Sample records for univariate cox regression

  1. The estimation of average hazard ratios by weighted Cox regression.

    PubMed

    Schemper, Michael; Wakounig, Samo; Heinze, Georg

    2009-08-30

    Often the effect of at least one of the prognostic factors in a Cox regression model changes over time, which violates the proportional hazards assumption of this model. As a consequence, the average hazard ratio for such a prognostic factor is under- or overestimated. While there are several methods to appropriately cope with non-proportional hazards, in particular by including parameters for time-dependent effects, weighted estimation in Cox regression is a parsimonious alternative without additional parameters. The methodology, which extends the weighted k-sample logrank tests of the Tarone-Ware scheme to models with multiple, binary and continuous covariates, has been introduced in the nineties of the last century and is further developed and re-evaluated in this contribution. The notion of an average hazard ratio is defined and its connection to the effect size measure P(X

  2. Analyzing Student Learning Outcomes: Usefulness of Logistic and Cox Regression Models. IR Applications, Volume 5

    ERIC Educational Resources Information Center

    Chen, Chau-Kuang

    2005-01-01

    Logistic and Cox regression methods are practical tools used to model the relationships between certain student learning outcomes and their relevant explanatory variables. The logistic regression model fits an S-shaped curve into a binary outcome with data points of zero and one. The Cox regression model allows investigators to study the duration…

  3. Factors associated with methadone treatment duration: a Cox regression analysis.

    PubMed

    Lin, Chao-Kuang; Hung, Chia-Chun; Peng, Ching-Yi; Chao, En; Lee, Tony Szu-Hsien

    2015-01-01

    This study examined retention rates and associated predictors of methadone maintenance treatment (MMT) duration among 128 newly admitted patients in Taiwan. A semi-structured questionnaire was used to obtain demographic and drug use history. Daily records of methadone taken and test results for HIV, HCV, and morphine toxicology were taken from a computerized medical registry. Cox regression analyses were performed to examine factors associated with MMT duration. MMT retention rates were 80.5%, 68.8%, 53.9%, and 41.4% for 3, 6, 12, and 18 months, respectively. Excluding 38 patients incarcerated during the study period, retention rates were 81.1%, 73.3%, 61.1%, and 48.9% for 3 months, 6 months, 12 months, and 18 months, respectively. No participant seroconverted to HIV and 1 died during the 18-months follow-up. Results showed that being female, imprisonment, a longer distance from house to clinic, having a lower methadone dose after 30 days, being HCV positive, and in the New Taipei city program predicted early patient dropout. The findings suggest favorable MMT outcomes of HIV seroincidence and mortality. Results indicate that the need to minimize travel distance and to provide programs that meet women's requirements justify expansion of MMT clinics in Taiwan. PMID:25875531

  4. The analysis of survival data in nephrology: basic concepts and methods of Cox regression

    Microsoft Academic Search

    Paul C van Dijk; Kitty J Jager; Aeilko H Zwinderman; Carmine Zoccali; Friedo W Dekker

    2008-01-01

    How much does the survival of one group differ from the survival of another group? How do differences in age in these two groups affect such a comparison? To obtain a quantity to compare the survival of different patient groups and to account for confounding effects, a multiple regression technique for survival data is needed. Cox regression is perhaps the

  5. Regression Is a Univariate General Linear Model Subsuming Other Parametric Methods as Special Cases.

    ERIC Educational Resources Information Center

    Vidal, Sherry

    Although the concept of the general linear model (GLM) has existed since the 1960s, other univariate analyses such as the t-test and the analysis of variance models have remained popular. The GLM produces an equation that minimizes the mean differences of independent variables as they are related to a dependent variable. From a computer printout…

  6. How To Handle Discrete Dependent Variables in the Univariate Case: A Primer on Logistic Regression.

    ERIC Educational Resources Information Center

    Brooks, B. Meade

    This paper presents an overview of logistic regression and illustrates the method with the data transformations that are conducted. It also discusses the interpretation of logistic regression results. To make the discussion more concrete, an analysis of a data set is presented in which logistic regression is used to predict the likelihood of a…

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

    PubMed

    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. PMID:24516328

  8. Non-asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso

    E-print Network

    Kong, Shengchun

    2012-01-01

    We consider the 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 difficulty caused by the lack of iid and Lipschitz property.

  9. Comparison of the performance of neural network methods and Cox regression for censored survival data

    Microsoft Academic Search

    Anny Xiang; Pablo Lapuerta; Alex Ryutov; Jonathan Buckley

    2000-01-01

    Strategies that have been developed to extend NN prediction methods to accommodate right-censored data include methods due to Faraggi–Simon, Liestol–Andersen–Andersen, and a modification of the Buckley–James method. In a Monte Carlo simulation study, we evaluated the performance of all three NN methods with that of Cox regression models which included main effects and interactions, when interactions exist. Using the EPILOG

  10. A global goodness-of-fit statistic for Cox regression models.

    PubMed

    Parzen, M; Lipsitz, S R

    1999-06-01

    In this paper, a global goodness-of-fit test statistic for a Cox regression model, which has an approximate chi-squared distribution when the model has been correctly specified, is proposed. Our goodness-of-fit statistic is global and has power to detect if interactions or higher order powers of covariates in the model are needed. The proposed statistic is similar to the Hosmer and Lemeshow (1980, Communications in Statistics A10, 1043-1069) goodness-of-fit statistic for binary data as well as Schoenfeld's (1980, Biometrika 67, 145-153) statistic for the Cox model. The methods are illustrated using data from a Mayo Clinic trial in primary billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes and Survival Analysis), in which the outcome is the time until liver transplantation or death. The are 17 possible covariates. Two Cox proportional hazards models are fit to the data, and the proposed goodness-of-fit statistic is applied to the fitted models. PMID:11318217

  11. Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

    PubMed Central

    Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

    2014-01-01

    The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

  12. The comparisons of prognostic indexes using data mining techniques and Cox regression analysis in the breast cancer data

    Microsoft Academic Search

    Mevlut Ture; Füsun Tokatli; Imran Kurt Omurlu

    2009-01-01

    The purpose of this study is to determine new prognostic indexes for the differentiation of subgroups of breast cancer patients with the techniques of decision tree algorithms (C&RT, CHAID, QUEST, ID3, C4.5 and C5.0) and Cox regression analysis for disease-free survival (DFS) in breast cancer patients. A retrospective analysis was performed in 381 breast cancer patients diagnosed. Age, menopausal status,

  13. Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

    NASA Technical Reports Server (NTRS)

    Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

    1998-01-01

    New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

  14. A comparison between univariate probabilistic and multivariate (logistic regression) methods for landslide susceptibility analysis: the example of the Febbraro valley (Northern Alps, Italy)

    NASA Astrophysics Data System (ADS)

    Rossi, M.; Apuani, T.; Felletti, F.

    2009-04-01

    The aim of this paper is to compare the results of two statistical methods for landslide susceptibility analysis: 1) univariate probabilistic method based on landslide susceptibility index, 2) multivariate method (logistic regression). The study area is the Febbraro valley, located in the central Italian Alps, where different types of metamorphic rocks croup out. On the eastern part of the studied basin a quaternary cover represented by colluvial and secondarily, by glacial deposits, is dominant. In this study 110 earth flows, mainly located toward NE portion of the catchment, were analyzed. They involve only the colluvial deposits and their extension mainly ranges from 36 to 3173 m2. Both statistical methods require to establish a spatial database, in which each landslide is described by several parameters that can be assigned using a main scarp central point of landslide. The spatial database is constructed using a Geographical Information System (GIS). Each landslide is described by several parameters corresponding to the value of main scarp central point of the landslide. Based on bibliographic review a total of 15 predisposing factors were utilized. The width of the intervals, in which the maps of the predisposing factors have to be reclassified, has been defined assuming constant intervals to: elevation (100 m), slope (5 °), solar radiation (0.1 MJ/cm2/year), profile curvature (1.2 1/m), tangential curvature (2.2 1/m), drainage density (0.5), lineament density (0.00126). For the other parameters have been used the results of the probability-probability plots analysis and the statistical indexes of landslides site. In particular slope length (0 ÷ 2, 2 ÷ 5, 5 ÷ 10, 10 ÷ 20, 20 ÷ 35, 35 ÷ 260), accumulation flow (0 ÷ 1, 1 ÷ 2, 2 ÷ 5, 5 ÷ 12, 12 ÷ 60, 60 ÷27265), Topographic Wetness Index 0 ÷ 0.74, 0.74 ÷ 1.94, 1.94 ÷ 2.62, 2.62 ÷ 3.48, 3.48 ÷ 6,00, 6.00 ÷ 9.44), Stream Power Index (0 ÷ 0.64, 0.64 ÷ 1.28, 1.28 ÷ 1.81, 1.81 ÷ 4.20, 4.20 ÷ 9.40). Geological map and land use map were also used, considering geological and land use properties as categorical variables. Appling the univariate probabilistic method the Landslide Susceptibility Index (LSI) is defined as the sum of the ratio Ra/Rb calculated for each predisposing factor, where Ra is the ratio between number of pixel of class and the total number of pixel of the study area, and Rb is the ratio between number of landslides respect to the pixel number of the interval area. From the analysis of the Ra/Rb ratio the relationship between landslide occurrence and predisposing factors were defined. Then the equation of LSI was used in GIS to trace the landslide susceptibility maps. The multivariate method for landslide susceptibility analysis, based on logistic regression, was performed starting from the density maps of the predisposing factors, calculated with the intervals defined above using the equation Rb/Rbtot, where Rbtot is a sum of all Rb values. Using stepwise forward algorithms the logistic regression was performed in two successive steps: first a univariate logistic regression is used to choose the most significant predisposing factors, then the multivariate logistic regression can be performed. The univariate regression highlighted the importance of the following factors: elevation, accumulation flow, drainage density, lineament density, geology and land use. When the multivariate regression was applied the number of controlling factors was reduced neglecting the geological properties. The resulting final susceptibility equation is: P = 1 / (1 + exp-(6.46-22.34*elevation-5.33*accumulation flow-7.99* drainage density-4.47*lineament density-17.31*land use)) and using this equation the susceptibility maps were obtained. To easy compare the results of the two methodologies, the susceptibility maps were reclassified in five susceptibility intervals (very high, high, moderate, low and very low) using natural breaks. Then the maps were validated using two cumulative distribution curves, one related to the landslides (number of landslides in e

  15. Maximum Likelihood Inference for the Cox Regression Model with Applications to Missing Covariates.

    PubMed

    Chen, Ming-Hui; Ibrahim, Joseph G; Shao, Qi-Man

    2009-10-01

    In this paper, we carry out an in-depth theoretical investigation for existence of maximum likelihood estimates for the Cox model (Cox, 1972, 1975) both in the full data setting as well as in the presence of missing covariate data. The main motivation for this work arises from missing data problems, where models can easily become difficult to estimate with certain missing data configurations or large missing data fractions. We establish necessary and sufficient conditions for existence of the maximum partial likelihood estimate (MPLE) for completely observed data (i.e., no missing data) settings as well as sufficient conditions for existence of the maximum likelihood estimate (MLE) for survival data with missing covariates via a profile likelihood method. Several theorems are given to establish these conditions. A real dataset from a cancer clinical trial is presented to further illustrate the proposed methodology. PMID:19802375

  16. Univariate and multiple linear regression analyses for 23 single nucleotide polymorphisms in 14 genes predisposing to chronic glomerular diseases and IgA nephropathy in Han Chinese.

    PubMed

    Wang, Hui; Sui, Weiguo; Xue, Wen; Wu, Junyong; Chen, Jiejing; Dai, Yong

    2014-09-01

    Immunoglobulin A nephropathy (IgAN) is a complex trait regulated by the interaction among multiple physiologic regulatory systems and probably involving numerous genes, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of IgAN nephropathy is based on multiple genes with minor effects. To learn the association between 23 single nucleotide polymorphisms (SNPs) in 14 genes predisposing to chronic glomerular diseases and IgAN in Han males, the 23 SNPs genotypes of 21 Han males were detected and analyzed with a BaiO gene chip, and their associations were analyzed with univariate analysis and multiple linear regression analysis. Analysis showed that CTLA4 rs231726 and CR2 rs1048971 revealed a significant association with IgAN. These findings support the multi-gene nature of the etiology of IgAN and propose a potential gene-gene interactive model for future studies. PMID:25193896

  17. High-dimensional, massive sample-size Cox proportional hazards regression for survival analysis.

    PubMed

    Mittal, Sushil; Madigan, David; Burd, Randall S; Suchard, Marc A

    2014-04-01

    Survival analysis endures as an old, yet active research field with applications that spread across many domains. Continuing improvements in data acquisition techniques pose constant challenges in applying existing survival analysis methods to these emerging data sets. In this paper, we present tools for fitting regularized Cox survival analysis models on high-dimensional, massive sample-size (HDMSS) data using a variant of the cyclic coordinate descent optimization technique tailored for the sparsity that HDMSS data often present. Experiments on two real data examples demonstrate that efficient analyses of HDMSS data using these tools result in improved predictive performance and calibration. PMID:24096388

  18. Including network knowledge into Cox regression models for biomarker signature discovery.

    PubMed

    Fröhlich, Holger

    2014-03-01

    Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step toward a better personalized medicine. During the last decade various methods have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Most of these methods focus on classification problems, that is learn a model from data that discriminates patients into distinct clinical groups. Far less has been published on approaches that predict a patient's event risk. In this paper, we investigate eight methods that integrate network information into multivariable Cox proportional hazard models for risk prediction in breast cancer. We compare the prediction performance of our tested algorithms via cross-validation as well as across different datasets. In addition, we highlight the stability and interpretability of obtained gene signatures. In conclusion, we find GeneRank-based filtering to be a simple, computationally cheap and highly predictive technique to integrate network information into event time prediction models. Signatures derived via this method are highly reproducible. PMID:24430933

  19. Integration of pathway structure information into a reweighted partial Cox regression approach for survival analysis on high-dimensional gene expression data.

    PubMed

    Liu, Wei; Wang, Qiuyu; Zhao, Jianmei; Zhang, Chunlong; Liu, Yuejuan; Zhang, Jian; Bai, Xuefeng; Li, Xuecang; Feng, Houming; Liao, Mingzhi; Wang, Wei; Li, Chunquan

    2015-06-16

    Accurately predicting the risk of cancer relapse or death is important for clinical utility. The emerging high-dimensional gene expression data provide the opportunity as well as the challenge to uncover the relationship between gene expression and censored survival outcome. While several Cox models have been proposed to deal with high-dimensional covariates and censored continuous survival data, they usually generalize poorly to independent datasets. Most methods build the Cox model exclusively on gene expression data, but ignore the molecular interaction relation among genes, which has been successfully integrated into molecular classification with categorical outcomes and improved predictive performance. Here, we integrate gene-interaction information into a Cox model and propose a reweighted partial Cox regression (RPCR) approach in order to accurately predict the risk of cancer events. RPCR improves the predictive accuracy and generalization of a Cox model by promoting genes with large topological importance, which is evaluated by a directed random walk in a reconstructed global pathway graph. We applied RPCR to the survival prediction of two cancer types and used two concordance statistic measures to assess the prediction performance. Both within-dataset experiments and cross-dataset experiments showed that RPCR could predict the risk of patients with higher accuracy and greater robustness. PMID:25891149

  20. Novel spectrophotometric determination of chloramphenicol and dexamethasone in the presence of non labeled interfering substances using univariate methods and multivariate regression model updating.

    PubMed

    Hegazy, Maha A; Lotfy, Hayam M; Rezk, Mamdouh R; Omran, Yasmin Rostom

    2015-04-01

    Smart and novel spectrophotometric and chemometric methods have been developed and validated for the simultaneous determination of a binary mixture of chloramphenicol (CPL) and dexamethasone sodium phosphate (DSP) in presence of interfering substances without prior separation. The first method depends upon derivative subtraction coupled with constant multiplication. The second one is ratio difference method at optimum wavelengths which were selected after applying derivative transformation method via multiplying by a decoding spectrum in order to cancel the contribution of non labeled interfering substances. The third method relies on partial least squares with regression model updating. They are so simple that they do not require any preliminary separation steps. Accuracy, precision and linearity ranges of these methods were determined. Moreover, specificity was assessed by analyzing synthetic mixtures of both drugs. The proposed methods were successfully applied for analysis of both drugs in their pharmaceutical formulation. The obtained results have been statistically compared to that of an official spectrophotometric method to give a conclusion that there is no significant difference between the proposed methods and the official ones with respect to accuracy and precision. PMID:25659506

  1. Novel spectrophotometric determination of chloramphenicol and dexamethasone in the presence of non labeled interfering substances using univariate methods and multivariate regression model updating

    NASA Astrophysics Data System (ADS)

    Hegazy, Maha A.; Lotfy, Hayam M.; Rezk, Mamdouh R.; Omran, Yasmin Rostom

    2015-04-01

    Smart and novel spectrophotometric and chemometric methods have been developed and validated for the simultaneous determination of a binary mixture of chloramphenicol (CPL) and dexamethasone sodium phosphate (DSP) in presence of interfering substances without prior separation. The first method depends upon derivative subtraction coupled with constant multiplication. The second one is ratio difference method at optimum wavelengths which were selected after applying derivative transformation method via multiplying by a decoding spectrum in order to cancel the contribution of non labeled interfering substances. The third method relies on partial least squares with regression model updating. They are so simple that they do not require any preliminary separation steps. Accuracy, precision and linearity ranges of these methods were determined. Moreover, specificity was assessed by analyzing synthetic mixtures of both drugs. The proposed methods were successfully applied for analysis of both drugs in their pharmaceutical formulation. The obtained results have been statistically compared to that of an official spectrophotometric method to give a conclusion that there is no significant difference between the proposed methods and the official ones with respect to accuracy and precision.

  2. Wavelet Based Estimation for Univariate Stable Laws

    E-print Network

    Gonçalves, Paulo

    Wavelet Based Estimation for Univariate Stable Laws Anestis Antoniadis Laboratoire IMAG to implement. This article describes a fast, wavelet-based, regression-type method for estimating the parameters of a stable distribution. Fourier domain representations, combined with a wavelet multiresolution

  3. Univariate Probability Distributions

    ERIC Educational Resources Information Center

    Leemis, Lawrence M.; Luckett, Daniel J.; Powell, Austin G.; Vermeer, Peter E.

    2012-01-01

    We describe a web-based interactive graphic that can be used as a resource in introductory classes in mathematical statistics. This interactive graphic presents 76 common univariate distributions and gives details on (a) various features of the distribution such as the functional form of the probability density function and cumulative distribution…

  4. Regression

    NSDL National Science Digital Library

    Laval, Philippe B.

    This page contains three applets on linear, quadratic and exponential regression. Each allows the user to investigate the relationship between the scatter plot of entered data and the regression equation.

  5. Regression

    NSDL National Science Digital Library

    Anderson-Cook, C.

    This applet, created by Virginia Tech's Department of Statistics, allows the user to generate bivariate data for analysis with simple linear regression. The page describes the equations used to generate the data and estimate the regression lines. Users manipulate data generated and create their own line of best fit to try and match the computer generated regression line.

  6. Univariate and Bivariate Data

    NSDL National Science Digital Library

    2010-01-01

    This lesson is designed to introduce students to the difference between univariate and bivariate data, and how the two can be represented graphically. This lesson provides links to discussions and activities related to graphical representations of data as well as suggested ways to integrate them into the lesson. Finally, the lesson provides links to follow-up lessons designed for use in succession with the current one.

  7. Assessing outcomes of large-scale public health interventions in the absence of baseline data using a mixture of Cox and binomial regressions

    PubMed Central

    2014-01-01

    Background Large-scale public health interventions with rapid scale-up are increasingly being implemented worldwide. Such implementation allows for a large target population to be reached in a short period of time. But when the time comes to investigate the effectiveness of these interventions, the rapid scale-up creates several methodological challenges, such as the lack of baseline data and the absence of control groups. One example of such an intervention is Avahan, the India HIV/AIDS initiative of the Bill & Melinda Gates Foundation. One question of interest is the effect of Avahan on condom use by female sex workers with their clients. By retrospectively reconstructing condom use and sex work history from survey data, it is possible to estimate how condom use rates evolve over time. However formal inference about how this rate changes at a given point in calendar time remains challenging. Methods We propose a new statistical procedure based on a mixture of binomial regression and Cox regression. We compare this new method to an existing approach based on generalized estimating equations through simulations and application to Indian data. Results Both methods are unbiased, but the proposed method is more powerful than the existing method, especially when initial condom use is high. When applied to the Indian data, the new method mostly agrees with the existing method, but seems to have corrected some implausible results of the latter in a few districts. We also show how the new method can be used to analyze the data of all districts combined. Conclusions The use of both methods can be recommended for exploratory data analysis. However for formal statistical inference, the new method has better power. PMID:24397563

  8. Sparse Shifts for Univariate Polynomials

    E-print Network

    Saunders, David

    of efficient algorithms for computing sparse representations for various classes of functions'' are power products of the variables involved. One can reasonably ask for sparse representations \\Gamma ff) 2 ; : : : Sparse univariate polynomial interpolation in the Chebyshev basis, the Pochhammer

  9. Global temperature predictability through univariate empirical modeling

    NASA Astrophysics Data System (ADS)

    Yoon, Chul Soon

    1998-11-01

    Temperature prediction in atmospheric science research has emphasized dynamical prediction models which use primitive equations and computational methods. For the extended-range (more than two-week) predictions and long- term predictions, the performance of dynamical models developed up to now in general is inferior to that of empirical models which use a historical data base to extract the hidden information. Univariate empirical prediction models are developed in this research for possible operational purposes. The brightness temperature anomalies from the Microwave Sounding Units (MSUs) on board the National Oceanic and Atmospheric Administration (NOAA) satellites are selected as the data base for global temperature prediction modeling. The emphasis is on data analysis and possible operational extended-range forecasts by one-dimensional time-series (global mean temperature anomalies) prediction models, two-dimensional (zonal mean temperature anomalies) prediction models and three- dimensional (global spherical variations of temperature anomalies) prediction models, respectively. In the one- dimensional linear prediction model, tropospheric temperature anomalies, which show more complicated phenomena than in other layers, are forecast. A multi- regression model is developed using monthly mean temperature anomalies. In the multi-regression model, Fourier spectrum analysis is used to investigate the possible physical relation on each atmospheric variable. The univariate Auto Regressive Integrated Moving Average (ARIMA) method is followed with the same data. Three- month lead global mean temperature anomaly prediction by the multi-regression model has a correlation of 0.72 with actual observations during 20-month test periods. The ARIMA model has an average correlation of 0.61 during twelve-month forecasts. In non-linear prediction models, analog methods are adopted to investigate the possibility of the extended- range prediction using daily mean brightness temperature anomalies. The statistical average skill score by correlation coefficients of the prediction with respect to the idealized observational data is about 0.3 for the 200-day prediction. The relatively short-term prediction skills show lower correlation but small mean square errors. For the theoretical establishment of the predictability, the ideas from dynamical systems (Lorenz model) are applied to the real MSU observational data. After the proposition on the predictability for the given data is established, possible operational models are developed for the given prediction ranges within a certain error bound. In two-dimensional models, tropospheric and stratospheric temperature anomalies are analyzed and forecast using daily MSU data. In two-dimensional predictions, two models are developed. In three-dimensional (monthly, gridpoint) predictions, lower-tropospheric, mid-tropospheric and lower- stratospheric temperature anomalies are forecast. Structural variations are emphasized in the analysis. Similar to the two-dimensional model, one-dimensional techniques are selected in the prediction model with additional mathematical manipulations. The univariate prediction model performs its forecasting economically. The results of each univariate empirical prediction model applied on the case studies, even though generalization is not possible now, show encouraging results for operational use. (Abstract shortened by UMI.)

  10. Cellulose I crystallinity determination using FT–Raman spectroscopy: univariate and multivariate methods

    Microsoft Academic Search

    Umesh P. AgarwalRichard; Richard S. Reiner; Sally A. Ralph

    2010-01-01

    Two new methods based on FT–Raman spectroscopy, one simple, based on band intensity ratio, and the other using a partial least\\u000a squares (PLS) regression model, are proposed to determine cellulose I crystallinity. In the simple method, crystallinity in\\u000a cellulose I samples was determined based on univariate regression that was first developed using the Raman band intensity\\u000a ratio of the 380

  11. Eliciting Univariate Probability Distributions Jeremy E. Oakley

    E-print Network

    Oakley, Jeremy

    Eliciting Univariate Probability Distributions Jeremy E. Oakley September 10, 2010 1 Introduction In this chapter we discuss the process of eliciting an expert's probability distribution: ex- tracting an expert beliefs with a probability distribution. We consider the case of a scalar continuous only, so

  12. Manuals for Univariate and Multivariate Statistics

    NSDL National Science Digital Library

    Wendorf, Craig A.

    These manuals were created for clarification of the basic concepts and as a refresher for those who may have long since forgotten those basics. Note that these guides do not include lengthy examples of the applications, but do include the theories, formulae, and assumptions inherent to univariate and multivariate techniques. Multiple choice quizzes on various topics are also available.

  13. Univariate time series forecasting with fuzzy CMAC

    Microsoft Academic Search

    Da-Ming Shi; Jun-Bin Gao; R. Tilani

    2004-01-01

    In financial and business areas, forecasting is a necessary tool that enables decision makers to predict changes in demands, plans and sales. This work applies a novel fuzzy cerebellar-model-articulation-controller (FCMAC) into univariate time-series forecasting and investigates its performance in comparison to established techniques such as single exponential smoothing, Holt's linear trend, Holt-Winter's additive and multiplicative methods and the Box-Jenkin's ARIMA

  14. Dennis Cox, USGS Volunteer

    USGS Multimedia Gallery

    Dennis Cox, a volunteer with the USGS Menlo Park Campus, helps visitors pan for gold at the 2009 Open House in Menlo Park. The 2012 Open House, to be held May 19-20, will include gold panning among its many activities. ...

  15. COX inhibitors and breast cancer

    Microsoft Academic Search

    D Mazhar; R Ang; J Waxman

    2006-01-01

    There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours,

  16. Proportional hazards regression for the analysis of clustered survival data from case-cohort studies

    PubMed Central

    Schaubel, Douglas E.; Kalbeisch, John D.

    2015-01-01

    Summary Case-cohort sampling is a commonly used and efficient method for studying large cohorts. Most existing methods of analysis for case-cohort data have concerned the analysis of univariate failure time data. However, clustered failure time data are commonly encountered in public health studies. For example, patients treated at the same center are unlikely to be independent. In this article, we consider methods based on estimating equations for case-cohort designs for clustered failure time data. We assume a marginal hazards model, with a common baseline hazard and common regression coefficient across clusters. The proposed estimators of the regression parameter and cumulative baseline hazard are shown to be consistent and asymptotically normal, and consistent estimators of the asymptotic covariance matrices are derived. The regression parameter estimator is easily computed using any standard Cox regression software that allows for offset terms. The proposed estimators are investigated in simulation studies, and demonstrated empirically to have increased efficiency relative to some existing methods. The proposed methods are applied to a study of mortality among Canadian dialysis patients. PMID:20560939

  17. Logistic Regression Vibhav Gogate

    E-print Network

    Gogate, Vibhav

    ;Univariate Linear Regression 3 hw(x) = w1x + w0 Loss(hw) = j=1 n L2(yj, hw(xj)) = j=1 n (yj - hw(xj))2 = j=1 n (yj ­ (w1xj+w0))2 #12;Understanding Weight Space 4 Loss(hw) = j=1 n (yj ­ (w1xj+w0))2 hw(x) = w1x + w0 #12;Understanding Weight Space 5 hw(x) = w1x + w0 Loss(hw) = j=1 n (yj ­ (w1xj+w0))2 #12;Finding

  18. Validated univariate and multivariate spectrophotometric methods for the determination of pharmaceuticals mixture in complex wastewater

    NASA Astrophysics Data System (ADS)

    Riad, Safaa M.; Salem, Hesham; Elbalkiny, Heba T.; Khattab, Fatma I.

    2015-04-01

    Five, accurate, precise, and sensitive univariate and multivariate spectrophotometric methods were developed for the simultaneous determination of a ternary mixture containing Trimethoprim (TMP), Sulphamethoxazole (SMZ) and Oxytetracycline (OTC) in waste water samples collected from different cites either production wastewater or livestock wastewater after their solid phase extraction using OASIS HLB cartridges. In univariate methods OTC was determined at its ?max 355.7 nm (0D), while (TMP) and (SMZ) were determined by three different univariate methods. Method (A) is based on successive spectrophotometric resolution technique (SSRT). The technique starts with the ratio subtraction method followed by ratio difference method for determination of TMP and SMZ. Method (B) is successive derivative ratio technique (SDR). Method (C) is mean centering of the ratio spectra (MCR). The developed multivariate methods are principle component regression (PCR) and partial least squares (PLS). The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures containing different ratios of the three drugs. The obtained results are statistically compared with those obtained by the official methods, showing no significant difference with respect to accuracy and precision at p = 0.05.

  19. Univariate Polynomial Real Root Isolation: Continued Fractions Revisited

    Microsoft Academic Search

    Elias P. Tsigaridas; Ioannis Z. Emiris

    2006-01-01

    We present algorithmic, complexity and implementation results concerning real root isola- tion of integer univariate polynomials using the continued fraction expansion of real algebraic numbers. One motivation is to explain the method's good performance in practice. We im- prove the previously known bound by a factor of d?, where d is the polynomial degree and ? bounds the coefficient bitsize,

  20. A Root Isolation Algorithm for Sparse Univariate Polynomials

    E-print Network

    Paris-Sud XI, Université de

    A Root Isolation Algorithm for Sparse Univariate Polynomials Maria Emilia Alonso Garcia root smaller or equal to d. Our target is to find for each real root of f an interval isolating this root from the others. The usual subdivision methods

  1. Individual Fitness and the Measurement of Univariate Selection

    E-print Network

    Walsh, Bruce

    28 Individual Fitness and the Measurement of Univariate Selection Draft Version 14 November 2008 of selection involves two related issues: measuring individual fitness and measuring how the phenotype of a particular character influences individual fitness. The latter question is often phrased in terms

  2. Univariate and Bivariate Loglinear Models for Discrete Test Score Distributions.

    ERIC Educational Resources Information Center

    Holland, Paul W.; Thayer, Dorothy T.

    2000-01-01

    Applied the theory of exponential families of distributions to the problem of fitting the univariate histograms and discrete bivariate frequency distributions that often arise in the analysis of test scores. Considers efficient computation of the maximum likelihood estimates of the parameters using Newton's Method and computationally efficient…

  3. Maximum Likelihood and Minimum Distance Applied to Univariate Mixture Distributions.

    ERIC Educational Resources Information Center

    Wang, Yuh-Yin Wu; Schafer, William D.

    This Monte-Carlo study compared modified Newton (NW), expectation-maximization algorithm (EM), and minimum Cramer-von Mises distance (MD), used to estimate parameters of univariate mixtures of two components. Data sets were fixed at size 160 and manipulated by mean separation, variance ratio, component proportion, and non-normality. Results…

  4. Parallel Performance We multiplied random univariate polynomials with 8192 terms.

    E-print Network

    Parallel Performance We multiplied random univariate polynomials with 8192 terms. Typical problems, Volume 8, Issue 3 (1974) 63­71. [2] Michael Monagan, Roman Pearce. Parallel Sparse Polyno- mial. Parallel Algorithm · Each thread uses a local heap to multiply some of the fi × g. · Intermediate results

  5. MDL Mean Function Selection in Semiparametric Kernel Regression Models

    Microsoft Academic Search

    Jan G. De Gooijer; Ao Yuan

    2008-01-01

    We study the problem of selecting the optimal functional form among a set of non nested, nonlinear mean functions for a semiparametric kernel based regression model. To this end we consider Rissanen's minimum description length (MDL) principle. We prove the consistency of the proposed MDL criterion. Its performance is examined via simulated data sets of univariate and bivariate nonlinear regression

  6. Prognostic models in coronary artery disease: Cox and network approaches

    PubMed Central

    Mora, Antonio; Sicari, Rosa; Cortigiani, Lauro; Carpeggiani, Clara; Picano, Eugenio; Capobianco, Enrico

    2015-01-01

    Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg?1 over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach.

  7. Curriculum Vitae John Vincent Cox

    E-print Network

    Cui, Yan

    Lievre Family Research Fellowship Award American Heart Association 1986-1987 American Heart Association Advanced Research Fellow #12;1988-1989 American Heart Association Senior Investigator 1998 DistinguishedCurriculum Vitae John Vincent Cox Associate Professor EDUCATION: 1975 B.S. in Biology Department

  8. COPAR Multivariate time series modeling using the COPula AutoRegressive model

    E-print Network

    Haug, Stephan

    into the dynamic relationship of the time series and often produce forecasts superior to independent univariate for common features of univariate economic and financial time series like skewness and heavy-tailedness whichCOPAR ­ Multivariate time series modeling using the COPula AutoRegressive model Eike Christian

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

    PubMed

    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. PMID:24086091

  10. Gastrointestinal Tolerability of the Selective Cyclooxygenase2 (COX2) Inhibitor Rofecoxib Compared With Nonselective COX1 and COX2 Inhibitors in Osteoarthritis

    Microsoft Academic Search

    Douglas J. Watson; Sean E. Harper; Peng-Liang Zhao; Hui Quan; James A. Bolognese; Thomas J. Simon

    2000-01-01

    Background: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the pathogenesis of these symp- toms are unclear. To test whether COX-2 inhibition with rofecoxib would have greater GI tolerability than non- selective COX-1 and COX-2 inhibition, we

  11. COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

    SciTech Connect

    Smith, Fraser M. [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland); Reynolds, John V. [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland)]. E-mail: reynoldsjv@stjames.ie; Kay, Elaine W. [Department of Histopathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin (Ireland); Crotty, Paul [Department of Histopathology, Adelaide and Meath Hospital, Tallaght, Dublin (Ireland); Murphy, James O. [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland); Hollywood, Donal [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland); Gaffney, Eoin F. [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland); Stephens, Richard B. [Departments of Surgery and Histopathology, and Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland); Kennedy, M. John [Departments of Surgery and Histopathology, Academic Unit of Clinical and Molecular Oncology, St. James's Hospital, Dublin (Ireland)

    2006-02-01

    Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

  12. Parallel Univariate Real Root Isolation on Multicore Processors

    NASA Astrophysics Data System (ADS)

    Chen, Changbo; Maza, Marc Moreno; Xie, Yuzhen

    2011-11-01

    We present parallel algorithms with optimal cache complexity for the kernel routine of many real root isolation algorithms, namely, Taylor shift, targeting multicore processors. We then report an efficient multithreaded implementation for isolating the real roots of univariate polynomials based on the parallel Taylor shift algorithms. For processing some well-known benchmark examples with sufficiently large size, our software tool reaches linear speedup on a 8-core machine. In addition, we show that our software is able to fully utilize the many cores and the memory space of a 32-core machine to tackle large problems that are out of reach for a desktop implementation.

  13. The pathways for intelligible speech: multivariate and univariate perspectives.

    PubMed

    Evans, S; Kyong, J S; Rosen, S; Golestani, N; Warren, J E; McGettigan, C; Mourão-Miranda, J; Wise, R J S; Scott, S K

    2014-09-01

    An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400-2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486-2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local "searchlights" and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing. PMID:23585519

  14. The Cox3p assembly module of yeast cytochrome oxidase.

    PubMed

    Su, Chen-Hsien; McStay, Gavin P; Tzagoloff, Alexander

    2014-04-01

    Yeast cytochrome oxidase (COX) was previously inferred to assemble from three modules, each containing one of the three mitochondrially encoded subunits and a different subset of the eight nuclear gene products that make up this respiratory complex. Pull-down assays of pulse-labeled mitochondria enabled us to characterize Cox3p subassemblies that behave as COX precursors and contain Cox4p, Cox7p, and Cox13p. Surprisingly, Cox4p is a constituent of two other complexes, one of which was previously proposed to be an intermediate of Cox1p biogenesis. This suggests that Cox4p, which contacts Cox1p and Cox3p in the holoenzyme, can be incorporated into COX by two alternative pathways. In addition to subunits of COX, some Cox3p intermediates contain Rcf1p, a protein associated with the supercomplex that stabilizes the interaction of COX with the bc1 (ubiquinol-cytochrome c reductase) complex. Finally, our results indicate that although assembly of the Cox1p module is not contingent on the presence of Cox3p, the converse is not true, as none of the Cox3p subassemblies were detected in a mutant blocked in translation of Cox1p. These studies support our proposal that Cox3p and Cox1p are separate assembly modules with unique compositions of ancillary factors and subunits derived from the nuclear genome. PMID:24478450

  15. Certified counting of roots of random univariate polynomials

    E-print Network

    Joseph Cleveland; Jeffrey Dzugan; Jonathan D. Hauenstein; Ian Haywood; Dhagash Mehta; Anthony Morse; Leonardo Robol; Taylor Schlenk

    2014-12-04

    A challenging problem in computational mathematics is to compute roots of a high-degree univariate random polynomial. We combine an efficient multiprecision implementation for solving high-degree random polynomials with two certification methods, namely Smale's $\\alpha$-theory and one based on Gerschgorin's theorem, for showing that a given numerical approximation is in the quadratic convergence region of Newton's method of some exact solution. With this combination, we can certifiably count the number of real roots of random polynomials. We quantify the difference between the two certification procedures and list the salient features of both of them. After benchmarking on random polynomials where the coefficients are drawn from the Gaussian distribution, we obtain novel experimental results for the Cauchy distribution case.

  16. RELATIONSHIP BETWEEN THE COX, LEHMANN, WEIBULL,

    E-print Network

    Loya, Paul

    Cox and Oakes (1984) claim: a model satisfies AL and PH iff it is Weibull. (see "Analysis of survivalRELATIONSHIP BETWEEN THE COX, LEHMANN, WEIBULL, ACCELERATED LIFETIME MODELS By Qiqing Yu Department variable (vector); , , , are parameters Important parametric model: Weibull model S(t|x) = exp

  17. Glycosylation of human cyclooxygenase-2 (COX-2) decreases the efficacy of certain COX-2 inhibitors.

    PubMed

    Sevigny, Mary B; Graham, Kamara; Ponce, Esmeralda; Louie, Maggie C; Mitchell, Kylie

    2012-04-01

    Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenase-2 (COX-2). COX-2 exists as two glycoforms, 72 and 74 kDa, the latter resulting from an additional glycosylation at Asn(580). In this study, Asn(580) was mutated, and the mutant and wild-type COX-2 genes were expressed in COS-1 cells to determine how glycosylation affects the inhibition of COX-2 activity by aspirin, flurbiprofen, ibuprofen, celecoxib, and etoricoxib. Results indicate that certain inhibitors were 2-5 times more effective at inhibiting COX-2 activity when the glycosylation site was eliminated, indicating that glycosylation of COX-2 at Asn(580) decreases the efficacy of some inhibitors. PMID:22245433

  18. COX2 Inhibitors And Cardiovascular Risk

    Microsoft Academic Search

    Daniel J. Salzberg; Matthew R. Weir

    The development of drugs that selectively inhibit cyclooxygenase-2 (COX-2) demonstrates translational research from bench\\u000a to bedside based on underlying knowledge of micro-cellular structure and function. However, theoretical concerns about potentially\\u000a pro-thrombotic effects of selective COX-2 inhibitors coupled with observations of increased cardiovascular risk have produced\\u000a significant consternation and lead to the withdrawal of two of these agents from the market.

  19. Sequential Monitoring of the Statistical Properties of the Univariate Affine Diffusion with Application to Interest Rates

    Microsoft Academic Search

    Wolfgang Schmid; Dobromir Tzotchev

    In the paper, the tools of statistical process control, and in particular control charts, are applied to sequentially detect a change in both the mean and the variance of the univariate affine diffusion. Different types of multivariate EWMA control charts are introduced and con- structed, taking into account the statistical properties of the univariate affine diffusion. The effectiveness of the

  20. Dynamic Cox modelling based on fractional polynomials: time-variations in gastric cancer prognosis.

    PubMed

    Berger, Ursula; Schäfer, Juliane; Ulm, Kurt

    2003-04-15

    The most popular model used for survival analysis is the proportional hazards regression model proposed by Cox. This is mainly due to its exceptional simplicity. Nevertheless the fundamental assumption of the Cox model is the proportionality of the hazards. For many applications, however, this assumption is doubtful. Proposals to extend the Cox model for non-proportional hazards to allow for dynamic effect structures usually either depend on prespecifications or require non-standard estimation techniques and are thus not favoured in application. Moreover, tests to verify the dynamic effect structures are not straightforward or lack omnibus power. In this paper we propose a flexible method for modelling dynamic effects in survival data within the Cox framework. The method is based on fractional polynomials as introduced by Royston and Altman. This allows for a transformation of the dynamic predictor which leads back to the conventional Cox model and hence fitting is straightforward using standard estimation techniques. In addition, it offers the possibility of easily verifying the existence of time-variation. We describe a model selection algorithm which selects time-varying effects only when evidence is given in the data. We illustrate the properties of the approach in a simulation study and compare it with other methods. In a survival study of gastric cancer patients, we apply the approach to analyse dynamic structures in the effects of prognostic factors. PMID:12652560

  1. 17-?-Estradiol upregulates COX2 in the rat oviduct

    Microsoft Academic Search

    S. Pérez Martínez; M. Hermoso; M. Farina; M. L. Ribeiro; M. Rapanelli; M. Espinosa; M. Villalón; A. Franchi

    2006-01-01

    We investigated the regulation of cyclooxygenase-2 (COX-2) by 17-?-estradiol (E2) in the rat oviduct. We observed that COX-2 is expressed mainly in proestrous and estrous stages, periods under estrogenic influence. While exogenous administration of E2 (1?g\\/rat) significantly increased COX-2 protein levels, progesterone did not modify it. COX-2 was mainly localized on oviductal epithelial cells from estrogenized rat. Induction of COX-2

  2. Select Dietary Phytochemicals Function as Inhibitors of COX-1 but Not COX-2

    PubMed Central

    Li, Haitao; Zhu, Feng; Sun, Yanwen; Li, Bing; Oi, Naomi; Chen, Hanyong; Lubet, Ronald A.; Bode, Ann M.; Dong, Zigang

    2013-01-01

    Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are reported to suppress carcinogenesis by targeting COX-2. A major question was accordingly raised: why has the lifelong use of phytochemicals that likely inhibit COX-2 presumably not been associated with adverse cardiovascular side effects. To answer this question, we selected a library of dietary-derived phytochemicals and evaluated their potential cardiovascular toxicity in human umbilical vein endothelial cells. Our data indicated that the possibility of cardiovascular toxicity of these dietary phytochemicals was low. Further mechanistic studies revealed that the actions of these phytochemicals were similar to aspirin in that they mainly inhibited COX-1 rather than COX-2, especially at low doses. PMID:24098505

  3. Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in mice.

    PubMed

    Sugimoto, M; Arai, I; Futaki, N; Hashimoto, Y; Honma, Y; Nakaike, S

    2006-07-01

    We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice. PMID:16815697

  4. Nonlinear models Nonlinear Regression

    E-print Network

    Penny, Will

    Nonlinear models Will Penny Nonlinear Regression Nonlinear Regression Priors Energies Posterior Metropolis-Hasting Proposal density References Nonlinear models Will Penny Bayesian Inference Course, WTCN, UCL, March 2013 #12;Nonlinear models Will Penny Nonlinear Regression Nonlinear Regression Priors

  5. Suppression mechanisms of COX assembly defects in yeast and human: Insights into the COX assembly process

    PubMed Central

    Barrientos, Antoni; Gouget, Karine; Horn, Darryl; Soto, Ileana C.; Fontanesi, Flavia

    2008-01-01

    Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin whose assembly is intricate and highly regulated. In addition to the structural subunits, a large number of accessory factors are required to build the holoenzyme. The function of these factors is required in all stages of the assembly process. They are relevant to human health because devastating human disorders have been associated with mutations in nuclear genes encoding conserved COX assembly factors. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to attain the current state of knowledge, even if still fragmentary, of the COX assembly process. After the identification of the genes involved, the isolation and characterization of genetic and metabolic suppressors of COX assembly defects, reviewed here, have become a profitable strategy to gain insight into their functions and the pathways in which they operate. Additionally, they have the potential to provide useful information for devising therapeutic approaches to combat human disorders associated with COX deficiency. PMID:18522805

  6. Linear Algebra in Situ Steven J. Cox

    E-print Network

    Linear Algebra in Situ Steven J. Cox #12;Poet, oracle and wit Like unsuccessful anglers. Following Gil Strang, I demonstrate throughout that Linear Algebra is both a tool for expressing these questions and for achieving, computing and representing their solutions. The theory needed to resolve

  7. Cox and Munk's Sea Surface Slope Variance

    Microsoft Academic Search

    Frank J. Wentz

    1976-01-01

    Cox and Munk's [1954, 1956] expressions for the sea surface slope variance are frequently cited in the literature. This paper reviews the basis of these expressions and emphasizes that they are rough approximations based on a rather arbitrary data extrapolation. However, an accurate lower bound to the variance can be deduced from the data. From photometric photographs of sun glitter

  8. COX-2 expression in nonepithelial ovarian malignancies.

    PubMed

    Menczer, Joseph; Schreiber, Letizia; Sukmanov, Oleg; Czernobilsky, Bernard; Berger, Esther; Golan, Abraham; Levi, Tally

    2011-01-01

    The aim of the study was to assess the expression of cyclooxygenases (COX)-2 in nonepithelial ovarian malignancies.COX-2 immunohistochemical staining was performed on newly prepared deparaffinized slides from formalin-fixed, paraffin-embedded archival tissue blocks of unselected nonepithelial ovarian malignancies diagnosed between January 1993 and October 2009 after reconfirmation of the diagnosis. Staining was assessed according to intensity of staining and the proportion of stained cells. Staining of more than 10% of the cells was considered positive.During the study period, 26 histologically proven nonepithelial ovarian malignancies were diagnosed. Of them, 16 were granulosa cell tumors and 10 were germ cell tumors (4 dysgerminomas and 6 immature teratomas). Five (31.2%) granulosa cell tumors had positive immunohistochemical COX-2 staining. Positive staining was observed only in 1 immature teratoma and in none of the dysgerminomas.Our data seem to indicate that COX-2 expression by immunohistochemical methods is not frequent in nonepithelial ovarian malignancies. PMID:21131835

  9. INFORMATION TRANSMISSION AND STEGANOGRAPHY Ingemar J. Cox

    E-print Network

    Cox, Ingemar J.

