including the eicosanoid pathway involving COX and LOX. A number of studies have been conducted that support curcumin-mediated regulation of COX and LOX pathways, which is an important mechanism by which curcumin prevents a number of disease processes, including the cancer. The specific regulation of 5-LOX and COX-2 by curcumin is not fully established; however, existing evidence indicates that curcumin regulates LOX and COX-2 predominately at the transcriptional level and, to a certain extent, the posttranslational level. Thus, the curcumin-selective transcriptional regulatory action of COX-2, and dual COX/LOX inhibitory potential of this naturally occurring agent provides distinctive advantages over synthetic COX/LOX inhibitors, such as nonsteroidal anti-inflammatory drugs. In this review, we discuss evidence that supports the regulation of COX and LOX enzymes by curcumin as the key mechanism for its beneficial effects in preventing various inflammatory diseases.

  17. Double Length Regressions for Testing the Box-Cox Difference Transformation.

    OpenAIRE

    Park, Timothy

    1991-01-01

    The Box-Cox difference transformation is used to determine the appropriate specification for estimation of hedge ratios and a new double length regression form of the Lagrange multiplier test is presented for the difference transformation. The Box-Cox difference transformation allows the testing of the first difference model and the returns model as special cases of the Box-Cox difference transformation. Copyright 1991 by MIT Press.

  18. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus

    This paper reviews useful results related to Palm distributions of spatial point processes and provides a new result regarding the characterization of Palm distributions for the class of log Gaussian Cox processes. This result is used to study functional summary statistics for a log Gaussian Cox...

  19. Estimating functions for inhomogeneous Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus

    2006-01-01

    Estimation methods are reviewed for inhomogeneous Cox processes with tractable first and second order properties. We illustrate the various suggestions by means of data examples.......Estimation methods are reviewed for inhomogeneous Cox processes with tractable first and second order properties. We illustrate the various suggestions by means of data examples....

  20. Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

    Science.gov (United States)

    Guerrera, Francesco; Errico, Luca; Evangelista, Andrea; Filosso, Pier Luigi; Ruffini, Enrico; Lisi, Elena; Bora, Giulia; Asteggiano, Elena; Olivetti, Stefania; Lausi, Paolo; Ardissone, Francesco; Oliaro, Alberto

    2015-06-01

    Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Predicting a future lifetime through Box-Cox transformation.

    Science.gov (United States)

    Yang, Z

    1999-09-01

    In predicting a future lifetime based on a sample of past lifetimes, the Box-Cox transformation method provides a simple and unified procedure that is shown in this article to meet or often outperform the corresponding frequentist solution in terms of coverage probability and average length of prediction intervals. Kullback-Leibler information and second-order asymptotic expansion are used to justify the Box-Cox procedure. Extensive Monte Carlo simulations are also performed to evaluate the small sample behavior of the procedure. Certain popular lifetime distributions, such as Weibull, inverse Gaussian and Birnbaum-Saunders are served as illustrative examples. One important advantage of the Box-Cox procedure lies in its easy extension to linear model predictions where the exact frequentist solutions are often not available.

  2. BOX-COX REGRESSION METHOD IN TIME SCALING

    Directory of Open Access Journals (Sweden)

    ATİLLA GÖKTAŞ

    2013-06-01

    Full Text Available Box-Cox regression method with λj, for j = 1, 2, ..., k, power transformation can be used when dependent variable and error term of the linear regression model do not satisfy the continuity and normality assumptions. The situation obtaining the smallest mean square error  when optimum power λj, transformation for j = 1, 2, ..., k, of Y has been discussed. Box-Cox regression method is especially appropriate to adjust existence skewness or heteroscedasticity of error terms for a nonlinear functional relationship between dependent and explanatory variables. In this study, the advantage and disadvantage use of Box-Cox regression method have been discussed in differentiation and differantial analysis of time scale concept.

  3. Evolutionary Stages of e-Tailors and Retailers: Firm Value Determinants Model

    OpenAIRE

    Jae K. Lee; Heegoo Kang; Hoe K. Lee; Han S. Lee

    2002-01-01

    We have studied the evolutionary stages of pure e-tailers, click & mortar (C&M) and brick & mortar (B&M) retailers for three points of time: June 1999, June 2000, and June 2001. To evaluate the dynamic stages of e-tailing business as an innovative venture, we propose four stages: exploration, breakeven, growth, and maturity. The stages are measured by the impact of revenue and income on the firm value, and a regression model is adopted to formulate the model. To empirically examine the stages...

  4. Comment on "Why reduced-form regression models of health effects versus exposures should not replace QRA: livestock production and infant mortality as an example," by Louis Anthony (Tony) Cox, Jr., Risk Analysis 2009, Vol. 29, No. 12.

    Science.gov (United States)

    Sneeringer, Stacy

    2010-04-01

    While a recent paper by Cox in this journal uses as its motivating factor the benefits of quantitative risk assessment, its content is entirely devoted to critiquing Sneeringer's article in the American Journal of Agricultural Economics. Cox's two main critiques of Sneeringer are fundamentally flawed and misrepresent the original article. Cox posits that Sneeringer did A and B, and then argues why A and B are incorrect. However, Sneeringer in fact did C and D; thus critiques of A and B are not applicable to Sneeringer's analysis.

  5. Statistical inference for Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Waagepetersen, Rasmus Plenge

    2002-01-01

    Research has generated a number of advances in methods for spatial cluster modelling in recent years, particularly in the area of Bayesian cluster modelling. Along with these advances has come an explosion of interest in the potential applications of this work, especially in epidemiology and genome...... research.   In one integrated volume, this book reviews the state-of-the-art in spatial clustering and spatial cluster modelling, bringing together research and applications previously scattered throughout the literature. It begins with an overview of the field, then presents a series of chapters...... that illuminate the nature and purpose of cluster modelling within different application areas, including astrophysics, epidemiology, ecology, and imaging. The focus then shifts to methods, with discussions on point and object process modelling, perfect sampling of cluster processes, partitioning in space...

  6. An experimentally validated simulation model for a four-stage spray dryer

    DEFF Research Database (Denmark)

    Petersen, Lars Norbert; Poulsen, Niels Kjølstad; Niemann, Hans Henrik

    2017-01-01

    mathematical model is an index-1 differential algebraic equation (DAE) model with 12 states, 9 inputs, 8 disturbances, and 30 parameters. The parameters in the model are identified from well-excited experimental data obtained from the industrialtype spray dryer. The simulated outputs ofthe model are validated...... is divided into four consecutive stages: a primary spray drying stage, two heated fluid bed stages, and a cooling fluid bed stage. Each of these stages in the model is assumed ideally mixed and the dynamics are described by mass- and energy balances. These balance equations are coupled with constitutive...... equations such as a thermodynamic model, the water evaporation rate, the heat transfer rates, and an equation for the stickiness of the powder (glass transition temperature). Laboratory data is used to model the equilibrium moisture content and the glass transition temperature of the powder. The resulting...

  7. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  8. Dynamic Modeling of Starting Aerodynamics and Stage Matching in an Axi-Centrifugal Compressor

    Science.gov (United States)

    Wilkes, Kevin; OBrien, Walter F.; Owen, A. Karl

    1996-01-01

    A DYNamic Turbine Engine Compressor Code (DYNTECC) has been modified to model speed transients from 0-100% of compressor design speed. The impetus for this enhancement was to investigate stage matching and stalling behavior during a start sequence as compared to rotating stall events above ground idle. The model can simulate speed and throttle excursions simultaneously as well as time varying bleed flow schedules. Results of a start simulation are presented and compared to experimental data obtained from an axi-centrifugal turboshaft engine and companion compressor rig. Stage by stage comparisons reveal the front stages to be operating in or near rotating stall through most of the start sequence. The model matches the starting operating line quite well in the forward stages with deviations appearing in the rearward stages near the start bleed. Overall, the performance of the model is very promising and adds significantly to the dynamic simulation capabilities of DYNTECC.

  9. Box-Cox transformation for QTL mapping.

    Science.gov (United States)

    Yang, Runqing; Yi, Nengjun; Xu, Shizhong

    2006-01-01

    The maximum likelihood method of QTL mapping assumes that the phenotypic values of a quantitative trait follow a normal distribution. If the assumption is violated, some forms of transformation should be taken to make the assumption approximately true. The Box-Cox transformation is a general transformation method which can be applied to many different types of data. The flexibility of the Box-Cox transformation is due to a variable, called transformation factor, appearing in the Box-Cox formula. We developed a maximum likelihood method that treats the transformation factor as an unknown parameter, which is estimated from the data simultaneously along with the QTL parameters. The method makes an objective choice of data transformation and thus can be applied to QTL analysis for many different types of data. Simulation studies show that (1) Box-Cox transformation can substantially increase the power of QTL detection; (2) Box-Cox transformation can replace some specialized transformation methods that are commonly used in QTL mapping; and (3) applying the Box-Cox transformation to data already normally distributed does not harm the result.

  10. Bootstrapping Cox’s Regression Model.

    Science.gov (United States)

    1985-11-01

    crucial points a multivariate martingale central limit theorem. Involved in this is a p x p covariance matrix Z with elements T j2= f {2(s8 ) - s(l)( s ,8o...1980). The statistical analaysis of failure time data. Wiley, New York. Meyer, P.-A. (1971). Square integrable martingales, a survey. Lecture Notes

  11. Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia.

    Science.gov (United States)

    Hong, Seok Kwan; Gul, Yunus A; Ithnin, Hairuszah; Talib, Arni; Seow, Heng Fong

    2004-01-01

    Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  12. Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

    Directory of Open Access Journals (Sweden)

    Cristina Mihaela Ghiciuc

    2017-11-01

    Full Text Available Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI and sodium form (NaCLI—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2 and cyclooxygenase 2 (cox-2 protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems.

  13. A proposed model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development.

    Science.gov (United States)

    Knight, Zelda Gillian

    2017-09-01

    Just as Freud used stages of psychosexual development to ground his model of psychoanalysis, it is possible to do the same with Erik Erikson's stages of development with regards to a model of psychodynamic psychotherapy. This paper proposes an eight-stage model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development. Various suggestions are offered. One such suggestion is that as each of Erikson's developmental stages is triggered by a crisis, in therapy it is triggered by the client's search. The resolution of the search often leads to the development of another search, which implies that the therapy process comprises a series of searches. This idea of a series of searches and resolutions leads to the understanding that identity is developmental and therapy is a space in which a new sense of identity may emerge. The notion of hope is linked to Erikson's stage of Basic Trust and the proposed model of therapy views hope and trust as essential for the therapy process. Two clinical vignettes are offered to illustrate these ideas. Psychotherapy can be approached as an eight-stage process and linked to Erikson's eight stages model of development. Psychotherapy may be viewed as a series of searches and thus as a developmental stage resolution process, which leads to the understanding that identity is ongoing throughout the life span. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Analysis of Three-dimension Viscous Flow in the Model Axial Compressor Stage K1002L

    Science.gov (United States)

    Tribunskaia, K.; Kozhukhov, Y. V.

    2017-08-01

    The main investigation subject considered in this paper is axial compressor model stage K1002L. Three simulation models were designed: Scheme 1 - inlet stage model consisting of IGV (Inlet Guide Vane), rotor and diffuser; Scheme 2 - two-stage model: IGV, first-stage rotor, first-stage diffuser, second-stage rotor, EGV (Exit Guide Vane); Scheme 3 - full-round model: IGV, rotor, diffuser. Numerical investigation of the model stage was held for four circumferential velocities at the outer diameter (Uout=125,160,180,210 m/s) within the range of flow coefficient: ϕ = 0.4 - 0.6. The computational domain was created with ANSYS CFX Workbench. According to simulation results, there were constructed aerodynamic characteristic curves of adiabatic efficiency and the adiabatic head coefficient calculated for total parameters were compared with data from the full-scale test received at the Central Boiler and Turbine Institution (CBTI), thus, verification of the calculated data was carried out. Moreover, there were conducted the following studies: comparison of aerodynamic characteristics of the schemes 1, 2; comparison of the sector and full-round models. The analysis and conclusions are supplemented by gas-dynamic method calculation for axial compressor stages.

  15. Chemval project report on stage 1: verification of speciation models

    International Nuclear Information System (INIS)

    Read, D.; Broyd, T.W.

    1989-01-01

    CHEMVAL is an international geochemical exercise, which aims at applicating and validating predictive computer programmes describing the chemistry of radionuclides in the geosphere. As a component of the CEC project MIRAGE- second phase (on migration of radionuclides in the geosphere), CHEMVAL is carried out in the framework of the third community R and D programme of radioactive waste management and storage. The present report is the first of a series devoted to the verification and validation of aqueous speciation and coupled chemical transport codes. Five cases systems are studied, namely, cement, clay, sandstore, granite and limestone. Overall, good agreement was obtained. Reasons for divergence in results have been explored and recommendations are made at the appropriate stages for enhancement of the thermodynamic data base. A listing of the preliminary CHEMVAL Project Data Base is provided

  16. Model Development for Atomic Force Microscope Stage Mechanisms

    National Research Council Canada - National Science Library

    Smith, Ralph C; Hatch, Andrew G; De, Tathagata; Salapaka, Murti V; Raye, Julie K; del Rosario, Ricardo C

    2005-01-01

    In this paper, we develop nonlinear constitutive equations and resulting system models quantifying the nonlinear and hysteretic field-displacement relations inherent to lead zirconate titanate (PZT...

  17. Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

    Science.gov (United States)

    Wu, Yu-Chung; Wei, Nien-Chih; Hung, Jung-Jyh; Yeh, Yi-Chen; Su, Li-Jen; Hsu, Wen-Hu; Chou, Teh-Ying

    2017-10-03

    Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I-IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB ( p model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

  18. A TWO-STAGE MODEL OF RADIOLOGICAL INSPECTION: SPENDING TIME

    International Nuclear Information System (INIS)

    BROWN, W.S.

    2000-01-01

    The paper describes a model that visually portrays radiological survey performance as basic parameters (surveyor efficiency and criteria, duration of pause, and probe speed) are varied; field and laboratory tests provided typical parameter values. The model is used to illustrate how practical constraints on the time allotted to the task can affect radiological inspection performance. Similar analyses are applicable to a variety of other tasks (airport baggage inspection, and certain types of non-destructive testing) with similar characteristics and constraints

  19. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  20. Pregnancy induced changes in Cox-1, Cox-2 and NOSIII vascular and renal expression.

    Science.gov (United States)

    Bobadilla, Rosa A; Bracho, Ismael; Alvarez, Victor M Pérez; Anguiano, Liliana; López, Pedro

    2004-01-01

    In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy, we measured the protein expression of COX-1, COX-2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant (21st day) Wistar rats. We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX-1 And COX-2 was found in the abdominal compared to the thoracic segment of the pregnant rats. An increased expression of NOS III was found in the abdominal segment of the aorta form pregnant rats. No changes were found between pregnant and no pregnant animals in the expression of COX-1 and COX-2 in the renal cortex or medulla while an increased expression of NOS III was found in the cortex from pregnant compared to non pregnant animals. These results suggest the influence of pregnancy is not homogeneous along the aorta and also that a balance between prostaglandins and nitric oxide is responsible of the blunted vascular reactivity during pregnancy in the rat.

  1. An appreciation of Richard Threlkeld Cox

    Science.gov (United States)

    Tribus, Myron

    2002-05-01

    Richard T. Cox's contributions to the foundations of probability theory and inductive logic are not generally appreciated or understood. This paper reviews his life and accomplishments, especially those in his book The Algebra of Probable Inference and his final publication Inference and Inquiry which, in this author's opinion, has the potential to influence in a significant way the design and analysis of self organizing systems which learn from experience. A simple application to the simulation of a neuron is presented as an example of the power of Cox's contribution.

  2. Thermal properties. Site descriptive modelling Forsmark - stage 2.2

    International Nuclear Information System (INIS)

    Back, Paer-Erik; Wrafter, John; Sundberg, Jan; Rosen, L ars

    2007-09-01

    The lithological data acquired from boreholes and mapping of the rock surface need to be reclassified into thermal rock classes, TRCs. The main reason is to simplify the simulations. The lithological data are used to construct models of the transition between different TRCs, thus describing the spatial statistical structure of each TRC. The result is a set of transition probability models that are used in the simulation of TRCs. The intermediate result of this first stochastic simulation is a number of realisations of the geology, each one equally probable. Based on the thermal data, a spatial statistical thermal model is constructed for each TRC. It consists of a statistical distribution and a variogram for each TRC. These are used in the stochastic simulation of thermal conductivity and the result is a number of equally probable realisations of thermal conductivity for the domain. In the next step, the realisations of TRCs (lithology) and thermal conductivity are merged, i.e. each realisation of geology is filled with simulated thermal conductivity values. The result is a set of realisations of thermal conductivity that considers both the difference in thermal properties between different TRCs, and the variability within each TRC. If the result is desired in a scale different from the simulation scale, i.e. the canister scale, upscaling of the realisations can be performed. The result is a set of equally probable realisations of thermal properties. The presented methodology was applied to rock domain RFM029 and RFM045. The main results are sets of realisations of thermal properties that can be used for further processing, most importantly for statistical analysis and numerical temperature simulations for the design of repository layout (distances between deposition holes). The main conclusions of the thermal modelling are: The choice of scale has a profound influence on the distribution of thermal conductivity values. The variance decreases and the lower tail

  3. Thermal properties. Site descriptive modelling Forsmark - stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Back, Paer-Erik; Wrafter, John; Sundberg, Jan [Geo Innova AB (Sweden); Rosen, L ars [Sweco Viak AB (Sweden)

    2007-09-15

    The lithological data acquired from boreholes and mapping of the rock surface need to be reclassified into thermal rock classes, TRCs. The main reason is to simplify the simulations. The lithological data are used to construct models of the transition between different TRCs, thus describing the spatial statistical structure of each TRC. The result is a set of transition probability models that are used in the simulation of TRCs. The intermediate result of this first stochastic simulation is a number of realisations of the geology, each one equally probable. Based on the thermal data, a spatial statistical thermal model is constructed for each TRC. It consists of a statistical distribution and a variogram for each TRC. These are used in the stochastic simulation of thermal conductivity and the result is a number of equally probable realisations of thermal conductivity for the domain. In the next step, the realisations of TRCs (lithology) and thermal conductivity are merged, i.e. each realisation of geology is filled with simulated thermal conductivity values. The result is a set of realisations of thermal conductivity that considers both the difference in thermal properties between different TRCs, and the variability within each TRC. If the result is desired in a scale different from the simulation scale, i.e. the canister scale, upscaling of the realisations can be performed. The result is a set of equally probable realisations of thermal properties. The presented methodology was applied to rock domain RFM029 and RFM045. The main results are sets of realisations of thermal properties that can be used for further processing, most importantly for statistical analysis and numerical temperature simulations for the design of repository layout (distances between deposition holes). The main conclusions of the thermal modelling are: The choice of scale has a profound influence on the distribution of thermal conductivity values. The variance decreases and the lower tail

  4. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

    Science.gov (United States)

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

  5. Relations of Transtheoretical Model Stage, Self-Efficacy, and Voluntary Physical Activity in African American Preadolescents

    Science.gov (United States)

    Annesi, James J.; Faigenbaum, Avery D.; Westcott, Wayne L.

    2010-01-01

    The transtheoretical model (TTM; Prochaska, DiClemente, & Norcross, 1992) suggests that, at any point, an individual is in one of five stages-of-change related to adopting a behavior. People sequentially advance in stage but may also maintain or even regress, based on personal and environmental factors (Nigg, 2005). A classic study published in…

  6. An empirical test of stage models of e-government development: evidence from Dutch municipalities

    NARCIS (Netherlands)

    Rooks, G.; Matzat, U.; Sadowski, B.M.

    2017-01-01

    In this article we empirically test stage models of e-government development. We use Lee's classification to make a distinction between four stages of e-government: informational, requests, personal, and e-democracy. We draw on a comprehensive data set on the adoption and development of e-government

  7. Exploring QSAR with E-state index: selectivity requirements for COX-2 versus COX-1 binding of terphenyl methyl sulfones and sulfonamides.

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2004-09-20

    An attempt has been made to explore selectivity requirements for cyclooxygenase-2 (COX-2) versus cyclooxygenase-1 (COX-1) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state (E-state) index and suitable indicator parameters. Multiple linear regression analyses produced statistically acceptable equations: the best relation based on 'all-possible-subsets regression' for COX-1 binding (n=18) showed predicted variance and explained variance of 0.675 and 0.777, respectively, while in case of the best equation for COX-2 binding (n=38), these values rose to 0.842 and 0.874, respectively. For the selectivity relation (n=17), predicted variance and explained variance values were 0.601 and 0.687, respectively. Based on the results of the analyses, three important sites have been suggested: sites A (methylsulfonyl or aminosulfonyl moiety), B (central phenyl ring), and C (terminal phenyl ring containing different substituents). All three sites are important for COX-2 binding while sites B and C are important for COX-1 binding. For COX-2 selectivity, only site C plays an important role. The study shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance.

  8. Investigating the performance of directional boundary layer model through staged modeling method

    Science.gov (United States)

    Jeong, Moon-Gyu; Lee, Won-Chan; Yang, Seung-Hune; Jang, Sung-Hoon; Shim, Seong-Bo; Kim, Young-Chang; Suh, Chun-Suk; Choi, Seong-Woon; Kim, Young-Hee

    2011-04-01

    BLM since the feasibility of the BLM has been investigated in many papers[4][5][6]. Instead of fitting the parameters to the wafer critical dimensions (CD) directly, we tried to use the aerial image (AI) from the rigorous simulator with the electromagnetic field (EMF) solver. Usually that kind of method is known as the staged modeling method. To see the advantages of this method we conducted several experiments and observed the results comparing the method of fitting to the wafer CD directly. Through the tests we could observe some remarkable results and confirmed that the staged modeling had better performance in many ways.

  9. "Cox orange\\" and \\"Elstar\\" Apple Cultivars

    African Journals Online (AJOL)

    Thinning trials were conducted in the apple orchards of Klein Altendorf experimental station near Bonn, Germany, using 7 year old CV, \\'Cox orange\\' in the year 2001 and 8 year old \\'Elstar\\' apple trees in 2002. The objective was to reduce the number of fruits per tree, yield, improve fruit quality, overcome alternate bearing ...

  10. Concerning modeling of double-stage water evaporation cooling

    Science.gov (United States)

    Shatskiy, V. P.; Fedulova, L. I.; Gridneva, I. V.

    2018-03-01

    The matter of need for setting technical norms for production, as well as acceptable microclimate parameters, such as temperature and humidity, at the work place, remains urgent. Use of certain units should be economically sound and that should be taken into account for construction, assembly, operation, technological, and environmental requirements. Water evaporation coolers are simple to maintain, environmentally friendly, and quite cheap, but the development of the most efficient solutions requires mathematical modeling of the heat and mass transfer processes that take place in them.

  11. A two-phase inspection model for a single component system with three-stage degradation

    International Nuclear Information System (INIS)

    Wang, Huiying; Wang, Wenbin; Peng, Rui

    2017-01-01

    This paper presents a two-phase inspection schedule and an age-based replacement policy for a single plant item contingent on a three-stage degradation process. The two phase inspection schedule can be observed in practice. The three stages are defined as the normal working stage, low-grade defective stage and critical defective stage. When an inspection detects that an item is in the low-grade defective stage, we may delay the preventive replacement action if the time to the age-based replacement is less than or equal to a threshold level. However, if it is above this threshold level, the item will be replaced immediately. If the item is found in the critical defective stage, it is replaced immediately. A hybrid bee colony algorithm is developed to find the optimal solution for the proposed model which has multiple decision variables. A numerical example is conducted to show the efficiency of this algorithm, and simulations are conducted to verify the correctness of the model. - Highlights: • A two-phase inspection model is studied. • The failure process has three stages. • The delayed replacement is considered.

  12. Staging workers' use of hearing protection devices: application of the transtheoretical model.

    Science.gov (United States)

    Raymond, Delbert M; Lusk, Sally L

    2006-04-01

    The threat of noise-induced hearing loss is a serious concern for many workers. This study explores use of the transtheoretical model as a framework for defining stages of workers' acceptance of hearing protection devices. A secondary analysis was performed using a cross-section of data from a randomized, controlled clinical trial of an intervention to increase use of hearing protection. Use of hearing protection devices was well distributed across the theorized stages of change. Chi-square analysis and analysis of variance revealed significant differences between stages for the variables studied. Discrete stages of hearing protection device use can be identified, laying the foundation for further work investigating use of the transtheoretical model for promoting hearing protection device use. The model can provide a framework for tailoring interventions and evaluating their effects. With further development of the transtheoretical model, nurses may be able to easily identify workers' readiness to use hearing protection devices and tailor training toward that goal.

  13. Modelling early stages of relativistic heavy-ion collisions

    Directory of Open Access Journals (Sweden)

    Ruggieri M.

    2016-01-01

    Full Text Available In this study we model early time dynamics of relativistic heavy ion collisions by an initial color-electric field which then decays to a plasma by the Schwinger mechanism. The dynamics of the many particles system produced by the decay is described by relativistic kinetic theory, taking into account the backreaction on the color field by solving self-consistently the kinetic and the field equations. Our main results concern isotropization and thermalization for a 1+1D expanding geometry. In case of small η/s (η/s ≲ 0.3 we find τisotropization ≈ 0.8 fm/c and τthermalization ≈ 1 fm/c in agreement with the common lore of hydrodynamics.

  14. Scrum integration in stage-gate models for collaborative product development

    DEFF Research Database (Denmark)

    Sommer, Anita Friis; Slavensky, Andreas; Nguyen, Vivi Thuy

    2013-01-01

    to differentiate from low-cost competitors and increase PD performance, some industrial manufacturers now seek competitive advantage by experimenting with new ways for collaborative PD. This includes integrating customer-focused agile process models, like Scrum, from the software industry into their existing PD...... models. Thus, instead of replacing traditional stage-gate models agile methods are currently integrated in existing PD models generating hybrid solution for collaborative PD. This paper includes a study of three industrial cases that have successfully integrated Scrum into a stage-gate process model...

  15. Numerical and experimental modelling of the centrifugal compressor stage – setting the model of impellers with 2D blades

    Directory of Open Access Journals (Sweden)

    Matas Richard

    2017-01-01

    Full Text Available The article deals with a description of results from research and development of a radial compressor stage. The experimental compressor and used numerical models are briefly described. In the first part, the comparisons of characteristics obtained experimentally and by numerical simulations for stage with vaneless diffuser are described. In the second part, the results for stage with vanned diffuser are presented. The results are relevant for next studies in research and development process.

  16. Numerical and experimental modelling of the centrifugal compressor stage - setting the model of impellers with 2D blades

    Science.gov (United States)

    Matas, Richard; Syka, Tomáš; Luňáček, Ondřej

    The article deals with a description of results from research and development of a radial compressor stage. The experimental compressor and used numerical models are briefly described. In the first part, the comparisons of characteristics obtained experimentally and by numerical simulations for stage with vaneless diffuser are described. In the second part, the results for stage with vanned diffuser are presented. The results are relevant for next studies in research and development process.

  17. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

    Directory of Open Access Journals (Sweden)

    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  18. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

    Bisnar, Paul O.; Dones, Rosa Angela S.A.; Serna, Paulene-Ver A.; Deocaris, Chester C.; Guttierez, Kalangitan V.; Deocaris, Custer C.

    2006-01-01

    The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins(PGs) as its major mediators. The two cyclooxygenase isoforms, cox-1 and cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: cox-1 selective; Celecoxib: cox-2 selective; and Indocid: cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy. (Author)

  19. Provisional safety analyses for SGT stage 2 -- Models, codes and general modelling approach

    International Nuclear Information System (INIS)

    2014-12-01

    In the framework of the provisional safety analyses for Stage 2 of the Sectoral Plan for Deep Geological Repositories (SGT), deterministic modelling of radionuclide release from the barrier system along the groundwater pathway during the post-closure period of a deep geological repository is carried out. The calculated radionuclide release rates are interpreted as annual effective dose for an individual and assessed against the regulatory protection criterion 1 of 0.1 mSv per year. These steps are referred to as dose calculations. Furthermore, from the results of the dose calculations so-called characteristic dose intervals are determined, which provide input to the safety-related comparison of the geological siting regions in SGT Stage 2. Finally, the results of the dose calculations are also used to illustrate and to evaluate the post-closure performance of the barrier systems under consideration. The principal objective of this report is to describe comprehensively the technical aspects of the dose calculations. These aspects comprise: · the generic conceptual models of radionuclide release from the solid waste forms, of radionuclide transport through the system of engineered and geological barriers, of radionuclide transfer in the biosphere, as well as of the potential radiation exposure of the population, · the mathematical models for the explicitly considered release and transport processes, as well as for the radiation exposure pathways that are included, · the implementation of the mathematical models in numerical codes, including an overview of these codes and the most relevant verification steps, · the general modelling approach when using the codes, in particular the generic assumptions needed to model the near field and the geosphere, along with some numerical details, · a description of the work flow related to the execution of the calculations and of the software tools that are used to facilitate the modelling process, and · an overview of the

  20. Provisional safety analyses for SGT stage 2 -- Models, codes and general modelling approach

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-12-15

    In the framework of the provisional safety analyses for Stage 2 of the Sectoral Plan for Deep Geological Repositories (SGT), deterministic modelling of radionuclide release from the barrier system along the groundwater pathway during the post-closure period of a deep geological repository is carried out. The calculated radionuclide release rates are interpreted as annual effective dose for an individual and assessed against the regulatory protection criterion 1 of 0.1 mSv per year. These steps are referred to as dose calculations. Furthermore, from the results of the dose calculations so-called characteristic dose intervals are determined, which provide input to the safety-related comparison of the geological siting regions in SGT Stage 2. Finally, the results of the dose calculations are also used to illustrate and to evaluate the post-closure performance of the barrier systems under consideration. The principal objective of this report is to describe comprehensively the technical aspects of the dose calculations. These aspects comprise: · the generic conceptual models of radionuclide release from the solid waste forms, of radionuclide transport through the system of engineered and geological barriers, of radionuclide transfer in the biosphere, as well as of the potential radiation exposure of the population, · the mathematical models for the explicitly considered release and transport processes, as well as for the radiation exposure pathways that are included, · the implementation of the mathematical models in numerical codes, including an overview of these codes and the most relevant verification steps, · the general modelling approach when using the codes, in particular the generic assumptions needed to model the near field and the geosphere, along with some numerical details, · a description of the work flow related to the execution of the calculations and of the software tools that are used to facilitate the modelling process, and · an overview of the

  1. Phototaxis during the slug stage of Dictyostelium discoideum: a model study

    NARCIS (Netherlands)

    Marée, A.F.M.; Panfilov, A.V.; Hogeweg, P.

    1999-01-01

    During the slug stage, the cellular slime mould Dictyostelium discoideum moves towards light sources. We have modelled this phototactic behaviour using a hybrid cellular automata/partial differential equation model. In our model, individual amoebae are not able to measure the direction from which

  2. 78 FR 8535 - Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement

    Science.gov (United States)

    2013-02-06

    ... develop and test innovative health care payment and service delivery models that show promise of reducing... test innovative payment and service delivery models that reduce spending under Medicare, Medicaid or...] Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement AGENCY: Centers for...

  3. Hydrogeological characterisation and modelling of deformation zones and fracture domains, Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Follin, Sven (SF GeoLogic AB, Taeby (SE)); Leven, Jakob (Swedish Nuclear Fuel and Waste Management Co., Stockholm (SE)); Hartley, Lee; Jackson, Peter; Joyce, Steve; Roberts, David; Swift, Ben (Serco Assurance, Harwell (GB))

    2007-09-15

    The work reported here collates the structural-hydraulic information gathered in 21 cored boreholes and 32 percussion-drilled boreholes belonging to Forsmark site description, modelling stage 2.2. The analyses carried out provide the hydrogeological input descriptions of the bedrock in Forsmark needed by the end users Repository Engineering, Safety Assessment and Environmental Impact Assessment; that is, hydraulic properties of deformation zones and fracture domains. The same information is also needed for constructing 3D groundwater flow models of the Forsmark site and surrounding area. The analyses carried out render the following conceptual model regarding the observed heterogeneity in deformation zone transmissivity: We find the geological division of the deterministically modelled deformation zones into eight categories (sets) useful from a hydrogeological point of view. Seven of the eight categories are steeply dipping, WNW, NW, NNW, NNE, NE, ENE and EW, and on is gently dipping, G. All deformation zones, regardless of orientation (strike and dip), are subjected to a substantial decrease in transmissivity with depth. The data gathered suggest a contrast of c. 20,000 times for the uppermost one kilometre of bedrock, i.e. more than four orders of magnitude. The hydraulic properties below this depth are not investigated. The lateral heterogeneity is also substantial but more irregular in its appearance. For instance, for a given elevation and deformation zone category (orientation), the spatial variability in transmissivity within a particular deformation zone appears to be as large as the variability between all deformation zones. This suggests that the lateral correlation length is shorter than the shortest distance between two adjacent observation points and shorter than the category spacing. The observation that the mean transmissivity of the gently-dipping deformation zones is c. one to two orders of magnitude greater than the mean transmissivities of all

  4. Internal stress model for pre-primary stage of low-stress creep

    International Nuclear Information System (INIS)

    Kloc, L

    2010-01-01

    Initial transient stage in low-stress creep experiments was observed in all such experiments. Recently, evidences were presented that this stage cannot be considered as a normal creep primary stage, though the shape of the creep curve is similar. The strain reached during this so called pre-primary stage is fully recoverable upon unloading; the internal stresses must play important role in the effect. Model of standard linear anelastic solid was modified by introduction of creeping body instead of viscous dashpot. Both power law and hyperbolic sine creep law were used to fit observed creep curves of model and structural materials. Mainly the model using hyeprbolic sine creep law provides good fit to individual creep curves and sets of creep curves at different stresses.