    INFORMATION TRANSMISSION AND STEGANOGRAPHY Ingemar J. Cox , Ton Kalker , Georg Pakura and Mathias Scheel ABSTRACT Recently there has been strong interest in developing models of steganography based. INTRODUCTION The history of steganography can be traced back thousands of years, examples of which

  10. Risk of Cardiovascular Events Associated With Selective COX2 Inhibitors

    Microsoft Academic Search

    Debabrata Mukherjee; Steven E. Nissen; Eric J. Topol

    2005-01-01

    Atherosclerosis is a process with inflammatory features and selective cy- clooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic ef- fects by virtue of inhibiting inflammation. However, by decreasing vasodi- latory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular ef- fects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients

  11. Epidermal COX2 Induction Following Ultraviolet Irradiation: Suggested Mechanism for the Role of COX2 Inhibition in Photoprotection

    Microsoft Academic Search

    Catherine S. Tripp; Eric A. G. Blomme; Kevin S. Chinn; Medora M. Hardy; Peter LaCelle; Alice P. Pentland

    2003-01-01

    The cyclooxygenase isoforms, COX-1 and COX-2, are involved in the biosynthesis of prostaglandin E2, a major prostaglandin involved in epidermal homeostasis and repair. Cancer originating in the epidermis can develop when keratinocyte proliferation and apoptosis become dysregulated, resulting in sustained epidermal hyperplasia. COX-2 inhibitors, which demonstrate significant in vivo selectivity relative to COX-1, suppress both ultraviolet-induced epidermal tumor development and

  12. Simple Logistic Regression

    NSDL National Science Digital Library

    Lowry, Richard, 1940-

    This page has two calculators. One will cacluate a simple logistic regression, while the other calculates the predicted probability and odds ratio. There is also a brief tutorial covering logistic regression using an example involving infant gestational age and breast feeding. Please note, however, that the logistic regression accomplished by this page is based on a simple, plain-vanilla empirical regression.

  13. Drug analogs of COX-2 selective inhibitors lumiracoxib and valdecoxib derived from in silico search and optimization.

    PubMed

    Bartzatt, Ronald

    2014-03-01

    The medicinal activity of COX-2 inhibitors are sufficiently beneficial to urge the search for new drug designs. This study presents 16 analogs of lumiracoxib and 10 analogs to valdecoxib having properties suitable as COX-2 inhibitors. For lumiracoxib analogs the mean Log P, polar surface area, and formula weight are 3.00, 70.46 A(2), and 276.60, respectively. For valdecoxib analogs the mean Log P, polar surface area, and formula weight are 3.65, 68.46 A(2), and 322.32, respectively. Grubb's test analysis of seven properties for seven known COX-2 selective inhibitors and those of 26 analog compounds indicated no outliers. The unpaired t-test compared Log P and polar surface area of seven known COX-2 inhibitors to all 26 analogs and found no difference. All 26 analogs showed no violation of the Rule of 5, this being an indicator of favorable bioavailability. Hierarchical cluster analysis by single linkage indicated lumiracoxib is most similar to analogs 2, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, and 17. Valdecoxib has highest similarity to analogs 8, 19, 21, 22, 23, 26, 27, and 28. Multiple regression analysis successfully produced equations for prediction of similar compounds to lumiracoxib and valdecoxib. Path analysis indicated that number of atoms, oxygen & nitrogen atoms, and Log P are the greatest determinants for formula weight for known COX-2 inhibitors. Criteria for molecular properties is established for identifying COX-2 inhibitors. These 26 analogs show much potential for active COX-2 inhibition. PMID:23984829

  14. REGULARIZATION FOR COX'S PROPORTIONAL HAZARDS MODEL WITH NP-DIMENSIONALITY.

    PubMed

    Bradic, Jelena; Fan, Jianqing; Jiang, Jiancheng

    2011-01-01

    High throughput genetic sequencing arrays with thousands of measurements per sample and a great amount of related censored clinical data have increased demanding need for better measurement specific model selection. In this paper we establish strong oracle properties of non-concave penalized methods for non-polynomial (NP) dimensional data with censoring in the framework of Cox's proportional hazards model. A class of folded-concave penalties are employed and both LASSO and SCAD are discussed specifically. We unveil the question under which dimensionality and correlation restrictions can an oracle estimator be constructed and grasped. It is demonstrated that non-concave penalties lead to significant reduction of the "irrepresentable condition" needed for LASSO model selection consistency. The large deviation result for martingales, bearing interests of its own, is developed for characterizing the strong oracle property. Moreover, the non-concave regularized estimator, is shown to achieve asymptotically the information bound of the oracle estimator. A coordinate-wise algorithm is developed for finding the grid of solution paths for penalized hazard regression problems, and its performance is evaluated on simulated and gene association study examples. PMID:23066171

  15. Univariate Polynomials: Nearly Optimal Algorithms for Numerical Factorization and Root-finding

    Microsoft Academic Search

    Victor Y. Pan

    2002-01-01

    To approximate all roots (zeros) of a univariate polynomial, we develop two eective algorithms and combine them in a single recursive process. One algorithm computes a basic well isolated zero-free annulus on the complex plane, whereas another algorithm numerically splits the input polynomial of the nth degree into two factors balanced in the degrees and with the zero sets separated

  16. Mass univariate analysis of event-related brain potentials/fields I: A critical tutorial review

    E-print Network

    Kutas, Marta

    REVIEW Mass univariate analysis of event-related brain potentials/fields I: A critical tutorial-related brain potential (ERP) and magnetic field (ERF) techniques are their ability to track subtle differences in rapidly changing neurally gen- erated electromagnetic fields at multiple spatial locations with mil

  17. Fault detection of univariate non-Gaussian data with Bayesian network

    E-print Network

    Paris-Sud XI, Université de

    Fault detection of univariate non-Gaussian data with Bayesian network Sylvain Verron, Teodor.verron@univ-angers.fr Abstract--The purpose of this article is to present a new method for fault detection with Bayesian network. The interest of this method is to propose a new structure of Bayesian network allowing to detect a fault

  18. The approximate GCD of inexact polynomials Part I: a univariate algorithm

    Microsoft Academic Search

    Zhonggang Zeng

    This paper presents a blackbox-type algorithm and soft- ware for computing the approximate GCD (greatest com- mon divisor) of univariate polynomials whose coecien ts may be inexact. For a given set of polynomials, a succes- sive matrix updating strategy is designed to identify the maximum degree of the approximate GCD through partial singular value decompositions of Sylvester subresultant ma- trices.

  19. How to Apply Nonlinear Subspace Techniques to Univariate Biomedical Time Series

    Microsoft Academic Search

    Ana R. Teixeira; Ana Maria Tomé; Matthias Böhm; Carlos García Puntonet; Elmar Wolfgang Lang

    2009-01-01

    In this paper, we propose an embedding technique for univariate single-channel biomedical signals to apply projective subspace techniques. Biomedical signals are often recorded as 1-D time series; hence, they need to be transformed to multidimensional signal vectors for subspace techniques to be applicable. The transformation can be achieved by embedding an observed signal in its delayed coordinates. We propose the

  20. Power of univariate and multivariate analyses of repeated measurements in controlled clinical trials.

    PubMed

    Overall, J E; Atlas, R S

    1999-04-01

    The power of univariate and multivariate tests of significance is compared in relation to linear and nonlinear patterns of treatment effects in a repeated measurement design. Bonferroni correction was used to control the experiment-wise error rate in combining results from univariate tests of significance accomplished separately on average level, linear, quadratic, and cubic trend components. Multivariate tests on these same components of the overall treatment effect, as well as a multivariate test for between-groups difference on the original repeated measurements, were also evaluated for power against the same representative patterns of treatment effects. Results emphasize the advantage of parsimony that is achieved by transforming multiple repeated measurements into a reduced set of mean ngful composite variables representing average levels and rates of change. The Bonferroni correction applied to the separate univariate tests provided experiment-wise protection against Type I error, produced slightly greater experiment-wise power than a multivariate test applied to the same components of the data patterns, and provided substantially greater power than a multivariate test on the complete set of original repeated measurements. The separate univariate tests provide interpretive advantage regarding locus of the treatment effects. PMID:10348408

  1. Selection Strategies for Univariate Loglinear Smoothing Models and Their Effect on Equating Function Accuracy

    ERIC Educational Resources Information Center

    Moses, Tim; Holland, Paul W.

    2009-01-01

    In this study, we compared 12 statistical strategies proposed for selecting loglinear models for smoothing univariate test score distributions and for enhancing the stability of equipercentile equating functions. The major focus was on evaluating the effects of the selection strategies on equating function accuracy. Selection strategies' influence…

  2. Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor

    PubMed Central

    Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah

    2014-01-01

    To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX), the three-dimensional (3D) structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117) was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2. PMID:25484897

  3. Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor.

    PubMed

    Raharjo, Sentot Joko; Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah

    2014-01-01

    To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX), the three-dimensional (3D) structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117) was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2. PMID:25484897

  4. The Mitochondrial Genome of Conus textile, coxI-coxII Intergenic Sequences and Conoidean Evolution

    PubMed Central

    Bandyopadhyay, Pradip K; Stevenson, Bradford J.; Ownby, John-Paul; Cady, Matthew T.; Watkins, Maren; Olivera, Baldomero M.

    2009-01-01

    The cone snails belong to the superfamily Conoidea, comprising ?10,000 venomous marine gastropods. We determined the complete mitochondrial DNA sequence of Conus textile. The gene order is identical in Conus textile, Lophiotoma cerithiformis (another Conoidean gastropod), and the neogastropod Ilyanassa obsoleta, (not in the superfamily Conoidea). However, the intergenic interval between the coxI/coxII genes, was much longer in C. textile (165 bp) than in any other previously analyzed gastropod. We used the intergenic region to evaluate evolutionary patterns. In most neogastropods and three conidean families the intergenic interval is small (<30 nucleotides). Within Conus, the variation is from 130-170 bp, and each different clade within Conus has a narrower size distribution. In Conasprella, a subgenus traditionally assigned to Conus, the intergenic regions vary between 200-500 bp, suggesting that the species in Conasprella are not congeneric with Conus. The intergenic region was used for phylogenetic analysis of a group of fish-hunting Conus, despite the short length resolution was better than using standard markers. Thus, the coxI/coxII intergenic region can be used both to define evolutionary relationships between species in a clade, and to understand broad evolutionary patterns across the large superfamily Conoidea. PMID:17936021

  5. Cyclooxygenase2 (COX2) in Inflammatory and Degenerative Brain Diseases

    Microsoft Academic Search

    LUISA MINGHETTI

    2004-01-01

    Cyclooxygenase (COX) catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites comprising prostaglandins, prostacyclin, and thromboxanes, and is a major target of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as constitutive and inducible isoforms. COX-2 is the inducible isoform, rapidly expressed in several cell types in response to growth factors, cytokines, and pro-inflammatory

  6. Robert M. Cox, Ph.D. Postdoctoral Researcher

    E-print Network

    Cox, Robert

    . Evolution (in press) 5. Cox, R.M., E.U. Parker*, D.M. Cheney*, A.L. Liebl, L.B. Martin, and R. CalsbeekRobert M. Cox, Ph.D. 1 Postdoctoral Researcher Dartmouth College Department of Biological Sciences 401 Gilman Hall Hanover, NH 03755 (USA) Lab/Office: 603-646-9916 Email: robert.m.cox@dartmouth.edu Web

  7. Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer

    PubMed Central

    Nath, Sritama; Roy, Lopamudra Das; Grover, Priyanka; Rao, Shanti; Mukherjee, Pinku

    2015-01-01

    Objective Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1high PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1. Methods Levels of COX-2 and MUC1 were determined in MUC1?/?, MUC1low, and MUC1high PDA cells and tumors using reverse transcriptase–polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene. Results Significantly higher levels of COX-2 mRNA and protein were detected in MUC1high versus MUC1low/null cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ?1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor ?B p65 associates with the COX-2 promoter. Conclusions Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients. PMID:26035123

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

    PubMed

    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. PMID:11461714

  9. Language regression in childhood

    Microsoft Academic Search

    Shlomo Shinnar; Isabelle Rapin; Susan Arnold; Roberto F Tuchman; Lisa Shulman; Karen Ballaban-Gil; Myint Maw; Ruthmary K Deuel; Fred R Volkmar

    2001-01-01

    Language regression is observed both in autistic regression and as part of acquired epileptic aphasia (Landau-Kleffner Syndrome). We prospectively identified 177 children with language regression at four major medical centers, and their clinical characteristics were recorded. Their mean age at regression was 22.8 months. The mean time-to-specialist referral was 38 months of age. Most children (88%) met criteria for autism

  10. BIOMETRICS55, 580-584 A Global Goodness-of-Fit Statistic for Cox Regression Models

    E-print Network

    Parzen, Michael

    trial in primary billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes. For example, between 1974 and 1984, the Mayo Clinic conducted a clinical trial in primary billiary cirrhosis

  11. Prognostic Factors for Early Gastric Cancer in France: Cox Regression Analysis of 332 Cases

    Microsoft Academic Search

    Frédéric Borie; Valerie Rigau; Abe Fingerhut; Bertrand Millat

    2004-01-01

    Early gastric cancer (EGC) is defined as a lesion in which the depth of invasion is limited to the mucosa, submucosa, or both regardless of lymph node status; moreover, it has an excellent prognosis, with a 5-year survival rate of more than 90%. We aimed to determine the prognostic factors for EGC in a large Western series. Over a 10-year

  12. Unitary Response Regression Models

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    The dependent variable in a regular linear regression is a numerical variable, and in a logistic regression it is a binary or categorical variable. In these models the dependent variable has varying values. However, there are problems yielding an identity output of a constant value which can also be modelled in a linear or logistic regression with…

  13. Linkage Disequilibrium and Haplotype Analysis of COX-2 and Risk of Colorectal Adenoma Development

    PubMed Central

    Kwagyan, John; Apprey, Victor; Ashktorab, Hassan

    2012-01-01

    Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of prostaglandins, have been reported to modulate the risk for many human cancers. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of 13 single nucleotide polymorphisms of the COX-2 gene and examined its susceptibility to adenoma development in 72 African American cases and 142 controls. Results revealed significant variation in LD patterns with consequence for adenoma development. Two distinct haplotype blocks were identified; one block covered the coding regions of exon 1, introns and a section of the 3?-unstranslated region (3?-UTR), whereas the second block resided solely in the 3?-UTR region. A haplotype in block 1 increased the risk of adenoma development by threefold (odds ratio [OR] = 2.9, confidence interval [CI] = 1.8–3.7, P = 0.002). Regression analysis showed, increase in copies of minor alleles of 6,064(T>C) polymorphism associated with increased odds of adenoma development by 80% (OR = 1.80, CI = 1.09–3.21, P = 0.034), 10,848(G>A) by 84% (OR = 1.84, CI = 1.05–3.23, P = 0.034) and 10,935(A>G) by 32% (OR = 1.32, CI = 1.12–3.69, P = 0.036). These results support the hypothesis that COX-2 gene might play a role in the etiology of colon cancer and warrant further investigation in other cancers. Besides, these variations should be taken into account for disease-based association studies in which the COX-2 polymorphism is considered as a candidate gene. PMID:22376259

  14. Statistical methods for astronomical data with upper limits. I - Univariate distributions

    NASA Technical Reports Server (NTRS)

    Feigelson, E. D.; Nelson, P. I.

    1985-01-01

    The statistical treatment of univariate censored data is discussed. A heuristic derivation of the Kaplan-Meier maximum-likelihood estimator from first principles is presented which results in an expression amenable to analytic error analysis. Methods for comparing two or more censored samples are given along with simple computational examples, stressing the fact that most astronomical problems involve upper limits while the standard mathematical methods require lower limits. The application of univariate survival analysis to six data sets in the recent astrophysical literature is described, and various aspects of the use of survival analysis in astronomy, such as the limitations of various two-sample tests and the role of parametric modelling, are discussed.

  15. Amentoflavone from Biophytum sensitivum and its effect on COX-1/COX-2 catalysed prostaglandin biosynthesis.

    PubMed

    Bucar, F; Jachak, S M; Noreem, Y; Kartnig, T; Perera, P; Bohlin, L; Schubert-Zsilavecz, M

    1998-05-01

    Amentoflavone (I3', II8-biapigenin) was isolated from the roots of Biophytum sensitivum DC. (Oxalidaceae) and proved to be a selective inhibitor of cyclooxygenase (COX)-1 catalysed prostaglandin biosynthesis when tested in vitro with an IC (50) value of 12.4 microM (standard: indomethacin, IC (50) = 1.1 microM). Doses of up to 37 microM showed only a slight inhibition in the corresponding COX-2 assay. Quantification of amentoflavone was carried out by reversed phase HPLC in methanolic and aqueous extracts of the roots, stems and leaves. Highest amounts of amentoflavone were detected in methanolic extracts of roots and stems (0.26-0.35%), while considerably lower amounts were detected in the corresponding water extracts. PMID:17253252

  16. Near-best univariate spline discrete quasi-interpolants on non-uniform partitions

    Microsoft Academic Search

    D. Barrera; M. J. Ibanez; Paul Sablonniere; D. Sbibih

    2004-01-01

    Univariate spline discrete quasi-interpolants (abbr. dQIs) are approximation operators using B-spline expansions with coefficients which are linear combinations of discrete values of the function to be approximated. When working with nonuniform partitions, the main challenge is to find dQIs which have both good approximation orders and bounded uniform norms independent of the given partition. Near-best dQIs are obtained by minimizing

  17. Near-Best Univariate Spline Discrete Quasi-Interpolants on Nonuniform Partitions

    Microsoft Academic Search

    D. Barrera; M. J. Ibáñez; P. Sablonnière; D. Sbibih

    2008-01-01

    The univariate spline quasi-interpolants (QIs) studied in this paper are approximation operators using B-spline expansions\\u000a with coefficients that are linear combinations of discrete values of the function to be approximated. When working with nonuniform\\u000a partitions, the main challenge is to find QIs that have both good approximation orders and uniform norms which are bounded\\u000a independently of the given partition. Near-best

  18. Univariate time series modeling and an application to future claims amount in SOCSO's invalidity pension scheme

    NASA Astrophysics Data System (ADS)

    Chek, Mohd Zaki Awang; Ahmad, Abu Bakar; Ridzwan, Ahmad Nur Azam Ahmad; Jelas, Imran Md.; Jamal, Nur Faezah; Ismail, Isma Liana; Zulkifli, Faiz; Noor, Syamsul Ikram Mohd

    2012-09-01

    The main objective of this study is to forecast the future claims amount of Invalidity Pension Scheme (IPS). All data were derived from SOCSO annual reports from year 1972 - 2010. These claims consist of all claims amount from 7 benefits offered by SOCSO such as Invalidity Pension, Invalidity Grant, Survivors Pension, Constant Attendance Allowance, Rehabilitation, Funeral and Education. Prediction of future claims of Invalidity Pension Scheme will be made using Univariate Forecasting Models to predict the future claims among workforce in Malaysia.

  19. An empirical comparison of univariate and multivariate meta-analyses for categorical outcomes.

    PubMed

    Trikalinos, Thomas A; Hoaglin, David C; Schmid, Christopher H

    2014-04-30

    Treatment effects for multiple outcomes can be meta-analyzed separately or jointly, but no systematic empirical comparison of the two approaches exists. From the Cochrane Library of Systematic Reviews, we identified 45 reviews, including 1473 trials and 258,675 patients, that contained two or three univariate meta-analyses of categorical outcomes for the same interventions that could also be analyzed jointly. Eligible were meta-analyses with at least seven trials reporting all outcomes for which the cross-classification tables were exactly recoverable (e.g., outcomes were mutually exclusive, or one was a subset of the other). This ensured known correlation structures. Outcomes in 40 reviews had an is-subset-of relationship, and those in 5 were mutually exclusive. We analyzed these data with univariate and multivariate models based on discrete and approximate likelihoods. Discrete models were fit in the Bayesian framework using slightly informative priors. The summary effects for each outcome were similar with univariate and multivariate meta-analyses (both using the approximate and discrete likelihoods); however, the multivariate model with the discrete likelihood gave smaller between-study variance estimates, and narrower predictive intervals for new studies. When differences in the summary treatment effects were examined, the multivariate models gave similar summary estimates but considerably longer (shorter) uncertainty intervals because of positive (negative) correlation between outcome treatment effects. It is unclear whether any of the examined reviews would change their overall conclusions based on multivariate versus univariate meta-analyses, because extra-analytical and context-specific considerations contribute to conclusions and, secondarily, because numerical differences were often modest. PMID:24285290

  20. CURRICULUM VITAE L. Clarke Cox, Ph.D.

    E-print Network

    Guenther, Frank

    Instruments 31: 12, (1980) ': Cox L.C., Hack, M., and Metz, DA, Brainstem evoked response audiometry; Normative data from the preterm infant. Audiology 20: 530, (1981). Cox, LC, Hack, M, Metz, DA, Brainstem.C., Hack, M., and Metz, D.A. Longitudinal ABR in the NICU infant. Int. J. Ped. ORL 4: 224, (1982) Lee, S

  1. Original article Potent, orally available, selective COX-2 inhibitors based

    E-print Network

    Hammock, Bruce D.

    Original article Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core inhibitors. While the majority of the compounds prepared using an earlier developed imidazoline N-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300

  2. Cyclooxygenase2 (COX2) in Carcinogenesis and Selective COX2 Inhibitors for Chemoprevention in Gastrointestinal Cancers

    Microsoft Academic Search

    Takashi Fujimura; Tetsuo Ohta; Katsunobu Oyama; Tomoharu Miyashita; Kochi Miwa

    2007-01-01

    Introduction  Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have a property to inhibit tumor development in some cancers\\u000a while it shows various side effects such as gastrointestinal bleeding and renal disorder. Selective cyclooxygenase (COX)-2\\u000a inhibitors (coxibs) were originally developed as one of anti-inflammatory drugs to avoid side effect of NSAIDs. Fortunately,\\u000a the coxibs was also proved to have an inhibiting

  3. The Relative Contributions of COX-1 and COX-2 to Vascular Biosynthesis of Prostacyclin and Thromboxane 

    E-print Network

    Osborn, Pamela

    2014-01-17

    . .............................. 41 Table 6: Effects of Calphostin, Ridogrel and Furegrelate on PGI2 and TxA2 Release. ... 43 x NOMENCLATURE AA Arachidonic acid COX CHD CVD DAG Cyclooxygenase Coronary heart disease Cardiovascular disease.... The novel use of NSAIDs as prevention from certain cardiovascular diseases (CVD) could potentially change the fate of millions of people. The World Health Organization (WHO) estimates that CVD is the single largest contributor to global mortality...

  4. Analyze Multivariate Phenotypes in Genetic Association Studies by Combining Univariate Association Tests

    PubMed Central

    Yang, Qiong; Wu, Hongsheng; Guo, Chao-Yu; Fox, Caroline S

    2011-01-01

    Multivariate phenotypes are frequently encountered in genome-wide association studies(GWAS). Such phenotypes contain more information than univariate phenotypes, but how to best exploit the information to increase the chance of detecting genetic variant of pleiotropic effect is not always clear. Moreover, when multivariate phenotypes contain a mixture of quantitative and qualitative measures, limited methods are applicable. In this paper, we first evaluated the approach originally proposed by O’Brien and by Wei and Johnson that combines the univariate test statistics and then we proposed two extensions to that approach. The original and proposed approaches are applicable to a multivariate phenotype containing any type of components including continuous, categorical and survival phenotypes, and applicable to samples consisting of families or unrelated samples. Simulation results suggested that all methods had valid type I error rates. Our extensions had a better power than O’Brien’s method with heterogeneous means among univariate test statistics, but were less powerful than O’Brien’s with homogeneous means among individual test statistics. All approaches have shown considerable increase in power compared to testing each component of a multivariate phenotype individually in some cases. We apply all the methods to GWAS of serum uric acid levels and gout with 550,000 SNPs in the Framingham Heart Study. PMID:20583287

  5. Unite and conquer: univariate and multivariate approaches for finding differentially expressed gene sets

    PubMed Central

    Glazko, Galina V.; Emmert-Streib, Frank

    2009-01-01

    Motivation: Recently, many univariate and several multivariate approaches have been suggested for testing differential expression of gene sets between different phenotypes. However, despite a wealth of literature studying their performance on simulated and real biological data, still there is a need to quantify their relative performance when they are testing different null hypotheses. Results: In this article, we compare the performance of univariate and multivariate tests on both simulated and biological data. In the simulation study we demonstrate that high correlations equally affect the power of both, univariate as well as multivariate tests. In addition, for most of them the power is similarly affected by the dimensionality of the gene set and by the percentage of genes in the set, for which expression is changing between two phenotypes. The application of different test statistics to biological data reveals that three statistics (sum of squared t-tests, Hotelling's T2, N-statistic), testing different null hypotheses, find some common but also some complementing differentially expressed gene sets under specific settings. This demonstrates that due to complementing null hypotheses each test projects on different aspects of the data and for the analysis of biological data it is beneficial to use all three tests simultaneously instead of focusing exclusively on just one. Contact: Galina_Glazko@urmc.rochester.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19574285

  6. The CoxD Protein, a Novel AAA+ ATPase Involved in Metal Cluster Assembly: Hydrolysis of Nucleotide-Triphosphates and Oligomerization

    PubMed Central

    Maisel, Tobias; Joseph, Stephanie; Mielke, Thorsten; Bürger, Jörg; Schwarzinger, Stephan; Meyer, Ortwin

    2012-01-01

    CoxD of the ?-proteobacterium Oligotropha carboxidovorans is a membrane protein which is involved in the posttranslational biosynthesis of the [CuSMoO2] cluster in the active site of the enzyme CO dehydrogenase. The bacteria synthesize CoxD only in the presence of CO. Recombinant CoxD produced in E. coli K38 pGP1-2/pETMW2 appeared in inclusion bodies from where it was solubilized by urea and refolded by stepwise dilution. Circular dichroism spectroscopy revealed the presence of secondary structural elements in refolded CoxD. CoxD is a P-loop ATPase of the AAA-protein family. Refolded CoxD catalyzed the hydrolysis of MgATP yielding MgADP and inorganic phosphate at a 1?1?1 molar ratio. The reaction was inhibited by the slow hydrolysable MgATP-?-S. GTPase activity of CoxD did not exceed 2% of the ATPase activity. Employing different methods (non linear regression, Hanes and Woolf, Lineweaver-Burk), preparations of CoxD revealed a mean KM value of 0.69±0.14 mM ATP and an apparent Vmax value of 19.3±2.3 nmol ATP hydrolyzed min?1 mg?1. Sucrose density gradient centrifugation and gel filtration showed that refolded CoxD can exist in various multimeric states (2-mer, 4-mer or 6-mer), preferentially as hexamer or dimer. Within weeks the hexamer dissociates into the dimer, a process which can be reversed by MgATP or MgATP-?-S within hours. Only the hexamers and the dimers exhibited MgATPase activity. Transmission electron microscopy of negatively stained CoxD preparations revealed distinct particles within a size range of 10–16 nm, which further corroborates the oligomeric organization. The 3D structure of CoxD was modeled with the 3D structure of BchI from Rhodobacter capsulatus as template. It has the key elements of an AAA+ domain in the same arrangement and at same positions as in BchI and displays the characteristic inserts of the PS-II-insert clade. Possible functions of CoxD in [CuSMoO2] cluster assembly are discussed. PMID:23077613

  7. Int J Cancer. Author manuscript COX-2 and p53 in human sinonasal cancer: COX-2 expression is

    E-print Network

    Paris-Sud XI, Université de

    of Occupational Health1 Finnish Institute of Occupational Health, Helsinki,FI Sant publique et pid miologie des d that activate COX-2 also induce tumour suppressor p53, a transcription factor central in cellular stress, and 27 squamous cell carcinomas (SCC); 48 analysed for COX-2; 41 for p53). Occupational histories

  8. Morse-Smale Regression

    Microsoft Academic Search

    Samuel Gerber; Oliver Rübel; Peer-Timo Bremer; Valerio Pascucci; Ross T. Whitaker

    2012-01-01

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduce a quality-of-fit-driven decomposition of the domain. The emphasis in this work is on a topologically meaningful segmentation. Thus, the proposed regression approach is based on a segmentation induced by a discrete approximation of the Morse-Smale complex. This yields a segmentation with partitions corresponding to

  9. Explorations in statistics: regression

    NSDL National Science Digital Library

    PhD Douglas Curran-Everett (National Jewish Medical and Research Center Div. Biostatistics, Depts. Prev. Med./Biometrics, Physiology/Biophys)

    2011-12-01

    This article explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive connection. Regression helps us answer three questions: does some variable Y depend on another variable X; if so, what is the nature of the relationship between Y and X; and for some value of X, what value of Y do we predict? Residual plots are an essential component of a thorough regression analysis: they help us decide if our statistical regression model of the relationship between Y and X is appropriate.

  10. Syst. Zool., 36(4):398-400, 1987 Univariate Analyses of Morphometric Variation Do Not Emulate the

    E-print Network

    Willig, Michael

    Syst. Zool., 36(4):398-400, 1987 Univariate Analyses of Morphometric Variation Do Not Emulate) compared the empirical results of univar- iate (ANOVA) and multivariate (MANO- VA) analyses of morphometric

  11. Function of cancer associated genes revealed by modern univariate and multivariate association tests.

    PubMed

    Gorfine, Malka; Goldstein, Boaz; Fishman, Alla; Heller, Ruth; Heller, Yair; Lamm, Ayelet T

    2015-01-01

    Copy number variation (CNV) plays a role in pathogenesis of many human diseases, especially cancer. Several whole genome CNV association studies have been performed for the purpose of identifying cancer associated CNVs. Here we undertook a novel approach to whole genome CNV analysis, with the goal being identification of associations between CNV of different genes (CNV-CNV) across 60 human cancer cell lines. We hypothesize that these associations point to the roles of the associated genes in cancer, and can be indicators of their position in gene networks of cancer-driving processes. Recent studies show that gene associations are often non-linear and non-monotone. In order to obtain a more complete picture of all CNV associations, we performed omnibus univariate analysis by utilizing dCov, MIC, and HHG association tests, which are capable of detecting any type of association, including non-monotone relationships. For comparison we used Spearman and Pearson association tests, which detect only linear or monotone relationships. Application of dCov, MIC and HHG tests resulted in identification of twice as many associations compared to those found by Spearman and Pearson alone. Interestingly, most of the new associations were detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform multivariate analysis. We tested for association between genes of unknown function and known cancer-related pathways. Our results indicate that multivariate analysis is much more effective than univariate analysis for the purpose of ascribing biological roles to genes of unknown function. We conclude that a combination of multivariate and univariate omnibus association tests can reveal significant information about gene networks of disease-driving processes. These methods can be applied to any large gene or pathway dataset, allowing more comprehensive analysis of biological processes. PMID:25965968

  12. Function of Cancer Associated Genes Revealed by Modern Univariate and Multivariate Association Tests

    PubMed Central

    Fishman, Alla; Heller, Ruth; Heller, Yair; Lamm, Ayelet T.

    2015-01-01

    Copy number variation (CNV) plays a role in pathogenesis of many human diseases, especially cancer. Several whole genome CNV association studies have been performed for the purpose of identifying cancer associated CNVs. Here we undertook a novel approach to whole genome CNV analysis, with the goal being identification of associations between CNV of different genes (CNV-CNV) across 60 human cancer cell lines. We hypothesize that these associations point to the roles of the associated genes in cancer, and can be indicators of their position in gene networks of cancer-driving processes. Recent studies show that gene associations are often non-linear and non-monotone. In order to obtain a more complete picture of all CNV associations, we performed omnibus univariate analysis by utilizing dCov, MIC, and HHG association tests, which are capable of detecting any type of association, including non-monotone relationships. For comparison we used Spearman and Pearson association tests, which detect only linear or monotone relationships. Application of dCov, MIC and HHG tests resulted in identification of twice as many associations compared to those found by Spearman and Pearson alone. Interestingly, most of the new associations were detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform multivariate analysis. We tested for association between genes of unknown function and known cancer-related pathways. Our results indicate that multivariate analysis is much more effective than univariate analysis for the purpose of ascribing biological roles to genes of unknown function. We conclude that a combination of multivariate and univariate omnibus association tests can reveal significant information about gene networks of disease-driving processes. These methods can be applied to any large gene or pathway dataset, allowing more comprehensive analysis of biological processes. PMID:25965968

  13. Language regression in childhood.

    PubMed

    Shinnar, S; Rapin, I; Arnold, S; Tuchman, R F; Shulman, L; Ballaban-Gil, K; Maw, M; Deuel, R K; Volkmar, F R

    2001-03-01

    Language regression is observed both in autistic regression and as part of acquired epileptic aphasia (Landau-Kleffner Syndrome). We prospectively identified 177 children with language regression at four major medical centers, and their clinical characteristics were recorded. Their mean age at regression was 22.8 months. The mean time-to-specialist referral was 38 months of age. Most children (88%) met criteria for autism or manifested autistic features. Males (P = 0.02) and children less than 3 years of age who regressed (P = 0.016) had a higher probability of developing autistic behaviors. Seizures were more common in children who regressed after they reached 3 years of age (P < 0.001), and children with seizures were less likely to have associated autistic regression (P < 0.001). Electroencephalogram abnormalities were reported in 37% of patients and were more common in children with seizures (P < 0.001). At last follow-up, language function was impaired in 88% of the children, although some improvement was noted in 57%. We conclude that the loss of previously acquired language at any age, even if that language only includes a few words or communicative gestures, is often associated with a more global regression in cognition and/or behavior and has serious implications for future function. Early identification and referral of these children is necessary to allow for diagnosis and intervention. PMID:11301218

  14. DISCUSS: Regression and Correlation

    NSDL National Science Digital Library

    Hunt, Neville

    This module introduces correlation and regression through topics like scatterplots, lines, slopes, intercepts, applications of regression analysis, the line of best fit, goodness of fit, assumptions and how to check them, prediction, interpolation, extrapolation, and reliability. Excel spreadsheets are used to provide examples and exercises.

  15. Morse-Smale Regression

    PubMed Central

    Gerber, Samuel; Rübel, Oliver; Bremer, Peer-Timo; Pascucci, Valerio; Whitaker, Ross T.

    2012-01-01

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduce a quality-of-fit-driven decomposition of the domain. The emphasis in this work is on a topologically meaningful segmentation. Thus, the proposed regression approach is based on a segmentation induced by a discrete approximation of the Morse-Smale complex. This yields a segmentation with partitions corresponding to regions of the function with a single minimum and maximum that are often well approximated by a linear model. This approach yields regression models that are amenable to interpretation and have good predictive capacity. Typically, regression estimates are quantified by their geometrical accuracy. For the proposed regression, an important aspect is the quality of the segmentation itself. Thus, this paper introduces a new criterion that measures the topological accuracy of the estimate. The topological accuracy provides a complementary measure to the classical geometrical error measures and is very sensitive to over-fitting. The Morse-Smale regression is compared to state-of-the-art approaches in terms of geometry and topology and yields comparable or improved fits in many cases. Finally, a detailed study on climate-simulation data demonstrates the application of the Morse-Smale regression. Supplementary materials are available online and contain an implementation of the proposed approach in the R package msr, an analysis and simulations on the stability of the Morse-Smale complex approximation and additional tables for the climate-simulation study. PMID:23687424

  16. Correlation and Regression

    NSDL National Science Digital Library

    Berger, Dale

    This applet allows the user to explore basic principles of correlation and regression. The user can manipulate points on a scatterplot. The user can then place a regression line on the plot and evaluate the resulting sums of squares error. An interesting feature of this applet is that it allows viewing of the sum of squares error as squares.

  17. Lesson 6: Linear Regression

    NSDL National Science Digital Library

    2011-01-01

    Using real world data, this lesson introduces linear regression using lines of best fit that may calculated by hand by selecting two pints that appear to fall on the line of best fit. The lesson could also be used with a calculator to find the actual regression line. Interpolation and extrapolation are also introduced as well as scatter plots.

  18. Improved Regression Calibration

    ERIC Educational Resources Information Center

    Skrondal, Anders; Kuha, Jouni

    2012-01-01

    The likelihood for generalized linear models with covariate measurement error cannot in general be expressed in closed form, which makes maximum likelihood estimation taxing. A popular alternative is regression calibration which is computationally efficient at the cost of inconsistent estimation. We propose an improved regression calibration…

  19. Online multiple instance regression

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-Gang; Zhao, Zeng-Shun; Zhang, Chang-Shui

    2013-09-01

    The multiple instance regression problem has become a hot research topic recently. There are several approaches to the multiple instance regression problem, such as Salience, Citation KNN, and MI-ClusterRegress. All of these solutions work in batch mode during the training step. However, in practice, examples usually arrive in sequence. Therefore, the training step cannot be accomplished once. In this paper, an online multiple instance regression method “OnlineMIR" is proposed. OnlineMIR can not only predict the label of a new bag, but also update the current regression model with the latest arrived bag. The experimental results show that OnlineMIR achieves good performances on both synthetic and real data sets.

  20. 32. SCIENTISTS ALLAN COX (SEATED), RICHARD DOELL, AND BRENT DALRYMPLE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. SCIENTISTS ALLAN COX (SEATED), RICHARD DOELL, AND BRENT DALRYMPLE AT CONTROL PANEL, ABOUT 1965. - U.S. Geological Survey, Rock Magnetics Laboratory, 345 Middlefield Road, Menlo Park, San Mateo County, CA

  1. Relationship of the Topological Distances and Activities between mPGES-1 and COX-2 versus COX-1: Implications of the Different Post-Translational Endoplasmic Reticulum Organizations of COX-1 and COX-2.

    PubMed

    Akasaka, Hironari; So, Shui-Ping; Ruan, Ke-He

    2015-06-16

    In vascular inflammation, prostaglandin E2 (PGE2) is largely biosynthesized by microsomal PGE2 synthase-1 (mPGES-1), competing with other downstream eicosanoid-synthesizing enzymes, such as PGIS, a synthase of a vascular protector prostacyclin (PGI2), to isomerize the cyclooxygenase (COX)-2-derived prostaglandin H2 (PGH2). In this study, we found that a majority of the product from the cells co-expressing human COX-2, mPGES-1, and PGIS was PGE2. We hypothesize that the molecular and cellular mechanisms are related to the post-translational endoplasmic reticulum (ER) arrangement of those enzymes. A set of fusion enzymes, COX-2-linker [10 amino acids (aa)]-PGIS and COX-2-linker (22 amino acids)-PGIS, were created as "The Bioruler", in which the 10 and 22 amino acids are defined linkers with known helical structures and distances (14.4 and 30.8 Å, respectively). Our experiments have shown that the efficiency of PGI2 biosynthesis was reduced when the separation distance increased from 10 to 22 amino acids. When COX-2-10aa-PGIS (with a 14.4 Å separation) was co-expressed with mPGES-1 on the ER membrane, a major product was PGE2, but not PGI2. However, expression of COX-2-10aa-PGIS and mPGES-1 on a separated ER with a distance of ?30.8 Å reduced the level of PGE2 production. These data indicated that the mPGES-1 is "complex-likely" colocalized with COX-2 within a distance of 14.4 Å. In addition, the cells co-expressing COX-1-10aa-PGIS and mPGES-1 produced PGI2 mainly, but not PGE2. This indicates that mPGES-1 is expressed much farther from COX-1. These findings have led to proposed models showing the different post-translational ER organization between COX-2 and COX-1 with respect to the topological arrangement of the mPGES-1 during vascular inflammation. PMID:25988363

  2. Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase.

    PubMed

    Bourens, Myriam; Boulet, Aren; Leary, Scot C; Barrientos, Antoni

    2014-06-01

    Cytochrome c oxidase (CIV) deficiency is one of the most common respiratory chain defects in patients presenting with mitochondrial encephalocardiomyopathies. CIV biogenesis is complicated by the dual genetic origin of its structural subunits, and assembly of a functional holoenzyme complex requires a large number of nucleus-encoded assembly factors. In general, the functions of these assembly factors remain poorly understood, and mechanistic investigations of human CIV biogenesis have been limited by the availability of model cell lines. Here, we have used small interference RNA and transcription activator-like effector nucleases (TALENs) technology to create knockdown and knockout human cell lines, respectively, to study the function of the CIV assembly factor COX20 (FAM36A). These cell lines exhibit a severe, isolated CIV deficiency due to instability of COX2, a mitochondrion-encoded CIV subunit. Mitochondria lacking COX20 accumulate CIV subassemblies containing COX1 and COX4, similar to those detected in fibroblasts from patients carrying mutations in the COX2 copper chaperones SCO1 and SCO2. These results imply that in the absence of COX20, COX2 is inefficiently incorporated into early CIV subassemblies. Immunoprecipitation assays using a stable COX20 knockout cell line expressing functional COX20-FLAG allowed us to identify an interaction between COX20 and newly synthesized COX2. Additionally, we show that SCO1 and SCO2 act on COX20-bound COX2. We propose that COX20 acts as a chaperone in the early steps of COX2 maturation, stabilizing the newly synthesized protein and presenting COX2 to its metallochaperone module, which in turn facilitates the incorporation of mature COX2 into the CIV assembly line. PMID:24403053

  3. Cox-Maze procedure for atrial fibrillation: Mayo Clinic experience

    Microsoft Academic Search

    HV Schaff; JA Dearani; RC Daly; TA Orszulak; GK Danielson

    2000-01-01

    The Cox-Maze procedure corrects atrial fibrillation in 90% of patients, and successful operation restores sinus rhythm, thereby reducing risks of thromboembolism and anticoagulant-associated hemorrhage. Symptoms such as palpitation and fatigability also improve with restoration of atrioventricular synchrony. At the Mayo Clinic, 221 Cox-Maze procedures were performed from March 1993 through March 1999. Over 75% of patients had associated cardiac disease

  4. Linear Regression and Support Vector Regression

    E-print Network

    Shi, Qinfeng "Javen"

    extraction and selection Regression Raw data Processed data + ++ + + ++ + Sex Age Hei ght Income M 20 1.7 25,000 F 30 1.6 55,000 M 1.8 30,000 ... Mis-entry (should have been 25!!!) Height and sex seem be represented as (w represents coefficients and b is an intercept) )},(),...,,(),,{( 2211 mm yyy xxx yn ,x n f

  5. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures. PMID:23626706

  6. Understanding logistic regression analysis.

    PubMed

    Sperandei, Sandro

    2014-01-01

    Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed. PMID:24627710

  7. Physiological COX-2 Expression in Breast Epithelium Associates with COX-2 Levels in Ductal Carcinoma in Situ and Invasive Breast Cancer in Young Women

    PubMed Central

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A.; Borges, Virginia F.; Schedin, Pepper

    2015-01-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population. PMID:24518566

  8. Basic Multiple Regression

    NSDL National Science Digital Library

    Lowry, Richard, 1940-

    This page will perform basic multiple regression analysis for the case where there are several independent predictor variables, X1, X2, etc., and one dependent or criterion variable, Y. Requires import of data from a spreadsheet.

  9. Multivariate Regression with Calibration*

    PubMed Central

    Liu, Han; Wang, Lie; Zhao, Tuo

    2014-01-01

    We propose a new method named calibrated multivariate regression (CMR) for fitting high dimensional multivariate regression models. Compared to existing methods, CMR calibrates the regularization for each regression task with respect to its noise level so that it is simultaneously tuning insensitive and achieves an improved finite-sample performance. Computationally, we develop an efficient smoothed proximal gradient algorithm which has a worst-case iteration complexity O(1/?), where ? is a pre-specified numerical accuracy. Theoretically, we prove that CMR achieves the optimal rate of convergence in parameter estimation. We illustrate the usefulness of CMR by thorough numerical simulations and show that CMR consistently outperforms other high dimensional multivariate regression methods. We also apply CMR on a brain activity prediction problem and find that CMR is as competitive as the handcrafted model created by human experts. PMID:25620861

  10. Reliability and Regression Analysis

    NSDL National Science Digital Library

    Lane, David M.

    This applet, by David M. Lane of Rice University, demonstrates how the reliability of X and Y affect various aspects of the regression of Y on X. Java 1.1 is required and a full set of instructions is given in order to get the full value from the applet. Exercises and definitions to key terms are also given to help students understand reliability and regression analysis.

  11. Trend and forecasting rate of cancer deaths at a public university hospital using univariate modeling

    NASA Astrophysics Data System (ADS)

    Ismail, A.; Hassan, Noor I.

    2013-09-01

    Cancer is one of the principal causes of death in Malaysia. This study was performed to determine the pattern of rate of cancer deaths at a public hospital in Malaysia over an 11 year period from year 2001 to 2011, to determine the best fitted model of forecasting the rate of cancer deaths using Univariate Modeling and to forecast the rates for the next two years (2012 to 2013). The medical records of the death of patients with cancer admitted at this Hospital over 11 year's period were reviewed, with a total of 663 cases. The cancers were classified according to 10th Revision International Classification of Diseases (ICD-10). Data collected include socio-demographic background of patients such as registration number, age, gender, ethnicity, ward and diagnosis. Data entry and analysis was accomplished using SPSS 19.0 and Minitab 16.0. The five Univariate Models used were Naïve with Trend Model, Average Percent Change Model (ACPM), Single Exponential Smoothing, Double Exponential Smoothing and Holt's Method. The overall 11 years rate of cancer deaths showed that at this hospital, Malay patients have the highest percentage (88.10%) compared to other ethnic groups with males (51.30%) higher than females. Lung and breast cancer have the most number of cancer deaths among gender. About 29.60% of the patients who died due to cancer were aged 61 years old and above. The best Univariate Model used for forecasting the rate of cancer deaths is Single Exponential Smoothing Technique with alpha of 0.10. The forecast for the rate of cancer deaths shows a horizontally or flat value. The forecasted mortality trend remains at 6.84% from January 2012 to December 2013. All the government and private sectors and non-governmental organizations need to highlight issues on cancer especially lung and breast cancers to the public through campaigns using mass media, media electronics, posters and pamphlets in the attempt to decrease the rate of cancer deaths in Malaysia.

  12. Dynamics of intracranial electroencephalographic recordings from epilepsy patients using univariate and bivariate recurrence networks

    NASA Astrophysics Data System (ADS)

    Subramaniyam, Narayan Puthanmadam; Hyttinen, Jari

    2015-02-01

    Recently Andrezejak et al. combined the randomness and nonlinear independence test with iterative amplitude adjusted Fourier transform (iAAFT) surrogates to distinguish between the dynamics of seizure-free intracranial electroencephalographic (EEG) signals recorded from epileptogenic (focal) and nonepileptogenic (nonfocal) brain areas of epileptic patients. However, stationarity is a part of the null hypothesis for iAAFT surrogates and thus nonstationarity can violate the null hypothesis. In this work we first propose the application of the randomness and nonlinear independence test based on recurrence network measures to distinguish between the dynamics of focal and nonfocal EEG signals. Furthermore, we combine these tests with both iAAFT and truncated Fourier transform (TFT) surrogate methods, which also preserves the nonstationarity of the original data in the surrogates along with its linear structure. Our results indicate that focal EEG signals exhibit an increased degree of structural complexity and interdependency compared to nonfocal EEG signals. In general, we find higher rejections for randomness and nonlinear independence tests for focal EEG signals compared to nonfocal EEG signals. In particular, the univariate recurrence network measures, the average clustering coefficient C and assortativity R , and the bivariate recurrence network measure, the average cross-clustering coefficient Ccross, can successfully distinguish between the focal and nonfocal EEG signals, even when the analysis is restricted to nonstationary signals, irrespective of the type of surrogates used. On the other hand, we find that the univariate recurrence network measures, the average path length L , and the average betweenness centrality BC fail to distinguish between the focal and nonfocal EEG signals when iAAFT surrogates are used. However, these two measures can distinguish between focal and nonfocal EEG signals when TFT surrogates are used for nonstationary signals. We also report an improvement in the performance of nonlinear prediction error N and nonlinear interdependence measure L used by Andrezejak et al., when TFT surrogates are used for nonstationary EEG signals. We also find that the outcome of the nonlinear independence test based on the average cross-clustering coefficient Ccross is independent of the outcome of the randomness test based on the average clustering coefficient C . Thus, the univariate and bivariate recurrence network measures provide independent information regarding the dynamics of the focal and nonfocal EEG signals. In conclusion, recurrence network analysis combined with nonstationary surrogates can be applied to derive reliable biomarkers to distinguish between epileptogenic and nonepileptogenic brain areas using EEG signals.

  13. Coupled variable selection for regression modeling of complex treatment patterns in a clinical cancer registry.

    PubMed

    Schmidtmann, I; Elsäßer, A; Weinmann, A; Binder, H

    2014-12-30

    For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns. PMID:25345575

  14. Suppression of Intestinal Polyposis in Apc ?716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX2)

    Microsoft Academic Search

    Masanobu Oshima; Joseph E Dinchuk; Stacia L Kargman; Hiroko Oshima; Bruno Hancock; Elizabeth Kwong; James M Trzaskos; Jilly F Evans; Makoto M Taketo

    1996-01-01

    Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H2: constitutive COX-1 and inducible COX-2. To assess the role of COX-2 in colorectal tumorigenisis, we determined the effects of COX-2 gene (Ptgs2) knockouts and a novel COX-2 inhibitor on Apc?716knockout mice, a model of human familial adenomatous polyposis. A Ptgs2null mutation reduced the number and size of the intestinal

  15. Knock-down of the COX3 and COX17 gene expression of cytochrome c oxidase in the unicellular green alga Chlamydomonas reinhardtii

    Microsoft Academic Search

    Claire Remacle; Nadine Coosemans; Frédéric Jans; Marc Hanikenne; Patrick Motte; Pierre Cardol

    2010-01-01

    The COX3 gene encodes a core subunit of mitochondrial cytochrome c oxidase (complex IV) whereas the COX17 gene encodes a chaperone delivering copper to the enzyme. Mutants of these two genes were isolated by RNA interference in\\u000a the microalga Chlamydomonas. The COX3 mRNA was completely lacking in the cox3-RNAi mutant and no activity and assembly of complex IV were detected.

  16. Spatiotemporal Linear Mixed Effects Modeling for the Mass-univariate Analysis of Longitudinal Neuroimage Data

    PubMed Central

    Bernal-Rusiel, Jorge L.; Reuter, Martin; Greve, Douglas N.; Fischl, Bruce; Sabuncu, Mert R.

    2013-01-01

    We present an extension of the Linear Mixed Effects (LME) modeling approach to be applied to the mass-univariate analysis of longitudinal neuroimaging (LNI) data. The proposed method, called spatiotemporal LME or ST-LME, builds on the flexible LME framework and exploits the spatial structure in image data. We instantiated ST-LME for the analysis of cortical surface measurements (e.g. thickness) computed by FreeSurfer, a widely-used brain Magnetic Resonance Image (MRI) analysis software package. We validate the proposed ST-LME method and provide a quantitative and objective empirical comparison with two popular alternative methods, using two brain MRI datasets obtained from the Alzheimer’s disease neuroimaging initiative (ADNI) and Open Access Series of Imaging Studies (OASIS). Our experiments revealed that ST-LME offers a dramatic gain in statistical power and repeatability of findings, while providing good control of the false positive rate. PMID:23702413

  17. Cyclooxygenase2 (COX2) immunoreactivity in human endometrial carcinoma and precursor lesions: the potential use of COX2 inhibitors in cancer chemoprevention and therapy

    Microsoft Academic Search

    A. Nasir; D. Boulware; H. E. Kaiser; J. M. Lancaster; D. Coppola; P. V. Smith; A. Hakam; S. E. Siegel; B. Bodey

    The design of new antineoplastic agents that can halt the progression of human malignancies with minimal systemic damage has been emerging in recent years, with COX-2 as a major tar- get molecule. With an aim to demonstrate the expression and role of COX-2, the principal puta- tive target of COX-2 inhibitor therapy, in endometrial adenocarcinoma (EACA) and precursor lesions, atypical

  18. The polypeptides COX2A and COX2B are essential components of the mitochondrial cytochrome c oxidase of Toxoplasma gondii.

    PubMed

    Morales-Sainz, Lorena; Escobar-Ramírez, Adelma; Cruz-Torres, Valentín; Reyes-Prieto, Adrián; Vázquez-Acevedo, Miriam; Lara-Martínez, Reyna; Jiménez-García, Luis Felipe; González-Halphen, Diego

    2008-02-01

    Two genes encoding cytochrome c oxidase subunits, Cox2a and Cox2b, are present in the nuclear genomes of apicomplexan parasites and show sequence similarity to corresponding genes in chlorophycean algae. We explored the presence of COX2A and COX2B subunits in the cytochrome c oxidase of Toxoplasma gondii. Antibodies were raised against a synthetic peptide containing a 14-residue fragment of the COX2A polypeptide and against a hexa-histidine-tagged recombinant COX2B protein. Two distinct immunochemical stainings localized the COX2A and COX2B proteins in the parasite's mitochondria. A mitochondria-enriched fraction exhibited cyanide-sensitive oxygen uptake in the presence of succinate. T. gondii mitochondria were solubilized and subjected to Blue Native Electrophoresis followed by second dimension electrophoresis. Selected protein spots from the 2D gels were subjected to mass spectrometry analysis and polypeptides of mitochondrial complexes III, IV and V were identified. Subunits COX2A and COX2B were detected immunochemically and found to co-migrate with complex IV; therefore, they are subunits of the parasite's cytochrome c oxidase. The apparent molecular mass of the T. gondii mature COX2A subunit differs from that of the chlorophycean alga Polytomella sp. The data suggest that during its biogenesis, the mitochondrial targeting sequence of the apicomplexan COX2A precursor protein may be processed differently than the one from its algal counterpart. PMID:18036550

  19. Expression of COX1 and COX2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids

    Microsoft Academic Search

    Isabelle St-Louis; Mohan Singh; Kevin Brasseur; Valérie Leblanc; Sophie Parent; Eric Asselin

    2010-01-01

    BACKGROUND: Cyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy

  20. Latent Regression Analysis.

    PubMed

    Tarpey, Thaddeus; Petkova, Eva

    2010-07-01

    Finite mixture models have come to play a very prominent role in modelling data. The finite mixture model is predicated on the assumption that distinct latent groups exist in the population. The finite mixture model therefore is based on a categorical latent variable that distinguishes the different groups. Often in practice distinct sub-populations do not actually exist. For example, disease severity (e.g. depression) may vary continuously and therefore, a distinction of diseased and not-diseased may not be based on the existence of distinct sub-populations. Thus, what is needed is a generalization of the finite mixture's discrete latent predictor to a continuous latent predictor. We cast the finite mixture model as a regression model with a latent Bernoulli predictor. A latent regression model is proposed by replacing the discrete Bernoulli predictor by a continuous latent predictor with a beta distribution. Motivation for the latent regression model arises from applications where distinct latent classes do not exist, but instead individuals vary according to a continuous latent variable. The shapes of the beta density are very flexible and can approximate the discrete Bernoulli distribution. Examples and a simulation are provided to illustrate the latent regression model. In particular, the latent regression model is used to model placebo effect among drug treated subjects in a depression study. PMID:20625443

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

    PubMed Central

    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

  2. Dual, but not selective, COX-1 and COX-2 inhibitors, attenuate acetic acid-evoked bladder irritation in the anaesthetised female cat.

    PubMed

    Wibberley, Alexandra; McCafferty, Gerald P; Evans, Christopher; Edwards, Richard M; Hieble, J Paul

    2006-05-01

    Non-selective cyclooxygenase (COX) inhibitors exert effects on lower urinary tract function in several species. The exact contributions of COX-1 and COX-2 isozymes have not been studied much. The present studies investigated the effects of non- and selective COX inhibitors on bladder irritation in the cat.Chloralose-anaesthetised female cats were catheterised through the bladder dome for cystometric evaluation of bladder responses to intravesical infusion of saline or acetic acid. Bladder capacity, voiding efficiency, threshold pressure, and reflex-evoked bladder contraction amplitude and duration were measured. The cat COX selectivity of the doses of inhibitors examined was determined using an in vitro whole-blood assay and analysis of plasma levels. Pretreatment with indomethacin or ketoprofen (non-selective COX inhibitors; 0.3 mg kg(-1) i.v.) inhibited acetic acid-evoked irritation (characterised by a decrease in bladder capacity in vehicle pretreated animals). FR-122047 (selective COX-1 inhibitor), NS-398 and nimesulide (selective COX-2 inhibitors; 1 and 3 mg kg(-1) i.v.) had no effects on bladder irritation. Analysis of plasma levels of the doses examined and determination of COX-1 and COX-2 inhibition in cat whole blood confirmed the reported selectivity of these compounds in this species. The present studies suggest that dual COX inhibition is required to attenuate acetic acid-evoked bladder irritation in the cat. PMID:16547526

  3. Boosting Methodology for Regression Problems

    Microsoft Academic Search

    Greg Ridgeway; David Madigan; Thomas Richardson

    1999-01-01

    Classification problems have dominated research on boosting to date. The application of boosting to regression problems, on the other hand, has received little investigation. In this paper we develop a new boosting method for regression problems. We cast the regression problem as a classification problem and apply an interpretable form of the boosted naïve Bayes classifier. This induces a regression

  4. Multiple Linear Regression

    NSDL National Science Digital Library

    Lacey, Michelle

    This site, created by Michelle Lacey of Yale University, gives an explanation, a definition and an example of multiple linear regression. Topics include: confidence intervals, tests of significance, and squared multiple correlation. While brief, this is still a valuable site for anyone interested in statistics.

  5. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

    Program rapidly selects best-suited set of coefficients. User supplies only vectors of independent and dependent data and specifies confidence level required. Program uses stepwise statistical procedure for relating minimal set of variables to set of observations; final regression contains only most statistically significant coefficients. Program is written in FORTRAN IV for batch execution and has been implemented on NOVA 1200.

  6. Modern Regression Discontinuity Analysis

    Microsoft Academic Search

    Howard S. Bloom

    2012-01-01

    This article provides a detailed discussion of the theory and practice of modern regression discontinuity (RD) analysis for estimating the effects of interventions or treatments. Part 1 briefly chronicles the history of RD analysis and summarizes its past applications. Part 2 explains how in theory an RD analysis can identify an average effect of treatment for a population and how

  7. classi cation, regression,

    E-print Network

    Roweis, Sam

    function K(x 1 ;x 2 ) called a kernel. #15; This has a very deep interpretation as mapping the dataLecture 13: Kernel Machines Sam Roweis December 4, 2002 Algorithms Based on Vector Data #15; Recall our normal approach to many classi#12;cation, regression, and unsupervised learning problems: Embed

  8. classi cation, regression,

    E-print Network

    Roweis, Sam

    Lecture 13: Kernel Machines Sam Roweis December 2, 2003 Algorithms Based on Vector Data #15; Recall our normal approach to many classi#12;cation, regression, and unsupervised learning problems: Embed operations. #15;We can often make our algorithms more powerful by embedding the data into a richer (larger

  9. Logistic Regression Diagnostics

    Microsoft Academic Search

    Daryl Pregibon

    1981-01-01

    A maximum likelihood fit of a logistic regression model (and other similar models) is extremely sensitive to outlying responses and extreme points in the design space. We develop diagnostic measures to aid the analyst in detecting such observations and in quantifying their effect on various aspects of the maximum likelihood fit. The elements of the fitting process which constitute the

  10. Multivariate Adaptive Regression Splines

    Microsoft Academic Search

    Jerome H. Friedman

    1991-01-01

    A new method is presented for flexible regression modeling of high dimensional data. The model takes the form of an expansion in product spline basis functions, where the number of basis functions as well as the parameters associated with each one (product degree and knot locations) are automatically determined by the data. This procedure is motivated by the recursive partitioning

  11. Introduction Linear Regression

    E-print Network

    Lega, Joceline

    (h(x(i) ) - y(i) )2 (1) Scary! Qiyam Tung Calculus and AI 1 #12;Introduction Linear Regression Exact Lines Estimating Lines Minimization Error = 1 m m i=1 (h(x(i) ) - y(i) )2 (1) Scary! Hold on... Qiyam

  12. Infinitely Imbalanced Logistic Regression

    Microsoft Academic Search

    Art B. Owen

    2007-01-01

    In binary classification problems it is common for the two classes to be imbalanced: one case is very rare compared to the other. In this paper we consider the infinitely imbalanced case where one class has a finite sample size and the other class's sample size grows without bound. For logistic regression, the infinitely imbalanced case often has a useful

  13. Explorations in Statistics: Regression

    ERIC Educational Resources Information Center

    Curran-Everett, Douglas

    2011-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This seventh installment of "Explorations in Statistics" explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive connection.…

  14. Multiple Linear Regressions Analysis

    NSDL National Science Digital Library

    Arsham, Hossein

    This online calculator allows users to enter sixteen observations with up to four dependent variables and calculates the regression equation, the fitted values, R-Squared, the F-Statistic, mean, variance, first order serial-correlation, second order serial-correlation, the Durbin-Watson statistic, and the mean absolute errors. It also tests normality and gives the i-th residuals.

  15. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

    This article provides a detailed discussion of the theory and practice of modern regression discontinuity (RD) analysis for estimating the effects of interventions or treatments. Part 1 briefly chronicles the history of RD analysis and summarizes its past applications. Part 2 explains how in theory an RD analysis can identify an average effect of…

  16. Analysis of meteorological droughts for the Saskatchewan River Basin using univariate and bivariate approaches

    NASA Astrophysics Data System (ADS)

    Masud, M. B.; Khaliq, M. N.; Wheater, H. S.

    2015-03-01

    This study is focused on the Saskatchewan River Basin (SRB) that spans southern parts of Alberta, Saskatchewan and Manitoba, the three Prairie Provinces of Canada, where most of the country's agricultural activities are concentrated. The SRB is confronted with immense water-related challenges and is now one of the ten GEWEX (Global Energy and Water Exchanges) Regional Hydroclimate Projects in the world. In the past, various multi-year droughts have been observed in this part of Canada that impacted agriculture, energy and socio-economic sectors. Therefore, proper understanding of the spatial and temporal characteristics of historical droughts is important for many water resources planning and management related activities across the basin. In the study, observed gridded data of daily precipitation and temperature and conventional univariate and copula-based bivariate frequency analyses are used to characterize drought events in terms of drought severity and duration on the basis of two drought indices, the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI). Within the framework of univariate and bivariate analyses, drought risk indicators are developed and mapped across the SRB to delineate the most vulnerable parts of the basin. Based on the results obtained, southern parts of the SRB (i.e., western part of the South Saskatchewan River, Seven Persons Creek and Bigstick Lake watersheds) are associated with a higher drought risk, while moderate risk is noted for the North Saskatchewan River (except its eastern parts), Red Deer River, Oldman River, Bow River, Sounding Creek, Carrot River and Battle River watersheds. Lower drought risk is found for the areas surrounding the Saskatchewan-Manitoba border (particularly, the Saskatchewan River watershed). It is also found that the areas characterized with higher drought severity are also associated with higher drought duration. A comparison of SPI- and SPEI-based analyses suggests only little effect of considering temperature, in the form of evapotranspiration, on identifying drought vulnerable areas. It is expected that the findings of the study will be helpful in the management and efficient utilization of the water resources of this important river basin in Canada.

  17. Daniel T. Cox Professor, Coastal and Ocean Engineering Program

    E-print Network

    Haller, Merrick

    Daniel T. Cox Professor, Coastal and Ocean Engineering Program 202 Owen Hall School of Civil of Constructed Facilities; Journal of Waterway, Port, Coastal and Ocean Engineering; Ocean Engineering. National 4/511 Introduction to Ocean Engineering 4. CE 4/515 Coastal Infrastructure 5. CE 631 Linear Wave

  18. Watermarking Is Not Cryptography Ingemar J. Cox1

    E-print Network

    Paris-Sud XI, Université de

    Watermarking Is Not Cryptography Ingemar J. Cox1 , Gwena¨el Do¨err1 , and Teddy Furon2 1 University have been made about watermarking. In this paper, we argue that these analogies are misleading of watermarking is the reliable embedding and detection of information and should therefore be considered a form

  19. Marine NOx and COx Emissions under Various Operating Conditions

    Microsoft Academic Search

    Osami Nishida; Tomohisa Kiuchi; Hirotsugu Fujita; Wataru Harano; Wataru Adati; Keisuke Kadowaki; Masahiro Taguti; Manami Morioka; Mitsuaki Kato

    This paper describes NOx and COx emissions from the diesel engine on mini-vessel such as 500GT class vessel under transient operating condition and entering and departing conditions, because the reduction of the marine exhaust emissions has been important subject. And the Intemational Maritime Organization (IMO) advances the prevention of air pollution from ships in 1989. The regulated level of NOx

  20. 296 IEEE TRANSACTIONS ON AUTOMATION SCIENCE AND ENGINEERING, VOL. 9, NO. 2, APRIL 2012 Performance Assessment and Design for Univariate

    E-print Network

    Wang, Jiandong

    Assessment and Design for Univariate Alarm Systems Based on FAR, MAR, and AAD Jianwei Xu, Jiandong Wang, Iman.edu.cn; jiandong@pku.edu. cn). I. Izadi is with Matrikon Inc., Edmonton, AB T5J 3N4, Canada (e-mail: iman. izadi

  1. Stress assessment based on EEG univariate features and functional connectivity measures.

    PubMed

    Alonso, J F; Romero, S; Ballester, M R; Antonijoan, R M; Mañanas, M A

    2015-07-01

    The biological response to stress originates in the brain but involves different biochemical and physiological effects. Many common clinical methods to assess stress are based on the presence of specific hormones and on features extracted from different signals, including electrocardiogram, blood pressure, skin temperature, or galvanic skin response. The aim of this paper was to assess stress using EEG-based variables obtained from univariate analysis and functional connectivity evaluation. Two different stressors, the Stroop test and sleep deprivation, were applied to 30 volunteers to find common EEG patterns related to stress effects. Results showed a decrease of the high alpha power (11 to 12?Hz), an increase in the high beta band (23 to 36?Hz, considered a busy brain indicator), and a decrease in the approximate entropy. Moreover, connectivity showed that the high beta coherence and the interhemispheric nonlinear couplings, measured by the cross mutual information function, increased significantly for both stressors, suggesting that useful stress indexes may be obtained from EEG-based features. PMID:26015439

  2. Potential interaction of natural dietary bioactive compounds with COX-2.

    PubMed

    Maldonado-Rojas, Wilson; Olivero-Verbel, Jesus

    2011-09-01

    Bioactive natural products present in the diet play an important role in several biological processes, and many have been involved in the alleviation and control of inflammation-related diseases. These actions have been linked to both gene expression modulation of pro-inflammatory enzymes, such as cyclooxygenase 2 (COX-2), and to an action involving a direct inhibitory binding on this protein. In this study, several food-related compounds with known gene regulatory action on inflammation have been examined in silico as COX-2 ligands, utilizing AutoDock Vina, GOLD and Surflex-Dock (SYBYL) as docking protocols. Curcumin and all-trans retinoic acid presented the maximum absolute AutoDock Vina-derived binding affinities (9.3 kcal/mol), but genistein, apigenin, cyanidin, kaempferol, and docosahexaenoic acid, were close to this value. AutoDock Vina affinities and GOLD scores for several known COX-2 inhibitors significatively correlated with reported median inhibitory concentrations (R² = 0.462, P < 0.001 and R² = 0.238, P = 0.029, respectively), supporting the computational reliability of the predictions made by our docking simulations. Moreover, docking analysis insinuate the synergistic action of curcumin on celecoxib-induced inhibition of COX-2 may occur allosterically, as this natural compound docks to a place different from the inhibitor binding site. These results suggest that the anti-inflammatory properties of some food-derived molecules could be the result of their direct binding capabilities to COX-2, and this process can be modeled using protein-ligand docking methodologies. PMID:21803623

  3. Ridge Regression Signal Processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

    The introduction of the Global Positioning System (GPS) into the National Airspace System (NAS) necessitates the development of Receiver Autonomous Integrity Monitoring (RAIM) techniques. In order to guarantee a certain level of integrity, a thorough understanding of modern estimation techniques applied to navigational problems is required. The extended Kalman filter (EKF) is derived and analyzed under poor geometry conditions. It was found that the performance of the EKF is difficult to predict, since the EKF is designed for a Gaussian environment. A novel approach is implemented which incorporates ridge regression to explain the behavior of an EKF in the presence of dynamics under poor geometry conditions. The basic principles of ridge regression theory are presented, followed by the derivation of a linearized recursive ridge estimator. Computer simulations are performed to confirm the underlying theory and to provide a comparative analysis of the EKF and the recursive ridge estimator.

  4. [Atypical tumor regression].

    PubMed

    Heitplatz, B; Müller, K-M

    2013-11-01

    A 67-year-old man presented with a poorly differentiated squamous cell carcinoma of the esophagus diagnosed by biopsy. After neoadjuvant radiochemotherapy the gastroesophagectomy specimen showed diffuse polymorphic and anuclear cell residues ranging from 35 µm to 46 µm in size. Immunohistochemically, PanCK and AE1-3 revealed a positive staining while CD68 and MIB1 showed a negative staining. The retrospective anamnesis revealed that the patient had chronic polyarthritis as underlying illness, for which reason he had been taking humira and methotrexate, a cytostatic drug, for many years. Therefore, the development of the tumor might have been enhanced by these drugs. Electron microscopic analysis confirmed that the avital akaryote cell residues represented a special type of tumor regression. Complete tumor regression level IV without vital rest tumor tissue based on Baldus et al. was diagnosed. PMID:24154755

  5. Diagnostic tools for bivariate accelerated life regression models.

    PubMed

    Choi, Yun-Hee; Matthews, David E

    2015-07-01

    We propose graphical diagnostic tools to assess the fit of a bivariate accelerated lifetime regression model. Using univariate residuals for each response measurement in a pair, we assess their dependence structure via the bivariate probability integral transformation of univariate residuals, which we call V-residuals. To reduce the computational burden associated with plots of V-residuals, as well as some uncertainty associated with parameter estimation, we next develop K-residuals. We also devise adjusted V- and K-residuals to account for right censoring of any response. Via simulation studies, we examine the statistical behaviour of Q-Q plots of the estimated K-residuals, and demonstrate the potential of these plots to identify an appropriate choice of frailty distribution in bivariate modeling. We apply our proposed diagnostic tools to the Diabetic Retinopathy Study and assess the goodness of fit of various models fitted to these study data using different choices of frailty distributions combined with several baseline survivor functions. PMID:25081129

  6. Forecast comparison of principal component regression and principal covariate regression

    Microsoft Academic Search

    Christiaan Heij; Patrick J. F. Groenen; Dick Van Dijk

    2007-01-01

    Forecasting with many predictors is of interest, for instance, in macroeconomics and finance. This paper compares two methods for dealing with many predictors, that is, principal component regression (PCR) and principal covariate regression (PCovR). The forecast performance of these methods is compared by simulating data from factor models and from regression models. The simulations show that, in general, PCR performs

  7. Female children with autism spectrum disorder: an insight from mass-univariate and pattern classification analyses.

    PubMed

    Calderoni, Sara; Retico, Alessandra; Biagi, Laura; Tancredi, Raffaella; Muratori, Filippo; Tosetti, Michela

    2012-01-16

    Several studies on structural MRI in children with autism spectrum disorders (ASD) have mainly focused on samples prevailingly consisting of males. Sex differences in brain structure are observable since infancy and therefore caution is required in transferring to females the results obtained for males. The neuroanatomical phenotype of female children with ASD (ASDf) represents indeed a neglected area of research. In this study, we investigated for the first time the anatomic brain structures of a sample entirely composed of ASDf (n=38; 2-7 years of age; mean=53 months; SD=18) with respect to 38 female age and non verbal IQ matched controls, using both mass-univariate and pattern classification approaches. The whole brain volumes of each group were compared using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure, allowing us to build a study-specific template. Significantly more gray matter (GM) was found in the left superior frontal gyrus (SFG) in ASDf subjects compared to controls. The GM segments obtained in the VBM-DARTEL preprocessing are also classified with a support vector machine (SVM), using the leave-pair-out cross-validation protocol. Then, the recursive feature elimination (SVM-RFE) approach allows for the identification of the most discriminating voxels in the GM segments and these prove extremely consistent with the SFG region identified by the VBM analysis. Furthermore, the SVM-RFE map obtained with the most discriminating set of voxels corresponding to the maximum Area Under the Receiver Operating Characteristic Curve (AUC(max)=0.80) highlighted a more complex circuitry of increased cortical volume in ASDf, involving bilaterally the SFG and the right temporo-parietal junction (TPJ). The SFG and TPJ abnormalities may be relevant to the pathophysiology of ASDf, since these structures participate in some core atypical features of autism. PMID:21896334

  8. caret: Classification and Regression Training

    NASA Astrophysics Data System (ADS)

    Kuhn, Max

    2015-05-01

    caret (Classification And REgression Training) provides functions for training and plotting classification and regression models. It contains tools for data splitting, pre-processing, feature selection, model tuning using resampling, and variable importance estimation, as well as other functionality.

  9. Sliced Regression for Dimension Reduction

    Microsoft Academic Search

    Hansheng Wang; Yingcun Xia

    2008-01-01

    By slicing the region of the response (Li, 1991, SIR) and applying local ker- nel regression (Xia et al., 2002, MAVE) to each slice, a new dimension reduction method is proposed. Compared with the traditional inverse regression methods, e.g. sliced inverse regression (Li, 1991), the new method is free of the linearity condition (Li, 1991) and enjoys much improved estimation

  10. Selective COX2 Inhibitors and Risk of Myocardial Infarction

    Microsoft Academic Search

    Florian Krötz; Thomas M. Schiele; Volker Klauss; Hae-Young Sohn

    2005-01-01

    Selective inhibitors of cyclooxygenase-2 (COX-2, ‘coxibs’) are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non-steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myo cardial infarction and atherothrombotic events. This has led

  11. (MIS)COMMUNICATING COX2 CLINICAL TRIAL RISKS

    Microsoft Academic Search

    Mark Hochhauser; Norman M. Goldfarb

    Would you take a drug that saved 1,000 lives last year but killed 1% of the patients? Summary The FDA has approved Cox-2 NSAID drugs to treat short-term acute pain and for long-term treatment of rheumatoid arthritis and osteoarthritis. These benefits, however, appear to come at the price of higher risks for heart attacks (cardiovascular events) and strokes (cerebrovascular events).

  12. Adaptive regression and ego identity.

    PubMed

    Bilsker, D; Marcia, J E

    1991-03-01

    An inventory of adaptively regressive experiences (Taft Ego Permissiveness Inventory) and the Identity Status Interview were administered to 71 college students (35 female, 36 male). As hypothesized, Moratorium status individuals (actively engaged in identity formation) showed a greater disposition to adaptive regression than did individuals in other statuses. This supports the view that adaptive regression may serve an important function in the identity formation process. Contrary to hypothesis, Achievement status individuals did not show greater disposition to adaptive regression than those in Foresclosure status. Females showed substantially greater disposition to adaptive regression than did males. PMID:2050867

  13. A Regularization Corrected Score Method for Nonlinear Regression Models with Covariate Error

    PubMed Central

    Zucker, David M.; Gorfine, Malka; Li, Yi; Tadesse, Mahlet; Spiegelman, Donna

    2012-01-01

    Summary Many regression analyses involve explanatory variables that are measured with error, and failing to account for this error is well known to lead to biased point and interval estimates of the regression coefficients. We present here a new general method for adjusting for covariate error. Our method consists of an approximate version of the Stefanski-Nakamura corrected score approach, using the method of regularization to obtain an approximate solution of the relevant integral equation. We develop the theory in the setting of classical likelihood models; this setting covers, for example, linear regression, nonlinear regression, logistic regression, and Poisson regression. The method is extremely general in terms of the types of measurement error models covered, and is a functional method in the sense of not involving assumptions on the distribution of the true covariate. We discuss the theoretical properties of the method and present simulation results in the logistic regression setting (univariate and multivariate). For illustration, we apply the method to data from the Harvard Nurses’ Health Study concerning the relationship between physical activity and breast cancer mortality in the period following a diagnosis of breast cancer. PMID:23379851

  14. Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats.

    PubMed

    Potenza, M A; Botrugno, O A; De Salvia, M A; Lerro, G; Nacci, C; Marasciulo, F L; Andriantsitohaina, R; Mitolo-Chieppa, D

    2002-09-01

    Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PGI(2) production by enzyme immunoassay of 6-keto-PGF(1alpha) was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PGF(1alpha) was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension. PMID:12181171

  15. Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

    PubMed Central

    Armstrong, Paul C.; Kirkby, Nicholas S.; Zain, Zetty N.; Emerson, Michael; Mitchell, Jane A.; Warner, Timothy D.

    2011-01-01

    Background Clinical use of selective inhibitors of cyclooxygenase (COX)-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. Methodology/Principal Findings A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control) diclofenac (1 mg.kg?1, i.v.) and parecoxib (0.5 mg.kg?1, i.v.) on thrombus formation induced by collagen or the thromboxane (TX) A2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. Conclusions/Significance Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA2, but not that induced by U46619, which is independent of platelet TXA2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis. PMID:21629780

  16. Linear regression applet

    NSDL National Science Digital Library

    Nicholas Exner

    2004-01-01

    To use this applet to model linear regression, the student can enter up to 50 points by clicking on a graph of the first quadrant. The applet displays a red line passing through the point representing the average x and average y values. A scroll bar is used to change the slope of the red line to approximate a line of best fit. With a button click, the applet also can display a blue line showing the calculated best fit line. The equations for the red approximate best fit line and the calculated blue best fit line are displayed along with a thermometer illustrating how well the approximate red line fits the data points. Copyright 2005 Eisenhower National Clearinghouse

  17. Regression to the Mean

    NSDL National Science Digital Library

    Lane, David M.

    Created by David Lane of Rice University, this is a simulation illustrating the regression toward the mean phenomenon. The author has created a specific case study to explore, he states it as: "In this simulation, a group of students takes a test made up of 100 true/false questions. Each student knows the answers to a specific number of questions and guesses at the remaining. Students get one point for each question they answer correctly and lose one point for each question they answer incorrectly." After completing this study, students can then input their data into the interactive applet. Eleven exercise questions will then test the students knowledge and understanding of their findings.

  18. THE DANTZIG SELECTOR IN COX'S PROPORTIONAL HAZARDS MODEL

    E-print Network

    Fryzlewicz, Piotr

    , such a framework, contrary to the LASSO, has never been used in regression models for survival data with censoring function regression models using a framework that extends the theory, the computational advantages not possess the oracle properties (Fan and Li (2002)). The SCAD estimator has better theoretical properties

  19. Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency

    Microsoft Academic Search

    Hana Antonicka; Scot C. Leary; Guy-Hellen Guercin; Jeffrey N. Agar; Rita Horvath; Nancy G. Kennaway; Cary O. Harding; Michaela Jaksch; Eric A. Shoubridge

    2003-01-01

    Deficiencies in the activity of cytochrome c oxidase (COX) are an important cause of autosomal recessive respiratory chain disorders. Patients with isolated COX deficiency are clinically and genetically heterogeneous, and mutations in several different assembly factors have been found to cause specific clinical phenotypes. Two of the most common clinical presentations, Leigh Syndrome and hypertrophic cardiomyopathy, have so far only

  20. Am. J. Hum. Genet. 72:101114, 2003 Mutations in COX15 Produce a Defect in the Mitochondrial Heme

    E-print Network

    Shoubridge, Eric

    for accessory proteins that play important roles in the assembly of the COX holoenzyme complex. Many patients COX assembly factors in these patients to identify the molecular basis for the COX deficiency and fibroblast mitochondria, and levels of heme O were increased in the patient's heart. COX activity

  1. Ku80 cooperates with CBP to promote COX-2 expression and tumor growth

    PubMed Central

    Qin, Yu; Xuan, Yang; Jia, Yunlu; Hu, Wenxian; Yu, Wendan; Dai, Meng; Li, Zhenglin; Yi, Canhui; Zhao, Shilei; Li, Mei; Du, Sha; Cheng, Wei; Xiao, Xiangsheng; Chen, Yiming; Wu, Taihua; Meng, Songshu; Yuan, Yuhui; Liu, Quentin; Huang, Wenlin; Guo, Wei; Wang, Shusen; Deng, Wuguo

    2015-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer. PMID:25797267

  2. Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib

    PubMed Central

    Ramer, Robert; Walther, Udo; Borchert, Philipp; Laufer, Stefan; Linnebacher, Michael; Hinz, Burkhard

    2013-01-01

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Among different structurally related COX-2 inhibitors, only celecoxib was found to cause apoptosis and cell death of human lung cancer cells (IC50 values of 19.96 µM [A549], 12.48 µM [H460], and 41.39 µM [H358]) that was paralleled by a time- and concentration-dependent upregulation of COX-2 and peroxisome proliferator-activated receptor ? (PPAR?) at mRNA and protein levels. Apoptotic death of celecoxib-treated cancer cells was suppressed by the PPAR? antagonist GW9662 and by siRNA targeting PPAR? and, surprisingly, also by the selective COX-2 inhibitor NS-398 and siRNA targeting COX-2. NS-398 (1 µM) was shown to suppress celecoxib-induced COX-2 activity. Among the COX-2-dependent prostaglandins (PG) induced upon celecoxib treatment, PGD2 and 15-deoxy-?12,14-PGJ2 were found to induce a cytosol-to-nucleus translocation of PPAR? as well as a PPAR?-dependent apoptosis. Celecoxib-elicited PPAR? translocation was inhibited by NS-398. Finally, a COX-2- and PPAR?-dependent cytotoxic action of celecoxib was proven for primary human lung tumor cells. Together, our data demonstrate a proapoptotic mechanism of celecoxib involving initial upregulation of COX-2 and PPAR? and a subsequent nuclear translocation of PPAR? by COX-2-dependent PGs. PMID:23943857

  3. Stretch-induced myoblast proliferation is dependent on the COX2 pathway

    SciTech Connect

    Otis, Jeffrey S. [Emory University School of Medicine, Department of Pharmacology, O.W. Rollins Research Building, Room 5027, Atlanta, GA 30322 (United States); Burkholder, Thomas J. [Georgia Institute of Technology, School of Applied Physiology, Atlanta, GA 30332 (United States); Pavlath, Grace K. [Emory University School of Medicine, Department of Pharmacology, O.W. Rollins Research Building, Room 5027, Atlanta, GA 30322 (United States)]. E-mail: gpavlat@emory.edu

    2005-11-01

    Skeletal muscle increases in size due to weight bearing loads or passive stretch. This growth response is dependent in part upon myoblast proliferation. Although skeletal muscles are responsive to mechanical forces, the effect on myoblast proliferation remains unknown. To investigate the effects of mechanical stretch on myoblast proliferation, primary myoblasts isolated from Balb/c mice were subjected to 25% cyclical uniaxial stretch for 5 h at 0.5 Hz. Stretch stimulated myoblast proliferation by 32% and increased cell number by 41% 24 and 48 h after stretch, respectively. COX2 mRNA increased 3.5-fold immediately poststretch. Prostaglandin E2 and F{sub 2{alpha}} increased 2.4- and 1.6-fold 6 h after stretch, respectively. Because COX2 has been implicated in regulating muscle growth and regeneration, we hypothesized that stretched myoblasts may proliferate via a COX2-dependent mechanism. We employed two different models to disrupt COX2 activity: (1) treatment with a COX2-selective drug, and (2) transgenic mice null for COX2. Treating myoblasts with a COX2-specific inhibitor blocked stretch-induced proliferation. Likewise, stretched COX2{sup -/-} myoblasts failed to proliferate compared to controls. However, supplementing stretched, COX2{sup -/-} myoblasts with prostaglandin E2 or fluprostenol increased proliferation. These data suggest that the COX2 pathway is critical for myoblast proliferation in response to stretch.

  4. A Modified Adaptive Lasso for Identifying Interactions in the Cox Model with the Heredity Constraint.

    PubMed

    Wang, Lu; Shen, Jincheng; Thall, Peter F

    2014-10-01

    In many biomedical studies, identifying effects of covariate interactions on survival is a major goal. Important examples are treatment-subgroup interactions in clinical trials, and gene-gene or gene-environment interactions in genomic studies. A common problem when implementing a variable selection algorithm in such settings is the requirement that the model must satisfy the strong heredity constraint, wherein an interaction may be included in the model only if the interaction's component variables are included as main effects. We propose a modified Lasso method for the Cox regression model that adaptively selects important single covariates and pairwise interactions while enforcing the strong heredity constraint. The proposed method is based on a modified log partial likelihood including two adaptively weighted penalties, one for main effects and one for interactions. A two-dimensional tuning parameter for the penalties is determined by generalized cross-validation. Asymptotic properties are established, including consistency and rate of convergence, and it is shown that the proposed selection procedure has oracle properties, given proper choice of regularization parameters. Simulations illustrate that the proposed method performs reliably across a range of different scenarios. PMID:25071299

  5. Bootstrapping a change-point Cox model for survival data

    PubMed Central

    Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

    2014-01-01

    This paper investigates the (in)-consistency of various bootstrap methods for making inference on a change-point in time in the Cox model with right censored survival data. A criterion is established for the consistency of any bootstrap method. It is shown that the usual nonparametric bootstrap is inconsistent for the maximum partial likelihood estimation of the change-point. A new model-based bootstrap approach is proposed and its consistency established. Simulation studies are carried out to assess the performance of various bootstrap schemes. PMID:25400719

  6. US Defense Intelligence Agency (DIA) Scoops Cox Report

    NSDL National Science Digital Library

    In light of the Final Report of the Select Committee on US National Security and Military/ Commercial Concerns with the People's Republic of China, or the Cox Report, the National Security Archive (NSA), located at George Washington University, has released a Defense Estimative Brief published by the US Defense Intelligence Agency in April 1984. The four-page brief, obtained by the NSA through a Freedom of Information Act request, details Chinese efforts to enhace its nuclear capability through "overt contact with US scientists and technology, and the covert acquisition of US technology."

  7. Multinomial logistic regression ensembles.

    PubMed

    Lee, Kyewon; Ahn, Hongshik; Moon, Hojin; Kodell, Ralph L; Chen, James J

    2013-05-01

    This article proposes a method for multiclass classification problems using ensembles of multinomial logistic regression models. A multinomial logit model is used as a base classifier in ensembles from random partitions of predictors. The multinomial logit model can be applied to each mutually exclusive subset of the feature space without variable selection. By combining multiple models the proposed method can handle a huge database without a constraint needed for analyzing high-dimensional data, and the random partition can improve the prediction accuracy by reducing the correlation among base classifiers. The proposed method is implemented using R, and the performance including overall prediction accuracy, sensitivity, and specificity for each category is evaluated on two real data sets and simulation data sets. To investigate the quality of prediction in terms of sensitivity and specificity, the area under the receiver operating characteristic (ROC) curve (AUC) is also examined. The performance of the proposed model is compared to a single multinomial logit model and it shows a substantial improvement in overall prediction accuracy. The proposed method is also compared with other classification methods such as the random forest, support vector machines, and random multinomial logit model. PMID:23611203

  8. The univariant curve liquid = forsterite + anorthite + diopside in the system CMAS at 1 bar: solid solutions and melt structure

    Microsoft Academic Search

    Guy Libourel; Pierre Boivin; Gordon M. Biggar

    1989-01-01

    One atmosphere liquid-present experiments were carried out in the CMAS system using an ordinary quench furnace apparatus. The runs, including reversal and duplicate experiments, describe the univariant curve l=fo+an+ di between the invariant points Q: l+fo+an=di+sp and F: l+fo=an+di+oen, located respectively at 1245±1° C and 1244±1° C. The thermal divide on this curve M3: l= fo+an+di is located at 1275±1°

  9. The scientific work (1957-1987) of Allan Cox

    NASA Astrophysics Data System (ADS)

    Banerjee, Subir K.

    1988-10-01

    During the summer of 1951 Allan Cox, then a 25-year-old chemistry major at the University of California, Berkeley, became curious about geology and worked as a geology field assistant to Clyde Wahrhaftig. Thus did Allan Cox begin a momentous career in geomagnetism, paleomagnetism, and plate tectonics which left its indelible mark in the sciences themselves, in the workings of earth sciences through his leadership roles in the American Geophysical Union, the Geological Society of America and the National Academy of Sciences, and most importantly, in the lives and works of many junior scientists in the United States and throughout the world. Twenty-three years ago I was one of those junior scientists whose life was touched and transformed by this unique individual over the course of ensuing years. It is quite possible that but for a chance meeting with Allan at the 1965 IAGA Assembly in Pittsburgh, I would have not seen for a long time the important ways by which basic rock magnetism can and does affect progress in geomagnetism and paleomagnetism.