  5. A Four-Stage Hybrid Model for Hydrological Time Series Forecasting

    Science.gov (United States)

    Di, Chongli; Yang, Xiaohua; Wang, Xiaochao

    2014-01-01

    Hydrological time series forecasting remains a difficult task due to its complicated nonlinear, non-stationary and multi-scale characteristics. To solve this difficulty and improve the prediction accuracy, a novel four-stage hybrid model is proposed for hydrological time series forecasting based on the principle of ‘denoising, decomposition and ensemble’. The proposed model has four stages, i.e., denoising, decomposition, components prediction and ensemble. In the denoising stage, the empirical mode decomposition (EMD) method is utilized to reduce the noises in the hydrological time series. Then, an improved method of EMD, the ensemble empirical mode decomposition (EEMD), is applied to decompose the denoised series into a number of intrinsic mode function (IMF) components and one residual component. Next, the radial basis function neural network (RBFNN) is adopted to predict the trend of all of the components obtained in the decomposition stage. In the final ensemble prediction stage, the forecasting results of all of the IMF and residual components obtained in the third stage are combined to generate the final prediction results, using a linear neural network (LNN) model. For illustration and verification, six hydrological cases with different characteristics are used to test the effectiveness of the proposed model. The proposed hybrid model performs better than conventional single models, the hybrid models without denoising or decomposition and the hybrid models based on other methods, such as the wavelet analysis (WA)-based hybrid models. In addition, the denoising and decomposition strategies decrease the complexity of the series and reduce the difficulties of the forecasting. With its effective denoising and accurate decomposition ability, high prediction precision and wide applicability, the new model is very promising for complex time series forecasting. This new forecast model is an extension of nonlinear prediction models. PMID:25111782

  6. A four-stage hybrid model for hydrological time series forecasting.

    Science.gov (United States)

    Di, Chongli; Yang, Xiaohua; Wang, Xiaochao

    2014-01-01

    Hydrological time series forecasting remains a difficult task due to its complicated nonlinear, non-stationary and multi-scale characteristics. To solve this difficulty and improve the prediction accuracy, a novel four-stage hybrid model is proposed for hydrological time series forecasting based on the principle of 'denoising, decomposition and ensemble'. The proposed model has four stages, i.e., denoising, decomposition, components prediction and ensemble. In the denoising stage, the empirical mode decomposition (EMD) method is utilized to reduce the noises in the hydrological time series. Then, an improved method of EMD, the ensemble empirical mode decomposition (EEMD), is applied to decompose the denoised series into a number of intrinsic mode function (IMF) components and one residual component. Next, the radial basis function neural network (RBFNN) is adopted to predict the trend of all of the components obtained in the decomposition stage. In the final ensemble prediction stage, the forecasting results of all of the IMF and residual components obtained in the third stage are combined to generate the final prediction results, using a linear neural network (LNN) model. For illustration and verification, six hydrological cases with different characteristics are used to test the effectiveness of the proposed model. The proposed hybrid model performs better than conventional single models, the hybrid models without denoising or decomposition and the hybrid models based on other methods, such as the wavelet analysis (WA)-based hybrid models. In addition, the denoising and decomposition strategies decrease the complexity of the series and reduce the difficulties of the forecasting. With its effective denoising and accurate decomposition ability, high prediction precision and wide applicability, the new model is very promising for complex time series forecasting. This new forecast model is an extension of nonlinear prediction models.

  7. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    Science.gov (United States)

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  8. An Enhanced Preventive Maintenance Optimization Model Based on a Three-Stage Failure Process

    Directory of Open Access Journals (Sweden)

    Ruifeng Yang

    2015-01-01

    Full Text Available Nuclear power plants are highly complex systems and the issues related to their safety are of primary importance. Probabilistic safety assessment is regarded as the most widespread methodology for studying the safety of nuclear power plants. As maintenance is one of the most important factors for affecting the reliability and safety, an enhanced preventive maintenance optimization model based on a three-stage failure process is proposed. Preventive maintenance is still a dominant maintenance policy due to its easy implementation. In order to correspond to the three-color scheme commonly used in practice, the lifetime of system before failure is divided into three stages, namely, normal, minor defective, and severe defective stages. When the minor defective stage is identified, two measures are considered for comparison: one is that halving the inspection interval only when the minor defective stage is identified at the first time; the other one is that if only identifying the minor defective stage, the subsequent inspection interval is halved. Maintenance is implemented immediately once the severe defective stage is identified. Minimizing the expected cost per unit time is our objective function to optimize the inspection interval. Finally, a numerical example is presented to illustrate the effectiveness of the proposed models.

  9. Distributed activation energy model for kinetic analysis of multi-stage hydropyrolysis of coal

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X.; Li, W.; Wang, N.; Li, B. [Chinese Academy of Sciences, Taiyuan (China). Inst. of Coal Chemistry

    2003-07-01

    Based on the new analysis of distributed activation energy model, a bicentral distribution model was introduced to the analysis of multi-stage hydropyrolysis of coal. The hydropyrolysis for linear temperature programming with and without holding stage were mathematically described and the corresponding kinetic expressions were achieved. Based on the kinetics, the hydropyrolysis (HyPr) and multi-stage hydropyrolysis (MHyPr) of Xundian brown coal was simulated. The results shows that both Mo catalyst and 2-stage holding can lower the apparent activation energy of hydropyrolysis and make activation energy distribution become narrow. Besides, there exists an optimum Mo loading of 0.2% for HyPy of Xundian lignite. 10 refs.

  10. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  11. Palaeotemperature reconstructions of the European permafrost zone during Oxygen Isotope Stage 3 compared with climate model results.

    NARCIS (Netherlands)

    van Huissteden, J.; Vandenberghe, J.; Pollard, D.

    2003-01-01

    A palaeotemperature reconstruction based on periglacial phenomena in Europe north of approximately 51 °N, is compared with high-resolution regional climate model simulations of the marine oxygen isotope Stage 3 (Stage 3) palaeoclimate. The experiments represent Stage 3 warm (interstadial), Stage 3

  12. Agil Stage-Gate®: ny model for udviklingsprojekter i mellemstore virksomheder

    DEFF Research Database (Denmark)

    Vedsmand, Tomas; Edwards, Kasper; Hvidt, Nicoline

    Lær at udvikle nye produkter hurtigere og med større træfsikkerhed – ved at arbejde i sprint med agile metoder og træffe de rigtige beslutninger med Stage-Gate® Se også tilhørende: "Værktøjskasse til Agil Stage-Gate®: Ny model for udviklingsprojekter i mellemstore virksomheder" på http://dx.doi.org...

  13. Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia

    OpenAIRE

    Lee, Tae Young; Kim, Minah; Kim, Sung Nyun; Kwon, Jun Soo

    2016-01-01

    The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influenc...

  14. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  15. Stability patterns for a size-structured population model and its stage-structured counterpart

    DEFF Research Database (Denmark)

    Zhang, Lai; Pedersen, Michael; Lin, Zhigui

    2015-01-01

    In this paper we compare a general size-structured population model, where a size-structured consumer feeds upon an unstructured resource, to its simplified stage-structured counterpart in terms of equilibrium stability. Stability of the size-structured model is understood in terms of an equivale...... to the population level....

  16. Why Are There Developmental Stages in Language Learning? A Developmental Robotics Model of Language Development.

    Science.gov (United States)

    Morse, Anthony F; Cangelosi, Angelo

    2017-02-01

    Most theories of learning would predict a gradual acquisition and refinement of skills as learning progresses, and while some highlight exponential growth, this fails to explain why natural cognitive development typically progresses in stages. Models that do span multiple developmental stages typically have parameters to "switch" between stages. We argue that by taking an embodied view, the interaction between learning mechanisms, the resulting behavior of the agent, and the opportunities for learning that the environment provides can account for the stage-wise development of cognitive abilities. We summarize work relevant to this hypothesis and suggest two simple mechanisms that account for some developmental transitions: neural readiness focuses on changes in the neural substrate resulting from ongoing learning, and perceptual readiness focuses on the perceptual requirements for learning new tasks. Previous work has demonstrated these mechanisms in replications of a wide variety of infant language experiments, spanning multiple developmental stages. Here we piece this work together as a single model of ongoing learning with no parameter changes at all. The model, an instance of the Epigenetic Robotics Architecture (Morse et al 2010) embodied on the iCub humanoid robot, exhibits ongoing multi-stage development while learning pre-linguistic and then basic language skills. Copyright © 2016 Cognitive Science Society, Inc.

  17. Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

    Directory of Open Access Journals (Sweden)

    Siemers Eric R

    2010-04-01

    Full Text Available Abstract Background Alzheimer's Disease (AD affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90. Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

  18. Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

    Science.gov (United States)

    Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

    2010-04-30

    Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

  19. The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.

    Science.gov (United States)

    McCann, Nicole C; Lynch, Terrie J; Kim, Soon Ok; Duffy, Diane M

    2013-12-01

    Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates. The COX-2 inhibitor meloxicam (or vehicle) was administered orally to proven fertile female cynomolgus macaques using one emergency contraceptive model and three monthly contraceptive models. In the emergency contraceptive model, females were bred with a proven fertile male once 2±1 days before ovulation, returned to the females' home cage, and then received 5 days of meloxicam treatment. In the monthly contraceptive models, females were co-caged for breeding with a proven fertile male for a total of 5 days beginning 2±1 days before ovulation. Animals received meloxicam treatment (1) cycle days 5-22, or (2) every day, or (3) each day of the 5-day breeding period. Female were then assessed for pregnancy. The pregnancy rate with meloxicam administration using the emergency contraception model was 6.5%, significantly lower than the pregnancy rate of 33.3% when vehicle without meloxicam was administered. Pregnancy rates with the three monthly contraceptive models (75%-100%) were not consistent with preventing pregnancy. Oral COX-2 inhibitor administration can prevent pregnancy after a single instance of breeding in primates. While meloxicam may be ineffective for regular contraception, pharmacological inhibition of COX-2 may be an effective method of emergency contraception for women. COX-2 inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs of this class has not been directly tested. This study, conducted in nonhuman primates, is the first to suggest that a COX-2 inhibitor may be effective as an emergency contraceptive.

  20. A two-stage stochastic rule-based model to determine pre-assembly buffer content

    Science.gov (United States)

    Gunay, Elif Elcin; Kula, Ufuk

    2018-01-01

    This study considers instant decision-making needs of the automobile manufactures for resequencing vehicles before final assembly (FA). We propose a rule-based two-stage stochastic model to determine the number of spare vehicles that should be kept in the pre-assembly buffer to restore the altered sequence due to paint defects and upstream department constraints. First stage of the model decides the spare vehicle quantities, where the second stage model recovers the scrambled sequence respect to pre-defined rules. The problem is solved by sample average approximation (SAA) algorithm. We conduct a numerical study to compare the solutions of heuristic model with optimal ones and provide following insights: (i) as the mismatch between paint entrance and scheduled sequence decreases, the rule-based heuristic model recovers the scrambled sequence as good as the optimal resequencing model, (ii) the rule-based model is more sensitive to the mismatch between the paint entrance and scheduled sequences for recovering the scrambled sequence, (iii) as the defect rate increases, the difference in recovery effectiveness between rule-based heuristic and optimal solutions increases, (iv) as buffer capacity increases, the recovery effectiveness of the optimization model outperforms heuristic model, (v) as expected the rule-based model holds more inventory than the optimization model.

  1. Waterhammer modeling for the Ares I Upper Stage Reaction Control System cold flow development test article

    Science.gov (United States)

    Williams, Jonathan Hunter

    The Upper Stage Reaction Control System provides in-flight three-axis attitude control for the Ares I Upper Stage. The system design must accommodate rapid thruster firing to maintain proper launch trajectory and thus allow for the possibility to pulse multiple thrusters simultaneously. Rapid thruster valve closure creates an increase in static pressure, known as waterhammer, which propagates throughout the propellant system at pressures exceeding nominal design values. A series of development tests conducted at Marshall Space Flight Center in 2009 were performed using a water-flow test article to better understand fluid characteristics of the Upper Stage Reaction Control System. A subset of the tests examined the waterhammer pressure and frequency response in the flight-representative system and provided data to anchor numerical models. This thesis presents a comparison of waterhammer test results with numerical model and analytical results. An overview of the flight system, test article, modeling and analysis are also provided.

  2. Constructing stage-structured matrix population models from life tables: comparison of methods

    Directory of Open Access Journals (Sweden)

    Masami Fujiwara

    2017-10-01

    Full Text Available A matrix population model is a convenient tool for summarizing per capita survival and reproduction rates (collectively vital rates of a population and can be used for calculating an asymptotic finite population growth rate (λ and generation time. These two pieces of information can be used for determining the status of a threatened species. The use of stage-structured population models has increased in recent years, and the vital rates in such models are often estimated using a life table analysis. However, potential bias introduced when converting age-structured vital rates estimated from a life table into parameters for a stage-structured population model has not been assessed comprehensively. The objective of this study was to investigate the performance of methods for such conversions using simulated life histories of organisms. The underlying models incorporate various types of life history and true population growth rates of varying levels. The performance was measured by comparing differences in λ and the generation time calculated using the Euler-Lotka equation, age-structured population matrices, and several stage-structured population matrices that were obtained by applying different conversion methods. The results show that the discretization of age introduces only small bias in λ or generation time. Similarly, assuming a fixed age of maturation at the mean age of maturation does not introduce much bias. However, aggregating age-specific survival rates into a stage-specific survival rate and estimating a stage-transition rate can introduce substantial bias depending on the organism’s life history type and the true values of λ. In order to aggregate survival rates, the use of the weighted arithmetic mean was the most robust method for estimating λ. Here, the weights are given by survivorship curve after discounting with λ. To estimate a stage-transition rate, matching the proportion of individuals transitioning, with λ used

  3. Kinetic Energy Losses and Efficiency of an Axial Turbine Stage in Numerical Modeling of Unsteady Flows

    Directory of Open Access Journals (Sweden)

    A. S. Laskin

    2015-01-01

    Full Text Available The article presents the results of numerical investigation of kinetic energy (KE loss and blading efficiency of the single-stage axial turbine under different operating conditions, characterized by the ratio u/C0. The calculations are performed by stationary (Stage method and nonstationary (Transient method methods using ANSYS CFX. The novelty of this work lies in the fact that the numerical simulation of steady and unsteady flows in a turbine stage is conducted, and the results are obtained to determine the loss of KE, both separately by the elements of the flow range and their total values, in the stage efficiency as well. The results obtained are compared with the calculated efficiency according to one-dimensional theory.To solve these problems was selected model of axial turbine stage with D/l = 13, blade profiles of rotor and stator of constant cross-section, similar to tested ones in inverted turbine when = 0.3. The degree of reactivity ρ = 0.27, the rotor speed was varied within the range 1000 ÷ 1800 rev/min.Results obtained allow us to draw the following conclusions:1. The level of averaged coefficients of total KE losses in the range of from 0.48 to 0.75 is from 18% to 21% when calculating by the Stage method and from 21% to 25% by the Transient one.2. The level of averaged coefficients of KE losses with the output speed of in the specified range is from 9% to 13%, and almost the same when in calculating by Stage and Transient methods.3. Levels of averaged coefficients of KE loss in blade tips (relative to the differential enthalpies per stage are changed in the range: from 4% to 3% (Stage and are stored to be equal to 5% (Transient; from 5% to 6% (Stage and from 6% to 8% (Transient.4. Coefficients of KE losses in blade tips GV and RB are higher in calculations of the model stage using the Transient method than the Stage one, respectively, by = 1.5 ÷ 2.5% and = 4 ÷ 5% of the absolute values. These are values to characterize the KE

  4. A two-stage stochastic programming model for the optimal design of distributed energy systems

    International Nuclear Information System (INIS)

    Zhou, Zhe; Zhang, Jianyun; Liu, Pei; Li, Zheng; Georgiadis, Michael C.; Pistikopoulos, Efstratios N.

    2013-01-01

    Highlights: ► The optimal design of distributed energy systems under uncertainty is studied. ► A stochastic model is developed using genetic algorithm and Monte Carlo method. ► The proposed system possesses inherent robustness under uncertainty. ► The inherent robustness is due to energy storage facilities and grid connection. -- Abstract: A distributed energy system is a multi-input and multi-output energy system with substantial energy, economic and environmental benefits. The optimal design of such a complex system under energy demand and supply uncertainty poses significant challenges in terms of both modelling and corresponding solution strategies. This paper proposes a two-stage stochastic programming model for the optimal design of distributed energy systems. A two-stage decomposition based solution strategy is used to solve the optimization problem with genetic algorithm performing the search on the first stage variables and a Monte Carlo method dealing with uncertainty in the second stage. The model is applied to the planning of a distributed energy system in a hotel. Detailed computational results are presented and compared with those generated by a deterministic model. The impacts of demand and supply uncertainty on the optimal design of distributed energy systems are systematically investigated using proposed modelling framework and solution approach.

  5. Modeling condom-use stage of change in low-income, single, urban women.

    Science.gov (United States)

    Morrison-Beedy, Dianne; Carey, Michael P; Lewis, Brian P

    2002-04-01

    This study was undertaken to identify and test a model of the cognitive antecedents to condom use stage of change in low-income, single, urban women. A convenience sample of 537 women (M=30 years old) attending two urban primary health care settings in western New York State anonymously completed questionnaires based primarily on two leading social-cognitive models, the transtheoretical model and the information-motivation-behavioral skills model. We used structural equation modeling to examine the direct and indirect effects of HIV-related knowledge, social norms of discussing HIV risk and prevention, familiarity with HIV-infected persons, general readiness to change sexual behaviors, perceived vulnerability to HIV, and pros and cons of condom use on condom-use stage of change. The results indicated two models that differ by partner type. Condom-use stage of change in women with steady main partners was influenced most by social norms and the pros of condom use. Condom-use stage of change in women with "other" types (multiple, casual, or new) of sexual partners was influenced by HIV-related knowledge, general readiness to change sexual behaviors, and the pros of condom use. These findings suggest implications for developing gender-relevant HIV-prevention interventions. Copyright 2002 Wiley Periodicals, Inc.

  6. Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

    OpenAIRE

    LI Dong; LU Zhonghua; GAN Jianhe

    2016-01-01

    ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin [lipopolysaccharide (LPS)]/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and ...

  7. Modelling of Two-Stage Methane Digestion With Pretreatment of Biomass

    Science.gov (United States)

    Dychko, A.; Remez, N.; Opolinskyi, I.; Kraychuk, S.; Ostapchuk, N.; Yevtieieva, L.

    2018-04-01

    Systems of anaerobic digestion should be used for processing of organic waste. Managing the process of anaerobic recycling of organic waste requires reliable predicting of biogas production. Development of mathematical model of process of organic waste digestion allows determining the rate of biogas output at the two-stage process of anaerobic digestion considering the first stage. Verification of Konto's model, based on the studied anaerobic processing of organic waste, is implemented. The dependencies of biogas output and its rate from time are set and may be used to predict the process of anaerobic processing of organic waste.

  8. Dynamic models of staged gasification processes. Documentation of gasification simulator; Dynamiske modeller a f trinopdelte forgasningsprocesser. Dokumentation til forgasser simulator

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-02-15

    In connection with the ERP project 'Dynamic modelling of staged gasification processes' a gasification simulator has been constructed. The simulator consists of: a mathematical model of the gasification process developed at Technical University of Denmark, a user interface programme, IGSS, and a communication interface between the two programmes. (BA)

  9. What makes us think? A three-stage dual-process model of analytic engagement.

    Science.gov (United States)

    Pennycook, Gordon; Fugelsang, Jonathan A; Koehler, Derek J

    2015-08-01

    The distinction between intuitive and analytic thinking is common in psychology. However, while often being quite clear on the characteristics of the two processes ('Type 1' processes are fast, autonomous, intuitive, etc. and 'Type 2' processes are slow, deliberative, analytic, etc.), dual-process theorists have been heavily criticized for being unclear on the factors that determine when an individual will think analytically or rely on their intuition. We address this issue by introducing a three-stage model that elucidates the bottom-up factors that cause individuals to engage Type 2 processing. According to the model, multiple Type 1 processes may be cued by a stimulus (Stage 1), leading to the potential for conflict detection (Stage 2). If successful, conflict detection leads to Type 2 processing (Stage 3), which may take the form of rationalization (i.e., the Type 1 output is verified post hoc) or decoupling (i.e., the Type 1 output is falsified). We tested key aspects of the model using a novel base-rate task where stereotypes and base-rate probabilities cued the same (non-conflict problems) or different (conflict problems) responses about group membership. Our results support two key predictions derived from the model: (1) conflict detection and decoupling are dissociable sources of Type 2 processing and (2) conflict detection sometimes fails. We argue that considering the potential stages of reasoning allows us to distinguish early (conflict detection) and late (decoupling) sources of analytic thought. Errors may occur at both stages and, as a consequence, bias arises from both conflict monitoring and decoupling failures. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling.

    Science.gov (United States)

    Terza, Joseph V; Basu, Anirban; Rathouz, Paul J

    2008-05-01

    The paper focuses on two estimation methods that have been widely used to address endogeneity in empirical research in health economics and health services research-two-stage predictor substitution (2SPS) and two-stage residual inclusion (2SRI). 2SPS is the rote extension (to nonlinear models) of the popular linear two-stage least squares estimator. The 2SRI estimator is similar except that in the second-stage regression, the endogenous variables are not replaced by first-stage predictors. Instead, first-stage residuals are included as additional regressors. In a generic parametric framework, we show that 2SRI is consistent and 2SPS is not. Results from a simulation study and an illustrative example also recommend against 2SPS and favor 2SRI. Our findings are important given that there are many prominent examples of the application of inconsistent 2SPS in the recent literature. This study can be used as a guide by future researchers in health economics who are confronted with endogeneity in their empirical work.

  11. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

    Directory of Open Access Journals (Sweden)

    Georgina Cosma

    Full Text Available The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA level, the biopsy most common tumor pattern (Primary Gleason pattern and the second most common tumor pattern (Secondary Gleason pattern in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD or Extra-Prostatic Disease (ED using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC, with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812. The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR

  12. Modeling and Nonlinear Control of Electric Power Stage in Hybrid Electric Vehicle

    DEFF Research Database (Denmark)

    Tahri, A.; El Fadil, H.; Guerrero, Josep M.

    2014-01-01

    This paper deals with the problem of modeling and controlling the electric power stage of hybrid electric vehicle. The controlled system consists of a fuel cell (FC) as a main source, a supercapacitor as an auxiliary source, two DC-DC power converters, an inverter and a traction induction motor...

  13. Numerical simulation of brain tumor growth model using two-stage ...

    African Journals Online (AJOL)

    In the recent years, the study of glioma growth to be an active field of research Mathematical models that describe the proliferation and diffusion properties of the growth have been developed by many researchers. In this work, the performance analysis of two-stage Gauss-Seidel (TSGS) method to solve the glioma growth ...

  14. Analysing outsourcing policies in an asset management context : A six-stage model

    NARCIS (Netherlands)

    Schoenmaker, R.; Verlaan, J.G.

    2013-01-01

    Asset managers of civil infrastructure are increasingly outsourcing their maintenance. Whereas maintenance is a cyclic process, decisions to outsource decisions are often project-based, and confusing the discussion on the degree of outsourcing. This paper presents a six-stage model that facilitates

  15. Using Five Stage Model to Design of Collaborative Learning Environments in Second Life

    Science.gov (United States)

    Orhan, Sevil; Karaman, M. Kemal

    2014-01-01

    Specifically Second Life (SL) among virtual worlds draws attention of researchers to form collaborative learning environments (Sutcliffe & Alrayes, 2012) since it could be used as a rich platform to simulate a real environment containing many collaborative learning characteristics and interaction tools within itself. Five Stage Model (FSM)…

  16. Violent Victimization and Perpetration during Adolescence: Developmental Stage Dependent Ecological Models

    Science.gov (United States)

    Matjasko, Jennifer L.; Needham, Belinda L.; Grunden, Leslie N.; Farb, Amy Feldman

    2010-01-01

    Using a variant of the ecological-transactional model and developmental theories of delinquency on a nationally representative sample of adolescents, the current study explored the ecological predictors of violent victimization, perpetration, and both for three different developmental stages during adolescence. We examined the relative influence…

  17. Cognitive behavioral interventions for alcohol and drug use disorders: Through the stage model and back again.

    Science.gov (United States)

    Carroll, Kathleen M; Kiluk, Brian D

    2017-12-01

    Cognitive-behavioral therapy (CBT) approaches have among the highest level of empirical support for the treatment of drug and alcohol use disorders. As Psychology of Addictive Behaviors marks its 30th anniversary, we review the evolution of CBT for the addictions through the lens of the Stage Model of Behavioral Therapies Development. The large evidence base from Stage II randomized clinical trials indicates a modest effect size with evidence of relatively durable effects, but limited diffusion in clinical practice, as is the case for most empirically validated approaches for mental health and addictive disorders. Technology may provide a means for CBT interventions to circumvent the "implementation cliff" in Stages III-V by offering a flexible, low-cost, standardized means of disseminating CBT in a range of novel settings and populations. Moreover, returning to Stage I to reconnect clinical applications of CBT to recent developments in cognitive science and neuroscience holds great promise for accelerating understanding of mechanisms of action. It is critical that CBT not be considered as a static intervention, but rather 1 that constantly evolves and is refined through the stage model until the field achieves a maximally powerful intervention that addresses core features of the addictions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Describing the Process of Adopting Nutrition and Fitness Apps: Behavior Stage Model Approach.

    Science.gov (United States)

    König, Laura M; Sproesser, Gudrun; Schupp, Harald T; Renner, Britta

    2018-03-13

    Although mobile technologies such as smartphone apps are promising means for motivating people to adopt a healthier lifestyle (mHealth apps), previous studies have shown low adoption and continued use rates. Developing the means to address this issue requires further understanding of mHealth app nonusers and adoption processes. This study utilized a stage model approach based on the Precaution Adoption Process Model (PAPM), which proposes that people pass through qualitatively different motivational stages when adopting a behavior. To establish a better understanding of between-stage transitions during app adoption, this study aimed to investigate the adoption process of nutrition and fitness app usage, and the sociodemographic and behavioral characteristics and decision-making style preferences of people at different adoption stages. Participants (N=1236) were recruited onsite within the cohort study Konstanz Life Study. Use of mobile devices and nutrition and fitness apps, 5 behavior adoption stages of using nutrition and fitness apps, preference for intuition and deliberation in eating decision-making (E-PID), healthy eating style, sociodemographic variables, and body mass index (BMI) were assessed. Analysis of the 5 behavior adoption stages showed that stage 1 ("unengaged") was the most prevalent motivational stage for both nutrition and fitness app use, with half of the participants stating that they had never thought about using a nutrition app (52.41%, 533/1017), whereas less than one-third stated they had never thought about using a fitness app (29.25%, 301/1029). "Unengaged" nonusers (stage 1) showed a higher preference for an intuitive decision-making style when making eating decisions, whereas those who were already "acting" (stage 4) showed a greater preference for a deliberative decision-making style (F 4,1012 =21.83, Pdigital interventions. This study highlights that new user groups might be better reached by apps designed to address a more intuitive

  19. A fast identification algorithm for Box-Cox transformation based radial basis function neural network.

    Science.gov (United States)

    Hong, Xia

    2006-07-01

    In this letter, a Box-Cox transformation-based radial basis function (RBF) neural network is introduced using the RBF neural network to represent the transformed system output. Initially a fixed and moderate sized RBF model base is derived based on a rank revealing orthogonal matrix triangularization (QR decomposition). Then a new fast identification algorithm is introduced using Gauss-Newton algorithm to derive the required Box-Cox transformation, based on a maximum likelihood estimator. The main contribution of this letter is to explore the special structure of the proposed RBF neural network for computational efficiency by utilizing the inverse of matrix block decomposition lemma. Finally, the Box-Cox transformation-based RBF neural network, with good generalization and sparsity, is identified based on the derived optimal Box-Cox transformation and a D-optimality-based orthogonal forward regression algorithm. The proposed algorithm and its efficacy are demonstrated with an illustrative example in comparison with support vector machine regression.

  20. Travelling wave and convergence in stage-structured reaction-diffusion competitive models with nonlocal delays

    International Nuclear Information System (INIS)

    Xu Rui; Chaplain, M.A.J.; Davidson, F.A.

    2006-01-01

    In this paper, we first investigate a stage-structured competitive model with time delays, harvesting, and nonlocal spatial effect. By using an iterative technique recently developed by Wu and Zou (Wu J, Zou X. Travelling wave fronts of reaction-diffusion systems with delay. J Dynam Differen Equat 2001;13:651-87), sufficient conditions are established for the existence of travelling front solution connecting the two boundary equilibria in the case when there is no positive equilibrium. The travelling wave front corresponds to an invasion by a stronger species which drives the weaker species to extinction. Secondly, we consider a stage-structured competitive model with time delays and nonlocal spatial effect when the domain is finite. We prove the global stability of each of the nonnegative equilibria and demonstrate that the more complex model studied here admits three possible long term behaviors: coexistence, bistability and dominance as is the case for the standard Lotka-Voltera competitive model

  1. A Two-Stage Queue Model to Optimize Layout of Urban Drainage System considering Extreme Rainstorms

    OpenAIRE

    He, Xinhua; Hu, Wenfa

    2017-01-01

    Extreme rainstorm is a main factor to cause urban floods when urban drainage system cannot discharge stormwater successfully. This paper investigates distribution feature of rainstorms and draining process of urban drainage systems and uses a two-stage single-counter queue method M/M/1→M/D/1 to model urban drainage system. The model emphasizes randomness of extreme rainstorms, fuzziness of draining process, and construction and operation cost of drainage system. Its two objectives are total c...

  2. Dynamics of a Stage Structured Pest Control Model in a Polluted Environment with Pulse Pollution Input

    OpenAIRE

    Liu, Bing; Xu, Ling; Kang, Baolin

    2013-01-01

    By using pollution model and impulsive delay differential equation, we formulate a pest control model with stage structure for natural enemy in a polluted environment by introducing a constant periodic pollutant input and killing pest at different fixed moments and investigate the dynamics of such a system. We assume only that the natural enemies are affected by pollution, and we choose the method to kill the pest without harming natural enemies. Sufficient conditions for global attractivity ...

  3. Bifurcation analysis on a delayed SIS epidemic model with stage structure

    Directory of Open Access Journals (Sweden)

    Kejun Zhuang

    2007-05-01

    Full Text Available In this paper, a delayed SIS (Susceptible Infectious Susceptible model with stage structure is investigated. We study the Hopf bifurcations and stability of the model. Applying the normal form theory and the center manifold argument, we derive the explicit formulas determining the properties of the bifurcating periodic solutions. The conditions to guarantee the global existence of periodic solutions are established. Also some numerical simulations for supporting the theoretical are given.

  4. Three Stage Maturity Model in SME’s towards Industry 4.0

    OpenAIRE

    Ganzarain, Jaione; Errasti, Nekane

    2016-01-01

    Purpose: To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the s...

  5. Mechanical and mathematical models of multi-stage horizontal fracturing strings and their application

    Directory of Open Access Journals (Sweden)

    Zhanghua Lian

    2015-03-01

    Full Text Available Multi-stage SRV fracturing in horizontal wells is a new technology developed at home and abroad in recent years to effectively develop shale gas or low-permeability reservoirs, but on the other hand makes the mechanical environment of fracturing strings more complicated at the same time. In view of this, based on the loading features of tubing strings during the multi-stage fracturing of a horizontal well, mechanical models were established for three working cases of multiple packer setting, open differential-pressure sliding sleeve, and open ball-injection sliding sleeve under a hold-down packer. Moreover, mathematical models were respectively built for the above three cases. According to the Lame formula and Von Mises stress calculation formula for the thick-walled cylinder in the theory of elastic mechanics, a mathematical model was also established to calculate the equivalent stress for tubing string safety evaluation when the fracturing string was under the combined action of inner pressure, external squeezing force and axial stress, and another mathematical model was built for the mechanical strength and safety evaluation of multi-stage fracturing strings. In addition, a practical software was developed for the mechanical safety evaluation of horizontal well multi-stage fracturing strings according to the mathematical model developed for the mechanical calculation of the multi-packer string in horizontal wells. The research results were applied and verified in a gas well of Tahe Oilfield in the Tarim Basin with excellent effects, providing a theoretical basis and a simple and reliable technical means for optimal design and safety evaluation of safe operational parameters of multi-stage fracturing strings in horizontal wells.

  6. Kidney function and mortality post-liver transplant in the Model for End-Stage Liver Disease era

    Directory of Open Access Journals (Sweden)

    Sethi A

    2011-11-01

    Full Text Available Aastha Sethi1, Michelle M Estrella1, Richard Ugarte2, Mohamed G Atta1 1Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD, USA; 2University of Maryland Medical Center, Department of Medicine, Baltimore, MD, USA Abstract: The Model for End-Stage Liver Disease (MELD score incorporates serum creatinine and was introduced to facilitate allocation of orthotopic liver transplantation (LT. The objective is to determine the impact of MELD and kidney function on all-cause mortality. Among LTs performed in a tertiary referral hospital between 1995 and 2009, 419 cases were studied. Cox proportional hazards models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD era, 57 and 63 deaths were observed, respectively. Those transplanted during the MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01, lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs 92.6 mL/min/1.73 m2, P < 0.01, and more pretransplantation renal replacement therapy (RRT (5% vs 1%; P < 0.01. All-cause mortality risk was similar in the MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58–1.65. The risk of death, however, was nearly 3-fold greater (95% CI: 1.14–6.60 among those requiring pre-transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m2 post-transplant was associated with a 2.5-fold higher mortality (95% CI: 1.48–4.11. The study suggests that MELD implementation had no impact on all-cause mortality post-LT. However, the need for pre-transplant RRT and post-transplant kidney dysfunction was associated with a more than 2-fold greater risk of subsequent death. Keywords: eGFR, mortality, MELD, liver transplant

  7. Screening for a Chronic Disease: A Multiple Stage Duration Model with Partial Observability.

    Science.gov (United States)

    Mroz, Thomas A; Picone, Gabriel; Sloan, Frank; Yashkin, Arseniy P

    2016-08-01

    We estimate a dynamic multi-stage duration model to investigate how early detection of diabetes can delay the onset of lower extremity complications and death. We allow for partial observability of the disease stage, unmeasured heterogeneity, and endogenous timing of diabetes screening. Timely diagnosis appears important. We evaluate the effectiveness of two potential policies to reduce the monetary costs of frequent screening in terms of lost longevity. Compared to the status quo, the more restrictive policy yields an implicit value for an additional year of life of about $50,000, while the less restrictive policy implies a value of about $120,000.

  8. Report on Stage 1 of project CHEMVAL/MIRAGE: verification of speciation models

    International Nuclear Information System (INIS)

    Read, D.; Broyd, T.W.

    1989-01-01

    This report describes the results of CHEMVAL Stage 1, an international chemical model verification exercise involving the active participation of 14 organisations within the CEC countries, Sweden, Switzerland and Finland. Five case systems were studied, namely, cement, clay, sandstone, granite and limestone. Overall, good agreement was obtained even for conceptually difficult geochemical simulations. Reasons for divergence in results have been explored and recommendations are made at the appropriate stages for enhancement of the thermodynamic database. A listing of the preliminary CHEMVAL Project Database is provided. (author)

  9. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

    The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2...... to development of cancer. Many signals that activate COX-2 also induce tumor suppressor p53, a transcription factor central in cellular stress response. We investigated COX-2 and p53 expressions by immunohistochemistry in 50 SNCs (23 adenocarcinomas, and 27 squamous cell carcinomas (SCC); 48 analyzed for COX-2...... displayed adenocarcinoma. COX-2 was expressed at higher levels in adenocarcinoma as compared to SSC (p COX-2 expression showed significant association with occupational exposure to wood dust (p = 0.024), and with nonsmoking status (p = 0.001). No statistically significant associations between...

  10. Numerical modeling of the initial fluctuation condensation stage with charge drops

    Science.gov (United States)

    Averina, T. A.; Zmievskaya, G. I.

    2016-11-01

    This paper deals with a mathematical model of the phase transition of the first kind at the initial stage of forming drops in a liquid or in melted state in a volume of steam with a fixed charge on drops. The model of the process is represented by superposition of random diffusion and jump stochastic processes. The algorithms for solving stochastic differential equations (SDEs) of the model of processes, which form the cluster size, allow one to calculate a distribution function of drops according to their size. The kinetic approach makes possible evaluate the role of the Rayleigh capillary instability at the initial condensation stage and to employ the analysis of electrodispersion mechanisms in the production of metal and semiconductor powders.

  11. A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

    Science.gov (United States)

    Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

    2014-08-01

    Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Combination Efficacy of Astragalus membranaceus and Curcuma wenyujin at Different Stages of Tumor Progression in an Imageable Orthotopic Nude Mouse Model of Metastatic Human Ovarian Cancer Expressing Red Fluorescent Protein.

    Science.gov (United States)

    Yin, Gang; Tang, Decai; Dai, Jianguo; Liu, Min; Wu, Mianhua; Sun, Y U; Yang, Zhijian; Hoffman, Robert M; Li, Lin; Zhang, Shuo; Guo, Xiuxia

    2015-06-01

    The present study determined the efficacy of extracts of Astragalus membranaceus (AM) and Curcuma wenyujin (CW), a traditional Chinese medicine herbal mixture, at different tumor stages of an orthotopic nude mouse model of human ovarian cancer expressing red fluorescent protein. The tumor-bearing mice were treated with cisplatinum (CDDP), AM, CW, or a combination of AM and CW in each of three tumor stages, using the same regimen. Group 1 received saline as negative control. Group 2 received CDDP i.p. as positive control with a dose of 2 mg/kg, every three days. Group 3 received AM daily via oral gavage, at a dose of 9120 mg/kg. Group 4 received CW daily via oral gavage, at a dose of 4560 mg/kg. Groups 5, 6 and 7 received combinations of AM and CW daily via oral gavage at low (AM, 2280 mg/kg; CW, 1140 mg/kg), medium (AM, 4560 mg/kg; CW 2280 mg/kg), and high (AM, 9120 mg/kg; CW, 4560 mg/kg) doses. The expression of angiogenesis- and apoptosis-related genes in the tumors were analyzed by immunohistochemistry for matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) fibroblast growth factor 2 (FGF-2), B-cell lymphoma 2 (Bcl-2) and cyclooxygenase 2 (Cox-2), and by polymerase chain reaction for MMP-2, FGF-2 and Bcl-2. CDDP, AM, and its combination with CW-induced significant growth inhibition of Stage I tumors. Strong efficacy of the combination of AM and CW at high dose was observed. Monotherapy with CDDP, AM, CW, and the combination treatments did not significantly inhibit Stage II and III tumors. The expression of MMP-2, VEGF, FGF-2, and Cox-2 was significantly reduced in Stage I tumors treated with AM, CW, and their combination, suggesting a possible role of these angiogenesis- and apoptosis-related genes in the observed efficacy of the agents tested. This study is the first report on the efficacy of anticancer agents at different stages of ovarian cancer in an orthotopic mouse model. As the tumor progressed, it became treatment

  13. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  14. Integrating life stages into ecological niche models: a case study on tiger beetles.

    Science.gov (United States)

    Taboada, Angela; von Wehrden, Henrik; Assmann, Thorsten

    2013-01-01

    Detailed understanding of a species' natural history and environmental needs across spatial scales is a primary requisite for effective conservation planning, particularly for species with complex life cycles in which different life stages occupy different niches and respond to the environment at different scales. However, niche models applied to conservation often neglect early life stages and are mostly performed at broad spatial scales. Using the endangered heath tiger beetle (Cicindela sylvatica) as a model species, we relate presence/absence and abundance data of locally dispersing adults and sedentary larvae to abiotic and biotic variables measured in a multiscale approach within the geographic extent relevant to active conservation management. At the scale of hundreds of meters, fine-grained abiotic conditions (i.e., vegetation structure) are fundamental determinants of the occurrence of both life stages, whereas the effect of biotic factors is mostly contained in the abiotic signature. The combination of dense heath vegetation and bare ground areas is thus the first requirement for the species' preservation, provided that accessibility to the suitable habitat is ensured. At a smaller scale (centimetres), the influence of abiotic factors on larval occurrence becomes negligible, suggesting the existence of important additional variables acting within larval proximity. Sustained significant correlations between neighbouring larvae in the models provide an indication of the potential impact of neighbourhood crowding on the larval niche within a few centimetres. Since the species spends the majority of its life cycle in the larval stage, it is essential to consider the hierarchical abiotic and biotic processes affecting the larvae when designing practical conservation guidelines for the species. This underlines the necessity for a more critical evaluation of the consequences of disregarding niche variation between life stages when estimating niches and

  15. Weibull aging models for the single protective channel unavailability analysis by the device of stages

    International Nuclear Information System (INIS)

    Nunes, M.E.C.; Noriega, H.C.; Melo, P.F.F.

    1997-01-01

    Among the features to take into account in the unavailability analysis of protective channels, there is one that plays a dominant role - that of considering the equipment aging. In this sense, the exponential failure model is not adequate, since some transition rates are no more constant. As a consequence, Markovian models cannot be used anymore. As an alternative, one may use the device of stages that allows for transforming a Non Markovian model into an equivalent Markovian one by insertion of a fictitious states set, called stages. For a given time-dependent transition rate, its failure density is analysed as to the best combination of exponential distributions and then the moments of the original distribution and those of the combination are matched to estimate the necessary parameters. In this paper, the aging of the protective channel is supposed to follow Weibull distributions. Typical means and variances for the times to failure are considered and combinations of stages are checked. Initial conditions features are discussed in connection with states that are fictitious and to check the validity of the developed models. Alternative solutions by the discretization of the failure rates are generated. The results obtained agree quite well. (author). 7 refs., 6 figs

  16. Two-stage stochastic programming model for the regional-scale electricity planning under demand uncertainty

    International Nuclear Information System (INIS)

    Huang, Yun-Hsun; Wu, Jung-Hua; Hsu, Yu-Ju

    2016-01-01

    Traditional electricity supply planning models regard the electricity demand as a deterministic parameter and require the total power output to satisfy the aggregate electricity demand. But in today's world, the electric system planners are facing tremendously complex environments full of uncertainties, where electricity demand is a key source of uncertainty. In addition, electricity demand patterns are considerably different for different regions. This paper developed a multi-region optimization model based on two-stage stochastic programming framework to incorporate the demand uncertainty. Furthermore, the decision tree method and Monte Carlo simulation approach are integrated into the model to simplify electricity demands in the form of nodes and determine the values and probabilities. The proposed model was successfully applied to a real case study (i.e. Taiwan's electricity sector) to show its applicability. Detail simulation results were presented and compared with those generated by a deterministic model. Finally, the long-term electricity development roadmap at a regional level could be provided on the basis of our simulation results. - Highlights: • A multi-region, two-stage stochastic programming model has been developed. • The decision tree and Monte Carlo simulation are integrated into the framework. • Taiwan's electricity sector is used to illustrate the applicability of the model. • The results under deterministic and stochastic cases are shown for comparison. • Optimal portfolios of regional generation technologies can be identified.

  17. Crack-tip chemistry modeling of stage I stress corrosion cracking

    International Nuclear Information System (INIS)

    Jones, R.H.; Simonen, E.P.

    1991-10-01

    Stage I stress corrosion cracking usually exhibits a very strong K dependence with Paris law exponents of up to 30. 2 Model calculations indicate that the crack velocity in this regime is controlled by transport through a salt film and that the K dependence results from crack opening controlled salt film dissolution. An ionic transport model that accounts for both electromigration through the resistive salt film and Fickian diffusion through the aqueous solution was used for these predictions. Predicted crack growth rates are in excellent agreement with measured values for Ni with P segregated to the grain boundaries and tested in IN H 2 SO 4 at +900 mV. This salt film dissolution may be applicable to stage I cracking of other materials

  18. Delineation of geochemical anomalies based on stream sediment data utilizing fractal modeling and staged factor analysis

    Science.gov (United States)

    Afzal, Peyman; Mirzaei, Misagh; Yousefi, Mahyar; Adib, Ahmad; Khalajmasoumi, Masoumeh; Zarifi, Afshar Zia; Foster, Patrick; Yasrebi, Amir Bijan

    2016-07-01

    Recognition of significant geochemical signatures and separation of geochemical anomalies from background are critical issues in interpretation of stream sediment data to define exploration targets. In this paper, we used staged factor analysis in conjunction with the concentration-number (C-N) fractal model to generate exploration targets for prospecting Cr and Fe mineralization in Balvard area, SE Iran. The results show coexistence of derived multi-element geochemical signatures of the deposit-type sought and ultramafic-mafic rocks in the NE and northern parts of the study area indicating significant chromite and iron ore prospects. In this regard, application of staged factor analysis and fractal modeling resulted in recognition of significant multi-element signatures that have a high spatial association with host lithological units of the deposit-type sought, and therefore, the generated targets are reliable for further prospecting of the deposit in the study area.

  19. Melanoma costs: a dynamic model comparing estimated overall costs of various clinical stages.

    Science.gov (United States)

    Alexandrescu, Doru Traian

    2009-11-15

    The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs. We designed a comprehensive model of expenses in melanoma that considers the dynamic costs generated by the natural progression of the disease, which produces costs associated with treatment, surveillance, loss of income, and terminal care. The complete range of initial clinical (TNM) stages of the disease and initial tumor stages were analyzed in this model and the total healthcare costs for the five years following melanoma presentation at each particular stage were calculated. We have observed dramatic incremental total costs associated with progressively higher initial stages of the disease, ranging from a total of $4,648.48 for in situ tumors to $159,808.17 for Stage IV melanoma. By stage, early lesions associate 30-55 percent of their costs for the treatment of the primary tumor, due to a low rate of recurrence (local, regional, or distant), which limits the need for additional interventions. For in situ melanoma, T1a, and T1b, surveillance is an important contributor to the medical costs, accounting for more than 25 percent of the total cost over 5 years. In contrast, late lesions incur a much larger proportion of their associated costs (up to 80-85%) from the diagnosis and treatment of metastatic disease because of the increased propensity of those lesions to disseminate. This cost increases with increasing tumor stage (from $2,442.17 for T1a to $6,678.00 for T4b). The most expensive items in the medical care of patients with melanoma consist of

  20. Self-consistent electronic structure of a model stage-1 graphite acceptor intercalate

    International Nuclear Information System (INIS)

    Campagnoli, G.; Tosatti, E.

    1981-04-01

    A simple but self-consistent LCAO scheme is used to study the π-electronic structure of an idealized stage-1 ordered graphite acceptor intercalate, modeled approximately on C 8 AsF 5 . The resulting non-uniform charge population within the carbon plane, band structure, optical and energy loss properties are discussed and compared with available spectroscopic evidence. The calculated total energy is used to estimate migration energy barriers, and the intercalate vibration mode frequency. (author)

  1. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied ...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  2. Cancerous Tumour Model Analysis and Constructing schemes of Anti-angiogenesis Therapy at an Early Stage

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

    Full Text Available Anti-angiogenesis therapy is an alternative and successfully employed method for treatment of cancerous tumour. However, this therapy isn't widely used in medicine because of expensive drugs. It leads naturally to elaboration of such treatment regimens which use minimum amount of drugs.The aim of the paper is to investigate the model of development of illness and elaborate appropriate treatment regimens in the case of early diagnosis of the disease. The given model reflects the therapy at an intermediate stage of the disease treatment. Further treatment is aimed to destroy cancer cells and may be continued by other means, which are not reflected in the model.Analysis of the main properties of the model was carried out with consideration of two types of auxiliary systems. In the first case, the system is considered without control, as a model of tumour development in the absence of medical treatment. The study of the equilibrium point and determination of its type allowed us to describe disease dynamics and to determine tumour size resulting in death. In the second case a model with a constant control was investigated. The study of its equilibrium point showed that continuous control is not sufficient to support satisfactory patient's condition, and it is necessary to elaborate more complex treatment regimens. For this purpose, we used the method of terminal problems consisting in the search for such program control which forces system to a given final state. Selecting the initial and final states is due to medical grounds.As a result, we found two treatment regimens | one-stage treatment regimen and multi-stage one. The properties of each treatment regimen are analyzed and compared. The total amount of used drugs was a criterion for comparing these two treatment regimens. The theoretical conclusions obtained in this work are supported by computer modeling in MATLAB environment.

  3. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  4. Fetal Origins of Life Stage Disease: A Zebrafish Model for the ...

    Science.gov (United States)

    In the U.S., childhood obesity has more than doubled in children and quadrupled in adolescents in the past 30 years, affects 35% of adults, and costs the U.S. healthcare industry >$200 billion annually. The chemical environment in the womb may cause susceptibility to different life-stage and life-long metabolic diseases including obesity. The challenge is to understand if exposures during developmentally sensitive windows impact life-stage disease, such as obesity, by increasing adipose tissue mass. In vitro models lack the integrated systems approach needed to assess adipose development, while mammalian models are impractical in a screen of thousands of chemicals. Therefore, an obesogen screening method was developed to interrogate bioactivity using a full systems approach, in a vertebrate zebrafish model with complete metabolic activity, at a time when the full signaling repertoire is expressed and active, to optimally examine how chemical dose and duration impact life-stage adipose mass. A time-line for adipose depot formation was mapped in zebrafish 6−14 days post fertilization (dpf) using the lipophilic dye, Nile Red, in combination with fluorescent microscopy. Those time points were then used to investigate the impact of embryonic tributyltin chloride (TBT, a known obesogen) exposure (10nM daily renewal, 0−5dpf) on adipose mass. Fluorescent microscopy revealed adipose depots that were larger and appeared 2 days earlier in TBT treated compared to contro

  5. Waterhammer Modeling for the Ares I Upper Stage Reaction Control System Cold Flow Development Test Article

    Science.gov (United States)

    Williams, Jonathan H.

    2010-01-01

    The Upper Stage Reaction Control System provides three-axis attitude control for the Ares I launch vehicle during active Upper Stage flight. The system design must accommodate rapid thruster firing to maintain the proper launch trajectory and thus allow for the possibility to pulse multiple thrusters simultaneously. Rapid thruster valve closure creates an increase in static pressure, known as waterhammer, which propagates throughout the propellant system at pressures exceeding nominal design values. A series of development tests conducted in the fall of 2009 at Marshall Space Flight Center were performed using a water-flow test article to better understand fluid performance characteristics of the Upper Stage Reaction Control System. A subset of the tests examined waterhammer along with the subsequent pressure and frequency response in the flight-representative system and provided data to anchor numerical models. This thesis presents a comparison of waterhammer test results with numerical model and analytical results. An overview of the flight system, test article, modeling and analysis are also provided.

  6. Adaptive Urban Stormwater Management Using a Two-stage Stochastic Optimization Model

    Science.gov (United States)

    Hung, F.; Hobbs, B. F.; McGarity, A. E.

    2014-12-01

    In many older cities, stormwater results in combined sewer overflows (CSOs) and consequent water quality impairments. Because of the expense of traditional approaches for controlling CSOs, cities are considering the use of green infrastructure (GI) to reduce runoff and pollutants. Examples of GI include tree trenches, rain gardens, green roofs, and rain barrels. However, the cost and effectiveness of GI are uncertain, especially at the watershed scale. We present a two-stage stochastic extension of the Stormwater Investment Strategy Evaluation (StormWISE) model (A. McGarity, JWRPM, 2012, 111-24) to explicitly model and optimize these uncertainties in an adaptive management framework. A two-stage model represents the immediate commitment of resources ("here & now") followed by later investment and adaptation decisions ("wait & see"). A case study is presented for Philadelphia, which intends to extensively deploy GI over the next two decades (PWD, "Green City, Clean Water - Implementation and Adaptive Management Plan," 2011). After first-stage decisions are made, the model updates the stochastic objective and constraints (learning). We model two types of "learning" about GI cost and performance. One assumes that learning occurs over time, is automatic, and does not depend on what has been done in stage one (basic model). The other considers learning resulting from active experimentation and learning-by-doing (advanced model). Both require expert probability elicitations, and learning from research and monitoring is modelled by Bayesian updating (as in S. Jacobi et al., JWRPM, 2013, 534-43). The model allocates limited financial resources to GI investments over time to achieve multiple objectives with a given reliability. Objectives include minimizing construction and O&M costs; achieving nutrient, sediment, and runoff volume targets; and community concerns, such as aesthetics, CO2 emissions, heat islands, and recreational values. CVaR (Conditional Value at Risk) and

  7. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

    Science.gov (United States)

    Limongelli, Vittorio; Bonomi, Massimiliano; Marinelli, Luciana; Gervasio, Francesco Luigi; Cavalli, Andrea; Novellino, Ettore; Parrinello, Michele

    2010-01-01

    The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational technique we have simulated the full dissociation process of a highly potent and selective inhibitor, SC-558, in both COX-1 and COX-2. We have found a previously unreported alternative binding mode in COX-2 explaining the time-dependent inhibition exhibited by this class of inhibitors and consequently their long residence time inside this isoform. Our metadynamics-based approach allows us to illuminate the highly dynamical character of the ligand/protein recognition process, thus explaining a wealth of experimental data and paving the way to an innovative strategy for designing new COX inhibitors with tuned selectivity. PMID:20215464

  8. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all...... time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible...

  9. The stage-value model: Implications for the changing standards of care.

    Science.gov (United States)

    Görtz, Daniel Patrik; Commons, Michael Lamport

    2015-01-01

    The standard of care is a legal and professional notion against which doctors and other medical personnel are held liable. The standard of care changes as new scientific findings and technological innovations within medicine, pharmacology, nursing and public health are developed and adopted. This study consists of four parts. Part 1 describes the problem and gives concrete examples of its occurrence. The second part discusses the application of the Model of Hierarchical Complexity on the field, giving examples of how standards of care are understood at different behavioral developmental stage. It presents the solution to the problem of standards of care at a Paradigmatic Stage 14. The solution at this stage is a deliberative, communicative process based around why certain norms should or should not apply in each specific case, by the use of "meta-norms". Part 3 proposes a Cross-Paradigmatic Stage 15 view of how the problem of changing standards of care can be solved. The proposed solution is to found the legal procedure in each case on well-established behavioral laws. We maintain that such a behavioristic, scientifically based justice would be much more proficient at effecting restorative legal interventions that create desired behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. A Three-Stage Mechanistic Model for Solidification Cracking During Welding of Steel

    Science.gov (United States)

    Aucott, L.; Huang, D.; Dong, H. B.; Wen, S. W.; Marsden, J.; Rack, A.; Cocks, A. C. F.

    2018-03-01

    A three-stage mechanistic model for solidification cracking during TIG welding of steel is proposed from in situ synchrotron X-ray imaging of solidification cracking and subsequent analysis of fracture surfaces. Stage 1—Nucleation of inter-granular hot cracks: cracks nucleate inter-granularly in sub-surface where maximum volumetric strain is localized and volume fraction of liquid is less than 0.1; the crack nuclei occur at solute-enriched liquid pockets which remain trapped in increasingly impermeable semi-solid skeleton. Stage 2—Coalescence of cracks via inter-granular fracture: as the applied strain increases, cracks coalesce through inter-granular fracture; the coalescence path is preferential to the direction of the heat source and propagates through the grain boundaries to solidifying dendrites. Stage 3—Propagation through inter-dendritic hot tearing: inter-dendritic hot tearing occurs along the boundaries between solidifying columnar dendrites with higher liquid fraction. It is recommended that future solidification cracking criterion shall be based on the application of multiphase mechanics and fracture mechanics to the failure of semi-solid materials.

  11. Chemval project report on stage 2: application of speciation models to laboratory and field data sets

    International Nuclear Information System (INIS)

    Read, D.

    1990-01-01

    This report describes the results of Chemval Stage 2, an international chemical model validation exercise involving the active participation of 14 organizations within EC countries, Sweden, Switzerland and Finland. Four different sites have been studied, representing a range of host rock types and proposed disposal facilities. It details the methodology employed and results obtained for 19 test cases of varying complexity, devised to allow comparison between modelling results and experimental measurements. Recommendations are made for enhancement of models and thermodynamic databases employed, as well as for the collection of field/laboratory data geared to the needs of model validation. This report complements a previous one, ref. EUR 12237 EN, devoted to the verification of speciation models. The work is part of the Community's Mirage project - Second phase, on migration of radionuclides in the geosphere

  12. A fractal derivative constitutive model for three stages in granite creep

    Directory of Open Access Journals (Sweden)

    R. Wang

    Full Text Available In this paper, by replacing the Newtonian dashpot with the fractal dashpot and considering damage effect, a new constitutive model is proposed in terms of time fractal derivative to describe the full creep regions of granite. The analytic solutions of the fractal derivative creep constitutive equation are derived via scaling transform. The conventional triaxial compression creep tests are performed on MTS 815 rock mechanics test system to verify the efficiency of the new model. The granite specimen is taken from Beishan site, the most potential area for the China’s high-level radioactive waste repository. It is shown that the proposed fractal model can characterize the creep behavior of granite especially in accelerating stage which the classical models cannot predict. The parametric sensitivity analysis is also conducted to investigate the effects of model parameters on the creep strain of granite. Keywords: Beishan granite, Fractal derivative, Damage evolution, Scaling transformation

  13. Modeling of thin films growth processes in the early stage for atoms with covalent bonds

    International Nuclear Information System (INIS)

    Tupik, V A; Margolin, V I; Su, Chu Trong

    2017-01-01

    Computer simulation for obtaining thin film’s growth process at an early stage with the proposed model of atoms with isotropic and anisotropic interactions been considered. Carrying out the procedure for analyzing the problem on the basis of the program being implemented, computer simulation of thin film growth processes has been carried out on several examples. The results of computer simulation of the growth process of thin film on a given substrate and an aggregate in a vacuum condition are shown. Some characteristic distributions of the obtained structure have been carried out to evaluate the proposed adequate model and to reflect the high complexity of thin films growth process. (paper)

  14. Simulation model of a single-stage lithium bromide-water absorption cooling unit

    Science.gov (United States)

    Miao, D.

    1978-01-01

    A computer model of a LiBr-H2O single-stage absorption machine was developed. The model, utilizing a given set of design data such as water-flow rates and inlet or outlet temperatures of these flow rates but without knowing the interior characteristics of the machine (heat transfer rates and surface areas), can be used to predict or simulate off-design performance. Results from 130 off-design cases for a given commercial machine agree with the published data within 2 percent.

  15. Weak instruments and the first stage F-statistic in IV models with a nonscalar error covariance structure

    NARCIS (Netherlands)

    Bun, M.; de Haan, M.

    2010-01-01

    We analyze the usefulness of the first stage F-statistic for detecting weak instruments in the IV model with a nonscalar error covariance structure. More in particular, we question the validity of the rule of thumb of a first stage F-statistic of 10 or higher for models with correlated errors

  16. Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2016-01-01

    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

  17. Cox-2 inhibitors and the risk of cardiovascular thrombotic events.

    LENUS (Irish Health Repository)

    Khan, M

    2012-04-01

    In 1971, Vane showed that the analgesic action of traditional NSAIDs relies on inhibition of the cyclo-oxygenase (COX) enzyme, which in turn results in reduced synthesis of proalgesic prostaglandins. Two decades later COX was shown to exist as two distinct isoforms. The constitutive isoform COX-1, supports the beneficial homeostatic functions whereas the inducible isoform, COX-2 becomes up regulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis. Despite the benefits of NSAIDs for acute and chronic pain one of the most clinically significant and well characterized adverse effect is on GI mucosa. The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. The COX-2 selective (COX-1 sparing) inhibitors are associated with reduced GI mucosal damage as demonstrated in several trials. In light of the overwhelming and sometimes contradictory information for patients and physicians regarding the safety of COX-2 agents this article will summarize the available evidence regarding cardiovascular (CV) safety data and contemporary recommendations for prescribing of COX-2-selective NSAIDs.

  18. A framework for 2-stage global sensitivity analysis of GastroPlus™ compartmental models.

    Science.gov (United States)

    Scherholz, Megerle L; Forder, James; Androulakis, Ioannis P

    2018-04-01

    Parameter sensitivity and uncertainty analysis for physiologically based pharmacokinetic (PBPK) models are becoming an important consideration for regulatory submissions, requiring further evaluation to establish the need for global sensitivity analysis. To demonstrate the benefits of an extensive analysis, global sensitivity was implemented for the GastroPlus™ model, a well-known commercially available platform, using four example drugs: acetaminophen, risperidone, atenolol, and furosemide. The capabilities of GastroPlus were expanded by developing an integrated framework to automate the GastroPlus graphical user interface with AutoIt and for execution of the sensitivity analysis in MATLAB ® . Global sensitivity analysis was performed in two stages using the Morris method to screen over 50 parameters for significant factors followed by quantitative assessment of variability using Sobol's sensitivity analysis. The 2-staged approach significantly reduced computational cost for the larger model without sacrificing interpretation of model behavior, showing that the sensitivity results were well aligned with the biopharmaceutical classification system. Both methods detected nonlinearities and parameter interactions that would have otherwise been missed by local approaches. Future work includes further exploration of how the input domain influences the calculated global sensitivity measures as well as extending the framework to consider a whole-body PBPK model.

  19. Structured model of bacterial growth and tests with activated sludge in a one-stage and two-stage chemostat

    NARCIS (Netherlands)

    Harder, A.

    1979-01-01

    A kinetic model for a growing culture of micro-organisms was developed that correlated the biochemical structure of cells with quantitative physiological behaviour. The three-compartment model was adequate for simulation of continuous, batch and transient experiments with activated sludge fed on

  20. Applying the Health Belief Model in Explaining the Stages of Exercise Change in Older Adults

    Directory of Open Access Journals (Sweden)

    Sas-Nowosielski Krzysztof

    2016-12-01

    Full Text Available Introduction. The benefits of physical activity (PA have been so well documented that there is no doubt about the significance of PA for personal and social health. Several theoretical models have been proposed with a view to understanding the phenomenon of PA and other health behaviours. The purpose of this study was to evaluate if and how the variables suggested in the Health Belief Model (HBM determine physical activity stages of change in older adults. Material and methods. A total of 172 students of Universities of the Third Age aged 54 to 75 (mean = 62.89 ± 4.83 years agreed to participate in the study, filling out an anonymous survey measuring their stage of exercise change and determinants of health behaviours proposed by the HBM, including: perceived benefits of physical activity, perceived barriers to physical activity, perceived severity of diseases associated with sedentary lifestyle, perceived susceptibility to these diseases, and self-efficacy. Results. The results only partially support the hypothesis that the HBM predicts intentions and behaviours related to the physical activity of older adults. Only two variables were moderately-to-strongly related to stages of exercise change, namely perceived barriers and self-efficacy. Conclusion. Interventions aimed at informing older adults about the benefits of physical activity and the threats associated with sedentary lifestyle can be expected to have rather a weak influence on their readiness for physical activity.

  1. Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

    Science.gov (United States)

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

  2. Design model for bending vibrations of single-stage tunnel fan rotor

    Science.gov (United States)

    Krasyuk, AM; Kosykh, PV

    2018-03-01

    Using of one-mass model of tunnel fan rotor is justified for estimation calculation of the natural bending vibrations frequency during the design stage. It’s shown that the evaluative computation of the main axial tunnel fan at the early design stage yields the acceptable accuracy. It is shown that after completion of the design, the mass of the stepped-type shaft differs from the mass of the calculated uniform-diameter shaft no more than by 40%. Inclusion of this additional mass in the estimation calculation makes it possible to improve the calculation accuracy. The region of the dimensionless rotor design parameters at which the relative difference of frequency in the evaluative and verification calculations is not higher than 5 % is determined.

  3. Automated Box-Cox Transformations for Improved Visual Encoding.

    Science.gov (United States)

    Maciejewski, Ross; Pattath, Avin; Ko, Sungahn; Hafen, Ryan; Cleveland, William S; Ebert, David S

    2013-01-01

    The concept of preconditioning data (utilizing a power transformation as an initial step) for analysis and visualization is well established within the statistical community and is employed as part of statistical modeling and analysis. Such transformations condition the data to various inherent assumptions of statistical inference procedures, as well as making the data more symmetric and easier to visualize and interpret. In this paper, we explore the use of the Box-Cox family of power transformations to semiautomatically adjust visual parameters. We focus on time-series scaling, axis transformations, and color binning for choropleth maps. We illustrate the usage of this transformation through various examples, and discuss the value and some issues in semiautomatically using these transformations for more effective data visualization.

  4. End-to-End Deep Learning Model For Automatic Sleep Staging Using Raw PSG Waveforms

    DEFF Research Database (Denmark)

    Olesen, Alexander Neergaard; Peppard, P. E.; Sorensen, H. B.

    2018-01-01

    Deep learning has seen significant progress over the last few years, especially in computer vision, where competitions such as the ImageNet challenge have been the driving factor behind many new model architectures far superior to humans in image recognition. We propose a novel method for automatic...... accuracy, precision and recall were 84.93%, 97.42% and 97.02%, respectively. Evaluating on the validation set yielded an overall accuracy of 85.07% and overall precision/recall of 98.54% and 95.72%, respectively. Conclusion: Preliminary results indicate that state of the art deep learning models can...... sleep staging, which relies on current advances in computer vision models eliminating the need for feature engineering or other transformations of input data. By exploiting the high capacity for complex learning in a state of the art object recognition model, we can effectively use raw PSG signals...

  5. Integrating Growth Stage Deficit Irrigation into a Process Based Crop Model

    Science.gov (United States)

    Lopez, Jose R.; Winter, Jonathan M.; Elliott, Joshua; Ruane, Alex C.; Porter, Cheryl; Hoogenboom, Gerrit

    2017-01-01

    Current rates of agricultural water use are unsustainable in many regions, creating an urgent need to identify improved irrigation strategies for water limited areas. Crop models can be used to quantify plant water requirements, predict the impact of water shortages on yield, and calculate water productivity (WP) to link water availability and crop yields for economic analyses. Many simulations of crop growth and development, especially in regional and global assessments, rely on automatic irrigation algorithms to estimate irrigation dates and amounts. However, these algorithms are not well suited for water limited regions because they have simplistic irrigation rules, such as a single soil-moisture based threshold, and assume unlimited water. To address this constraint, a new modeling framework to simulate agricultural production in water limited areas was developed. The framework consists of a new automatic irrigation algorithm for the simulation of growth stage based deficit irrigation under limited seasonal water availability; and optimization of growth stage specific parameters. The new automatic irrigation algorithm was used to simulate maize and soybean in Gainesville, Florida, and first used to evaluate the sensitivity of maize and soybean simulations to irrigation at different growth stages and then to test the hypothesis that water productivity calculated using simplistic irrigation rules underestimates WP. In the first experiment, the effect of irrigating at specific growth stages on yield and irrigation water use efficiency (IWUE) in maize and soybean was evaluated. In the reproductive stages, IWUE tended to be higher than in the vegetative stages (e.g. IWUE was 18% higher than the well watered treatment when irrigating only during R3 in soybean), and when rainfall events were less frequent. In the second experiment, water productivity (WP) was significantly greater with optimized irrigation schedules compared to non-optimized irrigation schedules in

  6. Modeling Remote I/O versus Staging Tradeoff in Multi-Data Center Computing

    International Nuclear Information System (INIS)

    Suslu, Ibrahim H

    2014-01-01

    In multi-data center computing, data to be processed is not always local to the computation. This is a major challenge especially for data-intensive Cloud computing applications, since large amount of data would need to be either moved the local sites (staging) or accessed remotely over the network (remote I/O). Cloud application developers generally chose between staging and remote I/O intuitively without making any scientific comparison specific to their application data access patterns since there is no generic model available that they can use. In this paper, we propose a generic model for the Cloud application developers which would help them to choose the most appropriate data access mechanism for their specific application workloads. We define the parameters that potentially affect the end-to-end performance of the multi-data center Cloud applications which need to access large datasets over the network. To test and validate our models, we implemented a series of synthetic benchmark applications to simulate the most common data access patterns encountered in Cloud applications. We show that our model provides promising results in different settings with different parameters, such as network bandwidth, server and client capabilities, and data access ratio

  7. Modeling of existing cooling towers in ASPEN PLUS using an equilibrium stage method

    International Nuclear Information System (INIS)

    Queiroz, João A.; Rodrigues, Vitor M.S.; Matos, Henrique A.; Martins, F.G.