  10. Activation of prophage P4 by the P2 Cox protein and the sites of action of the Cox protein on the two phage genomes.

    PubMed Central

    Saha, S; Haggård-Ljungquist, E; Nordström, K

    1989-01-01

    Phage P2 induces the unrelated prophage P4. In this paper we show that this is due to the activation of the P4 late promoter PII by the P2 Cox protein. This is in contrast to the effects of Cox on P2, for which it is known from previous work that it acts as a repressor of the promoter Pc, which is responsible for expression of the immunity repressor C. The activator role of Cox was revealed by its effect on replication of P4 DNA and on the formation of chloramphenicol acetyltransferase when a promoterless cat gene was inserted downstream of the P4 PII promoter. DNase I protection studies revealed that the Cox protein binds to the repressor promoter Pc of phage P2 and to the promoter PII of phage P4. In the latter case the Cox protein binds upstream of the -35 region, in analogy to several other activators of promoters. A weak binding was found in the promoters Pe of phage P2 and Ple of phage P4. The Cox protein is a case of viral transactivation of the replication genes of one phage by a control protein of the other. However, the effects of the Cox protein are totally different in the two phages, repressive in one case and activating in the other. Images PMID:2657731

  11. Prediction in random coefficient regression

    Microsoft Academic Search

    Rudolf Beran

    1995-01-01

    Random coefficient regression and autoregressive models are important in diverse applications such as the classical statistical analysis of random and mixed effects models, the modelling of certain econometric and biological time series, and as a means for image compression. This paper develops nonparametric prediction intervals for a random coefficient regression model. The construction of these intervals requires a consistent estimate

  12. Bootstrapping principal component regression models

    Microsoft Academic Search

    R. Wehrens; Linden van der W. E

    1997-01-01

    Bootstrap methods can be used as an alternative for cross-validation in regression procedures such as principal component regression (PCR). Several bootstrap methods for the estimation of prediction errors and confidence intervals are presented. It is shown that bootstrap error estimates are consistent with cross-validation estimates but exhibit less variability. This makes it easier to select the correct number of latent

  13. Logistic Regression: Concept and Application

    ERIC Educational Resources Information Center

    Cokluk, Omay

    2010-01-01

    The main focus of logistic regression analysis is classification of individuals in different groups. The aim of the present study is to explain basic concepts and processes of binary logistic regression analysis intended to determine the combination of independent variables which best explain the membership in certain groups called dichotomous…

  14. Precision Efficacy Analysis for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.

    When multiple linear regression is used to develop a prediction model, sample size must be large enough to ensure stable coefficients. If the derivation sample size is inadequate, the model may not predict well for future subjects. The precision efficacy analysis for regression (PEAR) method uses a cross- validity approach to select sample sizes…

  15. A general regression neural network

    Microsoft Academic Search

    Donald F. Specht

    1991-01-01

    A memory-based network that provides estimates of continuous variables and converges to the underlying (linear or nonlinear) regression surface is described. The general regression neural network (GRNN) is a one-pass learning algorithm with a highly parallel structure. It is shown that, even with sparse data in a multidimensional measurement space, the algorithm provides smooth transitions from one observed value to

  16. Restricted generalized poisson regression model

    Microsoft Academic Search

    Felix Famoye

    1993-01-01

    The family of generalized Poisson distribution has been found useful in describing over-dispersed and under-dispersed count data. We propose the use of restricted generalized Poisson regression model to predict a response variable affected by one or more explanatory variables. Approximate tests for the adequacy of the model and the estimation of the parameters are considered. Restricted generalized Poisson regression model

  17. COX2 Expression Does Not Correlate with Microvessel Density in Breast Cancer

    Microsoft Academic Search

    Mangesh A. Thorat; Sanjana Mehrotra; Akira Morimiya; Sunil Badve

    2009-01-01

    Background:Cyclooxygenase-2 (COX-2), implicated in carcinogenesis and tumour progression in many cancers including breast cancer, is hypothesised to cause progression by promoting angiogenesis. The exact mechanism of such action is not known and the clinical evidence of such interaction is weak. We studied COX-2 expression and microvessel density (MVD) in malignant breast tissues. Methods:COX-2 expression was analysed by immunohistochemistry in 89

  18. Pricing of catastrophe reinsurance and derivatives using the Cox process with shot noise intensity

    Microsoft Academic Search

    Angelos Dassios; Ji-Wook Jang

    2003-01-01

    .   We use the Cox process (or a doubly stochastic Poisson process) to model the claim arrival process for catastrophic events.\\u000a The shot noise process is used for the claim intensity function within the Cox process. The Cox process with shot noise intensity\\u000a is examined by piecewise deterministic Markov process theory. We apply the model to price stop-loss catastrophe reinsurance

  19. Regulation of COX-2 expression by miR-146a in lung cancer cells.

    PubMed

    Cornett, Ashley L; Lutz, Carol S

    2014-09-01

    Prostaglandins are a class of molecules that mediate cellular inflammatory responses and control cell growth. The oxidative conversion of arachidonic acid to prostaglandin H2 is carried out by two isozymes of cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed, while COX-2 can be transiently induced by external stimuli, such as pro-inflammatory cytokines. Interestingly, COX-2 is overexpressed in numerous cancers, including lung cancer. MicroRNAs (miRNAs) are small RNA molecules that function to regulate gene expression. Previous studies have implicated an important role for miRNAs in human cancer. We demonstrate here that miR-146a expression levels are significantly lower in lung cancer cells as compared with normal lung cells. Conversely, lung cancer cells have higher levels of COX-2 protein and mRNA expression. Introduction of miR-146a can specifically ablate COX-2 protein and the biological activity of COX-2 as measured by prostaglandin production. The regulation of COX-2 by miR-146a is mediated through a single miRNA-binding site present in the 3' UTR. Therefore, we propose that decreased miR-146a expression contributes to the up-regulation and overexpression of COX-2 in lung cancer cells. Since potential miRNA-mediated regulation is a functional consequence of alternative polyadenylation site choice, understanding the molecular mechanisms that regulate COX-2 mRNA alternative polyadenylation and miRNA targeting will give us key insights into how COX-2 expression is involved in the development of a metastatic condition. PMID:25047043

  20. Novel selective Cox2 inhibitors induce apoptosis in Caco-2 colorectal carcinoma cell line

    Microsoft Academic Search

    Reza Entezari Heravi; Farzin Hadizadeh; Mojtaba Sankian; Jalil Tavakol Afshari; Seyed Mohammad Taghdisi; Hanieh Jafarian; Javad Behravan

    2011-01-01

    The cyclooxygenase-2 (COX-2) inhibitors including celecoxib inhibit cell growth and induce apoptosis in cancer cells. As COX-2 is over expressed in solid tumors such as colorectal cancer, it can be a suitable target for cancer treatment studies. In this study we designed and synthesized 4,5-bisaryl imidazolyl imidazoles as novel COX-2 inhibitors and evaluated their apoptosis inducing activities. The ability of

  1. Fibroblast immuno-diagnosis of cytochrome oxidase (COX) deficiency in mitochondrial disease

    Microsoft Academic Search

    Ailian Du; Robert K. Naviaux; Thuy Le; Congfeng Xu; Steven S. Sommer; Richard H. Haas

    2011-01-01

    We studied cytochrome c oxidase (COX) expression patterns in nuclear and mtDNA gene defects. Using quantitative immunocytochemical assay for COX, heteroplasmic staining was seen in MELAS patients with mtDNA mutations but similar staining variability was seen in control cell lines and nuclear gene defects. All fibroblast lines showed a wide variability in cell-to-cell COX I staining intensity. All 8 patient

  2. Multimodal imaging: an evaluation of univariate and multivariate methods for simultaneous EEG/fMRI.

    PubMed

    De Martino, Federico; Valente, Giancarlo; de Borst, Aline W; Esposito, Fabrizio; Roebroeck, Alard; Goebel, Rainer; Formisano, Elia

    2010-10-01

    The combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has been proposed as a tool to study brain dynamics with both high temporal and high spatial resolution. Multimodal imaging techniques rely on the assumption of a common neuronal source for the different recorded signals. In order to maximally exploit the combination of these techniques, one needs to understand the coupling (i.e., the relation) between electroencephalographic (EEG) and fMRI blood oxygen level-dependent (BOLD) signals. Recently, simultaneous EEG-fMRI measurements have been used to investigate the relation between the two signals. Previous attempts at the analysis of simultaneous EEG-fMRI data reported significant correlations between regional BOLD activations and modulation of both event-related potential (ERP) and oscillatory EEG power, mostly in the alpha but also in other frequency bands. Beyond the correlation of the two measured brain signals, the relevant issue we address here is the ability of predicting the signal in one modality using information from the other modality. Using multivariate machine learning-based regression, we show how it is possible to predict EEG power oscillations from simultaneously acquired fMRI data during an eyes-open/eyes-closed task using either the original channels or the underlying cortically distributed sources as the relevant EEG signal for the analysis of multimodal data. PMID:20097029

  3. Multiple Use One-Sided Hypotheses Testing in Univariate Linear Calibration

    NASA Technical Reports Server (NTRS)

    Krishnamoorthy, K.; Kulkarni, Pandurang M.; Mathew, Thomas

    1996-01-01

    Consider a normally distributed response variable, related to an explanatory variable through the simple linear regression model. Data obtained on the response variable, corresponding to known values of the explanatory variable (i.e., calibration data), are to be used for testing hypotheses concerning unknown values of the explanatory variable. We consider the problem of testing an unlimited sequence of one sided hypotheses concerning the explanatory variable, using the corresponding sequence of values of the response variable and the same set of calibration data. This is the situation of multiple use of the calibration data. The tests derived in this context are characterized by two types of uncertainties: one uncertainty associated with the sequence of values of the response variable, and a second uncertainty associated with the calibration data. We derive tests based on a condition that incorporates both of these uncertainties. The solution has practical applications in the decision limit problem. We illustrate our results using an example dealing with the estimation of blood alcohol concentration based on breath estimates of the alcohol concentration. In the example, the problem is to test if the unknown blood alcohol concentration of an individual exceeds a threshold that is safe for driving.

  4. From the Cover: COX3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic\\/antipyretic drugs: Cloning, structure, and expression

    Microsoft Academic Search

    N. V. Chandrasekharan; Hu Dai; K. Lamar Turepu Roos; Nathan K. Evanson; Joshua Tomsik; Terry S. Elton; Daniel L. Simmons

    2002-01-01

    Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but

  5. Systematic review and meta-analysis of COX-2 expression and polymorphisms in prostate cancer.

    PubMed

    Shao, Ning; Feng, Ninghan; Wang, Yang; Mi, Yuanyuan; Li, Tian; Hua, LiXin

    2012-12-01

    Evidence is accumulating that cyclooxygenase-2 (COX-2) may play an important role in prostate cancer (PCa). Recently, gene polymorphisms in COX-2 have been implicated to alter the risk of PCa and overexpression of COX-2 may be associated with clinical and prognostic significance in PCa. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation of the relationships, we performed an updated meta-analysis. A comprehensive search was conducted to examine all the eligible studies of COX-2 polymorphism and expression in PCa. We used odds ratios (ORs) to assess the strength of the association and the 95 % confidence intervals (CIs) give a sense of the precision of the estimate. Overall, no significant associations between COX-2 polymorphism and PCa risk were found. However, high expression of COX-2 was significantly higher in T3-T4 stages of PCa than in T1-T2 stages of PCa (OR = 2.33, 95 %CI: 1.54-3.53, P < 0.0001). COX-2 might play an important role in the progress of PCa, overexpression of COX-2 correlates with T3-T4 stages of PCa. COX-2 might be a potential therapy target for PCa and work as a prognostic factor for PCa patients. PMID:23053989

  6. Virtual Screening for Finding Novel COX-2 Inhibitors as Antitumor Agents

    PubMed Central

    Badieyan, Zohreh S; Moallem, Seyed Adel; Mehri, Soghra; Shahsavand, Shabnam; Hadizadeh, Farzin

    2012-01-01

    The cyclooxygenase-2 (COX-2) enzyme binds to arachidonic acid resulting in the release of metabolites that induce pain and inflammatory responses. Recent studies have shown that strong COX-2 expression is highly correlated with increased tumor risk. Therefore, the development of potent COX-2 inhibitors to relieve pain and treat cancers requires further investigation. We used virtual screening to find three COX-2 inhibitors (Phar-95239, T0511-4424 and Zu- 4280011) from a huge zinc database containing 2000000 compounds. The effects of the compounds on COX-2 were compared to those on COX-1 using a colorimetric COX (ovine) screening assay kit. The selectivity index, the ratio of IC50 for COX-1 inhibition to that of COX-2, calculated were MTT assay was used to evaluate the cytotoxic activity of the compounds using different dilutions. The IC50 values were calculated. Based on the results of the MTT assay, the IC50 values for compounds Phar-95239, T0511-4424 and Zu-4280011 were 178.52, 143 and 97.61 µM, respectively, and the selectivity indices of the compounds were 11.36, 12.20 and 20.03, respectively. These results indicated a relationship between the selectivity index and anticancer activity. Zu-4280011 displayed the highest selectivity index and the best results in the MTT assay among selected componds. PMID:23115597

  7. Virtual Screening for Finding Novel COX-2 Inhibitors as Antitumor Agents.

    PubMed

    Badieyan, Zohreh S; Moallem, Seyed Adel; Mehri, Soghra; Shahsavand, Shabnam; Hadizadeh, Farzin

    2012-01-01

    The cyclooxygenase-2 (COX-2) enzyme binds to arachidonic acid resulting in the release of metabolites that induce pain and inflammatory responses. Recent studies have shown that strong COX-2 expression is highly correlated with increased tumor risk. Therefore, the development of potent COX-2 inhibitors to relieve pain and treat cancers requires further investigation. We used virtual screening to find three COX-2 inhibitors (Phar-95239, T0511-4424 and Zu- 4280011) from a huge zinc database containing 2000000 compounds. The effects of the compounds on COX-2 were compared to those on COX-1 using a colorimetric COX (ovine) screening assay kit. The selectivity index, the ratio of IC(50) for COX-1 inhibition to that of COX-2, calculated were MTT assay was used to evaluate the cytotoxic activity of the compounds using different dilutions. The IC(50) values were calculated. Based on the results of the MTT assay, the IC(50) values for compounds Phar-95239, T0511-4424 and Zu-4280011 were 178.52, 143 and 97.61 µM, respectively, and the selectivity indices of the compounds were 11.36, 12.20 and 20.03, respectively. These results indicated a relationship between the selectivity index and anticancer activity. Zu-4280011 displayed the highest selectivity index and the best results in the MTT assay among selected componds. PMID:23115597

  8. COX-2 inhibition, H. pylori infection and the risk of gastrointestinal complications.

    PubMed

    Chan, Francis K L

    2003-01-01

    Current data on the gastric safety of cyclooxygenase-2 (COX-2) inhibitors in the presence of H. pylori infection are largely derived from animal experiments and indirect clinical evidence. In animal models of H. pylori gastritis, COX-2 inhibitors suppressed prostaglandin synthesis and aggravated mucosal damage. In the human stomach, COX-1 appears to be the predominant source of prostaglandins despite the fact that COX-2 is upregulated in H. pylori gastritis. There are conflicting data on whether H. pylori alters the risk of ulcer in patients receiving COX-2 inhibitors. Among patients with H. pylori infection, rofecoxib reduced the risk of complicated gastric but not duodenal ulcers as compared to naproxen. The advantage of rofecoxib over naproxen also disappeared in patients with H. pylori infection and prior upper gastrointestinal events. In contrast, pooled data suggested that H. pylori increases the risk of ulcer in patients receiving nonselective nonsteroidal anti-inflammatory drugs but not in patients receiving celecoxib. In rodent gastric ulcers, COX-2 was upregulated in the granulation tissue and ulcer margin. Inhibition of COX-2 delayed healing of experimental gastric ulcer. Limited data showed that COX-2 expression was also increased in human gastric ulcer regardless of the H. pylori status. The functional significance of COX-2 in human gastric ulcer is unknown. PMID:14529402

  9. Novel selective COX-1 inhibitors suppress neuroinflammatory mediators in LPS-stimulated N13 microglial cells.

    PubMed

    Calvello, Rosa; Panaro, Maria Antonietta; Carbone, Maria Luigia; Cianciulli, Antonia; Perrone, Maria Grazia; Vitale, Paola; Malerba, Paola; Scilimati, Antonio

    2012-01-01

    COX-1 plays a previously unrecognized part in the neuroinflammation. Genetic ablation or pharmacological inhibition of COX-1 activity attenuates the inflammatory response and neuronal loss. In this context, the effects of selective COX-1 inhibitors (P6, P10, SC-560, aspirin) and coxibs (celecoxib and etoricoxib) on LPS-stimulated microglial cell function (a worldwide accepted neuroinflammation model) were investigated, and the effects on COX-1/COX-2, cPGES mRNA and iNOS expression, PGE(2) and NO production and NF-?B activation by I?B? phosphorylation were evaluated. The total suppression of the expression of both COX-1 and COX-2 by their respective selective inhibitors occurred. NF-?B remained almost completely inactive in the presence of coxibs, as expected, and totally inactive in the presence of P6. P6 also markedly counteracted LPS enhancing cPGES mRNA expression and PGE(2) production. Since COX-1 is predominantly localized in microglia, its high selective inhibition rather than COX-2 (by coxibs) is more likely to reduce neuroinflammation and has been further investigated as a potential therapeutic approach and prevention in neurodegenerative diseases with a marked inflammatory component. PMID:22001217

  10. Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

    SciTech Connect

    Pachkoria, Ketevan [Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoeping, Linkoeping (Sweden); Zhang Hong [Department of Dermatology, Institute of Biomedicine and Surgery, University of Linkoeping, Linkoeping (Sweden); Adell, Gunnar [Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoeping, Linkoeping (Sweden); Jarlsfelt, Ingvar [Department of Pathology and Cytology, Joenkoeping Hospital, Joenkoeping (Sweden); Sun Xiaofeng [Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoeping, Linkoeping (Sweden)]. E-mail: xiao-feng.sun@ibk.liu.se

    2005-11-01

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p {<=} 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.

  11. [Significance and creation of novel cyclooxygenase-1 (COX-1) selective inhibitors].

    PubMed

    Fukai, Ryosuke; Zheng, Xiaoxia; Motoshima, Kazunori; Kakuta, Hiroki

    2011-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve physical and mental pain, and to improve patients' quality of life. However, stomach irritation is a major side effect. Most NSAIDs inhibit cyclooxygenases (COXs), and inhibition of COX-1 on the stomach mucous membrane is thought to be responsible for the gastric disturb- ance. Consequently, development efforts have focused on COX-2-selective inhibitors, while COX-1-selective inhibitors have been rather neglected. Subsequently, however, it was shown that inhibition of either COX-1 or COX-2 alone does not induce gastric damage. Therefore, we have developed the COX-1-selective inhibitor N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), which shows analgesic activity without causing gastric damage. However, metabolism of TFAP generates a colored metabolite, resulting in red-purple coloration of urine after administration. In addition, the analgesic activity of TFAP is weaker than that of indomethacin. Thus, we designed a series of new COX-1-selective inhibitors, the 5-amino-2-ethoxy-N-(substituted)benzamide (ABEX) series, in order to avoid formation of the colored metabolite by modifying the diaminopyridine skeleton. As a result of structural modification and in vitro and in vivo testing of compounds in the ABEX series, we found a novel COX-1-selective inhibitor, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (ABEX-3TF), which shows better analgesic activity than indomethacin, and does not cause coloration of urine. PMID:21372527

  12. Chapter 2: Mechanistic Aspects of COX-2 Expression in Colorectal Neoplasia

    PubMed Central

    Dixon, Dan A.; Blanco, Fernando F.; Bruno, Annalisa; Patrignani, Paola

    2012-01-01

    The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states and a large amount of evidence has demonstrated constitutive COX-2 expression to be a contributing factor promoting colorectal cancer (CRC). Various genetic, epigenetic, and inflammatory pathways have been identified to be involved in the etiology and development of CRC. Alteration in these pathways can influence COX-2 expression at multiple stages of colon carcinogenesis allowing for elevated prostanoid biosynthesis to occur in the tumor microenvironment. In normal cells, COX-2 expression levels are potently regulated at the post-transcriptional level through various RNA sequence elements present within the mRNA 3?-untranslated region(3?UTR). A conserved AU-rich element(ARE) functions to target COX-2 mRNA for rapid decay and translational inhibition through association with various RNA-binding proteins to influence the fate of COX-2 mRNA. Specific microRNAs bind regions within the COX-2 3?UTR and control COX-2 expression. In this chapter, we discuss novel insights in the mechanisms of altered posttranscriptional regulation of COX-2 in CRC and how this knowledge may be used to develop novel strategies for cancer prevention and treatment. PMID:22893198

  13. COX-2 overexpression increases malignant potential of human glioma cells through Id1

    PubMed Central

    Xu, Kaiming; Wang, Lanfang; Shu, Hui-Kuo G.

    2014-01-01

    Increased COX-2 expression directly correlates with glioma grade and is associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also regulated by epidermal growth factor receptor signaling which is important in the pathogenesis of GBMs. However, COX-2 expression has not been previously shown to directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH) family of transcriptional repressors that act as dominant-negative inhibitors of basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast carcinoma cells and recent studies suggest that Id1 may also be involved in the genesis/progression of gliomas. We now show that COX-2 increases the aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma transformation/tumorigenesis. Furthermore, we find direct evidence of a role for Id1 with significant suppression of in vitro transformation and in vivo tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down. In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show greater migration/invasive potential and tumors that arise from these cells also display increased microvessel density, results in line with the increased malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of GBM cells through induction of Id1. PMID:24659686

  14. Rank regression: an alternative regression approach for data with outliers

    PubMed Central

    CHEN, Tian; TANG, Wan; LU, Ying; TU, Xin

    2014-01-01

    Summary Linear regression models are widely used in mental health and related health services research. However, the classic linear regression analysis assumes that the data are normally distributed, an assumption that is not met by the data obtained in many studies. One method of dealing with this problem is to use semi-parametric models, which do not require that the data be normally distributed. But semi-parametric models are quite sensitive to outlying observations, so the generated estimates are unreliable when study data includes outliers. In this situation, some researchers trim the extreme values prior to conducting the analysis, but the ad-hoc rules used for data trimming are based on subjective criteria so different methods of adjustment can yield different results. Rank regression provides a more objective approach to dealing with non-normal data that includes outliers. This paper uses simulated and real data to illustrate this useful regression approach for dealing with outliers and compares it to the results generated using classical regression models and semi-parametric regression models. PMID:25903082

  15. PREDICTING TEMPORAL LOBE VOLUME ON MRI FROM GENOTYPES USING L(1)-L(2) REGULARIZED REGRESSION.

    PubMed

    Kohannim, Omid; Hibar, Derrek P; Jahanshad, Neda; Stein, Jason L; Hua, Xue; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2012-01-01

    Penalized or sparse regression methods are gaining increasing attention in imaging genomics, as they can select optimal regressors from a large set of predictors whose individual effects are small or mostly zero. We applied a multivariate approach, based on L(1)-L(2)-regularized regression (elastic net) to predict a magnetic resonance imaging (MRI) tensor-based morphometry-derived measure of temporal lobe volume from a genome-wide scan in 740 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. We tuned the elastic net model's parameters using internal crossvalidation and evaluated the model on independent test sets. Compared to 100,000 permutations performed with randomized imaging measures, the predictions were found to be statistically significant (p ~ 0.001). The rs9933137 variant in the RBFOX1 gene was a highly contributory genotype, along with rs10845840 in GRIN2B and rs2456930, discovered previously in a univariate genomewide search. PMID:22903144

  16. On the comparison of population-level estimates of haplotype and nucleotide diversity: a case study using the gene cox1 in animals

    PubMed Central

    Goodall-Copestake, W P; Tarling, G A; Murphy, E J

    2012-01-01

    Estimates of genetic diversity represent a valuable resource for biodiversity assessments and are increasingly used to guide conservation and management programs. The most commonly reported estimates of DNA sequence diversity in animal populations are haplotype diversity (h) and nucleotide diversity (?) for the mitochondrial gene cytochrome c oxidase subunit I (cox1). However, several issues relevant to the comparison of h and ? within and between studies remain to be assessed. We used population-level cox1 data from peer-reviewed publications to quantify the extent to which data sets can be re-assembled, to provide a standardized summary of h and ? estimates, to explore the relationship between these metrics and to assess their sensitivity to under-sampling. Only 19 out of 42 selected publications had archived data that could be unambiguously re-assembled; this comprised 127 population-level data sets (n?15) from 23 animal species. Estimates of h and ? were calculated using a 456-base region of cox1 that was common to all the data sets (median h=0.70130, median ?=0.00356). Non-linear regression methods and Bayesian information criterion analysis revealed that the most parsimonious model describing the relationship between the estimates of h and ? was ?=0.0081h2. Deviations from this model can be used to detect outliers due to biological processes or methodological issues. Subsampling analyses indicated that samples of n>5 were sufficient to discriminate extremes of high from low population-level cox1 diversity, but samples of n?25 are recommended for greater accuracy. PMID:22434013

  17. COX2: Where are we in 2003? - Be strong and resolute: continue to use COX2 selective inhibitors at recommended dosages in appropriate patients

    Microsoft Academic Search

    Marc C Hochberg

    2003-01-01

    Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with

  18. Developing Stochastic Deep Drainage Surfaces In Cox's Creek Catchment

    NASA Astrophysics Data System (ADS)

    Bennett, S.; Vervoort, R. W.; Bishop, T. F.; Hydrology Research Lab

    2010-12-01

    Deep drainage (DD) can contribute to water table rise and salinity, and is a complex function of rainfall, land management and soil hydraulic properties. Because each of these components is uncertain and variable in time and space, this study developed a method to estimate DD risk based on the mechanistic soil water model SWAP using 50 realisations of stochastic rainfall, land use and soil hydraulic properties using a Monte Carlo approach. DD was predicted at 143 soil points in the Cox’s Creek catchment in northern NSW Australia. Realisations of the stochastic daily rainfall were generated at each soil point using an annual mean adjusted Poisson model, DD values were subsequently translated to probabilities of exceeding 100mm/year and spatially predicted over the study area to produce risk maps for the different scenarios. The results showed that DD is episodic with the predominantly summer rainfall in the area, the monthly variability of DD is extremely high depending on when heavy rainfall occurred in relation to different land uses. As expected, the highest probability exceeding 100mm/year DD was for irrigated crop rotations (99%) followed by continuous wheat (59%), then opportunity cropping (46%) and the least for native vegetation (12.5%). Opportunity cropping with sorghum (42%) had the lowest probability to exceed 100mm/year compared to continuous wheat and other opportunity cropping systems and could be one of options for reducing DD in the area. Variation in soil hydraulic properties had less impact on probability of exceeding 100mm/year than variations in land use, which might be explained by soil properties determining the suitability for a certain land use.

  19. Multiple Regression and Its Discontents

    ERIC Educational Resources Information Center

    Snell, Joel C.; Marsh, Mitchell

    2012-01-01

    Multiple regression is part of a larger statistical strategy originated by Gauss. The authors raise questions about the theory and suggest some changes that would make room for Mandelbrot and Serendipity.

  20. Multiple Correlation versus Multiple Regression.

    ERIC Educational Resources Information Center

    Huberty, Carl J.

    2003-01-01

    Describes differences between multiple correlation analysis (MCA) and multiple regression analysis (MRA), showing how these approaches involve different research questions and study designs, different inferential approaches, different analysis strategies, and different reported information. (SLD)

  1. Regression quantiles for time series

    E-print Network

    Cai, Zongwu

    2002-02-01

    In this paper we study nonparametric estimation of regression quantiles for time series data by inverting a weighted Nadaraya–Watson (WNW) estimator of conditional distribution function, which was first used by Hall, Wolff, and Yao (1999, Journal...

  2. Regression analysis with longitudinal measurements 

    E-print Network

    Ryu, Duchwan

    2005-08-29

    . As multiple covariates are involved, a generalized additive model is adopted, and the Bayesian backfitting algorithm is utilized for each component of the additive model. For the binary response, the logistic regression has been proposed, where the link...

  3. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  4. Introduction to Simple Linear Regression

    NSDL National Science Digital Library

    Dallal, Gerard E.

    This page, created by Gerard E. Dallal of Tufts University, explains simple linear regression with an example on muscle strength versus lean body mass. Dallal uses graphs, mathematical equations and text to illustrate this lesson. The author presents four main portions this method, they are: the regression equation, borrowing strength, interpolation and extrapolation. This would be a great example of a lesson plan for any interested in either study or instruction of statistics.

  5. Impact of Cox maze procedure on outcome in patients with atrial fibrillation and mitral valve disease

    Microsoft Academic Search

    Ko Bando; Junjiro Kobayashi; Yoshio Kosakai; Mitsuhiro Hirata; Yoshikado Sasako; Satoshi Nakatani; Toshikatsu Yagihara; Soichiro Kitamura

    2002-01-01

    Objective: We sought to determine whether the Cox maze procedure provides additional benefit to patients with atrial fibrillation undergoing mitral valve operations. Methods: Between May 1992 and August 2000, we performed 258 Cox maze procedures with mitral valve replacement (n = 147) or mitral valve repair (n = 111). We compared the outcomes of these patients with those of 61

  6. Outcome of valve repair and the cox maze procedure for mitral regurgitation and associated atrial fibrillation

    Microsoft Academic Search

    Nobuhiro Handa; Hartzell V. Schaff; James J. Morris; Betty J. Anderson; Stephen L. Kopecky; Maurice Enriquez-Sarano

    1999-01-01

    Objective: The objective was to determine whether the Cox maze procedure provides adjunctive benefit in patients with atrial fibrillation undergoing mitral valve repair. Methods: We compared the outcome of 39 patients who had the Cox maze procedure plus mitral valve repair between January 1993 and December 1996 (maze group) with that of 58 patients with preoperative atrial fibrillation who had

  7. Rationalizing cyclooxygenase (COX) inhibition for maximal efficacy and minimal adverse events

    Microsoft Academic Search

    James W Freston

    1999-01-01

    New information indicates that cyclooxygenase-2 (COX-2) is constitutively expressed in several tissues, including brain, lung, pancreas, kidney, and ovary, and plays an important role in renal and gastrointestinal function. Selective COX-2 inhibition has been associated in animal studies with impairment of ulcer healing and renal function and inhibition of prostacyclin, an effect that inhibits vasodilation without inhibiting platelet aggregation. The

  8. The COX-2 pathway is essential during early stages of skeletal muscle regeneration.

    PubMed

    Bondesen, Brenda A; Mills, Stephen T; Kegley, Kristy M; Pavlath, Grace K

    2004-08-01

    Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal anti-inflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2(-/-) muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2(-/-) muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease. PMID:15084473

  9. Immunohistochemical detection of COX-2 in feline and canine actinic keratoses and cutaneous squamous cell carcinoma.

    PubMed

    Bardagí, M; Fondevila, D; Ferrer, L

    2012-01-01

    Cyclooxygenase-2 (COX-2) overexpression and its causal role in epidermal carcinogenesis have been demonstrated in human actinic keratoses (AK) and cutaneous squamous cell carcinoma (SCC). The aim of this study was to determine immunohistochemically the level of expression of COX-2 in feline and canine AK (n=18), SCC (n=36) and inflammatory dermatoses (n=24). COX-2 immunoreactivity was detected in all feline and canine SCC. In all specimens, labelled basal and suprabasal neoplastic keratinocytes were localized within and below areas of superficial erosion or ulceration and only scattered deeper tumour cells were positively labelled. In most cases, positive immunoreactivity of keratinocytes was associated with the presence of granulocytes. COX-2 expression was detected in 3/9 canine and 4/9 feline cases of AK and in only one case was associated with inflammation. Inflammatory dermatoses were characterized by positively labelled epidermal and follicular basal and suprabasal keratinocytes that were always associated with granulocyte exocytosis. These results indicate that further study of the effect of using COX-2 inhibitors in the management and prevention of feline and canine cutaneous SCC is warranted. The association between inflammatory cells and COX-2 expressing epidermal cells opens a new line of research regarding the role of COX-2 in SCC oncogenesis. Moreover, further studies should investigate the role of COX-2 in the pathogenesis and management of AK in animals. PMID:21601872

  10. Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance.

    PubMed

    Dennerlein, Sven; Rehling, Peter

    2015-03-01

    Mitochondria provide the main portion of cellular energy in form of ATP produced by the F1Fo ATP synthase, which uses the electrochemical gradient, generated by the mitochondrial respiratory chain (MRC). In human mitochondria, the MRC is composed of four multisubunit enzyme complexes, with the cytochrome c oxidase (COX, also known as complex IV) as the terminal enzyme. COX comprises 14 structural subunits, of nuclear or mitochondrial origin. Hence, mitochondria are faced with the predicament of organizing and controlling COX assembly with subunits that are synthesized by different translation machineries and that reach the inner membrane by alternative transport routes. An increasing number of COX assembly factors have been identified in recent years. Interestingly, mutations in several of these factors have been associated with human disorders leading to COX deficiency. Recently, studies have provided mechanistic insights into crosstalk between assembly intermediates, import processes and the synthesis of COX subunits in mitochondria, thus linking conceptually separated functions. This Cell Science at a Glance article and the accompanying poster will focus on COX assembly and discuss recent discoveries in the field, the molecular functions of known factors, as well as new players and control mechanisms. Furthermore, these findings will be discussed in the context of human COX-related disorders. PMID:25663696

  11. Exploiting cyclooxygenase-(in)dependent properties of COX-2 inhibitors for malignant glioma therapy.

    PubMed

    Schönthal, Axel H

    2010-07-01

    Cyclooxygenase 2 (COX-2) is frequently found up-regulated during pathological conditions and in cancer, where it is thought to support carcinogenesis and tumor angiogenesis. The development of newer-generation non-steroidal anti-inflammatory drugs (NSAIDs) able to more selectively inhibit cyclooxygenase 2 (COX-2) raised expectations that these agents might be beneficial for cancer prevention and therapy. However, while chemopreventive effects of some selective COX-2 inhibitors have been established, it has remained unpersuasive whether these new NSAIDs, such as celecoxib, rofecoxib or etoricoxib, are able to exert cancer therapeutic effects, i.e., whether they would be beneficial for the treatment of advanced cancers that are already grown and established. This issue was further complicated by findings that celecoxib was able to exert pronounced pro-apoptotic effects in vitro and in vivo in the absence of any apparent involvement of COX-2. In fact, newly synthesized close structural analogs of the celecoxib molecule revealed that it was possible to separate COX-2 inhibitory function from the ability to trigger apoptosis; for example, the analog 2,5-dimethyl-celecoxib (DMC) has lost COX-2 inhibitory function, yet exerts increased cytotoxic potency. This review will summarize pertinent results from the exploratory therapeutic use of NSAIDs, in particular celecoxib, in preclinical and clinical studies of malignant glioma. Several COX-2 independent targets will be presented, and it will be discussed how DMC has helped to delineate their relevance for the surmised COX-2 independent tumoricidal effects of celecoxib. PMID:20879982

  12. RESEARCH ARTICLE Open Access Multiple recent horizontal transfers of the cox1

    E-print Network

    Olmstead, Richard

    RESEARCH ARTICLE Open Access Multiple recent horizontal transfers of the cox1 intron in Solanaceae has not yet been found in the ideal group for plant somatic genetics - the Solanaceae. We therefore of Solanaceae examined lack the cox1 intron, it is uniformly present in three phylogenetically disjunct clades

  13. A proportional hazards regression model with change-points in the baseline function.

    PubMed

    Oueslati, Abdullah; Lopez, Olivier

    2013-01-01

    In this article, we consider a new regression model for counting processes under a proportional hazards assumption. This model is motivated by the need of understanding the evolution of the booking process of a railway company. The main novelty of the approach consists in assuming that the baseline hazard function is piecewise constant, with unknown times of jump (these times of jump are estimated from the data as model parameters). Hence, the parameters of the model can be separated into two different types: parameters that measure the influence of the covariates, and parameters from a multiple change-point model for the baseline. Cox's semiparametric regression can be seen as a limit case of our model. We develop an iterative procedure to estimate the different parameters, and a test procedure that allows to perform change-point detection in the baseline. Our technique is supported by simulation studies and a real data analysis, which show that our model can be a reasonable alternative to Cox's regression model, particularly in the presence of tied event times. PMID:23054240

  14. Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells

    PubMed Central

    Onodera, Yuta; Teramura, Takeshi; Takehara, Toshiyuki; Shigi, Kanae; Fukuda, Kanji

    2015-01-01

    Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-?B through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases. PMID:26110105

  15. Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells.

    PubMed

    Onodera, Yuta; Teramura, Takeshi; Takehara, Toshiyuki; Shigi, Kanae; Fukuda, Kanji

    2015-01-01

    Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-?B through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases. PMID:26110105

  16. What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis.

    PubMed

    Davis, Tyler; LaRocque, Karen F; Mumford, Jeanette A; Norman, Kenneth A; Wagner, Anthony D; Poldrack, Russell A

    2014-08-15

    Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI data are analyzed and interpreted. Many studies now report both MVPA results and results from standard univariate voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA results can be sensitive to latent multidimensional representations and processes whereas univariate voxel-wise analysis cannot, one conclusion that is often drawn when MVPA and univariate results differ is that the activation patterns underlying MVPA results contain a multidimensional code. In the current study, we conducted simulations to formally test this assumption. Our findings reveal that MVPA tests are sensitive to the magnitude of voxel-level variability in the effect of a condition within subjects, even when the same linear relationship is coded in all voxels. We also find that MVPA is insensitive to subject-level variability in mean activation across an ROI, which is the primary variance component of interest in many standard univariate tests. Together, these results illustrate that differences between MVPA and univariate tests do not afford conclusions about the nature or dimensionality of the neural code. Instead, targeted tests of the informational content and/or dimensionality of activation patterns are critical for drawing strong conclusions about the representational codes that are indicated by significant MVPA results. PMID:24768930

  17. Novel selective Cox-2 inhibitors induce apoptosis in Caco-2 colorectal carcinoma cell line.

    PubMed

    Entezari Heravi, Reza; Hadizadeh, Farzin; Sankian, Mojtaba; Tavakol Afshari, Jalil; Taghdisi, Seyed Mohammad; Jafarian, Hanieh; Behravan, Javad

    2011-11-20

    The cyclooxygenase-2 (COX-2) inhibitors including celecoxib inhibit cell growth and induce apoptosis in cancer cells. As COX-2 is over expressed in solid tumors such as colorectal cancer, it can be a suitable target for cancer treatment studies. In this study we designed and synthesized 4,5-bisaryl imidazolyl imidazoles as novel COX-2 inhibitors and evaluated their apoptosis inducing activities. The ability of our synthetic compounds to inhibit ovine COX-1 and COX-2 was determined using a colorimetric method. The effects of these COX-2 inhibitors and celecoxib on the proliferation of Caco-2 cells were evaluated by MTT assay. Cell apoptosis was determined by flow cytometry and DNA fragmentation assay. cDNA microarray technique was used to evaluate the effects of these synthetic compounds on 112 genes involved in apoptosis pathways. The expression of five apoptosis-related genes Bak-1, Bcl-x, BIRC (Survivin), TNFSF10 and CASP3 were evaluated by quantitative real-time PCR. Among our synthetic compounds (3a-c), 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative (compound 3c) exhibited the highest COX-1/COX-2 selectivity index (SI=262.9) and lowest growth inhibitory concentration (IC(50)=21.20?M). In addition, compounds 3a-c could up-regulate pro-apoptotic genes and down-regulate anti-apoptotic genes. So, these synthetic compounds seem to be inducers of apoptosis in Caco-2 cell line. This study indicates that 4,5-bisaryl imidazolyl imidazole is a suitable scaffold to design COX-2 inhibitors and 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative exhibited highly COX-2 inhibitory potency and selectivity even more than celecoxib. It seems that it could induce apoptosis in Caco-2 colorectal carcinoma cell line. PMID:21939759

  18. Real-time defect detection of steel wire rods using wavelet filters optimized by univariate dynamic encoding algorithm for searches.

    PubMed

    Yun, Jong Pil; Jeon, Yong-Ju; Choi, Doo-chul; Kim, Sang Woo

    2012-05-01

    We propose a new defect detection algorithm for scale-covered steel wire rods. The algorithm incorporates an adaptive wavelet filter that is designed on the basis of lattice parameterization of orthogonal wavelet bases. This approach offers the opportunity to design orthogonal wavelet filters via optimization methods. To improve the performance and the flexibility of wavelet design, we propose the use of the undecimated discrete wavelet transform, and separate design of column and row wavelet filters but with a common cost function. The coefficients of the wavelet filters are optimized by the so-called univariate dynamic encoding algorithm for searches (uDEAS), which searches the minimum value of a cost function designed to maximize the energy difference between defects and background noise. Moreover, for improved detection accuracy, we propose an enhanced double-threshold method. Experimental results for steel wire rod surface images obtained from actual steel production lines show that the proposed algorithm is effective. PMID:22561939

  19. Bayesian Logistic Regression Sargur N. Srihari

    E-print Network

    Bayesian Logistic Regression Sargur N. Srihari University at Buffalo, State University of New York USA #12;Topics · Recap of Logistic Regression · Roadmap of Bayesian Logistic Regression · Laplace Approximation · Evaluation of posterior distribution ­Gaussian approximation · Predictive Distribution

  20. Regression with Life Data Table Of Contents

    E-print Network

    Langseth, Helge

    Regression with Life Data #12;#12;Table Of Contents Copyright © 2003­2005 Minitab Inc. All rights reserved. 3 Table Of Contents Regression with Life Data...................................................................................................................................................... 5 Regression with Life Data Overview

  1. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

    PubMed

    McCarty, Mark F

    2012-01-01

    A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth factors such as IGF-I increase cox-2 expression by several complementary mechanisms; hence, decreased cox-2 activity may play a role in the remarkably low mortality from "Western" cancers enjoyed by Third World cultures in which systemic growth factor activity was minimized by quasi-vegan diets complemented by leanness and excellent muscle insulin sensitivity. Practical strategies for achieving a modest degree of calorie restriction may also have potential for down-regulating cox-2 expression while decreasing cancer risk. Soy isoflavones, linked to reduced cancer risk in Asian epidemiology, may suppress cox-2 induction by activating ERbeta. In aggregate, these considerations suggest that a comprehensive lifestyle strategy targeting cox-2 expression and bioactivity may have tremendous potential for cancer prevention. PMID:22001128

  2. Late postoperative hemorrhage in a patient with undiagnosed COX-1 deficiency after third molar extractions.

    PubMed

    Doscher, Jesse C; Volpe, Fedele N

    2014-04-01

    Oral maxillofacial surgeons direct invasive procedures that often cause significant bleeding. Uncontrolled hemorrhage is a rare, yet serious, complication that can be seen in patients with thrombocytopathy. Platelets have 3 distinct roles in coagulation: initial adhesion, phospholipid externalization, and platelet aggregation.(1) Several types of platelet deficiencies, including defects of adhesion (Bernard-Soulier syndrome), defects of aggregation (Glanzmann thrombasthenia), and disorders of platelet secretion due to a deficiency of adenosine diphosphate (ADP) or cyclooxygenase-1 (COX-1).(2-4) COX has 2 isoforms: COX-1 and COX-2.(5,6) COX-1 is expressed constitutively in most tissues, and COX-2 is induced primarily by inflammatory mediators.(7,8) Although both isoforms are present in platelets, COX-1 is the major isoform that contributes to coagulation, because it is critically important in the formation of thromboxane A2 (TXA2) by way of the arachidonic acid (AA) pathway.(9) AA is a potent inducer of platelet aggregation.(1,3,4) When AA is exposed to an activating agent, such as ADP, it undergoes a series of enzymatic reactions that culminates in the production of TXA2.(10) TXA2 is the predominant product of the COX-1 pathway and is a major metabolite of AA in platelets. TXA2 is necessary for normal platelet function. Therefore, the inhibition of, or a deficiency in, COX-1 will compromise the AA pathway, thereby reducing platelet secretion and altering normal platelet aggregatory function.(1,3) COX-1 deficiencies are usually caused by drug interactions with the enzyme itself. In addition, studies have identified genetic mutations that can result in COX-1 deficiency.(2) We present the hospital course, management, and diagnosis of a patient with an undiagnosed COX-1 deficiency who had had third molars removed in a private office. To our knowledge, this is the first case of COX-1 deficiency diagnosed after exodontia documented in English studies. In addition, we reviewed the published data of this rare disorder that has significant clinical implications. PMID:24480756

  3. Diagnostics for multiple regression problems

    SciTech Connect

    Daly, J.C.

    1982-03-01

    In the last 10 to 15 years there has been much work done in trying to improve linear regression results. Individuals have analyzed the susceptibility of least-squares results to values far removed from the center of the independent variable observations. They have studied the problem of heavy-tailed residuals, and they have studied the problem of collinearity. From these studies have come ridge regression techniques, robust regression techniques, regression on principal components, etc. However, many practitioners view these methods with suspicion (and ignorance), and prefer to continue using the usual least-squares procedures to fit their models, even though their results might not be answering the question they think. In reaction to this, statisticians are spending more time analyzing how the individual observations affect the least squares results. In the last few years approximately 10 papers and one text have appeared that address the problem of how to study the influence of the individual observations. This report is a study of the recent work done in linear regression diagnostics. It is concerned with analyzing the effect of one case at a time, since the methods to analyze this situation are relatively straight-forward and are not prohibitive computationally.

  4. Logistic regression for dichotomized counts.

    PubMed

    Preisser, John S; Das, Kalyan; Benecha, Habtamu; Stamm, John W

    2014-05-26

    Sometimes there is interest in a dichotomized outcome indicating whether a count variable is positive or zero. Under this scenario, the application of ordinary logistic regression may result in efficiency loss, which is quantifiable under an assumed model for the counts. In such situations, a shared-parameter hurdle model is investigated for more efficient estimation of regression parameters relating to overall effects of covariates on the dichotomous outcome, while handling count data with many zeroes. One model part provides a logistic regression containing marginal log odds ratio effects of primary interest, while an ancillary model part describes the mean count of a Poisson or negative binomial process in terms of nuisance regression parameters. Asymptotic efficiency of the logistic model parameter estimators of the two-part models is evaluated with respect to ordinary logistic regression. Simulations are used to assess the properties of the models with respect to power and Type I error, the latter investigated under both misspecified and correctly specified models. The methods are applied to data from a randomized clinical trial of three toothpaste formulations to prevent incident dental caries in a large population of Scottish schoolchildren. PMID:24862513

  5. Survivin expression in in situ and invasive breast cancer relates to COX2 expression and DCIS recurrence

    Microsoft Academic Search

    N Barnes; P Haywood; P Flint; W F Knox; N J Bundred

    2006-01-01

    In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma

  6. Ciglitazone mediates COX-2 dependent suppression of PGE2 in human Non-Small Cell Lung Cancer cells

    PubMed Central

    Hazra, Saswati; Dubinett, Steven M

    2007-01-01

    Summary Background Cycloxygenase-2 (COX-2) overexpression and subsequent prostaglandin E2 (PGE2) production are frequently associated with human non-small cell lung cancer (NSCLC) and are involved in tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here we report that ciglitazone downregulates PGE2 in NSCLC cells. Methods PGE2 ELISA assay and COX-2 ELISA assay were performed for measuring PGE2 and COX-2 respectively in NSCLC. The mRNA level of COX-2 was measured by semi-quantitative RT-PCR. The transient transfection experiments were performed to measure COX-2 and PPRE promoter activity in NSCLC. Western blots were unitized to measure PGE synthase (PGES) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) protein expression. Results COX-2 ELISA assays suggested that ciglitazone-dependent inhibition of PGE2 occurs through the suppression of COX-2. Ciglitazone treatment suppressed COX-2 mRNA expression and COX-2 promoter activity while upregulating peroxisome proliferator-response element (PPRE) promoter activity. Ciglitazone did not modify the expression of enzymes downstream of COX-2 including PGES and 15-PGDH. Utilization of a dominant-negative PPAR? showed that the suppression of COX-2 and PGE2 by ciglitazone is mediated via non-PPAR pathways. Conclusion Taken together, our findings suggest that ciglitazone is a negative modulator of COX-2/PGE2 in NSCLC. PMID:17697767

  7. The influence of Cox-2 and bioactive lipids on hematological cancersa

    PubMed Central

    Ramon, Sesquile; Woeller, Collynn F.; Phipps, Richard P.

    2014-01-01

    Inflammation is implicated in the progression of multiple types of cancers including lung, colorectal, breast and hematological malignancies. Cyclooxygenases (Cox) -1 and -2 are important enzymes involved in the regulation of inflammation. Elevated Cox-2 expression is associated with a poor cancer prognosis. Hematological malignancies, which are among the top 10 most predominant cancers in the USA, express high levels of Cox-2. Current therapeutic approaches against hematological malignances are insufficient as many patients develop resistance or relapse. Therefore, targeting Cox-2 holds promise as a therapeutic approach to treat hematological malignancies. NSAIDs and Cox-2 selective inhibitors are anti-inflammatory drugs that decrease prostaglandin and thromboxane production while promoting the synthesis of specialized proresolving mediators. Here, we review the evidence regarding the applicability of NSAIDs, such as aspirin, as well as Cox-2 specific inhibitors, to treat hematological malignancies. Furthermore, we discuss how FDA-approved Cox inhibitors can be used as anti-cancer drugs alone or in combination with existing chemotherapeutic treatments. PMID:24883266

  8. Flavocoxid Inhibits Phospholipase A2, Peroxidase Moieties of the Cyclooxygenases (COX), and 5-Lipoxygenase, Modifies COX-2 Gene Expression, and Acts as an Antioxidant

    PubMed Central

    Burnett, Bruce P.; Bitto, Alessandra; Altavilla, Domenica; Squadrito, Francesco; Levy, Robert M.; Pillai, Lakshmi

    2011-01-01

    The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA2) (IC50 = 60??g/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC50 = 12.3) and COX-2 (IC50 = 11.3??g/mL) peroxidase (PO) moieties as well as 5-lipoxygenase (5-LOX) (IC50 = 110??g/mL). No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC50 = 38??g/mL) in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA) are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS). PMID:21765617

  9. Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

    PubMed

    Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

    2010-12-01

    Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity. PMID:20600289

  10. Robust, Adaptive Functional Regression in Functional Mixed Model Framework

    PubMed Central

    Zhu, Hongxiao; Brown, Philip J.; Morris, Jeffrey S.

    2012-01-01

    Functional data are increasingly encountered in scientific studies, and their high dimensionality and complexity lead to many analytical challenges. Various methods for functional data analysis have been developed, including functional response regression methods that involve regression of a functional response on univariate/multivariate predictors with nonparametrically represented functional coefficients. In existing methods, however, the functional regression can be sensitive to outlying curves and outlying regions of curves, so is not robust. In this paper, we introduce a new Bayesian method, robust functional mixed models (R-FMM), for performing robust functional regression within the general functional mixed model framework, which includes multiple continuous or categorical predictors and random effect functions accommodating potential between-function correlation induced by the experimental design. The underlying model involves a hierarchical scale mixture model for the fixed effects, random effect and residual error functions. These modeling assumptions across curves result in robust nonparametric estimators of the fixed and random effect functions which down-weight outlying curves and regions of curves, and produce statistics that can be used to flag global and local outliers. These assumptions also lead to distributions across wavelet coefficients that have outstanding sparsity and adaptive shrinkage properties, with great flexibility for the data to determine the sparsity and the heaviness of the tails. Together with the down-weighting of outliers, these within-curve properties lead to fixed and random effect function estimates that appear in our simulations to be remarkably adaptive in their ability to remove spurious features yet retain true features of the functions. We have developed general code to implement this fully Bayesian method that is automatic, requiring the user to only provide the functional data and design matrices. It is efficient enough to handle large data sets, and yields posterior samples of all model parameters that can be used to perform desired Bayesian estimation and inference. Although we present details for a specific implementation of the R-FMM using specific distributional choices in the hierarchical model, 1D functions, and wavelet transforms, the method can be applied more generally using other heavy-tailed distributions, higher dimensional functions (e.g. images), and using other invertible transformations as alternatives to wavelets. PMID:22308015

  11. Principal component regression analysis with SPSS

    Microsoft Academic Search

    R. X. Liu; J. Kuang; Q. Gong; X. L. Hou

    2003-01-01

    The paper introduces all indices of multicollinearity diagnoses, the basic principle of principal component regression and determination of ‘best’ equation method. The paper uses an example to describe how to do principal component regression analysis with spss 10.0: including all calculating processes of the principal component regression and all operations of linear regression, factor analysis, descriptives, compute variable and bivariate

  12. Independent contrasts and regression through the origin

    Microsoft Academic Search

    Pierre Legendre; Yves Desdevises

    2009-01-01

    Following the pioneering work of Felsenstein and Garland, phylogeneticists have been using regression through the origin to analyze comparative data using independent contrasts. The reason why regression through the origin must be used with such data was revisited. The demonstration led to the formulation of a permutation test for the coefficient of determination and the regression coefficient estimates in regression

  13. Independent contrasts and regression through the origin

    Microsoft Academic Search

    Pierre Legendre; Yves Desdevises

    2002-01-01

    Following the pioneering work of Felsenstein and Garland, phylogeneticists have been using regression through the origin to analyze comparative data using independent contrasts. The reason why regression through the origin must be used with such data was revisited. The demonstration led to the formulation of a permutation test for the coefficient of determination and the regression coefficient estimates in regression

  14. Hedonic Regressions: A Consumer Theory Approach

    Microsoft Academic Search

    Erwin Diewert

    A hedonic regression regresses the price of various models of a product (or service) on the characteristics that describe the product. The existing economic theory that justifies a hedonic regression is extremely complex. The present paper takes a very simple consumer theory approach in order to justify a family of functional forms for a hedonic regression. The main simplifying assumption

  15. Robust L1 orthogonal regression

    Microsoft Academic Search

    J. Paul Brooks; Edward L. Boone

    Abstract Assessing the linear relationship between a set of continuous predictors and a continuous re- sponse is a well studied problem in statistics and is applied in many data mining situations. L2 based methods such as ordinary least squares and principal components regression can be used to determine this relationship. However, both of these methods become impaired when mul- ticollinearity

  16. Fungible Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2008-01-01

    Every set of alternate weights (i.e., nonleast squares weights) in a multiple regression analysis with three or more predictors is associated with an infinite class of weights. All members of a given class can be deemed "fungible" because they yield identical "SSE" (sum of squared errors) and R[superscript 2] values. Equations for generating…

  17. Correlation Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.; Jones, Jeff A.

    2010-01-01

    A general theory on the use of correlation weights in linear prediction has yet to be proposed. In this paper we take initial steps in developing such a theory by describing the conditions under which correlation weights perform well in population regression models. Using OLS weights as a comparison, we define cases in which the two weighting…

  18. Least Median of Squares Regression

    Microsoft Academic Search

    Peter J. Rousseeuw

    1984-01-01

    Classical least squares regression consists of minimizing the sum of the squared residuals. Many authors have produced more robust versions of this estimator by replacing the square by something else, such as the absolute value. In this article a different approach is introduced in which the sum is replaced by the median of the squared residuals. The resulting estimator can

  19. Bandwidth Choice for Nonparametric Regression

    Microsoft Academic Search

    John Rice

    1984-01-01

    This paper is concerned with the problem of choosing a bandwidth parameter for nonparametric regression. We analyze a tapered Fourier series estimate and discuss the relationship of this estimate to a kernel estimate. We first consider a method based on an unbiased estimate of mean square error, and show that the bandwidth thus chosen is asymptotically optimal. Other methods are

  20. Multivariate Analysis with Linearizable Regressions.

    ERIC Educational Resources Information Center

    de Leeuw, Jan

    1988-01-01

    Multivariate distributions are studied in which all bivariate regressions can be linearized by separate transformation of each of the variables. A two-stage procedure, first scaling the variables optimally and then fitting a simultaneous equations model, is studied in detail. (SLD)

  1. Regression Models of Atlas Appearance

    PubMed Central

    Rohlfing, Torsten; Sullivan, Edith V.; Pfefferbaum, Adolf

    2010-01-01

    Models of object appearance based on principal components analysis provide powerful and versatile tools in computer vision and medical image analysis. A major shortcoming is that they rely entirely on the training data to extract principal modes of appearance variation and ignore underlying variables (e.g., subject age, gender). This paper introduces an appearance modeling framework based instead on generalized multi-linear regression. The training of regression appearance models is controlled by independent variables. This makes it straightforward to create model instances for specific values of these variables, which is akin to model interpolation. We demonstrate the new framework by creating an appearance model of the human brain from MR images of 36 subjects. Instances of the model created for different ages are compared with average shape atlases created from age-matched sub-populations. Relative tissue volumes vs. age in models are also compared with tissue volumes vs. subject age in the original images. In both experiments, we found excellent agreement between the regression models and the comparison data. We conclude that regression appearance models are a promising new technique for image analysis, with one potential application being the representation of a continuum of mutually consistent, age-specific atlases of the human brain. PMID:19694260

  2. Ridge Regression for Interactive Models.

    ERIC Educational Resources Information Center

    Tate, Richard L.

    1988-01-01

    An exploratory study of the value of ridge regression for interactive models is reported. Assuming that the linear terms in a simple interactive model are centered to eliminate non-essential multicollinearity, a variety of common models, representing both ordinal and disordinal interactions, are shown to have "orientations" that are favorable to…

  3. Regression Analysis of Count Data

    Microsoft Academic Search

    A. Colin Cameron; Pravin K. Trivedi

    1998-01-01

    Students in both the natural and social sciences often seek regression models to explain the frequency of events, such as visits to a doctor, auto accidents or job hiring. This analysis provides a comprehensive account of models and methods to interpret such data. The authors have conducted research in the field for nearly fifteen years and in this work combine

  4. NONNORMAL REGRESSION. I. SKEW DISTRIBUTIONS

    Microsoft Academic Search

    M. Qamarul Islam; Moti L. Tiku; F. Yildirim

    2001-01-01

    In a linear regression model of the type y= ? X+e, it is often assumed that the random error eis normally distributed. In numerous situations, e.g., when ymeasures life times or reaction times, etypically has a skew distribution. We consider two important families of skew distributions, (a) Weibull with support IR: (0, ?) on the real line, and (b) generalised

  5. The Bootstrap in Threshold Regression

    Microsoft Academic Search

    Ping Yu

    2009-01-01

    This paper shows that the nonparametric bootstrap is inconsistent, and the parametric bootstrap is consistent for inference of the threshold point in discontinuous threshold regression. An interesting phenomenon is that the asymptotic nonparametric bootstrap distribution of the threshold point is discrete and depends on the sampling path of the original data. Furthermore, the remedies to the nonparametric bootstrap failure in

  6. Regression

    MedlinePLUS

    ... the child-care center to talk with the caregivers about how they can help your child maintain her bathroom habits, or surround her potty in the new house with familiar objects from the old house. Ask your child ...

  7. The univariant curve liquid = forsterite + anorthite + diopside in the system CMAS at 1 bar: solid solutions and melt structure

    NASA Astrophysics Data System (ADS)

    Libourel, Guy; Boivin, Pierre; Biggar, Gordon M.

    1989-08-01

    One atmosphere liquid-present experiments were carried out in the CMAS system using an ordinary quench furnace apparatus. The runs, including reversal and duplicate experiments, describe the univariant curve l=fo+an+ di between the invariant points Q: l+fo+an=di+sp and F: l+fo=an+di+oen, located respectively at 1245±1° C and 1244±1° C. The thermal divide on this curve M3: l= fo+an+di is located at 1275±1° C and plots well within the silica-saturated field, in agreement with Longhi's (1987) experiments. Along the univariant curve l=fo+an+di, liquid composition evolves away from the thermal divide either toward invariant points Q or F and pierces the silica saturation plane, i.e., the join Di-An-En, in the silica saturated field. In this compositional range, the Al solubility in clinopyroxene changes drastically from one side of the thermal divide to the other, with great increase of Al solubility in the silica-undersaturated field. Four endmembers must be used to describe the complex solid solution of anorthite: CaAl2Si2O8, CaMgSi3O8, MgAl2Si2O8 and [] Si4O8. The last two of these are present only within the silica-saturated field. Unlike clinopyroxene, the Mg content of anorthite is insensitive to the thermal barrier but is only sensitive to silica-saturation plane. Olivine composition can be described by a binary solid solution of forsterite and monticellite with no Ca in the M2 site. As with anorthite, olivine compositions exhibit a marked change with crossing of the silica-saturation plane. The above features imply that the solubility of minor elements in crystalline phases (Al in clinopyroxene, Ca in olivine and Mg in anorthite) selectively respond to only one or another of these particular plane. Results have many important consequences. One is the likelihood of changes in melt speciation depending on position with respect to the thermal divide and the silica-saturation plane.

  8. Design and synthesis of new 2,4,5-triarylimidazole derivatives as selective cyclooxygenase (COX2) inhibitors

    Microsoft Academic Search

    A. Zarghi; S. Arfaei; R. Ghodsi

    A new group of 2,4,5-triarylimidazole derivatives, possessing a methyl sulfonyl pharmacophore, were synthesized and their\\u000a biological activities were evaluated for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1\\/COX-2 structure–activity\\u000a relationships were determined by varying the substituents at the para position of C-2 phenyl ring. Among the 2,4,5-triarylimidazoles, 2-(4-hydroxy phenyl)-4-(4-methylsulfonylphenyl)-5-phenyl-1H imidazole (11f) was identified as a selective COX-2 inhibitor (COX-2 IC50 = 0.15 ?M; selectivity

  9. Straight line fitting and predictions: On a marginal likelihood approach to linear regression and errors-in-variables models

    NASA Astrophysics Data System (ADS)

    Christiansen, Bo

    2015-04-01

    Linear regression methods are without doubt the most used approaches to describe and predict data in the physical sciences. They are often good first order approximations and they are in general easier to apply and interpret than more advanced methods. However, even the properties of univariate regression can lead to debate over the appropriateness of various models as witnessed by the recent discussion about climate reconstruction methods. Before linear regression is applied important choices have to be made regarding the origins of the noise terms and regarding which of the two variables under consideration that should be treated as the independent variable. These decisions are often not easy to make but they may have a considerable impact on the results. We seek to give a unified probabilistic - Bayesian with flat priors - treatment of univariate linear regression and prediction by taking, as starting point, the general errors-in-variables model (Christiansen, J. Clim., 27, 2014-2031, 2014). Other versions of linear regression can be obtained as limits of this model. We derive the likelihood of the model parameters and predictands of the general errors-in-variables model by marginalizing over the nuisance parameters. The resulting likelihood is relatively simple and easy to analyze and calculate. The well known unidentifiability of the errors-in-variables model is manifested as the absence of a well-defined maximum in the likelihood. However, this does not mean that probabilistic inference can not be made; the marginal likelihoods of model parameters and the predictands have, in general, well-defined maxima. We also include a probabilistic version of classical calibration and show how it is related to the errors-in-variables model. The results are illustrated by an example from the coupling between the lower stratosphere and the troposphere in the Northern Hemisphere winter.

  10. Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors

    PubMed Central

    Woodard, Dawn B.; Crainiceanu, Ciprian; Ruppert, David

    2013-01-01

    We propose a new method for regression using a parsimonious and scientifically interpretable representation of functional predictors. Our approach is designed for data that exhibit features such as spikes, dips, and plateaus whose frequency, location, size, and shape varies stochastically across subjects. We propose Bayesian inference of the joint functional and exposure models, and give a method for efficient computation. We contrast our approach with existing state-of-the-art methods for regression with functional predictors, and show that our method is more effective and efficient for data that include features occurring at varying locations. We apply our methodology to a large and complex dataset from the Sleep Heart Health Study, to quantify the association between sleep characteristics and health outcomes. Software and technical appendices are provided in online supplemental materials. PMID:24293988

  11. Etoricoxib: new drug. Avoid using cox-2 inhibitors for pain.

    PubMed

    2007-12-01

    (1) Paracetamol is the first-choice analgesic for joint pain. Nonsteroidal antiinflammatory drugs (NSAIDs), especially ibuprofen, are second-line options. Cox-2 inhibitors are no more effective than traditional NSAIDs and have no tangible advantages in terms of gastrointestinal tolerability. In contrast, they expose patients to an increased risk of cardiovascular adverse effects. (2) Etoricoxib is marketed in some European countries to relieve symptoms of osteoarthritis, rheumatoid arthritis, and gout attacks. (3) Many clinical trials have tested etoricoxib in these indications, as well as in ankylosing spondylitis, low back pain, and various types of acute pain. Etoricoxib was no more effective than other NSAIDs such as ibuprofen, naproxen or diclofenac in these situations. (4) Comparative trials showed a higher overall mortality rate with etoricoxib than with naproxen. A combined analysis of long-term comparative trials including 5441 patients, mainly versus naproxen, showed that etoricoxib does not reduce the risk of perforation, ulcer or severe gastrointestinal haemorrhage. Similarly, it does not reduce the risk of mild gastrointestinal events in at-risk patients: those with a history of gastrointestinal disorders, aspirin use, etc. (5) Three trials including a total of 34 701 patients (MEDAL programme) compared cardiovascular thrombotic events associated with etoricoxib and diclofenac. Overall, the cardiovascular risks appear to be similar but the thrombotic risk may be slightly higher with diclofenac than with other conventional NSAIDs. (6) Etoricoxib provoked arterial hypertension, oedema and heart failure during clinical trials. Serious skin reactions were reported both during clinical trials and after marketing, but their precise incidence is not known. Etoricoxib is partly metabolised by the cytochrome P450 isoenzyme CYP 3A4 and increases the bioavailability of ethinylestradiol. (7) When a NSAID is considered, drugs with which we have the most experience should be chosen, such as ibuprofen, and used at the lowest acceptable dose regimen (daily dose and length of treatment). Etoricoxib should be avoided. PMID:18084859

  12. Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner.

    PubMed

    Kim, So Ra; Park, Jung Hae; Lee, Mi Eun; Park, Jeong Soo; Park, Sang Chul; Han, Jeong A

    2008-12-01

    It has been recently proposed that pro-inflammatory genes such as cyclooxygenase-2 (COX-2) play a key role in the aging process. However, it remains unclear whether the pro-inflammatory activity of COX-2 is involved in the aging process and whether COX-2 inhibitors prevent aging. We therefore examined the effect of COX-2 inhibitors on aging in the cellular senescence model of human dermal fibroblasts (HDFs). While the catalytic activity of COX-2 was observed to increase in the senescence process, we found that among three selective COX-2 inhibitors studied, only NS-398 inhibited the senescence whereas celecoxib and nimesulide accelerated the senescence. Non-selective COX inhibitors including aspirin, ibuprofen and flurbiprofen accelerated the senescence. The senescence-regulating effect of selective COX-2 inhibitors had no correlation with cellular reactive oxygen species levels, NF-kappaB activities or protein levels of p53 and p21. We instead found that selective COX-2 inhibitors regulate caveolin-1 expression at transcriptional levels, which was closely associated with the inhibitors' effect on the senescence. Collectively, these results suggest that COX-2 catalytic activity does not mediate HDF senescence and that selective COX-2 inhibitors modulate HDF senescence by a catalytic activity-independent mechanism. PMID:18848576

  13. AgeDisplay: an EXCEL workbook to evaluate and display univariate geochronological data using binned frequency histograms and probability density distributions

    Microsoft Academic Search

    Keith N. Sircombe

    2004-01-01

    Univariate diagrams such as binned frequency histograms and probability density distributions are often used for the initial assessment and communication of geochronological data. Both diagram types are estimates of the sample distribution and both have inherent limitations that are not widely appreciated. Binned frequency histograms are effective at conveying frequency information, but analytical error is discarded and appearance is vulnerable

  14. What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis

    E-print Network

    Wagner, Anthony

    MRI analysis Dimensionality Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI dataWhat do differences between multi-voxel and univariate analysis mean? How subject-, voxel voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA

  15. Celebration of the contributions of Art Cox to stellar pulsation interpretations

    SciTech Connect

    Castor, J.I.

    1997-10-02

    A roughly chronological account is given of Arthur N. Coxs published work of 1953-1996 in, mostly, stellar pulsation theory, with a digression into stellar opacity. When possible, his work is placed in the context of the contemporary efforts.

  16. GETTING MILES AWAY FROM TERMAN: Did the CRPS Fund Catharine Cox Miles's Unsilenced Psychology of Sex?

    Microsoft Academic Search

    Peter Hegarty

    2012-01-01

    Psychologist Catharine Cox Miles (1890–1984) is often remembered as the junior author, with Lewis Terman, of Sex and Personality. Written with support from the Committee for Research on the Problems of Sex (CRPS), Sex and Personality introduced the \\

  17. COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1

    EPA Science Inventory

    Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary dis...

  18. Expression of COX-2 and HER-2 in colorectal cancer and their correlation

    PubMed Central

    Wu, Qi-Bing; Sun, Guo-Ping

    2015-01-01

    AIM: To detect the expression of COX-2 and HER-2 in colorectal cancer and to analyze their correlation and clinical significance. METHODS: A total of 1026 colorectal cancer surgical specimens were collected from patients treated from December 2002 to December 2007 at the First Affiliated Hospital of Anhui Medical University. All specimens were made into 4-?m slices. The expression of COX-2 and HER-2 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between COX-2 and HER-2 expression and colorectal cancer clinical features were analyzed. RESULTS: The positive rates of COX-2 and HER-2 expression in colorectal cancer were 77.97% (800/1026) and 46.20% (474/1026), respectively. There was a significant correlation between COX-2 and HER-2 expression in colorectal cancer (P < 0.05). In patients with tumor size ? 5 cm, the positive rates of COX-2 and HER-2 expression were 81.48% (308/378) and 57.94% (219/378), respectively. In patients with serosal invasion, the positive COX-2 and HER-2 expression rates were 80.53% (612/760) and 49.21% (374/760), respectively. In patients with lymph node metastasis, the positive expression rates were 85.04% (506/595) and 54.62% (325/595), respectively, and the positive expression rates differed significantly between patients with lymph node metastasis and those without (P < 0.05). In patients with Duke’s C and D colorectal cancer, the positive COX-2 and HER-2 expression rates were 82.80% (443/535) and 57.94% (310/535), respectively. In patients with poorly differentiated colorectal cancer, the positive expression rates were 74.49% (210/282) and 52.84% (149/282), respectively (P < 0.05). In patients with distant metastasis, the positive expression rates were 82.27% (116/141) and 53.90% (76/141), respectively (P < 0.05). These findings suggest that COX-2 and HER-2 have synergistic effects in colorectal cancer. COX-2 and HER-2 expression had no significant correlation with sex, age, or tumor location. CONCLUSION: COX-2 and HER-2 are important markers for invasion and metastasis of colorectal cancer, and they act together to regulate the invasion and metastasis of colorectal cancer.

  19. Bayesian inference for finite mixtures of univariate and multivariate skew-normal and skew-t distributions.

    PubMed

    Frühwirth-Schnatter, Sylvia; Pyne, Saumyadipta

    2010-04-01

    Skew-normal and skew-t distributions have proved to be useful for capturing skewness and kurtosis in data directly without transformation. Recently, finite mixtures of such distributions have been considered as a more general tool for handling heterogeneous data involving asymmetric behaviors across subpopulations. We consider such mixture models for both univariate as well as multivariate data. This allows robust modeling of high-dimensional multimodal and asymmetric data generated by popular biotechnological platforms such as flow cytometry. We develop Bayesian inference based on data augmentation and Markov chain Monte Carlo (MCMC) sampling. In addition to the latent allocations, data augmentation is based on a stochastic representation of the skew-normal distribution in terms of a random-effects model with truncated normal random effects. For finite mixtures of skew normals, this leads to a Gibbs sampling scheme that draws from standard densities only. This MCMC scheme is extended to mixtures of skew-t distributions based on representing the skew-t distribution as a scale mixture of skew normals. As an important application of our new method, we demonstrate how it provides a new computational framework for automated analysis of high-dimensional flow cytometric data. Using multivariate skew-normal and skew-t mixture models, we could model non-Gaussian cell populations rigorously and directly without transformation or projection to lower dimensions. PMID:20110247

  20. Gene transfer from mitochondrion to nucleus: novel mechanisms for gene activation from Cox2

    Microsoft Academic Search

    Daniel O. Daley; Keith L. Adams; Rachel Clifton; Svenja Qualmann; A. Harvey Millar; Jeffrey D. Palmer; Elke Pratje; James Whelan

    2002-01-01

    Summary The evolutionarily recent transfer of the gene for cytochrome c oxidase subunit 2 (cox2) from the mitochondrion to the nucleus in legumes is shown to have involved novel gene-activation steps. The acquired mitochondrial targeting presequence is bordered by two introns. Characterization of the import of soybean Cox2 indicates that the presequence is cleaved in a three-step process which is

  1. Mini-partial heart autotransplantation: a different way to perform the Cox-maze III.

    PubMed

    García-Villarreal, Ovidio A

    2015-08-01

    The Cox-maze III procedure is the gold standard for the surgical treatment of atrial fibrillation. Because of its complexity, this procedure has not been widely accepted by cardiac surgeons. We describe a technique that allows one to work on the mitral valve while more safely performing the standard 'cut-and-sew' Cox-maze III procedure at the same time. PMID:25956756

  2. Expression of IL-17 and COX2 gene in peripheral blood leukocytes of vitiligo patients.

    PubMed

    Esmaeili, Behnaz; Rezaee, Seyed Abdol Rahim; Layegh, Pouran; Tavakkol Afshari, Jalil; Dye, Phil; Ghayoor Karimiani, Ehsan; Kalalinia, Fatemeh; Rafatpanah, Houshang

    2011-06-01

    Vitiligo is a pigmentation disorder in which inflammatory mediators such as cytokines have a pivotal role in disease's pathogenesis. Interleukin 17 (IL-17A) is a proinflammatory cytokine which is involved in the induction of several proinflamatory mediators such as cyclooxygenase 2 (COX2). The aim of this study was to investigate the gene expression of IL-17 and COX2 in peripheral blood leukocytes of vitiligo's patients.Peripheral blood leukocytes from 15 patients with vitiligo and 15 healthy controls were separated using a gradient density centrifugation method. After total RNA isolation and cDNA synthesis, IL-17 and COX2 gene expression were quantified by real-time polymerase chain reaction (PCR). There were no significant differences in IL-17 and COX2 gene expression in lymphocytes of patients with vitiligo compared with control group (p<0.05). However there was an increased IL-17 and COX2 gene expression in neutrophils of patients compared to controls, but it did not reach statistical significance (p=0.05). We could not find any differences in IL-17 and Cox2 gene expression between clinical diseases subtypes, sex and age. There was a significant correlation between IL-17 and COX2 genes expression in the neutrophils of patients (p=0.00, r=0.80). Our results showed an increased expression in IL-17 and Cox-2 genes in neurophils of patients with vitiligo. This suggested that these two factors are involved in the inflammatory process. Further studies with a larger sample size might help to establish the role of these factors in the pathogenesis of diseases. PMID:21625016

  3. Cardiovascular and gastrointestinal effects of COX2 inhibitors and NSAIDs: achieving a balance

    Microsoft Academic Search

    Jeffrey S Borer; Lee S Simon

    2005-01-01

    Conventional 'nonselective' nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain and inflammation; however, the potential gastrointestinal risks associated with their use can be a cause for concern. In response to the adverse effects that can accompany nonselective NSAID use, selective cyclo-oxygenase (COX)-2 inhibitors were developed to target the COX-2 isoenzyme, thus providing anti-inflammatory and analgesic benefits

  4. Comparative QSAR modeling of COX2 inhibitor 1,2-diarylimidazoles using Estate and physicochemical parameters

    Microsoft Academic Search

    Santanu Chakraborty; Chandana Sengupta; Kunal Roy

    Considering importance of developing selective COX-2 inhibitors, COX-2 binding affinity data of 4-(2-aryl-1- imidazolyl)-phenyl methyl sulfones and sulfonamides (n = 83) have been modeled using electrotopological state (E-state) index as electronic parameter, hydrophobic substituent constant (?) and molar refractivity (MR) of aryl ring substituents as lipophilic and steric parameters, respectively. Additionally, suitable dummy parameters have been used for the development

  5. Statistical Surveillance of the Parameters of a One-Factor Cox–Ingersoll–Ross Model

    Microsoft Academic Search

    Wolfgang Schmid; Dobromir Tzotchev

    2004-01-01

    In the paper, the tools of statistical process control, and in particular control charts, are applied to sequentially detect a change in the parameters of the Cox–Ingersoll–Ross term-structure model. Different types of multivariate EWMA control charts are introduced and constructed, taking into account the peculiarities of the Cox– Ingersoll–Ross model. The effectiveness of the control charts is analysed on the

  6. Association between COX-2 polymorphisms and non-small cell lung cancer susceptibility

    PubMed Central

    Zhang, Tiancheng; Li, Jing; Xia, Tian; Zhang, Nan; Zhang, Yaozhou; Zhao, Jian

    2015-01-01

    Aim: To explore the association between COX-2 polymorphisms and non-small cell lung cancer (NSCLC) susceptibility. Methods: We collected fasting peripheral venous blood from 60 cases with NSCLC and 62 healthy controls through physical examinations, and applied PCR-RFLP to analyze COX-2 polymorphisms of two groups. Results: With respect to detecting COX-2 rs689466 and rs5275 polymorphisms, the distribution frequency of mutant genotype AA of COX-2 rs689466 in case group was higher than that in control group, which possessed significant difference between two groups (P < 0.05). Carriers with AA genotype were 4.05 times at risk of NSCLC than those with GG genotype (P = 0.04, OR=4.05, 95% CI = 1.14-14.43). The distribution of mutant genotype CC of COX-2 rs5275 was different between two groups, and carriers with genotype CC were at 5.70 times higher risk of NSCLC than those with genotype TT. After corrected by sex, gender, smoking and drinking factors, AA genotype of COX-2 rs689466 and CC genotype of COX-2 rs5275 still contributed to increased risk of NSCLC (OR=4.22, 95% CI=1.10-16.17, OR=6.95, 95% CI=1.27-38.11). After analyzed of linkage disequilibrium (LD) and haplotypes of alleles in two SNPs, the distribution frequency of A-C haplotype in case group was higher than that in control group, with significant difference between two groups (P < 0.05). After corrected by sex, gender, smoking and drinking factors, statistical difference was still found in the total distribution of A-C haplotype between two groups (P = 0.03, OR=6.11, 95% CI=1.16-32.2). Conclusions: COX-2 rs689466 and rs5275 polymorphisms may be related to NSCLC susceptibility. And A-C haplotype might be a susceptibility haplotype for NSCLC.

  7. Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells.

    PubMed

    Takeda, Shuso; Okazaki, Hiroyuki; Ikeda, Eriko; Abe, Satomi; Yoshioka, Yasushi; Watanabe, Kazuhito; Aramaki, Hironori

    2014-01-01

    Metastases are known to be responsible for approximately 90% of breast cancer-related deaths. Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells; it is expressed in 40% of human invasive breast cancers. To comprehensively analyze the effects of cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant (Takeda et al., 2008), on COX-2 expression and the genes involved in metastasis, we performed a DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are invasive breast cancer cells that express high levels of COX-2, treated with CBDA for 48 hr at 25 µM. The results obtained revealed that COX-2 and Id-1, a positive regulator of breast cancer metastasis, were down-regulated (0.19-fold and 0.52-fold, respectively), while SHARP1 (or BHLHE41), a suppressor of breast cancer metastasis, was up-regulated (1.72-fold) and CHIP (or STUB1) was unaffected (1.03-fold). These changes were confirmed by real-time RT-PCR analyses. Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro. PMID:25242400

  8. Functional Polymorphisms in COX-2 Gene Are Correlated with the Risk of Oral Cancer

    PubMed Central

    Li, Dong; Hao, Shu-Hong; Sun, Yan; Hu, Chun-Mei; Ma, Zhi-Hua; Wang, Zhi Ming; Liu, Jie; Liu, Hong Bo; Ye, Ming; Zhang, Yu Fei; Yang, Dong Sheng; Shi, Guang

    2015-01-01

    Background. This meta-analysis investigated the association between functional COX-2 gene polymorphisms and the risk of oral cancer. Methods. Several electronic databases were searched for published studies using combinations of keywords related to COX-2 gene polymorphisms and oral cancer. After selection of relevant studies, following strict inclusion and exclusion criteria, data was performed using STATA 12.0 software. Results. We retrieved 83 studies from database search using specific search terms. After multiple rounds of selection and elimination, 7 studies were finally identified as suitable to be included in our present meta-analysis, based on their relevance and data integrity. These 7 studies contained a combined total of 2,296 oral cancer patients and 3,647 healthy controls. Our findings demonstrated that +837 T > C (rs5275) polymorphism in COX-2 showed statistically significant differences in gene frequencies in case and control groups in allele model and dominant model. Similar results were obtained with COX-2 gene polymorphism 765 G > C (rs20417). On the other hand, 1195 A > G (rs689466) polymorphism in COX-2 did not confer susceptibility to oral cancers. Conclusion. Based on our results, COX-2 gene polymorphisms, +837 T > C (rs5275) and ?765G > C (rs20417), showed clear links with oral cancer susceptibility, and the 1195A > G (rs689466) polymorphism did not show such a correlation. PMID:25977924

  9. COX2 is involved in hypoxia-induced TNF-? expression in osteoblast.

    PubMed

    Xing, Yonggang; Wang, Renxian; Chen, Dafu; Mao, Jianping; Shi, Rui; Wu, Zhihong; Kang, Jun; Tian, Wei; Zhang, Chi

    2015-01-01

    Bone regeneration involves a series of events in a coordinated manner, including recruitment of mesenchymal stem cells, induction of immune response, inflammatory activity and vascular ingrowth. The microenvironment of bone regeneration is hypoxic. Low oxygen tension (hypoxia) promotes the upregulation of several signaling molecules. The primary mediating factor is the hypoxia-inducible factor-1 (HIF-1). Hypoxia stimulates the expression of a variety of cytokines from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. TNF-? is a key proinflammatory cytokine. The molecular events involved in osteoblast dysfunction under hypoxia are not fully understood. This study determined the effects of hypoxia on TNF-? in osteoblasts, and molecular mechanisms were explored. We observed that hypoxia induced TNF-? expression in a time-dependent manner in osteoblasts. Experiments using a potent HIF-1? activator DFO demonstrated that hypoxia-induced TNF-? was mediated by HIF-1-?. In addition, this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along with TNF-?. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 was involved in hypoxia-mediated TNF-? expression, and this observation was further confirmed by Small interfering RNA against COX2. On the other hand, TNF-? didn't lead to the activation of COX2 expression. We conclude that COX2 is involved in hypoxia-induced TNF-? expression in osteoblast. PMID:26066979

  10. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    PubMed Central

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    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. PMID:23875171

  11. COX2 is involved in hypoxia-induced TNF-? expression in osteoblast

    PubMed Central

    Xing, Yonggang; Wang, Renxian; Chen, Dafu; Mao, Jianping; Shi, Rui; Wu, Zhihong; Kang, Jun; Tian, Wei; Zhang, Chi

    2015-01-01

    Bone regeneration involves a series of events in a coordinated manner, including recruitment of mesenchymal stem cells, induction of immune response, inflammatory activity and vascular ingrowth. The microenvironment of bone regeneration is hypoxic. Low oxygen tension (hypoxia) promotes the upregulation of several signaling molecules. The primary mediating factor is the hypoxia-inducible factor-1 (HIF-1). Hypoxia stimulates the expression of a variety of cytokines from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. TNF-? is a key proinflammatory cytokine. The molecular events involved in osteoblast dysfunction under hypoxia are not fully understood. This study determined the effects of hypoxia on TNF-? in osteoblasts, and molecular mechanisms were explored. We observed that hypoxia induced TNF-? expression in a time-dependent manner in osteoblasts. Experiments using a potent HIF-1? activator DFO demonstrated that hypoxia-induced TNF-? was mediated by HIF-1-?. In addition, this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along with TNF-?. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 was involved in hypoxia-mediated TNF-? expression, and this observation was further confirmed by Small interfering RNA against COX2. On the other hand, TNF-? didn’t lead to the activation of COX2 expression. We conclude that COX2 is involved in hypoxia-induced TNF-? expression in osteoblast. PMID:26066979

  12. Scaling regression inputs by dividing by 2 sd Prior distribution for logistic regression

    E-print Network

    Gelman, Andrew

    Scaling regression inputs by dividing by 2 sd Prior distribution for logistic regression Comparing by dividing by 2 sd Prior distribution for logistic regression Comparing the upper third to the lower third regression inputs by dividing by 2 sd Prior distribution for logistic regression Comparing the upper third

  13. Covariate-adjusted nonlinear regression

    E-print Network

    Cui, Xia; Lin, Lu; Zhu, Lixing; 10.1214/08-AOS627

    2009-01-01

    In this paper, we propose a covariate-adjusted nonlinear regression model. In this model, both the response and predictors can only be observed after being distorted by some multiplicative factors. Because of nonlinearity, existing methods for the linear setting cannot be directly employed. To attack this problem, we propose estimating the distorting functions by nonparametrically regressing the predictors and response on the distorting covariate; then, nonlinear least squares estimators for the parameters are obtained using the estimated response and predictors. Root $n$-consistency and asymptotic normality are established. However, the limiting variance has a very complex structure with several unknown components, and confidence regions based on normal approximation are not efficient. Empirical likelihood-based confidence regions are proposed, and their accuracy is also verified due to its self-scale invariance. Furthermore, unlike the common results derived from the profile methods, even when plug-in estim...

  14. Local Regression: Automatic Kernel Carpentry

    Microsoft Academic Search

    Trevor Hastie; Clive Loader

    1993-01-01

    A kernel smoother is an intuitive estimate of a regression function or conditional expectation; at each point $x_0$ the estimate of $E(Y\\\\mid x_0)$ is a weighted mean of the sample $Y_i$, with observations close to $x_0$ receiving the largest weights. Unfortunately this simplicity has flaws. At the boundary of the predictor space, the kernel neighborhood is asymmetric and the estimate

  15. Logistic Regression Longitudinal Data Analysis

    E-print Network

    Bardsley, John

    the other predictors fixed. 2 ej represents the odds ratio associated with a unit change in xj , holding The above logistic regression model can be rewritten in terms of odds ratio as, p(x) 1 - p(x) = e0+1x = e0 (e1 )x . e0 is the odds of success when x = 0. For a unit change in x, the odds of success changes

  16. QUANTILE CALCULUS AND CENSORED REGRESSION.

    PubMed

    Huang, Yijian

    2010-06-01

    Quantile regression has been advocated in survival analysis to assess evolving covariate effects. However, challenges arise when the censoring time is not always observed and may be covariate-dependent, particularly in the presence of continuously-distributed covariates. In spite of several recent advances, existing methods either involve algorithmic complications or impose a probability grid. The former leads to difficulties in the implementation and asymptotics, whereas the latter introduces undesirable grid dependence. To resolve these issues, we develop fundamental and general quantile calculus on cumulative probability scale in this article, upon recognizing that probability and time scales do not always have a one-to-one mapping given a survival distribution. These results give rise to a novel estimation procedure for censored quantile regression, based on estimating integral equations. A numerically reliable and efficient Progressive Localized Minimization (PLMIN) algorithm is proposed for the computation. This procedure reduces exactly to the Kaplan-Meier method in the k-sample problem, and to standard uncensored quantile regression in the absence of censoring. Under regularity conditions, the proposed quantile coefficient estimator is uniformly consistent and converges weakly to a Gaussian process. Simulations show good statistical and algorithmic performance. The proposal is illustrated in the application to a clinical study. PMID:20592942

  17. In vitro import and assembly of the nucleus-encoded mitochondrial subunit III of cytochrome c oxidase (Cox3).

    PubMed

    Vázquez-Acevedo, Miriam; Rubalcava-Gracia, Diana; González-Halphen, Diego

    2014-11-01

    The cox3 gene, encoding subunit III of cytochrome c oxidase (Cox3) is in mitochondrial genomes except in chlorophycean algae, where it is localized in the nucleus. Therefore, algae like Chlamydomonas reinhardtii, Polytomella sp. and Volvox carteri, synthesize the Cox3 polypeptide in the cytosol, import it into mitochondria, and integrate it into the cytochrome c oxidase complex. In this work, we followed the in vitro internalization of the Cox3 precursor by isolated, import-competent mitochondria of Polytomella sp. In this colorless alga, the precursor Cox3 protein is synthesized with a long, cleavable, N-terminal mitochondrial targeting sequence (MTS) of 98 residues. In an import time course, a transient Cox3 intermediate was identified, suggesting that the long MTS is processed more than once. The first processing step is sensitive to the metalo-protease inhibitor 1,10-ortophenantroline, suggesting that it is probably carried out by the matrix-located Mitochondrial Processing Protease. Cox3 is readily imported through an energy-dependent import pathway and integrated into the inner mitochondrial membrane, becoming resistant to carbonate extraction. Furthermore, the imported Cox3 protein was assembled into cytochrome c oxidase, as judged by the presence of a labeled band co-migrating with complex IV in Blue Native Electrophoresis. A model for the biogenesis of Cox3 in chlorophycean algae is proposed. This is the first time that the in vitro mitochondrial import of a cytosol-synthesized Cox3 subunit is described. PMID:24561572

  18. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

    PubMed Central

    Huang, Jian; Zhang, Di; Xie, Fuqiang

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

  19. Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: anti-inflammatory and analgesic activities.

    PubMed

    Alanazi, Amer M; El-Azab, Adel S; Al-Suwaidan, Ibrahim A; ElTahir, Kamal Eldin H; Asiri, Yousif A; Abdel-Aziz, Naglaa I; Abdel-Aziz, Alaa A-M

    2015-03-01

    A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 0.36 ?M; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50 = 0.18 ?M), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 ?), Arg(513) (1.94, 2.83 ?), and Gln(192) (3.25 ?). PMID:25549551

  20. Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy.

    PubMed

    Abdulhag, Ulla Najwa; Soiferman, Devorah; Schueler-Furman, Ora; Miller, Chaya; Shaag, Avraham; Elpeleg, Orly; Edvardson, Simon; Saada, Ann

    2015-02-01

    Isolated cytochrome c oxidase (COX) deficiency is a prevalent cause of mitochondrial disease and is mostly caused by nuclear-encoded mutations in assembly factors while rarely by mutations in structural subunits. We hereby report a case of isolated COX deficiency manifesting with encephalomyopathy, hydrocephalus and hypertropic cardiomyopathy due to a missense p.R20C mutation in the COX6B1 gene, which encodes an integral, nuclear-encoded COX subunit. This novel mutation was predicted to be severe in silico. In accord, enzymatic activity was undetectable in muscle and fibroblasts, was severely decreased in lymphocytes and the COX6B1 protein was barely detectable in patient's muscle mitochondria. Complementation with the wild-type cDNA by a lentiviral construct restored COX activity, and mitochondrial function was improved by 5-aminoimidazole-4-carboxamide ribonucleotide, resveratrol and ascorbate in the patient's fibroblasts. We suggest that genetic analysis of COX6B1should be included in the investigation of isolated COX deficiency, including patients with cardiac defects. Initial measurement of COX activity in lymphocytes may be useful as it might circumvent the need for invasive muscle biopsy. The evaluation of ascorbate supplementation to patients with mutated COX6B1 is warranted. PMID:24781756

  1. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    SciTech Connect

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-?B dependent. Inhibition of NF-?B reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ? Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ? Cyclopamine and jervine induce COX-2 overexpression. ? COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ? Apoptotic potential of jervine is restrained by NF-?B pathway activation. ? PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  2. Impact of Medicaid Prior Authorization Requirement for COX-2 Inhibitor Drugs in Nebraska

    PubMed Central

    Siracuse, Mark V; Vuchetich, Phillip J

    2008-01-01

    Objective Determine the impact of a Prior Authorization Requirement (PAR) program on Medicaid pharmacy expenditures and utilization. Data Source Prescription claims for Nebraska Medicaid recipients who received a cyclooxygenase-2 (COX-2) inhibitor, a nonselective nonsteroidal antiinflammatory (NSAID) drug, or other pain relievers between July 2001 and June 2003. Study Design and Data Collection/Extraction This was a retrospective cross-sectional study with a 12-month pre-PAR implementation period and a 12-month post-PAR implementation period. Pharmacy transactions for COX-2 inhibitors, NSAIDs, other pain relievers, and gastroprotectants were identified by their National Drug Code (NDC) in a Microsoft SQL query. The PAR was designed to approve COX-2 inhibitor use only for recipients at high risk of GI side effects while restricting access to those patients at low to moderate risk of GI side effects. Principal Findings One year following implementation of the PAR, overall expenditures on COX-2 inhibitors for Nebraska Medicaid dropped 50 percent. The overall impact on pharmacy expenditures, including NSAIDs, pain relief medications, and gastroprotectants when necessary to relieve gastrointestinal (GI) side effects, for those recipients who switched from a COX-2 inhibitor to an NSAID or other pain relievers was a decline of approximately 35 percent. Conclusion and Implications for State Policy PAR for COX-2 inhibitors successfully reduced Medicaid prescription expenditures. Recipients at high risk for GI side effects appropriately received COX-2 inhibitors. Recipients at low to moderate risk for GI side effects who were switched to NSAIDs or other pain relievers had lower overall prescription expenditures. Further research is needed to determine the impact of PAR on overall health outcomes and costs. In this study, rather than take a “one size fits all” approach to prescription drug cost-saving strategies, Medicaid policy makers understood that patient variation required accurate identification of disease severity to determine when equally efficacious low-cost alternatives were appropriate. PMID:18199195

  3. NSAID-induced enteropathy: are the currently available selective COX-2 inhibitors all the same?

    PubMed

    Fornai, Matteo; Antonioli, Luca; Colucci, Rocchina; Pellegrini, Carolina; Giustarini, Giulio; Testai, Lara; Martelli, Alma; Matarangasi, Antuela; Natale, Gianfranco; Calderone, Vincenzo; Tuccori, Marco; Scarpignato, Carmelo; Blandizzi, Corrado

    2014-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal damage, but the underlying mechanisms remain poorly understood. The present study investigated the effects of celecoxib, etoricoxib, indomethacin, and diclofenac on small bowel integrity in rats. Male rats were treated orally with test drugs for 14 days. Animals were processed for assessment of blood hemoglobin levels and hepatic mitochondrial functions, microscopic evaluation of small intestinal damage, Western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2) expression, and assay of malondialdehyde (MDA), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) levels in small intestine. Indomethacin and diclofenac decreased blood hemoglobin levels, whereas etoricoxib and celecoxib were without effects. Celecoxib caused a lower degree of intestinal damage in comparison with the other test drugs. Indomethacin and diclofenac, but not etoricoxib or celecoxib, reduced intestinal PGE2 levels. Test drugs did not modify intestinal COX-1 expression, although they enhanced COX-2, with the exception of celecoxib, which downregulated COX-2. Indomethacin, diclofenac, and etoricoxib altered mitochondrial respiratory parameters, although celecoxib was without effects. Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters, whereas in the ileum, etoricoxib, but not celecoxib, increased both MDA and MPO levels. These findings suggest that nonselective NSAIDs and etoricoxib can induce enteropathy through a topic action, whereas celecoxib lacks relevant detrimental actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs and the related effects on prostaglandin production do not appear to play a major role in the pathogenesis of enteropathy. PMID:24135073

  4. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues

    PubMed Central

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    Objective: To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Methods: One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. Results: The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (P<0.05). Spearman’s correlation analysis showed that the expressions of COX-2 and GLUT-1 (r=0.207, P<0.05), COX-2 and VEGF (r=0.243, P<0.05), as well as GLUT-1 and VEGF (r=0.758, P<0.05) were positively correlated. Conclusion: COX-2, GLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer.