    2012-01-01

    Highlights: ► Simulation of cooling tower performance under different operating conditions. ► Cooling tower performance is simulated using ASPEN PLUS. ► Levenberg–Marquardt method used to adjust model parameters. ► Air and water outlet temperatures are in good accordance with experimental data. - Abstract: Simulation of cooling tower performance considering operating conditions away from design is typically based on the geometrical parameters provided by the cooling tower vendor, which are often unavailable or outdated. In this paper a different approach for cooling tower modeling based on equilibrium stages and Murphree efficiencies to describe heat and mass transfer is presented. This approach is validated with published data and with data collected from an industrial application. Cooling tower performance is simulated using ASPEN PLUS. Murphree stage efficiency values for the process simulator model were optimized by minimizing the squared difference between the experimental and calculated data using the Levenberg–Marquardt method. The minimization algorithm was implemented in Microsoft Excel with Visual Basic for Applications, integrated with the process simulator (ASPEN PLUS) using Aspen Simulation Workbook. The simulated cooling tower air and water outlet temperatures are in good accordance with experimental data when applying only the outlet water temperature to calibrate the model. The methodology is accurate for simulating cooling towers at different operational conditions.

  8. A two-stage storage routing model for green roof runoff detention.

    Science.gov (United States)

    Vesuviano, Gianni; Sonnenwald, Fred; Stovin, Virginia

    2014-01-01

    Green roofs have been adopted in urban drainage systems to control the total quantity and volumetric flow rate of runoff. Modern green roof designs are multi-layered, their main components being vegetation, substrate and, in almost all cases, a separate drainage layer. Most current hydrological models of green roofs combine the modelling of the separate layers into a single process; these models have limited predictive capability for roofs not sharing the same design. An adaptable, generic, two-stage model for a system consisting of a granular substrate over a hard plastic 'egg box'-style drainage layer and fibrous protection mat is presented. The substrate and drainage layer/protection mat are modelled separately by previously verified sub-models. Controlled storm events are applied to a green roof system in a rainfall simulator. The time-series modelled runoff is compared to the monitored runoff for each storm event. The modelled runoff profiles are accurate (mean Rt(2) = 0.971), but further characterization of the substrate component is required for the model to be generically applicable to other roof configurations with different substrate.

  9. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  10. Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages.

    Science.gov (United States)

    Loccisano, Anne E; Longnecker, Matthew P; Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2013-01-01

    Perfluoroalkyl acid carboxylates and sulfonates (PFAA) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential reproductive/developmental effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting results have been reported for associations between maternal PFAA levels and these outcomes. Risk assessments and interpretation of available human data during gestation and lactation are hindered due to lack of a framework for understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK). Physiologically based pharmacokinetic (PBPK) models were developed for PFOA and PFOS for the gestation and lactation life stages in humans to understand how the physiological changes associated with development affect pharmacokinetics of these compounds in the mother, fetus, and infant. These models were derived from PBPK models for PFOA/PFOS that were previously developed for adult humans and rats during gestation and lactation and from existing human pregnancy and lactation models developed for other chemicals. The models simulated PFOA and PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared to available data in humans, and also were used to estimate maternal exposure. The models reported here identified several research needs, which include (1) the identification of transporters involved in renal resorption to explain the multiyear half-lives of these compounds in humans, (2) factors affecting clearance of PFOA/PFOS during gestation and lactation, and (3) data to estimate clearance of PFOA/PFOS in infants. These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages.

  11. An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

    International Nuclear Information System (INIS)

    Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

    2004-01-01

    A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

  12. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were

  13. A transition-constrained discrete hidden Markov model for automatic sleep staging

    Directory of Open Access Journals (Sweden)

    Pan Shing-Tai

    2012-08-01

    Full Text Available Abstract Background Approximately one-third of the human lifespan is spent sleeping. To diagnose sleep problems, all-night polysomnographic (PSG recordings including electroencephalograms (EEGs, electrooculograms (EOGs and electromyograms (EMGs, are usually acquired from the patient and scored by a well-trained expert according to Rechtschaffen & Kales (R&K rules. Visual sleep scoring is a time-consuming and subjective process. Therefore, the development of an automatic sleep scoring method is desirable. Method The EEG, EOG and EMG signals from twenty subjects were measured. In addition to selecting sleep characteristics based on the 1968 R&K rules, features utilized in other research were collected. Thirteen features were utilized including temporal and spectrum analyses of the EEG, EOG and EMG signals, and a total of 158 hours of sleep data were recorded. Ten subjects were used to train the Discrete Hidden Markov Model (DHMM, and the remaining ten were tested by the trained DHMM for recognition. Furthermore, the 2-fold cross validation was performed during this experiment. Results Overall agreement between the expert and the results presented is 85.29%. With the exception of S1, the sensitivities of each stage were more than 81%. The most accurate stage was SWS (94.9%, and the least-accurately classified stage was S1 ( Conclusion The results of the experiments demonstrate that the proposed method significantly enhances the recognition rate when compared with prior studies.

  14. Modeling two-stage bunch compression with wakefields: Macroscopic properties and microbunching instability

    Directory of Open Access Journals (Sweden)

    R. A. Bosch

    2008-09-01

    Full Text Available In a two-stage compression and acceleration system, where each stage compresses a chirped bunch in a magnetic chicane, wakefields affect high-current bunches. The longitudinal wakes affect the macroscopic energy and current profiles of the compressed bunch and cause microbunching at short wavelengths. For macroscopic wavelengths, impedance formulas and tracking simulations show that the wakefields can be dominated by the resistive impedance of coherent edge radiation. For this case, we calculate the minimum initial bunch length that can be compressed without producing an upright tail in phase space and associated current spike. Formulas are also obtained for the jitter in the bunch arrival time downstream of the compressors that results from the bunch-to-bunch variation of current, energy, and chirp. Microbunching may occur at short wavelengths where the longitudinal space-charge wakes dominate or at longer wavelengths dominated by edge radiation. We model this range of wavelengths with frequency-dependent impedance before and after each stage of compression. The growth of current and energy modulations is described by analytic gain formulas that agree with simulations.

  15. Non-ideal magnetohydrodynamic simulations of the two-stage fragmentation model for cluster formation

    International Nuclear Information System (INIS)

    Bailey, Nicole D.; Basu, Shantanu

    2014-01-01

    We model molecular cloud fragmentation with thin-disk, non-ideal magnetohydrodynamic simulations that include ambipolar diffusion and partial ionization that transitions from primarily ultraviolet-dominated to cosmic-ray-dominated regimes. These simulations are used to determine the conditions required for star clusters to form through a two-stage fragmentation scenario. Recent linear analyses have shown that the fragmentation length scales and timescales can undergo a dramatic drop across the column density boundary that separates the ultraviolet- and cosmic-ray-dominated ionization regimes. As found in earlier studies, the absence of an ionization drop and regular perturbations leads to a single-stage fragmentation on pc scales in transcritical clouds, so that the nonlinear evolution yields the same fragment sizes as predicted by linear theory. However, we find that a combination of initial transcritical mass-to-flux ratio, evolution through a column density regime in which the ionization drop takes place, and regular small perturbations to the mass-to-flux ratio is sufficient to cause a second stage of fragmentation during the nonlinear evolution. Cores of size ∼0.1 pc are formed within an initial fragment of ∼pc size. Regular perturbations to the mass-to-flux ratio also accelerate the onset of runaway collapse.

  16. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  17. Numerical simulation model of hyperacute/acute stage white matter infarction.

    Science.gov (United States)

    Sakai, Koji; Yamada, Kei; Oouchi, Hiroyuki; Nishimura, Tsunehiko

    2008-01-01

    Although previous studies have revealed the mechanisms of changes in diffusivity (apparent diffusion coefficient [ADC]) in acute brain infarction, changes in diffusion anisotropy (fractional anisotropy [FA]) in white matter have not been examined. We hypothesized that membrane permeability as well as axonal swelling play important roles, and we therefore constructed a simulation model using random walk simulation to replicate the diffusion of water molecules. We implemented a numerical diffusion simulation model of normal and infarcted human brains using C++ language. We constructed this 2-pool model using simple tubes aligned in a single direction. Random walk simulation diffused water. Axon diameters and membrane permeability were then altered in step-wise fashion. To estimate the effects of axonal swelling, axon diameters were changed from 6 to 10 microm. Membrane permeability was altered from 0% to 40%. Finally, both elements were combined to explain increasing FA in the hyperacute stage of white matter infarction. The simulation demonstrated that simple water shift into the intracellular space reduces ADC and increases FA, but not to the extent expected from actual human cases (ADC approximately 50%; FA approximately +20%). Similarly, membrane permeability alone was insufficient to explain this phenomenon. However, a combination of both factors successfully replicated changes in diffusivity indices. Both axonal swelling and reduced membrane permeability appear important in explaining changes in ADC and FA based on eigenvalues in hyperacute-stage white matter infarction.

  18. Modelling and Control of the Multi-Stage Cable Pulley-Driven Flexible-Joint Robot

    Directory of Open Access Journals (Sweden)

    Phongsaen Pitakwatchara

    2014-07-01

    Full Text Available This work is concerned with the task space impedance control of a robot driven through a multi-stage nonlinear flexible transmission system. Specifically, a two degrees-of-freedom cable pulley-driven flexible-joint robot is considered. Realistic modelling of the system is developed within the bond graph modelling framework. The model captures the nonlinear compliance behaviour of the multi-stage cable pulley transmission system, the spring effect of the augmented counterbalancing mechanism, the major loss throughout the system elements, and the typical inertial dynamics of the robot. Next, a task space impedance controller based on limited information about the angle and the current of the motors is designed. The motor current is used to infer the transmitted torque, by which the motor inertia may be modulated. The motor angle is employed to estimate the stationary distal robot link angle and the robot joint velocity. They are used in the controller to generate the desired damping force and to shape the potential energy of the flexible joint robot system to the desired configuration. Simulation and experimental results of the controlled system signify the competency of the proposed control law.

  19. Modeling the fine fragmentation following the triggering stage of a vapor explosion

    International Nuclear Information System (INIS)

    Darbord, I.

    1997-01-01

    In the frame of PWR severe accidents, where the core melt, this thesis studies one of the stages of an FCI (fuel coolant interaction) or vapor explosion. An FCI is a rapid evaporation of a coolant when it comes into contact with a hot liquid. More precisely, the subject of this study is the triggering stage of the FCI, when a fuel drop of diameter around one centimeter breaks up into many fragments, diameter of which is around a hundred micrometers. The model describes the cyclic collapse and growth of a vapor bubble around the fuel droplet and its fragmentation. The main features of the model are: - the destabilization of the film or the vapor bubble due to the growth of Rayleigh-Taylor instabilities (those form coolant jets that contact the fuel surface); - The mechanisms of fragmentation, following the contacts (in the case of entrapment of a certain amount of coolant in the fuel, the entrapped coolant evaporates violently after it has been heated to the homogeneous nucleation temperature); - the transient heat transfer from the fragments to the coolant and the elevated vapor production, which leads to an important expansion of the bubble (about this point, the cooling of the fragments has been described by a transient heat transfer coefficient linked to nucleate boiling). The results of the model show good agreement with experimental data. (Author)

  20. Maximum likelihood estimation of signal detection model parameters for the assessment of two-stage diagnostic strategies.

    Science.gov (United States)

    Lirio, R B; Dondériz, I C; Pérez Abalo, M C

    1992-08-01

    The methodology of Receiver Operating Characteristic curves based on the signal detection model is extended to evaluate the accuracy of two-stage diagnostic strategies. A computer program is developed for the maximum likelihood estimation of parameters that characterize the sensitivity and specificity of two-stage classifiers according to this extended methodology. Its use is briefly illustrated with data collected in a two-stage screening for auditory defects.

  1. A two-stage value chain model for vegetable marketing chain efficiency evaluation: A transaction cost approach

    OpenAIRE

    Lu Hualiang

    2006-01-01

    We applied a two-stage value chain model to investigate the effects of input application and occasional transaction costs on vegetable marketing chain efficiencies with a farm household-level data set. In the first stage, the production efficiencies with the combination of resource endowments, capital and managerial inputs, and production techniques were evaluated; then at the second stage, the marketing technical efficiencies were determined under the marketing value of the vegetables for th...

  2. Statistical geological discrete fracture network model. Forsmark modelling stage 2.2

    International Nuclear Information System (INIS)

    Fox, Aaron; La Pointe, Paul; Simeonov, Assen; Hermanson, Jan; Oehman, Johan

    2007-11-01

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is performing site characterization at two different locations, Forsmark and Laxemar, in order to locate a site for a final geologic repository for spent nuclear fuel. The program is built upon the development of Site Descriptive Models (SDMs) at specific timed data freezes. Each SDM is formed from discipline-specific reports from across the scientific spectrum. This report describes the methods, analyses, and conclusions of the geological modeling team with respect to a geological and statistical model of fractures and minor deformation zones (henceforth referred to as the geological DFN), version 2.2, at the Forsmark site. The geological DFN builds upon the work of other geological modelers, including the deformation zone (DZ), rock domain (RD), and fracture domain (FD) models. The geological DFN is a statistical model for stochastically simulating rock fractures and minor deformation zones as a scale of less than 1,000 m (the lower cut-off of the DZ models). The geological DFN is valid within four specific fracture domains inside the local model region, and encompassing the candidate volume at Forsmark: FFM01, FFM02, FFM03, and FFM06. The models are build using data from detailed surface outcrop maps and the cored borehole record at Forsmark. The conceptual model for the Forsmark 2.2 geological revolves around the concept of orientation sets; for each fracture domain, other model parameters such as size and intensity are tied to the orientation sets. Two classes of orientation sets were described; Global sets, which are encountered everywhere in the model region, and Local sets, which represent highly localized stress environments. Orientation sets were described in terms of their general cardinal direction (NE, NW, etc). Two alternatives are presented for fracture size modeling: - the tectonic continuum approach (TCM, TCMF) described by coupled size-intensity scaling following power law distributions

  3. Statistical geological discrete fracture network model. Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Aaron; La Pointe, Paul [Golder Associates Inc (United States); Simeonov, Assen [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Hermanson, Jan; Oehman, Johan [Golder Associates AB, Stockholm (Sweden)

    2007-11-15

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is performing site characterization at two different locations, Forsmark and Laxemar, in order to locate a site for a final geologic repository for spent nuclear fuel. The program is built upon the development of Site Descriptive Models (SDMs) at specific timed data freezes. Each SDM is formed from discipline-specific reports from across the scientific spectrum. This report describes the methods, analyses, and conclusions of the geological modeling team with respect to a geological and statistical model of fractures and minor deformation zones (henceforth referred to as the geological DFN), version 2.2, at the Forsmark site. The geological DFN builds upon the work of other geological modelers, including the deformation zone (DZ), rock domain (RD), and fracture domain (FD) models. The geological DFN is a statistical model for stochastically simulating rock fractures and minor deformation zones as a scale of less than 1,000 m (the lower cut-off of the DZ models). The geological DFN is valid within four specific fracture domains inside the local model region, and encompassing the candidate volume at Forsmark: FFM01, FFM02, FFM03, and FFM06. The models are build using data from detailed surface outcrop maps and the cored borehole record at Forsmark. The conceptual model for the Forsmark 2.2 geological revolves around the concept of orientation sets; for each fracture domain, other model parameters such as size and intensity are tied to the orientation sets. Two classes of orientation sets were described; Global sets, which are encountered everywhere in the model region, and Local sets, which represent highly localized stress environments. Orientation sets were described in terms of their general cardinal direction (NE, NW, etc). Two alternatives are presented for fracture size modeling: - the tectonic continuum approach (TCM, TCMF) described by coupled size-intensity scaling following power law distributions

  4. A stage structure pest management model with impulsive state feedback control

    Science.gov (United States)

    Pang, Guoping; Chen, Lansun; Xu, Weijian; Fu, Gang

    2015-06-01

    A stage structure pest management model with impulsive state feedback control is investigated. We get the sufficient condition for the existence of the order-1 periodic solution by differential equation geometry theory and successor function. Further, we obtain a new judgement method for the stability of the order-1 periodic solution of the semi-continuous systems by referencing the stability analysis for limit cycles of continuous systems, which is different from the previous method of analog of Poincarè criterion. Finally, we analyze numerically the theoretical results obtained.

  5. EGovernment Stage Model: Evaluating the Rate of Web Development Progress of Government Websites in Saudi Arabia

    OpenAIRE

    Osama Alfarraj; Steve Drew; Rayed Abdullah AlGhamdi

    2011-01-01

    This paper contributes to the issue of eGovernment implementation in Saudi Arabia by discussing the current situation of ministry websites. It evaluates the rate of web development progress of vital government websites in Saudi Arabia using the eGovernment stage model. In 2010, Saudi Arabia ranked 58th in the world and 4th in the Gulf region in eGovernment readiness according to United Nations reports. In particular, Saudi Arabia has ranked 75th worldwide for its online service index and its ...

  6. Dynamic modeling of a three-stage low-temperature ethanol reformer for fuel cell application

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Vanesa M; Serra, Maria [Institut de Robotica i Informatica Industrial (CSIC-UPC), Llorens i Artigas 4-6, 08028 Barcelona (Spain); Lopez, Eduardo; Llorca, Jordi [Institut de Tecniques Energetiques, Universitat Politecnica de Catalunya, Diagonal 647, ed. ETSEIB, 08028 Barcelona (Spain)

    2009-07-01

    A low-temperature ethanol reformer based on a cobalt catalyst for the production of hydrogen has been designed aiming the feed of a fuel cell for an autonomous low-scale power production unit. The reformer comprises three stages: ethanol dehydrogenation to acetaldehyde and hydrogen over SnO{sub 2} followed by acetaldehyde steam reforming over Co(Fe)/ZnO catalyst and water gas shift reaction. Kinetic data have been obtained under different experimental conditions and a dynamic model has been developed for a tubular reformer loaded with catalytic monoliths for the production of the hydrogen required to feed a 1 kW PEMFC. (author)

  7. Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy.

    Science.gov (United States)

    Corsini, Chiara; Cervi, Elena; Migliavacca, Francesco; Schievano, Silvia; Hsia, Tain-Yen; Pennati, Giancarlo

    2017-09-01

    In this study, a mathematical model of the female circulation during pregnancy is presented in order to investigate the hemodynamic response to the cardiovascular changes associated with each trimester of pregnancy. First, a preliminary lumped parameter model of the circulation of a non-pregnant female was developed, including the heart, the systemic circulation with a specific block for the uterine district and the pulmonary circulation. The model was first tested at rest; then heart rate and vascular resistances were individually varied to verify the correct response to parameter alterations characterising pregnancy. In order to simulate hemodynamics during pregnancy at each trimester, the main changes applied to the model consisted in reducing vascular resistances, and simultaneously increasing heart rate and ventricular wall volumes. Overall, reasonable agreement was found between model outputs and in vivo data, with the trends of the cardiac hemodynamic quantities suggesting correct response of the heart model throughout pregnancy. Results were reported for uterine hemodynamics, with flow tracings resembling typical Doppler velocity waveforms at each stage, including pulsatility indexes. Such a model may be used to explore the changes that happen during pregnancy in female with cardiovascular diseases. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  8. Forecasts of non-Gaussian parameter spaces using Box-Cox transformations

    Science.gov (United States)

    Joachimi, B.; Taylor, A. N.

    2011-09-01

    Forecasts of statistical constraints on model parameters using the Fisher matrix abound in many fields of astrophysics. The Fisher matrix formalism involves the assumption of Gaussianity in parameter space and hence fails to predict complex features of posterior probability distributions. Combining the standard Fisher matrix with Box-Cox transformations, we propose a novel method that accurately predicts arbitrary posterior shapes. The Box-Cox transformations are applied to parameter space to render it approximately multivariate Gaussian, performing the Fisher matrix calculation on the transformed parameters. We demonstrate that, after the Box-Cox parameters have been determined from an initial likelihood evaluation, the method correctly predicts changes in the posterior when varying various parameters of the experimental setup and the data analysis, with marginally higher computational cost than a standard Fisher matrix calculation. We apply the Box-Cox-Fisher formalism to forecast cosmological parameter constraints by future weak gravitational lensing surveys. The characteristic non-linear degeneracy between matter density parameter and normalization of matter density fluctuations is reproduced for several cases, and the capabilities of breaking this degeneracy by weak-lensing three-point statistics is investigated. Possible applications of Box-Cox transformations of posterior distributions are discussed, including the prospects for performing statistical data analysis steps in the transformed Gaussianized parameter space.

  9. INHOMOGENEITY IN SPATIAL COX POINT PROCESSES – LOCATION DEPENDENT THINNING IS NOT THE ONLY OPTION

    Directory of Open Access Journals (Sweden)

    Michaela Prokešová

    2010-11-01

    Full Text Available In the literature on point processes the by far most popular option for introducing inhomogeneity into a point process model is the location dependent thinning (resulting in a second-order intensity-reweighted stationary point process. This produces a very tractable model and there are several fast estimation procedures available. Nevertheless, this model dilutes the interaction (or the geometrical structure of the original homogeneous model in a special way. When concerning the Markov point processes several alternative inhomogeneous models were suggested and investigated in the literature. But it is not so for the Cox point processes, the canonical models for clustered point patterns. In the contribution we discuss several other options how to define inhomogeneous Cox point process models that result in point patterns with different types of geometric structure. We further investigate the possible parameter estimation procedures for such models.

  10. Three stage maturity model in SME’s toward industry 4.0

    Energy Technology Data Exchange (ETDEWEB)

    Ganzarain, J.; Errasti, N.

    2016-07-01

    To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

  11. Three stage maturity model in SME’s toward industry 4.0

    International Nuclear Information System (INIS)

    Ganzarain, J.; Errasti, N.

    2016-01-01

    To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

  12. Chemical analysis of simulated high level waste glasses to support stage III sulfate solubility modeling

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-03-17

    The U.S. Department of Energy (DOE), Office of Environmental Management (EM) is sponsoring an international, collaborative project to develop a fundamental model for sulfate solubility in nuclear waste glass. The solubility of sulfate has a significant impact on the achievable waste loading for nuclear waste forms within the DOE complex. These wastes can contain relatively high concentrations of sulfate, which has low solubility in borosilicate glass. This is a significant issue for low-activity waste (LAW) glass and is projected to have a major impact on the Hanford Tank Waste Treatment and Immobilization Plant (WTP). Sulfate solubility has also been a limiting factor for recent high level waste (HLW) sludge processed at the Savannah River Site (SRS) Defense Waste Processing Facility (DWPF). The low solubility of sulfate in glass, along with melter and off-gas corrosion constraints, dictate that the waste be blended with lower sulfate concentration waste sources or washed to remove sulfate prior to vitrification. The development of enhanced borosilicate glass compositions with improved sulfate solubility will allow for higher waste loadings and accelerate mission completion.The objective of the current scope being pursued by SHU is to mature the sulfate solubility model to the point where it can be used to guide glass composition development for DWPF and WTP, allowing for enhanced waste loadings and waste throughput at these facilities. A series of targeted glass compositions was selected to resolve data gaps in the model and is identified as Stage III. SHU fabricated these glasses and sent samples to SRNL for chemical composition analysis. SHU will use the resulting data to enhance the sulfate solubility model and resolve any deficiencies. In this report, SRNL provides chemical analyses for the Stage III, simulated HLW glasses fabricated by SHU in support of the sulfate solubility model development.

  13. Modeling of filling gas centrifuge cascade for nickel isotope separation by feed flow input to different stages

    Directory of Open Access Journals (Sweden)

    Orlov Alexey A.

    2017-01-01

    Full Text Available The article presents results of research filling gas centrifuge cascade by process gas fed into different stages. The modeling of filling cascade was done for nickel isotope separation. Analysis of the research results shows that nickel isotope concentrations of light and heavy fraction flows after filling cascade depend on feed stage number.

  14. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  15. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    International Nuclear Information System (INIS)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

    2014-01-01

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification

  16. Stage-dependent analgesia of electro-acupuncture in a mouse model of cutaneous cancer pain.

    Science.gov (United States)

    Mao-Ying, Qi-Liang; Cui, Ke-Mi; Liu, Qiong; Dong, Zhi-Qiang; Wang, Wei; Wang, Jun; Sha, Hong; Wu, Gen-Cheng; Wang, Yan-Qing

    2006-11-01

    Acupuncture is one of the most effective alternative medical treatments in pain management with the advantages of simple application, low cost and minimal side effects. However its scientific evidence and laws of action are not very clear in cancer pain relieving. The aim of this study was to examine the immediate and therapeutic anti-hyperalgesic effect of electro-acupuncture (EA) on a mouse model of cutaneous cancer pain. B16-BL6 melanoma cells were inoculated into the plantar region of unilateral hind paw and the thermal hyperalgesia was measured by using radiant heat test and hot plate test. C57BL/6 mice showed moderate and marked hyperalgesia during days 8-12 and from day 14 after the orthotopic inoculation of B16-BL6 melanoma cells into the hind paw. Single EA on day 8 after inoculation showed significant analgesic effect immediately after the treatment, the analgesic effect reached its maximum within 15-30min and declined to its minimum at 50min after EA treatment. Single EA treatment on day 20 showed no significant analgesic effect; Repeated EA treatments (started from day 8, once every other day) showed therapeutic analgesic effect, while it showed no therapeutic effect when started from day 16, a relatively late stage of this cancer pain model. The results demonstrated that EA had anti-hyperalgesic effect on early stage of cutaneous cancer pain but not on late stage. These results indicated a tight correlation of EA anti-hyperalgesic effects with the time window of cancer pain.

  17. Tumor angiogenesis in advanced stage ovarian carcinoma.

    Science.gov (United States)

    Hollingsworth, H C; Kohn, E C; Steinberg, S M; Rothenberg, M L; Merino, M J

    1995-07-01

    Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

  18. Two-Stage Hidden Markov Model in Gesture Recognition for Human Robot Interaction

    Directory of Open Access Journals (Sweden)

    Nhan Nguyen-Duc-Thanh

    2012-07-01

    Full Text Available Hidden Markov Model (HMM is very rich in mathematical structure and hence can form the theoretical basis for use in a wide range of applications including gesture representation. Most research in this field, however, uses only HMM for recognizing simple gestures, while HMM can definitely be applied for whole gesture meaning recognition. This is very effectively applicable in Human-Robot Interaction (HRI. In this paper, we introduce an approach for HRI in which not only the human can naturally control the robot by hand gesture, but also the robot can recognize what kind of task it is executing. The main idea behind this method is the 2-stages Hidden Markov Model. The 1st HMM is to recognize the prime command-like gestures. Based on the sequence of prime gestures that are recognized from the 1st stage and which represent the whole action, the 2nd HMM plays a role in task recognition. Another contribution of this paper is that we use the output Mixed Gaussian distribution in HMM to improve the recognition rate. In the experiment, we also complete a comparison of the different number of hidden states and mixture components to obtain the optimal one, and compare to other methods to evaluate this performance.

  19. THE IMPLEMENTATION OF THE 5E MODEL STAGES TO BUILD STUDENTS’ VOCABULARY

    Directory of Open Access Journals (Sweden)

    Muhammad Rochman

    2015-12-01

    Full Text Available There are stages of human to learn something. In early ages, they will learn simplest things to the complicated ones. A learning process of human is started with and introductory and it tries to connect with their prior knowledge to the new one. Children begin to curious about what they want to know and start to make some questions about what they want to know. In the process of finding the answers of their own questions, they will interact with others and try to share the knowledge in this process. The result of this study illustrates that the implementation of the 5E model in teaching vocabulary that can enhance the students’ vocabulary achievement and successfully encourages them to actively and enthusiastically take part in the teaching-learning process of vocabulary through group task. Keywords: implementation, vocabulary, vocabulary course, and 5E model

  20. Computer modelling of structures with account of the construction stages and the time dependent material properties

    Directory of Open Access Journals (Sweden)

    Traykov Alexander

    2015-01-01

    Full Text Available Numerical studies are performed on computer models taking into account the stages of construction and time dependent material properties defined in two forms. A 2D model of three storey two spans frame is created. The first form deals with material defined in the usual design practice way - without taking into account the time dependent properties of the concrete. The second form creep and shrinkage of the concrete are taken into account. Displacements and internal forces in specific elements and sections are reported. The influence of the time dependent material properties on the displacement and the internal forces in the main structural elements is tracked down. The results corresponding to the two forms of material definition are compared together as well as with the results obtained by the usual design calculations. Conclusions on the influence of the concrete creep and shrinkage during the construction towards structural behaviour are made.

  1. Time Delayed Stage-Structured Predator-Prey Model with Birth Pulse and Pest Control Tactics

    Directory of Open Access Journals (Sweden)

    Mei Yan

    2014-01-01

    Full Text Available Normally, chemical pesticides kill not only pests but also their natural enemies. In order to better control the pests, two-time delayed stage-structured predator-prey models with birth pulse and pest control tactics are proposed and analyzed by using impulsive differential equations in present work. The stability threshold conditions for the mature prey-eradication periodic solutions of two models are derived, respectively. The effects of key parameters including killing efficiency rate, pulse period, the maximum birth effort per unit of time of natural enemy, and maturation time of prey on the threshold values are discussed in more detail. By comparing the two threshold values of mature prey-extinction, we provide the fact that the second control tactic is more effective than the first control method.

  2. Delimitation of the user in the creation stages, modeling and prototyping of the clothing product

    Directory of Open Access Journals (Sweden)

    Elen Makara

    2016-12-01

    Full Text Available Because of complaints of clothes that do not fit well and bother, or even the difficulty of acquiring a suitable outfit for an occasion, to the clothing industry may be failing to consider the user in developing their products. The aim of this paper was to determine whether the steps for creating, modeling and prototyping of garment products the user is being considered, as for a design project is right to consider it at all stages of development. For this a literature review and interviews with professionals was held. With the results we can see the difficulty that professionals have to define the public to create the pieces. We also found that most professionals understand the importance of measures table however end up adjusting the empirically, and the realization of prototype testing many choose models that does not match the reality of the public company

  3. [Quantitative models between canopy hyperspectrum and its component features at apple tree prosperous fruit stage].

    Science.gov (United States)

    Wang, Ling; Zhao, Geng-xing; Zhu, Xi-cun; Lei, Tong; Dong, Fang

    2010-10-01

    Hyperspectral technique has become the basis of quantitative remote sensing. Hyperspectrum of apple tree canopy at prosperous fruit stage consists of the complex information of fruits, leaves, stocks, soil and reflecting films, which was mostly affected by component features of canopy at this stage. First, the hyperspectrum of 18 sample apple trees with reflecting films was compared with that of 44 trees without reflecting films. It could be seen that the impact of reflecting films on reflectance was obvious, so the sample trees with ground reflecting films should be separated to analyze from those without ground films. Secondly, nine indexes of canopy components were built based on classified digital photos of 44 apple trees without ground films. Thirdly, the correlation between the nine indexes and canopy reflectance including some kinds of conversion data was analyzed. The results showed that the correlation between reflectance and the ratio of fruit to leaf was the best, among which the max coefficient reached 0.815, and the correlation between reflectance and the ratio of leaf was a little better than that between reflectance and the density of fruit. Then models of correlation analysis, linear regression, BP neural network and support vector regression were taken to explain the quantitative relationship between the hyperspectral reflectance and the ratio of fruit to leaf with the softwares of DPS and LIBSVM. It was feasible that all of the four models in 611-680 nm characteristic band are feasible to be used to predict, while the model accuracy of BP neural network and support vector regression was better than one-variable linear regression and multi-variable regression, and the accuracy of support vector regression model was the best. This study will be served as a reliable theoretical reference for the yield estimation of apples based on remote sensing data.

  4. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    2014-03-01

    Mar 1, 2014 ... Its underlying biological mechanism remains unclear and no well-documented drug and ... Objectives: To explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi. (GST-Pi) in the ..... in an animal model of Parkinson's disease: Therapeutic perspectives. Nutri-.

  5. Cox regression with missing covariate data using a modified partial likelihood method

    DEFF Research Database (Denmark)

    Martinussen, Torben; Holst, Klaus K.; Scheike, Thomas H.

    2016-01-01

    Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard...

  6. The genealogical decomposition of a matrix population model with applications to the aggregation of stages.

    Science.gov (United States)

    Bienvenu, François; Akçay, Erol; Legendre, Stéphane; McCandlish, David M

    2017-06-01

    Matrix projection models are a central tool in many areas of population biology. In most applications, one starts from the projection matrix to quantify the asymptotic growth rate of the population (the dominant eigenvalue), the stable stage distribution, and the reproductive values (the dominant right and left eigenvectors, respectively). Any primitive projection matrix also has an associated ergodic Markov chain that contains information about the genealogy of the population. In this paper, we show that these facts can be used to specify any matrix population model as a triple consisting of the ergodic Markov matrix, the dominant eigenvalue and one of the corresponding eigenvectors. This decomposition of the projection matrix separates properties associated with lineages from those associated with individuals. It also clarifies the relationships between many quantities commonly used to describe such models, including the relationship between eigenvalue sensitivities and elasticities. We illustrate the utility of such a decomposition by introducing a new method for aggregating classes in a matrix population model to produce a simpler model with a smaller number of classes. Unlike the standard method, our method has the advantage of preserving reproductive values and elasticities. It also has conceptually satisfying properties such as commuting with changes of units. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A preventive maintenance model with a two-level inspection policy based on a three-stage failure process

    International Nuclear Information System (INIS)

    Wang, Wenbin; Zhao, Fei; Peng, Rui

    2014-01-01

    Inspection is always an important preventive maintenance (PM) activity and can have different depths and cover all or part of plant systems. This paper introduces a two-level inspection policy model for a single component plant system based on a three-stage failure process. Such a failure process divides the system′s life into three stages: good, minor defective and severe defective stages. The first level of inspection, the minor inspection, can only identify the minor defective stage with a certain probability, but can always reveal the severe defective stage. The major inspection can however identify both defective stages perfectly. Once the system is found to be in the minor defective stage, a shortened inspection interval is adopted. If however the system is found to be in the severe defective stage, we may delay the maintenance action if the time to the next planned PM window is less than a threshold level, but otherwise, replace immediately. This corresponds to the well adopted maintenance policy in practice such as periodic inspections with planned PMs. A numerical example is presented to demonstrate the proposed model by comparing with other models. - Highlights: • The system′s deterioration goes through a three-stage process, namely, normal, minor defective and severe defective. • Two levels of inspections are proposed, e.g., minor and major inspections. • Once the minor defective stage is found, instead of taking a maintenance action, a shortened inspection interval is recommended. • When the severe defective stage is found, we delay the maintenance according to the threshold to the next PM. • The decision variables are the inspection intervals and the threshold to PM

  8. Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

    Science.gov (United States)

    A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolat...

  9. Værktøjskasse til Agil Stage-Gate®: Ny model for udviklingsprojekter i mellemstore virksomheder

    DEFF Research Database (Denmark)

    Vedsmand, Tomas; Edwards, Kasper; Hvidt, Nicoline

    Denne værktøjskasse er et tillæg for guiden Agil Stage-Gate: Ny model for udviklingsprojekter i mellemstore virksomheder. (http://dx.doi.org/10.11581/DTU:00000028)......Denne værktøjskasse er et tillæg for guiden Agil Stage-Gate: Ny model for udviklingsprojekter i mellemstore virksomheder. (http://dx.doi.org/10.11581/DTU:00000028)...

  10. Model for Physical Education Content Standards at Early Stages of Primary Education in the Republic of Macedonia

    OpenAIRE

    Klincarov, Ilija; Popeska, Biljana

    2011-01-01

    The aim of this article is to propose a model for designing national physical education content standards in early stages of primary education in the Republic of Macedonia. Proposed model is based on the findings about motor structure of children at the early stage of primary education obtained in researches realized in 5 primary schools in Skopje, the Republic of Macedonia, in relation with Macedonian PE curriculum, and overarching standards for children at this age in California, USA,chosen...

  11. A Smoothing Algorithm for a New Two-Stage Stochastic Model of Supply Chain Based on Sample Average Approximation

    OpenAIRE

    Liu Yang; Yao Xiong; Xiao-jiao Tong

    2017-01-01

    We construct a new two-stage stochastic model of supply chain with multiple factories and distributors for perishable product. By introducing a second-order stochastic dominance (SSD) constraint, we can describe the preference consistency of the risk taker while minimizing the expected cost of company. To solve this problem, we convert it into a one-stage stochastic model equivalently; then we use sample average approximation (SAA) method to approximate the expected values of the underlying r...

  12. Market splitting in Germany – New evidence from a three-stage numerical model of Europe

    International Nuclear Information System (INIS)

    Trepper, Katrin; Bucksteeg, Michael; Weber, Christoph

    2015-01-01

    With the sharp increase in redispatch measures seen during recent years, the importance of an efficient congestion management has increased, particularly in Germany. As the current market design, with a single bidding area, ignores the physical constraints of the transmission grid, there is an ongoing discussion about introducing price zones. Against this background, we develop a three-stage approach to model redispatch and market splitting for Germany while considering interactions with interconnected countries. We identify an increasing spatial imbalance between generation and load and delays in grid extension as being the main drivers for the increase of modeled redispatch volumes from 2012 to 2020. We show that market splitting reduces imminent congestion although results are sensitive to the zonal delimitation and corresponding net transfer capacities. The overall welfare effect is negligible, but price differences between the bidding areas investigated, i.e. one Northern and Southern price zone, result in considerable distributional effects. While consumers in Northern Germany would benefit – producer rents and in particular the value of wind energy would decrease – the opposite is true for Southern Germany. We conclude that market splitting constitutes a solution to reduce redispatch measures as long as transmission grid expansion is further delayed. - Highlights: • A three-stage approach to model redispatch and zonal pricing is proposed. • Energy transition will lead to a tripling of congestion in Germany until 2020. • Market splitting in Germany substantially reduces redispatch measures. • Overall welfare gain is negligible, but considerable distributional effects occur. • The beneficial effects of market splitting depend strongly on its design.

  13. Mechanical modelling of the Singoe deformation zone. Site descriptive modelling Forsmark stage 2.1

    Energy Technology Data Exchange (ETDEWEB)

    Glamheden, Rune; Maersk Hansen, Lars; Fredriksson, Anders; Bergkvist, Lars; Markstroem, Ingemar; Elfstroem, Mats [Golder Associates AB (Sweden)

    2007-02-15

    This project aims at demonstrating the theoretical approach developed by SKB for determination of mechanical properties of large deformation zones, in particular the Singoe deformation zone. Up to now, only bedrock and minor deformation zones have been characterized by means of this methodology, which has been modified for this project. The Singoe deformation zone is taken as a reference object to get a more comprehensive picture of the structure, which could be incorporated in a future version of the SDM of Forsmark. Furthermore, the Singoe Zone has been chosen because of available data from four tunnels. Scope of work has included compilation and analysis of geological information from site investigations and documentation of existing tunnels. Results have been analyzed and demonstrated by means of RVS-visualization. Numerical modelling has been used to obtain mechanical properties. Numerical modelling has also been carried out in order to verify the results by comparison of calculated and measured deformations. Compilation of various structures in the four tunnels coincides largely with a magnetic anomaly and also with the estimated width. Based on the study it is clear that the Singoe deformation zone has a heterogeneous nature. The number of fracture zones associated with the deformation zone varies on either side of the zone, as does the transition zone between host rock and the Singoe zone. The overall impression from the study is that the results demonstrate that the methodology used for simulating of equivalent mechanical properties is an applicable and adequate method, also in case of large deformation zones. Typical rock mechanical parameters of the Singoe deformations that can be used in the regional stress model considering the zone to be a single fracture are: 200 MPa/m in normal stiffness, 10-15 MPa/m in shear stiffness, 0.4 MPa in cohesion and 31.5 degrees in friction angle.

  14. Mechanical modelling of the Singoe deformation zone. Site descriptive modelling Forsmark stage 2.1

    International Nuclear Information System (INIS)

    Glamheden, Rune; Maersk Hansen, Lars; Fredriksson, Anders; Bergkvist, Lars; Markstroem, Ingemar; Elfstroem, Mats

    2007-02-01

    This project aims at demonstrating the theoretical approach developed by SKB for determination of mechanical properties of large deformation zones, in particular the Singoe deformation zone. Up to now, only bedrock and minor deformation zones have been characterized by means of this methodology, which has been modified for this project. The Singoe deformation zone is taken as a reference object to get a more comprehensive picture of the structure, which could be incorporated in a future version of the SDM of Forsmark. Furthermore, the Singoe Zone has been chosen because of available data from four tunnels. Scope of work has included compilation and analysis of geological information from site investigations and documentation of existing tunnels. Results have been analyzed and demonstrated by means of RVS-visualization. Numerical modelling has been used to obtain mechanical properties. Numerical modelling has also been carried out in order to verify the results by comparison of calculated and measured deformations. Compilation of various structures in the four tunnels coincides largely with a magnetic anomaly and also with the estimated width. Based on the study it is clear that the Singoe deformation zone has a heterogeneous nature. The number of fracture zones associated with the deformation zone varies on either side of the zone, as does the transition zone between host rock and the Singoe zone. The overall impression from the study is that the results demonstrate that the methodology used for simulating of equivalent mechanical properties is an applicable and adequate method, also in case of large deformation zones. Typical rock mechanical parameters of the Singoe deformations that can be used in the regional stress model considering the zone to be a single fracture are: 200 MPa/m in normal stiffness, 10-15 MPa/m in shear stiffness, 0.4 MPa in cohesion and 31.5 degrees in friction angle

  15. Modelling Pseudocalanus elongatus stage-structured population dynamics embedded in a water column ecosystem model for the northern North Sea

    Science.gov (United States)

    Moll, Andreas; Stegert, Christoph

    2007-01-01

    This paper outlines an approach to couple a structured zooplankton population model with state variables for eggs, nauplii, two copepodites stages and adults adapted to Pseudocalanus elongatus into the complex marine ecosystem model ECOHAM2 with 13 state variables resolving the carbon and nitrogen cycle. Different temperature and food scenarios derived from laboratory culture studies were examined to improve the process parameterisation for copepod stage dependent development processes. To study annual cycles under realistic weather and hydrographic conditions, the coupled ecosystem-zooplankton model is applied to a water column in the northern North Sea. The main ecosystem state variables were validated against observed monthly mean values. Then vertical profiles of selected state variables were compared to the physical forcing to study differences between zooplankton as one biomass state variable or partitioned into five population state variables. Simulated generation times are more affected by temperature than food conditions except during the spring phytoplankton bloom. Up to six generations within the annual cycle can be discerned in the simulation.

  16. Transcriptome profiling of the cysticercus stage of the laboratory model Taenia crassiceps, strain ORF.

    Science.gov (United States)

    García-Montoya, Gisela M; Mesa-Arango, Jairo A; Isaza-Agudelo, Juan P; Agudelo-Lopez, Sonia P; Cabarcas, Felipe; Barrera, Luis F; Alzate, Juan F

    2016-02-01

    Neurocysticercosis (NC) is a serious public health problem mainly in developing countries. NC caused by the cysticercus stage from cestode Taenia solium is considered by the WHO and ITFDE as a potentially eradicable disease. Definitive diagnosis of NC is challenging because of the unspecific clinical manifestations such as the non-definitive evidence presented by neuroimaging (in most cases) and the lack of definitive serological test. Taenia crassiceps (ORF strain) is a cestode closely related to T. solium and it has frequently been used as a source of antigens for immunodiagnostics. A murine model to study host immune response to infection has also been established by using T. crassiceps. Despite the extensive use of T. crassiceps for research, molecular information for this cestode is scarce in public databases. With the aim of providing more extensive information on T. crassiceps biology, an RNA-seq experiment and subsequent bioinformatic transcriptome processing of this cestode parasite mRNA in its cysticercus stage were carried out. A total of 227,082 read/ESTs were sequenced using the 454-GS FLX Titanium technology and assembled into 10,787 contigs. This transcriptome dataset represents new and valuable molecular information of the cestode T. crassiceps (ORF). This information will substantially improve public information and will help to achieve a better understanding of the biology of T. crassiceps and to identify target proteins for serodiagnosis and vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Modeling bacterial attachment to surfaces as an early stage of biofilm development.

    Science.gov (United States)

    El Moustaid, Fadoua; Eladdadi, Amina; Uys, Lafras

    2013-06-01

    Biofilms are present in all natural, medical and industrial surroundings where bacteria live. Biofilm formation is a key factor in the growth and transport of both beneficial and harmful bacteria. While much is known about the later stages of biofilm formation, less is known about its initiation which is an important first step in the biofilm formation. In this paper, we develop a non-linear system of partial differential equations of Keller-Segel type model in one-dimensional space, which couples the dynamics of bacterial movement to that of the sensing molecules. In this case, bacteria perform a biased random walk towards the sensing molecules. We derive the boundary conditions of the adhesion of bacteria to a surface using zero-Dirichlet boundary conditions, while the equation describing sensing molecules at the interface needed particular conditions to be set. The numerical results show the profile of bacteria within the space and the time evolution of the density within the free-space and on the surface. Testing different parameter values indicate that significant amount of sensing molecules present on the surface leads to a faster bacterial movement toward the surface which is the first step of biofilm initiation. Our work gives rise to results that agree with the biological description of the early stages of biofilm formation.

  18. One- and two-stage Arrhenius models for pharmaceutical shelf life prediction.

    Science.gov (United States)

    Fan, Zhewen; Zhang, Lanju

    2015-01-01

    One of the most challenging aspects of the pharmaceutical development is the demonstration and estimation of chemical stability. It is imperative that pharmaceutical products be stable for two or more years. Long-term stability studies are required to support such shelf life claim at registration. However, during drug development to facilitate formulation and dosage form selection, an accelerated stability study with stressed storage condition is preferred to quickly obtain a good prediction of shelf life under ambient storage conditions. Such a prediction typically uses Arrhenius equation that describes relationship between degradation rate and temperature (and humidity). Existing methods usually rely on the assumption of normality of the errors. In addition, shelf life projection is usually based on confidence band of a regression line. However, the coverage probability of a method is often overlooked or under-reported. In this paper, we introduce two nonparametric bootstrap procedures for shelf life estimation based on accelerated stability testing, and compare them with a one-stage nonlinear Arrhenius prediction model. Our simulation results demonstrate that one-stage nonlinear Arrhenius method has significant lower coverage than nominal levels. Our bootstrap method gave better coverage and led to a shelf life prediction closer to that based on long-term stability data.

  19. Mathematical Model of the One-stage Magneto-optical Sensor Based on Faraday Effect

    Science.gov (United States)

    Babaev, O. G.; Paranin, V. D.; Sinitsin, L. I.

    2018-01-01

    The aim of this work is to refine a model of magneto-optical sensors based on Faraday’s longitudinal magneto-optical effect. The tasks of the study include computer modeling and analysis of the transfer characteristic of a single-stage magneto-optical sensor for various polarization of the input beam and non-ideal optical components. The proposed mathematical model and software make it possible to take into account the non-ideal characteristics of film polaroids observed in operation in the near infrared region and at increased temperatures. On the basis of the results of the model analysis it was found that the dependence of normalized transmission T(γ2) has periodic nature. Choosing the angle (γ 2-γ 1) makes it possible to shift the initial operation point and change the sensitivity dT/dγ 2. The influence of the input beam polarization increases with the increase of polaroid parameter deviation from ideal and shows itself as reduction of modulation depth and angular shift of the sensor conversion response.

  20. A Risk-Based Interval Two-Stage Programming Model for Agricultural System Management under Uncertainty

    Directory of Open Access Journals (Sweden)

    Ye Xu

    2016-01-01

    Full Text Available Nonpoint source (NPS pollution caused by agricultural activities is main reason that water quality in watershed becomes worse, even leading to deterioration. Moreover, pollution control is accompanied with revenue’s fall for agricultural system. How to design and generate a cost-effective and environmentally friendly agricultural production pattern is a critical issue for local managers. In this study, a risk-based interval two-stage programming model (RBITSP was developed. Compared to general ITSP model, significant contribution made by RBITSP model was that it emphasized importance of financial risk under various probabilistic levels, rather than only being concentrated on expected economic benefit, where risk is expressed as the probability of not meeting target profit under each individual scenario realization. This way effectively avoided solutions’ inaccuracy caused by traditional expected objective function and generated a variety of solutions through adjusting weight coefficients, which reflected trade-off between system economy and reliability. A case study of agricultural production management with the Tai Lake watershed was used to demonstrate superiority of proposed model. Obtained results could be a base for designing land-structure adjustment patterns and farmland retirement schemes and realizing balance of system benefit, system-failure risk, and water-body protection.

  1. Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process

    Directory of Open Access Journals (Sweden)

    Konrad Krysiak-Baltyn

    2018-04-01

    Full Text Available Cost effective and scalable methods for phage production are required to meet an increasing demand for phage, as an alternative to antibiotics. Computational models can assist the optimization of such production processes. A model is developed here that can simulate the dynamics of phage population growth and production in a two-stage, self-cycling process. The model incorporates variable infection parameters as a function of bacterial growth rate and employs ordinary differential equations, allowing application to a setup with multiple reactors. The model provides simple cost estimates as a function of key operational parameters including substrate concentration, feed volume and cycling times. For the phage and bacteria pairing examined, costs and productivity varied by three orders of magnitude, with the lowest cost found to be most sensitive to the influent substrate concentration and low level setting in the first vessel. An example case study of phage production is also presented, showing how parameter values affect the production costs and estimating production times. The approach presented is flexible and can be used to optimize phage production at laboratory or factory scale by minimizing costs or maximizing productivity.

  2. Autobiography and Anorexia: A Qualitative Alternative to Prochaska and DiClemente's Stages of Change Model

    Directory of Open Access Journals (Sweden)

    Félix Díaz

    2012-11-01

    Full Text Available In this article, we propose a qualitative approach to the study of the ways in which people face good and poor health issues. During the last 30 years, Prochaska and DiClemente's "trans-theoretical model" (1982, 1983, 1984, 1986, 1992 has gained relevance as a model to assess disposition for change in patients. We revise the features of the model and its common techniques to assess stages of change, underlining its methodological and conceptual problems. Particularly, we discuss the paradoxes set by "pre-contemplation" as a concept; the exogenous definition of human problems in terms of institutional and clinical criteria; and the ambiguity of the model, where the purpose of accompanying and orienting the patient contrasts with the imposition of problem definitions and solution strategies. We propose a narrative analysis of autobiographies of patients as an alternative that recasts their own notions of "change," "problem," and "vital trajectory." We illustrate this possibility with the analysis of an autobiographic interview with a woman who has a history of anorexia. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1203209

  3. A cooperation model based on CVaR measure for a two-stage supply chain

    Science.gov (United States)

    Xu, Xinsheng; Meng, Zhiqing; Shen, Rui

    2015-07-01

    In this paper, we introduce a cooperation model (CM) for the two-stage supply chain consisting of a manufacturer and a retailer. In this model, it is supposed that the objective of the manufacturer is to maximise his/her profit while the objective of the retailer is to minimise his/her CVaR while controlling the risk originating from fluctuation in market demand. In reality, the manufacturer and the retailer would like to choose their own decisions as to wholesale price and order quantity to optimise their own objectives, resulting the fact that the expected decision of the manufacturer and that of the retailer may conflict with each other. Then, to achieve cooperation, the manufacturer and the retailer both need to give some concessions. The proposed model aims to coordinate the decisions of the manufacturer and the retailer, and balance the concessions of the two in their cooperation. We introduce an s* - optimal equilibrium solution in this model, which can decide the minimum concession that the manufacturer and the retailer need to give for their cooperation, and prove that the s* - optimal equilibrium solution can be obtained by solving a goal programming problem. Further, the case of different concessions made by the manufacturer and the retailer is also discussed. Numerical results show that the CM is efficient in dealing with the cooperations between the supplier and the retailer.

  4. An integrated multi-stage supply chain inventory model with imperfect production process

    Directory of Open Access Journals (Sweden)

    Soumita Kundu

    2015-09-01

    Full Text Available This paper deals with an integrated multi-stage supply chain inventory model with the objective of cost minimization by synchronizing the replenishment decisions for procurement, production and delivery activities. The supply chain structure examined here consists of a single manufacturer with multi-buyer where manufacturer orders a fixed quantity of raw material from outside suppliers, processes the materials and delivers the finished products in unequal shipments to each customer. In this paper, we consider an imperfect production system, which produces defective items randomly and assumes that all defective items could be reworked. A simple algorithm is developed to obtain an optimal production policy, which minimizes the expected average total cost of the integrated production-inventory system.

  5. The relative efficiency of Iranian's rural traffic police: a three-stage DEA model.

    Science.gov (United States)

    Rahimi, Habibollah; Soori, Hamid; Nazari, Seyed Saeed Hashemi; Motevalian, Seyed Abbas; Azar, Adel; Momeni, Eskandar; Javartani, Mehdi

    2017-10-13

    Road traffic Injuries (RTIs) as a health problem imposes governments to implement different interventions. Target achievement in this issue required effective and efficient measures. Efficiency evaluation of traffic police as one of the responsible administrators is necessary for resource management. Therefore, this study conducted to measure Iran's rural traffic police efficiency. This was an ecological study. To obtain pure efficiency score, three-stage DEA model was conducted with seven inputs and three output variables. At the first stage, crude efficiency score was measured with BCC-O model. Next, to extract the effects of socioeconomic, demographic, traffic count and road infrastructure as the environmental variables and statistical noise, the Stochastic Frontier Analysis (SFA) model was applied and the output values were modified according to similar environment and statistical noise conditions. Then, the pure efficiency score was measured using modified outputs and BCC-O model. In total, the efficiency score of 198 police stations from 24 provinces of 31 provinces were measured. The annual means (standard deviation) of damage, injury and fatal accidents were 247.7 (258.4), 184.9 (176.9), and 28.7 (19.5), respectively. Input averages were 5.9 (3.0) patrol teams, 0.5% (0.2) manpower proportions, 7.5 (2.9) patrol cars, 0.5 (1.3) motorcycles, 77,279.1 (46,794.7) penalties, 90.9 (2.8) cultural and educational activity score, 0.7 (2.4) speed cameras. The SFA model showed non-significant differences between police station performances and the most differences attributed to the environmental and random error. One-way main road, by road, traffic count and the number of household owning motorcycle had significant positive relations with inefficiency score. The length of freeway/highway and literacy rate variables had negative relations, significantly. Pure efficiency score was with mean of 0.95 and SD of 0.09. Iran's traffic police has potential opportunity to reduce

  6. Two-Stage orders sequencing system for mixed-model assembly

    Science.gov (United States)

    Zemczak, M.; Skolud, B.; Krenczyk, D.

    2015-11-01

    In the paper, the authors focus on the NP-hard problem of orders sequencing, formulated similarly to Car Sequencing Problem (CSP). The object of the research is the assembly line in an automotive industry company, on which few different models of products, each in a certain number of versions, are assembled on the shared resources, set in a line. Such production type is usually determined as a mixed-model production, and arose from the necessity of manufacturing customized products on the basis of very specific orders from single clients. The producers are nowadays obliged to provide each client the possibility to determine a huge amount of the features of the product they are willing to buy, as the competition in the automotive market is large. Due to the previously mentioned nature of the problem (NP-hard), in the given time period only satisfactory solutions are sought, as the optimal solution method has not yet been found. Most of the researchers that implemented inaccurate methods (e.g. evolutionary algorithms) to solving sequencing problems dropped the research after testing phase, as they were not able to obtain reproducible results, and met problems while determining the quality of the received solutions. Therefore a new approach to solving the problem, presented in this paper as a sequencing system is being developed. The sequencing system consists of a set of determined rules, implemented into computer environment. The system itself works in two stages. First of them is connected with the determination of a place in the storage buffer to which certain production orders should be sent. In the second stage of functioning, precise sets of sequences are determined and evaluated for certain parts of the storage buffer under certain criteria.

  7. Multi-stage IT project evaluation: The flexibility value obtained by implementing and resolving Berk, Green and Naik (2004) model

    Science.gov (United States)

    Abid, Fathi; Guermazi, Dorra

    2009-11-01

    In this paper, we evaluate a multi-stage information technology investment project, by implementing and resolving Berk, Green and Naik's (2004) model, which takes into account specific features of IT projects and considers the real option to suspend investment at each stage. We present a particular case of the model where the project value is the solution of an optimal control problem with a single state variable. In this case, the model is more intuitive and tractable. The case study confirms the practical potential of the model and highlights the importance of the real-option approach compared to classical discounted cash flow techniques in the valuation of IT projects.

  8. A Two-Stage Queue Model to Optimize Layout of Urban Drainage System considering Extreme Rainstorms

    Directory of Open Access Journals (Sweden)

    Xinhua He

    2017-01-01

    Full Text Available Extreme rainstorm is a main factor to cause urban floods when urban drainage system cannot discharge stormwater successfully. This paper investigates distribution feature of rainstorms and draining process of urban drainage systems and uses a two-stage single-counter queue method M/M/1→M/D/1 to model urban drainage system. The model emphasizes randomness of extreme rainstorms, fuzziness of draining process, and construction and operation cost of drainage system. Its two objectives are total cost of construction and operation and overall sojourn time of stormwater. An improved genetic algorithm is redesigned to solve this complex nondeterministic problem, which incorporates with stochastic and fuzzy characteristics in whole drainage process. A numerical example in Shanghai illustrates how to implement the model, and comparisons with alternative algorithms show its performance in computational flexibility and efficiency. Discussions on sensitivity of four main parameters, that is, quantity of pump stations, drainage pipe diameter, rainstorm precipitation intensity, and confidence levels, are also presented to provide guidance for designing urban drainage system.

  9. A stage-structured, spatially explicit migration model for Myotis bats: mortality location affects system dynamics

    Science.gov (United States)

    Erickson, Richard A.; Thogmartin, Wayne E.; Russell, Robin E.; Diffendorfer, James E.; Szymanski, Jennifer A.

    2014-01-01

    Bats are ecologically and economically important species because they consume insects, transport nutrients, and pollinate flowers.  Many species of bats, including those in the Myotis genus, are facing population decline and increased extinction risk.  Despite these conservation concerns, few models exist for providing insight into the population dynamics of bats in a spatially explicit context.  We developed a model for bats by considering the stage-structured colonial life history of Myotis bats with their annual migration behavior.  This model provided insight into network dynamics.  We specifically focused on two Myotis species living in the eastern United States: the Indiana bat (M. sodalis), which is a Federally listed endangered species, and the little brown bat (M. lucifugus), which is under consideration for listing as an endangered species.  We found that multiple equilibria exist for the local, migratory subpopulations even though the total population was constant.  These equilibria suggest the location and magnitude of stressors such as White-nose Syndrome, meteorological phenomena, or impacts of wind turbines on survival influence system dynamics and risk of population extirpation in difficult to predict ways.

  10. Spleen dynamic contrast-enhanced magnetic resonance imaging as a new method for staging liver fibrosis in a piglet model.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available OBJECTIVE: To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. MATERIALS AND METHODS: Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP, positive enhancement integral (PEI, maximum slope of increase (MSI and maximum slope of decrease (MSD of spleen were measured, and statistically analyzed to stage this disease. RESULTS: Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P0.05, and decreased from stage 2 to 4 (P0.05. Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1-4, between 0-1 and 2-4, between 0-2 and 3-4, or between 0-3 and 4 (all P<0.01. MSD could discriminate between 0-2 and 3-4 (P = 0.006, or between 0-3 and 4 (P = 0.012. MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively. PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively. CONCLUSION: Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.

  11. Stage-dependent alterations of progenitor cell proliferation and neurogenesis in an animal model of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Vetreno, Ryan P; Klintsova, Anna; Savage, Lisa M

    2011-05-19

    Alcohol-induced Wernicke-Korsakoff syndrome (WKS) culminates in bilateral diencephalic lesion and severe amnesia. Using the pyrithiamine-induced thiamine deficiency (PTD) animal paradigm of WKS, our laboratory has demonstrated hippocampal dysfunction in the absence of gross anatomical pathology. Extensive literature has revealed reduced hippocampal neurogenesis following a neuropathological insult, which might contribute to hippocampus-based learning and memory impairments. Thus, the current investigation was conducted to determine whether PTD treatment altered hippocampal neurogenesis in a stage-dependent fashion. Male Sprague-Dawley rats were assigned to one of 4 stages of thiamine deficiency based on behavioral symptoms: pre-symptomatic stage, ataxic stage, early post-opisthotonus stage, or the late post-opisthotonus stage. The S-phase mitotic marker 5'-bromo-2'-deoxyuridine (BrdU) was administered at the conclusion of each stage following thiamine restoration and subjects were perfused 24 hours or 28 days after BrdU to assess cellular proliferation or neurogenesis and survival, respectively. Dorsal hippocampal sections were immunostained for BrdU (proliferating cell marker), NeuN (neurons), GFAP (astrocytes), Iba-1 (microglia), and O4 (oligodendrocytes). The PTD treatment increased progenitor cell proliferation and survival during the early post-opisthotonus stage. However, levels of neurogenesis were reduced during this stage as well as the late post-opisthotonus stage where there was also an increase in astrocytogenesis. The diminished numbers of newly generated neurons (BrdU/NeuN co-localization) was paralleled by increased BrdU cells that did not co-localize with any of the phenotypic markers during these later stages. These data demonstrate that long-term alterations in neurogenesis and gliogenesis might contribute to the observed hippocampal dysfunction in the PTD model and human WKS. Published by Elsevier B.V.

  12. The Application of Extended Cox Proportional Hazard Method for Estimating Survival Time of Breast Cancer

    Science.gov (United States)

    Husain, Hartina; Astuti Thamrin, Sri; Tahir, Sulaiha; Mukhlisin, Ahmad; Mirna Apriani, M.

    2018-03-01

    Breast cancer is one type of cancer that is the leading cause of death worldwide. This study aims to model the factors that affect the survival time and rate of cure of breast cancer patients. The extended cox model, which is a modification of the proportional hazard cox model in which the proportional hazard assumptions are not met, is used in this study. The maximum likelihood estimation approach is used to estimate the parameters of the model. This method is then applied to medical record data of breast cancer patient in 2011-2016, which is taken from Hasanuddin University Education Hospital. The results obtained indicate that the factors that affect the survival time of breast cancer patients are malignancy and leukocyte levels.

  13. An experimental two-stage rat model of lung carcinoma initiated by radon exposure

    International Nuclear Information System (INIS)

    Poncy, J.L.; Laroque, P.; Fritsch, P.; Monchaux, G.; Masse, R.; Chameaud, J.

    1992-01-01

    We present the results of a two-stage biological model of lung carcinogenesis in rats. The histogenesis of these tumors was examined, and DNA content of lung cells was measured by flow cytometry during the evolving neoplastic stage. Tumors were induced in rat lungs after radon inhalation (1600 WLM) followed by a promoter treatment; six intramuscular injections of 5,6-benzoflavone (25 mg/kg of body weight/injection) every 2 wk. Less than 3 mo after the first injection of benzoflavone, squamous cell carcinoma was observed in the lungs of all rats exposed to radon. The preneoplastic lesions gradually developed as follows: hyperplastic bronchiolar-type cells migrated to the alveoli from cells that proliferated in bronchioles and alveolar ducts; initial lesions were observed in almost all respiratory bronchioles. From some hyperplasias, epidermoid metaplasias arose distally, forming nodular epidermoid lesions in alveoli, which progressed to form squamous papilloma and, finally, epidermoid carcinomas. The histogenesis of these experimentally induced epidermoid carcinomas showed the bronchioloalveolar origin of the tumor. This factor must be considered when comparing these with human lesions; in humans, lung epidermoid carcinomas are thought to arise mainly in the first bronchial generations. The labeling index of pulmonary tissue after incorporation of 3 H-thymidine by the cells was 0.2% in control rats. This index reached a value of 1 to 2% in the hyperplastic area of the bronchioles and 10 to 15% in epidermoid nodules and epidermoid tumors, respectively. DNA cytometric analysis was performed on cell suspensions obtained after enzymatic treatment of paraffin sections of lungs from rats sacrificed during different stags of neoplastic transformations. Data showed the early appearance of a triploid cell population that grew during the evolution of nodular epidermoid lesions to epidermoid carcinomas

  14. A comparison of two-component and quadratic models to assess survival of irradiated stage-7 oocytes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Peres, C.A.; Koo, J.O.

    1981-01-01

    In this paper, the quadratic model to analyse data of this kind, i.e. S/S 0 = exp(-αD-bD 2 ), where S and Ssub(o) are defined as before is proposed is shown that the same biological interpretation can be given to the parameters α and A and to the parameters β and B. Furthermore it is shown that the quadratic model involves one probabilistic stage more than the two-component model, and therefore the quadratic model would perhaps be more appropriate as a dose-response model for survival of irradiated stage-7 oocytes of Drosophila melanogaster. In order to apply these results, the data presented by Sankaranarayanan and Sankaranarayanan and Volkers are reanalysed using the quadratic model. It is shown that the quadratic model fits better than the two-component model to the data in most situations. (orig./AJ)

  15. Large animal model of functional tricuspid regurgitation in pacing induced end-stage heart failure.

    Science.gov (United States)

    Malinowski, Marcin; Proudfoot, Alistair G; Langholz, David; Eberhart, Lenora; Brown, Michael; Schubert, Hans; Wodarek, Jeremy; Timek, Tomasz A

    2017-06-01

    Functional tricuspid regurgitation (FTR) is common in patients with advanced heart failure and frequently complicates left ventricular assist device implantation yet remains poorly understood. We set out to establish large animal model of FTR that could serve as a research platform to investigate the pathogenesis of FTR associated with end-stage heart failure. : Through right thoracotomy, ten adult sheep underwent implantation of pacemaker with epicardial LV lead, five sonomicrometry crystals on the right ventricle, and left and right ventricular telemetry pressure sensors during a beating heart off-pump procedure. After 5 ± 1 days of recovery, baseline haemodynamic, echocardiographic and sonomicrometry data were collected. Animals were paced thereafter at a rate of 220-240 beats/min until the development of heart failure and concomitant tricuspid regurgitation. : Three animals died during early recovery period and one during the pacing phase. Six surviving animals were paced for a mean of 14 ± 5 days. Cardiac function was significantly depressed compared to baseline, with LV ejection fraction falling from 69 ± 2% to 22 ± 4% ( P  tricuspid annulus (from 29.5 ± 1.6 to 36.5 ± 4.5 mm; P  = 0.01) and right ventricle (from 21.9 ± 0.2 to 30.3 ± 0.6 mm; P  = 0.03). Sonomicrometry derived contractility of RV free wall was depressed and at least moderate tricuspid insufficiency developed in all animals. : Biventricular dysfunction, tricuspid annular dilatation and significant FTR were observed in our model of ovine tachycardia induced cardiomyopathy. This animal model reflects the clinical situation of end-stage heart failure patients presenting for mechanical support. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  16. An appreciation of Bruce and Young's (1986) serial stage model of face naming after 25 years.

    Science.gov (United States)

    Hanley, J Richard

    2011-11-01

    The current status of Bruce and Young's (1986) serial model of face naming is discussed 25 years after its original publication. In the first part of the paper, evidence for and against the serial model is reviewed. It is argued that there is no compelling reason why we should abandon Bruce and Young's claim that recall of a name is contingent upon prior retrieval of semantic information about the person. The current status of the claim that people's names are more difficult to recall than the names of objects is then evaluated. Finally, an account of the anatomical location in the brain of Bruce and Young's three processing stages (face familiarity, retrieval of semantic information, retrieval of names) is suggested. In particular, there is evidence that biographical knowledge about familiar people is stored in the right anterior temporal lobes (ATL) and that the left temporal pole (TP) is heavily involved in retrieval of the names of familiar people. The issue of whether these brain areas play a similar role in object processing is also discussed. ©2011 The British Psychological Society.

  17. A 3-stage model of patient-centered communication for addressing cancer patients' emotional distress.

    Science.gov (United States)

    Dean, Marleah; Street, Richard L

    2014-02-01

    To describe pathways through which clinicians can more effectively respond to patients' emotions in ways that contribute to betterment of the patient's health and well-being. A representative review of literature on managing emotions in clinical consultations was conducted. A three-stage, conceptual model for assisting clinicians to more effectively address the challenges of recognizing, exploring, and managing cancer patients' emotional distress in the clinical encounter was developed. To enhance and enact recognition of patients' emotions, clinicians can engage in mindfulness, self-situational awareness, active listening, and facilitative communication. To enact exploration, clinicians can acknowledge and validate emotions and provide empathy. Finally, clinicians can provide information empathetically, identify therapeutic resources, and give referrals and interventions as needed to help lessen patients' emotional distress. This model serves as a framework for future research examining pathways that link clinicians' emotional cue recognition to patient-centered responses exploring a patient's emotional distress to therapeutic actions that contribute to improved psychological and emotional health. Specific communicative and cognitive strategies are presented that can help clinicians better recognize a patient's emotional distress and respond in ways that have therapeutic value. Published by Elsevier Ireland Ltd.