  5. A refined method for multivariate meta-analysis and meta-regression.

    PubMed

    Jackson, Daniel; Riley, Richard D

    2014-02-20

    Making inferences about the average treatment effect using the random effects model for meta-analysis is problematic in the common situation where there is a small number of studies. This is because estimates of the between-study variance are not precise enough to accurately apply the conventional methods for testing and deriving a confidence interval for the average effect. We have found that a refined method for univariate meta-analysis, which applies a scaling factor to the estimated effects' standard error, provides more accurate inference. We explain how to extend this method to the multivariate scenario and show that our proposal for refined multivariate meta-analysis and meta-regression can provide more accurate inferences than the more conventional approach. We explain how our proposed approach can be implemented using standard output from multivariate meta-analysis software packages and apply our methodology to two real examples. PMID:23996351

  6. Regression calibration in semiparametric accelerated failure time models.

    PubMed

    Yu, Menggang; Nan, Bin

    2010-06-01

    In large cohort studies, it often happens that some covariates are expensive to measure and hence only measured on a validation set. On the other hand, relatively cheap but error-prone measurements of the covariates are available for all subjects. Regression calibration (RC) estimation method (Prentice, 1982, Biometrika 69, 331-342) is a popular method for analyzing such data and has been applied to the Cox model by Wang et al. (1997, Biometrics 53, 131-145) under normal measurement error and rare disease assumptions. In this article, we consider the RC estimation method for the semiparametric accelerated failure time model with covariates subject to measurement error. Asymptotic properties of the proposed method are investigated under a two-phase sampling scheme for validation data that are selected via stratified random sampling, resulting in neither independent nor identically distributed observations. We show that the estimates converge to some well-defined parameters. In particular, unbiased estimation is feasible under additive normal measurement error models for normal covariates and under Berkson error models. The proposed method performs well in finite-sample simulation studies. We also apply the proposed method to a depression mortality study. PMID:19645700

  7. Selective COX2 inhibitor versus nonselective COX1 and COX2 inhibitor in the prevention of heterotopic ossification after total hip arthroplasty: a meta-analysis of randomised trials

    Microsoft Academic Search

    Deting Xue; Qiang Zheng; Hang Li; Shengjun Qian; Bo Zhang; Zhijun Pan

    2011-01-01

    Whether selective cyclo-oxygenase-2 (COX-2) inhibitors are equally effective compared to nonselective NSAIDs for the prevention\\u000a of heterotopic ossification (HO) after total hip arthroplasty (THA) is still unclear. We carried out a comprehensive search\\u000a strategy, in which only randomised controlled trials were included. Two reviewers independently assessed methodological quality\\u000a and extracted outcome data. Analyses were performed using Stata version 10.0. Four

  8. TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE2 production in cells of the myeloid lineage

    Microsoft Academic Search

    Paola Secchiero; Arianna Gonelli; Giovanni Ciabattoni; Elisabetta Melloni; Vittorio Grill; Bianca Rocca; Giorgio Delbello; Giorgio Zauli

    Tumor necrosis factor-related apopto- sis-inducing ligand (TRAIL) up-regulated the ex- pression of constitutive cyclooxygenase (COX)-1 protein in HL-60 cells without affecting COX-2. The TRAIL-mediated COX-1 up-regulation was ac- companied by a significant increase of the PGE2 synthesis and release, which was suppressed by the COX-1 inhibitor valeryl salicylate but not by the COX-2 inhibitor NS-398. Experiments carried out by adding

  9. Semiparametric regression during 2003–2007*

    PubMed Central

    Ruppert, David; Wand, M.P.; Carroll, Raymond J.

    2010-01-01

    Semiparametric regression is a fusion between parametric regression and nonparametric regression that integrates low-rank penalized splines, mixed model and hierarchical Bayesian methodology – thus allowing more streamlined handling of longitudinal and spatial correlation. We review progress in the field over the five-year period between 2003 and 2007. We find semiparametric regression to be a vibrant field with substantial involvement and activity, continual enhancement and widespread application. PMID:20305800

  10. Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas

    PubMed Central

    Schmidt, T; Sicic, L; Blank, S; Becker, K; Weichert, W; Bruckner, T; Parakonthun, T; Langer, R; Büchler, M W; Siewert, J-R; Lordick, F; Ott, K

    2014-01-01

    Background: Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. Methods: In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. Results: Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. Conclusions: Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker. PMID:24569472

  11. Selective COX-2 inhibitor versus nonselective COX-1 and COX-2 inhibitor in the prevention of heterotopic ossification after total hip arthroplasty: a meta-analysis of randomised trials.

    PubMed

    Xue, Deting; Zheng, Qiang; Li, Hang; Qian, Shengjun; Zhang, Bo; Pan, Zhijun

    2011-01-01

    Whether selective cyclo-oxygenase-2 (COX-2) inhibitors are equally effective compared to nonselective NSAIDs for the prevention of heterotopic ossification (HO) after total hip arthroplasty (THA) is still unclear. We carried out a comprehensive search strategy, in which only randomised controlled trials were included. Two reviewers independently assessed methodological quality and extracted outcome data. Analyses were performed using Stata version 10.0. Four eligible randomised controlled trials totalling 808 patients were included. Meta-analysis results showed that no statistically significant difference was found in overall incidence of HO (RR 1.08; 95% CI 0.71-1.64), incidence of moderate severe HO (Brooker II and III) (RR 0.83; 95% CI 0.48-1.42) and any grade of Brooker classification between two groups. In summary, the selective COX-2 inhibitors are equally effective as nonselective NSAIDs for the prevention of HO after THA. Considering the gastrointestinal side effects of nonselective NSAIDs, we recommend selective COX-2 inhibitors for the prevention of HO after THA. However, future well-designed, randomised controlled trials are still needed to further confirm our results. PMID:19830425

  12. Partial least-squares regression: a tutorial

    Microsoft Academic Search

    PAUL GELADI; BRUCE R. KOWALSKI

    1986-01-01

    SUMMARY A tutorial on the partial least-squares (PLS) regression method is provided. Weak points in some other regression methods are outlined and PLS is developed as a remedy for those weaknesses. An algorithm for a predictive PLS and some practical hints for its use are given. The partial least-squares regression method (PLS) is gaining importance in many fields of chemistry;

  13. Standards for Standardized Logistic Regression Coefficients

    ERIC Educational Resources Information Center

    Menard, Scott

    2011-01-01

    Standardized coefficients in logistic regression analysis have the same utility as standardized coefficients in linear regression analysis. Although there has been no consensus on the best way to construct standardized logistic regression coefficients, there is now sufficient evidence to suggest a single best approach to the construction of a…

  14. Graphical Methods for Assessing Logistic Regression Models

    Microsoft Academic Search

    James M. Landwehr; Daryl Pregibon; Anne C. Shoemaker

    1984-01-01

    In ordinary linear regression, graphical diagnostic displays can be very useful for detecting and examining anomalous features in the fit of a model to data. For logistic regression models, the discreteness of binary data makes it difficult to interpret such displays. Modifications and extensions of linear model displays lead to three methods for diagnostic checking of logistic regression models. Local

  15. An Interactive Approach to Ridge Regression

    ERIC Educational Resources Information Center

    Marquette, J. F.; Dufala, M. M.

    1978-01-01

    Ridge regression is an approach to ameliorating the problem of large standard errors of regression estimates when predictor variables are highly intercorrelated. An interactive computer program is presented which allows for investigation of the effects of using various ridge regression adjustment values. (JKS)

  16. Building Regression Models: The Importance of Graphics.

    ERIC Educational Resources Information Center

    Dunn, Richard

    1989-01-01

    Points out reasons for using graphical methods to teach simple and multiple regression analysis. Argues that a graphically oriented approach has considerable pedagogic advantages in the exposition of simple and multiple regression. Shows that graphical methods may play a central role in the process of building regression models. (Author/LS)

  17. Developmental Regression in Autism: Maternal Perception.

    ERIC Educational Resources Information Center

    Davidovitch, Michael; Glick, Lilach; Holtzman, Gabriela; Tirosh, Emanuel; Safir, Marilyn P.

    2000-01-01

    This study interviewed 39 mothers of young children with autism of whom 19 reported their children had experienced developmental regression, especially in verbal and non-verbal communication and social skills. Mean age of regression was 24 months. There was little difference between children who regressed and those who did not in maternal…

  18. Developmental Regression in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rogers, Sally J.

    2004-01-01

    The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences.…

  19. Ridge Regression Learning Algorithm in Dual Variables

    Microsoft Academic Search

    Craig Saunders; Alexander Gammerman; Volodya Vovk

    1998-01-01

    In this paper we study a dual version of the Ridge Regression procedure. It allows us to perform non-linear regression by construct- ing a linear regression function in a high di- mensional feature space. The feature space representation can result in a large increase in the number of parameters used by the al- gorithm. In order to combat this \\

  20. Sparse multitask regression for identifying common mechanism of response to therapeutic targets

    PubMed Central

    Zhang, Kai; Gray, Joe W.; Parvin, Bahram

    2010-01-01

    Motivation: Molecular association of phenotypic responses is an important step in hypothesis generation and for initiating design of new experiments. Current practices for associating gene expression data with multidimensional phenotypic data are typically (i) performed one-to-one, i.e. each gene is examined independently with a phenotypic index and (ii) tested with one stress condition at a time, i.e. different perturbations are analyzed separately. As a result, the complex coordination among the genes responsible for a phenotypic profile is potentially lost. More importantly, univariate analysis can potentially hide new insights into common mechanism of response. Results: In this article, we propose a sparse, multitask regression model together with co-clustering analysis to explore the intrinsic grouping in associating the gene expression with phenotypic signatures. The global structure of association is captured by learning an intrinsic template that is shared among experimental conditions, with local perturbations introduced to integrate effects of therapeutic agents. We demonstrate the performance of our approach on both synthetic and experimental data. Synthetic data reveal that the multi-task regression has a superior reduction in the regression error when compared with traditional L1-and L2-regularized regression. On the other hand, experiments with cell cycle inhibitors over a panel of 14 breast cancer cell lines demonstrate the relevance of the computed molecular predictors with the cell cycle machinery, as well as the identification of hidden variables that are not captured by the baseline regression analysis. Accordingly, the system has identified CLCA2 as a hidden transcript and as a common mechanism of response for two therapeutic agents of CI-1040 and Iressa, which are currently in clinical use. Contact: b_parvin@lbl.gov PMID:20529943

  1. STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression.

    PubMed

    Wang, J-Y; Sun, J; Huang, M-Y; Wang, Y-S; Hou, M-F; Sun, Y; He, H; Krishna, N; Chiu, S-J; Lin, S; Yang, S; Chang, W-C

    2014-11-10

    Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.Oncogene advance online publication, 10 November 2014; doi:10.1038/onc.2014.366. PMID:25381814

  2. Effects of ?-glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2 (COX-2) in vitro.

    PubMed

    Zhang, Liuqiang; Feng, Li; Jia, Qi; Xu, Jinwen; Wang, Rui; Wang, Zhengtao; Wu, Yingchun; Li, Yiming

    2011-08-15

    Harpagide (1) and harpagoside (2) are two iridoid glycosides existing in many medicinal plants. Although they are believed to be the main bioactive compounds related to the anti-inflammatory efficacy of these plants, the mechanisms of their anti-inflammatory activities remain unclear. The results of our present study showed that 1 and 2 had no effects on inhibitions of cyclooxygenase (COX)-1/2 enzyme activity, tumor necrosis factor-? (TNF-?) release, and nitric oxide (NO) production in vitro. However, the hydrolyzed products of 1 and 2 with ?-glucosidase treatment showed a significant inhibitory effect on COX-2 activity at 2.5-100 ?M in a concentration-dependent manner. Our further study revealed that the hydrolyzed 2 product was structurally the same as the hydrolyzed 1 product (H-harpagide (3)). The structure of 3 was 2-(formylmethyl)-2,3,5-trihydroxy-5-methylcyclopentane carbaldehyde, with a backbone similar to prostaglandins and COX-2 inhibitors such as celecoxib. All of them have a pentatomic ring with two adjacent side chains. The result of molecular modeling and docking study showed that 3 could bind to the COX-2 active domain well through hydrophobic and hydrogen-bonding interactions, whereas 1 and 2 could not, implying that the hydrolysis of the glycosidic bond of 1 and 2 is a pre-requisite step for their COX-2 inhibitory activity. PMID:21775152

  3. Effects of selective cyclooxygenase-2 and non-selective COX inhibition on myocardial function and perfusion

    PubMed Central

    Robich, Michael P.; Chu, Louis M.; Burgess, Thomas A.; Feng, Jun; Bianchi, Cesario; Sellke, Frank W.

    2011-01-01

    Non-selective NSAIDs and selective cyclooxygenase-2 (COX-2) inhibitors are purported to increase adverse cardiovascular events. We hypothesized COX-2 inhibitors would alter myocardial blood flow, microvascular reactivity, oxidative stress, and prostaglandin levels. Adult Yorkshire swine were divided into three groups: no drug (control, n=7), a non-selective COX inhibitor (naproxen 400mg daily, NAP, n=7), or a selective COX-2 inhibitor (celecoxib 200mg daily, CBX, n=7). After 7 weeks physiologic measurements were taken and tissue harvested. Animals in the CBX group demonstrated significantly higher blood pressure and rate pressure product. The NAP and CBX groups demonstrated an increased microvascular contraction response to serotonin. The NAP group showed increased myocardial levels of thromboxane and lower levels of prostacyclin. Levels of protein oxidative stress were increased in the CBX group. Myocardial apoptosis was lowest in the NAP group. Immunoblotting demonstrated decreased VEGF and phospho-eNOS expression in the NAP and CBX groups. Myocardial TNF? was increased in both the NAP and CBX groups. Immunostaining for thromboxane A2 synthase and receptor demonstrated expression within the vascular smooth muscle and no observable differences between groups. Non-selective and selective COX inhibition does not alter myocardial perfusion, but results in altered myocardial and vascular physiology that may have implications regarding cardiovascular risk. PMID:21233641

  4. The Characterization And Role of Zinc Binding in Yeast Cox4

    SciTech Connect

    Coyne, H.J., III; Ciofi-Baffoni, S.; Banci, L.; Bertini, I.; Zhang, L.; George, G.N.; Winge, D.R.; /Utah U. /Florence U. /Saskatchewan U.

    2007-07-09

    Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two {beta} sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

  5. Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in human monocytic cells.

    PubMed

    Wu, Shu-Jing; Ng, Lean-Teik

    2007-01-01

    Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of hang-fang-chi (Stephania tetrandra S. Moore), is traditionally used in China for treating inflammation, hypertension and silicosis. In this study, our aim was to examine the anti-inflammatory mechanism of TET through measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1, and -2 (COX-1 and COX-2) expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin E2 (PGE2) generation in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. Results showed that TET remarkably suppressed the LPS (1 microg/ml) induction of NO release and PGE2 generation. It also significantly attenuated the LPS-induced transcription of proinflammatory cytokines (TNF-alpha, IL-4 and IL-8) in a dose-dependent manner. Furthermore, TET at 100 microM significantly blocked the LPS induction of iNOS and COX-2 expression, but not the COX-1. Taken together, these results suggest that TET exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression. PMID:17202660

  6. Apolipoprotein E3 Inhibits Rho to Regulate the Mechanosensitive Expression of Cox2

    PubMed Central

    Mui, Keeley L.; Liu, Shu-Lin; Assoian, Richard K.

    2015-01-01

    Apolipoprotein E3 (apoE3) is thought to protect against atherosclerosis by enhancing reverse cholesterol transport. However, apoE3 also has cholesterol-independent effects that contribute to its anti-atherogenic properties. These include altering extracellular matrix protein synthesis and inhibiting vascular smooth muscle cell proliferation. Both of these cholesterol-independent effects result from an apoE3-mediated induction of cyclooxygenase-2 (Cox2). Nevertheless, how apoE3 regulates Cox2 remains unknown. Here, we show that apoE3 inhibits the activation of Rho, which reduces the formation of actin stress fibers and focal adhesions and results in cellular softening. Inhibition of Rho-Rho kinase signaling or direct cellular softening recapitulates the effect of apoE3 on Cox2 expression while a constitutively active Rho mutant overrides the apoE3 effect on both intracellular stiffness and Cox2. Thus, our results describe a previously unidentified mechanism by which an atheroprotective apolipoprotein uses Rho to control cellular mechanics and Cox2. PMID:26068461

  7. Vitamin D inhibits COX-2 expression and inflammatory response by targeting thioesterase superfamily member 4.

    PubMed

    Wang, Qingsong; He, Yuhu; Shen, Yujun; Zhang, Qianqian; Chen, Di; Zuo, Caojian; Qin, Jing; Wang, Hui; Wang, Junwen; Yu, Ying

    2014-04-25

    Inadequate vitamin D status has been linked to increased risk of type 2 diabetes and cardiovascular disease. Inducible cyclooxygenase (COX) isoform COX-2 has been involved in the pathogenesis of such chronic inflammatory diseases. We found that the active form of vitamin D, 1,25(OH)2D produces dose-dependent inhibition of COX-2 expression in murine macrophages under both basal and LPS-stimulated conditions and suppresses proinflammatory mediators induced by LPS. Administration of 1,25(OH)2D significantly alleviated local inflammation in a carrageenan-induced paw edema mouse model. Strikingly, the phosphorylation of both Akt and its downstream target I?B? in macrophages were markedly suppressed by 1,25(OH)2D in the presence and absence of LPS stimulation through up-regulation of THEM4 (thioesterase superfamily member 4), an Akt modulator protein. Knockdown of both vitamin D receptor and THEM4 attenuated the inhibitory effect of 1,25(OH)2D on COX-2 expression in macrophages. A functional vitamin D-responsive element in the THEM4 promoter was identified by chromatin immunoprecipitation and luciferase reporter assay. Our results indicate that vitamin D restrains macrophage-mediated inflammatory processes by suppressing the Akt/NF-?B/COX-2 pathway, suggesting that vitamin D supplementation might be utilized for adjunctive therapy for inflammatory disease. PMID:24619416

  8. A univariate analysis of variance design for multiple-choice feeding-preference experiments: A hypothetical example with fruit-eating birds

    NASA Astrophysics Data System (ADS)

    Larrinaga, Asier R.

    2010-01-01

    I consider statistical problems in the analysis of multiple-choice food-preference experiments, and propose a univariate analysis of variance design for experiments of this type. I present an example experimental design, for a hypothetical comparison of fruit colour preferences between two frugivorous bird species. In each fictitious trial, four trays each containing a known weight of artificial fruits (red, blue, black, or green) are introduced into the cage, while four equivalent trays are left outside the cage, to control for tray weight loss due to other factors (notably desiccation). The proposed univariate approach allows data from such designs to be analysed with adequate power and no major violations of statistical assumptions. Nevertheless, there is no single "best" approach for experiments of this type: the best analysis in each case will depend on the particular aims and nature of the experiments.

  9. Reciprocal Benefits of Mass-Univariate and Multivariate Modeling in Brain Mapping: Applications to Event-Related Functional MRI, H2 15O-, and FDG-PET

    PubMed Central

    Habeck, Christian G.

    2006-01-01

    In brain mapping studies of sensory, cognitive, and motor operations, specific waveforms of dynamic neural activity are predicted based on theoretical models of human information processing. For example in event-related functional MRI (fMRI), the general linear model (GLM) is employed in mass-univariate analyses to identify the regions whose dynamic activity closely matches the expected waveforms. By comparison multivariate analyses based on PCA or ICA provide greater flexibility in detecting spatiotemporal properties of experimental data that may strongly support alternative neuroscientific explanations. We investigated conjoint multivariate and mass-univariate analyses that combine the capabilities to (1) verify activation of neural machinery we already understand and (2) discover reliable signatures of new neural machinery. We examined combinations of GLM and PCA that recover latent neural signals (waveforms and footprints) with greater accuracy than either method alone. Comparative results are illustrated with analyses of real fMRI data, adding to Monte Carlo simulation support. PMID:23165047

  10. Synthesis and biological evaluation of linear phenylethynylbenzenesulfonamide regioisomers as cyclooxygenase-1\\/-2 (COX1\\/-2) inhibitors

    Microsoft Academic Search

    Raymond Anana; P. N. Praveen Rao; Qiao-Hong Chen; Edward E. Knaus

    2006-01-01

    A group of regioisomeric phenylethynylbenzenesulfonamides possessing a COX-2 SO2NH2 pharmacophore at the para-, meta- or ortho-position of the C-1 phenyl ring, in conjunction with a C-2 substituted-phenyl (H, OMe, OH, Me, F) group, were synthesized and evaluated as inhibitors of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isozymes. The target 1,2-diphenylacetylenes were synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. In vitro

  11. Mechanisms of Vessel Pruning and Regression.

    PubMed

    Korn, Claudia; Augustin, Hellmut G

    2015-07-01

    The field of angiogenesis research has primarily focused on the mechanisms of sprouting angiogenesis. Yet vascular networks formed by vessel sprouting subsequently undergo extensive vascular remodeling to form a functional and mature vasculature. This "trimming" includes distinct processes of vascular pruning, the regression of selected vascular branches. In some situations complete vascular networks may undergo physiological regression. Vessel regression is an understudied yet emerging field of research. This review summarizes the state-of-the-art of vessel pruning and regression with a focus on the cellular processes and the molecular regulators of vessel maintenance and regression. PMID:26151903

  12. Factors Affecting the Survival of Patients with Gastric Cancer Undergone Surgery at Iran Cancer Institute: Univariate and Multivariate Analyses

    PubMed Central

    ZARE, Ali; MAHMOODI, Mahmood; MOHAMMAD, Kazem; ZERAATI, Hojjat; HOSSEINI, Mostafa; HOLAKOUIE NAIENI, Kourosh

    2014-01-01

    Abstract Background Gastric cancer is the most prevalent cancer among men and the third most prevalent cancer among women in Iran. Its most important reason for death is its belated diagnosis at the advanced stages of the disease. Various factors can be effective on the survival of these patients after surgery, which are the major concern in this study. Methods Data from 330 patients with Gastric cancer who had undergone surgery at Iran Cancer Institute from 1995 to 1999 were analyzed. The Survival Time of patients was determined after surgery and the effect of individual and demographic; clinical and diagnostic; and treatment and post-surgical factors on patients’ survival was studied. For data analysis, Kaplan- Meier, Log-Rank test and Proportional Hazards Model were used. Results The median of survival time was 16.33 months. The one-year, three-year, and five-year survival rates were, 0.66, 0.31, and 0.21. Based on univariate analysis results of age(P<0.001), metastases(P=0.012), disease stage(P=0.016), and number of renewed treatments(P<0.001), as well as multivariate analysis which was used to investigate the simultaneous effect of influencing variables on patients’ survival showed that age(61?70:HR=1.40,>70:HR=2.08), marital status(HR=0.39), number of renewed treatments(1:HR=0.54, 2:HR=0.30, 3:HR=0.22), relapse(HR=1.51), type of gastrectomy (Subtotal: HR=1.12, Distal:HR=0.49, Partial:HR=0.94, Proximal:HR=0.52), liver metastases (HR=1.79), distance metastases(HR=1.84), and disease stage(II:HR=1.28, III:HR=2.12, IV:HR=1.90) variables had a significant effect on patients’ survival. Conclusion Patients who call on doctors in early stages of disease will have a higher survival rate due to early diagnosis whereas disease progression will increase the risk and will decrease the survival. Identifying factors affecting patients’ survival and improving diagnostic methods can prevent disease progression and increase survival rate.

  13. 2-Carbaborane-3-phenyl-1H-indoles--synthesis via McMurry reaction and cyclooxygenase (COX) inhibition activity.

    PubMed

    Laube, Markus; Neumann, Wilma; Scholz, Matthias; Lönnecke, Peter; Crews, Brenda; Marnett, Lawrence J; Pietzsch, Jens; Kniess, Torsten; Hey-Hawkins, Evamarie

    2013-02-01

    Cyclooxygenase-2 (COX-2) inhibitors have been the focus of medicinal chemistry efforts for years, and many compounds that exhibit high selectivity and affinity have been developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX-2-selective 2,3-disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2-carbaborane-3-phenyl-1H-indoles could be synthesized by McMurry cyclization of the corresponding amides. Whereas the meta-carbaboranyl-substituted derivatives lacked COX inhibitory activity, an ortho-carbaboranyl analogue was active, but showed a selectivity shift toward COX-1. PMID:23303738

  14. Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE2 and HGF Expression via a Positive Feedback Loop

    PubMed Central

    Byun, Ji Yeon; Youn, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Woo, So-Yeon; Kang, Jihee Lee

    2014-01-01

    Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition. PMID:24959005

  15. Nectandra amazonum-derived flavonoids as COX-1 inhibitors: in vitro and docking studies.

    PubMed

    Valdés-Barrera, Iván Daniel; Cuca-Suarez, Luis Enrique; Coy-Barrera, Ericsson David

    2014-05-01

    The ability of eleven known flavonoids isolated from Nectandra amazonum (Lauraceae) was tested for in vitro PGHS (COX) inhibition. All test compounds exhibited a dose dependent activity at different levels, exhibiting selectivity towards COX-I inhibition. Autodock Vina was used to dock the compound structures within the active site of the PGHS-1 (PDB: 3N8V). In vitro results showed that chalcone and dihydrochalcone-related compounds exhibited reasonable inhibitory properties (IC50: 1.56-36.5 microM), with good correlation with docking results. Argl20 (or Tyr355) and Ser530 were found to be the key residues to dock the most active flavonoids, indicating such interaction might interfere with the formation of prostaglandin H2 in the active site of COX-I. PMID:25026711

  16. ?–3 Fatty Acids, Genetic Variants in COX-2 and Prostate Cancer

    PubMed Central

    Reese, Adam C.; Fradet, Vincent; Witte, John S.

    2009-01-01

    Dietary intake of fish and ?–3 polyunsaturated fatty acids (?–3 PUFAs) may decrease the risk of prostate cancer development and progression to advanced stage disease. This could reflect the anti-inflammatory effects of PUFAs, possibly through mediation of cyclooxygenase (COX), a key enzyme in fatty acid metabolism and inflammation. Despite promising experimental evidence, epidemiological studies have reported somewhat conflicting results regarding the effects of fish/PUFAs on prostate cancer development and progression. The literature suggests that fish, and particularly long-chain ?–3 PUFAs, may have a more pronounced protective effect on biologically aggressive tumors or on their progression, and less on early steps of carcinogenesis. Moreover, the impact of LC ?–3 PUFAs may be modified by variation of the COX-2 gene. Overall, results to date support the hypothesis that long-chain ?–3 PUFAs may impact prostate inflammation and carcinogenesis via the COX-2 enzymatic pathway. PMID:19776642

  17. Effusanin E Suppresses Nasopharyngeal Carcinoma Cell Growth by Inhibiting NF-?B and COX-2 Signaling

    PubMed Central

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    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-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  18. Population impact of regulatory activity restricting prescribing of COX-2 inhibitors: ecological study

    PubMed Central

    Wheeler, Benedict W; Metcalfe, Chris; Gunnell, David; Stephens, Peter; Martin, Richard M

    2009-01-01

    AIMS To investigate impacts of withdrawal and regulatory advice regarding cyclooxygenase-2 (COX-2) inhibitors on UK population rates of gastrointestinal haemorrhage and acute myocardial infarction (MI). METHODS Ecological time series study of prescribing, mortality and hospital admission trends in people aged ?55 years. RESULTS Withdrawal and regulatory advice limiting COX-2 inhibitor availability from 2004 were temporally associated with reversal of previously unfavourable trends in emergency MI admissions among people aged ?65 years. Annual admission rate trends changed from +4.6% to ?3.1% (P < 0.001) among women and from +2.1% to ?3.8% (P= 0.003) among men. Absolute changes in average annual trend in the number of individuals aged ?65 years admitted following MI were from +981 (1999–2004) to ?819 (2004–2006) per year for women and from +713 to ?995 for men. No change in trend was apparent among people aged 55–64 years, or in MI mortality trends. There was some suggestion of an unfavourable change in admission trends for gastrointestinal haemorrhage among 55?64-year-olds, although this appeared to occur prior to COX-2 inhibitor withdrawal/regulation by up to 2 years. These trends were not apparent in older people, or in gastrointestinal haemorrhage mortality rates. CONCLUSIONS Withdrawal/regulation of COX-2 inhibitors was temporally associated with a favourable reversal of population-level hospital admission trends in MI among people aged ?65 years. Unfavourable reversal of previous declines in gastrointestinal haemorrhage admissions probably occurred before changes in COX-2 inhibitor availability. Withdrawal/ regulation of COX-2 inhibitors did not appear to have any adverse impact on population health and may have been beneficial. PMID:19917000

  19. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-?B and COX-2 signaling.

    PubMed

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    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-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  20. The First Characterization of Free Radicals Formed From Cellular COX-Catalyzed Peroxidation

    PubMed Central

    Gu, Yan; Xu, Yi; Law, Benedict; Qian, Steven Y.

    2014-01-01

    Through free radical-mediated peroxidation, cyclooxygenase (COX) can metabolize dihomo-?-linolenic acid (DGLA) and arachidonic acid(AA) to form well-known bioactive metabolites, namely, the 1-series of prostaglandins (PGs1) and 2-series of prostaglandins(PGs2), respectively. Unlike PGs2, which are generally viewed as pro-inflammatory and pro-carcinogenic PGs, PGs1 may possess anti-inflammatory and anti-cancer activity. Previous studies using ovine COX along with spin trapping and the LC/ESR/MS technique have shown that certain exclusive free radicals are generated from different free radical reactions in DGLA and AA peroxidation. However, it has been unclear whether the differences were associated with the contrasting bioactivity of DGLA vs. AA. The aim of this study was to refine the LC/MS and spin-trapping technique to make it possible for the association between free radicals and cancer cell growth to be directly tested. Using a colon cancer cell line, HCA-7 colony 29, and LC/MS along with a solid phase extraction, we were able to characterize the reduced forms of radical adducts (hydroxylamines) as the free radicals generated from cellular COX-catalyzed peroxidation. For the first time, free radicals formed in the COX-catalyzed peroxidation of AA vs. DGLA and their association with cancer cell growth was assessed (cell proliferation via MTS and cell cycle distribution via PI staining) in the same experimental setting. The exclusive free radicals formed from the COX-catalyzed peroxidation of AA and DGLA were shown to be correlated with the cell growth response. Our results indicate that free radicals generated from the distinct radical reactions in COX-catalyzed peroxidation may represent the novel metabolites of AA and DGLA that correspond to their contrasting bioactivity. PMID:23261941

  1. Signal Transduction Pathway Analysis in Desmoid-type Fibromatosis: TGF?, COX2 and Sex Steroid Receptors

    PubMed Central

    Mignemi, Nicholas A.; Itani, Doha M.; Fasig, John H.; Keedy, Vicki L.; Hande, Kenneth R.; Whited, Brent W.; Homlar, Kelly C.; Correa, Hernan; Coffin, Cheryl M.; Black, Jennifer O.; Yi, Yajun; Halpern, Jennifer L.; Holt, Ginger E.; Schwartz, Herbert S.; Schoenecker, Jonathan G.; Cates, Justin M. M.

    2014-01-01

    Summary Despite reports of sex steroid receptor and COX2 expression in desmoid-type fibromatosis, responses to single agent therapy with anti-estrogens and nonsteroidal anti-inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co-express these targets. Clearly, a further understanding of the signaling pathways deregulated in desmoid tumors is essential for development of targeted molecular therapy. Transforming growth factor-? (TGF?) and bone morphogenetic proteins (BMPs) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGF? superfamily in fibromatosis. A tissue microarray representing 27 desmoid tumors was constructed; 14 samples of healing scar and 6 samples of normal fibrous tissue were included for comparison. Expression of selected receptors and activated downstream transcription factors of TGF? family signaling pathways, ?-catenin, sex steroid hormone receptors and COX2 were assessed by immunohistochemistry; patterns of co-expression were explored via correlational statistical analyses. In addition to ?-catenin, immunoreactivity for phosphorylated SMAD2/3 (indicative of active TGF? signaling) and COX2 was significantly increased in desmoid tumors compared to healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD1/5/8 were detected in only a minority of cases. TGF? receptor type 1 and androgen receptor were expressed in both desmoid tumors and scar, but not in fibrous tissue. Estrogen receptor-? was present in all cases studied. TGF? signaling appears to be activated in desmoid-type fibromatosis and phosphorylated SMAD2/3 and COX2 immunoreactivity may be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor-? and COX2 co-expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX2 inhibitors should be considered. PMID:23035734

  2. Effects of selective cyclooxygenase-2 and non-selective COX inhibition on ischemic myocardium

    PubMed Central

    Robich, Michael P.; Chu, Louis M.; Feng, Jun; Burgess, Thomas A.; Laham, Roger J.; Bianchi, Cesario; Sellke, Frank W.

    2010-01-01

    Objective We sought to explore the effects of non-selective COX and selective COX-2 inhibition on collateral development in a model of chronic myocardial ischemia. We hypothesized that COX-2 inhibitors will negatively effect angiogenic and inflammatory pathways. Methods Yorkshire swine were made chronically ischemic by placing an ameroid constrictor on the left circumflex coronary artery. Swine were divided into three groups and given: no drug (control, n=7), a non-selective COX inhibitor (naproxen 400mg daily, NAP, n=7), or a selective COX-2 inhibitor (celecoxib 200mg daily, CBX, n=7). After 7 weeks, coronary angiography was performed. Myocardial function and microvascular reactivity were assessed. Serum and myocardial tissue were analyzed for prostaglandin levels and markers of inflammation and angiogenesis. Results The CBX group demonstrated significantly increased mean arterial pressure and decreased left ventricular function. Myocardial perfusion in the CBX group was similar to the control, but less than in the NAP group. Coronary microvascular contraction in the collateral dependent territory was increased in the NAP group, but minimally affected in the CBX group. Oxidative stress and apoptosis were increased in the CBX group. Expression of angiogenic markers, VEGF and phospho-eNOS (ser1177), and tissue levels of prostacyclin were decreased in both the CBX and NAP groups. The NAP group had diminished expression of endostatin. Conclusion The effects of selective and non-selective COX inhibition are more complex than previously published, but they do not decrease collateral dependent blood flow to the myocardium in our model of chronic myocardial ischemia. PMID:20804993

  3. Recognition of caudal regression syndrome.

    PubMed

    Boulas, Mari M

    2009-04-01

    Caudal regression syndrome, also referred to as caudal dysplasia and sacral agenesis syndrome, is a rare congenital malformation characterized by varying degrees of developmental failure early in gestation. It involves the lower extremities, the lumbar and coccygeal vertebrae, and corresponding segments of the spinal cord. This is a rare disorder, and true pathogenesis is unclear. The etiology is thought to be related to maternal diabetes, genetic predisposition, and vascular hypoperfusion, but no true causative factor has been determined. Fetal diagnostic tools allow for early recognition of the syndrome, and careful examination of the newborn is essential to determine the extent of the disorder. Associated organ system dysfunction depends on the severity of the disease. Related defects are structural, and systematic problems including respiratory, cardiac, gastrointestinal, urinary, orthopedic, and neurologic can be present in varying degrees of severity and in different combinations. A multidisciplinary approach to management is crucial. Because the primary pathology is irreversible, treatment is only supportive. PMID:19363325

  4. Atomic structure and magnetic properties of Fe1-xCox alloys

    SciTech Connect

    Nguyen, Manh Cuong; Zhao, Xin; Ji, Min; Wang, Cai-Zhuang; Harmon, Bruce; Ho, Kai-Ming

    2012-03-09

    Using genetic algorithm with first-principle calculations, we searched for low-energy crystal structures of Fe1?xCox alloys. We found that Fe1?xCox alloys are highly configurationally degenerate with many additional off-stoichiometric stable structures to the well-known B2 structure. The average magnetic moment of Fe atom increases with concentration of Co in the alloy, while that of Co atom is almost constant, which are consistent with experiments and earlier studies. The magnetic moment of Fe atom is strongly dependent on the number of Co nearest neighbor and it increases with this number.

  5. Global structure in spatiotemporal chaos of the Matthews-Cox equations.

    PubMed

    Sakaguchi, Hidetsugu; Tanaka, Dan

    2007-08-01

    We find that an amplitude death state and a spatiotemporally chaotic state coexist spontaneously in the Matthews-Cox equations and this coexistence is robust. Although the entire system is far from equilibrium, the domain wall between the two states is stabilized by a negative-feedback effect due to a conservation law. This is analogous to the phase separation in conserved systems that exhibit spinodal decompositions. We observe similar phenomena also in the Nikolaevskii equation, from which the Matthews-Cox equations were derived. A Galilean invariance of the former equation corresponds to the conservation law of the latter equations. PMID:17930094

  6. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives.

    PubMed

    Cho, Heeyeong; Yun, Cheol-Won; Park, Woo-Kyu; Kong, Jae-Yang; Kim, Kyoung Soon; Park, Youmie; Lee, Sanghyun; Kim, Bak-Kwang

    2004-01-01

    Chrysin, a natural flavone compound found in plants, has anti-inflammatory activity that has been previously explained in part by the suppression of promoter activities of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Here we present evidence that several chrysin derivatives modulate the activities, as well as the expression, of COX-2 and iNOS enzymes. Nitrate production triggered by lipopolysaccharide (LPS) was suppressed by treatment of cultured Raw264.7 cells (mice macrophage/monocyte) with chrysin, 5-hydroxy-7-methoxyflavone (Ch-2), and 5,7-diacetylflavone (Ch-4). Interestingly, COX-2 enzyme was strongly inhibited by Ch-4 (IC(50)=2.7 microM) but not by other derivatives. Furthermore, the inhibition of COX enzyme by Ch-4 was selective for COX-2 over COX-1. Three-dimensional modeling showed that Ch-4 fits well into the binding pocket of COX-2. The modeling suggested that a hydrogen bond exists between the oxygen of the ketone group at the 7-position of Ch-4 and the hydroxyl group of Tyr355. Docking Ch-4 into the V523I mutant of COX-2 indicated that Ile523 of COX-1 might contribute to the selectivity of COX-2 over COX-1. Ch-4 showed no effect on iNOS activity. Chrysin and Ch-2 weakly inhibited iNOS enzyme activity in the hemoglobin assay, but the underlying mechanisms of inhibition of iNOS by chrysin are not understood. PMID:14597150

  7. Comparative study between univariate spectrophotometry and multivariate calibration as analytical tools for simultaneous quantitation of Moexipril and Hydrochlorothiazide.

    PubMed

    Tawakkol, Shereen M; Farouk, M; Elaziz, Omar Abd; Hemdan, A; Shehata, Mostafa A

    2014-12-10

    Three simple, accurate, reproducible, and selective methods have been developed and subsequently validated for the simultaneous determination of Moexipril (MOX) and Hydrochlorothiazide (HCTZ) in pharmaceutical dosage form. The first method is the new extended ratio subtraction method (EXRSM) coupled to ratio subtraction method (RSM) for determination of both drugs in commercial dosage form. The second and third methods are multivariate calibration which include Principal Component Regression (PCR) and Partial Least Squares (PLSs). A detailed validation of the methods was performed following the ICH guidelines and the standard curves were found to be linear in the range of 10-60 and 2-30 for MOX and HCTZ in EXRSM method, respectively, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits. PMID:24954754

  8. Hypnotic age regression and moral reasoning.

    PubMed

    Page, R A

    1985-01-01

    Moral reasoning was assessed with two dilemmas from the Kohlberg Moral Judgment Interview (1976) in 7 adults who were hypnotically age regressed to four ages: 15, 12, 9, and 6 years. Seven adults in a control group under task-motivation instructions were age regressed to the same ages and administered the dilemmas. Age-regressed moral maturity scores for both groups were compared to pretest scores, to data for actual 15-, 12-, 9-, and 6-year-olds from other studies, and to each other. Both groups were able to lower their moral reasoning scores when given age-regression instructions; however, hypnosis subjects not only scored lower than task-motivation subjects but also more closely resembled the levels of reasoning used by children at these ages. The results provide some support for a distinction between age regression through hypnosis and age regression through task-motivation instructions. PMID:3989741

  9. JTE-522, a selective COX2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats

    Microsoft Academic Search

    Hirotoshi Kobayashi; Hiroyuki Uetake; Tetsuro Higuchi; Masayuki Enomoto; Kenichi Sugihara

    2005-01-01

    BACKGROUND: Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model. METHODS: A suspension of 5 × 106 RCN-9 (rat colon cancer

  10. Chemical Engineering Journal 93 (2003) 6980 Production of COx-free hydrogen for fuel cells via step-wise hydrocarbon

    E-print Network

    Goodman, Wayne

    2003-01-01

    Chemical Engineering Journal 93 (2003) 69­80 Production of COx-free hydrogen for fuel cells via Abstract The stringent COx-free hydrogen requirement for the current low temperature fuel cells has Hydrogen is the most promising fuel for the low temper- ature fuel cells, however, chemical processes

  11. Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs

    PubMed Central

    Whiteley, Mary H.; Bell, Jerold S.; Rothman, Debby A.

    2011-01-01

    Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs. PMID:21346820

  12. Mutations in C12orf62, a Factor that Couples COX I Synthesis with Cytochrome c Oxidase

    E-print Network

    Shoubridge, Eric

    Assembly, Cause Fatal Neonatal Lactic Acidosis Woranontee Weraarpachai,1 Florin Sasarman,1 Tamiko Nishimura classical Leigh syndrome, the French-Canadian form of Leigh syndrome, fatal infantile COX deficiency, cardiomy- opathy, myopathy, fatal infantile lactic acidosis, and a reversible COX deficiency in muscles1

  13. Angiotensin-(1-7)-Induced Plasticity Changes in the Lateral Amygdala Are Mediated by COX-2 and NO

    ERIC Educational Resources Information Center

    Albrecht, Doris

    2007-01-01

    It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we…

  14. 1,2-Diaryl-2-hydroxyiminoethanones as dual COX-1 and ?-amyloid aggregation inhibitors: biological evaluation and in silico study.

    PubMed

    Irannejad, Hamid; Unsal Tan, Oya; Ozadali, Keriman; Dadashpour, Sakineh; Tuylu Kucukkilinc, Tuba; Ahangar, Nematollah; Ahmadnejad, Mahsa; Emami, Saeed

    2015-04-01

    To find out new agents for treating inflammatory-involved diseases such as Alzheimer's disease, a series of 1,2-diaryl-2-hydroxyiminoethanones containing vicinal diaryl pharmacophore of COX inhibitors were tested by a set of in vitro, in vivo, and computational studies. The in vivo study of compounds indicated their prominent anti-inflammatory ability at the doses of 10 and 20 mg/kg comparable to celecoxib (10 mg/kg). Further in vitro COX-1/COX-2 evaluations revealed that 4-methoxy derivative 3 had a high selective COX-1 inhibitory activity (COX-1, IC50=0.12 ?m, SI>833). To evaluate their potential use against Alzheimer's disease, in vitro evaluation of ?-amyloid fibril formation using A?(1-40) and A?(1-42) peptides was performed. The evaluation of their antiaggregation ability gave impressive results and comparable to rifampicin and indomethacin. Conformational study of compound 3 and subsequent docking of its restrained analogs on both active sites of COX-1 and COX-2 could provide a proof of its COX-1 selectivity as well as molecular dynamic simulation could elucidate and give more insight into the amyloid disaggregation mechanisms leading to rational design of inhibitors. PMID:25227162

  15. The role of COX2 in intestinal inflammation and colorectal cancer

    Microsoft Academic Search

    D Wang; R N DuBois

    2010-01-01

    Colorectal cancer (CRC) is a heterogeneous disease, including at least three major forms: hereditary, sporadic and colitis-associated CRC. A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet and lifestyle are the risk factors for CRC. As elevated cyclooxygenase-2 (COX-2) expression was found in most CRC tissue and is associated with worse survival among CRC patients,

  16. Catalytic ammonia decomposition: COx-free hydrogen production for fuel cell applications

    Microsoft Academic Search

    T. V. Choudhary; C. Sivadinarayana; D. W. Goodman

    2001-01-01

    Catalytic decomposition of ammonia has been investigated as a method to produce hydrogen for fuel cell applications. The absence of any undesirable by-products (unlike, e.g., COx, formed during reforming of hydrocarbons and alcohols) makes this process an ideal source of hydrogen for fuel cells. In this study a variety of supported metal catalysts have been studied. Supported Ru catalysts were

  17. Solvent Effects on the Barrier to Rotation in Christopher Cox and Thomas Lectka*

    E-print Network

    Lectka, Thomas

    Solvent Effects on the Barrier to Rotation in Carbamates Christopher Cox and Thomas Lectka and understand the barrier to rotation about the C-N bond in amides.1 Carbamates, which also exhibit amides and carbamates share common features, the additional oxygen of the carbamate functionality exerts

  18. Visual textures as realizations of multivariate log-Gaussian Cox processes

    Microsoft Academic Search

    Huu-Giao Nguyen; Ronan Fablet; Jean-Marc Boucher

    2011-01-01

    In this paper, we address invariant keypoint-based texture characterization and recognition. Viewing keypoint sets associated with visual textures as realizations of point processes, we investigate probabilistic texture models from multivariate log-Gaussian Cox processes. These models are parameterized by the covariance structure of the spatial patterns. Their implementation initially rely on the construction of a codebook of the visual signatures of

  19. Elevated COX2 expression and PGE2 production by downregulation of RXR? in senescent macrophages

    SciTech Connect

    Chen, Huimin, E-mail: huiminchen.jq@gmail.com [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China)] [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China); Ma, Feng [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China)] [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China); Hu, Xiaona; Jin, Ting; Xiong, Chuhui [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)] [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China); Teng, Xiaochun, E-mail: tengxiaochun@126.com [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)] [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)

    2013-10-11

    Highlights: •Downregulation of RXR? in senescent macrophage. •RXR? suppresses NF-?B activity and COX2 expression. •Increased PGE2 production due to downregulation of RXR?. -- Abstract: Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXR?, a nuclear receptor that can suppress NF-?B activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXR? agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXR? antagonist HX531 in young mice increases COX2, TNF-?, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-?B activity and PGE2 production in senescent macrophages, but also provides RXR? as a potential therapeutic target for treating the age-related diseases.

  20. Preoperative use of selective COX-II inhibitors for pain management in laparoscopic nissen fundoplication

    Microsoft Academic Search

    Z. Alanoglu; Y. Ate?; B. C. Orbey; A. G. Türkçapar

    2005-01-01

    Background: This randomized, double-blind, prospective, placebo controlled study was planned to determine the effectiveness of selective COX-II inhibitors used preoperatively to alleviate pain after Nissen fundoplication surgery. Methods: For this study, 60 patients were allocated to four groups at random: group C (celecoxib, 200 mg by mouth), group R (rofecoxib, 50 mg by mouth), group P (placebo, pill), or group

  1. COX2 is necessary for venous ligation-mediated bone adaptation in mice

    Microsoft Academic Search

    H. Y. Stevens; D. R. Meays; J. Yeh; L. M. Bjursten; J. A. Frangos

    2006-01-01

    In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by

  2. Distance-Dependent Proton Transfer along Water Wires Connecting Acid-Base Pairs M. Jocelyn Cox,

    E-print Network

    Agmon, Noam

    Distance-Dependent Proton Transfer along Water Wires Connecting Acid-Base Pairs M. Jocelyn Cox for the ultrafast acid-base reaction between photoexcited 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt that connect acid-base pairs in solution. The concerted nature of the proton transfer is supported by the fact

  3. Modeling Charitable Giving Using a Box-Cox Standard Tobit Model

    Microsoft Academic Search

    R. Hamilton Lankford; James S. Wyckoff

    1991-01-01

    There is a large literature investigating the determinants of charitable giving, in particular, price and income elasticities. We find that many of the most often reported results from this literature rely on a model specification that is inappropriate when applied to recent Federal Tax File data. We develop a standard Tobit model with a Box-Cox transformation parameter that nests a

  4. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization.