  18. Two-stage collaborative global optimization design model of the CHPG microgrid

    Science.gov (United States)

    Liao, Qingfen; Xu, Yeyan; Tang, Fei; Peng, Sicheng; Yang, Zheng

    2017-06-01

    With the continuous developing of technology and reducing of investment costs, renewable energy proportion in the power grid is becoming higher and higher because of the clean and environmental characteristics, which may need more larger-capacity energy storage devices, increasing the cost. A two-stage collaborative global optimization design model of the combined-heat-power-and-gas (abbreviated as CHPG) microgrid is proposed in this paper, to minimize the cost by using virtual storage without extending the existing storage system. P2G technology is used as virtual multi-energy storage in CHPG, which can coordinate the operation of electric energy network and natural gas network at the same time. Demand response is also one kind of good virtual storage, including economic guide for the DGs and heat pumps in demand side and priority scheduling of controllable loads. Two kinds of storage will coordinate to smooth the high-frequency fluctuations and low-frequency fluctuations of renewable energy respectively, and achieve a lower-cost operation scheme simultaneously. Finally, the feasibility and superiority of proposed design model is proved in a simulation of a CHPG microgrid.

  19. Simulation of the Two Stages Stretch-Blow Molding Process: Infrared Heating and Blowing Modeling

    International Nuclear Information System (INIS)

    Bordival, M.; Schmidt, F. M.; Le Maoult, Y.; Velay, V.

    2007-01-01

    In the Stretch-Blow Molding (SBM) process, the temperature distribution of the reheated perform affects drastically the blowing kinematic, the bottle thickness distribution, as well as the orientation induced by stretching. Consequently, mechanical and optical properties of the final bottle are closely related to heating conditions. In order to predict the 3D temperature distribution of a rotating preform, numerical software using control-volume method has been developed. Since PET behaves like a semi-transparent medium, the radiative flux absorption was computed using Beer Lambert law. In a second step, 2D axi-symmetric simulations of the SBM have been developed using the finite element package ABAQUS registered . Temperature profiles through the preform wall thickness and along its length were computed and applied as initial condition. Air pressure inside the preform was not considered as an input variable, but was automatically computed using a thermodynamic model. The heat transfer coefficient applied between the mold and the polymer was also measured. Finally, the G'sell law was used for modeling PET behavior. For both heating and blowing stage simulations, a good agreement has been observed with experimental measurements. This work is part of the European project ''APT P ACK'' (Advanced knowledge of Polymer deformation for Tomorrow's PACKaging)

  20. Simulation of the Two Stages Stretch-Blow Molding Process: Infrared Heating and Blowing Modeling

    Science.gov (United States)

    Bordival, M.; Schmidt, F. M.; Le Maoult, Y.; Velay, V.

    2007-05-01

    In the Stretch-Blow Molding (SBM) process, the temperature distribution of the reheated perform affects drastically the blowing kinematic, the bottle thickness distribution, as well as the orientation induced by stretching. Consequently, mechanical and optical properties of the final bottle are closely related to heating conditions. In order to predict the 3D temperature distribution of a rotating preform, numerical software using control-volume method has been developed. Since PET behaves like a semi-transparent medium, the radiative flux absorption was computed using Beer Lambert law. In a second step, 2D axi-symmetric simulations of the SBM have been developed using the finite element package ABAQUS®. Temperature profiles through the preform wall thickness and along its length were computed and applied as initial condition. Air pressure inside the preform was not considered as an input variable, but was automatically computed using a thermodynamic model. The heat transfer coefficient applied between the mold and the polymer was also measured. Finally, the G'sell law was used for modeling PET behavior. For both heating and blowing stage simulations, a good agreement has been observed with experimental measurements. This work is part of the European project "APT_PACK" (Advanced knowledge of Polymer deformation for Tomorrow's PACKaging).

  1. Utility-free heuristic models of two-option choice can mimic predictions of utility-stage models under many conditions

    Directory of Open Access Journals (Sweden)

    Steven T Piantadosi

    2015-04-01

    Full Text Available Economists often model choices as if decision-makers assign each option a scalar value variable, known as utility, and then select the option with the highest utility. It remains unclear whether as-if utility models describe real mental and neural steps in choice. Although choices alone cannot prove the existence of a utility stage in choice, utility transformations are often taken to provide the most parsimonious or psychologically plausible explanation for choice data. Here, we show that it is possible to mathematically transform a large set of common utility-stage two-option choice models (specifically ones in which dimensions are linearly separable into a psychologically plausible heuristic model (specifically, a dimensional prioritization heuristic that has no utility computation stage. We then show that under a range of plausible assumptions, both classes of model predict similar neural responses. These results highlight the difficulties in using neuroeconomic data to infer the existence of a value stage in choice.

  2. Utility-free heuristic models of two-option choice can mimic predictions of utility-stage models under many conditions

    Science.gov (United States)

    Piantadosi, Steven T.; Hayden, Benjamin Y.

    2015-01-01

    Economists often model choices as if decision-makers assign each option a scalar value variable, known as utility, and then select the option with the highest utility. It remains unclear whether as-if utility models describe real mental and neural steps in choice. Although choices alone cannot prove the existence of a utility stage, utility transformations are often taken to provide the most parsimonious or psychologically plausible explanation for choice data. Here, we show that it is possible to mathematically transform a large set of common utility-stage two-option choice models (specifically ones in which dimensions are can be decomposed into additive functions) into a heuristic model (specifically, a dimensional prioritization heuristic) that has no utility computation stage. We then show that under a range of plausible assumptions, both classes of model predict similar neural responses. These results highlight the difficulties in using neuroeconomic data to infer the existence of a value stage in choice. PMID:25914613

  3. Tracking cognitive processing stages with MEG : A spatio-temporal model of associative recognition in the brain

    NARCIS (Netherlands)

    Borst, Jelmer P; Ghuman, Avniel S; Anderson, John R

    2016-01-01

    In this study, we investigated the cognitive processing stages underlying associative recognition using MEG. Over the last four decades, a model of associative recognition has been developed in the ACT-R cognitive architecture. This model was first exclusively based on behavior, but was later

  4. Re-thinking stages of cognitive development: an appraisal of connectionist models on the balance scale task

    NARCIS (Netherlands)

    Quinlan, P.T.; van der Maas, H.L.J.; Jansen, B.R.J.; Booij, O.; Rendell, M.

    2007-01-01

    The present paper re-appraises connectionist attempts to explain how human cognitive development appears to progress through a series of sequential stages. Models of performance on the Piagetian balance scale task are the focus of attention. Limitations of these models are discussed and replications

  5. Two-stage Lagrangian modeling of ignition processes in ignition quality tester and constant volume combustion chambers

    KAUST Repository

    Alfazazi, Adamu; Kuti, Olawole Abiola; Naser, Nimal; Chung, Suk-Ho; Sarathy, Mani

    2016-01-01

    The ignition characteristics of isooctane and n-heptane in an ignition quality tester (IQT) were simulated using a two-stage Lagrangian (TSL) model, which is a zero-dimensional (0-D) reactor network method. The TSL model was also used to simulate

  6. An idealized model for tree-grass coexistence in savannas : The role of life stage structure and fire disturbances

    NARCIS (Netherlands)

    Baudena, Mara|info:eu-repo/dai/nl/340303867; D'Andrea, Fabio; Provenzale, A.

    2010-01-01

    1. We discuss a simple implicit-space model for the competition of trees and grasses in an idealized savanna environment. The model represents patch occupancy dynamics within the habitat and introduces life stage structure in the tree population, namely adults and seedlings. A tree can be

  7. Assessing vanadium and arsenic exposure of people living near a petrochemical complex with two-stage dispersion models

    International Nuclear Information System (INIS)

    Chio, Chia-Pin; Yuan, Tzu-Hsuen; Shie, Ruei-Hao; Chan, Chang-Chuan

    2014-01-01

    Highlights: • Two-stage dispersion models can estimate exposures to hazardous air pollutants. • Spatial distribution of V levels is derived for sources without known emission rates. • A distance-to-source gradient is found for V levels from a petrochemical complex. • Two-stage dispersion is useful for modeling air pollution in resource-limited areas. - Abstract: The goal of this study is to demonstrate that it is possible to construct a two-stage dispersion model empirically for the purpose of estimating air pollution levels in the vicinity of petrochemical plants. We studied oil refineries and coal-fired power plants in the No. 6 Naphtha Cracking Complex, an area of 2,603-ha situated on the central west coast of Taiwan. The pollutants targeted were vanadium (V) from oil refineries and arsenic (As) from coal-fired power plants. We applied a backward fitting method to determine emission rates of V and As, with 192 PM 10 filters originally collected between 2009 and 2012. Our first-stage model estimated emission rates of V and As (median and 95% confidence intervals at 0.0202 (0.0040–0.1063) and 0.1368 (0.0398–0.4782) g/s, respectively. In our second stage model, the predicted zone-average concentrations showed a strong correlation with V, but a poor correlation with As. Our findings show that two-stage dispersion models are relatively precise for estimating V levels at residents’ addresses near the petrochemical complex, but they did not work as well for As levels. In conclusion, our model-based approach can be widely used for modeling exposure to air pollution from industrial areas in countries with limited resources

  8. Two-stage model of development of heterogeneous uranium-lead systems in zircon

    International Nuclear Information System (INIS)

    Mel'nikov, N.N.; Zevchenkov, O.A.

    1985-01-01

    Behaviour of isotope systems of multiphase zircons at their two-stage distortion is considered. The results of calculations testify to the fact that linear correlations on the diagram with concordance can be explained including two-stage discovery of U-Pb systems of cogenetic zircons if zircon is considered physically heterogeneous and losing in its different part different ratios of accumulated radiogenic lead. ''Metamorphism ages'' obtained by these two-stage opening zircons are intermediate, and they not have geochronological significance while ''crystallization ages'' remain rather close to real ones. Two-stage opening zircons in some cases can be diagnosed by discordance of their crystal component

  9. Automated EEG sleep staging in the term-age baby using a generative modelling approach

    Science.gov (United States)

    Pillay, Kirubin; Dereymaeker, Anneleen; Jansen, Katrien; Naulaers, Gunnar; Van Huffel, Sabine; De Vos, Maarten

    2018-06-01

    Objective. We develop a method for automated four-state sleep classification of preterm and term-born babies at term-age of 38-40 weeks postmenstrual age (the age since the last menstrual cycle of the mother) using multichannel electroencephalogram (EEG) recordings. At this critical age, EEG differentiates from broader quiet sleep (QS) and active sleep (AS) stages to four, more complex states, and the quality and timing of this differentiation is indicative of the level of brain development. However, existing methods for automated sleep classification remain focussed only on QS and AS sleep classification. Approach. EEG features were calculated from 16 EEG recordings, in 30 s epochs, and personalized feature scaling used to correct for some of the inter-recording variability, by standardizing each recording’s feature data using its mean and standard deviation. Hidden Markov models (HMMs) and Gaussian mixture models (GMMs) were trained, with the HMM incorporating knowledge of the sleep state transition probabilities. Performance of the GMM and HMM (with and without scaling) were compared, and Cohen’s kappa agreement calculated between the estimates and clinicians’ visual labels. Main results. For four-state classification, the HMM proved superior to the GMM. With the inclusion of personalized feature scaling, mean kappa (±standard deviation) was 0.62 (±0.16) compared to the GMM value of 0.55 (±0.15). Without feature scaling, kappas for the HMM and GMM dropped to 0.56 (±0.18) and 0.51 (±0.15), respectively. Significance. This is the first study to present a successful method for the automated staging of four states in term-age sleep using multichannel EEG. Results suggested a benefit in incorporating transition information using an HMM, and correcting for inter-recording variability through personalized feature scaling. Determining the timing and quality of these states are indicative of developmental delays in both preterm and term-born babies that may

  10. Validity and reliability of an application review process using dedicated reviewers in one stage of a multi-stage admissions model.

    Science.gov (United States)

    Zeeman, Jacqueline M; McLaughlin, Jacqueline E; Cox, Wendy C

    2017-11-01

    With increased emphasis placed on non-academic skills in the workplace, a need exists to identify an admissions process that evaluates these skills. This study assessed the validity and reliability of an application review process involving three dedicated application reviewers in a multi-stage admissions model. A multi-stage admissions model was utilized during the 2014-2015 admissions cycle. After advancing through the academic review, each application was independently reviewed by two dedicated application reviewers utilizing a six-construct rubric (written communication, extracurricular and community service activities, leadership experience, pharmacy career appreciation, research experience, and resiliency). Rubric scores were extrapolated to a three-tier ranking to select candidates for on-site interviews. Kappa statistics were used to assess interrater reliability. A three-facet Many-Facet Rasch Model (MFRM) determined reviewer severity, candidate suitability, and rubric construct difficulty. The kappa statistic for candidates' tier rank score (n = 388 candidates) was 0.692 with a perfect agreement frequency of 84.3%. There was substantial interrater reliability between reviewers for the tier ranking (kappa: 0.654-0.710). Highest construct agreement occurred in written communication (kappa: 0.924-0.984). A three-facet MFRM analysis explained 36.9% of variance in the ratings, with 0.06% reflecting application reviewer scoring patterns (i.e., severity or leniency), 22.8% reflecting candidate suitability, and 14.1% reflecting construct difficulty. Utilization of dedicated application reviewers and a defined tiered rubric provided a valid and reliable method to effectively evaluate candidates during the application review process. These analyses provide insight into opportunities for improving the application review process among schools and colleges of pharmacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. DeepSleepNet: A Model for Automatic Sleep Stage Scoring Based on Raw Single-Channel EEG.

    Science.gov (United States)

    Supratak, Akara; Dong, Hao; Wu, Chao; Guo, Yike

    2017-11-01

    This paper proposes a deep learning model, named DeepSleepNet, for automatic sleep stage scoring based on raw single-channel EEG. Most of the existing methods rely on hand-engineered features, which require prior knowledge of sleep analysis. Only a few of them encode the temporal information, such as transition rules, which is important for identifying the next sleep stages, into the extracted features. In the proposed model, we utilize convolutional neural networks to extract time-invariant features, and bidirectional-long short-term memory to learn transition rules among sleep stages automatically from EEG epochs. We implement a two-step training algorithm to train our model efficiently. We evaluated our model using different single-channel EEGs (F4-EOG (left), Fpz-Cz, and Pz-Oz) from two public sleep data sets, that have different properties (e.g., sampling rate) and scoring standards (AASM and R&K). The results showed that our model achieved similar overall accuracy and macro F1-score (MASS: 86.2%-81.7, Sleep-EDF: 82.0%-76.9) compared with the state-of-the-art methods (MASS: 85.9%-80.5, Sleep-EDF: 78.9%-73.7) on both data sets. This demonstrated that, without changing the model architecture and the training algorithm, our model could automatically learn features for sleep stage scoring from different raw single-channel EEGs from different data sets without utilizing any hand-engineered features.

  12. A coupling model for the two-stage core calculation method with subchannel analysis for boiling water reactors

    International Nuclear Information System (INIS)

    Mitsuyasu, Takeshi; Aoyama, Motoo; Yamamoto, Akio

    2017-01-01

    Highlights: • A coupling model of the two-stage core calculation with subchannel analysis. • BWR fuel assembly parameters are assumed and verified. • The model was evaluated for heterogeneous problems. - Abstract: The two-stage core analysis method is widely used for BWR core analysis. The purpose of this study is to develop a core analysis model coupled with subchannel analysis within the two-stage calculation scheme using an assembly-based thermal-hydraulics calculation in the core analysis. The model changes the 2D lattice physics scheme, and couples with 3D subchannel analysis which evaluates the thermal-hydraulics characteristics within the coolant flow area divided as some subchannel regions. In order to couple with these two analyses, some BWR fuel assembly parameters are assumed and verified. The developed model is evaluated for the heterogeneous problem with and without a control rod. The present model is especially effective for the control rod inserted condition. The present model can incorporate the subchannel effect into the current two-stage core calculation method.

  13. A two-stage method for microcalcification cluster segmentation in mammography by deformable models

    International Nuclear Information System (INIS)

    Arikidis, N.; Kazantzi, A.; Skiadopoulos, S.; Karahaliou, A.; Costaridou, L.; Vassiou, K.

    2015-01-01

    Purpose: Segmentation of microcalcification (MC) clusters in x-ray mammography is a difficult task for radiologists. Accurate segmentation is prerequisite for quantitative image analysis of MC clusters and subsequent feature extraction and classification in computer-aided diagnosis schemes. Methods: In this study, a two-stage semiautomated segmentation method of MC clusters is investigated. The first stage is targeted to accurate and time efficient segmentation of the majority of the particles of a MC cluster, by means of a level set method. The second stage is targeted to shape refinement of selected individual MCs, by means of an active contour model. Both methods are applied in the framework of a rich scale-space representation, provided by the wavelet transform at integer scales. Segmentation reliability of the proposed method in terms of inter and intraobserver agreements was evaluated in a case sample of 80 MC clusters originating from the digital database for screening mammography, corresponding to 4 morphology types (punctate: 22, fine linear branching: 16, pleomorphic: 18, and amorphous: 24) of MC clusters, assessing radiologists’ segmentations quantitatively by two distance metrics (Hausdorff distance—HDIST cluster , average of minimum distance—AMINDIST cluster ) and the area overlap measure (AOM cluster ). The effect of the proposed segmentation method on MC cluster characterization accuracy was evaluated in a case sample of 162 pleomorphic MC clusters (72 malignant and 90 benign). Ten MC cluster features, targeted to capture morphologic properties of individual MCs in a cluster (area, major length, perimeter, compactness, and spread), were extracted and a correlation-based feature selection method yielded a feature subset to feed in a support vector machine classifier. Classification performance of the MC cluster features was estimated by means of the area under receiver operating characteristic curve (Az ± Standard Error) utilizing tenfold cross

  14. Modelling the enigmatic Late Pliocene Glacial Event - Marine Isotope Stage M2

    Science.gov (United States)

    Dolan, Aisling M.; Haywood, Alan M.; Hunter, Stephen J.; Tindall, Julia C.; Dowsett, Harry J.; Hill, Daniel J.; Pickering, Steven J.

    2015-01-01

    The Pliocene Epoch (5.2 to 2.58 Ma) has often been targeted to investigate the nature of warm climates. However, climate records for the Pliocene exhibit significant variability and show intervals that apparently experienced a cooler than modern climate. Marine Isotope Stage (MIS) M2 (~ 3.3 Ma) is a globally recognisable cooling event that disturbs an otherwise relatively (compared to present-day) warm background climate state. It remains unclear whether this event corresponds to significant ice sheet build-up in the Northern and Southern Hemisphere. Estimates of sea level for this interval vary, and range from modern values to estimates of 65 m sea level fall with respect to present day. Here we implement plausible M2 ice sheet configurations into a coupled atmosphere–ocean climate model to test the hypothesis that larger-than-modern ice sheet configurations may have existed at M2. Climate model results are compared with proxy climate data available for M2 to assess the plausibility of each ice sheet configuration. Whilst the outcomes of our data/model comparisons are not in all cases straight forward to interpret, there is little indication that results from model simulations in which significant ice masses have been prescribed in the Northern Hemisphere are incompatible with proxy data from the North Atlantic, Northeast Arctic Russia, North Africa and the Southern Ocean. Therefore, our model results do not preclude the possibility of the existence of larger ice masses during M2 in the Northern or Southern Hemisphere. Specifically they are not able to discount the possibility of significant ice masses in the Northern Hemisphere during the M2 event, consistent with a global sea-level fall of between 40 m and 60 m. This study highlights the general need for more focused and coordinated data generation in the future to improve the coverage and consistency in proxy records for M2, which will allow these and future M2 sensitivity tests to be interrogated

  15. Mathematical modeling of a continuous alcoholic fermentation process in a two-stage tower reactor cascade with flocculating yeast recycle.

    Science.gov (United States)

    de Oliveira, Samuel Conceição; de Castro, Heizir Ferreira; Visconti, Alexandre Eliseu Stourdze; Giudici, Reinaldo

    2015-03-01

    Experiments of continuous alcoholic fermentation of sugarcane juice with flocculating yeast recycle were conducted in a system of two 0.22-L tower bioreactors in series, operated at a range of dilution rates (D 1 = D 2 = 0.27-0.95 h(-1)), constant recycle ratio (α = F R /F = 4.0) and a sugar concentration in the feed stream (S 0) around 150 g/L. The data obtained in these experimental conditions were used to adjust the parameters of a mathematical model previously developed for the single-stage process. This model considers each of the tower bioreactors as a perfectly mixed continuous reactor and the kinetics of cell growth and product formation takes into account the limitation by substrate and the inhibition by ethanol and biomass, as well as the substrate consumption for cellular maintenance. The model predictions agreed satisfactorily with the measurements taken in both stages of the cascade. The major differences with respect to the kinetic parameters previously estimated for a single-stage system were observed for the maximum specific growth rate, for the inhibition constants of cell growth and for the specific rate of substrate consumption for cell maintenance. Mathematical models were validated and used to simulate alternative operating conditions as well as to analyze the performance of the two-stage process against that of the single-stage process.

  16. Classification of iRBD and Parkinson's patients using a general data-driven sleep staging model built on EEG

    DEFF Research Database (Denmark)

    Koch, Henriette; Christensen, Julie Anja Engelhard; Frandsen, Rune

    2013-01-01

    Sleep analysis is an important diagnostic tool for sleep disorders. However, the current manual sleep scoring is time-consuming as it is a crude discretization in time and stages. This study changes Esbroeck and Westover's [1] latent sleep staging model into a global model. The proposed data......-driven method trained a topic mixture model on 10 control subjects and was applied on 10 other control subjects, 10 iRBD patients and 10 Parkinson's patients. In that way 30 topic mixture diagrams were obtained from which features reflecting distinct sleep architectures between control subjects and patients...... were extracted. Two features calculated on basis of two latent sleep states classified subjects as “control” or “patient” by a simple clustering algorithm. The mean sleep staging accuracy compared to classical AASM scoring was 72.4% for control subjects and a clustering of the derived features resulted...

  17. Neutrino masses in the SO(10) model with intermediate stage of the symmetry breaking

    International Nuclear Information System (INIS)

    Svetovoj, V.B.

    1982-01-01

    An effect for the neutrino masses of an intermediate stage in the symmetry spontaneous breaking, different from SU(5), is investigated in some detail for the SO(1O) model. There are two possibilities depending on the composition of the Higgs sector: i) msub(ν) approximately msub(f)(Msub(W)/Msub(1)); ii) msub(ν) approximately msub(f)sub(b)/Msub(1))(M/Msub(1)), where M, M 1 and Msub) are the scales of the breaking of the original SO(10) simmetry, the intermediate symmetry, and the standard SUsub(c)(3)xSUsub(L)(2)xU(1) symmetry, respectively, and msub(f) is a typical fermion mass. It as shown that a Majorana mass of the right neutrino (νsub(R)) of a purely loop origin would result in a too large mass of the usual neutrinos, so a tree-graph contribution to the mass of νsub(R) is necessary. Numerical estimates for the neutrino masses are discussed [ru

  18. Neutrino masses in an SO(10) model with an intermediate stage of symmetry breaking

    International Nuclear Information System (INIS)

    Svetovoi, V.B.

    1982-01-01

    The effect on neutrino masses of an intermediate stage in symmetry breaking different from SU(5) is investigated in detail for the SO(10) model. There are two possibilities depending on the contents of the Higgs sector: i) m/sub ν/approx.m/sub f/(M/sub W//M 1 ); ii) m/sub ν/approx.m/sub f/(M/sub W//M 1 )(M/M 1 ), where M, M 1 and M/sub W/ are the scales of the breaking of the original SO(10) symmetry, the intermediate symmetry, and the standard SU/sub c/(3) x SU/sub L/(2) x U(1) symmetry, respectively, and m/sub f/ is a typical fermion mass. It is shown that a Majorana mass of the right-handed-neutrino (ν/sub R/) of a purely loop origin would result in too large a mass of the usual neutrinos, so a tree-graph contribution to the mass of ν/sub R/ is necessary. Numerical estimates for the neutrino masses are discussed

  19. Evaluation of carcinogenic potential of diuron in a rat mammary two-stage carcinogenesis model.

    Science.gov (United States)

    Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; de Camargo, João Lauro Viana; Barbisan, Luís Fernando

    2011-04-01

    This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-α (ER-α), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-α, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

  20. Implications of the two stage clonal expansion model to radiation risk estimation

    International Nuclear Information System (INIS)

    Curtis, S.B.; Hazelton, W.D.; Luebeck, E.G.; Moolgavkar, S.H.

    2003-01-01

    The Two Stage Clonal Expansion Model of carcinogenesis has been applied to the analysis of several cohorts of persons exposed to chronic exposures of high and low LET radiation. The results of these analyses are: (1) the importance of radiation-induced initiation is small and, if present at all, contributes to cancers only late in life and only if exposure begins early in life, (2) radiation-induced promotion dominates and produces the majority of cancers by accelerating proliferation of already-initiated cells, and (3) radiation-induced malignant conversion is important only during and immediately after exposure ceases and tends to dominate only late in life, acting on already initiated and promoted cells. Two populations, the Colorado Plateau miners (high-LET, radon exposed) and the Canadian radiation workers (low-LET, gamma ray exposed) are used as examples to show the time dependence of the hazard function and the relative importance of the three hypothesized processes (initiation, promotion and malignant conversion) for each radiation quality

  1. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  2. Optimal pulse fishing policy in stage-structured models with birth pulses

    International Nuclear Information System (INIS)

    Gao Shujing; Chen Lansun; Sun Lihua

    2005-01-01

    In this paper, we propose exploited models with stage structure for the dynamics in a fish population for which periodic birth pulse and pulse fishing occur at different fixed time. Using the stroboscopic map, we obtain an exact cycle of system, and obtain the threshold conditions for its stability. Bifurcation diagrams are constructed with the birth rate (or pulse fishing time or harvesting effort) as the bifurcation parameter, and these are observed to display complex dynamic behaviors, including chaotic bands with period windows, period-doubling, multi-period-halving and incomplete period-doubling bifurcation, pitch-fork and tangent bifurcation, non-unique dynamics (meaning that several attractors or attractor and chaos coexist) and attractor crisis. This suggests that birth pulse and pulse fishing provide a natural period or cyclicity that make the dynamical behaviors more complex. Moreover, we show that the pulse fishing has a strong impact on the persistence of the fish population, on the volume of mature fish stock and on the maximum annual-sustainable yield. An interesting result is obtained that, after the birth pulse, the population can sustain much higher harvesting effort if the mature fish is removed as early as possible

  3. Center variation in the use of nonstandardized model for end-stage liver disease exception points.

    Science.gov (United States)

    Goldberg, David S; Makar, George; Bittermann, Therese; French, Benjamin

    2013-12-01

    The Model for End-Stage Liver Disease (MELD) score is an imperfect prognosticator of waitlist dropout, so transplant centers may apply for exception points to increase a waitlist candidate's priority on the waitlist. Exception applications are categorized as recognized exceptional diagnoses (REDs; eg, hepatocellular carcinoma) and non-REDs (eg, cholangitis). Although prior work has demonstrated regional variation in the use of exceptions, no work has examined the between-center variability. We analyzed all new waitlist candidates from February 27, 2002 to June 3, 2011 to explore variations in the use of non-REDs, for which no strict exception criteria exist. There were 58,641 new waitlist candidates, and 4356 (7.4%) applied for a non-RED exception. The number of applications increased steadily over time, as did the approval rates for such applications: from variation to ensure the appropriate and equitable use of non-RED exceptions. © 2013 American Association for the Study of Liver Diseases.

  4. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  5. Rock Mechanics Forsmark. Site descriptive modelling Forsmark stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Glamheden, Rune; Fredriksson, Anders (Golder Associates AB (SE)); Roeshoff, Kennert; Karlsson, Johan (Berg Bygg Konsult AB (SE)); Hakami, Hossein (Itasca Geomekanik AB (SE)); Christiansson, Rolf (Swedish Nuclear Fuel and Waste Management Co., Stockholm (SE))

    2007-12-15

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is undertaking site characterisation at two different locations, Forsmark and Laxemar/Simpevarp, with the objective of siting a geological repository for spent nuclear fuel. The characterisation of a site is an integrated work carried out by several disciplines including geology, rock mechanics, thermal properties, hydrogeology, hydrogeochemistry and surface systems. This report presents the rock mechanics model of the Forsmark site up to stage 2.2. The scope of work has included compilation and analysis of primary data of intact rock and fractures, estimation of the rock mass mechanical properties and estimation of the in situ state of stress at the Forsmark site. The laboratory results on intact rock and fractures in the target volume demonstrate a good quality rock mass that is strong, stiff and relatively homogeneous. The homogeneity is also supported by the lithological and the hydrogeological models. The properties of the rock mass have been initially estimated by two separate modelling approaches, one empirical and one theoretical. An overall final estimate of the rock mass properties were achieved by integrating the results from the two models via a process termed 'Harmonization'. Both the tensile tests, carried out perpendicular and parallel to the foliation, and the theoretical analyses of the rock mass properties in directions parallel and perpendicular to the major principal stress, result in parameter values almost independent of direction. This indicates that the rock mass in the target volume is isotropic. The rock mass quality in the target volume appears to be of high and uniform quality. Those portions with reduced rock mass quality that do exist are mainly related to sections with increased fracture frequency. Such sections are associated with deformation zones according to the geological description. The results of adjacent rock domains and fracture domains of the target

  6. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Science.gov (United States)

    Pang, Lisa Y; Gatenby, Emma L; Kamida, Ayako; Whitelaw, Bruce A; Hupp, Ted R; Argyle, David J

    2014-01-01

    Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  7. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Directory of Open Access Journals (Sweden)

    Lisa Y Pang

    Full Text Available Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs, which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05, and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  8. FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

    Science.gov (United States)

    Liu, Shuo; Zhang, Cun; Zhang, Kuo; Gao, Yuan; Wang, Zhaowei; Li, Xiaoju; Cheng, Guang; Wang, Shuning; Xue, Xiaochang; Li, Weina; Zhang, Wei; Zhang, Yingqi; Xing, Xianghui; Li, Meng; Hao, Qiang

    2017-07-04

    Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

  9. Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

    Directory of Open Access Journals (Sweden)

    Rita Ghosh

    2007-11-01

    Full Text Available We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB. Cyclooxygenase (Cox-2, a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2 and suppresses apoptosis. Treatment of LNCaP cells with NexrutineR reduced tumor necrosis factor α-induced enzymatic as well as promoter activities of Cox-2. NexrutineR also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating NexrutineR response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01. We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like NexrutineR, demonstrating a prospective for development of NexrutineR for prostate cancer management.

  10. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  11. Designing a crisis management model in Iran’s archival centers: Pre-crisis stage

    Directory of Open Access Journals (Sweden)

    Maryam Nakhoda

    2018-03-01

    Full Text Available The purpose of this research is to design a crisis management model in the archival centers of Iran during the pre-crisis phase. The present study was conducted with a qualitative approach using the Grounded theory method. The necessary data was collected using semi-structured interviews. Data saturation was a major factor in determining the sample size. The research population included 20 crisis management specialists and managers of archives in Iran and the data analysis was performed in three stages: open, axial, and selective coding. The paradigmatic model derived from the findings of the research includes the sections of the causal conditions, strategies, intervening conditions and the underlying conditions and their outcomes. The causal conditions are located in two categories of internal crises such as biological crises and lack of proper management, and external crises such as natural disasters, fires and human-made crises. Intervener conditions and backgrounds include cat-egories such as lack of specialist staff training, lack of appropriate environmental conditions and management mechanisms, archival building and human resources issues. To prevent and mitigate the effects of the crisis in archives, some strategies are required such as modern education for resil-ience, teaching how to use documents, standardizing buildings and equipment (non-use of steel skeletons in building archives, use of concrete skeletons Armed or metal, as well as the use of walls and doors and floors of anti-fire covers in the building of archives and the establishment of multi-layer protective systems for the protection of documents.

  12. An adaptive two-stage analog/regression model for probabilistic prediction of small-scale precipitation in France

    Science.gov (United States)

    Chardon, Jérémy; Hingray, Benoit; Favre, Anne-Catherine

    2018-01-01

    Statistical downscaling models (SDMs) are often used to produce local weather scenarios from large-scale atmospheric information. SDMs include transfer functions which are based on a statistical link identified from observations between local weather and a set of large-scale predictors. As physical processes driving surface weather vary in time, the most relevant predictors and the regression link are likely to vary in time too. This is well known for precipitation for instance and the link is thus often estimated after some seasonal stratification of the data. In this study, we present a two-stage analog/regression model where the regression link is estimated from atmospheric analogs of the current prediction day. Atmospheric analogs are identified from fields of geopotential heights at 1000 and 500 hPa. For the regression stage, two generalized linear models are further used to model the probability of precipitation occurrence and the distribution of non-zero precipitation amounts, respectively. The two-stage model is evaluated for the probabilistic prediction of small-scale precipitation over France. It noticeably improves the skill of the prediction for both precipitation occurrence and amount. As the analog days vary from one prediction day to another, the atmospheric predictors selected in the regression stage and the value of the corresponding regression coefficients can vary from one prediction day to another. The model allows thus for a day-to-day adaptive and tailored downscaling. It can also reveal specific predictors for peculiar and non-frequent weather configurations.

  13. Seizure following the Use of the COX-2 Inhibitor Etoricoxib

    Directory of Open Access Journals (Sweden)

    Valentina Arnao

    2017-01-01

    Full Text Available We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

  14. Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models

    International Nuclear Information System (INIS)

    Schnabl, Bernd; Farshchi-Heydari, Salman; Loomba, Rohit; Mattrey, Robert F.; Hoh, Carl K.; Sirlin, Claude B.; Brenner, David A.; Behling, Cynthia A.; Vera, David R.