    PubMed

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. PMID:25770423

  5. RedFlag: Reducing Inadvertent Leaks by Personal Machines Landon P. Cox and Peter Gilbert

    E-print Network

    Cox, Landon

    RedFlag: Reducing Inadvertent Leaks by Personal Machines Landon P. Cox and Peter Gilbert Duke to prevent confidential data from leaking. Un- fortunately, sensitive data is increasingly stored on per their sensitive files. This often leads to misconfigured applications and dam- aging leaks. In this paper, we

  6. RNA editing of mitochondrial functional genes atp6 and cox2 in maize ( Zea mays L.)

    Microsoft Academic Search

    Jing Wang; Mo Ju Cao; Guang Tang Pan; Yan Li Lu; Ting Zhao Rong

    2009-01-01

    RNA editing of two mitochondrial or organs genes, atp6 and cox2, in different tissues were analyzed using homonucleic but alloplasmic, and homoplasmic but heteronucleic maize (zea mays L.) as experimental materials. A total of 18 and 26 editing sites for atp6 conservative region transcript were identified by direct and clone sequencing, respectively. By direct sequencing 23 and 22 editing sites

  7. ORIGINAL PAPER H. H. J. Cox T. T. Nguyen M. A. Deshusses

    E-print Network

    pollutant degradation in the liquid phase are identi®ed and discussed. Materials and methods ExperimentalORIGINAL PAPER H. H. J. Cox á T. T. Nguyen á M. A. Deshusses Toluene degradation in the recycle November 1999 / Accepted: 15 December 1999 Abstract Pollutant degradation in biotrickling ®lters for waste

  8. Food contaminant acrylamide increases expression of Cox-2 and nitric oxide synthase in breast epithelial cells.

    PubMed

    Lyn-Cook, Lascelles E; Tareke, Eden; Word, Beverly; Starlard-Davenport, Athena; Lyn-Cook, Beverly D; Hammons, George J

    2011-02-01

    Acrylamide has been discovered in foods cooked at high temperature. A potentially harmful effect of this dietary component has been suggested by data indicating its association with increased breast cancer. This study investigated the potential effects of acrylamide in nontumorigenic breast cells by assessing expression levels of inducible nitric oxide synthase (iNOS) and cycloogenase-2 (Cox-2) and NOS activity, which are known to be early molecular changes in disease formation. Treatment of cells with acrylamide increased levels of iNOS (both expression and activity) and Cox-2. Its potent metabolite, glycidamide, also induced both iNOS and Cox-2, with induction of iNOS occurring at a lower concentration. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), another food-borne carcinogen, was found to induce Cox-2 expression. Combining acrylamide with PhIP did not result in a further increase. These studies suggest that further research is needed to determine the role of carcinogens formed from cooking foods in inducing early molecular changes associated with breast cancer. PMID:20713430

  9. Phil Cox Takes on APPA Presidency with Energy, Experience, and Commitment.

    ERIC Educational Resources Information Center

    Thaler-Carter, Ruth E.

    2002-01-01

    Describes the background, experience, and goals of Philip L. Cox, the new president of APPA, the Association of Higher Education Facilities Officers, who currently serves as director of facilities management for Cornell University in Ithaca, New York. Explores his vision for APPA. (EV)

  10. Systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov (Hemiptera: Pseudococcidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov is presented. Nine species are treated, including D. millari which is described as new. The 8 previously described species are: Delottococcus aberiae (De Lotto), D. confusus (De Lotto), D. elisabethae (Brain), D. euphorbiae (E...

  11. Ruin probabilities and aggregrate claims distributions for shot noise Cox processes

    Microsoft Academic Search

    Hansjörg Albrecher; Søren Asmussen c

    2006-01-01

    We consider a risk process Rt where the claim arrival process is a superposition of a homogeneous Poisson process and a Cox process with a Poisson shot noise intensity process, capturing the effect of sudden increases of the claim intensity due to external events. The distribution of the aggregate claim size is investigated under these assumptions. For both light-tailed and

  12. MR Findings in Leigh Syndrome with COX Deficiency and SURF1 Mutations

    Microsoft Academic Search

    Laura Farina; Luisa Chiapparini; Graziella Uziel; Marianna Bugiani; Massimo Zeviani; Mario Savoiardo

    BACKGROUND AND PURPOSE: In a large number of patients with Leigh syndrome (LS) and cytochrome c oxidase (COX) deficiency, mutations of the SURF-1 gene were recently identified. The aim of the present study was to review the MR findings in patients with LS to verify if the genetically homogeneous patients with LS and SURF-1 mutations (LS SURF-1 patients) had a

  13. Extreme Value Distributions E Barndorff-Nielsen OE, Cox DR () Inference and asymptotics.

    E-print Network

    Alves, Maria Isabel Fraga

    Extreme Value Distributions E E Barndorff-Nielsen OE, Cox DR () Inference and asymptotics. Chapman an exponential family. Scand J Stat :­ Extreme Value Distributions I F A , C N Associate Professor, CEAUL of Aveiro, Aveiro, Portugal Introduction Extreme Value distributions arise as limiting distributions

  14. Phase evolution and magnetic properties of HoIn3-xCox

    NASA Astrophysics Data System (ADS)

    Chen, Songlin; Guo, Yongquan; He, Qiang

    2015-03-01

    The phase evolution of HoIn3-xCox exhibits the phase transformations from the original HoIn3 with cubic structure to the intermediated HoCo2In with orthorhombic structure and to the final HoCo3 with rhombohedral structure. The corresponding magnetic states are found to closely associate with the structural phase transformation of HoIn3-xCox.With increasing Co contents, HoIn3-xCox are paramagnetic in region of x < 0.6, mixture of paramagnetic and ferromagnetic in range of 0.6 < x < 1.8, and ferromagnetic in range of 3 > x > 2.4 at room temperature, respectively. The field dependence of magnetization curves follows an equation of M = M s ( 1 - /a H ) + ? H , where M s and ? are corresponding to the saturation moment and susceptibility; a is a parameter related to the external field. The fitting results show that the susceptibility increases with increasing Co contents and Ms depends upon the Co content as well. It implies that the evolution of magnetic phases in HoIn3-xCox might originate from the change of exchange interaction from the one between the isolated Co spins and the surrounding conduction electrons in Co-poor regime to the one between Co-Co pairs mediated by the conduction electrons in Co-rich regime.

  15. Design: Margaret Cox Printing: 100% post-consumer paper, processed chlorine free. Vegetable-based inks.

    E-print Network

    McGaughey, Alan

    #12;Design: Margaret Cox Printing: 100% post-consumer paper, processed chlorine free. VegetableFORBESAVEPITTSBURGH,PA15213 412.268.3618miller-gallery@andrew.cmu.edu Hours:Tues.-Sun.,12-6pm Admission:Free bedroom using homemade props and a remarkably clever remix of footage from the week's game, popular movies

  16. Technical Report: Battery Modeling and Performance Metrics Anthongy Harris, Robert Cox, and Asis Nasipuri

    E-print Network

    Nasipuri, Asis

    Technical Report: Battery Modeling and Performance Metrics Anthongy Harris, Robert Cox, and Asis Summary This document focuses on the development of techniques for monitoring the performance of batteries as energy storage devices in low-power systems. Section 2 provides a brief review of battery operation

  17. Insulin Resistance: Regression and Clustering

    PubMed Central

    Yoon, Sangho; Assimes, Themistocles L.; Quertermous, Thomas; Hsiao, Chin-Fu; Chuang, Lee-Ming; Hwu, Chii-Min; Rajaratnam, Bala; Olshen, Richard A.

    2014-01-01

    In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression. Defining data come from measurements that play major roles in medical practice. A precise statement of what the data are is in Section 1. Their family structures are described in detail. They concern levels of lipids and the results of an oral glucose tolerance test (OGTT). We apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and lipids on functions of age and BMI that are inferred from the data. A bootstrap procedure developed for our family data supplemented by insights from other approaches leads us to believe that two clusters are appropriate for defining IR precisely. One cluster consists of women who are IR, and the other of women who seem not to be. Genes and other features are used to predict cluster membership. We argue that prediction with “main effects” is not satisfactory, but prediction that includes interactions may be. PMID:24887437

  18. Insulin resistance: regression and clustering.

    PubMed

    Yoon, Sangho; Assimes, Themistocles L; Quertermous, Thomas; Hsiao, Chin-Fu; Chuang, Lee-Ming; Hwu, Chii-Min; Rajaratnam, Bala; Olshen, Richard A

    2014-01-01

    In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression. Defining data come from measurements that play major roles in medical practice. A precise statement of what the data are is in Section 1. Their family structures are described in detail. They concern levels of lipids and the results of an oral glucose tolerance test (OGTT). We apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and lipids on functions of age and BMI that are inferred from the data. A bootstrap procedure developed for our family data supplemented by insights from other approaches leads us to believe that two clusters are appropriate for defining IR precisely. One cluster consists of women who are IR, and the other of women who seem not to be. Genes and other features are used to predict cluster membership. We argue that prediction with "main effects" is not satisfactory, but prediction that includes interactions may be. PMID:24887437

  19. Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System.

    PubMed

    Chojnacka, Magdalena; Gornicka, Agnieszka; Oeljeklaus, Silke; Warscheid, Bettina; Chacinska, Agnieszka

    2015-06-12

    The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity. This interaction does not involve Sco1, a partner of Cox17 in transferring copper ions to cytochrome c oxidase. However, the Cox17-MICOS interaction is regulated by copper ions. We propose that Cox17 is a newly identified factor involved in maintaining the architecture of the MICOS complex. PMID:25918166

  20. Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System*

    PubMed Central

    Chojnacka, Magdalena; Gornicka, Agnieszka; Oeljeklaus, Silke; Warscheid, Bettina; Chacinska, Agnieszka

    2015-01-01

    The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity. This interaction does not involve Sco1, a partner of Cox17 in transferring copper ions to cytochrome c oxidase. However, the Cox17-MICOS interaction is regulated by copper ions. We propose that Cox17 is a newly identified factor involved in maintaining the architecture of the MICOS complex. PMID:25918166

  1. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2

    PubMed Central

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V–fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic agent for gastric cancer. PMID:25945055

  2. Glucocorticoids suppress hypoxia-induced COX-2 and hypoxia inducible factor-1? expression through the induction of glucocorticoidinduced leucine zipper

    PubMed Central

    Lim, Wonchung; Park, Choa; Shim, Myeong Kuk; Lee, Yong Hee; Lee, You Mie; Lee, YoungJoo

    2014-01-01

    Background and Purpose The COX-2/PGE2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumourigenesis. However, the mechanism by which glucocorticoid receptors (GRs) inhibit COX-2 during hypoxia has not been elucidated. Hence, we explored the mechanisms underlying glucocorticoid-mediated inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells. Experimental Approach The expressions of COX-2 and glucocorticoid-induced leucine zipper (GILZ) in A549 cells were determined by Western blot and/or quantitative real time-PCR respectively. The anti-invasive effect of GILZ on A549 cells was evaluated using the matrigel invasion assay. Key Results The hypoxia-induced increase in COX-2 protein and mRNA levels and promoter activity were suppressed by dexamethasone, and this effect of dexamethasone was antagonized by the GR antagonist RU486. Overexpression of GILZ in A549 cells also inhibited hypoxia-induced COX-2 expression levels and knockdown of GILZ reduced the glucocorticoid-mediated inhibition of hypoxia-induced COX-2 expression, indicating that the inhibitory effects of dexamethasone on hypoxia-induced COX-2 are mediated by GILZ. GILZ suppressed the expression of hypoxia inducible factor (HIF)-1? at the protein level and affected its signalling pathway. Hypoxia-induced cell invasion was also dramatically reduced by GILZ expression. Conclusion and Implications Dexamethasone-induced upregulation of GILZ not only inhibits the hypoxic-evoked induction of COX-2 expression and cell invasion but further blocks the HIF-1 pathway by destabilizing HIF-1? expression. Taken together, these findings suggest that the suppression of hypoxia-induced COX-2 by glucocorticoids is mediated by GILZ. Hence, GILZ is a potential key therapeutic target for suppression of inflammation under hypoxia. PMID:24172143

  3. COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

    PubMed Central

    Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

    2014-01-01

    Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (?765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

  4. Applying additive logistic regression to data derived from sensors monitoring behavioral and physiological characteristics of dairy cows to detect lameness.

    PubMed

    Kamphuis, C; Frank, E; Burke, J K; Verkerk, G A; Jago, J G

    2013-01-01

    The hypothesis was that sensors currently available on farm that monitor behavioral and physiological characteristics have potential for the detection of lameness in dairy cows. This was tested by applying additive logistic regression to variables derived from sensor data. Data were collected between November 2010 and June 2012 on 5 commercial pasture-based dairy farms. Sensor data from weigh scales (liveweight), pedometers (activity), and milk meters (milking order, unadjusted and adjusted milk yield in the first 2 min of milking, total milk yield, and milking duration) were collected at every milking from 4,904 cows. Lameness events were recorded by farmers who were trained in detecting lameness before the study commenced. A total of 318 lameness events affecting 292 cows were available for statistical analyses. For each lameness event, the lame cow's sensor data for a time period of 14 d before observation date were randomly matched by farm and date to 10 healthy cows (i.e., cows that were not lame and had no other health event recorded for the matched time period). Sensor data relating to the 14-d time periods were used for developing univariable (using one source of sensor data) and multivariable (using multiple sources of sensor data) models. Model development involved the use of additive logistic regression by applying the LogitBoost algorithm with a regression tree as base learner. The model's output was a probability estimate for lameness, given the sensor data collected during the 14-d time period. Models were validated using leave-one-farm-out cross-validation and, as a result of this validation, each cow in the data set (318 lame and 3,180 nonlame cows) received a probability estimate for lameness. Based on the area under the curve (AUC), results indicated that univariable models had low predictive potential, with the highest AUC values found for liveweight (AUC=0.66), activity (AUC=0.60), and milking order (AUC=0.65). Combining these 3 sensors improved AUC to 0.74. Detection performance of this combined model varied between farms but it consistently and significantly outperformed univariable models across farms at a fixed specificity of 80%. Still, detection performance was not high enough to be implemented in practice on large, pasture-based dairy farms. Future research may improve performance by developing variables based on sensor data of liveweight, activity, and milking order, but that better describe changes in sensor data patterns when cows go lame. PMID:24011945

  5. Time Series Regression with a Unit Root

    Microsoft Academic Search

    P. C. B. Phillips

    1987-01-01

    This paper studies the random walk in a general time series setting that allows for weakly dependent and heterogeneously distributed innovations. It is shown that simple least squares regression consistently estimates a unit root under very general conditions in spite of the presence of autocorrelated errors. The limiting distribution of the standardized estimator and the associated regression t statistic are

  6. Assumptions of Multiple Regression: Correcting Two Misconceptions

    ERIC Educational Resources Information Center

    Williams, Matt N.; Gomez Grajales, Carlos Alberto; Kurkiewicz, Dason

    2013-01-01

    In 2002, an article entitled "Four assumptions of multiple regression that researchers should always test" by Osborne and Waters was published in "PARE." This article has gone on to be viewed more than 275,000 times (as of August 2013), and it is one of the first results displayed in a Google search for "regression

  7. A Regression-Based Linear Classification Procedure.

    ERIC Educational Resources Information Center

    LaMotte, Lynn Roy; McWhorter, Archer, Jr.

    1981-01-01

    A linear regression function is developed for use in a classification procedure. The procedure is applied to faculty merit review data, resulting in an interpretable regression function and within-sample classifications as good as a four-funtion discriminant analysis. (Author/BW)

  8. Global Optimization With Multivariate Adaptive Regression Splines

    Microsoft Academic Search

    Scott Crino; Donald E. Brown

    2007-01-01

    This paper presents a novel procedure for approximating the global optimum in structural design by combining multivariate adaptive regression splines (MARS) with a response surface methodology (RSM). MARS is a flexible regression technique that uses a modified recursive partitioning strategy to simplify high-dimensional problems into smaller yet highly accurate models. Combining MARS and RSM improves the conventional RSM by addressing

  9. Adaptive nonparametric regression on spin fiber bundles

    Microsoft Academic Search

    Claudio Durastanti; Daryl Geller; Domenico Marinucci

    2012-01-01

    The construction of adaptive nonparametric procedures by means of wavelet thresholding techniques is now a classical topic in modern mathematical statistics. In this paper, we extend this framework to the analysis of nonparametric regression on sections of spin fiber bundles defined on the sphere. This can be viewed as a regression problem where the function to be estimated takes as

  10. Adaptive Nonparametric Regression on Spin Fiber Bundles

    Microsoft Academic Search

    Claudio Durastanti; Daryl Geller; Domenico Marinucci

    2010-01-01

    The construction of adaptive nonparametric procedures by means of wavelet thresholding techniques is now a classical topic in modern mathematical statistics. In this paper, we extend this framework to the analysis of nonparametric regression on sections of spin fiber bundles defined on the sphere. This can be viewed as a regression problem where the function to be estimated takes as

  11. Software Testing and Maintenance 1 Regression Testing

    E-print Network

    Lei, Jeff Yu

    1 Software Testing and Maintenance 1 Regression Testing Introduction Test Selection Test Minimization Test Prioritization Summary Software Testing and Maintenance 2 What is it? Regression testing refers to the portion of the test cycle in which a program is tested to ensure that changes do not affect

  12. Covariate Measurement Error in Logistic Regression

    Microsoft Academic Search

    Leonard A. Stefanski; Raymond J. Carroll

    1985-01-01

    In a logistic regression model when covariates are subject to measurement error the naive estimator, obtained by regressing on the observed covariates, is asymptotically biased. We introduce a bias-adjusted estimator and two estimators appropriate for normally distributed measurement errors -a functional maximum likelihood estimator and an estimator which exploits the consequences of sufficiency. The four proposals are studied asymptotically under

  13. Incremental Net Effects in Multiple Regression

    ERIC Educational Resources Information Center

    Lipovetsky, Stan; Conklin, Michael

    2005-01-01

    A regular problem in regression analysis is estimating the comparative importance of the predictors in the model. This work considers the 'net effects', or shares of the predictors in the coefficient of the multiple determination, which is a widely used characteristic of the quality of a regression model. Estimation of the net effects can be a…

  14. Developmental regression in autism spectrum disorders.

    PubMed

    Rogers, Sally J

    2004-01-01

    The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences. Counter to clinical intuition, the earlier development of social, language, and attachment behaviors followed by regression does not seem to support later recovery of skills or better developmental outcomes compared to children who never had speech or typical social responsivity. In fact, this regressive group may have somewhat greater developmental impairment than the nonregressive group, though the two groups do not appear to present different behavioral phenotypes. Although autism is not the only condition in which regression occurs, it appears to be the most frequent condition. Other disorders that demonstrate an early regression with no known etiology include total blindness from birth and childhood disintegrative disorder, both of which demonstrate behavioral relations to autism. In addition, two biological conditions with known etiologies also involve regression with some behaviors resembling autism behavioral phenotype: Rett syndrome (a genetic disorder; see Glaze, this issue) and Landau-Kleffner syndrome (see McVicar and Shinnar, this issue), which involves a seizure disorder. PMID:15362172

  15. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  16. Regression models, selection effects and sampling bias

    E-print Network

    McCullagh, Peter

    of treatment effect Problems with regression models A point process model Ways of thinking Consequences of auto; behavioural studies in ecology; marketing studies, with purchase events as units; public policy: crime type of regression models Clinical trials / market research / traffic studies / crime... (i) Operational

  17. Deriving the Regression Equation without Using Calculus

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.; Gordon, Florence S.

    2004-01-01

    Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

  18. Principles of Quantile Regression and an Application

    ERIC Educational Resources Information Center

    Chen, Fang; Chalhoub-Deville, Micheline

    2014-01-01

    Newer statistical procedures are typically introduced to help address the limitations of those already in practice or to deal with emerging research needs. Quantile regression (QR) is introduced in this paper as a relatively new methodology, which is intended to overcome some of the limitations of least squares mean regression (LMR). QR is more…

  19. Machine Learning ! ! ! ! !Srihari Linear Models for Regression

    E-print Network

    · Learning to Rank problem ­ t is discrete (eg, 1,2..6) in training set but a continuous value in [1,6] is learnt and used to rank objects #12;Machine Learning ! ! ! ! !Srihari 3 Types of Linear Regression Models ! ! ! ! !Srihari Regression: Learning To Rank ­ Log frequency of query in anchor text ­ Query word in color on page

  20. A PSEUDORIP FOR MULTIVARIATE REGRESSION CHRISTOPHE GIRAUD

    E-print Network

    Paris-Sud XI, Université de

    regression. This pseudo­RIP is compatible with the setting n framework a non­asymptotic point of view by Bunea et al. [3] and Giraud [4]. Both papers provide oracle bounds that the Assumption (2) coming from the general trace regression framework can be weaken for the multivariate

  1. Modern regression and Mortality Doug Nychka

    E-print Network

    Nychka, Douglas

    ;A Generalized Linear Model (GLM) Assume that mortality (Mt) is approximately Pois- son distributed is a useful motivation for understanding Poisson Regression Flexible regression models #12;Some data atributes Mean model with log link function Mt Poisson(µt) E(Mt) = µt model the log of the mean. log(µt) = f

  2. Privacy-preserving logistic regression Kamalika Chaudhuri

    E-print Network

    Smith, Adam D.

    Privacy-preserving logistic regression Kamalika Chaudhuri Information Theory and Applications on privacy-preserving logistic regression. First we apply an idea of Dwork et al. [6] to design a privacy-preserving, and perturbing the learned classifier with noise proportional to the sensitivity. We then provide a privacy-preserving

  3. Stepwise regression with PRESS and rank regression (program user's guide). [STEPWISE, up to 179 independent variables

    SciTech Connect

    Iman, R.L.; Davenport, J.M.; Frost, E.L.; Shortencarier, M.J.

    1980-01-01

    A stepwise multiple regression program is described. This program provides for either a forward stepwise or backward elimination solution to multiple regression problems. The program also provides PRESS values that can be used for subset selection as well as options for regression analysis on the ranks of the data and for a weighted regression analysis on either raw or rank transformed data. This document is written and designed for users of this STEPWISE program.

  4. Regression of Environmental Noise in LIGO Data

    E-print Network

    Tiwari, Vaibhav; Frolov, Valery; Klimenko, Sergey; Mitselmakher, Guenakh; Necula, Valentin; Prodi, Giovanni; Re, Virginia; Salemi, Francesco; Vedovato, Gabriele; Yakushin, Igor

    2015-01-01

    We address the problem of noise regression in the output of gravitational-wave (GW) interferometers, using data from the physical environmental monitors (PEM). The objective of the regression analysis is to predict environmental noise in the gravitational-wave channel from the PEM measurements. One of the most promising regression method is based on the construction of Wiener-Kolmogorov filters. Using this method, the seismic noise cancellation from the LIGO GW channel has already been performed. In the presented approach the Wiener-Kolmogorov method has been extended, incorporating banks of Wiener filters in the time-frequency domain, multi-channel analysis and regulation schemes, which greatly enhance the versatility of the regression analysis. Also we presents the first results on regression of the bi-coherent noise in the LIGO data.

  5. Regression of Environmental Noise in LIGO Data

    E-print Network

    Vaibhav Tiwari; Marco Drago; Valery Frolov; Sergey Klimenko; Guenakh Mitselmakher; Valentin Necula; Giovanni Prodi; Virginia Re; Francesco Salemi; Gabriele Vedovato; Igor Yakushin

    2015-03-25

    We address the problem of noise regression in the output of gravitational-wave (GW) interferometers, using data from the physical environmental monitors (PEM). The objective of the regression analysis is to predict environmental noise in the gravitational-wave channel from the PEM measurements. One of the most promising regression method is based on the construction of Wiener-Kolmogorov filters. Using this method, the seismic noise cancellation from the LIGO GW channel has already been performed. In the presented approach the Wiener-Kolmogorov method has been extended, incorporating banks of Wiener filters in the time-frequency domain, multi-channel analysis and regulation schemes, which greatly enhance the versatility of the regression analysis. Also we presents the first results on regression of the bi-coherent noise in the LIGO data.

  6. Logistic Regression Multiple linear regression is used when the response variable is quantitative,

    E-print Network

    Olive, David

    Chapter 10 Logistic Regression Multiple linear regression is used when the response variable random variables with Yi binomial(1, (xi)). The binary logistic regression (LR) model is the special|Y = j Nk(µj, ) for j = 0, 1. That is, the conditional distribution of x given Y = j follows

  7. CMARS: A New Contribution to Nonparametric Regression with Multivariate Adaptive Regression Splines Supported by Continuous Optimisation

    Microsoft Academic Search

    Gerhard-Wilhelm Weber; Inci Batmaz; Gulser Koksal; Pakize Taylan; Fatma Yerlikaya

    Regression analysis is a widely used statistical method for investigating and modelling relationships between variables. There are various forms of regression models, each is used for dierent purposes in engineering and sciences. Linear regression models (LRMs) is the most popular one among them. Although, these models are easy to develop and interpret, they may fail when underlying distributional assumptions are

  8. Locally-Weighted Regression: An Approach to Regression Analysis by Local Fitting

    Microsoft Academic Search

    William S. Cleveland; Susan J. Devlin; J. B. Wagenaar

    1988-01-01

    Locally weighted regression, or loess, is a way of estimating a regression surface through a multivariate smoothing procedure, fitting a function of the independent variables locally and in a moving fashion analogous to how a moving average is computed for a time series. With local fitting we can estimate a much wider class of regression surfaces than with the usual

  9. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1\\/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro

    Microsoft Academic Search

    J. Berg; H. Fellier; T. Christoph; J. Grarup; D. Stimmeder

    1999-01-01

    Objective: To investigate anti-inflammatory effects of lornoxicam in vitro on COX-1\\/COX-2, on NO formation from iNOS and on the formation of the pro-inflammatory cytokines TNF-!, IL-1#, IL-6, and IL-8.¶Materials and Methods: COX-1 inhibition in intact cells was assessed employing two systems: measurement of aggregation in human washed platelets and assessment of TXB2 formation in HEL cells. COX-2 inhibition was assessed

  10. Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression

    PubMed Central

    Kohannim, Omid; Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; de Zubicaray, Greig I.; McMahon, Katie L.; Hansell, Narelle K.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.

    2012-01-01

    We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8?±?2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. PMID:22888310

  11. Early Regression of Severe Left Ventricular Hypertrophy after Transcatheter Aortic Valve Replacement is Associated with Decreased Hospitalizations

    PubMed Central

    Lindman, Brian R.; Stewart, William J.; Pibarot, Philippe; Hahn, Rebecca T.; Otto, Catherine M.; Xu, Ke; Devereux, Richard B.; Weissman, Neil J.; Enriquez-Sarano, Maurice; Szeto, Wilson Y.; Makkar, Raj; Miller, D. Craig; Lerakis, Stamatios; Kapadia, Samir; Bowers, Bruce; Greason, Kevin L.; McAndrew, Thomas C.; Lei, Yang; Leon, Martin B.; Douglas, Pamela S.

    2014-01-01

    Objective Examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). Background LVM regression after valve replacement for aortic stenosis (AS) is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Methods Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 690 had both severe LVH (LVM index [LVMi] ³149 g/m2 men, ³122 g/m2 women) at baseline and an LVMi measurement 30 days post-TAVR. Clinical outcomes were compared for patients with greater than vs. lesser than median percent change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Results Compared to patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p=0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, HR 0.50; 95% CI, 0.32–0.78; p=0.002) and a lower rate of rehospitalizations specifically for heart failure (7.3% vs. 13.6%, p=0.01). The association with a lower rate of hospitalizations was consistent across sub-groups and remained significant after multivariable adjustment (HR 0.53; 95% CI, 0.34–0.84; p=0.007). Patients with greater LVMi regression had lower BNP (p=0.002) and a trend toward better quality of life (p=0.06) at 1 year compared to those with lesser regression. Conclusions In high-risk patients with severe AS and severe LVH undergoing TAVR, those with greater early LV mass regression had half the rate of rehospitalization over the subsequent year. PMID:24947722

  12. Has Cox2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

    Microsoft Academic Search

    C Mascaux; B Martin; M Paesmans; T Berghmans; M Dusart; A Haller; P Lothaire; A-P Meert; J-J Lafitte; J-P Sculier

    2006-01-01

    Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and

  13. The Spatiotemporal Role of COX-2 in Osteogenic and Chondrogenic Differentiation of Periosteum-Derived Mesenchymal Progenitors in Fracture Repair

    PubMed Central

    Huang, Chunlan; Xue, Ming; Chen, Hongli; Jiao, Jing; Herschman, Harvey R.; O'Keefe, Regis J.; Zhang, Xinping

    2014-01-01

    Periosteum provides a major source of mesenchymal progenitor cells for bone fracture repair. Combining cell-specific targeted Cox-2 gene deletion approaches with in vitro analyses of the differentiation of periosteum-derived mesenchymal progenitor cells (PDMPCs), here we demonstrate a spatial and temporal role for Cox-2 function in the modulation of osteogenic and chondrogenic differentiation of periosteal progenitors in fracture repair. Prx1Cre-targeted Cox-2 gene deletion in mesenchyme resulted in marked reduction of intramembraneous and endochondral bone repair, leading to accumulation of poorly differentiated mesenchyme and immature cartilage in periosteal callus. In contrast, Col2Cre-targeted Cox-2 gene deletion in cartilage resulted in a deficiency primarily in cartilage conversion into bone. Further cell culture analyses using Cox-2 deficient PDMPCs demonstrated reduced osteogenic differentiation in monolayer cultures, blocked chondrocyte differentiation and hypertrophy in high density micromass cultures. Gene expression microarray analyses demonstrated downregulation of a key set of genes associated with bone/cartilage formation and remodeling, namely Sox9, Runx2, Osx, MMP9, VDR and RANKL. Pathway analyses demonstrated dysregulation of the HIF-1, PI3K-AKT and Wnt pathways in Cox-2 deficient cells. Collectively, our data highlight a crucial role for Cox-2 from cells of mesenchymal lineages in modulating key pathways that control periosteal progenitor cell growth, differentiation, and angiogenesis in fracture repair. PMID:24988184

  14. Parallel evolution of cox genes in H2S-tolerant fish as key adaptation to a toxic environment.

    PubMed

    Pfenninger, Markus; Lerp, Hannes; Tobler, Michael; Passow, Courtney; Kelley, Joanna L; Funke, Elisabeth; Greshake, Bastian; Erkoc, Umut Kaan; Berberich, Thomas; Plath, Martin

    2014-01-01

    Populations that repeatedly adapt to the same environmental stressor offer a unique opportunity to study adaptation, especially if there are a priori predictions about the genetic basis underlying phenotypic evolution. Hydrogen sulphide (H2S) blocks the cytochrome-c oxidase complex (COX), predicting the evolution of decreased H2S susceptibility of the COX in three populations in the Poecilia mexicana complex that have colonized H2S-containing springs. Here, we demonstrate that decreased H2S susceptibility of COX evolved in parallel in two sulphide lineages, as evidenced by shared amino acid substitutions in cox1 and cox3 genes. One of the shared substitutions likely triggers conformational changes in COX1 blocking the access of H2S. In a third sulphide population, we detect no decreased H2S susceptibility of COX, suggesting that H2S resistance is achieved through another mechanism. Our study thus demonstrates that even closely related lineages follow both parallel and disparate molecular evolutionary paths to adaptation in response to the same selection pressure. PMID:24815812

  15. LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

    SciTech Connect

    Sun Haipeng [Interdisciplinary Graduate Program of Pharmacology and Toxicology, University of Arizona, 1501 N. Campbell Ave., Tucson, AZ 85724 (United States); Xu Beibei; Sheveleva, Elena [Department of Pharmacology, University of Arizona, 1501 N. Campbell Ave., Tucson, AZ 85724 (United States); Chen, Qin M. [Department of Pharmacology, University of Arizona, 1501 N. Campbell Ave., Tucson, AZ 85724 (United States)], E-mail: qchen@email.arizona.edu

    2008-10-01

    Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca{sup 2+} concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes.

  16. The Pet309 pentatricopeptide repeat motifs mediate efficient binding to the mitochondrial COX1 transcript in yeast

    PubMed Central

    Zamudio-Ochoa, Angélica; Camacho-Villasana, Yolanda; García-Guerrero, Aldo E; Pérez-Martínez, Xochitl

    2014-01-01

    Mitochondrial synthesis of Cox1, the largest subunit of the cytochrome c oxidase complex, is controlled by Mss51 and Pet309, two mRNA-specific translational activators that act via the COX1 mRNA 5?-UTR through an unknown mechanism. Pet309 belongs to the pentatricopeptide repeat (PPR) protein family, which is involved in RNA metabolism in mitochondria and chloroplasts, and its sequence predicts at least 12 PPR motifs in the central portion of the protein. Deletion of these motifs selectively disrupted translation but not accumulation of the COX1 mRNA. We used RNA coimmunoprecipitation assays to show that Pet309 interacts with the COX1 mRNA in vivo and that this association is present before processing of the COX1 mRNA from the ATP8/6 polycistronic mRNA. This association was not affected by deletion of 8 of the PPR motifs but was undetectable after deletion of the entire 12-PPR region. However, interaction of the Pet309 protein lacking 12 PPR motifs with the COX1 mRNA was detected after overexpression of the mutated form of the protein, suggesting that deletion of this region decreased the binding affinity for the COX1 mRNA without abolishing it entirely. Moreover, binding of Pet309 to the COX1 mRNA was affected by deletion of Mss51. This work demonstrates an in vivo physical interaction between a yeast mitochondrial translational activator and its target mRNA and shows the cooperativity of the PPR domains of Pet309 in interaction with the COX1 mRNA. PMID:25181249

  17. PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

    PubMed Central

    Uddin, Jashim; Vitale, Paola; Panella, Andrea; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; Nickels, Mike; Tantawy, Mohammed N.; Manning, H. Charles; Marnett, Lawrence J.; Scilimati, Antonio

    2015-01-01

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 ?M (purified oCOX-1) and 1.37 ?M (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radio-chemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. PMID:24832612

  18. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by ?CT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  19. Comparison of regression methods for phenology

    NASA Astrophysics Data System (ADS)

    Roberts, Adrian Mark Ikin

    2012-07-01

    Several methods exist for investigation of the relationship between records and weather data. These can be broadly classified into models that attempt to incorporate information about underlying biological processes, such as those based on the concept of thermal time, and linear regression methods. The latter are less driven by the biology but have the advantages of ease of use and flexibility. Regression can be used where there is no obvious mechanistic model or to suggest the form of a mechanistic or empirical model where there are several to choose from. Stepwise regression is commonly used in phenology. However, it requires aggregation of the weather records, resulting in loss of information. Penalised signal regression (PSR) was recently introduced to overcome this weakness. Here, we introduce a further method to the phenology context called fusion, which is a sparse version of PSR. In this paper, we compare the performance of these three regression methods based on simulations from two types of mechanistic models, the spring warming and sequential models. Given a suitable choice of temperature days as regression covariates, PSR and fusion performed better than stepwise regression for the spring warming model and PSR performed best for the sequential model. However, if a large number of redundant temperature days were included as covariates, the performance of PSR fell off whilst fusion was quite robust to this change. For this reason, it is best to use PSR and fusion methods in tandem, and to vary the number of covariates included.

  20. Comparison of regression methods for phenology.

    PubMed

    Roberts, Adrian Mark Ikin

    2012-07-01

    Several methods exist for investigation of the relationship between records and weather data. These can be broadly classified into models that attempt to incorporate information about underlying biological processes, such as those based on the concept of thermal time, and linear regression methods. The latter are less driven by the biology but have the advantages of ease of use and flexibility. Regression can be used where there is no obvious mechanistic model or to suggest the form of a mechanistic or empirical model where there are several to choose from. Stepwise regression is commonly used in phenology. However, it requires aggregation of the weather records, resulting in loss of information. Penalised signal regression (PSR) was recently introduced to overcome this weakness. Here, we introduce a further method to the phenology context called fusion, which is a sparse version of PSR. In this paper, we compare the performance of these three regression methods based on simulations from two types of mechanistic models, the spring warming and sequential models. Given a suitable choice of temperature days as regression covariates, PSR and fusion performed better than stepwise regression for the spring warming model and PSR performed best for the sequential model. However, if a large number of redundant temperature days were included as covariates, the performance of PSR fell off whilst fusion was quite robust to this change. For this reason, it is best to use PSR and fusion methods in tandem, and to vary the number of covariates included. PMID:21789728

  1. Prognostic factors for metachronous contralateral breast cancer: A comparison of the linear Cox regression model and its artificial neural network extension

    Microsoft Academic Search

    L. Mariani; D. Coradini; E. Biganzoli; P. Boracchi; E. Marubini; S. Pilotti; B. Salvadori; R. Silvestrini; U. Veronesi; R. Zucali; F. Rilke

    1997-01-01

    The purpose of the present study was toassess prognostic factors for metachronous contralateral recurrence ofbreast cancer (CBC). Two factors were of particularinterest, namely estrogen (ER) and progesterone (PgR) receptorsassayed with the biochemical method in primary tumortissue. Information was obtained from a prospective clinicaldatabase for 1763 axillary node-negative women who hadreceived curative surgery, mostly of the conservative type,and followed-up for a

  2. Relaxing the independent censoring assumption in the Cox proportional hazards model using multiple imputation

    PubMed Central

    Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James

    2014-01-01

    The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:25060703

  3. CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models.

    PubMed

    Kim, Sun-Hee; Margalit, Ofer; Katoh, Hiroshi; Wang, Dingzhi; Wu, Hong; Xia, Dianren; Holla, Vijaykumar R; Yang, Peiying; DuBois, Raymond N

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation. These pre-clinical findings suggest a need for further exploration of CG100649 for CRC prevention and treatment. The long-term safety profile of CG100649, particularly regarding its effect on cardiovascular risk, is yet to be determined. PMID:25085205

  4. Percolation processes and spin-reorientation of PrNi5-xCox

    Microsoft Academic Search

    D. L. Rocco; J. S. Amaral; J. V. Leitão; V. S. Amaral; M. S. Reis; R. P. Fernandes; A. M. Pereira; J. P. Araújo; Nuno V. Martins; P. B. Tavares; A. A. Coelho

    2009-01-01

    In the present work we report on the structural and magnetic behaviors of the PrNi5-xCox intermetallic compounds. Due to the competition between the anisotropy energies of both Co and Pr sublattices, this series has a spin-reorientation phenomenon at low temperature (140 K). The Curie temperature, as a function of Co content, has a sudden increase above a critical concentration xc˜1.9

  5. Verhogen selectieve COX2-remmers en traditionele NSAID’s het risico op vasculaire problemen?

    Microsoft Academic Search

    P. L. B. Bruijnzeel

    2007-01-01

    Samenvatting  Kearny et al. onderzochten met behulp van een metaanalyse van gerandomiseerde onderzoeken in hoeverre selectieve COX-2-remmers\\u000a en traditionele NSAID’s het risico op vaatproblemen verhoogden 1. De gegevens die voor deze analyse gebruikt werden, waren\\u000a gebaseerd op resultaten die in Medline en Embase waren gerapporteerd tussen januari 1966 en april 2005, daarnaast gegevens\\u000a van de FDA en data van Novartis, Pfizer

  6. Effects of ?-glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2 (COX2) in vitro

    Microsoft Academic Search

    Liuqiang Zhang; Li Feng; Qi Jia; Jinwen Xu; Rui Wang; Zhengtao Wang; Yingchun Wu; Yiming Li

    2011-01-01

    Harpagide (1) and harpagoside (2) are two iridoid glycosides existing in many medicinal plants. Although they are believed to be the main bioactive compounds related to the anti-inflammatory efficacy of these plants, the mechanisms of their anti-inflammatory activities remain unclear. The results of our present study showed that 1 and 2 had no effects on inhibitions of cyclooxygenase (COX)-1\\/2 enzyme

  7. Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors.

    PubMed

    Biava, Mariangela; Battilocchio, Claudio; Poce, Giovanna; Alfonso, Salvatore; Consalvi, Sara; Di Capua, Angela; Calderone, Vincenzo; Martelli, Alma; Testai, Lara; Sautebin, Lidia; Rossi, Antonietta; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Giordani, Antonio; Persiani, Stefano; Colovic, Milena; Dovizio, Melania; Patrignani, Paola; Anzini, Maurizio

    2014-01-15

    We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. PMID:24373735

  8. Citral, a component of lemongrass oil, activates PPAR? and ? and suppresses COX2 expression

    Microsoft Academic Search

    Michiko Katsukawa; Rieko Nakata; Yoshie Takizawa; Kazuyuki Hori; Saori Takahashi; Hiroyasu Inoue

    2010-01-01

    Lemongrass is a widely used herb as a food flavoring, as a perfume, and for its analgesic and anti-inflammatory purposes; however, the molecular mechanisms of these effects have not been elucidated. Previously, we identified carvacrol from the essential oil of thyme as a suppressor of cyclooxygenase (COX)-2, a key enzyme for prostaglandin synthesis, and also an activator of peroxisome proliferator-activated

  9. Magnetotransport in epitaxial films of the degenerate semiconductor Zn1-xCoxO

    Microsoft Academic Search

    R. C. Budhani; Prita Pant; R. K. Rakshit; K. Senapati; S. Mandal; N. K. Pandey; Jitendra Kumar

    2005-01-01

    Magnetotransport measurements are performed over a broad range of temperature (T) and magnetic field (H) on highly degenerate n-type Zn1-xCoxO (0 \\\\le x \\\\le 0.30) epitaxial films. The cobalt-free samples are characterized by a metallic resistivity rho(T) down to 2 K, a negative and predominantly isotropic magnetoresistance (MR) and optical transmission above 85% in the visible range of the electromagnetic

  10. COX2\\/VEGF-Dependent Facilitation of Tumor-Associated Angiogenesis and Tumor Growth in vivo

    Microsoft Academic Search

    Satoko Yoshida; Hideki Amano; Izumi Hayashi; Hidero Kitasato; Mariko Kamata; Madoka Inukai; Hirokuni Yoshimura; Masataka Majima

    2003-01-01

    Nonsteroidal anti-inflammatory drugs are known to suppress the occurrence and progression of malignancies such as colorectal cancers. However, the precise mechanism of these actions remains unknown. We have evaluated the role of an inducible cyclo-oxygenase (COX-2) in tumor-associated angiogenesis and tumor growth, and identified the downstream molecules involved using a ddy mouse model of sponge angiogenesis, which mimics tumor angiogenesis

  11. Suppression of colitis-related mouse colon carcinogenesis by a COX2 inhibitor and PPAR ligands

    Microsoft Academic Search

    Hiroyuki Kohno; Rikako Suzuki; Shigeyuki Sugie; Takuji Tanaka

    2005-01-01

    BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a

  12. cPLA2 Is Protective Against COX Inhibitor–Induced Intestinal Damage

    PubMed Central

    Montrose, David C.; Kadaveru, Krishna; Ilsley, Jillian N. M.; Root, Sierra H.; Rajan, Thiruchanduri V.; Ramesh, Manish; Nichols, Frank C.; Liang, Bruce T.; Sonin, Dmitry; Hand, Arthur R.; Zarini, Simona; Murphy, Robert C.; Belinsky, Glenn S.; Nakanishi, Masako; Rosenberg, Daniel W.

    2010-01-01

    Cytosolic phospholipase A2 (cPLA2) is the rate-limiting enzyme responsible for the generation of prostaglandins (PGs), which are bioactive lipids that play critical roles in maintaining gastrointestinal (GI) homeostasis. There has been a long-standing association between administration of cyclooxygenase (COX) inhibitors and GI toxicity. GI injury is thought to be induced by suppressed production of GI-protective PGs as well as direct injury to enterocytes. The present study sought to determine how pan-suppression of PG production via a genetic deletion of cPLA2 impacts the susceptibility to COX inhibitor–induced GI injury. A panel of COX inhibitors including celecoxib, rofecoxib, sulindac, and aspirin were administered via diet to cPLA2? / ? and cPLA2+ / + littermates. Administration of celecoxib, rofecoxib, and sulindac, but not aspirin, resulted in acute lethality (within 2 weeks) in cPLA2? / ? mice, but not in wild-type littermates. Histomorphological analysis revealed severe GI damage following celecoxib exposure associated with acute bacteremia and sepsis. Intestinal PG levels were reduced equivalently in both genotypes following celecoxib exposure, indicating that PG production was not likely responsible for the differential sensitivity. Gene expression profiling in the small intestines of mice identified drug-related changes among a panel of genes including those involved in mitochondrial function in cPLA2? / ? mice. Further analysis of enterocytic mitochondria showed abnormal morphology as well as impaired ATP production in the intestines from celecoxib-exposed cPLA2? / ? mice. Our data demonstrate that cPLA2 appears to be an important component in conferring protection against COX inhibitor–induced enteropathy, which may be mediated through affects on enterocytic mitochondria. PMID:20562220

  13. Inverse giant magnetoresistance in Fe\\/Cu\\/Gd1-xCox spin-valves

    Microsoft Academic Search

    D. Z. Yang; B. You; X. X. Zhang; T. R. Gao; S. M. Zhou; J. Du

    2006-01-01

    For bottom spin-valves of NiO\\/Fe\\/Cu\\/Gd1-xCox , giant magnetoresistance has been measured as a function of thickness and composition of GdCo layers as well as temperature. For all spin-valves involved here, the giant magnetoresistance has been attributed to contributions of spin-dependent scattering at interfaces and in bulk. The interfacial contribution produces positive giant magnetoresistance ratio for various compositions of GdCo alloys.

  14. Li\\/Fe1-xCoxS2 system thermal battery performance

    Microsoft Academic Search

    A. Awano; K. Haraguchi; H. Yamasaki

    1992-01-01

    Synthetic disulfides composed of iron and cobalt (Fe1-xCoxS2) were evaluated as cathode materials using a single cell. The discharge utilization was improved and the discharge curve exhibited an excellent plateau when compared with those of both FeS2 and FeS2+CoS2 and also the discharge time became longer with an increasing Co atomic ratio. The atomic ratio of iron and cobalt of

  15. Lattice, band, and spin engineering in Zn1-xCoxO

    NASA Astrophysics Data System (ADS)

    Matsui, Hiroaki; Tabata, Hitoshi

    2013-05-01

    This work was conducted to investigate lattice, band, and spin engineering of magnetic Zn1-xCoxO layers towards quantum barriers in ZnO. Lattice distortions by doping with Co ions caused a flat tetrahedron in the host, leading to an increase of spontaneous polarization in Zn1-xCoxO compared to ZnO based on the point-charge model. The band-gap energy increased linearly with the Co concentrations, which was very similar to the band-gap widening in Zn1-xMgxO derived from sp hybridization. The Co (3d) states were located in the mid-gap, which remained unchanged following changes in Co concentrations. Large magneto-optical effects were induced at the band edge due to sp-d exchange interactions. However, magneto-optical activity was reduced in heavily doping concentrations above x = 0.16 because of antiferromagnetic coupling between nearest-neighbor Co ions. The high magnetic activity at x = 0.10 is related to competition between the complex Co-related configurations, such as singles, pairs, open and closed triples, in Co-doped ZnO layers. Magnetic Zn1-xCoxO therefore has an effective layer composition for applications of quantum barriers.

  16. The Respiratory Chain Supercomplex Organization Is Independent of COX7a2l Isoforms

    PubMed Central

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-01-01

    Summary The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research. PMID:25470551

  17. Cox Proportional Hazards Models for Modeling the Time to Onset of Decompression Sickness in Hypobaric Environments

    NASA Technical Reports Server (NTRS)

    Thompson, Laura A.; Chhikara, Raj S.; Conkin, Johnny

    2003-01-01

    In this paper we fit Cox proportional hazards models to a subset of data from the Hypobaric Decompression Sickness Databank. The data bank contains records on the time to decompression sickness (DCS) and venous gas emboli (VGE) for over 130,000 person-exposures to high altitude in chamber tests. The subset we use contains 1,321 records, with 87% censoring, and has the most recent experimental tests on DCS made available from Johnson Space Center. We build on previous analyses of this data set by considering more expanded models and more detailed model assessments specific to the Cox model. Our model - which is stratified on the quartiles of the final ambient pressure at altitude - includes the final ambient pressure at altitude as a nonlinear continuous predictor, the computed tissue partial pressure of nitrogen at altitude, and whether exercise was done at altitude. We conduct various assessments of our model, many of which are recently developed in the statistical literature, and conclude where the model needs improvement. We consider the addition of frailties to the stratified Cox model, but found that no significant gain was attained above a model that does not include frailties. Finally, we validate some of the models that we fit.

  18. Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

    PubMed Central

    Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

    2013-01-01

    Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

  19. Extension of a Cox proportional hazards cure model when cure information is partially known.

    PubMed

    Wu, Yu; Lin, Yong; Lu, Shou-En; Li, Chin-Shang; Shih, Weichung Joe

    2014-07-01

    When there is evidence of long-term survivors, cure models are often used to model the survival curve. A cure model is a mixture model consisting of a cured fraction and an uncured fraction. Traditional cure models assume that the cured or uncured status in the censored set cannot be distinguished. But in many practices, some diagnostic procedures may provide partial information about the cured or uncured status relative to certain sensitivity and specificity. The traditional cure model does not take advantage of this additional information. Motivated by a clinical study on bone injury in pediatric patients, we propose a novel extension of a traditional Cox proportional hazards (PH) cure model that incorporates the additional information about the cured status. This extension can be applied when the latency part of the cure model is modeled by the Cox PH model. Extensive simulations demonstrated that the proposed extension provides more efficient and less biased estimations, and the higher efficiency and smaller bias is associated with higher sensitivity and specificity of diagnostic procedures. When the proposed extended Cox PH cure model was applied to the motivating example, there was a substantial improvement in the estimation. PMID:24511081

  20. Flexible Regression Modeling using Bayesian Nonparametric Mixtures

    E-print Network

    Lee, Herbie

    nonparametric mixture model for the joint distribution of response and covariates obtain full inference/distributions resulting in flexible inferences and more reliable predictions · Modeling utilizes Dirichlet processFlexible Regression Modeling using Bayesian Nonparametric Mixtures Athanasios Kottas Department

  1. Multiple Instance Regression with Structured Data

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran; Roper, Alex

    2008-01-01

    This slide presentation reviews the use of multiple instance regression with structured data from multiple and related data sets. It applies the concept to a practical problem, that of estimating crop yield using remote sensed country wide weekly observations.

  2. Genetics Home Reference: Caudal regression syndrome

    MedlinePLUS

    ... condition is likely caused by the interaction of multiple genetic and environmental factors. In many individuals, the development of caudal regression syndrome seems to be influenced by the presence ...

  3. Spatial variation decomposition via sparse regression

    E-print Network

    Zhang, Wangyang

    In this paper, we briefly discuss the recent development of a novel sparse regression technique that aims to accurately decompose process variation into two different components: (1) spatially correlated variation, and (2) ...

  4. Multiple-Regression Hidden Markov Model 

    E-print Network

    Fujinaga, Katsuhisa; Nakai, Mitsuru; Shimodaira, Hiroshi; Sagayama, Shigeki

    2001-01-01

    This paper proposes a new class of hidden Markov model (HMM) called multiple-regression HMM (MRHMM) that utilizes auxiliary features such as fundamental frequency (F0) and speaking styles that affect spectral parameters to ...

  5. REGRESSION ESTIMATES FOR TOPOLOGICAL-HYDROGRAPH INPUT.

    USGS Publications Warehouse

    Karlinger, Michael R.; Guertin, D. Phillip; Troutman, Brent M.

    1988-01-01

    Physiographic, hydrologic, and rainfall data from 18 small drainage basins in semiarid, central Wyoming were used to calibrate topological, unit-hydrograph models for celerity, the average rate of travel of a flood wave through the basin. The data set consisted of basin characteristics and hydrologic data for the 18 basins and rainfall data for 68 storms. Calibrated values of celerity and peak discharges subsequently were regressed as a function of the basin characteristics and excess rainfall volume. Predicted values obtained in this way can be used as input for estimating hydrographs in ungaged basins. The regression models included ordinary least-squares and seemingly unrelated regression. This latter regression model jointly estimated the celerity and peak discharge.

  6. Functional data analysis: classification and regression 

    E-print Network

    Lee, Ho-Jin

    2005-11-01

    Functional data refer to data which consist of observed functions or curves evaluated at a finite subset of some interval. In this dissertation, we discuss statistical analysis, especially classification and regression ...

  7. hp calculators HP 50g Cost Estimation using Linear Regression

    E-print Network

    Vetter, Frederick J.

    hp calculators HP 50g Cost Estimation using Linear Regression The STAT menu Cost Estimation using Linear Regression Practice estimating costs using linear regression #12;hp calculators HP 50g Cost Estimation using Linear Regression hp calculators - 2 - HP 50g Cost Estimation using Linear Regression

  8. Efficient Model Selection for Kernel Logistic Regression

    Microsoft Academic Search

    Gavin C. Cawley; Nicola L. C. Talbot

    2004-01-01

    Kernel logistic regression models, like their linear coun- terparts, can be trained using the efficient iteratively re- weighted least-squares (IRWLS) algorithm. This approach suggests an approximate leave-one-out cross-validation es- timator based on an existing method for exact leave-one-out cross-validation of least-squares models. Results compiled over seven benchmark datasets are presented for kernel logistic regression with model selection procedures based on

  9. Fuzzy multiple linear regression: A computational approach

    NASA Technical Reports Server (NTRS)

    Juang, C. H.; Huang, X. H.; Fleming, J. W.

    1992-01-01

    This paper presents a new computational approach for performing fuzzy regression. In contrast to Bardossy's approach, the new approach, while dealing with fuzzy variables, closely follows the conventional regression technique. In this approach, treatment of fuzzy input is more 'computational' than 'symbolic.' The following sections first outline the formulation of the new approach, then deal with the implementation and computational scheme, and this is followed by examples to illustrate the new procedure.

  10. Multivariate Locally Weighted Least Squares Regression

    Microsoft Academic Search

    D. Ruppert; M. P. Wand

    1994-01-01

    Nonparametric regression using locally weighted least squares was first discussed by Stone and by Cleveland. Recently, it was shown by Fan and by Fan and Gijbels that the local linear kernel-weighted least squares regression estimator has asymptotic properties making it superior, in certain senses, to the Nadaraya-Watson and Gasser-Muller kernel estimators. In this paper we extend their results on asymptotic

  11. There is No Quantum Regression Theorem

    SciTech Connect

    Ford, G.W. [Department of Physics, University of Michigan, Ann Arbor, Michigan 48109-1120 (United States)] [Department of Physics, University of Michigan, Ann Arbor, Michigan 48109-1120 (United States); OConnell, R.F. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803-4001 (United States)] [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803-4001 (United States)

    1996-07-01

    The Onsager regression hypothesis states that the regression of fluctuations is governed by macroscopic equations describing the approach to equilibrium. It is here asserted that this hypothesis fails in the quantum case. This is shown first by explicit calculation for the example of quantum Brownian motion of an oscillator and then in general from the fluctuation-dissipation theorem. It is asserted that the correct generalization of the Onsager hypothesis is the fluctuation-dissipation theorem. {copyright} {ital 1996 The American Physical Society.}

  12. Censored regression modeling in agricultural economics 

    E-print Network

    Khee-Guan Tan, Andrew

    1991-01-01

    a large number of observations reporting zero expenditures. The literature on censored regression modeling is quite extensive. Previous research focused on the development of various estimation techniques and tests for model adequacy. More... data, it is typical to encounter problems with non-reporting 27 Table 1. Agricultural Economic Studies Employing Censored Regression Models Author(s) Estimation Techniques S 'Sc tion Tests Non-Norm, Heterosced. Omit. Var. Consumer Demand Capps...

  13. Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug resistance protein 4 (MRP4) via PGE2-dependent pathway.

    PubMed

    Maeng, Han-Joo; Lee, Wook-Joo; Jin, Qing-Ri; Chang, Ji-Eun; Shim, Won-Sik

    2014-10-01

    It is apparent that lung cancer is associated with inflammation, with accompanying hallmark elevations of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) levels. However, the effects of these changes on MRP efflux transporters have not been thoroughly investigated before. Here, we report that upregulation of COX-2 can induce overexpression of MRP4 in both A549 non-small-cell lung cancer cell lines and mouse lung cancer models. In A549 cells, phorbol 12-myristate 13-acetate (PMA) treatment induced upregulation of COX-2 and MRP4 together, but not other MRP transporters. Transient overexpression of human COX-2 cDNA also specifically increased COX-2 and MRP4. Moreover, COX inhibitor treatment and COX-2-specific siRNA significantly inhibited the upregulation of MRP4. Additionally, PMA-treatment increased extracellular PGE2 levels, likely due to increased MRP4 function. Likewise, COX-2-specific siRNA reduced extracellular PGE2 levels. Furthermore, COX-2 upregulation resulted in an increase in mPGES-1, an enzyme responsible for PGE2 production. Finally, metastasized lung cancer model mice exhibited increased expression levels of COX-2 and MRP4, as well as mPGES-1. In conclusion, the present study suggests that overexpression of MRP4 in lung cancer may be attributable to COX-2 upregulation via a PGE2-dependent pathway. PMID:24909729

  14. Cytochrome oxidase assembly in yeast requires the product of COX11, a homolog of the P. denitrificans protein encoded by ORF3.

    PubMed Central

    Tzagoloff, A; Capitanio, N; Nobrega, M P; Gatti, D

    1990-01-01

    The synthesis of cytochrome oxidase in Saccharomyces cerevisiae was recently shown to require a protein encoded by the nuclear gene COX10. This protein was found to be homologous to the putative protein product of the open reading frame ORF1 reported in one of the cytochrome oxidase operons of Paracoccus denitrificans. In the present study we demonstrate the existence in yeast of a second nuclear gene, COX11, whose encoded protein is homologous to another open reading frame (ORF3) present in the same operon of P. denitrificans. Mutations in COX11 elicit a deficiency in cytochrome oxidase. In this and in other respects cox11 and cox10 mutants have very similar phenotypes. An antibody has been obtained against the yeast COX11 protein. The antibody recognizes a 28 kd protein in yeast mitochondria, consistent with the size of the protein predicted from the sequence of COX11. The COX11 protein is tightly associated with the mitochondrial membrane but is not a component of purified cytochrome oxidase. An analysis of cytochrome oxidase subunits in wild type and in a cox11 mutant suggests that the COX11 protein is not required either for synthesis or transport of the subunit polypeptides into mitochondria. It seems more probable that COX11 protein exerts its effect at some terminal stage of enzyme synthesis, perhaps in directing assembly of the subunits. Images Fig. 2. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:2167832

  15. 75 FR 14488 - Public Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox Dayton International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ...Administration Public Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox Dayton...proposal to change a portion of the airport from aeronautical use to non-aeronautical use and to authorize the release of...

  16. 2-Carbaborane-3-phenyl-1H-indoles – Synthesis via McMurry Reaction and COX Inhibition Activity

    PubMed Central

    Neumann, Wilma; Scholz, Matthias; Lönnecke, Peter; Crews, Brenda; Marnett, Lawrence J.; Pietzsch, Jens; Kniess, Torsten

    2013-01-01

    Cyclooxygenase-2 (COX-2) inhibitors have been in the focus of medicinal chemistry for years and many compounds exhibiting high selectivity and affinity were developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX-2-selective 2,3-disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2-carbaborane-3-phenyl-1H-indoles could be synthesized by McMurry cyclization of the corresponding amides. While the meta-carbaboranyl-substituted derivatives (3a-c) lacked COX inhibition activity, the ortho-carbaboranyl analog (3d) was active but showed a selectivity shift towards COX-1. PMID:23303738

  17. Synthesis of 2,3-diaryl-1,3-thiazolidine-4-one derivatives as selective cyclooxygenase (COX2) inhibitors

    Microsoft Academic Search

    Afshin Zarghi; Leila Najafnia; Bahram Daraee; Orkideh G. Dadrass; Mehdi Hedayati

    2007-01-01

    A group of 2,3-diaryl-1,3-thiazolidine-4-ones, possessing a methylsulfonyl pharmacophore, were synthesized and their biological activities were evaluated for cyclooxygenase-2 (COX-2) inhibitory activity.

  18. Multiple-Instance Regression with Structured Data

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran; Roper, Alex

    2008-01-01

    We present a multiple-instance regression algorithm that models internal bag structure to identify the items most relevant to the bag labels. Multiple-instance regression (MIR) operates on a set of bags with real-valued labels, each containing a set of unlabeled items, in which the relevance of each item to its bag label is unknown. The goal is to predict the labels of new bags from their contents. Unlike previous MIR methods, MI-ClusterRegress can operate on bags that are structured in that they contain items drawn from a number of distinct (but unknown) distributions. MI-ClusterRegress simultaneously learns a model of the bag's internal structure, the relevance of each item, and a regression model that accurately predicts labels for new bags. We evaluated this approach on the challenging MIR problem of crop yield prediction from remote sensing data. MI-ClusterRegress provided predictions that were more accurate than those obtained with non-multiple-instance approaches or MIR methods that do not model the bag structure.

  19. Specific inhibition of cyclooxygenase-2 (COX2) expression by dietary curcumin in HT29 human colon cancer cells q

    Microsoft Academic Search

    Ajay Goel; C. Richard Boland; Dharam P. Chauhan

    2001-01-01

    Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti- cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a

  20. Effects of COX2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells

    Microsoft Academic Search

    Yong Ming Zhu; Nor Saadah M Azahri; Danny CW Yu; Penella J Woll

    2008-01-01

    BACKGROUND: Cyclooxygenase (COX)-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC). We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in lung cancer cells. METHODS: The levels of IL-8, VEGF and prostaglandin E2 (PGE2) were measured by ELISA. Expression of

  1. Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX2) inhibitors

    Microsoft Academic Search

    Randall E Harris; Joanne Beebe-Donk; Galal A Alshafie

    2008-01-01

    BACKGROUND: Epidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A

  2. Quantitative Analysis of Breast Cancer Tissue Microarrays Shows High Cox2 Expression Is Associated with Poor Outcome

    Microsoft Academic Search

    Maciej P. Zerkowski; Robert L. Camp; Barbara A. Burtness; David L. Rimm; Gina G. Chung

    2007-01-01

    Epidemiologic and preclinical studies suggest that cyclooxygenase-2 (Cox-2) may promote tumor growth and spread by affecting angiogenesis and apoptosis in breast cancer. Using a tissue microarray (TMA), we analyzed the expression and subcellular localization of Cox-2 by AQUA and X-tile, our algorithms for quantitative analysis of protein expression and determi- nation of optimal cutpoints. Our TMA consisted of 669 Stage

  3. Universality of mitochondrial RNA editing in cytochrome- c oxidase subunit I ( coxI) among the land plants

    Microsoft Academic Search

    Ginger L. Sper-Whitis; Jeri L. Moody; Jack C. Vaughn

    1996-01-01

    Plant mitochondrial pre-mRNAs often undergo C-to-U conversions, a phenomenon termed RNA editing. The molecular source of specificity and phylogenetic depth of the editing machinery remain to be determined. We amplified coxI gene fragments via the polymerase chain reaction from a diversity of taxa within the land plants, and sequenced each. Alignment and comparison of 25 homologous coxI gene sequences with

  4. Expression of COX2 in gastric mucosa of atrophic gastritis caused by hot high-salt water in rats

    Microsoft Academic Search

    Mei Tao; Li Zhang; Ling-Xia Zhang; Mei Jiang; Guang-Zhou Cao

    2004-01-01

    AIM: To measure the expression of COX-2 in gastric mucosa of chronic atrophic gastritis (CAG) caused by hot high-salt water in rats and to study the pathogenesis of atrophic gastritis caused by hot high-salt diet. METHODS: The atrophic gastritis rat model was made by hot high-salt water ig perfusion. The expression of COX-2 in gastric mucosa in 4, 8, 12,

  5. Phylogenetic and phylogeographic relationships in Ixodes holocyclus and Ixodes cornuatus (Acari: Ixodidae) inferred from COX1 and ITS2 sequences

    Microsoft Academic Search

    Simon Song; Renfu Shao; Rick Atwell; Stephen Barker; Dianne Vankan

    2011-01-01

    We inferred the phylogenetic and phylogeographic relationships in ticks, which were identified morphologically as Ixodes holocyclus and Ixodes cornuatus, from mitochondrial cytochrome oxidase subunit 1 (COX1) and nuclear internal transcribed spacer 2 (ITS2) sequences. We obtained COX1 (640bp) and ITS2 (527–568bp) sequences from 429 ticks from 49 localities in Tasmania, Victoria, New South Wales and Queensland, Australia. Our analyses show

  6. Modulation of the activity of pro-inflammatory enzymes, COX2 and iNOS, by chrysin derivatives

    Microsoft Academic Search

    Heeyeong Cho; Cheol-Won Yun; Woo-Kyu Park; Jae-Yang Kong; Kyoung Soon Kim; Sanghyun Lee; Bak-Kwang Kim

    2004-01-01

    Chrysin, a natural flavone compound found in plants, has anti-inflammatory activity that has been previously explained in part by the suppression of promoter activities of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Here we present evidence that several chrysin derivatives modulate the activities, as well as the expression, of COX-2 and iNOS enzymes. Nitrate production triggered by

  7. Synthesis and biological evaluation of N-substituted indole esters as inhibitors of cyclo-oxygenase-2 (COX2)

    Microsoft Academic Search

    Süreyya Ölgen; Do?u Nebio?lu

    2002-01-01

    A series of novel N-substituted indole carboxylic, acetic and propionic acid esters have been prepared as possible cyclo-oxygenase-2 (COX-2) enzyme inhibitors. Compounds 20, 23 were found slightly active against COX-2. The synthesis of indole carboxylic, acetic and propionic acid esters were furnished by using dicyclohexyl carbodiimide (DCC), dimethylamino pyridine (DMAP) as carboxylate activators. N-substitution of indole esters was verified with

  8. Specific inhibition of cyclooxygenase-2 (COX2) expression by dietary curcumin in HT29 human colon cancer cells

    Microsoft Academic Search

    Ajay Goel; C. Richard Boland; Dharam P Chauhan

    2001-01-01

    Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration-

  9. COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

    PubMed

    Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

    2015-07-01

    Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. PMID:25841778

  10. Establishing the change in antibiotic resistance of Enterococcus faecium strains isolated from Dutch broilers by logistic regression and survival analysis.

    PubMed

    Stegeman, J A; Vernooij, J C M; Khalifa, O A; Van den Broek, J; Mevius, D J

    2006-04-17

    In this study, we investigated the change in the resistance of Enterococcus faecium strains isolated from Dutch broilers against erythromycin and virginiamycin in 1998, 1999 and 2001 by logistic regression analysis and survival analysis. The E. faecium strains were isolated from caecal samples that had been randomly collected from six slaughterhouses. Moreover, between the sample collection in 1998 and the sample collection in 1999, virginiamycin and the macrolide antibiotics (of which erythromycin is a member) have been banned in The Netherlands from use in broiler feeds as growth promoter. In the logistic regression analysis we used the internationally accepted cut-off values to determine whether bacteria were resistant or not. In the survival analysis, inhibition of bacterial growth was the event and time to event was replaced by concentration of antibiotic to event. As a consequence, changes in the growth of bacteria can be tested over an entire range of concentrations and no cut-off value for resistance has to be determined. We performed the survival analysis by use of a Cox logistic model with an odds ratio (OR) for the increase of the odds of the basic hazard rate as outcome. Both the logistic regression and the survival analyses showed that resistance to erythromycin and virginiamycin decreased during the study period. In the logistic regression model the ORs associated with the fraction of bacteria inhibited by the antibiotics in 2001 as compared to 1998 were 3.76 (2.57-5.49) for erythromycin and 11.65 (7.68-17.66) for virginiamycin. The corresponding ORs from the survival analysis were lower; 2.88 (2.21-3.76) and 2.11 (1.80-2.49), respectively. The reason for the differences between the ORs of the survival analysis and the logistic regression analysis is probably because most changes in resistance included the cut-off value and logistic regression specifically examines those changes. PMID:16488031

  11. Cooperation between COA6 and SCO2 in COX2 Maturation during Cytochrome c Oxidase Assembly Links Two Mitochondrial Cardiomyopathies.

    PubMed

    Pacheu-Grau, David; Bareth, Bettina; Dudek, Jan; Juris, Lisa; Vögtle, F-Nora; Wissel, Mirjam; Leary, Scot C; Dennerlein, Sven; Rehling, Peter; Deckers, Markus

    2015-06-01

    Three mitochondria-encoded subunits form the catalytic core of cytochrome c oxidase, the terminal enzyme of the respiratory chain. COX1 and COX2 contain heme and copper redox centers, which are integrated during assembly of the enzyme. Defects in this process lead to an enzyme deficiency and manifest as mitochondrial disorders in humans. Here we demonstrate that COA6 is specifically required for COX2 biogenesis. Absence of COA6 leads to fast turnover of newly synthesized COX2 and a concomitant reduction in cytochrome c oxidase levels. COA6 interacts transiently with the copper-containing catalytic domain of newly synthesized COX2. Interestingly, similar to the copper metallochaperone SCO2, loss of COA6 causes cardiomyopathy in humans. We show that COA6 and SCO2 interact and that corresponding pathogenic mutations in each protein affect complex formation. Our analyses define COA6 as a constituent of the mitochondrial copper relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase deficiency. PMID:25959673

  12. Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

    PubMed Central

    Shang, J.L.; Cheng, Q.; Yang, W.F.; Zhang, M.; Cui, Y.; Wang, Y.F.

    2014-01-01

    People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI. PMID:25387671

  13. Direct Sequencing of Cyclooxygenase-2 (COX-2) Revealed an Intronic Variant rs201231411 in Iranian Patients with Pancreatic Cancer

    PubMed Central

    Mohamadkhani, Ashraf; Akbari, Mohammad Reza; Ghanbari, Reza; Naderi, Elnaz; Rezanejad-Asl, Parisa; Pourshams, Akram

    2015-01-01

    BACKGROUND There are hoarding documents for the biological importance of cyclooxygenase-2 (COX-2) in pancreatic carcinogenesis. We aimed to thoroughly investigate the DNA sequence variations of whole COX-2 exons in a large case-control study of pancreatic cancer by direct sequencing. METHODS The entire exonic regions of COX-2 including 10 exons were sequenced in the germline DNA of 96 patients with pancreatic cancer. Selected variants within exons six to seven (E6E7) amplicon from the test panel were genotyped in 96 controls. RESULTS The COX-2 gene was demonstrated to be genetically conserved. Four missense mutations were found in three cases. However the common variant c.724-10_724-7delATTT (rs201231411) that is located in intron 6, showed significant difference between cases and controls (21 [21.9%] vs 11 [%11.5], p=0.05). CONCLUSION This study determined that COX-2 has a conservative sequence, which is required for its enzymatic activity and supports the important role of this enzyme’s expression in pancreatic cancer rather than any changes in its activity. The effect of intronic variant rs201231411 on COX-2 expression could be analyzed in future studies. PMID:25628848

  14. Chronic Nephropathies: Individual Risk for Progression to End-Stage Renal Failure as Predicted by an Integrated Probabilistic Model

    Microsoft Academic Search

    Borislav D. Dimitrov; Piero Ruggenenti; Rumen Stefanov; Annalisa Perna; Giuseppe Remuzzi

    2003-01-01

    Background\\/Aims: To predict risk of end-stage renal disease (ESRD) in individual patients with chronic nephropathy. Methods: Sequential use of univariate analyses and Cox regression to identify risk factors, artificial neural network to quantify their relative importance and Bayesian analysis to address uncertainty of relationships and incorporate ESRD prevalence information in 344 patients with chronic nephropathy enrolled in the Ramipril Efficacy

  15. "Secure" Logistic Regression of Horizontally and Vertically Partitioned Distributed Databases

    E-print Network

    Smith, Adam D.

    "Secure" Logistic Regression of Horizontally and Vertically Partitioned Distributed Databases a "secure" logistic regression on pooled data collected separately by several parties without directly combining their databases. We describe "secure" Newton- Raphson protocol for binary logistic regression

  16. Uma análise crítica sobre a viabilidade do Uso dos inibidores seletivos de coX2 em odontologia Viability Of the USe Of SeleCti Ve COX2 inhibit ORS in denti St Ry: CRiti Cal analy SiS

    Microsoft Academic Search

    Gilson Cesar; Nobre Franco; Douglas Moretti; Paulo Fernando; Cruz Cavalcante; Luciane Cruz Lopes

    Introduction: Nonsteroidal anti-inflammatory (NSAIDs) are the most common drugs used in treatment of pain and inflammation in dentistry. NSAIDs exert their therapeutic effect by inhibiting cyclooxygenase, which exists in 2 isoforms, known as cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2). Due to the discovery of different isoforms of cyclooxygenase and the initial proposal that COX-1 was constitutively ex - pressed, whereas COX-2

  17. Regression models for estimating coseismic landslide displacement

    USGS Publications Warehouse

    Jibson, R.W.

    2007-01-01

    Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived from a collection of 2270 strong-motion records from 30 worldwide earthquakes. The regression equations predict Newmark displacement in terms of (1) critical acceleration ratio, (2) critical acceleration ratio and earthquake magnitude, (3) Arias intensity and critical acceleration, and (4) Arias intensity and critical acceleration ratio. These equations are well constrained and fit the data well (71% < R2 < 88%), but they have standard deviations of about 0.5 log units, such that the range defined by the mean ?? one standard deviation spans about an order of magnitude. These regression models, therefore, are not recommended for use in site-specific design, but rather for regional-scale seismic landslide hazard mapping or for rapid preliminary screening of sites. ?? 2007 Elsevier B.V. All rights reserved.

  18. Regression analysis using dependent Polya trees.

    PubMed

    Schörgendorfer, Angela; Branscum, Adam J

    2013-11-30

    Many commonly used models for linear regression analysis force overly simplistic shape and scale constraints on the residual structure of data. We propose a semiparametric Bayesian model for regression analysis that produces data-driven inference by using a new type of dependent Polya tree prior to model arbitrary residual distributions that are allowed to evolve across increasing levels of an ordinal covariate (e.g., time, in repeated measurement studies). By modeling residual distributions at consecutive covariate levels or time points using separate, but dependent Polya tree priors, distributional information is pooled while allowing for broad pliability to accommodate many types of changing residual distributions. We can use the proposed dependent residual structure in a wide range of regression settings, including fixed-effects and mixed-effects linear and nonlinear models for cross-sectional, prospective, and repeated measurement data. A simulation study illustrates the flexibility of our novel semiparametric regression model to accurately capture evolving residual distributions. In an application to immune development data on immunoglobulin G antibodies in children, our new model outperforms several contemporary semiparametric regression models based on a predictive model selection criterion. PMID:23839794

  19. Multiple recent horizontal transfers of the cox1 intron in Solanaceae and extended co-conversion of flanking exons

    PubMed Central

    2011-01-01

    Background The most frequent case of horizontal transfer in plants involves a group I intron in the mitochondrial gene cox1, which has been acquired via some 80 separate plant-to-plant transfer events among 833 diverse angiosperms examined. This homing intron encodes an endonuclease thought to promote the intron's promiscuous behavior. A promising experimental approach to study endonuclease activity and intron transmission involves somatic cell hybridization, which in plants leads to mitochondrial fusion and genome recombination. However, the cox1 intron has not yet been found in the ideal group for plant somatic genetics - the Solanaceae. We therefore undertook an extensive survey of this family to find members with the intron and to learn more about the evolutionary history of this exceptionally mobile genetic element. Results Although 409 of the 426 species of Solanaceae examined lack the cox1 intron, it is uniformly present in three phylogenetically disjunct clades. Despite strong overall incongruence of cox1 intron phylogeny with angiosperm phylogeny, two of these clades possess nearly identical intron sequences and are monophyletic in intron phylogeny. These two clades, and possibly the third also, contain a co-conversion tract (CCT) downstream of the intron that is extended relative to all previously recognized CCTs in angiosperm cox1. Re-examination of all published cox1 genes uncovered additional cases of extended co-conversion and identified a rare case of putative intron loss, accompanied by full retention of the CCT. Conclusions We infer that the cox1 intron was separately and recently acquired by at least three different lineages of Solanaceae. The striking identity of the intron and CCT from two of these lineages suggests that one of these three intron captures may have occurred by a within-family transfer event. This is consistent with previous evidence that horizontal transfer in plants is biased towards phylogenetically local events. The discovery of extended co-conversion suggests that other cox1 conversions may be longer than realized but obscured by the exceptional conservation of plant mitochondrial sequences. Our findings provide further support for the rampant-transfer model of cox1 intron evolution and recommend the Solanaceae as a model system for the experimental analysis of cox1 intron transfer in plants. PMID:21943226

  20. COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus oncoprotein-v-FLIP.

    PubMed

    Sharma-Walia, N; Patel, K; Chandran, K; Marginean, A; Bottero, V; Kerur, N; Paul, A G

    2012-01-01

    Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent activator of NF-?B, has well-established roles in KSHV latency and oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2 and its inflammatory metabolite PGE2 in an NF-?B-dependent manner. In addition to our previous studies demonstrating COX-2/PGE2's role in transcriptional regulation of KSHV latency promoter and latent gene expression, the current study adds to the complexity that though LANA-1 (latency associated nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced v-FLIP/K13-mediated NF-?B induction, and extracellular matrix (ECM) interaction-mediated signaling, mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment-induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion of cytokines, and spindle cell differentiation activated the phosphorylation of p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13-HMVECs reduced inflammation and invasion/metastasis-related genes, along with reduced anchorage-independent colony formation via modulating 'extrinsic' as well as 'intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells drastically augmented cell death induced by removal of essential growth/survival factors secreted in the microenvironment. Transformed cells obtained from anchorage-independent colonies of COX-2 inhibitor-treated v-FLIP/K13-HMVEC cells expressed lower levels of endothelial-mesenchymal transition genes such as slug, snail and twist, and higher expression of the tumor-suppressor gene, E-cadherin. Taken together, our study provides strong evidences that FDA-approved COX-2 inhibitors have great potential in blocking tumorigenic events linked to KSHV's oncogenic protein v-FLIP/K13. PMID:23552603

  1. COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus oncoprotein-v-FLIP

    PubMed Central

    Sharma-Walia, N; Patel, K; Chandran, K; Marginean, A; Bottero, V; Kerur, N; Paul, A G

    2012-01-01

    Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent activator of NF-?B, has well-established roles in KSHV latency and oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2 and its inflammatory metabolite PGE2 in an NF-?B-dependent manner. In addition to our previous studies demonstrating COX-2/PGE2's role in transcriptional regulation of KSHV latency promoter and latent gene expression, the current study adds to the complexity that though LANA-1 (latency associated nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced v-FLIP/K13-mediated NF-?B induction, and extracellular matrix (ECM) interaction-mediated signaling, mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment-induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion of cytokines, and spindle cell differentiation activated the phosphorylation of p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13-HMVECs reduced inflammation and invasion/metastasis-related genes, along with reduced anchorage-independent colony formation via modulating ‘extrinsic' as well as ‘intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells drastically augmented cell death induced by removal of essential growth/survival factors secreted in the microenvironment. Transformed cells obtained from anchorage-independent colonies of COX-2 inhibitor-treated v-FLIP/K13-HMVEC cells expressed lower levels of endothelial–mesenchymal transition genes such as slug, snail and twist, and higher expression of the tumor-suppressor gene, E-cadherin. Taken together, our study provides strong evidences that FDA-approved COX-2 inhibitors have great potential in blocking tumorigenic events linked to KSHV's oncogenic protein v-FLIP/K13. PMID:23552603

  2. Expression of integrin ?3?1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    PubMed Central

    2014-01-01

    Background Expression of integrin ?3?1 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 ?3?1 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 ?3?1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Methods Immunohistochemistry was performed to assess co-expression of ?3 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 ?3 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. Results Although expression of integrin ?3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between ?3 and COX2 in both tissue microarrays (rs?=?0.49, p?COX2 and ?3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin ?3?1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of ?3?1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target ?3?1, and that ?3 expression might serve as an independent prognostic biomarker. PMID:24950714

  3. Efficient Regressions via Optimally Combining Quantile Information.

    PubMed

    Zhao, Zhibiao; Xiao, Zhijie

    2014-12-01

    We develop a generally applicable framework for constructing efficient estimators of regression models via quantile regressions. The proposed method is based on optimally combining information over multiple quantiles and can be applied to a broad range of parametric and nonparametric settings. When combining information over a fixed number of quantiles, we derive an upper bound on the distance between the efficiency of the proposed estimator and the Fisher information. As the number of quantiles increases, this upper bound decreases and the asymptotic variance of the proposed estimator approaches the Cramér-Rao lower bound under appropriate conditions. In the case of non-regular statistical estimation, the proposed estimator leads to super-efficient estimation. We illustrate the proposed method for several widely used regression models. Both asymptotic theory and Monte Carlo experiments show the superior performance over existing methods. PMID:25484481

  4. Pipe performance analysis with nonparametric regression

    NASA Astrophysics Data System (ADS)

    Liu, Zheng; Hu, Yafei; Wu, Wei

    2011-04-01

    Asbestos cement (AC) water mains were installed extensively in North America, Europe, and Australia during 1920s-1980s and subject to a high breakage rate in recent years in some utilities. It is essential to understand how the influential factors contribute to the degradation and failure of AC pipes. The historical failure data collected from twenty utilities are used in this study to explore the correlation between pipe condition and its working environment. In this paper, we applied four nonparametric regression methods to model the relationship between pipe failure represented by average break rates and influential variables including pipe age and internal and external working environmental parameters. The nonparametric regression models do not take a predetermined form but it needs information derived from data. The feasibility of using a nonparametric regression model for the condition assessment of AC pipes is investigated and understood.

  5. Testing the hypothesis of a generalized linear regression model using nonparametric regression estimation

    Microsoft Academic Search

    M. Celia Rodríguez-Campos; Wenceslao González-Manteiga; Ricardo Cao

    1998-01-01

    A new test statistic is introduced to test the hypothesis of a generalized linear model in a regression context with random design. The statistic is based on the distance between a nonparametric estimator of the regression function and some ?n-consistent estimator under the parametric model. The limit distribution of the test statistic is obtained. The validity of a bootstrap version

  6. REGRESSION AND SPARSE REGRESSION METHODS FOR VISCOSITY ESTIMATION OF ACID MILK FROM IT'S SLS FEATURES

    E-print Network

    REGRESSION AND SPARSE REGRESSION METHODS FOR VISCOSITY ESTIMATION OF ACID MILK FROM IT'S SLS to estimate the rheological char- acteristics of fermented milk from its SLS features. Acidified milk products the quality of the product. 1.1. Measurement of Rheological Properties The viscosity of acid milk increases

  7. Multi-task Regression using Minimal Penalties Multi-task Regression using Minimal Penalties

    E-print Network

    Abstract In this paper we study the kernel multiple ridge regression framework, which we refer to as multi penalty, which was previously used in the single-task regression framework to estimate the variance penalty leads to an oracle inequality. We illustrate the behavior of our algorithm on synthetic examples

  8. Cox2 and ?-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions12

    PubMed Central

    Kong, Jianping; Crissey, Mary Ann S; Stairs, Douglas B; Sepulveda, Antonia R; Lynch, John P

    2011-01-01

    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. PMID:21969813

  9. Vibrational modes in Zn1-xFexSe and Zn1-xCoxSe

    Microsoft Academic Search

    Chee-Leung Mak; R. Sooryakumar; B. T. Jonker; G. A. Prinz

    1992-01-01

    We report on a Raman study of lattice vibrations in the diluted magnetic semiconductors Zn1-xFexSe (0CoxSe (0

  10. Low-temperature transport, optical, magnetic and thermodynamic properties of Fe1-xCoxSi

    Microsoft Academic Search

    M. A. Chernikov; L. Degiorgi; E. Felder; S. Paschen; A. D. Bianchi; H. R. Ott; J. L. Sarrao; Z. Fisk; D. Mandrus

    1997-01-01

    We report measurements of the electrical conductivity sigma(T), the optical reflectivity R(omega,T), the low-field ac magnetic susceptibility chi'(T,f), and the specific heat Cp(T) for polycrystalline samples of Fe1-xCoxSi with 0<=x<=0.03 at low temperatures. Between 130 and 300 K the temperature variation of sigma(omega,T) is consistent with that of a hybridization-gap semiconductor and is very similar for all samples. Below 50

  11. Mixed-Phase Icing Simulation and Testing at the Cox Icing Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Al-Khalil, Kamel; Irani, Eddie; Miller, Dean

    2003-01-01

    A new capability was developed for indoor simulation of snow and mixed-phase icing conditions. This capability is useful for year-round testing in the Cox closed-loop Icing Wind Tunnel. Certification of aircraft for flight into these types of icing conditions is only required by the JAA in Europe. In an effort to harmonize certification requirements, the FAA in the US sponsored a preliminary program to study the effects of mixed-phase and fully glaciated icing conditions on the performance requirements of thermal ice protection systems. This paper describes the test program and the associated results.

  12. CoxC nanorod magnets: Highly magnetocrystalline anisotropy with lower Curie temperature for potential applications

    NASA Astrophysics Data System (ADS)

    El-Gendy, Ahmed A.; Almugaiteeb, Turki; Carpenter, Everett E.

    2013-12-01

    Magnetic CoxC nanorods with larger magnetocrystalline anisotropy of 5×105 J/m3 as well as larger coercivity and lower Curie temperature are introduced. The particles have an average diameter of 8 nm and shows three different magnetic behaviors. The sample shows ferromagnetism up to 400 K, superparamagnetism at temperature >400 K and

  13. Fluorescence imaging of dendritic spines of Golgi-Cox-stained neurons using brightening background

    NASA Astrophysics Data System (ADS)

    Ai, Min; Xiong, Hanqing; Yang, Tao; Shang, Zhenhua; Chen, Muqing; Liu, Xiuli; Zeng, Shaoqun

    2015-01-01

    We report a novel fluorescence imaging approach to imaging nonfluorescence-labeled biological tissue samples. The method was demonstrated by imaging neurons in Golgi-Cox-stained and epoxy-resin-embedded samples through the excitation of the background fluorescence of the specimens. The dark neurons stood out clearly against background fluorescence in the images, enabling the tracing of a single dendritic spine using both confocal and wide-field fluorescence microscopy. The results suggest that the reported fluorescence imaging method would provide an effective alternative solution to image nonfluorescence-labeled samples, and it allows tracing the dendritic spine structure of neurons.

  14. Celecoxib prevents tumor growth in an animal model by a COX2 independent mechanism

    Microsoft Academic Search

    Amanda Leite Bastos-Pereira; Daiana Lugarini; Adriana de Oliveira-Christoff; Thiago Vinicius Ávila; Simone Teixeira; Amanda do Rocio Andrade Pires; Sílvia Maria Suter Correia Cadena; Lucélia Donatti; Helena Cristina da Silva de Assis; Alexandra Acco

    2010-01-01

    Purpose  Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible\\u000a antineoplastic drugs are cyclooxygenase-2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were\\u000a evaluated in rats bearing Walker-256 (W256) tumor.\\u000a \\u000a \\u000a \\u000a Methods  W256 carcinosarcoma cells were inoculated subcutaneously (107 cells\\/rat) in rats submitted to treatment with celecoxib (25 mg kg?1) or vehicle for 14 days. Tumor growth,

  15. Nèel temperature variation of CoxNi1-xFe2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Niu, Ziping; Li, Fashen

    2015-04-01

    CoxNi1-xFe2O4 (x=0.1, 0.3, 0.5) nanoparticles were synthesized by the PVA Sol-Gel method, and all the samples were found to be single phase spinel by powder X-ray diffraction measurements. High temperature Mössbauer spectra were recorded by a Mössbauer spectrometer. Temperature dependence of hyperfine magnetic fields of two magnetic sextets indicates a "two Nèel temperatures" phenomenon in Co0.3Ni0.7Fe2O4 and Co0.5Ni0.5Fe2O4, which has been further demonstrated by the magnetic thermo-gravimetric analysis (MTGA).

  16. Contribution of tomato phenolics to suppression of COX-2 expression in KB cells.

    PubMed

    Shen, Y-C; Chen, S-L; Zhuang, S-R; Wang, C-K

    2008-01-01

    Tomatoes, which are consumed worldwide, contain abundant phenolics. The objective of this study was to understand the suppression effect of phenolics in fresh and heated tomatoes on the expression of cyclooxygenase 2 (COX-2). Both small and big tomatoes of fresh or heated (in boiling water for 30 min) treatments were used. Sephadex LH-20 gel was used to separate the noncondensed tannin containing and the condensed tannin containing fractions from the crude phenolic extracts of tomatoes. The condensed tannin containing fraction was rich in condensed tannins and simple phenolics. The noncondensed tannin containing fraction contained abundant nontannin flavans. This study explored the effect of tomato phenolic extracts on the regulation of 12-o-teradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in KB cells. HPLC showed that tomato phenolic profiles were similar between small and big tomatoes either by fresh or heated treatment. Fresh tomato extracts had 70.8 +/- 4.8% (mean +/- SD) noncondensed tannin containing polyphenols (6.68 +/- 0.09 mg/g dry weight), 27.4 +/- 6.9% condensed tannin containing polyphenols (3.52 +/- 0.24 mg/g dry weight), and 1.7 +/- 0.6% other residues. Instead, heated tomato had 53.3 +/- 4.3% noncondensed tannin containing polyphenols (2.70 +/- 0.20 mg/g dry weight), 24.2 +/- 1.7% condensed tannin containing polyphenols (7.37 +/- 0.03 mg/g dry weight), and 22.5 +/- 4.8% other residues. Cell studies showed that phenolic extracts of heated tomatoes resulted in increased suppression of COX-2 expression compared with that of fresh tomato. Noncondensed tannin containing fraction of fresh tomato greatly suppressed COX-2 expression (P < 0.05) that compared to the negative control, but both noncondensed tannin containing and condensed tannin containing fractions of heated tomatoes showed suppression on COX-2 expression. These results suggest that tomato phenolics may play an important role in the chemoprevention of cancer. PMID:18211342

  17. Structures and magnetic properties of wurtzite Zn1-xCoxO dilute magnetic semiconductor nanocomposites

    Microsoft Academic Search

    Tongfei Shi; Sanyuan Zhu; Zhihu Sun; Shiqiang Wei; Wenhan Liu

    2007-01-01

    Cobalt-doped ZnO dilute magnetic semiconductor nanocomposites Zn1-xCoxO with Co concentrations from 0.02 to 0.25 were prepared by the sol-gel method. The magnetic measurement shows paramagnetic behavior for all the samples. The structures of these composites were investigated by x-ray diffraction and fluorescence x-ray absorption fine structure spectroscopy. It is indicated that at low Co concentration (x=0.10), the secondary phase Co3O4

  18. Removing Malmquist bias from linear regressions

    NASA Technical Reports Server (NTRS)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  19. Salience Assignment for Multiple-Instance Regression

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran

    2007-01-01

    We present a Multiple-Instance Learning (MIL) algorithm for determining the salience of each item in each bag with respect to the bag's real-valued label. We use an alternating-projections constrained optimization approach to simultaneously learn a regression model and estimate all salience values. We evaluate this algorithm on a significant real-world problem, crop yield modeling, and demonstrate that it provides more extensive, intuitive, and stable salience models than Primary-Instance Regression, which selects a single relevant item from each bag.

  20. Topics in route-regression analysis

    USGS Publications Warehouse

    Geissler, P.H.; Sauer, J.R.

    1990-01-01

    The route-regression method has been used in recent years to analyze data from roadside surveys. With this method, a population trend is estimated for each route in a region, then regional trends are estimated as a weighted mean of the individual route trends. This method can accurately incorporate data that is unbalanced by changes in years surveyed and observer differences. We suggest that route-regression methodology is most efficient in the estimation of long-term (>5 year) trends, and tends to provide conservative results for low-density species.