    2016-01-01

    Objectives: The aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy. Methods: Galactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, 68 Ga, and injected (i.v., 45–95 μCi, 1.5 pmol/g TBW) into 44 healthy, 19 DEN-, and 22 CDAA-treated male rats. Quantification of liver function was achieved by calculating T90, defined as the time for the liver to accumulate 90 percent of the [ 68 Ga]GSA plateau value. All livers were excised immediately after imaging and prepared for a “blinded” histologic examination, which included fibrosis and fat content scores. Two sets of fibrosis scores were recorded for all of animals. The dominant fibrosis stage was recorded as the “Dominant Pattern” score and the “Maximum Pattern” score was assigned if a smaller distinct region with a higher fibrosis score was observed. Results: Animals with Dominant Pattern F0–F1 liver fibrosis (D − = 39) demonstrated significantly (P < 0.0001) faster accumulation of [ 68 Ga]GSA (2.40 ± 0.52 min) than those with moderate to advanced Dominant Pattern fibrosis F2 and F4 (D + = 26) (3.48 ± 1.01 min). ROC analysis (F0–F1 vs F2–F4) produced an area under the binormal curve (AUC) of 0.867 ± 0.045. Twenty-seven of the 65 rats had small regions with higher fibrosis scores. Six of these Maximum Pattern scores reclassified the animals from D − to D + . ROC analysis of F0–F1 versus F2–F4 rats without liver fat produced AUCs of 0.881 ± 0.053 for the Dominant Pattern Score and 0.944 ± 0.035 for the Maximum Pattern Score. Conclusions: PET Functional Imaging of [ 68 Ga]GSA accurately discriminates

  15. A MULTI-STAGE COLOR MODEL REVISITED: IMPLICATIONS FOR A GENE THERAPY CURE FOR RED-GREEN COLORBLINDNESS

    OpenAIRE

    Mancuso, Katherine; Mauck, Matthew C.; Kuchenbecker, James A.; Neitz, Maureen; Neitz, Jay

    2010-01-01

    In 1993, DeValois and DeValois proposed a “multi-stage color model” to explain how the cortex is ultimately able to deconfound the responses of neurons receiving input from three cone types in order to produce separate red-green and blue-yellow systems, as well as segregate luminance percepts (black-white) from color. This model extended the biological implementation of Hurvich and Jameson’s Opponent-Process Theory of color vision, a two-stage model encompassing the three cone types combined ...

  16. Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Martin Gorges

    Full Text Available The neuropathological process underlying amyotrophic lateral sclerosis (ALS can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks.To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model.Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments.Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001 between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS.Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading.

  17. 4-Stage Online Presence Model: Model for Module Design and Delivery Using Web 2.0 Technologies to Facilitate Critical Thinking Skills

    Science.gov (United States)

    Goh, WeiWei; Dexter, Barbara; Self, Richard

    2014-01-01

    The main purpose of this paper is to present a conceptual model for the use of web 2.0 online technologies in order to develop and enhance students' critical thinking skills at higher education level. Wiki is chosen as the main focus in this paper. The model integrates Salmon's 5-stage model (Salmon, 2002) with Garrison's Community of Inquiry…

  18. Bayesian analysis of log Gaussian Cox processes for disease mapping

    DEFF Research Database (Denmark)

    Benes, Viktor; Bodlák, Karel; Møller, Jesper

    We consider a data set of locations where people in Central Bohemia have been infected by tick-borne encephalitis, and where population census data and covariates concerning vegetation and altitude are available. The aims are to estimate the risk map of the disease and to study the dependence...... of the risk on the covariates. Instead of using the common area level approaches we consider a Bayesian analysis for a log Gaussian Cox point process with covariates. Posterior characteristics for a discretized version of the log Gaussian Cox process are computed using markov chain Monte Carlo methods...

  19. An inexact mixed risk-aversion two-stage stochastic programming model for water resources management under uncertainty.

    Science.gov (United States)

    Li, W; Wang, B; Xie, Y L; Huang, G H; Liu, L

    2015-02-01

    Uncertainties exist in the water resources system, while traditional two-stage stochastic programming is risk-neutral and compares the random variables (e.g., total benefit) to identify the best decisions. To deal with the risk issues, a risk-aversion inexact two-stage stochastic programming model is developed for water resources management under uncertainty. The model was a hybrid methodology of interval-parameter programming, conditional value-at-risk measure, and a general two-stage stochastic programming framework. The method extends on the traditional two-stage stochastic programming method by enabling uncertainties presented as probability density functions and discrete intervals to be effectively incorporated within the optimization framework. It could not only provide information on the benefits of the allocation plan to the decision makers but also measure the extreme expected loss on the second-stage penalty cost. The developed model was applied to a hypothetical case of water resources management. Results showed that that could help managers generate feasible and balanced risk-aversion allocation plans, and analyze the trade-offs between system stability and economy.

  20. Impact of two-stage turbocharging architectures on pumping losses of automotive engines based on an analytical model

    International Nuclear Information System (INIS)

    Galindo, J.; Serrano, J.R.; Climent, H.; Varnier, O.

    2010-01-01

    Present work presents an analytical study of two-stage turbocharging configuration performance. The aim of this work is to understand the influence of different two-stage-architecture parameters to optimize the use of exhaust manifold gases energy and to aid decision making process. An analytical model giving the relationship between global compression ratio and global expansion ratio is developed as a function of basic engine and turbocharging system parameters. Having an analytical solution, the influence of different variables, such as expansion ratio between HP and LP turbine, intercooler efficiency, turbochargers efficiency, cooling fluid temperature and exhaust temperature are studied independently. Engine simulations with proposed analytical model have been performed to analyze the influence of these different parameters on brake thermal efficiency and pumping mean effective pressure. The results obtained show the overall performance of the two-stage system for the whole operative range and characterize the optimum control of the elements for each operative condition. The model was also used to compare single-stage and two-stage architectures performance for the same engine operative conditions. Benefits and limits in terms of breathing capabilities and brake thermal efficiency of each type of system have been presented and analyzed.

  1. [Using (1)H-nuclear magnetic resonance metabolomics and gene ontology to establish pathological staging model for esophageal cancer patients].

    Science.gov (United States)

    Chen, X; Wang, K; Chen, W; Jiang, H; Deng, P C; Li, Z J; Peng, J; Zhou, Z Y; Yang, H; Huang, G X; Zeng, J

    2016-07-01

    By combining the metabolomics and computational biology, to explore the relationship between metabolic phenotype and pathological stage in esophageal cancer patients, to find the mechanism of metabolic network disturbance and develop a new method for fast preoperative clinical staging. A prospective cohort study (from April 2013 to January 2016) was conducted. The preoperative patients from Sichuan Provincial People's Hospital, who were diagnosed with esophageal cancer from May 2013 to April 2014 were included, and their serum samples were collected to detect (1)H-nuclear magnetic resonance (NMR) metabolomics for the purpose of drawing the metabolic fingerprinting in different stages of patients with esophageal cancer. The data were processed with these methods-principal components analysis: partial least squares regression and support vector machine, for the exploration of the enzyme-gene network regulatory mechanism in abnormal esophageal cancer metabolic network regulation and to build the quantitative prediction model of esophageal cancer staging in the end. All data were processed on high-performance computing platforms Matalab. The comparison of data had used Wilcoxon test, variance analysis, χ(2) test and Fisher exact test. Twenty patients with different stages of esophageal cancer were included; and their serum metabolic fingerprinting could differentiate different tumor stages. There were no difference among the five teams in the age (F=1.086, P>0.05), the body mass index (F=1.035, P>0.05), the distance from the incisors to tumor (F=1.078, P>0.05). Among the patients with different TNM stages, there was a significant difference in plasma metabolome. Compared to ⅡB, ⅢA, Ⅳstage patients, increased levels of butanone, ethanol amine, homocysteine, hydroxy acids and estriol, together with decreased levels of glycoprotein, creatine, choline, isobutyricacid, alanine, leucine, valine, were observed inⅠB, ⅡA stage patients. Four metabolic markers

  2. Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach.

    Science.gov (United States)

    Agrawal, A; Neale, M C; Jacobson, K C; Prescott, C A; Kendler, K S

    2005-06-01

    Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

  3. Bedrock geology Forsmark. Modelling stage 2.3. Implications for and verification of the deterministic geological models based on complementary data

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. (Geological Survey of Sweden, Uppsala (Sweden)); Simeonov, Assen (Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden)); Isaksson, Hans (GeoVista AB, Luleaa (Sweden))

    2008-12-15

    The Swedish Nuclear Fuel and Waste Management Company is in the process of completing site descriptive modelling at two locations in Sweden, with the objective to site a deep geological repository for spent nuclear fuel. At Forsmark, the results of the stage 2.2 geological modelling formed the input for downstream users. Since complementary ground and borehole geological and geophysical data, acquired after model stage 2.2, were not planned to be included in the deterministic rock domain, fracture domain and deformation zone models supplied to the users, it was deemed necessary to evaluate the implications of these stage 2.3 data for the stage 2.2 deterministic geological models and, if possible, to make use of these data to verify the models. This report presents the results of the analysis of the complementary stage 2.3 geological and geophysical data. Model verification from borehole data has been implemented in the form of a prediction-outcome test. The stage 2.3 geological and geophysical data at Forsmark mostly provide information on the bedrock outside the target volume. Additional high-resolution ground magnetic data and the data from the boreholes KFM02B, KFM11A, KFM12A and HFM33 to HFM37 can be included in this category. Other data complement older information of identical character, both inside and outside this volume. These include the character and kinematics of deformation zones and fracture mineralogy. In general terms, it can be stated that all these new data either confirm the geological modelling work completed during stage 2.2 or are in good agreement with the data that were used in this work. In particular, although the new high-resolution ground magnetic data modify slightly the position and trace length of some stage 2.2 deformation zones at the ground surface, no new or modified deformation zones with a trace length longer than 3,000 m at the ground surface have emerged. It is also apparent that the revision of fracture orientation data

  4. Bedrock geology Forsmark. Modelling stage 2.3. Implications for and verification of the deterministic geological models based on complementary data

    International Nuclear Information System (INIS)

    Stephens, Michael B.; Simeonov, Assen; Isaksson, Hans

    2008-12-01

    The Swedish Nuclear Fuel and Waste Management Company is in the process of completing site descriptive modelling at two locations in Sweden, with the objective to site a deep geological repository for spent nuclear fuel. At Forsmark, the results of the stage 2.2 geological modelling formed the input for downstream users. Since complementary ground and borehole geological and geophysical data, acquired after model stage 2.2, were not planned to be included in the deterministic rock domain, fracture domain and deformation zone models supplied to the users, it was deemed necessary to evaluate the implications of these stage 2.3 data for the stage 2.2 deterministic geological models and, if possible, to make use of these data to verify the models. This report presents the results of the analysis of the complementary stage 2.3 geological and geophysical data. Model verification from borehole data has been implemented in the form of a prediction-outcome test. The stage 2.3 geological and geophysical data at Forsmark mostly provide information on the bedrock outside the target volume. Additional high-resolution ground magnetic data and the data from the boreholes KFM02B, KFM11A, KFM12A and HFM33 to HFM37 can be included in this category. Other data complement older information of identical character, both inside and outside this volume. These include the character and kinematics of deformation zones and fracture mineralogy. In general terms, it can be stated that all these new data either confirm the geological modelling work completed during stage 2.2 or are in good agreement with the data that were used in this work. In particular, although the new high-resolution ground magnetic data modify slightly the position and trace length of some stage 2.2 deformation zones at the ground surface, no new or modified deformation zones with a trace length longer than 3,000 m at the ground surface have emerged. It is also apparent that the revision of fracture orientation data

  5. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

    Science.gov (United States)

    Rao, Sadia Saleem; Najam, Rahila

    2016-01-01

    Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

  6. Optimization of material flow in the nuclear fuel cycle using a cyclic multi-stage production-to-inventory model

    International Nuclear Information System (INIS)

    DePorter, E.L.

    1977-01-01

    The nuclear fuel cycle is modelled as a cyclic, multi-stage production-to-inventory system. The objective is to meet a known deterministic demand for energy while minimizing acquisition, production, and inventory holding costs for all stages of the fuel cycle. The model allows for cyclic flow (feedback) of materials, material flow conversion factors at each stage, production lag times at each stage, and for escalating costs of uranium ore. It does not allow shortages to occur in inventories. The model is optimized by the application of the calculus of variations and specifically through recently developed theorems on the solution of functionals constrained by inequalities. The solution is a set of optimal cumulative production trajectories which define the stagewise production rates. Analysis of these production rates reveals the optimal nuclear fuel cycle costs and that inventories (stockpiles) occur in uranium fields, enriched uranium hexafluoride, and fabricated fuel assemblies. An analysis of the sensitivity of the model to variation in three important parameters is performed

  7. Instrumental variables estimation under a structural Cox model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Nørbo Sørensen, Ditte; Vansteelandt, Stijn

    2017-01-01

    Instrumental variable (IV) analysis is an increasingly popular tool for inferring the effect of an exposure on an outcome, as witnessed by the growing number of IV applications in epidemiology, for instance. The majority of IV analyses of time-to-event endpoints are, however, dominated by heurist...

  8. A Conversation with Sally Coxe: A Primate Partnership Culture

    Directory of Open Access Journals (Sweden)

    Riane Eisler

    2017-10-01

    Full Text Available IJPS Editor-in-Chief Riane Eisler talks with Sally Coxe, founding director of the Bonobo Conservation Initiative (BCI, dedicated to protecting these uniquely peaceful primates who share more than 98 percent of our human species’ genes and are on the brink of extinction, as well as protecting their rainforest home.

  9. CoX zeolites and their exchange with deuterium

    Energy Technology Data Exchange (ETDEWEB)

    Novakova, J; Kubelkova, L; Jiru, P [Ceskoslovenska Akademie Ved, Prague. Ustav Fyzikalni Chemie

    1976-04-01

    An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D/sub 2/+OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D/sub 2/+H/sub 2/ exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm/sup -1/ band are exchanged more slowly than are the other hydrogens.

  10. Convergence of posteriors for discretized log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    2004-01-01

    In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...... when the cell sizes of the discretization tends to zero. The effect of discretization is studied in a data example....

  11. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  12. Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

    Directory of Open Access Journals (Sweden)

    Joseph Menczer

    2016-03-01

    Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

  13. COX-2 inhibition in osteoarthritis:effects on cartilage

    NARCIS (Netherlands)

    Mastbergen, Simon Carl

    2005-01-01

    The topic of this thesis was to provide more insight in the direct effects of one of the selective COX-2 inhibitors, celecoxib on articular cartilage. Issues of major relevance to clinical practice since it is essential that compounds used to treat osteoarthritis do not impair the ability of

  14. CoX zeolites and their exchange with deuterium

    International Nuclear Information System (INIS)

    Novakova, J.; Kubelkova, L.; Jiru, P.

    1976-01-01

    An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D 2 +OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D 2 +H 2 exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm -1 band are exchanged more slowly than are the other hydrogens. (author)

  15. Improving Your Data Transformations: Applying the Box-Cox Transformation

    Directory of Open Access Journals (Sweden)

    Jason W. Osborne

    2010-10-01

    Full Text Available Many of us in the social sciences deal with data that do not conform to assumptions of normality and/or homoscedasticity/homogeneity of variance. Some research has shown that parametric tests (e.g., multiple regression, ANOVA can be robust to modest violations of these assumptions. Yet the reality is that almost all analyses (even nonparametric tests benefit from improved the normality of variables, particularly where substantial non-normality is present. While many are familiar with select traditional transformations (e.g., square root, log, inverse for improving normality, the Box-Cox transformation (Box & Cox, 1964 represents a family of power transformations that incorporates and extends the traditional options to help researchers easily find the optimal normalizing transformation for each variable. As such, Box-Cox represents a potential best practice where normalizing data or equalizing variance is desired. This paper briefly presents an overview of traditional normalizing transformations and how Box-Cox incorporates, extends, and improves on these traditional approaches to normalizing data. Examples of applications are presented, and details of how to automate and use this technique in SPSS and SAS are included.

  16. A Decision-making Model for a Two-stage Production-delivery System in SCM Environment

    Science.gov (United States)

    Feng, Ding-Zhong; Yamashiro, Mitsuo

    A decision-making model is developed for an optimal production policy in a two-stage production-delivery system that incorporates a fixed quantity supply of finished goods to a buyer at a fixed interval of time. First, a general cost model is formulated considering both supplier (of raw materials) and buyer (of finished products) sides. Then an optimal solution to the problem is derived on basis of the cost model. Using the proposed model and its optimal solution, one can determine optimal production lot size for each stage, optimal number of transportation for semi-finished goods, and optimal quantity of semi-finished goods transported each time to meet the lumpy demand of consumers. Also, we examine the sensitivity of raw materials ordering and production lot size to changes in ordering cost, transportation cost and manufacturing setup cost. A pragmatic computation approach for operational situations is proposed to solve integer approximation solution. Finally, we give some numerical examples.

  17. Master-slave control with trajectory planning and Bouc-Wen model for tracking control of piezo-driven stage

    Science.gov (United States)

    Lu, Xiaojun; Liu, Changli; Chen, Lei

    2018-04-01

    In this paper, a redundant Piezo-driven stage having 3RRR compliant mechanism is introduced, we propose the master-slave control with trajectory planning (MSCTP) strategy and Bouc-Wen model to improve its micro-motion tracking performance. The advantage of the proposed controller lies in that its implementation only requires a simple control strategy without the complexity of modeling to avoid the master PEA's tracking error. The dynamic model of slave PEA system with Bouc-Wen hysteresis is established and identified via particle swarm optimization (PSO) approach. The Piezo-driven stage with operating period T=1s and 2s is implemented to track a prescribed circle. The simulation results show that MSCTP with Bouc-Wen model reduces the trajectory tracking errors to the range of the accuracy of our available measurement.

  18. Tumor Control Probability Modeling for Stereotactic Body Radiation Therapy of Early-Stage Lung Cancer Using Multiple Bio-physical Models

    Science.gov (United States)

    Liu, Feng; Tai, An; Lee, Percy; Biswas, Tithi; Ding, George X.; El Naqa, Isaam; Grimm, Jimm; Jackson, Andrew; Kong, Feng-Ming (Spring); LaCouture, Tamara; Loo, Billy; Miften, Moyed; Solberg, Timothy; Li, X Allen

    2017-01-01

    Purpose To analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). Method and Materials The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ2) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. Results The fits to the clinic data yield consistent results of large α/β ratios of about 20 Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1 Gy physical dose at isocenters per fraction (≤5 fractions) to achieve the optimal TCP when compared to the T1 tumors. Conclusion This systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/β ratios of about 20 Gy. The six models predict that a BED (calculated with α/β of 20) of 90 Gy is sufficient to achieve TCP ≥ 95%. Among the models considered, the regrowth model leads to a better fit to the clinical data. PMID:27871671

  19. CFD modeling of two-stage ignition in a rapid compression machine: Assessment of zero-dimensional approach

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Gaurav [Department of Mechanical Engineering, The University of Akron, Akron, OH 44325 (United States); Raju, Mandhapati P. [General Motor R and D Tech Center, Warren, MI 48090 (United States); Sung, Chih-Jen [Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269 (United States)

    2010-07-15

    In modeling rapid compression machine (RCM) experiments, zero-dimensional approach is commonly used along with an associated heat loss model. The adequacy of such approach has not been validated for hydrocarbon fuels. The existence of multi-dimensional effects inside an RCM due to the boundary layer, roll-up vortex, non-uniform heat release, and piston crevice could result in deviation from the zero-dimensional assumption, particularly for hydrocarbons exhibiting two-stage ignition and strong thermokinetic interactions. The objective of this investigation is to assess the adequacy of zero-dimensional approach in modeling RCM experiments under conditions of two-stage ignition and negative temperature coefficient (NTC) response. Computational fluid dynamics simulations are conducted for n-heptane ignition in an RCM and the validity of zero-dimensional approach is assessed through comparisons over the entire NTC region. Results show that the zero-dimensional model based on the approach of 'adiabatic volume expansion' performs very well in adequately predicting the first-stage ignition delays, although quantitative discrepancy for the prediction of the total ignition delays and pressure rise in the first-stage ignition is noted even when the roll-up vortex is suppressed and a well-defined homogeneous core is retained within an RCM. Furthermore, the discrepancy is pressure dependent and decreases as compressed pressure is increased. Also, as ignition response becomes single-stage at higher compressed temperatures, discrepancy from the zero-dimensional simulations reduces. Despite of some quantitative discrepancy, the zero-dimensional modeling approach is deemed satisfactory from the viewpoint of the ignition delay simulation. (author)

  20. Hourly cooling load forecasting using time-indexed ARX models with two-stage weighted least squares regression

    International Nuclear Information System (INIS)

    Guo, Yin; Nazarian, Ehsan; Ko, Jeonghan; Rajurkar, Kamlakar

    2014-01-01

    Highlights: • Developed hourly-indexed ARX models for robust cooling-load forecasting. • Proposed a two-stage weighted least-squares regression approach. • Considered the effect of outliers as well as trend of cooling load and weather patterns. • Included higher order terms and day type patterns in the forecasting models. • Demonstrated better accuracy compared with some ARX and ANN models. - Abstract: This paper presents a robust hourly cooling-load forecasting method based on time-indexed autoregressive with exogenous inputs (ARX) models, in which the coefficients are estimated through a two-stage weighted least squares regression. The prediction method includes a combination of two separate time-indexed ARX models to improve prediction accuracy of the cooling load over different forecasting periods. The two-stage weighted least-squares regression approach in this study is robust to outliers and suitable for fast and adaptive coefficient estimation. The proposed method is tested on a large-scale central cooling system in an academic institution. The numerical case studies show the proposed prediction method performs better than some ANN and ARX forecasting models for the given test data set

  1. A multi-stage color model revisited: implications for a gene therapy cure for red-green colorblindness.

    Science.gov (United States)

    Mancuso, Katherine; Mauck, Matthew C; Kuchenbecker, James A; Neitz, Maureen; Neitz, Jay

    2010-01-01

    In 1993, DeValois and DeValois proposed a 'multi-stage color model' to explain how the cortex is ultimately able to deconfound the responses of neurons receiving input from three cone types in order to produce separate red-green and blue-yellow systems, as well as segregate luminance percepts (black-white) from color. This model extended the biological implementation of Hurvich and Jameson's Opponent-Process Theory of color vision, a two-stage model encompassing the three cone types combined in a later opponent organization, which has been the accepted dogma in color vision. DeValois' model attempts to satisfy the long-remaining question of how the visual system separates luminance information from color, but what are the cellular mechanisms that establish the complicated neural wiring and higher-order operations required by the Multi-stage Model? During the last decade and a half, results from molecular biology have shed new light on the evolution of primate color vision, thus constraining the possibilities for the visual circuits. The evolutionary constraints allow for an extension of DeValois' model that is more explicit about the biology of color vision circuitry, and it predicts that human red-green colorblindness can be cured using a retinal gene therapy approach to add the missing photopigment, without any additional changes to the post-synaptic circuitry.

  2. Design and modelling of an innovative three-stage thermal storage system for direct steam generation CSP plants

    Science.gov (United States)

    Garcia, Pierre; Vuillerme, Valéry; Olcese, Marco; El Mourchid, Nadim

    2016-05-01

    Thermal Energy Storage systems (TES) for a Direct Steam Generation (DSG) solar plant feature preferably three stages in series including a latent heat storage module so that steam can be recovered with a limited temperature loss. The storage system designed within the Alsolen Sup project is characterized by an innovative combination of sensible and latent modules. A dynamic model of this three-stage storage has been developed and applied to size the storage system of the Alsolen Sup® plant demonstrator at CEA Cadarache. Results of this simulation show that this promising concept is an efficient way to store heat in DSG solar plants.

  3. [Identification of Clonorchis sinensis metacercariae based on PCR targeting ribosomal DNA ITS regions and COX1 gene].

    Science.gov (United States)

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Yang, Yi-Chao; Li, Hong-Mei; Chen, Ying-Dan; Zhou, Xiao-Nong

    2014-06-01

    To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.

  4. Comparative effectiveness of one-stage versus two-stage basilic vein transposition arteriovenous fistulas.

    Science.gov (United States)

    Ghaffarian, Amir A; Griffin, Claire L; Kraiss, Larry W; Sarfati, Mark R; Brooke, Benjamin S

    2018-02-01

    Basilic vein transposition (BVT) fistulas may be performed as either a one-stage or two-stage operation, although there is debate as to which technique is superior. This study was designed to evaluate the comparative clinical efficacy and cost-effectiveness of one-stage vs two-stage BVT. We identified all patients at a single large academic hospital who had undergone creation of either a one-stage or two-stage BVT between January 2007 and January 2015. Data evaluated included patient demographics, comorbidities, medication use, reasons for abandonment, and interventions performed to maintain patency. Costs were derived from the literature, and effectiveness was expressed in quality-adjusted life-years (QALYs). We analyzed primary and secondary functional patency outcomes as well as survival during follow-up between one-stage and two-stage BVT procedures using multivariate Cox proportional hazards models and Kaplan-Meier analysis with log-rank tests. The incremental cost-effectiveness ratio was used to determine cost savings. We identified 131 patients in whom 57 (44%) one-stage BVT and 74 (56%) two-stage BVT fistulas were created among 8 different vascular surgeons during the study period that each performed both procedures. There was no significant difference in the mean age, male gender, white race, diabetes, coronary disease, or medication profile among patients undergoing one- vs two-stage BVT. After fistula transposition, the median follow-up time was 8.3 months (interquartile range, 3-21 months). Primary patency rates of one-stage BVT were 56% at 12-month follow-up, whereas primary patency rates of two-stage BVT were 72% at 12-month follow-up. Patients undergoing two-stage BVT also had significantly higher rates of secondary functional patency at 12 months (57% for one-stage BVT vs 80% for two-stage BVT) and 24 months (44% for one-stage BVT vs 73% for two-stage BVT) of follow-up (P < .001 using log-rank test). However, there was no significant difference

  5. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP m...... osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2......(-/-) mice, but after WD plasma AVP was unchanged between COX-2(-/-) and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice. Medullary interstitial osmolality increased and did not differ between COX-2(-/-) and WT after WD. Aquaporin-2 (AQP2; cortex...

  6. Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice.

    Science.gov (United States)

    Sato, Taiki; Kishimoto, Yu; Asakawa, Sanki; Mizuno, Natsumi; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2016-07-01

    Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24h. NiCl2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl2 and further potentiated by PGE2. Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be

  7. Hydrological and thermal effects of hydropeaking on early life stages of salmonids: A modelling approach for implementing mitigation strategies.

    Science.gov (United States)

    Casas-Mulet, Roser; Saltveit, Svein Jakob; Alfredsen, Knut Tore

    2016-12-15

    Alterations in hydrological and thermal regimes can potentially affect salmonid early life stages development and survival. The dewatering of salmon spawning redds due to hydropeaking can lead to mortality in early life stages, with higher impact on the alevins as they have lower tolerance to dewatering than the eggs. Flow-related mitigation measures can reduce early life stage mortality. We present a set of modelling tools to assess impacts and mitigation options to minimise the risk of mortality in early life stages in hydropeaking rivers. We successfully modelled long-term hydrological and thermal alterations and consequences for development rates. We estimated the risk of early life stages mortality and assessed the cost-effectiveness of implementing three release-related mitigation options (A,B,C). The economic cost of mitigation was low and ranged between 0.7% and 2.6% of the annual hydropower production. Options reducing the flow during spawning (B and C) in addition to only release minimum flows during development (A) were considered more effective for egg and alevin survival. Options B and C were however constraint by water availability in the system for certain years, and therefore only option A was always feasible. The set of modelling tools used in this study were satisfactory and their applications can be useful especially in systems where little field data is available. Targeted measures built on well-informed modelling tools can be tested on their effectiveness to mitigate dewatering effects vs. the hydropower system capacity to release or conserve water for power production. Environmental flow releases targeting specific ecological objectives can provide better cost-effective options than conventional operational rules complying with general legislation. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A Smoothing Algorithm for a New Two-Stage Stochastic Model of Supply Chain Based on Sample Average Approximation

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2017-01-01

    Full Text Available We construct a new two-stage stochastic model of supply chain with multiple factories and distributors for perishable product. By introducing a second-order stochastic dominance (SSD constraint, we can describe the preference consistency of the risk taker while minimizing the expected cost of company. To solve this problem, we convert it into a one-stage stochastic model equivalently; then we use sample average approximation (SAA method to approximate the expected values of the underlying random functions. A smoothing approach is proposed with which we can get the global solution and avoid introducing new variables and constraints. Meanwhile, we investigate the convergence of an optimal value from solving the transformed model and show that, with probability approaching one at exponential rate, the optimal value converges to its counterpart as the sample size increases. Numerical results show the effectiveness of the proposed algorithm and analysis.

  9. Cox2 and β-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

    Directory of Open Access Journals (Sweden)

    Jianping Kong

    2011-09-01

    Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

  10. Convergent synthesis and evaluation of {sup 18}F-labeled azulenic COX2 probes for cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Peterson, Todd E. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Crews, Brenda C. [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Marnett, Larry [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Gore, John C. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN (United States); Pham, Wellington, E-mail: wellington.pham@vanderbilt.edu [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Neuroscience, Vanderbilt University, Nashville, TN (United States)

    2013-01-03

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel {sup 18}F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional {sup 18}F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an {sup 18}F labeling strategy that employed a much milder phosphate buffer. The {sup 18}F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for

  11. A Review of Application Building Information Modeling (BIM) During Pre-Construction Stage: Retrospective and Future Directions

    Science.gov (United States)

    Edra Nisa Lau, Santi; Zakaria, Rozana; Aminudin, Eeydzah; Saar, Chai Chang; Yusof, Aswadi; Fatihi Hafifi Che Wahid, Che Muhammad

    2018-04-01

    Pre-construction is one of the biggest areas of risk and uncertainty in construction project as it deals with subsurface ground conditions information. The amount of detail data needed in pre-construction especially for existing data modelling and site analysis should be sufficient enough to ensure that significant risks could not reasonably be anticipated. Current practicing method in interpreting data during this stage tasks reveal limitation. Construction industry faced many obstacles due to the depends on the traditional practice; paper-based document which missing and redundant data always happened. In recent years, there has been a shift in construction where people move to BIM application because of its potential to reduce the problem faced by infrastructure world. BIM has become a successful technology and widely popular in the construction world especially in developed countries because of its potential. Nowadays, people are moving one step ahead in BIM which is adoption of BIM during pre-construction stage. Thus, this paper review studies centered on BIM-integrated modelling during preconstruction stage. But there is lack of practical researches have been made during this stage. Although a large number of studies on BIM have been conducted in the past decade, a lack of consensus remains among researchers and practitioners regarding the applications of BIM during pre-construction stage, the availability of subsequent data integration tool for geotechnical activity. A comprehensive literature review was conducted for data collection and analysis. After in-depth review of journal articles widely cover the application of BIM, this study summarizes an overview and critical reflection of geotechnical data integration using BIM during pre-construction stage. The results are useful for the identification of research clusters and topics in the BIM community.

  12. The eHealth Behavior Management Model: a stage-based approach to behavior change and management.

    Science.gov (United States)

    Bensley, Robert J; Mercer, Nelda; Brusk, John J; Underhile, Ric; Rivas, Jason; Anderson, Judith; Kelleher, Deanne; Lupella, Melissa; de Jager, André C

    2004-10-01

    Although the Internet has become an important avenue for disseminating health information, theory-driven strategies for aiding individuals in changing or managing health behaviors are lacking. The eHealth Behavior Management Model combines the Transtheoretical Model, the behavioral intent aspect of the Theory of Planned Behavior, and persuasive communication to assist individuals in negotiating the Web toward stage-specific information. It is here - at the point of stage-specific information - that behavioral intent in moving toward more active stages of change occurs. The eHealth Behavior Management Model is applied in three demonstration projects that focus on behavior management issues: parent-child nutrition education among participants in the U.S. Department of Agriculture Special Supplemental Nutrition Program for Women, Infants and Children; asthma management among university staff and students; and human immunodeficiency virus prevention among South African women. Preliminary results have found the eHealth Behavior Management Model to be promising as a model for Internet-based behavior change programming. Further application and evaluation among other behavior and disease management issues are needed.

  13. Effects of the stages of change model-based education and motivational interview on exercise behavior in diabetic women.

    Science.gov (United States)

    Sekerci, Yasemin Gümüs; Kitis, Yeter

    2018-05-08

    In this study, we examined the effects of exercise education and a motivational interview program, based on the stages of change model (SCM), on stage of change, using cognitive and behavioral methods, perceived benefits and barriers and self-confidence in Turkish women with diabetes. This intervention study was carried out in 2015 on 55 women selected from a family health centers' population. An exercise guide was prepared based on the SCM for the intervention group. The intervention group was followed seven times at 1-month intervals via home visits, and exercise education and the motivational interview program were conducted to identify changes in behavior. The control group received no intervention. Data were collected from both groups using a personal description form, Exercise Stages of Change Scale, Exercise Processes of Change Scale, Exercise Decisional Balance Scale, and Exercise Self-Efficacy Scale. After the exercise program, each group was re-subjected to the same scales. We used a chi-square test and independent and paired sample t-tests to analyze the data. The stages of change, using cognitive and behavioral methods, perceived benefits and self-confidence for exercise in the intervention group significantly improved compared with that in the control group (p interview program based on SCM positively affected stages of change, using cognitive and behavioral methods, perceived benefits, perceived barriers, and self-confidence for exercise behavior in women with diabetes. We conclude that the education and motivational interview program based on SCM are effective in promoting exercise habit.

  14. An adaptive two-stage analog/regression model for probabilistic prediction of small-scale precipitation in France

    Directory of Open Access Journals (Sweden)

    J. Chardon

    2018-01-01

    Full Text Available Statistical downscaling models (SDMs are often used to produce local weather scenarios from large-scale atmospheric information. SDMs include transfer functions which are based on a statistical link identified from observations between local weather and a set of large-scale predictors. As physical processes driving surface weather vary in time, the most relevant predictors and the regression link are likely to vary in time too. This is well known for precipitation for instance and the link is thus often estimated after some seasonal stratification of the data. In this study, we present a two-stage analog/regression model where the regression link is estimated from atmospheric analogs of the current prediction day. Atmospheric analogs are identified from fields of geopotential heights at 1000 and 500 hPa. For the regression stage, two generalized linear models are further used to model the probability of precipitation occurrence and the distribution of non-zero precipitation amounts, respectively. The two-stage model is evaluated for the probabilistic prediction of small-scale precipitation over France. It noticeably improves the skill of the prediction for both precipitation occurrence and amount. As the analog days vary from one prediction day to another, the atmospheric predictors selected in the regression stage and the value of the corresponding regression coefficients can vary from one prediction day to another. The model allows thus for a day-to-day adaptive and tailored downscaling. It can also reveal specific predictors for peculiar and non-frequent weather configurations.

  15. The evolution of environmental management: from stage models to performance evaluation

    NARCIS (Netherlands)

    Kolk, A.; Mauser, A.

    2002-01-01

    In the past two decades, academics and practitioners have attempted to improve understanding of environmental management by classifying companies environmental behaviour, and evaluating their performance. Driven by both research and societal interest, this has resulted in a wave of stage or phase

  16. Setting safety stocks in multi-stage inventory systems under rolling horizon mathematical programming models

    NARCIS (Netherlands)

    Boulaksil, Y.; Fransoo, J.C.; van Halm, E.N.G.

    2009-01-01

    This paper considers the problem of determining safety stocks in multi-item multi-stage inventory systems that face demand uncertainties. Safety stocks are necessary to make the supply chain, which is driven by forecasts of customer orders, responsive to (demand) uncertainties and to achieve

  17. A Theoretical Model for the Four-Stage Music-Industry Internship Program.

    Science.gov (United States)

    Schenbeck, Lyn

    1996-01-01

    Describes student development through experiential learning in a four-stage internship within a college music-industry curriculum, and uses the Steinaker-Bell experiential taxonomy to show how embedding a multistage internship throughout the curriculum, rather than at the end, greatly enhances learning. Suggests ways in which the multistage…

  18. Building performance simulation in the early design stage: An introduction to integrated dynamic models

    DEFF Research Database (Denmark)

    Negendahl, Kristoffer

    2015-01-01

    , a visual programming language and a BPS to provide better support for the designer during the early stages of design as opposed to alternatives such as the current implementation of IFC or gbXML or the unaccompanied use of simulation packages. (C) 2015 Elsevier B.V. All rights reserved....

  19. Can metabolic tumor parameters on primary staging 18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

    Science.gov (United States)

    Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

    Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  20. Modeling the Hybrid Flow Shop Scheduling Problem Followed by an Assembly Stage Considering Aging Effects and Preventive Maintenance Activities

    Directory of Open Access Journals (Sweden)

    Seyyed Mohammad Hassan Hosseini

    2016-05-01

    Full Text Available Scheduling problem for the hybrid flow shop scheduling problem (HFSP followed by an assembly stage considering aging effects additional preventive and maintenance activities is studied in this paper. In this production system, a number of products of different kinds are produced. Each product is assembled with a set of several parts. The first stage is a hybrid flow shop to produce parts. All machines can process all kinds of parts in this stage but each machine can process only one part at the same time. The second stage is a single assembly machine or a single assembly team of workers. The aim is to schedule the parts on the machines and assembly sequence and also determine when the preventive maintenance activities get done in order to minimize the completion time of all products (makespan. A mathematical modeling is presented and its validation is shown by solving an example in small scale. Since this problem has been proved strongly NP-hard, in order to solve the problem in medium and large scale, four heuristic algorithms is proposed based on the Johnson’s algorithm. The numerical experiments are used to run the mathematical model and evaluate the performance of the proposed algorithms.

  1. A time consistent risk averse three-stage stochastic mixed integer optimization model for power generation capacity expansion

    International Nuclear Information System (INIS)

    Pisciella, P.; Vespucci, M.T.; Bertocchi, M.; Zigrino, S.

    2016-01-01

    We propose a multi-stage stochastic optimization model for the generation capacity expansion problem of a price-taker power producer. Uncertainties regarding the evolution of electricity prices and fuel costs play a major role in long term investment decisions, therefore the objective function represents a trade-off between expected profit and risk. The Conditional Value at Risk is the risk measure used and is defined by a nested formulation that guarantees time consistency in the multi-stage model. The proposed model allows one to determine a long term expansion plan which takes into account uncertainty, while the LCoE approach, currently used by decision makers, only allows one to determine which technology should be chosen for the next power plant to be built. A sensitivity analysis is performed with respect to the risk weighting factor and budget amount. - Highlights: • We propose a time consistent risk averse multi-stage model for capacity expansion. • We introduce a case study with uncertainty on electricity prices and fuel costs. • Increased budget moves the investment from gas towards renewables and then coal. • Increased risk aversion moves the investment from coal towards renewables. • Time inconsistency leads to a profit gap between planned and implemented policies.

  2. A Comparison of Two-Stage Approaches for Fitting Nonlinear Ordinary Differential Equation Models with Mixed Effects.

    Science.gov (United States)

    Chow, Sy-Miin; Bendezú, Jason J; Cole, Pamela M; Ram, Nilam

    2016-01-01

    Several approaches exist for estimating the derivatives of observed data for model exploration purposes, including functional data analysis (FDA; Ramsay & Silverman, 2005 ), generalized local linear approximation (GLLA; Boker, Deboeck, Edler, & Peel, 2010 ), and generalized orthogonal local derivative approximation (GOLD; Deboeck, 2010 ). These derivative estimation procedures can be used in a two-stage process to fit mixed effects ordinary differential equation (ODE) models. While the performance and utility of these routines for estimating linear ODEs have been established, they have not yet been evaluated in the context of nonlinear ODEs with mixed effects. We compared properties of the GLLA and GOLD to an FDA-based two-stage approach denoted herein as functional ordinary differential equation with mixed effects (FODEmixed) in a Monte Carlo (MC) study using a nonlinear coupled oscillators model with mixed effects. Simulation results showed that overall, the FODEmixed outperformed both the GLLA and GOLD across all the embedding dimensions considered, but a novel use of a fourth-order GLLA approach combined with very high embedding dimensions yielded estimation results that almost paralleled those from the FODEmixed. We discuss the strengths and limitations of each approach and demonstrate how output from each stage of FODEmixed may be used to inform empirical modeling of young children's self-regulation.

  3. Harvesting policy for a delayed stage-structured Holling II predator-prey model with impulsive stocking prey

    International Nuclear Information System (INIS)

    Jiao Jianjun; Meng Xinzhu; Chen Lansun

    2009-01-01

    A predator-prey model with a stage structure for the predator, which improves the assumption that each individual predator has the same ability to capture prey, is proposed by Wang et al. [Wang W, Mulone G, Salemi F, Salone V. Permanence and stability of a stage-structured predator-prey model. J Math Anal Appl 2001;262:499-528]. It is assumed that immature individuals and mature individuals of the predator are divided by a fixed age and that immature predators do not have the ability to attack prey. We do economic management behavior for Wang model [Wang et al., 2001] by continuous harvesting on predator and impulsive stocking on prey. Then, a delayed stage-structured Holling type II predator-prey model with impulsive stocking prey and continuous harvesting predator is established. It is also assumed that the predating products of the predator is only to increase its bearing ability. We obtain the sufficient conditions of the global attractivity of predator-extinction boundary periodic solution and the permanence of the system. Our results show that the behavior of impulsive stocking prey plays an important role for the permanence of the system, and provide tactical basis for the biological resource management. Further, the numerical analysis is also inserted to illuminate the dynamics of the system.

  4. The Application of CPA to Calculations of the Mean Magnetic Moment in the Gd1-xNi, Gd1-xFe, Gd1xCox, and Y1-xCox Intermetallic Compounds

    DEFF Research Database (Denmark)

    Szpunar, B.; Kozarzewski, B.

    1977-01-01

    with a narrow d-band is considered. The magnetic moment of the alloy at zero temperature is calculated within the molecular field and Hartree-Fock approximations. Disorder is treated in the coherent potential approximation. Results are in good agreement with the experimental data obtained for the crystalline......Calculations are made of the mean magnetic moment per atom of the transition metal and the rare-earth metal in the intermetallic compounds, Gd1-x,Nix, Gd1-x Fex, Gd1-x Cox, and Y1-x Cox. A simple model of the disordered alloy consisting of spins localized on the rare-earth atoms and interacting...

  5. A new approach to the Box-Cox transformation

    Directory of Open Access Journals (Sweden)

    Jorge Iván eVélez

    2015-10-01

    Full Text Available We propose a new methodology to estimate λ, the parameter of the Box-Cox transformation, as well as an alternative method to determine plausible values for it. The former is accomplished by defining a grid of values for λ and further perform a normality test on the λ -transformed data. The optimum value of λ, say λ * , is such that the p-value from the normality test is the highest. The set of plausible values is determined using the inverse probability method after plotting the p-values against the values of λ on the grid. Our methodology is illustrated with two real-world data sets. Furthermore, a simulation study suggests that our method improves the symmetry, kurtosis and, hence, the normality of data, making it a feasible alternative to the traditional Box-Cox transformation.

  6. Some functional limit theorems for compound Cox processes

    Energy Technology Data Exchange (ETDEWEB)

    Korolev, Victor Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Institute of Informatics Problems FRC CSC RAS (Russian Federation); Chertok, A. V. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Euphoria Group LLC (Russian Federation); Korchagin, A. Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Kossova, E. V. [Higher School of Economics National Research University, Moscow (Russian Federation); Zeifman, Alexander I. [Vologda State University, S.Orlova, 6, Vologda (Russian Federation); Institute of Informatics Problems FRC CSC RAS, ISEDT RAS (Russian Federation)

    2016-06-08

    An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

  7. Some functional limit theorems for compound Cox processes

    International Nuclear Information System (INIS)

    Korolev, Victor Yu.; Chertok, A. V.; Korchagin, A. Yu.; Kossova, E. V.; Zeifman, Alexander I.

    2016-01-01

    An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

  8. Enhancing the Predicting Accuracy of the Water Stage Using a Physical-Based Model and an Artificial Neural Network-Genetic Algorithm in a River System

    Directory of Open Access Journals (Sweden)

    Wen-Cheng Liu

    2014-06-01

    Full Text Available Accurate simulations of river stages during typhoon events are critically important for flood control and are necessary for disaster prevention and water resources management in Taiwan. This study applies two artificial neural network (ANN models, including the back propagation neural network (BPNN and genetic algorithm neural network (GANN techniques, to improve predictions from a one-dimensional flood routing hydrodynamic model regarding the water stages during typhoon events in the Danshuei River system in northern Taiwan. The hydrodynamic model is driven by freshwater discharges at the upstream boundary conditions and by the water levels at the downstream boundary condition. The model provides a sound physical basis for simulating water stages along the river. The simulated results of the hydrodynamic model show that the model cannot reproduce the water stages at different stations during typhoon events for the model calibration and verification phases. The BPNN and GANN models can improve the simulated water stages compared with the performance of the hydrodynamic model. The GANN model satisfactorily predicts water stages during the training and verification phases and exhibits the lowest values of mean absolute error, root-mean-square error and peak error compared with the simulated results at different stations using the hydrodynamic model and the BPNN model. Comparison of the simulated results shows that the GANN model can be successfully applied to predict the water stages of the Danshuei River system during typhoon events.

  9. COX-2 Inhibitors for Cancer Treatment in Dogs

    Directory of Open Access Journals (Sweden)

    Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

    2011-10-01

    Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

  10. Modelling quality of fresh-cut tomato based on stage of maturity and storage conditions

    OpenAIRE

    Moreira Lana, M.

    2005-01-01

    Fresh-cut or minimally processed vegetables are those which have been trimmed and/or peeled and/or cut into 100% usable product and still maintain freshness. Contrary to other processing methods (freezing, canning and drying for example) the minimal processing operations reduce the shelf life in relation to the raw material (intact product).In this thesis the changes in quality of tomato fruits after cutting into transversal slices were analysed and quantified in relation to the stage of matu...

  11. Modelling of an air-cooled two-stage Rankine cycle for electricity production

    International Nuclear Information System (INIS)

    Liu, Bo

    2014-01-01

    This work considers a two stage Rankine cycle architecture slightly different from a standard Rankine cycle for electricity generation. Instead of expanding the steam to extremely low pressure, the vapor leaves the turbine at a higher pressure then having a much smaller specific volume. It is thus possible to greatly reduce the size of the steam turbine. The remaining energy is recovered by a bottoming cycle using a working fluid which has a much higher density than the water steam. Thus, the turbines and heat exchangers are more compact; the turbine exhaust velocity loss is lower. This configuration enables to largely reduce the global size of the steam water turbine and facilitate the use of a dry cooling system. The main advantage of such an air cooled two stage Rankine cycle is the possibility to choose the installation site of a large or medium power plant without the need of a large and constantly available water source; in addition, as compared to water cooled cycles, the risk regarding future operations is reduced (climate conditions may affect water availability or temperature, and imply changes in the water supply regulatory rules). The concept has been investigated by EDF R and D. A 22 MW prototype was developed in the 1970's using ammonia as the working fluid of the bottoming cycle for its high density and high latent heat. However, this fluid is toxic. In order to search more suitable working fluids for the two stage Rankine cycle application and to identify the optimal cycle configuration, we have established a working fluid selection methodology. Some potential candidates have been identified. We have evaluated the performances of the two stage Rankine cycles operating with different working fluids in both design and off design conditions. For the most acceptable working fluids, components of the cycle have been sized. The power plant concept can then be evaluated on a life cycle cost basis. (author)

  12. Actuator Fault Diagnosis in a Boeing 747 Model via Adaptive Modified Two-Stage Kalman Filter

    Directory of Open Access Journals (Sweden)

    Fikret Caliskan

    2014-01-01

    Full Text Available An adaptive modified two-stage linear Kalman filtering algorithm is utilized to identify the loss of control effectiveness and the magnitude of low degree of stuck faults in a closed-loop nonlinear B747 aircraft. Control effectiveness factors and stuck magnitudes are used to quantify faults entering control systems through actuators. Pseudorandom excitation inputs are used to help distinguish partial loss and stuck faults. The partial loss and stuck faults in the stabilizer are isolated and identified successfully.

  13. Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

    International Nuclear Information System (INIS)

    Ichimura, Ryohei; Mizukami, Sayaka; Takahashi, Miwa; Taniai, Eriko; Kemmochi, Sayaka; Mitsumori, Kunitoshi; Shibutani, Makoto

    2010-01-01

    To clarify the involvement of signaling of transforming growth factor (TGF)-β during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P + foci, while Smad4, a nuclear transporter of Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P + lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P + foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P - foci induced by promotion with agonists of peroxisome proliferator-activated receptor-α did not change Smad expression, suggesting an aberration in the Smad-dependent signaling prerequisites for induction

  14. A two-stage flow-based intrusion detection model for next-generation networks.

    Science.gov (United States)

    Umer, Muhammad Fahad; Sher, Muhammad; Bi, Yaxin

    2018-01-01

    The next-generation network provides state-of-the-art access-independent services over converged mobile and fixed networks. Security in the converged network environment is a major challenge. Traditional packet and protocol-based intrusion detection techniques cannot be used in next-generation networks due to slow throughput, low accuracy and their inability to inspect encrypted payload. An alternative solution for protection of next-generation networks is to use network flow records for detection of malicious activity in the network traffic. The network flow records are independent of access networks and user applications. In this paper, we propose a two-stage flow-based intrusion detection system for next-generation networks. The first stage uses an enhanced unsupervised one-class support vector machine which separates malicious flows from normal network traffic. The second stage uses a self-organizing map which automatically groups malicious flows into different alert clusters. We validated the proposed approach on two flow-based datasets and obtained promising results.

  15. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    Directory of Open Access Journals (Sweden)

    STANCA CLAUDIA

    2007-01-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  16. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    Directory of Open Access Journals (Sweden)

    CLAUDIA STANCA

    2007-05-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  17. Two-stage Lagrangian modeling of ignition processes in ignition quality tester and constant volume combustion chambers

    KAUST Repository

    Alfazazi, Adamu

    2016-08-10

    The ignition characteristics of isooctane and n-heptane in an ignition quality tester (IQT) were simulated using a two-stage Lagrangian (TSL) model, which is a zero-dimensional (0-D) reactor network method. The TSL model was also used to simulate the ignition delay of n-dodecane and n-heptane in a constant volume combustion chamber (CVCC), which is archived in the engine combustion network (ECN) library (http://www.ca.sandia.gov/ecn). A detailed chemical kinetic model for gasoline surrogates from the Lawrence Livermore National Laboratory (LLNL) was utilized for the simulation of n-heptane and isooctane. Additional simulations were performed using an optimized gasoline surrogate mechanism from RWTH Aachen University. Validations of the simulated data were also performed with experimental results from an IQT at KAUST. For simulation of n-dodecane in the CVCC, two n-dodecane kinetic models from the literature were utilized. The primary aim of this study is to test the ability of TSL to replicate ignition timings in the IQT and the CVCC. The agreement between the model and the experiment is acceptable except for isooctane in the IQT and n-heptane and n-dodecane in the CVCC. The ability of the simulations to replicate observable trends in ignition delay times with regard to changes in ambient temperature and pressure allows the model to provide insights into the reactions contributing towards ignition. Thus, the TSL model was further employed to investigate the physical and chemical processes responsible for controlling the overall ignition under various conditions. The effects of exothermicity, ambient pressure, and ambient oxygen concentration on first stage ignition were also studied. Increasing ambient pressure and oxygen concentration was found to shorten the overall ignition delay time, but does not affect the timing of the first stage ignition. Additionally, the temperature at the end of the first stage ignition was found to increase at higher ambient pressure

  18. Three-stage steady-state model for biomass gasification in a dual circulating fluidized-bed

    International Nuclear Information System (INIS)

    Nguyen, Thanh D.B.; Ngo, Son Ich; Lim, Young-Il; Lee, Jeong Woo; Lee, Uen-Do; Song, Byung-Ho

    2012-01-01

    Highlights: ► Steam gasification of woodchips is examined in dual circulating fluidized-bed (DFB). ► We develop a three-stage model (TSM) for process performance evaluation. ► Effect of gasification temperature and steam to fuel ratio is investigated. ► Several effective operating conditions are found by parametric study. - Abstract: A three-stage steady state model (TSM) was developed for biomass steam gasification in a dual circulating fluidized-bed (DFB) to calculate the composition of producer gas, carbon conversion, heat recovery, cost efficiency, and heat demand needed for the endothermic gasification reactions. The model was divided into three stages including biomass pyrolysis, char–gas reactions, and gas–phase reaction. At each stage, an empirical equation was estimated from experimental data. It was assumed that both unconverted char and additional fuel were completely combusted at 950 °C in the combustor (riser) and the heat required for gasification reactions was provided by the bed material (silica sand). The model was validated with experimental data taken from the literature. The parametric study of the gasification temperature (T) and the steam to fuel ratio (γ) was then carried out to evaluate performance criteria of a 1.8 MW DFB gasifier using woodchips as a feedstock for the electric power generation. Effective operating conditions of the DFB gasifier were proposed by means of the contour of the solid circulation ratio, the heat recovery, the additional fuel ratio and the cost efficiency with respect to T and γ.

  19. Deleterious effects of lymphocytes at the early stage of neurodegeneration in an animal model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Nakatsuji Yuji

    2011-02-01

    Full Text Available Abstract Background Non-neuronal cells, such as microglia and lymphocytes, are thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS. Previous studies have demonstrated neuroprotective effects of lymphocytes at the end stage of ALS, partly through induction of alternatively activated microglia (M2 microglia, which are neuroprotective. In this study, we investigated the role of lymphocytes in the early stage of the disease using an animal model of inherited ALS. Methods We established a transgenic mouse line overexpressing the familial ALS-associated G93A-SOD1 mutation (harboring a single amino acid substitution of glycine to alanine at codon 93 with depletion of the Rag2 gene (mSOD1/RAG2-/- mice, an animal model of inherited ALS lacking mature lymphocytes. Body weights, clinical scores and motor performance (hanging wire test of mSOD1/RAG2-/- mice were compared to those of mutant human SOD1 transgenic mice (mSOD1/RAG2+/+ mice. Activation of glial cells in the spinal cords of these mice was determined immunohistochemically, and the expression of mRNA for various inflammatory and anti-inflammatory molecules was evaluated. Results Clinical onset in mSOD1/RAG2-/- mice was significantly delayed, and the number of lectin-positive cells in spinal cord was increased at the early stage of disease when compared to mSOD1/RAG2+/+ mice. Quantitative RT-PCR confirmed that mRNA for Ym1, an M2 microglial-related molecule, was significantly increased in mSOD1/RAG2-/- mouse spinal cords at the early disease stage. Conclusions Compared with mSOD1/RAG2+/+ mice, mSOD1/RAG2-/- mice displayed delayed onset and increased M2 microglial activation at the early stage of disease. Thus, lymphocytes at the early pathological phase of ALS display a deleterious effect via inhibition of M2 microglial activation.

  20. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Kang, Ju-Hee; Song, Ki-Hoon; Jeong, Kyung-Chae; Kim, Sunshin; Choi, Changsun; Lee, Chang Hoon; Oh, Seung Hyun

    2011-01-01

    A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

  1. Limitations of Cox Proportional Hazards Analysis in Mortality Prediction of Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Babińska Magdalena

    2015-12-01

    Full Text Available The aim of this study was to evaluate the possibility of incorrect assessment of mortality risk factors in a group of patients affected by acute coronary syndrome, due to the lack of hazard proportionality in the Cox regression model. One hundred and fifty consecutive patients with acute coronary syndrome (ACS and no age limit were enrolled. Univariable and multivariable Cox proportional hazard analyses were performed. The proportional hazard assumptions were verified using Schoenfeld residuals, χ2 test and rank correlation coefficient t between residuals and time. In the total group of 150 patients, 33 (22.0% deaths from any cause were registered in the follow-up time period of 64 months. The non-survivors were significantly older and had increased prevalence of diabetes and erythrocyturia, longer history of coronary artery disease, higher concentrations of serum creatinine, cystatin C, uric acid, glucose, C-reactive protein (CRP, homocysteine and B-type natriuretic peptide (NT-proBNP, and lower concentrations of serum sodium. No significant differences in echocardiography parameters were observed between groups. The following factors were risk of death factors and fulfilled the proportional hazard assumption in the univariable model: smoking, occurrence of diabetes and anaemia, duration of coronary artery disease, and abnormal serum concentrations of uric acid, sodium, homocysteine, cystatin C and NT-proBNP, while in the multivariable model, the risk of death factors were: smoking and elevated concentrations of homocysteine and NT-proBNP. The study has demonstrated that violation of the proportional hazard assumption in the Cox regression model may lead to creating a false model that does not include only time-independent predictive factors.

  2. Analysis of multi-species point patterns using multivariate log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus; Guan, Yongtao; Jalilian, Abdollah

    Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address t...... of the data. The selected number of common latent fields provides an index of complexity of the multivariate covariance structure. Hierarchical clustering is used to identify groups of species with similar patterns of dependence on the common latent fields.......Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address...... the problems of identifying parsimonious models and of extracting biologically relevant information from the fitted models. The latent multivariate Gaussian field is decomposed into components given in terms of random fields common to all species and components which are species specific. This allows...

  3. Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib.

    Science.gov (United States)

    Kirane, Amanda; Toombs, Jason E; Larsen, Jill E; Ostapoff, Katherine T; Meshaw, Kathryn R; Zaknoen, Sara; Brekken, Rolf A; Burrows, Francis J

    2012-09-01

    Although cyclooxygenase-2 (COX-2) inhibitors, such as the late stage development drug apricoxib, exhibit antitumor activity, their mechanisms of action have not been fully defined. In this study, we characterized the mechanisms of action of apricoxib in HT29 colorectal carcinoma. Apricoxib was weakly cytotoxic toward naive HT29 cells in vitro but inhibited tumor growth markedly in vivo. Pharmacokinetic analyses revealed that in vivo drug levels peaked at 2-4 µM and remained sufficient to completely inhibit prostaglandin E(2) production, but failed to reach concentrations cytotoxic for HT29 cells in monolayer culture. Despite this, apricoxib significantly inhibited tumor cell proliferation and induced apoptosis without affecting blood vessel density, although it did promote vascular normalization. Strikingly, apricoxib treatment induced a dose-dependent reversal of epithelial-mesenchymal transition (EMT), as shown by robust upregulation of E-cadherin and the virtual disappearance of vimentin and ZEB1 protein expression. In vitro, either anchorage-independent growth conditions or forced EMT sensitized HT29 and non-small cell lung cancer cells to apricoxib by 50-fold, suggesting that the occurrence of EMT may actually increase the dependence of colon and lung carcinoma cells on COX-2. Taken together, these data suggest that acquisition of mesenchymal characteristics sensitizes carcinoma cells to apricoxib resulting in significant single-agent antitumor activity.

  4. A Predictive Model of Multi-Stage Production Planning for Fixed Time Orders

    Directory of Open Access Journals (Sweden)

    Kozłowski Edward

    2014-09-01

    Full Text Available The traditional production planning model based upon a deterministic approach is well described in the literature. Due to the uncertain nature of manufacturing processes, such model can however incorrectly represent actual situations on the shop floor. This study develops a mathematical modeling framework for generating production plans in a multistage manufacturing process. The devised model takes into account the stochastic model for predicting the occurrence of faulty products. The aim of the control model is to determine the number of products which should be manufactured in each planning period to minimize both manufacturing costs and potential financial penalties for failing to fulfill the order completely.

  5. Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.

    Science.gov (United States)

    Fang, Xin; Reifman, Jaques; Wallqvist, Anders

    2014-10-01

    The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.

  6. A reliability model of the Angra 1 power system by the device of stages optimized by genetic algorithms

    International Nuclear Information System (INIS)

    Crossetti, Patricia Guimaraes

    2006-01-01

    This thesis proposes a probabilistic model to perform the reliability analysis of nuclear power plant systems under aging. This work analyses the Angra 1 power system. Systems subject to aging consist of components whose failure rates are not all constant, thus generating Non-Markovian models. Genetic algorithms were used for optimizing the application of the device of stages. Two approaches were used in the optimization, MCEF and MCEV. The results obtained for the Angra 1 power system show that the probability of a station blackout is negligible. (author)

  7. An Examination of Interactive Whiteboard Perceptions using the Concerns-Based Adoption Model Stages of Concern and the Apple Classrooms of Tomorrow Model of Instructional Evolution

    Science.gov (United States)

    Hall, Jeffrey; Chamblee, Gregory; Slough, Scott

    2013-01-01

    Two high school mathematics teachers who use Interactive Whiteboards (IWBs) in the classroom were interviewed annually over the course of three years regarding their perceptions of the technology. During the third year, the two teachers were asked to complete the Concerns-Based Adoption Model Stages of Concern Questionnaire. The data obtained from…

  8. Stage-structured matrix models for organisms with non-geometric development times

    Science.gov (United States)

    Andrew Birt; Richard M. Feldman; David M. Cairns; Robert N. Coulson; Maria Tchakerian; Weimin Xi; James M. Guldin

    2009-01-01

    Matrix models have been used to model population growth of organisms for many decades. They are popular because of both their conceptual simplicity and their computational efficiency. For some types of organisms they are relatively accurate in predicting population growth; however, for others the matrix approach does not adequately model...

  9. Prediction of bird-day carrying capacity on a staging site: a test of depletion models

    NARCIS (Netherlands)

    Nolet, B.A.; Gyimesi, A.; Klaassen, R.H.G.

    2006-01-01

    1. The carrying capacity of a site for migratory water birds, expressed in bird-days, can be of particular conservation value. Several attempts have been made to model this carrying capacity using ideal free distribution models such as, for instance, depletion models, in which the distribution is

  10. A two-stage preventive maintenance optimization model incorporating two-dimensional extended warranty

    International Nuclear Information System (INIS)

    Su, Chun; Wang, Xiaolin

    2016-01-01

    In practice, customers can decide whether to buy an extended warranty or not, at the time of item sale or at the end of the basic warranty. In this paper, by taking into account the moments of customers purchasing two-dimensional extended warranty, the optimization of imperfect preventive maintenance for repairable items is investigated from the manufacturer's perspective. A two-dimensional preventive maintenance strategy is proposed, under which the item is preventively maintained according to a specified age interval or usage interval, whichever occurs first. It is highlighted that when the extended warranty is purchased upon the expiration of the basic warranty, the manufacturer faces a two-stage preventive maintenance optimization problem. Moreover, in the second stage, the possibility of reducing the servicing cost over the extended warranty period is explored by classifying customers on the basis of their usage rates and then providing them with customized preventive maintenance programs. Numerical examples show that offering customized preventive maintenance programs can reduce the manufacturer's warranty cost, while a larger saving in warranty cost comes from encouraging customers to buy the extended warranty at the time of item sale. - Highlights: • A two-dimensional PM strategy is investigated. • Imperfect PM strategy is optimized by considering both two-dimensional BW and EW. • Customers are categorized based on their usage rates throughout the BW period. • Servicing cost of the EW is reduced by offering customized PM programs. • Customers buying the EW at the time of sale is preferred for the manufacturer.

  11. Estimating radiation-induced cancer risk using MVK two-stage model for carcinogenesis

    International Nuclear Information System (INIS)

    Kai, M.; Kusama, T.; Aoki, Y.

    1993-01-01

    Based on the carcinogenesis model as proposed by Moolgavkar et al., time-dependent relative risk models were derived for projecting the time variation in excess relative risk. If it is assumed that each process is described by time-independent linear dose-response relationship, the time variation in excess relative risk is influenced by the parameter related with the promotion process. The risk model based carcinogenesis theory would play a marked role in estimating radiation-induced cancer risk in constructing a projection model or transfer model

  12. Building fast well-balanced two-stage numerical schemes for a model of two-phase flows

    Science.gov (United States)

    Thanh, Mai Duc

    2014-06-01

    We present a set of well-balanced two-stage schemes for an isentropic model of two-phase flows arisen from the modeling of deflagration-to-detonation transition in granular materials. The first stage is to absorb the source term in nonconservative form into equilibria. Then in the second stage, these equilibria will be composed into a numerical flux formed by using a convex combination of the numerical flux of a stable Lax-Friedrichs-type scheme and the one of a higher-order Richtmyer-type scheme. Numerical schemes constructed in such a way are expected to get the interesting property: they are fast and stable. Tests show that the method works out until the parameter takes on the value CFL, and so any value of the parameter between zero and this value is expected to work as well. All the schemes in this family are shown to capture stationary waves and preserves the positivity of the volume fractions. The special values of the parameter 0,1/2,1/(1+CFL), and CFL in this family define the Lax-Friedrichs-type, FAST1, FAST2, and FAST3 schemes, respectively. These schemes are shown to give a desirable accuracy. The errors and the CPU time of these schemes and the Roe-type scheme are calculated and compared. The constructed schemes are shown to be well-balanced and faster than the Roe-type scheme.

  13. Two-stage Bayesian model to evaluate the effect of air pollution on chronic respiratory diseases using drug prescriptions.

    Science.gov (United States)

    Blangiardo, Marta; Finazzi, Francesco; Cameletti, Michela

    2016-08-01

    Exposure to high levels of air pollutant concentration is known to be associated with respiratory problems which can translate into higher morbidity and mortality rates. The link between air pollution and population health has mainly been assessed considering air quality and hospitalisation or mortality data. However, this approach limits the analysis to individuals characterised by severe conditions. In this paper we evaluate the link between air pollution and respiratory diseases using general practice drug prescriptions for chronic respiratory diseases, which allow to draw conclusions based on the general population. We propose a two-stage statistical approach: in the first stage we specify a space-time model to estimate the monthly NO2 concentration integrating several data sources characterised by different spatio-temporal resolution; in the second stage we link the concentration to the β2-agonists prescribed monthly by general practices in England and we model the prescription rates through a small area approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A manufacturing quality assessment model based-on two stages interval type-2 fuzzy logic

    Science.gov (United States)

    Purnomo, Muhammad Ridwan Andi; Helmi Shintya Dewi, Intan

    2016-01-01

    This paper presents the development of an assessment models for manufacturing quality using Interval Type-2 Fuzzy Logic (IT2-FL). The proposed model is developed based on one of building block in sustainable supply chain management (SSCM), which is benefit of SCM, and focuses more on quality. The proposed model can be used to predict the quality level of production chain in a company. The quality of production will affect to the quality of product. Practically, quality of production is unique for every type of production system. Hence, experts opinion will play major role in developing the assessment model. The model will become more complicated when the data contains ambiguity and uncertainty. In this study, IT2-FL is used to model the ambiguity and uncertainty. A case study taken from a company in Yogyakarta shows that the proposed manufacturing quality assessment model can work well in determining the quality level of production.

  15. A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

    Science.gov (United States)

    Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

    2017-06-01

    Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

  16. Method of using of the Box-Cox transformation at the application of the xbar and s chart

    Directory of Open Access Journals (Sweden)

    Eftimie Nicolae

    2017-01-01

    Full Text Available The application of the most statistical process control techniques is based on the assumption that the distribution of the measurements is normal. However, there are many situations in practice when the process data distribution is not normal. In certain cases, the Box-Cox transformation can be used for converting the process data distribution into a normal distribution. Considering these aspects, the paper presents a method of application for the xbar and s chart that can be used in the case when the measurements distribution is not normal. The proposed method consists of the following stages: the testing of normality of the process data, the application of the Box-Cox transformation and the testing of normality of the transformed data. In the case when the distribution of the transformed data is normal, they are used at the application of the xbar and s control chart.

  17. Box-Cox Test: the theoretical justification and US-China empirical study

    Directory of Open Access Journals (Sweden)

    Tam Bang Vu

    2011-01-01

    Full Text Available In econometrics, the derivation of a theoretical model leads sometimes to two econometric models, which can be considered justified based on their respective approximation approaches. Hence, the decision of choosing one between the two hinges on applied econometric tools. In this paper, the authors develop a theoretical econometrics consumer maximization model to measure the flow of durables’ expenditures where depreciation is added to former classical econometrics model. The proposed model was formulated in both linear and logarithmic forms. Box-Cox tests were used to choose the most appropriate one among them. The proposed model was then applied to the historical data from the U.S. and China for a comparative study and the results discussed.

  18. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

    Directory of Open Access Journals (Sweden)

    Mingzhu Zhuang

    Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment